ABSTRACT
BACKGROUND: Poloxamer 188 (P188) is a copolymer surfactant with plasma membrane stabilizing action. This study investigated the effects of P188 on blood volume and coagulation in pigs after traumatic hemorrhage and hypotensive resuscitation. METHODS: Femur fracture was performed in 17 anesthetized pigs, followed by hemorrhage of 55% of estimated blood volume and a 10âmin shock period. Afterwards, pigs were randomized to be resuscitated with either normal saline (nâ=â9, 4âmL/kg, NS group) or P188 (nâ=â8, 1.33âmL/kg at 150âmg/mL, plus 2.67âmL NS/kg, P188 group). Pigs were monitored for 2 h or until death. Hemodynamics were recorded and blood samples were taken at baseline (BL), after hemorrhage, shock, resuscitation, and at 2 h for blood and coagulation analysis using Rotem®. RESULTS: All but one pig in each group survived to 2 h. Femur fracture and hemorrhage reduced mean arterial pressure to half of the BL and elevated heart rate to double of the BL (both Pâ<â0.05). Resuscitation with NS or P188 did not return these measurements to BL. Compared to NS, resuscitation with P188 resulted in a smaller reduction of blood volume (76â±â3% in P188 and 60â±â2% in NS); higher base excess (3.3â±â0.9 vs. 0.5â±â0.9âmM); and lower hematocrit (24â±â1 vs. 28â±â1%) and Ca++ (24â±â1 vs. 28â±â1âmM). Resuscitation with P188 prolonged aPTT (43â±â12 vs. 22â±â3âs, all Pâ<â0.05). CONCLUSIONS: Following traumatic hemorrhage and hypotensive resuscitation, P188 improved circulation volume and base deficit, but induced slower clotting initiation in pigs. Thus, P188 may have limited benefit as an initial small volume resuscitation adjunct following hemorrhage.
Subject(s)
Hypotension , Shock, Hemorrhagic , Animals , Blood Coagulation , Hemorrhage/therapy , Poloxamer/pharmacology , Poloxamer/therapeutic use , Resuscitation/methods , Return of Spontaneous Circulation , Shock, Hemorrhagic/metabolism , SwineABSTRACT
INTRODUCTION: Current agents for the intravascular embolization of traumatic hemorrhage are used off-label and have been minimally studied with respect to their performance under differing coagulation conditions. We studied the hemorrhage control efficacy of a novel, liquid, polyethylene glycol-based hydrogel delivered as two liquid precursors that polymerize within the target vessel in a unique animal model of severe solid organ injury with and without dilutional coagulopathy. METHODS: Anesthetized swine (n = 36, 45 ± 3 kg) had laparotomy and splenic externalization. Half underwent 50% isovolemic hemodilution with 6% hetastarch and cooling to 33°C-35°C (coagulopathic group). All animals had controlled 20 mL/kg hemorrhage and endovascular proximal splenic artery access with a 4F catheter via a right femoral sheath. Splenic transection and 5-minute free bleeding were followed by treatment (n = 5/group) with 5 mL of gelfoam slurry, three 6-mm coils, up to 6 mL of hydrogel, or no treatment (n = 3, control). Animals received 15 mL/kg plasma and were monitored for 6 hours with continuous blood loss measurement. RESULTS: Coagulopathy was successfully established, with coagulopathic animals having greater pretreatment blood loss and earlier mean time to death regardless of the treatment group. All control animals died within 100 minutes. Overall survival without coagulopathy was 5/5 for hydrogel, 4/5 for coil, and 3/5 for gelfoam. With coagulopathy, one hydrogel animal survived to the end of the experiment, with 2/4 hydrogel deaths occurring in the final hour of observation. In noncoagulopathic animals, hydrogel demonstrated improved survival time (P < .01) and post-treatment blood loss (1.46 ± 0.8 mL/kg) over controls (18.8 ± 0.7, P = .001), gelfoam (4.7 ± 1.3, P > .05), and coils (4.6 ± 1.5, P > .05). In coagulopathic animals, hydrogel had improved survival time (P = .003) and decreased blood loss (4.2 ± 0.8 mL/kg) compared with control (20.4 ± 4.2, P = .003). CONCLUSIONS: The hydrogel demonstrated equivalent hemorrhage control performance to standard treatments under noncoagulopathic conditions and improved performance in the face of dilutional coagulopathy. This agent should be explored as a potential preferable treatment for the embolization of traumatic solid organ and other injuries. (JVS-Vascular Science 2021;2:43-51.). CLINICAL RELEVANCE: In a translational model of severe solid organ injury hemorrhage with and without coagulopathy, a novel hydrogel transarterial embolization agent demonstrated equivalent hemorrhage control performance to standard agents under noncoagulopathic conditions and improved performance in the face of dilutional coagulopathy. This agent represents a promising future treatment for the embolization of traumatic solid organ and other injuries.
