RESUMEN
INTRODUCTION: Previous randomized trials failed to demonstrate a decrease in mortality of patients with acute lung injury treated by exogenous surfactant. The aim of this prospective randomized study was to evaluate the effects of exogenous porcine-derived surfactant on pulmonary reaeration and lung tissue in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). METHODS: Twenty patients with ALI/ARDS were studied (10 treated by surfactant and 10 controls) in whom a spiral thoracic computed tomography scan was acquired before (baseline), 39 hours and 7 days after the first surfactant administration. In the surfactant group, 3 doses of porcine-derived lung surfactant (200 mg/kg/dose) were instilled in both lungs at 0, 12 and 36 hours. Each instillation was followed by recruitment maneuvers. Gas and tissue volumes were measured separately in poorly/nonaerated and normally aerated lung areas before and seven days after the first surfactant administration. Surfactant-induced lung reaeration was defined as an increase in gas volume in poorly/non-aerated lung areas between day seven and baseline compared to the control group. RESULTS: At day seven, surfactant induced a significant increase in volume of gas in poorly/non-aerated lung areas (320 ± 125 ml versus 135 ± 161 ml in controls, P = 0.01) and a significant increase in volume of tissue in normally aerated lung areas (189 ± 179 ml versus -15 ± 105 ml in controls, P < 0.01). PaO2/FiO2 ratio was not different between the surfactant treated group and control group after surfactant replacement. CONCLUSIONS: Intratracheal surfactant replacement induces a significant and prolonged lung reaeration. It also induces a significant increase in lung tissue in normally aerated lung areas, whose mechanisms remain to be elucidated. TRIAL REGISTRATION: NCT00742482.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Surfactantes Pulmonares/uso terapéutico , Lesión Pulmonar Aguda/diagnóstico por imagen , Lesión Pulmonar Aguda/fisiopatología , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/fisiopatología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: Lung tissue deposition of intravenous ceftazidime administered either continuously or intermittently was compared in ventilated piglets with experimental bronchopneumonia. DESIGN: Prospective experimental study ANIMALS: Eighteen anesthetized and ventilated piglets INTERVENTIONS: Bronchopneumonia was produced by the intrabronchial inoculation of Pseudomonas aeruginosa characterized by an impaired sensitivity to ceftazidime (MIC 16 mg/l). Ceftazidime was administered either through a continuous infusion of 90 mg/kg per 24 h after a bolus of 30 mg/kg or by an intermittent infusion of 30 mg/kg per 8 h. MEASUREMENTS AND RESULTS: Piglets were killed 24 h after the initiation of continuous ceftazidime (n = 6), and 1 h (peak, n = 6) and 8 h (trough, n = 6) after the third dose following intermittent administration. Lung tissue concentrations of ceftazidime, measured by HPLC, and lung bacterial burden were assessed on multiple postmortem lung specimens. During continuous administration ceftazidime lung tissue concentrations were 9.7 +/- 3.8 microg/g. Following intermittent administration peak and trough lung tissue concentrations were, respectively, 7.1 +/- 2.4 microg/g and 0.6 +/- 1 microg/g. Lung bacterial burden was different after continuous and intermittent administration (median 7.10(3) vs. 4.10(2) cfu/g). CONCLUSIONS: Continuous infusion of ceftazidime maintained higher tissue concentrations than intermittent administration.
Asunto(s)
Antibacterianos/uso terapéutico , Bronconeumonía/tratamiento farmacológico , Ceftazidima/uso terapéutico , Pulmón/metabolismo , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Ceftazidima/administración & dosificación , Ceftazidima/farmacocinética , Infusiones Intravenosas/métodos , PorcinosRESUMEN
PURPOSE: Emergence of multidrug-resistant strains in intensive care units has renewed interest in colistin, which often remains the only available antimicrobial agent active against resistant Pseudomonas aeruginosa. The aim of this study is to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administration of colistin in piglets with pneumonia caused by P. aeruginosa. METHODS: In ventilated piglets, colistimethate was administered 24 h following bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration of colistin = 2 microg ml(-1)) either by nebulization (8 mg kg(-1) every 12 h, n = 6) or by intravenous infusion (3.2 mg kg(-1) every 8 h, n = 6). All piglets were killed 49 h after inoculation. Colistin peak lung tissue concentrations and lung bacterial burden were assessed on multiple post mortem subpleural lung specimens. RESULTS: Median colistin peak lung concentration following nebulization was 2.8 microg g(-1) (25-75% interquartile range = 0.8-13.7 microg g(-1)). Colistin was undetected in lung tissue following intravenous infusion. In the aerosol group, peak lung tissue concentrations were significantly greater in lung segments with mild pneumonia (median = 10.0 microg g(-1), 25-75% interquartile range = 1.8-16.1 microg g(-1)) than in lung segments with severe pneumonia (median = 1.2 microg g(-1), 25-75% interquartile range = 0.5-3.3 microg g(-1)) (p < 0.01). After 24 h of treatment, 67% of pulmonary segments had bacterial counts <10(2) cfu g(-1) following nebulization and 28% following intravenous administration (p < 0.001). In control animals, 12% of lung segments had bacterial counts <10(2) cfu g(-1) 49 h following bronchial inoculation. CONCLUSION: Nebulized colistin provides rapid and efficient bacterial killing in ventilated piglets with inoculation pneumonia caused by Pseudomonas aeruginosa.
Asunto(s)
Antibacterianos/administración & dosificación , Colistina/administración & dosificación , Neumonía Bacteriana/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Administración por Inhalación , Animales , Antibacterianos/farmacocinética , Colistina/farmacocinética , Modelos Animales de Enfermedad , Farmacorresistencia Bacteriana Múltiple , Inyecciones Intravenosas , Nebulizadores y Vaporizadores , Neumonía Bacteriana/metabolismo , Neumonía Bacteriana/microbiología , Infecciones por Pseudomonas/metabolismo , Infecciones por Pseudomonas/microbiología , PorcinosRESUMEN
PURPOSE: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime is frequent in critically ill patients. The aim of the study was to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administrations of ceftazidime in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime. METHODS: Ceftazidime was administered 24 h following the intra-bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration = 16 microg ml(-1)), either by nebulization (25 mg kg(-1) every 3 h, n = 6) or by continuous intravenous infusion (90 mg kg(-1) over 24 h after an initial rapid infusion of 30 mg kg(-1), n = 6). Four non-treated inoculated animals served as controls. All piglets were killed 48 h (intravenous and control groups) or 51 h (aerosol group) after inoculation. Lung tissue concentrations and lung bacterial burden were assessed on multiple post-mortem sub-pleural lung specimens [(lower limit of quantitation = 10(2) colony forming unit (cfu g(-1))]. RESULTS: Ceftazidime trough lung tissue concentrations following nebulization were greater than steady-state lung tissue concentrations following continuous intravenous infusion [median and interquartile range, 24.8 (12.6-59.6) microg g(-1) vs. 6.1 (4.6-10.8) microg g(-1)] (p < 0.001). After 24 h of ceftazidime administration, 83% of pulmonary segments had bacterial counts <10(2) cfu g(-1) following nebulization and only 30% following intravenous administration (p < 0.001). In control animals, 10% of lung segments had bacterial counts <10(2) cfu g(-1) 48 h following bronchial inoculation. CONCLUSION: Nebulized ceftazidime provides more efficient bacterial killing in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime.