ABSTRACT
BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has become a standard adjunct for the management of life-threatening truncal hemorrhage, but the technique is limited by the sequalae of ischemia distal to occlusion. Partial REBOA addresses this limitation, and the recent Food and Drug Administration approval of a device designed to enable partial REBOA will broaden its application. We conducted a systematic review of the available animal and clinical literature on the methods, impacts, and outcomes associated with partial REBOA as a technique to enable targeted proximal perfusion and limit distal ischemic injury. We hypothesize that a systematic review of the published animal and human literature on partial REBOA will provide actionable insight for the use of partial REBOA in the context of future wider clinical implementation of this technique. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines, we conducted a search of the available literature which used partial inflation of a REBOA balloon catheter. Findings from 22 large animal studies and 14 clinical studies met inclusion criteria. RESULTS: Animal and clinical results support the benefits of partial REBOA including extending the resuscitative window extended safe occlusion time, improved survival, reduced proximal hypertension, and reduced resuscitation requirements. Clinical studies provide practical physiologic targets for partial REBOA including a period of total occlusion followed by gradual balloon deflation to achieve a target proximal pressure and/or target distal pressure. CONCLUSIONS: Partial REBOA has several benefits which have been observed in animal and clinical studies, most notably reduced ischemic insult to tissues distal to occlusion and improved outcomes compared with total occlusion. Practical clinical protocols are available for the implementation of partial REBOA in cases of life-threatening torso hemorrhage.
Subject(s)
Balloon Occlusion/methods , Endovascular Procedures/methods , Shock, Hemorrhagic/therapy , Animals , Aorta , Humans , Resuscitation/methodsABSTRACT
STUDY OBJECTIVE: We assess whether emergency tourniquet use for transfused war casualties admitted to military hospitals is associated with survival. METHODS: A retrospective review of trauma registry data was made of US casualties in Afghanistan and Iraq. Patients with major limb trauma, transfusion, and tourniquet use were compared with similar patients who did not receive tourniquet use. A propensity-matching analysis was performed by stratifying for injury type and severity by tourniquet-use status. Additionally, direct comparison without propensity matching was made between tourniquet use and no-tourniquet use groups. RESULTS: There were 720 casualties in the tourniquet use and 693 in the no-tourniquet use groups. Of the 1,413 casualties, 66% (928) also had nonextremity injury. Casualties with tourniquet use had worse signs of hemorrhagic shock (admission base deficit, admission hemoglobin, admission pulse, and transfusion units required) than those without. Survival rates were similar between the 2 groups (1% difference; 95% confidence interval -2.5% to 4.2%), but casualties who received tourniquets had worse shock and received more blood products. In propensity-matched casualties, survival rates were not different (2% difference; 95% confidence interval -6.7% to 2.7%) between the 2 groups. CONCLUSION: Tourniquet use was associated with worse shock and more transfusion requirements among hospital-admitted casualties, yet those who received tourniquets had survival rates similar to those of comparable, transfused casualties who did not receive tourniquets.
Subject(s)
Blood Transfusion , Shock/mortality , Tourniquets/adverse effects , Wounds and Injuries/mortality , Afghan Campaign 2001- , Humans , Injury Severity Score , Iraq War, 2003-2011 , Military Medicine/methods , Retrospective Studies , Shock/etiology , Shock/therapy , Survival Analysis , United States/epidemiology , Wounds and Injuries/complications , Wounds and Injuries/therapy , Young AdultABSTRACT
OBJECTIVE: This study was conducted to associate tourniquet use and survival in casualty care over a decade of war in order to provide evidence to emergency medical personnel for the implementation and efficacy of tourniquet use in a large trauma system. METHODS: This survey is a retrospective review of data extracted from a trauma registry. The decade (2001-2010) outcome trend analysis of tourniquet use in the current wars was made in order to associate tourniquet use and survival in an observational cohort design. RESULTS: Of 4,297 casualties with extremity trauma in the total study, 30% (1,272/4,297) had tourniquet use and 70% (3,025/4,297) did not. For all 4,297 casualties, the proportion of casualties with severe or critical extremity Abbreviated Injury Scales (AIS) increased during the years surveyed (p < 0.0001); the mean annual Injury Severity Score (ISS) rose from 13 to 21. Tourniquet use increased during the decade by almost tenfold from 4 to nearly 40% (p < 0.0001). Survival for casualties with isolated extremity injury varied by injury severity; the survival rate for AIS 3 (serious) was 98%, the rate for AIS 4 (severe) was 76%, and the rate for AIS 5 (critical) was 0%. Survival rates increased for casualties with injuries amenable to tourniquets but decreased for extremity injuries too proximal for tourniquets. CONCLUSIONS: Average injury severity increased during the decade of war for casualties with extremity injury. Both tourniquet use rates and casualty survival rates rose when injuries were amenable to tourniquets.