ABSTRACT
BACKGROUND: Compared with those of tourniquet application, tourniquet conversion concepts are underdeveloped. The purpose of this project was to develop tourniquet conversion concepts and generate hypotheses. METHODS: One person performed 100 tests of tourniquet application and conversion. Testing varied by conversion types, materials, and assessments. Conversions were from improvised or Combat Application Tourniquets (C-A-T) to another C-A-T, a new site (with initial C-A-T only), a pneumatic Emergency and Military Tourniquet (EMT), or a pressure dressing (compression bandage or a roll gauze and an elastic wrap). Simulated limbs were created using plastic bottle-based manikins, pool noodle-based manikins, plastic pipes, glass bottles, a rain downspout, and a cardboard poster tube. RESULTS: Tourniquet application, conversion, and total times averaged 105, 132, and 237 seconds, respectively. Improvised tourniquet time was longer than that of C-A-T (p ≤ .05, all three). By initial tourniquet site, the 2-3 inches site had longer conversion and total time (p ≤ .02, both) compared with highest site. By whether initial tourniquets placed were also used in conversion, total time was shorter if yes (p = .05). Conversion to a pressure dressing was longer in conversion and total time (p ≤ .02, both) compared with conversion to a tourniquet. One wrap was short; we switched to those longer to cover limbs better. Limb types varied for indentation. Conversion communications improved when we used abbreviations and symbols. CONCLUSIONS: This preliminary project simulated tourniquet conversion to develop clinical concepts and research hypotheses to build a better basis for later research.
Subject(s)
Military Personnel , Tourniquets , Bandages , Hemorrhage/therapy , Humans , ManikinsABSTRACT
BACKGROUND: Severe burn injury results in profound catabolic deterioration. Although burn-related catabolism has been well stated, it is unclear when the catabolic response begins. This study characterized acute changes of muscle protein breakdown at the admission and the day after in severely burned adults. METHODS: Twelve patients (43 ± 19 years old) with 40% ± 21% total body surface area burns were prospectively enrolled into an observational study approved by institutional review board. Urinary samples were collected on admission day and the day after (day 1). Patient demographic and clinical data of vital signs, blood gas and chemistry, and coagulation status were collected. Catabolic changes of muscle breakdown were quantified by urinary excretion of 3-methylhisitidine, determined by gas chromatography and mass spectrometry analysis. RESULTS: Compared with admission day, burned patients had elevated mean ± SD arterial pressure (from 90 ± 5 mm Hg to 108 ± 7 mm Hg) and heart rate (from 102 ± 7 beats per minute to 119 ± 4 beats per minute both p < 0.05) after 24 hours. Their 24-hour urinary output was 1,586 ± 813 mL at admission day to 1,911 ± 1,048 mL on day 1. The 24-hour urea excretion was elevated from 172 ± 101 mg/kg per day at admission day to 302 ± 183 mg/kg per day on day 1 (both p < 0.05), with no change in creatinine excretion. Urinary 3-methylhisitidine excretion increased from 0.75 ± 0.74 mg/kg per day at admission to 1.14 ± 0.86 mg/kg per day on day 1 (p < 0.05). The estimated skeletal muscle protein breakdown was increased from 1.1 ± 1.0 g/kg per day at admission day to 1.6 ± 1.2 g/kg per day on day 1 (p < 0.05). There were no changes in prothrombin time, activated partial thromboplastin time, or platelets. CONCLUSION: In severely burned patients, catabolic muscle protein breakdown is elevated within 24 hours after admission and before changes in coagulation. These findings suggest that early interventions may be needed to effectively attenuate the catabolic responses in burn patients. LEVEL OF EVIDENCE: Prospective and observational study, level II.
Subject(s)
Burns/complications , Muscle, Skeletal/pathology , Adult , Aged , Aged, 80 and over , Blood Glucose/analysis , Blood Proteins/analysis , Burns/pathology , Female , Gas Chromatography-Mass Spectrometry , Hemodynamics , Humans , Male , Metabolism , Methylhistidines/urine , Middle Aged , Muscle Proteins/metabolism , Muscle, Skeletal/metabolism , Prospective Studies , Time Factors , Water-Electrolyte Balance , Young AdultABSTRACT
BACKGROUND: We sought to determine the extent of loss of endothelial basement membrane (BM), leukocyte recruitment, and changes in coagulation after hemorrhagic shock, followed by limited-volume resuscitation (LVR) with 5% albumin (ALB). METHODS: Anesthetized rats were bled 40% of blood volume and assigned to treatment groups: untreated (n = 6), LVR with normal saline (NS; n = 8), or LVR with ALB (n = 8). Sham rats (n = 6) underwent all procedures except hemorrhage or resuscitation. Blood samples were assayed for active proteases, such as metalloproteinase 9 (MMP-9) and a disintegrin and metalloproteinase 10 (ADAM-10), BM-type heparan sulfate proteoglycan (perlecan), cell count, and coagulation function. Leukocyte transmigration was used to estimate the net efficiency of leukocyte recruitment in cremaster venules. RESULTS: Hemorrhage significantly lowered red cell count, but white cell and platelet counts did not change (vs. sham). Ionized calcium in plasma was significantly reduced in untreated and remained so after NS. In contrast, ionized calcium was normalized after ALB. Plasma expansion after NS and ALB further reduced leukocyte and platelet counts. Metalloproteinase 9, ADAM-10, and perlecan were significantly higher in untreated rats (vs. sham). Albumin normalized MMP-9, ADAM-10, and perlecan levels, while NS further increased MMP-9, ADAM-10, and perlecan (vs. sham). Transmigrated leukocytes doubled in the untreated group and remained elevated after NS (vs. sham) but normalized after ALB. Albumin reduced every stage of the leukocyte recruitment process to sham levels. CONCLUSION: Despite similar plasma expansion, NS weakened platelet function contrary to ALB. Plasma expansion with ALB resulted in restoration of BM integrity and attenuation of leukocyte recruitment to tissues, in contrast to NS. Albumin plays a critical role in restoring BM integrity, attenuating leukocyte recruitment to tissues, and optimizing hemostasis by increasing ionized calcium in plasma.
Subject(s)
Albumins/therapeutic use , Basement Membrane/drug effects , Endothelium, Vascular/drug effects , Hemostasis/drug effects , Shock, Hemorrhagic/metabolism , Animals , Basement Membrane/metabolism , Basement Membrane/physiopathology , Blood Cell Count , Disease Models, Animal , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Hemodynamics/drug effects , Hemodynamics/physiology , Hemostasis/physiology , Leukocytes/metabolism , Male , Rats , Rats, Sprague-Dawley , Resuscitation/methods , Shock, Hemorrhagic/pathology , Shock, Hemorrhagic/therapyABSTRACT
Adipose stem cells (ASCs) have shown therapeutic promise for various conditions, including burn injury. While ASCs have immunomodulatory properties, concerns exist over pro-coagulant activity after intravenous (IV) administration. In the present study, we examined IV human ASC delivery in terms of coagulation, organ function, and inflammation in a 40% total body surface area (TBSA) swine burn model. Anesthetized female Yorkshire swine were burned and randomized to receive 15 ml/kg Lactated Ringer's containing: no ASCs; a low dose (5 × 105 ASCs/kg); or a high dose (5 × 106 ASCs/kg). For biochemical analysis, blood was collected at baseline (BL), 3, 6, 12, and 24 h post-burn, while kidney and liver tissue was collected post-euthanasia. A significant, but transient, effect of ASCs was seen on prothrombin times and INR, wherein low doses revealed slight hypercoagulation. Burns increased partial thromboplastin time, fibrinogen, and d-dimer levels, which was unchanged with ASC administration. ASCs tended to exacerbate increases in bilirubin at 3 h, but this didn't reach statistical significance. A significant effect of ASCs on creatinine and BUN was seen, wherein low doses elevated levels at 24 h (creatinine, P = 0.0012; BUN, P = 0.0195). Hepatic and renal TUNEL staining were similar for all groups. A dose-dependent decrease in IL-8 was observed, while low doses significantly increased IL-1RA at 3h (P = 0.050), IL-12 at 12h (P = 0.021) and IL-6 at 24 h post-burn (P = 0.035). IV administration of xenogeneic ASCs slightly increased coagulation, but effects on burn-induced renal and hepatic dysfunction effects were minimal. Despite some significant immunomodulation, organ dysfunction effects were modest. Collectively, this study provides evidence to be skeptical about xenogeneic ASC administration in regards to burns.
