Prescription of fondaparinux in hospitalised patients.

Fondaparinux is an antithrombotic agent with unique properties that may offer benefit to patients beyond the current approved indications. To explore the off-label use versus approved use of fondaparinux, we initiated a single-center registry of fondaparinux use. During the 25-month study period, 219 patients were prescribed fondaparinux: 157 (71.7%) for prophylaxis and 62 (28.3%) patients for the treatment of thrombosis. When fondaparinux was used for prophylaxis in our registry, 94% of patients had documentation of heparin-induced thrombocytopenia (HIT). Fondaparinux warrants further evaluation in patients with HIT or suspected HIT. In the meantime, its off-label use may exceed its use for FDA-approved indications.

Heparin-induced thrombocytopenia (HIT): clinical and economic outcomes.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction that occurs following exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). HIT with thrombosis (HITT) can cause devastating venous thromboembolism or arterial clots, prolonged hospitalization, and increased costs. To explore the economic and clinical implications of HIT and HITT, we initiated a single-center patient registry. In this report, we describe patient characteristics, comorbidities, management strategies, clinical outcomes, and costs. We enrolled 349 hospitalized patients with an enzyme immunoassay-confirmed diagnosis of HIT over a 40-month period. Patients were assessed for the primary outcome of 30-day mortality, as well as baseline characteristics, development of thrombosis, and the economic impact of HIT. The primary outcome measure was 30-day mortality and occurred in 58 (16.6%) patients, 40 (15.3%) in the HIT group versus 18 (20.7%) in the HITT group (p = 0.25). The frequency of HIT was greater in patients exposed to UFH than in patients exposed to LMWH (0.8% vs. 0.2%, respectively, p < 0.001). Both HIT and HITT patients who were exposed to UFH had higher hospital costs than those exposed to LMWH ($113,100 vs. $56,352, respectively, p < 0.001). HIT remains an important clinical problem with a high mortality rate and significant cost, regardless of development of thrombosis. Prospective controlled trials need to be conducted to determine the optimal strategy to reduce the frequency of HIT.

Journal Club Standardization Tool: Helping participants get the JIST.

BACKGROUND AND PURPOSE: Clinical pharmacy practice relies on the ability to critically evaluate clinical trials and apply their findings to patient care. The development of these skills begins in pharmacy school, develops during residency programs, and continues to mature while practicing clinical pharmacy. The purpose of this analysis was to evaluate student attitudes and perceptions following implementation of the Journal Interpretation Summary Tool (JIST) into a pharmacy curriculum. EDUCATIONAL ACTIVITY AND SETTING: The "journal club" is an activity implemented in many curricula with the intent to hone these skills. The JIST is a standardized template aimed at improving the consistency of a journal review by organizing major elements of a trial, allowing the facilitator and participants to navigate through key information and guide the journal club discussion. FINDINGS: Implementation of JIST resulted in an increased level of confidence for a majority of students (63.3%) when conducting and critically evaluating a journal article. More than 80% of students reported they were better able to critically evaluate a published article using JIST, and 91.9% reported JIST provided structure to the journal club process. DISCUSSION AND SUMMARY: JIST provides the appropriate level of guidance and structure, particularly for the novice pharmacy student or pharmacist. The use of a standardized tool for journal club evaluation may lead to further improvements in applying literature to practice and other skills surrounding the critique of medical literature.

Adverse drug events in hospitalized cardiac patients.

