Glucose Management in Critically Ill Patients · Glucose Management in Critically Ill Patients...
Transcript of 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
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DISCLOSURES
• I do not have any relevant financial disclosures.
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THE IMPACT OF HYPERGLYCEMIA IN
CRITICALLY ILL 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
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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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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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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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
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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
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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
• 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
In-hospital mortality 25 (18.4%) 425 (9.2%) 0.0003
Insulin-treated
patients n=346 n=2699
In-hospital mortality 36 (10.4%) 276 (10.2%) 0.92
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
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
• 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.
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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 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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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
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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.
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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
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 #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
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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
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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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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
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Abbas E. Kitabchi et al. Dia Care 2009;32:1335-1343
MANAGEMENT OF
DKA/HHS
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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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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
Managing Diabetes and Hyperglycemia in the Hospital Setting: A Clinician’s Guide. Ed. Boris Draznin, 2016 Alexandria, Virginia
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
Managing Diabetes and Hyperglycemia in the Hospital Setting: A Clinician’s Guide. Ed. Boris Draznin, 2016 Alexandria, Virginia
10/11/2016
17
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!