Median arcuate ligament syndrome in athletes.

BACKGROUND: Exercise-related transient abdominal pain (ETAP) is a common entity in young athletes. Most occurrences are due to a "cramp" or "stitch," but an uncommon, and often overlooked, etiology of ETAP is median arcuate ligament syndrome (MALS). The initial presentation of MALS typically includes postprandial nausea, bloating, abdominal pain, and diarrhea, but in athletes, the initial presentation may be ETAP. METHODS: We present a case series of three athletes who presented with exercise-related transient abdominal pain and were ultimately diagnosed and treated for MALS. Unlike other patients with median arcuate ligament syndrome, these athletes presented with exercise-induced pain, rather than the common postprandial symptoms. These symptoms persisted despite conservative measures. Work-up of patients with suspected MALS include a computed tomography or magnetic resonance angiography showing compression of the celiac artery with post-stenotic dilation, or a celiac artery ultrasound demonstrating increased velocities (>200 cm/s2) with deep exhalation. RESULTS: All patients underwent a laparoscopic median arcuate ligament release. Postoperatively, there were no complications, and all were discharged home on postoperative day #2. All patients have subsequently returned to athletics with resolution of their symptoms. CONCLUSION: ETAP is common in athletes and often resolves with preventative or conservative strategies. When ETAP persists despite these methods, alternative causes, including MALS, should be considered. A combination of a thorough history and physical exam, as well as radiographic data, is essential to make the appropriate diagnosis and treatment strategy.

Robotic-assisted colorectal surgery in obese patients: a case-matched series.

BACKGROUND: Reports demonstrate laparoscopic colorectal surgery in obese patients is associated with higher conversion to laparotomy and complication rates. While several advantages of robotic-assisted surgery have been reported, outcomes in obese patients have not been adequately studied. Therefore, this study compares outcomes of robotic-assisted surgery in non-obese and obese patients. METHODS: A retrospective review of 331 consecutive robotic procedures performed at a single institution between 2009 and 2015 was performed. Patients were divided into non-obese (BMI <30 kg/m2) and obese (BMI ≥30 kg/m2) groups, and were clinically matched by gender, age, and procedure performed. Intraoperative and postoperative complications, operative time, estimated blood loss, and length of stay were examined. RESULTS: Following matching, each group included 108 patients comprised of 50 men and 58 women. Mean BMI was 24.6 ± 3.15 and 36.2 ± 5.67 kg/m2 (p < 0.0001), and the mean age was 59.2 ± 11.28 years for non-obese patients and 57.1 ± 12.44 for obese patients (p = 0.18). Surgeries included low anterior resection, right colectomy, left colectomy, sigmoid colectomy, excision of rectal endometriosis, total proctocolectomy, APR, subtotal colectomy, ileocecectomy, proctectomy, rectopexy, transanal excision of rectal mass, and colostomy site hernia repair. The mean operative time was 272.69 ± 115.43 and 282.42 ± 120.51 min (p = 0.55), estimated blood loss 195.23 ± 230.37 and 289.19 ± 509.27 mL (p = 0.08), conversion to laparotomy 6.48 and 9.26 % (p = 0.45), and length of stay 5.38 ± 4.94 and 4.56 ± 4.04 days (p = 0.18) for the non-obese and obese groups, respectively. Twenty of the non-obese patients had postoperative complications as compared to 27 of the obese patients (p = 0.30). However, the prevalence of wound complications was higher in obese patients (1.9 vs 9.3 %; p = 0.03). CONCLUSION: There is no difference in conversion to laparotomy and overall complication rates in non-obese and obese patients undergoing robotic-assisted colorectal surgery. However, obesity is associated with a higher prevalence of wound complications. Robotic-assisted surgery may minimize conversion to laparotomy and complications typically seen in obese patients due to improved visualization, instrumentation, and ergonomics.

Laparoscopic Puestow: lateral pancreaticojejunostomy.

