Ketamine as an opioid-sparing adjunct in ventilated patients

Design

prospective, double-blind, randomised, placebo-controlled trial in two university-affiliated intensive care units, 2022-2024

Population

120 mechanically ventilated adults receiving an opioid infusion for analgosedation, cardiac surgical patients excluded (59 ketamine, 61 placebo)

Primary outcome

hourly opioid dose in fentanyl equivalents

Effect

64 micrograms/hr (IQR 36-89) versus 77 (47-100); median difference -13.0 (95% credible interval -26.6 to 2.4), probability of benefit 95.1%; no difference in delirium or ventilator-free days

Opioid infusions dominate analgosedation in ventilated patients, and ketamine has been used as an adjunct for years on physiological reasoning rather than trial evidence. This double-blind, placebo-controlled trial in two university-affiliated Melbourne intensive care units randomised adults on mechanical ventilation and an opioid infusion, excluding cardiac surgical patients, to ketamine 0.15 mg/kg/hr or placebo for the duration of ventilation.

Of 538 screened, 413 were ineligible, leaving 120 patients analysed — 59 on ketamine and 61 on placebo. Median hourly opioid dose in fentanyl equivalents was 64 micrograms per hour (IQR 36-89) with ketamine and 77 (47-100) with placebo, a median difference of -13.0 with a 95% credible interval from -26.6 to 2.4 and a 95.1% probability of benefit. Delirium, ventilator-free days, intensive care and hospital-free days and serious adverse events showed no differences.

The honest summary is a small trial that supports what many units already do, without proving it matters to a patient. A 13 microgram per hour reduction is real but modest, the credible interval crosses zero, and no downstream outcome moved. Its most valuable contribution may be the absence of a safety signal: no excess delirium, which is the objection usually raised against ketamine in this setting. That is enough to make low-dose ketamine a defensible adjunct where opioid requirement is escalating, and not enough to make it routine.

• Consider low-dose ketamine where opioid requirement is climbing, not as first-line sedation
• 0.15 mg/kg/hr is the dose tested — much lower than procedural dosing
• No excess delirium was seen, which is the objection most often raised
• The screening ratio matters: 413 of 538 screened were ineligible, so this applies to a narrow group
• Do not expect shorter ventilation or intensive care stay; neither moved

The statistics, in plain English

This trial reports a Bayesian analysis: a 95.1% probability of benefit means that, given the data and the prior used, there is roughly a one in twenty chance the true effect runs the other way. The 95% credible interval from -26.6 to 2.4 includes zero, so under a conventional frequentist reading this would be a negative trial — the two framings describe the same uncertainty differently. With 120 patients, secondary outcomes such as delirium and ventilator-free days are badly underpowered, so 'no difference' there means 'not detected', not 'not present'.

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