History of High-Resolution Anoscopy.

High-resolution anoscopy (HRA) is a form of low-resolution anal microscopy currently utilized in the screening and management of anal squamous dysplasia. No randomized controlled trials, national or international guidelines exist on the use of HRA for this purpose. Much of our understanding of this entity has been adapted from the literature on cervical squamous dysplasia, including the technique of HRA itself. Epidemiologic evidence has shown that the prevalence and incidence of anal dysplasia is highest in HIV-positive populations. The history of this technique parallels the evolution of our understanding of anal dysplasia. To understand the history of the use of HRA and its place in the screening and management of anal squamous dysplasia, we discuss key advances in the understanding of human papillomavirus-related squamous dysplasia. We begin with early reports in the field establishing the link between this virus and squamous dysplasia, through the marked increase in anal cancer seen with the onset of the HIV epidemic, the identification of relevant populations at risk, the performance of the test itself, to its use today.

The use of lyophilized plasma in a severe multi-injury pig model.

BACKGROUND: Shock and severe tissue injury lead to an endogenous coagulopathy mediated by activation of Protein C and hyperfibrinolysis known as acute traumatic coagulopathy. Together, hemodilution, acidosis, inflammation, and hypothermia result in a global trauma-induced coagulopathy. Coagulopathy in trauma is associated with mortality. Early and effective hemostatic resuscitation is critical in restoring perfusion, correcting coagulopathy, and saving lives in exsanguinating trauma. Lyophilized plasma (LP) provides a logistically superior alternative to fresh frozen plasma (FFP). STUDY DESIGN AND METHODS: Plasma was lyophilized following whole blood collection from anesthetized swine. A series of studies were performed using anesthetized swine subjected to a validated model of polytrauma and hemorrhagic shock including a Grade V liver injury. Animals were randomized to resuscitation using reconstituted LP fluids. Physiologic data and blood loss were measured. Coagulation status and inflammatory mediators were evaluated. RESULTS: Full volume reconstituted LP (100%LP) retains on average 86% coagulation factor activity compared to fresh plasma and when used in 1:1 ratios with red blood cells demonstrated superior hemostatic efficacy compared to FFP. Hypertonic LP reconstituted using 50% of the original plasma volume (50%LP) had higher coagulation factor concentrations, was well tolerated in swine, and equally effective compared to 100%LP with respect to physiologic and hemostatic properties. Buffering with ascorbic acid resulted in significant reductions in serum levels of tumor necrosis factor alpha and interleukin-6. CONCLUSION: By minimizing the volume of reconstituted LP and optimizing its anti-inflammatory properties, an LP resuscitation fluid may be created to provide effective hemostatic resuscitation with superior logistical properties.

Blood volume analysis can distinguish true anemia from hemodilution in critically ill patients.

BACKGROUND: Peripheral hematocrit (pHct) is traditionally used as a marker for blood loss. In critically ill patients who are fluid resuscitated, pHct may not adequately represent red blood cell volume (RBCV). We hypothesize that the use of pHct alone may overestimate anemia, potentially leading to unnecessary interventions. METHODS: Patients admitted to the intensive care unit underwent blood volume analysis. Serial blood samples were collected after injection of I-albumin. Samples were then processed by the Blood Volume Analyzer-100. RBCV and total blood volume (TBV) were calculated using the directly measured plasma volume (PV) and pHct. A computed normalized hematocrit (nHct) adjusts pHct to the patient's ideal blood volume. RESULTS: Thirty-six patients (21 men), aged 49.8 years ± 18.4 years, Acute Physiology And Chronic Health Evaluation II score 14.9 ± 8.1, and injury severity score 29.4 ± 12.4 had 84 blood volume analyses performed on 3 consecutive days. Using ratios of TBV compared with ideal TBV, patients were stratified into three separate groups: hypovolemic (16 of 84), normovolemic (23 of 84), and hypervolemic (45 of 84). Mean differences between pHct and nHct in each group were 4.5% ± 3.1% (p≤0.01), 0.0% ± 1.2% (p=0.85), and -6.5% ± 4.1% (p≤0.01), respectively. pHct, when compared with nHct, diagnosed anemia (Hct <30) nearly equal within the hypovolemic and normovolemic groups. However, pHct overdiagnosed anemia in 46.7% of hypervolemic patients. CONCLUSION: Use of blood volume analysis in critically ill patients may help to distinguish true anemia from hemodilution, potentially preventing unnecessary interventions.

