Esophageal pressure monitoring and its clinical significance in severe blast lung injury.

Background: The incidence of blast lung injury (BLI) has been escalating annually due to military conflicts and industrial accidents. Currently, research into these injuries predominantly uses animal models. Despite the availability of various models, there remains a scarcity of studies focused on monitoring respiratory mechanics post-BLI. Consequently, our objective was to develop a model for monitoring esophageal pressure (Pes) following BLI using a biological shock tube (BST), aimed at providing immediate and precise monitoring of respiratory mechanics parameters post-injury. Methods: Six pigs were subjected to BLI using a BST, during which Pes was monitored. We assessed vital signs; conducted blood gas analysis, hemodynamics evaluations, and lung ultrasound; and measured respiratory mechanics before and after the inflicted injury. Furthermore, the gross anatomy of the lungs 3 h post-injury was examined, and hematoxylin and eosin staining was conducted on the injured lung tissues for further analysis. Results: The pressure in the experimental section of the BST reached 402.52 ± 17.95 KPa, with a peak pressure duration of 53.22 ± 1.69 ms. All six pigs exhibited an anatomical lung injury score ≥3, and pathology revealed classic signs of severe BLI. Post-injury vital signs showed an increase in HR and SI, along with a decrease in MAP (p < 0.05). Blood gas analyses indicated elevated levels of Lac, CO2-GAP, A-aDO2, HB, and HCT and reduced levels of DO2, OI, SaO2, and OER (p < 0.05). Hemodynamics and lung ultrasonography findings showed increased ELWI, PVPI, SVRI, and lung ultrasonography scores and decreased CI, SVI, GEDI, and ITBI (p < 0.05). Analysis of respiratory mechanics revealed increased Ppeak, Pplat, Driving P, MAP, PEF, Ri, lung elastance, MP, Ptp, Ppeak - Pplat, and ΔPes, while Cdyn, Cstat, and time constant were reduced (p < 0.05). Conclusion: We have successfully developed a novel respiratory mechanics monitoring model for severe BLI. This model is reliable, repeatable, stable, effective, and user-friendly. Pes monitoring offers a non-invasive and straightforward alternative to blood gas analysis, facilitating early clinical decision-making. Our animal study lays the groundwork for the early diagnosis and management of severe BLI in clinical settings.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics.

PURPOSE: To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment. METHODS: This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. RESULTS: Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation. CONCLUSIONS: Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Ex Vivo Pulmonary Oedema after In Vivo Blast-Induced Rat Lung Injury: Time Dependency, Blast Intensity and Beta-2 Adrenergic Receptor Role.

Objective: Current treatments for blast-induced lung injury are limited to supportive procedures including mechanical ventilation. The study aimed to investigate the role of post-trauma-induced oedema generation in the function of time and trauma intensity and the probable role of beta 2-adrenergic receptors (ß2-ARs) agonists on pulmonary oedema. The study is conducted using an ex vivo model after an experimental in vivo blast-induced thorax trauma in rats. Methods: Rats were randomised and divided into two groups, blast and sham. The blast group were anaesthetised and exposed to the blast wave (3.16 ± 0.43 bar) at a distance of 3.5 cm from the thorax level. The rats were sacrificed 10 min after the blast, the lungs explanted and treated with terbutaline, formoterol, propranolol or amiloride to assess the involvement of sodium transport. Other groups of rats were exposed to distances of 5 and 7 cm from the thorax to reduce the intensity of the injury. Further, one group of rats was studied after 180 min and one after 360 min after a 3.5 cm blast injury. Sham controls were exposed to identical procedures except for receiving blast overpressure. Results: Lung injury and oedema generation depended on time after injury and injury intensity. Perfusion with amiloride resulted in a further increase in oedema formation as indicated by weight gain (p < 0.001), diminished tidal volume (Tv) (p < 0.001), and increased airway resistance (p < 0.001). Formoterol caused a significant increase in the Tv (p < 0.001) and a significant decrease in the airway resistance (p < 0.01), while the lung weight was not influenced. Trauma-related oedema was significantly reduced by terbutaline in terms of lung weight gain (p < 0.01), Tv (p < 0.001), and airway resistance (p < 0.01) compared to control blast-injured lungs. Terbutaline-induced effects were completely blocked by the ß-receptor antagonist propranolol (p < 0.05). Similarly, amiloride, which was added to terbutaline perfusion, reversed terbutaline-induced weight gain reduction (p < 0.05). Conclusions: ß2-adrenoceptor stimulation had a beneficial impact by amiloride-dependent sodium and therefore, fluid transport mechanisms on the short-term ex vivo oedema generation in a trauma-induced in vivo lung injury of rats.