INTRODUCTION: Chronic pancreatitis is a painful inflammatory disease that leads to progressive and irreversible destruction of pancreatic parenchyma [1]. A lateral pancreaticojejunostomy, also known as the Puestow procedure, is performed for symptomatic chronic pancreatitis associated with a dilated pancreatic duct secondary to calcifications or strictures [4]. An open approach is used traditionally due to the complexity of the case, and there have only been a handful of laparoscopic case reports [2]. This video depicts a laparoscopic lateral pancreaticojejunostomy for chronic pancreatitis. METHODS: A 45-year-old gentleman with a 20-year history of chronic alcohol abuse presented with diffuse abdominal pain. His pain was worse postprandially and associated with loose stools. A computed tomography scan revealed multiple calcified deposits within the body and tail of the pancreas, and a dilated pancreatic duct measuring 1.4 cm with a proximal obstructing calcified stone. A 5-port foregut technique was used, and a 15-cm pancreatic ductotomy was performed with an ultrasonic scalpel. Calcified stones were cleared from the duct, and a roux-en-y pancreaticojejunostomy was performed using a hand-sewn technique. RESULTS: The patient had a relatively uncomplicated hospital course with return of bowel function on postoperative day 4. His patient-controlled analgesic device was discontinued on post operative day 3. He was ambulating, tolerating a regular diet and discharged home on postoperative day 5. At 12- and 26-month follow-up, he remains off narcotics, but still requires 1-2 tabs of pancreatic enzyme replacement per meal. Most importantly, he has not had any alcohol for over 2 years. CONCLUSION: The two primary goals in treating chronic pancreatitis include long-term pain relief and improvements in quality of life [3]. For patients with chronic pancreatitis and a dilated pancreatic duct, a laparoscopic lateral pancreaticojejunostomy may be an effective approach to decrease pain and improve quality of life.

Incisional and port-site hernias following robotic colorectal surgery.

BACKGROUND: The association between extraction site location, robotic trocar size, and the incidence of incisional hernias in robotic colorectal surgery remain unclear. Laparoscopic literature reports variable rates of incisional hernias versus open surgery, and variable rates of trocar site hernias. However, conclusions from these studies are confusing due to heterogeneity in closure techniques and may not be generalized to robotic cases. This study evaluates the effect of extraction site location on incisional hernia rates, as well as trocar hernia rates in robotic colorectal surgery. MATERIALS AND METHODS: A retrospective review of multiport and single incision robotic colorectal surgeries from a single institution was performed. Patients underwent subtotal, segmental, or proctocolectomies, and were compared based on the extraction site through either a muscle-splitting (MS) or midline (ML) incision. Hernias were identified by imaging and/or physical exam. Demographics and risk factors for hernias were assessed. Groups were compared using a multivariate logistic regression analysis. RESULTS: The study included 259 colorectal surgery patients comprising 146 with MS and 113 with ML extraction sites. Postoperative computed tomograms were performed on 155 patients (59.8 %) with a mean follow-up of 16.5 months. The overall incisional hernia rate was 5.8 %. A significantly higher hernia rate was found among the ML group compared to the MS group (12.4 vs. 0.68 %, p < 0.0001). Of the known risk factors assessed, only increased BMI was associated with incisional hernias (OR 1.18). No trocar site hernias were found. CONCLUSION: Midline extraction sites are associated with a significantly increased rate of incisional hernias compared to muscle-splitting extraction sites. There is little evidence to recommend fascia closure of 8-mm trocar sites.

Exercise-related transient abdominal pain secondary to median arcuate ligament syndrome: a case report.

Exercise-related transient abdominal pain is a common entity in young athletes. An uncommon aetiology of this type of pain is median arcuate ligament syndrome. This article details an 18-year-old field hockey player who presented with a 1-year history of exercise-related transient abdominal pain. Despite a trial of preventative strategies, the patient's pain persisted, prompting surgical intervention. Following a laparoscopic median arcuate ligament release, the patient's symptoms resolved. Therefore, when exercise-related transient abdominal pain persists despite precautionary measures, median arcuate ligament syndrome should be considered.

Antiplatelet therapy is associated with decreased transfusion-associated risk of lung dysfunction, multiple organ failure, and mortality in trauma patients.

