Efficacy and safety of ketamine in mechanically ventilated intensive care unit patients: a scoping review (erratum)

To the Editor: Following the publication or our article titled Efficacy and safety of ketamine in mechanically ventilated intensive care unit patients: a scoping review,¹ a further two randomised controlled trials comparing fentanyl with placebo in mechanically ventilated intensive care unit (ICU) patients have come to our attention.

The first trial was by Perbet and colleagues.² This was a randomised, placebo-controlled, double-blind trial of 162 adult mechanically ventilated patients in a tertiary general ICU of a university-affiliated hospital in France between 2011 and 2012. Patients were randomly assigned to receive low dose ketamine infusion at 3.3 μg/kg/min (0.20 mg/kg/h) or normal saline as placebo at the same rate. Remifentanil was used for analgesia and patients received either propofol or midazolam for sedation. The mean ages were 63 years in the ketamine group and 61 years in the placebo group, 40% and 43% had acute respiratory failure, and 35% and 32% had sepsis respectively. The mean durations of infusion or total doses of ketamine are not reported. Daily doses of remifentanil were not different between groups. The incidence of delirium was higher in the placebo group compared with the ketamine group (37% v 21%; P = 0.03). There was no difference in mechanical ventilation, sedative use, or ICU length of stay. ICU mortality was similar between groups (35% v 42% for ketamine v placebo; P = 0.32).

The second trial was by Amer and colleagues,³ published contemporaneously with our submission. This was a pilot, feasibility, open label randomised controlled trial of 83 mechanically ventilated ICU patients aged > 14 years at a single tertiary hospital in Saudi Arabia. Patients were randomly allocated to open label ketamine infusion at 2 μg/ kg/min (0.12 mg/kg/h) for the first 24 hours followed by 1 μg/kg/min (0.06 mg/kg/h) in the second 24 hours or to standard care between 2019 and 2020. The median age was 61 years, and 51% were male. Forty-eight per cent were medical admissions and > 90% were admitted for sepsis, septic shock, or acute respiratory distress syndrome. The median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 20 (interquartile range, 13–26). Sixty-two per cent of patients allocated to the ketamine group received a full 48 hours of therapy, with most of the remainder having ketamine ceased to assess for extubation. The mean duration of infusion, or total dose of ketamine were not reported. There were no differences between groups for any clinical outcomes, including haemodynamic changes, ventilator-free days, patients at goal Richmond Agitation Sedation Scale (RASS), ICU length of stay, hospital length of stay, uncontrolled agitation, hypersalivation, or use of antipsychotic medication or physical restraints. The 28-day mortality rate was 27.5% in the ketamine group versus 32.6% in the control group (P = 0.79). There were no differences in the amount of fentanyl, propofol, midazolam, dexmedetomidine or vasopressor agents prescribed.

Both studies are important additions to the body of literature examining ketamine’s use for analgosedation in adult mechanically ventilated ICU patients. Further adequately powered randomised controlled trials are required to ascertain the role of low dose ketamine infusions in such patients.

Competing interests

All authors declare that they do not have any potential conflict of interest in relation to this manuscript.