Sevoflurane in Subarachnoidal Haemorrhage (Sevoflurane)

May 28, 2020 updated by: Emanuela Keller, University of Zurich

Short Term Application of Sevoflurane in Patients With Subarachnoid Haemorrhage: a Feasibility and Safety Study

Feasibility and safety of short term application of sevoflurane in patients with SAH treated with aneurysm coiling or clipping in the setting of a neurointensive care unit.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

After admission to the ICU, before the coiling / clipping intervention has been performed, the patients are screened for eligibility. When the patients are coming back to the ICU, after successful aneurysm coiling or clipping, data of artificial ventilation, systemic and other cerebral parameters will be collected continuously by online monitoring, starting at baseline and stopping at discharge of the ICU. Sevoflurane will be vaporized and administrated by the MIRUS™System directly to the inspiratory part of the ventilation circuit for the next 4 hours. In the following 14 days of the stay on the ICU, standard monitoring parameters, the appearance of vasospasm and brain oedema will be recorded. Besides the continuous online monitoring, laboratory assessment will be performed daily. At day 7±2 and day 14±2 after bleeding a MRI or CT examination will be performed, according to the clinical condition of the patient, to detect secondary brain injuries, as ischemia or brain oedema. At ICU discharge, the neurological outcome will be assesses applying GOS.

Study Type

Interventional

Phase

  • Phase 2

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

  • Switzerland
      • Zurich, Switzerland, 8091
        • University Hospital Zurich

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 to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients of either sex aged 18-85 years
  • Patients with severe aneurysmal SAH, Hunt/Hess 3 to 5.
  • The ruptured aneurysm is successfully excluded with coiling or clipping
  • Sedation and mechanical ventilation necessary due to the clinical situation
  • ICP monitoring in use due to the clinical situation
  • ICP < 20mmHg without medical treatment
  • Systolic blood pressure values (BP syst) > 120 mmHg with no need for catecholamines
  • Female patients of childbearing potential with negative pre-treatment serum pregnancy test
  • Informed consent obtained

Exclusion Criteria:

  • Significant kidney disease, defined as plasma creatinine >120 µmol/l
  • Significant liver disease, defined as Aspartate-Aminotransferase (AST) >200 U/l
  • Significant elongation of the QTc interval: female < 470 msec/ male < 450 msec; based on 'Bazett's Formula'
  • History of epilepsia and/ or occurring seizures with aneurysm rupture
  • Pneumocephalus after surgery excluded by CT scan performed immediately after clipping
  • History of allergic disorders
  • History for, or relatives with a history for malignant hyperthermia
  • History or signs for neuromuscular disease
  • Pre-existing disability
  • Patients participating in an interventional clinical trial within the last 30 days before start of treatment

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sevoflurane

Sevoflurane postconditioning will start after the bleeding source is excluded by coiling or clipping as soon as the patient returns to the ICU and will be continued for 4 hours. 0.5-1.5vol% sevoflurane will be administrated into the ventilation circuit by a MIRUS™System.

