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Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study.

ABSTRACT: INTRODUCTION:Cerebral autoregulation (CA) is impaired in a multitude of neurological conditions. Increasingly, clinical studies are correlating the nature of this impairment with prognostic markers. In acute intracerebral haemorrhage (ICH), impairment of CA has been associated with worsening clinical outcomes including poorer Glasgow Coma Score and larger haematoma volume. Hypocapnia has been shown to improve CA despite concerns over hypoperfusion and consequent ischaemic risks, and it is therefore hypothesised that hypocapnia (via hyperventilation) in acute ICH may improve CA and consequently clinical outcome. BREATHE-ICH is a CA-targeted interventional study in acute ICH utilising a simple bedside hyperventilatory manoeuvre. METHODS AND ANALYSIS:Patients with acute ICH within 48?hours of onset will be included. The experimental set-up measures cerebral blood flow (cerebral blood velocity, transcranial Doppler), blood pressure (Finometer) and end tidal carbon dioxide (capnography) at baseline, and in response to hypocapnia (-5?mm and -10?mm Hg below baseline) achieved via a 90?s hyperventilatory manoeuvre. Autoregulation is evaluated with transfer function analysis and autoregulatory index calculations. Important classical endpoints associated with this before and after interventional study include death and disability at 14 days and the proportion of recruited individuals able to comply with the full measurement protocol. ETHICS AND DISSEMINATION:A favourable opinion was granted by the East Midlands-Nottingham 1 Research Ethics Committee (17/EM/0283). It is anticipated that the results of this study will be presented at national and international meetings, with reports being published in journals during late 2018. TRIAL REGISTRATION NUMBER:NCT03324321.

SUBMITTER: Minhas JS

PROVIDER: S-EPMC5875592 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study.

Minhas Jatinder S JS Panerai Ronney B RB Robinson Thompson G TG

BMJ open 20180327 3

<h4>Introduction</h4>Cerebral autoregulation (CA) is impaired in a multitude of neurological conditions. Increasingly, clinical studies are correlating the nature of this impairment with prognostic markers. In acute intracerebral haemorrhage (ICH), impairment of CA has been associated with worsening clinical outcomes including poorer Glasgow Coma Score and larger haematoma volume. Hypocapnia has been shown to improve CA despite concerns over hypoperfusion and consequent ischaemic risks, and it i ...[more]

PMID: 29593024

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Project description:Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ?2/?4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5-1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of ? 1 APOE ?4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted.

Project description:BackgroundClassically, cerebral autoregulation (CA) entails cerebral blood flow (CBF) remaining constant by cerebrovascular tone adapting to fluctuations in mean arterial pressure (MAP) between ∼60 and ∼150 mmHg. However, this is not an on-off mechanism; previous work has suggested that vasomotor tone is proportionally related to CA function. During propofol-based anaesthesia, there is cerebrovascular vasoconstriction, and static CA remains intact. Sevoflurane-based anaesthesia induces cerebral vasodilation and attenuates CA dose-dependently. It is unclear how this translates to dynamic CA across a range of blood pressures in the autoregulatory range.ObjectiveThe aim of this study was to quantify the effect of step-wise increases in MAP between 60 and 100 mmHg, using phenylephrine, on dynamic CA during propofol- and sevoflurane-based anaesthesia.DesignA nonrandomised interventional trial.SettingSingle centre enrolment started on 11 January 2019 and ended on 23 September 2019.PatientsWe studied American Society of Anesthesiologists (ASA) I/II patients undergoing noncardiothoracic, nonneurosurgical and nonlaparoscopic surgery under general anaesthesia.InterventionIn this study, cerebrovascular tone was manipulated in the autoregulatory range by increasing MAP step-wise using phenylephrine in patients receiving either propofol- or sevoflurane-based anaesthesia. MAP and mean middle cerebral artery blood velocity (MCA Vmean ) were measured in ASA I and II patients, anaesthetised with either propofol ( n = 26) or sevoflurane ( n = 28), during 10 mmHg step-wise increments of MAP between 60 and 100 mmHg. Static CA was determined by plotting 2-min averaged MCA Vmean versus MAP. Dynamic CA was determined using transfer function analysis and expressed as the phase lead (°) between MAP and MCA Vmean oscillations, created with positive pressure ventilation with a frequency of 6 min -1 .Main outcomesThe primary outcome of this study was the response of dynamic CA during step-wise increases in MAP during propofol- and sevoflurane-based anaesthesia.ResultsMAP levels achieved per step-wise increments were comparable between anaesthesia regiment (63 ± 3, 72 ± 2, 80 ± 2, 90 ± 2, 100 ± 3 mmHg, and 61 ± 4, 71 ± 2, 80 ± 2, 89 ± 2, 98 ± 4 mmHg for propofol and sevoflurane, respectively). MCA Vmean increased more during step-wise MAP increments for sevoflurane compared to propofol ( P ≤0.001). Dynamic CA improved during propofol (0.73° mmHg -1 , 95% CI 0.51 to 0.95; P ≤ 0.001)) and less pronounced during sevoflurane-based anaesthesia (0.21° mmHg -1 (95% CI 0.01 to 0.42, P = 0.04).ConclusionsDuring general anaesthesia, dynamic CA is dependent on MAP, also within the autoregulatory range. This phenomenon was more pronounced during propofol anaesthesia than during sevoflurane.Trial registrationNCT03816072 ( https://clinicaltrials.gov/ct2/show/NCT03816072 ).