Management of colonic injuries in the combat theater.

PURPOSE: Combat injuries are more often associated with blast, penetrating, and high-energy mechanisms than civilian trauma, generating controversy about the management of combat colonic injury. Despite implementation of mandatory colostomy in World War II, recent civilian data suggest that primary repair without diversion is safe and feasible. This study describes the modern management of battle-related colonic injuries and seeks to determine whether management strategy affects early complications. METHODS: Records from the combat theater (downrange) and tertiary referral center in Germany were retrospectively reviewed from 2005 to 2006. Patient characteristics, management strategy, treatment course, and early complications were recorded. Comparison groups by management strategy were as follows: primary repair, diversion, and damage control. RESULTS: A total of 133 (97% male) patients sustained colonic injuries from penetrating (71%), blunt (5%), and blast (23%) mechanisms. Average injury severity score was 21 and length of stay in the referral center was 7.1 days. Injury distribution was 21% ascending, 21% descending, 15% transverse, 27% sigmoid, and 25% rectum. Downrange complications for primary repair, initial ostomy, and damage control groups were 14%, 15%, and 30%, respectively. On discharge from the center, 62% of patients had undergone a diversion. The complication rate was 18% overall and was unrelated to management strategy (P = .16). Multivariate analysis did not identify independent predictors of complications. CONCLUSION: Early complications were similar by mechanism, anatomic location, severity of injury, and management strategy. More diversions were performed for rectosigmoid injury. Good surgical judgment allows for low morbidity and supports primary repair in selected cases. Damage control surgery is effective in a multinational theater of operations.

Red blood cells accelerate the onset of clot formation in polytrauma and hemorrhagic shock.

BACKGROUND: Hemorrhage and coagulopathy are major contributors to death after trauma. The contribution of red blood cells (RBCs) in correcting coagulopathy is poorly understood. Current methods of measuring coagulopathy may fail to accurately characterize in vivo clotting. We aimed to determine the effect of RBCs on clotting parameters by comparing resuscitation regimens containing RBCs and plasma with those containing plasma alone. METHODS: Thirty-two Yorkshire swine were anesthetized, subjected to a complex model of polytrauma and hemorrhagic shock, and resuscitated with either fresh frozen plasma, lyophilized plasma (LP), or 1:1 ratios of fresh frozen plasma:packed RBC (PRBC) or LP:PRBC. Activated clotting time, prothrombin time, partial thromboplastin time, and thrombelastography (TEG) were performed at 1 hour, 2 hours, 3 hours, and 4 hours after resuscitation. RESULTS: Animals treated with 1:1 LP:PRBC had less blood loss than the other groups (p < 0.05). The activated clotting time was shorter in the 1:1 groups when compared with the pure plasma groups at all time points (p < 0.05). The 1:1 groups had shorter TEG R times (time to onset of clotting) at 1 hour, 3 hours, and 4 hours compared with pure plasma groups (p < 0.05). Other TEG parameters did not differ between groups. Partial thromboplastin time was shorter in the pure plasma groups than the 1:1 groups at all time points (p < 0.05). CONCLUSIONS: Whole blood assays reveal that RBCs accelerate the onset of clot formation. Coagulation assays using spun plasma underestimate the effect of RBCs on clotting and do not completely characterize clot formation.

Use of leukoreduced blood does not reduce infection, organ failure, or mortality following trauma.

