Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy

NCT04076826 | Completed

• 1 other identifier: 4051
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Septic encephalopathy (SE) is defined as acute cerebral dysfunction in patients with sepsis or septic shock. SE occurs in up to 50% of critically ill patients with sepsis and is associated with a high mortality and morbidity. The pathophysiology of SE is complex and involves increased levels of inflammatory mediators such as tumor necrosis factor (TNF)-α, Interleukin (IL)-1 and IL-6, leading to blood brain barrier dysfunction and neuronal inflammation. Several biomarkers of neuronal injury have been proposed to identify patients with SE. Of these biomarkers, S100-β has the highest sensitivity and specificity. Sedation with Dexmedetomidine (DEX) is a promising strategy for the management of these patients, as DEX has been shown to decrease the production of inflammatory mediators in experimental models of sepsis. In clinical studies, DEX lowers the incidence of delirium and critical illness polyneuropathy. However, its effectiveness in treatment and prevention of SE remains unclear. The aim of the present study is to investigate the effect of two standard sedation protocols (Dexmedetomidine sedation vs. Propofol / Midazolam) on serum markers of SE in critically ill patients with sepsis who require sedation and mechanical ventilation.

Conditions

Sepsis-Associated Encephalopathy

Keywords

Sepsis; Dexmedetomidine; Sedation; S-100beta; Encephalopathy

Outcome Measures

Primary Outcomes (1)

• S100-ß

  Serum concentration of S100-ß

  at 48 hours after randomization

Secondary Outcomes (6)

• Neuron-specific enolase

  first 3 days after randomization

• Interleukin 1-beta

  first 3 days after randomization

• Interleukin 6

  first 3 days after randomization

• TNF alpha

  first 3 days after randomization

• Acetylcholinesterase activity

  first 3 days after randomization

Study Arms (2)

Protocol A (Dexmedetomidine)

EXPERIMENTAL

Dexmedetomidine will be administered in accordance with hospital standard operating procedures (SOP).

Drug: Dexmedetomidine; Diagnostic Test: Blood sampling

Protocol B (Propofol / Midazolam)

ACTIVE COMPARATOR

Propofol and/or Midazolam will be administered in accordance with hospital standard operating procedures (SOP).

Drug: Propofol or Midazolam; Diagnostic Test: Blood sampling

Interventions

Dexmedetomidine DRUG

Dexmedetomidine infusion will be commenced in accordance with the hospital's local sedation protocol, without a loading dose, at a rate of 0.1 - 1.4 mcg/kg/hour to maintain sedation as per Richmond Agitation-Sedation Scale (RASS) sedation range specified by the treating clinician. Infusion will be continued until sedation is no longer clinically indicated up to a maximum of 7 days after enrolment.

Also known as: Protocol A

Protocol A (Dexmedetomidine)

Propofol or Midazolam DRUG

Propofol and/or Midazolam will be used according to Hospital guidelines to maintain sedation as per Richmond Agitation-Sedation Scale (RASS) sedation range specified by the treating clinician.

Also known as: Protocol B

Protocol B (Propofol / Midazolam)

Blood sampling DIAGNOSTIC_TEST

In all participants, we will collect blood samples for measurement of neuronal and systemic biomarkers of inflammation at randomization (baseline), at day 1, day 2 and day 3 after randomization.

Protocol A (Dexmedetomidine); Protocol B (Propofol / Midazolam)

Eligibility Criteria

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

You may qualify if:

• The participant is aged 18 years or older
• The participant has been intubated and is receiving mechanical ventilation
• The participant requires sedative medication for comfort, safety or to facilitate the delivery of life support measures
• The participant has either a central venous or an arterial catheter inserted within 24 hours of admission
• The participant has a diagnosis of sepsis based on the recent SEPSIS-3 consensus clinical criteria.

You may not qualify if:

• Age \< 18 years
• The treating physician believes that the participant will remain intubated for \<24 hours or the participant has been intubated for diagnostic or therapeutic procedures as the sole reason for mechanical ventilation.
• Participants with any of the following admission diagnosis: acute cerebral vascular event, traumatic brain injury, epilepsy, hypoxic brain injury, meningitis, encephalitis
• Participants with history of melanoma (S 100-β is elevated in melanoma participants)
• Participants with schizophrenia or other chronic psychiatric conditions
• Admission for drug overdose
• Planned administration of ongoing neuromuscular blockade
• Heart rate \< 55 / min or an atrioventricular block \> grade 2a in the absence of a functioning pacemaker
• Known hypersensitivity or allergy to any of the sedative medications used in this study.
• DNR (do not resuscitate) or DNI (do not intubate) orders
• Death is deemed to be imminent or inevitable during this admission and either the attending physician, participant or substitute decision maker is not committed to active treatment
• Women who are pregnant or breast feeding
• Known or suspected non-compliance, drug or severe alcohol abuse
• Inability of the participant to understand the procedures of the study, e.g. due to language problems, psychological disorders, or dementia
• Previous enrolment into the current study

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Inselspital, Bern University Hospital

Bern, 3010, Switzerland

Location

Related Publications (1)

• Iten M, Bachmann K, Jakob SM, Grandgirard D, Leib SL, Cioccari L. Adjunctive Sedation with Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy: A Pilot Randomized Controlled Study. Crit Care Med. 2025 Jul 1;53(7):e1377-e1388. doi: 10.1097/CCM.0000000000006655. Epub 2025 Mar 31.

  PMID: 40162868 DERIVED

MeSH Terms

Conditions

Sepsis-Associated Encephalopathy; Sepsis; Brain Diseases

Interventions

Dexmedetomidine; Propofol; Midazolam; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Luca Cioccari, MD

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. med.

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: September 3, 2019
• Study Start: September 1, 2019
• Primary Completion: June 17, 2022
• Study Completion: July 8, 2022
• Last Updated: February 13, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)