Search

Background: Awareness of ventilator-induced lung injury contributed to increased use of extracorporeal interventions, but not immediately after injury, before acute respiratory distress syndrome (ARDS) ensues. Our objective was to evaluate the role of venovenous extracorporeal carbon dioxide removal (ECCO2R) in management of mechanically ventilated swine with smoke inhalation injury and 40% body surface area burns., Methods: Yorkshire swine (n = 29, 43.2 ± 0.5 kg) underwent anesthesia, instrumentation, severe smoke inhalation, and 40% body surface area burns, followed by 72 hours of round-the-clock intensive care unit care with mechanical ventilation, fluids, pressors, bronchoscopic cast removal, computer tomography scans, and arterial blood assays. Within 1 hour after injury, animals received ECCO2R with either MiniLung (Xenios AG, Heilbronn, Germany; n = 10) or Hemolung (ALung Technologies, Pittsburgh, PA; n = 10), or no ECCO2R in injured controls (INJC, n = 12)., Results: Immediate postinjury ECCO2R reduced minute ventilation (p < 0.001) and prevented ARDS in 37.5% of MiniLung and 11.1% of Hemolung animals. Time to ARDS (partial pressure of arterial oxygen to fraction of inspired oxygen ratio below 300) was shortest (14 ± 2.2 hours) in INJC, intermediate (21.6 ± 3.5 hours) in Hemolung (HEMO), and most delayed in MiniLung (31.1 ± 7.2 hours, p = 0.0121, log-rank test vs. INJC). Driving pressure was lower in MiniLung versus INJC (p < 0.0001) and HEMO versus INJC (p = 0.0005) at 48 hours. Extracorporeal CO2 removal reduced systemic levels of tumor necrosis factor α versus INJC., Conclusion: In swine with severe smoke inhalation and burns, immediate postinjury ECCO2R reduced ventilator settings, delayed or prevented ARDS, and reduced its severity. Proactive early percutaneous ECCO2R initiation via simplified, purpose-built devices should be considered as a low-maintenance lung injury management approach with significant disease modifying clinical benefit potential., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine ( n  = 32, 44.3 ± 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate ( n  = 10; 3 × 10 6 white blood cells and a mean of 56.6 × 10 6 platelets per dose), allogeneic MSCs ( n  = 10; 6.1 × 10 6 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals ( n  = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 ± 10 h) versus control animals (14 ± 2 h) ( P  = 0.004), reduced ARDS severity at 24 ( P  < 0.001) and 48 ( P  = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-α (tumor necrosis factor-α). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow-derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.

Integrating spontaneous breathing into mechanical ventilation (MV) can speed up liberation from it and reduce its invasiveness. On the other hand, inadequate and asynchronous spontaneous breathing has the potential to aggravate lung injury. During use of airway-pressure-release-ventilation (APRV), the assisted breaths are difficult to measure. We developed an algorithm to differentiate the breaths in a setting of lung injury in spontaneously breathing ewes. We hypothesized that differentiation of breaths into spontaneous, mechanical and assisted is feasible using a specially developed for this purpose algorithm. Ventilation parameters were recorded by software that integrated ventilator output variables. The flow signal, measured by the EVITA® XL (Lübeck, Germany), was measured every 2 ms by a custom Java-based computerized algorithm (Breath-Sep). By integrating the flow signal, tidal volume (V T ) of each breath was calculated. By using the flow curve the algorithm separated the different breaths and numbered them for each time point. Breaths were separated into mechanical, assisted and spontaneous. Bland Altman analysis was used to compare parameters. Comparing the values calculated by Breath-Sep with the data from the EVITA® using Bland-Altman analyses showed a mean bias of - 2.85% and 95% limits of agreement from - 25.76 to 20.06% for MV total . For respiratory rate (RR) RR set a bias of 0.84% with a SD of 1.21% and 95% limits of agreement from - 1.53 to 3.21% were found. In the cluster analysis of the 25th highest breaths of each group RR total was higher using the EVITA®. In the mechanical subgroup the values for RR spont and MV spont the EVITA® showed higher values compared to Breath-Sep. We developed a computerized method for respiratory flow-curve based differentiation of breathing cycle components during mechanical ventilation with superimposed spontaneous breathing. Further studies in humans and optimizing of this technique is necessary to allow for real-time use at the bedside., (© 2020. The Author(s).)

