Metabolomic profiling of pediatric post-tonsillectomy pain: A proof-of-concept study.

INTRODUCTION: Tonsillectomies are among the most common surgical procedures in children, with over 500 000 cases annually in the United States. Despite universal administration of intraoperative opioid analgesia, three out of five children undergoing tonsillectomy report moderate-to-severe pain upon recovering from anesthesia. The underlying molecular mechanisms of post-tonsillectomy pain are not well understood, limiting the development of targeted treatment strategies. Our study aimed to identify candidate serum metabolites associated with varying severity of post-tonsillectomy pain. METHODS: Venous blood samples and pain scores were obtained from 34 children undergoing tonsillectomy ± adenoidectomy, and metabolomic analysis was performed. Supervised orthogonal projections to latent structures discriminant analysis were employed to identify differentially expressed metabolites between children with severe and mild pain, as well as between moderate and mild pain. RESULTS: Pain scores differentiated children as mild (n = 6), moderate (n = 14), or severe (n = 14). Four metabolites (fatty acid 18:0(OH), thyroxine, phosphatidylcholine 38:5, and branched fatty acids C27H54O3) were identified as candidate biomarkers that differentiated severe vs. mild post-tonsillectomy pain, the combination of which yielded an AUC of 0.91. Similarly, four metabolites (sebacic acid, dicarboxylic acids C18H34O4, hydroxy fatty acids C18H34O3, and myristoleic acid) were identified as candidate biomarkers that differentiated moderate vs. mild post-tonsillectomy pain, with AUC values ranging from 0.85 to 0.95. CONCLUSION: This study identified novel candidate biomarker panels that effectively differentiated varying severity of post-tonsillectomy pain. Further research is needed to validate these data and to explore their clinical implications for personalized pain management in children undergoing painful surgeries.

Relationship of Viral Detection with Duration of Ventilation in Critically Ill Infants with Lower Respiratory Tract Infection.

Rationale: Although respiratory virus testing is frequently done for critically ill infants with bronchiolitis, the prognostic value of this testing is unknown for those requiring positive-pressure ventilation (PPV). Objectives: To determine the differences in PPV use according to viral detection and to explore the association between viral detection and duration of PPV in critically ill children with presumed respiratory infection. Methods: This is a retrospective cohort study in a quaternary pediatric intensive care unit from February 2014 until February 2017. We evaluated 984 children less than 1 year of age who received PPV for presumed respiratory infection without significant congenital heart disease, care limitations, baseline PPV usage, or tracheostomy. Respiratory viruses were identified using a PCR panel. Analyses of duration of PPV according to viral etiology were performed using univariate and multivariable logistic regression and truncated negative binomial regression with calculated mean marginal effects (MME). Results: Overall, 85 (9%) infants had no viruses identified, 629 (64%) had a single virus detected, most commonly respiratory syncytial virus (417, 42%) followed by rhinovirus/enterovirus (145, 15%), 230 (23%) had two viruses detected, and 40 (4%) had three viruses detected. Compared with those with one or no virus detected, infants with ⩾2 viruses received longer total PPV duration in adjusted analysis (relative risk [RR], 1.4; 95% confidence interval [CI], 1.2-1.6; P < 0.001; MME = 29 h). Detection of rhinovirus/enterovirus alone, compared with respiratory syncytial virus alone, was associated with significantly shorter duration of total PPV (RR, 0.7; 95% CI, 0.62-0.87; P = <0.001; MME = -23 h), noninvasive PPV (RR, 0.7; 95% CI, 0.60-0.85; P < 0.001; MME = -15 h), and invasive PPV (RR, 0.7; 95% CI, 0.54-0.83; P < 0.001; MME = -54 h) when adjusted for weight, prematurity, and administration of early antibiotic therapy. Conclusions: Identification of viral type and number in severe bronchiolitis is an important predictor of duration of PPV.