Derek P. McVay

The effects of tranexamic acid and prothrombin complex concentrate on the coagulopathy of trauma: An in vitro analysis of the impact of severe acidosis

BACKGROUND Bleeding is the most frequent cause of preventable death after severe injury. Our purposes were to study the efficacy of tranexamic acid (TXA) and prothrombin complex concentrate (PCC) on a traumatic coagulopathy with a severe native metabolic acidosis and compare the efficacy of PCC versus fresh frozen plasma (FFP) to reverse a dilutional coagulopathy. METHODS In vitro effects of TXA and PCC were assessed with standard laboratory analysis (prothrombin time [PT]/international normalized ratio [INR]) and rotational thromboelastometry in a porcine hemorrhage with ischemia-reperfusion (H/I) model. FFP was used in comparison with PCC. In vitro doses were calculated to be the equivalent of 1-g TXA, 100-mg tissue plasminogen activator, 45-IU/kg PCC, and 4-U FFP. Agents were tested at baseline and then with severe metabolic acidosis after 6 hours of resuscitation. RESULTS Thirty-one swine were studied. Baseline hematocrit was 24%, pH was 7.56, INR was 1.0, and lactate level was 1.47. Six hours after H/I, the hematocrit was 15.9%, pH was 7.1, INR was 1.7, and lactate level was 10.26. Rotational thromboelastometry revealed that maximum clot firmness at baseline was 71.71 mm and decreased to 0.29 mm with tissue plasminogen activator, representing severe fibrinolysis. Following TXA dosing, the maximum clot firmness was immediately corrected to 69.06 mm. There was no difference (p = 0.48) between TXA function at baseline pH (mean, 7.56) or acidotic pH (mean, 7.11). The mean baseline PT was 13 ± 0.49 seconds (INR, 1). After H/I and resuscitation, the mean PT was 23.03 seconds (INR, 2.1). PCC reduced the PT to 20 (INR, 1.75; p = 0.001) and FFP to 17.44 (INR, 1.47; p = 0.001). CONCLUSION Both TXA and PCC seem to function well in reversing a traumatic coagulopathy in vitro, and TXA seems to have no loss of function in a severe metabolic acidosis. Further investigations are warranted.

The efficacy of Combat Gauze in extreme physiologic conditions

INTRODUCTION Combat Gauze (CG) is currently the most widely used hemostatic dressing in combat. The testing of CG was initially performed in healthy and physiologically normal animals. The goal this study was to assess the efficacy in a model of severe acidosis and coagulopathy. METHODS To obtain an acidotic and coagulopathic model, Yorkshire swine sustained 35% blood volume hemorrhage followed by a 50-min supraceliac aortic ischemia-reperfusion injury with 6-h resuscitation (epinephrine to keep mean arterial pressure >40 and intravenous fluids to keep central venous pressure >4). We created a femoral artery injury and randomized the animals to CG versus a standard gauze (SG) dressing. We performed rotational thromboelastography with both CG and SG. RESULTS Using our model, 17 anesthetized Yorkshire swine developed appropriately significant coagulopathy, acidosis, and anemia. The SG failure rate was 100% on the first application and worked once on the second application. Combat Gauze was successful in achieving hemostasis 93% of the time on the first application and had 100% success with the second application. Rotational thromboelastography demonstrated that the only difference was a decreased clotting time with CG compared with SG (P = 0.012). CONCLUSIONS Combat Gauze significantly outperforms standard gauze dressings in a model of major vascular hemorrhage in acidotic and coagulopathic conditions. This effect appears to result from a decreased time lag between activation and first detectable clotting. Combat Gauze appears to maintain its efficacy even in the setting of severe acidosis and coagulopathy for the control of hemorrhage from vascular injury.

Examining the relevance of the physician's clinical assessment and the reliance on computed tomography in diagnosing acute appendicitis

BACKGROUND The aim of this study was to examine the relevance of clinical assessment in diagnosing appendicitis in the current medical environment, in which routine use of computed tomography (CT) has become the norm. METHODS A retrospective review was conducted, analyzing patient demographics, Alvarado clinical assessment scoring, and radiologic and pathologic results. RESULTS A total of 664 patients were identified. Higher Alvarado scores were significantly associated with pathologically confirmed appendicitis (low, 87%; moderate, 92%; high, 96%; P = .05). As clinical assessment scores increased, use of CT decreased significantly (low, 97%; moderate, 85%; high, 79%; P = .01). The negative appendectomy rate for patients with clinical assessments consistent with appendicitis was 4%, compared with 3% associated with CT. Regardless of assessment scores, 82% of the cohort underwent CT. From a random sample of 100 charts, 87% of initial emergency department plans stratified disposition on the basis of the results of CT. CONCLUSIONS Although physical examination remains crucial, CT has become the primary modality dictating care of patients with presumed appendicitis.

The impact of race on outcomes following emergency surgery: an American College of Surgeons National Surgical Quality Improvement Program assessment

BACKGROUND Despite significant evolutions in health care, outcome discrepancies exist among demographic cohorts. We sought to determine the impact of race on emergency surgery outcomes. METHODS This is a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database (2005 through 2009) for all patients aged ≥16 years undergoing emergency abdominal surgery. Primary outcomes included morbidity and mortality. RESULTS We identified 75,280 patients (mean age 48.2 ± 19.9 years, 51.7% female; 79% white, 9.9% black, 5.0% Hispanic, 3.7% Asian, 1.3% American Indian or Alaskan, .2% Pacific Islander). Annual rates of emergency operations ranged from 7.3% to 8.5% (P = .22). The overall complication (18.6%) and mortality rate (4.6%) was highest in the black population (24.3%, 5.3%) followed by whites (18.7%, 4.6%), with the lowest rate in Hispanic (11.7%, 1.8%) and Pacific Islander populations (10.2%, 1.8%; P < .001). Compared with whites, blacks had a 1.25-fold (1.17 to 1.34; P < .001) increased risk of complications, but similar mortality (P = .168). When combining minorities, overall complications were 1.059-fold (1.004 to 1.12; P = .034) higher, however, mortality was reduced 1.7-fold (1.07 to 1.34; P = .001). CONCLUSIONS Following emergency abdominal surgery, minority race is independently associated with increased complications and reduced mortality.

A simplified trauma triage system safely reduces overtriage and improves provider satisfaction: a prospective study.

BACKGROUND Standard triage systems result in high rates of overtriage to achieve acceptably low undertriage. We previously validated optimal triage variables and used these to implement a new simplified triage system (NEW) at our hospital. METHODS All trauma entries from May 2010 to Feb 2013 were prospectively reviewed. Calculation of the undertriage and overtriage rates was based on the need for any urgent or life-saving intervention. RESULTS We identified 704 trauma patients. Level 1 activations were reduced from 32% (OLD) to 19% in the NEW system (P < .05). Overtriage was reduced from 79% (OLD) to 44% in the NEW system (P < .01). The undertriage rate was 1.6% in the NEW system, compared with 1.2% in the OLD system (P = nonsignificant). Of all patients, 14% (63) required a life-saving intervention. There were no deaths among undertriaged patients. CONCLUSION The NEW simplified triage system significantly reduced the rate of overtriage, while safely maintaining a low undertriage rate.

Effects of histone deacetylase inhibition on 24-hour survival and end-organ injury in a porcine trauma model: a prospective, randomized trial.

