RESCUEicp: Decompressive Craniectomy in Traumatic Brain Injury (2016)

“Our trial showed that decompressive craniectomy was associated with lower mortality than ongoing medical care. However, it was also associated with higher rates of vegetative state, lower severe disability, and upper severe disability; rates of moderate disability and good recovery were similar in the two groups.”

  • The RESCUEicp Trial Collaborators

1. Publication Details

  • Trial Title: Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension
  • Citation: Hutchinson PJ, Kolias AG, Timofeev IS, et al. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension. N Engl J Med. 2016;375(12):1119-1130. DOI: 10.1056/NEJMoa1605215
  • Published: September 22, 2016, in The New England Journal of Medicine
  • Author: Peter J. Hutchinson, F.R.C.S.(SN), Ph.D.
  • Funding: UK Medical Research Council.

2. Keywords

  • Traumatic Brain Injury (TBI), Decompressive Craniectomy, Intracranial Hypertension, Neurosurgery, Critical Care, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients with traumatic brain injury (TBI) and refractory intracranial hypertension (Population), does a strategy of decompressive craniectomy (Intervention) compared to ongoing advanced medical management (Comparison) improve functional outcomes at 6 months (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Refractory intracranial hypertension (ICP) after TBI is a life-threatening condition. The DECRA trial (2011) had controversially found that an early craniectomy for diffuse injury resulted in worse functional outcomes. However, craniectomy was still widely used as a “last-ditch” or rescue therapy for more severe, sustained ICP elevation.
  • Knowledge Gap: A large, definitive randomized trial was needed to determine if decompressive craniectomy, used as a later, second-tier therapy for refractory ICP in a broader TBI population (including those with mass lesions), was beneficial or harmful.
  • Proposed Hypothesis: The authors hypothesized that a strategy of decompressive craniectomy would be superior to ongoing medical management in reducing death and severe disability in patients with TBI and refractory intracranial hypertension.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, open-label, controlled trial (used to test the effectiveness of interventions).
  • Setting: 52 intensive care units (ICUs) in the United Kingdom.
  • Trial Period: Enrollment ran from January 2004 to March 2014.
  • Population:
    • Inclusion Criteria: Adult patients (10-65 years) with a TBI and an ICP of >25 mm Hg for more than 1 to 12 hours that was refractory to initial, first-tier medical therapies.
    • Exclusion Criteria: Included patients with bilateral fixed and dilated pupils or those not expected to survive.
  • Intervention: Patients were randomized to undergo a decompressive craniectomy (either a large hemicraniectomy or a bifrontal craniectomy) plus standard medical care.
  • Control: Patients were randomized to continue with advanced medical management, including the option for barbiturate coma.
  • Management Common to Both Groups: All patients were managed with a protocolized, tiered approach to ICP management based on international guidelines.
  • Power and Sample Size: The authors calculated that a sample size of 400 patients would provide 80% power to detect a 12% absolute difference in the primary outcome. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: Functional outcome at 6 months, as assessed by the Extended Glasgow Outcome Scale (GOSE).
    • Secondary Outcomes: Included mortality at 6 months and the distribution of GOSE scores.

