Low-dose Dexmedetomidine in Mechanically Ventilated ICU Patients

Delirium Clinical Trial

Official title:

Low-dose Dexmedetomidine for Delirium Prevention in Mechanically Ventilated Patients in Intensive Care Unit: a Multicenter, Randomised, Double-blinded, Placebo-controlled Trial

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03172897
• Other study ID #: 2017[1319]
• Status: Suspended
• Phase: Phase 4
• Start date: August 20, 2017
• Est. completion date: November 2022

Study information

• Verified date: April 2022
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

For patients undergoing mechanical ventilation, light sedation is better than deep sedation for the outcomes, which is manifested as shortened length of ICU stay, shortened duration of mechanical ventilation, and decreased mortality. In a recent study of the investigators, low-dose dexmedetomidine without sedative effects (0.1 ug/kg/h) improved sleep quality and reduced the incidence of delirium in elderly patients admitted to the ICU after surgery. The investigators hypothesize that, for ICU patients with prolonged mechanical ventilation, low-dose dexmedetomidine infusion (0.1 ug/kg/h) may also be effective in decreasing delirium. The purpose of this study is to investigate whether low-dose dexmedetomidine infusion can reduce the incidence of delirium in ICU patients with prolonged duration of mechanical ventilation (>= 24 hours).

Description:

Delirium is an acutely occurred and transient brain dysfunction characterized with cognitive dysfunction, lowered consciousness, disturbed attention, abnormal psychoactivity, and disordered sleep-wake rhythm. Delirium is frequent in mechanically ventilated patients in the intensive care unit (ICU), with reported incidences up to 70% or 87%. Possible reasons leading to delirium include the intervention-heavy environment of the ICU, mechanical ventilation and sleep disturbances. The occurrence of delirium is associated with worse outcomes including prolonged mechanical ventilation and ICU stay, increased complications, prolonged hospital stay, higher mortality, and elevated medical expenses. It is also associated with worse long-term outcomes including declined cognitive function, lowered life quality, and elevated long-term mortality. Dexmedetomidine is a high selective alpha-2 adrenoceptor agonist with anxiolytic, sedative and analgesic effects. When used for sedation in mechanically ventilated patients (dose range 0.2-1.4 ug/kg/h), it reduces the consumption of other sedatives and analgesics, ameliorates the rhythm and structure of sleep, and decreases the occurrence of delirium. In recent studies of the investigators, low-dose dexmedetomidine infusion (0.1 ug/kg/h) ameliorated sleep quality; for elderly patients admitted to the ICU after surgery, prophylactic low-dose dexmedetomidine infusion reduced the incidence of delirium (for patients with mechanical ventilation: 28.8% with placebo vs. 11.5% with dexmedetomidine, P<0.0001; for patients without mechanical ventilation: 15.1% with placebo vs. 6.3% with dexmedetomidine, P=0.014). For patients undergoing mechanical ventilation, light sedation is better than deep sedation for the outcomes, which is manifested as shortened length of ICU stay, shortened duration of mechanical ventilation, and decreased mortality. Some authors even reported that no sedation (analgesia only) provides better outcome than light sedation, because it further shortens the durations of mechanical ventilation and ICU stay. In the above studies of the investigators, the recruited patients were less severe because the Acute Physiology and Chronic Health Evaluation II (APACHE II) score was low (mean score from 10.2 to 10.6) and the duration of mechanical ventilation was short (median 6.9 hours in the control group). The investigators hypothesize that, for ICU patients with prolonged mechanical ventilation, low-dose dexmedetomidine infusion (0.1 ug/kg/h) may also be effective in improving sleep and decreasing delirium. The purpose of this study is to investigate whether low-dose dexmedetomidine infusion can reduce the incidence of delirium in ICU patients with prolonged duration of mechanical ventilation (>= 24 hours).

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 260
• Est. completion date: November 2022
• Est. primary completion date: August 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• aged 18 years or older;
• admitted to the ICU;
• with expected duration of mechanical ventilation of more than 24 hours.

