Low-volume LC–MS/MS method for the pharmacokinetic investigation of carvedilol,enalapril and their metabolites in whole blood and plasma: Application to a paediatric clinical trial

Evidence-based pharmacotherapy with carvedilol and enalapril in children suffering from heart failure is insufficient owing to limited pharmacokinetic data. Although a few data sets regarding enalapril, its metabolite enalaprilat and carvedilol in children have been published, pharmacokinetic data on carvedilol metabolites are missing. However, for both drug substances, their active metabolites contribute substantially to drug efficacy. As data can hardly be derived from adults owing to the unknown impacts of enzymatic maturation and ontogeny during childhood, customised assays are important to facilitate paediatric evidence-based pharmacotherapy. Considering ethical paediatric constraints, a low-volume liquid chromatography coupled to mass spectrometry (LC–MS/MS) assay was developed using whole blood or plasma for the quantification of enalapril, enalaprilat, carvedilol, O-desmethyl carvedilol, 4- and 5-hydroxyphenyl carvedilol as well as 3- and 8-hydroxy carvedilol. To facilitate broader applications in adults, the elderly and children, a wide calibration range—between 0.024/0.049 and 50.000 ng/ml—was achieved with good linearity (r ≥ 0.995 for all analytes). In compliance with international bioanalytical guidelines, accuracy, precision, sensitivity and internal standard normalised matrix effects were further successfully validated with the exception of those for 3-hydroxy carvedilol, which was therefore assessed semi-quantitatively. Distinct haematocrits did not impact matrix effects or recoveries when analysing whole blood. Blood-to-plasma ratios were determined for all analytes to form the basis for pharmacokinetic modelling. Finally, incurred sample reanalysis of paediatric samples confirmed the reproducibility of the developed low-volume LC–MS/MS method during study sample analysis. The assay facilitates the reliable generation of important data and contributes towards a safe drug therapy in children.     

The challenges of caring for children who require complex medical care at home: ‘The go between for everyone is the parent and as the parent that’s an awful lot of responsibility’

BackgroundIncreasing numbers of children with complex health‐care needs are cared for at home by their family. The aim of this qualitative study was to explore the challenges experienced by families caring for children who need complex medical care at home.MethodsWe conducted a thematic analysis of eleven in‐depth interviews with parents who carry out specialist medical procedures (eg, enteral feeding, bowel washouts and tracheostomy care) for their children at home. Participants were purposely selected from an existing sample of interviews with parents whose child had abdominal surgery in the first year of life.ResultsWe identified three overarching themes: (a) responsibilities of the parent, (b) impact on daily life and (c) the parent journey over time. Parents have substantial responsibilities, including performing medical procedures, managing emergencies (sometimes life‐threatening), co‐ordinating care and advocating for their child. Their responsibilities have an enormous impact on the family: going out of the home becomes a challenge, there are constant constraints on time, parents are sleep‐deprived and there are wider impacts on siblings. The third theme explores the parent journey over time as parents become experts and make sense of the new normal.DiscussionThe burden of care on families caring for children with complex medical needs is much greater than is generally understood by either multidisciplinary health‐care teams or the general public. Families need to be better prepared and supported for the responsibilities they take on and the burden of care needs to be shared by others.     

Safety and efficacy of rescue flexible bronchoscopic intubation using the Bentson floppy‐tip guidewire via a supraglottic airway in critically ill children

Difficulty in tracheal intubation in paediatric intensive care patients is associated with increased morbidity and mortality. Delays to intubation and interruption to oxygenation and ventilation are poorly tolerated. We developed a safe and atraumatic tracheal intubation technique. A floppy‐tipped guidewire and airway exchange catheter were placed to a pre‐determined length under bronchoscopic guidance while oxygenation and ventilation was maintained via a supraglottic airway device (SAD). We performed a retrospective review of this technique on patients who were either known to have or who had an unexpected difficultly in intubation. We describe the safety and experience of this in a broad range of critically ill children. Thirteen patients, median (IQR [range]) (9.0 (5.0–10.0 [4.0–12.0]) kg and 15.4 (12.1–23.2 [3.3–49.7]) months) underwent emergency tracheal intubation using this technique, after unsuccessful attempts at intubation using standard laryngoscopy blades. All intubations were successful at the first attempt using this technique and no airway trauma or significant clinical deteriorations were recorded.