Validation of Preload Assessment Technologies at Altitude in a Porcine Model of Hemorrhage.

INTRODUCTION: Dynamic preload assessment measures including pulse pressure variation (PPV), stroke volume variation (SVV), pleth variability index (PVI), and hypotension prediction index (HPI) have been utilized clinically to guide fluid management decisions in critically ill patients. These values aid in the balance of correcting hypotension while avoiding over-resuscitation leading to respiratory failure and increased mortality. However, these measures have not been previously validated at altitude or in those with temporary abdominal closure (TAC). METHODS: Forty-eight female swine (39 ± 2 kg) were separated into eight groups (n = 6) including all combinations of flight versus ground, hemorrhage versus no hemorrhage, and TAC versus no TAC. Flight animals underwent simulated aeromedical evacuation via an altitude chamber at 8000 ft. Hemorrhagic shock was induced via stepwise hemorrhage removing 10% blood volume in 15-min increments to a total blood loss of 40% or a mean arterial pressure of 35 mmHg. Animals were then stepwise transfused with citrated shed blood with 10% volume every 15 min back to full blood volume. PPV, SVV, PVI, and HPI were monitored every 15 min throughout the simulated aeromedical evacuation or ground control. Blood samples were collected and analyzed for serum levels of serum IL-1ß, IL-6, IL-8, and TNF-α. RESULTS: Hemorrhage groups demonstrated significant increases in PPV, SVV, PVI, and HPI at each step compared to nonhemorrhage groups. Flight increased PPV (P = 0.004) and SVV (P = 0.003) in hemorrhaged animals. TAC at ground level increased PPV (P < 0.0001), SVV (P = 0.0003), and PVI (P < 0.0001). When TAC was present during flight, PPV (P = 0.004), SVV (P = 0.003), and PVI (P < 0.0001) values were decreased suggesting a dependent effect between altitude and TAC. There were no significant differences in serum IL-1ß, IL-6, IL-8, or TNF-α concentration between injury groups. CONCLUSIONS: Based on our study, PPV and SVV are increased during flight and in the presence of TAC. Pleth variability index is slightly increased with TAC at ground level. Hypotension prediction index demonstrated no significant changes regardless of altitude or TAC status, however this measure was less reliable once the resuscitation phase was initiated. Pleth variability index may be the most useful predictor of preload during aeromedical evacuation as it is a noninvasive modality.

Effectiveness of Negative Pressure Wound Therapy During Aeromedical Evacuation Following Soft Tissue Injury and Infection.

INTRODUCTION: Negative pressure wound therapy (NPWT) is utilized early after soft tissue injury to promote tissue granulation and wound contraction. Early post-injury transfers via aeromedical evacuation (AE) to definitive care centers may actually induce wound bacterial proliferation. However, the effectiveness of NPWT or instillation NPWT in limiting bacterial proliferation during post-injury AE has not been studied. We hypothesized that instillation NPWT during simulated AE would decrease bacterial colonization within simple and complex soft tissue wounds. METHODS: The porcine models were anesthetized before any experiments. For the simple tissue wound model, two 4-cm dorsal wounds were created in 34.9 ± 0.6 kg pigs and were inoculated with Acinetobacter baumannii (AB) or Staphylococcus aureus 24 hours before a 4-hour simulated AE or ground control. During AE, animals were randomized to one of the five groups: wet-to-dry (WTD) dressing, NPWT, instillation NPWT with normal saline (NS-NPWT), instillation NPWT with Normosol-R® (NM-NPWT), and RX-4-NPWT with the RX-4 system. For the complex musculoskeletal wound, hind-limb wounds in the skin, subcutaneous tissue, peroneus tertius muscle, and tibia were created and inoculated with AB 24 hours before simulated AE with WTD or RX-4-NPWT dressings. Blood samples were collected at baseline, pre-flight, and 72 hours post-flight for inflammatory cytokines interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor alpha. Wound biopsies were obtained at 24 hours and 72 hours post-flight, and the bacteria were quantified. Vital signs were measured continuously during simulated AE and at each wound reassessment. RESULTS: No significant differences in hemodynamics or serum cytokines were noted between ground or simulated flight groups or over time in either wound model. Simulated AE alone did not affect bacterial proliferation compared to ground controls. The simple tissue wound arm demonstrated a significant decrease in Staphylococcus aureus and AB colony-forming units at 72 hours after simulated AE using RX-4-NPWT. NS-NPWT during AE more effectively prevented bacterial proliferation than the WTD dressing. There was no difference in colony-forming units among the various treatment groups at the ground level. CONCLUSION: The hypoxic, hypobaric environment of AE did not independently affect the bacterial growth after simple tissue wound or complex musculoskeletal wound. RX-4-NPWT provided the most effective bacterial reduction following simulated AE, followed by NS-NPWT. Future research will be necessary to determine ideal instillation fluids, negative pressure settings, and dressing change frequency before and during AE.

