Hyperglycemia in inpatients: a call for intensive care

1
Hyperglycemia in inpatients a call for intensive
care

• Individualizing therapy for optimal results

2
Hyperglycemia-scope of the problem

• 5.7 million hosp annually, At least 1/4 have
  diabetes, unknown more have hospital related
  hyperglycemia
• Diabetes now 8 of the population. 20
  million! Hyperglycemia common in acute
  illness (50 of ACS patients).
• Patients not known to be diabetic are
  hyperglycemic in hospital
• undiagnosed, insulin-resistant population,
  hyperglycemia secondary to illness
• Cost of inpatient diabetes care-40 Bln
• DM pts 13,243 vs. 2,560 non-diabetics per
  admission
• The most expensive chronic illness in the US
• Source American Association of Endocrinologists

3
An evolving recognition of importance of glucose
control.

• Historically not an issue, no evidence for
  improved outcomes, even 1995 study no short term
  benefit.
• Hyperglycemia expected, even good? Stress
  hyperglycemia
• 1997- Higher CABG wound infection rates with
  hyperglycemia
• 1999- Increased mortality and LOS in CABG
  patients with hyperglycemia
• 2000- CVA 2001 SICU 2006 MICU
• 2003- AACE recommendations of hyperglycemia
• 2005- ADA guidelines
• 2006- AACE ADA

4
The dangers of hyperglycemia

• Patients with AMI, elevated glucose correlates
  with increased mortality and infarct size.
  Correlates with CHF 1
• CVA patients elevated glucose assoc with
  increased mortality 2
• Increasing blood glucose concentrations are
  associated with adverse clinical outcomes in
  patients with AECOPD 3
• Hyperglycemia on admission is independently
  associated with adverse outcomes in patients with
  CAP 4
• Increased risk of wound infection post-CABG 5
• 1. Inpatient diabetes and glycemic control A
  call to action. AACE, 2006
• 2. Parsons MW, et al. Acute hyperglycemia
  adversely affects stroke outcome a magnetic
  resonance imaging and spectroscopy study. Ann
  Neurol 20025220-8.
• 3. E H Baker, et al. Hyperglycaemia is associated
  with poor outcomes in patients admitted to
  hospital with acute exacerbations of chronic
  obstructive pulmonary disease Thorax, April 1,
  2006 61(4) 284 - 289.
• 4. F. A. McAlister, et al. The Relation Between
  Hyperglycemia and Outcomes in 2,471 Patients
  Admitted to the Hospital With Community-Acquired
  Pneumonia. Diabetes Care, April 1, 2005 28(4)
  810 - 815.
• 5. SH Golden, et al. Perioperative glycemic
  control and the risk of infectious complications
  in a cohort of adults with diabetes. Diabetes
  Care 22 1408-1414.

5
Current regimens

• Oral Hypoglycemics
• Sulfonylureas
• Metformin
• Alpha- Glycosidase inhibitors
• Incretin mimetics
• TZDs
• Meglitinides
• Combination drugs

• Insulins (IV, SQ, inhaled)
• Extended
• glargine, ultralente, detemir
• Intermediate
• NPH, lente
• Short
• Regular
• Rapid
• aspart, lispro

6
Theory

• Why so common?
• Counter regulatory hormones/ increased hepatic
  glucose prod/ reduced utilization/ decreased
  perfusion, FFA, cytokines?
• Uncontrolled hyperglycemia causes
• Infection due to Immune dysfunction
  (leukocytes), cytokines, superoxides
• Organ failure due to Inflammation/ endothelial
  damage/ neuronal damage/ increased thrombosis/
  Mitochondrial dysfunction?

7
Definitions

• Diabetes Fasting BS gt126 mg/dL, random gt200
• Hyperglycemia gt126
• Intensive control BS 80-110
• Hypoglycemia lt 60

8
Normoglycemia proven benefits

• 2001 study NEJM, SICU patients with strict BS
  control 80-110
• Reduced mortality by 34
• Sepsis 46
• Renal failure 41
• Transfusion 41
• Polyneuropathy 44
• Van Den Berghe G, Wouters P, Weekers F, et al.
  Intensive insulin therapy in critically ill
  patients. N Engl J Med. 20013451359-1367.

