David Putney

Assessment of Drug-Induced Torsade de Pointes Risk for Hospitalized High-Risk Patients Receiving QT-Prolonging Agents

Background: Although risk factors for torsade de pointes (TdP) are known, identifying hospitalized patients at greatest risk for QTcP who should receive cardiac monitoring is poorly defined. Objectives: Describe the prevalence of risk for TdP in patients and associations between risk factors and QTc prolongation (QTcP) at a tertiary teaching hospital. Methods: This retrospective analysis assessed physiological and pharmacological risk factors for TdP of adult patients receiving ≥1 QTc-prolonging medications (QTcMed) during hospitalization. The QTcMeds were stratified by risk for causing TdP (probable, possible, and conditional). Baseline electrocardiograms (ECGs) were assessed for QTcP associated with risk for TdP. Results: During a 6-month period, 12 401 (51%) hospitalizations received ≥1 QTcMed. A baseline ECG was obtained for 2381 (19%) patients. A total of 386 (16%) patients with a baseline ECG were found to have QTcP. Significant associations for QTcP were found with the following physiological risk factors: female (P = .021), left-ventricular ejection fraction <40% (P < .0001), cardiac arrest (P < .0001), and cardioversion (P = .007). Significantly more patients with QTcP (n = 209, 54%) received probable-risk QTcMeds than those without QTcP (n = 542, 27%; P < .0001). Probable-risk QTcMeds administered alone or concomitantly with other QTcMeds were more frequently associated with QTcP. No documented cases of TdP were identified. Conclusions: Of the population receiving QTcMeds, only a small portion had a baseline ECG, identifying a large population at risk of QTcP without appropriate monitoring. Patients with cardiac disease receiving probable-risk QTcMeds were associated with the highest risk of QTcP and should be monitored closely.

Evaluation and Pharmacokinetics of Treatment Dose Enoxaparin in Hospitalized Patients With Morbid Obesity

Background: The pharmacokinetic properties of enoxaparin may lead to supratherapeutic antifactor Xa (anti-Xa) levels and increased bleeding when standard treatment doses are used in patients with morbid obesity. Objective: To evaluate the dose of enoxaparin needed to achieve therapeutic anti-Xa levels in a prospective, masked observational cohort of heterogeneous inpatients with morbid obesity and to determine whether patients with morbid obesity treated with 1 mg/kg of enoxaparin are at increased risk of supratherapeutic levels and bleeding events compared to patients receiving lower doses. Methods: Hospitalized patients with a body mass index ≥40 kg/m2 or actual body weight ≥140 kg and prescribed treatment doses of enoxaparin >60 mg per day were enrolled and consented to phlebotomy for determination of anti-Xa levels. Results: Forty-one patients were included for data analysis. The dose of enoxaparin that resulted in therapeutic and supratherapeutic anti-Xa levels at steady state was 0.83 mg/kg and 0.98 mg/kg (−0.11; 95% confidence interval [CI] −0.20 to −0.01, P = .02), respectively. Enoxaparin dose as mg/kg of actual body weight was an independent predictor of having a supratherapeutic anti-Xa level. Patients with doses <0.95 mg/kg versus ≥0.95 mg/kg were less likely to have supratherapeutic levels (odds ratio 0.21 [95% CI 0.05-0.84], P = .02) and had similar rates of subtherapeutic levels. Doses <0.95 mg/kg and ≥0.95 mg/kg resulted in similar bleeding rates of 17.9% and 22.2% (P = .71), respectively. Conclusion: Patients with morbid obesity required less than the recommended 1 mg/kg enoxaparin dose to achieve therapeutic peak anti-Xa levels; therefore, initiation with lower dosages is prudent and anti-Xa monitoring should guide dosage adjustments.

