glucose management in critically ill patients · glucose management in critically ill patients...

10/11/2016

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Glucose Management in Critically Glucose Management in Critically Glucose Management in Critically Glucose Management in Critically

Ill PatientsIll PatientsIll PatientsIll Patients

Archana R. Sadhu, MD., FACEArchana R. Sadhu, MD., FACEArchana R. Sadhu, MD., FACEArchana R. Sadhu, MD., FACEDirector of System Diabetes ProgramDirector of System Diabetes ProgramDirector of System Diabetes ProgramDirector of System Diabetes Program

Director of Transplant EndocrinologyDirector of Transplant EndocrinologyDirector of Transplant EndocrinologyDirector of Transplant Endocrinology

Assistant Professor, Weill Cornell Medical CollegeAssistant Professor, Weill Cornell Medical CollegeAssistant Professor, Weill Cornell Medical CollegeAssistant Professor, Weill Cornell Medical College

Adjunct Assistant Professor, Texas A & M Medical SchoolAdjunct Assistant Professor, Texas A & M Medical SchoolAdjunct Assistant Professor, Texas A & M Medical SchoolAdjunct Assistant Professor, Texas A & M Medical School

Houston MethodistHouston MethodistHouston MethodistHouston Methodist

October 15, 2016October 15, 2016October 15, 2016October 15, 2016

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OBJECTIVES

• Understand the impact of glycemic control on

clinical outcomes for critically ill surgical and

medical patients

• Review current guidelines and glycemic targets

for critically ill patients

• Implement strategies for safe and effective

glycemic control during the ICU stay and on

transition out of the ICU

• Management of Hyperglycemic Crisis: DKA and

HHS

3

DISCLOSURES

• I do not have any relevant financial disclosures.

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THE IMPACT OF HYPERGLYCEMIA IN

CRITICALLY ILL PATIENTS

5

CAUSES OF INPATIENT

HYPERGLYCEMIA

• Illness related “stress” – counter regulatory

hormones and cytokines cause insulin

resistance

• Undiagnosed diabetes mellitus

• Medications: steroids, immunosuppressants,

sympathomimetics, anesthetic agents,

octreotide

• Parenteral and enteral nutrition

• Physical Inactivity

• Inappropriate insulin use e.g. Sliding scale

insulin

6

LINK BETWEEN LINK BETWEEN LINK BETWEEN LINK BETWEEN HYPERGLYCEMIA AND HYPERGLYCEMIA AND HYPERGLYCEMIA AND HYPERGLYCEMIA AND

POOR OUTCOMES: POTENTIAL POOR OUTCOMES: POTENTIAL POOR OUTCOMES: POTENTIAL POOR OUTCOMES: POTENTIAL

MECHANISMS MECHANISMS MECHANISMS MECHANISMS

Clement S et al. Diabetes Care , 2004; 27:553–591,

Immune dysfunction

Infection dissemination

Reactive O2 species

Secondary mediators

Transcription factors

Metabolic stress response

Stress hormones and peptides

GlucoseInsulin

FFAKetonesLactate

Cellular injury/apoptosisInflammationTissue damage

Altered tissue/wound repairAcidosis

Infarction/ischemia

Organ dysfunction

Prolonged hospital stayDisability

Death

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7

HOSPITAL MORTALITY RATE AND MEAN

GLUCOSE LEVELS IN CRITICALLY ILL

PATIENTS

0

5

10

15

20

25

30

35

40

45

80–99 100–119 120–139 140–159 160–179 180–199 200–249 250–299 > 300

Mor

talit

y R

ate

(%)

Mean Glucose Value (mg/dL)

Retrospective review of 1,826 consecutive intensive care unit patientsat The Stamford Hospital in Stamford, Connecticut. Krinsley JS. Mayo Clin Proc. 2003;78:1471–1478.

Mean Glucose ofSurvivors: 137.9Nonsurvivors: 172.0p < 0.0001

8 5

Hyperglycemia-related mortality in critically ill patients varies with admission

diagnosis *.

Falciglia, Mercedes; Freyberg, Ron; Almenoff, Peter; DAlessio, David; Render, Marta

Critical Care Medicine. 37(12):3001-3009, December 2009.

