Physical Restraints in Critically Ill Children: A Multicenter Longitudinal Point Prevalence Study.

OBJECTIVES: We elucidate to investigate the prevalence of and factors associated with the use of physical restraints among critically ill or injured children in PICUs. DESIGN: This was a multicenter, longitudinal point prevalence study. SETTING: We included 26 PICUs in Japan. PATIENTS: Included children were 1 month to 10 years old. We screened all admitted patients in the PICUs on three study dates (in March, June, and September 2019). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We collected prevalence and demographic characteristics of critically ill or injured children with physical restraints, as well as details of physical restraints, including indications and treatments provided. A total of 398 children were screened in the participating PICUs on the three data collection dates. The prevalence of children with physical restraints was 53% (211/398). Wrist restraint bands were the most frequently used means (55%, 117/211) for potential contingent events. The adjusted odds of using physical restraint in patients 1-2 years old was 2.3 (95% CI, 1.3-4.0) compared with children less than 1 year old. When looking at the individual hospital effect, units without a prespecified practice policy for physical restraints management or those with more than 10 beds were more likely to use physical restraints. CONCLUSIONS: The prevalence of physical restraints in critically ill or injured children was high, and significant variation was observed among PICUs. Our study findings suggested that patient age, unit size, and practice policy of physical restraint could be associated with more frequent use of physical restraints.

Plasma concentrations of tadalafil in children with pulmonary arterial hypertension.

BACKGROUND: There is no report documenting the plasma concentrations of tadalafil in children. This study was performed to evaluate the variability in the pharmacokinetics of tadalafil in children with pulmonary arterial hypertension (PAH) treated routinely with the drug. METHODS: Plasma samples were taken twice (post- and predose) after repetitive oral administration, and the pharmacokinetic parameters (CL/F and V/F) in individual patients were estimated by the Bayesian method using the nonlinear mixed effects model. We also determined the unbound concentration of tadalafil using ultrafiltration. RESULTS: Tadalafil was administered to 23 children aged between 0.25 and 17.4 years, with a mean age of 3.58 years. The mean (±SD) daily dose of tadalafil was 0.97 ± 0.41 mg/kg. Sixteen of the 23 children received bosentan concomitantly. The mean CL/F and V/F values of tadalafil were 0.149 L·h-1·kg-1 and 1.87 L/kg, respectively, which were higher than those reported in adults. No effects of age, bosentan, or the estimated glomerular filtration rate were observed on the CL/F value, indicating that other residual factors might account for the interindividual variability among children with PAH. The unbound tadalafil concentrations of the postdose samples ranged from 5.9 to 146 (46.9 ± 37.1) nmol/L, higher than the reported IC50 value of this phosphodiesterase-5 drug for humans (2-4 nmol/L, corresponding to 0.8-1.6 ng/mL). CONCLUSIONS: We demonstrated variability in the total and unbound plasma concentrations of tadalafil in children. However, all children received the empirical doses of the drug; a mean dose of 0.97 mg·kg-1·d-1 showed sufficient unbound concentrations needed for half-maximal inhibition of human phosphodiesterase-5 in vitro. These observations may provide information for the proper use of tadalafil to treat children with PAH.

Subclinical arterial stiffness in young children after Kawasaki disease.

BACKGROUND: Recent studies have revealed that atherosclerosis progresses faster than expected in young adults with a history of Kawasaki disease. However, it is unclear as to when these arterial changes become measurable. In this study, we evaluated subclinical arterial stiffness in young children with a history of Kawasaki disease using two-dimensional ultrasound speckle tracking. METHODS: A total of 75 children with a history of Kawasaki disease (mean age, 8.2 ± 2.8 years) and 50 healthy controls (mean age 8.3 ± 3.5 years) were included. The two regions of interest for speckle tracking were manually positioned at the anterior and posterior carotid arterial wall using a Philips iE33 (Philips Medical Systems, Bothell, WA, USA). The peak systolic strain, time to peak systolic strain, early systolic strain rate, and late systolic strain rate were continuously monitored between the two regions of interest. Furthermore, the intimal-medial thickness, stiffness ß, and pressure-elastic modulus, as conventional measures of arterial stiffness, were concurrently obtained. RESULTS: The peak systolic strain and late systolic strain rate differed significantly between the patients with Kawasaki disease and controls (6.69% versus 8.60%, p < 0.01, and -0.28/second versus -0.51/second, p < 0.0001, respectively). There was no difference in the time to peak systolic strain, early systolic strain rate, and conventional measures. CONCLUSIONS: The arteries of patients with Kawasaki disease appear to develop mild sclerotic changes shortly after the onset of the disease.

Thomsen-Friedenreich antigen exposure as a cause of Streptococcus pyogenes-associated hemolytic-uremic syndrome.

Infection with Streptococcus pyogenes, a Group A beta-hemolytic streptococcus (GAS), is a rare cause of hemolyticuremic syndrome (HUS). Invasive infections with Streptococcus pneumoniae that produce neuraminidase are a well-recognized cause of HUS without diarrhea. The Thomsen- Friedenreich antigen (T antigen) plays a role in the pathophysiology of pneumococcal HUS. We describe the case of a 3-year-old boy with GAS-associated HUS and show how T-antigen exposure was implicated in this case. He had no diarrhea and cultures for blood, urine, and stool were negative. The urinary pneumococcal antigen was negative; his direct Coombs test was positive. Glomerular capillary loops, tubular epithelium on his renal biopsy specimen, and red blood cells in his blood smear showed positive fluorescence with anti-T lectin. Although the pathogenesis of GAS-associated HUS is not well understood, T-antigen exposure may be implicated in some cases with GAS-associated HUS.

Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension.

We evaluated the pharmacokinetics of routinely administered bosentan in 46 Japanese pediatric patients with pulmonary arterial hypertension. Plasma samples were taken twice at times corresponding to the peak and trough concentrations following repetitive oral administration. The population pharmacokinetic parameters of bosentan were estimated by use of the NONMEM program, in which a one-compartment model with repetitive bolus dosing was parameterized in terms of the oral clearance (CL/F) and elimination rate constant (k). Polymorphisms of CYP3A5, SLCO1B1, SLCO1B3, and SLCO2B1 had no significant effect on the disposition of bosentan. In addition, the pharmacokinetics of bosentan was not altered by heart failure or coadministration of sildenafil. In contrast, weight (WT)-normalized values of CL/F were correlated negatively with age (AGE). The final population mean values of CL/F and k were estimated to be 0.409 · (1 - 0.0377 · (AGE - 3.81)) · WT L/h and 0.175 h(-1), respectively.

Recovery from lethal arrhythmia after weight gain in a patient with an eating disorder and epilepsy.

We report a 13-year-old girl with epilepsy who experienced syncope after rapid weight loss due to an eating disorder. She developed a lethal (atrioventricular block) arrhythmia, which improved after weight gain. This case suggests that energy depletion might be involved in lethal arrhythmia.