Risk Factors and Outcomes Associated with Prolonged Subtherapeutic Anticoagulation with Bivalirudin: A Retrospective Cohort Study.

BACKGROUND: Bivalirudin, a direct thrombin inhibitor, is a treatment option for the management of heparin-induced thrombocytopenia (HIT) and other coagulation disorders. To date, no published studies have identified patients at risk for or the consequence of subtherapeutic bivalirudin therapy. OBJECTIVES: The primary objective was to identify factors associated with failure to achieve early therapeutic anticoagulation (ETA) with bivalirudin, defined as achievement of two consecutive therapeutic activated partial thromboplastin times (aPTTs) within 24 hours. Secondary objectives included evaluating whether failure to achieve ETA was a risk factor for clinical outcomes of interest including thromboembolism, hemorrhage, and mortality. PATIENTS/METHODS: This was a retrospective cohort study. Patients between the ages of 18 and 89 years treated with bivalirudin for 24 hours or longer were identified and classified as either achieving or failing to achieve ETA. RESULTS: Nonadherence to the dosing protocol (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.07-2.71) and creatinine clearance (CrCl) of 60 ml/min or greater (OR 2.99, 95% CI 1.12-7.97) were significantly associated with failure to achieve ETA in univariate analyses. Conversely, increasing age (OR 0.98, 95% CI 0.97-0.99) was significantly associated with achievement of ETA. Failure to achieve ETA was associated with a 4-fold increase in the odds of thromboembolism. CONCLUSIONS: Younger age, normal renal function, and nonadherence to the dosing protocol when targeting therapeutic anticoagulation is associated with increased risk of failure to achieve ETA. This confers an elevated risk of thromboembolism when using bivalirudin for the management of HIT or other coagulation disorders.

Predictors of dexmedetomidine-associated hypotension in critically ill patients.

BACKGROUND: Dexmedetomidine is commonly used for sedation in the Intensive Care Unit (ICU), and its use may be associated with hypotension. We sought to determine predictors of dexmedetomidine-associated hypotension. METHODS: Retrospective, single-center study of 283 ICU patients in four adults ICUs over a 12 month period. Univariate analyses were performed to determine factors associated with dexmedetomidine-related hypotension. Risk factors significant at the 0.20 level in the univariate analysis were considered for inclusion into a step-wise multiple logistical regression model. RESULTS: Hypotension occurred in 121 (42.8%) patients with a median mean arterial pressure (MAP) nadir of 54 mmHg. Univariate analyses showed an association between hypotension and age (P = 0.03), Acute Physiology and Chronic Health Evaluation II (APACHE II) score (P = 0.02), baseline MAP (<0.001), admission to the cardiothoracic ICU (P = 0.05), history of coronary artery disease (P = 0.02), and postcardiac surgery (P = 0.0009). Admission to the medical ICU was associated with a decrease in development in hypotension (P = 0.03). There was a trend for hypotension with weight (P = 0.09) and history of congestive heart failure (P = 0.12) Only MAP prior to initiation (odds ratio [OR] 0.97, 95% confidence interval [95% CI] 0.95-0.99; P < 0.0001), APACHE II scores (OR 1.06, 95% CI 1.01-1.12; P = 0.017), and history of coronary artery disease (OR 0.48, 95% CI 0.26-0.90, P = 0.022) were independently associated with hypotension by multivariable analysis. CONCLUSIONS: Dexmedetomidine-associated hypotension is common. Preexisting low blood pressure, history of coronary artery disease, and higher acuity were identified as independent risk factors for dexmedetomidine-associated hypotension.

Statin desensitization in a patient with probable familial hypercholesterolemia.