Background: Non-compressible torso hemorrhage (NCTH) is the leading cause of potentially preventable death on the battlefield. Resuscitative endovascular balloon occlusion of the aorta (REBOA) aims to restore central blood pressure and control NCTH below the balloon, but risks ischemia-reperfusion injury to distal organs when prolonged. We tested a bilobed partial REBOA catheter (pREBOA), which permits some of the blood to flow past the balloon., Methods: Female swine (n = 37, 6 groups, n = 5-8/group), anesthetized and instrumented, were exponentially hemorrhaged 50% of estimated blood volume (all except time controls [TC]). Negative controls (NC) did not receive REBOA or resuscitation. Positive controls (PC) received retransfusion after 120 min. REBOA groups received REBOA for 120 min, then retransfusion. Balloon was fully inflated in the full REBOA group (FR), and was partially inflated in partial REBOA groups (P45 and P60) to achieve a distal systolic blood pressure of 45 mm Hg or 60 mm Hg., Results: Aortic occlusion restored baseline values of proximal mean arterial pressure, cardiac output, and carotid flow in pREBOA groups. Lactate reached high values during occlusion in all REBOA groups (9.9 ± 4.2, 8.0 ± 4.1, and 10.7 ± 2.9 for P45, P60, and FR), but normalized by 6 to 12 h post-deflation in the partial groups. All TC and P60 animals survived 24 h. The NC, PC, and P45 groups survived 18.2 ± 9.5, 19.3 ± 10.6, and 21.0 ± 8.4 h. For FR animals mean survival was 6.2 ± 5.8 h, significantly worse than all other animals (P < 0.01, logrank test)., Conclusions: In this porcine model of hemorrhagic shock, animals undergoing partial REBOA for 120 min survived longer than those undergoing full occlusion., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Background and Objective: Resuscitative Endovascular Balloon Occlusion of Aorta (REBOA) has emerged as a potential life-saving maneuver for the management of non-compressible torso hemorrhage in trauma patients. Complete REBOA (cREBOA) is inherently associated with the burden of ischemia reperfusion injury (IRI) and organ dysfunction. However, the distal organ inflammation and its association with organ injury have been little investigated. This study was conducted to assess these adverse effects of cREBOA following massive hemorrhage in swine., Methods: Spontaneously breathing and consciously sedated Sinclair pigs were subjected to exponential hemorrhage of 65% total blood volume over 60 minutes. Animals were randomized into 3 groups (n = 7): (1) Positive control (PC) received immediate transfusion of shed blood after hemorrhage, (2) 30min-cREBOA (A30) received Zone 1 cREBOA for 30 minutes, and (3) 60min-cREBOA (A60) given Zone 1 cREBOA for 60 minutes. The A30 and A60 groups were followed by resuscitation with shed blood post-cREBOA and observed for 4h. Metabolic and hemodynamic effects, coagulation parameters, inflammatory and end organ consequences were monitored and assessed., Results: Compared with 30min-cREBOA, 60min-cREBOA resulted in (1) increased IL-6, TNF-α, and IL-1β in distal organs (kidney, jejunum, and liver) (p < 0.05) and decreased reduced glutathione in kidney and liver (p < 0.05), (2) leukopenia, neutropenia, and coagulopathy (p < 0.05), (3) blood pressure decline (p < 0.05), (4) metabolic acidosis and hyperkalemia (p < 0.05), and (5) histological injury of kidney and jejunum (p < 0.05) as well as higher levels of creatinine, AST, and ALT (p < 0.05)., Conclusion: 30min-cREBOA seems to be a feasible and effective adjunct in supporting central perfusion during severe hemorrhage. However, prolonged cREBOA (60min) adverse effects such as distal organ inflammation and injury must be taken into serious consideration., Competing Interests: The authors declare that they have no conflicts of interest relevant to the manuscript. Although this research was funded partially by a subcontract between Prytime Medical and the Geneva Foundation, Tacoma, WA, for the work performed at the US Army Institute of Surgical Research, the commercial founder had no role in study design, data collection, analysis and interpretation, decision to publish, or preparation of the manuscript. This also does not alter our adherence to PLOS ONE policies on sharing data and materials. None of authors served as a consultant or a board member, participated in their patent and grants application, and received stock, share or travel funds from the commercial founders.

