Download Mortality - Society of Hospital Medicine

Hyperglycemic Control
in Hospitalized Patients:
Best Practice
Susan S. Braithwaite
Clinical Professor of Medicine
University of North Carolina
Glycemic Control Resource Room
November 5, 2006
Objectives – to discuss:
• Relationships of medical outcomes and cost
to presence of diabetes, glycemic control,
and / or treatment modality
• Target range glucose
• Intravenous infusion of insulin
• Subcutaneous insulin (scheduled and correction therapy)
• Prevention of hospital hypoglycemia
• Diabetes patient self-management
• Moving toward discharge
• Managing complexity – orders sets completed by
checking off boxes and filling in numbers,
protocols activated by a single signature, and computerization
Background
Observational studies
and comparisons of intensified regimens
against historical controls show correlation
between glycemic control and outcomes
• Stagnaro-Green. Mortality in hospitalized patients with
hypoglycemia and severe hyperglycemia. Mt. Sinai J Med
1995; 62: 422.
• Umperriez. Hyperglycemia: an independent marker of inhospital mortality in patients with undiagnosed diabetes. J Clin
Endocrinol Metab 2002; 897: 978-82, 2002.
• Finney. Glucose control and mortality in critically ill patients.
JAMA 2003; 290: 2041.
• Krinsley. Effect of an intensive glucose management protocol
on the mortality of critically ill adult patients. Mayo Clin Proc
2004; 79: 992-1000.
• Pittas. Insulin Therapy for Critically Ill Hospitalized Patients: A
Meta-analysis of Randomized Controlled Trials. Arch Int Med
1004; 164: 2005.
• Capes. Stress hyperglycemia and prognosis of stroke in
nondiabetic and diabetic patients: a systematic overview.
Stroke 2001; 32: 2426.
• Bruno. Admission glucose level and clinical outcomes in the
NINDS rt-PA stroke trial. Neurology 2002; 59: 669.
• Gentile. Blood glucose control after actue stroke: a
retrospective study. Academic Emergency Medicine 2003; 10:
432.
• Baird. Persistent poststroke hyperglycemia is independently
associated with infarct expansion and worse clinical outcome.
Stroke 2003; 34: 2208.
• Leigh. Predictors of hyperacute clinical worsening in ischemic
stroke patients receiving thrombolytic therapy. Stroke 2004; 35:
1903.
• Lindsberg. Hyperglycemia in acute stroke. Stroke 2004; 35:
1903.
• Gentile. Decreased mortality by normalizing blood glucose after
acute ischemic stroke. Academic Emergency Medicine 2006.
• Laird. Relationship of early hyperglycemia to mortality in trauma
patients. J Trauma 2004; 56: 1058.
• Thomas. Early perioperative hyperglycaemia and renal allograft
rejection in patients without diabetes. BMC Nephrology
2000;1:1.
• Thomas. Early peri-operative glycaemic control and allograft
rejection in patients with diabetes mellitus: a pilot study.
Transplantation 2001;72:1321.
• Melin. Protective effect of insulin on ischemic renal injury in
diabetes mellitus. Kidney International 2002;61:1383.
• Weiser. Relation between the duration of remission and
hyperglycemia in induction chemotherapy for acute lymphocytic
leukemia... Cancer 2004;100:1179-85.
•
Capes. Stress hyperglycaemia and increased risk of death after
myocardial infarction in patients with and without diabetes: a
systematic overview. Lancet 355:773-8, 2000
•
Foo. A single serum glucose measurement predicts adverse
outcomes across the whole range of acute coronary syndromes.
Heart 2003; 89: 512.
•
Schnell. Intensification of therapeutic approaches reduces mortality in
diabetic patients with acute myocardial infarction: the Munich registry.
Diabetes Care 2004; 27: 455.
•
Stranders. Admission blood glucose level as risk indicator of death
after myocardial infarction in patients with and without diabetes
mellitus. Arch Intern Med 2004; 164: 982.
•
Meier. Plasma glucose at hospital admission and previous metabolic
control determine myocardial infarct size and survival in patients with
and without type 2 diabetes. (LAMBDA study). Diabetes Care
2005;28:2551-2553.
•
Cheung. The hyperglycemia:intensive insulin infusion in infarction (HI5) study: a randomized controlled trial of insulin infusion therapy for
myocardial infarction. Diabetes Care 29:2006;765.
• Goyal. Prognostic significance of the change in glucose level in
the first 24h after acute myocardial infarction: results from the
CARDINAL study. European Heart Journal 2006;27:1289-1297.
• Barsheshet. Admission blood glucose level and mortality
among hospitalized nondiabetic patients with heart failure. Arch
Intern Med 2006;166:1613-1619.
• Chu. Early predictors of in-hospital death in infective
endocarditis. Circulation 2004; 109: 1745.
• Thomsen. Diabetes and outcome of community-acquired
pneumococcal bacteriemia. Diabetes Care 2004;27: 70.
• Falguera. Etiology and outcome of community-acquired
pneumonia in patients with diabetes mellitus. Chest 2005; 128:
3233.
• Pomposelli. Early postoperative glucose control predicts
nosocomial infection rate in diabetic patients. J Parenteral and
Enteral Nutrition; 1998; 22: 77.
• Golden. Perioperative glycemic control and the risk of infectious
complications in a cohort of adults with diabetes. Diabetes Care
1999; 22: 1408.
• Latham. The association of diabetes and glucose control with
surgical- site infections among cardiothoracic surgery patients.
Infection Control & Hospital Epidemiology. 2001;10:607.
• Vriesendorp. Early post-operative glucose levels are an
independent risk factor for infection after peripheral vascular
surgery. A retrospective study. Eur J Vasc Endovasc Surg
2004;5 : 520
• Szabo. Early postoperative outcome and medium-term survival in
540 diabetic and 2239 nondiabetic patients undergoing coronary
artery bypass grafting. Annals of Thoracic Surgery 2002; 74: 712.