Proteomic global proteins analysis in blast lung injury reveals the altered characteristics of crucial proteins in response to oxidative stress, oxidation-reduction process and lipid metabolic process.

Background: Blast lung injury (BLI) is the most common fatal blast injury induced by overpressure wave in the events of terrorist attack, gas and underground explosion. Our previous work revealed the characteristics of inflammationrelated key proteins involved in BLI, including those regulating inflammatory response, leukocyte transendothelial migration, phagocytosis, and immune process. However, the molecular characteristics of oxidative-related proteins in BLI ar still lacking. Methods: In this study, protein expression profiling of the blast lungs obtained by tandem mass tag (TMT) spectrometry quantitative proteomics were re-analyzed to identify the characteristics of oxidative-related key proteins. Forty-eight male C57BL/6 mice were randomly divided into six groups: control, 12 h, 24 h, 48 h, 72 h and 1 w after blast exposure. The differential protein expression was identified by bioinformatics analysis and verified by western blotting. Results: The results demonstrated that thoracic blast exposure induced reactive oxygen species generation and lipid peroxidation in the lungs. Analysis of global proteins and oxidative-related proteomes showed that 62, 59, 73, 69, 27 proteins (accounted for 204 distinct proteins) were identified to be associated with oxidative stress at 12 h, 24 h, 48 h, 72 h, and 1 week after blast exposure, respectively. These 204 distinct proteins were mainly enriched in response to oxidative stress, oxidation-reduction process and lipid metabolic process. We also validated these results by western blotting. Conclusions: These findings provided new perspectives on blast-induced oxidative injury in lung, which may potentially benefit the development of future treatment of BLI.

Metformin mitigates gas explosion-induced blast lung injuries through AMPK-mediated energy metabolism and NOX2-related oxidation pathway in rats.

Gas explosions are a recurrent event in coal mining that cause severe pulmonary damage due to shock waves, and there is currently no effective targeted treatment. To illustrate the mechanism of gas explosion-induced lung injury and to explore strategies for blast lung injury (BLI) treatment, the present study used a BLI rat model and supplementation with metformin (MET), an AMP-activated protein kinase (AMPK) activator, at a dose of 10 mg/kg body weight by intraperitoneal injection. Protein expression levels were detected by western blotting. Significantly decreased expression of phosphorylated (p)-AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and metabolic activity were observed in the BLI group compared with those in the control group. However, the mitochondrial stability, metabolic activity and expression of p-AMPK and PGC1α were elevated following MET treatment. These results suggested that MET could attenuate gas explosion-induced BLI by improving mitochondrial homeostasis. Meanwhile, high expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and low expression of catalase (CAT) were observed in the BLI group. The expression levels of NOX2 and CAT were restored in the BLI + MET group relative to changes in the BLI group, and the accumulation of oxidative stress was successfully reversed following MET treatment. Overall, these findings revealed that MET could alleviate BLI by activating the AMPK/PGC1α pathway and inhibiting oxidative stress caused by NOX2 activation.

Pre-hospital continuous positive airway pressure after blast lung injury and hypovolaemic shock: a modelling study.

