10/7/2015 1 Glucose Management in Critically Glucose Management in Critically Glucose Management in Critically Glucose Management in Critically Ill Patients Ill Patients Ill Patients Ill Patients Archana R. Sadhu, MD., FACE Archana R. Sadhu, MD., FACE Archana R. Sadhu, MD., FACE Archana R. Sadhu, MD., FACE Director of System Diabetes Program Director of System Diabetes Program Director of System Diabetes Program Director of System Diabetes Program Director of Transplant Endocrinology Director of Transplant Endocrinology Director of Transplant Endocrinology Director of Transplant Endocrinology Assistant Professor, Weill Cornell Medical College Assistant Professor, Weill Cornell Medical College Assistant Professor, Weill Cornell Medical College Assistant Professor, Weill Cornell Medical College Adjunct Assistant Professor, Texas A & M Medical School Adjunct Assistant Professor, Texas A & M Medical School Adjunct Assistant Professor, Texas A & M Medical School Adjunct Assistant Professor, Texas A & M Medical School Houston Methodist Houston Methodist Houston Methodist Houston Methodist October 17, 2015 October 17, 2015 October 17, 2015 October 17, 2015 2 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 THE IMPACT OF HYPERGLYCEMIA IN CRITICALLY ILL PATIENTS
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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
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
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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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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
8CABG= 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)Average Postoperative Glucose (mg/dL)
Cardiac-related mortality
Noncardiac-related mortality
PostPost--CABGCABG
0
2
4
6
8
10
12
14
16
<150 150–175 175–200 200–225 225–250 >250
Mo
rta
lity
%M
ort
ali
ty %
HYPERGLYCEMIA INCREASES
MORTALITY IN CABG PATIENTS
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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
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LINK BETWEEN LINK BETWEEN LINK BETWEEN LINK BETWEEN HYPERGLYCEMIA AND HYPERGLYCEMIA AND HYPERGLYCEMIA AND HYPERGLYCEMIA AND
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
• 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
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
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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
Two centers; N= 4946
•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
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HYPOGLYCEMIA
• Median time of hypoglycemia was over 3.5 hours3.5 hours3.5 hours3.5 hours
• Therapy at time of hypoglycemia:
- 32.7% were receiving insulin 32.7% were receiving insulin 32.7% were receiving insulin 32.7% were receiving insulin
---- 67.3% were not (spontaneous)67.3% were not (spontaneous)67.3% were not (spontaneous)67.3% were not (spontaneous)
• Insulin therapy was not a significant predictor of hospital mortality in a multivariate analysis
• Time to first episode of hypoglycemia and severity of hypoglycemia had significantly higher mortality
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 mg/dL
– Lower glucose targets (110-140 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
3. Start Insulin Infusion with a glucose target of 110-140 mg/dl
4. Start Insulin Infusion with a glucose target of 140-180 mg/dl
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INDICATIONS FOR INTRAVENOUS
INSULIN THERAPY: SUMMARY
• Diabetic ketoacidosis
• Nonketotic hyperosmolar state
• Critical care illness (surgical, medical)
• Postcardiac surgery
• Myocardial infarction or cardiogenic shock
• NPO status in Type 1 diabetes
• Labor and Delivery
American Association of Clinical Endocrinologists. Available at: http://www.aace.com/pub/ICC/inpatientStatement.php. Accessed March 17, 2004.
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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
3. Start Insulin Infusion with a glucose target of 110-140 mg/dl
4. Start Insulin Infusion with a glucose target of 140-180 mg/dl
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ADMISSION #1 –
CONTINUED
• Over the next 24 hours, the glucose control reaches target range
• 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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DANGERS OF SLIDING-SCALE
INSULIN REGIMENS
• Reactive to after hyperglycemia-- provides supplemental insulin after hyperglycemia occurs
• No basal (long term) insulin coverage:
� Will cause DKA in patients with Type 1 Will cause DKA in patients with Type 1 Will cause DKA in patients with Type 1 Will cause DKA in patients with Type 1 diabetesdiabetesdiabetesdiabetes
• Does not consider nutritional changes or diurnal insulin requirements
• Non physiologic dosing that results in:
– Increased incidence of hyperglycemic and hypoglycemic episodes1
1Queale WS et al. Arch Intern Med. 1997;157:545-552
• Use approxapproxapproxapprox. 50505050----70% of stable 24 hour IV insulin requi70% of stable 24 hour IV insulin requi70% of stable 24 hour IV insulin requi70% 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)
� 2/3 NPH - divided into two doses : 49 x 2/3 = 16 units before breakfast and bedtime
� 1/3 Nutritional, divided QAC = 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.
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CAUTIONS IN INSULIN
DOSING…
• Changing steroid doses
• Changing pressor requirement over past 24
hours
• Changing renal function (rapidly decreasing
urine output or GFR)
• Nutrition changes
• Improving infectious status
• Hypoglycemic Events
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ADMISSION #2 : FEVER
• 66 year old female admitted with fever of 103 F, SOB
and hypotension.
• Intubated and started 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 = 5.9% Creatinine = 1.8 AST/ALT =
normalHow should we treat this patient?
1. No therapy needed as this is acute hyperglycemia and not diabetes