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Take a look at a selection of our recent media coverage:
20th July 2023
A flexibly dosed, twice-weekly subcutaneous injection of ketamine over four weeks led to higher levels of clinical remission compared to midazolam in patients with treatment-resistant depression, according to a new phase III trial.
The trial by Australian researchers, which was published in the British Journal of Psychiatry, compared racemic ketamine with midazolam in two patient cohorts: one with fixed dosing and a second with a more flexible regimen.
The trial was initially designed to compare twice-weekly subcutaneous racemic ketamine (0.5 mg/kg) or midazolam (0.025 mg/kg) for four weeks, with at least three days between treatments. Data for these findings were referred to in the study as cohort one.
The dosing schedule was revised after a Data Safety Monitoring Board recommendation to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments. Data for these findings were referred to in the study as cohort two.
The primary outcome was remission, characterised by a Montgomery-Åsberg Rating Scale for Depression score of less than 10, after four weeks of treatment.
The final analysis comprised 68 patients in the fixed-dose cohort one and 106 in the flexible-dose cohort two.
Ketamine was found to be significantly more efficacious than midazolam in cohort two at achieving remission (odds ratio, OR = 12.1, 95% CI 2.1 – 69.2, p = 0.005). However, there was no significant different between the two treatments when given as a fixed dose in cohort one (OR = 1.3, 95% CI 0.2 – 8.2, p = 0.76).
In terms of safety, serious adverse events were rare and most were unrelated to the study drug. For instance, in cohort one, there were two serious adverse events in the midazolam group – a suicide attempt and mood deterioration – but both unrelated to the study medications. There were no serious adverse events in the ketamine group.
Among those in cohort two, there were three serious adverse events in the midazolam group: a suicide attempt, increased suicidal ideation and a wrist injury, which, again, were unrelated to the study treatments. In contrast, there were two serious adverse events in the ketamine group: one major dissociative episode and auditory hallucination, both of which were deemed to be related to treatment. No deaths were reported throughout the study.
Failing to respond to an adequate course of two or more treatments is referred to as treatment-resistant depression, and ketamine is a novel highly effective and rapidly acting treatment. It is available as an intravenous infusion of a racemic mixture and as a commercially developed single enantiomeric intranasal spray containing S-ketamine.
30th May 2023
Although ketamine use increases haemodynamic instability during rapid sequence intubation in trauma patients, it does not significantly affect the first-pass success rate compared to etomidate, according to a retrospective analysis.
Published in the journal BMC Emergency Medicine, Korean researchers considered whether the potential adverse effects of ketamine and etomidate could affect the first-pass success rate during rapid sequence intubation (RSI) in trauma patients.
The team retrospectively compared both sedatives, not only in terms of the effect on the first-pass success rate but also with respect to clinical outcomes. Patients given ketamine were propensity-matched 1:3 with etomidate and the results adjusted for injury severity and confounding baseline characteristics.
RSI represents the set of actions undertaken during induction of anaesthesia that secures the airway in trauma patients at risk of aspiration or regurgitation of gastric contents, to enable emergency orotracheal intubation. Ideally, the RSI procedure should allow for rapid and optimal intubation conditions through increasing the first-pass intubation rate whilst reducing adverse events in severely injured patients. Despite being a standard procedure, a recent survey identified significant variation in practice, prompting called for international RSI guidelines.
Both ketamine and etomidate are commonly used sedatives for RSI during emergency tracheal intubation. Nevertheless, both are associated with potential adverse effects which could affect clinical outcomes. For example, single dose use of etomidate may increase 28-day mortality, whereas ketamine use could increase the risk of cardiac arrest.
A total of 620 patients, of whom 19.9% received ketamine, were included in the retrospective analysis. The ketamine patients had a significantly faster initial heart rate (105.0 vs 97.7, p = 0.003) and were more hypotensive (114.2 vs 139.3 mmHg, p < 0.001) than those given etomidate.
However, when researchers considered the first-pass success rate, this was not significantly different (90.7% vs. 90.1%, ketamine vs etomidate, p > 0.999). Similarly, there were no differences in other clinical outcomes explored including final mortality (p = 0.348), length of intensive care unit stay (p = 0.99), ventilator days (p = 0.735) and overall hospital stay (p = 0.32).
The authors concluded that when used for RSI, although patients administered ketamine showed greater haemodynamic instability, this had no important impact on either the first-pass success rate or other relevant clinical outcomes.