Alternative Monitoring of Argatroban Using Plasma-Diluted Thrombin Time

OBJECTIVE To report a case of heparin-induced thrombocytopenia (HIT) in a patient with concurrent liver dysfunction and a prolonged baseline activated partial thromboplastin time (aPTT) in whom argatroban therapy was monitored with aPTT and a novel plasma-diluted thrombin assay. CASE SUMMARY An 80-year-old man with HIT and liver dysfunction was treated with argatroban, which was initiated at a dose of 0.5 μg/kg/min and gradually decreased to 0.09 μg/kg/min. The patient had a mildly prolonged aPTT at baseline (37.5 seconds). He was concurrently monitored with aPTT, per institution protocol, and plasma-diluted thrombin time. Plasma-diluted thrombin times were consistently lower than aPTTs, but mirrored the trend of the aPTTs. Eleven hours after argatroban was stopped, the aPTT remained elevated (53.9 seconds), while the plasma-diluted thrombin time returned to normal range (26.4 seconds). The patients therapy was transitioned to warfarin and he had a hospital course with no thrombotic or bleeding complications. DISCUSSION Plasma-diluted thrombin time is a novel laboratory test consisting of 1 part patient plasma diluted with 3 parts normal plasma. Plasma-diluted thrombin time has been shown to blunt the sensitivity of the thrombin time and may be more accurate for drug monitoring. A MEDLINE search revealed 2 studies using the plasma-diluted thrombin time assay. The first study compared aPTT and plasma-diluted thrombin times in blood samples mixed with argatroban, bivalirudin, or lepirudin at 3 different concentrations. Blood samples contained lupus inhibitors, vitamin k deficiency, or normal baseline aPTTs. The aPTT overestimated drug concentrations in all samples with lupus anticoagulant and vitamin k deficiency, while the plasma-diluted thrombin time correctly estimated drug concentrations in nearly all samples. The second study looked at monitoring dabigatran with plasma-diluted thrombin time and found a linear relationship between the plasma-diluted thrombin time and the dabigatran dose-response curve. CONCLUSIONS Plasma-diluted thrombin time may be an alternative for direct thrombin inhibitor monitoring in patients with elevated aPTT values at baseline. Further randomized control trials are needed to determine its applicability in clinical practice.

Discharge medication complexity and 30-day heart failure readmissions.

Background: Limited research exists regarding Medication Regimen Complexity Index (MRCI) and its utility in identifying patients at risk for hospital readmission. Objective: This study evaluates the association between discharge MRCI and 30‐day rehospitalization in patients with heart failure (HF) after discharge. Methods: The study involved a retrospective, cohort study at a large tertiary teaching facility from the University HealthSystem Consortium. The consortium database was used to identify HF patients hospitalized from January 2011 to December 2013. A 30‐day readmission was defined as being readmitted to the same hospital within 30 days of discharge with a principal discharge diagnosis of HF. Index hospitalizations was defined as the first hospitalization, and readmission was the subsequent hospitalization for HF. A pilot analysis was conducted to compare manual MRCI collection tool and a computerized scoring MRCI system. Multivariable logistic regression was used to examine the association of computerized MRCI (≥15) and 30‐day rehospitalization after controlling for other variables. Results: A total of 1,452 patients were included in the study with 81 patients (5.9%) readmitted within 30 days of discharge. The manual and computerized MRCIs were correlated with an R of 0.74 and R2 of 0.55. The multivariate logistic regression analysis found computerized MRCI ≥15 (OR: 1.62; 95% CI: 1.01–2.59) was associated with 30‐day rehospitalization after controlling for other factors. Patients prescribed angiotensin‐converting‐enzyme inhibitors or angiotensin receptor blockers, were less likely (OR: 0.54; CI: 0.33–0.89) to be readmitted 30 days after discharge, and patients with coronary artery disease were more likely (OR: 1.76; CI: 1.03–3.00) to be readmitted 30 days after discharge. Conclusions: The computerized MRCI score was moderately correlated with manual MRCI score. A significant association was found between computerized MRCI and 30‐day HF readmission. Such predictive tools may allow pharmacists to prioritize patient care and optimize patient outcomes through medication therapy management. Highlights:Medication Regimen Complexity Index (MRCI) is a validated tool to measure complexity.The manual and computerized MRCIs were correlated in patients with heart failure.Computerized MRCI ≥15 was associated with 30‐day rehospitalization.MRCI can help pharmacists to prioritize patient care and optimize patient outcomes.

Cardioprotective medication use after renal transplantation

Dawson KL, Patel SJ, Putney D, Suki WN, Gaber AO. Cardioprotective medication use after renal transplantation. 
Clin Transplant 2010: 24: E253–E256.

