Effect of sedation and analgesia on postoperative amplitude-integrated EEG in newborn cardiac patients

The aim of this study is to describe the effect of sedation and analgesia on postoperative amplitude-integrated EEG (aEEG) in newborns with congenital heart disease (CHD) undergoing heart surgery. This is a consecutive series of 26 newborns with CHD of which 16 patients underwent cardiopulmonary bypass (CPB) surgery and 10 patients did not. aEEG was monitored for at least 12 h preoperatively and started within the first 6 h postoperatively for 48 h. Outcome was assessed at 1 year of age. All 26 patients showed a normal preoperative continuous cerebral activity with sleep-wake cycles (SWC). The postoperative duration to return to normal background activity with SWC was similar for both groups. Independent of group assignment, patients requiring midazolam had a significantly later onset of a normal SWC than those without midazolam (p=0.03). Three patients in the CPB group and two in the non-CPB group showed continuous low voltage or flat trace after administration of fentanyl. These changes did not correlate with neurodevelopmental outcome. Sedation with midazolam has a transient effect on the background activity, whereas fentanyl can induce a severe pathologic background pattern. The significance of these changes on outcome is not yet clear. Thus, more attention should be paid to these effects when interpreting aEEG in this population

Standardization and chemical characterization of intravenous therapy in adult patients

Background: Intravenous drug administration is associated with potential complications, such as phlebitis. The physiochemical characteristics of the infusate play a very important role in some of these problems. Aim: The aim of this study was to standardize the dilutions of intravenous drugs most commonly used in hospitalized adult patients and to characterize their pH, osmolarity and cytotoxic nature to better guide the selection of the most appropriate vascular access. Methods: The project was conducted in three phases: (i) standardization of intravenous therapy, which was conducted using a modified double-round Delphi method; (ii) characterization of the dilutions agreed on in the previous phase by means of determining the osmolarity and pH of each of the agreed concentrations, and recording the vesicant nature based on the information in literature; and (iii) algorithm proposal for selecting the most appropriate vascular access, taking into account the information gathered in the previous phases. Results: In total, 112 drugs were standardized and 307 different admixtures were assessed for pH, osmolarity and vesicant nature. Of these, 123 admixtures (40%), had osmolarity values >600 mOsm/L, pH 9, or were classified as vesicants. In these cases, selection of the most suitable route of infusion and vascular access device is crucial to minimize the risk of phlebitis-type complications. Conclusions: Increasing safety of intravenous therapy should be a priority in the healthcare settings. Knowing the characteristics of drugs to assess the risk involved in their administration related to their physicochemical nature may be useful to guide decision making regarding the most appropriate vascular access and devices

Correction to: Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive Review

Fentanyl and its derivatives sufentanil, alfentanil, and remifentanil are potent opioids. A comprehensive review of the use of fentanyl and its derivatives in the pediatric population was performed using the National Library of Medicine PubMed. Studies were included if they contained original pharmacokinetic parameters or models using established routes of administration in patients younger than 18 years of age. Of 372 retrieved articles, 44 eligible pharmacokinetic studies contained data of 821 patients younger than 18 years of age, including more than 46 preterm infants, 64 full-term neonates, 115 infants/toddlers, 188 children, and 28 adolescents. Underlying diagnoses included congenital heart and pulmonary disease and abdominal disorders. Routes of drug administration were intravenous, epidural, oral-transmucosal, intranasal, and transdermal. Despite extensive use in daily clinical practice, few studies have been performed. Preterm and term infants have lower clearance and protein binding. Pharmacokinetics was not altered by chronic renal or hepatic disease. Analyses of the pooled individual patients’ data revealed that clearance maturation relating to body weight could be best described by the Hill function for sufentanil (R2 = 0.71, Bmax 876 mL/min, K50 16.3 kg) and alfentanil (R2 = 0.70, Bmax (fixed) 420 mL/min, K50 28 kg). The allometric exponent for estimation of clearance of sufentanil was 0.99 and 0.75 for alfentanil clearance. Maturation of remifentanil clearance was described by linear regression to bodyweight (R2 = 0.69). The allometric exponent for estimation of remifentanil clearance was 0.76. For fentanyl, linear regression showed only a weak correlation between clearance and bodyweight in preterm and term neonates (R2 = 0.22) owing to a lack of data in older age groups. A large heterogeneity regarding study design, clinical setting, drug administration, laboratory assays, and pharmacokinetic estimation was observed between studies introducing bias into the analyses performed in this review. A limitation of this review is that pharmacokinetic data, based on different modes of administration, dosing schemes, and parameter estimation methods, were combined