Antithrombin III levels in critically ill surgical patients: do they correlate with VTE?

Objective: Antithrombin III (ATIII) deficiency may result from hereditary or acquired reduction in ATIII levels and is associated with an increase in venous thromboembolism (VTE) in the general population. VTE is a potentially preventable complication in the critically ill surgical patients. The objective of this study was to evaluate the relation between ATIII levels and VTE in surgical intensive care unit (SICU) patients. Methods: All patients admitted to the SICU from January 2017 to April 2018 who had ATIII levels drawn were included in the study. An ATIII level below 80% of normal was considered low. The rate of VTE during the same admission was compared among patients with normal and low levels of ATIII. Prolonged length of stay (LOS >10 days) and mortality were also measured. Results: Of the 227 patients included, 59.9% were male. The median age was 60 years. Overall, 66.9% of patients had low ATIII levels. Trauma patients had a higher rate of normal ATIII levels, whereas those weighing more than 100 kg had a higher rate of low ATIII levels. Patients with low ATIII levels had higher VTE rates compared with those with normal ATIII levels (28.9% vs. 16%, p=0.04). Patients with low ATIII levels also had prolonged LOS (76.3% vs. 60%, p=0.01) and increased mortality (21.7% vs. 6.7%, p<0.01). Trauma patients with VTE were more likely to have normal ATIII levels (38.5% in low ATIII cohort vs. 61.5% VTE in normal ATIII cohort, p<0.01). Conclusion: Critically ill surgical patients with low ATIII levels have higher incidence of VTE, longer LOS, and higher mortality. In contrast, critically ill trauma patients may have high incidence of VTE even with normal ATIII levels. Level of evidence: III.

Inadequate Venous Thromboembolism Chemoprophylaxis Is Associated With Higher Venous Thromboembolism Rates Among Trauma Patients With Epidurals.

INTRODUCTION: Guidelines encourage higher doses of low molecular weight heparin (LMWH) for prophylaxis in trauma patients. The risks of LMWH must be considered for patients who require an epidural catheter. We compared adequate and inadequate prophylaxis to determine if venous thromboembolism (VTE) and complication rates differed among patients with epidural catheters. METHODS: Trauma patients who required an epidural catheter between 2012 and 2019 were reviewed for VTE and epidural-related complications. Adequate dosing was defined as enoxaparin 30 mg or 40 mg twice daily. Inadequate dosing was defined as unfractionated heparin subcutaneously or enoxaparin once daily. RESULTS: Over the 8-y study period, 113 trauma patients required an epidural catheter of which 64.6% were males with a mean age of 55.8 y and injury severity score of 14. Epidural catheters were associated with 11 (9.7%) patients developing an acute deep vein thrombosis (DVT) and 2 (1.8%) patients with an acute pulmonary embolism. Those patients who received adequate doses of enoxaparin were less likely to have any VTE or DVT. Complications associated with epidural catheters were not dependent on the type of pharmacological prophylaxis. CONCLUSIONS: Given the high VTE rate observed in trauma patients who required an epidural catheter, along with the low complication rate that was observed independent of the type of pharmacological prophylaxis given, the data indicate that current efforts for higher doses of LMWH appear to be safe and associated with a lower VTE rate.

Characterizing the delays in adequate thromboprophylaxis after TBI.

BACKGROUND: We sought to compare enoxaparin dosing for venous thromboembolism (VTE) prophylaxis in trauma patients with and without traumatic brain injury (TBI) to better understand the time and dose required to reach target anti-Xa levels. Our hypothesis was that patients with TBI have significant delays in the initiation of adequate pharmacological prophylaxis and require a higher enoxaparin dose than currently recommended. METHODS: The medical records of trauma patients who received enoxaparin dosing based on anti-Xa trough levels between August 2014 and October 2016 were reviewed. Patients were included if their anti-Xa trough level reached the target range (0.1 IU/mL to 0.2 IU/mL). RESULTS: A total of 163 patients had anti-Xa levels within the target range of which 41 (25.2%) had TBI. Patients with TBI had longer delays before initiating enoxaparin (7.5 days vs. 1.5 days after admission, p<0.01) and were more likely to receive unfractionated heparin prior to enoxaparin (46.3% vs. 11.5%, p<0.01). Anti-Xa levels reached the target range later in patients with TBI (11 days vs. 5 days after admission, p<0.01). Enoxaparin 40 mg two times per day was the median dose required to reach the target anti-Xa levels for both cohorts. VTE rates were higher among patients with TBI (22.0% vs. 9.0%, p=0.03). Four patients (9.8%) had progression of their intracranial hemorrhage prior to receiving enoxaparin, although none progressed during enoxaparin administration. CONCLUSION: Among patients with TBI who reached target anti-Xa levels, 11 days after admission were required to reach a median enoxaparin dose of 40 mg two times per day. Unfractionated heparin was used as pharmacological prophylaxis in about half of these patients. The delay in reaching the target anti-Xa levels and the use of unfractionated heparin likely contribute to the higher VTE rate in patients with TBI. LEVEL OF EVIDENCE: Level III, therapeutic.