• Estrada. Outcomes and perioperative hyperglycemia in patients
with or without diabetes mellitus undergoing coronary artery
bypass grafting. Ann Thorac Surg 2003; 75: 1392-99.
• McAlister. Diabetes and coronary artery bypass surgery: an
examination of perioperative glycemic control and outcomes.
Diabetes Care 2003; 26: 1518.
• Gandhi. Intraoperative hyperglycemia and perioperative
outcomes in cardiac surgery patients. Mayo Clin Proc 2005;
80:862-866.
• Furnary. Clinical effects of hyperglycemia in the cardiac surgery
population: the Portland Diabetic Project. Endocrine Practice
2006;12(suppl 3): 22-26.
• American Diabetes Association. Economic costs of diabetes in
the U.S. in 2002. Diabetes Care 2003; 26: 917-932.
• Ahmann A. Reduction of hospital costs and length of stay by
good control of blood glucose levels. Endocrine Practice 2004;
10 (suppl 2): 53-56.
• Vora. Improved perioperative glycemic control by continuous
insulin infusion under supervision of an endocrinologist does not
increase costs in patients with diabetes. Endocrine Practice
2004; 2: 112-118.
• Almbrand B. Cost- effectiveness of intense insulin treatment
after acute myocardial infarction in patients with diabetes
mellitus: results from the DIGAMI study. Eur Heart J 2000; 21:
733-739.
Background
Heart surgery
Portland: Deep sternal wound infection rate correlates
with quartile of blood glucose on postoperative day 1
Zerr. Ann Thorac Surg 1997;63:356-61.
Percent of patients on POD 1 with mean BG < 200 mg/dL
was increased by using insulin infusion
after cardiac surgical procedures
1499 in study group
968 historical controls
Furnary Ann Thorac Surg 1999;67:352-62.
Blood glucose differed among
patients having deep sternal wound infections
vs patients having no deep sternal wound infections
after cardiac surgical procedures
Furnary Ann Thorac Surg 1999;67:352-62.
Over time, average postoperative glucose has continued
to decline among patients undergoing heart surgery
Furnary 2006
BG
Introduce
Portland
Protocol
Year
Over time, mortality among patients with diabetes
has decreased dramatically.
Furnary 2006
At higher quintiles of blood glucose, the increase
in overall mortality among patients with diabetes
was overwhelmingly accounted for
by an increase in cardiac-related mortality. Furnary 2003
Cardiac related mortality
Non-cardiac related mortality
BG < 150
> 250
Myocardial infarction
DIGAMI I Study: Mortality was reduced
among suspected and known diabetes patients
by intensive insulin after acute myocardial infarction
(glucose-insulin infusion,
followed by at least 3 months of SQ insulin)
Malmberg. BMJ 1997;314:1512-15.
Hyperglycemia predicts 30-d and 1-year mortality in elderly patients
with myocardial infarction, particularly those without recognized diabetes
Mortality at given BG level
with no diabetes
with diabetes
with no diabetes
with diabetes
Direct comparison of risk-adjusted 30-day mortality (A) and 1-year mortality (B)
in patients with and without recognized diabetes across range of glucose values
Kosiborod, M. et al. Circulation 2005;111:3078-3086
In patients
both with
and without
type 2 diabetes,
hyperglycemia at
the time of MI is
associated with :
reduced
prospective
survival
nondiabetes
in diabetes,
higher A1C
Causality
cannot be
inferred;
the authors
called for
randomized trials at higher
of tight control
tertile of BG,
higher CK
Meier. LAMBDA study. Diabetes
Care 2005;28:2551-2553.
diabetes
Surgical ICU
Leuven, Belgium:
Morning blood glucose was reduced by intensive treatment
in Van den Berghe’s ICU trial of insulin infusion
( 13% had previous diabetes )
200
173
Subgroup on insulin
150
153
All in treatment group
100
103 mg/dL
50
Conventional
Intensive
Van den Berghe. N Engl J Med 2001;345:1359- 67
Survival increased with intensive insulin therapy
( nondiabetic patients included ) targeting BG 80-110 mg/dL
among patients who remained in ICU > 5 days
Van den Berghe. N Engl J Med 2001;345:1359- 67
Complications
correlated
with
average
blood glucose
Filled bars
< 110
Shaded bars
110-150
Open bars
> 150 mg/dL
Van den Berghe, Crit Care Med 2003
Although the
Van den Berghe study
was not designed
to determine
the threshold
above which
mortality increases,
mortality was higher
at glucose 110-150,
compared to
glucose < 110 mg/dL.
> 150 mg/dL
110-150
< 110
Van den Berghe, Crit Care Med 2003
Hartford: Nosocomial infections in SICU
N. Grey. Endocrine Practice 2004
125
vs
179 = av BG ( mg/dL)
IV device, blood stream, both, surgical site, UTI, nosocomial pneumonia
General and Medical ICU
Hospital mortality rate in critically ill patients vs mean BG
45
40
35
30
Mortality
Rate (%)
25
20
15
10
5
0
80–99
100–119
120–139
140–159
160–179
180–199
200–249
250–299
> 300
Mean Glucose Value (mg/dL)
Krinsley. Retrospective review of 1,826 consecutive intensive care unit patients
at The Stamford Hospital, Connecticut. Mayo Clin Proc. 2003;78:1471–1478.
Intensive management protocol,
reducing mean BG from 152.3 to 130.7 mg/dL
in medical-surgical adult ICU patients, reduced mortality
Percent reductions were
• glucose > 200 mg/dL

56.3
%
• new renal insufficiency

75
%
• RBC transfusions

18.7
%
• mortality

29.3
%
• length of ICU stay

10.8
%
Krinsley. Effect of an intensive glucose management protocol
on the mortality of critically ill adult patients. Mayo Clin Proc. 2004;79:992-1000.
Average blood sugar depicted in critically ill surgical patients
at Tufts-New England Medical Center in 1997, before implementation
of successive protocols dedicated to aggressively treating hyperglycemia.
By Spring of 2002, the mean glucose was < 130 mg/dL.