Subject(s)
Extremities/injuries , Hemorrhage/therapy , Military Medicine , Tourniquets/statistics & numerical data , Wounds and Injuries/therapy , Hemorrhage/mortality , Humans , Injury Severity Score , Registries , Retrospective Studies , Surveys and Questionnaires , Survival Rate , United States , Warfare , Wounds and Injuries/mortalityABSTRACT
OBJECTIVE: Improvised tourniquets in first aid are recommended when no scientifically designed tourniquet is available. Windlasses for mechanical advantage can be a stick or pencil and can be used singly or multiply in tightening a tourniquet band, but currently there is an absence of empiric knowledge of how well such windlasses work. The purpose of the present study was to determine the performance of improvised tourniquets in their use by the type and number of windlasses to improve tourniquet practice. METHODS: A simulated Leg Tourniquet Trainer was used as a manikin thigh to test the effectiveness of improvised tourniquets of a band-and-windlass design. Two users made 20 tests each with 3 types of windlasses. Tests started with 1 representative of a given type (eg, 1 pencil), then continued with increasing numbers of each windlass type until the user reached 100% effectiveness as determined by cessation of simulated blood flow. Windlass types included chopsticks, pencils, and craft sticks. RESULTS: Effectiveness percentages in stopping bleeding were associated inversely with breakage percentages. Pulse stoppage percentages were associated inversely with breakage. The windlass turn numbers, time to stop bleeding, the number of windlasses, and the under-tourniquet pressure were associated inversely with breakage. The windlass type was associated with breakage; at 2 windlasses, only chopsticks were without breakage. Of those windlass types that broke, 20.7% were chopsticks, 26.1% were pencils, and 53.2% were craft sticks. CONCLUSIONS: A pair of chopsticks as an improvised tourniquet windlass worked better than pencils or craft sticks.
Subject(s)
Hemorrhage/prevention & control , Tourniquets/standards , Wilderness Medicine/instrumentation , Equipment Design , Humans , Leg , ManikinsABSTRACT
In this study, we investigated the utility of antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii infection in a mouse burn model. A bioluminescent clinical isolate of multidrug-resistant A. baumannii was obtained. The susceptibility of A. baumannii to blue light (415 nm)-inactivation was compared in vitro to that of human keratinocytes. Repeated cycles of sublethal inactivation of bacterial by blue light were performed to investigate the potential resistance development of A. baumannii to blue light. A mouse model of third degree burn infected with A. baumannii was developed. A single exposure of blue light was initiated 30 minutes after bacterial inoculation to inactivate A. baumannii in mouse burns. It was found that the multidrug-resistant A. baumannii strain was significantly more susceptible than keratinocytes to blue light inactivation. Transmission electron microscopy revealed blue light-induced ultrastructural damage in A. baumannii cells. Fluorescence spectroscopy suggested that endogenous porphyrins exist in A. baumannii cells. Blue light at an exposure of 55.8 J/cm(2) significantly reduced the bacterial burden in mouse burns. No resistance development to blue light inactivation was observed in A. baumannii after 10 cycles of sublethal inactivation of bacteria. No significant DNA damage was detected in mouse skin by means of a skin TUNEL assay after a blue light exposure of 195 J/cm(2).
