SSiS: Sevoflurane Sedation in Patients With Septic Shock

Sponsor

University of Zurich (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT03643367

Collaborator

Kantonsspital Münsterlingen (Other), Triemli Hospital (Other), Waid City Hospital, Zurich (Other)

153

Enrollment

Locations

Arms

Anticipated Duration (Months)

38.3

Patients Per Site

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Recent in vivo studies from others as well as the investigators group demonstrated that volatile anesthetics immunomodulate sepsis and improve outcome. Also, several clinical trials have convincingly shown that application of a volatile anesthetic provides protection in patients undergoing major surgery.

Patients with sepsis are intubated and ventilated and therefore need sedation. So far, most ICU centers use intravenously applied sedatives in these patients. In the proposed study, we will switch sedation from an intravenous to a volatile anesthetic for a short period of time to explore if sepsis markers improve within the following 120 hours upon sevoflurane conditioning.

Condition or Disease	Intervention/Treatment	Phase
Shock, Septic	Drug: Sevoflurane Drug: Control Group	Phase 2

Detailed Description

This randomized controlled trial (RCT) will be conducted over a period of 48 months, to investigate if volatile anesthetics have a positive effect on the prognostic sepsis marker IL-6. All patients with septic shock are intubated, ventilated and sedated with an intravenous anesthetic. In this study, eligible patients diagnosed with septic shock will be randomized 1:1 to the 'volatile group' with interruption of the propofol infusion, followed by a 4-hour sedation with the volatile anesthetic sevoflurane, or a continuous intravenous sedation ('intravenous' =control group). In both groups, 'intravenous' and 'volatile', the inflammatory markers as well as clinical parameters will be determined. The investigators will explore if there is a difference between the course of sepsis markers of the two groups within 5 days after intervention in favor of the volatile group.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

153 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients with septic shock are intubated and ventilated and therefore need sedation. So far, most ICU centers use intravenously applied sedatives in these patients. In the proposed study, we will switch sedation from an intravenous to a volatile anesthetic for a short period of time (4 hours) to explore if sepsis markers improve within the following 120 hours upon sevoflurane conditioning.Patients with septic shock are intubated and ventilated and therefore need sedation. So far, most ICU centers use intravenously applied sedatives in these patients. In the proposed study, we will switch sedation from an intravenous to a volatile anesthetic for a short period of time (4 hours) to explore if sepsis markers improve within the following 120 hours upon sevoflurane conditioning.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Patients will not be informed about their group assignments, technicians, processing the samples, will not have any access to ICU or patient charts (= double blind trial)

Primary Purpose:

Treatment

Official Title:

Sevoflurane Sedation: A Potentially Promising Immunomodulation in Patients With Septic Shock

Anticipated Study Start Date :

Jan 1, 2025

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Nov 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sevoflurane Sedation Patients randomized into experimental group will be treated with sevoflurane during 4 hours	Drug: Sevoflurane Included patients, randomized in experimental group, intravenous sedation will be interrupted and followed by a 4 hour sedation with the volatile anesthetic sevoflurane.
Active Comparator: Propofol Sedation Patients randomized into Control Group will get continued intravenous sedation with propofol	Drug: Control Group Included patients randomized in control group, intravenouse sedation is continued with propofol Other Names: Propofol

Arm

Intervention/Treatment

Experimental: Sevoflurane Sedation

Patients randomized into experimental group will be treated with sevoflurane during 4 hours

Drug: Sevoflurane

Included patients, randomized in experimental group, intravenous sedation will be interrupted and followed by a 4 hour sedation with the volatile anesthetic sevoflurane.

Active Comparator: Propofol Sedation

Patients randomized into Control Group will get continued intravenous sedation with propofol

Drug: Control Group

Included patients randomized in control group, intravenouse sedation is continued with propofol

Other Names:

Propofol

Outcome Measures

Primary Outcome Measures

Concentration of interleukin-6 over time [5 days]
To see if the interleukin-6 decreases under the influence of sevoflurane

Secondary Outcome Measures

Pro-/anti-inflammatory mediators [5 days]
effect on inflammatory/anti- inflammatory mediators
Vasopressor support [5 days]
Use of vasopressor support (norepinephrine, dobutamine, vasopressin) will be determined.
Sequential organ failure score (SOFA Score) [5 days]
Sepsis related organ failure score
Richmond Agitation Sedation Scale [5 days]
A scale to measure the agitation or sedation level of a patient
Duration of mechanical ventilation [28 days]
Time of mechanical ventilation
Mortality [28 days]
Mortality information in intensive care unit and on the ward

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female patients, age 18 to 80 years
Intensive care Unit (ICU) patients with septic shock (despite fluid resuscitation vasopressors needed to maintain mean arterial pressure ≥65 millimeter of mercury (mmHg), and serum lactate >2mmol/l even with fluid application)
Treatment of septic shock on ICU with vasopressors not longer than 12 hours
Sedation and mechanical ventilation on ICU
Female patients of childbearing potential with negative pregnancy test
Informed Consent as documented by signature

Exclusion Criteria:

Previous surgery and/or anesthesia (within last 7 days)
Application of nitric oxide (NO)
Suspected or known intolerance by history to volatile anesthetics (malignant hyperthermia)
Immunosuppressive agents
Systemic corticosteroids in the phase before hospitalization (> 10mg/d prednisone)
Significant concomitant disease (acute cerebral vascular event, acute coronary syndrome, decompensated heart failure, acute pulmonary edema, major cardiac arrhythmia, seizure, burn, chronic kidney disease, end stage liver failure, neuromuscular disease)
AIDS
Autoimmune disease
Organ transplant
Subject with active malignancy receiving
chemotherapy or radiation treatment within last 60 days
Hepatitis B/C virus infection
Anti-tumor necrosis factor (TNF) therapy
Pregnancy and/or Breast feeding
Use of cytokine absorber
Enrollment in any other clinical trial during the course of this trial, 30 days prior to its beginning or 30 days after its completion

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Kantonasspital Münsterlingen	Münsterlingen	Switzerland	8596
2	University Hospital of Zurich	Zurich	Switzerland
3	Stadtspital Triemli	Zürich	Switzerland	8063
4	Waidspital Zürich	Zürich	Switzerland