Platelet and coagulation function before and after burn and smoke inhalation injury in sheep.

BACKGROUND: Smoke inhalation and burn injury remain a major source of morbidity and mortality. There is known dysregulation of hemostasis in burn patients, but either hypercoagulation or hypocoagulation states are reported. Sheep are an established animal model for studying burn pathology and provide robust data on hemostatic function at baseline and after injury. METHODS: After an IACUC-approved protocol, 15 sheep were anesthetized and subjected to a 40% full thickness burn with smoke inhalation. Blood was sampled at baseline, 1 day postinjury (early effects) and days 2, 3, and 4 (late effects) after injury. Assays at each timepoint assessed: hemostatic function by thromboelastography (TEG), platelet counts and function by flow cytometry and aggregometry, coagulation protein levels, and free hemoglobin. Data were analyzed by the Wilcoxon paired test (nonparametric) with significance set at less than 0.05. RESULTS: By 24 hours postinjury, platelet counts had dropped, whereas the percent activated platelets increased. Absolute platelet functional response to the agonist adenosine diphosphate (ADP) decreased, whereas response to collagen showed no significant difference. On a per platelet basis, ADP response was unchanged, whereas the collagen response was elevated. Prothrombin time and activated partial thromboplastin time were prolonged. TEG parameters decreased significantly from baseline. Fibrinogen and factor V were trending up; coagulation proteins ATIII, factors IX and X were decreased.Late effects were followed in six animals. At day 4, platelet counts remained depressed compared with baseline with a nadir at day 2; responses to agonist on a per platelet basis remained the same for ADP and stayed elevated for collagen. Platelets continued to have elevated activation levels. Fibrinogen and factor V remained significantly elevated, whereas TEG parameters and prothrombin time, factors IX and X returned to near baseline levels. CONCLUSION: Coagulation parameters and hemostasis are dysregulated in sheep after smoke inhalation and burn. By 24 hours, sheep were hypocoagulable and subsequently became hypercoagulable by day 4. These results suggest a three-stage coagulopathy in burn injuries with a known early consumptive hypercoagulable state which is followed by a relatively hypocoagulable state with increased bleeding risk and then a return to a relatively unknown hypercoagulability with increased susceptibility to thrombotic disorders.

Resuscitative endovascular balloon occlusion of the aorta (REBOA): Comparison with immediate transfusion following massive hemorrhage in swine.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is less invasive than emergency department thoracotomy for the treatment of massive hemorrhage. We evaluated the effects of REBOA on carotid blood flow (Qcarotid) in a porcine model of massive hemorrhage. We hypothesized that REBOA restores Qcarotid faster than reinfusion of blood. METHODS: Spontaneously breathing sedated Sinclair pigs underwent exponential hemorrhage of 65% total blood volume in 1 hour. They were randomized into three groups. Positive control (PC, n = 7) underwent immediate transfusion of shed blood. REBOA (n = 21) received a novel 7 Fr ER-REBOA catheter (Pryor Medical, Arvada, CO) placed into aortic Zone 1 via a femoral artery introducer for 30 minutes or 60 minutes, with transfusion either after deflation or midway through inflation. Negative control (n = 7) received no resuscitation. Qcarotid was recorded continuously using an ultrasonic flow probe. Survival and time between Qcarotid, min and both a stable maximal value (Qcarotid, max) and restoration of baseline flow (Qcarotid, new BL) were compared by Kaplan-Meier analysis. RESULTS: Median time to Qcarotid, max was 3.0 minutes in the REBOA group versus 9.6 minutes in the control group (p = 0.006). Median time to Qcarotid, new BL was 6.0 minutes in the REBOA group versus 20.5 minutes in the PC group (p = 0.11). Slope of the linear regression between Qcarotid, min and Qcarotid, new BL was 16.7 in REBOA and 10.4 in PC (p = 0.31). Four-hour survival was 95% (20 of 21) in the REBOA group versus 71% (5 of 7) in the PC group (p = 0.06) and 0% in the negative control group. CONCLUSION: REBOA resulted in the restoration of Qcarotid ("cerebrovascular resuscitation") at least as rapidly as retransfusion of shed blood, with equivalent 4-hour survival. Further studies of REBOA, to include mitigation of end-organ effects and longer follow-up, are needed.

Automated inhaled nitric oxide alerts for adult extracorporeal membrane oxygenation patient identification.

BACKGROUND: Recently, automated alerts have been used to identify patients with respiratory failure based on set criteria, which can be gleaned from the electronic medical record (EMR). Such an approach may also be useful for identifying patients with severe adult respiratory distress syndrome (ARDS) who may benefit from extracorporeal membrane oxygenation (ECMO). Inhaled nitric oxide (iNO) is a common rescue therapy for severe ARDS which can be easily tracked in the EMR, and some patients started on iNO may have indications for initiating ECMO. This case series summarizes our experience with using automated electronic alerts for ECMO team activation focused particularly on an alert triggered by the initiation of iNO. METHODS: After a brief trial evaluation, our Smart Alert system generated an automated page and e-mail alert to ECMO team members whenever a nonzero value for iNO appeared in the respiratory care section of our EMR. If iNO was initiated for severe respiratory failure, a detailed evaluation by the ECMO team determined if ECMO was indicated. For those patients managed with ECMO, we tabulated baseline characteristics, indication for ECMO, and outcomes. RESULTS: From September 2012 to July 2013, 45 iNO alerts were generated on 42 unique patients. Six patients (14%) met criteria for ECMO. Of these, four were identified exclusively by the iNO alert. At the time of the alert, the median PaO2-to-FIO2 ratio was 64 mm Hg (range, 55-107 mm Hg), the median age-adjusted oxygenation index was 73 (range, 51-96), and the median Murray score was 3.4 (range, 3-3.75), indicating severe respiratory failure. Median time from iNO alert to ECMO initiation was 81 hours (range, -2-292 hours). Survival to hospital discharge was 83% in those managed with ECMO. CONCLUSION: Automated alerts may be useful for identifying patients with severe ARDS who may be ECMO candidates. LEVEL OF EVIDENCE: Diagnostic test, level V.

Acute respiratory distress syndrome in wartime military burns: application of the Berlin criteria.

BACKGROUND: Acute respiratory distress syndrome (ARDS) prevalence and related outcomes in burned military casualties from Iraq and Afghanistan have not been described previously. The objective of this article was to report ARDS prevalence and its associated in-hospital mortality in military burn patients. METHODS: Demographic and physiologic data were collected retrospectively on mechanically ventilated military casualties admitted to our burn intensive care unit from January 2003 to December 2011. Patients with ARDS were identified in accordance with the new Berlin definition of ARDS. Subjects were categorized as having mild, moderate, or severe ARDS. Multivariate logistic regression identified independent risk factors for developing moderate-to-severe ARDS. The main outcome measure was the prevalence of ARDS in a cohort of patients burned as a result of recent combat operations. RESULTS: A total of 876 burned military casualties presented during the study period, of whom 291 (33.2%) required mechanical ventilation. Prevalence of ARDS in this cohort was 32.6%, with a crude overall mortality of 16.5%. Mortality increased significantly with ARDS severity: mild (11.1%), moderate (36.1%), and severe (43.8%) compared with no ARDS (8.7%) (p < 0.001). Predictors for the development of moderate or severe ARDS were inhalation injury (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.01-3.54; p = 0.046), Injury Severity Score (ISS) (OR, 1.04; 95% CI, 1.01-1.07; p = 0.0021), pneumonia (OR, 198; 95% CI, 1.07-3.66; p = 0.03), and transfusion of fresh frozen plasma (OR, 1.32; 95% CI, 1.01-1.72; p = 0.04). Size of burn was associated with moderate or severe ARDS by univariate analysis but was not an independent predictor of ARDS by multivariate logistic regression (p > 0.05). Age, size of burn, and moderate or severe ARDS were independent predictors of mortality. CONCLUSION: In this cohort of military casualties with thermal injuries, nearly a third required mechanical ventilation; of those, nearly one third developed ARDS, and nearly one third of patients with ARDS did not survive. Moderate and severe ARDS increased the odds of death by more than fourfold and ninefold, respectively. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.

