Lauzier et al: Anemia and Outcomes in Traumatic Brain Injury (2008)

“In this cohort of patients with moderate to severe TBI, we observed that anemia was frequent and independently associated with poor neurologic outcome, whereas RBC transfusion was not.”

— François Lauzier, M.D., M.Sc., et al.

1. Publication Details

  • Trial Title: Anemia and red blood cell transfusion in severe traumatic brain injury
  • Citation: Lauzier F, Boutin A, Moore L, et al. Anemia and red blood cell transfusion in severe traumatic brain injury. Crit Care Med. 2008;36(5):1499-1504. DOI: 10.1097/CCM.0b013e3181692b15
  • Published: May 2008, in Critical Care Medicine
  • Author: François Lauzier, M.D., M.Sc.
  • Funding: Canadian Institutes of Health Research.

2. Keywords

Traumatic Brain Injury (TBI), Anemia, Red Blood Cell Transfusion, Observational Study

3. The Clinical Question

In adult patients with moderate to severe traumatic brain injury (TBI) (Population), is anemia or the administration of a red blood cell (RBC) transfusion (Intervention/Exposure) independently associated with unfavorable neurologic outcome at 6 months (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Anemia is very common in critically ill patients, including those with TBI. While RBC transfusions are given to correct anemia and improve oxygen delivery, their benefit in TBI was uncertain. The landmark TRICC trial (1999) had shown that a restrictive transfusion strategy (hemoglobin trigger of 7 g/dL) was safe in a general ICU population, but patients with TBI were excluded from that trial.
  • Knowledge Gap: It was a major clinical question whether the findings of the TRICC trial could be applied to TBI patients, or if this population had a higher optimal hemoglobin target to ensure adequate cerebral oxygenation. It was unknown if anemia itself, or the act of transfusing, was the primary driver of poor outcomes.
  • Proposed Hypothesis: The authors hypothesized that both anemia and RBC transfusion would be independently associated with unfavorable neurologic outcomes. This dual hypothesis was designed to explore the clinical dilemma: is the primary harm from the underlying anemia (a “first hit” causing secondary brain injury from poor oxygen delivery), or does the treatment itself—transfusion, with its known inflammatory and immunomodulatory risks—also contribute to harm (a “second hit”)?

5. Study Design and Methods

  • Design: A prospective, multicenter, observational cohort study (used to identify risk factors and prognosis).
  • Setting: 3 tertiary care trauma centers in Canada.
  • Trial Period: Data was collected from April 2003 to October 2005.
  • Population:
    • Inclusion Criteria: Adult patients (≥16 years) with moderate to severe TBI (Glasgow Coma Scale score ≤ 12) who were admitted to the ICU.
    • Exclusion Criteria: Included patients who died within 48 hours of admission or who had a penetrating head injury.
  • Intervention: This was an observational study, so there was no assigned intervention. The exposures of interest were the presence of anemia (defined as a hemoglobin level < 10 g/dL) and the receipt of at least one RBC transfusion.
  • Control: There was no control group; patients were stratified based on the presence of anemia and their transfusion status.
  • Management Common to Both Groups: All aspects of patient care, including the decision to transfuse, were at the discretion of the treating clinicians.
  • Power and Sample Size: As an observational study, a formal power calculation was not performed. The study included 464 patients.
  • Outcomes:
    • Primary Outcome: Unfavorable neurologic outcome at 6 months, defined as a Glasgow Outcome Scale (GOS) score of 1-3 (death, vegetative state, or severe disability).
    • Secondary Outcomes: Not a major feature of this publication.

6. Key Results

  • Enrollment and Baseline: 464 patients with moderate to severe TBI were included in the analysis. Anemia was very common, occurring in 76% of patients.
  • Trial Status: The analysis was completed as planned.
  • Primary Outcome: After adjusting for multiple other variables, anemia was independently associated with a significantly higher risk of an unfavorable neurologic outcome at 6 months. In contrast, RBC transfusion was notindependently associated with a poor outcome.
  • Secondary Outcomes: Not applicable.
  • Adverse Events: Not applicable.

