Summary and conclusions A study was set up to assess the effect on the clinical course of subarachnoid haemorrhage (SAH) of giving propranolol 80 mg eight-hourly plus phentolamine 20 mg three-hourly by mouth for three weeks. Out of the 90 patients studied, 14 died. Two of the deaths occurred in an open pilot study of 10 patients, the remaining 12 deaths occurring in patients in a randomised doubleblind placebo-controlled study. Postmortem examination was carried out on 12 of the patients, six of whom had been receiving placebo and six propranolol plus phentolamine. Necrotic myocardial lesions were present in the hearts of all six patients (age range 30-59 years) who died while taking placebo (all had had abnormal electrocardiograms (ECGs)). In contrast, no necrotic lesions were found in the hearts of the six patients (age range 28-59) who died while receiving the drugs (all had previously had normal ECGs).We conclude that the necrotic myocardial lesions were induced by catecholamines and that propranolol had a cardioprotective effect. While death from a further haemorrhage in cases of SAH is not affected by propranolol and phentolamine, propranolol may have a beneficial effect in other potentially lethal stresses.

A total of 148 patients presenting within 48 hours of subarachnoid haemorrhage were assigned at random to receive standard management only or standard management and treatment with the adrenergic-blocking agents propranolol and phentolamine (or propranolol alone) for three weeks. One hundred and thirty-four patients completed the study. Assessment at four weeks showed a strong trend for less neurological deficit in the treated group, almost statistically significant (p=0053) in the women. During the first month the treated group suffered fewer episodes of clinical deterioration consistent with cerebral arterial spasm: thus more treated patients underwent operation and those who did had a better outcome (p=0 030).At one year fewer were dead or disabled (unable to work) in the treated group; a significant difference for women (p = 0-030). Possible mechanisms for these actions may include a reduction in pulmonary oedema, prevention of myocardial infarcts, a reduction in plasma renin activity, and a reduction in cerebral oxygen requirements.It is concluded that early adrenergic blockade benefits patients (particularly women) with subarachnoid haemorrhage for up to one year in terms of lesser neurological deficit. Beta-blockade rather than alpha-blockade

Previous studies have shown that ECG changes following a subarachnoid haemorrhage are associated with increased catecholamine levels, necrotic myocardial lesions, and a poor prognosis. Furthermore, beta-blockade using propranolol reverses some of the ECG changes and prevents necrotic myocardial lesions. This study was established to assess the affects of adrenergic blockade on morbidity and mortality following subarachnoid haemorrhage. Patients were admitted to the randomized double-blind between-patients study if they presented at the neurosurgical unit within 48 hours of a subarachnoid haemorrhage confirmed by lumbar puncture. Of 224 patients, the first 118 received an alpha-blocker, phentolamine 20 mg three-hourly, and either the beta-blocker propranolol 80 mg eight-hourly, or placebo. The last 106 patients received either propranolol or placebo. Treatment was continued for three weeks. Assessment at four weeks revealed significant improvements in the treated group for neurological deficit (p = 0.003) and death (p = 0.02). More treated patients underwent operation and those that did had a better outcome (p = 0.01). Assessment at one year showed that although patients had improved in both groups, patients in the treated group had significantly fewer neurological deficits (p = 0.003). There were fewer deaths in the treated group but this difference was not significant (p = 0.09). Possible mechanisms for this protective effect of propranolol may include a reduction in plasma renin activity, a reduction in pulmonary oedema, prevention of myocardial infarcts, and a reduction in cerebral oxygen requirements. It is concluded that early beta-blockade benefits patients with subarachnoid haemorrhage, in terms of fewer neurological deficits, for up to one year.

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