Subject(s)
Acinetobacter baumannii/radiation effects , Burns/therapy , Drug Resistance, Multiple, Bacterial , Phototherapy , Wound Infection/microbiology , Wound Infection/therapy , Acinetobacter Infections/therapy , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/ultrastructure , Animals , Anti-Infective Agents/therapeutic use , Burns/microbiology , DNA Damage/radiation effects , Disease Models, Animal , Female , Keratinocytes , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Microscopy, Electron, TransmissionABSTRACT
Major traumatic injuries to the body, such as large surface area burns, limit the availability of autologous stem cell populations for wound repair. This report demonstrates that even after severe burn trauma to the body, resident stem cells present within the subcutaneous adipose tissue survive and are available for therapeutic uses. Debrided skin from wounded areas contains subcutaneous adipose tissue and can yield approximately 1.5 × 10(5) to 2.5 × 10(5) cells per milliliter of tissue. This observation indicates that tissue, which is normally discarded, could be a valuable source of stem cells. Initial immunohistochemistry of the debrided tissue localized platelet-derived growth factor receptor beta(+) (PDGFR-ß(+) ) cells to perivascular niches of vascular beds. It was immunophenotypically confirmed that the cell isolates are stem cells and designated as debrided skin adipose-derived stem cells (dsASCs). Gene expression analysis of stem cell specific transcripts showed that the dsASCs maintained their stemness over serial passages. Furthermore, dsASCs were able to differentiate into adipogenic, osteogenic, and vascular cell lineages. Finally, an in vivo excision wound model in athymic rats demonstrated that the dsASCs are engrafted within a wound bed after 12 days. These data provide the first evidence that subcutaneous adipose tissue from discarded burned skin contains a viable population of stem cells that can be used for wound repair and skin regenerative therapies.
Subject(s)
Adult Stem Cells/pathology , Debridement , Skin/pathology , Transplantation, Autologous , Wound Healing , Adult , Adult Stem Cells/metabolism , Adult Stem Cells/transplantation , Animals , Antigens, CD/metabolism , Burns/pathology , Cell Differentiation , Cell Separation , Cell Tracking , Cells, Cultured , Humans , Male , Middle Aged , Rats , Rats, Nude , Regenerative Medicine/methods , Skin/injuries , Subcutaneous Fat/pathology , Subcutaneous Tissue/pathology , Transplantation, Heterologous , Young AdultABSTRACT
OBJECTIVES: Previously, we reported on the use of emergency tourniquets to stop bleeding in war casualties, but virtually all the data were from adults. Because no pediatric-specific cohort of casualties receiving emergency tourniquets existed, we aimed to fill knowledge gaps on the care and outcomes of this group by surveying data from a trauma registry to refine device designs and clinical training. METHODS: A retrospective review of data from a trauma registry yielded an observational cohort of 88 pediatric casualties at US military hospitals in theater on whom tourniquets were used from May 17, 2003, to December 25, 2009. RESULTS: Of the 88 casualties in the study group, 72 were male and 16 were female patients. Ages averaged 11 years (median, 11 years; range, 4-17 years). There were 7 dead and 81 survivor outcomes for a trauma survival rate of 93%. Survivor and dead casualties were similar in all independent variables measured except hospital stay duration (median, 5 days and 1 day, respectively). Six casualties (7%) had neither extremity nor external injury in that they had no lesion indicating tourniquet use. CONCLUSIONS: The survival rate of the present study's casualties is similar to that of 3 recent large nonpediatric-specific studies. Although current emergency tourniquets were ostensibly designed for modern adult soldiers, tourniquet makers, perhaps unknowingly, produced tourniquets that fit children. The rate of unindicated tourniquets, 7%, implied that potential users need better diagnostic training. LEVELS OF EVIDENCE: Level 4; case series, therapeutic study.
Subject(s)
Emergencies , Health Care Surveys , Hemorrhage/therapy , Hospitals, Military/statistics & numerical data , Mass Casualty Incidents , Registries , Tourniquets/statistics & numerical data , Warfare , Wounds and Injuries/epidemiology , Adolescent , Afghan Campaign 2001- , Arm Injuries/complications , Arm Injuries/epidemiology , Arm Injuries/therapy , Body Size , Child , Child, Preschool , Equipment Design , Female , Hemorrhage/epidemiology , Hemorrhage/etiology , Humans , Iraq War, 2003-2011 , Leg Injuries/complications , Leg Injuries/epidemiology , Leg Injuries/therapy , Length of Stay/statistics & numerical data , Male , Shock, Hemorrhagic/prevention & control , Trauma Severity Indices , United States , Unnecessary Procedures/statistics & numerical data , Wounds and Injuries/etiology , Wounds and Injuries/mortalityABSTRACT
Resuscitative endovascular balloon occlusion of the aorta (REBOA) devices grew out of a military-civilian partnership to develop new capabilities for hemorrhage control. With the advent of purpose-built devices, REBOA has become increasingly common in civilian trauma and acute care settings. Currently available REBOA catheters were designed as complete aortic occlusion devices. However, the therapeutic window for complete aortic occlusion is time-limited due to ischemia-reperfusion injury. The partial procedure allows blood flow past the level of occlusion while maintaining targeted proximal pressure, which has been shown to reduce distal ischemia and adjunctive resuscitation requirements in preclinical studies with prolonged occlusion times as compared to traditional complete occlusion. pREBOA-PRO is the first catheter designed to enable partial and complete aortic occlusion and is currently in limited market release at seven Level I trauma centers in North America. This paper will focus on procedural considerations for REBOA, including patient selection criteria and a comparison of complete and partial aortic occlusion in a simulator, along with highlighting critical steps to improve clinical outcomes. Additionally, this paper reviews a contrast-enhanced CT scan from a trauma patient that shows distal perfusion after 2 h of partial aortic occlusion using this newly designed catheter and discusses representative results from the limited market release to highlight the profound effect of technological innovation on outcomes in vascular emergencies.
