EAL

CI: Blood Glucose Control (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Purpose of this research was to determine the effect of blood glucose control on mortality and morbidity in patients in a surgical ICU.

Inclusion Criteria:

Adults receiving mechanical ventilation admitted to surgical intensive care unit between 2/2/2000 and 1/18/2001
Informed consent obtained from closest family member

Exclusion Criteria:

Patient participating in another trial
Moribund or DNR order

Description of Study Protocol:

Recruitment

Recruited from mechanically ventilated patients admitted to the surgical ICU.

Design

Prospective RCT

Blinding used (if applicable)

N/A

Intervention (if applicable)

Insulin infusion to maintain blood glucose level at treatment or control level

Statistical Analysis

Investigators had planned to enroll 2500 patients; however quarterly interim analyses of overall mortality in the ICU (two-sided alpha level < 0.01) led to early termination of the study after the 4^th interim analysis. The conventional treatment was inferior.

Base-line and outcome variables compared by Student's t-test, X2 test, or Mann-Whitney U test. Odds ratios estimated by multivariate logistic-regression analysis. Effect of intensive insulin therapy on time of death assessed by Kaplan-Meier analysis and Mantel-Cox log-rank test.

Data Collection Summary:

Timing of Measurements

BG values checked multiple times daily

Dependent Variables

Mortality (death)
Length of stay (days)
Duration of mechanical ventilation (days)
Renal complications (dialysis or continuous venovenous hemofiltration)
Septicemia (treatment with antibiotics)
Polyneuropathy (electromyography)
Cumulative TISS-28 scores (therapeutic intervention scoring system – each therapeutic intervention assigned 1 to 4 points and points are summed daily to obtain overall score)

Independent Variables

Blood glucose level

Control Variables

Description of Actual Data Sample:

Initial N: 1548 (71% male gender)

Attrition (final N): N/A

Age: Conventional trt: 62.2 ± 13.9; Intensive trt: 63.4 ± 13.6

Ethnicity: not described

Other relevant demographics:

APACHE II score median of 9; IQF 6-13 for both groups (2^nd 24-h period)

Anthropometrics

BMI (Conventional trt 25.8 ± 4.7 and Intensive trt 26.2 ± 4.4)
Reasons for ICU trt similar by diagnosis
APACHE II scores, history of cancer and history of diabetes NS different between groups

Location:

University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium

Summary of Results:

Variable	Conventional Treatment	Intensive Treatment	P Value
Mortality (death) – all patients	10.9%	7.2%	0.01
Mortality (death) - patients with median ICU LOS > 5 days	26.3%	16.8%	0.01
Median LOS in ICU—all patients	3d	3d	0.2
Median ICU LOS > 5 days	15d	12d	0.003
Duration of mechanical ventilation—all patients	2d	2d	0.06
Duration of mechanical ventilation for patients > 5 days ICU LOS	12	10	0.006
Patients requiring > 14 d mechanical ventilation	11.9%	7.5%	0.003
Patients requiring dialysis	8.2%	4.8%	0.007
Septicemia during ICU	7.8%	4.2%	0.003
Treatment with antibiotics > 10 d	17.1%	11.2%	0.001
Polyneuropathy	51.9%	28.7%	0.001
Median Cumulative TISS-28 scores for all patients	108	105	0.2
Median Cumulative TISS-28 scores for patients with > 5 d ICU LOS	563	431	0.001

Other Findings

No difference in mean days on mechanical ventilation for patients with ICU LOS < 5 d.

Author Conclusion:

Regardless of whether patients had a history of diabetes, use of exogenous insulin to maintain blood glucose between 80 and 110 mg/dL reduced morbidity and mortality among surgical critically ill patients.

Funding Source:

University/Hospital:

Catholic University of Leuven

Reviewer Comments:

Well designed, landmark study of mortality and morbidity as related to glucose control in critically ill patients. The study was stopped early as the intensive treatment to control BG between 80 and 110 mg/dL was clearly superior to conventional treatment.

Quality Criteria Checklist: Primary Research
Relevance Questions
	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

Validity Questions
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?	N/A
	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?		Yes
	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	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?	No
	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.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	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?	Yes
	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