DOI: 10.1097/CCM.0b013e3181b083f7

• Mortality risk from

hyperglycemia is

greater in patients

without a diagnosis

of diabetes.

• Patients with

diabetes: n = 78,142

• Patients without

diabetes: n =

180,898

HYPERGLYCEMIA AND

MORTALITY IN CRITICALLY ILL

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HYPERGLYCEMIA AND MORTALITY

IN ACUTE MYOCARDIAL

INFARCTION

Mikhail Kosiborod et al. Circulation. 2008;117:1018 -1027

16,871 patients with acute myocardial infarction

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10

HYPERGLYCEMIA INCREASES

MORTALITY IN CABG PATIENTS

Furnary AP, et al. Circulation. 1999;18:3113

1.8%

5.0%

Blood Glucose < 200 Blood Glucose > 200

(N = 2,110)

P = 0.001

6.1

4.9

3.7

2.4

1.2

0.0

Mortality(%)

5.0%

1.8%

Glucose <200 Glucose >200

11CABG= coronary artery bypass graft. Furnary AP et al. J Thorac Cardiovasc Surg. 2003;125:1007-1021

Mortality Increases With Increasesin Average Glucose Levels

Average Postoperative Glucose (mg/dL)

Cardiac-related mortality

Noncardiac-related mortality

Post-CABG

0

2

4

6

8

10

12

14

16

<150 150–175 175–200 200–225 225–250 >250

Mo

rta

lity

%

HYPERGLYCEMIA INCREASES

MORTALITY IN CABG PATIENTS

OUTCOMES OF TREATING

HYPERGLYCEMIA IN CRITICAL ILLNESS

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TNF-α IL-6

Iκß (inhibitor κß)

phosphorylation

Translocation to the nucleus

Proinflammatory genes

TNF-α IL-6 IL-8,MCP-1

Adhesion molecules

ICAM-1 VCAM-1 MMPs

APPs

transcription transcription

-

mixed meal

INSULIN -eNOS

NO

+

+

FFA-

+

-

E-selectin

iNOSNO

CRP

SAA

Endothelial CellMonocyte/Macrophage

liver

NF-Kβ

Nonmetabolic Insulin Action

http://resources.aace.com

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DIGAMI-1: INSULIN THERAPY IMPROVES

MORTALITY IN PATIENTS WITH DM AND

AMI

Malmberg K, et al. BMJ. 1997;314:1512–1515. (Reproduced with permission from the BMJ Publishing Group.)

All subjects

(N = 620)Risk reduction (28%)P = 0.011

Standard treatment

0

30

20

40

70

10

50

60

0 1

Follow-up (years)

2 3 4 5

Low-risk and not previously on insulin

(N = 272)

Risk reduction (51%)P = 0.0004

IV insulin 48 hours, then 4 injections dailywith target 126-180mg/dl

0

30

20

40

70

10

50

60

0 1

Follow-up (years)

2 3 4 5

DIGAMI = Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction.

Mortality(%)

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PORTLAND DIABETES PROJECT:

REDUCTION IN MORTALITY

Reprinted from Furnary AP, et al. J Thorac Cardiovasc Surg. 2003;125:1007–1021 with permission from American Association for Thoracic Surgery.

CII

10

8

6

4

0

Mortality

(%)

87 88 89 90 91 92 93 94 98 99 00

Year

Patients with diabetes

Patients withoutdiabetes

2

95 96 97 01

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PORTLAND DIABETES PROJECT:

REDUCTION IN DEEP STERNAL WOUND

INFECTION RATES

Anthony Furnary MD 1999 CCNM

0.0

0.5

1.0

1.5

2.0

SQI CII

Deep Wound Infection Rate (%)

2.0%

0.8%

P = 0.01

SQI = subcutaneous insulin; CII = continuous insulin infusion.

SQI CII

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INTENSIVE INSULIN THERAPY (IIT) IN

CRITICALLY ILL (SURGICAL) PATIENTS

van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367.Copyright ©2001 Massachusetts Medical Society. All rights reserved.

Conventional: insulin when blood glucose > 215 mg/dL.Intensive: insulin when glucose > 110 mg/dL and maintained at 80–110 mg/dL.