BACKGROUND: In non-traumatic respiratory failure, pre-hospital application of CPAP reduces the need for intubation. Primary blast lung injury (PBLI) accompanied by haemorrhagic shock is common after mass casualty incidents. We hypothesised that pre-hospital CPAP is also beneficial after PBLI accompanied by haemorrhagic shock. METHODS: We performed a computer-based simulation of the cardiopulmonary response to PBLI followed by haemorrhage, calibrated from published controlled porcine experiments exploring blast injury and haemorrhagic shock. The effect of different CPAP levels was simulated in three in silico patients who had sustained mild, moderate, or severe PBLI (10%, 25%, 50% contusion of the total lung) plus haemorrhagic shock. The primary outcome was arterial partial pressure of oxygen (Pao2) at the end of each simulation. RESULTS: In mild blast lung injury, 5 cm H2O ambient-air CPAP increased Pao2 from 10.6 to 12.6 kPa. Higher CPAP did not further improve Pao2. In moderate blast lung injury, 10 cm H2O CPAP produced a larger increase in Pao2 (from 8.5 to 11.1 kPa), but 15 cm H2O CPAP produced no further benefit. In severe blast lung injury, 5 cm H2O CPAP inceased Pao2 from 4.06 to 8.39 kPa. Further increasing CPAP to 10-15 cm H2O reduced Pao2 (7.99 and 7.90 kPa, respectively) as a result of haemodynamic impairment resulting from increased intrathoracic pressures. CONCLUSIONS: Our modelling study suggests that ambient air 5 cm H2O CPAP may benefit casualties suffering from blast lung injury, even with severe haemorrhagic shock. However, higher CPAP levels beyond 10 cm H2O after severe lung injury reduced oxygen delivery as a result of haemodynamic impairment.

NF-κB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves.

Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats' lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P<0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.

Gas explosion-induced acute blast lung injury assessment and biomarker identification by a LC-MS-based serum metabolomics analysis.

The objective of this study was to evaluate the histopathological effect of gas explosion on rats, and to explore the metabolic alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment using metabolomics analyses. All rats were exposed to the gas explosion source at different distance points (160 m and 240 m) except the control group. Respiratory function indexes were monitored and lung tissue analysis was performed to correlate histopathological effect to serum metabolomics. Their sera samples were collected to measure the metabolic alterations by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). HE staining in lung showed that the gas explosion caused obvious inflammatory pulmonary injury, which was consistent with respiratory function monitoring results and the serum metabolomics analysis results. The metabolomics identified 9 significantly metabolites different between the control- and ABLI rats. 2-aminoadipic acid, L-methionine, L-alanine, L-lysine, L-threonine, cholic acid and L-histidine were significantly increased in the exposed groups. Citric acid and aconitic acid were significantly decreased after exposure. Pathway analyses identified 8 perturbed metabolic pathways, which provided novel potential mechanisms for the gas explosion-induced ABLI. Therefore, metabolomics analysis identified both known and unknown alterations in circulating biomarkers, adding an integral mechanistic insight into the gas explosion-induced ABLI in real roadway environment.

Global gene expression profiling of blast lung injury of goats exposed to shock wave.

PURPOSE: Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear. METHODS: In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression. RESULTS: Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing. CONCLUSION: Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

Damage-Associated Molecular Patterns and Their Signaling Pathways in Primary Blast Lung Injury: New Research Progress and Future Directions.

Primary blast lung injury (PBLI) is a common cause of casualties in wars, terrorist attacks, and explosions. It can exist in the absence of any other outward signs of trauma, and further develop into acute lung injury (ALI) or a more severe acute respiratory distress syndrome (ARDS). The pathogenesis of PBLI at the cellular and molecular level has not been clear. Damage-associated molecular pattern (DAMP) is a general term for endogenous danger signals released by the body after injury, including intracellular protein molecules (HMGB1, histones, s100s, heat shock proteins, eCIRP, etc.), secretory protein factors (IL-1ß, IL-6, IL-10, TNF-α, VEGF, complements, etc.), purines and pyrimidines and their derived degradation products (nucleic acids, ATP, ADP, UDPG, uric acid, etc.), and extracellular matrix components (hyaluronic acid, fibronectin, heparin sulfate, biglycan, etc.). DAMPs can be detected by multiple receptors including pattern recognition receptors (PRRs). The study of DAMPs and their related signaling pathways, such as the mtDNA-triggered cGAS-YAP pathway, contributes to revealing the molecular mechanism of PBLI, and provides new therapeutic targets for controlling inflammatory diseases and alleviating their symptoms. In this review, we focus on the recent progress of research on DAMPs and their signaling pathways, as well as the potential therapeutic targets and future research directions in PBLI.

