understanding effective and timely administration of loop ... · 5 improving efficiency of diuretic...

132
Understanding Effective and Timely Administration of Loop Diuretics for the Treatment of Acute Heart Failure: A Quality Improvement Intervention and Evaluation by Alisa Maznytsya A thesis submitted in conformity with the requirements for the degree of Master of Science Institute of Medical Science University of Toronto © Copyright by Alisa Maznytsya 2016

Upload: others

Post on 24-Jul-2020

3 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

Understanding Effective and Timely Administration of Loop

Diuretics for the Treatment of Acute Heart Failure: A Quality

Improvement Intervention and Evaluation

by

Alisa Maznytsya

A thesis submitted in conformity with the requirements

for the degree of Master of Science

Institute of Medical Science

University of Toronto

© Copyright by Alisa Maznytsya 2016

Page 2: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

Understanding Effective and Timely Administration of Loop Diuretics for the

Treatment of Acute Heart Failure: A Quality Improvement Intervention and

Evaluation

Alisa Maznytsya

Master of Science

Institute of Medical Science

University of Toronto

2016

ABSTRACT

Objectives: Intravenous administration of loop diuretics is a cornerstone of therapy for acute

heart failure. We developed and evaluated the MSH La6 Protocol, a tool to standardize practices

for administration, monitoring and dose adjustment of IV furosemide over a 48-hour period and

delegated autonomy to the nurse at the point of care.

Results: There were no serious adverse events and no deaths. Between the pre- and post-

implementation period, a significant and stable improvement was observed in the monitoring of

patients receiving IV furosemide. A significantly larger proportion of patients treated using the

La6 Protocol had a furosemide dose increase in the 24-48 hour block versus patients treated with

usual care.

Conclusions: An intervention that resulted in improved adherence to practices for monitoring

was also associated with the observation that furosemide dosage was up titrated more frequently

early during hospital admission.

ii

Page 3: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

Acknowledgements

First and foremost, I would like to express my sincere gratitude to my supervisor, Dr.

Susanna Mak. Without her innovative thinking and tremendous dedication, this project would

not have been possible. I would also like to thank Dr. Mak for her continual mentorship and

support in my learning. Her devotion to teaching is unparalleled and valued by all the students

within our group.

I am grateful to my supervisory committee Dr. Chaim Bell and Dr. Douglas Lee for their

support and guidance throughout this project. I would like to sincerely thank Dr. Andrew Wyllie

for his valuable input and encouragement every step of the way. I would also like to

acknowledge Dr. Gary Newton for his insight and advice in developing this work.

I would like to thank all of the nursing staff and nursing administration on the cardiology

and medicine wards at Mount Sinai Hospital for participating in this practice change. I am also

thankful for the support I received in this initiative from the cardiologists at our institution.

I will never forget the never-ending support I received from the students in our group –

Sam Esfandiari, Daniela Malta, Kelsey McLaughlin, and Steve Wright. Their help and friendship

has meant the world.

This accomplishment would not have been possible without the support of my loving

husband and family. The gratitude I feel to my parents is immeasurable and all of my successes

are possible because of their unwavering love, strength and support. I dedicate this work to them.

iii

Page 4: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

Contributions

The following individuals contributed to this work:

Caitlin Chang – design, implementation, data collection

Sara Brade – design, implementation, data collection, analysis

Talal Al-Jabbary, MD – implementation, data collection, analysis

Robert Pearce, MD – data collection

Catherine Eta-Ndu, RN – design, implementation, knowledge/content expertise

Natalia Persad, BA BScPhm – data collection

Chaim Bell, MD PhD – analysis, knowledge/content expertise, manuscript review

Douglas S. Lee, MD PhD - analysis, knowledge/content expertise, manuscript review

Jocelyn Bennett, RN - design, implementation, knowledge/content expertise

Andrew Wyllie, BScPhm PharmD – design, implementation, knowledge/content expertise,

manuscript review

Susanna Mak, MD PhD – design, implementation, knowledge/content expertise, analysis,

manuscript review

iv

Page 5: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

Table of Contents

List of Tables.................................................................................................................................. x

List of Figures................................................................................................................................ xi

Abbreviated Terms....................................................................................................................... xii

1 Heart Failure............................................................................................................................. 1

1.1 Heart Failure: General Overview.................................................................................. 1

1.2 Acute Heart Failure (AHF) ......................................................................................... 8

1.2.1 Congestion in the Setting of Acute Heart Failure....................................... 9

1.3 Treatment of AHF....................................................................................................... 10

1.3.1 Evidence and Guidelines for Management of Acute Heart Failure.......... 10

1.3.2 Loop Diuretics.......................................................................................... 15

1.3.2.1 Mechanism of Action.................................................................... 15

1.3.2.2 Mode of Administration in Acute Heart Failure........................... 16

1.3.3 Assessment and Monitoring of Patients Receiving Intravenous Loop

Diuretics.................................................................................................... 18

1.3.3.1 Hypokalemia................................................................................. 20

2 Protocol Development............................................................................................................ 22

2.1 Quality of Care for AHF: The Gap Between Guideline Recommendations and Actual

Delivery of Care.......................................................................................................... 22

2.1.1 Safety in Diuretic Management................................................................... 22

2.1.2 Timeliness of Diuretic Management............................................................ 24

2.2 Description of MSH La6 Protocol and Components.................................................. 25

v

Page 6: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

2.2.1 Specific Objectives and Design of the MSH La6 Protocol.......................... 25

2.2.2 Physician Pre-printed Order Set (PPOS) .................................................... 26

i) Patient Selection.................................................................................... 29

ii) Standardized Orders for Monitoring Efficacy and Detection of Drug-

Related Adverse Events........................................................................ 29

iii) Furosemide Dosing Regimen.............................................................. 30

iv) Delegation to Nursing Staff................................................................. 31

2.2.3 Nomogram for Stepped Diuretic Care (Nomo-SDC).................................. 31

i) Selection, Timing and Titration of Diuretic Dosing.............................. 34

ii) Monitoring............................................................................................ 35

iii) Prevention, Detection and Treatment of Drug-Related Adverse

Events.................................................................................................... 36

iv) Completion of the Protocol and Transition to Usual Care.................. 38

2.3 Issues of Local Implementation.................................................................................. 38

2.4 Considerations for Education...................................................................................... 38

2.4.1 PPOS as an Educational Tool...................................................................... 39

2.4.2 Educational Packages................................................................................... 39

3 Hypothesis and Research Aims.............................................................................................. 41

4 Methods Of Evaluation........................................................................................................... 42

4.1 Overview of Quality Improvement............................................................................. 42

4.2 Process Measurement.................................................................................................. 42

4.2.1 Measuring adherence to a process............................................................... 43

vi

Page 7: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

4.2.2 Opportunity Based Scoring.......................................................................... 43

4.2.3 All-or-none scoring/Defect Free Scoring..................................................... 44

4.2.4 Shewhart control charts................................................................................ 44

4.3 Selection of Endpoints for Process Evaluation........................................................... 45

4.3.1 Selection of safety endpoints....................................................................... 45

i) Adherence to monitoring processes....................................................... 46

ii) Definition of potential adverse events: potassium homeostasis........... 47

iii) Definition of potential adverse events: renal function........................ 48

iv) Adverse Clinical Events...................................................................... 48

4.3.2 Selection Endpoints for outcome measurements......................................... 49

i) Furosemide Administration................................................................... 49

ii) Potassium Administration.................................................................... 50

4.4 Study Design............................................................................................................... 50

4.4.1 Pre and Post Design..................................................................................... 50

4.4.2 Patient populations....................................................................................... 50

4.4.3 Data collection............................................................................................. 52

5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart

Failure Using a Nurse Implemented Strategy: MSH La6 Protocol........................................ 61

5.1 Introduction................................................................................................................. 61

5.2 Methods....................................................................................................................... 63

5.2.1 The Physician Pre-Printed Order Set (PPOS).............................................. 63

i) Patient Selection.................................................................................... 63

vii

Page 8: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

ii) Standardized Orders for Monitoring Efficacy and Safety of Therapy. 63

5.2.2 The Nomogram for Stepped Diuretic Care (Nomo-SDC)........................... 63

i) Timing, and Titration of Furosemide Dosing........................................ 64

ii) Monitoring and Replacement of Electrolytes....................................... 64

iii) Completion or Early Termination of the Protocol.............................. 65

5.2.3 Evaluation of Patient Population, Feasibility and Safety............................. 65

5.2.4 Evaluation of Protocol Adherence............................................................... 66

5.2.5 Evaluation of Early Effectiveness................................................................ 67

5.2.6 Statistical Analysis....................................................................................... 67

5.3 Results......................................................................................................................... 68

5.3.1 Patient Population, Feasibility and Safety................................................... 68

5.3.2 Adherence to Monitoring Actions............................................................... 68

5.3.3 Adherence to Pre-specified Drug Administration........................................ 69

5.3.4 Treatment Effect.......................................................................................... 69

5.4 Discussion................................................................................................................... 73

6 Linking Improved Processes Of Care With Timeliness Of Intravenous Diuresis For Acute

Heart Failure........................................................................................................................... 76

6.1 Introduction................................................................................................................. 76

6.2 Methods....................................................................................................................... 78

6.2.1 Setting.......................................................................................................... 78

6.2.2 Quality Improvement Interventions............................................................. 78

6.2.3 Evaluation.................................................................................................... 80

viii

Page 9: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

6.2.4 Process and Outcome Measures................................................................... 81

6.2.5 Data Analysis............................................................................................... 82

6.3 Results......................................................................................................................... 84

6.3.1 Cohorts......................................................................................................... 84

6.3.2 Process Measures......................................................................................... 84

6.3.3 Furosemide Prescription Pre- and Post-Implementation............................. 84

6.3.4 Impact of the La6 Protocol.......................................................................... 84

6.4 Discussion................................................................................................................... 95

7 General Discussion................................................................................................................. 99

8 Conclusions and Future Directions....................................................................................... 105

References................................................................................................................................... 109

ix

Page 10: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

List of Tables

Table 1. Framingham Clinical Criteria for Diagnosis of Heart Failure......................................... 6

Table 2. Acute Heart Failure Management Guidelines – 2014 Summary................................... 12

Table 3. Sample Data Collection Form........................................................................................ 55

Table 4. Characteristics of the La6 Protocol Patients................................................................. 71

Table 5. Adherence to Furosemide and Potassium Administration as Guided

by the Nomo-SDC.......................................................................................................... 72

Table 6. Clinical Characteristics of the Pre-, Post- and Implementation Patient Cohorts........... 87

Table 7. Furosemide Dose Adjustment in Patients Eligible for the MSH La6 Protocol.............. 89

x

Page 11: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

List of Figures

Figure 1. Physician Pre-Printed Order Set (PPOS) ..................................................................... 28

Figure 2. Nomogram for Stepped Diuretic Care (Nomo-SDC) .................................................. 33

Figure 3. Potassium Replacement Nomogram............................................................................. 37

Figure 4. Analysis Cohorts........................................................................................................... 91

Figure 5. Hospital-Wide Acute Heart Failure Process Measures Shewhart Control Charts

5A. Opportunity-Based Score for Monitoring of Daily Serum Potassium, Serum

Creatinine and Weight............................................................................................... 92

5B. All-or-None Score for Monitoring of Daily Serum Potassium, Serum Creatinine

and Weight.................................................................................................................. 93

5C. Percent of Patients With At Least 2 Weight Measurements in 48 Hours.................. 94

xi

Page 12: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

Abbreviated Terms

ACB – aortocoronary bypass

ACE - angiotensin converting enzyme

ADHERE - Acute Decompensated Heart Failure National Registry

ADHF – acute decompensated heart failure

AHF – acute heart failure

AKI – acute kidney injury

ALP - alkaline phosphatase

ALT - alanine aminotransferase

ARB - angiotensin receptor blockers

AST - aspartate aminotransferase

BNP - brain natriuretic peptide

BP – blood pressure

BUN - blood urea nitrogen

Ca2+ - calcium

CARRESS-HF - The Cardiorenal Rescue Study in Acute Decompensated Heart Failure

CTU – clinical teaching unit

DIA - diastolic

DOSE - Diuretic Optimization Strategies Evaluation

ED – emergency department

EFFECT - Enhanced Feedback for Effective Cardiac Treatment

eGFR – estimated glomerular filtration rate

xii

Page 13: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

EPR – electronic patient record

ESRD – end stage renal disease

Hb – hemoglobin

HF – heart failure

HFpEF – heart failure with preserved ejection fraction

HFrEF – heart failure with reduced ejection fraction

Ht – hematocrit

HTN – hypertension

ICU – intensive care unit

INR – international normalized ratio

IOM – institute of medicine

IPC – interprofessional collaboration

IQR – interquartile range

IV - intravenous

JVP – jugular venous pressure

K - potassium

LOS – length of stay

MI – myocardial infarction

MRI – magnetic resonance imaging

MRP – most responsible physician

MSH – Mount Sinai Hospital

Na+ - sodium

xiii

Page 14: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

NICE - National Institute for Health and Clinical Excellence Guidance

NIH – National Institutes of Health

Nomo-SDC – Nomogram for Stepped Diuretic Care

NT-proBNP - N-terminal pro b-type natriuretic peptide

NYHA – New York Heart Association

PCI – percutaneous coronary intervention

PND – paroxysmal nocturnal dyspnea

PO – per os

PPOS – Physician Preprinted Order Set

QI – quality improvement

RCT – randomized control trial

RIFLE - Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease

RN – registered nurse

SBP – systolic blood pressure

SCr – serum creatinine

SD – standard deviation

SPSS - Statistical Package for the Social Sciences

SYS - systolic

UK-Heart - United Kingdom Heart Failure Evaluation and Assessment of Risk Trial

xiv

Page 15: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

1

1 Heart Failure

1.1 Heart Failure: General Overview

The purpose of this section is to provide a general summary and is not intended as an

exhaustive review. Heart Failure (HF) is a complex clinical syndrome that arises from a variety

of cardiac diseases and results in progressive impairment of systemic perfusion that is

insufficient to keep up with metabolic demands (Cowie et al., 1997). Although incidence has

steadily decreased over the past couple of decades, increasing size of the aging population has

resulted in a rise in prevalence of heart failure over time (W. H. Barker, Mullooly, & Getchell,

2006; Braunwald, 1997, 2013; Cowie et al., 1997; Heidenreich et al., 2013; Ho, Pinsky, Kannel,

& Levy, 1993; Levy et al., 2002; Mosterd & Hoes, 2007; Yeung et al., 2012). The lifetime risk

of HF is higher in women (1 in 6) versus men (1 in 9) at 40 years old; risk is also doubled in

those with blood pressure (BP) >160/90 mmHg versus those with BP <140/90 mmHg (Lloyd-

Jones et al., 2002). Two commonly utilized classification systems of heart failure summarize the

symptomatic state of the patient as well as the severity of disease. The first was developed by the

New York Heart Association (NYHA) and divides heart failure severity into 4 classes based on

the functional limitations of the patient.

Class I – Heart disease present; no limitation of physical activity.

Class II – Heart disease present; limitation of physical activity present during routine and

regular activity.

Class III – Heart disease present; limitation of physical activity present with less than

routine physical activity. No symptoms at rest.

Class IV – Heart disease present; symptoms present with any physical activity and at rest.

Page 16: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

2

The second classification system divides heart failure based on its stage of development and was

conceived by the American Heart Association. It identifies the following 4 stages of heart failure

(Yancy et al., 2013):

Stage A – High risk of heart failure; absence of structural heart disease or symptoms of

HF.

Stage B – Presence of structural heart disease; absence of signs or symptoms of HF.

Stage C – Presence of structural heart disease; presence of prior or current symptoms of

HF.

Stage D – Refractory HF requiring specialized care.

Both classification systems are valuable in establishing the presence and severity of heart failure

and therefore guiding therapeutic strategies.

Heart failure can be caused by a vast variety of illnesses affecting every layer of cardiac

tissue (pericardium, myocardium, endocardium) as well as the vasculature and valvular

apparatus (Cowie et al., 1997). e. The syndrome of heart failure related to left ventricular

chamber abnormalities is divided into patients that clearly demonstrate reduction of the left

ventricular ejection fraction (<40 percent) and is known as heart failure with reduced ejection

fraction (HFrEF), or previously, systolic heart failure. Another group of patients with heart

failure are presumed to have abnormalities of diastolic performance because the left ventricular

ejection fraction is reasonably preserved (>40 percent) and this is known as heart failure with

preserved ejection fraction or HFpEF. The older term for this subtype is diastolic heart failure.

Appropriate diagnosis of HFrEF or HFpEF is crucial for proper management of chronic heart

failure. The prevalence of cardiac diseases that lead to the development of heart failure has also

changed over the past few decades due to changes in socio-economic status as well as

Page 17: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

3

improvements in preventative strategies, diagnosis and therapeutics (Cowie et al., 1997; Kannel,

Ho, & Thom, 1994; Mozaffarian et al., 2016). The age-adjusted incidence and prevalence of

conditions such as hypertension and ischemic heart disease that contribute to the development of

heart failure are decreasing (He et al., 2001; Lloyd-Jones et al., 2002). However, these gains

have been offset by the increasing incidence of diabetes mellitus, a significant concern as a cause

of heart failure (Owan et al., 2006). In Canada, the self-reported prevalence of heart disease

(including myocardial infarction, angina and heart failure) is 4.2% in women and 5.3% in men

("Tracking Heart Disease and Stroke in Canada," 2009).

The diagnosis of symptomatic (Stage C and D) heart failure is based on a multifaceted

clinical assessment, composed of a carefully taken medical history of the patient as well as a

thorough physical examination as there is no single conclusive diagnostic test available. There

are 2 helpful diagnostic investigations that are commonly used to aid in the proper diagnosis of

heart failure for a patient presenting with suggestive symptoms. Serum B-type natriuretic peptide

(BNP) is secreted primarily by the ventricular myocyte in response to increased wall stress. It is

secreted as a pro-peptide and cleaved into the active peptide (BNP) and the N-terminal end (NT-

pro-BNP), both fragments can be measured in serum using commercially available assays. In the

setting of increased ventricular wall stress, both BNP and NT-pro-BNP will be elevated in the

blood. This marker is very helpful in establishing diagnosis when used in conjunction with a

careful history taking and physical examination. Current guidelines also present evidence

showing decreased mortality when BNP guided therapy is used to treat heart failure (Kelder et

al., 2011; Moe et al., 2015; Yancy et al., 2013). A second useful diagnostic tool is transthoracic

2-dimensional echocardiography combined with a Doppler ultrasound examination (Heart

Failure Society of et al., 2010; McKelvie et al., 2013; Yancy et al., 2013). This noninvasive

Page 18: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

4

diagnostic assessment examines hemodynamics and cardiac function in patients with signs and

symptoms of heart failure. A complete echocardiographic examination evaluates chamber sizes,

ventricular function and wall motion abnormalities and can often yield clues as to the etiology of

heart failure (Cheitlin et al., 2003). Other cardiac diagnostic tools include an electrocardiogram,

a chest x-ray, exercise stress testing, and advanced imaging such as magnetic resonance imaging

(MRI) (Pennell et al., 2004) and cardiac catheterization (Yancy et al., 2013). More specifically,

these tools are valuable in establishing the etiology of heart failure.

There are cardinal clinical signs and symptoms that suggest the diagnosis of heart failure.

They can be divided into those that reflect insufficient cardiac output and those that reflect fluid

congestion in various tissues. In cardiac conditions predisposing to heart failure, inadequate

increases in cardiac output occur during periods of increased metabolic demand such as exertion

and patients experience weakness and fatigue. The decrease in cardiac output, in turn, causes

neurohumoral activation and impaired intrarenal hemodynamics leading to worsening renal

function, and in some cases leading to the development of the cardiorenal syndrome (Liu, 2008).

These complex pathophysiological processes then lead to excess fluid accumulation in different

tissues (Braunwald, 2013; Liu, 2008). Symptoms associated with fluid accumulation are

dependent on the affected organ and include dyspnea and paroxysmal nocturnal dyspnea,

orthopnea, peripheral edema, right lower quadrant tenderness from hepatic congestion, and

ascites (Maisel et al., 2002). There may be many more signs and symptoms present based on the

underlying heart disease.

There are diagnostic criteria available to assist in the proper diagnosis of heart failure.

Several criteria have been validated, including the Framingham, Boston and Duke scales. The

Page 19: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

5

most widely used of the three is the modified Framingham clinical criteria for the diagnosis of

heart failure, which has excellent sensitivity and specificity and includes the following:

Page 20: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

6

Table 1. Framingham Clinical Criteria for Diagnosis of Heart Failure

Major Minor

Orthopnea Weight loss ≥4.5 kg in five days

Pulmonary rales Tachycardia (heart rate ≥120 beats/min)

Cardiomegaly on chest x-ray Pleural effusion

Pulmonary edema on chest x-ray Hepatomegaly

Paroxysmal nocturnal dyspnea Dyspnea on ordinary exertion

Elevated jugular venous pressure Nocturnal cough

Third heart sound Bilateral leg edema

Weight loss ≥4.5 kg in five days in response to

treatment of presumed heart failure*

Page 21: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

7

The diagnosis of heart failure based on the Framingham criteria requires 2 major or 1

major and 2 minor criteria.

Management of chronic Stage C and D heart failure encompasses a few important

components – education and control of risk factors, including coronary artery disease, cigarette

smoking, hypertension, obesity, diabetes and valvular heart disease (Gopal et al., 2012; He et al.,

2001, 2002; Nkomo et al., 2006) as well as lifestyle modification (Djousse, Driver, & Gaziano,

2009), and pharmacological therapy. The goals of therapy in stage C and D are aimed at

improving symptoms, reducing or slowing down the structural damage of the heart as well as

reducing mortality. Several clinical trials have shown benefit on reducing mortality with the

appropriate use of angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor

blockers (ARBs), hydralazine and nitrates, aldosterone antagonists and beta-blockers (McKelvie

et al., 2013; Pitt et al., 1999). Evidence for treatment of HFpEF is more limited.

In advanced heart failure, after guideline-directed medical therapy with the above-

mentioned drugs has been used, certain strategies exist to control ongoing symptoms of heart

failure, particularly those related to congestion. There are observational studies that show benefit

with salt restriction (Arcand et al., 2011; Bennett et al., 1998; He et al., 2002; Lennie et al., 2011;

Son, Lee, & Song, 2011; Tsuyuki et al., 2001) (2grams/day or 3grams/day based on source of

recommendation (Heart Failure Society of et al., 2010; McMurray et al., 2012; Yancy et al.,

2013)) and fluid restriction in refractory heart failure. Despite control of chronic symptoms of

heart failure and optimal medical therapy, patients still experience episodes during which

symptoms worsen. The next section describes the clinical entity of acute heart failure.

There are many factors that determine the prognosis of patients diagnosed with heart

failure. The etiology, patients’ demographics, management strategy, patient compliance, and

Page 22: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

8

hospitalizations are all important predictors. Although prevalence of heart failure has increased

over the years, in part due to increasing aging population and improved methods of heart failure

management, mortality reduction has steadily improved, as evidenced by numerous studies

(Brophy, 1992; Cowie et al., 1997).

1.2 Acute Heart Failure (AHF)

Although heart failure is considered a chronic and progressive condition, its course is

punctuated by episodes of acute worsening of symptoms due to a number of disease-specific as

well as external factors requiring specific therapy. The most current guidelines on management

have defined these episodes as ‘acute heart failure’(McKelvie et al., 2013), with some still

referring to the older term of ‘acute decompensated heart failure’(Gupta, Ghimire, & Hage,

2014; Heart Failure Society of et al., 2010; McKelvie et al., 2013). Acute heart failure presents

as an exacerbation of symptoms usually controlled with medication and lifestyle modification,

with the most common constellation of symptoms referred to as congestion, further discussed in

Section 1.2.1.

Acute heart failure is responsible for the majority of unplanned hospitalization for patients

either suffering from chronic heart failure, or as the initial presentation of heart failure. The

Canadian Institute for Health Information considers heart failure an ambulatory care sensitive

condition, such that appropriate ambulatory care may reduce the need for admission to hospital.

