Fast track — ArticlesSurgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial
Introduction
Patients with space-occupying hemispheric infarction have a poor prognosis. In intensive care-based series, the rates of case fatality were about 80%, and most survivors were left severely disabled.1, 2 No medical therapy has proved effective.3 Decompressive surgery—removal of part of the skull and duraplasty—has been proposed as a way to accommodate shifts of brain tissue and normalise intracranial pressure, thereby preserving cerebral blood flow and preventing transtentorial herniation and secondary damage.4 The results of observational studies that had historical controls suggest that surgical decompression reduces death rate, improves the functional outcome of patients with space-occupying hemispheric infarction, and has a greater benefit if done on the first day after stroke onset rather than later.4, 5
In the randomised trials DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction6) and DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY7), surgical decompression done within 30 or 36 h from stroke onset reduced case fatality compared with the best medical treatment; however, the numbers of patients were too small (38 and 32 patients, respectively) to prove the benefit of surgery on functional outcome.
In a meta-analysis of DECIMAL and DESTINY that included 23 patients from the then-ongoing randomised Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial (HAMLET),8 surgical decompression within 48 h of stroke onset doubled the chance of a favourable functional outcome, which was defined as a modified Rankin scale (mRS) score of 3 or lower.9 However, the effect of the operation on this outcome in patients categorised by the timing of treatment, age, or the presence of aphasia was uncertain. Furthermore, quality of life was assessed in only 12 of the 19 surviving patients in DECIMAL and in none of the patients in DESTINY. Symptoms of depression were not assessed in either trial. In addition, the effect of surgery done later than the first 2 days after stroke onset was not assessed in DECIMAL, DESTINY, or the pooled analysis, whereas space-occupying oedema usually manifests on the second to fourth day after stroke onset.1
We present the final results of HAMLET, which was designed to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction, and an updated meta-analysis of the results from the three trials.
Section snippets
Patients
Patients were enrolled between November, 2002, and October, 2007, at six centres in the Netherlands, according to a previously published protocol.10 The trial was approved by the institutional review board of each participating centre, and written informed consent was obtained from a legal representative of each patient. The eligibility criteria are summarised in panel 1.
Procedures
Patients were randomly assigned to surgical decompression or best medical treatment by use of a computerised randomisation
Results
The data monitoring committee advised that recruitment of patients into HAMLET was stopped after 50 patients had been seen and graded 1 year after randomisation. The reason for stopping the trial was that it was highly unlikely that a statistically significant difference would be seen for the primary outcome measure between the two treatment groups with the planned sample size. At this time, 64 patients had been recruited. During HAMLET, only one patient was operated on outside of the trial in
Discussion
The results of HAMLET show that surgical decompression within 4 days of symptom onset does not reduce poor outcome in patients with space-occupying hemispheric infarction, despite a substantial reduction in case fatality in these patients. Surgical decompression does, however, reduce the probability of a poor outcome in patients who were randomised within 48 h of symptom onset. Whether there is any benefit of surgical decompression on the third or fourth day after stroke onset is unknown.
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HAMLET investigators listed at end of report