Management of primary blast lung injury: a comparison of airway pressure release versus low tidal volume ventilation.

BACKGROUND: Primary blast lung injury (PBLI) presents as a syndrome of respiratory distress and haemoptysis resulting from explosive shock wave exposure and is a frequent cause of mortality and morbidity in both military conflicts and terrorist attacks. The optimal mode of mechanical ventilation for managing PBLI is not currently known, and clinical trials in humans are impossible due to the sporadic and violent nature of the disease. METHODS: A high-fidelity multi-organ computational simulator of PBLI pathophysiology was configured to replicate data from 14 PBLI casualties from the conflict in Afghanistan. Adaptive and responsive ventilatory protocols implementing low tidal volume (LTV) ventilation and airway pressure release ventilation (APRV) were applied to each simulated patient for 24 h, allowing direct quantitative comparison of their effects on gas exchange, ventilatory parameters, haemodynamics, extravascular lung water and indices of ventilator-induced lung injury. RESULTS: The simulated patients responded well to both ventilation strategies. Post 24-h investigation period, the APRV arm had similar PF ratios (137 mmHg vs 157 mmHg), lower sub-injury threshold levels of mechanical power (11.9 J/min vs 20.7 J/min) and lower levels of extravascular lung water (501 ml vs 600 ml) compared to conventional LTV. Driving pressure was higher in the APRV group (11.9 cmH2O vs 8.6 cmH2O), but still significantly less than levels associated with increased mortality. CONCLUSIONS: Appropriate use of APRV may offer casualties with PBLI important mortality-related benefits and should be considered for management of this challenging patient group.

Management of combined massive burn and blast injury: A 20-year experience.

INTRODUCTION: Blast injuries are complex types of physical trauma resulting from direct or indirect exposure to an explosion, which can be divided into four classes: primary, secondary, tertiary, and quaternary. Primary blast injury results in damage, principally, in gas-containing organs such as the lungs (blast lung injury, BLI). BLI is defined as radiological and clinical evidence of acute lung injury occurring within 12h of exposure to an explosion and not due to secondary or tertiary injury. BLI often combines with cutaneous thermal injury, a type of quaternary blast injury, either in terrorist bomb attacks or in civilian accidental explosions. This report summarizes our experience in the management of combined massive burn and BLI at a Shanghai Burn Center in China. METHODS: A retrospective observational analysis of clinical data was performed for massive burn patients with or without BLI during a 20-year interval. Patient characteristics, causes of injury, clinical parameters, management, and outcomes were recorded and evaluated. RESULTS: A total of 151 patients (120 males and 31 females) with severe burn injury (≥50% TBSA) treated at the Burn Center of Changhai Hospital in Shanghai between July 1997 and June 2017 were enrolled in this study. Their mean age was 38.6±17.8 (3-75) years. Among them, 28 patients had combined BLI and burn injury and 39 patients had no BLI or smoke inhalation injury (non-BLI-SII). No significant difference was observed in the burn area or full-thickness burn area between the two groups. The lowest PaO2/fraction of inspired oxygen (FiO2) ratio during the first 24h in BLI patients was significantly lower than that in non-BLI-SII patients. Exudative changes were observed by X-ray radiography in all BLI patients but not in non-BLI-SII patients within 6h after injury. A significantly higher proportion of colloids were used for fluid resuscitation in BLI patients than that in non-BLI-SII patients. A higher proportion and longer time of mechanical ventilation were needed for BLI patients than those for non-BLI-SII patients, and a higher proportion of patients received sedative agents in the BLI group than those in the non-BLI-SII group. The first escharectomy was performed relatively later in BLI patients than in non-BLI-SII patients because of more time taken by BLI patients to recover from lung injury. The length of ICU and hospital stay in BLI patients was significantly longer than that in non-BLI-SII patients. No significant difference in the overall mortality was detected between these two groups. CONCLUSION: It is a formidable challenge for clinicians to diagnose and manage massive burn patients combined with BLI. A comprehensive treatment approach is strongly recommended, including fluid resuscitation, airway management, mechanical ventilation, and surgical treatment. Given the high mortality of massive burn patients combined with BLI even in a recognized burn center, more prospective studies are encouraged to assess more effective strategies for the treatment of such patients.