7. Medical Statistics

  • Analysis Principle: The study used multivariable regression models to adjust for potential confounding variables.
  • Statistical Tests Used: The primary outcome was analyzed using a logistic regression model.
  • Primary Outcome Analysis: The analysis aimed to determine the independent association of anemia and transfusion with the odds of a poor outcome.
  • Key Statistic(s) Reported: Adjusted Odds Ratio (OR) for an unfavorable outcome.
  • Interpretation of Key Statistic(s):
    • Odds Ratio (OR):
      • Formula: Conceptually, OR = (Odds of event in exposed group) / (Odds of event in unexposed group).
      • Calculation: The paper reports the adjusted OR for anemia as 2.4 and for transfusion as 1.2.
      • Clinical Meaning: The OR of 2.4 for anemia means that patients with anemia had more than double the odds of having a poor neurologic outcome compared to non-anemic patients, even after accounting for other factors. The OR of 1.2 for transfusion was not statistically significant.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI for anemia was 1.2 to 4.7. The 95% CI for transfusion was 0.6 to 2.3.
      • Clinical Meaning: Since the CI for anemia is entirely above 1.0, it confirms that the association with harm is statistically significant. Since the CI for transfusion crosses 1.0, it confirms that there is no statistically significant association between transfusion and outcome.
    • P-value:
      • Calculation: The p-value was not explicitly reported for the ORs, but is <0.05 for anemia and >0.05 for transfusion.
      • Clinical Meaning: The statistical significance is determined by the confidence interval. Because the CI for anemia (1.2-4.7) does not cross 1.0, the association is statistically significant (P < .05). Because the CI for transfusion (0.6-2.3) does cross 1.0, the association is not statistically significant (P > .05).
  • Clinical Impact Measures: As this was an observational study showing association, not causation, NNT is not applicable.

8. Strengths of the Study

  • Study Design and Conduct: A well-conducted, prospective, multicenter observational study with robust statistical adjustment for confounders.
  • Generalizability: The inclusion of patients from three different trauma centers increases the applicability of the findings.
  • Patient-Centered Outcomes: The primary outcome of 6-month functional status is a robust and highly relevant patient-centered endpoint.

9. Limitations and Weaknesses

  • Internal Validity (Bias): As an observational study, it can only show association, not causation. It is susceptible to residual confounding; it is possible that unmeasured factors associated with both anemia and poor outcomes could explain the results.
  • External Validity (Generalizability): The findings are highly generalizable to patients with moderate to severe TBI.
  • Other: The study does not define an optimal hemoglobin trigger for transfusion, it only suggests that anemia is harmful and that transfusion (at the discretion of the clinicians) was not.

10. Conclusion of the Authors

The authors concluded that in patients with moderate to severe TBI, anemia is an independent predictor of poor neurologic outcome, whereas RBC transfusion is not.

11. To Summarize

  • Impact on Current Practice: This was a highly influential study that provided the first strong evidence that anemia is harmful in TBI and that a more liberal transfusion strategy than the one suggested by the TRICC trial might be warranted in this specific population.
  • Specific Recommendations:
    • Patient Selection: For adult patients with moderate to severe TBI.
    • Actionable Intervention: The findings support a strategy of actively monitoring for and correcting anemia with RBC transfusion to a target that is likely higher than the 7 g/dL used in the general ICU population.
  • What This Trial Does NOT Mean: This trial does NOT prove that transfusion is beneficial, only that it was not associated with harm in this study and that the underlying anemia was.
  • Implementation Caveats: The key takeaway is that TBI patients may be a special population that is less tolerant of anemia than general ICU patients.

12. Context and Related Studies

  • Building on Previous Evidence: The Lauzier et al. study (2008) directly addressed the major clinical question of whether the restrictive transfusion strategy from the TRICC trial (1999) was safe to apply to TBI patients.
  • Influence on Subsequent Research: The findings of this study, suggesting that TBI patients may be different, have been a major driver of subsequent randomized controlled trials specifically designed to determine the optimal transfusion threshold in TBI, such as the TRACTION trial.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: This observational study could not answer the key question of what the optimal hemoglobin trigger for transfusion should be in TBI.
  • Future Directions: The definitive answer to this question requires a large, multicenter randomized controlled trial comparing a restrictive versus a liberal transfusion strategy specifically in the TBI population.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a critical uncertainty in the management of a common and devastating condition.
  • Methods: The main methodological limitation is the observational design, which is subject to confounding. However, the prospective, multicenter nature of the study and the robust statistical analysis are major strengths.
  • Results: The study reported a strong and statistically significant association between anemia and poor outcomes, and importantly, no association between transfusion and poor outcomes.
  • Conclusions and Applicability: The authors’ conclusion is a fair and appropriate interpretation of their data. While not proving causation, this study provided powerful, hypothesis-generating evidence that has been highly influential in guiding clinical practice towards a more liberal transfusion threshold in TBI, pending the results of definitive randomized trials.

16. Disclaimer and Contact

This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.

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