BACKGROUND: Leukoreduced (LR) blood has been demonstrated to reduce morbidity and mortality in high-risk surgical patients, but not in trauma patients. The objective of the present study was to determine the effect of LR blood on morbidity and mortality. We hypothesized that the use of LR blood does not improve outcome in trauma patients. METHODS: This study was a retrospective cohort analysis of trauma patients transfused at a level 1 Trauma Center from 2001 to 2004. Between 2002 and 2003, LR blood was transfused. Prior to that time and subsequent to it, non-leukoreduced (NLR) blood was transfused. This created two historical comparison groups. Data collected included patient demographics, units of blood transfused, intensive care unit (ICU) and hospital days, ventilator days, injury severity score (ISS), mortality, presence of acute respiratory distress syndrome (ARDS), and infectious complications. A multiple organ dysfunction syndrome (MODS) score was calculated. RESULTS: The distribution of patients was as follows: 284 patients received only NLR blood, 153 received only LR blood, and 58 received at least one unit of each. The mean ISS was similar (NLR: 26, LR: 24; P > 0.1). No differences were seen between groups in units transfused (6.2 vs. 5.5), number of ICU days (8.2 vs. 9.0), number of hospital days (16.9 vs. 18.6), number of ventilator days (6.1 vs. 5.7), incidence of ARDS (8.3% vs. 8.5%), MODS score (5.5 vs. 5.9), mortality rate (15.1% vs. 15.7%), or infection rate (36% vs. 30%) (P > 0.1). CONCLUSIONS: This study represents the largest series comparing trauma patients who received either LR or standard blood transfusions. The use of LR blood does not improve outcome in trauma patients.

Thrombelastography versus AntiFactor Xa levels in the assessment of prophylactic-dose enoxaparin in critically ill patients.

BACKGROUND: A standard dose of enoxaparin is frequently used for deep venous thrombosis (DVT) prophylaxis. Evidence suggests inconsistent bioavailability in intensive care unit (ICU) patients. Antifactor Xa activity (anti-Xa) has been used to monitor enoxaparin dosing but its accuracy and availability are problematic. Thrombelastography (TEG) is used to evaluate coagulation in diverse settings. The purpose of this study was to analyze whether TEG could be used to predict which enoxaparin-treated patients would develop DVT. METHODS: Two hundred sixty-one simultaneous enoxaparin-active (active) and enoxaparin-neutralized (neutral) TEGs were performed in 61 surgical ICU patients over four consecutive days. Patient characteristics and anti-Xa were collected. DVT screening was per ICU protocol. RESULTS: Mean (+/-SEM) age was 54 (+/-2.3) years and Acute Physiology and Chronic Health Evaluation II score was 17 (+/-0.7). There were 30 trauma and 31 general surgery patients (69% men). The DVT rate was 28%. Time to clot formation (R) and percent lysis at 30 minutes were different between active versus neutralized blood (p < 0.001). R time was 1.5 minutes shorter in patients with DVT versus those without (p < 0.001) indicating hypercoagulability in DVT patients. Anti-Xa levels were similar in patients with (0.135 +/- 0.012) and without (0.135 +/- 0.007) DVT (p = 0.97). There were no differences in age, body mass index, injury severity score, Acute Physiology and Chronic Health Evaluation II score, or trauma status between DVT and non-DVT groups. CONCLUSIONS: TEG demonstrates differences between enoxaparin-neutralized and enoxaparin-active blood in ICU patients that may be used to guide dosing. TEG differentiates enoxaparin-treated patients who subsequently develop DVT while anti-Xa levels do not. TEG demonstrates an enoxaparin-related increase in fibrinolysis.

Testing of blood products in a polytrauma model: results of a multi-institutional randomized preclinical trial.

INTRODUCTION: Trauma-induced coagulopathy, acidosis, and hypothermia form a "lethal triad" that is difficult to treat and is associated with extremely high mortality. This study was performed at three academic centers to evaluate whether resuscitation with blood components could reverse the coagulopathy in a complex polytrauma model. METHODS: Yorkshire swine (40 +/- 5 kg) were subjected to a three-phase protocol: (a) "Prehospital" phase = femur fracture, hemorrhage (60% blood volume), and 30 minutes shock + infusion of saline (3x shed blood) + induction of hypothermia (33 degrees C); (b) "Early hospital" phase = grade V liver injury; and (c) "Operative" phase= liver packing. After liver packing, the animals (n = 60) were randomized to the following groups: (1) Sham-instrumentation and anesthesia without hemorrhage/injuries, (2) fresh whole blood (FWB), (3) 6% hetastarch (Hextend), (4) fresh frozen plasma/packed RBCs in 1:1 ratio (1:1 FFP/PRBC), and (5) FFP alone. Treatment volumes were equal to the volume of shed blood. Hemodynamic and physiologic parameters and coagulation profile (thrombelastography, prothrombin time, activated partial thromboplastin time, international normalized ratio, and platelets) were monitored during the experiment and for 4 hours posttreatment. RESULTS: At the end of prehospital phase, animals had developed significant acidosis (lactate >5 mmol/L and base deficit >9 mmol/L) and coagulopathy. Posttreatment mortality rates were 85% and 0% for the Hextend and blood component treated groups, respectively (p < 0.05). Hemodynamic parameters and survival rates were similar in groups that were treated with blood products (FWB, FFP, and FFP:PRBC). Animals treated with FFP and Hextend had significant anemia compared with the groups that received red blood cells (FWB and FFP:PRBC). Treatment with FFP and FFP:PRBC corrected the coagulopathy as effectively as FWB, whereas Hextend treatment worsened coagulopathy. CONCLUSIONS: In this reproducible model, we have shown that trauma-associated coagulopathy is made worse by hetastarch, but it can be rapidly reversed with the administration of blood components. Impressively, infusion of FFP, even without any red blood cells, can correct the coagulopathy and result in excellent early survival.