Postinjury Treatment to Mitigate the Effects of Aeromedical Evacuation After Traumatic Brain Injury in a Porcine Model.

INTRODUCTION: Early aeromedical evacuation after traumatic brain injury (TBI) has been associated with worse neurologic outcomes in murine studies and military populations. The goal of this study was to determine if commonly utilized medications, including allopurinol, propranolol, or tranexamic acid (TXA), could mitigate the secondary traumatic brain injury experienced during the hypobaric and hypoxic environment of aeromedical evacuation. METHODS: Porcine TBI was induced via controlled cortical injury. Twenty nonsurvival pigs were separated into four groups (n = 5 each): TBI+25 mL normal saline (NS), TBI+4 mg propranolol, TBI+100 mg allopurinol, and TBI+1g TXA. The pigs then underwent simulated AE to an altitude of 8000 ft for 4 h with an SpO2 of 82-85% and were sacrificed 4 h later. Hemodynamics, serum cytokines, and hippocampal p-tau accumulation were assessed. An additional survival cohort was partially completed with TBI/NS (n = 5), TBI/propranolol (n = 2) and TBI/allopurinol groups (n = 2) survived to postinjury day 7. RESULTS: There were no significant differences in hemodynamics, tissue oxygenation, cerebral blood flow, or physiologic markers between treatment groups and saline controls. Transient differences in IL-1b and IL-6 were noted but did not persist. Neurological Severity Score (NSS) was significantly lower in the TBI + allopurinol group on POD one compared to NS and propranolol groups. P-tau accumulation was decreased in the nonsurvival animals treated with allopurinol and TXA compared to the TBI/NS group. CONCLUSIONS: Allopurinol, propranolol, and TXA, following TBI, do not induce adverse changes in systemic or cerebral hemodynamics during or after a simulated postinjury flight. While transient changes were noted in systemic cytokines and p-tau accumulation, further investigation will be needed to determine any persistent neurological effects of injury, flight, and pharmacologic treatment.

Oxygenation and Respiratory System Compliance Associated With Pulmonary Contusion.

BACKGROUND: Blunt pulmonary contusions are associated with severe chest injuries and are independently associated with worse outcomes. Previous preclinical studies suggest that contusion progression precipitates poor pulmonary function; however, there are few current clinical data to corroborate this hypothesis. We examined pulmonary dynamics and oxygenation in subjects with pulmonary contusions to evaluate for impaired respiratory function. METHODS: A chest injury database was reviewed for pulmonary contusions over 5 years at an urban trauma center. This database was expanded to capture mechanical ventilation parameters for the first 7 days on all patients with pulmonary contusion and who were intubated. Daily [Formula: see text]:[Formula: see text], oxygenation indexes (OI), and dynamic compliances were calculated. Pulmonary contusions were stratified by severity. The Fisher exact and chi square tests were performed on categorical variables, and Mann-Whitney U-tests were performed on continuous variables. Significance was assessed at a level of 0.05. RESULTS A TOTAL OF: 1,176 patients presented with pulmonary contusions, of whom, 301 subjects (25.6%) required intubation and had available invasive mechanical ventilation data. Of these, 144 (47.8%) had mild-moderate pulmonary contusion and 157 (52.2%) had severe pulmonary contusion. Overall injury severity score was high, with a median injury severity score of 29 (interquartile range, 22-38). The median duration of mechanical ventilation for mild-moderate pulmonary contusion was 7 d versus 10 d for severe pulmonary contusion (P = .048). All the subjects displayed moderate hypoxemia, which worsened until day 4-5 after intubation. Severe pulmonary contusion was associated with significantly worse early hypoxia on day 1 and day 2 versus mild-moderate pulmonary contusion. Severe pulmonary contusion also had a higher oxygenation index than mild-moderate pulmonary contusion. This trend persisted after adjustment for other factors, including transfusion and fluid administration. CONCLUSIONS: Pulmonary contusions played an important role in the course of subjects who were acutely injured and required mechanical ventilation. Contusions were associated with hypoxemia not fully characterized by [Formula: see text]: [Formula: see text], and severe contusions had durable elevations in the oxygenation index despite confounders.