Subject(s)
Adipose Tissue/cytology , Disease Models, Animal , Mesenchymal Stem Cell Transplantation/methods , Stem Cell Transplantation/methods , Wound Healing/physiology , Administration, Intravenous , Animals , Body Surface Area , Burns , Cell Culture Techniques , SwineABSTRACT
BACKGROUND: Endovascular embolization is increasingly used in treating traumatic hemorrhage and other applications. No endovascular-capable translational large animal models exist and coagulopathy's effect on embolization techniques is unknown. We developed a coagulation-adaptable solid organ hemorrhage model in swine for investigation of embolization techniques. METHODS: Anesthetized swine (n = 26, 45 ± 3 kg) had laparotomy and splenic externalization. Half underwent 50% isovolemic hemodilution with 6% hetastarch and cooling to 33-35°C (COAG group). All had controlled 20 mL/kg hemorrhage and endovascular access to the proximal splenic artery with a 4F catheter via a right femoral sheath. Splenic transection and 5 min free bleeding were followed by treatment (n = 5/group) with 5 mL gelfoam slurry, three 6-mm coils, or no treatment (n = 3, control). Animals received 15 mL/kg plasma resuscitation and were monitored for 6 hr. Splenic blood loss was continuously measured and angiograms were performed at specified times. RESULTS: Coagulopathy was successfully established in COAG animals. Pre-treatment blood loss was greater in COAG (11 ± 6 mL/kg) than non-COAG (7 ± 3 mL/kg, P = 0.04) animals. Splenic hemorrhage was universally fatal without treatment. Non-COAG coil survival was 4/5 (326 ± 75 min) and non-COAG Gelfoam 3/5 (311 ± 67 min) versus non-COAG Control 0/3 (82 ± 18 min, P < 0.05 for both). Neither COAG Coil (0/5, 195 ± 117 min) nor COAG Gelfoam (0/5, 125 ± 32 min) treatment improved survival over COAG Control (0/3, 56 ± 19 min). Post-treatment blood loss was 4.6 ± 3.4 mL/kg in non-COAG Coil and 4.6 ± 2.9 mL/kg in non-COAG Gelfoam, both lower than non-COAG Control (18 ± 1.3 mL/kg, P = 0.05). Neither COAG Coil (8.4 ± 5.4 mL/kg) nor COAG Gelfoam (15 ± 11 ml/kg) had significantly less blood loss than COAG Control (20 ± 1.2 mL/kg). Both non-COAG treatment groups had minimal blood loss during observation, while COAG groups had ongoing slow blood loss. In the COAG Gelfoam group, there was an increase in hemorrhage between 30 and 60 min following treatment. CONCLUSIONS: A swine model of coagulation-adaptable fatal splenic hemorrhage suitable for endovascular treatment was developed. Coagulopathy had profound negative effects on coil and gelfoam efficacy in controlling bleeding, with implications for trauma and elective embolization procedures.
Subject(s)
Blood Coagulation , Embolization, Therapeutic/instrumentation , Gelatin Sponge, Absorbable/administration & dosage , Hemorrhage/therapy , Splenic Diseases/therapy , Animals , Arterial Pressure , Disease Models, Animal , Hemodilution , Hemorrhage/blood , Hemorrhage/physiopathology , Splenic Diseases/blood , Splenic Diseases/physiopathology , Sus scrofa , Time FactorsABSTRACT
ABSTRACT: Decompensation is a major prehospital threat to survival from trauma/hemorrhage shock (T/HS) after controlling bleeding. We recently showed higher than expected mortality from a combat-relevant rat model of T/HS (27âmL/kg hemorrhage) with tourniquet (TQ) and permissive hypotensive resuscitation (PHR) with Plasmalyte. Mortality and fluid requirements were reduced by resuscitation with 25% albumin presaturated with oleic acid (OA-sat) compared with fatty-acid -free albumin or Plasmalyte. The objective of this follow-up analysis was to determine the role of decompensation and individual compensatory mechanisms in those outcomes. We observed two forms of decompensation: slow (accelerating fluid volumes needed to maintain blood pressure) and acute (continuous fluid administration unable to prevent pressure drop). Combined incidence of decompensation was 71%. Nearly all deaths (21 of 22) were caused by acute decompensations that began as slow decompensations. The best hemodynamic measure for predicting acute decompensation was diastolic arterial pressure. Decompensation was due to vascular decompensation rather than loss of cardiac performance. Albumin concentration was lower in decompensating groups, suggesting decreased stressed volume, which may explain the association of low albumin on admission with poor outcomes after trauma. Our findings suggest that acute decompensation may be common after trauma and severe hemorrhage treated with TQ and PHR and OA-sat albumin may benefit early survival and reduce transfusion volume by improving venous constriction and preventing decompensation.
