Update on the Management of Subarachnoid Hemorrhage

Katja E Wartenberg


Future Neurology. 2013;8(2):205-224. 

In This Article

Prevention of DCI

Aside from high vigilance for symptoms of DCI, several pharmacological interventions have been investigated for their potential to prevent DCI.

Nimodipine, a dihydropyridine calcium channel blocker, was found to improve neurological outcome after SAH based on neuroprotection rather than an effect on the vasculature. Oral nimodipine (60 mg every 4 h) should be administered from day 1 to day 21.[29,56,133]

Magnesium, a physiologic calcium antagonist, blocks voltage-gated calcium channels, reduces the release of glutamate and entry of calcium into cells. Its vasodilatative effect and safety in SAH was repeatedly confirmed. The IMASH trial enrolled 327 patients randomized to receive magnesium or placebo within 48 h of symptom onset for 10–14 days. A difference in primary outcome, defined as favorable outcome at 6 months according to the extended Glasgow Outcome Scale, could not be demonstrated.[134] Only one trial with 107 patients showed a reduction of DCI, defined as ischemic infarction by 29% in the magnesium group (64 mmol/day for 14 days), which did not result in a better long-term outcome or reduced mortality at 6 months.[135] These findings were confirmed by a meta-analysis including a total of 875 patients.[136] Therefore, administration of additional magnesium is not recommended at this point. However, hypomagnesemia should be treated.[56]

Statins have been evaluated in small randomized, controlled trials for safety, their neuroprotective effect and their potential to decrease the incidence of DCI after SAH. In a recent meta-analysis, a reduction of DCI and a small effect on mortality could be shown; the remainder of the results were heterogeneous.[137] A multicenter trial studying the effect of simvastatin 40 mg daily for 21 days on DCI versus placebo, STASH, is ongoing.[301] As the use of statins is safe in SAH, patients already on statins prior to SAH should continue their medication, and starting statins may be considered in patients presenting with SAH.[56]

Clot removal and intrathecal administration of recombinant tissue plasminogen activator or urokinase during craniotomy to promote fibrinolysis, as well as head shaking aimed at clot dissolution, are still under investigation.[138,139] Endothelin receptor antagonists such as clazosentan reduced the incidence of angiographic vasospasm, but did not affect clinical outcome.[140]

Management of DCI

The treatment of DCI involves hemodynamic and endovascular management. Hemodynamic augmentation encompasses aggressive volume expansion with crystalloid or colloid solutions, as well as elevation of blood pressure and cardiac output in order to improve CBF through arteries in spasm and without autoregulatory capacity. This management strategy is often referred to as the 'triple H therapy': hypervolemia, hypertension and hemodilution, and is considered the standard therapy of DCI. However, only limited data are available about its effect.[141–146] Most of these small studies report hypervolemia and/or administration of vasopressors, such as dopamine or norepinephrine, to be safe with variable effects on CBF and DCI. Phenylephrine was found to be safe to elevate the MAP by 20–35% in the setting of DCI.[147] In the presence of cardiac dysfunction, dobutamine or milrinone infusions are alternatives to maintain sufficient cardiac output, as measured by cardiac index.[148–150] However, dobutamine may lower the MAP and require an increase in vasopressor dosage. The available evidence mostly supports the use of dobutamine.[56] Hemodilution is not recommended because of a reduction of oxygen delivery to the brain.[151] If DCI is suspected, saline bolus administration and a trial of stepwise-induced hypertension with a vasopressor or inotropic drug should be undertaken, with periodic neurological assessments of the patient to define the MAP target. If nimodipine administration leads to temporary hypotension, the dosing intervals may be changed or the drug discontinued.[29,56] If DCI is refractory to maximal induced hypertension and hypervolemia, or limited by complications such as congestive heart failure, myocardial ischemia or pulmonary edema, cerebral balloon angioplasty and/or administration of intra-arterial papaverine, nicardipine or verapamil may lead to reversal of neurological deterioration. Intracranial pressure and arterial blood pressure should be monitored during administration of intra-arterial vasodilators. The timing of endovascular therapy should take into account the level and tolerance of hemodynamic augmentation, prior evidence of vasospasm and the availability of endovascular procedures.[29,56,152–155]