Ketamine administration and postoperative mortality after major cancer surgery

Ketamine is commonly used perioperatively as an anaesthetic and analgesic adjunct and has demonstrated potential antitumour effects in preclinical studies. However, clinical and epidemiological data on its association with long-term outcomes after oncologic surgery remain limited.

We conducted a retrospective cohort study using the TriNetX US Collaborative Network, including adults (≥18 yr) undergoing major solid tumour cancer surgery between January 1, 2014, and April 1, 2023. The primary exposure was ketamine administration on the day of surgery. Propensity score matching (1:1) was performed using patient characteristics, comorbidities, oncologic diagnoses, and surgery type. The primary outcome was 3-yr mortality, and the secondary outcome was 5-yr mortality.

Among 176 149 eligible patients, 29 547 matched pairs were analysed. Perioperative ketamine administration was not associated with lower 3-yr mortality (16.7% vs 16.0%; hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00–1.09; q=0.187). There was no difference in 5-yr mortality. Across sensitivity and subgroup analyses by cancer type and perioperative exposures, ketamine was not associated with improved survival after adjustment for multiple comparisons. In an exploratory analysis, ketamine exposure was associated with a lower risk of a composite of surrogate markers suggestive of cancer progression or advanced disease, including initiation of chemotherapy, radiotherapy, or palliative care ≥6 months after surgery (HR, 0.82; 95% CI, 0.74–0.92; q=0.013).

In this research network study, perioperative ketamine use was not associated with reduced mortality after major cancer surgery. This finding aligns with previous large-scale studies showing no long-term survival benefit for specific anaesthetic agents in oncologic surgery.