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Completed

NCT Number: NCT04076826

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

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.

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Key information

Conditions

Sepsis-Associated Encephalopathy Brain Diseases Central Nervous System Diseases Infections Inflammation Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Sepsis Systemic Inflammatory Response Syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Inselspital, Bern University Hospital

Bern, 3010, Switzerland

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: Protocol A

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.

Other names: Protocol B

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.

Primary outcomes

  1. S100-ß

    Time frame: at 48 hours after randomization

    Serum concentration of S100-ß

Secondary outcomes

  1. Neuron-specific enolase

    Time frame: first 3 days after randomization

    Serum concentration of Neuron-specific enolase

  2. Interleukin 1-beta

    Time frame: first 3 days after randomization

    Serum concentration of Interleukin 1-beta

  3. Interleukin 6

    Time frame: first 3 days after randomization

    Serum concentration of Interleukin 6

  4. TNF alpha

    Time frame: first 3 days after randomization

    Serum concentration of TNF alpha

  5. Acetylcholinesterase activity

    Time frame: first 3 days after randomization

    Acetylcholinesterase activity will be measured using a point-of-care device and reported as Units/grams Haemoglobin

  6. Butyrylcholinesterase activity

    Time frame: first 3 days after randomization

    Butyrylcholinesterase activity will be measured using a point-of-care device and reported as Units/L

Sponsors and collaborators

Lead sponsor

Insel Gruppe AG, University Hospital Bern

Other

Registry information

Official study title

Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy: a Pilot Randomized Controlled Study.

Acronym: ADVISE

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Sep 3, 2019
Registry last updated
Feb 13, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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