Samantha J. Underwood

Transfusion of aged packed red blood cells results in decreased tissue oxygenation in critically injured trauma patients.

BACKGROUND Blood transfusion is a common event in the treatment of injured patients. The effect of red blood cell transfusion on tissue oxygenation is unclear. The transfusion of older blood has been shown to be detrimental in retrospective studies. This study aims to study the effect of the age of the blood transfused on the tissue oxygenation using near infrared spectroscopy. METHODS Thirty-two critically injured trauma patients for whom a blood transfusion had been ordered were recruited. Each patient had a transcutaneous probe placed on the thenar eminence. The probe was placed 1 hour before the transfusion and left in place until 4 hours after transfusion. Tissue oxygen saturation (Sto2) was recorded every 2 minutes. The Sto2 area under the curve (AUC) over time periods was calculated. A control group (n = 16), not transfused, was recruited. The transfusion group was divided into two groups by blood age. One group received blood less than 21 days old, (new blood, n = 15) and the other received blood 21 days old or greater (old blood, n = 17). The data were analyzed for significance with Kendalls W and Wilcoxons signed rank test (p < 0.05). RESULTS Baseline characteristics such were not significantly different between groups. The baseline AUC did not differ between groups. The old blood group demonstrated a significant decline in Sto2 comparing its baseline period to its transfusion period (p < 0.05). There was no similar decline in the control group or the new blood group. The posttransfusion period AUC for the old blood group was also lower versus baseline (p = 0.06). There was a moderate correlation between increasing age of blood and decrease in oxygenation (r = 0.5). CONCLUSIONS There was a decrease in peripheral tissue oxygenation in patients receiving older red blood cells. There was no oxygenation decrease in patients receiving blood less than 21 days. This indicates that factors in stored blood may influence the peripheral vasculature and oxygen delivery.

Management and outcome of pneumatosis intestinalis.

BACKGROUND Pneumatosis intestinalis (PI), infiltration of gas into the bowel wall, has traditionally been associated with immediate operative intervention and a high mortality rate. METHODS We retrospectively reviewed the diagnosis and management of pneumatosis in an attempt to characterize the disease, and examined management strategies. RESULTS Ninety-seven patients had a computed tomography (CT) diagnosis of pneumatosis. The location of pneumatosis was as follows: 46% colon, 27% small bowel, 5% stomach, and 7% both small and large bowel. Fourteen patients also had portal venous gas and 6 (43%) of these patients died. Management strategy was non-operative in 52%, operative in 33%, and futile care in 15%. The overall mortality rate was 22% (16% operative, 6% non-operative, and 87% futile). Patients who died had a higher mean APACHE II score (25 vs 11, P <.001). CONCLUSIONS Approximately 50% of patients with pneumatosis can be successfully managed non-operatively. The combination of PI and portal venous gas may confer a higher mortality rate.

Thrombelastography versus AntiFactor Xa levels in the assessment of prophylactic-dose enoxaparin in critically ill patients.

BACKGROUND A standard dose of enoxaparin is frequently used for deep venous thrombosis (DVT) prophylaxis. Evidence suggests inconsistent bioavailability in intensive care unit (ICU) patients. Antifactor Xa activity (anti-Xa) has been used to monitor enoxaparin dosing but its accuracy and availability are problematic. Thrombelastography (TEG) is used to evaluate coagulation in diverse settings. The purpose of this study was to analyze whether TEG could be used to predict which enoxaparin-treated patients would develop DVT. METHODS Two hundred sixty-one simultaneous enoxaparin-active (active) and enoxaparin-neutralized (neutral) TEGs were performed in 61 surgical ICU patients over four consecutive days. Patient characteristics and anti-Xa were collected. DVT screening was per ICU protocol. RESULTS Mean (+/-SEM) age was 54 (+/-2.3) years and Acute Physiology and Chronic Health Evaluation II score was 17 (+/-0.7). There were 30 trauma and 31 general surgery patients (69% men). The DVT rate was 28%. Time to clot formation (R) and percent lysis at 30 minutes were different between active versus neutralized blood (p < 0.001). R time was 1.5 minutes shorter in patients with DVT versus those without (p < 0.001) indicating hypercoagulability in DVT patients. Anti-Xa levels were similar in patients with (0.135 +/- 0.012) and without (0.135 +/- 0.007) DVT (p = 0.97). There were no differences in age, body mass index, injury severity score, Acute Physiology and Chronic Health Evaluation II score, or trauma status between DVT and non-DVT groups. CONCLUSIONS TEG demonstrates differences between enoxaparin-neutralized and enoxaparin-active blood in ICU patients that may be used to guide dosing. TEG differentiates enoxaparin-treated patients who subsequently develop DVT while anti-Xa levels do not. TEG demonstrates an enoxaparin-related increase in fibrinolysis.