The hospitalization rate for heart failure is expressed as age-standardized acute care

hospitalization rate per 100,000 population younger than age 75, (Health Indicators 2013:

Definitions, Data Sources and Rationale, May 2013, 2013) calculated as the total number of

acute care hospitalizations for ambulatory care sensitive conditions younger than age 75 ∕ total

mid-year population younger than age 75) × 100,000 (age adjusted). The age adjusted admission

Page 23: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

9

rate to hospital with the primary diagnosis of heart failure has steadily declined around the world

in the last 20 years (Chen, Normand, Wang, & Krumholz, 2011; Jhund et al., 2009;

Schaufelberger, Swedberg, Koster, Rosen, & Rosengren, 2004; Tu, Nardi, et al., 2009). In

Canada hospitalization rate fell 27.2% between 1994 and 2004 (Tu, Nardi, et al., 2009). It is

hypothesized that the decline in incidence of heart failure contributed to this change in

hospitalization rate. Age-adjusted mortality has also declined (Roger et al., 2004). However, the

combination of improved survival and the increasing size of the elderly population is such that

the total burden of hospitalization remains very high (Fang, Mensah, Croft, & Keenan, 2008; Lee

et al., 2004).

Despite the improvement, several studies have shown that mortality and rehospitalization

rates remain high following a hospitalization (Krumholz et al., 1997; Roger et al., 2004;

Solomon et al., 2007). The need for hospitalization remains an important determinant of short-

term prognosis in heart failure patients. Mortality was found to be highest within one month of

discharge for heart failure (Solomon et al., 2007).

1.2.1 Congestion in the Setting of Acute Heart Failure

Congestion refers to the accumulation of fluid in the body that occurs as a consequence of

several compensatory mechanisms the body utilizes in response to the decreased cardiac output

in heart failure. The compensatory neurohormonal adaptations initially work to maintain

systemic pressure and perfusion of vital organs as well as restore normal cardiac output.

However, with time, these adaptations lead to a constellation of negative consequences that,

when combined, present as clinical signs and symptoms of congestion (Francis, Goldsmith,

Levine, Olivari, & Cohn, 1984). One of the compensatory neurohormonal adaptations is the

activation of the renin-angiotensin-aldosterone system. Within this mechanism, Angiotensin II

Page 24: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

10

causes sodium reabsorption, which in turn causes an expansion of extracellular fluid and an

increase in diastolic pressures. Although initially acting as a compensatory mechanism meant to

restore cardiac output, with time the increased venous return causes an elevation in capillary

pressures and the development of pulmonary and peripheral congestion. Fluid accumulation in

the lungs results in symptoms of dyspnea, fatigue, paroxysmal nocturnal dyspnea (PND) and

orthopnea. Peripheral venous congestion manifests as symptoms of peripheral edema, extending

from the lower limbs all the way up to the abdominal cavity, as well as an elevated jugular

venous pressure, ascites and poor appetite.

Several large databases have recorded high quality data on patients admitted with acute heart

failure and extensively describe multiple clinical characteristics of patients admitted to hospital.

The Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study includes Canada’s

largest databases of acute heart failure patients from 86 hospital corporations in Ontario. The

study included 9293 patients admitted to hospital with AHF. The results revealed the patients

mean age to be 77 years old, with 51% being female (Tu, Donovan, et al., 2009). Similar

demographics were demonstrated in the Acute Decompensated Heart Failure National Registry

(ADHERE), which collected data in patients hospitalized with the primary diagnosis of acute

heart failure in 263 hospitals in the United States. The study included 105 388 patients and

showed the proportion of patients displaying the above-mentioned clinical symptoms of

congestion. Symptoms consistent with pulmonary edema were present in 88% of patients, and

specifically included fatigue in 30% of patients, and dyspnea in 91% of patients. Peripheral

edema on examination was found in 66% of patients (W. F. t. Peacock et al., 2008).

1.3 Treatment of Acute Heart Failure

Page 25: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

11

The evidence base for the treatment of chronic heart failure in the ambulatory care setting is

well developed. However, a substantial portion of heart failure care is directed at acute heart

failure, these episodes of clinical worsening that are unpredictable and frequently require urgent

or emergent care, usually in a hospital based setting and often require admission. The approach

to management of AHF is similar for both patients with HFrEF or HFpEF . Patients seen in the

emergency department in acute distress from symptoms of AHF, such as acute pulmonary edema

leading to acute respiratory distress, require prompt evaluation and stabilization. Methods for

management of such emergent situations will not be further discussed here.

The goals of management of AHF, as recommended by the Heart Failure Society of

American, include, firstly, the improvement of symptoms of congestion, improvement of

oxygenation, the optimization of volume status and minimizing side effects. The majority of

patients is stable and primarily requires intravenous loop diuretic therapy for treatment of signs

and symptoms of congestion.

1.3.1 Evidence and Guidelines for Management of Acute Heart Failure

Table 2 summarizes the recommendations of the Canadian Cardiovascular Society, the Heart

Failure Society of America and the American Heart Association/American College of

Cardiology. All three societies provide general guidelines for the care of acute heart failure. All

three societies recommend adequate monitoring practices for patients receiving intravenous loop

diuretics. Recommendations for monitoring patients in hospital include daily measurement of

fluid balance, including fluid intake and urine output, weights taken at the same time each day,

and monitoring for serum biochemistry, particularly assessment of potassium homeostasis and

potential depletion, and serum creatinine as a measure of pre-renal azotemia. Vital signs are

recommended to be evaluated more than once daily.

Page 26: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

12

Table 2: Acute Heart Failure Management Guidelines – 2014 Summary

Society Definitions Monitoring Management

Biochemistry Weights Drug Dosage

Canadian

Cardiovascular

Society(McKelvie

et al., 2013)

2013

Acute Heart Failure

- The diagnosis of

AHF is based on a

constellation of

symptoms (eg,

orthopnea and

shortness of breath

on exertion) and

signs (eg, edema and

respiratory crackles).

Physical examination

evaluates systemic

perfusion and

presence of

congestion (cold or

warm, wet or dry)

Response to initial therapy and the need for

additional therapy should be assessed less than

2 h after treatment initiation (class IIb, level C).

2006.

Acute renal dysfunction would generally be

diagnosed when serum creatinine levels

increase by more than 30% of baseline value

over several days or when oliguria and rising

serum creatinine are present. 2007.

All patients with AHF should have careful

monitoring of fluid balance, including urine

output, and this may require bladder

catheterization (class I, level C). 2007.

We recommend a thorough clinical evaluation

of the patient to assess their clinical

hemodynamic profile (Strong

Recommendation, Low-Quality Evidence).

2012.

We recommend that in the clinical scenario

when the clinical diagnosis of AHF is of

intermediate pretest probability, NP level be

obtained to rule out (brain NP [BNP] 100

pg/mL; N-terminal [NT]-proBNP 300 pg/mL)

or rule in (BNP 500 pg/mL; NT-proBNP 900

pg/mL if age 50-75 years, NT proBNP 1800 if

age 75 years) AHF as the cause for the

presenting symptoms suspicious of AHF

(Strong Recommendation, Moderate-Quality

Evidence). 2012.

Initial blood tests should include: complete

blood count, creatinine, blood urea nitrogen,

glucose, sodium, potassium, and troponin.

2012.

No specific

recommendations

We recommend

intravenous

diuretics be given

as firstline therapy

for patients with

congestion

(Strong

Recommendation,

Moderate-Quality

Evidence). 2012.

We recommend

for patients

requiring

intravenous

diuretic therapy,

furosemide may

be dosed

intermittently (eg,

twice daily) or as

a continuous

infusion (Strong

Recommendation,

Moderate-Quality

Evidence). 2012.

In heart failure

patients not

responding

adequately to more

than 240 mg

intravenous

furosemide daily,

treatment options

include:

– More frequent or

higher doses of

intravenous boluses

of diuretic (class

IIb, level C);

– Combination with

thiazide diuretic, eg,

hydrochlorothiazide

or metolazone (class

IIA, level B); or

– Continuous

intravenous

furosemide infusion

(class IIa, level B).

2007

Page 27: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

13

Table 2: Acute Heart Failure Management Guidelines – 2014 Summary continued

Society Definitions Monitoring Management Biochemistry Weights Drug Dosage

American Heart

Association/

American College

of

Cardiology(Yancy

et al., 2013)

2013

Acute Heart Failure

- There is no widely

accepted

nomenclature for HF

syndromes requiring

hospitalization.

Patients are described

as having “acute HF,”

“acute HF

syndromes,” or

“acute(ly)

decompensated HF”;

while the third has

gained greatest

acceptance, it too has

limitations, for it does

not make the

important distinction

between those with a

de novo presentation

of HF from those with

worsening of

previously chronic

stable HF

The effect of HF treatment should

be monitored with careful

measurement of fluid intake and

output, vital signs, body weight

that is determined at the same

time each day, and clinical signs

and symptoms of systemic

perfusion and congestion. Daily

serum electrolytes, urea nitrogen,

and creatinine concentrations

should be measured during the use

of intravenous diuretics or active

titration of HF medications.

(Level of Evidence: Class I, C).

2013.

Performance measures based on

professionally developed clinical

practice guidelines should be used

with the goal of improving quality

of care for HF. (Level of

Evidence: Class I, B). 2013.

No specific

recommendation

s

Patients with HF admitted

with evidence of significant

fluid overload should be

promptly treated with

intravenous loop diuretics to

reduce morbidity. (Level of

Evidence: Class I, B). 2013.

When diuresis is inadequate

to relieve symptoms, it is

reasonable to intensify the

diuretic regimen using

either: a. higher doses of

intravenous loop diuretics

(Level of Evidence: B); b.

addition of a second (eg,

thiazide) diuretic. (Level of

Evidence: Class IIa, B).

2013.

If patients are already

receiving loop diuretic

therapy, the initial

intravenous dose should

equal or exceed their

chronic oral daily dose

and should be given as

either intermittent

boluses or continuous

infusion. (Level of

Evidence: Class I, B).

2013.

Page 28: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

14

Table 2: Acute Heart Failure Management Guidelines – 2014 Summary continued

Society Definitions Monitoring Management

Biochemistry Weights Drug Dosage

Heart

Failure

Society of

America(H

eart Failure

Society of

et al.,

2010)

2010

No clear

definition When the diagnosis is uncertain,

determination of plasma B-type

natriuretic peptide (BNP) or N-terminal

pro-B-type natriuretic peptide

(NTproBNP) concentration is

recommended in patients being

evaluated for dyspnea who have signs

and symptoms compatible with HF.

(Strength of Evidence = A). 2010.

It is recommended that serum potassium

and magnesium levels be monitored at

least daily and maintained in the normal

range. More frequent monitoring may be

necessary when diuresis is rapid.

(Strength of Evidence = C). 2010.

Vital signs monitoring recommended

more than daily. (Strength of Evidence =

C). 2010.

Serum sodium monitoring recommended

at least daily. (Strength of Evidence =

C). 2010.

Renal function (BUN, Creatinine)

monitoring recommended at least daily.

(Strength of Evidence = C). 2010.

Fluid restriction (<2 L/day) is

recommended in patients with moderate

hyponatremia (serum sodium<130

mEq/L) and should be considered to

assist in treatment of fluid overload.

(Strength of Evidence = C). 2010.

A low sodium diet (2 g daily) is

recommended for most hospitalized

patients. (Strength of Evidence = C).

2010.

Monitoring of

daily weights,

intake, and output

is recommended

to assess clinical

efficacy of

diuretic therapy.

(Strength of

Evidence = C).

2010.

Determine after

voiding in the

morning

Account for

possible increased

food intake due to

improved appetite

It is recommended that

patients admitted with

ADHF and evidence of

fluid overload be treated

initially with loop

diuretics - usually given

intravenously rather

than orally. (Strength of

Evidence = B). 2010.

It is recommended that

diuretics be administered at

doses needed to produce a

rate of diuresis sufficient to

achieve optimal volume

status with relief of signs

and symptoms of congestion

(edema, elevated JVP,

dyspnea), without inducing

an excessively rapid

reduction in 1) intravascular

volume, which may result in

symptomatic hypotension

and/or worsening renal

function, or 2) serum

electrolytes, which may

precipitate arrhythmias or

muscle cramps. (Strength of

Evidence = C). 2010.

Page 29: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

15

1.3.2 Loop Diuretics

As indicated in Table 2 a mainstay of treatment for acute heart failure is to relieve

symptoms of congestion achieved with the use of loop diuretics. During admission to hospital for

acute heart failure, management of extravascular fluid volume overload is commonly achieved

with intravenous (IV) loop diuretics. The Acute Decompensated HEart Failure National REgistry

(ADHERE) showed that 88% of patients admitted to hospital with HF receive IV loop diuretics

(W. F. Peacock et al., 2009). Although it is possible to relieve symptoms of congestion with oral

loop medication, congestion requiring admission to hospital is usually treated with intravenous

administration of loop diuretics. Commonly used loop diuretics are furosemide, torsemide and

bumetanide, with furosemide being the most commonly used (Leto, Aspromonte, & Feola, 2014;

Wargo & Banta, 2009). There is, however, limited data on the comparative efficacy of these loop

diuretics in the setting of treatment of heart failure (Muller, Gamba, Jaquet, & Hess, 2003; M. D.

Murray et al., 2001; Patterson, Adams, Applefeld, Corder, & Masse, 1994; Wargo & Banta,

2009).

1.3.2.1 Mechanism of Action

Intravenous loop diuretics act on the thick ascending limb of the loop of Henle,

preventing sodium chloride reabsorption through the blockade of the Na-K-2Cl carrier and the

inhibition of active chloride transport (Matzke & St Peter, 1990; Rose, 1991). The excretion of

sodium chloride causes a decrease in the high medullary osmolality, which in turn decreases

water reabsorption. Loop diuretics are capable of excreting up to 25% of filtered sodium.

Additionally, increased excretion of sodium chloride causes enhanced sodium-potassium

exchange in the distal part of the nephron, leading to increased potassium excretion (Matzke &

St Peter, 1990).

Page 30: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

16

The bioavailability of oral loop diuretics, more specifically furosemide, is extremely

variable – 10 to 90% (Brater, 1998; M. D. Murray, Haag, Black, Hall, & Brater, 1997). The drug

is protein bound and is delivered to the proximal tubule for its action. Fifty-percent of the drug is

then excreted in the urine unchanged and the other 50% in metabolized in the kidney. One of the

consequences of congestion is edema of the gastrointestinal tract, which in turn may further

decrease absorption of orally administered loop diuretics, making it difficult to achieve

efficacious serum concentrations of the drug (Vasko, Cartwright, Knochel, Nixon, & Brater,

1985). Intravenous administration is thus recommended due to better and more constant drug

bioavailability. The intravenous dosage equivalent is half of the oral dose.

Loop diuretics have a threshold dose and a dose-responsive effect; that is to say a

minimal dose is required to elicit any effect and that effect will increase with an increase in dose.

Additionally, loop diuretics reach a ceiling dose, which is a dose that causes maximal fractional

sodium excretion. In patients with HF, the dose-response curve is shifted downward and to the

right, which signals that the maximal fractional sodium excretion to be achieved is decreased

(Brater, 1994).

1.3.2.2 Mode of Administration in Acute Heart Failure

Intravenous furosemide can be administered as a bolus dose or as a continuous infusion,

with onset of diuresis occurring after 5 minutes; peak of diuresis at 1 to 2 hours (Brater, 1998;

Rose, 1991). When administered as a bolus dose, the maximum effective dose in serum is

reached more quickly and therefore sodium excretion peaks at 2 hours, gradually decreasing until

the next bolus dose is given (Brater, 1998). A continuous infusion of furosemide allows for a

steady excretion of the drug, which thus maintains a more constant rate of sodium excretion

(Wilcox et al., 1983). When this mode of administration is chosen, a bolus is usually given first

Page 31: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

17

in order to achieve a therapeutic drug concentration faster. The superiority of one mode of

administration of IV furosemide over the other has long been debated (Alqahtani, Koulouridis,

Susantitaphong, Dahal, & Jaber, 2014; Dormans et al., 1996; Salvador, Rey, Ramos, & Punzalan,

2005; Thomson et al., 2010) and the current best evidence comes from a recent large clinical trial

as well as a meta-analysis. The DOSE (Diuretic Optimization Strategies Evaluation) trial was the

first large-scale multicenter double-blinded randomized trial to determine whether an IV bolus or

continuous infusion mode of administration of furosemide was better (Felker et al., 2011). A

second goal of this trial was to evaluate whether a low-dose approach (equivalent to the patient’s

oral dose) or a high-dose approach (2.5 times the oral dose) led to better outcomes. A total of 308

patients were enrolled in the trial and assigned to either low or high dose furosemide, and either

bolus dosing or continuous infusion in a two by two factorial design. Patients were selected with

the following criteria: admission to hospital with the primary diagnosis of acute heart failure

(based on appropriate symptoms and physical signs), an established history of chronic heart

failure, and a home dose of oral furosemide taken for at least 1 month prior to admission.

Patients were excluded if they exhibited hypotension (SBP<90 mmHg), elevated serum levels of

creatinine (>265micromol/liter) or the need for vasodilators or inotropic agents. Treatment was

continued for 72 hours, with the treating physician having the ability to adjust diuretic therapy at

48 hours based on clinical response, with the treatment method remaining concealed. The

primary efficacy endpoint was the patients’ global assessment of symptoms and the primary

safety endpoint was the change in serum creatinine at 72 hours. Secondary endpoints included

patient-reported dyspnea, freedom from congestion at 72 hours, change in weight at 72 hours, net

fluid loss at 72 hours, change in NT-proBNP at 72 hours, worsening or persistent HF, treatment

failure, increase in creatinine >0.3mg/dL after 72 hours, and length of stay (LOS). The results of

Page 32: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

18

the trial showed that there were no significant differences in either primary endpoints when

comparing the mode of administration (IV bolus versus continuous infusion) or the furosemide

dose (high versus low). There were also no significant differences in secondary endpoints

between the two modes of administration. Additionally, a meta-analysis performed at the

National Institute for Health and Clinical Excellence Guidance (NICE) in 2014 (Dworzynski et

al., 2014) that included 7 randomized control trials that evaluated differences in outcomes in

patients receiving IV bolus versus IV continuous infusion furosemide. No significant differences

were found in outcomes, including weight loss, urine output or change in renal function and

therefore the recommendation stated that either strategy can be used in the management of AHF.

Therapy with intravenous administration of furosemide continues until the patient’s acute

symptoms of congestion have been stabilized or eliminated, at which point it is recommended to

switch to an oral dose of furosemide in preparation of discharge from hospital. Choice of

discharge dose of oral furosemide depends on the patient’s previous home oral dose as well as

response to intravenous dose while in hospital. Current recommendation states that the oral dose

will approximately equal to twice the IV dose administered in hospital.

1.3.3 Assessment and Monitoring of Patients Receiving Intravenous Loop Diuretics

There are several practice issues to be considered with diuretic therapy in AHF including

dose of diuretic, hemodynamic changes following diuresis as well as effect of the loop diuretic

on kidney function. Monitoring of the patient has the goals of assessing the efficacy of

furosemide and the detection of possible adverse events associated with drug.

There are several components to the proper assessment of decongestion efficacy when

using IV furosemide. It is customary for physician assessment to note clinical evidence of

decongestion, such as patient symptoms, evaluation of pulmonary congestion, peripheral edema

Page 33: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

19

and assessment of the jugular venous pressure. Evidence of decongestion is obtained by a few

objective measurements. Weight loss is currently considered the best and most objective method

of measuring and documenting diuresis (O'Brien, Menon, Stephens, Mazur, & Chung, 2012). As

stated in Section 1.3.1, weight should be measured at least daily, at the same time each morning,

prior to eating. Other specific recommendations for the proper measurement and record of

efficacy markers are described in the current recommendations in Section 1.3.1.

Serial measurements of NT-proBNP in the setting of acute heart failure treatment can be

used to monitor the effect of therapy because the half-life of NT-proBNP is relatively short.

However, evidence of benefit is limited and small studies have shown conflicting results

(Nohria, Mielniczuk, & Stevenson, 2005), (Bhardwaj & Januzzi, 2009). The benefit is also

absent in patients with certain etiologies of heart failure that present without an elevation in NT-

proBNP. These include patients with mitral stenosis and constrictive pericarditis.

Detection of potential adverse events associated with diuretic therapy includes electrolyte

abnormalities, including hypokalemia and hypomagnesaemia, evidence of hypotension or acute

kidney injury, and metabolic alkalosis. As a potassium-wasting drug, furosemide use can lead to

hypokalemia, which if left untreated, may lead to cardiac arrhythmias. The DOSE (Diuretic

Optimization Strategies Evaluation) trial had a 1% incidence of hypokalemia in each of their 4

treatment groups (discussed in Section 1.3.2.2) (Felker et al., 2011). The Cardiorenal Rescue

Study in Acute Decompensated Heart Failure (CARRESS-HF) trial showed a similar incidence

of 3% for electrolyte disturbances; this, however, included hyperkalemia, hypokalemia,

hypernatremia, hyponatremia, and hyperuricemia (Bart et al., 2012). Similarly,

hypomagnesaemia can lead to potentially serious cardiac arrhythmias. When diuresis occurs

rapidly and intravascular fluid is quickly removed by the kidney, the rate of interstitial fluid

Page 34: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

20

moving into the intravascular space is slower and therefore can lead to symptomatic or

asymptomatic hypotension. When this occurs, the rate of diuresis is slowed through the reduction

of furosemide dose. Recommendation for kidney function monitoring is to measure serum

creatinine, as a marker of kidney function. With ongoing diuresis, decreased perfusion of the

kidney causes a decrease in the glomerular filtration rate and therefore a decrease in the filtration

of creatinine. Its accumulation in the intravascular space acts as a surrogate marker of kidney

function. Detection of evidence of acute kidney injury is associated with worse prognosis;

however, a balance must be reached between adequately diuresing a patient with AHF as well as

potential kidney injury. Metabolic alkalosis is caused as a result of a combination of factors

including the activation of the renin-angiotensin system, and hypokalemia, which then leads to

bicarbonate retention.

1.3.3.1 Hypokalemia

As mentioned in Section 1.3.2.1, diuresis or excessive diuresis with IV furosemide can

cause an increased secretion of potassium. The extent of hypokalemia seen in patients receiving

IV furosemide is dependent of the dose of the loop diuretic received; higher doses are more

likely to cause hypokalemia than lower doses (Gennari, 1998). Hypokalemia is defined as serum

potassium < 3.5mmol/L. Patients with heart failure have an increased risk of arrhythmias, cardiac

arrest and syncope, which in turn causes them to experience more complications as a result of

hypokalemia (Leier, Dei Cas, & Metra, 1994). United Kingdom Heart Failure Evaluation and

Assessment of Risk Trial (UK-Heart) showed that HF patients with decreased serum potassium

levels exhibited higher incidence of sudden cardiac death (J. Nolan et al., 1998). Based on these

findings, the UK-Heart group recommended that all patients with chronic heart failure should

receive potassium supplementation. Thus the National Council on Potassium in Clinical Practice

Page 35: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

21

recommends that HF patients should receive potassium supplementation if serum potassium is

below 4.0mmol/L (Cohn, Kowey, Whelton, & Prisant, 2000).

Page 36: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

22

2 Protocol Development

2.1 Quality of Care for AHF: The Gap Between Guideline Recommendations

and Actual Delivery of Care

As discussed in Section 1.3, several guideline documents exist informing clinicians as to

appropriate care for patients with AHF. However studies have shown that adherence to

recommended guidelines is not always optimal (Cabana et al., 1999). Objectives used to develop

guideline recommendations for diuretic therapy center around principles of good quality of care.

The Institute of Medicine (IOM) has defined quality of care as "the degree to which health

services for individuals and populations increase the likelihood of desired health outcomes and

are consistent with current professional knowledge" (Lohr, 1990). The IOM further describes 6

principles that act as specific aims for quality care improvement. Care practices should be (1)

safe, (2) effective, (3) patient-centered, (4) timely, (5) efficient and (6) equitable. In this thesis,

two key principles of focus are safety, and timeliness. Safety refers to prevention of injury or

adverse events to patients from the care they are receiving. Timeliness refers to reduction of

potentially harmful delays and waits for both patients and care providers. Potential barriers to

safety, and timeliness of diuretic management are now discussed.

