Pharmacokinetics of Levetiracetam Seizure Prophylaxis in Severe Traumatic Brain Injury.

BACKGROUND: Drug pharmacokinetics (PK) are altered in neurocritically ill patients, and optimal levetiracetam dosing for seizure prophylaxis is unknown. OBJECTIVE: This study evaluates levetiracetam PK in critically ill patients with severe traumatic brain injury (sTBI) receiving intravenous levetiracetam 1000 mg every 8 (LEV8) to 12 (LEV12) hours for seizure prophylaxis. METHODS: This prospective, open-label study was conducted at a level 1 trauma, academic, quaternary care center. Patients with sTBI receiving seizure prophylaxis with LEV8 or LEV12 were eligible for enrollment. Five sequential, steady-state, postdose serum levetiracetam concentrations were obtained. Non-compartmental analysis (NCA) and compartmental approaches were employed for estimating pharmacokinetic parameters and projecting steady-state trough concentrations. Pharmacokinetic parameters were compared between LEV8 and LEV12 patients. Monte Carlo simulations (MCS) were performed to determine probability of target trough attainment (PTA) of 6 to 20 mg/L. A secondary analysis evaluated PTA for weight-tiered levetiracetam dosing. RESULTS: Ten male patients (5 LEV8; 5 LEV12) were included. The NCA-based systemic clearance and elimination half-life were 5.3 ± 1.2 L/h and 4.8 ± 0.64 hours. A one-compartment model provided a higher steady-state trough concentration for the LEV8 group compared with the LEV12 group (13.7 ± 4.3 mg/L vs 6.3 ± 1.7 mg/L; P = 0.008). Monte Carlo simulations predicted regimens of 500 mg every 6 hours, 1000 mg every 8 hours, and 2000 mg every 12 hours achieved therapeutic target attainment. Weight-tiered dosing regimens achieved therapeutic target attainment using a 75 kg breakpoint. CONCLUSION AND RELEVANCE: Neurocritically ill patients exhibit rapid levetiracetam clearance resulting in a short elimination half-life. Findings of this study suggest regimens of levetiracetam 500 mg every 6 hours, 1000 mg every 8 hours, or 2000 mg every 12 hours may be required for optimal therapeutic target attainment. Patient weight of 75 kg may serve as a breakpoint for weight-guided dosing to optimize levetiracetam therapeutic target attainment for seizure prophylaxis.

Clinical Experience, Characteristics, and Performance of an Acetaminophen Absorption Test in Critically Ill Patients.

BACKGROUND: Altered drug and nutrient absorption presents a unique challenge in critically ill patients. Performing an acetaminophen absorption test (AAT) has been used as a marker for gastric motility and upper small bowel absorption; thus, it may provide objective data regarding enteral absorptive ability in critically ill patients. STUDY QUESTION: What is the clinical experience with AAT when used as a surrogate marker for enteral absorption in critically ill patients? STUDY DESIGN: This single-center, retrospective, cohort study evaluated serum acetaminophen concentrations within 180 minutes following 1-time enteral administration of an AAT. Patients admitted to the surgical and medical intensive care units and medical intensive care units over a 7-year period were evaluated. Groups were defined as positive (acetaminophen concentration of ≥10 mg/L) or negative (acetaminophen concentration of <10 mg/L) AAT. MEASURES AND OUTCOMES: The outcomes were to describe the clinical experience, characteristics, and performance of AAT. RESULTS: Forty-eight patients were included. Patients were 58.5 ± 14 years of age, mostly male (58.3%), and admitted to the surgical intensive care unit (66.7%). Median hospital length of stay was 47.5 (27-78.8) days. Thirty-four patients (70.8%) had a positive AAT [median concentration, 14 (12-18) mg/L]. Median time to first detectable concentration was 37 (33-64) minutes. AAT characteristics were similar between the groups including total dose, weight-based dose, time to first and second assays, drug formulation, and site of administration between groups. There were no independent risk factors identified on regression analysis for negative AAT. CONCLUSIONS: An acetaminophen dose of 15 mg/kg with 2 coordinated serum concentrations approximately 30 and 60 minutes after administration is a reasonable construct for AAT. Future research is needed to assess AAT utility, safety, and clinical outcomes for predicting patient ability to absorb enteral feeds and medications.

Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-Analysis.

PURPOSE: Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients. METHODS: We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology. RESULTS: We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40-0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30-0.78) or any VTE (aOR: 0.54, 95% CI: 0.42-0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85-1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50-1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions. CONCLUSION: Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results.

Applying Cefepime Population Pharmacokinetics to Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

Patients admitted to the intensive care unit (ICU) may need continuous renal replacement therapy (CRRT) due to acute kidney injury or worsening of underlying chronic kidney disease. This will affect their antimicrobial exposure and may have a significant impact on the treatment. We aim to develop a cefepime pharmacokinetic (PK) model in CRRT ICU patients and generate the posterior predictions for a group and assess their therapy outcomes. Adult patients, who were admitted to the ICU, received cefepime, and had its concentration measured while on CRRT were included from three different data sets. In two data sets, samples were collected from the predialyzer, postdialyzer ports, and effluent fluid at different times within the same dosing interval. The third data set had only cefepime plasma concentration measured as part of clinical service. Patients' demographics, cefepime regimens and concentration, CRRT parameters, and therapy outcomes were recorded. NPAG was used for population PK and posterior predictions. A total of 125 patients were included. Cefepime was described by a five-compartment model, and the CRRT flow rates described the rates of cefepime transfer between compartments. The posterior predictions were generated for the third data set and the median (range) fT>MIC was 100% (27%-100%) and fT>4×MIC was 64% (0%-100%). The mortality rate was 53%. There was no difference in target attainment in terms of clinical cure and 30-day mortality. This model can be used as a precision dosing tool in CRRT patients. Future studies may address other PK/PD targets in a larger population.

Intercostal liposomal bupivacaine injection for rib fractures: A prospective randomized controlled trial.

BACKGROUND: Blunt chest wall injury accounts for 15% of trauma admissions. Previous studies have shown that the number of rib fractures predicts inpatient opioid requirements, raising concerns for pharmacologic consequences, including hypotension, delirium, and opioid dependence. We hypothesized that intercostal injection of liposomal bupivacaine would reduce analgesia needs and improve spirometry metrics in trauma patients with rib fractures. METHODS: A prospective, double-blinded, randomized placebo-control study was conducted at a Level I trauma center as a Food and Drug Administration investigational new drug study. Enrollment criteria included patients 18 years or older admitted to the intensive care unit with blunt chest wall trauma who could not achieve greater than 50% goal inspiratory capacity. Patients were randomized to liposomal bupivacaine or saline injections in up to six intercostal spaces. Primary outcome was to examine pain scores and breakthrough pain medications for 96-hour duration. The secondary endpoint was to evaluate the effects of analgesia on pulmonary physiology. RESULTS: One hundred patients were enrolled, 50 per cohort, with similar demographics (Injury Severity Score, 17.9 bupivacaine 17.6 control) and comorbidities. Enrolled patients had a mean age of 60.5 years, and 47% were female. Rib fracture number, distribution, and targets for injection were similar between groups. While both groups displayed a decrease in opioid use over time, there was no change in mean daily pain scores. The bupivacaine group achieved higher incentive spirometry volumes over Days 1 and 2 (1095 mL, 1063 mL bupivacaine vs. 900 mL, 866 mL control). Hospital and intensive care unit lengths of stay were similar and there were no differences in postinjection pneumonia, use of epidural catheters or adverse events bet ween groups. CONCLUSION: While intercostal liposomal bupivacaine injection is a safe method for rib fracture-related analgesia, it was not effective in reducing pain scores, opioid requirements, or hospital length of stay. Bupivacaine injection transiently improved incentive spirometry volumes, but without a reduction in the development of pneumonia. LEVEL OF EVIDENCE: Therapeutic/care management, Level II.

Impact of a Multimodal Analgesia Protocol on Inpatient and Outpatient Opioid Use in Acute Trauma.