BACKGROUND Valproic acid (VPA) is a histone deacetylase inhibitor that has been shown to improve early resuscitation from hemorrhagic shock. We sought to examine whether there is a sustained benefit of VPA in a survival model of severe injury. METHODS Yorkshire swine (n = 36) were randomized to three groups as follows: (a) control, (b) VPA (single dose), and (c) VPA (two doses at 12 hours apart). Animals underwent a 35% volume-controlled hemorrhage, followed by aortic cross-clamping for 50-minute duration, at which time VPA (400 mg/kg) was administered intravenously. Animals then underwent protocol guided resuscitation with crystalloid and vasopressor infusions for up to 24 hours. The primary end point was animal survival; secondary end points included hemodynamics, physiology, and histologic evidence of end-organ injury. RESULTS Mean duration of survival was significantly longer in the control group (15.8 hours, n = 11) compared with single-dose VPA (12.6 hours, n = 9, p < 0.02). Redosing VPA at 12 hours provided no survival benefit. During cross-clamp, animals that received VPA required significantly less lidocaine compared with the control animals (32.8 mg vs. 159.4 mg, p = 0.03). Animals that received VPA also required significantly greater quantities of intravenous fluids per hour (p < 0.01) and higher epinephrine doses (p = 0.01). VPA administration was associated with earlier evidence of cardiac suppression (decreased cardiac output, increased pulmonary wedge pressures, and systemic vascular resistance; p < 0.05). VPA was associated with renal end-organ histologic protection and improved levels of blood urea nitrogen and creatinine at all time points (p < 0.05). CONCLUSION Despite previous reports citing improved early outcomes with VPA administration, VPA did not improve resuscitation or mortality in a survival model with severe injury. VPA did show some evidence of prolonged renal protection. No benefit of redosing VPA was identified. VPA had a cardiac depressant effect that may be dose dependent and should be studied further.

Biliary Leak Rates After Cholecystectomy and Intraoperative Cholangiogram in Surgical Residency

Postoperative bile leak (BL) after cholecystectomy is a rare but dreaded complication, and is felt to be increased during surgical training. We sought to determine the incidence of BL after selective intraoperative cholangiogram (IOC) at a teaching hospital and identify risk factors for predicting BLs. A retrospective review was performed analyzing all cholecystectomy with IOCs between September 2004 and September 2011. Residents performed under staff supervision. Of 1,799 cholecystectomies performed during the study period, only 96 (5.3%) were with IOCs (mean age 43, 65% female) and 4 BLs occurred (4.2%, 1 major duct injury, 3 cystic duct stump leaks). Univariate analysis demonstrated that male gender, significant medical comorbidities, case duration, preoperative endoscopic retrograde cholangiopancreatography, and surgery type (laparoscopic versus open) increased the patients risk of BL; however, age, performance of secondary procedures, common bile duct exploration, resident level (PGY), and diagnosis did not increase BL risk. Multivariate regression revealed that only surgery type lead to an increased risk of BL (p = 0.001) (OR 31.61, 95% CI 3.96-252.18). Patient factors and PGY level did not significantly affect BL rates, although open and converted procedures were associated with higher rates, suggesting an increased risk of a BL with more complex cases.

Clinical practice guideline adherence during Operation Inherent Resolve

BACKGROUND The Joint Trauma System (JTS) clinical practice guidelines (CPGs) contributed to the decrease in battlefield mortality over the past 15 years. However, it is unknown to what degree the guidelines are being followed in current military operations. METHODS A retrospective review was performed of all patients treated at three separate US Army Role II facilities during the first 10 months of Operation Inherent Resolve in Iraq. Charts were reviewed for patient demographics, clinical care, and outcomes. Charts were also reviewed for compliance with JTS CPGs and Tactical Combat Casualty Care recommendations. RESULTS A total of 114 trauma patients were treated during the time period. The mean age was 26.9 ± 10.1 years, 90% were males, and 96% were host nation patients. The most common mechanisms of injury were blast (49%) and gunshot (42%). Records were compliant with documenting a complete set of vitals in 58% and a pain score in 50% of patients. Recommendations for treatment of hypothermia were followed for 97% of patients. Tranexamic acid was given outside guidelines for 6% of patients, and for 40%, it was not determined if the guidelines were followed. Recommendations for initial resuscitative fluid were followed for 41% of patients. Recommendations for antibiotic prophylaxis were followed for 40% of intra-abdominal and 73% of soft tissue injuries. Recommendations for tetanus prophylaxis were followed for 90% of patients. Deep vein thrombosis prophylaxis was given to 32% of patients and contraindicated in 27%. The recommended transfusion ratio was followed for 56% of massive transfusion patients. Recommendations for calcium administration were followed for 40% of patients. When composite scores were created for individual surgeons, there was significant variability between surgeons with regard to adherence to guidelines. CONCLUSIONS There is significant deviation in the adherence to the CPGs. LEVEL OF EVIDENCE Epidemiologic study, level IV.