Nasraway. Journal of Parenteral and Enteral Nutrition, Vol. 30, No. 3, 2006 254-258
Hyperglycemia responded to aggressive institution of
successive intensive insulin protocols from 1997 to 2002. By 2002,
the desired endpoint of blood glucose < 130 mg/dL was achieved.
During the same interval, patient mortality was observed
to have significantly declined, in spite of increasing severity of illness.
Nasraway. Journal of Parenteral and Enteral Nutrition, Vol. 30, No. 3, 2006 254-258
Effect of Intensive Insulin Therapy on Morbidity
in Medical ICU
Van den Berghe, G. et al.
N Engl J Med 2006;354:449-461
Kaplan-Meier Curves for In-Hospital Survival
Van den Berghe, G. et al.
N Engl J Med 2006;354:449-461
Implication:
Hospitals should focus
on prevention of hyperglycemia
as an important patient safety factor
Target range blood glucose (AACE 2004)
• Preprandial
< 110 mg / dL
• Peak postprandial:
< 180 mg / dL
• Critically ill surgical patients:
80 -110 mg / dL
The targets for critically ill patients were determined
from the Leuven, Belgium study, in which
whole blood glucose methodologies were used
Target range blood glucose
• Noncritically ill
(ADA 2005)
Premeal blood glucose
as close to 90-130 mg/dL as possible
(midpoint 110 mg/dL)
Postprandial blood glucose
< 180 mg/dL
• Critically ill
Blood glucose
as close to 110 mg/dL as possible
and generally < 180 mg/dL
These patients
generally will require IV insulin
Can benefits of glycemic control be shown
for diseases sometimes managed
outside of the ICU, with subcutaneous therapy ?
What specific outcomes might be improved ?
For hypoglycemia vs. tight glycemic control,
what is the risk - benefit analysis
in the setting of the general hospital ward ?
Stroke
Maintaining near normal BG levels after stroke
may improve outcome (n = 765 with ischemic stroke)
Percent Mortality
Percent mortality
by 48-hr BG control
among 561 patients
with BG 130 or higher
on admission
Euglycemic (n=204)
Hyperglycemic
25
< 130
20
15
60
10
40
5
20
0
0
130-180
>180
Gentile. Blood glucose control after acute stroke: a retrospective study.
Academic Emergency Medicine 2003; 10: 432.
Persistent poststroke hyperglycemia
is independently associated with infarct expansion
Baird. Persistent poststroke hyperglycemia is independently associated with
infarct expansion and worse clinical outcome. Stroke 2003; 34: 2208.
Pneumococcal Sepsis
With pneumococcal bacteremia, the 30- d mortality
is higher in the presence of diabetes
mortality
diabetes
no diabetes
Thomsen. Diabetes and outcome of community-acquired pneumococcal
bacteriemia. Diabetes Care 2004;27: 70.
Kidney Transplant
In 50 patients with diabetes undergoing
their first cadaveric renal transplantation,
poor perioperative glycemic control
in the first 100 postoperative hours
was associated with an increased incidence
of acute rejection
• With mean BG < 200 mg / dL,
only 3 of 27 patients
had rejection episodes
( 11% )
• With worse control,
the majority had rejection episodes
( 58% )
Thomas. Early peri-operative glycaemic control and allograft rejection in
patients with diabetes mellitus: a pilot study. Transplantation 2001;72:1321.
Among patients with vs without subsequent rejection:
mean perioperative glucose in 1st 100 hours differed
BG
270
BG
180
these patients had
subsequent acute
rejection
these patients
did not
48 – 72h
In the 50 patients with diabetes
undergoing their first cadaveric renal transplantation,
postoperative infection ( POI ) occurred in 35, or 70%,
at a mean of 10.8 days after transplantation
Every patient with mean BG > 202 mg / dL
over 1st 100 h after surgery developed infection ( n = 23 ).
BG values below are for postop day 1.
• Without POI,
mean glucose 167 mg/dL
• With POI,
mean glucose 248 mg/dL
Thomas. Early peri-operative glycaemic control and allograft rejection in
patients with diabetes mellitus: a pilot study. Transplantation 2001;72:1321.
Acute Lymphocytic Leukemia
Duration of complete remission / median survival were
shorter among 103 hyperglycemic patients
( 37% ) with acute lymphocytic leukemia
Weiser
Hyperglycemia:
≥ 2 BG of ≥ 200 mg / dL w / 30 d of induction chemo
complete remission :
24 vs 52 mo
median survival :
29 vs 88 mo
Sepsis or any complicated infection
(sepsis, pneumonia, or fungal) appeared more often
in the hyperglycemic patients with ALL
38.8
40
Percent
Sepsis
30
25.1
20
10
16.5
8
Any
complicated
infection
0
Nonhyperglycemic
Hyperglycemic
Weiser. Relation between the duration of remission and hyperglycemia during
induction chemotherapy for acute lymphocytic leukemia with a
hyperfractionated cyclophosphamide, vincristine, doxorubicin, and
dexamethasone/methotrexate-cytarabine regimen. Cancer 2004; 110:1179.
Nosocomial Infections
Among 100 consecutive diabetic elective surgery patients,
nosocomial infection rate within first 14 postoperative days
(overall 25.8 %), correlated significantly
with BG on postoperative day 1 (POD 1).
35
31.3
30
25
Percent
20
Developing
Infection 15
≤ 220
> 220
11.5
10
5
0
Preop
POD1
POD2
Pomposelli. Early postoperative glucose control predicts nosocomial infection
rate in diabetic patients. J Parenteral and Enteral Nutrition; 1998; 22: 77.
Early hyperglycemia ≥ 200 mg/dL in trauma patients
was associated with higher infection and mortality rates
independent of injury characteristics
40
34
32
Percent
30
22
20
13
Nonhyperglycemic
Hyperglycemic
10
0
Infection
Mortality
Laird. Relationship of early hyperglycemia to mortality in trauma patients. J
Trauma 2004; 56: 1058.
