Cerebral Autoregulation in Patients With Aneurysmal SubArachnoid Haemorrhage (CASAH)

October 22, 2021 updated by: Markus Harboe Olsen, Rigshospitalet, Denmark

The purpose is, in patients with aneurysmal subarachnoid haemorrhage in the early phase after ictus, to examine the following:

  1. 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;
  2. 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;
  3. 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Anticipated)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Capital Region
      • Copenhagen, Capital Region, Denmark, 2200
        • Department of Neuroanaesthesiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria, patients:

  • Admittance to neurointensive care unit, Rigshospitalet
  • Age ≥ 18 years old
  • Aneurysmal subarachnoid haemorrhage
  • Clinical indication for placement of an external ventricular drain
  • Measurements can be done within 3 days of ictus
  • Closest relatives understand written and spoken danish

Exclusion Criteria, patients:

  • No aneurysm identified
  • Conservative og failed treatment of aneurysm
  • Pupils dilated and do not react to light
  • Incarceration before inclusion
  • Expected death within 48 hours
  • Acute or chronic diseases associated with impaired autoregulation
  • Severe chronic lung failure with a PaCO2 > 6.5 kPa or PaO2 < 8 kPa.

Inclusion Criteria, healthy subjects:

  • Age ≥ 18 years old;
  • Understands written and spoken danish
  • Oral and written consent
  • No medication expect hay fever medications
  • Alcohol consumption within the limits from the danish health care board
  • Healthy without previous or current cerebrovascular diseases
  • Insonation is possible from the middle cerebral artery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: All patients
Patients included in the study.
Other: Hypertension

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Middle cerebral artery flow velocity (MCAv) + induced hypertension
Time Frame: within 5 days after ictus, for 10 minutes after steady state
Measuring MCAv after induced hypertension
within 5 days after ictus, for 10 minutes after steady state

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial pressure (ICP) + induced hypertension
Time Frame: within 5 days after ictus
Measuring changes in ICP after induced hypertension
within 5 days after ictus
Partial brain tissue oxygenation (PbtO2) + induced hypertension
Time Frame: within 5 days after ictus
Measuring changes in ICP after induced hypertension
within 5 days after ictus
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
within 5 days after ictus, for 10 minutes after steady state
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
within 5 days after ictus, for 10 minutes after steady state
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
within 5 days after ictus, for 10 minutes after steady state
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
within 5 days after ictus, for 10 minutes after steady state

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2019

Primary Completion (Actual)

October 1, 2021

Study Completion (Anticipated)

March 1, 2022

Study Registration Dates

First Submitted

June 11, 2019

First Submitted That Met QC Criteria

June 13, 2019

First Posted (Actual)

June 14, 2019

Study Record Updates

Last Update Posted (Actual)

October 29, 2021

Last Update Submitted That Met QC Criteria

October 22, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-19017185

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Data from each individual participant will be available after publication of planned manuscripts, with a valid reason, and after signing a data processing agreement.

IPD Sharing Time Frame

The approved study protocol will be available upon request until publication of the study results

IPD Sharing Access Criteria

Valid reason and contact with author

IPD Sharing Supporting Information Type

  • Study Protocol

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Subarachnoid Hemorrhage, Aneurysmal

Clinical Trials on Hypertension

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Croatia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe