Slava Belenkiy

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.

Noninvasive Carbon Dioxide Monitoring in a Porcine Model of Acute Lung Injury Due to Smoke Inhalation and Burns

ABSTRACT In critically ill intubated patients, assessment of adequacy of ventilation relies on measuring partial pressure of arterial carbon dioxide (PaCO2), which requires invasive arterial blood gas analysis. Alternative noninvasive technologies include transcutaneous CO2 (tPCO2) and end-tidal CO2 (EtCO2) monitoring. We evaluated accuracy of tPCO2 and EtCO2 monitoring in a porcine model of acute lung injury (ALI) due to smoke inhalation and burns. Eight anesthetized Yorkshire pigs underwent mechanical ventilation, wood-bark smoke inhalation injury, and 40% total body surface area thermal injury. tPCO2 was measured with a SenTec system (SenTec AG, Therwil, Switzerland) and EtCO2 with a Capnostream-20 (Oridion Medical, Jerusalem, Israel). These values were compared with PaCO2 measurements from an arterial blood gas analyzer. Paired measurements of EtCO2-PaCO2 (n = 276) and tPCO2-PaCO2 (n = 250) were recorded in the PaCO2 range of 25 to 85 mmHg. Overlapping data sets were analyzed based on respiratory and hemodynamic status of animals. Acute lung injury was defined as PaO2/FIO2 ⩽ 300 mmHg; hemodynamic instability was defined as mean arterial pressure ⩽ 60 mmHg. Before ALI, EtCO2 demonstrated moderate correlation with PaCO2 (R2 = 0.45; P < 0.0001), which deteriorated after onset of ALI (R2 = 0.12; P < 0.0001). Before ALI, tPCO2 demonstrated moderate correlation (R2 = 0.51, P < 0.0001), which was sustained after onset of ALI (R2 = 0.78; P < 0.0001). During hemodynamic stability, EtCO2 demonstrated moderate correlation with PaCO2 (R2 = 0.44; P < 0.0001). During hemodynamic instability, EtCO2 did not correlate with PaCO2 (R2 = 0.03; P = 0.29). tPCO2 monitoring demonstrated strong correlation with PaCO2 during hemodynamic stability (R2 = 0.80, P < 0.0001), which deteriorated under hemodynamically unstable conditions (R2 = 0.39; P < 0.0001). Noninvasive carbon dioxide monitors are acceptable for monitoring trends in PaCO2 under conditions of hemodynamic and pulmonary stability. Under unstable conditions, reevaluation of patient status and increased caution in the interpretation of results are required.

Resuscitative endovascular balloon occlusion of the aorta for hemorrhage control: Past, present, and future.

D the past 5 years, resuscitative endovascular balloon occlusion of the aorta (REBOA), an endovascular technique for hemorrhage control and resuscitation, has been reappraised in large animal models and increasingly used in clinical care. This review provides a historical perspective on the development of REBOA and presents a summary of clinical and translational research spearheading further advances and transformation of the technology. Hemorrhage is an important cause of mortality worldwide in both civilian and military trauma patients. Recently, a new definition of noncompressible torso hemorrhage (NCTH) was introduced; it includes bleeding into the chest, abdominal cavity, and/or pelvis, which is difficult or impossible to control with direct pressure. In their recent review of the epidemiology of US combat fatalities in Iraq and Afghanistan, Eastridge et al. determined that among the potentially survivable injuries seen on the battlefield before arrival at a medical treatment facility, 91% of deaths were caused by truncal (67.3%), junctional (19.2%), and extremity (13.5%) hemorrhage. A similar percentage (85.5%) was cited in a recent British study. Combat-related trauma differs in several important respects from that observed in the civilian setting in that the former consists of more severe injuries with a higher incidence of penetrating and explosivemechanisms. However, even in the civilian environment, mortality from NCTH is high at approximately 45%. With advancements in the understanding of the pathophysiology of hemorrhage and resuscitation coupled with technological improvements, more patients with NCTH survive to hospital admission. Emergency resuscitative thoracotomy is one option for the treatment of exsanguination from NCTH, with a history much longer than that of REBOA (Fig. 1). The purpose of this procedure is threefold. First, it allows for control of bleeding from chest injuries and drainage of pericardial tamponade if present. Second, the procedure increases cerebral and coronary blood flow and allows initiation of direct cardiac massage. Third, cross-clamping of the descending aorta permits some degree of control of noncompressible torso, junctional, and even extremity hemorrhage. In 2001, the American College of Surgeons published practice management guidelines for emergency department thoracotomy (EDT), which reported an overall survival rate of approximately 8%. The rate was higher for penetrating injuries (approximately 11%) and as high as 31% for penetrating cardiac injuries. The American College of Surgeons guidelines recommended EDT for trauma patients with penetrating thoracic injuries or exsanguinating abdominal hemorrhage and signs of life. Clearly, EDT has an important role to play in a subset of critically injured patients. However, since EDT is highly invasive and exposes providers to a risk of blood-borne diseases, REBOA is an attractive alternative that offers a lower risk of exposure. What are the origins of the REBOA concept?