Post- operative glucose levels in the first 48 hr
were an independent risk factor for infection
after peripheral vascular surgery
postoperative
infection rate
BG > 151 mg/ dL
BG < 103
Vriesendorp. Early post-operative glucose levels are an independent risk factor
for infection after peripheral vascular surgery. A retrospective study. Eur J Vasc
Endovasc Surg 2004;5 : 520
Overall Mortality
Total inpatient mortality was highest
with newly recognized hyperglycemia
Umpierrez. Hyperglycemia: an independent marker of in-hospital mortality in
patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002; 897: 97882, 2002.
Length of Stay and Cost
Length of stay was highest
with newly recognized hyperglycemia
10
9
8
6
Days
5.5
4
4.5
2
0
Normoglycemia
Known Diabetes
New Hyperglycemia
Umpierrez. J Clin Endocrinol Metab 2002; 897: 978-82, 2002.
Economic Costs of Diabetes
in the US in 2002
Diabetes Care 2003; 26: 917
Per capita medical
expenditures per year
• Without diabetes:
2, 560
• With diabetes:
$ 13, 243
Expenditures
in diabetes:
$
• Office visits
10.9 %
• Nursing home care
15.1%
• Inpatient days
43.9%
Deciding
on a Treatment Plan in the Hospital
to Maintain Glucose
in the Target Range
Deciding
whether to maintain
the ambulatory treatment
plan in the hospital
Metformin?
Probably
contraindicated !
Stop metformin
in the hospital
Insulin: components of daily
requirement defined physiologically
Units
Stress / Drugs
IV's / TF's
Prandial
True Basal
Other orals ?
Normal oral intake,
drugs not renally
excreted, no
contraindications ?
May be OK to continue
other oral agents
Healthy
Sick
Sick / NPO
The Pattern of Insulin Requirement
during Normal Health, Meal Plan, and Activity
is Not Necessarily Reproduced in the Hospital
8
12
6
10
Insulin Requirement
Continuous D5, TPN, or tube feeds
6 am
12 pm
6 pm
12 am
Insulin Requirement
Overnight Enternal Feedings /
Daytime “Grazing”
8
12
6
10
Insulin Requirement
Transitional Meal Plan with “Grazing”
8
12
6
10
Insulin Requirement
High a.m. dose corticosteroids
8
12
6
10
Scheduled subcutaneous insulin
Which pattern of carbohydrate exposure describes
the patient ?
• Discrete meals
• Negligible carbohydrate
• Continuous carbohydrate exposure
• Transitional meal plan / grazing
• Daytime grazing / overnight enteral feedings
Generalizations
about subcutaneous insulin therapy
in the hospital
Subcutaneous insulin in the hospital
has 3 components
• basal
• nutritional (or prandial)
• correction therapy
Additional directions are attached
to specific scheduled insulin orders,
or are specified under protocols
• “do not withhold” basal insulin for type 1 diabetes
• “hold” or “reduce” prandial insulin
for poor oral intake
• “hold” nutritional insulin
for interruption of dextrose-containing fluids,
enteral nutrition, or other exposure to carbohydrate
• “hold” regular insulin or rapid acting analog
for low BG
Standardized order sets are completed with check- marks and numbers
Subcutaneous scheduled daily
insulin
Check appropriate times
or meal times to right, and
fill in insulin doses below.
Rapid-acting insulin analog
Short-acting insulin Regular
Intermediate-acting insulin
NPH
Long-acting insulin analog
Other insulin:
______________________
 0600
 1200
 1800
 2400
or
or
or
or
 Lunch
 Supper
 Bedtime
________
units
________
units
________
units
________
units
________
units
________
units
________
units
________
units
________
units
________
units
________
units
________
units
 Breakfast
________
units
________
units
________
units
________
units
________
units
________
units
Twilight of the “Sliding Scale,”
and “Today’s Insulin” Dawning
Relative risk of hyperglycemic episodes (BG >300 mg/dL)
among 171 hospitalized diabetes patients
was greatest with sliding scale, when comparing
antihyperglycemic drug therapies to nontreatment
Queale 1997
4
3
2
1
0
Scheduled insulin
Conservative
Aggressive sliding
or oral agents sliding scale alone
scale alone
A1C monitoring and use of scheduled insulin improved
as a result of housestaff education on scheduled insulin
combined with prohibition of sliding scale
A1C drawn
100
Percent of
Patients
75
Scheduled insulin BID
Sliding
Scale
Use:
100 %
D50 needed
99
68
Sliding
Scale
Use:
0%
50
25
32
32
30
26
0
Historical Controls
Intervention Group
Baldwin. Eliminating inpatient sliding scale. Diabetes Care 2005;28:1008.
BG control improved as a result
of housestaff education on scheduled insulin
combined with sliding scale prohibition
for treatment of hyperglycemic patients
250
200
Mean
Glucose
mg / dL
200 ± 51
150 ± 37
150
100
50
0
Historical Controls
Intervention Group
Baldwin. Eliminating inpatient sliding scale. Diabetes Care 2005;28:1008.