Background: We investigated effects of mesenchymal stem cells (MSC) or low-flow extracorporeal life support (ECLS) as adjunctive treatments for acute respiratory distress syndrome (ARDS) due to inhalation injury and burns. We hypothesized that these interventions decrease histological end-organ damage., Methods: Anesthetized female swine underwent smoke inhalation injury and 40% TBSA burns, then critical care for 72h. The following groups were studied: CTR (no injury, n = 4), ICTR (injured untreated, n = 10), Allo (injured treated with allogenic MSC, n = 10), Auto (injured treated with autologous MSC, n = 10), Hemo (injured and treated with the Hemolung low flow ECLS system, n = 9), and Nova (injured and treated with the NovaLung low flow ECLS system, n = 8). Histology scores from lung, kidneys, liver, and jejunum were calculated. Data are presented as means±SEM., Results: Survival at 72h was 100% in CTR; 40% in ICTR; 50% in Allo; 90% in Auto; 33% in Hemo; 63% in Nova. ARDS developed in 0/10 CTR; 10/10 ICTR; 8/9 Hemo; 5/8 Nova; 9/10 Allo; 6/10 Auto. Diffuse alveolar damage (DAD) was present in all injured groups. MSC groups had significantly lower DAD scores than ICTR animals (Allo 26.6 ± 3.4 and Auto 18.9 ± 1.5 vs. ICTR 46.8 ± 2.1, p < 0.001). MSC groups also had lower DAD scores than ECLS animals (Allo vs. Nova, p < 0.05, Allo vs. Hemo p < 0.001, Auto vs. Nova p < 0.001, Auto vs. Hemo, p < 0.001). Kidney injury ICTR (p < 0.05) and Hemo (p < 0.01) were higher than in CTR. By logistic regression, a PaO 2 -to-FiO 2 ratio (PFR) < 300 was a function of the DAD score: logit (PFR < 300) = 0.84 + 0.072*DAD Score, odds ratio 1.074 (1.007, 1.147, p < 0.05) with a ROC AUC of 0.76, p < 0.001., Conclusion: Treatment with Auto MSC followed by Allo and then Nova were most effective in mitigating ARDS and MOF severity in this model. Further studies will elucidate the role of combination therapies of MSC and ECLS as comprehensive treatments for ARDS and MOF., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Burn injury initiates a hypermetabolic response leading to muscle catabolism and organ dysfunction but has not been well-characterized by high-throughput metabolomics. We examined changes in metabolism over the first 72 h post-burn using proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy and serum from a porcine model of severe burn injury. We sought to quantify the changes in metabolism that occur over time in response to severe burn and smoke inhalation in this preliminary study. Fifteen pigs received 40% total body surface area (TBSA) burns with additional pine bark smoke inhalation. Arterial blood was drawn at baseline (pre-burn) and every 24 h until 72 h post-injury or death. The aqueous portion of each serum sample was analyzed using 1 H-NMR spectroscopy and metabolite concentrations were used for principal component analysis (PCA). Thirty-eight metabolites were quantified in 39 samples. Of these, 31 showed significant concentration changes over time ( p < 0.05). PCA revealed clustering of samples by time point on a 2D scores plot. The first 48 h post-burn were characterized by high concentrations of histamine, alanine, phenylalanine, and tyrosine. Later timepoints were characterized by rising concentrations of 2-hydroxybutyrate, 3-hydroxybutyrate, acetoacetate, and isovalerate. No significant differences in metabolism related to mortality were observed. Our work highlights the accumulation of organic acids resulting from fatty acid catabolism and oxidative stress. Further studies will be required to relate accumulation of the four organic carboxylates identified in this analysis to outcomes from burn injury.

