Blood Pressure Management After Intracerebral and Subarachnoid Hemorrhage

The Knowns and Known Unknowns

Jatinder S. Minhas, MD; Tom J. Moullaali, MD, PhD; Gabriel J.E. Rinkel, MD, PhD; Craig S. Anderson, MD, PhD


Stroke. 2022;53(4):1065-1073. 

In This Article

Evidence to Support BP Control After SAH

Acute Phase

Observations that high BP after aneurysmal SAH is related to poor outcome, and that treating high BP can reduce rebleeding, have existed from almost half a century.[30] Moreover, the lack of any apparent benefit on clinical outcome from BP lowering on rebleeding has been explained by the treatment being offset by an increased risk of DCI,[31] and subsequently little progress has been made in resolving this dichotomy. In a recent study that compared rebleeding between a hospital with a policy of aggressive BP lowering versus one with a more liberal approach, the trend was for rebleeding to be lower in the former, but this was not statistically significant.[32] Nevertheless, given the relation between high BP and risk of rebleeding, and of rebleeding and poor outcome, guidelines recommend that high BP should be treated in the acute phase of SAH. The European Stroke Organization guidelines, for example, recommend treatment if systolic BP exceeds 180 mm Hg, starting with analgesics and nimodipine, and continuing as necessary to maintain a mean arterial pressure of >90 mm Hg.[17] The American Heart Association/American Stroke Association guidelines similarly recommend treatment with a titratable agent but according to a lower threshold of systolic BP <160 mm Hg.[18]

An RCT is clearly required to provide the necessary evidence to define the balance of potential benefits and risks of BP lowering in the acute phase of SAH. However, since the risk of rebleeding in patients undergoing early aneurysm occlusion is around 10% to 15%, and strict BP control does not eliminate rebleeding, such an RCT would need to include several thousands of patients, making it an ambitious endeavour.[33,34] Since emergency clipping, that is clipping within the initial hours after admission on a 24/7 basis, has a modest treatment effect, if at all, and its cost-effectiveness is uncertain due to the high burden on resources,[35] a RCT of BP lowering should be a high priority, as it is a promising strategy to improve outcome that could be initiated during the transport of patients by ambulance to an appropriate facility.

Subacute Phase

After aneurysm occlusion, the most important complication is DCI, which typically occurs between 4 and 12 days after SAH. Traditionally, DCI has been linked to vasospasm, and to such an extent that the terms are used synonymously. However, since not all patients with vasospasm develop DCI, and not all patients with DCI have vasospasm, vasospasm is neither a sufficient nor a necessary factor, for the development of DCI. Given the relation between vasospasm and DCI, and the observation that it is associated with hypovolemia, the combination of hemodilution, hypervolemia and hypertension, the so-called triple H therapy, has been the mainstay of medical prevention and treatment of DCI for decades. The rationale behind this treatment is to improve cerebral perfusion, but supporting RCT evidence has been lacking.[36] A systematic review showed no evidence from controlled studies for a positive effect of triple-H or its separate components on cerebral blood flow (CBF) in SAH,[37] but uncontrolled studies have suggested that hypertension is more effective than hemodilution or hypervolemia at increasing CBF.

These findings led to the HIMALAIA (Hypertension Induction in the Management of Aneurysmal Subarachnoid Haemorrhage With Secondary Ischemia) RCT to determine the effectiveness of induced hypertension in patients with symptoms of DCI after SAH. Unfortunately, the RCT was stopped prematurely after the first interim analysis, due to slow patient recruitment and futility of the treatment on CBF. Despite a higher mean arterial BP in the intervention group, there was no statistical difference in CBF between the intervention and control groups.[38] Although the RCT lacked statistical power for reliable estimates due to early termination, there was no hint of improved functional outcome from the intervention,[39] but rather of a trend towards more serious adverse events (odds ratio, 2.1 [95% CI, 0.9–5.0]). A systematic review performed to put the results into context identified no other controlled studies on the effect of induced hypertension. There were 9 uncontrolled studies (totalling 187 patients), reporting on clinical improvement after instalment of induced hypertension, in some combined with hypervolemia, or in case of no response, with balloon angioplasty or intraarterial treatment with vasodilators. Most studies reported clinical improvement in most patients but seven (285 patients) reported complications, the most serious being cardiac arrhythmia, pulmonary edema, hemorrhagic transformation, and intracranial bleeding in up to 50%, and death in up to 25%, of patients.[39] Thus, despite the possibility of an initial clinical improvement with induced hypertension, there is uncertainty as to whether this treatment improves overall outcome, yet there is reasonable evidence that it increases the risk of serious complications. Other explanations for the lack of efficacy of induced hypertension is that it only benefits the subgroup of patients who develop DCI, or that the increase of BP is too little, too late, or too short. Thus, another RCT is clearly warranted, but again this will require a large international effort.