9
Normoglycemia proven benefits!

• Recent study in MICU
• For patients who stayed gt3 days, reduced
  mortality 18, less renal dysfunction, prolonged
  mechanical ventilation.
• Patients lt 3 days, increased mortality?? 1
• Recent meta-analysis showed 15 decrease in
  mortality in a variety of settings. 2
• 1. Van den Berghe G, Wilmer A, Hermans G, et al.
  Intensive insulin therapy in the medical ICU N
  Engl J Med. 2006 354449-61.
• 2. Pittas AG, Siegel RD, Lau J. Insulin therapy
  for critically ill hospitalized patientsa
  meta-analysis of randomized, control trials. Arch
  Inter Med. 2004 1642005-2011.

10
Normoglycemia proven benefits

• DIGAMI- intensive insulin therapy 29 reduction
  in mortality at 1 year. (Independent effect of
  insulin?)
• CABG patients Intensive therapy reduces sternal
  infections by 57, 66 reduction in mortality 1
• MICU patients intensive therapy catheter sepsis
  decrease 33.5, LOS 0.25 days 2
• 1. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A.
  Continuous intravenous insulin infusion reduces
  the incidence of deep sternal wound infection in
  diabetic patients after cardiac surgical
  procedures. Ann Thorac Surg 199967352-62.

11
Normoglycemia How to do it?

• Goal physiologic mimicry
• Options
• Oral meds ? ProblemsDiscontinue? OralInsulins?
• Change to insulin for better control? SQ or IV?
• Sliding scale?
• Meal time insulins?
• Drip? Pumps?

12
Sliding scale insulin

• History and whats wrong
• Abandoned! Retroactive not proactive
• Chasing our tail, esp. Type I
• Basal insulin
• Mealtimes/ eating
• Variation in disease state
• Dangers of hypoglycemia

13
Its as easy as BBC

• FS Glucose qAC and qHS
• Check HbA1C
• Then
• BASAL NPH/Glargine 0.2units/kg/day or drip
• BOLUS Aspart/ Lispro 0.05units/kg meals
• CORRECTION Both long acting and short acting

14
General recommendations for SQ insulin therapy

• Treatment goal for patient on SQ regimen is
  pre-prandial glucose level of 80-150 mg/dL,
  Insulin therapy should provide both basal and
  prandial insulin support when needed
• Basal insulin
• --Long-acting (glargine, detemir) - provides
  peakless insulin coverage for 24 hours
• --Intermediate-acting (NPH) - Peak effect 4-6
  hours after administration with about 12 hour
  duration of activity
• Prandial and correction insulin
• --Short-acting (Regular) - Peak effect 2-3
  hours after administration with about 6 hour
  duration of activity.
• --Rapid-acting (lispro, aspart, glulisine) - Peak
  effect 1 hour after administration with about 2
  hour duration of activity.

15
Initiating SQ insulin therapy Already on
Insulin

• All patients with type 1 diabetes and most
  patients with insulin-dependent type 2 diabetes
  require basal insulin, even when NPO.
• 1. Estimate starting daily insulin dosesFor
  patients with insulin dependent diabetes If
  good oral intake is expected, continue usual home
  insulin regimen If poor oral intake is
  expected or if NPO o basal insulin
  glargine, detemir at 75 of home dose OR
  o intermediate-acting insulin NPH at 50 of
  home dose o short-acting insulin hold
  rapid-acting (lispro, aspart, glulisine) and
  replace with Regular insulin sliding scale.
  

16
Considerations

Lower dose Higher dose
No previous DM Elevated HbA1C
Glucose sl elevated Glucose high
Poor PO good to excessive PO
Impaired renal function Metabolic stress
Corticosteroids
17
Initiating insulin New to Insulin

• For most patients with type 2 diabetes (or
  being initiated to insulin therapy), total daily
  insulin dose can be estimated at 0.3 to 0.6
  units/kg/day The dosing range represents varying
  degrees of insulin resistance
  

dose kg 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
50 5 10 15 20 25 30 35 40 45 50
60 6 12 18 24 30 36 42 48 54 60
70 7 14 21 25 35 42 43 56 63 70
80 8 16 24 32 40 48 56 64 72 80
90 9 18 27 36 45 54 63 72 81 90
100 10 20 30 40 50 60 70 80 90 100
18

