Hypoglycemia in the Hypoglycemia in the HospitalHospital
Sara Alexanian, MDSara Alexanian, MDDirector, Inpatient Diabetes Director, Inpatient Diabetes
ProgramProgramDepartment of Endocrinology, Department of Endocrinology,
Diabetes and NutritionDiabetes and Nutrition
AgendaAgenda
Glycemic goalsGlycemic goals PhysiologyPhysiology Epidemiology and risks of Epidemiology and risks of
hypoglycemiahypoglycemia Preventing and avoiding Preventing and avoiding
hypoglycemiahypoglycemia
Hyperglycemia in the Hospital: Hyperglycemia in the Hospital: the Factsthe Facts
Hyperglycemia is noted in 20-40% of Hyperglycemia is noted in 20-40% of hospitalized patients.hospitalized patients.
Hyperglycemia, irrespective of it’s cause, Hyperglycemia, irrespective of it’s cause, is unequivocally associated with adverse is unequivocally associated with adverse clinical outcomes.clinical outcomes.
Intervention studies directed at BG control Intervention studies directed at BG control have resulted in improved outcomes in have resulted in improved outcomes in some, but not all studies.some, but not all studies.
Insulin therapy, in particular (“intensive Insulin therapy, in particular (“intensive glycemic control”) carries a risk of glycemic control”) carries a risk of hypoglycemia. hypoglycemia.
What are the recommendations What are the recommendations for glucose control in the for glucose control in the
hospital?hospital?
AACE/ADA Target Glucose Levels AACE/ADA Target Glucose Levels in Nonin Non––ICU PatientsICU Patients
NonNon––ICU setting:ICU setting:– Premeal glucose targets <140 mg/dL Premeal glucose targets <140 mg/dL – Random BG <180 mg/dLRandom BG <180 mg/dL– To avoid hypoglycemia, reassess insulin To avoid hypoglycemia, reassess insulin
regimen if BG levels fall below 100 mg/dLregimen if BG levels fall below 100 mg/dL– Occasional patients may be maintained Occasional patients may be maintained
with a glucose range below and/or above with a glucose range below and/or above these cut-points these cut-points
AACE/ADA Target Glucose Level AACE/ADA Target Glucose Level in ICU Patientsin ICU Patients
ICU setting:– Starting threshold of no higher than 180 mg/dLStarting threshold of no higher than 180 mg/dL– Once IV insulin is started, the glucose level should be Once IV insulin is started, the glucose level should be
maintained between 140 and 180 mg/dL maintained between 140 and 180 mg/dL – Lower glucose targets (110-140 mg/dL) may be Lower glucose targets (110-140 mg/dL) may be
appropriate in selected patients appropriate in selected patients – Targets <110 mg/dL or >180 mg/dL are not Targets <110 mg/dL or >180 mg/dL are not
recommendedrecommended Recommended
140-180Acceptable
110-140Not recommended
<110Not recommended
>180
Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4).
http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf.
Case #1Case #1
60 year-old female with a history of COPD admitted with respiratory failure, intubated, and started on tube feeds in the ICU.
The patient is started on an insulin drip to control glucose. After returning from a CT during which tube feeds were discontinued, her glucose is noted to be 55 mg/dL. The patient is asymptomatic, she is treated with dextrose and tube feeds are restarted.
Question: What, if anything, does this low glucose mean for the patients’ prognosis?
Hypoglycemia: what and what Hypoglycemia: what and what is happeningis happening
BackgroundBackground60-120 mg/dL
glucagon
Glucoseinsulin
“fed” state
“post-absorptive”state
G
GG
G
G
G
G
G
Defining HypoglycemiaDefining Hypoglycemia
Symptomatic hypoglycemia: symptoms Symptomatic hypoglycemia: symptoms and BG <70 mg/dLand BG <70 mg/dL
Severe hypoglycemia: event requiring Severe hypoglycemia: event requiring assistance from another person to assistance from another person to administer treatmentadminister treatment
Relative hypoglycemia: symptoms and Relative hypoglycemia: symptoms and BG >70 mg/dL in patient with chronically BG >70 mg/dL in patient with chronically poorly controlled DMpoorly controlled DM
Limited utility in studiesLimited utility in studies
<80 <60 <50 <40<70
normalCounterregulatory hormone release
Adrenergic symptoms
Neuroglycopenic symptoms
lethargycomaseizure
9070
60
50
40
3020
Hypoglycemia Symptoms
Chronic and Recurrent hypoglycemia
Hypoglycemia in Diabetes
Proposed mechanism of Proposed mechanism of increased mortalityincreased mortality
Prolonged, profound hypoglycemia Prolonged, profound hypoglycemia can cause brain death.can cause brain death.
