RESUMEN
Hepatorenal syndrome (HRS) is defined as the development of renal insufficiency in chronic liver disease with portal hypertension when other causes of functional renal failure are excluded. Incidence in patients with refractory ascites is 8%, with an overall incidence of renal failure in end stage liver disease being 75%. HRS is predictive for the prognosis of end stage liver failure but its pathogenesis is complex and currently not fully understood.
Asunto(s)
Síndrome Hepatorrenal/patología , Diagnóstico Diferencial , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/fisiopatología , Síndrome Hepatorrenal/terapia , Humanos , Trasplante de Riñón , Trasplante de Hígado , Derivación Portosistémica Quirúrgica , Sistema Renina-Angiotensina/fisiología , Terminología como AsuntoRESUMEN
OBJECTIVES: To determine possible additive effects of combined high-dose partial liquid ventilation (PLV) and almitrine bismesylate (ALM) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). DESIGN AND SETTING: Prospective, controlled animal study in an animal research facility of a university hospital. INTERVENTIONS: ALI was induced in 12 anesthetized and mechanically ventilated pigs by repeated wash-out of surfactant. After initiation of PLV with 30 ml/kg perfluorocarbon the animals were randomly assigned to receive either accumulating doses of ALM (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 micrograms/kg per minute) for 30 min each (n = 6) or the solvent malic acid (n = 6). MEASUREMENT AND RESULTS: Pulmonary gas exchange and hemodynamics were measured at the end of each infusion period. Compared to ALI, PLV alone significantly increased arterial oxygen partial pressure (PaO2) and decreased venous admixture (QVA/QT) and mean pulmonary artery pressure (MPAP). Administration of ALM did not result in a further improvement in PaO2, QVA/QT or MPAP compared to PLV alone but decreased PaO2 and increased QVA/QT and MPAP when 16 micrograms/kg per min ALM was compared to PLV alone. CONCLUSIONS: In an animal model of surfactant depletion induced ALI the combined treatment of PLV and ALM induced no significant improvement in pulmonary gas exchange or hemodynamics when compared to PLV alone. Moreover, high-dose ALM significantly impaired gas exchange and pulmonary hemodynamics.
Asunto(s)
Almitrina/administración & dosificación , Modelos Animales de Enfermedad , Fluorocarburos/administración & dosificación , Hemodinámica/efectos de los fármacos , Ventilación Liquida/métodos , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/terapia , Fármacos del Sistema Respiratorio/administración & dosificación , Almitrina/farmacología , Animales , Análisis de los Gases de la Sangre , Terapia Combinada , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Fluorocarburos/farmacología , Hidrocarburos Bromados , Estudios Prospectivos , Presión Esfenoidal Pulmonar/efectos de los fármacos , Distribución Aleatoria , Respiración Artificial , Síndrome de Dificultad Respiratoria/metabolismo , Fármacos del Sistema Respiratorio/farmacologíaRESUMEN
OBJECTIVE: To determine the dose-response relationship of almitrine (Alm) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). DESIGN: Prospective, randomized, controlled study. METHODS: Twenty anesthetized, tracheotomized and mechanically ventilated (FIO2 1.0) pigs underwent induction of ALI by repeated saline washout of surfactant. Animals were randomly assigned to either receive cumulating doses of Alm intravenously (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 micrograms.kg-1.min-1) for 30 min each (treatment; n = 10) or to receive the solvent malic acid (controls; n = 10). MEASUREMENTS AND RESULTS: Measurements of pulmonary gas exchange and hemodynamics were performed at the end of each infusion period. Alm < 4.0 micrograms.kg-1.min-1 improved arterial oxygen pressure (PaO2) (105 +/- 9 mmHg for Alm 1.0 vs 59 +/- 5 mmHg) and decreased intrapulmonary shunt (Qs/Qt) (32 +/- 4% for Alm 1.0 vs 46 +/- 4%) (P < 0.05). Alm > or = 8.0 micrograms.kg-1.min-1 did not improve pulmonary gas exchange compared to controls. When compared to low doses of Alm < 4.0 micrograms.kg-1.min-1, high doses > or = 8.0 micrograms.kg1.min-1 decreased PaO2 (58 +/- 11 mmHg for Alm 16.0) and increased Qs/Qt (67 +/- 10% for Alm 16.0) (P < 0.05). CONCLUSIONS: In experimental ALI, effects of almitrine on oxygenation are dose-dependent. Almitrine is most effective when used at low doses known to mimic hypoxic pulmonary vasoconstriction.
Asunto(s)
Almitrina/farmacología , Hemodinámica/efectos de los fármacos , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Insuficiencia Respiratoria/tratamiento farmacológico , Fármacos del Sistema Respiratorio/farmacología , Almitrina/administración & dosificación , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Estudios Prospectivos , Insuficiencia Respiratoria/fisiopatología , Fármacos del Sistema Respiratorio/administración & dosificación , PorcinosRESUMEN
This study was undertaken to determine the effects of superimposing incremental levels of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) on gas exchange, respiratory mechanics and morphological changes in experimental acute lung injury (ALI). In a prospective trial, six pigs weighing 30+/-5 kg (mean+/-SD) were tracheotomized, submitted to pressure-controlled mechanical ventilation (pc-CMV) and depleted of surfactant by lung lavage. Animals were then mechanically ventilated with three levels of PEEP: 0.5, 1.0 and 1.5 kPa. PLV was then initiated by intratracheal instillation of 30 mL x kg(-1) perfluorocarbon, followed by pc-CMV with PEEP 0.5, 1.0 and 1.5 kPa. Computed tomography (CT)-based analyses of lung volumes and density were obtained after lung lavage, in PLV and during the combined application of PLV and PEEP. Simultaneously, haemodynamics, gas exchange, dynamic compliance (Cdyn) and dynamic resistance (Rdyn) were determined. Statistical analysis was performed using multivariate analyses of variance for repeated measures (p<0.05). In ALI and before PLV, the application of PEEP significantly reduced cardiac output and intrapulmonary shunt. Arterial oxygen tension (Pa,O2) was increased from 6.9 kPa (52 (42, 54) mmHg) (median, (25th and 75th percentile)) to 8.6 kPa (65 (52, 133) mmHg) (PEEP 1.0 kPa) and 15.6 kPa (117 (90, 195) mmHg) (PEEP 15 kPa) (p<0.05). The lung volume obtained by CT increased, CT density was reduced (p<0.05), Cdyn tended to increase and Rdyn to decrease (nonsignificant). PLV increased arterial carbon dioxide tension and reduced pH (p<0.05). CT lung volume and lung density were increased (p<0.05). Superimposing PEEP on PLV increased Pa,O2 from 9.3 kPa (70 (52,124) mmHg) (PEEP 0.5 kPa) to 12.9 kPa (97 (55, 233) mmHg) (PEEP 1.0 kPa) and 403 kPa (303 (64, 426) mmHg) (PEEP 1.5 kPa) (p<0.05), but had no significant effect on CT lung volume and density. It was concluded that in experimental lung injury, positive end-expiratory pressure provided alveolar recruitment. The combined application of positive end-expiratory pressure and partial liquid ventilation significantly augmented oxygenation and might eventually allow either a reduction in the volumes of perfluorocarbons required, or a reduction in positive end-expiratory pressure necessary to maintain pulmonary gas exchange in acute lung injury.