BACKGROUND: Multimodal analgesia protocols have been implemented after elective surgery to reduce opioid use, however there is limited data on utility after polytrauma. Therefore, we investigated the impact of a multimodal analgesia protocol on inpatient and post-discharge outpatient opioid use after polytrauma. METHODS: A retrospective review of patients admitted to a Level I trauma center between September 2017-February 2018 (prior to multimodal protocol; "pre-cohort") and October 2018-April 2019 (after multimodal protocol; "post-cohort") was performed. An outpatient controlled substance registry was utilized to capture morphine milligram equivalents (MME) and gabapentin dispensed in the 6 mo after injury. RESULTS: 620 patients were included (295 pre-cohort, 325 post-cohort). Total inpatient MME decreased from 177.5 mg-130 mg (P= 0.01) between the cohorts. Daily inpatient MME decreased from 70.8 mg-44.7 mg (P< 0.01). Intravenous hydromorphone decreased from 2 mg in the pre-cohort to 1 mg in the post-cohort (P= 0.02). Inpatient oxycodone decreased from 45 mg-30 mg (P= 0.01). Concurrently, gabapentin increased from 0 mg-400 mg in the post-cohort (P< 0.01). Patients in the post-cohort were prescribed fewer MMEs than the pre-cohort at discharge (P< 0.05). However, the number of patients prescribed gabapentin increased from 6.1%-16% (P< 0.01). CONCLUSION: Implementation of an updated multimodal analgesia protocol decreased total MME, daily MME, hydromorphone, and oxycodone consumed while increasing gabapentin use. This suggests that while reducing opioid usage in-hospital is critical to reducing outpatient usage, multimodal pain protocols may lead to an increase in gabapentin prescriptions and utilization after discharge.

Cefepime Population Pharmacokinetics and Target Attainment in Critically Ill Patients on Continuous Renal Replacement Therapy.

Sepsis causes half of acute kidney injuries in the intensive care unit (ICU). ICU patients may need continuous renal replacement therapy (CRRT), which will affect their antimicrobial exposure. We aimed to build a cefepime population pharmacokinetic (PK) model in CRRT ICU patients and perform simulations to assess target attainment. Patients who were ≥18 years old, were admitted to the ICU, and received cefepime 2 g every 8 h as a 4-h infusion while on CRRT were enrolled prospectively. Samples were collected from the predialyzer ports, postdialyzer ports, and effluent fluid at 1, 2, 3, 4, and 8 h after the first dose and at steady state. Age, sex, weight, urine output, and CRRT parameters were recorded. Pmetrics was used for population PK and simulations. The target exposure was 100% of the dosing interval during which the free beta-lactam concentration is above the MIC (fT>MIC). Ten patients were included; their mean age was 53 years, and mean weight was 119 kg. Seventy percent were males. Cefepime was described by a five-compartment model. The downtime was applied to the CRRT flow rates, which were used to describe the rates of transfer between the compartments. At MICs of ≤8 mg/liter, intermittent infusion of 2 g cefepime every 8 h achieved good target attainment both early in therapy and at steady state. Only extended- and continuous-infusion regimens achieved good target attainment at MICs of 16 mg/liter. In conclusion, 2 g cefepime infused over 30 min followed by extended infusion of 2 g every 8 h achieved good target attainment at MICs of ≤16 mg/liter with different CRRT flow rates and may be considered in resistant bacterial infections.

Admission thrombelastography does not guide dose adjustment of enoxaparin in trauma patients.

BACKGROUND: Enoxaparin is used as chemoprophylaxis to reduce incidence of venous thromboembolism and its complications following trauma. Serum anti-Xa monitoring is used to assess efficacy but requires several doses to be administered. Thrombelastography assesses hypercoagulability and may have utility identifying high-risk patients for venous thromboembolism. The objective was to evaluate whether thrombelastography parameters could identify trauma patients requiring enoxaparin dose adjustment earlier than serum anti-Xa concentrations. METHODS: A single-center, retrospective medical record review evaluated patients admitted to a regional level I trauma center that received an admission thrombelastography and a dose of enoxaparin with a serum trough anti-Xa concentration drawn. Patients were divided into standard-dose or dose-adjusted enoxaparin. Venous thromboembolism incidence between groups and risk factors for enoxaparin dose adjustment and venous thromboembolism development were evaluated. RESULTS: A total of 204 patients were included. Differences observed between groups included age (standard-dose enoxaparin, 48.5 [29.3-72] vs dose-adjusted enoxaparin, 38.5 [25-55.7] years; P = .005), admission creatinine clearance (standard-dose enoxaparin, 92.9 [67.4-113.4] vs dose-adjusted enoxaparin, 102.1 [83.8-129.2] mL/min; P = .017), and time to venous thromboembolism prophylaxis initiation (standard-dose enoxaparin, 23.8 [11.2-36.4] vs dose-adjusted enoxaparin, 34.5 [18.3-52.7] hours; P = .004). No differences in thrombelastography parameters or venous thromboembolism incidence were observed. No independent risk factors for enoxaparin dose adjustment were identified; however, risk assessment profile score > 10 was an independent risk factor for venous thromboembolism development. CONCLUSION: No relationship between admission thrombelastography and need for enoxaparin dose adjustment in trauma patients was observed. As thrombelastography continues growing in clinical use, it is prudent to investigate other potential applications. Currently, thrombelastography should not be used to guide enoxaparin dosing.

