Feasibility of improving cerebral autoregulation in acute intracerebral hemorrhage (BREATHE-ICH) study: Results from an experimental interventional study

Abstract

Background Cerebral autoregulation is impaired in a multitude of neurological conditions. Increasingly, clinical studies are correlating the nature of this impairment with prognostic markers. In acute intracerebral hemorrhage, impairment of cerebral autoregulation has been associated with worsening clinical outcomes including poorer Glasgow Coma Score and larger hematoma volume. Hypocapnia has been shown to improve cerebral autoregulation despite concerns over hypoperfusion and consequent ischemic risks, and it is therefore hypothesized that hypocapnia (via hyperventilation) in acute intracerebral hemorrhage may improve cerebral autoregulation and consequently clinical outcome. Aims To assess the feasibility and acceptability of the first cerebral autoregulation-targeted intervention in acute intracerebral hemorrhage utilizing a simple bed-side hyperventilatory maneuver. Methods Twelve patients with acute intracerebral hemorrhage within 48 h of onset were enrolled. The experimental setup measured cerebral blood flow velocity (transcranial Doppler), blood pressure (Finometer), and end-tidal CO2 (EtCO2, capnography) at baseline, and in response to hypocapnia (−5 mmHg below baseline) achieved via a 90-s hyperventilatory maneuver. Cerebral autoregulation was evaluated with transfer function analysis and autoregulatory index calculations. Results We observed tolerance to the protocol in a cohort of mild (National Institutes of Health Scale 4) supratentorial intracerebral hemorrhage patients with small volume hematomas without intraventricular extension. Importantly, a significant difference was noted between ipsilateral autoregulatory index at baseline 4.8 (1.7) and autoregulatory index during hypocapnic intervention 7.0 (0.8) (p = 0.0004), reflecting improved cerebral autoregulation, though a dose-dependent effect of EtCO2 on autoregulatory index was not observed. Conclusions In this small study, there was no observed effect on 14-day death and disability in recruited participants. This is the first report of improvement in cerebral autoregulation in acute intracerebral hemorrhage using a non-invasive interventional maneuver, through induction of hypocapnia via hyperventilation. ClinicalTrials.gov Identifier: NCT03324321 URL: https://clinicaltrials.gov/ct2/show/NCT03324321