Survival in ICU (%)

100

96

92

88

800

84

0 20 40 60 80 100 120 140 160

Intensive treatment

Conventional treatment

Days After Admission

N = 1,548

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INTENSIVE INSULIN THERAPY IN

CRITICALLY ILL (SURGICAL) PATIENTS

Intensive Insulin Therapy = BG target 80Intensive Insulin Therapy = BG target 80Intensive Insulin Therapy = BG target 80Intensive Insulin Therapy = BG target 80----110 mg/dL110 mg/dL110 mg/dL110 mg/dL

van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367.

-60

-50

-40

-30

-20

-10

0

% R

educ

tion

Mortality Sepsis Dialysis PolyneuropathyBlood

Transfusion

34%

46%41% 44%

50%

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19

IIT IN CRITICALLY ILL MIXED (MEDICAL

AND SURGICAL) ICU PATIENTS

Krinsley JS. Mayo Clin Proc. 2004;79:992–1000

Red

uctio

n(%

)

MortalityNew Renal

Insufficiency ICU LOSBlood

Transfusion

29.3%

75%

18%11.1%

N = 1,600

*Infectious complications were not statistically significant

BG target 80-140 mg/dl

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Study Setting Population Clinical Outcome

Furnary, 1999 ICUDM undergoing open

heart surgery65% ↓↓↓↓ infection

Furnary, 2003 ICU DM undergoing CABG 57% ↓↓↓↓ mortality

Krinsley, 2004Medical/surgical

ICU Mixed, no Cardiac 29% ↓↓↓↓ mortality

Malmberg, 1995 CCU Mixed28% ↓↓↓↓ mortality

After 1 year

Van den Berghe, 2001* Surgical ICU Mixed, with CABG 42% ↓↓↓↓ mortality

Lazar, 2004 OR and ICU CABG and DM60% ↓↓↓↓ A Fib post op

survival 2 yr

*RCT, randomized clinical trial.

Kitabchi & Umpierrez. Metabolism. 2008;57:116-120.

BENEFITS OF TIGHT GLYCEMIC CONTROL:

OBSERVATIONAL STUDIES AND EARLY

INTERVENTION TRIALS

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• 1253 T2 DM patients with AMI

• Randomized to 3 groups:

• #1 – iv insulin + glucose > 24 hours followed by MDI SC insulin

• #2 – iv insulin + glucose > 24 hours followed by usual care

• #3 – Usual Care by physician

• No differences in mortality

• Deficiencies:

1. Only 50% recruitment

2. Underpowered analysis

3. Target glucose levels NOT met

DIGAMI 2 – A NEGATIVE

STUDY

Malmberg K, et al. Eur Heart J. 2005; 26:650-661

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22Van den Berghe, G. et al. N Engl J Med 2006;354:449-461

Not statistically significant P = 0.02

P value = 0.02

IIT IN MEDICAL ICU

PATIENTS

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Trial N Setting Primary

Outcome ARR RRROdds Ratio

(95% CI) P-value

Van den Berghe2006 1200 MICU

Hospitalmortality

2.7% 7.0% 0.94*(0.84-1.06)

N.S.

HI-52006

240CCU AMI 6-mo

mortality -1.8%* -30%* NR N.S.

Glucontrol2007 1101 ICU

ICU mortality

-1.5% -10% 1.10*(0.84-1.44)

N.S.

VISEP2008 537 ICU

28-dmortality

1.3% 5.0% 0.89*(0.58-1.38)

N.S.

De La Rosa 2008 504

SICU

MICU

28-d mortality -4.2% * -13%* NR N.S.

NICE-SUGAR2009 6104 ICU

3-mo mortality

-2.6% -10.61.14

(1.02-1.28)< 0.05

* not significant

INTENSIVE GLUCOSE MANAGEMENT IN INTENSIVE GLUCOSE MANAGEMENT IN INTENSIVE GLUCOSE MANAGEMENT IN INTENSIVE GLUCOSE MANAGEMENT IN

RCTS SHOWING NO BENEFIT RCTS SHOWING NO BENEFIT RCTS SHOWING NO BENEFIT RCTS SHOWING NO BENEFIT

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NICE-SUGAR TRIAL : IDEAL

TARGET IN ICU PATIENTS

The NICE-SUGAR Study Investigators. N Engl J Med 2009;360:1283-1297

• Average am glucose 118 (IIT) vs. 145 mg/dl

• Increased mortality in IIT27.5% (IIT) vs. 24.9%

• OR for death = 1.4 (except in trauma and corticosteroid therapy)