Early Identification of Acute Lung Injury in a Porcine Model of Hemorrhagic Shock.

BACKGROUND: Acute lung injury (ALI) is a frequent complication after severe trauma. Lung-protective ventilation strategies and damage control resuscitation have been proposed for the prevention of ALI; however, there are no clinical or laboratory parameters to predict who is at risk of developing ALI after trauma. In the present study, we explored pulmonary inflammatory markers as a potential predictor of ALI using a porcine model of hemorrhagic shock. MATERIALS AND METHODS: Female swine were randomized to mechanical ventilation with low tidal volume (VT) (6 mL/kg) or high VT (12 mL/kg). After equilibration, animals underwent pressure-controlled hemorrhage (mean arterial pressure [MAP] 35 ± 5 mmHg) for 1 h, followed by resuscitation with fresh whole blood or Hextend. They were maintained at MAP of 50 ± 5 mmHg for 3 h in the postresuscitation phase. Bronchoalveolar lavage fluids were collected hourly and analyzed for inflammatory markers. Lung samples were taken, and porcine neutrophil antibody staining was used to evaluate the presence of neutrophils. ELISA evaluated serum porcine surfactant protein D levels. Sham animals were used as negative controls. RESULTS: Pigs that underwent hemorrhagic shock had higher heart rates, lower cardiac output, lower MAPs, and worse acidosis compared with sham at the early time points (P < 0.05 each). There were no significant differences in central venous pressure or pulmonary capillary wedge pressure between groups. Pulmonary neutrophil infiltration, as defined by neutrophil antibody staining on lung samples, was greater in the shock groups regardless of resuscitation fluid (P < 0.05 each). Bronchoalveolar lavage fluid neutrophil levels were not different between groups. There were no differences in levels of porcine surfactant protein D between groups at any time points, and the levels did not change over time in each respective group. CONCLUSIONS: Our study demonstrates the reproducibility of a porcine model of hemorrhagic shock that is consistent with physiologic changes in humans in hemorrhagic shock. Pulmonary neutrophil infiltration may serve as an early marker for ALI; however, the practicality of this finding has yet to be determined.

Portable mechanical ventilation with closed-loop control of inspired fraction of oxygen maintains oxygenation in the setting of hemorrhage and lung injury.

BACKGROUND: Closed-loop controllers (CLCs) embedded within portable mechanical ventilators may allow for autonomous weaning. The ability of CLCs to maintain adequate oxygenation in the setting of hemorrhage and lung injury is unknown. We hypothesized that a portable ventilator with a CLC for inspired fraction of oxygen (FIO2) could provide oxygenation in a porcine model of hemorrhage and lung injury. METHODS: Female pigs randomized to the study group (n = 6) underwent a pressure-controlled bleed (mean arterial pressure = 40 mm Hg for 30 minutes). Acute lung injury was induced by saline lung lavage followed by intentional infliction of barotrauma. Sham pigs (n = 6) underwent placement of monitoring devices without hemorrhage or lung injury. All pigs were then placed on a portable ventilator modified with a CLC algorithm, which uses feedback from pulse oximetry (SpO2) and FIO2 trends to adjust FIO2 and maintain a target SpO2 of 94% (2%). The initial FIO2 was set at 0.60. Tidal volume, positive end-expiratory pressure, rate, and inspiratory-to-expiratory ratio were constant unless changes were required clinically. RESULTS: Study pigs had lower mean arterial pressures than shams at all time points except baseline. PaO2/FIO2 ratios were less than 300 and significantly lower than both baseline values and corresponding sham values at all time points. The CLC weaned the FIO2 at a reduced rate in study pigs relative to shams with a final mean FIO2 of 0.54 and 0.29 in study and sham pigs, respectively (p < 0.05). There was a significant divergence in the study and sham FIO2 curves but no significant difference in oxygen saturation or hypoxemia. CONCLUSION: Adequate oxygenation can be maintained in the setting of hemorrhage and lung injury using a portable ventilator embedded with a CLC of FIO2 based on pulse oximetry. These devices may be valuable for providing advanced medical care in resource-limited environments.

