Randal P. Marchessault

Percutaneous femoral venous catheterizations: A prospective study of complications

In a prospective, 45-month study, we compared the complication rates of percutaneously placed femoral and nonfemoral central venous catheters in critically ill pediatric patients. Forty-one percent of the 395 central venous catheters placed during this interval were femoral. Noninfectious complications were recognized for 2.5% of femoral catheters and 2.1% of nonfemoral catheters. Only three complications occurred with catheter insertion, all during nonfemoral attempts. Systemic infections that were possibly attributable to the central venous catheter were found in 3.7% of patients with femoral catheters and 7.3% of those with nonfemoral catheters. Femoral venous catheterization offers several practical advantages for central access over other sites. The low incidence of complications documented in this study suggests that the femoral vein is the preferred site in most critically ill children when central venous catheterization is indicated.

Percutaneous central venous catheterization in a pediatric intensive care unit: a survival analysis of complications

We investigated the relationship between the duration of percutaneous central venous catheterization and the occurrence of catheter-related complications in critically ill children by survival analysis techniques. Data were collected prospectively and analyzed for infectious and noninfectious complications from 379 pediatric patients in whom central venous catheters had been placed in the pediatric ICU over a 45-month period. Cumulative survival rate analysis revealed a linear decrease in the number of complication-free catheters with time. The median duration of complication-free catheter survival was projected to be 23.3 days. The risk of catheter complication did not increase with increasing daily duration of catheter use as demonstrated by probability density function: catheter complication rates were similar on the first day after insertion (1.06 +/- 0.5%), the seventh day (4.27 +/- 1.6%), and the 24th day (2.48 +/- 2.4%). Therefore, in this population, routine catheter replacement would not be expected to lower the incidence of catheter-related complications, but may unnecessarily increase the number of insertion-related complications.

Disposition of sodium benzoate in newborninfants with hyperammonemia

Sodium benzoate lowers serum ammonia concentrations by the activation of a non-urea cycle pathway of ammonia removal. The disposition of sodium benzoate was monitored in four hyperammonemic newborn infants, using a simple and newly developed assay for benzoate and hippurate, to assess (1) the metabolic capability of patients of this age to utilize this pathway for nitrogen removal, (2) the potential risks of benzoate toxicity at clinically achieved serum benzoate concentrations, and (3) the value of routine monitoring of serum benzoate concentrations in this patient population. In three of the four infants, more than half of the administered benzoate was converted to hippurate. Hippurate was effectively cleared by the neonatal kidney, although removal of unconjugated benzoate by peritoneal dialysis or urinary excretion was slow compared with the metabolic conversion to hippurate. There was a considerable interpatient variability in benzoate metabolism; consequently, an eight-fold range in serum benzoate concentrations (2.14 to 16.0 mM/L) was found after patients had received benzoate for longer than 24 hours. These serum benzoate concentrations were calculated to be capable of producing substantial (four to 25 times) increases in free bilirubin concentrations in jaundiced infants. Although sodium benzoate offers considerable promise for the treatment of hyperammonemia, toxicity appears likely in some infants receiving this drug in currently recommended doses. Monitoring of serum concentrations appears to be warranted. Dosage reduction in jaundiced infants and in those with demonstrated insufficiency of benzoate metabolism is recommended.

DEVELOPMENTAL STUDY OF AMRINONE DISPOSITION IN INFANTS

Amrinone (AMR) is an orally effective, positive inotropic agent and vasodilator unrelated pharmacologically to other available drugs, including catecholamines and cardiac glycosides. Clinical studies in adult subjects have demonstrated a close relationship between AMR plasma concentrations and improvement in cardiac index. The disposition of AMR was studied in 6 children (3 neonates and 3 infants <12 mo) receiving the drug for pulmonary hypertension which was unresponsive to other vasodilators.Subjects received doses of 1-3 mg/kg AMR iv and elimination kinetics were determined following the last dose. In this population the volume of distribution (1.54±.85 L/kg) and drug clearance rate (.29±.21 L/kg/h) of AMR showed marked inter-individual variability. This was attributable to increases in volume of distribution (r=.78, p<.1) and drug clearance rate (r=.91, p<.02) with age. Elimination half-life was similar in neonates (4.9±3.0 h) and infants (3.7±.8h). Hemodynamic and oxymetric data suggested that AMR produced selective although transient pulmonary vasodilitation in the infants but not in the neonates in this study. This difference in response occurred despite a trend to higher AMR peak serum concentrations in the neonatal group than in older infants (6.4±4.1 μg/ml vs. 3.5±1.8 μg/ml).Important changes in pharmacokinetic and pharmacodynamic properties of AMR occur during the first year of life and will warrant therapeutic drug monitoring of AMR and similar compounds.

1770 PULMONARY ENDOTHELIAL PERMEABILITY IN ASTHMA

The hypothesis that pulmonary endothelial permeability (PEP) is increased in asthma was tested in a guinea pig model. Animals were sensitized to ovalbumin by subcutaneous injection two weeks prior to testing (asthmatic group). Normal animals did not receive the sensitizing ovalbumin. A third group of animals was desensitized by repeated exposure to nebulized ovalbumin, with epinephrine rescue, over a 4-6 week period (desensitized group). Pulmonary function was assessed by plethysmography in each group during a control period and after challenge with nebulized ovalbumin. PEP was assessed by the rate of appearance of the albumin tag, Evans blue, in the lung, and systemic endothelial permeability (SEP) by the rate of decline of serum concentrations of Evans blue. All groups had comparable pulmonary function during the control period. Ovalbumin inhalation produced a decrease in dynamic lung compliance and an increase in airway resistance only in the asthmatic group. PEP was increased in the asthmatic animals, while SEP was comparable in all groups. Pulmonary edema occurred in both the asthmatic and desensitized groups.Pulmonary dysfunction in asthma is accompanied by increased PEP. Pulmonary edema, alone, does not explain these changes.