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Diabetes

Management in
Hospital Based -
Insulin Therapy
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Diabetes in Hospitalized Patients

Prevalence of DM in hospitalized patients 12-26%


Fourth most common co-morbid condition among
hospitalized patients
>1012% of all hospital discharges
29% of all cardiac surgery patients
13 days longer hospital stay
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Hogan P, et al. Diabetes Care. 2003;26:917932.


American Association of Clinical Endocrinologists. Available at:
http://www.aace.com/pub/ICC/inpatientStatement.php. Accessed March 17, 2004.

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Higher Costs: Diabetes in
Hospitalized Patients
Higher rate of hospitalization
Longer stays
More procedures, meds.
Chronic complications
More arteriosclerotic disease-
More infection
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Hyperglycemia in Patients with
Undiagnosed Diabetes

Hyperglycemia occurred in 38% of patients


admitted to the hospital
26% had known history of diabetes
12% had no history of diabetes
Newly discovered hyperglycemia was
associated with:
Higher in-hospital mortality rate (16%) compared
with patients with a history of diabetes (3%) and
patients with normoglycemia (1.7%; both P < 0.01)
Longer hospital stays; higher admission rates to
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intensive care units


Less chance to be discharged to home (required
more transitional or nursing home care)
Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87:978982.
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Total In-patient Mortality
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Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: an independent marker of in-
hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2002;87(3):978-82.

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The Increasing Rate of Diabetes Among
Hospitalized Patients

48%
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Available at: http://www.cdc.gov/diabetes/statistics/dmany/fig1.html | 6


and increased mortality in critically ill
patients
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Krinsley, Mayo Clin Proc 2003 | 7


Identification of Hyperglycemia in
Hospitalized Patients

Mandatory screen of all high risk patients:


- ICU patients
- Cardiovascular patients
- Steroid treated patients
- TPN patients
- Patients with infections
- Pregnant patients
- Surgery / Ortho patients
- ? All patients
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Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87:978982.


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Potential Consequences of
Hyperglycemia in the Hospital
Impaired
leukocyte Electrolyte fluxes
function Volume depletion
Chemotaxis
Worsened
Adherence
gastroparesis
Phagocytosis
Bactericidal killing Additional -cell
impairment in type
Poor wound 2
healing
Insulin resistance
Increased
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infection rate A signal to the


patient that
with TPN glucose control is
Risk of ischemia unimportant | 9
Recent Associations Between Glucose
Levels and Inpatient Outcomes

Hyperglycemia a risk factor for:


Complications of strokes
Complications of MI
Complications of vascular and cardiac
surgery
Mortality in critically ill
Mortality in trauma patients
Complications of orthopedic surgery
Aggressive insulin treatment
improves:
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Cardiac surgery outcomes


MI outcomes
Intensive care unit outcomes | 10
Consequences of Poor Glycemic Control in
Hospital Patients

Hyperglycemia, with or without a diagnosis of


diabetes, can result in
Increased Mortality
Increased Morbidity
Admission to the ICU
Need for extended care
Overall poor outcomes
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Umpierrez GE et al. J Clin Endocrinol Metab. 2002;87:978-982. Bolk J et al. Int J Cardiol. 2001;79:207-214.
Williams LS et al. Neurology. 2002;59:67-71. Malmberg K, et al. BMJ. 1997;314:1512. Van den Berghe G et al. N
Engl J Med. 2001;345:1359-1367. Capes SE et al. Stroke. 2001;32:2426-2432.

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Proposed Pathophysiology of Glucose Damage
Hyperglycemia and Poor Hospital Outcome
Metabolic stress response

stress hormones and peptides

Glucose
Insulin
Reactive O2 species
Immune dysfunction
FFA
Ketones Transcription
Lactate factors
Infection dissemination
Secondary
Cellular injury/apoptosis mediators
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Inflammation
Tissue damage
Altered tissue wound repair

Prolonged hospital stay Clement| et12al,


Disability / Death Diabetes Care 27:553-591, 2004
Proven Poor Outcomes Linked to Hyperglycemia
in In-Patients

Meta-analysis of post-MI patients - BG >110 mg/dl associated with higher


mortality and CHF.

Post CVA - BG >110 mg/dl greater in-hospital mortality.


BG 180 vs. 90 increased infarct size and worse function

General wards - newly identified diabetes with FBG >126 mg/dl or random
>200 mg/dl 10-fold increase in mortality and longer hospital stays.
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Post-surgery - BS > 220 day post-op day 1 near 6-fold increase in serious
infections.