Background: Smoke inhalation injury (SII) causes 30% to 40% mortality and will increase as a cause of death during prolonged field care. We used a combat relevant model of acute respiratory distress syndrome due to SII to study temporal changes in ventilation-perfusion (V/Q) matching, computed tomography (CT) scan data, and histopathology and hypothesized that SII leads to increase in shunt (Qshunt), V/Q mismatch, lung consolidation, and diffuse alveolar damage., Methods: Swine received severe SII and airway pressure release ventilation (APRV, n = 6), or conventional ARDSNet mechanical ventilation (MV) (CMV, n = 8). A control group without injury received volume controlled MV (CTRL, n = 6), The multiple inert gas elimination technique and CT were performed at baseline (BL), 0.5 hours, 1 hours, 2 hours, 24 hours, and 48 hours after injury. Diffuse alveolar damage scoring was performed post mortem. Significance at p less than 0.05: APRV versus CTRL; CMV versus CTRL; APRV versus CMV*; denotes changes versus BL., Results: (1) SII caused increases in Qshunt more so in APRV than CMV group. Qshunt did not change in CTRL. (2) PaO2-to-FIO2 ratio (PFR) was lower in APRV versus CTRL at 2 hours (375 ± 62‡ vs. 549 ± 40) and 24 hours (126 ± 34‡* vs. 445 ± 5) and 48 hours (120 ± 41‡& vs. 430 ± 13). In CMV animals, PFR was lower versus CTRL and BL at 24 hours (238 ± 33) and 48 hours (98 ± 27). Qshunt correlated with PFR (r = 0.75, p < 0.0001, APRV and (r = 0.65, p < 0.0001, CMV). CT showed decrease in normally aerated lung, while poorly and nonaerated lung increased., Conclusion: Smoke inhalation injury leads to early development of shunt, V/Q mismatch, lung consolidation, and diffuse alveolar damage. These data substantiate the need for new point of injury interventions in the prolonged field care setting., Level of Evidence: Animal research.

Background: The prevalence of acute respiratory distress syndrome (ARDS) in mechanically ventilated burn patients is 33%, with mortality varying from 11-46% depending on ARDS severity. Despite the new Berlin definition for ARDS, prompt bedside diagnosis is lacking. We developed and tested a bedside technique of fiberoptic-bronchoscopy-based optical coherence tomography (OCT) measurement of airway mucosal thickness (MT) for diagnosis of ARDS following smoke inhalation injury (SII) and burns., Methods: 16 female Yorkshire pigs received SII and 40% thermal burns. OCT MT and PaO 2 -to-FiO 2 ratio (PFR) measurements were taken at baseline, after injury, and at 24, 48, and 72h after injury., Results: Injury led to thickening of MT which was sustained in animals that developed ARDS. Significant correlations were found between MT, PFR, peak inspiratory pressure (PIP), and total infused fluid volume., Conclusions: OCT is a useful tool to quantify MT changes in the airway following SII and burns. OCT may be effective as a diagnostic tool in the early stages of SII-induced ARDS and should be tested in humans., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

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.

Purpose: Compare virtual bronchoscopy (VB) to fiberoptic bronchoscopy (FOB) for scoring smoke inhalation injury (SII)., Methods: Swine underwent computerized tomography (CT) with VB and FOB before (0) and 24 and 48 h after SII. VB and FOB images were scored by 5 providers off line., Results: FOB and VB scores increased over time (p<0.001) with FOB scoring higher than VB at 0 (0.30±0.79 vs. 0.03±0.17), 24 h (4.21±1.68 vs. 2.47±1.50), and 48h (4.55±1.83 vs. 1.94±1.29). FOB and VB showed association with PaO2-to-FiO2 ratios (PFR) with areas under receiver operating characteristic curves (ROC): for PFR≤300, VB 0.830, FOB 0.863; for PFR≤200, VB 0.794, FOB 0.825; for PFR≤100, VB 0.747, FOB 0.777 (all p<0.001). FOB showed 80.3% specificity, 77% sensitivity, 88.8% negative-predictive value (NPV), and 62.3% positive-predictive value (PPV) for PFR≤300 and VB showed 67.2% specificity, 85.5% sensitivity, 91.3% NPV, and 53.4% PPV., Conclusions: VB provided similar injury severity scores to FOB, correlated with PFR, and reliably detected airway narrowing. VB performed during admission CT may be a useful screening tool specifically to demonstrate airway narrowing induced by SII., (Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.)