Extracorporeal gas exchange and spontaneous breathing for the treatment of acute respiratory distress syndrome: an alternative to mechanical ventilation?*.

OBJECTIVES: Venovenous extracorporeal gas exchange is increasingly used in awake, spontaneously breathing patients as a bridge to lung transplantation. Limited data are available on a similar use of extracorporeal gas exchange in patients with acute respiratory distress syndrome. The aim of this study was to investigate the use of extracorporeal gas exchange in awake, spontaneously breathing sheep with healthy lungs and with acute respiratory distress syndrome and describe the interactions between the native lung (healthy and diseased) and the artificial lung (extracorporeal gas exchange) in this setting. DESIGN: Laboratory investigation. SETTING: Animal ICU of a governmental laboratory. SUBJECTS: Eleven awake, spontaneously breathing sheep on extracorporeal gas exchange. INTERVENTIONS: Sheep were studied before (healthy lungs) and after the induction of acute respiratory distress syndrome via IV injection of oleic acid. Six gas flow settings (1-10 L/min), resulting in different amounts of extracorporeal CO2 removal (20-100% of total CO2 production), were tested in each animal before and after the injury. MEASUREMENTS AND MAIN RESULTS: Respiratory variables and gas exchange were measured for every gas flow setting. Both healthy and injured sheep reduced minute ventilation according to the amount of extracorporeal CO2 removal, up to complete apnea. However, compared with healthy sheep, sheep with acute respiratory distress syndrome presented significantly increased esophageal pressure variations (25 ± 9 vs 6 ± 3 cm H2O; p < 0.001), which could be reduced only with very high amounts of CO2 removal (> 80% of total CO2 production). CONCLUSIONS: Spontaneous ventilation of both healthy sheep and sheep with acute respiratory distress syndrome can be controlled via extracorporeal gas exchange. If this holds true in humans, extracorporeal gas exchange could be used in awake, spontaneously breathing patients with acute respiratory distress syndrome to support gas exchange. A deeper understanding of the pathophysiology of spontaneous breathing during acute respiratory distress syndrome is however warranted in order to be able to propose extracorporeal gas exchange as a safe and valuable alternative to mechanical ventilation for the treatment of patients with acute respiratory distress syndrome.

Pressure-guided positioning of bicaval dual-lumen catheters for venovenous extracorporeal gas exchange.

PURPOSE: Bicaval dual-lumen catheters allow for single-site cannulation venovenous extracorporeal gas exchange and facilitate early mobilization of patients. Using these catheters blood is drained from the superior and inferior venae cavae, pumped through a respiratory membrane, and returned into the right atrium. The insertion of these catheters is challenging as their correct positioning is fundamental to reduce recirculation and avoid severe complications. We describe here a new technique for the positioning of bicaval dual-lumen catheters. MATERIALS AND METHODS: The right internal jugular vein was percutaneously cannulated in nine sheep. The distance between skin and tricuspid valve was measured from the point of pressure change in the waveform of a Swan-Ganz catheter being retracted from the right ventricle into the right atrium. The atrium-tricuspid valve-ventricle axis was determined by observing the fluctuations of the tip of the Swan-Ganz entering the ventricle during fluoroscopy. A bicaval dual-lumen catheter was placed on the basis of these evaluations and connected to an extracorporeal respiratory support system. RESULTS: The position of the catheter was verified at necropsy approximately 18 h after insertion. In all cases the catheter was correctly placed, with the central port situated in front of the tricuspid valve. CONCLUSIONS: The described technique may help to position bicaval dual-lumen catheters for venovenous extracorporeal gas exchange without the use of transesophageal echocardiography or contrast media during fluoroscopy.