OBJECTIVE: To determine whether prehospital antiplatelet therapy was associated with reduced incidence of acute lung dysfunction, multiple organ failure, and mortality in blunt trauma patients. DESIGN: Secondary analysis of a cohort enrolled in the National Institute of General Medical Sciences Trauma Glue Grant database. SETTING: Multicenter study including nine U.S. level-1 trauma centers. PATIENTS: A total of 839 severely injured blunt trauma patients at risk for multiple organ failure (age > 45 yr, base deficit > 6 mEq/L or systolic blood pressure < 90 mm Hg, who received a blood transfusion). Severe/isolated head injuries were excluded. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were lung dysfunction (defined as grades 2-3 by the Denver multiple organ failure score), multiple organ failure (Denver multiple organ failure score >3), and mortality. Patients were documented as on antiplatelet therapy if taking acetylsalicylic acid, clopidogrel, and/or ticlopidine. Fifteen percent were taking antiplatelet therapy prior to injury. Median injury severity score was 30 (interquartile range 22-51), mean age 61 + 0.4 yr and median RBCs volume transfused was 1700 mL (interquartile range 800-3150 mL). Overall, 63% developed lung dysfunction, 19% had multiple organ failure, and 21% died. After adjustment for age, gender, comorbidities, blood products, crystalloid/12 hrs, presence of any head injury, injury severity score, and 12 hrs base deficit > 8 mEq/L, 12 hrs RBC transfusion was associated with a significantly smaller risk of lung dysfunction and multiple organ failure among the group receiving antiplatelet therapy compared with those not receiving it (lung dysfunction p = 0.0116, multiple organ failure p = 0.0291). In addition, antiplatelet therapy had a smaller risk (albeit not significant, p = 0.06) of death for patients receiving RBC compared to those not on antiplatelet therapy after adjustment for confounders, CONCLUSIONS: Pre-injury antiplatelet therapy is associated with a decreased risk of lung dysfunction, multiple organ failure, and possibly mortality in high-risk blunt trauma patients who received blood transfusions. These findings suggest platelets have a role in organ dysfunction development and have potential therapeutic implications.

Nebulized hypertonic saline attenuates acute lung injury following trauma and hemorrhagic shock via inhibition of matrix metalloproteinase-13.

OBJECTIVE: We hypothesized that aerosolized inhaled hypertonic saline given at the onset of resuscitation will decrease acute lung injury following hemorrhagic shock, by inhibiting the release of epithelial derived proinflammatory mediators. DESIGN: Animal study. SETTING: Animal-care facility procedure room in a medical center. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Rats underwent hemorrhagic shock followed by 2 hrs of resuscitation and 1 hr of observation. In the study group, nebulized hypertonic saline was delivered at the end of the shock period and after 1 hr and 2 hrs of resuscitation. MEASUREMENTS AND MAIN RESULTS: Shock provoked acute lung injury, which was attenuated with inhaled hypertonic saline (1.56 ± 0.2 mg protein/mL vs. 0.95 ± 0.3 mg protein/mL bronchoalveolar lavage fluid, shock vs. shock + hypertonic saline, p < .01). Nebulized hypertonic saline reduced inflammation (cytokine-induced neutrophil chemoattractant-1 accumulation in bronchoalveolar lavage fluid 5999 ± 1267 pg/mL vs. 3342 ± 859 pg/mL, shock vs. shock + hypertonic saline, p = .006). Additionally, nebulized hypertonic saline inhibited matrix -metalloproteinase-13 accumulation in the bronchoalveolar lavage fluid (1513 ± 337 pg/mL bronchoalveolar lavage fluid vs. 230 ± 19 pg/mL, shock vs. shock + hypertonic saline, p = .009) and pretreatment with a matrix metalloproteinase-13 inhibitor was sufficient to attenuate postshock acute lung injury (1.42 ± 0.09 mg/mL vs. 0.77 ± 0.23 mg/mL bronchoalveolar lavage protein, shock vs. shock + matrix metalloproteinase-13 inhibitor CL-82198, p = .002). CONCLUSION: Inhaled hypertonic saline attenuates postshock acute lung injury by exerting an anti-inflammatory effect on the pulmonary epithelium, suggesting a new clinical strategy to treat acute lung injury/acute respiratory distress syndrome.

