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

Not Applicable

Completed

• Conditions: Sepsis-Associated Encephalopathy
• Interventions: Drug: Propofol or Midazolam; Drug: Dexmedetomidine; Diagnostic Test: Blood sampling

• Registration Number: NCT04076826
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-08-22
• Study First Submitted QC: 2019-08-29
• Study Start: 2019-09-01
• Study First Posted: 2019-09-03
• Primary Completion: 2022-06-17
• Study Completion: 2022-07-08
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-10
• Last Update Posted: 2023-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• 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.

Read More

Exclusion Criteria

• 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
• Enrolment of the investigator, his/her family members, employees and other dependent persons

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Protocol B (Propofol / Midazolam)	Propofol or Midazolam	Propofol and/or Midazolam will be administered in accordance with hospital standard operating procedures (SOP).
Protocol A (Dexmedetomidine)	Blood sampling	Dexmedetomidine will be administered in accordance with hospital standard operating procedures (SOP).
Protocol B (Propofol / Midazolam)	Blood sampling	Propofol and/or Midazolam will be administered in accordance with hospital standard operating procedures (SOP).
Protocol A (Dexmedetomidine)	Dexmedetomidine	Dexmedetomidine will be administered in accordance with hospital standard operating procedures (SOP).

Primary Outcome Measures

Name	Time	Method
S100-ß	at 48 hours after randomization	Serum concentration of S100-ß

Secondary Outcome Measures

Name	Time	Method
Neuron-specific enolase	first 3 days after randomization	Serum concentration of Neuron-specific enolase
Interleukin 1-beta	first 3 days after randomization	Serum concentration of Interleukin 1-beta
TNF alpha	first 3 days after randomization	Serum concentration of TNF alpha
Butyrylcholinesterase activity	first 3 days after randomization	Butyrylcholinesterase activity will be measured using a point-of-care device and reported as Units/L
Interleukin 6	first 3 days after randomization	Serum concentration of Interleukin 6
Acetylcholinesterase activity	first 3 days after randomization	Acetylcholinesterase activity will be measured using a point-of-care device and reported as Units/grams Haemoglobin

Trial Locations

Locations (1)

Inselspital, Bern University Hospital; 🇨🇭 Bern, Switzerland