Pharmacokinetics, hemodynamic and metabolic effects of epinephrine to prevent post-operative low cardiac output syndrome in children.

INTRODUCTION: The response to exogenous epinephrine (Ep) is difficult to predict given the multitude of factors involved such as broad pharmacokinetic and pharmacodynamic between-subject variabilities, which may be more pronounced in children. We investigated the pharmacokinetics and pharmacodynamics of Ep, co-administered with milrinone, in children who underwent open heart surgical repair for congenital defects following cardiopulmonary bypass, including associated variability factors. METHODS: Thirty-nine children with a high risk of low cardiac output syndrome were prospectively enrolled. Ep pharmacokinetics, hemodynamic and metabolic effects were analyzed using the non-linear mixed effects modeling software MONOLIX. According to the final model, an Ep dosing simulation was suggested. RESULTS: Ep dosing infusions ranged from 0.01 to 0.23 µg.kg-1.min-1 in children whose weight ranged from 2.5 to 58 kg. A one-compartment open model with linear elimination adequately described the Ep concentration-time courses. Bodyweight (BW) was the main covariate influencing clearance (CL) and endogenous Ep production rate (q0) via an allometric relationship: CL(BWi) = θCL x (BWi)3/4 and q0(BWi) = θq0 x (BWi )3/4. The increase in heart rate (HR) and mean arterial pressure (MAP) as a function of Ep concentration were well described using an Emax model. The effect of age was significant on HR and MAP basal level parameters. Assuming that Ep stimulated the production rate of plasma glucose, the increases in plasma glucose and lactate levels were well described by turnover models without any significant effect of age, BW or exogenous glucose supply. CONCLUSIONS: According to this population analysis, the developmental effects of BW and age explained a part of the pharmacokinetic and pharmacodynamics between-subject variabilities of Ep administration in critically ill children. This approach ultimately leads to a valuable Ep dosing simulation which should help clinicians to determine an appropriate a priori dosing regimen.

Use of human umbilical cord blood mononuclear cells to prevent perinatal brain injury: a preclinical study.

Cerebral palsy (CP) is the most frequent neurological disorder associated with perinatal injury of the developing brain. Major brain lesions associated with CP are white matter damage (WMD) in preterm infants and cortico-subcortical lesions in term newborns. Cell therapy is considered promising for the repair of brain damage. Human umbilical cord blood mononuclear cells (hUCB-MNCs) are a rich source of various stem cells that could be of interest in repairing perinatal brain damage. Our goal was to investigate the potential of hUCB-MNCs to prevent or repair brain lesions in an animal model of excitotoxic brain injury. We induced neonatal brain lesions using intracranial injections of ibotenate, a glutamate agonist, in 5-day-old rat pups. hUCB-MNCs were injected either intraperitoneally (i.p.) or intravenously (i.v.) soon or 24 h after ibotenate injection, and their neurological effects were assessed using histology and immunohistochemistry. hUCB-MNCs injected i.p. did not reach the systemic circulation but high amounts induced a significant systemic inflammatory response and increased the WMD induced by the excitotoxic insult. This effect was associated with a significant 40% increase in microglial activation around the white matter lesion. hUCB-MNCs injected i.v. soon or 24 h after the excitotoxic insult did not affect lesion size, microglial activation, astroglial cell density, or cell proliferation within the developing white matter or cortical plate at any concentration used. We demonstrated that hUCB-MNCs could not integrate into the developing brain or promote subsequent repair in most conditions tested. We found that the intraperitoneal injection of high amounts of hUCB-MNCs aggravated WMD and was associated with systemic inflammation.

Bilateral vocal palsy following coin cell lithium battery ingestion: a case report and review.

UNLABELLED: Button battery ingestion in children is not a rare occurrence and may be unwitnessed and can be soon life-threatening or responsible for severe sequelae. We report herein an original history of previously healthy 16-month-old boy with an unwitnessed and misdiagnosis of lithium cell coin battery ingestion which leads to bilateral vocal palsy. The patient underwent a unilateral posterior cordotomy and was successfully extubated. CONCLUSION: Early recognition of a lithium cell coin battery for rapid removal, even if insufficient at first, is the main condition to limit complications. Unusual upper respiratory distress in a young child should alert practitioners in performing a chest and neck X-ray without undue delay.

Factors influencing neurological outcome of children with bacterial meningitis at the emergency department.

We performed a cohort study of children who survived bacterial meningitis after the neonatal period at a single pediatric center in France over a 10-year period (1995-2004) to identify predictors of death and long-term neurological deficits in children with bacterial meningitis. We performed multivariate regression to determine independent predictors of death and neurologic deficits. We identified 101 children with bacterial meningitis of which 19 died during initial hospitalization. Need for mechanical ventilation [hazard ratio (HR) 11.5, 95 % confidence interval (CI) 2.4-55.5)] and thrombocytopenia defined as a platelet count <150 × 10(9) per liter (HR 0.6, 95 % CI 0.4-0.9) at presentation were associated with death during initial hospitalization. At final assessment, 42 of the 70 survivors had no neurologic deficits identified; 20 had a single deficit, and eight had multiple deficits. A delay in initiation of antibiotics (HR 1.3, 95 % CI 1.1-1.7) and hydrocephalus on computed tomographic scan (HR 2.6, 95 % CI 1.1-6.0) were associated with having one or more long-term neurologic deficits. Identification of children at risk of death or long-term neurologic sequelae may allow therapeutic interventions to be directed to children at the highest risk.