The use of the Wittmann Patch facilitates a high rate of fascial closure in severely injured trauma patients and critically ill emergency surgery patients.

BACKGROUND: The open abdomen after severe intra-abdominal trauma and emergency surgery is a major operative challenge. It is associated with high morbidity and prolonged hospital stays. Several management strategies have been developed to assist with fascial closure but no single method has emerged as the best. The Wittmann Patch (Starsurgical, Burlington, WI) is a unique device which uses velcro to permit progressive abdominal closure without necessitating serial operations. The purpose of this study was to determine the fascial closure rate using the Wittmann patch. We hypothesized that use of the patch would result in a high closure rate. METHODS: Hospital billing codes were reviewed to identify those patients who underwent Wittmann patch placement. During the period from June 2002 to May of 2006, 29 patients were identified. These included 19 trauma patients and 10 other surgical patients. Other patients included vascular, bariatric, and emergency general surgery patients. The trauma registry and the patients' medical records were reviewed to determine injury severity, Acute Physiology and Chronic Health Evaluation II scores, fluid requirements, patch placement, management, and patient outcomes. RESULTS: Twenty-two (76%) of the 29 patients survived to discharge. The average Acute Physiology and Chronic Health Evaluation II score was 25 +/- 6 in all patients, 22.9 +/- 6 in survivors, and 31 +/- 3 in those who died (p = 0.004). Mean injury severity scale and abdominal abbreviated injury scale scores in trauma patients were 28 +/- 10 and 3 +/- 2, respectively. The mean volume of fluid given during the 24 hours before having an open abdomen or patch placement was 17.6 L +/- 10.1 L. Twenty-five (86.2%) of 29 patients had at least one abdominal operation before placement of the patch (mean 1.3 +/- 1.0). Eighteen (82%) of 22 patients who survived to discharge had successful facial closure. Three patients (14%) required mesh placement for abdominal closure. The remaining patient had his patch removed and ultimately underwent skin grafting and subsequent component separation closure. Successful fascial closure was achieved after 15.5 days +/- 10.2 days (range, 5-42 days). The skin was left open in half of the patients. There were four abdominal complications that were noted while the patch was in place. Three of four complications were related to the primary disease, and in the fourth complication the patch became infected and had to be removed. There were no eviscerations or enterocutaneous fistulas after primary fascial closure. The median length of stay was 28 days (Interquartile range, 14-39 days). CONCLUSIONS: Use of the Wittmann Patch can achieve a high rate of delayed fascial closure in severe trauma and critically ill emergency surgery patients with open abdomens. Most of the complications associated with use of the patch were wound infections after fascial closure and closure of the skin.

A novel highly porous silica and chitosan-based hemostatic dressing is superior to HemCon and gauze sponges.

