In the broad sense, prevention and management of vasospasm were asked about in Question 10 from the first paper of 2007, and again in Question 5 from the first paper of 2013. None of these specifically made nimodipine the focus. It came up as one of the topics of Question 24 from the second paper of 2017, which asked the candidates to "briefly discuss" various strategies, including discredited approaches like the "Triple H" therapy. The aim of this chapter is to bring together all the evidence for nimodipine so that it is accessible in one place. An ideal starting point for reading about nimodipine and vasospasm in general is Oliver Flower's LITFL article on this topic.
In order to tailor this chapter to CICM SAQ revision, it has been organised into a familiar framework, as if to answer a question like "critically evaluate the use of nimodipine in cerebral vasospasm".
Allen et al (1983): multicenter RCT; 125 patients randomised to nimodipine or placebo
Philippon et al (1986): RCT; 70 patients randomised to nimodipine or placebo.
Petruk et al (1988): multicentre RCT of 188 patients, this time only those with "poor grade SAH"
Pickard et al (1989) - the BRANT trial: multicentre RCT of 554 patients
Many trials were done in the subsequent decade. Rather than eroding his neurons into nubs trying to analyse them all, this author has yielded to the expertise of Feigin et al (1998) who had put together a meta-analysis and systematic review of the then-available evidence. By this stage, 10 trials totalling 2756 patients were available.The salient findings of this meta-analysis were as follows:
At the time of writing, in late 2015, the most recent meta-analysis is a 2008 Cochrane review by Mees et al. Again, ten years had passed since the last systematic review. This time, sixteen trials totalling 3361 patients were available. To spare the revising candidate trawling through more statistics, it will suffice to say that the abovelisted benefits were redemonstrated. The authors concluded that though the efficacy of nimodipine "is not beyond all doubt", the relatively high safety of this drug merits a recommendation for its routine use.
In correlation with these findings, the AHA has (in its 2012 guidelines statement) quoted the abovementioned meta-analysis and made a Class I, Level A recommendation that "Oral nimodipine should be administered to all patients with aSAH". In fact, looking through that guidelines statement, this is the strongest recommendation made by the AHA regarding the management of subarachnoid haemorrhage - even intra-arterial vasodilator therapy merited only a lukewarm Class IIa Level B recommendation.
In short, there is widespread support for the use of (oral or IV) nimodipine, and it is the standard of care for SAH survivors.
Chapter 51 (pp. 568) Acute cerebrovascular complications by Bernard Riley and Thearina de Beer
LITFL offer this reference as a follow-on to their chapter:
Dabus, Guilherme, and Raul G. Nogueira. "Current Options for the Management of Aneurysmal Subarachnoid Hemorrhage-Induced Cerebral Vasospasm: A Comprehensive Review of the Literature." Interventional Neurology 2.1 (2013): 30-51.
Pickard, J. D., et al. "Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial."BMJ: British Medical Journal 298.6674 (1989): 636.
Ohtsuka, Minoru, et al. "New generation dihydropyridine calcium entry blockers: in search of greater selectivity for one tissue subtype." General Pharmacology: The Vascular System 20.5 (1989): 539-556.
Kazda, S., and R. Towart. "Nimodipine: a new calcium antagonistic drug with a preferential cerebrovascular action." Acta neurochirurgica 63.1-4 (1982): 259-265.
Allen, George S., et al. "Cerebral arterial spasm–a controlled trial of nimodipine in patients with subarachnoid hemorrhage." New England Journal of Medicine 308.11 (1983): 619-624.
Philippon, J., et al. "Prevention of vasospasm in subarachnoid haemorrhage. A controlled study with nimodipine." Acta neurochirurgica 82.3-4 (1986): 110-114.
Petruk, Kenneth C., et al. "Nimodipine treatment in poor-grade aneurysm patients: results of a multicenter double-blind placebo-controlled trial." Journal of neurosurgery 68.4 (1988): 505-517.
Feigin, V. L., et al. "Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage A systematic review." Neurology 50.4 (1998): 876-883.
Rabinstein, Alejandro A. "Critical Care of Aneurysmal Subarachnoid Hemorrhage: State of the Art." Neurovascular Events After Subarachnoid Hemorrhage. Springer International Publishing, 2015. 239-242.
Mees, Sanne M. Dorhout, et al. "Calcium antagonists for aneurysmal subarachnoid hemorrhage." Stroke 39.2 (2008): 514-515.
Connolly, E. Sander, et al. "Guidelines for the management of aneurysmal subarachnoid hemorrhage a guideline for healthcare professionals from the American heart association/American stroke association." Stroke 43.6 (2012): 1711-1737.