Prophylactic Enoxaparin in Critically Ill Trauma Patients: Evaluation of the Initial Dose.

Background: Trauma patients are at increased risk of developing venous thromboembolism given alterations in the coagulation cascade. Chemoprophylaxis with standard dosing of enoxaparin 30 mg subcutaneously twice daily has evolved to incorporate the use of anti-factor Xa (AFXa) trough level monitoring given concerns for decreased enoxaparin bioavailability in this patient population. Current available evidence suggests low rates of goal AFXa trough level achievement with standard enoxaparin dosing. Our study aims to identify the incidence of critically ill trauma patients that did not achieve goal AFXa trough levels and attempts to identify predictors that may influence the lack of achievement of goal levels. Methods: This was a retrospective, cohort analysis performed at a single academic medical center. Adult patients 18 years or older admitted to the surgical intensive care unit secondary to trauma who were initiated on standard prophylactic enoxaparin and had at least 1 AFXa trough level representative of steady state were included. Patient demographics and clinical data were collected, and descriptive statistics were utilized. All statistical tests were 2-tailed and a P < .05 was considered significant. Variables with a P < .10 on univariable analysis were included in a multivariable logistic regression analysis. Results: A majority of our patient population did not achieve goal AFXa trough levels while receiving standard doses of prophylactic enoxaparin (82.4% [108/131]). Sub-target AFXa levels were associated with higher creatinine clearance values. Positive predictors of obtaining target AFXa levels included automobile versus pedestrian mechanism of injury and requiring an enoxaparin dose escalation to at least 40 mg twice daily. Conclusions: Our study found low rates of achievement of goal AFXa trough levels in critically ill trauma patients receiving standard prophylactic enoxaparin dosing. Certain variables were identified as negative and positive predictors for achievement of goal AFXa trough levels, although the biologic plausibility of these predictors is questionable and requires further investigation.

Validation of Methicillin-Resistant Staphylococcus aureus (MRSA) Risk Factors in Predicting MRSA Community-Acquired Pneumonia at an Academic Medical Center.

Background: The 2019 Infectious Diseases Society of America community-acquired pneumonia (CAP) guidelines recommend antimethicillin- resistant Staphylococcus aureus (MRSA) therapy in patients with CAP based on previously identified risk factors for MRSA with an emphasis on local epidemiology and institutional validation of risk. Thus, we sought to assess the ability of guideline-recognized risk factors to predict MRSA CAP at our institution. Methods: This was a single-center, retrospective cohort study from January 2016 to March 2020. Patients were included if they were >18 years old, diagnosed with CAP, and had a MRSA nasal screen and respiratory culture obtained on admission. Patients were excluded if CAP diagnosis was not met, respiratory cultures were not obtained within 48 hours of antibiotic initiation, or they had cystic fibrosis. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratios (LR) were calculated using Vasser Stats 2019. Pre/post-test odds and pre/post-test probabilities were calculated using Excel 2019. Results: Of 705 screened patients, 221 were included. MRSA prevalence in CAP patients at our institution was 3.6%. History of MRSA isolated from a respiratory specimen had high specificity (98%), high positive LR of 20 (95% CI 5.3-74.8), and high post-test probability of 42.8%. Receipt of IV antibiotics during hospitalization within the past 90 days had a positive LR of 1.9 (95% CI 0.74-4.84). A positive MRSA nasal screen on admission had a positive LR of 6.9 (95% CI 4.0-12.1), negative LR 0.28 (95% CI 0.08-0.93), positive post-test probability of 20.7%, and negative post-test probability of 1.04%. Conclusion: Our study utilized institutional data to validate guideline recognized risk factors for MRSA CAP specifically at our institution. Risk factors including history of MRSA isolated from a respiratory specimen, and positive post-admission MRSA nasal screen were validated as significant risk factors; receipt of IV antibiotics during hospitalization within the past 90 days was not shown to be a risk factor for MRSA CAP based on our institutional data. Validated risk factors may help providers discern which patients with CAP at our institution would benefit most from empiric MRSA treatment.

Andexanet alfa effectiveness and safety versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage while on apixaban or rivaroxaban: A single-center, retrospective, matched cohort analysis.

