Population Pharmacokinetics of Unbound and Total Teicoplanin in Critically Ill Pediatric Patients.

BACKGROUND AND OBJECTIVES: Teicoplanin is a highly protein-bound antibiotic, increasingly used to treat serious Gram-positive infections in critically ill children. Maturational and pathophysiological intensive care unit-related changes often lead to altered pharmacokinetics. In this study, the objectives were to develop a pediatric population-pharmacokinetic model of unbound and total teicoplanin concentrations, to investigate the impact of plasma albumin levels and renal function on teicoplanin pharmacokinetics, and to evaluate the efficacy of the current weight-based dosing regimen. METHODS: An observational pharmacokinetic study was performed and blood samples were collected for quantification of unbound and total concentrations of teicoplanin after the first dose and in assumed steady-state conditions. A population-pharmacokinetic analysis was conducted using a standard sequential approach and Monte Carlo simulations were performed for a probability of target attainment analysis using previously published pharmacokinetic-pharmacodynamic targets. RESULTS: A two-compartment model with allometric scaling of pharmacokinetic parameters and non-linear plasma protein binding best described the data. Neither the inclusion of albumin nor the renal function significantly improved the model and no other covariates were supported for inclusion in the final model. The probability of target attainment analysis showed that the standard dosing regimen does not satisfactory attain the majority of the proposed targets. CONCLUSIONS: We successfully characterized the pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. The highly variable unbound fraction of teicoplanin could not be predicted using albumin levels, which may support the use of therapeutic drug monitoring of unbound concentrations. Poor target attainment was shown for the most commonly used dosing regimen, regardless of the pharmacokinetic-pharmacodynamic target evaluated.

Meso-Rex shunt using deep femoral vein conduit: first report.

The Meso-Rex shunt (MRS) procedure was first described in 1992 by de VILLE et al. for the treatment of extrahepatic portal vein obstruction (EHPVO) in paediatric liver transplant patients. This technique provides more physiological relief of portal hypertension compared to the porto-systemic shunts, which can lead to long-term complications such as hyperammonaemia and hepato-pulmonary syndrome. Different conduits as autologous and cryopreserved veins or prosthetic grafts have been previously reported. We present herein the first case of a MRS using the autologous deep femoral vein in a 17-year-old female patient affected by EHPVO from unknown reasons.

Care of the potential pediatric organ donor.

Although all of this information may create the impression that caring for a potential organ donor is an exceedingly complex task, in the authors' experience, this often is not true, and much energy can--and should--be devoted to the care of the bereaved family. Of crucial importance are the early recognition of brain death and the consequent radical switch of the treatment goal from preservation of the patient's brain and life to preservation of organs for the lives of others. Care for the donor is the natural extension of care for a critically ill or injured patient. During the foregoing discussion, the authors had to stress the absence of sound evidence on many points. Because many reports originate from transplant centers dedicated to a specific organ, gaining a comprehensive view on management options in the ICU further is hampered. Thus, this situation leaves another field in which investigations originating from pediatric intensivists could provide evidence urgently needed to make optimal choices. The next decade should see the thyroid hormone controversy solved by at least one controlled prospective study and the differential applicability of inotropic, vasoactive, or fluid-centered strategies. It seems self-evident that only graft survival and related parameters can form adequate endpoints for future studies.

Markers of tissue hypoperfusion in pediatric septic shock.

OBJECTIVE: To describe measurements of global oxygenation parameters, markers of splanchnic hypoperfusion and those of metabolic activity related to cellular energy production among critically ill children with septic shock. DESIGN: Clinical study of a series of cases. PATIENTS AND PARTICIPANTS: 11 previously healthy children with septic shock admitted to the pediatric intensive care unit (ICU) of a university hospital. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Oxygen consumption, oxygen delivery (DO(2)), serum bicarbonate, arterial pH, gastric intramucosal pH (pHi), gastroarterial carbon dioxide tension gradient, serum lactate, pyruvate, lactate to pyruvate ratio (L/P), ketone body ratio, and the esterified to free carnitine ratio were measured serially at 0, 6, 12, 24, 36, and 48 h after admission to the pediatric ICU. All children survived. One patient failed to show supranormal DO(2) ( > 570 ml/min per m(2)). Normalization of serum bicarbonate and lactate were associated with patient recovery. One patient presented an increasingly abnormal L/P ratio with normal lactate levels, suggesting an increased utilization of pyruvate rather than an increased cytosolic redox potential. Although values of gastric pHi < 7.30 were observed in 43 % of samples, serial measurements in individuals showed significant variability and unpredictable trends. Free fatty acid concentrations, ketone body production, and carnitine levels remained within the normal range. CONCLUSIONS: In this study, trends in serum bicarbonate and lactate somewhat characterized the recovery of children with septic shock. Based on our data, it is unclear how other markers may have been used to modify therapy.

Protected specimen brush or bronchoalveolar lavage to diagnose bacterial nosocomial pneumonia in ventilated adults: a meta-analysis.

