Essential medicines containing ethanol elevate blood acetaldehyde concentrations in neonates.

UNLABELLED: Neonates administered ethanol-containing medicines are potentially at risk of dose-dependent injury through exposure to ethanol and its metabolite, acetaldehyde. Here, we determine blood ethanol and acetaldehyde concentrations in 49 preterm infants (median birth weight = 1190 g) dosed with iron or furosemide, medicines that contain different amounts of ethanol, and in 11 control group infants (median birth weight = 1920 g) who were not on any medications. Median ethanol concentrations in neonates administered iron or furosemide were 0.33 (range = 0-4.92) mg/L, 0.39 (range = 0-72.77) mg/L and in control group infants were 0.15 (range = 0.03-5.4) mg/L. Median acetaldehyde concentrations in neonates administered iron or furosemide were 0.16 (range = 0-8.89) mg/L, 0.21 (range = 0-2.43) mg/L and in control group infants were 0.01 (range = 0-0.14) mg/L. There was no discernible relationship between blood ethanol or acetaldehyde concentrations and time after medication dose. CONCLUSION: Although infants dosed with iron or furosemide had low blood ethanol concentrations, blood acetaldehyde concentrations were consistent with moderate alcohol exposure. The data suggest the need to account for the effects of acetaldehyde in the benefit-risk analysis of administering ethanol-containing medicines to neonates. WHAT IS KNOWN: • Neonates are commonly treated with ethanol-containing medicines, such as iron and furosemide. • However, there is no data on whether this leads to appreciable increases in blood concentrations of ethanol or its metabolite, acetaldehyde. What is New: • In this study, we find low blood ethanol concentrations in neonates administered iron and/or furosemide but markedly elevated blood acetaldehyde concentrations in some infants receiving these medicines. • Our data suggest that ethanol in drugs may cause elevation of blood acetaldehyde, a potentially toxic metabolite.

Intravenous salbutamol for childhood asthma: evidence-based medicine?

Intravenous salbutamol is commonly used to treat children with severe asthma unresponsive to inhaled ß2-agonist therapy. However, in this setting, there is little clinical trial data demonstrating its effectiveness. Additionally, there are significant concerns that intravenous salbutamol-dosing recommendations for children with acute asthma are excessive, and unnecessarily raise the potential for adverse reactions, such as lactic acidosis and tachycardia which, by increasing respiratory workload, exacerbate respiratory failure. Here, we review salbutamol clinical pharmacology and toxicology, evidence relating to its use in acute asthma and highlight gaps in the evidence base.

Assessment of liquid captopril formulations used in children.

OBJECTIVE: Unlicensed liquid captopril formulations are commonly used to treat children with heart disease. This study assessed the bioequivalence of two liquid preparations against a licensed tablet form. DESIGN: An open label, single dose, three-treatment, three-period, crossover trial. SETTING: Outpatient. PATIENTS: Healthy adult volunteers (n=18). INTERVENTIONS: Each subject was randomly assigned to one of six dosing sequences, and dosed with 25 mg captopril on each of three dosing visits separated by a washout of at least 14 days. Blood samples for pharmacokinetic analysis were taken at regular intervals (0 min to 10 h) post-dose. MAIN OUTCOME MEASURES: Bioequivalence of the formulations would be concluded if the 90% CI for the estimated ratio of the means of C(max) (maximum plasma concentrations) and area under curve(AUC) (extent of absorption) lay entirely within the range 0.8 to 1.25 RESULTS: Both liquid formulations failed the bioequivalence assessment with respect to C(max) and AUC. The 90% CI of the mean ratios of liquid/licensed tablet for both C(max) and AUC, fell outside the 0.8 to 1.25 limits. There was also considerable within-subject variability in C(max) (97.5%) and AUC (78.5%). CONCLUSIONS: Unlicensed captopril formulations are not bioequivalent to the licensed tablet form, or to each other, and so cannot be assumed to behave similarly in therapeutic use. Thus formulation substitution must be done with care and may require a period of increased monitoring of the patient. There is also significant within-subject variability in performance which has clinical implications with respect to titrating to an optimum therapeutic dose.

Toxic additives in medication for preterm infants.

