Therapeutic Hypercapnia After Aneurysmal Subarachnoid Hemorrhage - Optimum Duration of Hypercapnia

Therapeutic Hypercapnia After Aneurysmal Subarachnoid Hemorrhage - Study for the Optimum Duration of Hypercapnia

Temporary hypercapnia leads to a reproducible increase of cerebral blood flow (CBF) and brain tissue oxygenation (StiO2) as shown in a previous study (Trial-Identification: NCT01799525). The aim of this study now was to measure the course of carbon dioxide partial pressure (pCO2) reactivity after prolonged hypercapnia, and to evaluate the therapeutic effect of graded hypercapnia.

Study Overview

• Status: Completed
• Conditions: Vasospasm Intracranial
• Intervention / Treatment: Procedure: Temporary hypercapnia

Detailed Description

Cerebral vasospasm still is the leading cause of delayed cerebral ischemia (DCI) and secondary ischemic deficits after aneurysmal subarachnoid hemorrhage (SAH). Hypercapnia leads to a reproducible increase of cerebral blood flow (CBF) and brain tissue oxygenation (StiO2) as shown in a previous study (Trial-Identification: NCT01799525). Furthermore, the increase of CBF and StiO2 sustained after normalization of ventilation and no rebound effect was found. So, a possible optimization of the hypercapnic period may lead to prolonged effects of increased CBF and StiO2. Aim of this stuy is to find the ideal duration of hypercapnia and to evaluate the therapeutic effect of graded hypercapnia. For this, intubated and mechanically ventilated patients with an aneurysmal SAH Hunt/Hess 3-5, Fisher grade 2-4 on the initial CT scan and supplied with an external ventricular drainage will be included within the first 96 hours after ictus. Between day 4 and 14 they undergo a trial intervention in which the respiratory minute volume will be reduced in order to maintain a target PaCO2 of 50 - 55 mmHg for 2 hours. Arterial blood gas analysis (ABG) and transcranial Doppler sonography (TCD) is performed in 15-minute intervals. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cardiovascular parameters are monitored continuously, serial measurement of CBF and StiO2 under continous hypercapnia is performed. Primary endpoint of this trial is change of CBF under hypercapnia, secondary endpoints are StiO2, measures non-invasively with near-infrared spectroscopy, mean flow velocity of intracranial vessels in TCD, delayed cerebral infarction in cranial CT and Glasgow Outcome Score (GOS) after 6 months.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Participation Criteria

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:

• Aneurysmal SAH
• Aneurysm occluded by clipping/coiling within 96 hours
• Hunt/Hess 3-5
• Fisher 2-4 on initial CT scan
• Intubated, sedated and mechanically ventilated patient
• Continous drainage of cerebrospinal fluid (CSF)

Exclusion Criteria:

• Age under 18 years
• Pregnancy
• Common obstructive lung disease (COLD)
• potential of hydrogen (pH) in ABG < 7,25
• ICP > 20 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Optimum duration of hypercapnia; Daily serial measurement of 2 hours under target hypercapnia of pCO2 50 - 55 mmHg by changes of respirator settings once per day	Procedure: Temporary hypercapnia; Temporary daily hypercapnia for 2 hours between day 4 and 14 after SAH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral blood flow (CBF)	Changes of CBF (absolute, ml/100g tissue/min) under changes of arterial pCO2	2-4 hours, day 4-14 after SAH

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral tissue oxygen saturation	Changes of tissue oxygen saturation measured by near-infrared spectroscopy (NIRS)	2-4 hours, day 4-14 after SAH
Glasgow Outcome Score (GOS)	Glasgow Outcome Score (GOS 1 - 5, GOS 1 = Death, GOS 5 = none or low disability) after 14 days, after discharge and 6 months	up to 6 months

Collaborators and Investigators

• Sponsor: University of Wuerzburg

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: December 28, 2020
• First Posted (Actual): December 29, 2020

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 28, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: SAH; Hypercapnia; DCI
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Hypercapnia
• Other Study ID Numbers: AZ230/14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided