Gordon M. Riha

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.

Prognostic factors and treatment outcome in mesenteric vein thrombosis

Background Mesenteric vein thrombosis (MVT) can result in intestinal ischemia and is associated with high morbidity and mortality due in part to its frequent delay in diagnosis. The purpose of this study was to evaluate clinical presentation, diagnostic evaluation, and treatment outcome of MVT. Methods Hospital records and clinical data of all patients treated for MVT were reviewed during a recent 14-year period. Clinical outcome and factors affecting survival were analyzed. Results A total of 68 patients were included in the study. Abdominal exploration was performed in 23 patients (34%), and second-look operation was necessary in 18 patients (26%). Three patients (4%) underwent unsuccessful operative mesenteric vein thrombectomy, whereas percutaneous transhepatic mesenteric thrombectomy was performed successfully in 3 patients (4%). The 30-day mortality rate was 20%. Forty-six of the 54 survivors were treated with long-term oral anticoagulation therapy. Actuarial survival at 2, 4, 6, and 10 years was 68%, 57%, 43%, and 22%, respectively. Risk factor analysis showed malignancy (P < .002), age >60 years (P < .005), cirrhosis (P < .02), symptom duration (P < .005), and bowel resection (P < .03) were associated with mortality. Logistic regression analysis showed age >60 years (odds ratio [OR], 3.64; P = .03), malignancy (OR, 3.88; P = .02), and prolonged symptom duration (OR, 5.62; P = .01) were independent predictors of mortality. Conclusions MVT is associated with significant mortality. Prompt diagnostic evaluation with computed tomography may reduce potential treatment delay. Underlying malignancy, advanced age, and prolonged symptom duration are predictive of poor outcome.

Coagulopathy after a liver resection: is it over diagnosed and over treated?

BACKGROUND Prothrombin time-international normalized ratio (PT-INR) is widely utilized to guide plasma therapy and initiation of thromboprophylaxis after a hepatectomy. Thrombelastography (TEG) monitors shear elasticity, which is sensitive to cellular and plasma components in blood, allowing for functional assessment of the life of the clot. The objective of this study was to prospectively compare PT-INR and TEG in liver resection patients. METHODS Forty patients were enrolled before undergoing an elective hepatectomy. Patients underwent a liver resection utilizing a low central venous pressure (CVP) anaesthetic technique and intermittent Pringle manoeuver. PT-INR and TEG were drawn prior to incision, post-operatively, and post-operative days 1, 3 and 5. RESULTS All post-operative PT-INR values increased significantly when compared with pre-operative PT-INR (P < 0.01). The time of onset to clot (R-value) decreased significantly at the post-operative time point (P = 0.04), consistent with a relative hypercoagulability. Subsequent R-values were not different compared with the pre-operative R-value. The strength of the clot (maximum amplitude, MA) was unchanged when comparing pre- and post-operative time points. DISCUSSION In spite of an elevation in PT-INR, patients undergoing a liver resection demonstrated a brief hypercoagulable state, followed by normal coagulation function based on TEG. These data call into question the practice of utilizing PT-INR to guide plasma transfusion and timing of prophylactic anticoagulation after a liver resection.

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 (&Dgr;R) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using &Dgr;R-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 &Dgr;R 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 &Dgr;R 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 &Dgr;R 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.

Hextend and 7.5% hypertonic saline with Dextran are equivalent to Lactated Ringer's in a swine model of initial resuscitation of uncontrolled hemorrhagic shock.

BACKGROUND The optimal fluid strategy for the early treatment of trauma patients remains highly debated. Our objective was to determine the efficacy of an initial bolus of resuscitative fluids used in military and civilian settings on the physiologic response to uncontrolled hemorrhagic shock in a prospective, randomized, blinded animal study. METHODS Fifty anesthetized swine underwent central venous and arterial catheterization followed by celiotomy. Grade V liver injury was performed, followed by 30 minutes of uncontrolled hemorrhage. Then, liver packing was completed, and fluid resuscitation was initiated over 12 minutes with 2 L normal saline (NS), 2 L Lactated Ringers (LR), 250 mL 7.5% hypertonic saline with 3% Dextran (HTS), 500 mL Hextend (HEX), or no fluid (NF). Animals were monitored for 2 hours postinjury. Blood loss after initial hemorrhage, mean arterial pressure (MAP), tissue oxygen saturation (StO2), hematocrit, pH, base excess, and lactate were measured at baseline, 1 hour, and 2 hours. RESULTS NF group had less post-treatment blood loss compared with other groups. MAP and StO2 for HEX, HTS, and LR at 1 hour and 2 hours were similar and higher than NF. MAP and StO2 did not differ between NS and NF, but NS resulted in decreased pH and base excess. CONCLUSIONS Withholding resuscitative fluid results in the least amount of posttreatment blood loss. In clinically used volumes, HEX and HTS are equivalent to LR with regard to physiologic outcomes and superior to NF. NS did not provide a measurable improvement in outcome compared with NF and resulted in increased acidosis.

