Transcript Glycemic Control: Hospitalized Patients

Glycemic Control: Hospitalized Patients
Review of Guidelines
Lukasz Materek
Endocrine Rounds
September 2011
• Objectives:
– Review available guidelines
• ACP
• ADA
• CDA
– Discuss evidence for glycemic control
inhospitalized patients
– Review approach to common hospital scenarios
ACP Guidelines: February 2011
• Does the use of IIT (intensive insulin therapy)
to achieve tight control compared to less tight
control improve outcome?
• Which population?
• Are there harms?
• ITT:
– Intravenous insulin
– Common Target 4.4-6.1 mmol/L
MICU
• 5 trials (fair); 1 trial (poor)
• Target 4.4-6.1 mmol/L vs. 7.8-11 mmol/L
• No mortality difference
SICU
• 3 trials (fair); 2 trials (poor)
• Target 4.4-8.3 mmol/L vs. 10-12 mmol/L
• No mortality benefits
• NICE-SUGAR
– Target 4.4-6 mmol/L vs <10 mmol/L
– Increased mortality (RR 1.31 CI 1.07 – 1.61)
• Intensive insulin therapy in the critically ill patients
– Target 4.4-6.1 mmol/L vs 10.0-11.1 mmol/L
– Decreased mortality (RR 0.58 CI 0.38 – 0.78)
Mixed ICU (MICU/SICU)
• 5 Trials (fair)
• Target 4.0 – 6.1 mmol/L vs 7.8 – 11.1 mmol/L
• No mortality benefit
Short-term mortality in studies of intensive insulin therapy, by the mean glucose level
achieved in the intervention group. Short-term mortality includes death occurring within 28 d
of or during the ICU or hospital stay; we used 28-d mortality in the meta-an...
BG < 6.66
BG > 6.66
Not reported
Kansagara D et al. Ann Intern Med 2011;154:268-282
©2011 by American College of Physicians
Mortality at 90 or 180 d in studies of intensive insulin therapy, by inpatient setting.
ICU
Studie
s
NonICU
Studie
s
Kansagara D et al. Ann Intern Med 2011;154:268-282
©2011 by American College of Physicians
Short-term mortality in studies of intensive insulin therapy, by inpatient setting.Short-term
mortality includes death occurring within 28 d of or during the ICU or hospital stay; we used
28-d mortality in the meta-analysis when a study reported >1 outcome.
ICU
Studies
Non-ICU
Studies
Kansagara D et al. Ann Intern Med 2011;154:268-282
©2011 by American College of Physicians
General Medical Ward
• 0 Trials
Myocardial Infarction
• 3 Trials (fair); 2 Trials (poor)
• Target 4.0-11.0 mmol/L vs unspecified
• Target 7.0-11.0 mmol/L + insulin on discharge
– Mortality reduction (RR 0.69 CI 0.49 – 0.96)
• Overall, no mortality reduction
Stroke / ABI
• 2 Trials (fair); 2 Trials (poor)
• Target 4.4 – 8.0 mmol/L vs <10.0 / <17.0 mmol/L
• Overall, no mortality reduction
Perioperative Control
• 1 Trial (fair); 2 Trials (poor)
• Target 3.9 – 10.0 mmol/L vs unspecified
• No difference in health outcomes
– Small studies
– Low event rates
Infection Risk
• 9 Trials (fair); 7 Trials (poor)
• Sepsis
– Reduction of sepsis with IIT
– RR 0.79 CI 0.62 – 1.00
• Pooled result of wound infection, UTI,
pneumonia or combination
– No significance
– RR 0.68 CI 0.36 – 1.30
Effects of intensive insulin therapy on rates of infection in various inpatient settings.We
included inpatients in the MICU, SICU, and perioperative settings as well as patients with
stroke or acute brain injury.
sepsis
infx
Kansagara D et al. Ann Intern Med 2011;154:268-282
©2011 by American College of Physicians
Hypoglycemia
• Critically ill patients and IIT
– RR 5.32 CI 4.21 – 6.73
• No data for general medical unit patients
• Is hypoglycemia a marker of severe illness or
causative factor for excess
mortality/morbidity?
Risk for hypoglycemia in studies of intensive insulin therapy in various inpatient settings.We
included inpatients in the MICU, SICU, and perioperative settings as well as patients with
traumatic brain injury.
