November 2014

Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest N Neilsen et al N Engl J Med 2013; 369:2197-2206 December 5, 2013 950 unconscious patients following cardiac arrest in a multicentre international study were randomly allocated to Targeted Temperature Management (TTM) at either 33^oC or 36^oC. The TTM was achieved as quickly as possible and maintained for 28 hours post arrest before temperature was gradually allowed to rise back towards normal. Of note, although the targets were relaxed, patients were maintained with a temperature below 37.5^oC for 72 hours post arrest. All surviving patients were followed up for 180 days after enrolment of the last patient and underwent neurological outcome scoring. The most important conclusion was that cooling to the lower temperature did not confer any advantage in terms of outcome i.e. death/poor outcome was 54% in 33^oC group as opposed to 52% in 36^oC group. Of course the cooling after cardiac arrest enthusiasts were unhappy about the results even though it was such a large and well constructed study. But perhaps this is the beginning of the debunking of the typical medical reaction that if pyrexia is bad for you, hypothermia must be good for you. With the early termination of the Eurotherm Trial, perhaps we are entering a phase of aggressively preventing pyrexia, which is often much more difficult to achieve, rather than cooling to arbitrary figures. What was useful was the better definition of findings that allowed early withdrawal:

• Brain death due to cerebral herniation
• Severe myoclonus status in the first 24 hours after admission and a bilateral absence of N20-peak on median nerve SSEP
• Minimum 72 hours after the intervention period: persisting coma with a Glasgow Motor Score 1-2 and bilateral absence of N20-peak on median nerve SSEP.
• Minimum 72 hours after the end of the intervention period: persisting coma with a Glasgow Motor Score 1-2 and a treatment refractory status epilepticus.

Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial Peter J Kirkpatrick FMedSciet alThe Lancet Neurology, Volume 13, Issue 7, Pages 666 – 675, July 2014 This multi-centre, randomised, double-blind trial recruited 803 patients to receive either simvastatin 40 mg per day or placebo from within 96 hours from ictus to a total of 3 weeks treatment. The primary outcome was the distribution of the modified Rankin scores measured at 6 months which was achieved in 97% of participants. The good news was that of those, 72% were judged to have had a favourable outcome (mRS 0-2) but disappointingly there was no significant difference between the groups. Equally, there was no significant difference for both death and serious complications between the groups. The authors concluded that “The STASH trial did not detect any benefit in the use of simvastatin for long-term or short-term outcome in patients with aneurysmal subarachnoid haemorrhage”. This trial was developed on the back of promising results for the use of pravastatin in 2005 which reported an 83% decrease in vasospasm related delayed ischaemic deficits¹. Simvastatin was chosen for this trial as it is meant to exert a greater effect on endothelium. So is this the end of statins in managing vasospasm? Although it probably is, some investigators believe that the endothelial inflammatory response lasts far longer than the 3 weeks historically allocated for the nimodipine trial and that longer treatment may confer some benefits². I doubt there is the appetite to test that in a clinical trial after such a disappointing result. 1) Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial. Tseng MY¹, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Stroke 2005 Aug; 36(8):1627-32 2) Simvastatin in subarachnoid haemorrhage: beyond the short-term. Frederick Lombard, Gavin W Britz, David S Warner The Lancet Neurology, Volume 13, Issue 11, Page 1073, November 2014 Flurbiprofen and hypertension but not hydroxyethyl starch are associated with post-craniotomy intracranial haematoma requiring surgery. Jian M, Li X, Wang A, Zhang L, Han R, Gelb AW. Br J Anaesth. 2014 Nov;113(5):832-9. This was a case-control study of 42359 patients undergoing elective craniotomy in Beijing between 2006 and 2011. Their incidence of post-craniotomy intracranial haematoma requiring surgery was 0.48%. These cases were matched by age, pathologic diagnosis, tumour location and surgeon with cases that did not have a postoperative haematoma. Intra- and post-operative systolic blood pressures greater than 160mmHg, MAP > 110mmHg and the intraoperative administration of flurbiprofen were all significant risk factors in those requiring craniotomy for the evacuation of a postoperative haematoma. Of less interest in present practice was that hydroxyethyl starch was not associated with increased risk. Firstly, the incidence of significant post-operative haematoma is perhaps lower than I would have anticipated from my experience. Secondly, the paper illustrates the importance of avoiding hypertensive peaks in neuroanaesthesia which we are probably less aggressive in managing than 15-20 years ago. Finally, it also confirms my view, which I know is not shared by all my colleagues, that NSAID’s should be avoided intra-operatively during craniotomy. November 2014