The addition of tramadol to the standard of IV acetaminophen and morphine infusion for postoperative analgesia in neonates offers no clinical benefit: a randomized placebo-controlled trial

Background Tramadol is used following neonatal cardiac and general surgery. However, its ability to opioid-spare or facilitate earlier extubation in postoperative neonates is unquantified. Objective This randomized placebo-controlled trial aimed to assess whether tramadol's addition to standard analgesia resulted in earlier extubation or reduced analgesic/sedative requirements in postsurgical neonates. Methods Neonates born 32weeks postmenstrual age received either tramadol [T] 2mgkg(-1) or placebo [P] 6-hourly for up to 5days postthoracoabdominal surgery in addition to morphine (commenced at 20mcgkg(-1)h(-1)) and 6-hourly IV acetaminophen. Time to extubation, morphine and midazolam amounts, hourly pain scores, and seizure activity were compared using an intention-to-treat and per-protocol analysis. Results Seventy-one neonates participated. Median survival time to extubation was similar between the groups (T 67h [95% CI 51, 84] vs P 52h [95%CI 43, 65]; P=0.4), and similar numbers were extubated by 96h (T 69% vs P 77%; difference -8%, 95%CI -28, 13%). Morphine and midazolam exposure was similar, with low pain scores in both groups (mean percentage of time with a pain score >5/20 during the 5days: T 13% vs P 11%, difference in means 2.8 [95% CI -1.8, 7.6], P=0.20). Most participants had normal cranial ultrasounds (T 86% vs P 86%); no seizures occurred clinically or electroencephalographically. Conclusion Tramadol's addition to standard analgesia in this small group of postsurgical neonates did not appear to have any positive effect on time to extubation, morphine or midazolam exposure, or pain scores. This questions the benefit of tramadol for postsurgical neonates. Importantly, no seizures occurred in these ill neonates who may potentially be at greater risk of tramadol toxicity compared with adults.