Hemodilution is not critical in the pathogenesis of the acute coagulopathy of trauma.

BACKGROUND: The acute coagulopathy of trauma is multifactorial, but generally believed to be aggravated by coexisting acidosis, hypothermia, and hemodilution. While acidosis and hypothermia have been extensively evaluated, there is a paucity of data on the independent role of hemodilution in this scenario. We therefore hypothesized that hemodilution will impair coagulation following experimental trauma and hemorrhagic shock. METHODS: Adult male Spraque-Dawley rats underwent trauma and hemorrhagic shock, followed by resuscitation with 2 × SBV using normal saline (NS). Thrombelastography (TEG) was performed before and after shock. RESULTS: In this trauma model, resuscitation resulted in a hemodilution of 50% (43% ± 4.05% versus 19.8% ± 3.96% Hct pre-shock versus post-shock , P < 0.0001). Despite the substantial hemodilution, there was no significant change in clot strength (12.96 ± 2.84 versus 11.79 ± 1.28 dynes/cm(2) G pre-shock versus post-shock, P = 0.13). Similarly, the onset of coagulation (R time) was not impaired (1.68 ± 1.74 s versus 1.75 ± 0.63 s R time pre-shock versus post-shock, P = 0.45). CONCLUSION: In the absence of hypothermia and acidosis, hemodilution (≤ 50%) has a trivial effect on coagulation following trauma and hemorrhagic shock. These data call to question the commonly held belief that hemodilution per se is critical in the development of post-injury coagulopathy.

Cross-transfusion of postshock mesenteric lymph provokes acute lung injury.

OBJECTIVE: Substantial investigation has implicated mesenteric lymph as the mechanistic link between gut ischemia/reperfusion (I/R) and distant organ injury. Specifically, lymph diversion prevents acute lung injury (ALI) in vitro, and bioactive lipids and proteins isolated from postshock mesenteric lymph (PSML) maintain bioactivity in vitro. However, Koch's postulates remain to be satisfied via direct cross-transfusion into a naïve animal. We therefore hypothesized that real time cross-transfusion of postshock mesenteric lymph provokes acute lung injury. METHODS: One set of Sprague-Dawley rats (lymph donors) was anesthetized, with the mesenteric lymph ducts cannulated and exteriorized to drain freely into a siliconates plastic cup; concurrently, a second group of rats ( lymph recipients) was anesthetized, with a cannula inserted into the animal's right internal jugular vein. Blood was removed from the donor rats to induce hemorrhagic shock (MAP of 35 mmHg × 45 min). The recipient rats were positioned 10 cm below the plastic cup, which emptied into the jugular vein cannula. Thus, mesenteric lymph from the shocked donor rat was delivered to the recipient rat at the rate generated during shock and the subsequent 3 h of resuscitation. RESULTS: Neutrophil (PMN) accumulation in the lungs was substantially elevated in the postshock lymph cross-transfusion group compared to both sham lymph cross-transfusion and instrumented control (MPO: 9.42 ± 1.55 versus 2.81 ± 0.82 U/mg lung tissue in postshock versus sham lymph cross-transfusion, n = 6 in each group, P = 0.02). Additionally, cross-transfusion of PSML induced oxidative stress in the lung (0.21 ± 0.03 versus 0.10 ± 0.01 micromoles MDA per mg lung tissue in lymph cross-transfusion versus instrumented control, n = 6 in each group, P = 0.046). Furthermore, transfusion of PSML provoked lung injury (BAL protein 0.77 ± 0.18 versus 0.15 ± 0.02 mg/mL protein in BALF, postshock versus sham lymph cross-transfusion, n = 6 in each group, P = 0.004). CONCLUSION: Cross-transfusion of PSML into a naïve animal leads to PMN accumulation and provokes ALI. These data provide evidence that postshock agents released into mesenteric lymph are capable of provoking distant organ injury.

The acute coagulopathy of trauma is due to impaired initial thrombin generation but not clot formation or clot strength.