Little information is available concerning adverse drug events (ADEs) in cardiac patients. Therefore, the investigators report the results of cardiac patients in an ADE surveillance program, with the intent of reducing the frequency of future events. All reported adverse drug reactions and medication errors in cardiac patients over a 5-year period at Brigham and Women's Hospital were reviewed. There were 547 ADEs in cardiac patients, a rate of 1.9 events for every 100 patient admissions. Preventable ADEs most often occurred during medication administration (34.2%), with wrong rate or frequency of medication administration the most widespread event. Cardiovascular agents (29.8%), anticoagulants (28.5%), and antimicrobial agents (10.8%) were the most common drug classes associated with ADEs. Injury or prolonged hospitalization occurred in 5.3% of patients. ADEs occurred most frequently on the admission day, on weekdays, and in the early morning hours. Peak frequencies of ADEs coincided with nursing shift changes. In conclusion, ADEs occur often in hospitalized cardiac patients and affect 2 of every 100 patient admissions. Given the high percentage of ADEs associated with drug administration, more resources should be directed at this step of medication use. Focusing interventions around nursing shift changes may further enhance preventive strategies.

Sedation and analgesia in the intensive care unit: evaluating the role of dexmedetomidine.

PURPOSE: A review highlighting the application of sedatives and analgesics in the intensive care unit (ICU) setting, with a focus on the use of dexmedetomidine, is presented. SUMMARY: Relevant and applicable clinical trials that resulted from a search of the literature from 1966 to July 2006 using key search terms such as dexmedetomidine, intensive care unit, sedation, delirium, and analgesia were evaluated. Many agents have been evaluated in the search of the optimal regimen for sedation and analgesia in the ICU, including opioids, benzodiazepines, propofol, and antipsychotic agents. Dexmedetomidine has demonstrated efficacy as a sedative analgesic on the basis of its ability to lower opioid, benzodiazepine, and propofol requirements in clinical trials. The role of dexmedetomidine in ICU clinical practice is limited because of a lack of mortality and other morbidity endpoints, such as ICU length of stay, hospital length of stay, time to extubation, long-term complications after discharge from the ICU, and delirium. The most commonly reported adverse effects of dexmedetomidine are secondary to its effects as an alpha(2)-receptor agonist and are cardiac in nature. A detailed cost analysis may be warranted to justify the relatively high acquisition cost of dexmedetomidine. CONCLUSION: Dexmedetomidine may be an effective agent for ICU sedation and analgesia. However, the lack of clinically relevant endpoints in trials, the concern about adverse cardiovascular effects, and the relatively high acquisition cost of this drug limit its use to a select number of patients who may benefit from its distinguished mechanism of action.

Azacitidine-induced interstitial and alveolar fibrosis in a patient with myelodysplastic syndrome.

A 71-year-old Caucasian man diagnosed with myelodysplastic syndrome developed interstitial and alveolar fibrosis after receiving a 7-day course of azacitidine therapy. The patient's pulmonary function began to deteriorate immediately after the administration of his chemotherapy regimen. Other potential causes of pulmonary toxicity were ruled out such as viral, fungal, and bacterial pathogens, as well as other concomitant drugs. To our knowledge, this is the first case report documenting biopsy-proven interstitial and alveolar fibrosis associated with azacitidine. The frequency of this adverse drug reaction is unknown but may become more evident with increasing exposure of the population to azacitidine.

Interaction between nesiritide and a heparin-coated pulmonary artery line during an infusion for decompensated heart failure.

STUDY OBJECTIVE: Because it is known that intravenous nesiritide is not compatible with unfractionated heparin, we sought to determine the effect that heparin coating on a pulmonary artery catheter may have on the efficacy of a nesiritide infusion. METHODS: The efficacy of a nesiritide infusion given through a heparin-coated pulmonary artery line was compared with that of a nesiritide infusion administered in the same patient through a heparin-free peripheral line. RESULTS: The rate of infusion was titrated to maintain consistent hemodynamic parameters. When nesiritide was administered through a heparin-coated line, the infusion rate escalated from 0.01 microg/kg/minute to 0.07 microg/kg/minute. After the route of administration was switched to a heparin-free line, the same hemodynamic parameters were maintained. The heparin-free line made it possible to reduce the infusion rate by 57.1% over the next 24 hours to 0.03 microg/kg/minute. CONCLUSION: The interaction of nesiritide with heparin-coated pulmonary artery lines has the potential to be clinically significant. Clinicians should be educated about this potential interaction. Nesiritide should be infused only through heparin-free lines.

Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction.

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and beta-blockers, or the newer agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. Beta-blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine-induced nephrotoxicity. When compared with beta-blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long-term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to beta-blockers, diuretics, and ACE inhibitors.

Efficacy and safety of low-dose valganciclovir for prevention of cytomegalovirus disease in renal transplant recipients: a single-center, retrospective analysis.

STUDY OBJECTIVE: To evaluate the safety and efficacy of valganciclovir 450 mg/day for 6 months for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. DESIGN: Single-center, retrospective analysis. SETTING: Urban, academic medical center. PATIENTS: Fifty-eight patients who received de novo renal transplants from August 1, 2001-November 21, 2002. INTERVENTION: Valganciclovir 450 mg/day was administered to all renal transplant recipients at risk for CMV disease. Therapy was begun postoperatively and was dose adjusted to renal function. MEASUREMENTS AND MAIN RESULTS: Data collected from renal transplant recipients were demographics, immunosuppressive and antiviral drug therapy, and occurrence of CMV disease, acute rejection, allograft loss, and hematologic adverse events. Donor (D)/recipient (R) CMV serostatus was 37.9% D+/R+, 29.3% D-/R+, 17.3% D+/R-, and 15.5% D-/R-. Antithymocyte globulin (ATG) was administered to 62.1% of patients. Most of the transplant recipients received triple immunosuppression as maintenance therapy. Median follow-up was 20 months. The frequency of CMV disease was 1.7% within 6 months after transplantation and 5.2% at any point after transplantation. All patients who developed CMV disease were D+/R- and had received ATG. Leukopenia and thrombocytopenia associated with valganciclovir were seen in 28% and 24% of patients, respectively. One patient developed acute cellular rejection. No graft losses or deaths occurred. Early discontinuation of valganciclovir occurred in 20% of patients secondary to severe, persistent leukopenia, thrombocytopenia, and/or diarrhea. None of these patients developed CMV disease. CONCLUSION: A high rate of CMV disease was noted among the D+/R- population. Administration of ATG as an induction agent also increased the frequency of CMV disease. Despite the low dosage of valganciclovir, hematologic adverse events were common. However, valganciclovir, administered at 450 mg/day for 6 months, was effective and relatively safe for prophylaxis of CMV disease in renal transplant recipients.

Treating gout in kidney transplant recipients.

OBJECTIVE: To review the etiology, treatment, and preventive strategies of hyperuricemia and gout in kidney transplant recipients. DATA SOURCES: Primary literature was obtained via Medline (1966-June 2003). STUDY SELECTION AND DATA EXTRACTION: Studies evaluating treatment and prevention of hyperuricemia and gout in kidney transplantation were considered for evaluation. English-language studies were selected for inclusion. DATA SYNTHESIS: Approximately 14,000 kidney transplantations were performed in the United States in 2003, and of those transplant recipients, nearly 13% will experience a new onset of gout. The prevalence of hyperuricemia is even greater. There are several mechanisms by which hyperuricemia and gout develop in kidney transplant recipients. Medication-induced hyperuricemia and renal dysfunction are 2 of the more common mechanisms. Prophylactic and treatment options include allopurinol, colchicine, corticosteroids, and, if absolutely necessary, nonsteroidal antiinflammatory drugs. CONCLUSION: It is generally recommended to decide whether the risks of prophylactic therapy and treatment outweigh the benefits. Often, the risk of adverse events associated with agents to treat these ailments tends to outweigh the benefits; therefore, treatment is usually reserved for symptomatic episodes of acute gout. Practitioners must also decide if changes in immunosuppressive regimens may be of benefit on a patient-by-patient basis.

Thrombosis in suspected heparin-induced thrombocytopenia occurs more often with high antibody levels.