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Potential Benefits Of Improved Glucose
Control In The Hospital
Reduced Mortality

Reduced Morbidity

Reduced Costs Of Care


Length of stay (LOS)
Cost of inpatient complications
Antibiotics and other meds
Mechanical ventilation
Dialysis
Diagnostic procedures
Ischemic events or added ischemic injury
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Reduced re-hospitalization/ delayed morbidity


Reduced extended care

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Intensive Insulin Therapy in Critically Ill
PatientsMorbidity and Mortality Benefits

Blood
Mortality Sepsis Dialysis Transfusion Polyneuropathy

Percent
Reduction
34%
41%
44%
46%
50%
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van den Berghe G, et al. N Engl J Med. 2001;345:13591367.


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Consensus Conference of American College of
Endocrinology - December 2003

Strongly support the need for


early detection of hyperglycemia
in the hospital and an aggressive
management approach to
improve outcomes
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Insulin: The Most Effective Treatment
for Inpatient Glycemic Control
Adaptable to increased insulin requirement
during acute illness
Basal insulin administration can prevent
excess gluconeogenesis and ketogenesis
Dose can be adapted to various categories
of patient nutrition status
IV dextrose
Total parenteral nutrition
Enteral feeding
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Nutritional supplements

Clement S et al. Diabetes Care. 2004;27:553-591. | 17


AACE - Consensus Conference Blood
Glucose Targets

Upper Limit Inpatient Glycemic


Targets:
ICU: 110 mg/dl (6.1 mmol/L)

Non-critical care (limited data)


Pre-prandial: 110 mg/dl (6.1 mM)
Maximum: 180 mg/dL (10 mM)

The current ADA guideline for pre-


prandial plasma glucose levels is 90
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130 mg/dl
AACE- Endocrine Practice 10 (1): 77-82, 2004
ADA- Diabetes Care 27: 553-591, 2004

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AACE-ADA Consensus Statement
on Inpatient Glycemic Control: ICU

Tighter targets ( <110 mg/dl ) not


safe; >180 mg/dl not acceptable.

Lower target ( 110-140 mg/dl )


acceptable in selected patients if
hospital achieving this successfully.

Start IV insulin at threshold


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no higher than 180 mg/dl.

Glucose target = 140-180 mg/dl


Moghissi E et al., Diabetes Care 2009;32:1344;
Moghissi E et al., Endocrine Practice 2009;15:353
? Greater benefit at lower end | 19
How can we be more
successful in
achieving glycaemic
goals?
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Inpatient Management Principles

OHA use discouraged in most


inpatients.

Match insulin program to eating status


of patient.
Discourage sliding scales.

Dosing based on standardized


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protocols.

Aggressive BS management.
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Control highs, minimize lows.
Potential Effects Of Insulin Therapy

Reduction of hyperglycemia

Delivery of glucose substrate


Applicable to Glucose-Insulin-Potassium
(GIK) infusions

Direct effects of insulin


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Reported Benefits of Insulin Therapy Acute and
Chronic

Anti-inflammatory effect
Reduced CRP
Reduced ROS generation in monocytes
Reduced monocyte chemoattractant protein-1
(MCP-1)
Reduced NFB activation
Induction of eNOS and increased NO
Inhibition of growth response gene-1 (Egr-1)

Anti-fibrinolytic effect
Reduced PAI-1 levels
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Reduced fibrinogen

Increased neutrophil counts


Melidonis A. etand
al. Clinical Cardiology 23:160, 2000
phagocytic activity Rask-Madsen C et al. Diabetes 50:2611, 2001
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Dandona P et al. JCEM 86:3257, 2001
Reported Benefits of Insulin Therapy Acute and
Chronic (cont)

Improved endothelial cell function

Direct arterial vasodilation


Including evidence of increased myocardial blood
flow

Reduced free fatty acids

Reduced infarct size in animal models of MI

Reduced muscle catabolism in catabolic states such


as burns
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Protection from ischemic brain damage in animal


models of stroke

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Methods For Managing Hospitalized Persons
with Diabetes

Intravenous therapy : Continuous Variable


Rate IV Insulin Drips if : Acute & severe cond,
majorsurgery, Unstable, MI, DKA,
Hyperglycemia, Steroids, Gastroparesis,
Delivery, etc

Subcutaneuos therapy : Basal / Bolus Therapy


when eating
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Sliding scale insulin Former regimen

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NO to Sliding Scales!!

WHY?