Subject(s)
Albumins/administration & dosage , Fatty Acids/administration & dosage , Resuscitation , Shock, Hemorrhagic/therapy , Tourniquets , Animals , Combined Modality Therapy , Disease Models, Animal , Male , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: We sought to gather data about the effects of personal protective equipment (PPE) use on tourniquet interventions by preliminarily developing a way to simulate delay effects, particularly on time and blood loss. Such knowledge might aid readiness. Field calls to emergency departments may indicate donning of PPE before patient arrival. The purpose of this study was to investigate (1) delay effects of donning the PPE studied on field-tourniquet control of hemorrhage and (2) delay effects of wearing the PPE on application of a field tourniquet and its conversion to a pneumatic tourniquet. METHODS: The experiment simulated 30 tests of nonpneumatic field tourniquet use (http://www.combattourniquet.com/wp -content). The research intervention was the use of PPE. Data were grouped. The control group had no PPE (PPE0). PPE1 and PPE2 groups had mostly improvised and off-the-shelf equipment, respectively. PPE1 included donning a coat, goggles, face covering, cap, booties, and gloves. PPE2 had analogous items. The group order was randomized. A test included paired trials: field tourniquet, followed by conversion. An investigator simulated the caregiver. A task trainer simulated a thigh amputation. Donning delays were evaluated as differences in mean times to stop bleeding compared with PPE0. Blood loss results from donning PPE were calculated as the delay multiplied by its bleeding rate, 500mL/min. RESULTS: PPE0 had no delay: its mean blood loss was 392mL. PPE1 had 805mL more blood loss than PPE0 did. PPE2 exceeded PPE0 by 1004mL. Donning time (blood loss) for PPE1 and PPE2 were 1.4 minutes (712mL) and 1.7 minutes (863mL), respectively. The wearing of PPE did not slow down field tourniquet application or its conversion. CONCLUSIONS: How long it took to don PPE delayed the time to stop bleeding and increased blood loss, but wearing PPE slowed down neither field tourniquet application nor its conversion.
Subject(s)
Personal Protective Equipment , Tourniquets , Gloves, Protective , Health Personnel , Hemorrhage/prevention & control , HumansABSTRACT
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-1ß 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.
Subject(s)
Balloon Occlusion/adverse effects , Resuscitation/methods , Shock, Hemorrhagic/physiopathology , Animals , Aorta/physiopathology , Balloon Occlusion/methods , Blood Pressure , Blood Pressure Determination , Blood Transfusion , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Hemodynamics , Hemorrhage , Inflammation , Liver/physiopathology , Male , Models, Animal , Reperfusion Injury/physiopathology , Shock, Hemorrhagic/metabolism , Swine , Torso/physiopathologyABSTRACT
We investigated whether a statistical model could predict mean arterial pressure (MAP) during uncontrolled hemorrhage; such a model could be used for automated decision support, to help clinicians decide when to provide intravascular volume to achieve MAP goals. This was a secondary analysis of adult swine subjects during uncontrolled splenic bleeding. By protocol, after developing severe hypotension (MAP < 60 mmHg), subjects were resuscitated with either saline (NS) or fresh frozen plasma (FFP), determined randomly. Vital signs were documented at quasi-regular time-step intervals, until either subject death or 300 min. Subjects were randomly separated 50%/50% into training/validation sets, and regression models were developed to predict MAP for each subsequent (i.e., future) time-step. Median time-steps for serially recorded vital signs were +15 min. 5 subjects survived the protocol; 17 died after a median time of 87 min (IQR 78 - 134). The final model consisted of: current MAP; heart rate (HR); prior NS; imminent NS; and imminent FFP. The 95% limits-of-agreement between true subsequent MAP vs. predicted subsequent MAP were +10/-11 mmHg for the 79 time-steps in the training set; and +14/-13 for the 64 time-steps in the validation set. A total of 10 sudden death events (i.e., rapid, fatal MAP decrease within one single time-step) were excluded from analysis. In conclusion, for uncontrolled hemorrhage in a swine model, it was possible to estimate the next documented MAP value on the basis of the subject's current documented MAP; HR; prior NS; and the volume of resuscitation about to be administered. However, the model was unable to predict "sudden death" events. The applicability to populations with wider heterogeneity of hemorrhage patterns and with comorbidities requires further investigation.
Subject(s)
Shock, Hemorrhagic , Animals , Disease Models, Animal , Hemodynamics , Hemorrhage/therapy , Resuscitation , Shock, Hemorrhagic/therapy , SwineABSTRACT
Fluid resuscitation improves clinical outcomes of burn patients; however, its execution in resource-poor environments may have to be amended with limited-volume strategies. Liver dysfunction is common in burn patients and gut dysbiosis is an understudied aspect of burn sequelae. Here, the swine gut microbiota and liver transcripts were investigated to determine the impact of standard-of-care modified Brooke (MB), limited-volume colloid (LV-Co), and limited-volume crystalloid (LV-Cr) resuscitation on the gut microbiota, and to evaluate its' potential relationship with liver dysfunction. Independent of resuscitation strategy, bacterial diversity was reduced 24 h post-injury, and remained perturbed at 48 h. Changes in community structure were most pronounced with LV-Co, and correlated with biomarkers of hepatocellular damage. Hierarchical clustering revealed a group of samples that was suggestive of dysbiosis, and LV-Co increased the risk of association with this group. Compared with MB, LV-Co and LV-Cr significantly altered cellular stress and ATP pathways, and gene expression of these perturbed pathways was correlated with major dysbiosis-associated bacteria. Taken together, LV-Co resuscitation exacerbated the loss of bacterial diversity and increased the risk of dysbiosis. Moreover, we present evidence of a linkage between liver (dys)function and the gut microbiota in the acute setting of burn injury.
