Liposomal Bupivacaine Enhances the Pain-Control Benefits of Uniportal Thoracoscopic Lobectomy.

BACKGROUND: Liposomal bupivacaine field block is gaining popularity as a critical element of enhanced recovery after surgery protocols in thoracic surgery. Uniportal thoracoscopic surgery has been reported to result in less narcotic consumption compared with traditional video-assisted thoracoscopic surgery. The objective of this study was to evaluate the postoperative narcotic consumption of patients undergoing uniportal thoracoscopic lobectomy with the use of 0.25% bupivacaine vs patients treated with liposomal bupivacaine. METHODS: All consecutive patients undergoing uniportal thoracoscopic lobectomy at an academic medical institution were recorded between October 2015 and February 2018. Narcotic consumption was converted to oral morphine equivalents by using standard formulas. Patients underwent posterior serratus and intercostal nerve blocks with 0.25% bupivacaine or liposomal bupivacaine, transitioning to liposomal bupivacaine in March 2017. Other adjuncts such as gabapentin or cyclooxygenase-2 inhibitors were not administered. RESULTS: Data were reviewed on 32 patients receiving field blocks with 0.25% bupivacaine and on 50 patients receiving liposomal bupivacaine. There was no difference between groups with regard to age, sex, chest tube duration, or length of stay. Patients undergoing field blocks with liposomal bupivacaine consumed less narcotic medication. CONCLUSIONS: The study investigators have previously demonstrated decreased narcotic consumption with the use of uniportal technique over traditional multi-incision thoracoscopic surgery. The use of liposomal bupivacaine for posterior serratus and intercostal field blocks enhanced pain control and decreased narcotic consumption.

Thrombelastography-Based Dosing of Enoxaparin for Thromboprophylaxis in Trauma and Surgical Patients: A Randomized Clinical Trial.

Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE. Objective: To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients. Design, Setting, and Participants: This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30 mg twice daily) with TEG-adjusted enoxaparin dosing (35 mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States. Main Outcomes and Measures: The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency. Results: Of the 185 trial participants, 89 were randomized to the control group (median age, 44.0 years; 55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0% male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35 mg vs 30 mg twice daily; P < .001). Anti-Factor Xa levels in intervention patients were not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved a difference in reaction time greater than 1 minute, which was similar between the control and intervention groups (10.4% vs 13.5%; P = .68). The time to enoxaparin initiation was similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dose was also similar (43 [48.3%] vs 54 [56.3%]; P = .30). Rates of VTE (6 [6.7%] vs 6 [6.3%]; P > .99) were similar, but the difference in bleeding complications (5 [5.6%] vs 13 [13.5%]; P = .08) was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated as weight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8% vs 2.5%; P = .05). Conclusions and Relevance: The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported. Trial Registration: clinicaltrials.gov Identifier: NCT00990236.

Reconstitution fluid type does not affect pulmonary inflammation or DNA damage following infusion of lyophilized plasma.

BACKGROUND: Dysfunctional inflammation following traumatic hemorrhage can lead to multiple-organ failure and death. In our polytrauma swine model, lyophilized plasma (LP) reconstituted with sterile water and ascorbic acid suppressed systemic inflammation and attenuated DNA damage. However, it remains unknown whether the inflammatory response is affected by the type of fluid used to reconstitute LP. We hypothesized that common resuscitation fluids such as normal saline (LP-NS), lactated Ringer's solution (LP-LR), Hextend (LP-HX), or sterile water (LP-SW) would yield similar inflammation profiles and DNA damage following LP reconstitution and transfusion. METHODS: This was a randomized, prospective, blinded animal study. LP was reconstituted to 50% of original volume with NS, LR, HX, or SW buffered with 15-mM ascorbic acid. Forty swine were subjected to a validated model of polytrauma, hemorrhagic shock, and Grade V liver injury and resuscitated with LP. Serum interleukin 6 (IL-6), IL-10, plasma C-reactive protein, and 8-hydroxy-2-deoxyguanosine concentrations were assessed for systemic inflammation and DNA damage at baseline, 2 hours, and 4 hours following liver injury. Lung inflammation was evaluated by Real Time Polymerize Chain Reaction (RT-PCR). RESULTS: Reconstituted LP pH was similar between groups before resuscitation. IL-6 and IL-10 increased at 2 hours and 4 hours compared with baseline in all groups (p < 0.017). DNA damage increased at 2 hours and 4 hours compared with baseline and from 2 hours to 4 hours in the LP-NS, LP-LR, and LP-SW groups (all p < 0.017). Animals resuscitated with LP-HX not only demonstrated increased DNA damage at 4 hours versus baseline but also had the lowest C-reactive protein level at 2 hours and 4-hours (p < 0.017). Overall, differences between groups were similar for DNA damage and lung inflammation. CONCLUSION: Reconstitution fluid type does not affect inflammatory cytokine profiles or DNA damage following LP transfusion in this swine polytrauma model. Based on universal availability, these data suggest that sterile water is the most logical choice for LP reconstitution in humans. LEVEL OF EVIDENCE: Prognostic, level II.

