in hospital dm lecture part 1

7/30/2019 In Hospital DM Lecture Part 1

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By

DR: MOKHTAR , Abdel Rahman

Consultant Internist ( NWAFH )

In hospital Management of

Hyperglycemia


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Why ?

Huge Implementation Gap

Regulatory guidelines etc.

Can be cost effective

Inpatient hyperglycemia is very strongly

associated with poor outcomes

Improved glycemic control is associatedwith improved outcomes

Society of Hospital Medicine. http://www.hospitalmedicine.org/ResourceRoomRedesign/

pdf/GC_Workbook.pdf.


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Hyperglycemia*: A Common Comorbidityin Medical-Surgical Patients in Hospitals

64%(1.7% mortality)

12%(16% mortality)

26%3% mortality

Normoglycemia

Known Diabetes

New Hyperglycemia

Umpierrez G et al, J Clin Endocrinol Metabol 87:978, 2002

n = 2,020

* Hyperglycemia: Fasting BG 126 mg/dlor Random BG 200 mg/dl X 2


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Landmark trials favoring tight glycemiccontrol for inpatients and outpatients

Inpatient

DIGAMI (1997)

van den Berghe (2001):IV insulin in SICU

Outpatient

DCCT

UKPDS


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van den Berghe (2001) ,Leuven Belgium

IV insulin in SICU


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Intensive Insulin Therapy in Critically Ill SurgicalPatients: Morbidity and Mortality Benefits

van den Berghe G, et al. N Engl J Med. 2001;345:13591367.

-60

-50

-40

-30

-20

-10

0

Reduction

(%)

Mortality Sepsis Dialysis PolyneuropathyBlood

Transfusion

34%

46%41%

44%

50%

N = 1,548


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Van den Berghe, Crit Care Med 2003

Filled bars

< 110

Shaded bars110-150

Open bars

> 150 mg/dL

Complications

correlated

withaverage

blood glucose


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Van den Berghe, Crit Care Med 2003

Although the

Van den Berghe study

was not designed

to determine

the threshold

above which

mortality increases,

mortality was higherat glucose 110-150,

compared to

glucose < 110 mg/dL. < 110

110-150

> 150 mg/dL


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Baird. Persistent post stroke hyperglycemia is independentlyassociated with infarct expansion and worse clinical outcome.

Stroke 2003; 34: 2208.


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The results of the Leuven studies have led

to a worldwide increase in the

implementation of strict glycemic control in

the intensive care units (ICU). Themortality reduction in these landmark trials

was attributed to the strict lowering of

mean glucose (target 80110 mg/dL)during admission in the intervention group.


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ACE / ADA Position Statement onDiabetes and Metabolic Control 2004

ICU Non-ICUPreprandial

Non-ICUMaximal

AACE/ACE

ADA

110 mg/dL

100 mg/dL

110 mg/dL

90-130 mg/dL

180 mg/dL

180 mg/dL


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Limitations of the van denBerghe studies

1- It was not blinded.

2- Most cases were recruited after cardiac surgery !!.

3- Patients received IV glucose on arrival to ICU of 200300 g/day ( 2-3 L of D10% ).

4- Parentral N , enteral feeding , or combined feeding wasprovided to all patients within 24 h of ICU admission !!.

5- The mortality of patients in the control group was twicethe national average of Australia for ex !!!.

6- Intrinsic limitations of single center studies make themunsuitable for level I evidence.

( Bellomo and Egi ,Mayo Clinic Proc. May , 2009 ; 84 ( 5 ): 400 402 )


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The tight glucose control expressseemed unstoppable ...till 2009


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Normoglycemiain Intensive CareEvaluationSurvival Using Glucose

Algorithm Regulation

(NICE-SUGAR) trial 2009 -This is the second largest randomized study sample in

the history of critical care medicine :

- 6100 patients included.

- One million glucose and insulin dose

measurement included.


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Methodology:Within 24 hours after admissionto an intensive care unit (ICU), Patients were

randomly assigned to undergo either :

Intensive glucose control, with a target blood

glucose range of 81 to 108 mg per deciliter (4.5to 6.0 mmol per liter), or

Conventional glucose control, with a target of

180 mg or less per deciliter (10.0 mmol or lessper liter).

The primary end point was death from any

cause within 90 days after randomization.


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Investigators found that, compared with conventional therapy . IIT wasassociated with an increased mortality 90 days after randomization.This detrimental IIT mortality effect in the NICE-SUGAR trial occurredin all subgroups, including surgical patients.

Severe hypoglycemia (blood glucose

below 40 mg/dl) occurred in

approximately 6.8 percent of

intensively treated patients compared

to 0.5 percent of conventionally treated

patients.


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American Association of Clinical EndocrinologistsAnd American Diabetes AssociationCONSENSUS STATEMENT ON INPATIENTGLYCEMIC CONTROL


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h b ( ) d


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The American Diabetes Association (ADA) andthe American Association of Clinical

Endocrinologists (AACE Until more information is available, it

seems reasonable for clinicians to treat

critical care patients with the less intensive

" yet good - glucose control strategiesused in the conventional arm of the NICE-

SUGAR trial.