6. Key Results

  • Enrollment and Baseline: 408 patients were randomized (206 to craniectomy and 202 to medical care). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: The distribution of functional outcomes on the GOSE at 6 months was significantly different between the groups, favoring the surgical group in terms of survival but not necessarily good functional recovery.
  • Secondary Outcomes: Mortality at 6 months was dramatically lower in the craniectomy group: 55 of 206 patients (26.7%) died, compared with 96 of 202 patients (47.5%) in the medical-care group (p<0.001). However, the rate of patients in a vegetative state was significantly higher in the craniectomy group (6.2% vs. 1.5%).
  • Adverse Events: The incidence of adverse events was high in both groups, consistent with the severity of the injury.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using an ordinal logistic regression model (shift analysis).
  • Primary Outcome Analysis: The primary outcome was a comparison of the overall distribution of GOSE scores between the two groups.
  • Key Statistic(s) Reported: The key statistics were the rates of death and the distribution of functional outcomes.
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of <0.001 for the difference in 6-month mortality is extremely low, indicating a highly statistically significant survival benefit for craniectomy.
  • Clinical Impact Measures (for mortality):
    • Absolute Risk Reduction (ARR):
      • Formula: ARR = (Risk in Control Group) – (Risk in Intervention Group)
      • Calculation: ARR = 47.5% – 26.7% = 20.8%.
      • Clinical Meaning: For every 100 patients treated with craniectomy, about 21 additional deaths were prevented at 6 months.
    • Number Needed to Treat (NNT):
      • Formula: NNT = 1 / ARR
      • Calculation: NNT = 1 / 0.208 = 4.8, which is rounded up to 5.
      • Clinical Meaning: You would only need to treat 5 patients with decompressive craniectomy to prevent one additional death.
  • Subgroup Analyses: The benefit of craniectomy was consistent across subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The large, multicenter, randomized, controlled design provided high-quality evidence on a critical clinical question.
  • Generalizability: The pragmatic design and inclusion of a large number of diverse centers make the findings highly generalizable to real-world practice.
  • Statistical Power: The study was large and adequately powered for its primary outcome.
  • Patient-Centered Outcomes: The study focused on the crucial outcomes of mortality and long-term functional status.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which is an unavoidable limitation for a major surgical trial.
  • External Validity (Generalizability): The findings are highly generalizable to the broad population of TBI patients with refractory intracranial hypertension.
  • Other: The most important limitation is the ethical complexity of the outcome: the intervention was highly effective at saving lives but did so at the cost of increasing the number of survivors with severe disability or in a vegetative state.

10. Conclusion of the Authors

  • The authors concluded that in patients with TBI and refractory intracranial hypertension, decompressive craniectomy resulted in lower mortality but higher rates of vegetative state and severe disability.

11. To Summarize

  • Impact on Current Practice: This was a landmark trial that provided a clear and sobering picture of the true risk-benefit trade-off of decompressive craniectomy. It confirmed that the surgery is life-saving but forced a major shift in how clinicians discuss the likely outcomes with families.
  • Specific Recommendations:
    • Patient Selection: For adult patients with TBI and refractory intracranial hypertension.
    • Actionable Intervention: Decompressive craniectomy can be offered as a life-saving therapy.
    • Expected Benefit: This intervention has a very large effect on survival, with an NNT of only 5 to prevent one death.
  • What This Trial Does NOT Mean: This trial does NOT mean that all survivors will have a poor functional outcome, but it highlights that a significant proportion will be left with severe, life-altering disability.
  • Implementation Caveats: The key takeaway is the critical importance of a detailed and honest shared decision-making process with the patient’s family, explicitly discussing the high probability that survival will come at the cost of significant disability.

12. Context and Related Studies

  • Building on Previous Evidence: The RESCUEicp trial (2016) was a direct response to the controversial negative findings of the DECRA trial (2011). By studying a sicker population with more sustained ICP elevation and including patients with mass lesions, RESCUEicp was designed to test the surgery in a “last resort” scenario.
  • Influence on Subsequent Research: The findings of this trial have been highly influential in shaping guidelines and, more importantly, in emphasizing the central role of shared decision-making and goals-of-care discussions in neurocritical care.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The key unresolved question from this trial is not a scientific one, but an ethical one: how do patients, families, and societies value survival with severe disability?
  • Future Directions: Future research is focused on improving neuro-rehabilitation and on identifying which patients might be more likely to have a more favorable functional recovery after this life-saving surgery.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, seeking to provide a definitive answer on the role of a major surgical intervention for a devastating condition, particularly in light of the conflicting results of the earlier DECRA trial.
  • Methods: The multicenter RCT design was appropriate and robust. The main methodological limitation is the open-label design, which is unavoidable for this type of intervention.
  • Results: The study reported a clear and dramatic reduction in mortality. However, it also clearly showed that this survival benefit did not translate into an increase in survival without severe disability; in fact, it increased the number of patients in a vegetative state. This complex and nuanced result is the most important finding of the trial.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The trial is a landmark in neurocritical care, not just for its scientific findings, but for the profound ethical and clinical questions it raises about the goals of care. Its findings are highly applicable, but they come with the major caveat that the intervention must be preceded by a detailed discussion about the likely outcomes.

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.
Scroll to Top