BACKGROUND: There is limited information directly comparing andexanet alfa (AA) versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage (ICH) on apixaban or rivaroxaban. OBJECTIVE: The objective of this study was to compare the effectiveness and safety of AA versus 4F-PCC in ICH on apixaban or rivaroxaban. METHODS: This retrospective, matched, cohort analysis was conducted at a single healthcare system. Patients were matched based on baseline ICH volume. The primary outcome was good or excellent ICH hemostasis, which was defined as a 35% or less increase in ICH volume within 24 h following AA or 4F-PCC administration. The secondary outcome was thrombotic events within 14 days following AA or 4F-PCC administration. RESULTS: In total, 26 AA and 26 4F-PCC patients were included in this matched cohort analysis. Both groups had comparable rates of good or excellent ICH hemostasis (AA: 92.3% vs. 4F-PCC: 88.5%, p = 1.000). Thrombotic events within 14-days were not significantly different (AA: 26.9% vs. 4F-PCC: 11.5%, p = 0.159). CONCLUSION AND RELEVANCE: This study found no significant differences in good or excellent ICH hemostasis within 24-h or new thrombotic events within 14-days in a cohort given AA or 4F-PCC for ICH while on apixaban or rivaroxaban. However, this single-center analysis is underpowered due to sample size constraints, therefore further high-quality research comparing AA safety and effectiveness versus 4F-PCC is needed.

Use of an argatroban systemic infusion and purge solution in a patient with a percutaneous ventricular assist device with suspected heparin-induced thrombocytopenia.

PURPOSE: Thrombocytopenia can occur when using an Impella percutaneous ventricular assist device (pVAD), and heparin-induced thrombocytopenia (HIT) is often suspected. Data on heparin- and anticoagulant-free purge solutions in these devices are limited. Previous case reports have described argatroban-based purge solutions, both with and without systemic argatroban, at varying concentrations in patients with known or suspected HIT. SUMMARY: A 33-year-old male was transferred to our institution and emergently initiated on life support with venoarterial extracorporeal membrane oxygenation (ECMO), an Impella pVAD, and continuous venovenous hemofiltration to receive an urgent aortic valve replacement. Over the next several days, the patient's platelet count declined with a nadir of 17 × 103/µL on hospital day 13. The patient's 4T score for probability of HIT was calculated as 4. All heparin products were discontinued on hospital day 15, and the patient was initiated on systemic infusion with argatroban 1,000 µg/mL at a rate of 0.2 µg/kg/min with a purge solution of argatroban 0.05 mg/mL. The systemic infusion remained at a rate of 0.2 µg/kg/min, and the total argatroban dose was, on average, less than 0.25 µg/kg/min. On hospital day 21, the patient was transferred to another institution. CONCLUSION: Systemic infusion and a purge solution with argatroban were used in a patient with an Impella pVAD with multisystem organ dysfunction and suspected HIT. The patient achieved therapeutic activated partial thromboplastin times without adjustment of the systemic argatroban infusion and did not experience bleeding or thrombosis. Further studies concerning the safety and effectiveness of argatroban-based purge solutions in patients with pVADs are needed.

Trust your gut: Effect of a pharmacist-driven pilot project to decrease alvimopan use past gastrointestinal recovery in postsurgical patients.

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Alvimopan is a peripherally acting opioid receptor antagonist indicated to accelerate gastrointestinal (GI) recovery following surgery, but its benefits past GI recovery are unknown and evidence suggests that it may increase risk for myocardial infarction. The purpose of this study was to evaluate the efficacy of a pilot alvimopan stewardship program aimed at intervening to discontinue alvimopan use following GI recovery. METHODS: This was a retrospective, observational study examining the first 5 months of the alvimopan stewardship pilot program. During this initial period, a pharmacy resident assessed whether each patient met criteria for GI recovery, defined as solid food toleration and first bowel movement or flatus. If a patient met the criteria for GI recovery, the resident intervened and recommended that the primary team discontinue alvimopan. Primary outcomes were the percentage of patients with alvimopan continued past GI recovery and the percentage of patients for whom alvimopan ordered past GI recovery was discontinued following intervention by stewardship. Secondary outcomes included the percentage of accepted recommendations to discontinue alvimopan following GI recovery and the number of alvimopan doses ordered following GI recovery. RESULTS: In total, 73 patients were included in the study analysis, all of whom underwent abdominal and/or urologic surgery. Alvimopan was ordered to be administered in 35.6% (26/73) of patients after GI recovery. The stewardship program intervened and recommended discontinuation on 50% (13/26) of the alvimopan doses ordered past GI recovery. Recommendations were accepted by the primary team for 92.3% (12/13) of the patients. A total of 51 doses of alvimopan were ordered for administration past GI recovery, with an average of 2 doses per patient. CONCLUSION: A pilot pharmacy-driven alvimopan stewardship program was able to identify and intervene on alvimopan orders continued past GI recovery. Interventions decreasing alvimopan use past GI recovery could be of benefit by minimizing potential risk and decreasing potential costs without a negative impact on patient outcomes.