Correction Dose Algorithms
Algorithm 1
Algorithm 2
Algorithm 3
Algorithm 4
Algorithm 5
Algorithm 6
Rapid-acting
analog
[ TDDI ≈ 24
( < 28 ) units, or
wt < 56 kg]
Rapid-acting
analog
[ TDDI ≈ 30
(28–36) units, or
wt 56–73.9 kg]
Rapid-acting
analog
[ TDDI ≈ 45
( 37–55) units, or
wt 74–111.9 kg]
Rapid-acting
analog
[ TDDI ≈ 72
(56 –90) units, or
wt 112–181.9 kg]
Rapid-acting
analog
[ TDDI ≈ 120
(91–144) units, or
wt  182 kg]
Rapid-acting
analog
[ TDDI ≈ 180
( > 144 ) units]
Regular insulin
[ TDDI ≈ 20
( < 23 ) units, or
wt < 46 kg]
Regular insulin
[ TDDI ≈ 25
( 23–30) units, or
wt 46–61.9 kg]
Regular insulin
[ TDD I ≈ 37½
(31– 46) units, or
wt 62–93.9 kg]
Regular insulin
[ TDDI ≈ 60
(47–75) units, or
wt 94–151.9 kg]
Regular insulin
[ TDDI ≈ 100
( 76 – 120) units,
or wt  152 kg]
Regular insulin
[ TDDI ≈ 150
( > 120) units]
BG
BG
BG
BG
BG
BG
units
units
units
units
units
units
150-224
1
150-209
1
150-189
1
150-199
2
150-209
4
150-199
5
225-299
2
210-269
2
190-229
2
200-249
4
210-269
8
200-249
10
300-374
3
270-329
3
230-269
3
250-299
6
270-329
12
250-299
15
375-449
4
330-389
4
270-309
4
300-349
8
330-389 16
 450
5
 390
5
310-349
5
350-399
10
350-389
6
 400
12
 390
7
 390
20
300-349 20
 350
25
Admitting a hyperglycemic patient
who is eating
Subcutaneous insulin therapy in the hospital
for patients eating discrete meals
Insulin therapy
in normal health (%)
Insulin release
in normal physiology (%’s)
Basal
Prandial
Basal
Prandial
Correction
Consistent carbohydrate diet ;
fixed prandial insulin doses
Patients who are eating
Glargine
( ~ 50 % )
Rapid- acting analog ( ~ 50 % )
Insulin requirement
8
12
6
10
Advanced carbohydrate counting
Glargine
Rapid- acting analog
8
12
6
8
12
6
10
Insulin by pump
Rapid- acting analog
10
8
12
6
10
A preferred hospital regimen for use
with a consistent carbohydrate diet
Glargine
Lispro / aspart / glulisine
8
12
6
( ~ 50 % )
( ~ 50 % )
10
The patient who is eating
and running high blood glucose ...
• Use insulin analogs
• Use basal – prandial – correction therapy
• “Just say no” to sliding scale
Insulin analogs are the preferred therapy
for patients who are eating
Rapid- acting analogs
(aspart, lispro, glulisine) are best reserved
for prandial and correction dose therapy
(not basal),
whereas long- acting analog therapy
(glargine, detemir) is best reserved
for basal coverage (not nutritional)
A Bad Practice:
70/30 Insulin plus Sliding Scale
Scheduled or routine
Sliding Scale
• BID, or
• Q4HRS, or
0800 & 1700
0200, 0600, 1000,
1400, 1800, 2200
This means 8 shots daily.
There is a risk of stacking, & BG tests fail to synchronize:
0200, 0600, 0800, 1000, 1400, 1700, 1800, 2200
Tease out the basal and prandial components
for patients admitted on premixed insulins
• meal omission is inevitable
• premixeds won’t work
• the argument for analogs
is reduction of hypoglycemia
Apportion or reapportion the insulin
• About 50% basal
• About 50% prandial
“ Teasing out ” the basal and prandial
components of insulin in type 2 diabetes
for a patient admitted on premixed insulin
• Suppose Robert normally takes 70 / 30 insulin,
60 units at breakfast and 30 units at supper
He sometimes has fairly severe lows
• A SQ regimen is needed
to permit occasional meal omission
Basal insulin in type 2 diabetes
is 40- 50 % of the usual total daily dose
A regimen of scheduled insulin might be:
– glargine 36 units
(“cut 50% if NPO”)
qHS
– aspart 12 units
(“hold if NPO”)
WMEALS
– aspart 2 units prn BG 150 -199
WMEALS, HS, 0300
– aspart 4 units prn BG
WMEALS, HS, 0300
>199
“ Teasing out ” and “locking in”
the basal insulin component in type 1 diabetes
Requirement for exogenous insulin
during prolonged fasting
may disappear in type 2 DM,
but even during prolonged fasting
it is absolute in type 1 DM
requirement
for exogenous basal insulin
vs time fasting
type 1 DM
type 2 DM
Corticosteroids
High a.m. dose corticosteroids
Insulin Requirement
Solution a.
NPH —
R
---
8
12
6
Glargine
during
cortico steroids
( ~ 30 % )
Solution b.
Rapid- acting
analog
8
12
10
6
10
8 am
12
6
10
Solution c.
NPH added for prednisone “on” days
Rapid- acting analog
NPH
8
12
Glargine
6
10
Procedures, brief NPO status,
or anesthesia < 1hr
Lispro, aspart
or glulisine
Procedures, anesthesia
and surgery
Glargine
Established basal therapy with
peakless long- acting insulin analog
8 am
12
6
10
Prolonged NPO status
or anesthesia > 1hr
Glargine Doses
today’s
yesterday’s
Yesterday’s Glargine Dose
6 am
12 pm
6 pm
12 am
Insulin drip
6 am
12 pm
6 pm
12 am
Preoperative planning in the office ....
For patients receiving insufficient prandial coverage,
overdoses of long-acting analog (glargine or detemir)
established as home therapy may spell hypoglycemia
once the patient is in the hospital ...
Glargine or detemir, given daily,
playing catchup
NPO status
BG
BG
8
12
6
10 pm
8
12
6
10 pm
Glargine or determinr,
overdosed to play catchup,
plus sliding scale !
BG
8
12
6
10 pm
During NPO status, among type 1 diabetes patients,
a previously established glargine dose
maintains normoglycemia
Mucha, Diabetes Care: 2004
Control days
Fasting days
Requirement for exogenous insulin
during prolonged fasting or calorie restriction
shows variability in Type 2 DM
type 2 DM
patient A
patient B
Long -acting analog > 50% of total insulin?
On the night preoperatively, cut long -acting analog dose
to be no more than 50% of daily total insulin,
and consider 10 -20% further reduction
ambulatory plan
glargine 72 units qHS
metformin
sulfonylureas
the night preoperatively
 glargine 36 units
Long -acting analog < 50% of total insulin?
