Objectives The aims of this study were to develop a population pharmacokinetic model for intravenous paracetamol in preterm and term neonates and to assess the generalizability of the model by testing its predictive performance in an external dataset. Methods Nonlinear mixed-effects models were constructed from paracetamol concentration–time data in NONMEM 7.2. Potential covariates included body weight, gestational age, postnatal age, postmenstrual age, sex, race, total bilirubin, and estimated glomerular filtration rate. An external dataset was used to test the predictive performance of the model through calculation of bias, precision, and normalized prediction distribution errors. Results The model-building dataset included 260 observations from 35 neonates with a mean gestational age of 33.6 weeks [standard deviation (SD) 6.6]. Data were well-described by a one-compartment model with first-order elimination. Weight predicted paracetamol clearance and volume of distribution, which were estimated as 0.348 L/h (5.5 % relative standard error; 30.8 % coefficient of variation) and 2.46 L (3.5 % relative standard error; 14.3 % coefficient of variation), respectively, at the mean subject weight of 2.30 kg. An external evaluation was performed on an independent dataset that included 436 observations from 60 neonates with a mean gestational age of 35.6 weeks (SD 4.3). The median prediction error was 10.1 % [95 % confidence interval (CI) 6.1–14.3] and the median absolute prediction error was 25.3 % (95 % CI 23.1–28.1). Conclusions Weight predicted intravenous paracetamol pharmacokinetics in neonates ranging from extreme preterm to full-term gestational status. External evaluation suggested that these findings should be generalizable to other similar patient populations.

Objectives This study aimed to model the population pharmacokinetics of intravenous paracetamol and its major metabolites in neonates and to identify influential patient characteristics, especially those affecting the formation clearance (CLformation) of oxidative pathway metabolites. Methods Neonates with a clinical indication for intravenous analgesia received five 15-mg/kg doses of paracetamol at 12-h intervals (<28 weeks’ gestation) or seven 15-mg/kg doses at 8-h intervals (≥28 weeks’ gestation). Plasma and urine were sampled throughout the 72-h study period. Concentration-time data for paracetamol, paracetamol-glucuronide, paracetamol-sulfate, and the combined oxidative pathway metabolites (paracetamol-cysteine and paracetamol-N-acetylcysteine) were simultaneously modeled in NONMEM 7.2. Results The model incorporated 259 plasma and 350 urine samples from 35 neonates with a mean gestational age of 33.6 weeks (standard deviation 6.6). CLformation for all metabolites increased with weight; CLformation for glucuronidation and oxidation also increased with postnatal age. At the mean weight (2.3 kg) and postnatal age (7.5 days), CLformation estimates (bootstrap 95% confidence interval; between-subject variability) were 0.049 L/h (0.038–0.062; 62 %) for glucuronidation, 0.21 L/h (0.17–0.24; 33 %) for sulfation, and 0.058 L/h (0.044–0.078; 72 %) for oxidation. Expression of individual oxidation CLformation as a fraction of total individual paracetamol clearance showed that, on average, fractional oxidation CLformation increased <15 % when plotted against weight or postnatal age. Conclusions The parent-metabolite model successfully characterized the pharmacokinetics of intravenous paracetamol and its metabolites in neonates. Maturational changes in the fraction of paracetamol undergoing oxidation were small relative to between-subject variability.

Since the first description in 1961, several case reports have documented an increased incidence of anesthesia-related cardiac arrest in patients with Williams-Beuren syndrome, commonly known as Williams syndrome (WS). Widespread arteriopathy secondary to an elastin gene defect results in various cardiac defects, including supravalvar aortic stenosis (SVAS) and coronary artery anomalies, which can increase the risk of myocardial ischemia. Even though patients with WS are known to have increased risk of adverse events during anesthesia and sedation, they often undergo several procedures that require anesthesia during their lifetimes, and cases of perianesthetic cardiac arrest continue to be reported. To date, no prospective studies have been reported that quantify anesthetic risk in individual patients with WS. In this article, we review the clinical manifestations of WS, propose a consensus, expert-informed method to estimate anesthetic risk based on the current literature, and provide recommendations for periprocedural management of this patient population.