OBJECTIVE: We conducted a meta-analysis by using summary receiver operating characteristic curves to compare the diagnostic value for bacterial nosocomial pneumonia of the following: a) quantitative culture (colony-forming units per milliliter or CFU/mL) of respiratory secretions collected with a bronchoscopic protected specimen brush (PSB); b) quantitative culture of a bronchoscopic bronchoalveolar lavage (BAL); and c) the percentage of infected cells (IC) in BAL. DATA SOURCES: All studies published in the English or the French language, through January 1, 1995, on the evaluation of PSB or BAL for the diagnosis of pneumonia were considered for analysis. The relevant literature was identified through computer and reference searching and by experts in the field. STUDY SELECTION: A study was included if at least two of three independent readers regarded its purpose as the evaluation of CFU-PSB, CFU-BAL, or IC-BAL for the diagnosis in human beings of bacterial nosocomial pneumonia in ventilated adults and if the study was prospective and published in a peer-reviewed journal. DATA EXTRACTION: Three readers reviewed all published articles and decided whether to include each study; consensus was defined as agreement by at least two readers. The authors of each original article included in the meta-analysis were asked to complete a questionnaire in which they were asked to check and to correct the data extracted by one of the independent readers. DATA SYNTHESIS: Summary receiver operating characteristic curves were used to compare the efficacy of three diagnostic tests. Eighteen studies on CFU-PSB (795 patients) were included, as well as 11 studies on CFU-BAL (435 patients) and 11 on IC-BAL (766 patients). The accuracy of these tests was not different. However, it seems that administration of previous antibiotics markedly decreased accuracy of CFU-PSB (p = .0002) but not the accuracy of CFU-BAL and that of IC-BAL. CONCLUSION: Both PSB and BAL are reliable to diagnose bacterial nosocomial pneumonia. Because CFU-BAL and IC-BAL seemed more resistant to the effects of antibiotics, we recommend BAL rather than PSB if the patient is already receiving antibiotics.

Use of Western-based HIV risk-reduction interventions targeting adolescents in an African setting.

PURPOSE: To evaluate an intervention (based on one which had previously been successful in reducing adolescent human immunodeficiency virus (HIV) risk behaviors in the United States) among adolescents residing in Namibia, a country located in sub-Saharan Africa. METHODS: A randomized trial of a 14-session face-to-face intervention emphasizing abstinence and safer sex was conducted among 515 youth (median age 17 years; median grade 11) attending 10 secondary schools located in two districts in Namibia. Knowledge, attitudes, intentions, and HIV risk behaviors were assessed at baseline and in the immediate postintervention period. RESULTS: Knowledge increased significantly among intervention compared to control youth (88% vs. 82%; correct responses, p < .0001). At postintervention follow-up, more intervention than control youth believed that they could be intimate without having sex, could have a girlfriend or boyfriend for a long time without having sex, could explain the process of impregnation, knew how to use a condom, and could ask for condoms in a clinic. Fewer intervention than control youth believed that if a girl refused to have sex with her boyfriend it was permissible for him to strike her, and that condoms took away a boy's pleasure. More intervention than control youth anticipated using a condom when they did have sex, and fewer expected to drink alcohol. Finally, after intervention, there was a trend for increased condom use. There were significant gender-related differences at baseline, although intervention impact was generally equivalent. CONCLUSIONS: These findings provide support for the judicious adaptation of successful Western HIV prevention programs in other cultural settings. A single intervention approach appears to be effective in short-term follow-up with both genders.

Markers of cellular dysoxia during orthotopic liver transplantation in pigs.

OBJECTIVE: To characterize global, regional, and end-organ markers of cellular dysoxia during orthotopic liver transplantation and early reperfusion in pigs. DESIGN: Descriptive study. SETTING: University hospital research laboratory. ANIMALS AND INTERVENTIONS: 7 fasted, anesthetized, and mechanically ventilated Yorkshire pigs underwent orthotopic liver transplantation. Oxygen consumption (VO2) and oxygen delivery (DO2) were both calculated using standard formulae. Gastric interstitial pH and the gastroarterial partial pressure of carbon dioxide (PCO2) gradient were measured with a gastric tonometer. The following were determined from arterial blood samples: serum lactate to pyruvate ratio, serum 3-hydroxybutyrate to acetoacetate ratio, plasma free fatty acids, and plasma free and total carnitine levels. MEASUREMENTS AND RESULTS: Data were collected 1 h after induction of anesthesia (I), at the end of the anhepatic phase (A), and 1 h after reperfusion (R), Median (range) VO2 values obtained at the specified time points were: I 318 (206-1860), A 210 (152-408), R 330 (214-424) ml/kg per min, respectively (NS); DO2 values were: I 1828 (1382-3259), A 1219 (452-2492), R 1741 (1345-12,071) ml/kg per min, respectively (NS). The lactate to pyruvate ratio, reflecting the redox potential of the cytosol, progressively increased: I 22 (9-46), A 29 (16-68), R 43 (23-55), (p < 0.05). Gastric interstitial pH, as well as the gastroarterial PCO2 gradient values at the specified time points did not reach statistical significance. Levels of ketone bodies (3-hydroxybutyrate+acetoacetate) remained lower than 0.120 mmol/l. The ketone body ratio did not significantly vary over time (NS). Plasma esterified and free carnitine concentrations and free fatty acid values remained within normal limits (NS). Among these markers, the ketone body ratio presented the largest area under the receiver operating characteristic curve as a marker of postoperative mortality, with an inflexion point at 0.9. CONCLUSION: In this study, orthotopic liver transplantation was associated with significant variations over time in the redox potential of the cytosol. Postoperative mortality was, however, related to the redox state of the liver mitochondria. Our data suggest the occurrence of abnormal tissue oxygenation during liver transplantation.