(insulin infusion begun if blood glucose was over 180 mg/dl,

and discontinued if blood glucose dropped below 144 mg/dl).


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Hermanides et al., 2010


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Glucose variability :

Hermanides and associates 2010 , Publishedthe results of another large study in

Amsterdam that included 5728 patients

aiming at : Measuring GV over time in a largestrict glucose control-treated ICU populationacross several ranges of mean glucose andto investigate the association of GV and

mean glucose values with ICU and in-hospital mortality.

Variability was measured by , MAG ( Mean

absolute Glucose change per hour ) & SD.


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Figure 1. Two fictitious patients with identical mean glucose and sdbut different patterns of variability expressed by mean absolute glucose

change (MAG).


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RESULT :

In this retrospective cohort study, it has been shownthat GV, expressed as MAG, is highly associated withICU death in both high and low ranges of mean

glucose. In combination with a high mean glucose, GVseems most detrimental.

There appears to be a synergistic negative effect ofhigh mean glucose in combination with high GV.

For those with persistently high mean glucose valuesduring admission, low GV seems protective.

DISCUSSION


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DISCUSSION : From a pathophysiological viewpoint, acausal relationship can be substantiated; in vitro, varyingglucose levels have been shown to enhance cellapoptosis.[24] In rats,

Glycemic reperfusion after hypoglycemia caused neuronaldeath,[25] and altering glucose levels were impairingendothelial function in healthy volunteers.[26]

Even more, tubulointerstitial cells exposed to intermittenthigh glucose concentrations showed enhanced cell growthand collagen syntheses compared with stable high glucoseconcentrations.[27]

Possibly, the adaptive cell mechanisms that are initiated incase of constant hyperglycemia are ineffective when thehyperglycemia is not constant but varying, explaining thetoxicity of GV.[28]

Managing Diabetes in the Hospital Presents


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Managing Diabetes in the Hospital PresentsDifferent Challenges than Managing

Diabetes in the Outpatient Arena!


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- Much of the management of diabetes inoutpatients is predicated on stability in the

lifestyle regimen.

- Diabetes patients are generally instructed to

eat consistent amounts of carbohydrate, takethe prescribed doses of insulin, and doregular exercise, each day.

- The hospital, however, results in a high levelof instability in these and other variables thatimpact blood glucose.

The hospital is also associated with:


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The hospital is also associated with:

- Acute illness, stress-related hyperglycemia

- Use of medications that impact glycemic control

COMMONLYASSOCIATED

Steroids

Catecholamines

Tacrolimus

Cyclosporine

Gatifloxacin

TPN

SIGNIFICANT butLESS PROMINENT

Oral contraceptivepills

Thiazides

Atypical

antipsychotics

Calcium-channel

blocking agents

Protease inhibitors

Managing diabetes &


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Managing diabetes &hyperglycemia in thislabile environment

requires a flexiblemanagementstrategy.


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Oral agents can be continued instable patients with normal

nutritional intake, normal blood

glucose levels, and stable renal and

cardiac function. However, there

are several potential disadvantages

to using these medications in

hospital patients:

Oral Anti diabetes Agents in the Hospital
http://www.google.com.sa/imgres?imgurl=http://living.oneindia.in/img/2010/08/19-diabetes-tablets-190810.jpg&imgrefurl=http://living.oneindia.in/health/disorders-and-ailments/2010/diabetes-tablet-treatment-190810.html&usg=__NfPbeEhurAhi0yZiXzK6mCwLZ5k=&h=150&w=200&sz=7&hl=ar&start=21&zoom=1&itbs=1&tbnid=R3FB-9-ueZyhuM:&tbnh=78&tbnw=104&prev=/images%3Fq%3DDiabetes%2Boral%2Btablets%26start%3D20%26hl%3Dar%26safe%3Dactive%26sa%3DN%26gbv%3D2%26ndsp%3D20%26tbs%3Disch:1http://www.google.com.sa/imgres?imgurl=http://living.oneindia.in/img/2010/08/19-diabetes-tablets-190810.jpg&imgrefurl=http://living.oneindia.in/health/disorders-and-ailments/2010/diabetes-tablet-treatment-190810.html&usg=__NfPbeEhurAhi0yZiXzK6mCwLZ5k=&h=150&w=200&sz=7&hl=ar&start=21&zoom=1&itbs=1&tbnid=R3FB-9-ueZyhuM:&tbnh=78&tbnw=104&prev=/images%3Fq%3DDiabetes%2Boral%2Btablets%26start%3D20%26hl%3Dar%26safe%3Dactive%26sa%3DN%26gbv%3D2%26ndsp%3D20%26tbs%3Disch:1http://www.google.com.sa/imgres?imgurl=http://living.oneindia.in/img/2010/08/19-diabetes-tablets-190810.jpg&imgrefurl=http://living.oneindia.in/health/disorders-and-ailments/2010/diabetes-tablet-treatment-190810.html&usg=__NfPbeEhurAhi0yZiXzK6mCwLZ5k=&h=150&w=200&sz=7&hl=ar&start=21&zoom=1&itbs=1&tbnid=R3FB-9-ueZyhuM:&tbnh=78&tbnw=104&prev=/images%3Fq%3DDiabetes%2Boral%2Btablets%26start%3D20%26hl%3Dar%26safe%3Dactive%26sa%3DN%26gbv%3D2%26ndsp%3D20%26tbs%3Disch:1