2.1.1 Safety in Diuretic Management

An important implication for inclusion of monitoring practices in guideline directed care of

patients treated with loop diuretics is the potential for harm with respect to electrolyte

derangement, hemodynamic compromise and renal injury. Evidence from the Medicare Patient

Safety Monitoring System database in the United States has shown that between 2005 and 2011

the rate of adverse events in patients admitted to hospital with AHF has significantly declined;

however, mortality risk and length of stay in hospital remains significantly higher in patients

Page 37: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

23

who experienced adverse events in hospital (Wang et al., 2014). The safe administration of

diuretics is thus dependent on assessment of safety markers that inform the need for readjustment

of therapy.

Effective diuresis occurs over days (Bart et al., 2012; Felker et al., 2011) with the potential

for involving several caregivers. As such, continuity of care, or lack thereof, by physicians or by

bedside caregivers may affect safety. In the Canadian academic hospital environment, the

clinical teaching unit (CTU) is the predominant model of inpatient care. The clinical teaching

unit consists of several physicians, including an attending staff physician, several medical

residents and students. Although evidence exists to show the benefits of CTUs, several barriers

to quality care of patients have also been identified in numerous studies. These include

physicians of different degrees of experience (Lindenauer et al., 2007; Pattani, Wu, & Dhalla,

2014; Volpp & Grande, 2003) as well as frequent handoffs between physicians (Arora, Johnson,

Lovinger, Humphrey, & Meltzer, 2005; Gandhi, 2005; Horwitz, Moin, Krumholz, Wang, &

Bradley, 2008; Petersen, Brennan, O'Neil, Cook, & Lee, 1994; Philibert, 2009; Press, 2001). A

handoff is defined as “the exchange between health professionals of information about a patient

accompanying either a transfer of control over, or of responsibility for, the patient.” (Cohen &

Hilligoss, 2010; Keyes, 2000). Proper handoffs between physicians are crucial to providing

appropriate continuity of care and high quality safe patient care (Starmer et al., 2014). A

systematic review focusing on physicians’ handoffs was conducted in 2009 with the goal of

identifying barriers and proposed strategies (Riesenberg et al., 2009). In the 46 studies that met

inclusion criteria, the most common handoff barrier identified in 31% of cases was

communication. Of the handoff strategies proposed in the studies included in the review, the

most common strategy category was standardization (44.3%), which has shown evidence of

Page 38: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

24

being beneficial to improving quality care (Burgmeier, 2002; Luther et al., 2002). The

conclusion stated that inadequate physicians’ handoffs have detrimental consequences; however,

high quality handoff outcome studies are needed as well as strategies for best practices (Cohen &

Hilligoss, 2010). Similarly, challenges have also been identified in handovers between the

nursing staff (Ebright, Urden, Patterson, & Chalko, 2004; Hays, 2003).

An additional consequence of the CTU structure that contributes to delays in communication,

is the inability to identify the specific roles played by multiple physicians, including the most

responsible physician (MRP). One study, performed in an academic U.S hospital, showed that a

barrier rated highly by nurses was difficulty in being able to identify the MRP (O'Leary, Ritter,

et al., 2010). Further significance and evidence on interprofessional communication is discussed

in Section 2.1.2.

2.1.2 Timeliness of Diuretic Management

As stated in Section 2.1, timeliness of care refers to the reduction of potentially harmful

delays to both patients and medical staff. This is achieved through timely reassessment of

patients receiving drugs in hospital (in this case IV loop diuretics) as well as timely

communication between the nursing staff and medical team on the ward. Timely communication

is also commonly integrated into the concept of interprofessional collaboration (IPC); however,

many variable definitions of IPC exist with limited high quality data regarding its significance

(O'Leary, Thompson, et al., 2010). A Cochrane Database Review, conducted in 2009, identified

5 main elements crucial to effective IPC – “the involvement of numerous participants in care

coordination, the necessity of coordination, the importance of participants having knowledge of

one’s own and others’ roles, and the importance of information exchange.” (Zwarenstein,

Goldman, & Reeves, 2009) This review focused on evaluation of practice-based IPC

Page 39: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

25

interventions, which were defined as “work through the incorporation of a tool or routine into

practice that supports the type of interaction (e.g. communication, coordination) amongst

different healthcare professionals that is thought to be necessary to improve a particular area of

health care.” Results suggested that such IPC interventions improve healthcare processes and

outcomes. Furthermore, multiple studies have shown that communication delays and

miscommunication between the nursing and medical staff lead to errors in patient care (Baggs et

al., 1999; Chassin & Becher, 2002; Leape et al., 1991; Sutcliffe, Lewton, & Rosenthal, 2004;

Wilson et al., 1995). Results from the Harvard Medical Practice Study showed that, in 1133

adverse events identified in 30195 hospital patient records, inadequate reporting or

communication was present as a cause in 26% of cases, inadequate follow-up of therapy in 45%,

and avoidable delay in treatment in 14% of cases (Leape et al., 1991). Another study from a U.S

teaching hospital, identifying medical mishaps involving medical residents, reported

communication failure as a cause in 91% of instances (Sutcliffe et al., 2004).

2.2 Description of the MSH La6 Protocol and Components

2.2.1 Specific Objectives and Design of the MSH La6 Protocol

As discussed above, barriers may exist to achieving good adherence to guideline-directed

practices for monitoring and drug administration, based on the structure of the medical care team

and the interprofessional cooperation required. These barriers in turn may affect the safety and

timeliness of intravenous diuretic therapy in hospital. The La6 Protocol was a 48-hour

intervention designed to optimize the safety and timeliness of establishing effective decongestion

early during admission.

To address safety particularly in a CTU setting the intervention guided appropriate

patient selection. Safety was also addressed by enforcing adherence to best practices for

Page 40: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

26

consistent and adequate monitoring for adverse effects of IV diuretic therapy. Safety was also

addressed by directing appropriate interprofessional communication when a potentially adverse

event was recorded. Literature has shown that up to 50% of drug adverse events experienced in

hospital are preventable and most happen at the ordering and administering stages(Bates et al.,

1995).

To address timeliness the intervention employed several strategies. Prescription of dosage

and frequency of administration was evidence-based as such discouraging selection of, and

persistence with, ineffective dosages. Additionally, the process of diuresis requires repeated

collection and interpretation of several clinical measurement variables with a potential for delays

within and between cycles of furosemide administration and reassessment. Strategies were

employed to optimize interprofessional cooperation and minimize delays in reassessment and

dose adjustment.

The process was entitled the Mount Sinai Hospital Lasix Protocol (MSH La6 Protocol)

and consisted of 2 paper-based tools, the Physician Pre-Printed Order Set (PPOS) and the

Nomogram for Stepped Diuretic Care (Nomo-SDC). The specific components of the protocol

that address our objectives are now discussed.

2.2.2 Physician Pre-printed Order Set (PPOS)

The Physician Pre-Printed Order Set (PPOS) was the first component of the MSH La6

Protocol (Figure 1). The goals of the PPOS were to provide appropriate patient selection criteria,

based on contemporary evidence supporting multi-dose delivery of IV furosemide and best

practices for monitoring of safety and efficacy. The PPOS was completed by the treating

physician. Upon completion, the treating physician delegated authority to the registered nurse to

Page 41: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

27

monitor the patient and administer IV furosemide for 48 hours. The PPOS was designed with the

following objectives:

Page 42: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

28

Figure 1. Physician Pre-Printed Order Set (PPOS)

First component of the MSH La6 Protocol, completed by the treating medical team. The PPOS

contains criteria for patient selection, baseline patient information, alert notifications, and

furosemide dosing regimen.

Page 43: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

29

i) Patient Selection

The diagnosis of acute heart failure can be challenging and inclusion criteria were

organized to encourage physicians to provide clinical evidence of the appropriate diagnosis

(McCullough et al., 2002). A checklist method was employed by which physicians could

document appropriate patient selection. These inclusion criteria were: 1) a mandatory previous

diagnosis of heart failure and home dose of oral furosemide, 2) an elevated jugular venous

pressure (JVP), 3) evidence of pulmonary or peripheral edema, 4) ascites, 5) two or more

kilograms of weight to lose on examination, and 6) a serum NT-pro BNP of greater than

135pmol/L. The ordering physician was advised the patients were suitable if they met the

mandatory criteria as well as at least one other clinical criterion. The PPOS also specified

exclusion criteria to prevent use of the protocol in patients who were not included in clinical

trials of multi-dose furosemide administration. These were as follows: 1) patients with a new

diagnosis of heart failure on admission and 2) those who are furosemide naïve (no home dose of

oral furosemide). Caution for use was noted for those with a systolic blood pressure of less than

90 mmHg and/or with a serum creatinine greater than 260 micromol/L.

ii) Standardized Orders for Monitoring Efficacy and Detection of Drug-Related

Adverse Events

Firstly, the PPOS required documentation of baseline patient information, including

home dose of furosemide, weight on arrival to the ward, as well as baseline SBP, serum

creatinine and serum potassium. The PPOS then provided standardized orders for daily weights,

serum biochemistry, vital signs and monitoring of urine output. The PPOS also provided

specific criteria that automatically suspended the process and mandated notification of the

physician team for reassessment (termed ‘alert notifications’). As noted in section 2.1.1 (Safety

Page 44: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

30

of Diuretic Management) the PPOS recommended specific thresholds by which the potential

adverse effects of diuretic therapy could be identified. For all patients, these thresholds included

a serum sodium less than 125 mmol/L and a SBP less than 90mmHg. The PPOS recommended

an alert notification for serum creatinine determined based on an increase of 35% from the

patient’s initial creatinine measurement. Finally, the PPOS also recommended an alert

notification for serum potassium measurement above a threshold prespecified by the MD. The

standardized orders for monitoring and pre-specified alert notifications were designed to identify

and prevent potential adverse events associated with IV furosemide therapy.

Next, the PPOS established an efficacy target and managing strategies. Based on weight

recorded on ward admission, physicians prespecified a target weight loss of at least 2kg to be

achieved after 48 hours of therapy. Diet and fluid restriction orders were also enforced and gave

the ordering physician a choice in a low sodium diet of less than 2 or 3 grams per day (Heart

Failure Society of et al., 2010; Yancy et al., 2013) and a fluid intake of 1500 or 2000 ml per day

(Yancy et al., 2013). IV doses received in the emergency department prior to admission were

also recorded.

iii) Furosemide Dosing Regimen

Two principles, 1) consideration of renal function (estimated glomerular filtration rate <

or > 60ml/min) and 2) administering an IV dose at least equivalent to the total daily oral loop

diuretic dose, guided selection of a lower or a higher dosing schedule. For patients without renal

insufficiency or a relatively small home dose of furosemide, a lower dosage regimen of 40mg IV

was chosen. If renal function was impaired or the home dose of furosemide above 80mg daily,

the higher dosing regimen, of 80mg IV was selected. Importantly, the DOSE trial (Felker et al.,

2011) (discussed in Section 1.3.2.2) established that multiple bolus administration was as

Page 45: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

31

effective as a continuous infusion with acceptable safety in the context of a randomized clinical

trial. As such, 4 cycles of furosemide administration and assessment of efficacy and surveillance

for adverse effect occurs within a 48-hour period. Therefore, a key design element of the Nomo-

SDC was the use of twice daily bolus administration to coordinate actions of the Nomo-SDC

with a standard 12-hour nursing shift.

iv) Delegation to Nursing Staff

Once the patient’s eligibility was confirmed, safety parameters set, and dosing regimen

indicated, the treating physician authorized the bedside caregiver to initiate the algorithm and

proceed with necessary monitoring and dose adjustments for 48 hours. Authorization to initiate

the process required the signature of an ordering physician and the bedside caregiver.

2.2.3 Nomogram for Stepped Diuretic Care (Nomo-SDC)

The Nomogram for Stepped Diuretic Care (Nomo-SDC) was the second component of

the MSH La6 Protocol (Figure 2). The Nomo-SDC was an algorithm tool designed for use by

personnel at the point of care, which in our institution is the bedside registered nurse. The

essential change in delivery of care required to initiate effective diuresis was designed to address

two quality components. Firstly, timeliness of diuretic administration and monitoring (discussed

in Section 2.1.2), more specifically to eliminate communication delays that occur in collating and

acting upon data needed to administer IV furosemide. Secondly, prescription of standardized

furosemide doses was designed to address efficiency of care and resource allocation. The tool

allowed for moderate escalation of furosemide dosing based on bedside measures of efficacy and

safety criteria without requiring additional orders from a physician. As such, the Nomo-SDC was

conducted in its entirety by the bedside RNs, without physician consultation unless notification

of the physician team was specified by the protocol. This change in practice consisted of two

Page 46: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

32

parts: firstly, delegating authority to the bedside RN to order and administer the furosemide dose

initially prescribed by the Nomo-SDC and secondly, delegating authority to the bedside RN to

adjust the furosemide dose according to monitoring markers measured every 12 hours. The

Nomo-SDC was designed with the following objectives:

Page 47: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

33

Figure 2. Nomogram for Stepped Diuretic Care (Nomo-SDC)

Second component of the MSH La6 Protocol, completed by a registered nurse. Monitoring,

electrolyte replacement, and furosemide prescription is detailed on the left half of the protocol.

Corresponding documentation of clinical monitoring markers and drug dose administration is

recorded on the right half of the protocol.

Page 48: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

34

i) Selection, Timing, and Titration of Diuretic Dosing

Shifts for RNs begin at 8:00am and continue for 12 hours. Once ordered, the protocol

was initiated at 8:00am (with the range of 7:00am and 10:00am) the following morning in order

to facilitate nursing flow and increase efficiency of daily bloodwork and clinical reassessment, as

well as adhere to current monitoring guidelines (McKelvie et al., 2013; Yancy et al., 2013)

which state that weights should be recorded at the same time daily. If, however, the protocol was

ordered outside of the above-mentioned time range, the medical team was responsible for any

intravenous furosemide doses administered to the patient prior to the initiation of the protocol.

The selection of doses was left up to the discretion of the treating physician. In such a case, the

nursing staff initiated the nomogram the following morning.

Populating clinical markers of efficacy within the Nomo-SDC led to selection of the

subsequent furosemide dose. Efficacy at 12 and 36 hours was defined as 800 ml of urine output

over the preceding 12 hours. At the 12-hour reassessment, if this efficacy marker was achieved,

the nomogram called for the dose to remain the same for the next time point (24-hour mark). If

urine output was less than 800ml, the furosemide dose was increased by 40mg from the starting

dose. Similarly, at 36 hours, if urine output was found to equal or be greater than 800ml, the dose

of furosemide remained stable. If the urine output was below this value, the nurse was instructed

by the nomogram to contact the treating physician. At 24 hours, reassessment of dosage occurred

based on the patient’s weight and weight loss. Monitoring, according to the nomogram, required

the patient to be weighed daily as stated in Section 2.2.3, a target weight to be achieved in 48

hours on protocol was preset by the prescribing physician. Weight loss was measured every 24

hours with a target weight loss to be achieved in 48 hours. This timeline was guided by similar

Page 49: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

35

weight loss assessment in the NIH DOSE trial. In that study, weight loss was also measured

every 24 hours, up to 96 hours (Felker et al., 2011). In addition, the treating physician allowed

drug administration to occur for the first 48 hours before dose adjustment could occur based on

clinical response. Three possible outcomes were possible at this time. If weight loss was found to

be less than 1 kg over the previous 24 hours, the dose of furosemide was escalated based on the

dose given at 12 hours. If weight loss was greater than 1 kg but less than the target weight preset

in the PPOS, the dose of furosemide remained stable from the 12-hour mark. Lastly, if target

weight was reached, the protocol was stopped and the medical team notified. Finally,

reassessment at 48 hours was based on the target weight preset and dictated that if the target

weight was not reached by 48 hours, the last dose of furosemide was given and the medical team

notified of the protocol’s completion. If target weight was reached by this point, no furosemide

was given, the protocol was deemed complete, and the medical team notified.

ii) Monitoring

Monitoring as prescribed by the Nomo-SDC was delegated to the nursing staff at each

time point starting at initiation of the protocol. Serum sodium, potassium and creatinine were

measured at initiation of the Nomo-SDC and every 24 hours until completion or termination of

the protocol. The nursing staff completed additional measurements of potassium at 12 and 36

hours, if potassium supplementation was given at the previous assessment. Weight

measurements were ordered by the Nomo-SDC to be completed at 0 hours, 24 hours and 48

hours, accompanied by the calculation of weight loss. This calculation further directed

furosemide dose administration. Blood pressure was recorded every 12 hours. Similarly, urine

output was recorded at every 12-hour point, and served as an efficacy marker at the 12 and 36-

hour points, directing subsequent furosemide dose selection.

Page 50: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

36

iii) Prevention, Detection and Treatment of Drug-Related Adverse Events

The Nomo-SDC also specified standardized biochemical monitoring and potassium

replacement without requiring additional orders from a physician. If supplemental potassium was

administered, serum potassium was repeated at 12 hours. A potassium replacement nomogram

was embedded in the Nomo-SDC as shown in Figure 3.

Page 51: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

37

Figure 3. Potassium Replacement Nomogram

The Potassium Protocol is embedded within the Nomo-SDC. It contains details on appropriate

potassium supplementation dosing depending on the risk of or severity of hypokalemia present.

Page 52: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

38

iv) Completion of the Protocol and Transition to Usual Care

As noted, actions to populate the Nomo-SDC occurred every 12 hours up to and

including 48 hours. Completing each 12-hour segment of the protocol resulted in either selection

of the subsequent dose or identification of an alert notification that suspended the protocol and

mandated reassessment by the MD. The medical team could choose to resume care within the

Nomo-SDC or discontinue the protocol. Early completion of the protocol could also occur as

prescribed by the Nomo-SDC if the therapeutic target for weight was achieved at 24 hours.

Completion of the MSH La6 protocol required physician signature to acknowledge that further

diuretic prescription and monitoring reverted to usual care and was at the discretion of the

medical team. The practice of the RN reverted to usual bedside care and routine charting.

2.3 Issues of Local Implementation

The process change described was undertaken at a single center. The Mount Sinai

Hospital is an academic health care facility in the metropolitan area of Toronto, Ontario Canada.

These tools were developed during a 6-month process of review of the literature, consensus

building to assess needs and objectives, protocol drafting and revision with input from a multi-

disciplinary personnel including cardiology, hospital pharmacy, nursing administration and

nursing education. At Mount Sinai Hospital, institution practice changes are reviewed by Clinical

Practice Committee, Joint Health and Safety Committee, Risk Management, and Health Records,

with final approval occurring from the Medical Advisory Committee. As an academic institution,

in this experience, the PPOS was populated and initiated by the physician care team that

functioned as a CTU.

At Mount Sinai Hospital, bedside care of patients is delivered by registered nurses (RN).

2.4 Considerations for Education

Page 53: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

39

2.4.1 PPOS as an Educational Tool

The Physician Pre-Printed Order Set was utilized as an educational tool in several ways.

Firstly, populating the PPOS provided an explanation of the underlying rationale for patient

selection. In addition to setting alert notification for MD reassessment, as discussed in Section

2.2.1, the ordering physician was provided with clinical scenarios (admission to the ICU, renal

insufficiency, hypotension) that warrant caution. Furosemide dosing regimen selection was

accompanied by guideline concerning the potential need for or lack of need for a continuous

infusion of furosemide, based on up to date evidence (Felker et al., 2011). For each alert

notification, guidelines for patient reassessment, documentation, and appropriate responses were

provided. Lastly, the PPOS provided practice tips for using the loop diuretic protocol, which

included an overview of AHF, an in-depth rationale for appropriate patient selection as well as

additional information regarding the biochemical and clinical monitoring markers.

2.4.2 Educational Packages

Education of medical staff, including staff physicians, medical residents and students as

well as nursing staff, about the implementation of a new quality improvement initiative has been

shown to effectively improve learners’ knowledge and consequently confidence in performing a

new practice (Boonyasai et al., 2007; Wong, Etchells, Kuper, Levinson, & Shojania, 2010). Prior

to the implementation of the protocol education packages including oral, visual, and written

materials were prepared and focused sessions were conducted with all active nursing staff on 2

hospital wards, as well as attending medical staff and residents. Education also required RNs to

perform a mock run through of the nomogram, populating each step and following through to the

next. Goals of education included the principles of therapy for decongestion in heart failure, use

of net fluid balance and daily weights as monitoring parameters. On medical floors, weight

Page 54: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

40

scales were inventoried and calibrated and procedures to ensure daily access to the same scale

for all ambulatory and semi-ambulatory inpatients were consolidated. Following implementation,

medical staff was educated with monthly in-service presentations, information posters and

pocket cards to heighten awareness of the protocol and accessibility of the pre-printed order set.

Two hospital pharmacists, thoroughly educated on the MSH La6 Protocol were also available to

support medical and nursing staff. The decision to use the protocol was left at the discretion of

the attending physician and clinical team. No additional clinical resources and no changes in

nurse to patient ratios were engaged in this process.

Page 55: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

41

3 Hypothesis and Research Aims

The purpose of this quality improvement intervention was to identify current barriers to

safe and timely administration of intravenous furosemide to AHF patients and address them with

the implementation of a nurse-run clinical algorithm in the first 48 hours after admission to

hospital. The hypothesis stated that quality of care would improve in these patients with the use

of the MSH La6 Protocol by addressing several issues. Firstly, the protocol would improve

adherence to guideline-directed monitoring of AHF patients by setting prespecified, guideline

recommended markers to be measured by the RN every 12 hours in order to assess safety and

clinical progress of the patient. Secondly, the Nomogram for Stepped Diuretic Care would aim to

improve evidence-based furosemide dose selection and administration as well as streamline

interprofessional communication among medical and nursing staff.

In order to test this hypothesis, a pre and post, time series design was used to evaluate

adherence to guideline-directed monitoring of AHF patients. Data was collected for 32 months

prior to the implementation of the protocol and for 8 months after. Opportunity-based scores, all-

or-none scores (defect-free scores), and Shewhart control charts were used for specific

measurements. Safety of the protocol was measured through adherence to specific algorithm

steps using the above-mentioned scores, as well as incidence of adverse events, which included

hypokalemia and acute kidney injury. Incidence of adverse clinical events was also recorded,

including death or transfers to an acute care setting, and protocol suspension. Furosemide

prescription was measured by recording IV furosemide doses given in the first 24 hours of

hospital admission, second 24 hours and total over 48 hours. Details of evaluation are discussed

in Section 4.

Page 56: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

42

4 Methods of Evaluation

4.1 Overview of Quality Improvement Assessment

Quality improvement in health care is based on the principle that there is an opportunity

for improvement in every process that occurs in medical practice (Berwick, 1998). In Evaluating

the Quality of Medical Care, Donabedian suggested the quality of health care could be measured

by assessing its structure, processes and outcomes (Donabedian, 2005). Several strategies of

quality improvement exist, and include intervention at the level of the provider and at the level of

the patient. Quality improvement strategies include, but are not limited to, facilitated relay of

clinical data to providers, provider education, and organizational change (Shojania, McDonald,

Wachter, & Owens, 2004). The protocol evaluated in this project encompassed an organizational

change that altered the relationship between multidisciplinary providers (the bedside RN and the

ordering physician) and included several interventions for the providers. The process drove

utilization of best practice, and strategies utilized include uptake of an algorithmic tool for

decision support, provider education, and mandated population of quality indicators. Two

dimensions of quality were assessed in this project are safety, defined as patient care that is free

of potential adverse events, and timeliness, defined as patient care that is free of delays and waits

(Lohr, 1990) (further discussed in Section 2.1). The evaluation of this intervention fits into a

model of a feasibility study (Bowen et al., 2009). Studying the feasibility of a new evidence-

based intervention answers questions about its possible efficacy, effectiveness, and future

directions. In the case of the MSH La6 protocol, the feasibility evaluation performed addressed

three of eight possible areas of feasibility focus, and included implementation, integration and

limited-efficacy testing. The methodology for process measurement and outcome assessment are

presented in this chapter. Specific results for the evaluation are presented in Chapters 5 and 6.

Page 57: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

43

4.2 Process Measurement

Process measurement in a quality improvement project is crucial to understanding the

effects of that project on the system where it is implemented. Process measurement consists of

understanding the process and outcomes of a starting system, the implementation of the

initiative, and the monitoring of changes made through the implementation of the initiative

("Measurement for Quality Improvement," 2013). Proper measurement of a process is vital to its

success.