On the night preoperatively, no dose reduction
ambulatory plan
glargine 12 units qHS
glulisine 6 units
WMEALS
the night preoperatively
glargine 12 units
Insulin by pump
8
12
6
10
A 35 year old woman with type 1 diabetes
• She is having bariatric surgery
• Normally she wears an insulin pump
• She is in your office
asking for preoperative advice
For procedures or NPO status,
pump patient can hold the prandial insulin
but maintain true basal insulin
Lispro or aspart
8
12
6
10
A caution on subcutaneous therapy
Delayed response and late snowballing
from repeated insulin doses
may occur among patients with poor perfusion
of subcutaneous sites, as with
• hypoalbuminemia
• edema
• hypotension
• pressors
Intravenous Infusion of Insulin:
the only insulin treatment strategy
specifically developed for use in the hospital
Indications for intravenous insulin infusion
•
Diabetic ketoacidosis
•
Non-ketotic hyperosmolar state
•
Critical care illness
•
Myocardial infarction or cardiogenic shock
•
Post- operative period following heart surgery
•
NPO status in type 1 diabetes
•
General pre-, intra- and post- operative care
•
Organ transplantation
•
Stroke (possibly)
•
Exacerbated hyperglycemia during high- dose glucocorticoid therapy
•
Dose-finding strategy, anticipatory to initiation or reinitiation
of subcutaneous insulin in type 1 or type 2 diabetes
•
Labor and delivery
•
Any illness for which prompt glycemic control is important to recovery
Intravenous Infusion of Insulin:
a well- designed protocol damps the swings of BG
BG levels with insulin drip
with no protocol
BG levels with insulin drip
with good protocol
Using an algorithm that considers
BG, insulin rate, and velocity of change,
Goldberg and colleagues safely approached target
Goldberg et al. Diabetes Care 27: 461, 2004
The BG results compared favorably
with those of historical controls
Goldberg et al. Diabetes Care 27: 461, 2004
First 72 Hours of Insulin Infusion, 24 Patients, 27 Runs
350
point of care BG,
mg / dL,
mean and SD
300
70
insulin infusion rate,
units / hr,
mean and SD
60
insulin infusion rate, mean
point of care BG, mean
250
50
200
40
150
30
100
20
50
10
0
0
0
6
12
18
24
30
36
42
48
54
60
66
72
hours of insulin infusion
Braithwaite et al. Diabetes Technology and Therapeutics 2006; 8 (4):476
Intravenous Insulin Infusion Targeting BG 80-110 mg/dL
Column 1
Column 2
Column 3
Column 4
Column 5
Column 6
BG
units/h
BG
units/h
BG
units/h
BG
units/h
BG
units/h
BG
units/h
< 70
0.05
< 70
0.05
< 70
0.05
< 70
0.05
< 70
0.05
70- 74
0.1
70- 74
0.1
70- 74
0.1
70- 74
0.1
70- 74
0.1
75- 79
0.1
75- 79
0.2
75- 79
0.2
75- 79
0.2
75- 79
0.2
80- 84
0.2
80- 84
0.2
80- 84
0.3
80- 84
0.3
80- 84
0.3
80- 84
0.3
85- 89
0.3
85- 89
0.4
85- 89
0.4
85- 89
0.5
85- 89
0.6
85- 89
0.6
90- 94
0.4
90- 94
0.6
90- 94
0.7
90- 94
0.8
90- 94
1.0
90- 94
1.2
95- 99
0.5
95- 99
0.8
95- 99
1.1
95- 99
1.4
95- 99
1.9
95- 99
2.3
100-104
0.7
100-104
1.3
100-104
1.8
100-104
2.4
100-104
3.3
100-104
4.3
105-109
1
105-109
2
105-109
3
105-109
4
105-109
6
105-109
8
110-127
1.2
110-121
2.3
110-122
3.5
110-127
5
110-122
7
110-127
10
128-144
1.5
122-133
2.6
123-134
4
128-144
6
123-134
8
128-144
12
145-162
1.7
134-144
3
135-147
4.5
145-179
8
135-159
10
145-162
14
163-179
2
145-162
3.5
148-159
5
180-214
10
160-184
12
163-179
16
180-249
3
163-179
4
160-209
7
215-249
12
185-209
14
180-214
20
250-319
4
180-249
6
210-259
9
250-319
16
210-259
18
215-249
24
320-389 5
250-319 8
390
320
6
10
260-309 11
310
13
320-389 20
390
24
260-309 22
310
26
250-319 32
320
40
Braithwaite et al. Diabetes Technology and Therapeutics 2006; 8 (4):476
Blood Glucose (BG) Distribution after First Reaching BG < 110 mg/dL ,
Analysis Shown Using BG or Patient Run as the Unit of Observation
23 patients, 1537 BG’s,
25 / 27 patient runs;
%
50
2 patients did not reach BG < 110
before interruption of infusion
40
BG
Patient Run
30
20
10
0
BG < 70
70 ≤ BG
< 110
110 ≤ BG BG ≥ 140
< 140
in this series of 1537 BG measurements, among the 23 patients or 25 runs
in which target BG < 110 was reached, there were
31 BG measurements < 70 mg/dL, and in this series none < 50 mg/dL.
Prevalence of 60 ≤ BG < 70, 16 / 25 runs
Prevalence of 50 ≤ BG < 60,
60 ≤ BG < 70
8 / 25 runs
50 ≤ BG < 60
Trauma Patient with Type 2 Diabetes, Tube Feeds at Target
450
70
insulin infusion rate
point of care BG
400
60
capillary BG,
350
mg/dL,
mean and SD
insulin infusion,
units / hr,
mean and 50
SD
Changing to higher column here
alters assumed maintenance rate
from 4 to 6 units per hour.
300
250
40
Changing to higher column here
alters assumed maintenance rate
from 6 to 8 units per hour.
Changing to lower column here
alters assumed maintenance rate
from 8 to 6 units per hour.