The used dose (0.5-1.5vol%) is a lower dose as used for anaesthesia for a surgical intervention (0.5-3vol%), but high enough to provide sufficient sedation.
Drug: Sevoflurane
Postconditioning with sevoflurane (0.5-1.5vol%) for 4 hours after coiling or clipping of cerebral aneurysm in patients with severe SAH
Other Names:
  • Sevorane®
Device: MIRUS™System
The MIRUS™System is the normally used standard equipment for the administration of volatile anaesthetics to patients.
Active Comparator: Propofol or Midazolam
Propofol or midazolam will be administrated intravenously before and after the postconditioning with sevoflurane as in the standard sedation regimen of the Neurointensive Care Unit, University Hospital Zurich (propofol 0.3-4.0mg/kg/h cont. i.v.; midazolam 0.03-0.2mg/kg/h cont. i.v.)
Drug: Propofol
Before and after postconditioning with sevoflurane the patients will be sedated with intravenous sedatives (midazolam or propofol). The quality of sedation before the postconditioning (propofol or midazolam) will be compared to the sedation one hour after starting the postconditioning (sevoflurane) in the same patient.
Other Names:
  • Disoprivan®
Drug: Midazolam
Before and after postconditioning with sevoflurane the patients will be sedated with intravenous sedatives (midazolam or propofol). The quality of sedation before the postconditioning (propofol or midazolam) will be compared to the sedation one hour after starting the postconditioning (sevoflurane) in the same patient.
Other Names:
  • Dormicum®
Other: MIRUS™System
MIRUS™ is a newly developed device, considered as vaporizer system, which can be used in the setting of operating rooms or in intensive care units. The MIRUS™System is successfully in use in daily clinical practice. This type of device is similar to the well-known AnaConDa® system (AnaConDa®, Sedana Medical, Uppsala, S) with several advantages. Since 2005 the anaesthetic-conserving device AnaConDa® facilitates, from a technical viewpoint, the routine use of volatile anaesthetics in intensive care patients as part of prolonged sedation, using ICU ventilators (Soukup J et al., 2009). The MIRUS™System forms a closed loop. It measures the end-tidal concentration of the anaesthetic gas and governs the application of the anaesthetic gas according to these values and the ventilation parameters.
Drug: Sevoflurane
Postconditioning with sevoflurane (0.5-1.5vol%) for 4 hours after coiling or clipping of cerebral aneurysm in patients with severe SAH
Other Names:
  • Sevorane®
Device: MIRUS™System
The MIRUS™System is the normally used standard equipment for the administration of volatile anaesthetics to patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility: Incidence of concerns/problems in the use of sevoflurane by intensivist and ICU nurse at the stopping of sevoflurane postconditioning.
Time Frame: 4 hours
  • Incidence of concerns of users in relation to the application of standard sedation with propofol or midazolam
  • Incidence of complications with sevoflurane preparation, sevoflurane application, MIRUS™-installation, MIRUS™-function, MIRUS™-removal
  • User friendliness compared to settings for artificial ventilation supplemented with NO
4 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of sedation
Time Frame: 5 hours

  • Incidence of insufficient sedation during postconditioning with sevoflurane, measured with:

    • Ramsay Sedation Scale (RSS <2)
    • Richmond Agitation-Sedation Scale (RASS >0)
    • Bispectral index (BIS >30)
    • Incidence of use of additional sedative medication as midazolam, propofol
  • in relation to the sedation regimen before and after the postconditioning (dose and use of additional sedative medication as midazolam, propofol)
5 hours
Neuroprotective effects
Time Frame: 14 days

  • Number of days during the 14 days monitoring period with signs of DIND

    • incidence of new neurological deficits on daily clinical visits
    • incidence of 2 consecutive metabolic crisis identified by microdialysis, defined as lactate/pyrovate-ratio (L/P-ratio) >40
    • incidence of PtiO2 <20mmHg at least 60 minutes- immediately before the measurement
    • incidence of new perfusion deficits in perfusion-CT and/ or -MRI, new infarctions in contrast enhanced CT/ MRI
  • Neurological outcome (GOS) will be assessed at ICU discharge and compared to data from the literature.
14 days

Collaborators and Investigators

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

Sponsor

University of Zurich

Investigators

  • Principal Investigator: Emanuela Keller, MD Prof., University of Zurich

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)

November 1, 2015

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

December 31, 2019

Study Registration Dates

First Submitted

October 7, 2016

First Submitted That Met QC Criteria

October 24, 2016

First Posted (Estimate)

October 27, 2016

Study Record Updates

Last Update Posted (Actual)

June 2, 2020

Last Update Submitted That Met QC Criteria

May 28, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014-0397
  • 2015DR2134 (Other Identifier: Swissmedic)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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.

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