BACKGROUND: Acute coagulopathy of trauma (ACOT) has been described as a very early hypocoagulable state, but the mechanism remains controversial. One proposed mechanism is tissue hypoperfusion leading to protein C activation, with subsequent inhibition of Factors V and VIII. Variability in trauma has impeded the use of clinical data towards the elucidation of the mechanisms of ACOT, but thrombelastography (TEG) may provide insight by assessing hemostatic function from initial thrombin activation to fibrinolysis. We hypothesized that in a controlled animal model of trauma/hemorrhagic shock, clotting factor dysfunction is the predominant mechanism in early ACOT. METHODS: Rats anesthetized by inhaled isoflurane (n = 6) underwent laparotomy, and hemorrhage was induced to maintain a MAP of 35 mm Hg for 30 min. Rats were then resuscitated with twice their shed blood volume in normal saline. TEG was performed at baseline, shock, and post-resuscitation periods. No heparin was given. Statistical analysis was performed by ANOVA with post-hoc Fisher's test. RESULTS: Coagulation factor function was significantly impaired in the early stages of trauma/hemorrhagic shock. TEG R and SP-values were significantly increased from baseline to shock (P < 0.001) and from shock to post-resuscitation periods (P < 0.05). Delta (R-SP), a measure of thrombin generation, showed a significant increase (P < 0.05) from baseline to shock. No significant changes were found in K, Angle, MA, and LY30 values. CONCLUSION: Clotting factor derangement leading to impaired thrombin generation is the principle etiology of ACOT in this model and not the dynamics of clot formation, fibrin cross-linking, clot strength/platelet function, or fibrinolysis.

The effect of obesity on laparoscopic and robotic-assisted colorectal surgery outcomes: an ACS-NSQIP database analysis.

Advantages of robotic-assisted colorectal surgery have been reported, but the effect on outcomes between obese and non-obese patients undergoing laparoscopic and robotic-assisted colorectal surgery remains unclear. Patients who underwent elective laparoscopic and robotic colon or rectal resections between 2012 and 2014 were identified in the ACS-NSQIP database. Propensity score matching was performed to determine the effect of obesity on laparoscopic and robotic-assisted 30-day surgical outcomes. 29,172 patients met inclusion criteria; 27,693 (94.9%) underwent laparoscopic colorectal surgery while 1479 (5.1%) underwent robotic-assisted surgery. Mean BMI was 28.4 kg/m2 and 35% of patients had a BMI ≥30 kg/m2. A 10-to-1 propensity matching of laparoscopic to robotic approaches was performed, resulting in 14,770 (90.9%) laparoscopic patients and 1477 (9.1%) robotic-assisted patients available for analysis. Robotic-assisted surgery was associated with lower conversion to laparotomy (2.4 vs 3.4%; p = 0.04) and decreased length-of-stay (4.5±3.2 vs 5.1±4.5 days; p < 0.0001). After adjusting for BMI and surgical approach, obese patients undergoing robotic-assisted surgery had a reduced odds ratio for developing prolonged ileus (p = 0.03). Robotic-assisted colorectal surgery is associated with fewer conversions to laparotomy and shorter length-of-stays compared to laparoscopic surgery. Risk of prolonged ileus is significantly reduced in obese patients undergoing a robotic-assisted approach.

Laparoscopic Repair of Paraesophageal Hernias with a Falciform Ligament Buttress.

BACKGROUND: Buttressing the crura in paraesophageal hernia (PEH) repairs with synthetic mesh may be associated with erosions and dysphagia, while biologic buttresses are expensive and do not decrease long-term recurrence rates. This study documents outcomes following laparoscopic PEH repairs using the falciform ligament as a buttress. METHODS: This is a prospective study of laparoscopic PEH repairs with a falciform ligament buttress. Preoperatively and at 6 months follow-up, medications, radiologic studies and symptom scores were recorded. Patients included had a hiatal defect greater than 5 cm, while recurrent PEH or prior gastric surgery patients were excluded. RESULTS: Thirty-four patients were included with a mean age of 61 years, and 33 patients completed postoperative evaluation with a mean follow-up of 7.1 months. The mean symptom severity decreased from 11.24 ± 1.71 to 3.24 ± 0.84, mean symptom frequency decreased from 11.62 ± 1.70 to 3.45 ± 0.85, and mean total symptom score decreased from 22.85 ± 3.40 to 6.69 ± 1.69 (p < 0.0001). Three patients had recurrences on the upper gastrointestinal (UGI) series. Only one required reoperation. CONCLUSIONS: Laparoscopic PEH repair with a falciform ligament buttress is a viable option. Ongoing follow-up will demonstrate the utility of this approach to decrease morbidity and recurrence rates for paraesophageal hernia repairs.

