Transfusion-related acute lung injury in cardiac surgery patients is characterized by pulmonary inflammation and coagulopathy: a prospective nested case-control study.

OBJECTIVE: Transfusion-related acute lung injury is the leading cause of transfusion-related morbidity and mortality. Clinical data on the pathogenesis of transfusion-related acute lung injury are sparse. The objective of the present study was to determine inflammation and coagulation pathways involved in the onset of transfusion-related acute lung injury. DESIGN: Nested case-control study. SETTING: Operating theatre and intensive care department of a tertiary referral hospital. PATIENTS: Elective cardiac surgery patients requiring postsurgery intensive care admission. INTERVENTIONS: None. MEASUREMENTS: Cardiac surgery patients (n=668) were prospectively screened for the onset of transfusion-related acute lung injury. Transfusion-related acute lung injury cases (n=16) were randomly assigned to transfused and nontransfused cardiac surgery controls in a 1:2 ratio. Blood samples were taken pre- and postoperatively and at onset of transfusion-related acute lung injury. In addition, at onset of transfusion-related acute lung injury, bronchoalveolar lavage fluid was obtained. In plasma and bronchoalveolar lavage fluid, levels of interleukin-6, interleukin-8, elastase-α1-antitrypsin complexes, thrombin-antithrombin complexes, plasminogen activator activity, and plasminogen activator inhibitor-1 were determined by means of enzyme-linked immunosorbent assay. MAIN RESULTS: In all patients, cardiac surgery was associated with systemic inflammation, evidenced by an increase in plasma levels of interleukin-6, interleukin-8, and elastase-α1-antitrypsin complexes compared with presurgery levels (p<.001). Prior to onset of transfusion-related acute lung injury, systemic interleukin-8 and interleukin-6 levels were higher compared with nontransfused controls (p<.01). In transfusion-related acute lung injury cases, bronchoalveolar lavage fluid levels of interleukin-8, interleukin-6, and elastase-α1-antitrypsin complexes were elevated compared with control groups (p<.05). Both plasma and bronchoalveolar lavage fluid levels of thrombin-antithrombin complexes were enhanced in transfusion-related acute lung injury cases compared with control groups (p<.01). Bronchoalveolar lavage fluid levels of plasminogen activator activity were decreased due to an increase in plasminogen activator inhibitor-1 levels in transfusion-related acute lung injury cases compared with control groups (p<.01), indicating suppressed fibrinolysis. CONCLUSIONS: Prior to onset of transfusion-related acute lung injury, there is systemic inflammation and neutrophil sequestration. Transfusion-related acute lung injury is characterized by both systemic and pulmonary inflammation and activation of neutrophils, as well as enhanced coagulation and suppressed fibrinolysis.

Lung-protective mechanical ventilation does not protect against acute kidney injury in patients without lung injury at onset of mechanical ventilation.

INTRODUCTION: Preclinical and clinical studies suggest that mechanical ventilation contributes to the development of acute kidney injury (AKI), particularly in the setting of lung-injurious ventilator strategies. OBJECTIVE: To determine whether ventilator settings in critically ill patients without acute lung injury (ALI) at onset of mechanical ventilation affect the development of AKI. DESIGN, SETTING, AND PATIENTS: Secondary analysis of a randomized controlled trial (N = 150), comparing conventional tidal volume (V(T), 10 mL/kg) with low tidal volume (V(T), 6 mL/kg) mechanical ventilation in critically ill patients without ALI at randomization. During the first 5 days of mechanical ventilation, the RIFLE class was determined daily, whereas neutrophil gelatinase-associated lipocalin and cystatin C levels were measured in plasma collected on days 0, 2, and 4. RESULTS: Eighty-six patients had no AKI at inclusion, and 18 patients (21%) subsequently developed AKI, but without significant difference between ventilation strategies. (Cumulative hazard, 0.26 vs 0.23; P = .88.) The courses of neutrophil gelatinase-associated lipocalin and cystatin C plasma levels did not differ significantly between randomization groups. CONCLUSION: In the present study in critically patients without ALI at onset of mechanical ventilation, lower tidal volume ventilation did not reduce the development or worsening of AKI compared with conventional tidal volume ventilation.

The incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of cardiac surgery patients: a prospective nested case-control study.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Both antibodies and bioactive lipids that have accumulated during storage of blood have been implicated in TRALI pathogenesis. In a single-center, nested, case-control study, patients were prospectively observed for onset of TRALI according to the consensus definition. Of 668 patients, 16 patients (2.4%) developed TRALI. Patient-related risk factors for onset of TRALI were age and time on the cardiopulmonary bypass. Transfusion-related risk factors were total amount of blood products (odds ratio [OR] = 1.2; 95% confidence interval [CI], 1.03-1.44), number of red blood cells stored more than 14 days (OR = 1.6; 95% CI, 1.04-2.37), total amount of plasma (OR = 1.2; 95% CI, 1.03-1.44), presence of antibodies in donor plasma (OR = 8.8; 95% CI, 1.8-44), and total amount of transfused bioactive lipids (OR = 1.0; 95% CI, 1.00-1.07). When adjusted for patient risk factors, only the presence of antibodies in the associated blood products remained a risk factor for TRALI (OR = 14.2; 95% CI, 1.5-132). In-hospital mortality of TRALI was 13% compared with 0% and 3% in transfused and nontransfused patients, respectively (P < .05). In conclusion, the incidence of TRALI is high in cardiac surgery patients and associated with adverse outcome. Our results suggest that cardiac surgery patients may benefit from exclusion of blood products containing HLA/HNA antibodies.

sTREM-1 is a potential useful biomarker for exclusion of ongoing infection in patients with secondary peritonitis.