BACKGROUND: Little is known about exposure of preterm infants to excipients during routine clinical care. OBJECTIVE: To document excipient exposure in vulnerable preterm babies in a single centre, taking into account chronic lung disease (CLD) as a marker of illness severity. DESIGN: Excipient exposure after treatment with eight oral liquid medications was determined by retrospectively analysing the drug charts of infants admitted to a neonatal unit. SETTING: The Leicester Neonatal Service. PARTICIPANTS: 38 infants born between June 2005 and July 2006 who were less than 30 weeks' gestation and 1500 g in weight at birth and managed in Leicester to discharge. RESULTS: The 38 infants represented 53% of the eligible target group; 7/38 infants had CLD. During their in-patient stay, infants were exposed to over 20 excipients including ethanol and propylene glycol, chemicals associated with neurotoxicity. Infants with CLD were exposed to higher concentrations of these toxins. Infants were also exposed to high concentrations of sorbitol, with some infants being exposed to concentrations in excess of recommended guidelines for maximum exposure in adults. CONCLUSIONS: Preterm infants are commonly exposed to excipients, some of which are potentially toxic. Strategies aimed at reducing excipient load in preterm infants are urgently required.

Developmental outcome in newborn infants treated for acute respiratory failure with extracorporeal membrane oxygenation: present experience.

OBJECTIVE: To describe the later health status of newborn infants who received extracorporeal membrane oxygenation (ECMO) for acute respiratory failure in the era after the UK ECMO trial. DESIGN: Prospective follow up study of newborn infants who received ECMO at a single centre between January 1997 and January 2001. SETTING: Departments of ECMO and Paediatric Intensive Care, University Hospitals of Leicester. PATIENTS: All babies who received ECMO within 14 days of birth. INTERVENTIONS: Neurodevelopment screening using the schedule for growing skills-II (SGS-II) assessment tool. MAIN OUTCOME MEASURES: Survival at 12 months of age by disease and functional development at follow up. RESULTS: A total of 145 neonates received ECMO for treatment of respiratory failure. Of these, 108 (75%) were alive at 1 year of age. There were no deaths in children treated for respiratory failure secondary to meconium aspiration syndrome (73/145). Ninety three (86% of survivors) infants attended a follow up visit at 11-19 months postnatal age. Eighty two were classed as normal, seven as having "impairment", and four as having "severe disability". CONCLUSIONS: Most newborn infants with acute respiratory failure treated with ECMO will have a normal neurodevelopment screening assessment at 11-19 months of postnatal age. There is no evidence to suggest that changes in neonatal practice since the UK ECMO trial have led to changes in outcome of infants undergoing ECMO therapy.

Extracorporeal life support for children with meningococcal septicaemia.

OBJECTIVE: To describe the short-term outcome of children with meningococcal sepsis treated with extracorporeal membrane oxygenation (ECMO) in a single centre. DESIGN: Retrospective analysis of case notes. SETTING: The Heartlink ECMO Centre, Glenfield Hospital, Leicester. PATIENTS: Eleven children (8 boys) out of a total caseload of 800 patients were treated for meningococcal sepsis with ECMO. INTERVENTIONS: Extracorporeal membrane oxygenation. RESULTS: All children with meningococcal sepsis treated with ECMO had a Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS) > or = 12 (positive predictive risk of death of approximately 90%). Five children had adult respiratory distress syndrome (ARDS) and six had refractory shock with multi-organ dysfunction syndrome (MODS) at presentation for ECMO. All five children in the ARDS group survived, four of five receiving veno-venous (VV-) ECMO therapy. In contrast, only one of six children with refractory shock with MODS survived, all of whom required veno-arterial (VA-) ECMO therapy. CONCLUSIONS: Most children with meningococcal sepsis and severe ARDS can be successfully treated with VV-ECMO. In contrast, children with refractory shock and MODS die despite treatment with VA-ECMO. This report does not resolve whether ECMO therapy offers any advantage over conventional therapy in treating severe meningococcal sepsis.

Chronic lung disease of prematurity: clinical and pathophysiological correlates.

Chronic lung disease of prematurity (CLD) is largely confined to preterm infants who require mechanical ventilation in the newborn period. Its development is associated with preterm labour and pulmonary inflammation secondary to oxidant stress, barotrauma of mechanical ventilation and antenatally--or postnatally--acquired respiratory tract infection. Pathological studies have shown that infants dying of established CLD have airway wall thickening secondary to increased airway wall smooth muscle mass, alveolar hypoplasia and pulmonary vascular re-modelling. These structural abnormalities are likely to account for the clinical problems of arterial hypoxemia and hypercapnia, tachypnea, recurrent wheezing and decreased exercise tolerance. Severity of the structural components may account for the clinical variation that is observed in a particular child. Management of CLD is aimed at decreasing the effects of hypoxemia and in maximising somatic, and by implication lung, growth. Low flow domiciliary oxygen and bronchodilators are used for arterial hypoxemia and recurrent wheezing. Systemic and inhaled corticosteroids may be beneficial but it is unclear if such treatment alters the natural history of CLD in the developing lung. Gastro-esophageal reflux should be sought in these infants and they should receive immunizations or immunoprophylaxis against respiratory tract pathogens. There is considerable concern that survivors of CLD may develop respiratory failure in early--or late--middle age.