Hyperglycemia in the Hospital

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Hyperglycemia in the Hospital
Scott K. Ober, MD, MBA Clinical Manager Community
Outpatient Services
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Case Example

• 68 y/o female admitted with several days of chest
  pain.
• PMHx notable for DM, last A1C 9.6, , HTN,
  hyperlipidemia
• Meds Glyburide 1000 bid, Lisinopril 20 mg bid
  Metoprolol 25 bid
• PE Afeb 142/94 P 110
• Lungs basilar rales.
• Cor Tachy No murmurs
• EKG ST elevation II, III AVF, WBC 6.3, Glu 258,
  Cr 1.4, ECHO inferior hypokinesis, EF 38
• Admitted CICU Glyburide was held, ASA Lovenox
  added, B-blocker increased Cath and stented in
  RCA for near total occlusion
• Sliding Scale Regular 150-200 2units 201-150 4
  units, 251-300 6 units 301-350 8 units, 351-400
  10 units, gt400 call House Officer

• Hospital Course
• Stabilized in 48 hours
• PO intake adequate
• Glucose day 2 280 (serum)
• Glucose day 3 245 (serum)
• Unclear fingerstick values, ordered but not
  commented on in chart
• Difficult to find amount of insulin given with
  sliding scale
• Discharge day 6 on Glyburide to follow-up with
  Primary Care Physician

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Inpatient Hyperglycemia

• Prevalence 20 or higher
• higher in teaching hospitals
• Effects
• Immune function
• Small studies, various populations
• Phagocyte dysfunction
• Pathway alteration
• Reduced superoxide formation from aldose
  reductase, alterations Protein kinase C, and
  other mediators

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More effects

• Heart Acute Hyperglycemia
• Impairs ischemic preconditioning, protective
  mechanism limits infarct size
• induce myocyte death through apoptosis
• exaggerates ischemia reperfusion injury cellular
  injury
• Thrombosis increased
• Increased platelet activation
• Inflammation
• Increases variety of factors IL-6, TNF-alpha,
  Nuclear Factor (NF)-kB
• Linked to detrimental vascular effects
• Endothelial cell dysfunction
• inhibits vasodilatation

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Even More Effects

• Brain
• enhanced neuronal damage
• increased tissue acidosis and lactate levels
• accumulation glutamate
• predicts neuronal damage
• Oxidative Stress
• Direct tissue damage or activation of mediators

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Is there a threshold?

• General Surgery
• Observational 97 pts. with DM undergoing surgery
• Blood glucose gt 220 POD 1 predicted infections
• Gen Med - Review 2030 admissions
• Normoglycemia 108 mg/dl
• New Onset Hyperglycemia (12) 189 mg/dl
• Diabetic Patients (26) 230 mg/dl
• Results Mortality

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Cardiac Studies

• Meta-analysis of 15 studies of AMI patients
  (Capes, et al) and admission glucose values
• threshold 110 for patients w/out DM Rel Risk is
  3.9 in-hospital mortality
• threshold 180 for patients with DM Rel Risk is
  1.7 in-hospital mortality
• Consecutive admissions of all patients with AMI
  (Bolk, et al)
• 1 year mortality was about 20 for glucose lt 100
  and rose to 44 for glucose gt 200
• Diabetes and Insulin-Glucose Infusion in Acute
  MI DIGAMI, Malberg, et al, 1995
• prospective 620 DM with AMI, Randomized
• Intervention Maintain Glucose 126-196, followed
  intensive outpt SQ Insulin
• results baseline glucose 270's, decreased to 170
  within 1st 24 hrs vs 210 control
• Hospital mortality (12 vs. 5) Rel. reduction
  58 plt0.05
• One year mortality was 26 vs. 19. plt0.05

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More Cardiac Studies

• Two more studies (DIGAMI 2, CREATE-ECLA, 2005)
  used an insulin-glucose infusion showed that
  blood glucose levels were positively correlated
  with mortality although this was not reduced.
• Malberg et al. DIGAMI 2, Eur Heart J
  26650-661,2005
• Mehta et al, CREATE-ECLA JAMA 293437-446,2005

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Cardiac Surgery

• Observational study
• 1987-1991 SC Insulin
• 1991-1998 IV Insulin Target 150-200
• 1999-2000 IV Insulin Target 125-175
• 2001-2003 IV InsulinTarget 100-150
• Trends for decreased wound infection and hospital
  mortality

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Critical Care

• Randomized Controlled Trial 1548 SICU patients on
  Mechanical Ventilation
• Intensive Insulin Tx. Target 80-110
• Conventional Target 180-200
• Results Reduction in-hospital mortality 34,
  linear association, both DM and non-DM

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Critical Care

• MICU study, similar to SICU protocol studied one
  group with intensive insulin tx (mean glucose
  110) vs. conventional tx (mean 160)
• Reduced morbidity and reduced mortality for
  patients treated gt 3days but unable to identify
  prospectively
• van der Berge G. intensive insulin tx in the
  MICU, NEJM 354449-461, 2006

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Neurology

• Observational Studies
• In general, hyperglycemia assoc. with worsened
  outcomes in stroke and head injury Glucose
  Insulin Stroke Trial GIST
• Assess safety of lowered glucose in acute stroke
• target 72-126 mg/dl appeared acceptable
• No data suggests control improves clinical
  outcomes
• The American Heart Association/American Stroke
  Association guidelines recommend treatment with
  insulin in patients glucose concentrations gt140
  to 185 mg/dL
• European Stroke Initiative guidelines recommend
  treatment for glucose gt180 mg/dL
• European Stroke Initiative Recommendations for
  Stroke Management-update 2003. Cerebrovasc Dis
  200316(4)311-37.

