Calcium antagonists in the management of subarachnoid haemorrhage

The development of delayed cerebral ischaemia and hence neurological deficit remains a serious problem following subarachnoid haemorrhage. Over recent years, attention has focussed on the use of the dihydropyridine class of calcium channel blocking agents ("calcium antagonists"), in particular nimodipine, as drug therapy in the prophylaxis and treatment of this condition. The theoretical basis for this is briefly discussed and then the clinical experience of the use of calcium antagonists following subarachnoid haemorrhage reviewed. In particular, attention is focussed on the randomised controlled trials that have eventually been able to show that such treatment is beneficial, both in terms of reduction of ischaemic deficit attributable to cerebral "vasospasm" and in clinical outcome, when given prophylactically, although not apparently therapeutically once deficit has developed. The evidence of the mode of action of calcium antagonists in this situation is discussed, again with particular reference to clinical data obtained in situ in the course of such trials. Although the mechanism of action remains unclear, it appears likely that it is at least in part due to the selective cerebral vasodilation induced by these compounds. The necessity for large well-controlled, prospective, randomised clinical trials in the assessment of therapeutic efficacy is stressed.