Ineffective- Treats hyperglycemia after it has already


occurred, instead of preventing the occurrence of
hyperglycemia

This reactive approach can lead to rapid changes in


blood glucose levels, exacerbating both hyperglycemia
and hypoglycemia
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Queale, W. Arch Intern Med/Vol 157, Mar 10, 1997, 545-552.


Smith, WD, Am J Health Syst Pharm. 2005 Apr 1; 62(7): 714-9.
Schoeffler JM, Ann Pharmacother. 2005 Oct; 39(10) 1606-9.

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Physiologic Insulin needs

ILLNESS-
RELATED

SUPPLEMENTAL/Correction

NUTRITIONAL
BASAL
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Insulin Terminology
There are three components to subcutaneous
insulin therapy:

Basal insulin to control blood glucose between meals


(Controls hepatic glucose production)

Meal or Nutritional or prandial or bolus Short-acting


insulin given with meals in anticipation of
carbohydrate load glycemic spike insulin to cover
the CHO load at the meal
(Based on meal CHD content)
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Correction / Suplemen insulin to bring a high blood


glucose into target range.
(Treats acute elevation in blood glucose)
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Basal and Bolus Insulin Pharmacodynamics

Formulation Coverage Duration (hr) Dosing


Glargine Basal 24 Once daily
Bas

Detemir Basal 20 Once to twice daily


al

NPH Basal 13 Twice daily

Lispro Prandial 34 15 min premeal to


Prandial/B

immediately postmeal
Aspart Prandial 34 15 min premeal to
olus

immediately postmeal
Glulisine Prandial 34 15 min premeal to
20 min postmeal
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RHI Prandial 68 30 min premeal

RHI = regular human insulin


Flood TM. J Fam Practice.
2007;56(suppl):S1-12.| 31
Insulin Analogues compared with Human
Insulins: Action Profiles

Action Profiles of Insulins


Aspart, glulisine, lispro 45 hours
Plasma Regular 68 hours
insulin NPH 1216 hours
levels
Detemir ~14 hours
Ultralente 1820 hours
Glargine ~24 hours
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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Hours
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Burge MR, Schade DS. Endocrinol Metab Clin North Am. 1997;26:575-598; Barlocco D. Curr Opin Invest
Drugs. 2003;4:1240-1244; Danne T et al. Diabetes Care. 2003;26:3087-3092
Ideal Basal Insulin

Closely mimic normal pancreatic basal insulin


secretion
No distinct peak effect
Continued effect over 24 hours
Reduce nocturnal hypoglycemia
Once-daily administration for patient
compliance
Predictable absorption pattern
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Basal/Bolus Treatment with Rapid-acting & Long-
acting Insulin Analogs
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Starting Basal-Bolus
Calculate starting total daily dose (TDD)
0.3 units/kg/day (hypoglycemia risk factors,
nave patient)
0.4 units/kg/day (conservative for most
patients)
0.5 0.6 units/kg/day (overweight to
obese)
Adjust TDD up or down based on
Past response to insulin
Presence of hyperglycemia inducing agents,
stress
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This Is very conservative and safe (adjust


up as needed)
Basal insulin = 40-50% of TDD
Prandial & Suplement : 50 60 % of TDD | 35
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 doses:


For 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
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dose
o short-acting insulin: hold rapid-acting (lispro, aspart,
glulisine)

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Initiating SQ insulin therapy

2. Estimate scheduled doses.


Glargine insulin - about 50% of total daily dose
Glulisine 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
- Glulisine 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
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and 4 units SQ at hs
- Regular insulin 5 units SQ before breakfast
and 4 units SQ before supper meal

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nitiating 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
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
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next meal and at hs

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Insulin Administration Guidelines
Test capillary blood glucose before meals,
bedtime and when appropriate at 3 AM.
If BG is in target range at meal time give the
meal bolus within 15 minutes of the start of
the meal
If the BG is above target range at meal time
give the meal bolus plus the correction bolus
The basal insulin is administered whether the patient is eating or
not.
Corrections are given whether the patient is eating or not.
The meal bolus is held if the patient is not eating or is adjusted
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based on the amount of carb consumed at the meal.