• Hypoglycemia (BG < 40)6.8% (IIT) vs. 0.5%

• No significant benefits in • secondary outcomes

N= 6104 ICU patients -- Intensive: Glucose 80-110 mg/dL --Conventional: Glucose 140-180 mg/dL

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GLUCO-CABG: IDEAL TARGET IN

CABG PATIENTS

• RCT, N=302 with 2 targets: 100-140 mg/dL vs 140-180

mg/dL

• Insulin infusion in ICU if glucose >140 mg/dl followed by SC

insulin regimen during the entire hospital stay and for 90 days

postop

• Composite postoperative complications: mortality, wound infection,

pneumonia, bacteremia, respiratory failure, acute kidney injury and major

cardiovascular events

• In patients without diabetesIn patients without diabetesIn patients without diabetesIn patients without diabetes, there were ~ 20% fewer , there were ~ 20% fewer , there were ~ 20% fewer , there were ~ 20% fewer

postoperative complications postoperative complications postoperative complications postoperative complications

• In patients with diabetesIn patients with diabetesIn patients with diabetesIn patients with diabetes, no difference, no difference, no difference, no difference

Umpierrez et al.Diabetes Care 2015; 38:1665-1672

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DIGAMI 1DIGAMI 1DIGAMI 1DIGAMI 1

• Gain in life-years: 0.94 0.94 0.94 0.94 yearsyearsyearsyears

• Cost per life-year gained: Euro 16,900Euro 16,900Euro 16,900Euro 16,900

• Per Swedish standards, this is highly cost effectivehighly cost effectivehighly cost effectivehighly cost effective

CABG PatientsCABG PatientsCABG PatientsCABG Patients• Each 50 mg/dL BG

increase was associated with:

-Longer Post op days: 0.76 days0.76 days0.76 days0.76 days

-Higher hospital Charges: $2,824$2,824$2,824$2,824

-Higher hospital costs:$1,769$1,769$1,769$1,769

HEALTHCARE UTILIZATION

AND COSTS

Almbrand et al. Euro Heart Journal 2000, 21:733-739 Estrada, C et al. Ann Thorac Surg 2003,75:1392-1399

27

Leuven StudyLeuven StudyLeuven StudyLeuven Study

• Decreased ICU length of stay: 2.0 days2.0 days2.0 days2.0 days

• Decreased ICU costs: 2,638 Euros/patient2,638 Euros/patient2,638 Euros/patient2,638 Euros/patient

• No difference in ward length of stay

Stamford StudyStamford StudyStamford StudyStamford Study

• Net decrease in costs: $1,580 per patient$1,580 per patient$1,580 per patient$1,580 per patient

• Decrease in ICU LOS: 0.3 median days 0.3 median days 0.3 median days 0.3 median days (p=0.005)

• Decrease in Non-ICU days: 1 calendar day1 calendar day1 calendar day1 calendar day

(p=0.54)

COSTS IN INTENSIVE CARE

UNIT

Van den Berghe, et. al. Crit Care Med 2006; 34(3): 612-616 Krinsley J, Jones R, Chest 2006; 129(3): 644-650

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*Denotes significance at p ≤ .05. 95% empirical, bias-corrected bootstrapped confidence intervals shown in parentheses. ** Glucose readings are from 2004 to 2007** Glucose readings are from 2004 to 2007.Costs are CPI adjusted

OutcomeChange in Outcome

(Deceased Patients Included)N= 11,129 (2003 to 2007)

Total LOS Costs -$7,580(-$13,643, -$1,180)*

Direct Variable Costs -$4,960 (-$8,998, -$850)*

Total ICU costs -$9,919(-$17,995, -$2175)*

Direct variable ICU costs -$3,216 (-$6,219, -$371)*

Total LOS -0.25 (-1.55, .99)

ICU days -1.80 (-2.78, -0.89)*

Mortality -.026 (-.06,.00006)

Average glucose per patient day (mg/dL)**

-9.18 (-12.49, -5.97)*

Sadhu et al. Abstract - ADA 70 th Scientific Session 2010Sadhu et al. Diabetes Care 2008; 31(8): 1556-1661

