Major sedative study informs intensive care practice
Findings from a national trial are guiding the use of sedatives in intensive care.
Sedation is essential for keeping critically ill patients comfortable and supporting mechanical ventilation.
In the A2B trial, researchers compared two alternative drugs with propofol - the most widely used sedative medication. The alternatives were clonidine and dexmedetomidine.
Their results, published in JAMA, showed no clear benefits. For example, patients who received the alternatives were on average not able to come off the ventilator (be extubated) any sooner.
With both clonidine and dexmedetomidine, there was an increase in adverse effects. These were most severe with dexmedetomidine.
The trial involved over 1,400 patients across the UK. It was led by Professor Timothy Walsh from the University of Edinburgh.
Southampton’s Dr Cathy McKenzie led the UK’s intensive care pharmacy involvement in the trial. Dr Rebecca Cusack led recruitment in the region.
Sedation in intensive care
Around one in three patients admitted to intensive care need mechanical ventilation. This helps them to breathe when they are unable to do so on their own.
Most of these patients also need sedation to relieve pain and anxiety caused by mechanical ventilation and the severity of their illness. It also prompts sleepiness.
Propofol is the most widely used sedative medication in intensive care units. However, it is not a pain killer. This means that additional medicines are used, mostly opioid analgesics.
Previous trials have suggested that another sedative medication called dexmedetomidine may be more effective. It has been linked with potentially spending less time on a ventilator and reduced confusion (delirium).
Dexmedetomidine belongs to a group of drugs called α2-adrenergic receptor agonists. Unlike propofol, they provide pain relief as well as sedation. Clonidine belongs to the same class of agents and is widely used in the UK.
Informing future care
Patients were recruited from 41 intensive care units (ICUs) in the UK between 2018 and 2023, including University Hospital Southampton (UHS). They were all expected to need mechanical ventilation for two days or longer.
Patients were randomly assigned to receive one of three sedative medications: propofol, dexmedetomidine and clonidine. They all received additional pain relief as needed.
The results reveal that each group spent similar amounts of time on a ventilator.
There was no evidence of less problems like delirium among those who received dexmedetomidine or clonidine. Mortality rates were also similar across the three groups.
However, adverse effects were higher with clonidine and dexmedetomidine.
Dr McKenzie is a Consultant Pharmacist in Critical Care at UHS and an Associate Professor in Critical Care Pharmacology at the University of Southampton. She is part of the NIHR Southampton Biomedical Research Centre (BRC). She is also an awardee in the UHS Research Leaders Programme (RLP) and holds an NIHR Senior Clinical Practitioner Award.
Dr McKenzie said: “The A2B trial was very important for intensive care sedation practice. It gives us assurance that while propofol is not the ideal sedative for every patient that is ventilated, it is probably indicated for most short-term ventilation (48 hours or less).
“We thank participants, their families and the study team in Southampton for their part in this important research. Our hope is that these findings will help patients receive the best possible treatment in intensive care in the future.”
Cost of treatment
Researchers also assessed the cost-effectiveness of the three medications.
They found no significant economic benefit to using dexmedetomidine or clonidine instead of propofol. These results have also been published in JAMA.
Dr Cusack is a Consultant and Associate Professor in Critical Care Medicine at UHS and the University of Southampton. She holds a UHS RLP award. She is also part of the NIHR Southampton BRC.
Dr Cusack said: “This cost effective analysis should give assurance to ICUs all over the world. The analysis shows us that sedative choice should not be based on cost alone but should be tailored to the individual patient.”