Hemorrhagic shock (HS) is a setting in which both pulmonary and cutaneous perfusion may be impaired. The goals of this study were to evaluate the relationship between end-tidal (etCO2), transcutaneous (tPCO2), arterial carbon dioxide (PaCO2) and lactate during lethal HS and to assess the effect of progressive HS on those variables and on a new variable, the noninvasive CO2 gradient ([NICO2G] or the difference between tPCO2 and etCO2). Ten consciously sedated swine were hemorrhaged, by means of a computerized exponential protocol, of up to 80% estimated blood volume for 20 min. End-tidal carbon dioxide, tPCO2, PaCO2, and lactate measurements were taken at baseline and every 5 min thereafter, that is, after 25%, 44%, and 62% total blood volume hemorrhage (TBVH) and at cardiac arrest. Cardiac arrest occurred on average at 67% TBVH. Data were analyzed by linear regression and one-way repeated-measures analysis of variance and are presented as means ± SD. Forty-nine paired measurements were made. There was no overall relationship between NICO2 variables and PaCO2: PaCO2 vs. tPCO2 (r2 = 0.002, P = 0.78); PaCO2 vs. etCO2 (r2 = 0.0002, P = 0.93). Rather, NICO2G increased at each level of blood loss: 4.0 ± 24.9 at baseline, 6.3 ± 35.7 at 25% TBVH, 25.0 ± 37.6 at 44% TBVH, 55.0 ± 33.9 at 62% TBVH, and 70.0 ± 33.2 at cardiac arrest (P < 0.05). Similarly, tPCO2 increased and etCO2 decreased at each level. Linear regression of NICO2G and lactate showed a better correlation than was observed for the other two variables: NICO2G, r2 = 0.58; tPCO2, r2 = 0.46; etCO2, r2 = 0.26. During HS, NICO2 monitors lose accuracy for approximating the PaCO2 but gain usefulness as hemodynamic monitors. Also, by combining data from two different organ systems, NICO2G demonstrated improved correlation with lactate than did either etCO2 or tPCO2 alone.

Purpose: We found that heart rate (HR) complexity metrics such as sample entropy (SampEn) identified patients with trauma receiving lifesaving interventions (LSIs). We now aimed (1) to test a multiscale entropy (MSE) index, (2) to compare it to single-scale measures including SampEn, and (3) to assess different parameter values for calculation of SampEn and MSE., Methods: This was a study of combat casualties in an emergency department in Iraq. Electrocardiograms of 70 acutely injured adults were recorded. Twelve underwent LSIs and 58 did not. Lifesaving interventions included endotracheal intubation (9), tube thoracostomy (9), and emergency transfusion (4). From each electrocardiogram, a segment of 800 consecutive beats was selected. Offline, R waves were detected and R-to-R interval time series were generated. Sample entropy, MSE, and time-domain measures of HR variability (mean HR, SD, the proportion of pairs of consecutive NN intervals that differ by more than 20 and 50 milliseconds, square root of the mean of the squares of differences between adjacent NN intervals) were computed., Results: Differences in mean HR (LSI: 111 ± 33, non-LSI: 90 ± 17 beats/min) were not significant. Systolic arterial pressure was statistically but not clinically different (LSI: 123 ± 19, non-LSI: 135 ± 19 mm Hg). Sample entropy (LSI: 0.90 ± 0.42, non-LSI: 1.19 ± 0.35; P < .05) and MSE index (LSI: 2.58 ± 2.55, non-LSI: 5.67 ± 2.48; P < .001) differed significantly., Conclusions: Complexity of HR dynamics over a range of time scales was lower in high-risk than in low-risk combat casualties and outperformed traditional vital signs., (© 2013.)

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 (R = 0.45; P < 0.0001), which deteriorated after onset of ALI (R = 0.12; P < 0.0001). Before ALI, tPCO2 demonstrated moderate correlation (R = 0.51, P < 0.0001), which was sustained after onset of ALI (R = 0.78; P < 0.0001). During hemodynamic stability, EtCO2 demonstrated moderate correlation with PaCO2 (R = 0.44; P < 0.0001). During hemodynamic instability, EtCO2 did not correlate with PaCO2 (R = 0.03; P = 0.29). tPCO2 monitoring demonstrated strong correlation with PaCO2 during hemodynamic stability (R = 0.80, P < 0.0001), which deteriorated under hemodynamically unstable conditions (R = 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.