Low molecular weight heparin dosing and monitoring in solid organ transplant recipients

Anti‐Xa monitoring for low molecular weight heparin (LMWH) is currently recommended in obese, renally impaired, and pregnant patients. Substantial evidence indicates that solid organ transplant (SOT) patients are at an increased risk of renal impairment, thus representing a population at risk of LMWH accumulation. The purpose of this study was to review our experience with LMWH dosing and monitoring in a cohort of transplant recipients. This was a retrospective, single‐center review of 96 SOT patients receiving enoxaparin treatment and anti‐Xa monitoring. The percent of patients with supratherapeutic anti‐Xas (>1 IU/mL) was determined, as was the relationship between enoxaparin dosages and anti‐Xa levels and bleeding. The cohort had a mean age of 62 yr and creatinine clearance of 59 mL/min and was primarily lung transplant recipients (73%). The mean enoxaparin dose was 0.82 mg/kg, which resulted in a mean anti‐Xa level of 0.98 IU/mL. Despite the reduced enoxaparin dose, 44% of patients experienced a supratherapeutic anti‐Xa level. Patients with supratherapeutic anti‐Xas had higher doses than those within the therapeutic range (0.89 mg/kg vs. 0.77 mg/kg; p = 0.002). No major bleeds occurred. Supratherapeutic anti‐Xa levels are common in transplant patients receiving enoxaparin therapy. Empirically reduced dosing of enoxaparin and monitoring may warrant consideration in this population.

Case report: Severe hypercalcemia mimicking ST-segment elevation myocardial infarction.

The identification of ST-segment elevation on the electrocardiogram is an integral part of decision making in patients who present with suspected ischemia. Unfortunately, ST-segment elevation is nonspecific and may be caused by noncardiac causes such as electrolyte abnormalities. We present a case of ST-segment elevation secondary to hypercalcemia in a patient with metastatic cancer.

IN-HOSPITAL USE OF POTENTIALLY HARMFUL DRUGS IN HEART FAILURE: IMPACT ON LENGTH OF STAY AND MORTALITY

To evaluate prevalence of in-hospital use of potentially harmful drugs (PHD) in heart failure (HF) patients and analyze their impact on length of stay and in-hospital mortality. The University HealthSystem Consortium Database was queried for admissions with the primary diagnosis of HF during 2011-

In-hospital use of non-steroidal anti-inflammatory drugs in patients with heart failure in academic centers in the United States

BACKGROUND Non-steroidal anti-inflammatory drugs are considered potentially harmful for patients with heart failure. OBJECTIVE To determine the prevalence of in-hospital NSAID use, their type, associated diagnosis and impact in clinical outcomes among patients with a diagnosis of heart failure. METHODS The University Health System Consortium Database was used to identify all first hospitalizations with an International Classification of Diseases-9 discharge diagnosis code of systolic heart failure as the primary diagnosis between January 1, 2011, and December 31st 2014. RESULTS Among 65,902 patients admitted for a primary diagnosis of SHF, 2675 (4.1%) were exposed to NSAID. The most frequent NSAID used was ibuprofen (51.63%), followed by ketorolac (29.38%) naproxen (8.07%) celecoxib (5.61%), and others. On multivariable analyses, the length of stay of patients exposed to NSAID was longer compared to non-exposed (OR: 4.67, p < 0.001, 95% CI 4.10-5.25), but differences in mortality were not statistically different (OR: 0.90, p = 0.476, 95% CI 0.69-1.19). CONCLUSION The use of NSAID in patients admitted with a primary diagnosis of systolic heart failure was low but was associated with longer length of stay. Further studies are needed to understand the impact of NSAID use in this patient population.

IN HOSPITAL USE OF NON-STEROIDAL ANTI-INFLAMMATORY AGENTS IN PATIENTS WITH A PRINCIPAL DIAGNOSIS OF HEART FAILURE IS ASSOCIATED WITH INCREASED LENGTH OF STAY AND 30-DAY READMISSION RATE

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are associated with increased risk of worsening heart failure. The objective of this study was to estimate the frequency and clinical consequences of in-hospital NSAIDs use among patients admitted with a principal diagnosis of heart failure.