Sevoflurane Sedation in Patients With Septic Shock

NCT03643367 | Not Yet Recruiting Phase 2

• 1 other identifier: SSiS
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 4

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.

Conditions

Shock, Septic

Keywords

Sepsis; Septic Shock; Sevoflurane Conditioning

Outcome Measures

Primary Outcomes (1)

• Concentration of interleukin-6 over time

  To see if the interleukin-6 decreases under the influence of sevoflurane

  5 days

Secondary Outcomes (6)

• 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

Study Arms (2)

Sevoflurane Sedation

EXPERIMENTAL

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

Drug: Sevoflurane

Propofol Sedation

ACTIVE COMPARATOR

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

Drug: Control Group

Interventions

Sevoflurane DRUG

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

Sevoflurane Sedation

Control Group DRUG

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

Also known as: Propofol

Propofol Sedation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead
• Kantonsspital Münsterlingen: collaborator
• Triemli Hospital: collaborator
• Waid City Hospital, Zurich: collaborator

Study Sites (4)

Kantonasspital Münsterlingen

Münsterlingen, 8596, Switzerland

Location

Stadtspital Triemli

Zurich, 8063, Switzerland

Location

University Hospital of Zurich

Zurich, Switzerland

Location

Waidspital Zürich

Zurich, Switzerland

Location

Related Publications (8)

• Tang BM, McLean AS, Dawes IW, Huang SJ, Lin RC. The use of gene-expression profiling to identify candidate genes in human sepsis. Am J Respir Crit Care Med. 2007 Oct 1;176(7):676-84. doi: 10.1164/rccm.200612-1819OC. Epub 2007 Jun 15.

  PMID: 17575094 BACKGROUND

• Lu Y, Wang J, Yan J, Yang Y, Sun Y, Huang Y, Hu R, Zhang Y, Jiang H. Sevoflurane attenuate hypoxia-induced VEGF level in tongue squamous cell carcinoma cell by upregulating the DNA methylation states of the promoter region. Biomed Pharmacother. 2015 Apr;71:139-45. doi: 10.1016/j.biopha.2015.02.032. Epub 2015 Mar 3.

  PMID: 25960229 BACKGROUND

• Klag T, Cantara G, Sechtem U, Athanasiadis A. Interleukin-6 Kinetics can be Useful for Early Treatment Monitoring of Severe Bacterial Sepsis and Septic Shock. Infect Dis Rep. 2016 Mar 21;8(1):6213. doi: 10.4081/idr.2016.6213. eCollection 2016 Mar 21.

  PMID: 27103972 BACKGROUND

• Rios-Toro JJ, Marquez-Coello M, Garcia-Alvarez JM, Martin-Aspas A, Rivera-Fernandez R, Saez de Benito A, Giron-Gonzalez JA. Soluble membrane receptors, interleukin 6, procalcitonin and C reactive protein as prognostic markers in patients with severe sepsis and septic shock. PLoS One. 2017 Apr 5;12(4):e0175254. doi: 10.1371/journal.pone.0175254. eCollection 2017.

  PMID: 28380034 BACKGROUND

• Tschaikowsky K, Hedwig-Geissing M, Braun GG, Radespiel-Troeger M. Predictive value of procalcitonin, interleukin-6, and C-reactive protein for survival in postoperative patients with severe sepsis. J Crit Care. 2011 Feb;26(1):54-64. doi: 10.1016/j.jcrc.2010.04.011. Epub 2010 Jun 19.

  PMID: 20646905 BACKGROUND

• Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016 Aug 2;316(5):509-18. doi: 10.1001/jama.2016.10485.

  PMID: 27483065 BACKGROUND

• Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC, Reinhart K; International Forum of Acute Care Trialists. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2016 Feb 1;193(3):259-72. doi: 10.1164/rccm.201504-0781OC.

  PMID: 26414292 BACKGROUND

• Kellner P, Muller M, Piegeler T, Eugster P, Booy C, Schlapfer M, Beck-Schimmer B. Sevoflurane Abolishes Oxygenation Impairment in a Long-Term Rat Model of Acute Lung Injury. Anesth Analg. 2017 Jan;124(1):194-203. doi: 10.1213/ANE.0000000000001530.

  PMID: 27782948 BACKGROUND

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Sevoflurane; Control Groups; Propofol

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Martin Schlaepfer, PD

  University of Zurich

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Schlaepfer, PD

CONTACT

+41 44 255 4690; martin.schlaepfer@usz.ch

Martin Schläpfer, PD

CONTACT

+41 44 255 4690; martin.schlaepfer@usz.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 20, 2017
• First Posted: August 22, 2018
• Study Start: January 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (4)