Pascale Piednoir

Alveolar fibrocyte percentage is an independent predictor of poor outcome in patients with acute lung injury.

Objective:Fibrocytes are mesenchymal progenitors involved in normal and pathologic repair. The aims of this study were: 1) to quantify fibrocytes in bronchoalveolar lavage fluid from patients with or without acute lung injury and acute respiratory distress syndrome; and 2) to evaluate the prognostic value of bronchoalveolar lavage fibrocyte percentage in patients with acute lung injury and acute respiratory distress syndrome. Design:Prospective cohort study. Setting:Three intensive care units of a large tertiary referral center. Patients:One hundred twenty-two ventilated patients requiring bronchoalveolar lavage were enrolled (62 acute respiratory distress syndrome, 30 acute lung injury, 30-ventilated patients without acute lung injury and acute respiratory distress syndrome). Interventions:After bronchoalveolar lavage collection during standard care, the patients were followed up for 28 days and clinical outcome was recorded. Fibrocytes (CD45+/collagen 1+) were quantified in bronchoalveolar lavage by flow cytometry. Comparison of bronchoalveolar lavage fibrocyte percentage from patients with or without acute lung injury and acute respiratory distress syndrome was performed using a Wilcoxon test. A multivariate analysis using a Cox model was performed to study the independent predictors of survival. Measurements and Main Results:Fibrocytes were detected in 90 of 92 (98%) bronchoalveolar lavages from patients with acute lung injury and acute respiratory distress syndrome. The median percentage of bronchoalveolar lavage fibrocytes was significantly higher in patients with acute lung injury and acute respiratory distress syndrome (5.0%) in comparison with ventilated control subjects (0.9%, p < .0001). After adjustment for age, comorbidity of malignancy, and severity of illness, a bronchoalveolar lavage fibrocyte percentage >6% was independently associated with a higher 28-day mortality in patients with acute lung injury and acute respiratory distress syndrome (hazard ratio [95% confidence interval] 6.15 [2.78–13.64], p ⩽ .0001). Addition of bronchoalveolar lavage fibrocyte percentage in a clinical model predicting mortality in patients with acute lung injury and acute respiratory distress syndrome improved global fit and discriminatory capacity (c-statistic, 0.78–0.85; p = .007). Conclusions:Fibrocytes are detectable in bronchoalveolar lavage during acute lung injury and acute respiratory distress syndrome. A bronchoalveolar lavage fibrocyte percentage >6% provides an additive prognostic value to clinical predictors and may be useful to identify patients with acute lung injury and acute respiratory distress syndrome at highest risk of an adverse outcome.

Preoperative iron deficiency increases transfusion requirements and fatigue in cardiac surgery patients: a prospective observational study.

Background Iron deficiency is the commonest cause of anaemia. It is apparent preoperatively in cardiac surgery patients and may influence transfusion requirements. In addition, iron deficiency per se is associated with fatigue. Objective To determine the prevalence of preoperative iron deficiency and its association with perioperative anaemia, blood transfusions and fatigue in cardiac surgery patients. Setting Academic hospital in Paris, France. Patients One hundred consecutive patients without known iron disorder and scheduled for cardiac surgery were prospectively included in this observational study. Intervention No intervention was performed. Measurements A biological iron profile (transferrin saturation, ferritin, soluble transferrin receptor and C-reactive protein) was assessed on the day of surgery. Diagnosis of iron deficiency was defined using a previously published algorithm. Patient fatigue was assessed before surgery and 1 week afterwards (day 7) using the Multidimensional Fatigue Inventory (MFI-20) score that quotes five distinctive dimensions of fatigue. Results Thirty-seven out of 100 patients were diagnosed with iron deficiency. These patients were younger [median (first-third quartile) 63 (43–70) vs. 70 (59–77) years (P = 0.004)], and more often female (51 vs. 21%, P = 0.003), than no iron deficiency patients. Preoperative iron deficiency was associated with lower preoperative haemoglobin levels (P = 0.006) and higher perioperative transfusion rates during the first week (62 vs. 35%, P = 0.019). Patients with iron deficiency but without anaemia (n = 25) received more packed red blood cells units than those without iron deficiency or anaemia (n = 50) [2 (0–2) vs. 0 (0–0) units, P < 0.05). Preoperative iron deficiency was associated with higher score of physical fatigue on day 7 (P = 0.01). Conclusion Preoperative iron deficiency is frequent among cardiac surgery patients and is associated with anaemia, higher transfusion requirements and postoperative fatigue.

Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study

IntroductionHeparin-induced thrombocytopenia is an immune-mediated adverse drug reaction that is associated with a procoagulant state and both arterial and venous thrombosis. After observing two cases of repeated hemofiltration-filter clotting associated with high anti-PF4/heparin antibody concentrations, we systematically measured the anti-PF4/heparin antibody concentration in all cases of unexpected and repeated hemofiltration-filter clotting during continuous veno-venous hemofiltration (CVVH). The aim of this study was to identify factors associated with positive anti-PF4/heparin antibody in the case of repeated hemofiltration-filter clotting.MethodsWe reviewed the charts of all patients who had an anti-PF4/heparin antibody assay performed for repeated hemofiltration-filter clotting between November 2004 and May 2006 in our surgical intensive care unit. We used an enzyme-linked immunoabsorbent assay (heparin-platelet factor 4-induced antibody) with an optical density (OD) of greater than 1 IU considered positive.ResultsDuring the study period, anti-PF4/heparin antibody assay was performed in 28 out of 87 patients receiving CVVH. Seven patients were positive for anti-PF4/heparin antibodies (OD 2.00 [1.36 to 2.22] IU) and 21 were antibody-negative (OD 0.20 [0.10 to 0.32] IU). Baseline characteristics, platelet counts, and activated partial thromboplastin time ratios were not different between the two groups. CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion. Anti-PF4/heparin antibody concentration was inversely correlated with CVVH duration. The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83). CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion.ConclusionRepeated hemofiltration-filter clotting in less than 6 hours was often associated with the presence of anti-PF4/heparin antibodies, regardless of the platelet count. In antibody-positive patients, replacement of heparin by danaparoid sodium allowed the restoration of CVVH duration and efficiency.

Incidence and risk factors of early thromboembolic events after mechanical heart valve replacement in patients treated with intravenous unfractionated heparin

Objective: To evaluate the incidence and risk factors, including timing and intensity of anticoagulation, of early thromboembolic events (TE) after mechanical heart valve replacement (MHVR) in patients treated by intravenous unfractionated heparin (IVUH). Design: Prospective observational study, conducted between December 2005 and May 2007. Setting: Haemostasis laboratory, surgical intensive care unit and ward in a university hospital. Patients: Three hundred consecutive patients undergoing MHVR. Mitral or double MHVR was performed in 149 patients, and aortic MHVR in 151 patients. Postoperative anticoagulation was achieved with continuous IVUH according to a standardised protocol. The timing of efficient anticoagulation was recorded for each patient. Main outcome measures: The end point was the occurrence of any arterial TE from day 1 to day 30. Transoesophageal echocardiography was systematically performed after mitral MHVR. Results: Early TE occurred in 22 patients (14.8%; 95% CI 9% to 20%) after a mitral or double MHVR and in two patients (1.3%; 95% CI 0% to 3%) after an aortic MHVR (p = 0.005). After adjustment for diabetes mellitus (adjusted OR (aOR) = 3.3; 95% CI 1.0 to 10.9, p = 0.049), and for the presence of predisposing factors (heparin-induced thrombocytopenia or bradycardia requiring definitive pacemaker implantation) (aOR = 12.8; 95% CI 3.1 to 53.3, p<0.001), effective anticoagulation on day 3 was a protective factor (aOR = 0.28; 95% CI 0.1 to 0.8, p = 0.018) for early TE after mitral MHVR. Conclusions: Despite the use of IVUH, the rate of early TE after mitral MHVR remained elevated. These results suggest that early effective anticoagulation is required after mitral MHVR, since inappropriate anticoagulation on day 3 was significantly associated with early TE.

Heparin-Induced Thrombocytopenia After Cardiac Surgery: An Observational Study of 1,722 Patients

OBJECTIVES To assess the characteristics and prognosis of patients in whom heparin-induced thrombocytopenia (HIT) was confirmed (HIT+) among suspected HIT patients after having cardiac surgery and to assess the accuracy of two HIT scoring systems. DESIGN An observational prospective study. SETTING A cardiac surgery unit of a tertiary center from November 2005 to September 2007. PARTICIPANTS Of the 1,722 patients who underwent cardiac surgery, 63 were suspected of HIT based on a platelet count <100 × 10(9)/L, a decrease in platelet count of >30%, or the occurrence of a thrombotic event. INTERVENTION The HIT criteria were as follows: (1) the absence of another cause of thrombocytopenia, (2) positive antiplatelet factor 4 (PF4) antibodies (>0.5 optical density [OD]/mn) on enzyme-linked immunoabsorbent assay, and (3) recovery in platelet count after the discontinuation of heparin and substitution by danaparoid sodium. MEASUREMENTS AND MAIN RESULTS HIT was confirmed in 24 patients (1.4% [0.8%-1.9%]); 23 belonged to the 984 treated by intravenous unfractionated heparin (IVUH) (2.3% IQ [1.4%-3.3%]) and 1 to the 738 treated by low-molecularweight heparin (0.14% [0.13%-0.4%]) (OD = 17.6; 95% confidence interval, 2.4-131; p < 0.0001). In the HIT+ patients compared with the unconfirmed HIT patients, thrombocytopenia occurred 7 (range, 6-9) days after surgery versus 3 (range, 3-5) days (p < 0.0001), and kinetics of platelet count showed a biphasic pattern. Six HIT+ patients (25% [7.7-42.3]) presented with an arterial thromboembolic event. Diagnosis performances of HIT scoring systems were low. CONCLUSIONS Confirmed HIT occurred predominantly in patients treated with IVUH. The timing of thrombocytopenia and the variation pattern of the postoperative platelet count are key factors in diagnosing HIT. The overall incidence of intracardiac thrombotic events was noted to be high.

