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A Raszynski

Publications and source records attributed to A Raszynski.

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Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in sheep.

BACKGROUND AND METHODS: Critically ill infants undergoing extracorporeal membrane oxygenation (ECMO) therapy often receive multiple pharmacologic agents. Although the disposition of many drugs has been assessed in patients undergoing cardiopulmonary bypass and in patients receiving mechanical ventilation, only limited data exist for selected medications in patients undergoing ECMO. To evaluate the potential influence of ECMO on aminoglycoside pharmacokinetics, we studied the disposition of tobramycin in ten sheep before and during ECMO therapy. Each sheep received a single iv dose of tobramycin during a control period before ECMO and on a study day during ECMO. Identically timed serial blood samples over 4 hrs were obtained after each tobramycin dose. Paired serum tobramycin concentrations were obtained pre- and postmembrane oxygenator during ECMO in six sheep. RESULTS: Alterations in specific pharmacokinetic variables for tobramycin were observed as a result of ECMO. Estimates of elimination half-life and volume of distribution for tobramycin were significantly increased during ECMO as compared with control (pre-ECMO) values (1.8 +/- 0.3 vs. 2.7 +/- 0.8 [SD] hrs [p < .01] and 0.3 +/- 0.1 vs. 0.5 +/- 0.2 L/kg [p < .005], respectively). Tobramycin body clearance was unaffected by the procedure (1.8 +/- 0.8 vs. 1.7 +/- 0.4 mL/min/kg). Paired serum tobramycin concentrations obtained pre- and postmembrane oxygenator demonstrated no drug removal. CONCLUSIONS: These data suggest that ECMO circuitry does not sequester tobramycin and that the prolonged elimination half-life observed during ECMO therapy is not due to a change in drug clearance but is due to an ECMO-induced increase in tobramycin volume of distribution. To achieve and maintain preselected target tobramycin serum concentrations during ECMO, the usual dosage interval should remain unchanged, but the dose should be increased to compensate for the alteration in the drug's volume of distribution. The clinical applicability of these findings needs to be confirmed in carefully controlled clinical studies involving infants receiving ECMO therapy.

Animals

[The significance of the initial respiratory parameters in assessing the severity of ARDS in children].

In adults, the course and outcome of the acquired respiratory distress syndrome (ARDS) are closely related to the initial respiratory situation. Respiratory indices are frequently used for prognostic purposes and hence for the institution of new techniques such as extracorporeal lung support. The validity of these indices to predict the outcome in pediatric ARDS patients has not been examined as yet. We studied respiratory indices in 69 pediatric ARDS patients. METHODS. Out of 69 pediatric ARDS patients with various underlying diseases (Table 1), we chose 21 with a paO2/FiO2 ratio less than 150 mm Hg at some point to test the prognostic significance of a respiratory severity index (RSI), i.e., mean airway pressure x alveolar-arterial pO2 difference (A-aDo2)/paO2, a respiratory index (RI), i.e., A-aDO2-paO2/paO2, and other respiratory parameters (Table 2). Postsurgical patients, patients with incurable diseases, clearly non-respiratory deaths, and those treated with extracorporeal membrane oxygenation were excluded. We looked for statistical differences between survivors and nonsurvivors and correlations between ventilator days, intensive care unit (ICU) days, and hospital days and these indices. RESULTS. We did not find a significant difference between all respiratory indices tested at admission to the ICU and 24 h later between survivors and nonsurvivors (Table 3). Nonsurvivors initially had significantly higher blood pressures and lower heart rates. Both RSI and RI were significantly correlated to days on the ventilator, days in the ICU, and days in the hospital (Table 4). Initial multiorgan failure was significantly more common in nonsurvivors. CONCLUSIONS. Initial lung dysfunction as indicated by respiratory indices does not predict the outcome in pediatric ARDS. The underlying disease, hemodynamic situation, and age have to be considered in relation to the degree of lung dysfunction to determine new therapeutic strategies such as extracorporeal support.

Child

Intussusception.

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Adolescent