Sevoflurane Sedation in Patients With Septic Shock

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Shock, Septic

Intervention / Treatment
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* Drug: Sevoflurane
* Drug: Control Group


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of interleukin-6 over time | To see if the interleukin-6 decreases under the influence of sevoflurane | 5 days | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Septic Shock, Sevoflurane Conditioning