Alveolar fluid in acute respiratory distress syndrome promotes fibroblast migration: role of platelet-derived growth factor pathway*.

Objectives:Fibroblast migration is an initiating step in fibroproliferation; its involvement during acute lung injury and acute respiratory distress syndrome remains poorly understood. The aims of this study were: 1) to determine whether bronchoalveolar lavage fluids from patients with acute lung injury/acute respiratory distress syndrome modulate lung fibroblast migration; 2) to assess lung fibroblast migration’s clinical relevance; and 3) to evaluate the role of the platelet-derived growth factor pathway in this effect. Design:Prospective cohort study. Setting:Three intensive care units of a large tertiary referral center. Patients:Ninety-three ventilated patients requiring bronchoalveolar lavage fluids were enrolled (48 with acute respiratory distress syndrome, 33 with acute lung injury, and 12 ventilated patients without acute lung injury/acute respiratory distress syndrome). Interventions:After bronchoalveolar lavage fluids collection during standard care, the patients were followed up for 28 days and clinical outcomes were recorded. Migration assays were performed by using a Transwell model; bronchoalveolar lavage fluids platelet-derived growth factor and soluble platelet-derived growth factor receptor-&agr; were characterized by Western blot and measured by ELISA. Measurements and Main Results:Most of the bronchoalveolar lavage fluids inhibited basal fibroblast migration. Bronchoalveolar lavage fluids chemotactic index increased with severity of lung injury (28% in patients without acute lung injury/acute respiratory distress syndrome and with acute lung injury vs. 91% in acute respiratory distress syndrome patients; p = .016). In acute lung injury/acute respiratory distress syndrome patients, inhibition of basal fibroblast migration by bronchoalveolar lavage fluids below 52% was independently associated with a lower 28-day mortality (odds ratio [95% confidence interval] 0.313 [0.10–0.98], p = .046). Platelet-derived growth factor–related peptides and soluble platelet-derived growth factor-R&agr; were detected in all bronchoalveolar lavage fluids from acute lung injury/acute respiratory distress syndrome patients. The effect of bronchoalveolar lavage fluids stimulating migration was inhibited by a specific platelet-derived growth factor receptor inhibitor (AG1296). Bronchoalveolar lavage fluids inhibiting migration reversed the effect of rh-platelet-derived growth factor-BB and reduced by 40% the binding of 125I-platelet-derived growth factor-BB to fibroblast cell surface in favor of a role for platelet-derived growth factor-sR&agr;. Conclusions:Together, our results suggest that during acute lung injury, fibroblast migration is modulated by bronchoalveolar lavage fluids through a platelet-derived growth factor/platelet-derived growth factor-sR&agr; balance. Migration is associated with clinical severity and patient 28-day mortality.

Does IV Iron Induce Plasma Oxidative Stress in Critically Ill Patients? A Comparison With Healthy Volunteers.

Objective:To compare the oxidative stress induced by IV iron infusion in critically ill patients and in healthy volunteers. Design:Multicenter, interventional study. Setting:Two ICUs and one clinical research center. Subjects:Anemic critically ill patients treated with IV iron and healthy volunteers. Interventions:IV infusion of 100 mg of iron sucrose. Measurements and Main Results:Thirty-eight anemic patients (hemoglobin, median [interquartile range] = 8.4 g/dL [7.7–9.2]) (men, 25 [66%]; aged 68 yr [48–77]; Simplified Acute Physiology Score II, 48.5 [39–59]) and 39 healthy volunteers (men, 18 [46%]; aged 42.1 yr [29–50]) were included. Blood samples were drawn before (H0) and 2, 6, and 24 hours (H2, H6, and H24) after a 60-minute iron infusion for the determination of nontransferrin bound iron, markers of lipid peroxidation—8&agr;-isoprostanes, protein oxidation—advanced oxidized protein product, and glutathione reduced/oxidized. Iron infusion had no effect on hemodynamic parameter in patients and volunteers. At baseline, patients had much higher interleukin-6, C-reactive protein, and hepcidin levels. 8&agr;-isoprostanes was also higher in patients at baseline (8.5 pmol/L [6.5–12.9] vs 4.6 pmol/L [3.5–5.5]), but the area under the curve above baseline from H0 to H6 was not different (p = 0.38). Neither was it for advanced oxidized protein product and nontransferrin bound iron. The area under the curve above baseline from H0 to H6 (glutathione reduced/oxidized) was lower in volunteers (p = 0.009). Eight patients had a second set of dosages (after the fourth iron infusion), showing higher increase in 8&agr;-isoprostanes. Conclusions:In our observation, IV iron infusion does not induce more nontransferrin bound iron, lipid, or protein oxidation in patients compared with volunteers, despite higher inflammation, oxidative stress, and hepcidin levels and lower antioxidant at baseline. In contrary, iron induces a greater decrease in antioxidant, compatible with higher oxidative stress in volunteers than in critically ill patients.