4.2.1 Measuring Adherence to a Process

Evaluation of a change to the provision of health care requires assessment of feasibility in

order to understand if the intervention is being implemented as intended. To implement the

Nomo-SDC appropriately, several actions by more than one caregiver over a specified duration

within the algorithmic tool had to be performed correctly. Safety of the process was also

predicated on timely and appropriate population of the Nomo-SDC. Therefore, methodology to

measure the adherence was selected. Adherence to any process can be evaluated using objective

measures of performance in providing quality care. A composite performance measure is defined

as a value encompassing multiple indicators of provider or healthcare performance required in a

process (Peterson et al., 2010). A composite value summarizes and allows for evaluation of a

complex process, in this case adherence to a multi-step, longitudinal clinical algorithm.

Evaluation of the MSH La6 Protocol included the opportunity-based composite score and the all-

or-none composite score.

4.2.2 Opportunity-based scoring

Opportunity-based scoring within a process is defined as the proportion of completed

individual process measures that are mandated. The score is calculated by dividing the number of

Page 58: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

44

times a process measure was completed (or given) over the number of times a process measure

was prescribed or mandated (Peterson et al., 2010). The advantage of an opportunity score is the

proportional weight of each individual measure based on the number of times it is prescribed.

However, this can potentially lead to a disadvantage if the most common individual process

measures are not the most important but greatly influence the composite score with a higher

weight proportion.

4.2.3 All-or-none Scoring/Defect-Free Scoring

All-or-none scoring (also known as defect-free scoring) is defined as the proportion of

patients that receive all process measures for which they are eligible (Peterson et al., 2010). This

type of score is also defined as proportion of patients that receive perfect care and therefore

measures performance on a patient level. The advantage of a defect-free score is the inherent

emphasis on excellent care (T. Nolan & Berwick, 2006). The disadvantage is that this score

could potentially simplify a complex process and omit important achievements within it.

4.2.4 Shewhart Control Charts

Shewhart control charts, also known as statistical process control charts, are a type of an

analytical tool used to detect variation in a process. They were originally developed by Walter

Shewhart to measure performance in the manufacturing industry (Shewhart, 1931). Two types of

variation are detected using a control chart: common cause variation and special cause variation

(Mohammed, Cheng, Rouse, & Marshall, 2001). Common cause variation is intrinsic to any

process and points to the process being in statistical stability. Special cause of variation is found

because of an extrinsic factor acting on the process and changing it. Shewhart control charts are

plotted with time on the x-axis, and the measurement in question on the y-axis (Benneyan,

Lloyd, & Plsek, 2003; Mohammed, Worthington, & Woodall, 2008). Three additional lines are

Page 59: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

45

also present. The central line indicates the mean of the data and 2 additional lines demonstrate

the upper and lower control limits, usually placed 3 standard deviations (SDs) away from the

mean. If all data points are confined within the control limits, the process is considered to be

stable, displaying common stable variation. If a data point or multiple data points fall outside of

the control limits, Shewhart rules are used to look for special causes of variation. Eight

consecutive data points showing evidence of unstable variation represent a sustained change in

the process and a new mean central line is calculated for the process.

Until the late 1980s control charts were used for primarily monitoring quality in

industrial sectors. At that time, however, interest gained in the healthcare sector and Shewhart

control charts increased in utilization. Although potential benefits in using control charts in

evaluation of processes were demonstrated (Glasziou, Irwig, & Mant, 2005), gathered interest

was moderate and mostly applied in monitoring hospital performance and public health

observation (Benneyan, 1998; Mohammed et al., 2001; Morton et al., 2001). In 2007, 2

systematic reviews were conducted by groups in England (Tennant, Mohammed, Coleman, &

Martin, 2007) and Sweden (Thor et al., 2007) to evaluate the use of control charts in monitoring

clinical variables in patients, with results highlighting that control charts were found to be simple

and effective with good sensitivity and specificity characteristics (Tennant et al., 2007). The

conclusion stated that this form of evaluation was promising but largely underutilized.

To evaluate the impact of the MSH La6 Protocol, Shewhart control charts were used to

determine whether process measures of heart failure care changed over time during the 32

months pre-implementation of protocol and for 8 months after.

4.3 Selection of Endpoints for Process Measurement

4.3.1 Selection of Safety Endpoints

Page 60: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

46

Safety of the MSH La6 Protocol was evaluated in several ways. The concept of safety

within such practice change encompassed several components, including adherence to

monitoring actions prescribed by the Nomo-SDC (further discussed in Sections 2.2.1 and 2.2.2),

and potential clinical adverse events. These components are described in greater detail below.

i) Adherence to Monitoring Actions

As noted in 3.2.1, safety of the process was predicated on adherence to the actions for

patient monitoring prescribed by the Nomo SDC, throughout the duration of treatment on the

MSH La6 Protocol. The Nomo-SDC monitoring actions were ideal for consideration as

opportunities for care and therefore an opportunity-based score was calculated for 1. Daily

weight measurement, 2. Total daily urine output, 3. Blood pressure, 4. Daily measurement of

serum sodium, 5. Daily measurement of serum potassium, and 6. Daily measurement of serum

creatinine. A composite opportunity-based score that combined all of the above individual

measures was also calculated. A composite opportunity-based score was also calculated per

patient, where up to 23 monitoring care processes were included to derive a monitoring

completion score for each patient. Each patient had a different number of total monitoring care

processes deemed eligible because the duration of the protocol varied based on each individual

case. The maximum number of 23 monitoring care processes was calculated if the patient was

placed on protocol for a full 48 hours. Patient level care was considered by deriving an all-or-

none score (or a “defect-free score”), defined as the proportion of patients receiving all of the

pre-specified care processes for which they are eligible (Peterson et al., 2010). Thus, this score

reflected the proportion of patients receiving ‘perfect’ care. Adherence measured in this manner

was performed in a sample of patients treated with the La6 Protocol and presented in chapter 4.

Page 61: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

47

The actions prescribed in the Nomo SDC simply describe an optimal standard of care, as

described in Section 1.3.1, that also applies to any patient admitted for acute heart failure

receiving intravenous diuretic therapy for relief of congestion. Therefore, similar metrics to

evaluate processes of care were applicable to patients receiving usual care, either prior to

implementation of the La6 Protocol or for whom the protocol was not employed. Adherence to

daily monitoring of patients receiving IV loop diuretics as currently recommended by major

cardiovascular societies was evaluated. Monitoring measures comprising the composite score

included daily serum potassium, daily serum creatinine and daily ward weight. Compliance to

these measures was determined using two methodologies, opportunity-based scoring (discussed

in Section 4.2.2) and all-or-none scoring (discussed in Section 4.2.3). The composite

opportunity-based score was calculated as the total number of monitoring measures completed

divided by the total number of actions required (3 daily measurements; baseline, 24 and 48

hours).

Additionally, the proportion of patients with a minimum of 2 ward weight measurements

in the first 48-hour was calculated as a minimum pre-requisite measure that demonstrated

diuretic progress was being monitored. All process measures were also expressed as group

means calculated each consecutive month throughout the pre- and post- implementation time

periods. By evaluating these opportunities for care in a similar manner, an evaluation of overall

variation in care was possible using Shewhart control charts. These results are presented in

Chapter 5.

ii) Definition of potential adverse events: potassium homeostasis

The significance of potassium homeostasis and the consequences of its disruption were

discussed in Section 1.3.3. Thus, abnormalities of serum biochemistry were examined over the 0-

Page 62: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

48

24h and 24-48h interval of the protocol. Hypokalemia was considered an adverse effect of

diuretic therapy and was classified as: severe hypokalemia (serum K+ <3.0mmol/L, considered a

serious adverse event), hypokalemia (serum K+ >3.0 and <3.5mmol/L), and a risk of

hypokalemia (serum K+ >3.5 and <4.0mmol/L). Since potassium replacement was included in

the Nomo-SDC, hyperkalemia (serum K+ >5.0 mmol/L) was also considered a serious adverse

event.

iii) Definition of potential adverse events: renal function

A rise in serum creatinine >50% above baseline at anytime was considered a serious

adverse event, based on the RIFLE criteria for acute kidney injury (AKI). The RIFLE Criteria

(Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) is a classification

system developed in 2004 that stratifies the severity of acute kidney injury based on the increase

of serum creatinine, or decrease of estimated glomerular filtration rate (eGFR), or decrease of

urine output (Bellomo et al., 2004). The severity of AKI is graded based on the following rules:

Risk – 50% increase in the serum creatinine, or a decrease in GFR by 25 percent, or urine

output <0.5 mL/kg per hour for six hours.

Injury – 100% increase in the serum creatinine, or a decrease in GFR by 50 percent, or

urine output <0.5 mL/kg per hour for 12 hours.

Failure – 300% increase in the serum creatinine, or a decrease in GFR by 75 percent, or

urine output of <0.3 mL/kg per hour for 24 hours, or anuria for 12 hours.

Loss – Loss of kidney function for more than 4 weeks.

ESRD (End-Stage Renal Disease) – Loss of kidney function for more than 3 months.

For evaluation of protocol safety, presence of AKI was assessed through change in serum

creatinine in the RIFLE criteria.

Page 63: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

49

iv) Adverse Clinical Events

Identification and prevention of adverse events are particularly important due to the

above-discussed issues of safety and timeliness of therapy but also due to the high mortality risk

of AHF. Canada’s in-hospital mortality rate was found to be 9.5 deaths per 100 patients in their

index hospitalization in the late 1990s (Lee et al., 2004). In Ontario, that rate was 9.2. The age-

and sex-adjusted inhospital mortality rate significantly increased for patients over 75 years of

age.

In evaluating the MSH La6 Protocol, several adverse clinical events were considered

critical and were recorded. Deaths or transfers to a higher acuity setting during use of the

protocol were recorded. Events in which the protocol was suspended unexpectedly or by an alert

notification were recorded. The alert notifications included a rise in serum potassium

>5.0mmol/L, serum sodium <125mmol/L, systolic BP <90mmHg, and a rise in serum creatinine

of at least 30% above baseline.

4.3.2 Selection of Endpoints for Outcome Measurements

i) Furosemide Administration

The organizational change mandated by treatment in the La6 Protocol was to improve

timeliness of furosemide administration and the appropriate patient assessment required.

Therefore, amounts of furosemide administered to patients treated within the Lasix protocol were

assessed by evaluating adherence to protocol furosemide prescription. Adherence to the Nomo-

SDC-prescribed administration of furosemide was expressed as the ratio of the dose administered

compared to the planned dose ordered by correct interpretation of the Nomo-SDC. Opportunity-

based scoring was calculated for each patient based on up to 6 opportunities the bedside RN had

to administer furosemide over the duration of the protocol. From initiation of the protocol, six

Page 64: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

50

opportunities for furosemide administration included 0 hours, 6 hours, 12 hours, 24 hours, 36

hours and 48 hours on protocol. The opportunity-based score was reported for the entire cohort.

An all-or-none score, based on patients receiving every pre-specified furosemide dose in the

correct amount was also calculated.

To assess impact of the La6 Protocol on furosemide administration, total furosemide

doses given were recorded in the 0-24 hour block, 24-48 hour block and 0-48 hours in the pre-

and post-implementation cohorts. The proportion of patients who had an increase in furosemide

dose in the second 24-hour block was determined.

ii) Potassium Administration

Adherence to potassium replacement was examined in a similar fashion to adherence to

furosemide administration. Replacement for hypokalemia or risk of hypokalemia, was calculated

as an opportunity-based score for any supplementation administered for serum potassium

<4.0mmol/L. An all-or-none score was calculated based on the correct dosage given for the

appropriate pre-specified threshold of serum potassium at the correct time.

4.4 Study Design

4.4.1 Pre and Post Design

The pre-implementation cohort was retrospective and collected from the EPR system at

Mount Sinai Hospital. This cohort represented the standard routine practice at the institution

provided to AHF patients. Patients admitted to hospital with the primary diagnosis of AHF were

identified, to be compared to the post-implementation group after the rollout of the protocol. The

key advantage of this cohort was that patients in this group were not affected or biased with the

use of the protocol. This group represented the real world approach to the treatment of AHF at a

tertiary academic institution.

Page 65: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

51

The implementation of the protocol and its evaluation was performed as an observational,

prospective cohort study. The post-implementation group was thus collected prospectively and

similarly, included all patients admitted to MSH with the primary diagnosis of AHF. The use of

the protocol was left at the discretion of the treating physician. Although the La6 Protocol has

specific and evidence-based inclusion and exclusion criteria, it was recognized that the treating

physician, examining the patient on admission, was best quipped to make the proper clinical

judgment about eligibility of the protocol in each specific case. This provided the advantage of

evaluating the impact of the protocol in a real-world setting and test true uptake and effect.

Although formal scientific experiment designs, such as randomized control trials (RCTs),

are highly valuable in testing important hypotheses and do so with as little bias as possible, a set

of specific challenges come with testing the impact of a process change(Berwick, 1998). Process

related interventions are specifically complex and impart their influence in a specific setting and

on an entire process. By definition, a formal study design such as an RCT is meant to disperse

the majority of the ‘noise’ of a real world system, in order to allow the independent variable of

interest to produce a signal. This, however, comes to a disadvantage when variation in an entire

system (or process) is to be tested.

4.4.2 Patient populations

The pre-implementation cohort was assembled using the EPR system to retrospectively

identify all patients admitted with a primary diagnosis of AHF over a 32-month period prior to

the implementation of the MSH La6 Protocol between March 3rd, 2010 and October 24th, 2012.

Inclusion criteria was composed of 1) patients admitted to MSH with a primary diagnosis of

AHF who had received at least one dose of bolus intravenous (IV) furosemide within 24 hours of

admission. Patients who received a continuous infusion of furosemide within the first 48 hours of

Page 66: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

52

admission to hospital and/or those who did not received at least one dose of bolus IV furosemide

within 24 hours of admission were excluded. The post-implementation cohort was collected

prospectively and consisted of all consecutive patients admitted to MSH with the primary

diagnosis of AHF over 8 months between July 1st, 2013 and February 27th, 2014. The same

inclusion and exclusion criteria for the pre-implementation were used to select the post-

implementation cohort and therefore included patients who were treated using the protocol, and

patients who received routine care.

The entire population from both the pre- and post-implementation cohorts was also

evaluated as eligible or ineligible for treatment by the MSH La6 protocol, based on the inclusion

and exclusion criteria specified in the PPOS, regardless of whether patients were treated using

the protocol or not. Finally, the implementation cohort consisted of consecutive patients treated

using the La6 Protocol between December 15th, 2012 and June 30th, 2013.

4.4.3 Data collection

In the post implementation cohort, charts of all patients admitted with a primary

diagnosis of AHF were prospectively reviewed daily, regardless of La6 Protocol use. Patient data

was collected from multiple sources over the first 48 hours after admission to hospital. For those

patients placed on the La6 Protocol, the PPOS and the Nomo-SDC were also collected for

analysis. Information on patient’s presentation to hospital was collected from physician and

nursing notes in the emergency department (ED). This data was comprised of date and time of

presentation and admission to hospital, patient’s vital signs including blood pressure, heart rate,

respiratory rate and oxygen saturation level, weight measurement, intravenous furosemide dose

and time of administration and total ED urine output and time of measurement. Bloodwork done

in the ED was collected from the patient’s electronic patient record (EPR) and the following

Page 67: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

53

markers recorded – hemoglobin, hematocrit, white cell count, platelets, sodium, potassium, urea,

creatinine, estimated glomerular filtration rate (eGFR), bilirubin, alkaline phosphatase (ALP),

aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, international

normalized ratio (INR), serum B-type natriuretic peptide (BNP), and troponin. Data on the

patient’s medical and social history was collected from a consultation note written by a physician

in the ED. Recorded history included date and time of consultation, a previous recorded history

of chronic heart failure and date of diagnosis (if available), admission to hospital with the

primary diagnosis of AHF in the previous year, history of percutaneous coronary intervention

(PCI), myocardial infarction (MI), aortocoronary bypass (ACB), pacemaker or defibrillator,

diabetes, hypertension, or smoking. Clinical signs and symptoms of the patient’s presentation to

the hospital were recorded and included symptoms of fatigue, dyspnea, orthopnea, and

paroxysmal nocturnal dyspnea (PND) as well as clinical signs of peripheral edema, and a jugular

venous pressure (JVP) measurement. Patient’s list of home medications and dosage that were

recorded included a loop diuretic, thiazide diuretic, spironolactone or eplerenone, angiotensin

converting enzyme (ACE) inhibitor, angiotensin II receptor antagonist, -adrenergic receptor

antagonist, digoxin, calcium channel blocker, anti-arrhythmic medication, anti-platelet

medication, anti-coagulation medication, vasodilator medication, or lipid medication. This data

was collected from the physician consultation note in the ED and confirmed through a hospital

pharmacist note in EPR. Following admission to the cardiology or medicine ward, clinical

patient data was collected for 48 hours. In each 24-hour time block data was collected from EPR

on several clinical markers as well as furosemide and potassium administration. Intravenous

furosemide and potassium replacement data included every ordered dose, administered dose and

time of every administration. Clinical markers recorded consisted of serum sodium, potassium

Page 68: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

54

and creatinine, total urine output in 24 hours, and every weight measurement recorded.

Additionally, final weight measurement prior to discharge (defined as discharge weight) and

length of stay were recorded for every patient.

Data collection of patients placed on protocol began from the first use of the La6 protocol

during the implementation period on December 15th, 2012. Following completion of the

implementation period on June 30th, 2013, during which data was collected only on patients

treated using the protocol, data collection began on all patients admitted to Mount Sinai Hospital

with the primary diagnosis of AHF. Data collection was completed on February 28th, 2014.

Subsequently, patients were grouped as eligible or ineligible based on inclusion and exclusion

criteria defined in the PPOS. Permission to perform prospective data collection was approved by

the Mount Sinai Hospital Research Ethics Board.

Data collected for both cohorts consisted of patient demographics, home medications,

serum potassium and creatinine, weight measurements, and total furosemide and potassium

doses received in the first 48 hours of admission to hospital. Home medications recorded

included loop diuretic, thiazide diuretic, spironolactone or eplerenone, angiotensin converting

enzyme (ACE) inhibitor, angiotensin II receptor antagonist, -adrenergic receptor antagonist,

digoxin, or calcium channel blocker. All weight measurements taken in the first 48 hours of

admission to hospital were recorded.

Page 69: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

55

Table 3. Sample Data Collection Form

TA COLLECTION SHEET:

Patient Identifier: ____________________

Age: _____

Sex: M F

Ward: _______

Service Admitted: medicine | cardiology

(If patient not admitted through ER, go to consultation.)

Weighed: Y N ____ kg Time recorded (hh:mm):

___:___

Heart rate: Y N ____ bpm

Respiration rate: Y N ____ bpm

O2 saturation: Y N ____%

Blood pressure: Y N SYS/DIA: ___/___

Lasix administered: Y N Dosage: _____ mg

Time of administration (hh:mm): ___:___

Urine output recorded: Y N Volume: _____ mL

Time of measurement (hh:mm): ___:___

DEMOGRAPHICS (FACESHEET)

DATA COLLECTION SHEET for PATIENTS ENROLLED IN THE PROTOCOL

Primary diagnosis: ___________________ ___________________

EMERGENCY ROOM ASSESSMENT (ER SHEET REVIEW)

Date of Registration (yy/mm/dd): ___/___/___ Triage Time (hh:mm): ___:___ Time of Registration (hh:mm): ___:___ Time Seen (hh:mm): ___:___

Presenting complaint: ___________________ ___________________

Date of Admission (yy/mm/dd): ___/___/___ Time of Admission (hh:mm): ___:___ Date of Discharge (yy/mm/dd): ___/___/___ Time of Discharge (hh:mm): ___:___

Page 70: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

56

Date of Collection (yy/mm/dd): ___/___/___ Time of Collection (hh:mm): ___:___

Previous Medical History

Previous diagnosis for HF: Y N U Date (yy/mm/dd): ____/____/____

Previous admission for HF within 12 mths: Y N U Date (yy/mm/dd): ____/____/____

(REFER TO PREVIOUS REPORT)

Previous PCI: Y N U

Previous MI: Y N U

Previous ACB: Y N U

Pacemaker/Defibrillator: Y N U

Diabetes: Y N U

HTN: Y N U

Smoking: Y N U Comments:_____________________

History

Fatigue Y N U

Dyspnea Y N U

Orthopnea Y N U

PND Y N U

Physical Examination

Edema : Y N Comments:_____________________

JVP estimate:

Blood Test Measurement

Haemoglobin (Hb)

Hematocrit (Ht)

White Cell Count

Platelets

Sodium

Potassium

Urea

Creatinine

eGFR

Blood Test Measurement

Bilirubin

ALP

AST

ALT

Albumin

INR

BNP

Troponin

ER BLOODWORK (POWERCHART)

ER BLOODWORK (POWERCHART)

CONSULTATION WITH FIRST MED/CARD CONTACT (PINK CONSULT SHEET OR 1ST DOCUMENTED NOTE)

YES NO UNSPECIFIED

Date of Consult (yy/mm/dd): ___/___/___ Time of Consult (hh:mm): ___:___

Page 71: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

57

Diuretic use: Y N

Loop Diuretic: Medication: _____________________

Y N Daily dose: _______ mg

Change in diuretic dose within past 1 month: Y / N

Thiazide Diuretic: Medication: _____________________

Y N Daily dose: _______ mg

Change in diuretic dose within past 1 month: Y / N

Spironolactone/Eplerenone: Medication: _____________________

Y N Daily dose: _______ mg

Change in diuretic dose within past 1 month: Y / N

Ace Inhibitors: Medication: _____________________

Y N Daily dose: _______ mg

Angiotensin II Blockers: Medication: _____________________

Y N Daily dose: _______ mg

Beta-blockers: Medication: _____________________

Y N Daily dose: _______ mg

Digoxin: Medication: _____________________

Y N Daily dose: _______ mg

Ca2+ Channel blockers: Medication: _____________________

Y N Daily dose: _______ mg

Anti-Arrhythmics: Medication: _____________________

Y N Daily dose: _______ mg

Anti-Platelets: Medication: _____________________

Y N Daily dose: _______ mg

Anti-Coagulants: Medication: _____________________

Y N Daily dose: _______ mg

Other Vasodilators: Medication: _____________________

Y N Daily dose: _______ mg

Lipid Medication: Medication: _____________________

Y N Daily dose: _______ mg

CURRENT MEDICATIONS

Page 72: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

58

(CHECK MAR SUMMARY)

Lasix Ordered

Y N Dose: ____ Time: ____

Lasix Given

1st: Y N Dose: ____ Time: ____

2nd: Y N Dose: ____ Time: ____

3rd: Y N Dose: ____ Time: ____

K+ replacement

1st: Y N Dose: ____ Time: ____

2nd: Y N Dose: ____ Time: ____

Review Labs

Na+ Y N ____mmol/L Time: ____

K+ Y N ____mmol/L Time: ____

SCr Y N ____μmol/L Time: ____

Urine output (CHECK CLINICAL DOCUMENTATION)

Y N ____mL Time: ____

Weight (ALL WEIGHTS WITHIN 24 HOURS)

Y N ____kg Time: ____

WARD ADMISSION (POWERCHART REVIEW OF 24 HOURS)

0 HOURS Date of Admission (yy/mm/dd): ___/___/___ Time of Admission (hh:mm): ___:___

24 HOURS Date at 24 Hours (yy/mm/dd): ___/___/___ Time at 24 Hours: (hh:mm): ___:___

Page 73: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

59

(CHECK MAR SUMMARY)

Lasix Ordered

Y N Dose: ____ Time: ____

Lasix Given

1st: Y N Dose: ____ Time: ____

2nd: Y N Dose: ____ Time: ____

3rd: Y N Dose: ____ Time: ____

K+ replacement

1st: Y N Dose: ____ Time: ____

2nd: Y N Dose: ____ Time: ____

Review Labs

Na+ Y N ____mmol/L Time: ____

K+ Y N ____mmol/L Time: ____

SCr Y N ____μmol/L Time: ____

Urine output (CHECK CLINICAL DOCUMENTATION)

Y N ____mL Time: ____

Weight (ALL WEIGHTS WITHIN 24 HOURS)

Y N ____kg Time: ____

Discharge Weight (LAST WEIGHT ON THE WARD)

____kg Time + Date: _______________________

24 HOURS Date at 24 Hours (yy/mm/dd): ___/___/___ Time at 24 Hours (hh:mm): ___:___

48 HOURS Date at 48 Hours (yy/mm/dd): ___/___/___ Time at 48 Hours (hh:mm): ___:___

WARD ADMISSION (POWERCHART REVIEW OF 48 HOURS)

Page 74: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

60

WHY PATIENT WAS

NOT ENROLLED IN PROTOCOL

INCLUSION CRITERIA

EXCLUSION CRITERIA

CONCLUSION

Dyspnea Edema Increased BNP (>100) Elevated JVP (>4cm)

New diagnosis of HF Loop diuretic naïve SBP < 90 mmHg SCr > 260 mmol/L No inclusion criteria Treated with PO Lasix on ward

Protocol Eligible (1 or more inclusions and no exclusions) Protocol Ineligible (1 or more exclusions regardless of any inclusions)

Page 75: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

61

5 Improving Efficiency of Diuretic Care for Patients Hospitalized

with Decompensated Heart Failure Using a Nurse Implemented

Strategy: MSH La6 Protocol

5.1 Introduction

Hospitals are faced with the challenge of treating acutely decompensated heart failure

(ADHF), attempting to minimize costs and length of stay while at the same time improving

quality of care (Yeung et al., 2012). Processes of care should be rational and evidence based.

