CI: Blood Glucose Control (2009)
Krinsley JS Effect of an intensive glucose management protocol on the mortality of critically ill patients. Mayo Clin Proc Nov 15, 2004. 2004;79(8):992-1000.PubMed ID: 15301325
The purpose of this research was to test the effect of an intensive glycemic management protocol on outcomes in critically ill patients. The investigators were testing a protocol developed to maintain blood glucose levels at < 140 mg/dL. Continuous IV insulin was administered if CBG > 200 on 2 successive occasions. Patients were then changed to long-acting insulin or hypoglycemic agents as soon as appropriate.
There were two cohorts:
- 800 patients admitted to ICU immediately before protocol initiated
- next 800 patients admitted to ICU after protocol initiated
- non ICU patients
Recruitment n/a; subjects from database maintained by ICU director
Design Nonconcurrent Cohort Study (database study)
Blinding used (not applicable)
Intervention: maintain blood glucose levels at < 140 mg/dL
glucose (mg/dL), age (years), length of stay (0.1 hr increments), and APACHE II scores expressed as median and interquartile range
X2 statistic used to asasess differences between baseline and treatment groups regarding sex, race, % with diabetes, % of medical versus surgical services, % of patients requring red blood cell transfusions, and mortality rates.
Fisher exact test used to assess differences between baseline and reatment groups in development of new renal insufficiency during ICU stay.
Statistical significance defined a priori as P<.05. All results 2-tailed.
There were no multivariate statistical analyses.
Timing of Measurements
Protocol was nurse-driven. If no plasma glucose value was available, nurses obtained fingerstick for capillary blood glucose levels q 3 hours. If glucose values were stable, values were obtained less frequently.
- New renal problems (measured creatinine)
- Need for transfusions (measured transfusions given)
- Length of ICU stay ((LOS) was measured in 0.1 hr increments)
- mortality (final discharge status: death or survival)
- Blood glucose level
Initial N: 1600
Attrition (final N): 1600(same as above)
Age: median age 70 and 69 for control and treatment groups, respectively (p =.71)
Ethnicity: No significant differences based on race
Other relevant demographics:
Median APACHE II similar for baseline and trt groups: median 15; IQR (10-23)
Number of diabetic patients similar: 16.4% (baseline) and 18.1% (treatment); Groups were similar by diagnosis:
|Diagnosis||Baseline (% pt)||Trt (% pt)||Apache II Score per diagnosis||Baseline||Trt|
|other medical||10.8||11.6||other medical||16||15|
|septic shock||4.3||5.1||septic shock||28||25|
|general surgery||17.9||15.3||general surgery||14||13|
|median APACHE score||16||15|
Anthropometrics - no statistically significant differences
Location:The Stamford Hospital, Stamford, CT
Measures and confidence intervals
Measures and confidence intervals
Statistical Significance of Group Difference
130.7 (107-172) mg/dL
|glucose > 200 mg/dL||7.1 %||16.2 %||p<.001|
|severe hypoglycemia (glucose < 40 mg/dL)||0.35%||0.34%||p=.89|
|new renal dysfunction||3%||12%||p=.03|
|ICU acquired infections||NS differences|
|median length of stay (LOS)||1.6 day||1.9 day||
10.8% reduction in median LOS p=.01
mean length of stay (LOS)
29.3% lower mortality in treatment group; Most striking improvement was during patients with septic shock who had a decrease in mortality from 60.4% in baseline to 33.3% (p=.02) in the treatment group.
Survival was not better among patients with APACHE II scores > 35, but survivial for patients on treatment protocol was significantly improved.
|APACHE II score||
Base # pt
Trt # pt
|Change in Mortality for protocol patients||P value|
Protocol did not require change in staffing requiremens in ICU.
Protocol led to significantly improved glucose levels without a significant increase in episodes of hyperglycemia.
During the two periods there was:
- 29.3% decrease in mortality.
- Mean LOS in the ICU decreased from 3.58 days in baseline group to 3.19 days in treatment group, however this was not statistically significant (p=.11).
- 10% reduction in median (interquartile range) LOS in the ICU. LOS decreased from 1.9 (1.0 - 3.9) days in baseline group to 1.6 (0.9-3.3) days in the treatment group (p=.01)
- 42.4% increase in plasma glucose values in the 60 - 99 range.
- 56.3% decrease in plasma glucose values > 200 mg/dL.
