Impact of Propofol Exposure on Neurocognitive Outcomes in Children With High-Risk ALL

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In an analysis from the Children’s Oncology Group phase III AALL1131 study reported in the Journal of Clinical Oncology, Alexander et al found that exposure to propofol was associated with an increased risk of impairment in reaction time/processing speed at 1 year after treatment in children with high-risk B-cell acute lymphoblastic leukemia (B-ALL).

Study Details

The study involved 144 consenting patients aged 6 to 12 years (mean age = 9.1 years) from the trial who underwent prospective uniform assessments of neurocognitive function during therapy and at 1 year after completion of therapy. The primary neurocognitive outcome was reaction time/processing speed at 1 year; Z-scores were computed using age-based normative data, with lower scores indicating worse performance.

Key Findings

Patients underwent a median of 27 anesthetic episodes (range = 1–37). Of the 144 patients, 140 (97.2%) were exposed to propofol, with a mean cumulative dose of 112.3 mg/kg.

At 1 year after completion of therapy, the proportion of patients with impaired reaction time/processing speed (Z-score ≤ –1.5) was significantly higher compared with a normative sample (24.2% vs 8.4%, P < .001).

In multivariate analysis adjusting for baseline neurocognitive score, age, sex, race/ethnicity, insurance status, and leukemia risk group, cumulative exposure to propofol was associated with a 0.05 Z-score decrease in reaction time/processing speed for each 10-mg/kg propofol exposure (P = .03).

The investigators concluded, “In a multicenter and uniformly treated cohort of children with B-ALL, cumulative exposure to propofol was an independent risk factor for impairment in reaction time/processing speed 1 year after therapy. Anesthesia exposure is a modifiable risk, and opportunities to minimize propofol use should be considered.”

Sarah Alexander, MD, of the Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Institutes of Health, National Cancer Institute, American Lebanese Syrian Associated Charities, and St. Baldrick’s Foundation. For full disclosures of the study authors, visit

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