Positive blood alcohol is associated with reduced DVT in trauma.

INTRODUCTION: Trauma patients exhibit a complex coagulopathy which is not fully understood and deep venous thrombosis (DVT) rates remain high. The effects of alcohol (EtOH) consumption on coagulopathy in trauma patients have not been studied. We hypothesized that acute EtOH intoxication would produce a relative hypocoagulable state as measured by thrombelastography (TEG) and would be associated with reduced DVT rates. METHODS: Data were prospectively collected on 213 trauma patients at a level 1 trauma centre and analyzed in a retrospective secondary analysis. Thrombelastography (TEG), standard laboratory tests and ETOH levels were performed. If the level was positive, patients were grouped as EtOH+ and all patients were screened for DVT using a standard protocol. Statistical significance was p<0.05. RESULTS: The EtOH+ group was predominantly male (76%), was younger (p<0.05), had a lower BMI (p<0.05), demonstrated a lower AIS extremity score (p<0.01) and was less likely to have a blunt injury (p<0.01) than the EtOH- group. Gender, ISS and other AIS scores were not significantly different. TEG values in the alcohol group demonstrated a relative hypocoagulable state that was associated with a reduced DVT incidence, 1.4% versus 16.2%, (p<0.01). This difference was not detected with conventional assays. A multivariate logistic regression was performed, controlling for common risk factors for DVT and a positive EtOH level on admission was independently associated with reduced DVT incidence. CONCLUSIONS: Alcohol consumption is associated with a relative hypocoagulable state on TEG that is associated with a decreased DVT incidence. This difference is not detected by conventional assays.

The international normalized ratio overestimates coagulopathy in patients after major hepatectomy.

BACKGROUND: The International Normalized Ratio (INR) is commonly used to guide therapy after hepatectomy. We hypothesized that the use of thrombelastography (TEG) would demonstrate a decreased incidence of hypocoagulability in this patient population. METHODS: Seventy-eight patients were prospectively enrolled before undergoing hepatectomy. INR, TEG, and coagulation factors were drawn before incision, postoperatively, and on postoperative days 1, 3, and 5. RESULTS: Patients demonstrated an elevated INR at all postoperative time points. However, TEG demonstrated a decreased R value postoperatively, with subsequent normalization. Other TEG measurements were equivalent to preoperative values. All procoagulant factors save factor VIII decreased postoperatively, with a simultaneous decrease in protein C. CONCLUSIONS: TEG demonstrated a brief hypercoagulable state after major hepatectomy, with coagulation subsequently normalizing. The INR significantly overestimates hypocoagulability after hepatectomy and these data call into question current practices using the INR to guide therapy in this patient population.

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.

Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.

BACKGROUND: The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. METHODS: A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. RESULTS: A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. CONCLUSION: TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. LEVEL OF EVIDENCE: Therapeutic study, level III.

Comparison of the hemostatic efficacy of low-volume lyophilized plasma reconstituted using sterile water, lactated Ringer's, normal saline, and Hextend solutions.

BACKGROUND: Low-volume ascorbic acid-buffered reconstituted lyophilized plasma (LP) provides logistic advantages, reduces the risks for large-volume resuscitation, modulates inflammation, and is equally effective for hemostatic resuscitation as full-volume LP. We compared the physiologic effects of resuscitation using LP reconstituted with sterile water (LP-SW), lactated Ringer's solution (LP-LR), normal saline (LP-NS), and Hextend (LP-Hx). METHODS: Plasma was collected from swine, lyophilized, and then reconstituted into four test solutions: LP-SW, LP-LR, LP-NS, or LP-Hx. Forty swine were anesthetized and subjected to a validated model of polytrauma and hemorrhagic shock (including a Grade V liver injury), then randomized to receive one of the four test solutions. Physiologic parameters, blood loss, lactate, and hematocrit were followed up. Coagulation status was evaluated using thrombelastography. Inflammatory mediator expression was evaluated by multiplex serum assay. RESULTS: Forty animals were included in the study (10 animals per group). One animal died following LP-Hx resuscitation. There was less blood loss in the LP-SW and LP-LR groups compared with the LP-NS and LP-Hx groups (p < 0.05). The LP-SW group exhibited less early coagulopathic changes by thrombelastography, and the LP-Hx group had persistently elevated international normalized ratios at the end of the study period (p < 0.05). Serum interleukin 6 was lower after 4 hours in the LP-SW group compared with LP-NS (p < 0.05). CONCLUSION: Resuscitation using low-volume LP-SW and LP-LR buffered with ascorbic acid confers an anti-inflammatory benefit and results in less blood loss. Sterile water is a safe, cost-effective, and universally available fluid for creating a low-volume hemostatic LP resuscitation solution.