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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]

The article describes a case of management of postesophagectomy respiratory failure in a 63-year-old man who underwent transthoracic esophagectomy for adenocarcinoma with noninvasive ventilation. His pulmonary function test revealed a forced expiratory volume of 3 liters per second and a forced vital capacity of 3.43 liters as the patient was a former smoker but stopped 5 years before surgery. Blood gas values for the main stages of clinical course in the end of first postoperative day and before paravertebral block second postoperative day.

Adenosine (ADO) is an endogenous nucleoside, which has been involved in blood pressure failure during severe systemic inflammatory response syndrome (severe SIRS) after cardiac surgery with cardiopulmonary bypass (CPB). Adenosine acts via its receptor subtypes, namely A1, A2A, A2B, or A3. Because A2A receptors are implicated in vascular tone, their expression might contribute to severe SIRS. We compared adenosine plasma levels (APLs) and A2A ADO receptor expression (ie, B, K, and mRNA amount) in patients with or without postoperative SIRS.This was a prospective comparative observational study. Forty-four patients who underwent cardiac surgery involving CPB. Ten healthy subjects served as controls.Among the patients, 11 presented operative vasoplegia and postoperative SIRS (named complicated patients) and 33 were without vasoplegia or SIRS (named uncomplicated patients). Adenosine plasma levels, K, B, and mRNA amount (mean ± SD) were measured on peripheral blood mononuclear cells. Adenosine plasma levels, B, and K were significantly higher in complicated patients than in uncomplicated patients (APLs: 2.7 ± 1.0 vs 1.0 ± 0.5 μmol l-1, P < 0.05; B: 210 ± 43 vs 65 ± 26 fmol/mg, P < 0.05; K: 35 ± 10 vs 2 ± 1 nM, P < 0.05). In uncomplicated patients, APLs remain higher than in controls (1 ± 0.5 vs 0.6 ± 0.25 μmol/L; P < 0.05).Mean arterial pressure was inversely correlated to APLs (R = -0.58; P < 0.001) and B (R = -0.64; P < 0.001) leading to an increased requirement of vasoactive drugs during the postoperative period in vasoplegic patients.High expression of A2A ADO receptor and high APLs may be a predictive factor of postoperative severe SIRS after CPB. [ABSTRACT FROM AUTHOR]

Abstract: Background: Respiratory complications are the most frequent concern following oesophagectomy. We aimed to assess the postoperative inflammatory response after oesophagectomy and to determine its reliability to predict the occurrence of pulmonary complications. Methods: A total of 97 patients were enrolled in this prospective observational study. All patients underwent a transthoracic oesophagectomy for cancer. From D0 to D3, plasmatic cytokine levels (interleukin (IL)-1, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α), short synacthen test (SST), PaO2/FiO2 ratio and clinical factors determining the systemic inflammatory response syndrome (SIRS) were monitored and compared between patients who experienced pulmonary complications (group I) and those who did not (group II). Results: The overall in-hospital mortality was 5%. Postoperative pulmonary complications occurred in 33 patients (34%). Sputum retention was the first step of pulmonary complications in 26 patients (occurring at a mean of 2.8±1 days after the operation), leading to pneumonia in 22 patients (4.7±1 days) and acute respiratory distress syndrome (ARDS) in 10 (6.9±3 days). At day 2, group I patients had significantly higher plasmatic levels of IL-6, IL-10 and TNF-α than group II patients. PaO2/FiO2 was impaired accordingly (215 vs 348; p =0.006). SST was negative in 38% of group I patients and in 30% of group II patients (p =0.51). SIRS was present in 33% and 6% of group I and group II patients, respectively (p ≤0.01). At multivariate analysis, early occurrence of SIRS was the sole significant predictor of pulmonary complications (p =0.005; odds ratio (OR):11.4, confidence interval (CI): 2–63). Conclusions: The vast majority of postoperative pulmonary complications after oesophagectomy occur after the 4th postoperative day. The earlier detection (first 48h) of SIRS, high plasmatic cytokine levels and impairment of PaO2/FiO2 predicts the onset of these complications. This finding suggests that early pharmacological intervention may have a beneficial impact. [Copyright &y& Elsevier]