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Disadvantages of most oral agents:

Slow-acting/difficult to titrate

Disadvantages of insulin secretagogues (e.g.sulfonylureas and meglitinides such as glyburide,glypizide, repaglinide, etc.):

Hypoglycemia if caloric intake is reduced

Some are long-acting (hypoglycemia may beprolonged)

Disadvantages of metformin:

Lactic acidosis can occur when used in the setting ofrenal dysfunction, circulatory compromise, orhypoxemia

Slow onset of action

GI complications: Nausea, diarrhea

Disadvantages of thiazoladinediones :


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_ Disadvantages of thiazoladinediones :

Slow onset of action (2-3 weeks)

Can cause fluid retention (particularly when used with

insulin), and increase risk for CHF

Disadvantages of alpha-glucosidase inhibitors (e.g.acarbose, miglitol)

Abdominal bloating and flatus Need pure glucose to treat hypoglycemia

Disadvantages of GLP-1 mimetics (e.g. exenatide)

Newer agents without data to support use in thehospital

Abdominal bloating and nausea secondary to delayed

gastric emptying


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Managing diabetes &


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Managing diabetes &hyperglycemia in thislabile environment

requires a flexiblemanagementstrategy.


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The winning card


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The story of Tom and Harry

65 year old twins

Diabetes: on NPH 20 units and OHGs with

poor control, neither sees MD regularly Smokers

At a Gentlemans Club when both

developed chest pain. After 6 hours.. Tom: goes to Hospital A

Harry: Hospital A full, so Harry goescross town to Hospital B


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Tom at Hospital A

Admitted to CCU, MI confirmed

Glucose 230 mg/dL

No infusion started for 18 hours Infusion control poor, glycemic excursions

when Tom eats.

Recurrent hypoglycemia, treatedinconsistently, especially with trips to

Radiology

Finally controlled on infusion day 4.


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Tom at Hospital A contd

Transition to ward: Tom on sliding scale Recurrent hyperglycemia to 300

Brief return to unit .

Confusion with various insulin regimens asTom goes from eating to NPO severaltimes.

No mention of hyperglycemia in dischargesummary

Tom discharged on same meds as admit

LOS 6 days, EF 35% at 1 month


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Tom: 3 years later

Follows up with Cardiology only .

Glycemic control remains poor

Recurrent CV events Recurrent hospitalizations


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Harry at Hospital B

Admit CCU, MI confirmed, glu 230 mg / dL

Infusion started by protocol when glucose >140 mg/dL x 2.

Glycemic excursions with meals covered w/subcutaneous RAA-I per protocol.

Minor hypoglycemia covered routinely

Transitioned to ward on basal / bolusregimen, TDD of 80 units.

A1C obtained: 10


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Harry at Hospital B contd

When Harry goes NPO for test, nursescontinue basal insulin, hold nutritionalinsulin (as per protocol )

Education on smoking cessation and DM Information about DM / glucose control

included in DC summary.

Hospitalist arranges for PMC, dischargeregimen of Glargine 35 units, 10 unitsRAA-I w/ meals prescribed.

LOS 5 days, EF at 1 month 45%


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Harry: 3 years later

Quits smoking

A1c = 6.2

Not re-hospitalized

What can you do to make sure all patientswith hyperglycemia are treated likeHarryevery time?

d d f l


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Despite wide spread use of InsulinImplementation gap is their

One-third with mean glucose > 200 mg/dL

60%-70% of insulin regimens sliding scale only

(even if horrible control)

>10% with hypoglycemic episodes. Uneven training amongst staff

Poor coordination of tray delivery, monitoring,

and insulin Inconsistent transitions

Patients often confused or angry

l h l b h


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Not only the tool but the wayusing the tool

How Do We Close the Gap?


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How Do We Close the Gap?Essential Elements

Institutional support and multidisciplinary teams Standardized order sets Infusion

Subcutaneous which promote basal / bolus regimens

Algorithms / protocols / policies Address dosing Nutritional intake

Special situations: TPN, enteral tube feedings,perioperative insulin, steroids

Safety issues Transitions in care and discharge planning

Metrics:How will you know youve made adifference?

Comprehensive educational program


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in hospital dm lecture part 1

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