BACKGROUND: Hemostatic dressings have become increasingly popular as the optimal initial treatment for severe hemorrhage. The purpose of this study was to compare the hemostatic properties of a novel highly porous silica and chitosan-based dressing (TraumaStat) to HemCon, and gauze dressing in a severe groin injury model in swine. METHODS: Thirty swine were blindly randomized to receive TraumaStat, HemCon, or standard gauze dressing for hemostatic control. A complex groin injury involving complete transaction of the femoral artery and vein was made. After 30 seconds of uncontrolled hemorrhage, the randomized dressing was applied and pressure was held for 5 minutes. Fluid resuscitation was initiated to achieve and maintain the baseline mean arterial pressure and the wound was inspected for bleeding. Failure of hemostasis was defined as pooling of blood outside of the wound. Animals were then monitored for 120 minutes and surviving animals were euthanized. RESULTS: Blood loss before treatment was similar between groups (p > 0.1). TraumaStat had one failure, compared with five for gauze, and eight for HemCon (p = 0.005, TraumaStat vs. HemCon). TraumaStat significantly reduced median blood loss when compared with both HemCon and gauze (117 vs. 774 and 268 mL respectively, p < 0.05). At study conclusion, TraumaStat animals had a greater median hematocrit than both HemCon (24 vs. 19, p = 0.033), and gauze (24 vs. 19, p = 0.049) animals. Median volume of fluid resuscitation and mortality were not different between groups (p > 0.1). CONCLUSIONS: TraumaStat was superior to HemCon and gauze dressings in controlling bleeding from a severe groin injury. TraumaStat may be a better hemostatic dressing for control of active hemorrhage than current standards of care.

Correlation of missed doses of enoxaparin with increased incidence of deep vein thrombosis in trauma and general surgery patients.

IMPORTANCE: Enoxaparin sodium is widely used for deep vein thrombosis (DVT) prophylaxis, yet DVT rates remain high in the trauma and general surgery populations. Missed doses during hospitalization are common. OBJECTIVE: To determine if missed doses of enoxaparin correlate with DVT formation. DESIGN, SETTING, AND PARTICIPANTS: Data were prospectively collected among 202 trauma and general surgery patients admitted to a level I trauma center. MAIN OUTCOMES AND MEASURES: Deep vein thrombosis screening was performed using a rigorous standardized protocol. RESULTS: The overall incidence of DVT was 15.8%. In total, 58.9% of patients missed at least 1 dose of enoxaparin. The DVTs occurred in 23.5% of patients who missed at least 1 dose and in 4.8% of patients who did not (P < .01). On univariate analysis, the need for mechanical ventilation (71.8% vs 44.1%), the performance of more than 1 operation (59.3% vs 40.0%), and male sex (75% vs 56%) were associated with DVT formation (P < .05 for all). A bivariate logistic regression was then performed, which revealed age 50 years or older and interrupted enoxaparin therapy as the only independent risk factors for DVT formation. The DVT rate did not differ between trauma and general surgery populations or in patients receiving once-daily vs twice-daily dosing regimens. CONCLUSIONS AND RELEVANCE: Interrupted enoxaparin therapy and age 50 years or older are associated with DVT formation among trauma and general surgery patients. Missed doses occur commonly and are the only identified risk factor for DVT that can be ameliorated by physicians. Efforts to minimize interrupted enoxaparin prophylaxis in patients at risk for DVT should be optimized.

Management of the open abdomen during the global war on terror.

OBJECTIVE: To evaluate factors that are predictive of delayed abdominal closure in patients injured during military conflict. DESIGN, SETTING, AND PATIENTS: Seventy-one patients managed with an open abdomen were identified from records at Landstuhl Regional Medical Center from 2005 and 2006. Follow-up data were available from Walter Reed Army Medical Center. Records were reviewed through all echelons of care. Ordinal logistic regression was used to predict delayed abdominal closure. RESULTS: Patients sustained injury from blunt (n = 2), penetrating (n = 30), and blast (n = 39) mechanisms. The median Injury Severity Score was 25 (interquartile range, 17-34). Abdominal injury was observed in 85% of patients, and 48% underwent a massive transfusion. The median time to transfer to the United States was 5.3 days (interquartile range, 4.3-6.8 days). Abdomens were definitively closed downrange (11%), at Landstuhl Regional Medical Center (33%), or at Walter Reed Army Medical Center (56%). The median time until abdominal closure was 13 days (interquartile range, 4-40 days) in 2005 compared with 4 days (interquartile range, 1-14.5 days) in 2006 (P = .02). The multivariate model identified massive transfusion (odds ratio, 3.9), presence of complications (odds ratio, 5.1), and an injury date in 2005 (odds ratio, 3.4) as independently predictive variables for later abdominal closure. CONCLUSIONS: Massive transfusion, occurrence of complications, and earlier injury date were predictive of delayed abdominal closure in casualties managed with an open abdomen. These data suggest an evolving approach to the management of severely injured combat casualties that involves earlier abdominal closure.