Most deaths are presumed to be due Most deaths are presumed to be due to arrhythmia:to arrhythmia:– HypokalemiaHypokalemia– Sympathoadrenal activationSympathoadrenal activation– Prolonged QTProlonged QT
Potential mechanism of iatrogenic hypoglycemia-induced hypoglycemia-associated autonomic
failure (HAAF) mediated sudden death in diabetes
Cryer. Am J Med 24: 993-996, 2011
Inpatient Hypoglycemia: FrequencyInpatient Hypoglycemia: FrequencyHospital Location Frequency
SICU <40 mg/dL1
5.1%
MICU <40 mg/dL1
18.9%
SICU/MICU <40 mg/dL2
0.34%
ICU <40 mg/dL3
16%
ICU <45 mg/dL4
6.8%
ICU <81 mg/dL5
13.8%
Wards ≤50 mg/dL6
7.7%1. Van den Berge G et al, Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes 2006;55(11):3151-9. 2. Krinsley JS et al, The effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clinic Proc 2004;79(992-1000). 3. Arabi YM et al, Hypoglycemia with intensive insulin therapy in critically ill patients. Crit Care Med 2009;37(9):2536-44. 4. Vriesendorp TM et al, Evaluation of short term consequences of hypoglycemia in an ICU. Crit Care Med 2006;34(11)2714-8. 5. Bagshaw SM et al, the impact of early hypoglycemia and blood glucose variability on outcomes in critical illness. Crit Care Med 2009;13(3):R91. 6. Turchin A et al, Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabetes Care 2009;32(7):1153-7.
Inpatient Hypoglycemia: MortalityInpatient Hypoglycemia: Mortality
1. Egi M et al, Hypoglycemia and outcomes in critically ill patients. Mayo Clin Proc 2010;85(3):217-24. 2. Bagshaw SM et al, the impact of early hypoglycemia and blood glucose variability on outcomes in critical illness. Crit Care Med 2009;13(3):R91 3. Van den Berge et al, Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes 2006;55(11):3151-9. 4. Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA 2009;301(15):1556-64. 5. Turchin A et al, Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabetes Care 2009;32(7):1153-7.
Hospital Location No hypos Hypos
ICU (<81 mg/dL)1 19.7% 36.6%
ICU (<81 mg/dL)2 15.5% 25.6%
ICU (≤40 mg/dL)3 23% 52%
AMI (<60 mg/dl)4 9.6% 12.7%
Wards (≤50 mg/dL)5 0.82% 2.96%
Bagshaw SM et al, the impact of early hypoglycemia and blood glucose variability on outcomes in critical illness. Crit Care Med 2009;13(3):R91
<36 mg/dL
38-4445-52
53-6263-70
71-80≥80
We hold these truths to be self-We hold these truths to be self-evident…evident…
is all hypoglycemia equal?is all hypoglycemia equal?
““Spontaneous” HypoglycemiaSpontaneous” Hypoglycemia
Hypoglycemia occurring without prior Hypoglycemia occurring without prior insulin or anti-hyperglycemic therapy.insulin or anti-hyperglycemic therapy.
Increased in critical illness: mechanical Increased in critical illness: mechanical ventilation, sepsis, renal insufficiency, ventilation, sepsis, renal insufficiency, higher APACHE II score.higher APACHE II score.
Frequency: Frequency: – 26% of all ICU pts with hypoglycemia26% of all ICU pts with hypoglycemia
1 1
– 28% of patients admitted with acute MI28% of patients admitted with acute MI22
1. Krinsley JS et al, The effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clinic Proc 2004;79(992-1000). 2. Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA 2009;301(15):1556-64.
Risk of therapy or marker of Risk of therapy or marker of illness?illness?
Treated with insulin?: AMITreated with insulin?: AMI– Mortality with spontaneous Mortality with spontaneous
hypoglycemia: 18.4%( increased from hypoglycemia: 18.4%( increased from control)control)
– Mortality of insulin-associated Mortality of insulin-associated hypoglycemia: 10.4% (NO increase from hypoglycemia: 10.4% (NO increase from control)control)
Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality in
patients hospitalized with acute myocardial infarction. JAMA 2009;301(15):1556-64.
Kosiborod M et al, Relationship between spontaneous and iatrogenic hypoglycemia and mortality in
patients hospitalized with acute myocardial infarction. JAMA 2009;301(15):1556-64.