Exploring ethical conflicts in emergency trauma research: the COMBAT (Control of Major Bleeding after Trauma) study experience.

BACKGROUND: Up to 25% of severely injured patients develop trauma-induced coagulopathy. To study interventions for this vulnerable population for whom consent cannot be obtained easily, the Food and Drug Administration issued regulations for emergency research with an exception from informed consent (ER-EIC). We describe the community consultation and public disclosure (CC/PD) process in preparation for an ER-EIC study, namely the Control Of Major Bleeding After Trauma (COMBAT) study. METHODS: The CC/PD was guided by the four bioethical principles. We used a multimedia approach, including one-way communications (newspaper ads, brochures, television, radio, and web) and two-way communications (interactive in-person presentations at community meetings, printed and online feedback forms) to reach the trials catchment area (Denver County's population: 643,000 and the Denver larger metro area where commuters reside: 2.9 million). Particular attention was given to special-interests groups (eg, Jehovah Witnesses, homeless) and to Spanish-speaking communities (brochures and presentations in Spanish). Opt-out materials were available during on-site presentations or via the COMBAT study website. RESULTS: A total of 227 community organizations were contacted. Brochures were distributed to 11 medical clinics and 3 homeless shelters. The multimedia campaign had the potential to reach an estimated audience of 1.5 million individuals in large metro Denver area, the majority via one-way communication and 1900 in two-way communications. This resource intensive process cost more than $84,000. CONCLUSION: The CC/PD process is resource-intensive, costly, and complex. Although the multimedia CC/PD reached a large audience, the effectiveness of this process remains elusive. The templates can be helpful to similar ER-EIC studies.

Postinjury hyperfibrinogenemia compromises efficacy of heparin-based venous thromboembolism prophylaxis.

BACKGROUND: Venous thromboembolism (VTE) prophylaxis remains debated following trauma, and recommendations have not been established. Although hyperfibrinogenemia is a marker of proinflammatory states, it also contributes to thrombus formation. Postinjury hyperfibrinogenemia is common, but the effect of hyperfibrinogenemia on VTE prophylaxis has not been fully elucidated. Therefore, we hypothesized that heparin is less effective for VTE prophylaxis following severe injury due to hyperfibrinogenemia. METHODS: In vitro studies evaluated thromboelastography (TEG) parameters in 10 healthy volunteers after the addition of fibrinogen concentrate and heparin. Data from a recent randomized controlled trial, conducted at an academic level I trauma center surgical intensive care unit, were reviewed. Critically injured patients were randomized to standard VTE prophylaxis (5,000 U low-molecular-weight heparin daily) or TEG-guided prophylaxis (up to 10,000 U low-molecular-weight heparin daily) and were followed up for 5 days. Analysis was performed to evaluate the relationship between fibrinogen levels, measures of anticoagulation, and TEG parameters. RESULTS: In vitro studies revealed increased fibrinogen reversed the effects of heparin as measured by TEG. Fifty patients were enrolled in the clinical study with 25 in each arm. Thromboelastography parameters, fibrinogen, platelet count, and anti-Xa levels did not differ between groups despite treatment provided. Fibrinogen levels increased over the 5-day study period (597 ± 24.0 to 689.3 ± 25.0), as well as clot strength (9.8 ± 0.4 to 14.5 ± 0.6), which had a significant correlation coefficient (P < 0.01). Moreover, there was a moderate inverse correlation between fibrinogen level and the effect of heparin (RF), which was significant on study days 1 and 3, implicating hyperfibrinogenemia in heparin resistance. CONCLUSIONS: Hypercoagulability and heparin resistance are common following trauma. The preclinical and clinical relationships between fibrinogen levels and hypercoagulability implicate hyperfibrinogenemia as a potential factor in heparin resistance.

