Christopher R. Porta

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.

Training Surgeons and the Informed Consent Process: Routine Disclosure of Trainee Participation and Its Effect on Patient Willingness and Consent Rates

OBJECTIVES To examine patient perceptions and willingness to participate in resident education and to assess the effect on patient willingness and consent rates. DESIGN Anonymous questionnaire designed to capture demographics, overall opinions of teaching programs, and willingness to consent to various scenarios of trainee participation. Descriptive and univariate analyses were performed. SETTING Tertiary-level referral center. PATIENTS Three hundred sixteen individuals scheduled for elective surgery. MAIN OUTCOME MEASURES Consent rates for various scenarios. RESULTS Of the 316 patients who completed the questionnaire, most expressed overall support of resident training: 91.2% opined that their care would be equivalent to or better than that of a private hospital, 68.3% believed they derived benefit from participation, and most consented to having an intern (85.0%) or a resident (94.0%) participate in their surgical procedure. However, when given specific, realistic scenarios involving trainee participation, major variations in the consent rate were observed. Affirmative consent rates decreased from 94.0% to 18.2% as the level of resident participation increased. Patients also were more willing to consent to the participation of a senior resident (83.1%) vs a junior resident (57.6%) or an intern (54.5%). Patients overwhelmingly opined that they should be informed of the level of resident participation and that this information could change their decision of whether to consent. CONCLUSIONS Most patients expressed approval of teaching facilities and resident education. However, consent rates were significantly altered when more detailed information was provided and they declined with increasing levels of resident participation. Providing detailed informed consent is preferred by patients but it could adversely affect resident participation and training.

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.

Tranexamic acid corrects fibrinolysis in the presence of acidemia in a swine model of severe ischemic reperfusion.

BACKGROUND Tranexamic acid (TXA) is an antifibrinolytic with anti-inflammatory properties associated with improved outcomes when administered to trauma patients at risk for bleeding; however, its efficacy is unknown in acidemia. We evaluated the efficacy of TXA on hyperfibrinolysis using an established porcine traumatic hemorrhage ischemic shock model. METHODS Ten Yorkshire swine underwent a controlled hemorrhage followed by supraceliac aortic cross-clamping. During standard resuscitation, control animals received recombinant tissue plasminogen activator (rtPA) after cross-clamp removal, and experimental animals received rtPA followed by TXA. Rotational thromboelastometry analysis was performed at baseline, 5 minutes and 15 minutes after rtPA dosing, and 4 hours after cross-clamp removal. RESULTS Control and experimental animals had similar hemodynamics and routine laboratory values at baseline and throughout resuscitation. At the time of TXA administration, average pH was 7.2. Clot formation time was prolonged from baseline and all resuscitation time points in both groups, with no difference at any time point. Maximum clot firmness decreased from baseline at all resuscitation time points in both groups. Maximum lysis increased from baseline (9% control vs. 9% TXA) after tissue plasminogen activator administration in both groups (100% control vs. 99% TXA). In experimental animals, maximum lysis returned to baseline 10 minutes after TXA administration (92% vs. 9%, p < 0.001). CONCLUSION TXA rapidly and fully reverses hyperfibrinolysis despite severe acidemia in a porcine trauma model. TXA is a promising adjunct to trauma resuscitation that is easily administered in austere or prehospital settings.

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.

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.

The weekend effect: does time of admission impact management and outcomes of small bowel obstruction?

Aims: To determine whether day and time of admission influences the practice patterns of the admitting general surgeon and subsequent outcomes for patients diagnosed with small bowel obstruction. Methods: A retrospective database review was carried out, covering patients admitted with the presumed diagnosis of partial small bowel obstruction from 2004–2011. Results: A total of 404 patients met the inclusion criteria. One hundred and thirty-nine were admitted during the day, 93 at night and 172 on the weekend. Overall 30.2% of the patients were managed operatively with no significant difference between the groups (P = 0.89); however, of patients taken to the operating room, patients admitted during the day received operative intervention over 24 hours earlier than those admitted at a weekend, 0.79 days vs 1.90 days, respectively (P = 0.05). Overall mortality was low at 1.7%, with no difference noted between the groups (P = 0.35). Likewise there was no difference in morbidity rates between the three groups (P = 0.90). Conclusions: Despite a faster time to operative intervention in those patients admitted during the day, our study revealed that time of admission does not appear to correlate to patient outcome or mortality.

Initial Operative Time and Metastatic Disease Recurrence

Colon cancer metastases are a major source of morbidity and mortality for patients following oncologic resection. The purpose of this study was to identify whether operative time as a surrogate for resident involvement increased the risk of future liver metastases. We performed a retrospective review of patients undergoing curative colon resection from 2001 to 2010 at two military residency training hospitals. Intraoperative time as well as preoperative comorbidities and perioperative factors were gathered from electronic medical records. Liver metastases were identified from the tumor registry and inpatient records. A total of 106 patients underwent resection for colon cancer (Stage I-III) from 2001 to 2005 with 5-year follow-up through 2010. Operative times in patients who had recurrence was 205 +/- 60 minutes and those without recurrence was 187 +/- 73 minutes (p = 0.398). There was no correlation between operative time and time to recurrence (p = 0.452), and Cox regression demonstrated that case duration had no impact on time to metastatic recurrence (p = 0.461). Within our cohort, operative time had no impact on metastatic cancer recurrence. Surgeons should continue to focus on proper oncologic principles and tumor biology rather than the concern that increased operative time or resident training leads to increased metastatic recurrence.