Subject(s)
Aortic Diseases , Balloon Occlusion , Endovascular Procedures , Shock, Hemorrhagic , Aorta/surgery , Balloon Occlusion/methods , Endovascular Procedures/methods , Hemorrhage/therapy , Humans , Resuscitation/methods , Shock, Hemorrhagic/therapyABSTRACT
INTRODUCTION: Targeted regional optimization (TRO) describes partial resuscitative endovascular balloon occlusion of the aorta strategy that allows for controlled distal perfusion to balance hemostasis and tissue perfusion. This study characterized hemodynamics at specific targeted distal flow rates in a swine model of uncontrolled hemorrhage to determine if precise TRO by volume was possible. METHODS: Anesthetized swine were subjected to liver laceration and randomized into TRO at distal flows of 300âmL/min (nâ=â8), 500âmL/min (nâ=â8), or 700âmL/min (nâ=â8). After 90âmin, the animals received damage control packing and were monitored for 6âh. Hemodynamic parameters were measured continuously, and hematology and serologic labs obtained at predetermined intervals. RESULTS: During TRO, the average percent deviation from the targeted flow was lower than 15.9% for all cohorts. Average renal flow rates were significantly different across all cohorts during TRO phase (Pâ<â0.0001; TRO300â=â63.1â±â1.2; TRO500â=â133.70â±â1.93; TRO700â=â109.3â±â2.0), with the TRO700 cohort having less renal flow than TRO500. The TRO500 and TRO700 average renal flow rates inverted during the intensive care unit phase (Pâ<â0.0001; TRO300â=â86.20â±â0.40; TRO500â=â148.50â±â1.45; TRO700â=â181.1â±â0.70). There was higher blood urea nitrogen, creatinine, and potassium in the TRO300 cohort at the end of the experiment, but no difference in lactate or pH between cohorts. CONCLUSION: This study demonstrated technical feasibility of TRO as a strategy to improve outcomes after prolonged periods of aortic occlusion and resuscitation in the setting of ongoing solid organ hemorrhage. A dose-dependent ischemic end-organ injury occurs beginning with partial aortic occlusion that progresses through the critical care phase, with exaggerated effect on renal function.
Subject(s)
Balloon Occlusion , Shock, Hemorrhagic , Animals , Aorta , Disease Models, Animal , Hemorrhage/therapy , Humans , Liver/injuries , Resuscitation , Shock, Hemorrhagic/therapy , SwineABSTRACT
BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic that inhibits both plasminogen activation and plasmin activity, thus preventing clot break-down rather than promoting new clot formation. TXA has been used around the world to safely control bleeding since the 1960s. A large randomized trial recently conducted in >20,000 trauma patients adds to the large body of data documenting the usefulness of TXA in promoting hemostasis. METHODS: We reviewed the literature describing use of TXA in a variety of settings including trauma. RESULTS: TXA has been safely used across a wide range of clinical settings to control hemorrhage. The results of a large, randomized, placebo-controlled trial support the use of TXA to treat bleeding trauma patients. CONCLUSIONS: This inexpensive and safe drug should be incorporated into trauma clinical practice guidelines and treatment protocols. Further research on possible alternate mechanisms of action and dosing regimens for TXA should be undertaken. Concurrent to these endeavors, TXA should be adopted for use in bleeding trauma patients because it is the only drug with prospective clinical evidence to support this application.