Retrospective Evaluation of Venous Thromboembolism Prophylaxis in Elderly, High-Risk Trauma Patients.

BACKGROUND: Venous thromboembolism (VTE) risk increases with age. Scarce data exist for patients age ≥65 y. This study evaluated VTE incidence in elderly, high-risk trauma patients receiving unfractionated heparin (UFH) or enoxaparin chemoprophylaxis. MATERIALS AND METHODS: This retrospective, single-center, cohort study included trauma patients age ≥ 65 y with risk assessment profile (RAP) ≥ 5 who received UFH or enoxaparin chemoprophylaxis. The primary outcome was VTE incidence requiring therapeutic anticoagulation. An age-modified RAP (RAP-AM) was calculated as RAP without age distribution points. Logistic regression analyses were performed to identify independent predictors for VTE development and chemoprophylactic agent selection. Bleeding incidence compared packed red blood cells utilized. RESULTS: A total of 1090 patients were included (UFH, n = 655; enoxaparin, n = 435). VTE occurred in 39 (3.6%) patients with no difference between groups in proximal deep vein thrombosis (2.1% versus 3.0%, P = 0.52) or pulmonary embolism (1.2% versus 1.4%, P = 0.96). Weight ≥125 kg (OR 4.12, 95% CI 1.06-16.11) and RAP-AM ≥ 5 (OR 6.52, 95% CI 2.65-16.03) were independently associated with VTE development. Increasing age (OR 1.04, 95% CI 1.03-1.06), initiation ≤ 24 h (OR 2.17, 95% CI 1.66-2.84) and creatinine clearance ≤ 30 mL/min (OR 1.61, 95% CI 1.17-2.21) were independent predictors of receiving UFH whereas increasing ISS (OR 0.97, 95% CI 0.95-0.99) was associated with receiving enoxaparin. CONCLUSIONS: VTE incidence may be similar for high-risk, elderly trauma patients receiving UFH and enoxaparin chemoprophylaxis. Further research is necessary to determine noninferiority of UFH to enoxaparin in this patient population.

Pharmacokinetics and Pharmacodynamics of Extended-Infusion Cefepime in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Prospective, Open-Label Study.

