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Sevoflurane in Subarachnoidal Haemorrhage

Phase 2
Withdrawn
Conditions
Subarachnoid Haemorrhage (SAH)
Interventions
Registration Number
NCT02946437
Lead Sponsor
University of Zurich
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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SevofluraneMIRUS™SystemSevoflurane 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.
MIRUS™SystemMIRUS™SystemMIRUS™ 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.
SevofluraneSevofluraneSevoflurane 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.
Propofol or MidazolamPropofolPropofol 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.)
MIRUS™SystemSevofluraneMIRUS™ 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.
Propofol or MidazolamMidazolamPropofol 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.)
Primary Outcome Measures
NameTimeMethod
Feasibility: Incidence of concerns/problems in the use of sevoflurane by intensivist and ICU nurse at the stopping of sevoflurane postconditioning.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

Secondary Outcome Measures
NameTimeMethod
Quality of sedation5 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)

Neuroprotective effects14 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.

Trial Locations

Locations (1)

University Hospital Zurich

🇨🇭

Zurich, Switzerland

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