PROBLEM OVERVIEW: With cardiovascular disease being the leading cause of morbidity and mortality in the United States, cholesterol-lowering medications have become a prominent focus of medical management and cardiovascular risk reduction, including the use of statins making them the most widely prescribed class of medications in the United States and are the cornerstone of management of hyperlipidemia. This case report describes a 29-year-old female with probable familial hypercholesterolemia (FH) who had allergic reactions to statin therapy on two separate occasions. She required statin therapy based on her elevated carotid intima media thickness test, historic LDL-C ≥ 190 mg/dL, elevated Lp(a), and family history significant for premature coronary heart disease. In this report, we document a case of successful oral desensitization to rosuvastatin and propose a replicable statin desensitization protocol. MAJOR MANAGEMENT: The patient was admitted for rosuvastatin desensitization following predetermined protocols, utilizing an interdisciplinary team, and monitored for 24 hours following completion of administration prior to discharge. She successfully completed desensitization to rosuvastatin 10mg by mouth daily without anaphylactic reaction. She continued to tolerate rosuvastatin 10mg daily through most recent follow-up, and with this addition, significant improvement in lipid levels was achieved. CONCLUSION: This case report presented a patient with probable FH who was previously intolerant to other statin therapies that underwent successful desensitization to rosuvastatin with subsequent achievement of therapy goals.

Development and implementation of a nurse-driven, sliding-scale nomogram for bivalirudin in the management of heparin-induced thrombocytopenia.

PURPOSE: A simplified dosing nomogram to assist nurses in adjusting the rate of i.v. bivalirudin administration in cases of heparin-induced thrombocytopenia (HIT) is described. SUMMARY: To facilitate the availability of bivalirudin [corrected] as an alternative direct thrombin inhibitor (DTI) for patients with HIT at The Ohio State University Wexner Medical Center (OSUWMC), a team of clinical pharmacists developed a nomogram designed to simplify infusion dosage adjustments by nurses. In contrast to bivalirudin nomograms requiring patient-specific, percentage-based dose adjustments, the nomogram developed at OSUWMC specifies fixed adjustments (0.005 or 0.01 mg/kg/hr) according to the current activated partial thromboplastin time (aPTT) value relative to aPTT goals. During pilot testing over three years, the nomogram was used to guide dosage adjustments in 65 adult patients receiving continuous infusions of bivalirudin for suspected or confirmed HIT in intensive care units. Overall, the use of the nomogram resulted in adequate anticoagulation, with 53.7% of all measured aPTT values in the target range; 30.5% of aPTT values were below target, and 15.8% of values were above target. The median time to steady state was 11.0 hours (range, 5.0-31.8 hours), and bleeding rates were consistent with those reported in the literature. Nurse adherence to the nomogram was 100%, and no dosing errors occurred during a total of 487 dosage changes. Based on the pilot study results, the nomogram was refined to improve initial dosing for patients with creatinine clearance values of >30 mL/min; other refinements were made to enhance the safety of bivalirudin therapy for HIT in patients with severe renal impairment. CONCLUSION: A nurse-driven, sliding-scale nomogram for bivalirudin therapy in patients with HIT provided a simple dosing protocol and resulted in a high rate of adherence by nurses.

Bleeding outcomes associated with coronary artery bypass graft surgery and recent clopidogrel exposure.

BACKGROUND: Guidelines recommend discontinuing clopidogrel for at least 5 days before elective coronary artery bypass graft surgery (CABG) to limit blood transfusions and for at least 24 hours before urgent CABG to reduce major bleeding complications. Studies have produced conflicting results regarding whether recent exposure to clopidogrel increases bleeding, the need for intraoperative and postoperative blood products, postoperative complications, and hospital length of stay. We evaluated the effect of clopidogrel exposure on major bleeding at our institution within 5 days of CABG. METHODS: We conducted a retrospective review of patients who underwent CABG at a tertiary academic medical center. The primary outcome was major bleeding, defined as transfusion of 4 units of packed red blood cells (PRBCs) and/or a need for reexploration. Secondary outcomes included non-life-threatening bleeding, defined as transfusion of 2 units but <4 units of PRBCs; postoperative complications; hospital length of stay; readmission within 30 days of the procedure; and hospital mortality. Major bleeding events were analyzed with a logistic regression model that adjusted for covariates of bleeding risk factors. RESULTS: Of the 715 patients we reviewed, 169 patients received clopidogrel within 5 days before CABG, and 546 patients did not. A significantly higher incidence of major bleeding was observed in the clopidogrel group compared with the group not exposed to clopidogrel (32% versus 17%, P = .002). After adjusting for covariates, patients exposed to clopidogrel had significantly higher odds of major bleeding (odds ratio, 2.1; 95% confidence interval, 1.3-3.4; P = .003). The groups were similar with respect to postoperative complications, except for infection. The clopidogrel-exposed group had a significantly higher rate of leg site infections (3% versus 0.2%, P = .003). CONCLUSIONS: Clopidogrel exposure within 5 days of CABG is associated with an increased risk of major bleeding.