COST SAVINGS IN PATIENTS TREATED

WITH IIT- TIRUMPH STUDY

Pre and post implementation of Intensive Insulin Protocols in ICU

29

HYPOGLYCEMIA IN CRITICALLY HYPOGLYCEMIA IN CRITICALLY HYPOGLYCEMIA IN CRITICALLY HYPOGLYCEMIA IN CRITICALLY

ILL PATIENTSILL PATIENTSILL PATIENTSILL PATIENTS

Egi M et al. Mayo Clin Proc. 2010;85:217-224

• 22.4% of patients had hypoglycemia defined as glucose ≤ 81 mg/dL at least once

• Mortality Rates:

Hypoglycemia� 36.6%

No hypoglycemia � 19.7%

• Mortality increased with severity of hypoglycemia

• Therapy at time of hypoglycemia:- 32.7% were receiving insulin - 67.3% were not (spontaneous)

• Insulin therapy was not a significant predictor of hospital mortality in a multivariate analysis

Two centers; N= 4946

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HYPOGLYCEMIA DUE TO

INSULIN THERAPY

Hypoglycemia No hypoglycemia p-value

All Patients n=482 n=7338

In-hospital mortality 61 (12.7%) 701 (9.6%) 0.026

No insulin treatment n=136 n=4639


Insulin-treated

patients n=346 n=2699


Kosiborod M, et al. JAMA. 2009;301:1556-1564.

40 hospitals; 7820 acute myocardial infarction patients admitted with hyperglycemia

Subsequent hypoglycemia during hospitalization (< 60 mg/dL)

• Increased in-hospital mortality if hypoglycemia occurred• Hypoglycemia was associated with increased mortality in non insulin treated patients

BUT NOT in patients treated with insulin .

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AACE/ADA/STS TARGET GLUCOSE

LEVELS IN ICU PATIENTS• ICU setting:ICU setting:ICU setting:ICU setting:

– Starting threshold of no higher than 180 mg/dL

– Once IV insulin is started, the glucose level should be maintained between 140 and 180 140 and 180 140 and 180 140 and 180 mg/dL

– Lower glucose targets (110110110110----140 140 140 140 mg/dL) may be appropriate in selected patients (Cardiothoracic surgery)

– Targets <110 mg/dL or >180 mg/dL are NOT recommended

Recommended140-180

Acceptable110-140

Not recommended<110

Not recommended>180

Moghissi ES et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15:353-369. http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf.Lazar, HL et al. The Society of Thoracic Surgeons Practice Guidelines Series: Blood Glucose Management After Adult Cardiac Surgery. Ann Thorac Surg, 2009; 87:663-9

STRATEGIES TO ACHIEVE GLYCEMIC

CONTROL IN CRITICALLY ILL PATIENTS

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ADMISSION #1 – CHEST PAIN

• 68 year old male admitted with chest pain and found to have AMI

and CHF

• Type 2 DM for 14 years, HTN, Hyperlipidemia, Gout

• Outpatient DM Meds: Metformin 1000mg bid, Glyburide 5mg bid

• Exam: Lungs with rales, 2+ LE edema

• Labs: Admission glucose 316 mg/dL HgbA1c 9.3%, creatinine 2.5,

LFT’s- 2.5 X upper limit of normal

• Echo shows LVEF 25%

• Admitted to CCU after cardiac catheterization with glucose now

250 mg/dL

How should we treat this patient?

1. Continue metformin and increase the dose of glyburide to 10 mg

bid

2. Start SLIDING SCALE SLIDING SCALE SLIDING SCALE SLIDING SCALE subcutaneous insulin Q4-6 hours

3. Start Insulin Infusion with a glucose target of 110-140 mg/dl


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INDICATIONS FOR INTRAVENOUS

INSULIN THERAPY: SUMMARY

• Diabetic Ketoacidosis

• Hyperglycemic Hyperosmolar Syndrome

• Critical care illness (surgical, medical)

• Post cardiac surgery

• Myocardial infarction or cardiogenic shock

• NPO status in Type 1 diabetes

• Labor and Delivery

• Organ Transplantation

American Association of Clinical Endocrinologists. Available at: http://www.aace.com/pub/ICC/inpatientStatement.php. Accessed March 17, 2004.

