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(Stroke. 1998;29:1477-1478.)
© 1998 American Heart Association, Inc.

Letters to the Editor

Surgery for Primary Intracerebral Hemorrhage: Meta-analysis of CT-Era Studies

Jeffrey L. Saver, MD

Department of Neurology, UCLA Stroke Center, Los Angeles, California

To the Editor:

I read with interest Hankey and Hon's recent review of studies of surgery for primary intracerebral hemorrhage.¹ Their systematic review of case series is a novel contribution to the literature. There is some precedent, however, for their meta-analysis of extant randomized controlled trials of surgical versus medical therapy. The authors may have been unaware of my brief meta-analysis of the same 4 trials, published 3 years earlier, as it appeared in a book chapter rather than a Medline article.² Contrasts between the two meta-analyses are illuminating.

My formal systematic overview examined the clinical end point of mortality rather than the combined clinical end point of death or dependency used by Hankey and Hon. Collating all 4 studies, I found no major effect of surgery, with an odds ratio of fatal outcome of 0.97 (95% confidence interval [CI], 0.64 to 1.48). This finding is similar that of Hankey and Hon for the combined death or dependency end point. Theirs is, I will add, the more clinically relevant end point.

However, I additionally chose to cluster for separate analysis the 3 modern, CT-era trials. Strong arguments can be made that the large, early trial of McKissock et al,³ now 37 years old, should not be mingled with the 3 later studies from the past decade. McKissock and colleagues were not able to use CT scans for planning of operative approach and did not have modern microsurgical techniques to deploy intraoperatively. The surgical mortality rate in the McKissock trial exceeded that of later studies by 15% to 23%. And because the McKissock trial sample size was larger than that of the 3 later trials combined, its data are likely to mask trends latent in the smaller, modern studies.

Pooling results from the modern era studies of Juvela et al,⁴ Auer et al,⁵ and Batjer et al,⁶ I found a statistically significant benefit of surgery on mortality, with odds of death of 0.50 (95% CI, 0.28 to 0.92). Employing Hankey and Hon's abstraction of data, pooled analysis of these 3 studies for the end point of death or dependency reveals a trend toward lower odds of death or dependency at 6 months (odds ratio, 0.72; 95% CI, 0.38 to 1.44).

These promising trends should encourage further clinical trials of decompressive surgery for primary intracerebral hemorrhage. Our current database is pitiably small, even in pooled analysis. As Hankey and Hon note, a trial large enough to definitively identify the benefits and risks of surgery is urgently needed.

References

1. Hankey GJ, Hon C. Surgery for primary intracerebral hemorrhage: is it safe and effective? Stroke.. 1997;28:2126–2132.[Abstract/Free Full Text]

2. Saver JL. Surgical therapy. In: Feldmann E, ed. Intracerebral Hemorrhage. Armonk, NY: Futura Publishing Co; 1994:303–332.

3. McKissock W, Richardson A, Taylor J. Primary intracerebral hemorrhage: a controlled trial of surgical and conservative treatment. Lancet.. 1961;2:221–226.

4. Juvela S, Heiskanen O, Poranen A, Valtonen S, Kuurne T, Kaste M, Troupp H. The treatment of spontaneous intracerebral hemorrhage: a prospective randomised trial of surgical and conservative treatment. J Neurosurg.. 1989;70:755–758.[Medline] [Order article via Infotrieve]

5. Auer LM, Deinsberger W, Niederkorn K, Gell G, Kleinert R, Schneider G, Holzer P, Bone G, Mokry M, Korner E, Kleinert G, Hanusch S. Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomised study. J Neurosurg.. 1989;70:530–535.[Medline] [Order article via Infotrieve]

6. Batjer HH, Reich JS, Allen BC, Plaizier LJ, Jen Su C. Failure of surgery to improve outcome in hypertensive putaminal hemorrhage: a prospective randomised trial. Arch Neurol.. 1990;47:1103–1106.[Abstract/Free Full Text]

Response

Graeme J. Hankey, MBBS, MD, FRCP; FRCP Edin, FRACP; Christine S. Hon, MBBS

Stroke Unit, Department of Neurology, Royal Perth Hospital, Perth, Western Australia

We thank Dr Saver for his interest in our paper and for drawing our attention to his meta-analysis of the trials of surgery for primary intracerebral hemorrhage,¹ which we had not identified.

We agree that the trial of McKissock et al,² carried out in the pre-CT era, is now perhaps anachronistic, but we included it in our overview because one of the principles of a sound meta-analysis is to include all the evidence (ie, randomized trials) and not just selective studies. Having done that, however, we then examined the data from the 3 more recent trials in which primary intracerebral hemorrhage was diagnosed by CT brain scan. Because the combined sample size was so small (only 85 in the control group and 84 in the surgically treated group) and the 95% confidence intervals of the odds ratio (0.72) of death or dependency so wide (ranging from 0.38 [surgery being very effective] to 1.44 [surgery being harmful]), we elected not to present this analysis in our paper. We did not carry out a further analysis of the effect of surgery on mortality in the 3 CT-era trials but are interested to see Dr Saver's results, which suggest that surgery may reduce the odds of death by 8% to 72%. However, because these results are derived from a post hoc analysis of a very small number of outcome events (death), they are statistically unstable and imprecise, and hypothesis generating rather than conclusive. Furthermore, the effect of surgery on functional outcome among survivors is unknown. There remains considerable uncertainty surrounding the risks and benefits of surgery for primary intracerebral hemorrhage and the need for more data from randomized controlled trials. The results of Saver's analysis of the effects of surgery for primary intracerebral hemorrhage on mortality should not precipitate any ethical restraint on the conduct of future large randomized controlled trials.

Since the publication of our article,³ we have been informed that Prof David Mendelow and Dr M.S. Siddique at the Department of Surgery (Neurosurgery), University of Newcastle, UK, have initiated a multicenter (UK and Germany), randomized controlled trial of surgery for primary intracerebral hemorrhage. To date, 35 patients have been recruited, and the target is 1000 patients. We congratulate them on this endeavor and wish them well.

References

1. Saver JL. Surgical therapy. In: Feldmann E, ed. Intracerebral Hemorrhage. Armonk, NY: Futura Publishing Co; 1994:303–332.

2. McKissock W, Richardson A, Tayloer J. Primary intracerebral hemorrhage: a controlled trial of surgical and conservative treatment. Lancet.. 1961;2:221–226.

3. Hankey GJ, Hon C. Surgery for primary intracerebral hemorrhage: is it safe and effective? Stroke.. 1997;28:2126–2132.

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