A Systems-based Approach to Reduce Deep Venous Thrombosis and Pulmonary Embolism in Trauma Patients.

BACKGROUND: Venous thromboembolism (VTE) in trauma patients carries significant morbidity and mortality. We previously described how titrating enoxaparin dosing by anti-Xa trough levels was associated with a lower VTE rate. We combined this strategy with a higher initial enoxaparin dose for a majority of patients and modified the electronic medical record (EMR) to encourage immediate dosing. We sought to determine if this systems-based approach was associated with a decrease in VTE rate. STUDY DESIGN: A retrospective review was conducted of all trauma patients on prophylactic enoxaparin at an academic, Level I Trauma Center from 01/2013 to 05/2014 (PRE) and 06/2015 to 02/2018 (POST). The patients in PRE were prescribed enoxaparin 30 mg twice daily without dose adjustments. The patients in POST received 40 mg twice daily unless exclusion criteria applied, with doses titrated to maintain anti-Xa trough levels between 0.1 and 0.2 IU/mL. RESULTS: There were 478 patients in the PRE and 1306 in the POST. Compared to PRE, POST patients were of similar age and were as likely to present after blunt trauma, although POST patients had lower injury severity scores (10 vs. 9, p < 0.01). The overall VTE rate was lower in POST (6.9% vs. 3.6%, p < 0.01). The adjusted risk of VTE (AOR 0.61, adjusted p = 0.04) was lower in POST and POST was independently protective for VTE (AOR 0.54; p = 0.01). CONCLUSION: By implementing system changes to improve enoxaparin dosing after trauma, a significant reduction in VTE rate was observed. Wider application of this strategy should be considered.

Which Trauma Patients Require Lower Enoxaparin Dosing for Venous Thromboembolism Prophylaxis?

Trauma patients have a high risk for venous thromboembolism (VTE) such that an increased enoxaparin dose is necessary to reduce related complications. Given that most trauma patients require an enoxaparin dose of at least 40 mg every 12 hours for VTE prophylaxis, we sought to identify which patients require enoxaparin 30 mg every 12 hours and hypothesized that both weight and low creatinine clearance (CrCl) would more likely determine enoxaparin dosing than age, body mass index (BMI), or body surface area (BSA). Single institution data were collected on trauma patients between August 2014 and February 2018 to compare trauma patients who required enoxaparin 30 mg to those who required ≥40 mg every 12 hours. Of the 245 patients included, 86 (35.1%) required enoxaparin at 30 mg to achieve the goal anti-factor Xa trough level. Factors associated with low dose enoxaparin were older age (59.6 vs. 46.2 years, P ≤ .01) and lower CrCl (81.5 mL/min vs. 93.7 mL/min, P ≤ .01). Weight, BSA, and BMI did not alter the dose of enoxaparin. A regression model determined that only CrCl predicted the need for low dose enoxaparin (adjusted odds ratio .982, 95% CI: .975-.990, P < .01). Although an initial dose of enoxaparin 40 mg is appropriate for most trauma patients, patients with low CrCl should receive 30 mg. Increased age and low weight were not associated with the need for a lower enoxaparin dose.

Vasopressors in traumatic brain injury: Quantifying their effect on mortality.

BACKGROUND: The benefits of vasopressor (VP) use to improve clinical outcomes in traumatic brain injury (TBI) is unknown. We sought to characterize the use of VP in TBI patients and evaluate its impact on mortality. METHODS: A retrospective review was conducted of all TBI patients admitted to an ICU at a Level I trauma center from January 2014 to August 2016. Patients who had any VP administered (VP+) were compared to those who did not (VP-). RESULTS: Among the 556 patients analyzed, 83 (14.9%) received VP. The overall mortality was 9.2%, significantly higher in the VP + cohort (42.2% vs. 3.4%, p < 0.01). After adjusting for confounding factors, VP + patients had a significantly higher risk for in-hospital mortality (Adjusted Hazard Ratio: 2.77, adjusted p = 0.01). CONCLUSION: Although VP may be temporarily useful in avoiding secondary insult to the brain in TBI patients, their use is not associated with improved survival.