35

ADMISSION #1 –

CONTINUED

• Over the next 24 hours, the glucose control improved into the desired target and he is medically optimized

• He now has proceeds to surgery and has a 3 vessel CABG

• Postop, he is admitted to the surgical ICU on epinephrine and vasopressin drips for hypotension

• His initial glucose in the ICU is 251 mg/dl

How do we manage his glucose?

1. SLIDING SCALE insulin Q 4-6 hours

2. Start long and short acting insulin for basal- bolus insulin therapy



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ADMISSION #1 –

CONTINUED

• Over the next 24 hours, the glucose control reaches target range and has been stable

• Pressors are weaned off and he is extubated

• A diet is ordered and plans are started to transfer to the floor

What do we do next?

1. Restart metformin and increase glyburide dose to 10mg bid

2. Turn off insulin infusion and immediately start SLIDING SCALE

insulin Q 4-6 hours

3. Transition to a long + short acting insulin for basal- bolus insulin

therapy

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37

TRANSITION FROM IV TO SC

INSULIN – FACTORS TO CONSIDER

1. Stability of the insulin infusion rate – Initial rates when glucose is uncontrolled can be high and then as it

stabilizes, the rates may decrease

– Ideally use at least 6 hours of stable glucose and infusion rates

2. Nutrition status while on infusion– If patient was eating without prandial insulin coverage, the glucose

abruptly rises after food, followed by significant increase in insulin infusion rates

– If the patient was on TPN or tube feedings, will there be a upcoming change in nutrition

3. Level of glucose control– Some % of the total iv insulin requirements is used to calculate the

SC insulin doses.

– If glucose was not at target, may need to increase the conversion factor

4. Other factors influencing insulin infusion rate– Medications: Corticosteroids, vasopressors

– Organ function: acute renal failure

– Resolving infection

38

TRANSITION FROM IV TO SC

INSULIN - EXAMPLE

• Use approxapproxapproxapprox. 50505050----80% of stable 24 hour IV insulin requirements80% of stable 24 hour IV insulin requirements80% of stable 24 hour IV insulin requirements80% of stable 24 hour IV insulin requirements: (if not avail for 24 hours, can extrapolate over a recent stable period)

� 70 units x .7 = 49 units ( totaltotaltotaltotal 24 hour SC insulin dose)

• For glargine/detemir + lispro/aspart regimenFor glargine/detemir + lispro/aspart regimenFor glargine/detemir + lispro/aspart regimenFor glargine/detemir + lispro/aspart regimen:

� 50% Basal : 49 x 0.5 = 25 units

� 50 % Nutritional divided QAC : 8 units

� Use a corrective algorithm in addition to scheduled prandial

• For NPH + lispro/aspart regimenFor NPH + lispro/aspart regimenFor NPH + lispro/aspart regimenFor NPH + lispro/aspart regimen:

� 2/3 NPH - divided into two doses : 49 x 2/3 = 16 units before breakfast and bedtime

� 1/3 Nutritional, divided TID with meals = 5 units before each meal

• Always discontinue the insulin drip two hours afterdiscontinue the insulin drip two hours afterdiscontinue the insulin drip two hours afterdiscontinue the insulin drip two hours after the first long acting subcutaneous insulin dose.

39

ADMISSION #2 : FEVER

• 66 year old female admitted with fever of 103◦◦◦◦ F, SOB

and hypotension.

• Intubated, on pressors and admitted to Medical ICU

• Found to have a multilobar pneumonia with SIRS

• No history of Type 2 Diabetes but has HTN ,

Hyperlipidemia, CAD, COPD

• Labs: Glucose= 225 mg/dL, repeat accucheck 253

mg/dL HgbA1c = 6.3% Creatinine = 1.8 AST/ALT =

normalHow should we treat this patient?

1. No therapy needed as this is acute hyperglycemia and not diabetes

2. Start SLIDING SCALE SLIDING SCALE SLIDING SCALE SLIDING SCALE subcutaneous insulin Q4-6 hours



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ADMISSION #2:

CONTINUED

• Patient was managed on insulin infusion and reached the

target

• Over the next 48 hours, patient is supported with

mechanical ventilation, Norepinephrine, stress dose

hydrocortisone, iv antibiotics

• Still not improved and TPN is started due to ileus

• Insulin infusion has been titrated up to 6-10 units/hr and

she is requiring >180 units of IV insulin per 24 hours

• Labs: Cr = 2.6, LFTS now 3x normal

What is the next step?