Subject(s)
Burns/microbiology , Burns/therapy , Gastrointestinal Microbiome , Liver/physiopathology , Animals , Burns/metabolism , Burns/physiopathology , Dysbiosis/complications , Gene Expression Regulation , Liver/metabolism , SwineABSTRACT
BACKGROUND: Given little data to assess guidelines, we sought a way to exchange one type of intervention, field tourniquet use, for another, use of a pressure dressing. The study purpose was to test performance of controlling simulated bleeding with a stepwise procedure of tourniquet conversion. METHODS: An experiment was designed to assess 15 tests of a caregiver making tourniquet-dressing conversions. Tests were divided into trials: tourniquet use and its conversion. In laboratory conditions, the tourniquet trial was care under gunfire; then, the conversion trial was emergency healthcare. A HapMed Leg Tourniquet Trainer simulated a limb amputation. An investigator provided healthcare. RESULTS: Mean (± standard deviation [SD]) test time and blood loss were 9 ± 3.6 minutes and 334 ± 353.9mL, respectively. The first test took 17 minutes. By test number, times decreased; the last six took ≤7 minutes. All tourniquet trials controlled bleeding. Mean (±SD) tourniquet pressure and blood loss were 222 ± 18.0mmHg and 146 ± 40.9mL, respectively. Bleeding remained uncontrolled in one conversion. Initial attempts to wrap a dressing were effective in 73% of tries (n = 11 of 15). Four of 15 wrap attempts (27%) were repeated to troubleshoot bleeding recurrence, and the first three tests required a repetition. Mean (±SD) dressing pressures and blood losses were 141 ± 17.6mmHg and 188 ± 327.4mL, respectively. Unsatisfactory conversion trials had a dressing pressure <137mmHg. Dressings and wraps hid the wound to impair assessment of bleeding. CONCLUSIONS: In testing a method of converting a limb tourniquet to a pressure dressing, the caregiver performed faster with experience accrual. The tourniquet results were uniformly good, but conversion results were worse and more varied. Simulating conversion was disappointing on a manikin and indicated that its redesign might be needed to suit this method. The procedural method constituted a start for further development.
Subject(s)
Bandages , Tourniquets , First Aid , Hemorrhage/therapy , Humans , ManikinsABSTRACT
BACKGROUND: We sought new knowledge by further developing a model of using calculations in the simulation of a first-aid task. The purpose of this study was to develop the model to investigate the performance of tourniquet use in its component steps. METHODS: We aimed to design an experiment on a desktop computer by mathematically manipulating simulated data in tourniquet use. A time factor of tourniquet use was ranged widely through time challenges in five degrees from ideal to worst performances. Redesigning the task was assessed by time costs and blood losses. RESULTS: The step of tourniquet application took 17% of the trial time and securing the tourniquet after bleeding control took the longest amount of the trial time, 31%. A minority of the time (48% [17% + 31%] to apply tourniquet plus secure it) was spent after the tourniquet touched the patient, whereas most of the time (52%) was spent before the tourniquet touched the patient. The step of tourniquet application lost 14% of the total blood lost, whereas no blood was lost during securing the tourniquet, because that was the moment of bleeding control despite securing the tourniquet taking much time (31%). Most (86%) of blood lost occurred before the tourniquet touched the patient. But blood losses differed 10-fold, with a maximum of 2,434mL, which, when added to a pretask indication blood loss of 177mL, summed to 2,611mL. Before redesigning the task, costs of donning gloves and calling 9-1-1 included uncontrolled bleeding, but gloving mitigated risk of spreading pathogens among people. By step and person, redesigns of the task altered the risk-benefit profile. CONCLUSIONS: The model was useful because it simulated where most of the bleeding occurred before the tourniquet touched the patient. Modeling simulated redesigns of the task, which showed changes in the task's risk-benefit profile by step and among persons. The model generated hypotheses for future research, including the capability to screen candidate ideas among task designs.