Risk of therapy or marker of Risk of therapy or marker of illness?illness?
Correct for comorbid illness:Correct for comorbid illness:– Study #1: case control correcting for Study #1: case control correcting for
age, sex, duration of ICU stay, APACHE II age, sex, duration of ICU stay, APACHE II score: no association with incidental score: no association with incidental hypoglycemia and death (41% vs. 27%, hypoglycemia and death (41% vs. 27%, not significant)not significant)11..
– Study #2: case control correcting for Study #2: case control correcting for diagnosis, APACHE II, age diabetes diagnosis, APACHE II, age diabetes history: Increase mortality associated history: Increase mortality associated with hypoglycemia (55.9% vs. 39.5%)with hypoglycemia (55.9% vs. 39.5%)22..
1. Vriesendorp TM et al, Evaluation of short term consequences of hypoglycemia in an ICU. Crit Care Med 2006;34(11)2714-8. 2. Krinsley JS et al, The effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clinic Proc 2004;79(992-1000).
……butbut
Time from hypoglycemic episode to Time from hypoglycemic episode to death:death:– 221 hours (54-530 hours)221 hours (54-530 hours)11 – 152 hours (87-407 hours)152 hours (87-407 hours)11
– 11 days (0-204 days)11 days (0-204 days)22
1. Van den Berghe, Intensive insulin therapy in mixed medical/surgical intensive care units. Diabetes 2006;55(11):3151-9. 2. Vriesendorp TM et al, Evaluation of short term consequences of hypoglycemia in an ICU. Crit Care Med 2006;34(11)2714-8.
Case #1Case #1
60 year-old female with a history of COPD admitted with respiratory failure, intubated, and started on tube feeds in the ICU.
The patient is started on an insulin drip to control glucose. After returning from a CT during which tube feeds were discontinued, her glucose is noted to be 55 mg/dL. The patient is asymptomatic, she is treated with dextrose and tube feeds are restarted.
Question: What, if anything, does this low glucose mean for the patients’ prognosis?
?????
So…hypoglycemia is bad. So…hypoglycemia is bad. However there is confounding from However there is confounding from
illness, and spontaneous illness, and spontaneous hypoglycema.hypoglycema.
However, we should avoid it. However, we should avoid it.
So what can I do?So what can I do?
Know the Risk FactorsKnow the Risk Factors
Advanced ageAdvanced age Slender and or longstanding diabetesSlender and or longstanding diabetes MalnutritionMalnutrition Active cancerActive cancer Renal diseaseRenal disease Liver disease Liver disease Congestive heart failureCongestive heart failure History of heavy alcohol intakeHistory of heavy alcohol intake Chronic pancreatitisChronic pancreatitis Critical illnessCritical illness
Know who is at most risk to suffer Know who is at most risk to suffer adverse consequencesadverse consequences
Inability to recognize or communicate Inability to recognize or communicate hypoglycemic symptomshypoglycemic symptoms
Stroke patientsStroke patientsDementiaDementiaAltered Mental Status: sedation, Altered Mental Status: sedation,
intubated, previous hypoglycemiaintubated, previous hypoglycemia
Treating your patients’ Treating your patients’ hyperglycemiahyperglycemia
Always use weight-based insulinAlways use weight-based insulin Do not simply order a patients’ outpatient Do not simply order a patients’ outpatient
regimen if it does not appear safe. Beware regimen if it does not appear safe. Beware of programs > 1 unit/kg/day.of programs > 1 unit/kg/day.
Review your patients glucose levels at Review your patients glucose levels at least twice per dayleast twice per day
Consider a change if a glucose is <100.Consider a change if a glucose is <100. Ask yourself, why is my patient low? Why Ask yourself, why is my patient low? Why
is my patient high?is my patient high?
Case #2Case #2
76 yo M with DM2 on admitted from 76 yo M with DM2 on admitted from NH when found confused, BG 58 NH when found confused, BG 58 mg/dL.mg/dL.
Patient with prior CVA, CKD, HTN.Patient with prior CVA, CKD, HTN. Labs on admit: BG 121, Cr 2.72 Labs on admit: BG 121, Cr 2.72
mg/dL, normal LFTs.mg/dL, normal LFTs. Weight: 98 kg.Weight: 98 kg.
Case #2Case #2
Outpatient program: glargine 45 Outpatient program: glargine 45 units at HS, novolog 35 units units at HS, novolog 35 units prebreakfast and presupper.prebreakfast and presupper.
Per NH, FS run 90-180Per NH, FS run 90-180 Most recent A1c 1 month ago 5.1%.Most recent A1c 1 month ago 5.1%.
