Abstract
Down syndrome (DS) is frequently comorbid with congenital heart disease and has recently been shown to reduce the sedative effect of benzodiazepine (BDZ)-class anesthesia but this effect in a clinical setting has not been studied. Therefore, this study compared midazolam sedation after heart surgery in DS and normal children. We retrospectively reviewed patient records in our pediatric intensive care unit (PICU) of pediatric cardiovascular operations between March 2015 and March 2018. We selected five days of continuous post-operative data just after termination of muscle relaxants. Midazolam sedation was estimated by Bayesian inference for generalized linear mixed models. We enrolled 104 patients (average age 26 weeks) of which 16 (15%) had DS. DS patients had a high probability of receiving a higher midazolam dosage and dexmedetomidine dosage over the study period (probability = 0.99, probability = 0.97) while depth of sedation was not different in DS patients (probability = 0.35). Multi regression modeling included severity scores and demographic data showed DS decreases midazolam sedation compared with controls (posterior OR = 1.32, 95% CrI = 1.01–1.75). In conclusion, midazolam dosages should be carefully adjusted as DS significantly decreases midazolam sedative effect in pediatric heart surgery patients.
Highlights
We retrospectively reviewed records of 131 consecutive patients admitted to the University of Tsukuba Affiliated Hospital pediatric intensive care unit (PICU) who underwent cardiovascular operations between March 2015 and March 2018
Two patients with another form of trisomy were excluded from this study
There were no instances of stroke and epilepsy but 25 patients were excluded for a PICU stay of less than 5 days
Summary
We recorded patient information, including age, sex, surgical procedure, and daily severity data (including severity of organ dysfunction and sedative/muscle relaxant dosages) during PICU stays for five days after the end of muscle relaxant usage. For adjustment of our model, additional covariates were chosen a priori: sex, age, RACHS-1, dose of dexmedetomidine, vecuronium dosage status (received/ not received) and PELOD-2 (without the central nervous system component). To deal with population outliers in pharmaco-resistance studies, Bayesian modeling[23,24] and Bayesian inference for generalized linear mixed models (GLMM) via Markov chain Monte Carlo (MCMC) has been reported[25,26]. We used an opt-out methodology coupled with informed consent for this study that was approved by the Institutional Review Board of the University of Tsukuba (Approval # H29-134).
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