Retrospective Assessment of Desmopressin Effectiveness and Safety in Patients With Antiplatelet-Associated Intracranial Hemorrhage.

OBJECTIVE: Current international guidelines offer a conditional recommendation to consider a single dose of IV desmopressin (DDAVP) for antiplatelet-associated intracranial hemorrhage based on low-quality evidence. We provide the first comparative assessment analyzing DDAVP effectiveness and safety in antiplatelet-associated intracranial hemorrhage. DESIGN: Retrospective chart review. SETTING: Single tertiary care academic medical center. PATIENTS: Adult patients taking at least one antiplatelet agent based on presenting history and documented evidence of intracranial hemorrhage on cerebral CT scan were included. Patients were excluded for the following reasons: repeat cerebral CT scan not performed within the first 24 hours, noncomparative repeat cerebral CT scan, chronic anticoagulation, administration of fibrinolytic medications, concurrent ischemic stroke, and neurosurgical intervention. In total, 124 patients were included, 55 received DDAVP and 69 did not. INTERVENTIONS: DDAVP treatment at recognition of antiplatelet-associated intracranial hemorrhage versus nontreatment. MEASUREMENTS AND MAIN RESULTS: Primary effectiveness outcome was intracranial hemorrhage expansion greater than or equal to 3 mL during the first 24 hospital hours. Primary safety outcomes were the largest absolute decrease from baseline serum sodium during the first 3 treatment days and new-onset thrombotic events during the first 7 days. DDAVP was associated with 88% decreased likelihood of intracranial hemorrhage expansion during the first 24 hours ([+] DDAVP, 10.9% vs [-] DDAVP, 36.2%; p = 0.002; odds ratio [95% CI], 0.22 [0.08-0.57]). Largest median absolute decrease from baseline serum sodium ([+] DDAVP, 0 mEq/L [0-5 mEq/L] vs [-] DDAVP, 0 mEq/L [0-2 mEq/L]; p = 0.089) and thrombotic events ([+] DDAVP, 7.3% vs [-] DDAVP, 1.4%; p = 0.170; odds ratio [95% CI], 5.33 [0.58-49.16]) were similar between groups. CONCLUSIONS: DDAVP was associated with a decreased likelihood of intracranial hemorrhage expansion during the first 24 hours. DDAVP administration did not significantly affect serum sodium and thrombotic events during the study period.

Pharmacist recommendations for prophylactic enoxaparin monitoring and dose adjustment in trauma patients admitted to a surgical intensive care unit.

