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COPD and Sepsis

What you need to know!

John Trapp, M.D.

COPD and Sepsis Update

• Review COPD assessment and staging

• Review COPD treatment options

• Learn how to more effectively recognize sepsis syndromes

• Learn management strategies for sepsis to improve outcomes

COPD: Who to evaluate

• Chronic cough

• Chronic sputum production

• Shortness of breath

• Wheezing

• Recurrent bronchitis, chest colds, pneumonia

• History of exposure: smoking, second hand smoke, agricultural/ occupational dusts

COPD: Evaluation

• History

• Exam

• Spirometry, pre and post (lung volumes, DLCO)

• Chest X-ray

• Oximetry – walking and consider ONO study

• ABG (serum bicarb elevated, severe COPD)

• Alpha-1-antitrypsin (AAT) Screen

• Exclude other causes (CHF, ILD/OLD, PE, PH)

COPD: Staging

BODE Index for COPD survival prediction

• FEV1 % Predicted After Bronchodialator Approx 4 year Survival○ >=65% (0 points) 0-2 points: 80%○ 50-64% (1 point) 3-4 Points 67%○ 36-49% (2 points) 5-6 Points 57%○ <=35% (3 points) 7-10 Points 18%

• 6 Minute Walk Distance ○ >=350 Meters (0 points)○ 250-349 Meters (1 point)○ 150-249 Meters (2 points)○ <=149 Meters (3 points)

• MMRC (Modified Medical Research Council Scale) Dyspnea Scale (4 is worst) ○ MMRC 0: Dyspneic on strenuous excercise (0 points)○ MMRC 1: Dyspneic on walking a slight hill (0 points)○ MMRC 2: Dyspneic on walking level ground; must stop occasionally due to

breathlessness (1 point)○ MMRC 3: Must stop for breathlessness after walking 100 yards or after a few

minutes (2 points)○ MMRC 4: Cannot leave house; breathless on dressing/undressing (3 points)

• Body Mass Index BODE – Body mass index, airflow Obstruction, ○ >21 (0 points) Dyspnea, Exercise capacity○ <=21 (1 point)

COPD: Non-Pharmacologic Treatment

• Smoking cessation

• Reduction of other risk factors

• Oxygen

• Pulmonary Rehabilitation/ Exercise/ Education

• Vaccinations

TORCH and UPLIFT Trials

• TOwards a Revolution in COPD Health

• Large study

• Demonstrated a statistically significant improvement in time to exacerbation in salmeterol arm compared to placebo arm

• Demonstrated statistically significant reduced rates of exacerbation with combination salmeterol/fluticasone

• Understanding Potential Long-term Impacts on Function with Tiotropium

• Demonstrated reduced exacerbations with tiotropiumcompared with placebo

• LABA▫ Salmeterol (Serevent) – 50 mcg BID▫ Formoterol (Foradil) – 1 cap 12 mcg BID▫ Arformoterol (Brovana) – 15 mcg BID▫ Indacaterol (Arcapta Neohaler) 1 cap (75mcg) daily▫ Olodaterol (Striverdi Respimat) 2 inhs daily

• LAMA▫ Tiotropium (Spiriva Handihaler) 1 cap (18mcg)

daily, (Spiriva Respimat) 2.5 mcg/activation, 2 inhsdaily

▫ Umeclidinium (Incruse Ellipta) 1 inh (62.5mcg) daily

▫ Aclidinium (Tudorza Pressair) 1 inh (400mcg) twice daily

• LAMA/LABA

▫ Umeclidinium 62.5mcg/Vilanterol 25mcg (AnoroEllipta) 1 inh daily

▫ Glycopyrrolate 15.6mcg/indacaterol 27.5mcg (Utibro Breezhaler) 1 cap inh daily

• ICS/LABA

▫ Fluticasone/Salmeterol ( Advair) BID

▫ Budesonide/Formoterol (Symbicort) BID

▫ Mometasone/Formoterol (Dulera) BID

▫ Fluticasone 100mcg or 200mcg/vilanterol 25mcg (Breo Ellipta) 1 inh daily

COPD: Pharmacologic Treatment

• Less Symptomatic, GOLD 1,2▫ SABA, SAMA alone▫ LAMA or LABA + SABA PRN

• More Symptomatic, GOLD 1,2 ( ≥ 2 AE per year)▫ LABA + SABA PRN▫ LABA + LAMA + SABA PRN