140 mg% is a safe, achievable goal. The study was not powered adeuately to allow subgroup analysis, but mortality trended to decrease, especially with neurological patients (21 to 8.5% decrease in mortality p = .007) and septic shock patients (decreased from 0.4% to 33.3% p = .02).
The authors did not address clinical significance of reduced LOS of 0.3 days (7.2 hr) reported in this article. However, in a later article (Krinsley and Jones, 2006) they performed cost analyses based on actual services such as laboratory and imaging.
Quality Criteria Checklist: Primary Research
|1.||Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)||Yes|
|2.||Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?||Yes|
|3.||Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?||Yes|
|4.||Is the intervention or procedure feasible? (NA for some epidemiological studies)||Yes|
|1.||Was the research question clearly stated?||Yes|
|1.1.||Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?||Yes|
|1.2.||Was (were) the outcome(s) [dependent variable(s)] clearly indicated?||Yes|
|1.3.||Were the target population and setting specified?||Yes|
|2.||Was the selection of study subjects/patients free from bias?||Yes|
|2.1.||Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?||Yes|
|2.2.||Were criteria applied equally to all study groups?||Yes|
|2.3.||Were health, demographics, and other characteristics of subjects described?||Yes|
|2.4.||Were the subjects/patients a representative sample of the relevant population?||Yes|
|3.||Were study groups comparable?||Yes|
|3.1.||Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)||Yes|
|3.2.||Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?||Yes|
|3.3.||Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)||Yes|
|3.4.||If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?||Yes|
|3.5.||If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)||N/A|
|3.6.||If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?||N/A|
|4.||Was method of handling withdrawals described?||N/A|
|4.1.||Were follow-up methods described and the same for all groups?||Yes|
|4.2.||Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)||N/A|
|4.3.||Were all enrolled subjects/patients (in the original sample) accounted for?||Yes|
|4.4.||Were reasons for withdrawals similar across groups?||Yes|
|4.5.||If diagnostic test, was decision to perform reference test not dependent on results of test under study?||N/A|
|5.||Was blinding used to prevent introduction of bias?||N/A|
|5.1.||In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?||N/A|
|5.2.||Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)||N/A|
|5.3.||In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?||Yes|
|5.4.||In case control study, was case definition explicit and case ascertainment not influenced by exposure status?||N/A|
|5.5.||In diagnostic study, were test results blinded to patient history and other test results?||N/A|
|6.||Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?||N/A|
|6.1.||In RCT or other intervention trial, were protocols described for all regimens studied?||Yes|
|6.2.||In observational study, were interventions, study settings, and clinicians/provider described?||N/A|
|6.3.||Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?||Yes|
|6.4.||Was the amount of exposure and, if relevant, subject/patient compliance measured?||Yes|
|6.5.||Were co-interventions (e.g., ancillary treatments, other therapies) described?||Yes|
|6.6.||Were extra or unplanned treatments described?||Yes|
|6.7.||Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?||Yes|
|6.8.||In diagnostic study, were details of test administration and replication sufficient?||N/A|
|7.||Were outcomes clearly defined and the measurements valid and reliable?||Yes|
|7.1.||Were primary and secondary endpoints described and relevant to the question?||Yes|
|7.2.||Were nutrition measures appropriate to question and outcomes of concern?||N/A|
|7.3.||Was the period of follow-up long enough for important outcome(s) to occur?||Yes|
|7.4.||Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?||Yes|
|7.5.||Was the measurement of effect at an appropriate level of precision?||Yes|
|7.6.||Were other factors accounted for (measured) that could affect outcomes?||Yes|
|7.7.||Were the measurements conducted consistently across groups?||Yes|
|8.||Was the statistical analysis appropriate for the study design and type of outcome indicators?||Yes|
|8.1.||Were statistical analyses adequately described and the results reported appropriately?||Yes|
|8.2.||Were correct statistical tests used and assumptions of test not violated?||Yes|
|8.3.||Were statistics reported with levels of significance and/or confidence intervals?||Yes|
|8.4.||Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?||N/A|
|8.5.||Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?||Yes|
|8.6.||Was clinical significance as well as statistical significance reported?||Yes|
|8.7.||If negative findings, was a power calculation reported to address type 2 error?||N/A|
|9.||Are conclusions supported by results with biases and limitations taken into consideration?||Yes|
|9.1.||Is there a discussion of findings?||Yes|
|9.2.||Are biases and study limitations identified and discussed?||Yes|
|10.||Is bias due to study's funding or sponsorship unlikely?||Yes|
|10.1.||Were sources of funding and investigators' affiliations described?||Yes|
|10.2.||Was the study free from apparent conflict of interest?||Yes|