A highly porous silica and chitosan-based hemostatic dressing is superior in controlling hemorrhage in a severe groin injury model in swine.

BACKGROUND: This study compared the efficacy of 3 hemostatic dressings in a severe groin injury model in swine. METHODS: Twenty-three swine received TraumaStat (OreMedix, Lebanon, OR), Chitoflex (HemCon, Inc., Portland, OR), or standard gauze for hemostasis. Complete femoral vessel transections were followed by 30 seconds of uncontrolled hemorrhage. The groin was packed with the randomized dressing followed by 30 seconds of compression. Resuscitation with lactated Ringer's solution commenced immediately postcompression to the preinjury mean arterial blood pressure. Hemostasis failure was defined as blood pooling outside the wound. Animals were monitored and maintained at the preinjury mean arterial pressure for 120 minutes, culminating with euthanization. RESULTS: There were no differences in baseline values between groups. TraumaStat resulted in less hemostasis failure (P < .05), decreased postcompression blood loss (P < .05), and decreased fluid requirement (P < .05). No significant difference in mortality was seen between groups. There were no differences between standard gauze and Chitoflex with respect to dressing failure, posttreatment blood loss, or fluid resuscitation. CONCLUSIONS: TraumaStat performed significantly better than Chitoflex and standard gauze in controlling hemorrhage from a severe groin injury in swine.

Analysis of 29 consecutive thoracoscopic repairs of congenital diaphragmatic hernia in neonates compared to historical controls.

PURPOSE: The applicability of minimally invasive surgical techniques to pediatric surgical diseases continues to grow. Surgeons have hesitated to apply these methods to congenital diaphragmatic hernia (CDH) of Bochdalek because of the disease-associated pulmonary hypertension and patient fragility. We began performing thoracoscopic repair (CDH-T) in 2004 and have since completed 29 sequential repairs. To evaluate feasibility and outcomes, we compared this experience to a historical control group who underwent open repair (CDH-O) at the same institution by the same surgeons from 2001 to 2004. METHODS: From January 2001 through November 2007, 72 neonates were evaluated jointly by the Neonatology and Pediatric Surgical services for CDH. Fifteen infants died before any corrective operation and were excluded from analysis. Demographics including gestational age, birth weight, Apgar scores, percent outborn, usage of extracorporeal life support, and associated anomalies were recorded. End points were complications, additional operative procedures, initial patch closure, recurrence, length of stay in non-extracorporeal membrane oxygenation patients, and postoperative mortality. RESULTS: Demographic characteristics were similar between the 2 groups. There were no statistically significant differences in complications (71.5% vs 55%, P = .28), additional related operative procedures (42.9% vs 34.5%, P = .59), use of prosthetic patch (42.8% vs 51.7%, P = .60), recurrence (6.9% vs 20.7%, P = .25), length of stay (24 vs 34 days, P = .11), or postoperative mortality (21.4% vs 6.9%, P = .14) between the CDH-O and CDH-T groups, respectively. There was one conversion in the CDH-T group (3.4%). CONCLUSIONS: To our knowledge, this is the largest reported series of CDH-T of neonatal CDH of Bochdalek. We have demonstrated the feasibility of performing this procedure thoracoscopically in an unselected population including children who have undergone prior extracorporeal life support. These results compare favorably with CDH-O, although further follow-up is required to determine the durability of the approach.

Lyophilized plasma for resuscitation in a swine model of severe injury.

