Impact of a vancomycin loading dose on the achievement of target vancomycin exposure in the first 24 h and on the accompanying risk of nephrotoxicity in critically ill patients.

BACKGROUND: The advocated pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin, AUC/MIC ≥ 400 mg·h/L, may not be reached with a conventional fixed starting dose of 1000 mg in critically ill patients, but increasing the dose may cause nephrotoxicity. OBJECTIVES: To evaluate the effect of a weight-based loading dose of 25 mg/kg vancomycin on PK/PD target attainment in the first 24 h (AUC0-24) in critically ill patients and to evaluate whether this increases the risk of acute kidney injury (AKI). PATIENTS AND METHODS: A prospective observational before/after study was performed in ICU patients, comparing the percentage of vancomycin courses with AUC0-24 ≥ 400 mg·h/L and the incidence of AKI, defined as worsening of the risk, injury, failure, loss of kidney function and end-stage kidney disease (RIFLE) score. The conventional dose group received 1000 mg of vancomycin as initial dose; the loading dose group received a weight-based loading dose of 25 mg/kg. A population PK model developed using non-linear mixed-effects modelling was used to estimate AUC0-24 in all patients. RESULTS: One hundred and four courses from 82 patients were included. With a loading dose, the percentage of courses achieving AUC0-24 ≥ 400 mg·h/L increased significantly from 53.8% to 88.0% (P = 0.0006). The percentage of patients with new-onset AKI was not significantly higher when receiving a 25 mg/kg loading dose (28.6% versus 37.8%; P = 0.48). However, the risk of AKI was significantly higher in patients achieving AUC0-24 > 400 mg·h/L compared with patients achieving AUC < 400 mg·h/L (39.0% versus 14.8%; P = 0.031). CONCLUSIONS: A weight-based loading dose of 25 mg/kg vancomycin led to significantly more patients achieving AUC0-24 ≥ 400 mg·h/L without increased risk of AKI. However, some harm cannot be ruled out since higher exposure was associated with increased risk of AKI.

Polymorphisms in the fetal progesterone receptor and a calcium-activated potassium channel isoform are associated with preterm birth in an Argentinian population.

OBJECTIVE: To investigate genetic etiologies of preterm birth (PTB) in Argentina through evaluation of single-nucleotide polymorphisms (SNPs) in candidate genes and population genetic admixture. STUDY DESIGN: Genotyping was performed in 389 families. Maternal, paternal and fetal effects were studied separately. Mitochondrial DNA (mtDNA) was sequenced in 50 males and 50 females. Y-chromosome anthropological markers were evaluated in 50 males. RESULT: Fetal association with PTB was found in the progesterone receptor (PGR, rs1942836; P=0.004). Maternal association with PTB was found in small conductance calcium activated potassium channel isoform 3 (KCNN3, rs883319; P=0.01). Gestational age associated with PTB in PGR rs1942836 at 32-36 weeks (P=0.0004). MtDNA sequencing determined 88 individuals had Amerindian consistent haplogroups. Two individuals had Amerindian Y-chromosome consistent haplotypes. CONCLUSION: This study replicates single locus fetal associations with PTB in PGR, maternal association in KCNN3, and demonstrates possible effects for divergent racial admixture on PTB.

Nasopharyngeal CPAP: a nursing art.

CPAP, the use of continuous positive airway pressure as a means of providing respiratory support to the infant, has been studied since the early 1970s. A variety of delivery methods has been used. One method, that of providing CPAP through a single nasopharvngeal tube, is reviewed here. The process of delivering nasopharyngeal CPAP can be technically difficult, and requires careful attention to the infant and the CPAP system. The ability to anticipate and troubleshoot problems is essential. Done well, this process truly shows off the art of nursing.

Saline for peripheral intravenous locks in neonates: evaluating a change in practice.

PURPOSE: To evaluate the efficacy of saline versus 10 units/ml heparin for peripheral i.v. flushes in neonates. DESIGN: A nonexperimental group design was used to compare the longevity of heparin and saline i.v. locks. A research utilization method was chosen to increase the study power while simultaneously implementing a practice change and evaluating the outcomes. Power analysis showed that a sample size of approximately 120 per group was needed to decrease the risk of beta error to 0.1. SAMPLE: Subjects included neonates in the Special Care Nurseries at a Level III large midwestern university teaching hospital. Data were collected from a convenience sample of 123 neonates receiving 10 units/ml heparin flush into a peripheral i.v. Practice was then changed to preservative-free normal saline, and data collection continued for 117 neonates. MAIN OUTCOME VARIABLE: I.v. catheter longevity. RESULTS: There was no significant statistical difference in i.v. catheter longevity between i.v. locks flushed with 10 units/ml heparin and those flushed with normal saline. Patient weight accounted for a significant proportion of the variance in i.v. catheter life.

Lateralized effects of subclinical epileptiform EEG discharges on scholastic performance in children.

The interaction between lateralization of subclinical epileptiform discharges and cognitive tasks was investigated in 21 children (12 girls and 9 boys, mean age 10.6 years). Seventeen had a diagnosis of epilepsy (partial or secondarily generalized). Testing was by reading, arithmetic, and intelligence subtests during continuous telemetric EEG and video monitoring. Children with left-sided discharges had significantly lower reading performance than children with right-sided discharges. During reading, epileptiform discharges occurred relatively less frequently and with a shorter total duration over the left hemisphere than the right. This supports the view that cognitive tasks suppress epileptiform discharges when they activate a region of the brain within the epileptogenic zone. Discharges from other epileptogenic zones not directly activated by the tasks are increased, however.