Intravenous MELAtonin for prevention of Postoperative Agitation and Emergence Delirium in children (MELA-PAED): A protocol and statistical analysis plan for a randomized clinical trial.

BACKGROUND: Emergence agitation and delirium in children remain a common clinical challenge in the post-anesthetic care unit. Preoperative oral melatonin has been suggested as an effective preventive drug with a favorable safety profile. The oral bioavailability of melatonin, however, is low. Therefore, the MELA-PAED trial aims to investigate the efficacy and safety of intraoperative intravenous melatonin for the prevention of emergence agitation in pediatric surgical patients. METHODS: MELA-PAED is a randomized, double-blind, parallel two-arm, multi-center, superiority trial comparing intravenous melatonin with placebo. Four hundred participants aged 1-6 years will be randomized 1:1 to either the intervention or placebo. The intervention consists of intravenous melatonin 0.15 mg/kg administered approximately 30 min before the end of surgery. Participants will be monitored in the post-anesthetic care unit (PACU), and the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) will be performed on days 1, 7, and 14 after the intervention. Serious Adverse Events (SAE) will be assessed up to 30 days after the intervention. RESULTS: The primary outcome is the incidence of emergence agitation, assessed dichotomously as any Watcha score >2 during the participant's stay in the post-anesthetic care unit. Secondary outcomes are opioid consumption in the post-anesthetic care unit and adverse events. Exploratory outcomes include SAEs, postoperative pain, postoperative nausea and vomiting, and time to awakening, to first oral intake, and to discharge readiness. CONCLUSION: The MELA-PAED trial investigates the efficacy of intravenous intraoperative melatonin for the prevention of emergence agitation in pediatric surgical patients. Results may provide further knowledge concerning the use of melatonin in pediatric perioperative care.

Clonidine for preventing emergence agitation in infants (PREVENT AGITATION II): Protocol and statistical analysis plan.

BACKGROUND: Emergence agitation is a common clinical condition in children. Symptoms pertaining to the spectrum of early postoperative negative behavior typically occur upon emergence from anesthesia. Clonidine is an effective adjunctive agent for the prevention of emergence agitation in children, but evidence in the smallest age groups is sparse We aim to investigate the efficacy and safety of an intraoperative bolus of intravenous clonidine for preventing emergence agitation in children 3-12 months of age. METHODS: This is a randomized, placebo-controlled, double-blind trial. We will enroll 320 patients aged 3-12 months who have been scheduled for general anesthesia maintained with sevoflurane and opioid. The randomization is parallel and stratified by age group, sex, and site. The investigational medicinal product will be administered intravenously ~20 min before the anticipated end of the surgical procedure. The intervention is clonidine 3 µg/kg and placebo is isotonic saline in a corresponding volume. RESULTS: The primary outcome is the incidence of emergence agitation as assessed on the Watcha scale, that is, any Watcha score >2 during participants' stay in the postanesthetic care unit. Secondary outcomes are the proportion of participants with postoperative pain, with postoperative nausea and vomiting, and a composite safety outcome. Statistical analysis will be conducted according to the Statistical Analysis Plan with the intention-to-treat population for our primary analyses. CONCLUSION: The PREVENT AGITATION II trial will contribute valuable knowledge on efficacy for the prevention of emergence agitation and safety in infants.

The increased susceptibility to airway infections after preterm birth does not persist into adolescence.

INTRODUCTION: Preterm birth is associated with increased risk of airway infections in childhood, more frequent purchase of prescription antibiotics and hospital admissions for airway infections. With this study, we aimed to investigate whether this association persists into adolescence. METHODS: We conducted a longitudinal observational register-based study of a national cohort of all infants born in Denmark in 1992-2007. We used purchase of antibiotics, including penicillins and macrolides, and hospital admissions as proxies for milder and more severe forms of airway infections respectively in 1995-2010. Associations between gestational age (GA), age, year and repeated cross-sectional evaluations of antibiotic purchase and hospital admissions were explored by logistic regression analyses. RESULTS: We included 1,043,411 children in our study population. We found a statistically significant association between GA and prescription of antibiotics as well as hospital admissions due to airway infections. In the youngest age groups, children with higher GA had lower adjusted mean rates of prescribed antibiotics for airway infections, but from the age of 10-11 years the opposite trend was noted in what appears to be a dose-response relationship. During childhood, we found an inverse dose-response relationship where ex-preterms with GA 23-27 at age 4-5 years had twice the odds of hospital admission compared to children in the same age group born at term. During adolescence, these higher odds diminished and appeared equivalent among teenagers born at term and preterm. We only found statistically significant interactions between gestational age and age. CONCLUSION: We confirmed that preterm birth is associated with higher rates of prescribed antibiotics and higher odds of hospitalization for airway infections during childhood. However, in adolescence we found that there was no increase in hospital admissions for airway infections among ex-preterms, whereas adolescents with low GA actually appeared to purchase less prescribed antibiotics. Whether this trend persists into adulthood and the physiological explanation therefor remains to be investigated.