Sevoflurane Sedation: a Potentially Promising Immunomodulation in Patients with Septic Shock
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- University of Zurich
- Enrollment
- 153
- Locations
- 4
- Primary Endpoint
- Concentration of interleukin-6 over time
Study Overview
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.
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
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- 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)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
- •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
Arms & Interventions
Sevoflurane Sedation
Patients randomized into experimental group will be treated with sevoflurane during 4 hours
Intervention: Sevoflurane (Drug)
Propofol Sedation
Patients randomized into Control Group will get continued intravenous sedation with propofol
Intervention: Control Group (Drug)
Outcomes
Primary Outcomes
Concentration of interleukin-6 over time
Time Frame: 5 days
To see if the interleukin-6 decreases under the influence of sevoflurane
Secondary Outcomes
- Pro-/anti-inflammatory mediators(5 days)
- Vasopressor support(5 days)
- Sequential organ failure score (SOFA Score)(5 days)
- Richmond Agitation Sedation Scale(5 days)
- Duration of mechanical ventilation(28 days)
- Mortality(28 days)