1. Change to sliding scale insulin

2. Transition to basal bolus subcutaneous insulin regimen

3. Add NPH or Lantus in addition to iv insulin infusion

4. Add Regular insulin into the TPN formula

41

ADMISSION # 2 - ADDING

INSULIN IN TPN

• Insulin is more effective when added to the TPN

• Delay in preparation of TPN, often 12-24 hours later

requires planning

• Watch for clinical and medication changes and plan

insulin in TPN in advance to avoid hypoglycemia.

• Evidence for dosing is limited but expert opinionexpert opinionexpert opinionexpert opinion1111:

– DM : 1 unit per 12-15 grams of dextrose in

addition to basal bolus insulin regimen

– No DM: 1 units per 15-20 grams of dextrose with

rapid acting correction insulin

1. Managing Diabetes and Hyperglycemia in the Hospital Setting: A Clinician’s Guide. Ed. Boris Draznin 2016

42

ADMISSION #3

• 33 year old female with Type 1 Diabetes

managed on an insulin pump

• Developed nausea and vomiting and was

brought to ED due to increasing lethargy

• On presentation: Shallow and rapid

respirations, minimally responsive Glucose 750

mg/dl, Sodium 129 mg/dl, Bicarb 9, Cr 1.4

What is the diagnosis?

1. Gastroenteritis

2. Insulin pump failure

3. Acute kidney Injury

4. All of the above

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43

DKA AND HHS :

DIAGNOSTIC CRITERIA

DKA HHS

Mild (plasma

glucose >250

mg/dl)

Moderate

(plasma

glucose >250

mg/dl)

Severe

(plasma

glucose >250

mg/dl)

Plasma

glucose >600

mg/dl

Arterial pH 7.25–7.30 7.00 to <7.24 <7.00 >7.30

Serum

bicarbonate

(mEq/l)

15–18 10 to <15 <10 >18

Urine ketone Positive Positive Positive Small

Serum ketone Positive Positive Positive Small

Effective

serum

osmolality

Variable Variable Variable>320

mOsm/kg

Anion gap >10 >12 >12 Variable

Mental status Alert Alert/drowsy Stupor/coma Stupor/coma

Umpierrez GE, et al. Diabetes Care 2009 Vol 36 (7):2112

44

Abbas E. Kitabchi et al. Dia Care 2009;32:1335-1343

MANAGEMENT OF

DKA/HHS

45

DKA/HHS TREATMENT

PROTOCOL

• IV Fluids

1. 0.9% Saline at 500-1,000 ml/h for 2 h, then

2. 0.45% saline at 250-500 mL/h until blood glucose

<250 mg/dL, then

3. Dextrose 5% in 0.45% saline at 150-250 ml/h

until resolution of DKA

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46

DKA/HHS TREATMENT

PROTOCOL

• Potassium Replacement

1. If initial K+ > 5.5 mmol/L, do not give K but

recheck every 2 hours

2. Add K + as needed based on subsequent values

1. K + = 4-5.5 mmol/L, add 20 mmol/L of KCL to IV fluid

2. K + = 3-<4 mmol/L, add 40 mmol/L of KCL to IV fluid

3. K + = <3 mmol/L, give 10-20 mmol of KCL per hour until

serum K >3 mmol/L, then add 40 mmol/L of KCL to iv

fluid

Managing Diabetes and Hyperglycemia in the Hospital Setting: A Clinician’s Guide. Ed. Boris Draznin, 2016 Alexandria, Virginia

47

DKA/HHS TREATMENT

PROTOCOL

• IV Insulin Therapy

1. Give IV bolus of regular insulin of 0.1 U/kg

2. Start continuous insulin infusion at 0.1

U/kg/h

3. When blood glucose <250 mg/dL:

�Change IV fluids to D5%-0.45% saline

�Reduce insulin infusion rate to 0.05

units/kg/h to keep glucose ≈ 200 mg/dL

until resolution of DKA


48

DKA/HHS TREATMENT

PROTOCOL

• Transition to SQ insulin therapy

– Continue insulin infusion until resolution

• DKA : glucose <200 mg/dL, bicarbonate ≥ 18

mEq/L, pH ≥ 7.30, and anion gap ≥ 14 mEq/L)