Kansagara D et al. Ann Intern Med 2011;154:268-282
©2011 by American College of Physicians
• ACP Recommendations:
– ACP recommends not using intensive insulin
therapy to strictly control blood glucose in nonSICU/MICU patients
– Strong recommendation
– Moderate quality of evidence
• Avoid targets <7.8
• Targets not precisely defined
• ACP Recommendations:
– ACP recommends not using ITT to normalize blood
glucose in SICU/MICU patients
– Strong recommendation
– High quality of evidence
• No benefit of ITT (target 4.4 – 6.1 mmol/L)
• Excess hypoglycemia
• ACP Recommendations:
– ACP recommends a target blood glucose level of
7.8 – 11.1 mmol/L if insulin therapy is used in
SICU/MICU patients
– Weak recommendation
– Moderate quality of evidence
– Limited data for 10.0 – 11.1 mmol/L range
ADA:
Diabetes Care January 2011
• Summary of recommendations
Critically Ill Patients
• Initiate insulin therapy for treatment of
persistent hyperglycemia:
– threshold 10 mmol/L
– Target 7.8 – 10.0 mmol/L
– More stringent goals may be appropriate in
selected patients if hypoglycemia is avoided
• Traget 6.1 – 7.8 mmol/L
– Target of <6.1 mmol/L not recommended
NICE-SUGAR
• Largest RCT (6104 subjects)
• Compared targets
• 4.5 – 6 mmol/L; mean achieved 6.4 mmol/L
• 8 – 10 mmol/L; mean achieved 8 mmol/L
• Bottom line 6.4 vs 8.0 mmol/L in critically ill
90-day mortality
• 27.5% vs 24.9%
• p value=0.02
• 78 more deaths in the lower glycemic target
group
Mortality from CVS cause
• 41.6% vs 35.8%
• p value=0.02
• 76 more deaths in the lower glycemic target
group
Hypoglycemia
• 6.8% vs 0.5%
• p value < 0.001
• More hypoglycemia in the lower glycemic
target group
Intensive Insulin Therapy in Critically Ill Patients
Van den Berghe et al. 2001
• intensive insulin therapy
– maintenance of blood glucose at a level between
4.4 and 6.1 mmol/L
• conventional treatment
– infusion of insulin only if the blood glucose level
exceeded 11.9 mmol/L and maintenance of
glucose at a level between 10 and 11 mmol/L
• Achieved AM BG levels in the study
• 5.7±1.1 mmol/L vs. 8.5±1.8 mmol/L
• Only 39 percent of the patients treated with
the conventional approach received insulin;
9.6±1.8 mmol/L, as compared with 7.8±1.4
mmol/L in the patients who did not receive
insulin.
• Thirty-five patients in the intensive-treatment
group (4.6 percent) died during intensive care,
as compared with 63 patients (8.0 percent) in
the conventional-treatment group
• apparent risk reduction of 42%
– confidence interval 22-62%
• after adjustment for repeated interim analyses
the median unbiased estimate of the
reduction in mortality was 32 %
– Adjusted confidence interval, 2 to 55 %; P<0.04
26 Trial Meta-Analysis
• IIT vs Conventional Therapy
• Relative Risk of Death
– 0.93 (CI 0.83 – 1.04)
ICU Subgroup Analysis
• Benefit of IIT in the surgical ICU
– RR 0.63 (CI 0.44 – 0.91)
• Benefit of IIT in the medical ICU
– RR 1.0 (CI 0.78 – 1.28)
• Benefit if IIT in the mixed ICU
– RR 0.99 (VI 0.86 – 1.12)
Non-critically Ill
• No clear evidence for specific blood glucose
goals
• If eating, premeal target <7.8 mmol/L and
random levels of < 10 mmol/L
• Less stringent goals if multiple comorbidities
• Scheduled insulin with correction scale should
be utilized (not Sliding Scale)
Non-critically Ill
• Reassess regimen if BG < 5.6 mmol/L
• Modify regimen if BG < 3.9 mmol/L
• Scheduled insulin which delivers basal,
nutritional and correction insulin is preferred
CDA: 2008
• Critically ill patients:
– Van den Berghe et al 2001
• Critically ill patients (large surgical group)
– Meta-analysis Lau et al. 2004
– Van den Berghe et al 2006
• Medical ICU Patients
• No difference in primery end point of in-hospital
mortality
Recommendation
• IV Insulin strategy should be used to achieve
targets of 4.5 -6 mmol/L in post-op ventilated
ICU patients
• Medical ICU patients when BG is
>6.1 mmom/L
Stroke
• 1 small study n=25
– BG > 7, increased infarct size
• GIST-UK; 2007: RTC n=933
– GIK vs NS infusions
– No mortality or morbidity difference
• Subgroup of Van den Berghe et al 2006
• Medical ICU Patients with neurological conditions
• No benefit
Medical in-patients
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No recommendations for targets
Use proactive approach, not Sliding Scale