Subject(s)
Antifibrinolytic Agents/therapeutic use , Tranexamic Acid/therapeutic use , Wounds and Injuries/drug therapy , Clinical Trials as Topic , Hemorrhage/drug therapy , Humans , Injury Severity ScoreABSTRACT
BACKGROUND: In a previous study conducted at a combat support hospital in Iraq, we reported the major lifesaving benefits of emergency tourniquets to stop bleeding in major limb trauma. Morbidity associated with tourniquet use was minor. STUDY OBJECTIVES: The objective of this study is to further analyze emergency tourniquet use in combat casualty care. DESIGN AND SETTING: This report is a continuation of our previous study of tourniquet use in casualties admitted to a combat support hospital (NCT00517166 at www.ClinicalTrials.gov). METHODS: After verifying comparable methodologies for the first study and the current study, we compared patient results for these two time periods and then pooled data to analyze outcomes with a larger sample size. RESULTS: The total study population was 499 (232 in the previous study and 267 in the current study). In all, 862 tourniquets were applied on 651 limbs. Survival was 87% for both study periods. Morbidity rates for palsies at the level of the tourniquet were 1.7% for study 1 and 1.5% for study 2; major limb shortening was 0.4% for both. Survival was associated with prehospital application (89% vs. 78% hospital, p < 0.01) and application before the onset of shock (96% vs. 4% after). CONCLUSIONS: This study shows consistent lifesaving benefits and low risk of emergency tourniquets to stop bleeding in major limb trauma.
Subject(s)
Emergency Treatment/methods , Extremities/injuries , Hemorrhage/mortality , Hemorrhage/therapy , Military Personnel , Tourniquets , Adolescent , Adult , Aged , Child , Emergency Service, Hospital , Female , Humans , Iraq/epidemiology , Male , Middle Aged , Survival Analysis , Young AdultABSTRACT
OBJECTIVE: The purpose of this study is to report the device lessons learned from an emergency tourniquet program and, in particular, to emphasize analysis of discarded devices recovered after clinical use. METHODS: Discarded tourniquet devices were analyzed after use in emergency care of war casualties to determine wear and tear patterns, effectiveness rates, and associations among device designs. RESULTS: The 159 devices recovered comprised seven designs. Emergency & Military Tourniquet (92%) and Combat Application Tourniquet (79%) effectiveness rates were significantly different from each other and better than other tourniquets (p < 0.002) as the most effective ambulance and field tourniquets, respectively. Designs had specific pitfalls (e.g., sand-clogged ratchets) and strengths (the pneumatic design was least painful). Every device had wear, abrasions, or deformity about the band edges or bladder. User understanding of how devices work best helped attain better results. Some desirable traits (e.g., one-handed application, use for entrapped limbs) were rarely needed. Tourniquets fit casualty limbs well. CONCLUSIONS: Correct user actions (e.g., following the instructions to remove slack before twisting) led to device effectiveness, but misuse did not. Users often assumed that optimal use required more force, but this was associated with misuse. Training should include tourniquet pearls and pitfalls.
Subject(s)
Emergency Treatment/instrumentation , Extremities/injuries , Military Medicine , Tourniquets , Equipment Design , Humans , Inservice TrainingABSTRACT
BACKGROUND: In prior reports of active data collection, we demonstrated that early use of emergency tourniquets is associated with improved survival and only minor morbidity. To check these new and important results, we continued critical evaluation of tourniquet use for 6 more months in the current study to see if results were consistent. METHODS: We continued a prospective survey of casualties and their records at a combat support hospital in Baghdad who had tourniquets used at a combat hospital in Baghdad (NCT00517166 at ClinicalTrials.gov). RESULTS: After comparable methods were verified for both the first and current studies, we report the results of 499 patients who had 862 tourniquets applied on 651 limbs. The clinical results were consistent. No limbs were lost from tourniquet use. CONCLUSION: We found that morbidity was minor in light of major survival benefits consistent with prior reports.