Application of preoperative brain natriuretic peptide levels in clinical practice

The purpose of the study was to determine the clinical utility and practical application of preoperative brain natriuretic peptide (BNP) levels. This is a retrospective review of operating room procedures from November 2006 to March 2009. Preoperative history and physical were reviewed and BNP laboratory levels obtained prior to all procedures and the postoperative course reviewed for incidence of 30-day cardiac complications. A receiver operator curve analysis demonstrated that a preoperative BNP threshold ≥95.5 pg/mL correctly identified 75% of patients with cardiac complications and values ≤18.5 pg/mL identified 100% of patients without adverse postoperative cardiac complications. Multivariable analysis also revealed a history of peripheral arterial disease as the most significant preoperative predictor of cardiac complications followed by BNP above the threshold (odds ratio = 3.7), hypothyroidism, coronary artery disease and prior myocardial infarction. In conclusion, preoperative BNP levels are a useful adjunct in clinical practice to help identify those patients with a high postoperative risk and those with a minimal postoperative risk.

Optimum cystic duct closure: a comparative study using metallic clips, ENSEAL, and ENDOLOOP in swine.

BACKGROUND Metal clips are commonly used to secure the cystic duct during cholecystectomy, although use of an ENDOLOOP (Ethicon Endo-Surgery, Blue Ash, OH) is often touted as a more secure closure when postoperative endoscopic retrograde cholangiopancreatography (ERCP) is anticipated. The objective of this study was to test the strength of 3 different cystic duct closure methods in a model simulating postoperative biliary insufflation. METHODS The extrahepatic biliary system, including common bile duct, gallbladder, and cystic duct, was harvested en bloc from 22 swine postmortem. A cholecystectomy was performed and the cystic duct was secured using 1 of 3 randomly assigned methods: metallic clips (Ethicon Endo-Surgery), an ENDOLOOP (Ethicon Endo-Surgery), or an ENSEAL tissue sealing device (Ethicon Endo-Surgery). The common bile duct was cannulated with a pressure-monitoring system and insufflated with air. The burst pressures, location of rupture, and size of the common bile duct and cystic duct were recorded and compared. RESULTS There were 7 pigs each in the ENDOLOOP and ENSEAL groups and 8 in the metallic clip group, with no statistical significance between cystic and common bile duct size. Mean burst pressure was 432 mm Hg for metallic clips, 371 mm Hg for the ENDOLOOP, and 238 mm Hg for the ENSEAL device (P = .02). Post hoc analysis revealed clips to be statistically superior when compared with the ENSEAL (P= .01). There was no statistical difference between the ENDOLOOP and metal clips or between the ENDOLOOP and the ENSEAL. CONCLUSIONS All 3 closure methods successfully secured the cystic duct, with mean burst pressures exceeding 195 mm Hg. Metallic clips demonstrated the highest burst pressures and no cystic duct stump leaks. This study challenges the traditional dogma of additionally securing the cystic duct with an ENDOLOOP when postoperative biliary instrumentation is expected and also suggests that an adequately secure closure may be obtained with thermal sealing devices.