Vaporized perfluorocarbon inhalation attenuates primary blast lung injury in canines by inhibiting mitogen-activated protein kinase/nuclear factor-κB activation and inducing nuclear factor, erythroid 2 like 2 pathway.

Blast lung injury is associated with high morbidity and mortality. Vaporized perfluorocarbon (PFC) inhalation has been reported to attenuate acute respiratory distress syndrome in humans and animal models. However, the effect of vaporized PFC on blast lung injury is still unknown. In this study, we investigated the protective effects and potential underlying mechanisms of action of vaporized PFC on blast lung injury in a canine model. This was a prospective, controlled, animal study in adult male hybrid dogs randomized to sham, blast (B), blast plus mechanical ventilation (B + M), and blast plus PFC (B + P) groups. All groups except for the sham were exposed to blast wave. The B + P group was treated with vaporized PFC for 1.5 h followed by 5.5 h mechanical ventilation. B + M group received 7.5 h mechanical ventilation and B group was observed for 7.5 h. Blast lung injury was induced using a shock tube. Blood gas, inflammatory cytokines, and oxidative stress were measured. Expression of nuclear factor (NF)-κB activation, mitogen-activated protein kinase (MAPK) and nuclear factor, erythroid 2 like 2 (Nrf2) were measured using western blot. Lung injury observed after blast exposure was marked by increased histopathological scores, ratio of lung wet to dry weight. PFC treatment attenuated blast lung injury as indicated by histopathological scores and ratio of lung wet to dry weight. PFC treatment downregulated interleukin (IL)-6, tumor necrosis factor (TNF)-α, and malondialdehyde (MDA), and upregulated superoxide dismutase (SOD) activity. PFC also suppressed expression of MAPK/NF-κB and Nrf2 protein levels. Our results suggest that PFC attenuated blast-induced acute lung injury by inhibiting MAPK/NF-κB activation and inducing Nrf2 expression in dogs.

Blast injures to the thorax.

One out of 10 of military casualties and 6-9 out of 10 civilian victims of terror incidents suffer pulmonary blast injuries when the attackers use explosives as weapon. No specific therapy exists for the primary, shock-wave injury to the lung. The treatment protocols are based on mechanical ventilation, intensive therapy and supportive care. Secondary and tertiary blast structural injuries to the thorax require damage control surgery, dominated by pleural space management (drainage) and haemorrhage control (thoracotomy if needed). Parenchyma resection of irreversibly destroyed lung is rarely needed, and non-anatomical resections are to be preferred. Delayed chest wall reconstruction follows haemodynamic stabilisation and completion of demarcation process. Blast injury to the chest requires a multidisciplinary approach, where the outcome is strongly influenced by the concomitant injuries.

Computational Modeling of Primary Blast Lung Injury: Implications for Ventilator Management.

Primary blast lung injury (PBLI) caused by exposure to high-intensity pressure waves is associated with parenchymal tissue injury and severe ventilation-perfusion mismatch. Although supportive ventilation is often required in patients with PBLI, maldistribution of gas flow in mechanically heterogeneous lungs may lead to further injury due to increased parenchymal strain and strain rate, which are difficult to predict in vivo. In this study, we developed a computational lung model with mechanical properties consistent with healthy and PBLI conditions. PBLI conditions were simulated with bilateral derecruitment and increased perihilar tissue stiffness. As a result of these tissue abnormalities, airway flow was heterogeneously distributed in the model under PBLI conditions, during both conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation. PBLI conditions resulted in over three-fold higher parenchymal strains compared to the healthy condition during CMV, with flow distributed according to regional tissue stiffness. During high-frequency oscillatory ventilation, flow distribution became increasingly heterogeneous and frequency-dependent. We conclude that the distribution and rate of parenchymal distension during mechanical ventilation depend on PBLI severity as well as ventilatory modality. These simulations may allow realistic assessment of the risks associated with ventilator-induced lung injury following PBLI, and facilitate the development of alternative lung-protective ventilation modalities.

