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Objective: To compare lung injury induced by a hemorrhagic shock resuscitated with normal saline or with small volumes of a hypertonic/hyperoncotic solution.Design and Setting: Randomized, controlled, laboratory study in an animal research laboratory.Subjects: Nineteen pigs (43 +/- 4 kg).Interventions: After anesthesia and mechanical ventilation animals were bled to induce a 2-h deep shock and resuscitated for 2 h using normal saline (NS, 2 ml/kg per minute, n = 7) or the association of 7.2% NaCl with 6% hydroxyethylstarch 200/0.5 (HSHES, 4 ml/kg in 10 min followed by 0.2 ml/kg per minute, n = 7) to reach cardiac index and mixed venous oxygen saturation goals. Lungs were removed 6[Symbol: see text]h after the initiation of hemorrhage. Five animals were used as controls without hemorrhage.Measurements and Results: Resuscitation goals were achieved using 90 +/- 17 ml/kg NS or 6.8 +/- 1.9 ml/kg HSHES. Lung injury was noted in both hemorrhage groups but was not influenced by the type of resuscitation. Extravascular lung water was measured at 9.6 +/- 1.8 ml/kg in the NS group, 9.2 +/- 1.6 ml/kg in the HSHES, group and 6.4 +/- 1 m/kg in the control group. The degree of histological alveolar membrane focal thickening and interstitial neutrophil infiltration were significantly more pronounced in the hemorrhage groups with no difference between the two types of fluid loading. Finally, pulmonary levels of IL-8 were higher after hemorrhage regardless of the type of resuscitation.Conclusions: When included in an optimized and goal directed resuscitation, the use of normal saline or a small volume of hypertonic/hyperoncotic solution does not result in a different early hemorrhage-induced lung injury. [ABSTRACT FROM AUTHOR]

Introduction: Caspofungin treatment is frequently initiated in shock patients. In the present study, we investigated the influence of hypovolaemic shock requiring fluid loading on the plasma and pulmonary pharmacokinetic parameters of caspofungin in the pig. Methods: After being anaesthetised and mechanically ventilated, 12 pigs were bled to induce a two-hour deep shock and resuscitated using normal saline based on haemodynamic goals. A one-hour infusion of 70 mg of caspofungin was started at the beginning of the resuscitation period. The lungs were removed four hours after caspofungin administration. Sixteen animals served as controls without haemorrhage. Caspofungin concentrations were measured by using high-performance liquid chromatography, and a two-compartment population pharmacokinetic analysis was performed. Results: In the shock group, the volume of blood removed was 39 ± 7 mL/kg and a volume of 90 ± 17 mL/kg saline was infused throughout the resuscitation period. The extravascular lung water index was higher in the shock group (9.3 ± 1.6 mL/kg vs 5.7 ± 1 mL/kg in the control group; P < 0.01). In the shock group, the median (interquartile range) maximal plasma concentration was 37% lower than in the control group (21.6 μg/mL (20.7 to 22.3) vs 33.1 μg/mL (28.1 to 38.3); P < 0.01). The median area under curve (AUC) from zero to four hours was 25% lower in the shock group than in the control group (60.3 hours × μg/mL (58.4 to 66.4) vs 80.8 hours × μg/mL (78.3 to 96.9); P < 0.01), as was the median lung caspofungin concentration (1.22 μg/g (0.89 to 1.46) vs 1.64 μg/g (1.22 to 2.01); P < 0.01). However, the plasma-to-tissue ratios were not different between the groups, indicating that lung diffusion of caspofungin was not affected after shock followed by fluid loading. Pharmacokinetic analysis showed that the peripheral volume of distribution of caspofungin and intercompartmental clearance were significantly higher in the shock group, as was the total apparent volume of distribution. Conclusions: Hypovolaemic shock followed by fluid loading in the pig results in a significant increase in the apparent volume of distribution of caspofungin and in a decrease in its plasma and pulmonary exposition. Although our model was associated with capillary leakage and pulmonary oedema, our results should be generalised to the septic shock with caution. Future investigations should focus on monitoring plasma caspofungin concentrations and optimal caspofungin dosing in shock patients. [ABSTRACT FROM AUTHOR]