• HHS: serum osmolality <320 mOsm/kg and glucose

≤ 250 mg/dL with recovery of mental status

– SQ insulin therapy

• Previous DM: restart home insulin regimen if

adequate glycemic control before admission

• New diagnosis: Total daily dose of 0.5-0.8 U/kg/day

of body weight

• REMEMBER to administer the first basal SQ dose 2-4

hours PRIOR to discontinuation of IV insulin therapy


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49

DKA/HHS TREATMENT

PROTOCOL

• BicarbonateBicarbonateBicarbonateBicarbonate

1. If arterial pH < 6.9, administer 44.6 mEq of sodium

bicarbonate in 200ml of 0.45% saline over 1 h until

pH increases to 6.9-7.0

2. Do not give bicarbonate if pH > 7.0

• Laboratory AssessmentLaboratory AssessmentLaboratory AssessmentLaboratory Assessment

Admission: CBC with differential, complete metabolic

panel, venous or arterial pH, and serum ß-hydroxybutarate,

HgbA1c. Consider cardiac, CVA, infection or substance

abuse workup if indicated

During Treatment: basic metabolic profile, venous pH,

phosphorus, and ß-hydroxybutarate

Glucose monitoring: capillary blood glucose every 1-2 h at

the bedside

Managing Diabet4es and Hyperglycemia in the Hospital Setting: A Clinician’s Guide. Ed. Boris Draznin, 2016 Alexandria, Virginia

50

SQ INSULIN PROTOCOLS

• SQ rapid acting insulin every 1 h (SQSQ rapid acting insulin every 1 h (SQSQ rapid acting insulin every 1 h (SQSQ rapid acting insulin every 1 h (SQ----1h): 1h): 1h): 1h):

1. Initial dose SQ: 0.2 U/kg of body weight, followed by 0.1

U/kg/h

2. When BG <250 mg/dL, change IVF to D5%-0.45%

saline and reduce SQ rapid acting insulin to 0.05

unit/kg/h to keep glucose ≈ 200 mg/dL until resolution

of DKA

• SQ rapid acting insulin every 2 h (SQSQ rapid acting insulin every 2 h (SQSQ rapid acting insulin every 2 h (SQSQ rapid acting insulin every 2 h (SQ----2h):2h):2h):2h):

1. Initial dose SQ: 0.3 U/kg of body weight, followed by 0.2

U/kg 1 h later, then

2. SQ rapid acting insulin at 0.2 U/kg every 2 h

3. When BG <250 mg/dL, change IVF to D5%-0.45%

saline and reduce SQ rapid acting insulin to 0.1 U/kg

every 2 h to keep glucose ≈ 200 mg/dL until resolution

of DKAManaging Diabetes and Hyperglycemia in the Hospital Setting: A Clinician’s Guide. Ed. Boris Draznin, 2016 Alexandria, Virginia

51

SQ LISPRO VS IV REGULAR

INFUSION FOR DKA

Vincent and Nobecourt. Diabetes & Metabol 39: 299-305, 2013

10/11/2016

18

52

Advantages:• Glucose dependent insulin

stimulation prevents hypoglycemia

• Glucagon inhibition may be useful in

the maladaptation of the stress

response

• Suppression of hepatic glucose

• Increased tissue insulin sensitivity

• Potential cardiovascular benefits

with improved cardiac function,

reduced infarct size

• Less nursing time to monitor

glucose and administer insulin

Disadvantages:• Small, limited studies investigating

use in critically ill patients

• Usually compared to placebo, not

insulin

• High incidence of GI side effects

• Rescue insulin therapy often

needed

• Long term effects unknown

• More studies needed

GLP-1 RECEPTOR ANTAGONIST

THERAPY IN CRITICALLY ILL

PATIENTS

Schwartz S, DeFronzo, RA. Diabetes Care 2013 Vol 36 (7):2107

Umpierrez GE, Korytkowski M. Diabetes Care 2013 Vol 36 (7):2112

THANK YOU FOR YOUR

ATTENTION!

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