Pathophysiology of primary blast injury.

The majority of patients injured in the recent conflicts in Iraq and Afghanistan were as a result of explosion, and terrorist incidents have brought blast injuries to the front door of many civilian hospitals that had not previously encountered such devastation. This article reviews the physics and pathophysiology of blast injury with particular relevance to the presentation and management of primary blast injury, which is the mechanism least familiar to most clinicians and which may cause devastating injury without externals signs.

The Feasibility of Venovenous ECMO at Role-2 Facilities in Austere Military Environments.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been gaining use to bridge the recovery from acute respiratory distress syndrome (ARDS) refractory to conventional treatment. However, these interventions are often limited to higher echelons of military care. We present a case of lung salvage from severe ARDS in an Afghani soldier with VV-ECMO at a Role-2 (R2) facility in an austere military environment in Afghanistan. CASE: A 25-year-old Afghani soldier presented to an R2 facility with blast lung injury and multiple penetrating injuries following an explosion. The patient underwent immediate damage control laparotomy. The abdomen was left open for subsequent washouts and ongoing resuscitation. Due to his ineligibility for evacuation and worsening ARDS, despite 5 d of conventional ventilation strategies, he was started on VV-ECMO. The patient had immediate improvements in oxygenation, which continued for 10 d. Moreover, he underwent three transportations to the operating room without accidental decannulation or disruption of the VV-ECMO device. Despite significant improvements, the patient expired on postoperative day 15, due to an overwhelming intra-abdominal sepsis. CONCLUSION: As future advancements are sought, VV-ECMO may become a consideration for casualties with severe ARDS at the point of injury and at lower echelons of military care.

The role of neutrophil gelatinase-associated lipocalin (NGAL) in the detection of blast lung injury in a military population.

PURPOSE: To study the relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) and military blast and gunshot wound (GSW) to establish whether potential exists for NGAL as a biomarker for blast lung injury (BLI). METHOD: Patients from the intensive care unit (ICU) of the Role 3 Medical Treatment Facility at Camp Bastion, Helmand Province, Afghanistan were studied over a five month period commencing in 2012. Age, mechanism, trauma injury severity score (TRISS) and serum NGAL were recorded on ICU admission (NGAL1). Serum NGAL (NGAL2) and PaO2/FiO2 ratio (P/F ratio2) were recorded at 24h. RESULTS: 33 patients were injured by blast and 23 by GSW. NGAL1 inversely correlated with TRISS (p=0.020), pH (p=0.002) and P/F ratio 2 (p=0.009) overall. When data was stratified into blast and GSW, NGAL1 also inversely correlated with P/F ratio 2 in the blast injured group (p=0.008) but not GSW group (p=0.27). CONCLUSION: Raised NGAL correlated with increased severity of injury (worse survival probability i.e. TRISS and low pH) in both patient groups. There was an inverse correlation between admission NGAL and a marker of blast lung injury (low P/F ratio) at 24h in blast injured group but not GSW group that warrants further investigation.

Noradrenalin effectively rescues mice from blast lung injury caused by laser-induced shock waves.