Background: Hypertonic saline may be administered in the setting of lung transplantation but may affect the development of ischemia–reperfusion lung injury. This study investigated the effects of the pre-treatment by intravenous hypertonic saline in a pig model of single lung ischemia–reperfusion. Methods: Forty-three pigs (34 ± 4 kg) under mechanical ventilation were randomly assigned to a left lung ischemia–reperfusion alone or preceded by 4-ml/kg 7.5% hypertonic saline, 33-ml/kg normal saline, or by the infusion of the vasodilator nicardipine. Animals without ischemia served as controls. After euthanasia, the left lung was sampled for histologic analysis and measurement of lung water and alveolar–capillary permeability. Results: Ischemia–reperfusion resulted in high-permeability pulmonary edema, hypoxemia, and increased interleukin-6 serum level. Hypertonic saline pre-treatment worsened pulmonary edema of the left lung (6.6 ± 0.7 vs 4.8 ± 0.8 ml/kg of body weight, p < 0.05) and resulted in a higher ratio of the protein level in the alveolar fluid to the serum protein level (0.41 ± 0.04 vs 0.21 ± 0.09, p < 0.05) and in a higher histologic damage score (11 [range, 9–11.75] vs 6.5 [range, 4.5–7.5], p < 0.05) without promoting pulmonary or systemic inflammation. Lung injury was affected neither by normal saline nor by nicardipine pre-treatment. Nicardipine did not influence the deleterious effect of hypertonic saline. Conclusions: Pre-treatment by intravenous hypertonic saline worsened ischemia–reperfusion lung injury independently of its effects on the cardiac index or pulmonary circulation but probably through a direct effect of hyperosmolarity on endothelial permeability. [Copyright &y& Elsevier]

Background: Respiratory complications are the most frequent concern following oesophagectomy. We aimed to assess the postoperative inflammatory response after oesophagectomy and to determine its reliability to predict the occurrence of pulmonary complications., Methods: A total of 97 patients were enrolled in this prospective observational study. All patients underwent a transthoracic oesophagectomy for cancer. From D0 to D3, plasmatic cytokine levels (interleukin (IL)-1, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha), short synacthen test (SST), PaO(2)/FiO(2) ratio and clinical factors determining the systemic inflammatory response syndrome (SIRS) were monitored and compared between patients who experienced pulmonary complications (group I) and those who did not (group II)., Results: The overall in-hospital mortality was 5%. Postoperative pulmonary complications occurred in 33 patients (34%). Sputum retention was the first step of pulmonary complications in 26 patients (occurring at a mean of 2.8+/-1 days after the operation), leading to pneumonia in 22 patients (4.7+/-1 days) and acute respiratory distress syndrome (ARDS) in 10 (6.9+/-3 days). At day 2, group I patients had significantly higher plasmatic levels of IL-6, IL-10 and TNF-alpha than group II patients. PaO(2)/FiO(2) was impaired accordingly (215 vs 348; p=0.006). SST was negative in 38% of group I patients and in 30% of group II patients (p=0.51). SIRS was present in 33% and 6% of group I and group II patients, respectively (p< or =0.01). At multivariate analysis, early occurrence of SIRS was the sole significant predictor of pulmonary complications (p=0.005; odds ratio (OR):11.4, confidence interval (CI): 2-63)., Conclusions: The vast majority of postoperative pulmonary complications after oesophagectomy occur after the 4th postoperative day. The earlier detection (first 48 h) of SIRS, high plasmatic cytokine levels and impairment of PaO(2)/FiO(2) predicts the onset of these complications. This finding suggests that early pharmacological intervention may have a beneficial impact., (Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)