Elsevier

The Lancet Neurology

Volume 6, Issue 3, March 2007, Pages 215-222
The Lancet Neurology

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Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials

https://doi.org/10.1016/S1474-4422(07)70036-4Get rights and content

Summary

Background

Malignant infarction of the middle cerebral artery (MCA) is associated with an 80% mortality rate. Non-randomised studies have suggested that decompressive surgery reduces this mortality without increasing the number of severely disabled survivors. To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery, results from three European randomised controlled trials (DECIMAL, DESTINY, HAMLET) were pooled. The trials were ongoing when the pooled analysis was planned.

Methods

Individual data for patients aged between 18 years and 60 years, with space-occupying MCA infarction, included in one of the three trials, and treated within 48 h after stroke onset were pooled for analysis. The protocol was designed prospectively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials. The primary outcome measure was the score on the modified Rankin scale (mRS) at 1 year dichotomised between favourable (0–4) and unfavourable (5 and death) outcome. Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0–3 and 4 to death. Data analysis was done by an independent data monitoring committee.

Findings

93 patients were included in the pooled analysis. More patients in the decompressive-surgery group than in the control group had an mRS≤4 (75% vs 24%; pooled absolute risk reduction 51% [95% CI 34–69]), an mRS≤3 (43% vs 21%; 23% [5–41]), and survived (78% vs 29%; 50% [33–67]), indicating numbers needed to treat of two for survival with mRS≤4, four for survival with mRS≤3, and two for survival irrespective of functional outcome. The effect of surgery was highly consistent across the three trials.

Interpretation

In patients with malignant MCA infarction, decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome. The decision to perform decompressive surgery should, however, be made on an individual basis in every patient.

Introduction

Life-threatening, space-occupying brain oedema occurs in 1–10% of patients with a supratentorial infarct and usually manifests itself between the second and fifth day after stroke onset.1, 2, 3 However, up to a third of patients can have neurological deterioration within 24 h of symptom onset.4 The prognosis of these space-occupying or malignant middle cerebral artery (MCA) infarctions is poor, with case fatality rates in intensive care-based series of nearly 80%.5, 6 No medical treatment has been proven effective.7 Different predictors of fatal brain oedema formation have been identified, such as major early CT hypodensity involving more than 50% of the MCA territory and other vascular territories.8 However, up to now no single prognostic factor with sufficient prognostic value has been identified.

Non-randomised studies have suggested that decompressive surgery, consisting of a hemicraniectomy and duraplasty, reduces mortality in patients with malignant MCA infarction without increasing the number of severely disabled survivors.9, 10, 11, 12 However, evidence from randomised trials is lacking. Whereas most clinicians agree that the procedure is probably life-saving, no convincing data are available regarding functional outcome of survivors.

The effect of decompressive surgery on functional outcome in patients with malignant MCA infarction has been studied in three European randomised controlled trials: the French DECIMAL (decompressive craniectomy in malignant middle cerebral artery infarcts) trial; the German DESTINY (decompressive surgery for the treatment of malignant infarction of the middle cerebral artery) trial; and the Dutch trial HAMLET (hemicraniectomy after middle cerebral artery infarction with life-threatening edema trial).13 Two of these trials interrupted recruitment early in 2006: DECIMAL because of slow recruitment and a significant difference in mortality between the treatment groups favouring surgery; and DESTINY because a predefined sequential analysis showed a significant benefit of surgery on mortality. HAMLET is ongoing.

As the three trials have a similar design and share the same primary outcome measure—ie, favourable versus unfavourable functional outcome as determined by the score on the modified Rankin scale (mRS)14—a collaborative protocol for a pooled analysis of individual patient data from the three trials was planned before the interruption of the first two trials. The principal aim of this pooled analysis was to obtain sufficient data to reliably estimate the effects of decompressive surgery as soon as possible so as to avoid unnecessary (and unethical) continuation of randomisation in the individual trials.

Section snippets

Trials

We combined individual patient data from DECIMAL (NCT00190203), DESTINY (ISRCTN01258591), and HAMLET (ISRCTN94237756), which are multicentre, randomised, controlled clinical trials assessing the effect of decompressive surgery in patients with space-occupying MCA infarction. When the pooled analysis was planned the trials were still ongoing and there was no knowledge of outcome data except for mortality rates in DECIMAL and DESTINY. At the time of the analysis, DECIMAL and DESTINY had been

Results

All patients randomised in DECIMAL (38 patients) and DESTINY (32 patients) and 23 patients randomised in HAMLET were eligible for the pooled analysis. From HAMLET, 34 of a total of 57 patients were excluded because they were randomised after 45 h from stroke onset or were included after Nov 1, 2005. For all other patients there were no missing data on primary or secondary outcome measures. Thus, 93 patients were included, of whom 51 were randomised to decompressive surgery and 42 to

Discussion

This pooled analysis of randomised trials confirms suggestions from non-randomised studies that decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome after malignant hemispheric infarction.9, 10, 12 Patients with massive space-occupying hemispheric infarction have a poor prognosis: in intensive-care based series of patients not treated with decompressive surgery, the case fatality rate was about

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