Subject(s)
First Aid , Hemorrhage/therapy , Tourniquets , Computer Simulation , Humans , Time FactorsABSTRACT
BACKGROUND: This study compared the resuscitation effects of platelets and fibrinogen concentrate (FC) on coagulation and hemodynamics in pigs with traumatic hemorrhage and reduced platelet counts. METHODS: Thirty pigs (40 ± 3 kg) were anesthetized and catheterized with an apheresis catheter to remove platelets using the Haemonetics 9000 (Haemonetics, Braintree, MA). Afterward, a femur fracture was induced, followed by hemorrhage of 35% the estimated blood volume. Pigs were then randomized to be resuscitated with 5% human albumin (12.5 mL/kg), FC (250 mg/kg, 12.5 mL/kg), or platelets collected from apheresis (11.0 ± 0.5 mL/kg). Animals were monitored for 2 hours or until death. Blood samples were collected before (baseline [BL]) and after apheresis, after hemorrhage, and after resuscitation to assess changes in hemodynamics and coagulation using Rotem. RESULTS: No change in mean arterial pressure (MAP) or heart rate (HR) was observed by platelet apheresis. Hemorrhage reduced MAP to 57% ± 5% and elevated HR to 212% ± 20% of BL (both p < 0.05). Resuscitation with albumin, FC, or platelets did not revert MAP or HR to BL. Platelet counts were reduced by apheresis from BL 383 ± 20 × 10/µL to 141 ± 14 × 10/µL and were reduced further after resuscitation with albumin (88 ± 18 × 10/µL) or FC (97 ± 13 × 10/µL, all p < 0.05), but improved with platelet resuscitation (307 ± 24 × 10/µL). Fibrinogen concentration was reduced by apheresis from BL 225 ± 9 mg/dL to 194 ± 8 mg/dL, fell after albumin infusion (134 ± 11 mg/dL), increased to 269 ± 10 mg/dL after FC resuscitation (all p < 0.05), and was not affected by platelet resuscitation. Rotem α-angle decreased from 79 ± 2 degrees to 69 ± 1 degrees by apheresis and hemorrhage (p < 0.05), and recovered similarly by resuscitation with FC (87 ± 1 degrees) or platelets (78 ± 2 degrees), but not by albumin (63 ± 3 degrees). Similar responses were observed in Rotem maximum clot firmness. CONCLUSION: In this traumatic hemorrhage swine model, low-volume resuscitation with FC or platelets was similarly effective in restoring coagulation.
Subject(s)
Blood Platelets , Fibrinogen/therapeutic use , Hemorrhage/therapy , Resuscitation/methods , Albumins/therapeutic use , Animals , Blood Component Removal , Cardiac Output , Disease Models, Animal , Fibrinogen/administration & dosage , Fibrinogen/analysis , Hemodynamics , Hemorrhage/physiopathology , Platelet Count , SwineABSTRACT
The acute systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction (MOD) that occur in large burn injuries may be attributed, in part, to immunosuppressive responses such as decreased lymphocytes. However, the mitochondrial bioenergetics of lymphocytes after severe burn injury are poorly understood. The purpose of this study was to examine mitochondrial function of lymphocytes following severe burns in a swine model. Anesthetized Yorkshire swine (n = 17) sustained 40% total body surface area full-thickness contact burns. Blood was collected at pre-injury (Baseline; BL) and at 24 and 48 h after injury for complete blood cell analysis, flow cytometry, cytokine analysis, and ficoll separation of intact lymphocytes for high-resolution mitochondrial respirometry analysis. While neutrophil numbers increased, a concomitant decrease was found in lymphocytes (P < 0.001) after burn injury, which was not specific to CD4+ or CD8+ lymphocytes. No changes in immune cell population were observed from 24 h to 48 h post-injury. IL 12-23 decreased while a transient increase in IL 4 was found from BL to 24h (P < 0.05). CRP progressively increased from BL to 24h (P < 0.05) and 48h (P < 0.001) post-injury. Routine and maximal mitochondrial respiration progressively increased from BL to 24h (P < 0.05) and 48 h post-injury (P < 0.001). No changes were found in leak respiration or residual oxygen consumption. When considering the reduction in lymphocyte number, the total peripheral lymphocyte bioenergetics per volume of blood significantly decreased from BL to 24h and 48h (P < 0.05). For the first time, we were able to measure mitochondrial activity in intact lymphocyte mitochondria through high-resolution respirometry in a severely burned swine model. Our data showed that the non-specific reduction in peripheral T cells after injury was larger than the increased mitochondrial activity in those cells, which may be a compensatory mechanism for the total reduction in lymphocytes. Additional studies in the metabolic activation of T cell subpopulations may provide diagnostic or therapeutic targets after severe burn injury.