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 patients 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.

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.

Uncontrolled hemorrhagic shock results in a hypercoagulable state modulated by initial fluid resuscitation regimens

BACKGROUND Previous studies have shown large-volume resuscitation modulates coagulopathy and inflammation. Our objective was to analyze the effects of initial bolus fluids used in military and civilian settings on coagulation and inflammation in a prospective, randomized, blinded trial of resuscitation of uncontrolled hemorrhage. METHODS Fifty swine were anesthetized, intubated, and ventilated and had monitoring lines placed. A Grade V liver injury was performed followed by 30 minutes of hemorrhage. After 30 minutes, the liver was packed, and randomized fluid resuscitation was initiated during a 12-minute period with 2 L of normal saline, 2 L of lactated Ringer’s solution, 250 mL of 7.5% saline with 3% Dextran, 500 mL of Hextend, or no fluid (NF). Animals were monitored for 2 hours after injury. Thrombelastograms (TEGs), prothrombin time (PT), partial thromboplastin time, fibrinogen as well as serum interleukin 6, interleukin 8, and tumor necrosis factor &agr; levels were drawn at baseline and after 1 hour and 2 hours. RESULTS The NF group had less posttreatment blood loss compared with other groups (p < 0.01). Blood loss was similar in the other groups. TEG R values in each group decreased from baseline at 1 and 2 hours (p < 0.02). The groups receiving 2 L of normal saline, 250 mL of 7.5% saline with 3% Dextran, or 500 mL of Hextend had lower TEG maximum amplitude values compared with NF group (p < 0.02). All fluids except lactated Ringer’s solution resulted in significant increases in PT compared with NF, whereas all fluids resulted in significant decreases in fibrinogen compared with NF (p < 0.02). Fluid resuscitation groups as well as NF group demonstrated significant increases in inflammatory cytokines from baseline to 1 hour and baseline to 2 hours. There were no significant differences in inflammatory cytokines between groups at 2 hours. CONCLUSION Withholding fluid resulted in the least significant change in PT, fibrinogen, and maximum amplitude and in the lowest posttreatment blood loss. Resuscitation with different initial fluid resuscitation strategies did not result in increased proinflammatory mediators compared with animals that did not receive fluid.

Incidence of deep vein thrombosis is increased with 30 mg twice daily dosing of enoxaparin compared with 40 mg daily

BACKGROUND The purpose of this study was to analyze whether 2 standard dosing regimens of enoxaparin (30 mg twice daily vs 40 mg once daily) would result in different deep vein thrombosis (DVT) rates and anti-factor Xa activity (anti-Xa) in surgical patients. METHODS Patients who required enoxaparin for prophylaxis were followed prospectively. Demographics were recorded. Patients underwent standardized duplex screening. Peak anti-Xa levels were drawn on 4 consecutive days. RESULTS Sixty-three patients were followed up (28 patients on 30 mg twice daily, 35 patients on 40 mg once daily). There was no significant difference in demographics between groups. Twenty-five percent of patients on 30 mg twice daily developed a DVT, whereas 2.9% of patients on 40 mg once daily developed a DVT. Patients on 30 mg twice daily had significantly lower anti-Xa levels. CONCLUSIONS The incidence of DVT is increased in surgical patients who receive 30 mg twice daily dosing of enoxaparin compared with 40 mg daily. Dosing of 40 mg once daily results in significantly higher peak anti-Xa levels compared with 30 mg twice daily.

Update and new developments in the management of the exsanguinating patient

Definitive management of the exsanguinating patient continues to challenge providers in multiple specialties. Significant hemorrhage may be encountered in a variety of patient care circumstances. Over the past two decades, the vast majority of data and evidence regarding transfusion in the exsanguinating patient has been based upon the trauma literature, and a large amount of recent research has investigated this subject area. In addition to the care of trauma patients, the data which have emerged can also be extrapolated to the treatment of nontrauma patients undergoing transfusion for major hemorrhage. The concept of massive transfusion is an evolving paradigm, and numerous investigations have challenged old principles while creating new controversies. The current review will examine the latest developments in the management of patients with profound hemorrhage. The challenges of dealing with the “lethal triad” will be discussed, as will the various aspects of damage control and hemostatic resuscitation. The latest literature and controversy regarding massive transfusions and massive transfusion protocols will be elucidated with inclusion of data from recent military experiences. Finally, adjuncts including the most recent advances in hemorrhage control, identification of early predictors for massive transfusion, and utilization of pharmacologic and complementary factor agent therapy will be discussed.