Respiratory Trials·org

Topic

Sedation, analgesia & delirium

Sedation depth, agent choice, and delirium prevention.

Depth of sedation is what matters; the drug used to achieve it does not. Daily sedation interruption cut ventilation from 7.3 to 4.9 days when the comparator was deep continuous sedation (Kress 2000), and added nothing once sedation was already protocolised and light (SLEAP). The benefit was never the interruption itself.

Three large trials then found sedative choice irrelevant: dexmedetomidine did not beat usual care (SPICE III), matched propofol under light-sedation targets (MENDS2), and neither it nor clonidine improved time to extubation (A2B). The one clear winner is what dexmedetomidine *did* beat — midazolam, with less delirium and less ventilator time (SEDCOM). What was really established is that benzodiazepines are the problem.

Delirium is consequential and pharmacologically untreatable. Three quarters of ventilated patients became delirious, and 40% had brain-injury-level cognitive impairment three months later (BRAIN-ICU). Neither haloperidol nor ziprasidone shortened it (MIND-USA, AID-ICU). Prevention through lighter sedation remains the only strategy with support.

Choice of sedative

Trial Year Therapy Effect Finding
A2B 2025 Alpha-2 agonist sedation Neither dexmedetomidine nor clonidine beat propofol for time to extubation
MENDS2 2021 Dexmedetomidine Dexmedetomidine and propofol were equivalent when sedation was kept light
SPICE III 2019 Dexmedetomidine Early dexmedetomidine did not reduce mortality and often needed topping up
SEDCOM 2009 Dexmedetomidine Dexmedetomidine matched midazolam for sedation depth but caused less delirium and shorter ventilation

Sedation interruption

Trial Year Therapy Effect Finding
SLEAP 2012 Daily sedation interruption Sedation holds added nothing once sedation was already protocolised and light
Kress 2000 2000 Daily sedation interruption Waking patients daily cut two and a half days off mechanical ventilation

Treating delirium

Trial Year Therapy Effect Finding
AID-ICU 2022 Haloperidol Haloperidol did not improve outcomes in ICU delirium
MIND-USA 2018 Haloperidol or ziprasidone Neither antipsychotic shortened ICU delirium

Consequences of delirium

Trial Year Therapy Effect Finding
BRAIN-ICU prospective cohort 2013 Observation Three quarters became delirious, and 40% had brain-injury-level cognitive impairment three months later

Key references

Guidelines, standards and reviews for this topic.