Identification of patients with ongoing abdominal infection after emergency surgery for abdominal sepsis is difficult. The purpose of this study was to evaluate whether plasma and abdominal fluid sTREM-1 levels can adequately select patients with ongoing abdominal infection. In a single center retrospective observational study, plasma and abdominal fluid samples were collected every 24 h for 4 days in patients who underwent an emergency laparotomy for severe secondary peritonitis. Patients after elective esophagus surgery served as controls. sTREM-1 levels were measured with an ELISA. Plasma sTREM-1 levels were not elevated compared to controls. Abdominal fluid sTREM-1 levels were initially high (median (246 [IQR 121-455] pg/ml), and declined 24 h after surgery (P=0.01). On day 2 and 3, patients with ongoing infection had significantly higher abdominal fluid sTREM-1 levels (319 [180-671] and 245 [173-541] pg/ml, respectively) compared to patients without infection (85 [49-306] and 121 [20-196] pg/ml, respectively). sTREM-1 levels were moderately predictive for persistent infection but had a high negative predictive value (0.86 (95% CI 0.69-0.94) below a cut-off level of 160 pg/ml. In clinical practice, abdominal fluid sTREM-1 levels may be useful for exclusion but not detection of ongoing abdominal infection after surgery for secondary peritonitis.

Lung epithelial injury markers are not influenced by use of lower tidal volumes during elective surgery in patients without preexisting lung injury.

Clara cell protein levels are elevated in plasma of individuals with mild or subclinical lung injury. We studied the influence of two mechanical ventilation strategies on local and systemic levels of Clara cell protein (CC16) and compared them with levels of soluble receptor for advanced glycation end products (sRAGE) and surfactant proteins (SP)-A and -D in patients undergoing elective surgery. Saved samples from a previously reported investigation were used for the study. Forty patients planned for elective surgery were randomized to mechanical ventilation with either a conventional tidal volume (V(T)) of 12 ml/kg without positive end-expiratory pressure (PEEP) or low V(T) of 6 ml/kg and 10 cmH(2)O PEEP. Plasma and bronchoalveolar lavage fluid (BALF) was collected directly after intubation and after 5 h of mechanical ventilation. While systemic levels of SP-A and SP-D remained unchanged, systemic levels of CC16 and sRAGE increased significantly in both groups after 5 h (P < 0.001 for both). BALF levels of SP-A, SP-D, CC16, and sRAGE remained unaffected. No differences were found between the two mechanical ventilation strategies regarding any of the measured biological markers. In conclusion, systemic levels of CC16 and sRAGE rise after 5 h in patients receiving mechanical ventilation for elective surgery. Mechanical ventilation with lower tidal volumes and PEEP did not have a different effect on levels of biomarkers of lung epithelial injury compared with conventional mechanical ventilation.

CT colonography at different radiation dose levels: feasibility of dose reduction.

PURPOSE: To investigate the sensitivity and specificity of polyp detection and the image quality of computed tomographic (CT) colonography at different radiation dose levels and to study effective doses reported in literature on CT colonography. MATERIALS AND METHODS: CT colonography and colonoscopy were performed with 100 mAs in 50 consecutive patients at high risk for colorectal cancer; 50- and 30-mAs CT colonographic examinations were simulated with controlled addition of noise to raw transmission measurements. One radiologist randomly evaluated all original and simulated images for the presence of polyps and scored image quality. Differences in image quality were assessed with the Wilcoxon rank test. Scan protocols from the literature and recent (unpublished) updates were collected. RESULTS: In nine of 10 patients with polyps 5 mm in diameter or larger (sensitivity, 90%) and in seven of 17 patients with polyps smaller than 5 mm, polyps were correctly identified with CT colonography at all dose levels. Specificity for patients without polyps 5 mm or larger was 53%-60% at all dose levels and for patients without any polyps was 26% (at 100 and 50 mAs) and 48% (at 30 mAs). Image quality decreased significantly as the dose level decreased. The median effective doses (supine and prone positions) calculated from protocols reported in the literature and updates were 7.8 and 8.8 mSv, respectively. CONCLUSION: Although image quality decreases significantly at 30 mAs (3.6 mSv), polyp detection remains unimpaired. The median dose for CT colonography at institutions that perform CT colonographic research is currently 8.8 mSv.