Lifting the lid on a ‘proven therapy’

This blogpost is co-authored by Chris Nickson and Andrew Udy, intensivists at The Alfred ICU in Melbourne, Australia.

The publication of the RescueICP trial, a ‘sequel’ to the landmark DECRA trial, was eagerly awaited by those of us who look after critically ill patients with traumatic brain injury. Decompressive craniectomy is a controversial therapy, and the importance of the RescueICP trial was discussed in a recent NEJM editorial by Shutter and Timmons¹. In a nutshell, RescueICP showed that decompressive craniectomy reduced intracranial pressure but had longer-term patient-centered outcomes that were less clear-cut. Specifically, while 6-month mortality was lower after surgical intervention, higher rates of vegetative state, “lower severe disability”, and “upper severe disability” were noted in comparison to medical care. In other words, these findings raise legitimate concerns about the likelihood of generating highly dependent survivors as a result of surgical intervention.

In their editorial examining the rationale for decompressive craniectomy, Shutter and Timmons assert that:

“This surgery … has a proven benefit in the management of malignant cerebral edema after ischemic stroke”.

We believe there are important caveats to this statement that warrant consideration given the findings of RescueICP.

Let’s look at the evidence for decompressive hemicraniectomy for malignant middle cerebral artery (MCA) ischaemic stroke:

1. Empiric evidence for decompressive hemicraniectomy in this setting is primarily derived from three small trials (the DESTINY, DECIMAL and HAMLET trials) ^2-4. Although each study demonstrated greater survival among patients treated with decompressive hemicraniectomy, no statistically significant difference in functional outcomes (as assessed using the modified Rankin Scale; mRS) was identified. DESTINY and HAMLET were stopped early due to survival benefit and DECIMAL was stopped primarily due to slow recruitment.
2. Data from these studies was subsequently pooled by Vahedi and colleagues⁵. Their analysis found that the 93 patients aged < 60 years with severe stroke that had surgery within 48-hours of symptom onset had better functional outcomes: 43%, compared with 21% of non-surgical patients, had a modified Rankin Scale (mRS) ≤3 at 12 months ⁵. The caveat is that only 14% of surgical survivors could look after their own affairs without assistance (mRS score, 2).
3. A subsequent trial, DESTINY-II, found lower mortality without severe disability following surgery in patients aged >60 years. However, worryingly, most survivors required “assistance with most bodily needs” (only 7% had mRS of ≤3) ⁶.

Thus decompressive craniectomy for malignant MCA ischaemic stroke can only be considered in younger patients when performed early, and few survivors will avoid substantial disability. This outcome, and these odds, may or may not be acceptable to our patients.

The key question, both for decompressive craniectomy and for neurocritical care in general, is what is an ‘acceptable’ outcome following catastrophic brain injury? Studies that simply dichotomize functional outcome scales (such as the mRS) at varying points will often generate differing conclusions, particularly as the threshold for an ‘acceptable’ level of disability is often an arbitrary investigator-driven decision. This may or may not be meaningful to individual patients and their families, depending on a variety of individual, cultural, and societal factors. Thus, decompressive hemicraniectomy for malignant ischemic stroke – as for traumatic brain injury – should be considered in this context, and we strongly caution against the view that it is of ‘proven benefit’. For some patients, the risk of severe disability and dependence may outweigh an improved chance of survival.

References

1. Shutter LA, Timmons SD. Intracranial Pressure Rescued by Decompressive Surgery after Traumatic Brain Injury. N Engl J Med. 375(12):1183-4. 2016
2. Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB; HAMLET investigators. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol. 2009 Apr;8(4):326-33.
3. Jüttler E, Schwab S, Schmiedek P, Unterberg A, Hennerici M, Woitzik J, Witte S, Jenetzky E, Hacke W; DESTINY Study Group. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke. 2007 Sep;38(9):2518-25.
4. Vahedi K, Vicaut E, Mateo J, Kurtz A, Orabi M, Guichard JP, Boutron C, Couvreur G, Rouanet F, Touzé E, Guillon B, Carpentier A, Yelnik A, George B, Payen D, Bousser MG; DECIMAL Investigators. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial). Stroke. 2007 Sep;38(9):2506-17.
5. Vahedi K, Hofmeijer J, Juettler E, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. The Lancet Neurology 2007;6:215-22.
6. Jüttler E, Unterberg A, Woitzik J, Bösel J, Amiri H, Sakowitz OW, Gondan M, Schiller P, Limprecht R, Luntz S, Schneider H, Pinzer T, Hobohm C, Meixensberger J, Hacke W; DESTINY II Investigators. Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke. N Engl J Med. 2014 Mar 20;370(12):1091-100.

Learn more about Decompressive Hemicraniectomy for Malignant MCA infarction in LITFL’s CCC.