Case #2Case #2
What are the red flags here?What are the red flags here?– High outpatient doseHigh outpatient dose– Low A1cLow A1c– DementiaDementia– CKDCKD– Advanced ageAdvanced age
What insulin program do YOU What insulin program do YOU recommend?recommend?
Average insulin need: 0.5 u/kg/day Advance age: -0.1 u/kg/day Renal insufficiency: -.0 1 u/kg/day Initial TDD : 0.3 u/kg/day
50% basal15 units of glargine
50% nutritional5 units lispro TID
CorrectionCF 1:50, start at 200 HS
98 kg x 0.3 = apx 30 u/day
How did he do?How did he do?
Fasting Bg on chemistry: 99 mg/dLFasting Bg on chemistry: 99 mg/dL
2 POC: 127 mg/dL, 157 mg/dL2 POC: 127 mg/dL, 157 mg/dL
Case #3Case #3
23 yo M with type 1 diabetes.23 yo M with type 1 diabetes. Weight: 58 kgWeight: 58 kg Inpatient insulin program: 16 units Inpatient insulin program: 16 units
of glargine at HS, lispro 5 TID with of glargine at HS, lispro 5 TID with meals, lispro SS. TDD: 30 units. meals, lispro SS. TDD: 30 units.
Case #3Case #3
C7287
lunch313
supper330
Bedtime257
MN>600
5:40 AM30
Meal insulin and SS
Lispro 9SS
Lispro 10X 1
2:45 AM405
Lispro 10X 1
TDD 30 units/day
Truth and ConsequencesTruth and Consequences Hyperglycemia is a common problem that Hyperglycemia is a common problem that
requires treatment.requires treatment. Insulin treatment carries a risk of Insulin treatment carries a risk of
hypoglycemia (even just “sliding scale”).hypoglycemia (even just “sliding scale”). Both hyper- and hypoglycemia are Both hyper- and hypoglycemia are
associated with an increase in hospital associated with an increase in hospital mortality, hospital cost, and increase LOS.mortality, hospital cost, and increase LOS.
Frequency of hypoglycemia can be Frequency of hypoglycemia can be mitigated by following current guidelines mitigated by following current guidelines for BG targets, tailoring insulin programs, for BG targets, tailoring insulin programs, and being active in assessing your insulin and being active in assessing your insulin program.program.
What can you do? What can you do? Critically evaluate your patients insulin Critically evaluate your patients insulin
program, on admission and daily.program, on admission and daily. Tailor your program to your patientTailor your program to your patient Be aware of insulin “stacking” and Be aware of insulin “stacking” and
appropriate correction insulin dosesappropriate correction insulin doses Always re-evaluate a program if the BG is low, Always re-evaluate a program if the BG is low,
and reconsider if <100.and reconsider if <100. Take the time to figure out what is happening.Take the time to figure out what is happening. Consult the GLUC or NP service if you need Consult the GLUC or NP service if you need
help.help.
Thanks!Thanks!
What do i do for an insulin What do i do for an insulin program?program?
Remaining QuestionsRemaining Questions
What cutoffs should define What cutoffs should define hypoglycemia in studies?hypoglycemia in studies?
How do we sort out the risk of How do we sort out the risk of iatrogenic hypoglycemia from iatrogenic hypoglycemia from hypoglycemia as a marker of hypoglycemia as a marker of disease?disease?
How does hypoglycemia increase How does hypoglycemia increase mortality?mortality?
Hypoglycemia in Patients with Diabetes: Hypoglycemia in Patients with Diabetes: contributing factorscontributing factors
Medication/iatrogenic: insulin, Medication/iatrogenic: insulin, sulfonylureas, meglitinidessulfonylureas, meglitinides
Abnormal hormonal counter-regulationAbnormal hormonal counter-regulation Hypoglycemic unawarenessHypoglycemic unawareness autonomic dysregulationautonomic dysregulation exerciseexercise
Hypoglycemia in patients with Hypoglycemia in patients with Diabetes: contributing factorsDiabetes: contributing factors
Medications/iatrogenic: insulin, Medications/iatrogenic: insulin, sulfonylureas, meglitinidessulfonylureas, meglitinides
Abnormal hormonal counter-regulationAbnormal hormonal counter-regulation Hypoglycemic unawarenessHypoglycemic unawareness Renal and hepatic dysfunctionRenal and hepatic dysfunction Autonomic dysregulationAutonomic dysregulation AgeAge ExerciseExercise AlcoholAlcohol