Subject(s)
Emergency Treatment , Extremities/injuries , Hemorrhage/therapy , Tourniquets , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Military Medicine , Polyneuropathies/etiology , Prospective Studies , Tourniquets/adverse effects , Young AdultABSTRACT
ABSTRACT: Resuscitative endovascular balloon occlusion of the aorta (REBOA) allows for effective temporization of exsanguination from non-compressible hemorrhage (NCTH) below the diaphragm. However, the therapeutic window for aortic occlusion is time-limited given the ischemia-reperfusion injury generated. Significant effort has been put into translational research to develop new strategies to alleviate the ischemia-reperfusion injury and extend the application of endoaortic occlusion. Targeted regional optimization (TRO) is a partial REBOA strategy to augment proximal aortic and cerebral blood flow while targeting minimal threshold of distal perfusion beyond the zone of partial aortic occlusion. The objective of TRO is to reduce the degree of ischemia caused by complete aortic occlusion while providing control of distal hemorrhage. This review provides a synopsis of the concept of TRO, pre-clinical, translational experiences with TRO and early clinical outcomes. Early results from TRO strategies are promising; however, further studies are needed prior to large-scale implementation into clinical practice.
Subject(s)
Aorta/surgery , Balloon Occlusion , Endovascular Procedures , Resuscitation , Shock, Hemorrhagic/therapy , Wounds and Injuries/complications , Humans , Shock, Hemorrhagic/etiology , Time Factors , Wounds and Injuries/therapyABSTRACT
BACKGROUND: Clinicians have postulated that decreased atmospheric pressure during air evacuation exacerbates muscle edema and necrosis in injured limbs. The present study investigated whether the mild hypobaric, hypoxic conditions of simulated flight during muscle reperfusion worsened muscle edema and muscle injury in an established animal model. METHODS: Twenty male Sprague-Dawley rats underwent tourniquet-induced hind limb ischemia for 2h. After removal of the tourniquet, rats were divided into two groups (n=10/group), and exposed to either (1) hypobaric, hypoxic conditions (HB) of 522 mm Hg (simulating 10,000 feet, the upper limit of normal aircraft cabin pressure), or (2) normobaric, normoxic conditions (NB) of 760 mm Hg (sea level), for 6h. Muscle wet weight, muscle dry:wet weight ratios, viability, and routine histology were measured on the gastrocnemius and tibialis anterior muscles. Blood samples were analyzed for percentage hematocrit, leukocyte count, and coagulation status. RESULTS: Ischemia resulted in significant edema in both groups (P<0.05). Normobaric normoxia caused greater edema in the gastrocnemius compared with hypobaric hypoxia; the tibialis anterior was not significantly different between groups. The decrease in body weight for NB and HB was 3.4+/-1.4 and 10.7+/-1.2g, respectively (P<0.05). Hematocrit was 44.7+/-0.5 and 42.6+/-0.6 (P<0.05). CONCLUSIONS: The hypobaric, hypoxic conditions of simulated medical air evacuation were not associated with increased muscle edema following 2h of ischemic injury. This suggests that other factors, such as resuscitation, may be the cause of muscle edema in flight-evacuated patients.
Subject(s)
Edema/physiopathology , Hypoxia/physiopathology , Muscle, Skeletal/physiopathology , Reperfusion Injury/physiopathology , Altitude , Animals , Atmosphere Exposure Chambers , Atmospheric Pressure , Body Weight , Cell Survival , Compartment Syndromes/metabolism , Compartment Syndromes/pathology , Compartment Syndromes/physiopathology , Disease Models, Animal , Edema/metabolism , Edema/pathology , Hypoxia/metabolism , Hypoxia/pathology , Male , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Necrosis , Organ Size , Oxidative Stress , Rats , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 10(8) A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections.
Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter Infections/etiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/radiation effects , Burns/complications , Photochemotherapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Animals , Dimethyl Sulfoxide/chemistry , Dimethyl Sulfoxide/therapeutic use , Female , Mice , Mice, Inbred BALB C , Photosensitizing Agents/chemistry , Polyethyleneimine/chemistry , Polyethyleneimine/therapeutic use , Porphyrins/chemistry , Porphyrins/therapeutic useABSTRACT
OBJECTIVE: The purpose of this study was to determine if emergency tourniquet use saved lives. SUMMARY BACKGROUND DATA: Tourniquets have been proposed as lifesaving devices in the current war and are now issued to all soldiers. Few studies, however, describe their actual use in combat casualties. METHODS: A prospective survey of injured who required tourniquets was performed over 7 months in 2006 (NCT00517166 at ClinicalTrials.gov). Follow-up averaged 28 days. The study was at a combat support hospital in Baghdad. Among 2,838 injured and admitted civilian and military casualties with major limb trauma, 232 (8%) had 428 tourniquets applied on 309 injured limbs. We looked at emergency tourniquet use, and casualties were evaluated for shock (weak or absent radial pulse) and prehospital versus emergency department (ED) tourniquet use. We also looked at those casualties indicated for tourniquets but had none used. We assessed survival rates and limb outcome. RESULTS: There were 31 deaths (13%). Tourniquet use when shock was absent was strongly associated with survival (90% vs. 10%; P < 0.001). Prehospital tourniquets were applied in 194 patients of which 22 died (11% mortality), whereas 38 patients had ED application of which 9 died (24% mortality; P = 0.05). The 5 casualties indicated for tourniquets but had none used had a survival rate of 0% versus 87% for those casualties with tourniquets used (P < 0.001). Four patients (1.7%) sustained transient nerve palsy at the level of the tourniquet. No amputations resulted solely from tourniquet use. CONCLUSIONS: Tourniquet use when shock was absent was strongly associated with saved lives, and prehospital use was also strongly associated with lifesaving. No limbs were lost due to tourniquet use. Education and fielding of prehospital tourniquets in the military environment should continue.
Subject(s)
Emergency Treatment , Extremities/injuries , Hemorrhage/mortality , Hemorrhage/therapy , Military Personnel , Tourniquets , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Hemorrhage/etiology , Humans , Injury Severity Score , Iraq , Male , Middle Aged , Prospective Studies , Survival Rate , United States , Warfare , Young AdultABSTRACT
Enhancing survival to hemorrhage of both civilian and military patients is a major emphasis for trauma research. Previous observations in humans and outbred rats show differential survival to similar levels of hemorrhage. In an initial attempt to determine potential genetic components of such differential outcomes, survival time after a controlled hemorrhage was measured in 15 inbred strains of rats. Anesthetized rats were catheterized, and approximately 24 h later, 55% of the calculated blood volume was removed during a 26-min period from conscious unrestrained animals. Rats were observed for a maximum of 6 h. Survival time was 7.7-fold longer in the longest-lived strain (Brown Norway/Medical College of Wisconsin; 306 +/- 36 min; mean +/- SEM) than in the shortest-lived strain (DA; 40 +/- 5 min; P < or = 0.01). Mean survival times for the remaining inbred strains ranged from 273 +/- 44 to 49 +/- 4 min (Dahl-Salt Sensitive > Brown Norway > Munich Wistar Fromter> Dahl-Salt Resistant > Copenhagen > Noble > Spontaneous-hypertensive > Lewis > BDIX > Fawn Hooded Hypertensive > FISCHER 344 > Black agouti > PVG). The variance in the hazard of death attributable to different strains was estimated to be 1.22 log-hazard units, corresponding to a heritability of approximately 48%. Graded and divergent survival times to hemorrhage in inbred rat strains are remarkable and suggest multiple genetic components for this characteristic. However, this interpretation of differential responses to hemorrhage may be confounded by potential strain-associated differences related to the surgical preparation. Identification of inbred strains divergent in survival time to hemorrhage provides the opportunity for future use of these strains to identify genes associated with this complex response.
Subject(s)
Hemorrhage/genetics , Quantitative Trait Loci/genetics , Animals , Hemorrhage/mortality , Humans , Rats , Rats, Inbred Strains , Species SpecificityABSTRACT
BACKGROUND: Although the use of potable water for wound irrigation is attractive in an austere environment, its effectiveness has not been tested. We sought to compare the effectiveness of potable water irrigation in reducing bacterial number with that of normal saline irrigation. METHODS: We used an established caprine model involving the creation of a reproducible complex musculoskeletal wound followed by inoculation with luminescent bacteria that allowed for quantitative analysis with a photon-counting camera system. Six hours after injury and inoculation, wound irrigations were performed using pulsatile lavage. Fourteen goats were randomized into two treatment groups: irrigation with 9 L potable water versus irrigation with 9 L normal saline. Images obtained after irrigation were compared with baseline images to determine the reduction in bacterial luminescence resulting from treatment. RESULTS: The irrigation in both groups reduced the bacterial counts by 71% from the preirrigation levels. CONCLUSION: Potable water reduced the bacterial load as effectively as normal saline in our model.