Stability of diluted adenosine solutions in polyolefin infusion bags.

BACKGROUND: Intravenous or intracoronary adenosine is used in the cardiac catherization lab to achieve maximal coronary blood flow and determine fractional flow reserve. OBJECTIVE: To determine the stability of adenosine 10 and 50 µg/mL in either 0.9% sodium chloride injection or 5% dextrose injection in polyolefin infusion bags stored at 2 temperatures, refrigeration (2°C-8°C) or controlled room temperature (20°C-25°C). METHODS: Adenosine 10 µg/mL and 50 µg/mL solutions were prepared in 50 mL polyolefin infusion bags containing 0.9% sodium chloride injection or 5% dextrose injection and stored at controlled room temperature or under refrigeration. Each combination of concentration, diluent, and storage was prepared in triplicate. Samples were assayed using stability-indicating, reversed-phase high-performance liquid chromatography immediately at time 0 and at 24 hours, 48 hours, 7 days, and 14 days. Stability was defined as retaining 90% to 110% of the initial adenosine concentration. The samples were also visually inspected against a light background for clarity, color, and the presence of particulate matter. RESULTS: After 14 days, all samples retained 99% to 101% of the initial adenosine concentration. No considerable change in pH or visual appearance was noted. The stability data indicated no significant loss of drug due to chemical degradation or physical interactions during storage. CONCLUSION: Adenosine solutions of 10 and 50 µg/mL were stable for at least 14 days in 50 mL polyolefin infusion bags of 0.9% sodium chloride injection or 5% dextrose injection stored at controlled room temperature and refrigerated conditions.

Drug-induced exanthem following dabigatran.

OBJECTIVE: To report an incident of a drug-induced exanthem during treatment with dabigatran in a patient without prior exposure to the drug. CASE SUMMARY: A 20-year-old white male was prescribed oral dabigatran 150 mg twice daily for thromboembolic prevention because of nonvalvular atrial fibrillation. After 2 weeks of dabigatran therapy, a raised, pruritic, erythematous rash developed on the patient's inner thigh and forearm. Upon discontinuation of dabigatran and initiation of oral corticosteroid treatment, the rash resolved. Dabigatran therapy was not readministered and thromboembolic prevention therapy with warfarin was instituted. DISCUSSION: The clinical evidence for efficacy of dabigatran was derived largely from the RE-LY trial, which provided an open-label comparison with warfarin for the reduction of stroke and systemic embolism in nonvalvular atrial fibrillation. The most frequent adverse reactions leading to discontinuation of dabigatran were bleeding and gastrointestinal events. In the RE-LY study, drug hyper-sensitivity, allergic edema, anaphylactic reaction, and anaphylactic shock were reported in <0.1% of patients receiving dabigatran. Despite the low incidence of hypersensitivity reported in the RE-LY trial, the use of the Naranjo probability scale indicated a probable relationship between the rash and dabigatran therapy in this patient. CONCLUSIONS: Upon initiation of dabigatran therapy, surveillance for hyper-sensitivity reactions should be included as part of routine drug monitoring.

Nesiritide compared with milrinone for cardiac surgery.

Management of patients with low cardiac output syndromes is difficult. Current therapies (ie, inotropes) have associated adverse effects and have not been shown to impact clinical outcomes such as decreased mortality or length of stay. Patients unable to recover from low cardiac output states have end organ damage, increased lengths of stay, increased hospital costs, and readmissions. Nesiritide has been suggested as an alternative or adjunct medication to treat cardiac surgery patients. Recent trials have provided information on the effects of some of these agents on clinical outcomes including respiratory failure, length of stay, and mortality.