OBJECTIVE: The study objective was to determine whether higher antiplatelet factor 4 (PF4)/heparin antibody levels using an enzyme-linked immunosorbent assay are associated with more frequent thrombotic events in patients with clinically suspected heparin-induced thrombocytopenia. Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction. An enzyme-linked immunosorbent assay detects anti-PF4/heparin antibodies to support a suspected clinical diagnosis of heparin-induced thrombocytopenia. The utility of quantitative enzyme-linked immunosorbent assay results is uncertain. METHODS: Our single-centered study evaluated quantitative anti-PF4/heparin antibody levels using an enzyme-linked immunosorbent assay in consecutive hospitalized patients with a clinical suspicion of heparin-induced thrombocytopenia and positive anti-PF4/heparin antibody levels between July 2003 and December 2006. RESULTS: Overall, anti-PF4/heparin antibody values were available for 318 patients with clinically suspected heparin-induced thrombocytopenia. The median level was 0.85 optical density units (range 0.31-4.0). The overall rate of arterial or venous thrombosis was 23.3%. A 1-unit increase in anti-PF4/heparin antibody level was associated with an approximate doubling in the odds of thrombosis by 30 days (odds ratio, 1.9; 95% confidence interval, 1.5-2.6; P=.0001). The proportion of patients with pulmonary embolism increased with higher anti-PF4/heparin antibody levels. CONCLUSION: Higher levels of anti-PF4/heparin antibody are associated with increased thrombosis risk among patients with clinically suspected heparin-induced thrombocytopenia and might have clinical utility for prediction of true heparin-induced thrombocytopenia and the development of thrombosis.

Everolimus: a proliferation signal inhibitor with clinical applications in organ transplantation, oncology, and cardiology.

Everolimus, a proliferation signal inhibitor in the mammalian target of rapamycin (mTOR) drug class, has many clinical applications, including in organ transplantation, oncology, and cardiology. It currently has United States Food and Drug Administration (FDA) approval for prophylaxis against rejection in de novo renal transplant recipients, treatment of renal cell carcinoma, and use as a drug-eluting stent. To review the pharmacology, pharmacokinetics, efficacy, and safety of everolimus, we performed a search of the MEDLINE database (January 1997-April 2010) for all English-language articles of in vitro and in vivo studies that evaluated everolimus, as well as abstracts from recent scientific meetings and the manufacturer. In transplantation, everolimus demonstrates immunosuppressive properties and has been used to prevent acute rejection in cardiac, liver, lung, and renal transplant recipients. It appears that this agent may be potent enough to allow for the minimization or removal of calcineurin inhibitors in the long-term management of renal transplant recipients. In oncology, everolimus has been proven effective for the management of treatment-resistant renal cell carcinoma. In cardiology, everolimus is available as a drug-coated stent and is used in percutaneous coronary interventions for prevention of restenosis. In transplant recipients and patients with renal cell carcinoma, everolimus appears to have an extensive adverse-event profile. The pharmacologic properties of everolimus differentiate this agent from other drugs used in these clinical areas, and its pharmacokinetic properties differentiate it from sirolimus.

Dronedarone: a review of characteristics and clinical data.

Atrial fibrillation (AF) is a common arrhythmia associated with increased cardiovascular mortality, stroke, and hospitalization in the United States. Amiodarone is generally considered as the agent with the best efficacy for maintaining normal sinus rhythm. Despite its efficacy, amiodarone use is often limited by its extensive side effect profile. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been recently approved by the Food and Drug Administration to reduce cardiovascular hospitalization in patients with AF or atrial flutter. Structural modification of dronedarone was introduced to shorten the half-life, decrease lipophilicity, and minimize noncardiovascular toxicity as compared to amiodarone. This article reviews the pharmacology, adverse effects, and clinical evidence available to date of the use of dronedarone in the management of AF.