Objectives: Mechanical ventilation is injurious to the lung. Use of lung-protective strategies may complicate patient management, motivating a search for better lung-replacement approaches. We investigated the ability of a novel extracorporeal venovenous CO2 removal device to reduce minute ventilation while maintaining normocarbia., Design: Prospective animal study., Setting: Government laboratory animal intensive care unit., Subjects: Seven sedated swine., Interventions: Tracheostomy, volume-controlled mechanical ventilation, and 72 hrs of round-the-clock intensive care unit care. A 15-F dual-lumen catheter was inserted in the external jugular vein and connected to the Hemolung, an extracorporeal pump-driven venovenous CO2 removal device. Minute ventilation was reduced, and normocarbia (Paco2 35-45 mm Hg) maintained. Heparinization was maintained at an activated clotting time of 150-180 secs., Measurements and Main Results: Minute ventilation (L/min), CO2 removal by Hemolung (mL/min), Hemolung blood flow, O2 consumption (mL/min), CO2 production by the lung (mL/min), Paco2, and plasma-free hemoglobin (g/dL) were measured at baseline (where applicable), 2 hrs after device insertion, and every 6 hrs thereafter. Minute ventilation was reduced from 5.6 L/min at baseline to 2.6 L/min 2 hrs after device insertion and was maintained at 3 L/min until the end of the study. CO2 removal by Hemolung remained steady over 72 hrs, averaging 72 ± 1.2 mL/min at blood flows of 447 ± 5 mL/min. After insertion, O2 consumption did not change; CO2 production by the lung decreased by 50% and stayed at that level (p < .001). As the arterial PCO2 rose or fell, so did CO2 removal by Hemolung. Plasma-free hemoglobin did not change., Conclusions: Venovenous CO2 removal enabled a 50% reduction in minute ventilation while maintaining normocarbia and may be an effective lung-protective adjunct to mechanical ventilation.

Objective: To determine whether lower complexity of interbreath interval as measured with nonlinear analysis techniques will identify patients who fail to separate from mechanical ventilation after 30-minute spontaneous breathing trials (SBTs)., Methods: Respiratory waveforms from SBT of patients in surgical or burn intensive care units were recorded for later analysis. The decision to extubate was made by attending physician. Extubated patients were observed for 48 hours; during this time, reintubation or noninvasive positive pressure ventilation was considered as a failure. Analysis of waveform data by software was performed post hoc. Sample entropy (SampEn) and other nonlinear measures were 48 hours of extubation., Results: Thirty-two patients (24 burn, 8 trauma/surgical admissions; mean age, 40.2 +/- 16.9 years; 26 men and 6 women) who were intubated >24 hours were extubated after SBT. Twenty-four patients were successfully separated from mechanical ventilation and eight failed. Age, gender, and mechanism of injury did not influence outcome. SampEn calculated for the two groups presented in this study was different with the cohort that failed extubation having a lower mean value (1.35 +/- 0.39 vs. 1.87 +/- 0.27; p < 0.001). Other nonlinear metrics were moved in concert with SampEn. The stationarity in the respiratory signal was not different between groups., Conclusion: In intubated patients, the interbreath interval in those who were successfully separated from mechanical ventilation was more irregular than those who failed, as measured by nonlinear techniques. When available at bedside, these metrics may be useful markers of pulmonary health and assist in clinical decision making.

Background: Traditional vital signs such as heart rate, blood pressure, and oxygen saturation are not ideal for timely and accurate assessment of physiologic status after trauma (TR) and hemorrhagic shock (HS). Analysis of the complex beat-to-beat variability present in the heart-rate time series has been proposed as a "new vital sign" in this setting. We determined the effect of chest TR and HS on heart-rate complexity (HRC) in a porcine model., Methods: Anesthetized swine in group II (n = 20) underwent blunt right chest TR with a modified captive-bolt stunner; then, 10 minutes later, hemorrhage of 12 mL/kg over 10 minutes, followed by resuscitation with lactated Ringer's solution, and reinfusion of blood. Group I (n = 15) served as time controls. Two hundred beat sections of EKG waveforms were analyzed at 7 time points: at baseline, after TR, immediately after hemorrhage (HS), and 1 hour, 2 hours, 4 hours, and 5 hours after HS. Several computationally different measures of HRC were calculated, including sample entropy, similarity of distribution, and point correlation dimension., Results: HRC was decreased after TR, HS, and at 1 hour, manifested by decreased sample entropy and point correlation dimension and increased similarity of distribution. These HRC measures were all restored by resuscitation., Conclusions: Several independent measures demonstrated decreased HRC after combined TR/HS and restored HRC with resuscitation. Complexity analysis may be useful for diagnosis of TR/HS and for monitoring resuscitation.