Availability of glucose especially when NPO
Avoid hypoglycemia
Glucagon should be available
Perioperative control
• CABG
– Intraoperative target 5.5 – 10.0 mmol/L
– Reduced mortality and infection risk
– Use of IIT for target 4.4 – 5.6 mmol/L showed no
benefit of IIT
Perioperative control
• Minor or Moderate OR
• Small studies
• Limited ecidence
• Target 5 – 11 mmol/L
– Note: monocular phacoemulsification cataract surgery
with mod-severe nonproliferative diabetic neuropathy
in patients with hyperglycemia could worsen
retinopathy and maculopathy with rapid glycemic
correction
Summary
• ACP supports the most “less tight control”
• ADA based on recent evidence but support a a
lower target in the ICU setting
• CDA limited as guidelines established before
the recent trials published
Approach to Hospitalized Patient with
severe insulin resistance
• J Clin Endocrinol Metab Sept 2011
Causes of insulin resistance in
hospitalized patients
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Stress response
Obesity
Electrolyte disturbance: low K/Ca/Mg or high Ca
Feeds
Fatty emulsion eg. Propofol
Steroids/Tacrolimus/Sirolimus
Anesthetic Agents: volatile agents
Hormonal agents: octreotide, leuprolide, bicalutamide
Hormonal disorders: Cushing’s Syndrome, Acromegaly,
Hyperaldosteronism, Pheochromocytoma
Approach to Patient
• Rule-out pseudo-resistance
– Check IV bag, tubing, IV site
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Review medications
Assess for concurrent diseases
Check electrolytes
Check if dextrose is used
Assess feeds, Intralipid
• If patient receiving SC
– Change to IV insulin infusion
– SC insulin may be poorly absorbed due to edema
poor perfusion etc
Feeds/TPN
• May consider adding regular insulin to TPN
bag
– Will decrease risk of hypoglycemia if TPN held
– Max dose 50% of daily requirement of insulin
• Change feed to enteral feeds
• Decrease or hold TPN with consultation
• Decrease Intralipid
– Changing from FFA infusion to soybean fat
Transition form IV to SC
• Suggestions by authors
– Larsen and Goldner (2011)
Patient on and staying on continuous
feeds
• Requirement for Basal and Supplemental
Insulin
– Estimates 24hr insulin requirements from the IV
infusion (eg. units/hr x 24 hrs)
– Options:
• 1/3 dose as NPH q8h
• ½ dose as glargine or detemir q12h
• Full dose as glargine or detemir q24h
• Overlap IV with SC for 3 hrs; sorter if glucose
falls < 5.5 mmol/L
• Change BG checks to q4h once IV is off
• Add fast acting analog or regular insulin q4h
• Reassess and adjust
Currently on continuous feeds with
plans to stop and advance diet
• Requirement for Basal, Bolus and
Supplemental insulin
– Stop feeds while continuing with the IV infusion
– After 4-5 hrs estimate basal requirements
• New rate while off feeds eg. 2 units/hr
• ~24hr req 48 units
– Options
• Give entire basal dose as once daily glargine or detemir
or use split dosing half in the morning, half at HS
• Use NPH: 2/3 ACB and 1/3 evening or 50:50 split
• Estimate requirement for meals
– Give fast acting analog or regular using a CHO ratio with
meals, if previous ratio unknown start with 1:15; if
resistant use 1:7  1:5
– Use fixed dose approx 50% of basal insulin dose divided for
each meal
• (units of basal/3 = units for each meal)
– If limited intake may need small doses with adjustment as
intake improves
• Overlap IV insulin
• Blood glucose checks AC meals and HS, consider 3 AM
checks
Currently on continuous feeds with plan for
intermittent or overnight feeds
• Scheduled overnight feeds
– Calculate 24hr requirements as previously
– At initiation of feeds: administer NPH in the
evening with additional 5-10 units of fast acting
analog or regular insulin
– Check BG at 3AM and at the end of the feeds
– Adjust as required
– If patient eating during the day assess BG levels
and treat if required
• If bolus feeds
– Add fast acting insulin at the time of planned
feeds
– Base dose on CHO count and use a ratio or fixed
dose insulin
Steroids
• May need additional insulin
• NPH may be used in the AM when steroids are
given and adjusted as the dose of steroids is
tapered
• Meal time insulin may also need to be
increased for 4 – 8 hrs after the steroid is
given
• Multiple doses of dex have a long T1/2
The End
• Questions