Accuracy of noninvasive hemoglobin monitoring in patients at risk for hemorrhage.

BACKGROUND: Monitoring for acute blood loss is critical in surgical patients, and delays in identifying hemorrhage can result in poor outcomes. The current standard of care for monitoring patients at risk for bleeding is serial measurement of hemoglobin (Hgb) by standard laboratory complete blood count (CBC). Point-of-care testing (i.e., iSTAT) can be a rapid method of evaluating Hgb, and spectrophotometry-based devices (i.e., Radical-7) offer the advantages of being continuous and noninvasive. We sought to evaluate the accuracy of Radical-7 and iSTAT in measuring Hgb and assessing for blood loss when compared with the criterion standard CBC. METHODS: Adult patients at risk for hemorrhage admitted to the surgical intensive care unit of a tertiary referral, Level I trauma center were eligible for this study. Serial CBC Hgb measurements were drawn as clinically indicated. The Radical-7 device was placed on the patient for noninvasive Hgb measurements (SpHb), and at each CBC measurement, concurrent iSTAT Hgb measurements were obtained. Bland-Altman analysis was used to compare the three methods of measuring Hgb with accuracy defined as measurements within 1.0-g/dL CBC Hgb. Concordance measurements were also performed to compare trends between values. RESULTS: Eighty-eight patients were enrolled and underwent 572 CBC measurements. Bland-Altman analysis of SpHb versus CBC resulted in an estimated bias of 1.49 g/dL, with 95% limits of agreement of -2.2 g/dL to 5.0 g/dL. iSTAT versus CBC resulted in an estimated bias of -0.63 g/dL, with 95% limits of agreement of -3.4 g/dL to 2.2 g/dL. Changes in SpHb had concordance with CBC Hgb 60% of the time, compared with 76% for iSTAT versus CBC CONCLUSION: Radical-7 SpHb was inaccurate when compared with CBC Hgb levels, and serial SpHb achieved concordance with CBC Hgb 60% of the time. As such, the clinical utility of Radical-7 as a rapid, noninvasive predictor of acute hemorrhage may be limited. LEVEL OF EVIDENCE: Diagnostic study, level II; care management, level III.

Managing endotracheal tube cuff pressure at altitude: a comparison of four methods.

BACKGROUND: Ascent to altitude results in the expansion of gases in closed spaces. The management of overinflation of the endotracheal tube (ETT) cuff at altitude is critical to prevent mucosal injury. METHODS: We continuously measured ETT cuff pressures during a Critical Care Air Transport Team training flight to 8,000-ft cabin pressure using four methods of cuff pressure management. ETTs were placed in a tracheal model, and mechanical ventilation was performed. In the control ETT, the cuff was inflated to 20 mm Hg to 22 mm Hg and not manipulated. The manual method used a pressure manometer to adjust pressure at cruising altitude and after landing. A PressureEasy device was connected to the pilot balloon of the third tube and set to a pressure of 20 mm Hg to 22 mm Hg. The final method filled the balloon with 10 mL of saline. Both size 8.0-mm and 7.5-mm ETT were studied during three flights. RESULTS: In the control tube, pressure exceeded 70 mm Hg at cruising altitude. Manual management corrected for pressure at altitude but resulted in low cuff pressures upon landing (<10 mm Hg). The PressureEasy reduced the pressure change to a maximum of 36 mm Hg, but on landing, cuff pressures were less than 15 mm Hg. Saline inflation ameliorated cuff pressure changes at altitude, but initial pressures were 40 mm Hg. CONCLUSION: None of the three methods using air inflation managed to maintain cuff pressures below those associated with tracheal damage at altitude or above pressures associated with secretion aspiration during descent. Saline inflation minimizes altitude-related alteration in cuff pressure but creates excessive pressures at sea level. New techniques need to be developed.