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

Emerging Mechanistic Concepts Underlying BP Lowering

Improved understanding of systemic hemodynamics and cerebral autoregulation may provide insights to allow BP lowering strategies to be optimized in acute ICH,[45] as well as other hypertensive emergencies, without compromising cerebral perfusion.[46] In SAH, systolic BP peaks >150 mm Hg are associated with increased risk of re-rupture of a cerebral aneurysm, which has a high (>50%) case fatality. A recent comprehensive review involving 95 patients over three ICH studies and 413 patients over 8 SAH studies showed that impairment of dynamic cerebral autoregulation, mainly measured by transcranial doppler, is associated with poor outcome.[45]

Although ICH patients have a significant burden of cerebral small vessel disease, where CBF and autoregulation are likely impaired, this does not appear to modify the effects of intensive BP lowering.[47–49] Data from patients after symptomatic lacunar infarction (which is a component of cerebral small vessel disease) show impaired dynamic cerebral autoregulation globally (middle cerebral and posterior cerebral arteries) which is maintained consistently over the subsequent 6 months.[50] Similarly, meta-analyses have demonstrated lower CBF velocity and cerebral autoregulation ipsilaterally in acute ICH.[51,52] Again moderate BP lowering does not appear to significantly influence these parameters[53] but may reduce perihematomal edema.[54]

Yet, impaired cerebrovascular tone and resistance are implicated in acute ICH, systemic BP change may drive alterations in cerebral autoregulation, and thus tone, that triggers a vasoconstrictor cascade. While this may be a protective mechanism, designed to maintain perfusion in the presence of a hematoma and potential penumbra, hemodynamic disturbance that arises from intensive BP lowering may compromise homeostatic mechanisms on CBF in a damaged vascular network.

In the era of increasing magnetic resonance imaging (MRI) in acute ICH, ischemic complications after ICH are increasingly recognized but their cause and prognosis remains uncertain. ICH patients with a high burden of white matter hyperintensities on MRI imaging do appear to have worse ICH-related outcomes.[49] However, data are contradictory with regard to the severity of white matter hyperintensities, with mild grades being associating with risk of ischemic stroke and advanced grades with ICH. There are reassuring perfusion data during hypertensive states after acute ischemic stroke, with labetalol and sublingual GTN precipitating increased volumes of hypoperfused tissue,[55] but again the cause and prognosis of such lesions remains unclear. While exploratory data have raised questions as to whether diffusion-weighted MRI hyperintense lesions are associated with BP lowering or indeed predict poor outcome,[56] definitive data are lacking and specifically regarding the temporal relationship between BP change after ICH in relation to various vasoactive and perfusion altering factors on BP (prelowering and postlowering), carbon dioxide (CO2) level,[57] and head position.[58] Reassuringly, CBF appears to remain stable with acute BP lowering in ICH, which suggests that cerebral autoregulation is maintained in this state, albeit in those with mild-moderate sized hematomas. Importantly, the lack of foresight over various central and peripherally influencing hemodynamic factors, post hoc analyses of RCTs have largely disregarded hemodynamic perturbations as the cause for adverse diffusion-weighted MRI ischemic lesions in ICH.[56]

Spontaneous hyperventilation (defined as PaCO2 <35 mm Hg and pH >7.45) occurs in SAH and ICH,[57,59] where it is associated with DCI and poor neurological outcome in the former.[59] In ICH, there is evidence that lower pCO2 (secondary spontaneous hyperventilation) is associated with increased risk of ischemic lesions in the context of BP reduction, and that hypocapnia alters CBF by widening the plateau on the autoregulatory curve. It appears, therefore, that hypocapnia is an important mediator of cerebral ischemia.

The phenomenon of cerebral ischemia being precipitated by uncontrolled ICP and low cerebral perfusion pressure (CPP) after SAH is well recognized. Thus, strategies to avoid increased ICP and support high CPP values where there is the potential for vasospasm may improve outcome after SAH.[60] A focus on cerebral autoregulation after SAH has long preceded investigation in ICH,[61] with noninvasive ultrasound based technologies being embedded into clinical practice to assess for vasospasm, determine CBF, and assess static and dynamic cerebral autoregulation.[62] Several large studies have confirmed impaired cerebral autoregulation in SAH, with granularity over pathophysiology and response to interventions being particularly informative. Specifically, impaired autoregulation is related to reduce level of consciousness,[63] despite there being no difference in autoregulation between those with and without symptomatic vasospasm.[64]