BACKGROUND: Blast lung injuries (BLI) caused by blast waves are extremely critical in the prehospital setting, and hypotension is thought to be the main cause of death in such cases. The present study aimed to elucidate the pathophysiology of severe BLI using laser-induced shock wave (LISW) and identify the initial treatment. METHODS: The current investigation comprised two parts. For the validation study, mice were randomly allocated to groups that received a single shot of 1.2, 1.3, or 1.4 J/cm(2) LISW to both lungs. The survival rates, systolic blood pressure (sBP), heart rate (HR), peripheral oxyhemoglobin saturation (SpO2), and shock index were monitored for 60 min, and lung tissues were analyzed histopathologically. The study evaluated the effects of catecholamines as follows. Randomly assigned mice received 1.4 J/cm(2) LISW followed by the immediate intraperitoneal administration of dobutamine, noradrenalin, or normal saline. The primary outcome was the survival rate. Additionally, sBP, HR, SpO2, and the shock index were measured before and 5 and 10 min after LISW, and the cardiac output, left ventricular ejection fraction, and systemic vascular resistance (SVR) were determined before and 1 min after LISW. RESULTS: The triad of BLI (hypotension, bradycardia, and hypoxemia) was evident immediately after LISW. The survival rates worsened with increasing doses of LISW (100 % in 1.2 J/cm(2) vs. 60 % in 1.3 J/cm(2), 10 % in 1.4 J/cm(2)). The histopathological findings were compatible with those of human BLI. The survival rate in LISW high group (1.4 J/cm(2)) was highest in the group that received noradrenalin (100 %), with significantly elevated SVR values (from 565 to 1451 dyn s/min(5)). In contrast, the survival rates in the dobutamine and normal saline groups were 40 and 10 %, respectively, and the SVR values did not change significantly after LISW in either group. CONCLUSIONS: The main cause of death during the initial phase of severe BLI is hypotension due to the absence of peripheral vasoconstriction. Therefore, the immediate administration of noradrenalin may be an effective treatment during the initial phase of severe BLI.

Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH) - a review of a new treatment paradigm.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a clinical syndrome with typical symptoms dyspnea and hemoptysis. DAH is a complication of specific diseases, in some cases with acute catastrophic hemoptysis, while other patients present low grade alveolar bleeding with a need of chronic transfusion as in pulmonary hemosiderosis. METHODS: Current literature in the PubMed database and other sources was reviewed in order to evaluate the current treatment recommendations, efficacy of this treatment, and finally the risk of complications after off-label use of rFVIIa in respect to DAH. OBJECTIVES: (i) To elucidate the clinical aspects of alveolar hemorrhage, (ii) to develop a simple diagnostic algorithm in order to separate DAH from other important pulmonary diseases with similar clinical picture and comparably high mortality. Such an algorithm has important therapeutic consequences because these diseases: acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and bronchiolitis obliterans organizing pneumonia (BOOP) have different therapies, (iii) to evaluate and discuss whether local pulmonary administration may improve outcome and reduce mortality in DAH, and (iv) to suggest a treatment schedule. RESULTS: Hitherto the diagnosis and treatment of DAH has been based on anecdotal reports. The treatment has relied on different unspecific treatment modalities based on a mixture of treatment of the underlying disease and treatment without evidence targeted to stop the alveolar bleeding. However, recently a number of publications have advocated the use of intrapulmonary rFVIIa. Even in severe bleeding DAH has been shown to respond promptly without thromboembolic complication when FVIIa was administered locally via the air side, because the FVIIa does not penetrate the alveolo-capillary membrane to the blood-side. The incidence of DAH (in the US and Europe is 100,000-150,000, and 50,000 patients annually are at risk of developing DAH following hematopoietic stem cell transplant (HSCT) and autoimmune diseases. Finally 50,000-100,000 patients may be falsely categorized as having acute respiratory distress syndrome/acute lung injury (ARDS/ALI) because DAH and ARDS cannot be separated clinically. A new treatment paradigm of DAH is proposed as no other intervention has been able to ensure pulmonary hemostasis in DAH. The diagnosis of DAH is simple, a series of broncho-alveolar washes which become increasingly bloody. This test should be performed in all patients with pulmonary opacities in order to separate ARDS/ALI from DAH. FVIIa administrated via pulmonary route is "drug of choice", because it stops bleeding in the life-threatening syndrome DAH. Hemostasis is obtained after only one to two small doses of FVIIa (50 µg/kg body weight per dose) and after hemostasis the oxygen transport quickly improves. CONCLUSION: Intrapulmonary administration of rFVIIa is recommended as the treatment of choice for DAH and blast lung injury (BLI) because the treatment has been shown to be successful and uncomplicated in spite of the fact that only a small series of DAH has been documented.