BACKGROUND: There is limited information describing pharmacist participation in prophylactic enoxaparin monitoring in the surgical intensive care unit (SICU). OBJECTIVE: Our study sought to: 1) characterize pharmacist recommendations for enoxaparin monitoring in trauma patients admitted to the SICU, 2) describe the frequency that medical providers accept pharmacist recommendations for enoxaparin monitoring in trauma patients admitted to the SICU, and 3) illustrate the frequency that trauma patients admitted to our SICU service achieve anti-factor Xa trough concentrations (AFXa-TRs) of 0.11 - 0.20 IU/mL following pharmacist recommendation to adjust prophylactic enoxaparin dosing. METHODS: Adult patients who had an AFXa-TR drawn after at least three consecutive prophylactic enoxaparin doses between June 1, 2017 and March 1, 2018 were identified through chart review and included in this study. Patients were excluded based on the following criteria: 1) age less than 18 years, 2) anti-factor Xa (AFXa) level not representative of a trough concentration, 3) AFXa-TR not representative of steady state concentration, and 4) non-trauma based prophylactic enoxaparin dosing. This study was exempt from IRB review. RESULTS: The final analysis consisted of 42 patients. A pharmacist provided at least one recommendation in 97.6% (41/42) of trauma patients with enoxaparin monitoring during their SICU stay. In total, a pharmacist made 170 recommendations, mean of 4.2 (SD 1.8) recommendations per patient. Recommendations were: 1) obtain an AFXa-TR, n=90; 2) adjust enoxaparin dose based on AFXa-TR, n=58; and 3) maintain enoxaparin dose based on AFXa-TR, n=22. Medical providers accepted 89.4% (152/170) of pharmacist recommendations for enoxaparin monitoring. Dose adjustments were made in 33 patients following pharmacist recommendation; of these, 27 had a repeat AFXa-TR following at least one dose adjustment. Target AFXa-TRs were achieved in 19/27 patients, indicating 70.4% had recommended AFXa concentrations. CONCLUSIONS: Pharmacists provided recommendations for prophylactic enoxaparin monitoring and dose adjustment in trauma patients admitted to the SICU. Medical providers regularly accepted pharmacist recommendations and trauma patients commonly achieved target AFXa-TR following pharmacist recommendation for dose adjustment. Further research is required to identify the optimal enoxaparin dose for VTE prophylaxis in trauma patients.

Price-Performance Ratio Analysis Of Enteral Vitamin K Formulations.

BACKGROUND: Vitamin K compounded oral solution costs significantly less on a per-milligram basis compared with tablet formulations. Current literature has shown that international normalized ratio (INR) lowering in the reversal of vitamin K antagonists (VKAs) occurs to a similar degree when using vitamin K oral solution compared with tablet formulations. OBJECTIVE: To compare drug spending on vitamin K oral solution versus tablet using a price-performance ratio (PPR). METHODS: A retrospective chart review was conducted at a tertiary care academic medical center to compare INR reversal of VKA-induced coagulopathy on a price basis for vitamin K oral solution versus tablet. The price of the oral solution accounted for supplies and labor. A PPR was calculated based upon the following formula: vitamin K formulation cost divided by the hourly percent change in INR following vitamin K administration. RESULTS: The PPR for vitamin K tablets was 27.0 compared with 5.8 for the oral solution (P = 0.006). CONCLUSIONS: Utilization of vitamin K solution resulted in a significantly reduced cost per INR-lowering effect relative to commercially available tablets. Utilization of a compounded vitamin K solution represents an enticing means of cost-savings in the hospital setting.

Acute Hepatocellular Jaundice After Dofetilide Initiation: A Case Report.

Dofetilide's hepatotoxicity is not well described. In this case report, we describe acute hepatocellular jaundice related to dofetilide use in a 33-year-old male being treated for atrial fibrillation. Both viral and ischemic causes of hepatocellular damage were ruled out as unlikely in this case. This case report outlines a rare yet probable report of idiosyncratic dofetilide-induced liver injury.

Pharmacy impact on medication reconciliation in the medical intensive care unit.

OBJECTIVE: Pharmacy-driven medication history (MH) programs have been shown to reduce the number of serious or potentially life-threatening (S/PLT) medication discrepancies (MDs) in many settings, but not Intensive Care Units (ICUs). METHODS: MHs were repeated over a 6-week period. Demographics, number, and nature of MDs were documented. Discrepancy severity was graded using a previously published method. Primary outcome was the proportion of MHs containing >1 S/PLT MDs. FINDINGS: Sixty-three MHs were repeated. Pharmacy MHs were less likely to contain ≥1 S/PLT MDs (0% vs. 50%, P < 0.001). CONCLUSION: Pharmacy MHs contained fewer S/PLT MDs in this small sample. S/PLT MDs on admission and home medication lists were common in patients admitted to the medical ICU. Pharmacy-driven medication reconciliation (MR) reduced the number and frequency of these discrepancies. Further research is required to improve current MR procedures.