Evaluation of dexmedetomidine versus propofol-based sedation therapy in mechanically ventilated cardiac surgery patients at a tertiary academic medical center.

Management of pain and sedation therapy is a vital component of optimizing patient outcomes; however, the ideal pharmacotherapy regimen has not been identified in the postoperative cardiac surgery population. We sought to evaluate efficacy and safety outcomes between postoperative mechanically ventilated cardiac surgery patients receiving dexmedetomidine versus propofol therapy upon arrival to the intensive care unit (ICU). We conducted a single center, descriptive study of clinical practice at a 20-bed cardiac surgery ICU in a tertiary academic medical center. Adult mechanically ventilated postcardiac surgery patients who received either dexmedetomidine or propofol for sedation therapy upon admission to the ICU between October 20, 2006 and December 15, 2006 were evaluated. A pharmacy database was used to identify patients receiving dexmedetomidine or propofol therapy for perioperative sedation during cardiac surgery. Patients were matched according to surgical procedure type. Fifty-six patients who received either dexmedetomidine (n = 28) or propofol (n = 28) were included in the analysis. No differences in the ICU length of stay (58.67 ± 32.61 vs. 61 ± 33.1 hours; P = 0.79) and duration of mechanical ventilation (16.21 ± 6.05 vs. 13.97 ± 4.62 hours; P = 0.13) were seen between the propofol and dexmedetomidine groups, respectively. Hypotension (17 [61%] vs. 9 [32%]; P = 0.04), morphine use (11 [39.3%] vs. 1 [3.6%]; P = 0.002), and nonsteroidal anti-inflammatory use (7 [25%] vs. 1 [3.6%]; P = 0.05) occurred more during dexmedetomidine therapy versus propofol. Dexmedetomidine therapy resulted in a higher incidence of hypotension and analgesic consumption compared with propofol-based sedation therapy. Further evaluation is needed to assess differences in clinical outcomes of propofol and dexmedetomidine-based therapy in mechanically ventilated cardiac surgery patients.

Implementation of a Hospital-wide Protocol for Induced Hypothermia Following Successfully Resuscitated Cardiac Arrest.

Permanent neurologic impairment following cardiac arrest is often severely debilitating, even after successful resuscitation. Therapeutic hypothermia decreases anoxic brain injury and subsequent cognitive deficits. Current practice guidelines recommend therapeutic hypothermia in comatose survivors of cardiac arrest. To address the multifacets of therapeutic hypothermia, we assembled a multidisciplinary task force including members from various specialties to create an evidence-based guideline with transparency across disciplines and consistency of care. We describe our institutional guidelines for the initiation and management of induced hypothermia in patients successfully resuscitated from a cardiac arrest.

Once daily enoxaparin for outpatient treatment of acute venous thromboembolism: a case-control study.

We studied the efficacy and safety of an investigational enoxaparin regimen, 1.5 mg/kg once daily, as a bridge to warfarin for the outpatient treatment of acute venous thromboembolism. We undertook a case-control design. We enrolled 40 acute venous thromboembolism cases prospectively and matched them by age, gender, and location of venous thromboembolism to 80 previously treated controls. All controls had received enoxaparin 1 mg/kg twice daily. The primary end point was recurrent venous thromboembolism. We followed the cases for 30 days. We discontinued enoxaparin after we achieved the target international normalized ratio between 2.0 and 3.0. One case (2.9%) and three controls (3.8%) had recurrent venous thromboembolic events (P = 1.00). There were no major bleeding complications in the case group, compared to 3 (3.8%) in the control group (P = .55). Once daily enoxaparin, 1.5 mg/kg, as a bridge to warfarin was as effective with a similar safety profile as twice daily enoxaparin, 1mg/kg, for initial treatment of acute venous thromboembolism in the outpatient setting. This case-control study provides the rationale for undertaking a randomized controlled trial comparing enoxaparin 1.5 mg/kg once daily versus enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin in outpatients with acute venous thromboembolism.