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If the Patient is NPO or unable to eat

Insulin basal should still be given

Accuchecks every 6 hours

Prandial insulin not needed

Correction insulin should still be given


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BG goal 90-130 mg/dl

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Correction Factor Insulinthe new, improved
sliding scale

To correct pre-meal hyperglycemia

Given in addition to scheduled


mealtime insulin as one injection after
the meal

Algorithms based upon the total


insulin dose per day
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Correction Factor Insulin
Premeal Prandial Premeal Prandial
Premeal Prandial
BG Insulin BG Insulin
BG Insulin
130-170 1 unit 130-170 3 unit
130-170 1 unit
171-220 2 units 171-220 3 units 171-220 5 units

221-270 3 units 221-270 5 units 221-270 7 units

271-320 4 units 271-320 7 units 271-320 9 units

>320 5 units
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>320 9 units >320 11 units

40 units insulin/day 41-80 units insulin/day >80 units insulin/day

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Adjusting Basal Insulin
Fasting BG Change
Make daily Basal
adjustments of basal Insulin
insulin based on <70 20%
fasting (AM) BG
71-90 10%
90-130 no change
131-180 by 10%
181-230 20%
231-280 30%
>281 40%
Correction Bolus (Supplement)

Must determine how much glucose is lowered


by 1 unit of rapid-acting insulin

This number is known as the correction factor


(CF) :
1. Use the 1700 rule or Weight to estimate
the CF
CF = 1700 divided by the total daily dose
(TDD)
[ex: if TDD = 50 units, then CF = 1700/50
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= ~30
meaning 1 unit will lower the BG ~30
mg/dl ]
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Formula
Current BG - Ideal BG
Glucose Correction factor

Example:
Current BG: 250 mg/dl
Ideal BG: 100 mg/dl
Glucose Correction Factor: 30 mg/dl
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250 - 100
30 = 5.0 u
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Initiating SC Basal Bolus

Contoh : Pasien di rawat di RS dgn glukosa 300 mg/dl,


Berat badan 60
kg dan target glukosa yg diinginkan 120 mg/dl
Starting total dose = 0.5 x wgt. in kg
Wt. is 60 kg; 0.5 x 60 = 30 units
Basal dose (Glargine) = 50% of starting dose
0.5 x 30 = 15 units
Bolus/prandial doses (Lispro, Aspart, Glulisine) = 50% of
starting dose
0.5 x 30 = 15 divided by 3 = ~ 5 units pc (tid)
Correction bolus = (BG - 100)/ CF,
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CF = 1700/total daily dose (30) ; CF = 57


Jadi dosis insulin koreksi :
300 120 / 57 = 3 unit Aspart / glulisine yang
ditambahkan pada dosis prandial
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Insulin Drip

Advantages Disadvantages
Frequent monitoring
Tightest control (ICU needed?)
Good absorption Nursing time!
Rapid adjustments Catheter
Easy standardized complications
Problems when
switching to SQ
regimen
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Rapid Glucose shifts?

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Indications for IV Insulin Drip - Think
broad.
Diabetic Labor and delivery
ketoacidosis High-dose
glucocorticoid
Nonketotic therapy
hyperosmolar state Perioperative period
Critical care illness After organ
(surgical, medical) transplant
Postcardiac surgery Total parenteral
nutrition therapy
Myocardial
infarction or
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cardiogenic shock
American Association of Clinical Endocrinologists. Available at:
http://www.aace.com/pub/ICC/inpatientStatement.php. Accessed March 17, 2004.

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Threshold blood glucose in mg/dL for
starting IV insulin infusion
Peri-operative care: > 140
ICU care: > 110 - 140 *
Non-surgical illness: > 140 - 180 * *
Pregnancy > 100

* Van den Berghes study supports 110;


Finneys study supports 145
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* * If drip indication is failure of SQ therapy, use 180 ;


if indication is specific condition ( DM 1/ NPO, MI,
etc ), use 140
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Intensive versus Conventional Glucose Control in
Critically Ill Patients
The NICE-SUGAR Study, New Engl J Med March 2009
6104 ICU pts, IV insulin to achieve a BG target of 81 to
108 (115) in the intensive group and 144 to 180 (144)
in the conventional group.
3% increase in primary end point, death at 90 days
(27.5%, vs. 24.9%, a 10% higher relative mortality). A
significantly higher rate of severe hypoglycemia in the
intensive-control group (6.8% vs. 0.5%)
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Optimal Glucose Targets in Hospital Patients:
The ADA-ACE Consensus Statement
based on the results of NICE-SUGAR
Diabetes Care, May 2009
Critically ill patients
Use IV insulin in the majority of patients in the ICU
setting
Maintain glucose levels between 140 and 180 mg/dL
Targets less than 110 mg/dL are NOT recommended
Noncritically ill (floor) patients
Recommendations are based on clinical experience
and judgment
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Premeal glucose targets should generally be <140


mg/dL
Not recommended Acceptable Recommended Not recommended
Random
< 110 glucose values <180
110-140 mg/dL
140-180 >180
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ADA/AACE Inpatient Task Force
Endocrine Practice 2009;15;1-17
The Ideal IV Insulin
Protocol
Easily ordered (signature only)
Effective (Gets to goal quickly)
Safe (Minimal risk of hypoglycemia)
Easily implemented
Able to be used hospital wide