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.

Evaluation of the Cytosorb™ Hemoadsorptive Column in a Pig Model of Severe Smoke and Burn Injury.

Introduction: Host inflammatory response to any form of tissue injury, including burn, trauma, or shock, has been well documented. After significant burns, cytokines can increase substantially within the first 24 h after injury and may contribute to subsequent organ failure. Hemoadsorption by cytokine-adsorbing columns may attenuate this maladaptive response, thereby improving outcomes. The aim of this study was to investigate the feasibility, technical safety, and efficacy of cytokine and myoglobin removal by early use of a cytokine absorbing column (CytoSorb) in a porcine model of smoke inhalation and burn injury. Methods: Anesthetized female Yorkshire pigs (n = 15) were injured by wood bark smoke inhalation and a 40% total body surface area deep burn and observed for 72 h or death. The animals were randomized to hemoadsorption treatment (n = 9) or a sham group (n = 6) before injury. A 6-h hemoadsorption or sham session was performed on days one, two, and three. Serum cytokines (IL-1b, IL-6, IL-8, IL-10, TNF-alpha) and myoglobin were measured systemically, locally in bronchoalveolar lavage fluid and also in circulating blood before and after the adsorbing column to evaluate single pass clearance by the device. Results: Hemoadsorption caused significant removal of IL-1b, IL-6, IL-10, and myoglobin across the device mainly during the first run, ranging from 22% for IL-6 to 29% for IL-1b and 41% removal rates for myoglobin after 15 min of treatment. Systemic cytokine or myoglobin serum concentrations did not change. Conclusions: In a porcine model of smoke and burn injury, hemoadsorption using the CytoSorb cartridge did not result in significant systemic or pulmonary reductions in the measured cytokines or myoglobin despite efficient transmembrane reductions. Further investigations are needed to optimize the efficiency of mediator clearance to affect both circulating levels and clinically relevant outcomes.

Modular extracorporeal life support: effects of ultrafiltrate recirculation on the performance of an extracorporeal carbon dioxide removal device

The combination of extracorporeal carbon dioxide removal (ECCO2R) and hemofiltration is a possible therapeutic strategy for patients needing both lung and renal support. We tested the effects of the recirculation of ultrafiltrate on membrane lung (ML) CO2 removal (VCO2ML). Three conscious, spontaneously breathing sheep were connected to a commercially produced ECCO2R device (Hemolung; Alung Technologies, Pittsburgh, PA) with a blood flow of 250 ml/min and a gas flow of 10 L/min. A hemofilter (NxStage, NxStage Medical, Lawrence, MA) was interposed in series after the ML. Ultrafiltrate flow was generated and recirculated before the ML. We tested four ultrafiltrate flows (0, 50, 100, and 150 ml/min) for 25 min each, eight times per animal, resulting in 24 randomized test repetitions. We recorded VCO2ML, hemodynamics and ventilatory variables, and natural lung CO2 transfer (VCO2NL) and collected arterial and circuitry blood samples. VCO2ML was unchanged by application of ultrafiltrate recirculation (40.5 ± 4.0, 39.7 ± 4.2, 39.8 ± 4.2, and 39.2 ± 4.1 ml/min, respectively, at ultrafiltrate flow of 0, 50, 100, and 150 ml/min). Minute ventilation, respiratory rate, VCO2NL, and arterial blood analyses were not affected by ultrafiltrate recirculation. In the tested configuration, ultrafiltrate recirculation did not affect VCO2ML. This modular technology may provide a suitable platform for coupling CO2 removal with various forms of blood purification.