Trauma patients with lower extremity and pelvic fractures: Should anti-factor Xa trough level guide prophylactic enoxaparin dose?

BACKGROUND: Adequate venous thromboembolism (VTE) prophylaxis is essential after trauma, especially in patients with lower extremity and/or pelvic fractures. We sought to investigate if prophylactic enoxaparin dosed by anti-Xa trough levels could reduce clinically evident VTE in trauma patients with lower extremity or pelvic injury. METHODS: Prospective data was collected on trauma patients admitted for at least two days with any lower extremity and/or pelvic fracture and who received enoxaparin for VTE prophylaxis between October 2013 and January 2016. Patients in the control cohort received enoxaparin at 30 mg twice daily. Patients in the adjustment cohort had anti-Xa trough levels measured after three or more consecutive doses of enoxaparin. Those with a trough level of 0.1 IU/mL or lower had their dosage increased by 10-mg increments. RESULTS: Of the 159 patients included, 58 (36.5%) were monitored with anti-Xa trough levels. The cohorts were similar in age, sex, regional AIS, ISS score, ICU and hospital length of stay, proportion of patients with diagnostic testing for VTE, and time to first enoxaparin dose. Initial enoxaparin dosing in the majority of patients (84.5%) who had anti-Xa trough levels measured was subprophylactic. Patients receiving enoxaparin dosed by anti-Xa trough level had a significantly lower VTE rate than those who did not (1.7% v. 13.9%, p = 0.03). CONCLUSIONS: Prophylactic enoxaparin adjusted by anti-factor Xa level may lead to a decreased rate of clinically evident VTE among trauma patients with lower extremity and/or pelvic fractures. Our findings indicate that the initial dose of enoxaparin was frequently too low.

Association Between Enoxaparin Dosage Adjusted by Anti-Factor Xa Trough Level and Clinically Evident Venous Thromboembolism After Trauma.

Importance: Trauma patients are at high risk for developing venous thromboembolism (VTE). The VTE rate when enoxaparin sodium is dosed by anti-factor Xa (anti-Xa) trough level is not well described. Objective: To determine whether targeting a prophylactic anti-Xa trough level by adjusting the enoxaparin dose would reduce the VTE rate in trauma patients. Design, Setting, and Participants: Single-institution, historic vs prospective cohort comparison study at an urban, academic, level I trauma center. The prospective cohort was enrolled from August 2014 to May 2015 and compared with a historic cohort admitted from August 2013 to May 2014. Trauma patients who received enoxaparin adjusted by anti-Xa trough level (adjustment group) were compared with those who received enoxaparin sodium at a dosage of 30 mg twice daily (control group). Patients were excluded if they were younger than 18 years, had a length of hospital stay less than 2 days, or had preexisting deep vein thrombosis. Patients were excluded from the adjustment group for changes in the choice of thromboprophylaxis (heparin, enoxaparin once-daily dosing, early ambulation), hospital discharge before initial trough levels could be drawn, or incorrect timing of trough levels. Exposures: Anti-Xa trough levels were monitored in patients in the adjustment group receiving 3 or more consecutive doses of enoxaparin sodium, 30 mg twice daily. Patients with a trough level of 0.1 IU/mL or lower received enoxaparin sodium increased by 10-mg increments. After providing 3 adjusted doses of enoxaparin, the trough level was redrawn and the dosage was adjusted as necessary. Patients in the control group received enoxaparin sodium at a dosage of 30 mg twice daily without adjustments. Main Outcomes and Measures: Rates of symptomatic VTE (deep vein thrombosis and pulmonary embolism, confirmed by duplex ultrasonography and chest computed tomographic angiography, respectively) and bleeding risk. Results: A total of 205 patients (mean [SD] age, 41.3 [18.2] years; 75.1% male) were studied, 87 in the adjustment group and 118 in the control group, with similar baseline characteristics and injury profiles. Subprophylactic anti-Xa troughs were noted in 73 of 87 patients (83.9%) in the adjustment group, and the majority of patients (57 of 87 patients [65.5%]) required dosage adjustment of enoxaparin sodium to 40 mg twice daily. Incidence of VTE was significantly lower in the adjustment group than in the control group (1.1% vs 7.6%, respectively; P = .046). When the adjustment group was compared with the control group, no significant difference was noted in the rate of packed red blood cell transfusion (6.9% vs 12.7%, respectively; P = .18) or mean (SD) hematocrit at discharge (34.5% [6.3%] vs 33.4% [6.8%], respectively [to convert to proportion of 1.0, multiply by 0.01]; P = .19). Conclusions and Relevance: In this study, subprophylactic anti-Xa trough levels were common in trauma patients. Enoxaparin dosage adjustment may lead to a reduced rate of VTE without an increased risk of bleeding.

