Cerebral Autoregulation in Patients With Aneurysmal SubArachnoid Haemorrhage (CASAH)
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|ClinicalTrials.gov Identifier: NCT03987139|
Recruitment Status : Recruiting
First Posted : June 14, 2019
Last Update Posted : September 10, 2019
The purpose is, in patients with aneurysmal subarachnoid haemorrhage in the early phase after ictus, to examine the following:
- The effect of spontaneous and induced changes on the brain's static and dynamic autoregulation calculated by transcranial Doppler (TCD), ICP and MAP (primary purposes) and ICP and PbtO2;
- The effect of mild hyper- and hypocapnia as well as of mild hyper- and hypoxia on the brain's static and dynamic autoregulation, ICP and PbtO2;
- The relationship between brain autoregulation, mild hyper- and hypocapnia, as well as of mild hyper- and hypoxia and metabolism in microdialysate on the one hand and the occurrence of DCI during hospitalization and poor neurological outcome one year after ictus on the other.
|Condition or disease||Intervention/treatment||Phase|
|Subarachnoid Hemorrhage, Aneurysmal||Other: Hypertension Other: Hyper- and hypoxia Other: Hyper- and hypocapnia||Not Applicable|
Spontaneous aneurysm subarachnoid hemorrhage (SAH) occurs annually in approximately 400 people in Denmark. SAH is most commonly seen in younger (median age 56 years) and women (71%), have a high mortality (21-44%) and result in a poor neurological outcome in about 50% of patients. Due to the relatively young patient population and high mortality and morbidity, SAH in the population causes the same number of lost working years as blood clots in the brain.
The occurrence of complications like hydrocephalus and re-bleeding can be minimized by rapid external ventricular drainage and aneurysm closure, and so-called delayed cerebral ischaemia (DCI) is currently considered to be the most frequent serious complication of SAH. DCI occurs in 20-30% of patients, most often within the first 14 days, is characterized by a reduction in consciousness or focal neurological deficit lasting at least one hour without any other underlying cause and is associated with a significantly increased risk of a poor outcome. The cause and treatment of DCI is controversial, and the previous hypothesis of vasospasm as the sole contributor is currently supplemented by a broader focus on several other mechanisms, including the brain's blood supply and its regulation.
The brain's blood supply (CBF) is kept relatively constant in healthy by changing cardiac diameter and thus the cerebrovascular resistance (CVR) during changes in brain perfusion pressure (CPP, measured as mean arterial pressure (MAP) minus intracranial pressure (ICP)) within certain limits. This mechanism is known as cerebral autoregulation. Outside these limits, respectively. decreases and increases CBF, with the consequent risk of hypoperfusion/ischemia and hyperperfusion/vasogenic edema with prolonged changes.
Weakened autoregulation, i.e. that CBF varies passively with CPP also within the normal autoregulation limits, is described in e.g. traumatic brain injury (TBI), ischemic stroke, acute liver failure and meningitis, with complete or partial restoration of autoregulation by hyperventilation (mild hypocapnia). SAH also describes impaired autoregulation with varying association with disease severity, DCI and outcome. It is not known whether mild hypocapnia restores autoregulation in patients with SAH, whereas animal experimental studies suggest this.
Reduced intracerebral oxygenation (PbtO2) is associated with a worse outcome after SAH. Cerebral microdialysis measures the concentration of certain metabolites in the brain and can provide an insight into whether metabolic activity is affected by oxygen deficiency, and so-called anaerobic combustion occurs. Microdialysis measurements with elevated lactate concentration, which is a metabolic product, among other things. Anaerobic combustion appears to occur prior to clinical signs of DCI, as well as during the DCI episodes, decreasing PbtO2. It is possible that these findings could be due to a condition of impaired autoregulation and too low perfusion pressure to meet brain metabolic needs, but this has not previously been elucidated. It is also unknown if it is possible to improve brain metabolism by increasing the brain's perfusion pressure.
The purpose of this study is therefore to investigate brain autoregulation in patients with SAH.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
Intervention is performed once in both patients (after the aneurysm is closed and max. 5 days after ictus) and controls. The procedure consists of the following sessions:
In session 2 (hyper- / hypoxia or hyper- / hypocapnia), patients are randomized to order the interventions.
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Cerebral Autoregulation in Patients With Aneurysmal SubArachnoid Haemorrhage|
|Actual Study Start Date :||June 15, 2019|
|Estimated Primary Completion Date :||January 1, 2021|
|Estimated Study Completion Date :||January 1, 2021|
Patients included in the study.
Hypertension is induced by an infusion of noradrenaline within acceptable limits Baseline recording (10 minutes) is performed. MAP gradually increases in steps of 5-10 mmHg during ongoing TCD. When the desired maximum MAP is reached, measurement is made at steady state (10 minutes).
Noradrenaline infusion is stopped. When MAP is stabilized, new baseline is measured for 10 minutes.
Other: Hyper- and hypoxia
The mechanical ventilator is adjusted to mild hypoxia, normoxia and mild hyperoxia. Measurements are made for 10 minutes at normoxia and after steady state is reached, respectively. hyperoxia and hypoxia. Oxygenation is controlled by arterial blood gas before and during steady state.
Other: Hyper- and hypocapnia
The mechanical ventilator is adjusted to a delta PaCO2 on the ventilator for both hypocapnia and hypercapnia. Measurements are made for 10 minutes at normocapnia and after steady state is reached, respectively. hyper- and hypocapnia.
- Mean flow index (Mxa) + induced hypertension [ Time Frame: within 5 days after ictus, for 10 minutes after steady state ]Measuring Mxa after induced hypertension
- Intracranial pressure (ICP) + induced hypertension [ Time Frame: within 5 days after ictus ]Measuring changes in ICP after induced hypertension
- Partial brain tissue oxygenation (PbtO2) + induced hypertension [ Time Frame: within 5 days after ictus ]Measuring changes in ICP after induced hypertension
- Mean flow index (Mxa) + hyper- and hypocapnia [ Time Frame: within 5 days after ictus, for 10 minutes after steady state ]Measuring during induction of hyper- and hypocapnia
- Intracranial pressure (ICP) + hyper- and hypocapnia [ Time Frame: within 5 days after ictus, for 10 minutes after steady state ]Measuring during induction of hyper- and hypocapnia
- Partial brain tissue oxygenation (PbtO2) + hyper- and hypocapnia [ Time Frame: within 5 days after ictus, for 10 minutes after steady state ]Measuring during induction of hyper- and hypocapnia
- Mean flow index (Mxa) + hyper- and hypoxia [ Time Frame: within 5 days after ictus, for 10 minutes after steady state ]Measuring during induction of hyper- and hypoxia
- Intracranial pressure (ICP) + hyper- and hypoxia [ Time Frame: within 5 days after ictus, for 10 minutes after steady state ]Measuring during induction of hyper- and hypoxia
- Partial brain tissue oxygenation (PbtO2) + hyper- and hypoxia [ Time Frame: within 5 days after ictus, for 10 minutes after steady state ]Measuring during induction of hyper- and hypoxia
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03987139
|Contact: Markus Olsen, M.D.||+firstname.lastname@example.org|
|Contact: Kirsten Møller, email@example.com|