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LFA increased exhaled and inspired CO and increased COHb% in children <2 yr of age. Thus, LFA resulted in re-breathing of exhaled CO and exposure, especially in the youngest children. Re-breathing exhaled gas during LFA could pose a risk for an acute CO exposure in patients who have elevated COHb and high baseline levels of exhaled CO. If practitioners match or exceed minute ventilation with FGF to avoid LFA, CO re-breathing can be limited.

While most children have anxiety and fears in the hospital environment, especially prior to having surgery, there are several common behavioral and emotional disorders in children that can pose a challenge in the perioperative setting. These include anxiety, depression, oppositional defiant disorder, conduct disorder, attention deficit hyperactivity disorder, obsessive compulsive disorder, post-traumatic stress disorder, and autism spectrum disorder. The aim of this review article is to provide a brief overview of each disorder, explore the impact on anesthesia and perioperative care, and highlight some management techniques that can be used to facilitate a smooth perioperative course.

Background Previous attempts to support the single ventricle circulation mechanically have suggested that a custom-built assist device is needed to push rather than pull through the pulmonary circulation. We hypothesized that using a conventional ventricular assist device, with or without conversion of a total cavopulmonary connection to a bidirectional Glenn cavopulmonary connection would allow assistance by pulling blood through the circuit and improve cardiac index (CI). Methods Cavopulmonary connections were established in each of five Yorkshire pigs (25kg) using ePTFE conduits in a “Y” configuration with appropriate clamping of limbs of the Y to achieve: total cavopulmonary Fontan connection (TCPC), SVC cavopulmonary connection (SVC Glenn) and IVC cavopulmonary connection (IVC Glenn). A common atrium had been established previously by balloon septostomy. Mechanical circulatory assistance of the single systemic ventricle was achieved using a centrifugal pump with common atrial inflow and proximal ascending aortic outflow. CI was calculated using an ultrasonic flow meter placed on the distal ascending aorta and compared between assisted and non-assisted circulation for 3 conditions: TCPC, SVC Glenn and IVC Glenn. Mean pulmonary artery pressure (PAP), common atrial pressure (LAP), arterial oxygen saturation (SAT), partial pressure of arterial oxygen (PO2) and oxygen delivery (DO2) were calculated. Results Unassisted SVC Glenn CI tended to be higher than TCPC or IVC Glenn (Figure 1). Significant augmentation of total CI was achieved with mechanical assistance for SVC Glenn (109% ± 24%, P =.04) and also with TCPC (130% ± 109%, P = .01). Assisted CI achieved at least mean baseline biventricular CI for all 3-support modes. Oxygen delivery was highest for assisted SVC Glenn 1786 ± 1307 ml/l/min and lowest with TCPC 1146 ± 386 ml/l/min, with a trend toward lower common atrial pressure and lower pulmonary artery pressure for SVC Glenn. Conclusions SVC bidirectional Glenn circulation may allow optimal augmentation of cardiac index and oxygen delivery in a failing single ventricle using a conventional pediatric ventricular assist device. Our model also suggests that the Fontan circulation itself can be supported with systemic ventricular assistance of the single ventricle.

Summary Cardiac catheterization is an integral part of medical management for pediatric patients with congenital heart disease. Owing to age and lack of cooperation in children who need this procedure, general anesthesia is typically required. These patients have increased anesthesia risk secondary to cardiac pathology. Furthermore, multiple catheterization procedures result in exposure to harmful ionizing radiation. Magnetic resonance imaging‐guided right‐heart catheterization offers decreased radiation exposure and diagnostic imaging benefits over traditional fluoroscopy but potentially increases anesthetic complexity and risk. We describe our early experience with anesthetic techniques and challenges for pediatric magnetic resonance imaging‐guided right‐heart catheterization.