In vivo detection of inhalation injury in large airway using three-dimensional long-range swept-source optical coherence tomography

Abstract. We report on the feasibility of using long-range swept-source optical coherence tomography (OCT) to detect airway changes following smoke inhalation in a sheep model. The long-range OCT system (with axial imaging range of 25 mm) and probe are capable of rapidly obtaining a series of high-resolution full cross-sectional images and three-dimensional reconstructions covering 20-cm length of tracheal and bronchial airways with airway diameter up to 25 mm, regardless of the position of the probe within the airway lumen. Measurements of airway thickness were performed at baseline and postinjury to show mucosal thickness changes following smoke inhalation.

Enhanced Extracorporeal CO2 Removal by Regional Blood Acidification: Effect of Infusion of Three Metabolizable Acids.

Acidification of blood entering a membrane lung (ML) with lactic acid enhances CO2 removal (VCO2ML). We compared the effects of infusion of acetic, citric, and lactic acids on VCO2ML. Three sheep were connected to a custom-made circuit, consisting of a Hemolung device (Alung Technologies, Pittsburgh, PA), a hemofilter (NxStage, NxStage Medical, Lawrence, MA), and a peristaltic pump recirculating ultrafiltrate before the ML. Blood flow was set at 250 ml/min, gas flow (GF) at 10 L/min, and recirculating ultrafiltrate flow at 100 ml/min. Acetic (4.4 M), citric (0.4 M), or lactic (4.4 M) acids were infused in the ultrafiltrate at 1.5 mEq/min, for 2 hours each, in randomized fashion. VCO2ML was measured by the Hemolung built-in capnometer. Circuit and arterial blood gas samples were collected at baseline and during acid infusion. Hemodynamics and ventilation were monitored. Acetic, citric, or lactic acids similarly enhanced VCO2ML (+35%), from 37.4 ± 3.6 to 50.6 ± 7.4, 49.8 ± 5.6, and 52.0 ± 8.2 ml/min, respectively. Acids similarly decreased pH, increased pCO2, and reduced HCO3− of the post-acid extracorporeal blood sample. No significant effects on arterial gas values, ventilation, or hemodynamics were observed. In conclusion, it is possible to increase VCO2ML by more than one-third using any one of the three metabolizable acids.

Early Utilization of Extracorporeal CO2 Removal for Treatment of Acute Respiratory Distress Syndrome Due to Smoke Inhalation and Burns in Sheep.

Introduction: In thermally injured patients, inhalation injury is often associated with acute respiratory distress syndrome (ARDS), and is an independent predictor of increased morbidity and mortality. Extracorporeal CO2 removal (ECCO2R) therapy offers new possibilities in protective mechanical ventilation in ARDS patients. We performed an early application of ECCO2R in mild-to-moderate ARDS in sheep ventilated in BiPAP mode. Our aim was to investigate its effect on severity of the lung injury. Material and Methods: Non-pregnant farm-bred ewes (n = 15) were anesthetized and injured by a combination of wood-bark smoke inhalation and a 40% total body surface area full-thickness burn, and were observed for 72 h or death. The animals were randomized to a Hemolung group (n = 7) or a Control group (n = 8) at time of ARDS onset. ECCO2R was performed in the Hemolung group after onset of ARDS. Histopathology, CT scans, systemic and pulmonary variables, and CO2 removal were examined. Results: Early application of ECCO2R therapy with Hemolung in spontaneously breathing sheep decreased PaCO2 significantly, while the device removed about 70 mL of CO2 per minute. This did not result in lower minute ventilation in the Hemolung group. Lungpathology and CT scans did not show a difference between groups. Conclusion: In an ovine model of ARDS due to smoke inhalation and burn injury, early institution of ECCO2R in spontaneously breathing animals was effective in removing CO2 and in reducing PaCO2. However, it had no effect on reducing the severity of lung injury or mortality. Further studies are necessary to detail the interaction between extracorporeal CO2 removal and pulmonary physiology.