STUDY OBJECTIVE: To evaluate extended-infusion (EI) cefepime pharmacokinetics (PK) and pharmacodynamic target attainment in critically ill patients receiving continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD). DESIGN: Prospective, open-label, PK study. SETTING: Intensive care units at a large, academic, tertiary-care medical center. PATIENTS: Ten critically ill adults who were receiving cefepime 2 g intravenously every 8 hours as a 4-hour infusion while receiving CVVH (eight patients) or CVVHD (two patients). INTERVENTION: Two sets of five serum cefepime concentrations were collected for each patient to assess pharmacokinetics before and during presumed steady state. Concurrent serum and CRRT effluent samples were collected at hours 1, 2, 3, 4, and 8 after the first cefepime dose and after either the fourth, fifth, or sixth (steady-state) cefepime doses. MEASUREMENTS AND MAIN RESULTS: Reversed-phase high-performance liquid chromatography was used to determine free cefepime concentrations. PK analyses included CRRT clearance, half-life, and sieving coefficient or saturation coefficient. Cefepime peak (4 hrs) concentrations, trough (8 hrs) concentrations (Cmin ), and minimum inhibitory concentration breakpoint of 8 µg/ml for the pathogen (MIC8 ) were used to evaluate attainment of pharmacodynamic targets: 100% of the dosing interval that free drug remains above MIC8 (100% fT > MIC8 ), 100% fT > 4 × MIC8 (optimal), percentage of time fT > 4 × MIC8 (%fT > 4 × MIC8 ) at steady state, and ratio of Cmin to MIC8 (fCmin /MIC8 ). Total CRRT effluent flow rate was a mean ± SD of 30.1 ± 5.4 ml/kg/hr, CRRT clearance was 39.6 ± 9.9 ml/min, and half-life was 5.3 ± 1.7 hours. Sieving coefficient or saturation coefficient were 0.83 ± 0.13 and 0.69 ± 0.22, respectively. First and steady-state dose Cmin were 23.4 ± 10.1 µg/ml and 45.2 ± 14.6 µg/ml, respectively. All patients achieved 100% fT > MIC8 on first and steady-state doses. First and steady-state dose 100% fT > 4 × MIC8 were achieved in 22% (2/9 patients) and 87.5% (7/8 patients) of patients, respectively. The mean %fT > 4 × MIC8 at steady state was 97.5%. The fCmin /MIC8 was 2.92 ± 1.26 for the first dose and 5.65 ± 1.83 at steady state. CONCLUSION: Extended-infusion cefepime dosing in critically ill patients receiving CRRT successfully attained 100% fT > MIC8 in all patients and an appropriate fCmin /MIC8 for both first and steady-state doses. All but one patient achieved 100% fT > 4 × MIC8 at steady state. No significant differences were observed in PK properties between first and steady-state doses among or between patients. It may be reasonable to initiate an empiric or definitive regimen of EI cefepime in critically ill patients receiving concurrent CRRT who are at risk for resistant organisms. Further research is needed to identify the optimal dosing regimen of EI cefepime in this patient population.

Ketamine versus hydromorphone patient-controlled analgesia for acute pain in trauma patients.

BACKGROUND: It is unknown whether ketamine administered via patient-controlled analgesia (PCA) provides adequate analgesia while reducing opioid consumption in the traumatically injured patient. Differences in opioid consumption, pain scores, and adverse effects between ketamine and hydromorphone PCA were studied. MATERIALS AND METHODS: This is an investigator-initiated, single-center, double-blinded, randomized, pilot trial conducted from 2014 to 2016 at a level 1 trauma center. Nonintubated trauma patients in intensive care, who were receiving PCA, were randomized to ketamine or hydromorphone PCA plus opioid analgesics for breakthrough pain. RESULTS: Twenty subjects were randomized. There was no difference in median daily breakthrough opioid use (10 [0.63-19.38] mg versus 10 [4.38-22.5] mg, P = 0.55). Subjects in the ketamine group had lower median cumulative opioid use on therapy day 1 than the hydromorphone group (4.6 [2.5-15] mg versus 41.8 [31.8-50] mg, P < 0.001), as well as in the first 48 h (10 [3.3-15] mg versus 48.5 [32.1-67.5] mg, P < 0.001) and first 72 h (10 [4.2-15] mg versus 42.5 [31.7-65.2] mg, P < 0.001) of therapy. Daily oxygen supplementation requirements were lower in the ketamine group (0.5 [0-1.5] L/min versus 2 [0.5-3] L/min, P = 0.020). Hallucinations occurred more frequently in the ketamine group (40% versus 0%, P = 0.090). CONCLUSIONS: Ketamine PCA led to lower cumulative opioid consumption and lower oxygen supplementation requirements, though hallucinations occurred more frequently with use of ketamine. Additional studies are needed to investigate the tolerability of ketamine as an alternative to traditional opioid-based PCA.

Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis.

Sepsis is associated with marked mortality, which may be reduced by prompt initiation of adequate, appropriate doses of antibiotic. Critically ill patients often have physiological changes that reduce blood and tissue concentrations of antibiotic and high rates of multidrug-resistant pathogens, which may affect patients' outcomes. All critical care professionals, including critical care nurses, should understand antibiotic pharmacokinetics and pharmacodynamics to ensure sound antibiotic dosing and administration strategies for optimal microbial killing and patients' outcomes. Effective pathogen eradication occurs when the dose of antibiotic reaches or maintains optimal concentrations relative to the minimum inhibitory concentration for the pathogen. Time-dependent antibiotics, such as ß-lactams, can be given as extended or continuous infusions. Concentration-dependent antibiotics such as aminoglycosides are optimized by using high, once-daily dosing strategies with serum concentration monitoring. Vancomycin and fluoroquinolones are dependent on both time and concentration above the minimum inhibitory concentration.