Intravenous (IV) loop diuretic therapy remains the cornerstone of inpatient heart failure (HF) (W.

F. Peacock et al., 2009) care requiring appropriate dose selection then evaluation of efficacy and

adverse events in a cycle of actions that recurs throughout admission. The tasks of prescription

and drug administration are commonly divided between the ordering physician team and

registered nurses and carried over frequent transfer of care responsibility between both nurses

and clinicians with variable levels of training (Devlin, Kozij, Kiss, Richardson, & Wong, 2014).

Variation in dosing and delays in communication between caregivers may impair the efficiency

of achieving diuresis.

At our institution, a practice change to optimize the efficiency of loop diuretic

administration was developed and tested. The MSH La6 Protocol is a 48-hour intervention

implemented early during admission with the intent of achieving high quality and efficiency of

care. The objective was not to test the well-understood efficacy of loop diuretic therapy; rather to

implement a process to achieve diuresis while eliminating communication delays that occur

between clinical personnel. Additional objectives included standardization of furosemide

Page 76: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

62

prescription and best practices for monitoring efficacy and adverse effects. The current study

presents the development, initial adherence and safety of the MSH La6 Protocol.

Page 77: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

63

5.2 Methods

The MSH La6 Protocol consists of 2 paper-based tools: I. Physician Pre-Printed Order

Set (PPOS), and II. Nomogram for Stepped Diuretic Care (Nomo-SDC), which allows

autonomous action to deliver and adjust diuretics by a bedside caregiver without delays for

physician approval.

5.2.1 The Physician Pre-Printed Order Set (PPOS)

The PPOS (Figure 1) consolidated the tasks of the ordering physician, fulfilling the

following objectives:

i) Patient Selection

The target population for this intervention was loop diuretic-experienced patients with a

previous history of HF, for whom the primary treatment objective was relief of systemic and

pulmonary venous congestion. The recommended goal of therapy was a target weight loss of >

2kg over 48 hours. Inclusion and exclusion criteria were verified by the medical team using a

checklist.

ii) Standardized Orders for Monitoring Efficacy and Safety of Therapy

The PPOS standardized orders for clinical and biochemical monitoring and importantly

prespecified criteria by which scheduled diuretic therapy could proceed without physician

consultation. The PPOS also specified ‘alert notifications’ for potentially dangerous situations

that automatically suspended the process and mandated reassessment by the medical team. For

each alert notification, guidelines for patient reassessment and documentation were provided.

5.2.2 The Nomogram for Stepped Diuretic Care (Nomo-SDC)

The Nomo-SDC (Figure 2) was an algorithm tool that allowed delivery and escalation of

IV furosemide dosing based on bedside measures of efficacy and safety without physician

Page 78: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

64

consultation unless notification of the physician team was specified by the protocol. In our

institution, the bedside registered nurse directed the Nomo-SDC. After training, no additional

clinical resources and no changes in nurse-to-patient ratios were required. The following

considerations further informed the Nomo-SDC design:

i) Timing, and Titration of Furosemide Dosing

Recent evidence informed our approach to the safe and effective IV loop diuretic

administration particularly for HF patients already established on oral loop diuretic therapy (Bart

et al., 2012; Felker et al., 2011). Furosemide prescription also complied with current guidelines

for the treatment of acute heart failure in hospital (McKelvie et al., 2013; Yancy et al., 2013).

Two principles, 1) consideration of renal function (estimated glomerular filtration rate < or >

60ml/min) and 2) administering an IV dose at least equivalent to the total daily oral loop diuretic

dose, guided selection of a lower or a higher dosing schedule. Importantly, the NIH DOSE trial

established that multiple bolus administration was as effective as a continuous infusion (Felker et

al., 2011). Therefore, a key design element of the Nomo-SDC was the use of twice daily bolus

administration to coordinate actions of the Nomo-SDC with a standard 12-hour nursing shift.

Identifying clinical markers of efficacy within the Nomo-SDC led to selection of the subsequent

furosemide dose. If urine output was < 800ml/12 hours, or weight loss was < 1kg/24 hours, an

escalation of the IV furosemide dose was triggered, with subsequent reassessment occurring

every 12 hours. If efficacy targets were not met by 36 hours, the Nomo-SDC compelled

notification of the medical team for reassessment.

ii) Monitoring and Replacement of Electrolytes

Actions for monitoring electrolytes and renal function were also aligned with standard

12-hour nursing shifts. A nomogram for potassium monitoring and replacement without

Page 79: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

65

physician consultation was embedded in the Nomo-SDC (Figure 2). Potassium replacement at

adjusted doses was indicated for serum K+ <4.0mmol/L.

iii) Completion or Early Termination of the Protocol

Completing each 12-hour segment of the protocol resulted in either selection of the

subsequent dose, identification of an alert notification for suspension, or therapeutic target

weight loss achievement. After 48 hours, further diuretic therapy reverted to usual care and

communication between the medical team and RN.

5.2.3. Evaluation of Patient Population, Feasibility and Safety

The decision to use the protocol was left at the discretion of the attending physician.

Charts of all patients admitted with a primary diagnosis of AHF were prospectively reviewed

daily, regardless of La6 Protocol use. Patients were grouped as eligible or ineligible based on

inclusion and exclusion criteria defined in the PPOS. The electronic patient records were

reviewed to extract presenting history, demographics, past medical and medication history

including admissions for AHF, serum biochemistry and IV loop diuretic administration. Length

of stay in hospital was recorded. Permission to perform prospective data collection was approved

by the Mount Sinai Hospital Research Ethics Board.

The primary feasibility endpoint was the proportion of patients initiated on the La6

Protocol who then completed the entire 48 hours or reached target weight loss early while on

protocol.

Safety was examined in multiple ways. Deaths or transfers to a higher acuity setting

during use of the protocol were recorded. Events in which the protocol was suspended

unexpectedly or by an alert notification were recorded. The alert notifications included a rise in

serum potassium >5.0mmol/L, serum sodium <125mmol/L, systolic BP <90mmHg, and a rise in

Page 80: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

66

serum creatinine of at least 30% above baseline. Abnormalities of serum biochemistry were

examined over the 0-24h and 24-48h interval of the protocol. Hypokalemia was considered an

adverse effect of diuretic therapy and was classified as: severe hypokalemia (serum K+

<3.0mmol/L, considered a serious adverse event), hypokalemia (serum K+ >3.0 and

<3.5mmol/L), and at risk of hypokalemia (serum K+ >3.5 and <4.0mmol/L)(Gennari, 1998).

Since potassium replacement was included in the Nomo-SDC, hyperkalemia (serum K+ >5.0

mmol/L) was also considered a serious adverse event. A rise in serum creatinine >50% above

baseline at anytime was considered a serious adverse event, based on the RIFLE criteria(Bellomo

et al., 2004; Zhang et al., 2015) for acute kidney injury (AKI).

5.2.4 Evaluation of Protocol Adherence

The protocol was considered initiated if the PPOS was completed and at least one dose of

furosemide was administered. We evaluated specific Nomo-SDC monitoring actions as

opportunities for care and calculated an opportunity-based score for patient weights, urine

output, blood pressure, serum electrolyte and creatinine measurements. The score was calculated

as the total number of actions completed divided by the total number of actions required by the

Nomo-SDC. A composite opportunity-based score of these performance measures was also

calculated. A composite opportunity-based score was also calculated per patient, where up to 23

monitoring care processes were included to derive a monitoring completion score for each

patient. Patient level care was considered by deriving an all-or-none score (or a “defect-free

score”), defined as the proportion of patients receiving all of the pre-specified care processes for

which they are eligible (Peterson et al., 2010). Thus, this score reflected the proportion of

patients receiving ‘perfect’ care.

Page 81: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

67

Adherence to the Nomo-SDC-prescribed administration of furosemide was expressed as the ratio

of the actual dose administered compared to the planned dose dictated by correct interpretation

of the Nomo-SDC. Opportunity-based scoring was calculated for each patient based on up to 6

opportunities the bedside RN had to administer furosemide over the duration of the protocol, and

reported for the entire cohort. An all-or-none score, based on patients receiving every pre-

specified furosemide dose in the correct amount was also calculated.

Adherence to Nomo-SDC prescribed potassium replacement was examined for

hypokalemia or risk of hypokalemia, calculated as an opportunity-based score for any

supplementation administered for serum potassium <4.0mmol/L. An all-or-none score was

calculated based on the correct dosage given for the appropriate pre-specified threshold of serum

potassium at the correct time.

5.2.5 Evaluation of Early Effectiveness

Effectiveness of diuresis was evaluated as weight loss per 24 hours on protocol. Total

weight loss during admission was also recorded.

5.2.6 Statistical Analysis

Data is presented as mean ± standard deviation or median and interquartile range, as

appropriate. Dose prescription, administration, and measures of adherence were compared

between the 0-24 hour block and 24-48 hour block using unpaired t-tests or chi squared analysis

for continuous and categorical variables, respectively. Percent changes in serum creatinine from

the baseline at 24 and 48 hours were analyzed using a one-sample t-test. A value of P ≤0.05 was

considered statistically significant. Statistical calculations were performed using SPSS Statistics

software v20 (IBM Inc).

Page 82: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

68

5.3 Results

5.3.1 Patient Population, Feasibility and Safety

Fifty consecutive protocols were initiated over a span of 15 months. Over this period, the

rate of admissions for AHF was 16.5 per month, of which 58% were eligible for treatment by the

MSH La6 protocol. The mean age of the patients was 81 years; 56% were male (Table 4). The

primary feasibility endpoint was reached in 36 patients (72%) who completed the protocol; of

these, 19 continued protocol treatment for the full 48 hours and 17 completed the protocol early

because target weight had been achieved at 24 hours. The mean duration that patients were

treated within the Nomo-SDC was 33±15 hours.

The protocol was discontinued for 14 patients prior to completion or achievement of

target weight. Seven of 14 were discontinued after alert notifications were reached. The protocol

was discontinued in the remaining 7 patients for reasons unrelated to the Nomo-SDC, including

patient non-compliance with medications and urine output measurements or extended ward

absence for procedures.

During protocol treatment, there were no deaths and no transfers to an acute care setting.

One patient was documented to have suffered a stroke. Safety markers for potassium

homeostasis and changes in creatinine are also presented in Table 4. After initiation, there were

no instances of severe hypokalemia. Hypokalemia occurred in 7% of patients at 24 hours and in

21% at 48 hours, requiring supplementation. Although 2 patients were withdrawn after meeting

the alert notification for an increase in serum creatinine, no significant changes in serum

creatinine were observed over the duration of the protocol. There were no instances in which

serum creatinine increased >50% from baseline.

5.3.2 Adherence to Monitoring Actions

Page 83: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

69

Opportunity-based scores for pre-specified monitoring actions were 100% (weights),

85% (urine output) and 88% (blood pressure). Similarly, scores for monitoring markers were

98% (serum sodium), 91% (potassium) and 95% (creatinine). The cohort opportunity score for

combined clinical and biochemical monitoring was 91%. The median opportunity-based score

per patient was 96% (IQR 87-100). The all-or-none score (patients receiving “perfect”

monitoring) was 48%.

5.3.3 Adherence to Pre-specified Drug Administration

Between the 0-24 hour and 24-48 hour blocks, the mean IV furosemide dose

administered increased significantly demonstrating dose titration was occurring within the

protocol (Table 5). The cohort opportunity score for adherence to furosemide administration as

prescribed by the Nomo-SDC was 92%. Per patient, the median opportunity-based score to

complete up to 6 opportunities for furosemide administration during protocol treatment was

100% (IQR 88-100). The all-or-none score for furosemide administration as guided by the

Nomo-SDC was 74%. Adherence to potassium replacement expressed as an opportunity score

was 93% for hypokalemia and 71% for patients at risk of hypokalemia. The median opportunity-

based score per patient to complete up to 5 opportunities for potassium replacement was 75%

(IQR 50-100). The all-or-none score for potassium replacement as guided by the Nomo-SDC

was 58%.

5.3.4 Treatment Effect

During the first 24 hours of the protocol, 90% of patients lost weight, with a median loss

of 1.4kg (IQR 0.8-2.2). In the second 24 hours 73% of remaining patients lost a median of 0.8kg

(IQR 0.4-1.2). Over the duration of protocol treatment, the median weight loss was 1.8kg

Page 84: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

70

(IQR1.3-3.8). The median weight loss for the duration of hospital admission was 4.8kg (2.4-8.6).

Median length of stay for patients treated in the MSH La6 protocol was 7 days (5-16).

Page 85: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

71

Table 4. Characteristics of the La6 Protocol Patients

Clinical Characteristics N = 50

Age, y (mean ± SD) 81 ± 12

Males 56%

HF as primary admitting diagnosis 94%

Previous diagnosis of HF 84%

Admission for HF exacerbation within the previous year 44%

History of Diabetes Mellitus 40%

History of Hypertension 74%

Medications at Home: Loop Diuretic 86%

ACE Inhibitors/ARBs 48%

-adrenergic Receptor Antagonists 72%

Systolic Blood Pressure, mmHg (mean ± SD) 127 ± 23

Heart Rate, bmin-1 84 ± 23

Respiratory Rate, min-1 21 ± 5

NT-proBNP, pg/ml 1091± 946

Sodium, mmol/L 137 ± 5

Serum potassium and creatinine at baseline and during protocol treatment

Potassium at baseline, mmol/L (mean ± SD) 4.3 ± 0.9

% severe hypokalemia (K<3.0mmol/L), (0h, 24h, 48h) 4, 0, 0

% hypokalemia (K<3.5) 34, 7, 21

% at risk of hypokalemia (< 4.0) 58, 66, 47

% with hyperkalemia (>5.0) 5, 4, 0

Creatinine at baseline, μmol/l (mg/dl) 137 ± 60 (1.55 ± 0.68)

Creatinine, % change from baseline, median (IQR)

0-24 hours 1.8 (-3.8 – 8.3)

24-48 hours 0 (-7.6 – 9.7)

0 hours – end of protocol 1.4 (-4.0 – 8.3)

HF, heart failure; NT-proBNP, N-terminal of the prohormone brain natriuretic peptide; ACE,

angiotension-converting enzyme; ARB, angiotension receptor blocker.

Page 86: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

72

Table 5. Adherence to Furosemide and Potassium Administration as Guided by the Nomo-

SDC

Drug 0-24hrs 24-48hrs Total

Furosemide (mg; Mean dose ± SD)

Planned 138 ± 54 220 ± 130* 261 ± 179

Given 138 ± 54 205 ± 130* 252 ± 173

Adherence to Nomo-SDC Furosemide Dosing

Cohort opportunity score (%) 92

Per-patient opportunity score

median [IQR], %

100 (88-100)

All-or-none score (%) 74

K Replacement (mEq; Mean dose ± SD)

Planned 71 ± 29 80 ± 42 102 ± 59

Given 63 ± 27 56 ± 41 81 ± 56

Adherence to Nomo-SDC Potassium

Replacement Dosing

Cohort opportunity score (%)

Hypokalemia

Risk of hypokalemia

93

71

Per-patient opportunity score

median [IQR], %

75 (50-100)

All-or-none score (%) 58

*, p<0.05 vs. 0-24hrs.

Page 87: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

73

5.4 Discussion

The goal for this quality improvement innovation was to optimize the efficiency of

diuretic therapy for patients admitted with acute heart failure. After ensuring appropriate patient

selection by the medical team, we demonstrated that it was feasible to empower a bedside

caregiver group over an extended duration to assess efficacy, adjust diuresis and identify adverse

effects, independent of physician reassessment unless pre-specified signs of intolerance or lack

of effectiveness were identified. Our initial experiences suggest that this process was safe,

resulted in excellent documentation of markers of quality care such as daily weights, and that

clinical treatment targets could be achieved.

Like other standardized order sets (Group, 2009), the PPOS conveniently grouped

medical orders decreasing variation in care and enhancing compliance with treatment guidelines.

The PPOS was populated by information gleaned from routine medical consultation, identifying

patients for whom diuresis was the central goal of therapy. The resultant treatment cohort was

typical of community-based patients with AHF enrolled in registry studies, predominantly

elderly with a moderate degree of renal insufficiency (Adams et al., 2005; Yeung et al., 2012).

The algorithm for stepped diuretic care was based on procedures used in clinical trials (Bart et

al., 2012; Felker et al., 2011) and deployed in a “real world” hospital ward setting, without

mobilizing additional care provider resources per patient. The procedures required objective

clinical measurements within the existing skill set of the nursing group, and did not mandate

acquisition of new skills such as clinical volume assessment. An important consideration in

design and safety of the Nomo-SDC was optimization of the human factor elements (Flin R,

2009) which may be reflected by adherence measures. When considering the uptake of all

opportunities to perform monitoring activities, the high opportunity scores (>85%) suggested

Page 88: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

74

that the Nomo-SDC directed process was well integrated into the workflow of the bedside RN

and continued successfully over changes in shift personnel. Interestingly, this contrasted with

poorer scores when adherence was evaluated by all-or-none methodology, likely owing to the

multi-task process that constitutes evidence-based diuretic care. Other nomogram-driven

therapies such as anticoagulation with intravenous unfractionated heparin (Cruickshank, Levine,

Hirsh, Roberts, & Siguenza, 1991; Flaker, Bartolozzi, Davis, McCabe, & Cannon, 1994) may be

simpler given one drug infusion to maintain a single laboratory measurement within a

therapeutic range. Diuretic therapy for HF involves clinical and laboratory monitoring and an

evolving therapeutic target over time. As such, all-or-none scoring, so-called “perfect care”

could be compromised based on omission of single measurements.

Similar to monitoring actions, good adherence to the Nomo-SDC by the RN for

furosemide administration and potassium supplementation for any hypokalemia was observed.

The furosemide dosage increased during the 24-48 hour interval of the protocol, suggesting the

initial dosage selection was conservative, supportive of the relative safety of the Nomo-SDC.

Moreover, the design of the Nomo-SDC prompted dosage escalation every 12 hours if

inadequate diuresis was noted by the point of care nurse. As such, efficiency may be enhanced

compared to either fixed standing diuretic orders or awaiting daily assessment and prescription

by the medical team. Every 12 hours, the Nomo-SDC also identified patients for selective

reassessment by the medical team if prespecified safety endpoints, or insufficient efficacy targets

were reached. These attributes of the MSH La6 Protocol contributed to safety, but equally

avoided persistence with ineffective dosing. Adherence to the full dose of furosemide and

potassium replacement prescribed by the Nomo-SDC was highest during the initial 24 hours, but

tended to decline between 24-48 hours. Variability between individual patients likely increases

Page 89: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

75

with respect to clinical status, goals of care and need for further therapy which may impede

protocolized care over time and supports limiting the protocol duration to 48 hours..

This study has a number of limitations that merit acknowledgement. The number of

patients included in this initial analysis is small and taken from a single center; however, the

study cohort was representative of patients typically admitted with AHF to Mount Sinai Hospital

and other academic and community centers. The MSH La6 Protocol is currently a paper based

process and, for optimal monitoring of adherence and dissemination, adapting the tools to a

computer order entry process would be an essential future direction. Automation would also

likely reduce training requirements and may further improve uptake and adherence.

Our study also has strengths deserving of mention. The Mount Sinai La6 Protocol was

designed with an interdisciplinary approach and appropriately pilot tested. Its design was based

on the most recent and appropriate prior evidence. Analysis was performed on 50 consecutive

patients, representing true uptake and adherence. In our institution, the MSH La6 Protocol

impacted approximately one third of all admissions to HF. It is a process that could also be

implemented by other care personnel such as physician assistants. Potential additional

advantages to the Nomo-SDC included facilitated handover between shift RNs, with a graphical

flow sheet of patient progress and an action plan for the subsequent 12-hour shift. A larger

evaluation of markers of quality, efficacy and length of stay for patients treated by the MSH La6

Protocol compared to usual care is ongoing.

Page 90: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

76

6 Linking Improved Processes Of Care With Timeliness Of

Intravenous Diuresis For Acute Heart Failure

6.1 Introduction

The increasing prevalence of heart failure is reflected in the large population of patients

experiencing episodes of decompensation and hospitalization for acute heart failure (AHF)

(Yeung et al., 2012). Intravenous (IV) loop diuretic therapy is the current mainstay of in-hospital

treatment (Heart Failure Society of et al., 2010; McKelvie et al., 2013; Yancy et al., 2013) for

AHF. Efficient and effective treatment requires rational dose selection, as well as repeated

actions to provide adequate monitoring of safety and evaluation of efficacy. The Canadian

Cardiovascular Society, American Heart Association and the Heart Failure Society of America

(Heart Failure Society of et al., 2010; McKelvie et al., 2013; Yancy et al., 2013) have published

specific recommendations regarding appropriate monitoring of patients receiving IV loop

diuretics in the setting of AHF. The quality of care indicators include, but are not limited to,

daily measurements of serum potassium and creatinine, daily weights and fluid balance.

Adherence to these recommendations is intended to reduce adverse events and, in the case of

diuretic therapy, possibly improves the timeliness of appropriate dose adjustment and early

efficacy of decongestion.

Accordingly, at our institution, a practice innovation was implemented to standardize and

optimize the process of diuretic administration. Locally named the Mount Sinai Hospital (MSH)

La6 Protocol, the objective of the process was to initiate effective diuresis within a 48-hour

period after hospital admission. An algorithmic tool was designed to consolidate the actions

required to monitor the effects of furosemide, and direct safe adjustment and administration of

Page 91: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

77

multiple doses. The tool also delegated prescribing autonomy to the nurse at the point of care,

with the intent of minimizing delays arising from frequent consultation between point of care

medical staff and ordering physicians. The current analysis examines the impact of this quality

improvement (QI) initiative on markers of quality heart failure (HF) care and rational diuretic

prescription at our institution.

Page 92: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

78

6.2 Methods

6.2.1 Setting

The QI initiative was conducted at MSH, an academic healthcare center in Toronto,

Ontario, Canada. The MSH La6 Protocol consisted of 2 paper-based tools, the Physician Pre-

Printed Order Set (PPOS) and the Nomogram for Stepped Diuretic Care (Nomo-SDC). These

tools were developed during a 6-month process, beginning with a review of the literature and

consensus building to assess needs and objectives. The protocol was then drafted and revised by

a multi-disciplinary panel including cardiology, hospital pharmacy, nursing administration and

nursing education. At our institution, practice changes are reviewed by the Clinical Practice

Committee, the Joint Health and Safety Committee, Risk Management, and Health Records, with

final approval by the Medical Advisory Committee. Data collection was approved by the MSH

Research Ethics Board.

6.2.2 Quality Improvement Interventions

The first tool employed after initial evaluation of the patient was the Physician Pre-

Printed Order Set (PPOS). This tool was completed by the treating physician and met several

objectives. The first objective of the PPOS was to guide selection of appropriate AHF patients

for whom the primary treatment goal was relief of fluid congestion associated with AHF. The

target population for this QI project was chronic heart failure patients with previous use of oral

loop diuretics admitted to a hospital ward setting. A checklist was provided to specify inclusion

and exclusion criteria. Inclusion checkbox criteria were: 1) a mandatory previous diagnosis of

HF and home dose of oral furosemide, 2) an elevated jugular venous pressure (JVP), 3) evidence

of pulmonary or peripheral edema, 4) ascites, 5) ≥2 kilograms of weight to lose by physician

estimate, and 6) a serum NT-pro BNP >135pmol/L (Maisel et al., 2002; McKelvie et al., 2013).

Page 93: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

79

Patients were deemed eligible if they met the mandatory criteria (checkbox 1) as well as at least

one checkbox 2 to 6. Exclusion checkboxes were also listed to prevent use of the protocol in

patients who would have been excluded from clinical trials of multi-dose furosemide

administration (Bart et al., 2012; Felker et al., 2011). Exclusion checkbox criteria were: 1)

patients with a new diagnosis of heart failure on admission and 2) furosemide naïve (not taking

oral furosemide at home), 3) systolic blood pressure of less than 90 mmHg and 4) a serum

creatinine greater than 260 micromol/L.

The second objective of the PPOS was to standardize initial twice-daily bolus furosemide

prescription, to standardize monitoring procedures and to specify a target weight loss to be met

after 48 hours. The third objective of the PPOS was to have the treating physician provide

conditional orders that enabled scheduled diuretic therapy to proceed without further physician

consultation. The PPOS also compelled the treating physician to provide standardized

conditional orders that automatically suspended the protocol and mandate notification of the

physician team for reassessment based on changes in systolic blood pressure, electrolyte

abnormalities, changes in serum creatinine and failure to meet weight loss targets.

The second tool employed was the nomogram for stepped diuretic care (Nomo-SDC)

implemented by the caregiver at the bedside. The Nomo-SDC employed an evidence-based

algorithm for twice daily assessment and selection of furosemide dosing as well as monitoring of

serum biochemistry and prescription of potassium replacement. Patient reassessment within the

Nomo-SDC was coordinated with a standard 12 hour nursing shift for minimal disruption of

workflow. Markers of efficacy and safety were collated within the Nomo-SDC, and population

of the algorithm tool then led to selection of the next dose of furosemide, without requiring

additional reassessment by the medical team.

Page 94: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

80

Implementation of the QI project included preparation of education packages including

oral, visual, and written materials and focused sessions were conducted with all active nursing

staff on two hospital wards, as well as attending medical staff and residents. On medical floors,

weight scales were inventoried, calibrated and procedures to ensure daily access to the same

scale for all ambulatory and semi-ambulatory inpatients. Education also required RNs to perform

a mock run through of the nomogram, populating each step and following through to the next.

Two hospital pharmacists, thoroughly educated on the MSH La6 Protocol were also available to

support medical and nursing staff. The decision to use the protocol was left at the discretion of

the attending physician. There were no additional clinical resources and no changes in nurse to

patient ratio required to complete this initiative.

6.2.3 Evaluation

We performed a pre and post-implementation observational study of this QI initiative

following an implementation period. Data on demographics, home medications, serum sodium,

serum potassium, serum creatinine, and all recorded weights, if available, were collected from

the initial 48 hour period of admission and the length of stay was recorded for all patients

included in this analysis.

The pre-implementation cohort was assembled using the electronic patient records system

(Cerner Powerchart) to retrospectively identify consecutive patients admitted with a primary

diagnosis of AHF over a 32-month period prior to the implementation of the MSH La6 Protocol

between March 3rd, 2010 and October 24th, 2012. Patients with a primary diagnosis of AHF

during admission to MSH who had received at least one dose of bolus intravenous (IV)

furosemide within 24 hours of admission were included. Patients who received a continuous

Page 95: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

81

infusion of furosemide within the first 48 hours of admission to hospital and/or those who did not

received at least one dose of bolus IV furosemide within 24 hours of admission were excluded.

The post-implementation cohort was collected prospectively and consisted of all

consecutive patients admitted to MSH with the primary diagnosis of AHF over 8 months

between July 1st, 2013 and February 27th, 2014. The same inclusion and exclusion criteria used

for the pre-implementation were also used to select the post-implementation cohort, regardless of

use of the La6 Protocol and therefore included patients who were treated using the protocol, and

patients who received routine care.

The entire populations from both the pre- and post-implementation cohorts were also

evaluated as eligible or ineligible for treatment by the MSH La6 protocol, based on the inclusion

and exclusion criteria specified in the PPOS. Finally, consecutive patients treated using the La6

Protocol between December 15th, 2012 to June 30th, 2013 formed the implementation cohort.

6.2.4 Process and outcome measures

The primary process measure was adherence to daily monitoring of patients receiving IV

loop diuretics as currently recommended by major cardiovascular societies. In our QI program,

monitoring measures included daily serum potassium, daily serum creatinine and daily ward

weight. Compliance to these best practices measures was determined using two methodologies.

Firstly, a composite opportunity-based score was determined for both cohorts. The score was

calculated as the total number of monitoring measures completed divided by the total number of

actions required (3 daily measurements; baseline, 24 and 48 hours). Patient level care was

evaluated by deriving an all-or-none score (or a “defect-free score”), defined as the proportion of

patients having all of the pre-specified monitoring markers measured for which they are eligible

(T. Nolan & Berwick, 2006; Peterson et al., 2010). Thus, this score reflected the proportion of

Page 96: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

82

patients receiving ‘perfect’ care. Additionally, the proportion of patients with a minimum of 2

ward weights recorded during the 48-hour period was calculated as a minimum pre-requisite

measure that demonstrated diuretic progress was being monitored. All process measures were

also expressed as group means calculated each consecutive month throughout the pre- and post-

implementation time periods for the purpose of constructing process control charts.

Outcome measurements were selected to demonstrate evidence of rational diuretic

prescription and dose adjustment in the first 48 hours. Total furosemide doses administered were

recorded in the 0-24 hour block, 24-48 hour block and 0-48 hours. The proportion of patients

who had an increase in furosemide dose in the second 24-hour block was determined. Other

outcome measurements included change in weight over 48 hours and length of stay.

Safety was examined in multiple ways. Deaths or transfers to a higher acuity setting

during use of the protocol were recorded. Abnormalities of serum biochemistry were examined

over the 0-24h and 24-48h time periods during the first 48 hours of admission for all cohorts.

Hypokalemia was considered an adverse effect of diuretic therapy and was classified as: severe

hypokalemia (serum K+ <3.0mmol/L, considered a serious adverse event) and hypokalemia

(Gennari, 1998) (serum K+ >3.0 and <3.5mmol/L). Since potassium replacement was included in

the Nomo-SDC, hyperkalemia (serum K+ >5.0 mmol/L) was also considered a serious adverse

event. A rise in serum creatinine >50% above baseline at anytime was considered a serious

adverse event, based on the RIFLE criteria (Bellomo et al., 2004; Zhang et al., 2015) for acute

kidney injury (AKI).

6.2.5 Data analysis

Data are presented as mean ± standard deviation or median and interquartile range, as

appropriate. Normality was assessed using the Kolmogorov-Smirnov test. Between group

Page 97: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

83

differences in baseline characteristics and safety markers were compared using the Mann-

Whitney U test or chi squared analysis for continuous and categorical variables, respectively.

Similarly, differences in furosemide doses between cohorts were compared using Mann-Whitney

U tests. Within group differences in furosemide doses between consecutive 24-hour time

intervals were compared using Friedman’s test. A value of P ≤0.05 was considered statistically

significant for all tests. Statistical calculations were performed using SPSS Statistics software

v20 (IBM Inc).

As noted, group means for process measure scores were calculated on a monthly basis for

the entire pre- and post- implementation cohorts. Statistical process control charts, also known as

Shewhart control charts, were used to determine if these process measures of heart failure care

changed over time during the 32 months pre-implementation of our QI initiative and for 8

months after. Charts were displayed with time on the x-axis, and on the y-axis the measurement

in question and 3 additional lines (Benneyan et al., 2003; Mohammed et al., 2008). The central

line indicated mean and 2 additional lines demonstrated the upper and lower control limits, 3

standard deviations (SDs) away from the mean. If all data points were contained within the

control limits, the process was considered to be stable, displaying common stable variation. If a

data point or multiple data points fell outside of control limits, Shewhart rules were used to look

for special causes of variation. Eight consecutive data points showing evidence of unstable

variation represented a sustained change in the process and a new mean central line was

calculated. Shewhart control charts were created using CHARTrunner Lean v3.0 (PQ Systems

Inc).

Page 98: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

84

6.3 Results

6.3.1 Cohorts

The pre-implementation cohort was comprised of 338 patients (Figure 4). Of these, 177

would have been eligible for the La6 Protocol. The first use of the La6 Protocol for treatment of

AHF occurred on December 15th, 2012. During the implementation period, 9 patients were

treated using the La6 Protocol. The post-implementation cohort consisted of 121 patients. Of

these, 71 patients were eligible for treatment using the La6 Protocol, 38 of whom were treated

using the protocol (ON). Of the total post-implementation cohort, 83 patients were treated by

usual-care practices (OFF) at our institution. Baseline characteristics for the pre-, post- and

implementation cohorts are presented in Table 6. There were small differences between the pre

and post implementation cohorts. Compared to the pre-implementation cohort, the post-

implementation cohort was slightly older with an equal distribution of men and women.

During protocol treatment, there were no deaths and no transfers to an acute care setting.

Safety markers for potassium homeostasis and changes in creatinine are also presented in Table

6. There was no significant difference between the pre- and post-implementation cohorts in

serum potassium and creatinine measurements on admission to hospital. Similarly, there was so

significant difference in incidence of severe hypokalemia, hypokalemia, or percent change in

serum creatinine from baseline between the two groups. Incidence of hyperkalemia was

significantly higher in the post-implementation cohort at 5% compared to 0.6% in the pre-

implementation cohort in the 24-48 hour time period.

6.3.2 Process measures

Shewhart control charts demonstrated significant improvement in adherence to best

practices for monitoring the safety and efficacy of diuresis. Between the pre and post

Page 99: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

85

implementation period, a significant improvement was observed in the opportunity-based

composite score from a mean of 82% to 90% and the all-or-none score from 30% to 57%

(Figures 5A and 1B). The post-implementation improvement appeared stable. Similarly, the

proportion of patients who had a minimum of 2 weight measurements recorded within 48 hours

of admission to hospital also increased significantly from 45% to 81% (Figure 5C).

6.3.3 Furosemide Prescription Pre- and Post-Implementation

Total furosemide doses administered over 48 hours in the pre and post implementation

cohorts are summarized in Table 6. The median furosemide doses given in the first and second

24-hour blocks were similar between the pre and post implementation cohorts. Within the pre-

implementation cohort, the mean furosemide dose significantly decreased between the 0-24 and

24-48h time block, while no significant change was observed within the post-implementation

cohort.

6.3.4 Impact of the La6 Protocol

To examine the impact of the MSH La6 Protocol on furosemide administration in more

detail, we evaluated only patients who were eligible for treatment within the protocol (Table 7).

Compared to the pre-implementation cohort, the mean furosemide dose was significantly higher

in the 24-48 hour time block in the post implementation eligible patients. Among the post

implementation eligible cohort, furosemide doses in the 24-48 hour block and over the entire 48

hours were higher in patients treated ON protocol compared to OFF. Considering all patients

treated ON protocol in the implementation and the post-implementation cohorts, compared to the

first 24 hours, furosemide doses increased significantly in the second 24 hours.

As noted in the process measures, only 45% of the pre-implementation cohort had a

minimum of 2 weights to evaluate response to diuretic treatment. Of those, 70% had a

Page 100: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

86

documented weight loss of 1.8 ± 1.7 kg. In the post implementation cohort, a significantly higher

proportion of patients, 86%, had a minimum of 2 weights and the mean change in weight was 1.9

± 1.6 kg. The proportion of patients treated ON protocol with at least 2 weight measurements

was 89%, with 94% demonstrating weight loss. The mean weight loss in the ON protocol group

was 2.3 ± 1.6 kg. For comparison, the implementation cohort of patients, consisting of 47

patients treated ON protocol, had a mean weight loss of 2.2 ± 1.8 kg, with 93% demonstrating

weight loss. The median length of stay did not change between the pre and post-implementation

periods.

Page 101: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

87

Table 6. Clinical Characteristics of the Pre-, Post- and Implementation Patient Cohorts

PRE

N = 338

POST

N = 121

p-value Total ON

N=47

Age, y [median (IQR)] 81 (72 - 88) 84 (77 - 89) 0.01 81 ± 12

Males 46% 47% 0.21 55%

Medications at Home:

Loop Diuretic 55% 66% 0.04 85%

Thiazide diuretics 9% 7% 0.58 2%

Spironolactone/Eplerenone 11% 10% 0.86 11%

ACE Inhibitors/ARBs 37% 49% 0.03 49%

-adrenergic Receptor Antagonists 45% 60% 0.01 70%

Digoxin 11% 15% 0.26 26%

Ca 2+ channel blocker 23% 36% 0.01 28%

Total Furosemide Dose (mg; Mean dose ± SD)

0 -24 hours 94 ± 62 99 ± 63 0.40 121 ± 62

24 – 48 hours 87 ± 56* 103 ± 70 0.11 132 ± 73

Total: 0 – 48 hours 159 ± 109 173 ± 122 0.39 237 ± 117

Safety Markers

Potassium at baseline, mmol/L [median (IQR)] 4.2 (3.9 - 4.6) 4.2 (3.8 - 4.6) 0.48 4.3 ± 0.9

% severe hypokalemia (K<3.0mmol/L), at 24h, 48h 4, 2 5, 0 0.57, 0.21 7, 0

% hypokalemia (K<3.5) 17, 20 23, 14 0.29, 0.16 31, 7

% hyperkalemia (>5.0) 2, 0.6 2, 5 1, 0.01 2, 4

Page 102: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

88

Creatinine at baseline, μmol/l (mg/dl) 104 (77 – 145) 108 (79 – 143) 0.68 127 (93 – 171)

Creatinine, % change from baseline, median (IQR)

0-24 hours -1.1

(-5.4 – 7.1)

1.6

(-3.4 – 6.4) 0.19

0

(-2.9 – 4.2)

24-48 hours 2.1

(-3.3 – 9.2)

4.6

(-3.1 – 13.2) 0.16

1.4

(-3.3 – 9.7)

0-48 hours 2.7

(-6.1 – 14.3)

4.6

(-2.7 – 19.4) 0.13

2.0

(-4.0 – 13.4)

*, sig difference in furosemide dose between 0-24 hours and 24-48 hours within the same cohort.

ON protocol (n=47) cohort presented for visually comparative purposes.

Page 103: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

89

Table 7. Furosemide Dose Adjustment in Patients Eligible for the MSH La6 Protocol

Overall Eligible

Post Implementation

Implementation +

post-

implementation

Time period

from

admission

PRE

N=177

POST

N=71

p-value

OFF

N=33

ON

N=38

p-value

ON

N=47

0 -24 hours 103 ± 63 115 ± 68 0.20 119 ± 85 111 ± 50 0.67 121 ± 62

24 – 48 hours 98 ± 60§ 122 ± 73 0.03 115 ± 79 128 ± 70 0.28 132 ± 73

0 – 48 hours 179 ± 116 210 ± 129 0.08 196 ± 155 222 ± 101 0.07 237 ± 117

% of patients

with an increase

in dosage

17% 27% 0.08 15% 37% 0.04 34%

% of patients

demonstrating

weight loss

70% 86% 0.01 80% 94% 0.10 93%

*, sig difference in furosemide doses within groups between 0-24 hours and 24-48 hours.

ON protocol (n=47) cohort presented for visually comparative purposes.

Page 104: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

90

Page 105: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

91

Figure 4. Analysis Cohorts

Each cohort was divided into patients eligible for the protocol and those who were not. The post-

implementation cohort was further divided into patients treated using the protocol and those

treated with usual (routine) care. The implementation period was comprised of 9 patients treated

on the protocol and was not included in the final pre –and post-implementation impact analysis.

Page 106: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

92

Figure 5. Hospital-Wide Acute Heart Failure Process Measures Shewhart Control Charts

5A. Opportunity-Based Score for Monitoring of Daily Serum Potassium, Serum Creatinine

and Weight

Cohort Opportunity-Based Score change between the pre and post-implementation periods. The

process was deemed stable prior to and post implementation of the La6 Protocol in July of 2013,

with a significant improvement from 82% to 90%. Eight data points of collection post-

implementation signal sustained change. Implementation period between November 2012 and

June 2013 removed.

Page 107: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

93

5B. All-or-None Score for Monitoring of Daily Serum Potassium, Serum Creatinine and

Weight

Cohort All-Or-None Score change between the pre and post-implementation periods. Eight data

points of collection post-implementation signal sustained change, with a significant improvement

from 30% to 57%. Implementation period between November 2012 and June 2013 removed.

Page 108: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

94

5C. Proportion of Patients With At Least 2 Weight Measurements in 48 Hours

The mean proportion of patients with a minimum of 2 weight measurements recorded in the first

48 hours of admission improved significantly from 45% pre-implementation to 81% after the

implementation of the La6 protocol in July of 2013. The process was deemed stable in both

periods, and the change sustained. Implementation period between November 2012 and June

2013 removed.

Page 109: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

95

6.4 Discussion

Recent studies have provided clinicians with data to inform rational selection of diuretic

therapy for acute heart failure as well as an improved understanding of expected efficacy of

treatment, side effects and requirements for monitoring (Bart et al., 2012; Felker et al., 2011). At

our institution, such knowledge was incorporated into practice by implementing a tool that

promoted rational IV furosemide dose selection and subsequent adjustment. Use of these tools

additionally improved adherence to monitoring guidelines, with the goal of ensuring that diuresis

remained safe at the same time as effective. Another objective of our QI initiative was to

improve the timeliness of diuretic therapy by empowering bedside personnel, the registered

nurse at our institution, to identify adverse events and adjust diuretic dosing according to an

evidence-based algorithm, without delays to consult the medical team. Our results demonstrated

the impact of the intervention to improve documentation of markers of quality care such as daily

weights, and serum biochemistry. Moreover, the intervention appeared to reverse a pattern of

decline in diuretic dosing after the first hospital day, and this practice appeared safe despite

delivery of a higher total dose of furosemide. A higher proportion of patients both in the post-

implementation phase and further treated with the La6 Protocol appeared to lose weight over the

initial 48 hours. These findings were consistent with the hypothesis that implementation of this

practice change resulted in improved early efficacy of diuretic therapy due to timelier dose

adjustment.

The patient population evaluated was typical of published registry experience (Adams et

al., 2005; Yeung et al., 2012), clearly older than patients enrolled in clinical trials, with a higher

proportion of women. Importantly, the pre-implementation cohort demonstrated relative stability

in quality of care and was collected after the publication of significant clinical trials (Bart et al.,

Page 110: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

96

2012; Felker et al., 2011) that may have affected diuretic practices. In the post-implementation

cohort, the proportion of patients admitted with AHF who were eligible for treatment by the La6

Protocol was similar to the pre-implementation cohort at approximately 50%. The use of the La6

Protocol was not mandated and uptake amongst eligible patients was not complete. The

explanations for incomplete uptake were not clear. However, the La6 Protocol required adoption

of a practice change by both attending medical teams as well as nursing and resistance to change

may not therefore be surprising. Even without full uptake of the practice change, medical staff

was exposed to the education regarding best practices for administering diuretics, offered during

implementation of the La6 Protocol. This may have contributed to the sustained improvement

with respect to processes of care that we observed in the post-implementation period, particularly

optimal monitoring of patients.

In the evaluation of this QI initiative, we considered process measures as specific steps

that can drive improvement of a valuable outcome. We observed that better monitoring of

patients receiving IV loop diuretics in the post-implementation period was associated with

evidence of improved timeliness of therapy and improved early efficacy. Several observations of

patterns of furosemide prescription suggested timelier dose adjustment in the second 24 hours

after admission. In the pre-implementation period, total furosemide dose actually decreased

significantly which was demonstrated using data from the drug administration record of the

electronic patient chart. It is unlikely that furosemide doses were systematically reordered in

smaller amounts on the second day of admission. However, delays in furosemide reassessment

and reordering may have contributed to a longer interval between doses administered and a net

decrease in total dose over a 24-hour period. In the post-implementation period, this trend was

reversed as no decline in furosemide dosing was observed in the 24-48 hour period. Importantly,

Page 111: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

97

this occurred with no increase in hypokalemia or adverse changes in serum renal function,

possibly attributed to improved adherence to monitoring and systematic practices for potassium

replacement.

As noted, evidence of a sustained change in practice was observed in the post-

implementation period whether the La6 Protocol was engaged or not. However, we observed

further impact when the protocol was engaged. A principle of the protocol design was to link

actions for monitoring to actions that optimized efficacy of diuresis, allowing safe titration of the

diuretic dosage by a single care-giver group, the RN. Indeed in the post-implementation period,

the proportion of patients for which an increase in diuretic dosage was observed and the

proportion of patients with recorded weight loss over the initial 2 days of hospitalization were

highest in patients treated with the La6 protocol. Our observations also demonstrated the need to

implement directive processes to translate new knowledge into clinical practice. In the pre-

implementation period, we observed processes of clinical care appeared stable with obvious

opportunities for improvement even though the DOSE study (Felker et al., 2011) had been

published prior. After rollout of the La6 Protocol we observed the largest impact on patterns of

furosemide prescription in patients treated on the La6 Protocol. This supported an assumption

made during formulation of the protocol, that administration of loop diuretics can be an empiric

practice based on variable experiences of ordering physicians.

The specific change in practice delegated clinical and prescriptive activity to a non-

physician point-of-care group over an extended duration of time. Although algorithms for

stepped diuretic care have been employed within clinical trials (Bart et al., 2012; Felker et al.,

2011), this intervention occurred in a real world setting, a standard hospital ward, without

mobilizing additional care provider resources per patient. Progress in the protocol was informed

Page 112: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

98

by objective clinical measurements that were within the existing skill set of the RN group, and

did not mandate acquisition of new skills such as clinical volume assessment. The process would

also be applicable to other personnel with continuous presence of hospital wards such as

physician assistants.

Limitations to our reported experience included the fact that the MSH La6 protocol was

an initiative undertaken and evaluated at a single Canadian center and can not be generalized to

other hospital settings. We were unable to examine actual patient weight loss in the first 48 hours

after admission in the pre-implementation cohort due to insufficient numbers of weight

measurements. It is possible then that diuretic efficacy with respect to weight and fluid loss in

the pre-implementation cohort was actually comparable to the post-implementation cohort,

despite poorer process measure scores. However, this supports our contention that adherence to

best practices with respect to monitoring is essential to proper evaluation of diuretic therapy in

clinical practice. We did not observe an impact of our intervention on length of stay over 8

months, possibly because there was insufficient uptake of the protocol for eligible patients. The

MSH La6 Protocol is currently a paper based process and, for optimal monitoring of adherence

and dissemination, adapting the tools to a computer order entry process would be an essential

future direction. Automation may further improve uptake and adherence.

In conclusion, a quality improvement initiative to improve and standardize processes of

care for IV diuresis was undertaken. Our experience demonstrated that higher adherence to

practices for monitoring was not more time-consuming, and was instead linked to evidence of

better timeliness of care.

Page 113: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

99

7 General Discussion

Principles of quality improvement in healthcare were employed in the design,

implementation and evaluation of a clinical tool to provide standardized evidence-based, safe

and timely loop diuretic therapy for patients admitted to hospital with acute heart failure. An

important strategy to improve timeliness used in the process was empowerment of the bedside

caregiver to autonomously assess efficacy markers of diuresis, appropriately adjust dosing and

identify adverse events for 48 hours after initial clinical assessment at the time of admission.

The objectives of this quality improvement innovation were to impact the safety and

timeliness of decongestion for heart failure. The hypothesis of this project was that safety and

timely administration of diuretics would improve after employing strategies to enforce guideline-

directed patient monitoring, enforce evidence-based rational selection and administration of

diuretics and, bypassing barriers to interprofessional communication. The evaluation

demonstrated several findings in support of our objectives and hypotheses: 1) The pre and post

implementation cohorts, including patients treated within the La6 Protocol, were representative

of community-based patients with acute heart failure enrolled in registry studies, elderly with a

moderate degree of renal insufficiency, 2) Adherence to the monitoring tasks, furosemide

administration and potassium replacement was measured and shown to be excellent, supporting

feasibility of the process, 3) Excellent adherence to the protocol appeared to translate to

improvement in guideline-directed patient monitoring compared to the pre-implementation

period, 4) With respect to safety, no increase in incidence of adverse events was detected, despite

improved surveillance of patients, 5) In the pre-implementation period, a significant decline in

furosemide doses was observed between the first 24 hours of admission and the second 24 hours,

a trend that was clearly reversed in the post-implementation cohort. Reversal of this trend was

Page 114: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

100

most evident when the La6 Protocol was employed, supporting the contention that the process

enhanced timeliness of furosemide administration, and 6) No impact on length of stay was noted

in the post-implementation period.