Subject(s)
Burns/metabolism , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Lymphocytes/pathology , Mitochondria/metabolism , Animals , Burns/immunology , Cell Count , Cell Respiration , Cells, Cultured , Cytokines/blood , Disease Models, Animal , Humans , Oxidative Phosphorylation , SwineABSTRACT
BACKGROUND: Junctional hemorrhage is a leading contributor to battlefield mortality. The Abdominal Aortic and Junctional Tourniquet (AAJT) and infrarenal (zone III) resuscitative endovascular balloon occlusion of the aorta (REBOA) are emerging strategies for controlling junctional hemorrhage, with AAJT currently available in select forward deployed settings and increasing interest in applying REBOA in the military prehospital environment. This study compared the hemostatic, hemodynamic, and metabolic effects of these devices used for junctional hemorrhage control. METHODS: Shock was induced in anesthetized, mechanically ventilated swine with a controlled hemorrhage (20 mL/kg) and closed femur fracture followed by uncontrolled hemorrhage from a partial femoral artery transection (40% total hemorrhage volume). Residual femoral hemorrhage was recorded during 60-minute AAJT (n = 10) or zone III REBOA (n = 10) deployment, and the arterial injury was repaired subsequently. Animals were resuscitated with 15 mL/kg autologous whole blood and observed for 6 hours. RESULTS: One animal in each group died during observation. Both devices achieved hemostasis with mean residual femoral blood loss in the AAJT and REBOA groups of 0.38 ± 0.59 mL/kg and 0.10 ± 0.07 mL/kg (p = 0.16), respectively, during the 60-minute intervention. The AAJT and REBOA augmented proximal blood pressure equally with AAJT allowing higher distal pressure than REBOA during intervention (p < 0.01). Following device deflation, AAJT animals had transiently lower mean arterial blood pressure than REBOA pigs (39 ± 6 vs. 54 ± 11 mm Hg p = 0.01). Both interventions resulted in similar degrees of lactic acidemia which resolved during observation. Similar cardiac and renal effects were observed between AAJT and REBOA. CONCLUSION: The AAJT and REBOA produced similar hemostatic, resuscitative, and metabolic effects in this model of severe shock with junctional hemorrhage. Both interventions may have utility in future military medical operations.
Subject(s)
Aorta, Abdominal/surgery , Balloon Occlusion/methods , Endovascular Procedures/methods , Hemorrhage/physiopathology , Hemorrhage/surgery , Hemostasis, Surgical/instrumentation , Animals , Female , Femoral Artery/injuries , Hemodynamics , Hemorrhage/etiology , Hemostasis, Surgical/adverse effects , Hemostasis, Surgical/methods , Models, Anatomic , Models, Animal , Swine , Trauma Severity Indices , Vascular System Injuries/complications , Vascular System Injuries/surgeryABSTRACT
In humans, the leading cause of potentially preventable death on the modern battlefield is undoubtedly exsanguination from massive hemorrhage. The US military and allied nations have devoted enormous effort to combat hemorrhagic shock and massive hemorrhage. This has yielded numerous advances designed to stop bleeding and save lives. The development of extremity, junctional and truncal tourniquets applied by first responders have saved countless lives both on the battlefield and in civilian settings. Additional devices such as resuscitative endovascular balloon occlusion of the aorta (REBOA) and intraperitoneal hemostatic foams show great promise to address control the most difficult forms (non-compressible) of hemorrhage. The development of next generation hemostatic dressings has reduced bleeding both in the prehospital setting as well as in the operating room. Furthermore, the research and fielding of antifibrinolytics such as tranexamic acid have shown incredible promise to ameliorate the effects of acute traumatic coagulopathy which has led to significant morbidity and mortality in service members. Advances from lessons learned on the battlefield have numerous potential parallels in veterinary medicine and these lessons are ripe for translation to veterinary medicine.
ABSTRACT
BACKGROUND: Hemodynamic aberrations after severe burns are treated with aggressive intravenous (IV) fluid resuscitation however, oral resuscitation has been proposed in resource poor scenarios. Previously we have shown that animals receiving oral fluid following burns were able to recover kidney function. However, immune function such as circulating and splenic immune cell populations after oral or intravenous fluid administration was not examined. Herein, we perform a follow up analysis of splenic tissue and plasma from the previous animal study to examine the splenic response following these resuscitation strategies after burn injury. METHODS: Eighteen anesthetized Yorkshire swine receiving 40%TBSA contact burns were randomized to receive either: (1) no fluids (Fluid Restricted; negative control), (2) 70 mL/kg/d Oral Rehydration Salt solution (Oral), or (3) 2 mL/kg/%TBSA/d of lactated Ringer's solution IV. Blood was drawn for blood cell analysis, and CT scans were performed before and 48 h post-burn, at which point spleens were harvested for histological, Western blot, and RT-PCR analyses. RESULTS: Splenic artery diameter decreased by -0.97 ± 0.14 mm in fluid-restricted animals, while IV led to an increase of 0.68 ± 0.30 mm. No significant differences were detected in white and red pulp. IV fluids reduced the population of splenic monocytes (CD163; P = 0.001) and neutrophils (MPO protein; P = 0.13), as well as cytokines IL-8 (P = 0.003), IFN-γ (P = 0.11) and TNFα (P = 0.05). Additionally, withholding IV fluids consistently decreased the expression of FoxP3, CCR6, and IL17ß in spleen, suggesting a shift in T-cell phenotype with IV resuscitation. CONCLUSIONS: The route of fluid administration has a minor influence on the changes in circulating and splenic leukocytes post-burn in the acute phase. Further research is needed to help guide resuscitation approaches using immunologic markers of splenic function following burns.