• Less symptomatic, GOLD 3,4▫ LABA/ICS or LAMA + SABA PRN▫ LABA + LAMA + SABA PRN▫ Add phosphodiesterase-4 inhibitor (roflumilast)

• More Symptomatic, GOLD 3,4 (≥ 2 AE per year)▫ LABA/ICS + LAMA + SABA PRN▫ LABA/ICS + phosphodiesterase-4 inhibitor▫ LABA + LAMA + SABA PRN

Less Severe

COPD Severity

More Severe

Medications NOT routinely

recommended for Stable COPD

• Systemic steroids (chronic prednisone)• Mucoactive agents (expectorants, guaifenesin,

iodine preparations, inhaled dornase alpha, hypertonic saline, hydration, inhaled NAC)

• Chronic antibiotic therapy (however macrolides– azithromycin may be beneficial as chronic therapy – 250 mg daily or 3x/week)▫ Trial of over 1100 patients showed daily use of

azithromycin significantly reduced time to first exacerbation over 1 year

PDE4 Inhibitor (Roflumilast)

• Indicated for the treatment of stable COPD patients in high risk patients with severe COPD and recurrent exacerbations

• Mode of therapy is to suppress inflammation and improve lung function resulting in fewer exacerbations

• Adverse effects – nausea, diarrhea, weight loss, and headache

Additional COPD Nuggets

• Nutrition

• Sleep disorders

• Cancer screening

Reduced Lung-Cancer Mortality with Low-Dose

Computed Tomographic Screening

• The National Lung Screening Trial (NLST), a randomized trial conducted under the auspices of the National Cancer Institute, compared annual screening by low-dose chest CT scanning with chest x-ray for three years in 53,454 high-risk persons at 33 US medical centers.

• Participants were men and women 55 to 74 years of age with a history of at least 30 pack-years of smoking, and included current smokers and those who had discontinued smoking within 15 years of enrollment.

New England Journal of MedicineVolume 365(5):395-409

August 4, 2011

The National Lung Screening Trial Research Team. N Engl J Med 2011;365:395-409

Lung Cancer Screening• Smoking cessation is a more proven and powerful intervention for preventing

death and complications from lung cancer and other diseases than screening.• Lung cancer screening requires an ongoing commitment; cancers are detected

on initial and annual studies, and a single baseline study is insufficient.• The most likely "positive" result of screening is detection of benign nodules

requiring further evaluation, and this evaluation may require invasive studies, possibly even surgery.

• For patients who would opt to be screened after appropriate counseling, and pending results of cost-effectiveness analyses and ongoing randomized trials, we suggest screening with low-dose helical CT scanning only for those who meet all of the following criteria:

• Are in general good health.• Are at increased risk for lung cancer. High-risk criteria for participation in the

NLST were age 55 to 74 years, a history of smoking at least 30 pack-years and, if former smoker, had quit within the previous 15 years.

• Have access to centers whose radiologic, pathologic, surgical, and other treatment capabilities in the management of indeterminate lung lesions are equivalent to those in the NLST trial.

• Are able to manage the cost of annual screening and the possible need for subsequent evaluation of abnormal findings. Many insurance programs now cover the cost of screening.

Switching Gears….

COPD SEPSIS

Sepsis Update• Sepsis is the 6th most common reason for

hospitalization; 1 in 23 patients (2011)• The incidence of sepsis is increasing• Sepsis contributes to approximately 1 in 3 deaths

in hospitals with the majority of these patients having sepsis on presentation (2014).

• Septic shock kills approximately 7X as many surgical patients as MI and PE combined (2010).

• Sepsis is the most costly inpatient hospital condition (20B in 2011)

• Sepsis accounts for 21.3% of all Medicare readmissions (2014).

• Sepsis bundle CMS Core Measure data collection began October 2015.

Sepsis is a Medical Emergency!

“Mortality rates from sepsis are higher than heart attack,

stroke, or trauma. Sepsis needs to be viewed with the same

urgency as these other life-threatening conditions because

we know early treatment can decrease mortality.”

