Hypercapnia to Prevent Secondary Ischemia in SAH

Study Overview
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Brief Summary
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Delayed cerebral vasospasm and secondary ischemic infarction are feared complications after aneurysmal subarachnoid hemorrhage (aSAH). To date, there is no effective therapy to prevent these ischemic complications. The arterial partial pressure of carbon dioxide (PaCO2) is one of the main determinants of cerebral blood flow (CBF) in healthy subjects. It is yet largely unknown, if and to what extent modulations of PaCO2 can influence CBF in patients after aSAH. The trial is a phase 1 study in which the feasibility of hypercapnia in SAH patients is tested. PaCO2 is gradually raised to 60 mmHg in 10 mechanically ventilated aSAH patients. Cerebral oxygen saturation measured by NIRS and CBF determined by an intracerebral thermodilution probe are the primary end points. If the feasibility is confirmed, this trial will be followed by a phase 2 dose finding study.

Detailed Description
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The course of aneurysmal subarachnoid hemorrhage (aSAH) is determined by the sequence of several ischemic episodes. Immediately after aSAH, an increase of ICP causes an increase of CBF. It is followed by an acute vasoconstriction over the next hours and days. Typically between day 4 and 10 after aSAH, delayed arterial narrowing and a decrease of CBF occurs in approximately 50 % of aSAH patients and may result in cerebral ischemia and infarction. After the failure of the CONSCIOUS-trial to improve outcome after aSAH, there is no specific treatment in sight to effectively prevent cerebral ischemic events after aSAH. Under physiological conditions, the arterial partial pressure of carbon dioxide (PaCO2) is one of the main determinants of cerebral blood flow (CBF). An elevation of PaCO2 may also be a useful treatment on aSAH patients. This trial is designed as a phase 1 study to test the feasibility of controlled hypercapnia in mechanically ventilated aSAH patients with poor-grade SAH. Monitoring is performed by an external ventricular drainage (ICP), near infrared spectroscopy (tissue oxygenation) and a thermodilution probe (CBF). The latter monitoring tools represent the primary end points of this study. In case of affirmed feasibility, a dose finding study will be launched as a next step.

Official Title
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Therapeutical Hypercapnia to Prevent Secondary Ischemic Events in Aneurysmal Subarachnoid Hemorrhage (aSAH)

Conditions
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Aneurysmal Subarachnoid Hemorrhage

Intervention / Treatment
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* Procedure: Hypercapnia by reduction of respiratory volume


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aneurysmal SAH SAH Hunt/Hess Grade 3-5 SAH Fisher Grade 2-4 Mechanically ventilated external ventricular drainage/ICP measurement Exclusion Criteria: Age under 18 ICP > 25 mmHg for > 2 minutes pH < 7.250

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypercapnia<br>Intervention: SAH patients are subjected to gradual hypercapnia by reduction of respiratory volume in one trial session every day. PaCO2 is raised from normocapnia to 50 mmHg for 10 - 15 minutes and 60 mmHg for 10 - 15 minutes. | Procedure: Hypercapnia by reduction of respiratory volume<br>* By reduction of the respiratory volume, PaCO2 is raised while paO2 is kept constant by modulation of the oxygen supply through the respirator,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Blood Flow | Between day 4 and 14, PaCO2 is gradually raised from normocapnic values (40 mmHg) to hypercapnic values (50 and 60 mmHg). CBF is continuously measured during this intervention. Patients are clinically and radiologically followed for 6 months. | For an average of two weeks after aSAH | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral oxygen saturation | Oxygen saturation by NIRS is measured continuously for 2 weeks after aSAH. | For an average of two weeks after aSAH | 
| intracranial pressure (ICP) | ICP is continuously measured by an external ventricular drainage throughout the intervention period. | For an average of two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aneurysm, subarachnoid hemorrhage, vasospasm, cerebral ischemia, stroke