Essentials of a good IV Insulin Algorithm


Easily implemented by nursing staff
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Able to seek BG range via:


- Hourly BG monitoring
- Adjusts to the insulin sensitivity of the patient

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Various Protocols Exist

Atlanta Multiplier Method

Van den Berghe (studied in critical care setting)

Portland Protocol (used in surgical setting)

Markovitz (studied in postoperative heart surgery


patients)
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Yale Protocol (studied in medical intensive care


setting)
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IV insulin infusion protocols: Comparison of
targets and recommendations

Author
Target glucose Bolus Initial Insulin infused Highest hourly
(mg/dL) (U) infusion rate BG >200mg/dL dose
(U/hr) (U) (U)

Bode 100150 0 8 41 11
Boord 120180 0 1 14.3 4.3
Chant 90144 0 6 42 15

Furnary 100150 12 6.5 59.5 18.5


Goldberg 100139 4.5 4.5 26 9
Kanji 80110 3 3 41 12
Krinsley <140 0 10 40 10
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Marks 120180 0 1 54 18
Van den Berghe 80110 0 4 40 15
Zimmerman 101150 10 4 88 21
Wilson M et al. Diabetes Care.
2007;30:1005-11.| 54
No Ideal Insulin Infusion
Protocol
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Wilson M et al, Diabetes Care. 2007;30(4):1005-11 | 55


MANY INSTITUTES ARE
MODIFYING THEIR PROTOCOLS
ACCORDING TO NEW GUIDELINES
Goldberg PA, et al. Diabetes Care. 2004;27:461-467; Malmberg K. BMJ. 1997;314:1512-1515; Markovitz LJ, et al.
Endocr Pract. 2002;8:10-18; van den Berghe G, et al. N Engl J Med. 2001;345:1359-1367.
Converting to SC insulin

If More than 0.5 u/hr IV insulin required


with normal BG, start long-acting insulin
Exception: if no prior DM and normal A1C,
may not need SC insulin

Must start SC insulin at least 1 to 2 hours


before stopping IV insulin

Some centers start long-acting insulin on


initiation of IV insulin or the night before
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stopping the drip

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Converting from IV to SC insulin

Establish 24 hr Insulin Requirement


Extrapolate from average over last 6-8 hr if stable
Give One-Half Amount As Basal
Give One-Half Amount As Total Bolus
Give post meal based on portion of food consumed
or
Give 1.5 units Rapid-acting for every CHO
consumed
Monitor a.c. tid, hs, and 3 am
Correction Bolus for All BG >140 mg/dl
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Stepwise approach to moving from IV to SC insulin

Calculate how much IV insulin the patient has


been requiring.

Was this insulin supplying Basal


requirements, or Basal and Nutritional
requirements? Translate into the
subcutaneous regimen.

Consider any nutritional changes that may be


implemented at the time of the transition off
of the drip
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Make sure SC insulin is given before


discontinuation of the IV insulin
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Transition from Drip to SQ Insulin - When
patient is able to eat

Insulin drip stable at a rate of 2 units/hour


Insulin Basal calculated as 2 X 20 = 40 units
Insulin Basal/Lantus 20 units SQ given and drip
stopped 2 hours later
Patient to start eating
Total Prandial insulin dose to be 20 units per day so
20/3 7 units with each meal
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Protocol for Treatment of Hypoglycemia

Any BG <60 mg/dl: D 40% = (100-BG) x 0.4 ml IV

Recheck in 15 minutes and retreat if needed

If eating, may use 15 gm of rapid CHO (prefer


glucose tablets)

Do Not Hold Insulin When BG Normal


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Discharge

Patient with Type 2 Diabetes

HbA1C >7% represents suboptimal diabetic


control and anti-diabetic Rx should be
improved prior to discharge.

Each oral diabetic agent will only lower HbA1C


by 1-2%. A pt w/ HbA1C of 12% on 2 oral
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agents will require insulin to reach goal <7%.

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Patients without History of
Diabetes

In patients without a history of diabetes and normal hemoglobin


A1C
insulin basal dose can be TAPERED by 20% of the first dose per day
and they can be discharged without treatment
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Take-home Points
All hospital patients should
have normal glucose
Be aware of glucose targets

Plan ahead: IV insulin, transition from IV to SC,


discharge planning

Communicate with patients and other health care


professionals
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