“Physicians should be looking for organ dysfunction every

time they suspect infection. Conversely, they need to be

looking for infection whenever a patient presents with

organ dysfunction,”

Craig M. Coopersmith, MD, FCCM, a sepsis task force member immediate past president of SCCM

Time Sensitive Diseases

AMI – Time is Muscle

STROKE – Time is Brain

TRAUMA – Golden Hour

SEPSIS – Time is Tissue

Early Identification

• The 2016 SCCM task force has described an assessment score for patients outside the ICU as a way to facilitate the identification of patients at risk of dying from sepsis

• SOFA – Sequential (Sepsis-related) Organ Failure Assessment Score

• Quick SOFA - qSOFA

Quick SOFA

• Respiratory rate ≥ 22 1 point

• Altered mentation 1 point

• SBP ≤ 100 1 point

• A score ≥ 2 is associated with poor outcomes due to sepsis

SOFA

• SOFA uses simple measurements of major organ function to calculate a severity score, which is available at the following site http://clincalc.com/IcuMortality/SOFA.aspx

• App: Mediquations Medical Calculator. $4.99• The scores are calculated on admit, 24 hours after

admission to the ICU and every 48 hours thereafter (thus, the term "Sequential" Organ Failure Assessment)

• The mean and the highest scores are most predictive of mortality. In addition, scores that increase by about 30 percent are associated with a mortality of at least 50 percent

SOFA Severity Score

• Respiratory system – the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2)

• Cardiovascular system – the amount of vasoactivemedication necessary to prevent hypotension

• Hepatic system – the bilirubin level

• Coagulation system – the platelet count

• Neurologic system – the Glasgow Coma Score

• Renal system – the serum creatinine or urine output

SOFA Conclusions

• Initial scores of more than 11 (mortality rate > 90%),• A decreasing score during the first 48 hours was

associated with a mortality rate of less than 6%• An unchanged or increasing score was associated

with a mortality rate of 37% when the initial score was 2 to 7 and 60% when the initial score was 8 to 11.

• STUDY CONCLUSIONS: Sequential assessment of organ dysfunction during the first 48 hours of ICU admission is a good indicator of prognosis. The mean SOFA score, highest SOFA score, and rate of change are particularly useful predictors of outcome.

Caution!

• The SOFA score does not diagnose sepsis, identify those whose organ dysfunction is truly due to infection, or determine individual treatment strategies or individual outcome.

• Rather, the SOFA score helps identify patients, as a group, who potentially have a high risk of death from infection

Sepsis and Septic Shock (March 2016)

• Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, where life-threatening organ dysfunction is identified by an increase in the SOFA score ≥2 and is associated with a mortality of ≥10 percent.

• Septic shock is defined as a subset of patients with sepsis having profound circulatory, cellular, and metabolic abnormalities who have an elevated lactate >2 mmol/L and a vasopressor requirement despite adequate fluid resuscitation; these patients have a predicted mortality of ≥40 percent

Time is Tissue!

Suspect Sepsis Septic Shock

Within 3 hours

Initial Lactate level

Blood culture collection prior to antibiotics

Broad spectrum IV antibiotic administration

Within 6 hours

Repeat lactate if initial lactate > 2

Within 3 hours Resuscitation with 30 ml/kg of

crystalloid for hypotension (SBP < 90 or MAP < 70) or lactate > 4mmol/L

Within 6 hours Apply vasopressors for

hypotension that does not respond to initial fluid resuscitation to maintain a MAP > 65mmHg

Repeating the volume status and tissue perfusion assessment

EGDT Targets

• Mean arterial pressure (MAP) ≥65 mmHg (MAP = [(2 x diastolic) + systolic]/3)

• Urine output ≥0.5 mL/kg/hour• Static or dynamic predictors of fluid responsiveness,

eg, CVP 8 to 12 mmHg when central access is available (static measurement) or respiratory changes in the radial artery pulse pressure (dynamic measurement).

• Central venous (superior vena cava) oxyhemoglobinsaturation (ScvO2) ≥70 percent (when central access is available) or mixed venous oxyhemoglobinsaturation (SvO2) ≥65 percent

Additional therapies

• Glucorticoids - in septic shock with persistent hypotension

• Intensive insulin therapy – BG 140-180

• VTE prevention – pharmacologic preferred

• Nutrition – assessment of nutrition status in all critically ill patients with early administration of enteral nutrition (within 48 hours)

Now that you know

what you need to

know….

Questions?