HYPOTHESIS: Lyophilized plasma (LP) is as safe and effective as fresh frozen plasma (FFP) for resuscitation after severe trauma. DESIGN: Multicenter animal study. SETTING: Animal laboratories, 2 level I trauma centers. PARTICIPANTS: Thirty-two Yorkshire crossbred swine. INTERVENTIONS: Lyophilized plasma was analyzed for factor levels and clotting activity before lyophilization and after reconstitution. Swine were subjected to complex multiple trauma including extremity fracture, hemorrhage, severe liver injury, acidosis, and hypothermia. They were then resuscitated with FFP, LP, FFP and packed red blood cells (PRBCs) in a ratio of 1:1, or 1:1 LP and PRBCs. MAIN OUTCOME MEASURES: Residual clotting activity of LP after reconstitution, swine mortality, hemodynamic measures, total blood loss, coagulation profiles, and inflammatory measures. RESULTS: Lyophilization decreased clotting factor activity by an average of 14%. Survival and heart rate were similar between all groups. Swine resuscitated with LP had equivalent or higher mean arterial pressures. Swine treated with LP had similar coagulation profiles, plasma lactate levels, and postinjury blood loss compared with those treated with FFP. Swine treated with 1:1 FFP-PRBCs were similar to those treated with 1:1 LP-PRBCs. Resuscitation with LP resulted in a reduction in postresuscitation interleukin 6 expression compared with resuscitation with FFP. CONCLUSIONS: The process of lyophilization and reconstitution of plasma reduces coagulation factor activity by 14%, without acute differences in blood loss. Lyophilized plasma can be used for resuscitation in a severe multiple trauma and hemorrhagic shock swine model with efficacy equal to that of FFP and with decreased interleukin 6 production.

Reproducibility of an animal model simulating complex combat-related injury in a multiple-institution format.

We developed a complex combat-relevant model of abdominal and extremity trauma, hemorrhagic shock, hypothermia, and acidosis. We then simulated injury, preoperative, and operative phases. We hypothesized that this model is reproducible and useful for randomized multicenter preclinical trials. Yorkshire swine were anesthetized, intubated, and instrumented. They then underwent femur fracture, 60% total blood volume hemorrhage, a 30-min shock period, induced hypothermia to 33 degrees C, and hemorrhage volume replacement with 3:1 isotonic sodium chloride solution (NS) at each of three centers. Hemodynamic parameters were measured continuously. Thromboelastography, arterial blood gas, and laboratory values were collected at baseline, after the shock period, and after NS replacement. Thirty-seven animals were used for model development. Eight (21%) died before completion of the study period. Twenty-nine survivors were included in the analysis. MAP (+/-SEM) after the shock period was 32 +/- 2 mmHg and was similar between centers (P = 0.4). Mean pH, base deficit, and lactate levels were 7.29 +/- 0.02, 8.20 +/- 0.65 mmol/L, and 5.29 +/- 0.44 mmol/L, respectively, after NS replacement. These were similar between centers (P > 0.05). Prothrombin time values increased significantly over time at all centers, reflecting a progressive coagulopathy (P < 0.02). Thromboelastography maximum amplitude values were similar among centers (P > 0.05) and demonstrated progressively weakened platelet interaction over time (P < 0.03). Hematocrit was similar after controlled hemorrhage (P = 0.15) and dilution (P = 0.9). The pH, lactate, base deficit, and coagulation tests reflect a severely injured state. A complex porcine model of polytrauma and shock can be used for multi-institutional study with excellent reproducibility. A consistent severe injury profile was achieved, after which experimental interventions can be applied. This is the first report of a reproducible multicenter trauma and resuscitation-related animal model.

Management and outcome of pneumatosis intestinalis.

BACKGROUND: Pneumatosis intestinalis (PI), infiltration of gas into the bowel wall, has traditionally been associated with immediate operative intervention and a high mortality rate. METHODS: We retrospectively reviewed the diagnosis and management of pneumatosis in an attempt to characterize the disease, and examined management strategies. RESULTS: Ninety-seven patients had a computed tomography (CT) diagnosis of pneumatosis. The location of pneumatosis was as follows: 46% colon, 27% small bowel, 5% stomach, and 7% both small and large bowel. Fourteen patients also had portal venous gas and 6 (43%) of these patients died. Management strategy was non-operative in 52%, operative in 33%, and futile care in 15%. The overall mortality rate was 22% (16% operative, 6% non-operative, and 87% futile). Patients who died had a higher mean APACHE II score (25 vs 11, P <.001). CONCLUSIONS: Approximately 50% of patients with pneumatosis can be successfully managed non-operatively. The combination of PI and portal venous gas may confer a higher mortality rate.