Low-Dose Dexmedetomidine for Delirium Prevention in Mechanically Ventilated Septic Patients

Low-Dose Dexmedetomidine for Delirium Prevention in Mechanically Ventilated Septic Patients in Intensive Care Unit: a Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04876937

Enrollment

Registered

2021-05-07

Start date

2021-05-28

Completion date

2024-03-02

Last updated

2025-08-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adult, Delirium, Dexmedetomidine, Intensive Care Unit, Mechanical Ventilation, Sepsis

Keywords

Adult, Intensive care unit, Sepsis, Mechanical ventilation, Delirium, Dexmedetomidine

Brief summary

Delirium is common in septic patients, especially those receiving mechanical ventilation in the intensive care unit (ICU). Dexmedetomidine is a highly selective α2 adrenoreceptor agonist with anxiolytic, sedative, analgesic, and anti-inflammatory effects. Use of dexmedetomidine in mechanically ventilated ICU patients is associated with less delirium and improved outcomes. However, dexmedetomidine infusion produces dose-dependent bradycardia and hypotension; these limited the use of dexmedetomidine in ICU patients. This study is designed to test the hypothesis that low-dose dexmedetomidine infusion can also reduce delirium in mechanically ventilated ICU patients with sepsis.

Detailed description

Delirium is an acutely occurred and fluctuating disorder of consciousness, attention, and cognition. The occurrence of delirium is associated with worse outcomes including prolonged mechanical ventilation, prolonged length of stay in ICU and hospital, increased complications, higher in-hospital mortality, and evaluated medical expenses. It is also associated with worse long-term outcomes including cognitive decline, worse quality of life, and shortened long-term survival. Dexmedetomidine is a highly selective α2 adrenoreceptor agonist with anxiolytic, sedative, analgesic, and anti-inflammatory effects. Studies showed that use of dexmedetomidine is associated with less delirium in ICU patients. Potential mechanisms may include better sleep quality, less consumption of opioids and benzodiazepines, and suppressed inflammatory response. The incidence of sepsis in ICU patients is as high as 47.2%; 93% of septic patients relying on mechanical ventilation. Delirium is common in septic patients; the reported incidences varies from 20% to 50%. The incidence of delirium in critically ill patients with mechanical ventilation is up to 60-84%. However, the majority of mechanically ventilated ICU patients are sedated with propofol; only 10% of them are given dexmedetomidine. A main reason is that dexmedetomidine infusion is associated with dose-related bradycardia and hypotension. In a previous study, might-time low-dose dexmedetomidine infusion (0.1 μg/kg/h) improved subjective sleep quality and reduced delirium in elderly patients admitted to ICU after surgery. In another study of ICU patients receiving mechanical ventilation, low-dose dexmedetomidine infusion (0-0.5 μg/kg/h) based on protocol sedation also reduced delirium and shortened mechanical ventilation without increasing adverse events. We hypothesized that, in ICU septic patients with mechanical ventilation, low-dose dexmedetomidine infusion (0.1-0.2 μg/kg/h) might also reduce delirium. The purpose of this study is to investigate the effect of low-dose dexmedetomidine infusion on incidence of delirium in ICU septic patients with mechanical ventilation.

Interventions

DRUGDexmedetomidine

Dexmedetomidine is infused at a rate of 0.1-0.2 μg/kg/h (0.025-0.05 ml/kg/h) from study recruitment in the ICU during mechanical ventilation, for no more than 7 days.

DRUGPlacebo (normal saline)

Placebo (normal saline) is infused at a rate of 0.025-0.05 ml/kg/h from study recruitment in the ICU during mechanical ventilation, for no more than 7 days.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Aged 18 years or older; 2. Admitted to the ICU; 3. With expected mechanical ventilation duration ≥12 hours; 4. Meet the diagnostic criteria of sepsis (sepsis 3.0; patient with infection and a sequential organ failure assessment score ≥2).

Exclusion criteria

1. Refuse to participate in; 2. Pregnancy; 3. History of schizophrenia, epilepsy, parkinsonism, or myasthenia gravis; 4. Inability to communicate (coma, profound dementia, or language barrier); 5. Brain injury or neurosurgery; 6. Left ventricular ejection fraction (LVEF) less than 30%, sick sinus syndrome, severe sinus bradycardia (\<50 beats per min \[bpm\]), or second degree or greater atrioventricular block without pacemaker; 7. Serious hepatic dysfunction (Child-Pugh class C); 8. Serious renal dysfunction (undergoing dialysis); 9. With expected survival for no more than 24 hours; 10. Allergic to dexmedetomidine; 11. Other conditions that were considered unsuitable for study participation.

Design outcomes

Primary

Measure	Time frame	Description
Incidence of delirium within the first 7 days after enrollment	Up to 7 days after enrollment	Delirium is assessed twice daily (from 06:00 to 10:00 and from 18:00 to 20:00) with the Confusion Assessment Method for the intensive care unit (CAM-ICU).

Secondary

Measure	Time frame	Description
Duration of mechanical ventilation.	Up to 30 days after enrollment	Duration of mechanical ventilation after study enrollment.
Length of stay in the ICU.	Up to 30 days after enrollment	Length of stay in the ICU after study enrollment.
Length of stay in the hospital.	Up to 30 days after enrollment	Length of stay in the hospital after study enrollment.
Incidence of non-delirium complications.	Up to 30 days after enrollment	Non-delirium complications are defined as newly occurred medical conditions other than delirium that required therapeutic intervention, i.e., grade 2 or higher on Clavien-Dindo classification.
All-cause 30-day mortality	Up to 30 days after enrollment	All-cause 30-day mortality after study enrollment.
30-day cognitive function	On the 30th day after enrollment.	Cognitive function is assessed with the Modified Telephone Interview for Cognitive Status (TICS-m) which is a 12-item questionnaire that verbally assesses global cognitive function via telephone. The score ranges from 0 to 50, with higher score indicating better function.
30-day quality of life	On the 30th day after enrollment.	Quality-of-life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF) which is a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.

Other

Measure	Time frame	Description
Pain intensity.	Up to 7 days after enrollment.	Assessed twice daily (from 06:00 to 10:00 and from 18:00 to 20:00) with the Numeric Rating Scale (NRS, an 11-point scale where 0 indicated no pain and 10 indicated the worst possible pain).
Subjective sleep quality.	Up to 7 days after enrollment.	Assessment once daily (from 06:00 to 10:00) with the Numeric Rating Scale (NRS, an 11-point scale where 0 indicated the best possible sleep and 10 indicated the worst possible sleep).
Score of Acute Physiology and Chronic Health Evaluation II (APACHE II).	Within 24 hours after enrollment.	Score of Acute Physiology and Chronic Health Evaluation II (APACHE II).
6-month cognitive function.	At the end of 6 months after enrollment.	Cognitive function is assessed with the Modified Telephone Interview for Cognitive Status (TICS-m) which is a 12-item questionnaire that verbally assesses global cognitive function via telephone. The score ranges from 0 to 50, with higher score indicating better function.
6-month quality of life.	At the end of 6 months after enrollment.	Quality-of-life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF) which is a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.
Overall survival	Up to 1 year after enrollment.	Overall survival
1-year cognitive function.	At the end of 1 year after enrollment.	Cognitive function is assessed with the Modified Telephone Interview for Cognitive Status (TICS-m) which is a 12-item questionnaire that verbally assesses global cognitive function via telephone. The score ranges from 0 to 50, with higher score indicating better function.
1-year quality of life.	At the end of 1 year after enrollment.	Quality-of-life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF) which is a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.

Countries

China

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026