Esketamine moved day-one pulmonary complications and then the effect vanished

Design

randomised, double-blind controlled trial

Population

80 adults undergoing thoracoscopic radical resection for lung cancer

Primary outcome

incidence of postoperative pulmonary complications on postoperative day 1

Effect

37.5% with esketamine vs 72.5% control (P = .002); no difference at day 3 or 7 or in any secondary outcome

Eighty adults having thoracoscopic radical resection for lung cancer were randomised, double-blind, to perioperative esketamine or control. The primary outcome was the incidence of postoperative pulmonary complications on day 1.

That outcome moved substantially: 37.5 per cent with esketamine against 72.5 per cent without (P = .002). Nothing else did. Pulmonary complications at days 3 and 7, complication severity score, nausea and vomiting, length of stay, drain duration, 24-hour resting pain score, unplanned intensive care admission and mortality were all unchanged.

That pattern deserves scepticism. A difference that exists on day 1 and not on day 3 in the same patients suggests either a transient effect on how complications were detected — atelectasis on an early film, for instance — or chance in a trial of 40 per arm. A 72.5 per cent day-one complication rate in the control group is also very high, which raises questions about the definition used. This is a signal worth a larger trial with a clinically anchored endpoint, not a reason to add esketamine to a thoracic anaesthetic.

• Do not add esketamine to thoracic anaesthesia on this evidence
• When reading a trial like this, check whether the effect persists past the first measurement
• Note the control-group event rate — 72.5 per cent suggests a broad complication definition
• Keep lung-protective ventilation and early mobilisation as the interventions with outcome evidence

Why it matters

It is a clean illustration of why a day-one surrogate is not a pulmonary complication.

Don't overread it

A single-centre trial of 80 patients with a positive primary outcome that did not persist and no secondary outcome supporting it.

The statistics, in plain English

With 40 patients per arm, a single significant result among many outcomes is what chance produces regularly. The disappearance of the effect by day 3 is the important detail: a real reduction in pulmonary complications would not resolve in 48 hours while the patients were still in hospital.

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