200
30
150
20
100
10
50
0
0
0
6
12
18
24
30
36
42
hours of insulin infusion
48
54
60
66
72
Insulin to cover TPN
• Distribution of insulin, desired
– 67-80 % of the insulin in the TPN bag
– 20 -33 % as correction therapy
by SQ injection or IV infusion
• Redistribution strategy
– add 2 /3’s of yesterdays correction therapy
to today’s bag
Intravenous insulin infusion under basal conditions
correlates well with subsequent subcutaneous
insulin requirement
Hawkins. Endocrine Practice: 1995
Total IV vs SQ 24h Insulin Requirements
Units SQ
Units IV
Proposed predictors of successful transition
from intravenous insulin to SQ insulin after CABG
• Type 2 diabetes or nondiabetes
( hospital hyperglycemia )
• Uncomplicated CABG and / or valve surgery
• Patient extubated, no pressor support, eating
• Transfer orders written
• Stable BG < 130 mg/dL
• Insulin infusion ≤ 2 units / h overnight
• Projected insulin dose  48 units / d
Possible predictors of hyperglycemia
after early transition to SQ insulin after heart surgery
• Type 1 diabetes
• COPD
• Morbid obesity
• Bilateral internal thoracic artery harvesting
• Heart transplant
• Ventilator dependency, pressor support, IABP, NPO status
• Corticosteroids
• No transfer orders written
• Glucose > 130 mg / dL while on the insulin infusion
• Infusion rate > 2 units / h overnight
• Projected insulin dose > 48 units / d
Transition off intravenous insulin infusion ....
Constructing a profile
for scheduled subcutaneous insulin ….
Lispro / Aspart / Glulisine
SQ Regular
NPH
Glargine
6 pm
12 am
6 am
12 pm
The Time Arrives to Stop Insulin Drip
Discrete
meals?
No
NPH and
regular insulin
Yes
Glargine and
rapid-acting analog
In the following case of a patient who is eating,
if transfer orders are written ....
what is needed for glycemic
management ?
Estimating initial SQ basal insulin from drip
It is 8 am on the morning of postop day 3 after CABG.
The patient is well, still on insulin drip. There were
no overnight pressors or dextrose. Since yesterday, as
prandial insulin, 4 units aspart are given with each meal.
Based on the insulin requirement during 8 hr overnight,
if nothing changes, what is the 24h basal requirement?
• 12 -2 am
1.5 unit / hr
•
2 -4 am
1.0 unit / hr
•
4 -6 am
1.5 unit / hr
•
6 -8 am
2.0 unit / hr
Answer:
• Average hourly insulin was 1.5 units / hr
• 24 hr basal requirement is 36 units
• Consider ~ 20 -33 % basal dose reduction
each day during recovery
• Adjust prandial doses upward each day
• Eventual goal: 50% basal and 50% prandial
The hyperglycemic patient
receiving continuous exposure to carbohydrate,
or no carbohydrate ....
Insulin requirement during
continuous D5, TPN or enteral feedings
8
12
6
10
Prolonged
NPO Status
Glargine (not more than basal)
Regular (at least 50 %)
----
Regimens for patient
while NPO, on IV’s,
or receiving continuous
enteral feedings
6
NPH
6
12
6
10
2
6
10
2
NPH q 6 hr (~ 67 %)
—
R
---
q 6 hr (~ 33 %, hold if low)
12
6
12
6
12
Long- acting insulin doses
should not exceed basal requirements
during continuous enteral feedings
Prescribe glargine
Corpak falls out
BG q 2 hr, dextrose if < 120
6 pm
12 am
6 am
12 pm
Mixtures of NPH and regular insulin q 6 – 8 h
maintain a flat- line, safe and rapidly reversible
insulin effect for a patient while NPO, on IV’s,
or receiving continuous enteral feedings
—
NPH q 6 hr (~ 67 %)
R
q 6 hr (~ 33 %, hold if low)
6
12
6
---
12
In the following case of a patient not eating,
if transfer orders are written...
what is needed
for glycemic management ?
Estimating combined basal and nutritional coverage
from drip
A stable ventilator- dependent trauma patient
has had a tracheostomy and PEG procedure.
Over the past 24h he has received
72 units of insulin daily by intravenous infusion
to cover enteral feedings,
which have been at target for 24 hr.
How might subcutaneous orders be written
to permit transition off of the insulin infusion?
One acceptable answer :
• NPH 12 units q 6 h ( hold if tube feeds stop )
• Regular insulin 6 units subcutaneously q 6 h
( hold if tube feeds stop, hold if BG < 100 )
• Correction dose regular insulin “prn”
– BG 150 - 199
+ 2 units
– BG 200 - 249
+ 4 units
– BG 250 or higher
+ 6 units
• Stop insulin drip
2 h after first dose of subcutaneous insulin
Grazing
( transitional meal plans,
nutritional supplements ) ....
Grazing
Insulin Requirement
Transitional Meal Plan with “Grazing”
NPH and Regular Insulin
Transitional Meal Plan with “Grazing”
NPH —
R
---
8
12
6
10
8 am
12
6
10
Insulin regimen, no tube feeds,
for patients attempting to eat
( transitional meal plan with “grazing”)
• Estimate daily insulin requirement
and split 2/ 3 in AM, 1/ 3 in PM
• 2/ 3 of AM dose as NPH, 1/ 3 as regular
• 1/ 2 of PM dose as regular at 1700
• 1/ 2 of PM dose as NPH at 2200
• Hold scheduled regular for BG < 90
Example of a “grazing” patient
• A postoperative patient
receives nutritional supplements between meals and grazes on trays
• 36 units of insulin are required daily
• Sample insulin orders:
– NPH 16 units
before breakfast
– regular insulin SC 8 units
before breakfast
– regular insulin SC 6 units
before supper
– NPH 6 units
qHS
– regular insulin 2 units
prn BG 150 -199
WMEALS, HS
– regular insulin 4 units
prn BG
WMEALS, HS
> 199
Overnight tube feeds ....
Ovenight enteral feedings / daytime grazing
Insulin Requirement
NPH and Regular Insulin
NPH —
R
---
8
12
6
10
8 am
12
6
12
70 / 30
change
dose
change
frequency
to “QPM
enter
additional
directions
free text
pre- med for TF’s,
hold if no TF’s
select
" pre- med"
for priority
Today’s Insulin Dose
How much?
