Tryptophan Supplementation and Postoperative Delirium—A Randomized Controlled Trial

Randomized, double-blind, placebo-controlled trial; 325 participants aged 60 years and older undergoing major elective operations requiring postoperative ICU admission.

L-tryptophan, 1 g orally three times daily, started on the evening of the operation and continued for up to 3 days postoperatively (nine total doses) or until discharge from the surgical intensive care unit.

Tryptophan supplementation did not reduce the incidence of excitatory delirium (mixed and hyperactive) or overall delirium, nor affect duration or time to onset of delirium, compared with placebo. Delirium occurred in 39% of participants overall; excitatory delirium occurred in 13%. Postoperative tryptophan levels were higher with supplementation (65±26 umol/L vs 41±15 umol/L; p<0.001) but this biochemical change did not translate to delirium improvement. Therefore, there is no evidence to support routine postoperative tryptophan use for delirium prevention in this elderly high-risk surgical population.

Predominantly male veterans; limited generalizability to females and non-veteran populations. Study population underwent major surgeries with ICU admission, which may limit applicability to all postoperative patients. Dosing optimization not evaluated (potential for higher dose or earlier initiation).