Major publications in the critical care pharmacotherapy literature: January-December 2014.

PURPOSE: Nine recently published articles and one guideline with important implications for critical care pharmacy practice are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group includes more than 40 experienced critical care pharmacists across the United States. Group members monitor 29 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on applicability to practice, relevance, and study design and strength. Hundreds of relevant articles were evaluated by the group in 2014, of which 114 were summarized and disseminated to CCPLU group members. From among those 114 publications, 10 deemed to be of particularly high utility to the critical care practitioner were selected for inclusion in this review for their potential to change practice or reinforce current evidence-based practice. One of the selected articles presents updated recommendations on the management of patients with atrial fibrillation (AF); the other 9 address topics such as albumin replacement in patients with severe sepsis, use of enteral statins for acute respiratory distress syndrome, fibrinolysis for patients with intermediate-risk pulmonary embolism, the use of unfractionated heparin versus bivalirudin for primary percutaneous coronary intervention, and early protocol-based care for septic shock. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2014, including a joint guideline for the management of AF and reports of clinical trials.

Effect of a dalteparin prophylaxis protocol using anti-factor Xa concentrations on venous thromboembolism in high-risk trauma patients.

BACKGROUND: Low anti-factor Xa (anti-Xa) concentrations with twice-daily enoxaparin are associated with venous thromboembolism (VTE) in high-risk trauma patients. Concerns have been raised with once-daily dalteparin regarding effectiveness and achievable anti-Xa concentrations. The purpose of this before-and-after study was to evaluate the effectiveness of a VTE prophylaxis protocol using anti-Xa concentrations and associated dalteparin dose adjustment in high-risk trauma patients. METHODS: Adult trauma patients receiving VTE chemoprophylaxis and hospitalized for at least 3 days were prospectively followed during two 6-month epochs before (PRE) and after (POST) implementation of anti-Xa monitoring. In both groups, high-risk patients received dalteparin 5,000 U subcutaneously once daily; low-risk patients received subcutaneous unfractionated heparin. High-risk POST patients with anti-Xa less than 0.1 IU/mL 12 hours after initial dalteparin dose received dalteparin every 12 hours. All patients underwent routine VTE ultrasound surveillance of the lower extremities. The primary outcome was incidence of VTE. RESULTS: A total of 785 patients (PRE, n = 428; POST, n = 357) were included. Demographics, injury patterns, Injury Severity Score (ISS), red blood cell transfusions, intensive care unit and hospital stays, and mortality did not differ between groups. Overall, POST patients had lower VTE (7.0% vs. 13%, p = 0.009) including acute VTE (6.4% vs. 12%, p = 0.01) and proximal deep vein thromboembolism (2.2% vs. 5.7%, p = 0.019). Between high-risk patients, VTE occurred in 53 (16.3%) PRE compared with 24 (9.0%) POST patients (p = 0.01); there was no difference in VTE between low-risk patients (PRE, 2.0% vs. POST, 1.1%; p = 0.86). Among 190 high-risk POST patients with anti-Xa, 97 (51%) were less than 0.1 IU/mL. Patients with low anti-Xa had higher rates of VTE (14.0% vs. 5.4%, p = 0.05) and deep vein thromboembolism (14.4% vs. 3.2%, p = 0.01). Younger age (odds ratio, 0.97; 95% confidence interval, 0.95-0.99) and greater weight (odds ratio, 1.02; 95% confidence interval, 1.00-1.03) predicted low anti-Xa on multivariate regression. CONCLUSION: A VTE prophylaxis protocol using anti-Xa-based dalteparin dosage adjustment in high-risk trauma patients was associated with decreased VTE. Once-daily dalteparin 12-hour anti-Xa concentrations are suboptimal in a majority of patients and associated with VTE. LEVEL OF EVIDENCE: Therapeutic study, level IV.