The Critical Vector · ICU Analgosedation

KALME: Ketamine Didn't Move the Outcomes That Matter

Critical care pharmacology. Traced to its registered protocol and investigator group. September 2026.

VERIFIED: KALME is a real, registered phase 2 RCT — Casamento, Serpa Neto, Bellomo; Austin Hospital Melbourne / ANZICRC (Monash University). The protocol (posted July 2024) specifies adjunctive ketamine 0.15 mg/kg/h (max 15 mg/h, capped at 100 kg) or placebo, added to an opioid infusion in mechanically ventilated adults — matching the source reel's design description exactly.
PARTIAL VERIFICATION: the trial's protocol, investigators, and design check out cleanly. The specific effect-size numbers below (64 vs. 77 µg/h, credible interval, probability of benefit) are as reported by the source and were not independently re-checked against the final published article text — the doi:10.1097/CCM.0000000000007341 record was not independently retrievable at time of writing. Treat as reported-and-plausible-given-the-protocol, not line-by-line re-verified.
01

Trial Design

KALME — Ketamine for AnaLgesia in MEchanically Ventilated Adults. Phase 2 RCT, 2 centers, 120 adults. Adjunctive ketamine 0.15 mg/kg/h (0.075 mL/kg/h, max 15 mg/h, capped at 100 kg actual body weight), no bolus, added to an opioid infusion during mechanical ventilation, vs. placebo. Sedation driven by nursing protocol rather than fixed titration.

Same Austin Hospital / ANZICRC group behind the ANALGESIC fentanyl-vs-morphine analgosedation trial and several other ketamine-in-ICU studies — an established program, not a one-off.

02

Reported Results

Primary outcome — hourly opioid dose:

64
µg/h, ketamine
77
µg/h, placebo
−13
µg/h, median diff.
95.1%
prob. of benefit
OutcomeResult
95% credible interval (opioid dose difference)−26.6 to 2.4 µg/h
Ventilator-free daysNo signal
DeliriumNo signal
ICU / hospital length of stayNo signal
MortalityNo signal
Adverse events attributed to study drugNone
03

Interpretation

Textbook small-phase-2-with-Bayesian-analysis result: a credible interval that leans favorable but straddles clinical near-zero, on a surrogate (opioid dose) rather than a patient-centered endpoint.

Consistent with the broader ketamine-in-ICU literature: opioid-sparing signals show up reasonably often; downstream benefit (LOS, delirium, mortality) essentially never does in adequately powered work. File under "reasonable adjunct, not a practice-changer" until a larger multicenter trial with a patient-centered primary endpoint says otherwise.

04

Primary Sources

  • Casamento A, Serpa Neto A, Bellomo R. KALME trial protocol and statistical analysis plan. Monash University / Austin Health, July 2024.
  • Casamento A, et al. [Reported] Crit Care Med. 2026. doi:10.1097/CCM.0000000000007341