Exclusion Criteria:

• refused to participate;
• aged less than 18 years;
• pregnant;
• preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis;
• inability to communicate in the preoperative period (coma, profound dementia, or language barrier);
• brain injury or neurosurgery;
• known preoperative left ventricular ejection fraction less than 30%, sick sinus syndrome, severe sinus bradycardia (<50 beats per min [bpm]), or second degree or greater atrioventricular block without pacemaker;
• severe hepatic dysfunction (Child-Pugh class C);
• severe renal dysfunction (undergoing dialysis before surgery);
• less likely to survive for more than 24 hours.

Related Conditions & MeSH terms

• Adult Disease
• Delirium
• Dexmedetomidine
• Intensive Care Unit Syndrome
• Mechanical Ventilation Complication

Intervention

Drug:
• Dexmedetomidine
Dexmedetomidine is administered as a continuous intravenous infusion at a rate of 0.025 mL/kg per h (0.1 µg/kg per h) from study recruitment in the ICU for no more than 72 hours.
• Placebo (normal saline)
Placebo (normal saline) is administered as a continuous intravenous infusion at a rate of 0.025 mL/kg per h from study recruitment in the ICU for no more than 72 hours.

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University First Hospital	Peking University Third Hospital

Country where clinical trial is conducted

China, 

References & Publications (29)

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Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR, Dittus RS, Ely EW. Costs associated with delirium in mechanically ventilated patients. Crit Care Med. 2004 Apr;32(4):955-62. — View Citation

Mo Y, Zimmermann AE. Role of dexmedetomidine for the prevention and treatment of delirium in intensive care unit patients. Ann Pharmacother. 2013 Jun;47(6):869-76. doi: 10.1345/aph.1AR708. Review. — View Citation

Nedergaard HK, Jensen HI, Lauridsen JT, Sjøgaard G, Toft P. Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation--effects on physical function: study protocol for a randomized controlled trial: a substudy of the NONSEDA trial. Trials. 2015 Jul 23;16:310. doi: 10.1186/s13063-015-0856-1. — View Citation

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Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16. — View Citation

Toft P, Olsen HT, Jørgensen HK, Strøm T, Nibro HL, Oxlund J, Wian KA, Ytrebø LM, Kroken BA, Chew M. Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial): study protocol for a randomised controlled trial. Trials. 2014 Dec 20;15:499. doi: 10.1186/1745-6215-15-499. — View Citation

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pain intensity	Assessed twice daily (in the morning from 0600 h to 1000 h and in the evening from 1800 h to 2000 h) with the Numeric Rating Scale (NRS, an 11 point scale where 0 indicated no pain and 10 indicated the worst possible pain).	From enrollment until 7 days.
Other	Subjective sleep quality	Assessed in the morning with the NRS (an 11 point scale where 0 indicated the best possible sleep and 10 indicated the worst possible sleep).	From enrollment until 7 days.
Primary	Incidence of delirium within the first 7 days after enrollment	Assessment twice daily (in the morning from 0600 h to 1000 h and in the evening from 1800 h to 2000 h) with the Confusion Assessment Method for the ICU (CAM-ICU).	From enrollment until 7 days.
Secondary	Duration of mechanical ventilation	Duration of mechanical ventilation after study enrollment.	From enrollment until extubation or 30 days.
Secondary	Length of stay in the ICU	Length of stay in the ICU after study enrollment.	From enrollment until ICU discharge or 30 days.
Secondary	Length of stay in the hospital	Length of stay in the hospital after study enrollment.	From enrollment until hospital discharge or 30 days.
Secondary	Occurrence of non-delirium complications	Occurrence of complications other than delirium after study enrollment.	From enrollment until 30 days.
Secondary	All-cause 30-day mortality	All-cause 30-day mortality after study enrollment.	On the 30th day after enrollment.
Secondary	30-day cognitive function	Assessed with the Telephone Interview of Cognitive Status-Modified (TICS-m).	On the 30th day after enrollment.
Secondary	30-day life quality	Assessed with the WHOQOL-Bref.	On the 30th day after enrollment.