Mesenteric lymph diversion abrogates 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock.

BACKGROUND: Early acute kidney injury (AKI) following trauma is associated with multiorgan failure and mortality. Leukotrienes have been implicated both in AKI and in acute lung injury. Activated 5-lipoxygenase (5-LO) colocalizes with 5-LO-activating protein (FLAP) in the first step of leukotriene production following trauma and hemorrhagic shock (T/HS). Diversion of postshock mesenteric lymph, which is rich in the 5-LO substrate of arachidonate, attenuates lung injury and decreases 5-LO/FLAP associations in the lung after T/HS. We hypothesized that mesenteric lymph diversion (MLD) will also attenuate postshock 5-LO-mediated AKI. METHODS: Rats underwent T/HS (laparotomy, hemorrhagic shock to a mean arterial pressure of 30 mm Hg for 45 minutes, and resuscitation), and MLD was accomplished via cannulation of the mesenteric duct. Extent of kidney injury was determined via histology score and verified by urinary neutrophil gelatinase-associated lipocalin assay. Kidney sections were immunostained for 5-LO and FLAP, and colocalization was determined by fluorescence resonance energy transfer signal intensity. The end leukotriene products of 5-LO were determined in urine. RESULTS: AKI was evident in the T/HS group by derangement in kidney tubule architecture and confirmed by neutrophil gelatinase-associated lipocalin assay, whereas MLD during T/HS preserved renal tubule morphology at a sham level. MLD during T/HS decreased the associations between 5-LO and FLAP demonstrated by fluorescence resonance energy transfer microscopy and decreased leukotriene production in urine. CONCLUSION: 5-LO and FLAP colocalize in the interstitium of the renal medulla following T/HS. MLD attenuates this phenomenon, which coincides with pathologic changes seen in tubules during kidney injury and biochemical evidence of AKI. These data suggest that gut-derived leukotriene substrate predisposes the kidney and the lung to subsequent injury.

Platelets are dominant contributors to hypercoagulability after injury.

BACKGROUND: Venous thromboembolic (VTE) disease has a high incidence following trauma, but debate remains regarding optimal prophylaxis. Thrombelastography (TEG) has been suggested to be optimal in guiding prophylaxis. Thus, we designed a phase II randomized controlled trial to test the hypothesis that TEG-guided prophylaxis with escalating low-molecular weight heparin (LMWH), followed by antiplatelet therapy would reduce VTE incidence. METHODS: Surgical intensive care unit trauma patients (n = 50) were randomized to receive 5,000 IU of LMWH daily (control) or to TEG-guided prophylaxis, up to 5,000 IU twice daily with the addition of aspirin, and were followed up for 5 days. In vitro studies were also conducted in which apheresis platelets were added to blood from healthy volunteers (n = 10). RESULTS: Control (n = 25) and TEG-guided prophylaxis (n = 25) groups were similar in age, body mass index, Injury Severity Score, and male sex. Fibrinogen levels and platelet counts did not differ, and increased LMWH did not affect clot strength between the control and study groups. The correlation of clot strength (G value) with fibrinogen was stronger on Days 1 and 2 but was superseded by platelet count on Days 3, 4, and 5. There was also a trend in increased platelet contribution to clot strength in patients receiving increased LMWH. In vitro studies demonstrated apheresis platelets significantly increased clot strength (7.19 ± 0.35 to 10.34 ± 0.29), as well as thrombus generation (713.86 ± 12.19 to 814.42 ± 7.97) and fibrin production (274.03 ± 15.82 to 427.95 ± 16.58). CONCLUSION: Increased LMWH seemed to increase platelet contribution to clot strength early in the study but failed to affect the overall rise clot strength. Over time, platelet count had the strongest correlation with clot strength, and in vitro studies demonstrated that increased platelet counts increase fibrin production and thrombus generation. In sum, these data suggest an important role for antiplatelet therapy in VTE prophylaxis following trauma, particularly after 48 hours. LEVEL OF EVIDENCE: Therapeutic study, level III.

Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following trauma.