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Common Errors in Management

• Admission Orders
• Usually continued from outpatient regimen
  Failure to modify
• High Glycemic Targets
• ADA for hospitalized patients
• Preprandial less than 110
• Postprandial less than 180

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Common Errors in Management

• Lack of Therapeutic Adjustment
• Day of discharge, team realizes patient has been
  on regular insulin during entire hospital stay
• Overutilization of Sliding Scales
• Underutilization of Insulin Infusions

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Whats our practice at Wade Park?

• DM inpatient nurse managers
• Monitor all patients who have a glucose less than
  70
• Nurse run inpatient programs are the trend
• Improved patient satisfaction
• Reduced length of stay
• Sampson, et al. Trends in bed occupancy for
  inpatients with diabetes before and after the
  introduction of a diabetes inpatient specialist
  nurse service. Diabetic Medicine 23, 1008-1015
  (2006)

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Summary ADA Major recommendations for hospital
management of hyperglycemia

• Target plasma Glucose lt110 preprandial and lt180
  postprandial, flexible
• Scheduled insulin improve blood glucose control
  compared to sliding scale alone
• Intensive IV insulin tx, goal of glucose 80-100,
  may reduce morbidity and mortality among
  critically ill patients but risk of hypoglycemia
• IV insulin infusion is safe and effective (not
  available on Wards yet)
• Team based approach with std. hospital protocols
  reduces hyper and hypo-glycemics events
• Essential components are education, nutrition tx
  and proper discharge planning

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How to achieve target levels ?

• Oral hypoglycemics
• do not allow rapid dose changes
• may be contraindicated
• Metformin, TZDs
• Insulin Sliding Scale without other intermediate
  or long acting insulins
• Ineffective vs. Dangerous
• Not modified during admission
• Treats after the fact
• Reason that no regular insulin is given at
  bedtime

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Conceptualizing Insulin

• Basal
• Infusion, NPH, Glargine
• Prandial/Nutritional
• Regular, Lispro and Aspart
• Carb Counting
• Correction - functional sliding scale

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Pharmacokinetics

• NPH
• Onset 2-4 hours
• Peak 4-10 hours
• Duration 12-18 hours
• Glargine
• Onset 2-4 hours
• Peak None
• Duration 20-24 hours

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Pharmacokinetics

• Regular
• Onset 30-60 minutes
• Peak 2-3 hours
• Duration 8-10 hours
• Lispro
• Onset 5-15 minutes
• Peak 30-90 minutes
• Duration 4-6 hours

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Insulin Infusion

• Insulin infusion started at 1 unit/hr
  assumption that 50 of the ambulatory daily
  insulin dose is the basal requirement may also be
  used to estimate initial hourly requirements ---
  Alternatively, 0.02 units/kg per hr
• Use lower rate for patients with renal or hepatic
  failure
• Check glucose q. hour until stable about 6-8
  hours then every 2-3 hours
• Transition to SQ insulin

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Calculating Insulin Dose

• 1. Start with 70 (60 if EGFRlt60) of Total home
  Daily Dose.
• 2. If not on insulin at home, then estimate the
  total daily dose based on 0.4 units/Kg.
• 3. In general, half can be given as long acting
  and half can be given
• pre- meals.
• 4. In case of NPH (which is ½ the total daily
  insulin), split the dose by 2 and give q AM q
  HS.
• 5. In case of Glargine (which is ½ the total
  daily insulin) give the full dose at bedtime.
• 6. Short acting insulin (which is ½ the total
  daily insulin) can be divided by three and given
  prior to meals.
• 7. Supplemental Sliding scale is added to the
  prandial dosages.
• 8. If patient is NPO, then only ½ the
  long-acting insulin should be used.
• 9. Continuous Tube Feeding Reg Insulin q. 6
  hours, Bolus tube feeding bolus Reg insulin or
  consult Endocrinology

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Case Example Revisited

• 68 y/o female admitted with several days of chest
  pain.
• PMHx notable for DM, last A1C 9.6, , HTN,
  hyperlipidemia
• Meds Glyburide 10 bid, Lisinopril 20 mg bid
  Metoprolol 50 bid
• PE Afeb 142/94 P 110
• Lungs basilar rales.
• Cor Tachy No murmurs
• EKG ST elevation II, III AVF, WBC 6.3, Glu 258,
  Cr 1.4, ECHO inferior hypokinesis, EF 38
• Admitted CICU Glyburide was held, ASA Lovenox
  added, B-blocker increased Cath and stented in
  RCA for near total occlusion
• Sliding Scale Regular 150-200 2units 201-150 4
  units, 251-300 6 units 301-350 8 units, 351-400
  10 units, gt400 call House Officer

• Outpatient DM meds restarted after cath
• Start Glargine or NPH HS
• Use Correction Scale of Lispro/Regular
• Increase Glargine/NPH as needed
• Target Preprandial lt110, Post prandial lt180
• Better long term outcomes?

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More Cases

• 78 y/o woman with DM type 2, A1c 7.6, takes
  Metformin 1g bid and 10mg glyburide, admitted
  with USA.
• Cath to occur in AM, npo after midnite.
• Admission Glucose 132.
• How should she be treated?

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More cases (cont)

• If pt. npo, hold oral agents
• D/C Metformin until 48 hours after procedure
• Patient should be monitored off meds and given
  her hx. of controlled DM should not require
  insulin

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More cases (cont)

• 61 y/o male with 12 yr. Hx DM type II,
  hospitalized with LLE cellulitis. Outpt. Meds are
  Glyburide 10 BID and Metformin 1 g bid. Admission
  Glucose is 248 and HbA1c 11.4
• How to treat this patient?

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More cases (cont)

• Hospitalization offers opportunity to change
  regimen
• Value of adding TZD?
• Consult Nutritionist
• Bedtime NPH Insulin