• How much to start with?
• How much for today?
Initial insulin calculation,
hospitalized patient, type 2 diabetes
No clue where to start ?
start low....
• basal insulin requirement
 0.15 units /k
• basal + prandial insulin
 0.3 units /k if eating
Known preadmission TDDI (total daily dose of insulin) ?
• basal insulin requirement
if no longer eating
 20 - 25 %
of preadmission
TDDI
During continuous nutritional support
or IV dextrose infusion,
• provide basal insulin 0.15 units per kilo
• provide nutritional insulin,
initially estimated
as 1 unit per 10 gm carbohydrate
• cover both needs continuously
For type 2 diabetes -If insulin is required at all
• the requirement for exogenous insulin
may vanish during caloric restriction
or development of organ dysfunction
• calculations on a “per kilo” basis
may overestimate basal needs
when overnutrition ceases
How much to start with ?
• Melinda: weight 80 kilos
• Problem: ovarian carcinoma, type 2 diabetes
• Status: postop, NPO, D5 in 0.45 at 100 cc/hr
• Basal insulin:
________ units per 24 hr
• Insulin to cover D5: ________ units per 24 hr
• Total insulin / 24 hr: ________ units per 24 hr
Type 2 diabetes, NPO, continuous D 5 W
• Melinda: weight 80 kilos
• Status: postop, NPO, D5 in 0.45 at 100 cc/hr
• Basal insulin:
12 units per 24 hr
• Insulin to cover D5:
12 units per 24 hr
• Total insulin / 24 hr:
24 units per 24 hr
• SQ insulin orders:
– 4 units NPH
q 6h (hold if D5 stops )
– 2 units regular insulin
q 6h (hold if D5 stops, hold if BG < 90 )
– Correction dose algorithm for highs
Correction therapy signals the need
for a change of scheduled therapy
to prevent recurrent hyperglycemia
It is common early in the admission
to rely excessively on correction doses
and to underestimate the need for scheduled insulin
when using subcutaneous therapy
Units
Correction
Scheduled
Day 1
Day 3
Dose- finding strategy
• Determine yesterday’s total insulin dose
actually administered
• Review yesterday’s glycemic control
• Calculate today’s scheduled insulin dose
(this example uses peak glucose targets
appropriate during D5 or tube feeds)
– some BG < 90
 80 % of yesterday’s total
– BG’s
 100 % of yesterday’s total
90 - 179
– some BG ≥ 180, no BG < 90
 110 % of yesterday’s total
How much for today ?
A patient on tube feeds
received 6 units NPH and 3 units regular insulin
as scheduled every 6 hr, total 36 units for the day,
plus the following correction doses
of regular insulin:
0600 BG 157
+ 1 unit
1200 BG 207
+ 2 units
1800 BG 199
+ 2 unit
2400 BG 263
+ 3 units
Assuming nothing else has changed,
what is today’s dose of scheduled insulin?
A. 24 units
B. 34 units
C. 44 units
D. 48 units
Answer (doing it one doctor’s way):
• Total dose given yesterday was 44 units
• 110 % of yesterday’s dose is 48 units
• Today’s insulin dose is 48 units,
8 N, 4 R at 0600, 1200, 1800, and 2400
Prevention
of Hospital Hypoglycemia
An analysis of proximate causes
of hospital hypoglycemia
suggests that iatrogenic hypoglycemia
usually is predictable and preventable
(Fischer):
Decreased intake of calories
Adjustment of insulin dosage
Incorrect dose of insulin given
No cause identified
Insulin or secretogogue previously prescribed.
Triggering Events for Hypoglycemia
• Transportation off ward causing meal delay
• New NPO status
• Interruption of intravenous dextrose
• Interruption of TPN
• Interruption of enteral feedings
• Interruption of continuous renal replacement rx
Insulin previously prescribed.
Triggering events for hypoglycemia ?
Yes
No
Insulin
given?
Except for basal insulin
in type 1 diabetes and correction doses:
Hold insulin
Yes
Increase BG monitoring to q 2 hr
for timeframe of action of the insulin, and:
Give carbohydrate for BG < 120 mg/dL -oral, IV dextrose infusion, or, for volume restricted patients,
concentrated dextrose
Moving toward Discharge
Was it just “hospital hyperglycemia?”
• Review A1C from first day of admission
– > 6.0 % ?
– < 5.2% ?
• Followup BG in outpatient setting
Greci. Diabetes Care 2003
A1C- driven therapeutic modifications
were followed by improvement of A1C
( 34 of 98 patients were evaluable after 12 mo )
Baldwin. Eliminating inpatient sliding scale. Diabetes Care 2005;28:1008.
How will change be promoted ?
Managing Complexity :
Standardized Order Sets
and Computerized Order Entry
• Consistent carbohydrate meal plan
• Intravenous infusion of insulin
• Diabetes hospital patient self-management
• Scheduled subcutaneous insulin
• Oral antihyperglycemic agents
• Combination insulin / oral antihyperglycemics
• Point-of-care glucose monitoring
• Correction dose insulin
Standardized order sets can guide and teach
Summary
Summary
• Hyperglycemia is a patient safety factor.
• At the time of transition from intravenous insulin therapy,
“scheduled” or “routine” or “programmed” subcutaneous insulin
is the mainstay of glycemic management.
• Good care involves discovery and ongoing revision of daily insulin dose,
replacing “correction” therapy with “scheduled” subcutaneous insulin.
• Hypoglycemia in the hospital is mostly preventable
(by means other than undertreatment of diabetes).
• Sliding scale is ineffective and dangerous and should be eliminated.
• Patients conscious, eating, and experienced
in self-management should continue self-management in the hospital.
• Nation-wide opportunities for improvement include
preadmission and preanesthetic planning,
facilitation of insulin drip therapy, protocols for hypoglycemia prevention,
standardization of diabetes order sets and correction dose algorithms,
computerized order entry that guides and teaches, and
enabling policies with safety provisions on patient self-management,
patient education, and discharge planning.