Clinical trial NCT04076826: Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy
Official title: Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy: a Pilot Randomized Controlled Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis-Associated Encephalopathy
Keywords: Sepsis
Dexmedetomidine
Sedation
S-100beta
Encephalopathy
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2019-09-03
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

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

Primary outcomes:
measure: S100-ß
timeFrame: at 48 hours after randomization
Secondary outcomes:
measure: Neuron-specific enolase
timeFrame: first 3 days after randomization
measure: Interleukin 1-beta
timeFrame: first 3 days after randomization
measure: Interleukin 6
timeFrame: first 3 days after randomization
measure: TNF alpha
timeFrame: first 3 days after randomization
measure: Acetylcholinesterase activity
timeFrame: first 3 days after randomization
measure: Butyrylcholinesterase activity
timeFrame: first 3 days after randomization
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Inselspital, Bern University Hospital
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Luca Cioccari, MD
role: PRINCIPAL_INVESTIGATOR
References: