RESUMO
BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial showed that 15% of patients developed venous thromboembolism (VTE) following hemorrhage, but the mechanisms are unknown. Since inflammation is associated with hypercoagulability and thrombosis, our goal was to compare the temporal inflammatory profile following hemorrhagic shock in patients with and without VTE. STUDY DESIGN: Secondary analysis was performed on data collected from PROPPR. Blood samples collected at 0 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours following admission were assayed on a 27-target cytokine panel, and compared between VTE (n = 83) and non-VTE (n = 475) patients. p < 0.05 indicated significance. RESULTS: Over time, both groups exhibited elevations in proinflammatory mediators interleukin (IL)-6, IL-8, IL-10, granulocyte colony-stimulating factor 57, monocyte chemoattractant protein 1 and macrophage inflammatory protein 1ß, and anti-inflammatory mediators IL-1ra and IL-10 (p < 0.05 vs. admission). Venous thromboembolism patients showed amplified responses for IL-6 (6-72 hours) and IL-8 (6-24 hours), which peaked at later time points, and granulocyte colony-stimulating factor 57 (12-24 hours), monocyte chemoattractant protein 1 (6-72 hours), and macrophage inflammatory protein-1 ß (2-12 hours) (p < 0.05 vs. non-VTE per time point) that peaked at similar time points to non-VTE patients. The anti-inflammatory responses were similar between groups, but the interleukin-mediated proinflammatory responses continued to rise after the peak anti-inflammatory response in the VTE group. The occurrence rate of adverse events was higher in VTE (97%) versus non-VTE (87%, p = 0.009) and was associated with higher inflammation. CONCLUSION: Patients with VTE following hemorrhagic shock exhibited a prolonged and amplified proinflammatory responses mediated by select interleukin, chemotactic, and glycoprotein cytokines that are not antagonized by anti-inflammatory mediators. This response is not related to randomization group, injury severity or degree of shock, but may be linked to adverse events. LEVEL OF EVIDENCE: Prognostic, level III.
Assuntos
Anti-Inflamatórios/uso terapêutico , Inflamação/complicações , Choque Hemorrágico/complicações , Tromboembolia Venosa/etiologia , Adulto , Anticoagulantes/uso terapêutico , Citocinas/metabolismo , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Método Simples-Cego , Estados Unidos , Tromboembolia Venosa/metabolismo , Adulto JovemRESUMO
BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study evaluated the effects of plasma and platelets on hemostasis and mortality after hemorrhage. The pulmonary consequences of resuscitation strategies that mimic whole blood, remain unknown. METHODS: A secondary analysis of the PROPPR study was performed. Injured patients predicted to receive a massive transfusion were randomized to 1:1:1 versus 1:1:2 plasma-platelet-red blood cell ratios at 12 Level I North American trauma centers. Patients with survival >24âh, an intensive care unit (ICU) stay, and a recorded PaO2/FiO2â(P/F) ratio were included. Acute respiratory distress syndrome (ARDS) was defined as a P/F ratioâ<â200, with bilateral pulmonary infiltrates, and adjudicated by investigators. RESULTS: Four hundred fifty-four patients were reviewed (230 received 1:1:1, 224 1:1:2). Age, sex, injury mechanism, and regional abbreviated injury scale (AIS) scores did not differ between cohorts. Tidal volume, positive end-expiratory pressure, and lowest P/F ratio did not differ. No significant differences in ARDS rates (14.8% vs. 18.4%), ventilator-free (24 vs. 24) or ICU-free days (17.5 vs. 18), hospital length of stay (22 days vs. 18 days), or 30-day mortality were found (28% vs. 28%). ARDS was associated with blunt injury (OR 3.61 [1.53-8.81] Pâ<â0.01) and increasing chest AIS (OR 1.40 [1.15-1.71] Pâ<â0.01). Each 500âmL of crystalloid infused during hours 0 to 6 was associated with a 9% increase in the rate of ARDS (OR 1.09 [1.04-1.14] Pâ<â0.01). Blood given at 0 to 6 or 7 to 24âh were not risk factors for lung injury. CONCLUSION: Acute crystalloid exposure, but not blood products, is a potentially modifiable risk factor for the prevention of ARDS following hemorrhage.