Reducing acute kidney injury due to vancomycin in trauma patients.

BACKGROUND: Supratherapeutic vancomycin trough levels are common after trauma and associated with both increased acute kidney injury (AKI) and mortality. We sought to limit the adverse effects of vancomycin in trauma patients through more frequent trough monitoring. METHODS: Beginning in January 2011, trauma patients treated with vancomycin had trough levels (VT) monitored daily until steady state was reached. Trauma patients admitted from January 2011 to May 2015 (POST) were compared with those admitted from January 2006 to December 2010 (PRE). Inclusion criteria required administration of intravenous vancomycin, admission serum creatinine (SCr), and SCr within 72 hours of highest VT. Acute kidney injury was defined as an increase in SCr of at least 0.3 mg/dL or 50% from admission to post-vancomycin administration. Those in the POST group were prospectively followed up until discharge or death. RESULTS: Two hundred sixty-three patients met inclusion criteria in the PRE-phase and 115 in the POST-phase. The two groups were similar in age, gender, race, body mass index, pre-existing comorbidities, admission systolic blood pressure, Glasgow Coma Scale, and head Abbreviated Injury Scale. Injury Severity Score was higher in the POST cohort (18 PRE vs. 25 POST, p < 0.001). Compared with PRE, the POST cohort had lower rates of supratherapeutic VT (>20 mg/L) (34.6% PRE vs. 22.6% POST, p = 0.02) and AKI (30.4% PRE vs. 19.1% POST, p = 0.026). After adjusting for confounders, the POST group had a significantly lower risk of AKI with an adjusted odds ratio of 0.457 (p = 0.027). There was a trend toward decreased mortality in the POST cohort, but this did not reach significance (10% PRE vs. 5.2% POST, p = 0.162). CONCLUSIONS: A reduction in AKI was observed in trauma patients with daily vancomycin trough levels monitored until steady state. Increased awareness regarding closer surveillance of VT in trauma patients may limit the incidence of vancomycin-related nephrotoxicity. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Body mass index strongly impacts the diagnosis and incidence of heparin-induced thrombocytopenia in the surgical intensive care unit.

BACKGROUND: The obese state has been linked to several immune-mediated conditions. Our objective was to examine the association of body mass index (BMI) with the diagnosis of heparin-induced thrombocytopenia (HIT). METHODS: Prospectively collected data on patients in the surgical and cardiac intensive care unit suspected of having HIT between January 2007 and August 2014 were analyzed. Patients were categorized into five discrete BMI (kg/m) groups and compared. Data collected included Warkentin 4-T scores, antiplatelet factor 4 (anti-PF4OD) values, serotonin release assay values, and thromboembolic diseases. HIT positivity was defined as serotonin release assay value greater than 20%. RESULTS: Of 304 patients meeting inclusion criteria, mean (SD) age was 62.1 (16.5) years, 59% were male, and mean (SD) BMI was 27 (6) kg/m. Thirty-six (12%) were positive for HIT. Incidence of HIT increased progressively with BMI (0%, 8%, 11%, 19%, 36%; p < 0.001). Compared with patients with normal BMI, patients with a BMI of 30 kg/m to 39.9 kg/m had a 200% increase in the odds for HIT (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.20-7.54; p = 0.019), while patients with a BMI of 40 kg/m or greater had a 600% increase (OR, 6.98; 95% CI, 1.59-28.2; p = 0.012). After regression analysis, BMI remained an independent predictor of the development of HIT (adjusted OR per kg/m, 1.08; 95% CI, 1.02-1.14; p = 0.010). Anti-PF4OD values greater than or equal to 2.0 also increased with BMI (p < 0.001). In-hospital mortality increased significantly with BMI above normal (p = 0.026). Warkentin 4-T scores, deep venous thrombosis, pulmonary embolism, and stroke incidence did not correlate with changes in BMI. CONCLUSION: Increasing BMI seems to be strongly associated with increased rates of HIT in intensive care unit patients. Obesity is an important new clinical variable for estimating the pretest probability of HIT, and patient "thickness" could be considered a fifth "T" of the 4-T scoring system. Additional biochemical work is indicated to decipher the role of obesity in this immune-mediated condition. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.