Sevoflurane in Subarachnoidal Haemorrhage

NCT ID: NCT02946437

Last Updated: 2020-06-02

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-01
• Study Completion Date: 2019-12-31

Brief Summary

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.

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.

Conditions

Subarachnoid Haemorrhage (SAH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Sevoflurane

Intervention Type: DRUG

Postconditioning with sevoflurane (0.5-1.5vol%) for 4 hours after coiling or clipping of cerebral aneurysm in patients with severe SAH

MIRUS™System

Intervention Type: DEVICE

The MIRUS™System is the normally used standard equipment for the administration of volatile anaesthetics to patients.

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.)

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

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.

Midazolam

Intervention Type: DRUG

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.

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.

Group Type: OTHER

Sevoflurane

Intervention Type: DRUG

Postconditioning with sevoflurane (0.5-1.5vol%) for 4 hours after coiling or clipping of cerebral aneurysm in patients with severe SAH

MIRUS™System

Intervention Type: DEVICE

The MIRUS™System is the normally used standard equipment for the administration of volatile anaesthetics to patients.

Interventions

Sevoflurane

Postconditioning with sevoflurane (0.5-1.5vol%) for 4 hours after coiling or clipping of cerebral aneurysm in patients with severe SAH

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

MIRUS™System

The MIRUS™System is the normally used standard equipment for the administration of volatile anaesthetics to patients.

Intervention Type: DEVICE

Other Intervention Names

Sevorane®; Disoprivan®; Dormicum®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Emanuela Keller

Prof. Dr. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Emanuela Keller, MD Prof.

Role: PRINCIPAL_INVESTIGATOR

University of Zurich

Locations

University Hospital Zurich

Zurich, , Switzerland

Countries

Switzerland

Other Identifiers

2015DR2134

Identifier Type: OTHER

Identifier Source: secondary_id

2014-0397

Identifier Type: -

Identifier Source: org_study_id