The objective of this study was to investigate early changes in oxygenation by means of the multiple inert gas elimination technique and in coagulation by means of thromboelastography (TEG) after right-sided pulmonary contusion (PC) in swine. Anesthetized swine (group 1; n = 8) sustained a right-chest PC by a captive-bolt stunner. Multiple inert gas elimination technique, TEG, and thoracic computed tomography (CT) scans were performed before and 10, 30, 60, and 120 min after injury. Three-dimensional CT scan reconstruction enabled measurement of volumes of poorly (Vol(Poor)) and nonaerated (Vol(Non)) lung. Eight animals (group 0) were used as uninjured controls. Pulmonary contusion led to sustained tachycardia and transient hypotension. Partial pressure of arterial oxygen (PaO2) decreased from 83.9 +/- 4.2 mmHg at baseline to 51.3 +/- 2.8 mmHg 10 min after PC (P < 0.001). Vol(Poor) and Vol(Non) on the right increased significantly after PC, followed by gradual progression in injury marked by decreased Vol(Poor) and increased Vol(Non). By the multiple inert gas elimination technique, blood flow to the true shunt compartment increased from 4.4% +/- 1.0% at baseline to 21.2% +/- 4.9% 10 min after PC, P < 0.001, peaked at 33.2% +/- 7.5% 30 min after PC, P < 0.001, and remained significantly higher compared with controls. Transient increase in blood flow to low and very low ventilation-perfusion (V/Q) compartments was also seen. Clot reaction time and formation rate by TEG increased at 2 h after PC. True shunt is the major cause of hypoxemia after PC, but V/Q mismatch also contributes significantly early after injury. By CT, PC leads to significant loss of functional lung volume on the side of injury. A mild hypocoagulable state was identified 2 h after injury.

Heart rate complexity (HRC) is an emerging "new vital sign" for critically ill and injured patients. Traditionally, 800-beat data sets have been used to calculate HRC variables, thus limiting their practical use in an emergency. We sought to investigate whether data set reductions diminish the use of HRC to predict mortality in prehospital trauma patients. Ectopy-free, 800-beat sections of electrocardiogram (EKG) were collected from 31 prehospital trauma patients during their helicopter transport to a level 1 trauma center. Twenty patients survived (survivors) and 11 died (nonsurvivors) after admission. HRC was assessed via approximate entropy (ApEn), sample entropy (SampEn), and similarity of distributions (SOD). The amplitude of high-frequency oscillations was measured via the method of complex demodulation. This analysis was repeated in data sets of 800, 600, 400, 200, and 100 beats. For 800 beats, ApEn and SampEn were lower in nonsurvivors than in survivors, and SOD was higher. With data set reduction, ApEn in survivors and nonsurvivors gradually approached each other but remained different until the 200-beat dataset. Sample entropy did not change with data shortening and remained lower in nonsurvivors in all data sets. Similarity of distributions was nearly constant within groups for all data sets and discriminated survivors from nonsurvivors in 800- and 100-beat data sets. High-frequency amplitude distinguished survivors from nonsurvivors in 400-, 200-, and 100-beat data sets. Logistic regression was performed for the 800-, 200-, and 100-beat data sets, retaining SampEn as a predictor of mortality (area under the receiver-operating-characteristic curves, 0.821-0.895). HRC decreased in nonsurvivors versus survivors. This finding was confirmed for data sets as short as 100 beats by computationally different metrics. SampEn, SOD, and complex demodulation were relatively unaffected by data set reduction. These metrics may be useful for rapid identification of trauma patients with potentially lethal injuries using short EKG data sets.