Thromboelastography (TEG) is emerging as the standard in the management of acute coagulopathies in injured patients. Although TEG is sensitive in detecting abnormalities in clot strength, one shortcoming is differentiating between fibrinogen and platelet contributions to clot integrity. Current American algorithms suggest platelet transfusion, whereas European guidelines suggest fibrinogen concentrates for correcting low clot strength. Therefore, we hypothesized that a TEG-based functional fibrinogen (FF) assay would assess the contribution of fibrinogen and platelets to clot strength and provide insight to transfusion priorities. Blood samples were obtained from trauma patients on arrival to the emergency department or who were admitted to the surgical intensive care unit (n = 68). Citrated kaolin TEG, FF, and von Clauss fibrinogen levels (plasma-based clinical standard) were measured. Correlations were assessed using linear regression models. In vitro studies were also performed with adding fibrinogen concentrates to blood collected from healthy volunteers (n = 10). Functional fibrinogen and citrated kaolin TEG parameters were measured. Functional fibrinogen strongly correlated with von Clauss fibrinogen levels (R = 0.87) and clot strength (R = 0.80). The mean fibrinogen contribution to clot strength was 30%; however, there was a direct linear relationship with fibrinogen level and percent fibrinogen contribution to clot strength (R = 0.83). Traditional TEG parameters associated with fibrinogen activity (α angle and kinetic time) had significantly lower correlations with FF (R = 0.70 and 0.35). Furthermore, platelet count had only a moderate correlation to clot strength (R = 0.51). The addition of fibrinogen concentrate in in vitro studies increased clot strength (MA) (60.44 ± 1.48 to 68.12 ± 1.39) and percent fibrinogen contribution to clot strength (23.8% ± 1.8% to 37.7% ± 2.5%). Functional fibrinogen can be performed rapidly with TEG and correlates well with the standard von Clauss fibrinogen assay. Both fibrinogen and platelet contribution of clot strength can be derived from FF. Moreover, FF had a stronger correlation to clot strength, and increased levels were directly associated with increased percent contribution to clot strength. In vitro studies also demonstrated an increase in FF, clot strength, and percent fibrinogen contribution to clot strength with the addition of fibrinogen concentrate. These data suggest that fibrinogen should be addressed early in trauma patients manifesting acute coagulopathy of trauma.

Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy.

BACKGROUND: The acute coagulopathy of trauma is present in up to one third of patients by the time of admission, and the recent CRASH-2 and MATTERs trials have focused worldwide attention on hyperfibrinolysis as a component of acute coagulopathy of trauma. Thromboelastography (TEG) is a powerful tool for analyzing fibrinolyis, but a clinically relevant threshold for defining hyperfibrinolysis has yet to be determined. Recent data suggest that the accepted normal upper bound of 7.5% for 30-minute fibrinolysis (LY30) by TEG is inappropriate in severe trauma, as the risk of death rises at much lower levels of clot lysis. We wished to determine the validity of this hypothesis and establish a threshold value to treat fibrinolysis, based on prediction of massive transfusion requirement and risk of mortality. METHODS: Patients with uncontrolled hemorrhage, meeting the massive transfusion protocol (MTP) criteria at admission (n = 73), represent the most severely injured trauma population at our center (median Injury Severity Score [ISS], 30; interquartile range, 20-38). Citrated kaolin TEG was performed at admission blood samples from this population, stratified by LY30, and evaluated for transfusion requirement and 28-day mortality. The same analysis was conducted on available field blood samples from all non-MTP trauma patients (n = 216) in the same period. These represent the general trauma population. RESULTS: Within the MTP-activating population, the cohort of patients with LY30 of 3% or greater was shown to be at much higher risk for requiring a massive transfusion (90.9% vs. 30.5%, p = 0.0008) and dying of hemorrhage (45.5% vs. 4.8%, p = 0.0014) than those with LY30 less than 3%. Similar trends were seen in the general trauma population. CONCLUSION: LY30 of 3% or greater defines clinically relevant hyperfibrinolysis and strongly predicts the requirement for massive transfusion and an increased risk of mortality in trauma patients presenting with uncontrolled hemorrhage. This threshold value for LY30 represents a critical indication for the treatment of fibrinolysis. LEVEL OF EVIDENCE: Prognostic study, level III.