Ischemia-modified albumin and adenosine plasma concentrations are associated with severe systemic inflammatory response syndrome after cardiopulmonary bypass.

PURPOSE: Severe systemic inflammatory response syndrome (SIRS) occurring after cardiopulmonary bypass (CPB) is a common cause of mortality during cardiac surgery. These syndromes are characterized by vasoplegia and ischemia-reperfusion phenomenom. Adenosine is a strong endogenous vasodilating agent, which may be involved in blood pressure failure during CPB induced by severe SIRS. Ischemia-modified albumin (IMA) is considered as a sensitive marker of tissue ischemia. We examined whether the IMA or adenosine plasma concentrations (APCs) change during a severe SIRS-induced blood pressure failure during CPB. MATERIALS AND METHODS: Plasma concentration and IMA (median [range]) were measured before, during, and after surgery in 86 patients who underwent coronary revascularization under CBP and were correlated to postoperative clinical course. RESULTS: Preoperative APC values (1.45 [0.52-2.11] µmol L(-1) vs 0.36 [0.12-0.66] µmol L(-1)) and IMA (144 [91-198] IU mL(-1) vs 109 [61-183] U mL(-1)) were significantly increased in patients presenting postoperative severe SIRS. Mean durations of mechanical ventilation, stay in the intensive care unit, and requirement of vasoactive drugs were significantly higher in patients with higher APC and IMA, but APC was the best predictive marker a postoperative severe. CONCLUSIONS: Adenosine plasma concentration and IMA concentration are associated with postoperative severe SIRS after CPB.

Effect of fluid loading during hypovolaemic shock on caspofungin pharmacokinetic parameters in pig.

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.

An early inflammatory response to oesophagectomy predicts the occurrence of pulmonary complications.

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.

Effect of hypertonic saline pre-treatment on ischemia-reperfusion lung injury in pig.

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.

Adenosine A2A receptor hyperexpression in patients with severe SIRS after cardiopulmonary bypass.

OBJECTIVE: 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. PATIENTS: : This was a prospective comparative observational study. Forty-four patients who underwent cardiac surgery involving CPB. Ten healthy subjects served as controls. MEASUREMENTS AND RESULTS: 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 micromol l, 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 micromol/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. CONCLUSIONS: High expression of A2A ADO receptor and high APLs may be a predictive factor of postoperative severe SIRS after CPB.

Comparison of lung injury after normal or small volume optimized resuscitation in a model of hemorrhagic shock.

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.

Accuracy and limits of transpulmonary dilution methods in estimating extravascular lung water after pneumonectomy.

STUDY OBJECTIVES: The measurement of extravascular lung water index by double indicator (EVLWIdi) or the measurement of extravascular lung water index by transpulmonary thermodilution (EVLWItt) could be useful after pneumonectomy. Since pulmonary blood flow and volume are altered after pneumonectomy, the validity of these methods is uncertain. This study has compared measurements of EVLWIdi and EVLWItt with measurement of extravascular lung water index by gravimetry (EVLWIg) in a porcine model of pulmonary edema induced after right pneumonectomy. DESIGN: Randomized laboratory study. SETTING: Animal research laboratory. SUBJECTS: Twenty-seven female pigs; mean weight, 35 +/- 5 kg (+/- SD). INTERVENTIONS: The pigs were anesthetized, placed on mechanical ventilation, and allocated to a two-lung group (n = 10) or a right pneumonectomy group (n = 17). EVLWIdi and EVLWItt were measured at baseline, 60 min after pneumonectomy, and 60 min after IV injection of oleic acid (OA). MEASUREMENTS AND RESULTS: There was a good correlation between EVLWIg and EVLWIdi values (r = 0.96, p < 0.0001 in the two-lung group; and r = 0.81, p = 0.02 in the pneumonectomy group). EVLWIdi underestimated EVLWIg in the two-lung group (- 3 mL/kg; 95% confidence interval [CI], - 7 to + 2 mL/kg) and in the pneumonectomy group (- 0.9 mL/kg; 95% CI, - 3.3 to + 1.5 mL/kg). After pneumonectomy, EVLWItt decreased in mean by 27% and increased in mean by 70% after OA acid. There was a good correlation between EVLWIg and EVLWItt values (r = 0.96, p < 0.0001 in the two-lung group; and r = 0.90, p < 0.0001 after pneumonectomy). EVLWItt slightly overestimated gravimetric value in the two-lung group (+ 1.5 mL/kg; 95% CI, - 1.5 to + 4.2 mL/kg) and largely overestimated gravimetric value after pneumonectomy (+ 5 mL/kg; 95% CI, + 3.4 to + 6.8 mL/kg). CONCLUSION: Double-indicator and transpulmonary thermodilution methods could be useful in monitoring extravascular lung water index (EVLWI) after pneumonectomy, but transpulmonary thermodilution largely overestimates EVLWI.