Project description:BackgroundPrevious randomised controlled trials could not demonstrate that surgical evacuation of intracerebral haemorrhage (ICH) improves functional outcome. Increasing evidence suggests that minimally invasive surgery may be beneficial, in particular when performed early after symptom onset. The aim of this study was to investigate safety and technical efficacy of early minimally invasive endoscopy-guided surgery in patients with spontaneous supratentorial ICH.MethodsThe Dutch Intracerebral Haemorrhage Surgery Trial pilot study was a prospective intervention study with blinded outcome assessment in three neurosurgical centres in the Netherlands. We included adult patients with spontaneous supratentorial ICH ≥10mL and National Institute of Health Stroke Scale (NIHSS) score ≥2 for minimally invasive endoscopy-guided surgery within 8 h after symptom onset in addition to medical management. Primary safety outcome was death or increase in NIHSS ≥4 points at 24 h. Secondary safety outcomes were procedure-related serious adverse events (SAEs) within 7 days and death within 30 days. Primary technical efficacy outcome was ICH volume reduction (%) at 24 h.ResultsWe included 40 patients (median age 61 years; IQR 51-67; 28 men). Median baseline NIHSS was 19.5 (IQR 13.3-22.0) and median ICH volume 47.7mL (IQR 29.4-72.0). Six patients had a primary safety outcome, of whom two already deteriorated before surgery and one died within 24 h. Sixteen other SAEs were reported within 7 days in 11 patients (of whom two patients that already had a primary safety outcome), none device related. In total, four (10%) patients died within 30 days. Median ICH volume reduction at 24 h was 78% (IQR 50-89) and median postoperative ICH volume 10.5mL (IQR 5.1-23.8).ConclusionsMinimally invasive endoscopy-guided surgery within 8 h after symptom onset for supratentorial ICH appears to be safe and can effectively reduce ICH volume. Randomised controlled trials are needed to determine whether this intervention also improves functional outcome.Trial registrationClinicaltrials.gov : NCT03608423, August 1st, 2018.

Project description:BackgroundGlibenclamide is a promising agent for treating brain oedema, but whether it improves clinical outcomes in patients with intracerebral haemorrhage (ICH) remains unclear. In this study, we aimed to explore the efficacy and safety of glibenclamide treatment in patients with acute ICH.MethodsThe Glibenclamide Advantage in Treating Oedema after Intracerebral Haemorrhage (GATE-ICH) study was a randomised controlled phase 2 clinical trial conducted in 26 hospitals in the northwest of China, recruiting patients with acute ganglia ICH no more than 72 h after onset from Dec 12, 2018 to Sept 23, 2020. During the first 7 days after enrolment, patients randomly assigned to the glibenclamide group were given glibenclamide orally (1.25 mg, 3/day) and standard care, while patients randomly assigned to the control group were given standard care alone. The computer-generated randomisation sequence was prepared by a statistician not involved in the rest of the study. Randomisation was computer-generated with a block size of four. The allocation results were unblinded to participants and investigators. The primary outcome was the percentage of patients with poor outcome (defined as modified Rankin Scale [mRS] score of ≥3) at day 90. The trial was registered at ClinicalTrials.gov (NCT03741530).Findings220 participants were randomised and 200 participants (mean [standard deviation] age, 56 [11] years; sex, 128 [64.0%] male and 72 [36.0%] female) were included in the final analysis, with 101 participants randomly assigned to the control group and 99 to the glibenclamide group. The incidence of poor outcome at day 90 was 20/99 (20.2%) in glibenclamide group and 30/101 (29.7%) in control group (absolute difference, 9.5%; 95% confidence interval [CI], -3.2%-21.8%; P = 0.121) with adjusted odds ratios of 0.54 (95% CI, 0.24-1.20; P = 0.129). No significant difference was found in the overall rates of adverse events or serious adverse events between groups. However, the incidence of asymptomatic hypoglycaemia was significantly higher in glibenclamide group than control group (15/99 [15.2%] vs 0/101 [0.0%]; absolute difference, 15.2%; 95% CI, 7.5%-24.1%; P < 0.001).InterpretationOur study provides no evidence that glibenclamide (1.25 mg, 3/day) significantly reduces the proportion of poor outcome at day 90 after ICH. In addition, glibenclamide could result in higher incidence of hypoglycaemia. Larger trials of glibenclamide with optimised medication regimen are warranted.FundingShaanxi Province Key Research and Development Project (2017DCXL-SF-02-02) and Shaanxi Province Special Support Program for Leading Talents in Scientific and Technological Innovation (tzjhjw).

Dataset Information

Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study.

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Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study.

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