Prehospital intravenous fluid is associated with increased survival in trauma patients.

BACKGROUND Delivery of intravenous crystalloid fluids (IVF) remains a tradition-based priority during prehospital resuscitation of trauma patients. Hypotensive and targeted resuscitation algorithms have been shown to improve patient outcomes. We hypothesized that receiving any prehospital IVF is associated with increased survival in trauma patients compared with receiving no prehospital IVF. METHODS Prospective data from 10 Level 1 trauma centers were collected. Patient demographics, prehospital IVF volume, prehospital and emergency department vital signs, lifesaving interventions, laboratory values, outcomes, and complications were collected and analyzed. Patients who did or did not receive prehospital IVF were compared. Tests for nonparametric data were used to assess significant differences between groups (p ⩽ 0.05). Cox regression analyses were performed to determine the independent influence of IVF on outcome and complications. RESULTS The study population consisted of 1,245 trauma patients; 45 were excluded owing to incomplete data; 84% (n = 1,009) received prehospital IVF, and 16% (n = 191) did not. There was no difference between the groups with respect to sex, age, and Injury Severity Score (ISS). The on-scene systolic blood pressure was lower in the IVF group (110 mm Hg vs. 100 mm Hg, p < 0.04) and did not change significantly after IVF, measured at emergency department admission (110 mm Hg vs. 105 mm Hg, p = 0.05). Hematocrit/hemoglobin, fibrinogen, and platelets were lower (p < 0.05), and prothrombin time/international normalized ratio and partial thromboplastin time were higher (p < 0.001) in the IVF group. The IVF group received a median fluid volume of 700 mL (interquartile range, 300–1,300). The Cox regression revealed that prehospital fluid administration was associated with increased survival (hazard ratio, 0.84; 95% confidence interval, 0.72–0.98; p = 0.03). Site differences in ISS and fluid volumes were demonstrated (p < 0.001). CONCLUSION Prehospital IVF volumes commonly used by PRospective Observational Multicenter Massive Transfusion Study (PROMMTT) investigators do not result in increased systolic blood pressure but are associated with decreased in-hospital mortality in trauma patients compared with patients who did not receive prehospital IVF. LEVEL OF EVIDENCE Therapeutic study, level IV.

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.

A novel highly porous silica and chitosan-based hemostatic dressing is superior to HemCon and gauze sponges.

BACKGROUND Hemostatic dressings have become increasingly popular as the optimal initial treatment for severe hemorrhage. The purpose of this study was to compare the hemostatic properties of a novel highly porous silica and chitosan-based dressing (TraumaStat) to HemCon, and gauze dressing in a severe groin injury model in swine. METHODS Thirty swine were blindly randomized to receive TraumaStat, HemCon, or standard gauze dressing for hemostatic control. A complex groin injury involving complete transaction of the femoral artery and vein was made. After 30 seconds of uncontrolled hemorrhage, the randomized dressing was applied and pressure was held for 5 minutes. Fluid resuscitation was initiated to achieve and maintain the baseline mean arterial pressure and the wound was inspected for bleeding. Failure of hemostasis was defined as pooling of blood outside of the wound. Animals were then monitored for 120 minutes and surviving animals were euthanized. RESULTS Blood loss before treatment was similar between groups (p > 0.1). TraumaStat had one failure, compared with five for gauze, and eight for HemCon (p = 0.005, TraumaStat vs. HemCon). TraumaStat significantly reduced median blood loss when compared with both HemCon and gauze (117 vs. 774 and 268 mL respectively, p < 0.05). At study conclusion, TraumaStat animals had a greater median hematocrit than both HemCon (24 vs. 19, p = 0.033), and gauze (24 vs. 19, p = 0.049) animals. Median volume of fluid resuscitation and mortality were not different between groups (p > 0.1). CONCLUSIONS TraumaStat was superior to HemCon and gauze dressings in controlling bleeding from a severe groin injury. TraumaStat may be a better hemostatic dressing for control of active hemorrhage than current standards of care.

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.

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.