CI: Blood Glucose Control (2009)


Oddo M, Schmidt M, Carrera E, Badjatia N, Connolly ES, Presciutti M, Ostapkovich ND, Levind J, Le Roux P and Mayer S. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: A microdialysis study. Crit Care Med. 2008; 36: 3,233.

PubMed ID: 18936695
Study Design:
Retrospective Cohort Study
B - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:


The purpose was to analyze effect of tight BG control on cerebral glucose metabolism in patients with severe brain injury.


Inclusion Criteria:
  • Trauma patient with intraparenchymal intracranial pressure (ICP), brain tissue oxygenation (PbtO2), and cerebromicrodialysis (CMD) monitoring as part of their clinical care
  • CMD monitoring initiated if GCS ≤ 8.


Exclusion Criteria:

No CMD monitoring required

Description of Study Protocol:


Patients in ICU who required CMD 


Prospective cohort study 

Blinding used

Not applicable 


Outcome of interest: Mortality related to tight blood glucose control

Statistical Analysis

  • Univariate analyses with Student's T-test for continuous variables and x2 for categorical variables
  • Multivariable logistic regression with regression link function and modeling within subject dependencies with the autoregressive process.
Data Collection Summary:

Timing of Measurements

CMD glucose, lactate and pyruvate were analyzed hourly

Independent Variables

Blood glucose control:

  • Low (less than 80mg/dl)
  • Tight (80-110mg/dl)
  • Intermediate (111-180mg/dl)
  • High (greater than 180mg/dl).

Dependent Variable

Brain energy crisis (defined as  a cerebral microdialysis glucose less than 0.7mmol/L with a lactate/pyruvate ratio greater than 40).

Control Variables

Serum glucose, insulin dose, CPP, ICP and GCS were covariates; all patients received EN.



Description of Actual Data Sample:

Initial N

20 (45% male)


Mean 59 (range 36-76)


Not described

Other relevant demographics

  • Median admission GCS 7 (range 3-10);
  • Median admission APACHE II score 23 (range 14-30).

Anthropometrics (e.g., were groups same or different on important measures)


Department of Neurology (MO, JMS, EC, NB, MP, NDO, SAM), Critical Care Division, Care (JML) and Department of Neurosurgery (PLR), University of Pennsylvania School of Medicine, Philadelphia, PA.








Summary of Results:


Variables Tight Serum BG Group Intermediate Serum BG Group Statistical Significance of Group Difference
Low CMD Glucose  65%  36%  P<0.01
Brain Energy Crisis   25%  17%  P<0.01

Multivariate analyses adjusting for intracranial pressure and cerebral perfusion pressure:

  • Systemic glucose concentration (adjusted OR 1.23, 95% CI 1.10-1.37)
  • For each 1mmol/L decrease, adjusted OR 1.10, 95% CI 1.04-1.17)
  • For each 1mmol/L increase
  • Cerebral microdialysis glucose lower in non-survivors than in survivors (0.46 0.23 vs. 1.04 0.56mmol/L P,0.05)
  • Brain energy crisis associated with increased mortality at hospital discharge (adjusted OR 7.36, 95% CI 1.37-39.51, P=0.02.




Author Conclusion:

Intensive insulin therapy may impair cerebral glucose metabolism after severe brain injury. In these patients, tightly controlling serum glucose is associated with reduced cerebral glucose availability and increased prevalence of energy crisis. This correlates with higher mortality.

Funding Source:
Government: Swiss National Science Foundation
SICPA Foundation of Lausanne, Switzerland
Reviewer Comments:
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? ???
  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? ???
  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? ???
  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? 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? Yes
  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.) Yes
  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? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  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? No
  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? N/A
  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)? No
  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? No
  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? N/A
  10.1. Were sources of funding and investigators' affiliations described? N/A
  10.2. Was the study free from apparent conflict of interest? N/A