Initiating SQ insulin therapy

• 2. Estimate scheduled doses.
• Glargine insulin - about 50 of total daily dose
• Lispro insulin - about 50 of total daily dose
• divided into the 3 meals Example For an
  80 kg patient who is new to insulin - -
  glargine insulin 12 units SQ at hs - lispro
  insulin 4 units SQ before each meal (hold if
  NPO or intake poor)
• NPH insulin - about 44 of total daily dose
  before breakfast meal, and about 17 of total
  daily dose at hs Regular insulin - about 22 of
  total daily dose before breakfast meal, and
  about 17 of total daily dose before supper
  meal Example For an 80 kg patient who is
  new to insulin - - NPH insulin 11 units SQ
  before breakfast and 4 units SQ at hs -
  Regular insulin 5 units SQ before breakfast
  and 4 units SQ before supper meal

19
Initiating SQ insulin therapy

• 3. Add correction insulin doses as desired
• Monitoring of glucose levels and titration of
  insulin doses at least daily a. If blood
  glucose levels are consistently too high/low, the
  total daily insulin dose can be adjusted by
  shifting to a column to the right/left on the
  total daily dose table above b. Insulin doses
  are adjusted based on subsequent glucose
  levels i. glargine and evening NPH
  insulin doses based on glucose levels
  at 0200 and before breakfast ii. mealtime
  insulin doses based on glucose levels before the
  next meal and at hs
• c. RN may administer as little as 50 of
  SCHEDULED insulin dose if
• i. Patient has had change to NPO status
  and blood glucose is lt 150 mg/dL.
  ii. Patient has had decline in PO intake to less
  than 33 from previous and blood
  glucose is lt 150 mg/dL.

20
Insulin drip

• Indication for intravenous insulin infusion among
  nonpregnant adults with established diabetes or
  hyperglycemia
• Diabetic ketoacidosis and nonketotic hyperosmolar
  state A
• General preoperative, intraoperative, and
  postoperative care C
• Postoperative period following heart surgery B
• Organ transplantation E
• MI or cardiogenic shock A
• Stroke E
• Exacerbated hyperglycemia during high-dose
  steroid therapy E
• NPO status in type 1 diabetes E
• Critically ill surgical patient requiring
  mechanical ventilation A
• Dose-finding strategy, anticipatory to initiation
  or reinitiating of subcutaneous insulin therapy
  in type 1 or type 2 diabetes C

21
Insulin drip

• Advantages
• Tightest control
• Good absorption
• Rapid adjustments
• Easy standardized

• Disadvantages
• Frequent monitoring (ICU/IMCU needed?)
• Nursing time!
• Catheter complications
• Problems when switching to SQ regimen
• Rapid Glucose shifts?

22
What about hypoglycemia ?

• BG level 40 mg/dL was 5.2 in intensive
  insulin-treated patients versus 0.8 in
  conventionally treated patients.1
• But In a national survey, Cohen et al. found
  that 11 of serious medication errors resulted
  from insulin misadministration.2
• Need for frequent monitoring
• Need for separate protocol, oral and IV D50
  administration. Prevents overshooting
• van den Berghe G, Wouters PJ, Bouillon R, Weekers
  F, Verwaest C, Schetz M, et al. Outcome benefit
  of intensive insulin therapy in the critically
  ill insulin dose versus glycemic control. Crit
  Care Med 200331359-66.
• Cohen MR, Proulx SM, Crawford SY. Survey of
  hospital system and common serious medication
  errors. J Healthc Risk Manag 19981816-27.

23
Logistics

• Multidisciplinary steering committee
• Standardized order sets
• Glycemic management team.
• Monitoring results.
• Hypoglycemic protocol
• Nutrition
• Diabetes education

24
Cost vs. benefits

• Each increased 50 mg/dL of blood glucose added
  0.76 LOS in diabetic CABG patients.1
• Use of diabetes team 56 reduction LOS
  2353/patient.2
• Intensive therapy in SICU saves 40K/year.
• Furnary AP, et al. Postoperative hyperglycemia
  prolongs length of stay in hospitalized patients
  with diabetic CABG patients. Circulation. 2000
  102 (18) II-556.
• Koproski J et al. Effects of an intervention by a
  diabetes team in hospitalized patients with
  diabetes. Diabetes Care. 1997 201553-1555.

25
Barriers

• Fear of hypoglycemia
• Nursing time, data collection.
• Lack of standardization
• Changing insulin requirements
• Skepticism to benefits of good control.
• Multiple transfers of patients.

26
Further research

• Refinement of protocols
• Impact of hyperglycemia in development of DM
• Non critically ill patients goals?
• Continuous monitoring (pulse ox of the future)
• Role of feedings