The Canadian Society of Hospital Pharmacists defines an order set ‘as a predetermined,

evidence-based prescribing tool to help physicians and other healthcare professionals to

effectively and efficiently implement best practices.’ ("How to Promote Best Practice and Safety

through the Use of Order Sets. From Paper to Practice: Incorporating Evidence Into Your

Pharmacy Practice. CSHP 2015 Toolkit.," 2015) Algorithmic tools and standardized order sets

are common in clinical care (Cruickshank et al., 1991; Goldberg et al., 2004; Raschke, Reilly,

Guidry, Fontana, & Srinivas, 1993). Multiple systematic reviews have concluded that the use of

order sets leads to an improvement in guideline adherence, treatment outcomes, and processes of

care, efficiency and cost (Chan et al., 2012; Group, 2009). Order sets can be divided into those

that aid diagnosis and treatment. The MSH La6 Protocol was innovative in designing a combined

tool that both aided the medical team in proper diagnosis of congestion in the setting of AHF as

well as served as a prescription and monitoring tool for the beside RN. Specifically, the Pre-

Printed Physician Order Set (PPOS) grouped medical orders, providing the rationale necessary to

understand current guideline recommendations and therefore decrease variation in orders and the

Nomo-SDC prescribed and adjusted furosemide dosing administered by the ward RN. In

comparison to other order sets that have a single preset clinical endpoint, the Nomo-SDC design

was novel as a treatment algorithm in having adaptable drug dosages and endpoints that changed

according to the monitoring completed by the responsible nurse. In this way, the appropriate

treatment depended on careful and complete monitoring of the patient.

Page 115: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

101

It was hypothesized that timeliness would be favourably impacted by the strategy to

empower bedside caregivers, the ward RN, to enable therapy with minimal delays for

consultation with the physician team. The clinical assessment and dose adjustment performed by

the bedside RN were within their current skill set and did not require additional training, beyond

understanding the algorithm itself. The design of the protocol took into account integration into

nursing shift workflow and served as a graphical hand-over tool between nursing staff. The high

opportunity scores suggested that adherence to the La6 Protocol by RNs was feasible.

Evaluating timeliness in a quality improvement intervention involves, firstly, identifying

and defining measures related to timeliness. Timeliness is evaluated directly through time

measurements, including time to treatment, waiting times, or events within a specific time

period. Therefore timeliness was assessed in this project by measuring events relating to

furosemide treatment within a specified time period after admission to hospital, which would

also take into account time to treatment. Markers of timeliness measured included furosemide

dosages administered in each 24-hour block as well as weight loss achieved. The pre- and post-

implementation analysis suggested that timeliness of diuretic therapy was in fact improved. The

intervention appeared to reverse a decline in furosemide dosing after the first hospital day, and

with a higher total dose of furosemide administered in the first 48 hours. In the pre-

implementation period, there was a significant decrease in the total dose of furosemide received

in the second 24-hour block. It seems unlikely that reordering smaller doses of furosemide on the

second day of admission was intentional. Instead, delays in furosemide reassessment and

reordering may have led to a longer interval between doses administered and a net decrease in

total dose over a 24-hour period. In the post-implementation period, this trend was reversed as no

decline in furosemide dosing was observed in the 24-48 hour period. No increase in the

Page 116: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

102

incidence of adverse events were observed with these results, possibly attributed to the improved

adherence to monitoring and systematic practices for potassium replacement observed.

The greatest impact on the behavior of diuretic administration in the post-implementation

cohort was observed in patients treated using the La6 protocol. The increase in diuretic dosage

and the proportion of patients with recorded weight loss over 48 hours was highest in these

patients. These findings were supportive of the hypothesis that implementation of this practice

change resulted in the improvement of timely dose adjustment and consequently early efficacy of

therapy. The design of the protocol supported systematic up-titration of the furosemide dose

based on markers of diuretic progress or lack thereof. By contrast, the DOSE trial derived a

rational dosing regimen that was fixed for the initial 48 hours prior to reassessment by the

treating physician (Felker et al., 2011). The La6 Protocol is similar to CARRESS-HF trial in a

more active adjustment of diuretics (Bart et al., 2012).

We observed an association between improved adherence to monitoring processes and

the outcome of apparent improvement in timeliness of diuretic administration. In the pre-

implementation cohort, it was not possible to meaningfully examine weight loss in the first 48

hours after admission due to insufficient numbers of weight measurements. This was observed at

the same time a decline in dosage was observed between the first and the second 24 hours. The

experience of the post-implementation cohort suggests it is possible that a simple intervention to

improve adherence to monitoring alone, may confer several benefits to diuretic care. Monitoring

actions demonstrate the progress or lack of progress in decongestion and likely actively drive the

adjustment of dosages, and thus timeliness of treatment, even in the absence of the titration

algorithm for diuretics. Detection of adverse events is important, but appropriate monitoring also

facilitates safe up-titration of diuretics. In the current era, there is a growing movement to

Page 117: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

103

compel reporting of metrics that indicate good quality of care. Without sufficient monitoring

data, neither adequacy nor deficiency of care can be measured appropriately.

A significant limitation in fully understanding the potential impact of this quality

improvement intervention was the incomplete uptake of the La6 Protocol in eligible patients.

This challenge has been reported by multiple studies evaluating adoption of new order sets

(O'Connor, Adhikari, DeCaire, & Friedrich, 2009; Sano, Waddell, Solimando, Doulaveris, &

Myhand, 2005). Despite evidence, in this study as well as other quality improvement projects,

showing that unfavorable variation in drug prescription can lead to poorer patient outcomes,

resistance to change in clinical practice is commonplace among medical staff (Group, 2009).

One possible reason for incomplete uptake is the structure of the CTU at an academic institution

(previously discussed in Section 2.1.1), in which there is a constant rotation of trainees in

medicine through different specialties. This can potentially lead to suboptimal awareness of a

new tool or protocol, despite best efforts for ongoing education. Another possible hindrance to

uptake is the paper format of the protocol. Adaptation into computer based order form entry

could lead to improved uptake. Suboptimal uptake may have contributed to the null result with

respect to length of stay in hospital. Effect on length of stay may be possible with wider

dissemination of the intervention to other institutions as has been shown in other studies

(Fishbane et al., 2007). Despite incomplete uptake of the La6 protocol itself, whether treated on

or off the protocol, sustained improvement with respect to processes of care were observed in the

post-implementation cohort particularly optimal monitoring of patients. Education regarding

evidence on diuretic therapy and proper monitoring, provided to all medical and nursing staff,

may have contributed to this change.

Page 118: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

104

Limitations of the study design of this quality improvement intervention also merit

discussion. A pre-and-post design was used for evaluation between the pre-cohort, which was

studied retrospectively, and the post cohort, studied prospectively. Improvement in monitoring

adherence was tested using a time series design. This design is beneficial in evaluating whether

an intervention has an effect on a system while still considering the underlying stable trend that

exists within the system (Cook TD, 1979; Eccles, Grimshaw, Campbell, & Ramsay, 2003). In

this way, a significant change in practice can be attributed to the intervention with more

confidence because a system is evaluated for stability before and after the implementation of the

intervention. This type of design was considered a better option to a patient randomized

controlled trial within one institution, in which it would have been difficult to maintain a control

group that was not contaminated by the intervention and education of the medical staff.

However, a pre and post design or comparison to a historic control has a few recognized

limitations. Although this type of study is considered superior to simple observational studies,

there is a risk of over estimating the effect of the quality intervention (Lipsey & Wilson, 1993).

Alternatively, a cluster-randomized trial can be used for this type of evaluation and may be

considered the best option for quality evaluation (Klar & Donner, 2001; D. M. Murray, Varnell,

& Blitstein, 2004; Parry & Power, 2016). Clusters would be formed at a hospital level, with

some acting as controls and others implementing the intervention. Data would then be collected

on a patient level and impact of the intervention evaluated. Having too few clusters for

randomization can create bias and a statistical imbalance therefore sample cluster size for

randomization needs to be inflated to increase statistical efficiency (Eccles et al., 2003). As such,

the decision was made to test the MSH La6 Protocol on an institutional level for safety and

adherence prior to application at multiple centers in a randomized design.

Page 119: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

105

8 Conclusions and Future Directions

In conclusion, the MSH La6 Protocol was developed to improve the safety and timeliness

of IV furosemide administration in the first 48 hours of admission to hospital in patients with

AHF. Evaluation demonstrated that the practice change was safe in both adherence to nomogram

steps and no increased incidence of adverse events in comparison with routine practice.

Timeliness of diuretic administration was improved through rational dose selection and

adjustment by the bedside RN as well as streamlined communication between medical and

nursing personnel.

The implications of these findings can be interpreted in context of 3 structural levels of

the healthcare system. Firstly, the micro level refers to the patient and the clinical team. The

MSH La6 Protocol was developed with the goal of improving patient care on an individual level.

In addition to whole cohort measurements and improvement evaluation, assessment also

included patient level adherence. Care process markers were measured and scores calculated on a

per-patient level. Results demonstrated good adherence to monitoring and safety for each

individual patient placed on the protocol. Pre- and post-implementation evaluation also showed

significant improvements in patient monitoring as recommended by guidelines. This

demonstrated the significance of patient care processes to the safety of hospital care in each

patient’s management plan. Developing the Nomo-SDC to be evidence-based was also an

integral part of ensuring that patient care was up to best standards. Improvement in patient care

processes is also crucial to patient health outcomes. Thus, impacting the micro system of patient

care, the MSH La6 Protocol has important implications on patient health outcomes as well.

Next the protocol had implications on a meso level, which is defined as impact of a

quality improvement initiative analyzed on an organizational or community level, in this case the

Page 120: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

106

entire institution. This project set out to appropriately standardize care of patients on IV diuretic

therapy. Evaluation of institutional practices revealed significant variation in furosemide dose

selection in AHF patients. The same evaluation revealed similar substantial variation in dose

adjustment in the first 48 hours of admission to hospital. This variation was hypothesized to lead

to ineffective dosing and consequent delays in therapy and hospital stay. The implementation of

this protocol, more specifically the Pre-Printed Order Set, allowed for an education tool and

rationale to be readily available to the medical team, which was composed of physicians of

various levels of experience. This availability of pre-selected rational dosing regimens of IV

furosemide led to a decrease in the large variation previously seen. Further evaluation also

revealed an impact of the La6 protocol on improved timeliness with no increase in adverse

effect. On an institutional level, this practice change also impacted interprofessional

communication and collaboration. The protocol was designed to change the pre-existing

accepted relationship between the medical staff and beside RNs. Utilizing a concise monitoring

tool and pre-set boundaries allowed for the restructuring of interprofessional allocation of

responsibilities. Nurses were empowered to adjust furosemide dosing within 48 hours of protocol

care, without delays in communication with various medical team members. In potential future

uses at other institutions, other healthcare professionals, including nurse practitioners, could use

this protocol. However, at the institutional level, we did not achieve sufficient uptake of the

intervention to properly assess impact on hospital length of stay and we have not performed an

analysis of cost efficiency, which would be an important future direction. A large proportion of

patients not eligible to be placed on the La6 protocol were Lasix-naïve patients, specifically

those who were not taking a home dose of oral furosemide. To benefit these patients, a Lasix-

naïve protocol was also developed using a very similar design, with lower starting doses of IV

Page 121: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

107

furosemide. As this protocol was in the early stages of development and implementation,

evaluation was not performed. In the future, utilizing a protocol specific to patients who are

Lasix naïve, in addition to a protocol geared toward Lasix-experienced patients, would increase

coverage of care and potentially impact heart failure processes of care on a greater meso level

scale.

The last important level of impact to be addressed is the macro level. Assessment of this

intervention on a macro level would require scaling the intervention to be implemented in

multiple institutions, both smaller and larger, across the region. As discussed in Section 6, this

next step would involve designing a cluster-randomized trial with a sufficient sample of hospital

sites to produce statistically efficient results, or to rollout to multiple institutions in a stepped

wedge study design. This step would fit into the Institute for Healthcare Improvement’s

Framework for Spread. This framework is designed to help institutions properly scale their pilot

interventions through identification of 6 major factors that contribute to successful spread of an

innovation (P. M. Barker, Reid, & Schall, 2016; K. Nolan, Schall, Erb, & Nolan, 2005). These

factors include social science, organizational structure, networks and strong leadership

behaviour. In addition to the process and outcome measures evaluated in this work, there are

several potential additional markers that would be beneficial to assess in a multi-center analysis.

As mentioned above, hospital length of stay is a clinical marker that could be used to assess

global impact of such an intervention at an institution. It must, however, be said that length of

stay is a very complex and crude marker for evaluating a practice change in a specific population

of classically older patients, who potentially have other comorbid conditions usually

complicating their hospital stay. A potentially balancing marker of hospital length of stay is the

readmission rate of AHF patients treated on the protocol. This could serve as a valuable

Page 122: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

108

balancing measure in future assessments. Additional balancing measures could include

qualitative evaluation of medical and nursing staff satisfaction upon utilization as well as patient

perceptions about the quality of care change.

The work presented in this thesis document suggests that the La6 protocol intervention to

improve diuretic management in acute heart failure patients admitted to hospital warrants further

study to examine feasibility and impact of the intervention on a broader, multi-site scale.

Page 123: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

109

References

Adams, K. F., Jr., Fonarow, G. C., Emerman, C. L., LeJemtel, T. H., Costanzo, M. R., Abraham, W. T., . . . Investigators. (2005). Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J, 149(2), 209-216. doi: 10.1016/j.ahj.2004.08.005

Alqahtani, F., Koulouridis, I., Susantitaphong, P., Dahal, K., & Jaber, B. L. (2014). A meta-analysis of continuous vs intermittent infusion of loop diuretics in hospitalized patients. J Crit Care, 29(1), 10-17. doi: 10.1016/j.jcrc.2013.03.015

Arcand, J., Ivanov, J., Sasson, A., Floras, V., Al-Hesayen, A., Azevedo, E. R., . . . Newton, G. E. (2011). A high-sodium diet is associated with acute decompensated heart failure in ambulatory heart failure patients: a prospective follow-up study. Am J Clin Nutr, 93(2), 332-337. doi: 10.3945/ajcn.110.000174

Arora, V., Johnson, J., Lovinger, D., Humphrey, H. J., & Meltzer, D. O. (2005). Communication failures in patient sign-out and suggestions for improvement: a critical incident analysis. Qual Saf Health Care, 14(6), 401-407. doi: 10.1136/qshc.2005.015107

Baggs, J. G., Schmitt, M. H., Mushlin, A. I., Mitchell, P. H., Eldredge, D. H., Oakes, D., & Hutson, A. D. (1999). Association between nurse-physician collaboration and patient outcomes in three intensive care units. Crit Care Med, 27(9), 1991-1998.

Barker, P. M., Reid, A., & Schall, M. W. (2016). A framework for scaling up health interventions: lessons from large-scale improvement initiatives in Africa. Implement Sci, 11, 12. doi: 10.1186/s13012-016-0374-x

Barker, W. H., Mullooly, J. P., & Getchell, W. (2006). Changing incidence and survival for heart failure in a well-defined older population, 1970-1974 and 1990-1994. Circulation, 113(6), 799-805. doi: 10.1161/CIRCULATIONAHA.104.492033

Bart, B. A., Goldsmith, S. R., Lee, K. L., Givertz, M. M., O'Connor, C. M., Bull, D. A., . . . Heart Failure Clinical Research, N. (2012). Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med, 367(24), 2296-2304. doi: 10.1056/NEJMoa1210357

Bates, D. W., Cullen, D. J., Laird, N., Petersen, L. A., Small, S. D., Servi, D., . . . et al. (1995). Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA, 274(1), 29-34.

Bellomo, R., Ronco, C., Kellum, J. A., Mehta, R. L., Palevsky, P., & Acute Dialysis Quality Initiative, w. (2004). Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care, 8(4), R204-212. doi: 10.1186/cc2872

Bennett, S. J., Huster, G. A., Baker, S. L., Milgrom, L. B., Kirchgassner, A., Birt, J., & Pressler, M. L. (1998). Characterization of the precipitants of hospitalization for heart failure decompensation. Am J Crit Care, 7(3), 168-174.

Benneyan, J. C. (1998). Statistical quality control methods in infection control and hospital epidemiology, part I: Introduction and basic theory. Infect Control Hosp Epidemiol, 19(3), 194-214.

Page 124: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

110

Benneyan, J. C., Lloyd, R. C., & Plsek, P. E. (2003). Statistical process control as a tool for research and healthcare improvement. Qual Saf Health Care, 12(6), 458-464.

Berwick, D. M. (1998). Developing and testing changes in delivery of care. Ann Intern Med, 128(8), 651-656.

Bhardwaj, A., & Januzzi, J. L., Jr. (2009). Natriuretic peptide-guided management of acutely destabilized heart failure: rationale and treatment algorithm. Crit Pathw Cardiol, 8(4), 146-150. doi: 10.1097/HPC.0b013e3181c4a0c6

Boonyasai, R. T., Windish, D. M., Chakraborti, C., Feldman, L. S., Rubin, H. R., & Bass, E. B. (2007). Effectiveness of teaching quality improvement to clinicians: a systematic review. JAMA, 298(9), 1023-1037. doi: 10.1001/jama.298.9.1023

Bowen, D. J., Kreuter, M., Spring, B., Cofta-Woerpel, L., Linnan, L., Weiner, D., . . . Fernandez, M. (2009). How we design feasibility studies. Am J Prev Med, 36(5), 452-457. doi: 10.1016/j.amepre.2009.02.002

Brater, D. C. (1994). Pharmacokinetics of loop diuretics in congestive heart failure. Br Heart J, 72(2 Suppl), S40-43.

Brater, D. C. (1998). Diuretic therapy. N Engl J Med, 339(6), 387-395. doi: 10.1056/NEJM199808063390607

Braunwald, E. (1997). Shattuck lecture--cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med, 337(19), 1360-1369. doi: 10.1056/NEJM199711063371906

Braunwald, E. (2013). Heart failure. JACC Heart Fail, 1(1), 1-20. doi: 10.1016/j.jchf.2012.10.002

Brophy, J. M. (1992). Epidemiology of congestive heart failure: Canadian data from 1970 to 1989. Can J Cardiol, 8(5), 495-498.

Burgmeier, J. (2002). Failure mode and effect analysis: an application in reducing risk in blood transfusion. Jt Comm J Qual Improv, 28(6), 331-339.

Cabana, M. D., Rand, C. S., Powe, N. R., Wu, A. W., Wilson, M. H., Abboud, P. A., & Rubin, H. R. (1999). Why don't physicians follow clinical practice guidelines? A framework for improvement. JAMA, 282(15), 1458-1465.

Chan, A. J., Chan, J., Cafazzo, J. A., Rossos, P. G., Tripp, T., Shojania, K., . . . Easty, A. C. (2012). Order sets in health care: a systematic review of their effects. Int J Technol Assess Health Care, 28(3), 235-240. doi: 10.1017/S0266462312000281

Chassin, M. R., & Becher, E. C. (2002). The wrong patient. Ann Intern Med, 136(11), 826-833. Cheitlin, M. D., Armstrong, W. F., Aurigemma, G. P., Beller, G. A., Bierman, F. Z., Davis, J. L., . . .

American Society of, E. (2003). ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). Circulation, 108(9), 1146-1162. doi: 10.1161/01.CIR.0000073597.57414.A9

Chen, J., Normand, S. L., Wang, Y., & Krumholz, H. M. (2011). National and regional trends in heart failure hospitalization and mortality rates for Medicare beneficiaries, 1998-2008. JAMA, 306(15), 1669-1678. doi: 10.1001/jama.2011.1474

Cohen, M. D., & Hilligoss, P. B. (2010). The published literature on handoffs in hospitals: deficiencies identified in an extensive review. Qual Saf Health Care, 19(6), 493-497. doi: 10.1136/qshc.2009.033480

Page 125: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

111

Cohn, J. N., Kowey, P. R., Whelton, P. K., & Prisant, L. M. (2000). New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med, 160(16), 2429-2436.

Cook TD, C. D. (1979). Quasi-experimentation: design and analysis issues for field settings. Cowie, M. R., Mosterd, A., Wood, D. A., Deckers, J. W., Poole-Wilson, P. A., Sutton, G. C., &

Grobbee, D. E. (1997). The epidemiology of heart failure. Eur Heart J, 18(2), 208-225. Cruickshank, M. K., Levine, M. N., Hirsh, J., Roberts, R., & Siguenza, M. (1991). A standard

heparin nomogram for the management of heparin therapy. Arch Intern Med, 151(2), 333-337.

Devlin, M. K., Kozij, N. K., Kiss, A., Richardson, L., & Wong, B. M. (2014). Morning handover of on-call issues: opportunities for improvement. JAMA Intern Med, 174(9), 1479-1485. doi: 10.1001/jamainternmed.2014.3033

Djousse, L., Driver, J. A., & Gaziano, J. M. (2009). Relation between modifiable lifestyle factors and lifetime risk of heart failure. JAMA, 302(4), 394-400. doi: 10.1001/jama.2009.1062

Donabedian, A. (2005). Evaluating the quality of medical care. 1966. Milbank Q, 83(4), 691-729. doi: 10.1111/j.1468-0009.2005.00397.x

Dormans, T. P., van Meyel, J. J., Gerlag, P. G., Tan, Y., Russel, F. G., & Smits, P. (1996). Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion. J Am Coll Cardiol, 28(2), 376-382. doi: 10.1016/0735-1097(96)00161-1

Dworzynski, K., Roberts, E., Ludman, A., Mant, J., Guideline Development Group of the National Institute for, H., & Care, E. (2014). Diagnosing and managing acute heart failure in adults: summary of NICE guidance. BMJ, 349, g5695. doi: 10.1136/bmj.g5695

Ebright, P. R., Urden, L., Patterson, E., & Chalko, B. (2004). Themes surrounding novice nurse near-miss and adverse-event situations. J Nurs Adm, 34(11), 531-538.

Eccles, M., Grimshaw, J., Campbell, M., & Ramsay, C. (2003). Research designs for studies evaluating the effectiveness of change and improvement strategies. Qual Saf Health Care, 12(1), 47-52.

Fang, J., Mensah, G. A., Croft, J. B., & Keenan, N. L. (2008). Heart failure-related hospitalization in the U.S., 1979 to 2004. J Am Coll Cardiol, 52(6), 428-434. doi: 10.1016/j.jacc.2008.03.061

Felker, G. M., Lee, K. L., Bull, D. A., Redfield, M. M., Stevenson, L. W., Goldsmith, S. R., . . . Network, N. H. F. C. R. (2011). Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med, 364(9), 797-805. doi: 10.1056/NEJMoa1005419

Fishbane, S., Niederman, M. S., Daly, C., Magin, A., Kawabata, M., de Corla-Souza, A., . . . Parker, S. (2007). The impact of standardized order sets and intensive clinical case management on outcomes in community-acquired pneumonia. Arch Intern Med, 167(15), 1664-1669. doi: 10.1001/archinte.167.15.1664

Flaker, G. C., Bartolozzi, J., Davis, V., McCabe, C., & Cannon, C. P. (1994). Use of a standardized heparin nomogram to achieve therapeutic anticoagulation after thrombolytic therapy in myocardial infarction. TIMI 4 investigators. Thrombolysis in Myocardial Infarction. Arch Intern Med, 154(13), 1492-1496.

Page 126: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

112

Flin R, W. J., Sarac C, Raduma M. (2009). Human Factors in Patient Safety. Review of Topics and Tools. Report for Methods and Measures Working. Geneva: WHO.

Francis, G. S., Goldsmith, S. R., Levine, T. B., Olivari, M. T., & Cohn, J. N. (1984). The neurohumoral axis in congestive heart failure. Ann Intern Med, 101(3), 370-377.

Gandhi, T. K. (2005). Fumbled handoffs: one dropped ball after another. Ann Intern Med, 142(5), 352-358.

