Incidence of iatrogenic withdrawal syndrome and associated factors in surgical pediatric intensive care.

BACKGROUND: Iatrogenic withdrawal syndrome (IWS) is a complication of prolonged sedation/analgesia in pediatric intensive care unit (PICU) patients. The epidemiology of IWS is poorly understood, as validated diagnostic tools are rarely used. The main objective of our study was to use the WAT-1 score to assess the incidence of IWS in our unit. The secondary objectives were to evaluate the consequences of IWS, associated factors, and management modalities. MATERIAL AND METHODS: From July 2018 to January 2019, 48 children receiving endotracheal ventilation and sedation/analgesia by continuous infusion (>48 h) of benzodiazepines and/or opioids were included. As soon as sedation/analgesia was decreased and until 72 h after its complete discontinuation, the WAT-1 score was determined every 12 h. Substitution therapy was used for 98% of patients upon opioid and/or benzodiazepine withdrawal. IWS was defined as a WAT-1 score ≥3. Factors associated with IWS were assessed by univariate analysis. RESULTS: IWS occurred in 25 (52%) patients. IWS was associated with a higher number of ventilator-associated pneumonia episodes (17 [68%] vs. one [4%]) and a longer PICU stay (13 [7; 25] vs. 9.0 [5.0; 10.5]) (p<0.001). Overall, 11 patients developed IWS after less than 5 days of sedation/analgesia. Severe head injury was associated with IWS (p = 0.03). Neither sedation discontinuation nor IWS prevention was standardized. CONCLUSION: The high incidence and adverse consequences of IWS require improved prevention. Risk groups should be defined and a standardized withdrawal protocol established. The occurrence of IWS should be monitored routinely using a validated score.

Quantitative trait Loci influencing abdominal fat deposition and functional variability of the HPA axis in the rat.

With the aim to reveal common genomic regions influencing phenotypes related to HPA axis function and metabolism, we did a quantitative trait loci (QTL) study in a F2 population obtained from the cross-breeding between 2 contrasted rat strains, LOU/C and Fischer 344. QTL determining phenotypes related first to corticotropic function were searched: plasma corticosterone (Cort) in control and stress conditions, after a dexamethasone suppression treatment (glucocorticoid receptor related-effect), and mineralocorticoid receptor-mediated urinary response to aldosterone. Then, phenotypes related to metabolism were studied on the same animals: body composition, basal and post-insulin plasma glucose, plasma free fatty acids, leptin, and insulin. Finally, we analyzed the overlapping regions between these QTL and looked for candidate genes within these regions. The gene NR3C1 encoding the glucocorticoid receptor was confirmed to be central in the link between hypothalamic-pituitary-adrenal (HPA) axis function and fat deposition, and its metabolic consequences. Among the other candidate genes detected, most contain a glucocorticoid responsive element, strengthening our hypothesis of common genetic determinism between HPA axis and metabolism.