Gennari, F. J. (1998). Hypokalemia. N Engl J Med, 339(7), 451-458. doi: 10.1056/NEJM199808133390707

Glasziou, P., Irwig, L., & Mant, D. (2005). Monitoring in chronic disease: a rational approach. BMJ, 330(7492), 644-648. doi: 10.1136/bmj.330.7492.644

Goldberg, P. A., Siegel, M. D., Sherwin, R. S., Halickman, J. I., Lee, M., Bailey, V. A., . . . Inzucchi, S. E. (2004). Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. Diabetes Care, 27(2), 461-467.

Gopal, D. M., Kalogeropoulos, A. P., Georgiopoulou, V. V., Smith, A. L., Bauer, D. C., Newman, A. B., . . . Butler, J. (2012). Cigarette smoking exposure and heart failure risk in older adults: the Health, Aging, and Body Composition Study. Am Heart J, 164(2), 236-242. doi: 10.1016/j.ahj.2012.05.013

Group, H. H. F. (2009). Order Sets in Healthcare: An Evidence-based Analysis. Toronto: Centre for Global Health Innovation, UHN.

Gupta, A., Ghimire, G., & Hage, F. G. (2014). Guidelines in review: 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Nucl Cardiol, 21(2), 397-399. doi: 10.1007/s12350-013-9832-x

Hays, M. M. (2003). The phenomenal shift report: a paradox. J Nurses Staff Dev, 19(1), 25-33.

He, J., Ogden, L. G., Bazzano, L. A., Vupputuri, S., Loria, C., & Whelton, P. K. (2001). Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med, 161(7), 996-1002.

He, J., Ogden, L. G., Bazzano, L. A., Vupputuri, S., Loria, C., & Whelton, P. K. (2002). Dietary sodium intake and incidence of congestive heart failure in overweight US men and women: first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Arch Intern Med, 162(14), 1619-1624.

. Health Indicators 2013: Definitions, Data Sources and Rationale, May 2013. (2013). Canadian Institute for Health Information. Statistics Canada.

Heart Failure Society of, A., Lindenfeld, J., Albert, N. M., Boehmer, J. P., Collins, S. P., Ezekowitz, J. A., . . . Walsh, M. N. (2010). HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail, 16(6), e1-194. doi: 10.1016/j.cardfail.2010.04.004

Heidenreich, P. A., Albert, N. M., Allen, L. A., Bluemke, D. A., Butler, J., Fonarow, G. C., . . . Stroke, C. (2013). Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail, 6(3), 606-619. doi: 10.1161/HHF.0b013e318291329a

Ho, K. K., Pinsky, J. L., Kannel, W. B., & Levy, D. (1993). The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol, 22(4 Suppl A), 6A-13A.

Horwitz, L. I., Moin, T., Krumholz, H. M., Wang, L., & Bradley, E. H. (2008). Consequences of inadequate sign-out for patient care. Arch Intern Med, 168(16), 1755-1760. doi: 10.1001/archinte.168.16.1755

Page 127: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

113

How to Promote Best Practice and Safety through the Use of Order Sets. From Paper to Practice: Incorporating Evidence Into Your Pharmacy Practice. CSHP 2015 Toolkit. (2015). Canadian Society of Hospital Pharmacists.

Jhund, P. S., Macintyre, K., Simpson, C. R., Lewsey, J. D., Stewart, S., Redpath, A., . . . McMurray, J. J. (2009). Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people. Circulation, 119(4), 515-523. doi: 10.1161/CIRCULATIONAHA.108.812172

Kannel, W. B., Ho, K., & Thom, T. (1994). Changing epidemiological features of cardiac failure. Br Heart J, 72(2 Suppl), S3-9.

Kelder, J. C., Cramer, M. J., van Wijngaarden, J., van Tooren, R., Mosterd, A., Moons, K. G., . . . Hoes, A. W. (2011). The diagnostic value of physical examination and additional testing in primary care patients with suspected heart failure. Circulation, 124(25), 2865-2873. doi: 10.1161/CIRCULATIONAHA.111.019216

Keyes, C. (2000). Coordination of care provision: the role of the 'handoff'. Int J Qual Health Care, 12(6), 519.

Klar, N., & Donner, A. (2001). Current and future challenges in the design and analysis of cluster randomization trials. Stat Med, 20(24), 3729-3740.

Krumholz, H. M., Parent, E. M., Tu, N., Vaccarino, V., Wang, Y., Radford, M. J., & Hennen, J. (1997). Readmission after hospitalization for congestive heart failure among Medicare beneficiaries. Arch Intern Med, 157(1), 99-104.

Leape, L. L., Brennan, T. A., Laird, N., Lawthers, A. G., Localio, A. R., Barnes, B. A., . . . Hiatt, H. (1991). The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II. N Engl J Med, 324(6), 377-384. doi: 10.1056/NEJM199102073240605

Lee, D. S., Johansen, H., Gong, Y., Hall, R. E., Tu, J. V., Cox, J. L., & Canadian Cardiovascular Outcomes Research, T. (2004). Regional outcomes of heart failure in Canada. Can J Cardiol, 20(6), 599-607.

Leier, C. V., Dei Cas, L., & Metra, M. (1994). Clinical relevance and management of the major electrolyte abnormalities in congestive heart failure: hyponatremia, hypokalemia, and hypomagnesemia. Am Heart J, 128(3), 564-574.

Lennie, T. A., Song, E. K., Wu, J. R., Chung, M. L., Dunbar, S. B., Pressler, S. J., & Moser, D. K. (2011). Three gram sodium intake is associated with longer event-free survival only in patients with advanced heart failure. J Card Fail, 17(4), 325-330. doi: 10.1016/j.cardfail.2010.11.008

Leto, L., Aspromonte, N., & Feola, M. (2014). Efficacy and safety of loop diuretic therapy in acute decompensated heart failure: a clinical review. Heart Fail Rev, 19(2), 237-246. doi: 10.1007/s10741-012-9354-7

Levy, D., Kenchaiah, S., Larson, M. G., Benjamin, E. J., Kupka, M. J., Ho, K. K., . . . Vasan, R. S. (2002). Long-term trends in the incidence of and survival with heart failure. N Engl J Med, 347(18), 1397-1402. doi: 10.1056/NEJMoa020265

Lindenauer, P. K., Rothberg, M. B., Pekow, P. S., Kenwood, C., Benjamin, E. M., & Auerbach, A. D. (2007). Outcomes of care by hospitalists, general internists, and family physicians. N Engl J Med, 357(25), 2589-2600. doi: 10.1056/NEJMsa067735

Lipsey, M. W., & Wilson, D. B. (1993). The efficacy of psychological, educational, and behavioral treatment. Confirmation from meta-analysis. Am Psychol, 48(12), 1181-1209.

Page 128: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

114

Liu, P. P. (2008). Cardiorenal syndrome in heart failure: a cardiologist's perspective. Can J Cardiol, 24 Suppl B, 25B-29B.

Lloyd-Jones, D. M., Larson, M. G., Leip, E. P., Beiser, A., D'Agostino, R. B., Kannel, W. B., . . . Framingham Heart, S. (2002). Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Circulation, 106(24), 3068-3072.

Lohr, K. N. (1990) Medicare: A Strategy for Quality Assurance: VOLUME II Sources and Methods. Washington (DC).

Luther, K. M., Maguire, L., Mazabob, J., Sexton, J. B., Helmreich, R. L., & Thomas, E. (2002). Engaging nurses in patient safety. Crit Care Nurs Clin North Am, 14(4), 341-346.

Maisel, A. S., Krishnaswamy, P., Nowak, R. M., McCord, J., Hollander, J. E., Duc, P., . . . Breathing Not Properly Multinational Study, I. (2002). Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med, 347(3), 161-167. doi: 10.1056/NEJMoa020233

Matzke, G. R., & St Peter, W. L. (1990). Clinical pharmacokinetics 1990. Clin Pharmacokinet, 18(1), 1-19.

McCullough, P. A., Nowak, R. M., McCord, J., Hollander, J. E., Herrmann, H. C., Steg, P. G., . . . Maisel, A. S. (2002). B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation, 106(4), 416-422.

McKelvie, R. S., Moe, G. W., Ezekowitz, J. A., Heckman, G. A., Costigan, J., Ducharme, A., . . . Sussex, B. (2013). The 2012 Canadian Cardiovascular Society heart failure management guidelines update: focus on acute and chronic heart failure. Can J Cardiol, 29(2), 168-181. doi: 10.1016/j.cjca.2012.10.007

McMurray, J. J., Adamopoulos, S., Anker, S. D., Auricchio, A., Bohm, M., Dickstein, K., . . . Guidelines, E. S. C. C. f. P. (2012). ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J, 33(14), 1787-1847. doi: 10.1093/eurheartj/ehs104

Measurement for Quality Improvement. (2013). Health Quality Ontario. Moe, G. W., Ezekowitz, J. A., O'Meara, E., Lepage, S., Howlett, J. G., Fremes, S., . . . Canadian

Cardiovascular, S. (2015). The 2014 Canadian Cardiovascular Society Heart Failure Management Guidelines Focus Update: anemia, biomarkers, and recent therapeutic trial implications. Can J Cardiol, 31(1), 3-16. doi: 10.1016/j.cjca.2014.10.022

Mohammed, M. A., Cheng, K. K., Rouse, A., & Marshall, T. (2001). Bristol, Shipman, and clinical governance: Shewhart's forgotten lessons. Lancet, 357(9254), 463-467.

Mohammed, M. A., Worthington, P., & Woodall, W. H. (2008). Plotting basic control charts: tutorial notes for healthcare practitioners. Qual Saf Health Care, 17(2), 137-145. doi: 10.1136/qshc.2004.012047

Morton, A. P., Whitby, M., McLaws, M. L., Dobson, A., McElwain, S., Looke, D., . . . Sartor, A. (2001). The application of statistical process control charts to the detection and monitoring of hospital-acquired infections. J Qual Clin Pract, 21(4), 112-117.

Mosterd, A., & Hoes, A. W. (2007). Clinical epidemiology of heart failure. Heart, 93(9), 1137-1146. doi: 10.1136/hrt.2003.025270

Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., . . . Stroke Statistics, S. (2016). Heart Disease and Stroke Statistics-2016 Update: A Report

Page 129: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

115

From the American Heart Association. Circulation, 133(4), e38-e360. doi: 10.1161/CIR.0000000000000350

Muller, K., Gamba, G., Jaquet, F., & Hess, B. (2003). Torasemide vs. furosemide in primary care patients with chronic heart failure NYHA II to IV--efficacy and quality of life. Eur J Heart Fail, 5(6), 793-801.

Murray, D. M., Varnell, S. P., & Blitstein, J. L. (2004). Design and analysis of group-randomized trials: a review of recent methodological developments. Am J Public Health, 94(3), 423-432.

Murray, M. D., Deer, M. M., Ferguson, J. A., Dexter, P. R., Bennett, S. J., Perkins, S. M., . . . Brater, D. C. (2001). Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Am J Med, 111(7), 513-520.

Murray, M. D., Haag, K. M., Black, P. K., Hall, S. D., & Brater, D. C. (1997). Variable furosemide absorption and poor predictability of response in elderly patients. Pharmacotherapy, 17(1), 98-106.

Nkomo, V. T., Gardin, J. M., Skelton, T. N., Gottdiener, J. S., Scott, C. G., & Enriquez-Sarano, M. (2006). Burden of valvular heart diseases: a population-based study. Lancet, 368(9540), 1005-1011. doi: 10.1016/S0140-6736(06)69208-8

Nohria, A., Mielniczuk, L. M., & Stevenson, L. W. (2005). Evaluation and monitoring of patients with acute heart failure syndromes. Am J Cardiol, 96(6A), 32G-40G. doi: 10.1016/j.amjcard.2005.07.019

Nolan, J., Batin, P. D., Andrews, R., Lindsay, S. J., Brooksby, P., Mullen, M., . . . Fox, K. A. (1998). Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation, 98(15), 1510-1516.

Nolan, K., Schall, M. W., Erb, F., & Nolan, T. (2005). Using a framework for spread: The case of patient access in the Veterans Health Administration. Jt Comm J Qual Patient Saf, 31(6), 339-347.

Nolan, T., & Berwick, D. M. (2006). All-or-none measurement raises the bar on performance. JAMA, 295(10), 1168-1170. doi: 10.1001/jama.295.10.1168

O'Brien, T. M., Menon, S., Stephens, T., Mazur, W., & Chung, E. S. (2012). Algorithm-based assessment of target weight removal in acute decompensated heart failure. Congest Heart Fail, 18(1), 43-46. doi: 10.1111/j.1751-7133.2011.00251.x

O'Connor, C., Adhikari, N. K., DeCaire, K., & Friedrich, J. O. (2009). Medical admission order sets to improve deep vein thrombosis prophylaxis rates and other outcomes. J Hosp Med, 4(2), 81-89. doi: 10.1002/jhm.399

O'Leary, K. J., Ritter, C. D., Wheeler, H., Szekendi, M. K., Brinton, T. S., & Williams, M. V. (2010). Teamwork on inpatient medical units: assessing attitudes and barriers. Qual Saf Health Care, 19(2), 117-121. doi: 10.1136/qshc.2008.028795

O'Leary, K. J., Thompson, J. A., Landler, M. P., Kulkarni, N., Haviley, C., Hahn, K., . . . Williams, M. V. (2010). Patterns of nurse-physician communication and agreement on the plan of care. Qual Saf Health Care, 19(3), 195-199. doi: 10.1136/qshc.2008.030221

Owan, T. E., Hodge, D. O., Herges, R. M., Jacobsen, S. J., Roger, V. L., & Redfield, M. M. (2006). Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med, 355(3), 251-259. doi: 10.1056/NEJMoa052256

Page 130: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

116

Parry, G., & Power, M. (2016). To RCT or not to RCT? The ongoing saga of randomised trials in quality improvement. BMJ Qual Saf, 25(4), 221-223. doi: 10.1136/bmjqs-2015-004862

Pattani, R., Wu, P. E., & Dhalla, I. A. (2014). Resident duty hours in Canada: past, present and future. CMAJ, 186(10), 761-765. doi: 10.1503/cmaj.131053

Patterson, J. H., Adams, K. F., Jr., Applefeld, M. M., Corder, C. N., & Masse, B. R. (1994). Oral torsemide in patients with chronic congestive heart failure: effects on body weight, edema, and electrolyte excretion. Torsemide Investigators Group. Pharmacotherapy, 14(5), 514-521.

Peacock, W. F., Costanzo, M. R., De Marco, T., Lopatin, M., Wynne, J., Mills, R. M., . . . Investigators. (2009). Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. Cardiology, 113(1), 12-19. doi: 10.1159/000164149

Peacock, W. F. t., De Marco, T., Fonarow, G. C., Diercks, D., Wynne, J., Apple, F. S., . . . Investigators, A. (2008). Cardiac troponin and outcome in acute heart failure. N Engl J Med, 358(20), 2117-2126. doi: 10.1056/NEJMoa0706824

Pennell, D. J., Sechtem, U. P., Higgins, C. B., Manning, W. J., Pohost, G. M., Rademakers, F. E., . . . Working Group on Cardiovascular Magnetic Resonance of the European Society of, C. (2004). Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report. Eur Heart J, 25(21), 1940-1965. doi: 10.1016/j.ehj.2004.06.040

Petersen, L. A., Brennan, T. A., O'Neil, A. C., Cook, E. F., & Lee, T. H. (1994). Does housestaff discontinuity of care increase the risk for preventable adverse events? Ann Intern Med, 121(11), 866-872.

Peterson, E. D., Delong, E. R., Masoudi, F. A., O'Brien, S. M., Peterson, P. N., Rumsfeld, J. S., . . . Radford, M. J. (2010). ACCF/AHA 2010 Position Statement on Composite Measures for Healthcare Performance Assessment: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures (Writing Committee to develop a position statement on composite measures). Circulation, 121(15), 1780-1791. doi: 10.1161/CIR.0b013e3181d2ab98

Philibert, I. (2009). Use of strategies from high-reliability organisations to the patient hand-off by resident physicians: practical implications. Qual Saf Health Care, 18(4), 261-266. doi: 10.1136/qshc.2008.031609

Pitt, B., Zannad, F., Remme, W. J., Cody, R., Castaigne, A., Perez, A., . . . Wittes, J. (1999). The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med, 341(10), 709-717. doi: 10.1056/NEJM199909023411001

Press, N. A. (2001). Crossing the Quality Chasm: A New Health System for the 21st Century Crossing the Quality Chasm: A New Health System for the 21st Century. Washington (DC).

Raschke, R. A., Reilly, B. M., Guidry, J. R., Fontana, J. R., & Srinivas, S. (1993). The weight-based heparin dosing nomogram compared with a "standard care" nomogram. A randomized controlled trial. Ann Intern Med, 119(9), 874-881.

Riesenberg, L. A., Leitzsch, J., Massucci, J. L., Jaeger, J., Rosenfeld, J. C., Patow, C., . . . Karpovich, K. P. (2009). Residents' and attending physicians' handoffs: a systematic

Page 131: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

117

review of the literature. Acad Med, 84(12), 1775-1787. doi: 10.1097/ACM.0b013e3181bf51a6

Roger, V. L., Weston, S. A., Redfield, M. M., Hellermann-Homan, J. P., Killian, J., Yawn, B. P., & Jacobsen, S. J. (2004). Trends in heart failure incidence and survival in a community-based population. JAMA, 292(3), 344-350. doi: 10.1001/jama.292.3.344

Rose, B. D. (1991). Diuretics. Kidney Int, 39(2), 336-352. Salvador, D. R., Rey, N. R., Ramos, G. C., & Punzalan, F. E. (2005). Continuous infusion versus

bolus injection of loop diuretics in congestive heart failure. Cochrane Database Syst Rev(3), CD003178. doi: 10.1002/14651858.CD003178.pub3

Sano, H. S., Waddell, J. A., Solimando, D. A., Jr., Doulaveris, P., & Myhand, R. (2005). Study of the effect of standardized chemotherapy order forms on prescribing errors and anti-emetic cost. J Oncol Pharm Pract, 11(1), 21-30. doi: 10.1191/1078155205jp149oa

Schaufelberger, M., Swedberg, K., Koster, M., Rosen, M., & Rosengren, A. (2004). Decreasing one-year mortality and hospitalization rates for heart failure in Sweden; Data from the Swedish Hospital Discharge Registry 1988 to 2000. Eur Heart J, 25(4), 300-307. doi: 10.1016/j.ehj.2003.12.012

Shewhart, W. A. (1931). Economic control of quality of manufactured product. New York,: D. Van Nostrand Company, Inc.

Shojania, K. G., McDonald, K. M., Wachter, R. M., & Owens, D. K. (2004). Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies (Vol. 1: Series Overview and Methodology). Rockville (MD).

Solomon, S. D., Dobson, J., Pocock, S., Skali, H., McMurray, J. J., Granger, C. B., . . . morbidity, I. (2007). Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure. Circulation, 116(13), 1482-1487. doi: 10.1161/CIRCULATIONAHA.107.696906

Son, Y. J., Lee, Y., & Song, E. K. (2011). Adherence to a sodium-restricted diet is associated with lower symptom burden and longer cardiac event-free survival in patients with heart failure. J Clin Nurs, 20(21-22), 3029-3038. doi: 10.1111/j.1365-2702.2011.03755.x

Starmer, A. J., Spector, N. D., Srivastava, R., West, D. C., Rosenbluth, G., Allen, A. D., . . . Group, I. P. S. (2014). Changes in medical errors after implementation of a handoff program. N Engl J Med, 371(19), 1803-1812. doi: 10.1056/NEJMsa1405556

Sutcliffe, K. M., Lewton, E., & Rosenthal, M. M. (2004). Communication failures: an insidious contributor to medical mishaps. Acad Med, 79(2), 186-194.

Tennant, R., Mohammed, M. A., Coleman, J. J., & Martin, U. (2007). Monitoring patients using control charts: a systematic review. Int J Qual Health Care, 19(4), 187-194. doi: 10.1093/intqhc/mzm015

Thomson, M. R., Nappi, J. M., Dunn, S. P., Hollis, I. B., Rodgers, J. E., & Van Bakel, A. B. (2010). Continuous versus intermittent infusion of furosemide in acute decompensated heart failure. J Card Fail, 16(3), 188-193. doi: 10.1016/j.cardfail.2009.11.005

Thor, J., Lundberg, J., Ask, J., Olsson, J., Carli, C., Harenstam, K. P., & Brommels, M. (2007). Application of statistical process control in healthcare improvement: systematic review. Qual Saf Health Care, 16(5), 387-399. doi: 10.1136/qshc.2006.022194

Tracking Heart Disease and Stroke in Canada. (2009).

Page 132: Understanding Effective and Timely Administration of Loop ... · 5 Improving Efficiency of Diuretic Care for Patients Hospitalized with Decompensated Heart ... The Cardiorenal Rescue

118

Tsuyuki, R. T., McKelvie, R. S., Arnold, J. M., Avezum, A., Jr., Barretto, A. C., Carvalho, A. C., . . . Yusuf, S. (2001). Acute precipitants of congestive heart failure exacerbations. Arch Intern Med, 161(19), 2337-2342.

Tu, J. V., Donovan, L. R., Lee, D. S., Wang, J. T., Austin, P. C., Alter, D. A., & Ko, D. T. (2009). Effectiveness of public report cards for improving the quality of cardiac care: the EFFECT study: a randomized trial. JAMA, 302(21), 2330-2337. doi: 10.1001/jama.2009.1731

Tu, J. V., Nardi, L., Fang, J., Liu, J., Khalid, L., Johansen, H., & Canadian Cardiovascular Outcomes Research, T. (2009). National trends in rates of death and hospital admissions related to acute myocardial infarction, heart failure and stroke, 1994-2004. CMAJ, 180(13), E118-125. doi: 10.1503/cmaj.081197

Vasko, M. R., Cartwright, D. B., Knochel, J. P., Nixon, J. V., & Brater, D. C. (1985). Furosemide absorption altered in decompensated congestive heart failure. Ann Intern Med, 102(3), 314-318.

Volpp, K. G., & Grande, D. (2003). Residents' suggestions for reducing errors in teaching hospitals. N Engl J Med, 348(9), 851-855. doi: 10.1056/NEJMsb021667

Wang, Y., Eldridge, N., Metersky, M. L., Verzier, N. R., Meehan, T. P., Pandolfi, M. M., . . . Battles, J. (2014). National trends in patient safety for four common conditions, 2005-2011. N Engl J Med, 370(4), 341-351. doi: 10.1056/NEJMsa1300991

Wargo, K. A., & Banta, W. M. (2009). A comprehensive review of the loop diuretics: should furosemide be first line? Ann Pharmacother, 43(11), 1836-1847. doi: 10.1345/aph.1M177

Wilcox, C. S., Mitch, W. E., Kelly, R. A., Skorecki, K., Meyer, T. W., Friedman, P. A., & Souney, P. F. (1983). Response of the kidney to furosemide. I. Effects of salt intake and renal compensation. J Lab Clin Med, 102(3), 450-458.

Wilson, R. M., Runciman, W. B., Gibberd, R. W., Harrison, B. T., Newby, L., & Hamilton, J. D. (1995). The Quality in Australian Health Care Study. Med J Aust, 163(9), 458-471.

Wong, B. M., Etchells, E. E., Kuper, A., Levinson, W., & Shojania, K. G. (2010). Teaching quality improvement and patient safety to trainees: a systematic review. Acad Med, 85(9), 1425-1439. doi: 10.1097/ACM.0b013e3181e2d0c6

Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Jr., Drazner, M. H., . . . Wilkoff, B. L. (2013). 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation, 128(16), 1810-1852. doi: 10.1161/CIR.0b013e31829e8807

Yeung, D. F., Boom, N. K., Guo, H., Lee, D. S., Schultz, S. E., & Tu, J. V. (2012). Trends in the incidence and outcomes of heart failure in Ontario, Canada: 1997 to 2007. CMAJ, 184(14), E765-773. doi: 10.1503/cmaj.111958

Zhang, W., Wen, D., Zou, Y. F., Shen, P. Y., Xu, Y. W., Shi, H., . . . Chen, N. (2015). One-year survival and renal function recovery of acute kidney injury patients with chronic heart failure. Cardiorenal Med, 5(1), 40-47. doi: 10.1159/000369834

Zwarenstein, M., Goldman, J., & Reeves, S. (2009). Interprofessional collaboration: effects of practice-based interventions on professional practice and healthcare outcomes. Cochrane Database Syst Rev(3), CD000072. doi: 10.1002/14651858.CD000072.pub2