Christopher K. Finch

Fondaparinux for the treatment of patients with acute heparininduced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. We prospectively treated seven subjects with acute HIT with fondaparinux and compared the results to a similar historical control population from the same hospital. Six of the seven fondaparinux-treated subjects were transitioned to warfarin, beginning after platelet count recovery occurred. Ten historical controls were treated with a direct thrombin inhibitor (DTI), eight of which were transitioned to warfarin. The primary study outcome was platelet count recovery which was defined as an increase from baseline by at least 30% of nadir to greater than 100,000/mm(3) by day seven. Seven subjects were prospectively treated with fondaparinux for a median of eight days. Six of the seven had HIT with thrombosis at the time of enrollment. All fondaparinux treated subjects had a complete platelet count recovery, and none experienced a new thromboembolic complication, major bleeding or death by week four. One subject underwent limb amputation. Ten historical controls were treated with a DTI for a median duration of eleven days. Platelet count recovery occurred in eight of the ten historical controls. No new thromboembolic complications or major bleeds occurred but limb gangrene occurred in four controls. The development of limb gangrene in the historical controls may have been a result of delayed recognition of HIT and/or inappropriately early institution of warfarin in the historical controls. This pilot study suggests that fondaparinux may be useful in patients with acute HIT.

Update on rifampin and rifabutin drug interactions.

Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes as well as the P-glycoprotein transport system. Several examples of well-documented clinically significant interactions include warfarin, oral contraceptives, cyclosporine, itraconazole, digoxin, verapamil, nifedipine, simvastatin, midazolam, and human immunodeficiency virus–related protease inhibitors. Rifabutin reduces serum concentrations of antiretroviral agents, but less so than rifampin. Examples of clinically relevant interactions demonstrated by recent reports include everolimus, atorvastatin, rosiglitazone/pioglitazone, celecoxib, clarithromycin, caspofungin, and lorazepam. To avoid a decreased therapeutic response, therapeutic failure, or toxic reactions when rifampin is added to or discontinued from medication regimens, clinicians need to be cognizant of these interactions. Studies and cases of rifampin drug interactions continue to increase rapidly. This review is a timely reminder to clinicians to be vigilant.

The clinical and economic burden of chronic obstructive pulmonary disease in the USA

Chronic obstructive pulmonary disease (COPD) is the third most common cause of death in the USA. In 2010, the cost of COPD in the USA was projected to be approximately US

Update on rifampin, rifabutin, and rifapentine drug interactions.

50 billion, which includes

Early vs Delayed Enteral Nutrition in Critically Ill Medical Patients

20 billion in indirect costs and

Anticonvulsant hypersensitivity syndrome: treatment with corticosteroids and intravenous immunoglobulin.

30 billion in direct health care expenditures. These costs can be expected to continue to rise with this progressive disease. Costs increase with increasing severity of disease, and hospital stays account for the majority of these costs. Patients are diagnosed with COPD following a multifactorial assessment that includes spirometry, clinical presentation, symptomatology, and risk factors. Smoking cessation interventions are the most influential factor in COPD management. The primary goal of chronic COPD management is stabilization of chronic disease and prevention of acute exacerbations. Bronchodilators are the mainstay of COPD therapy. Patients with few symptoms and low exacerbation risk should be treated with a short-acting bronchodilator as needed for breathlessness. Progression of symptoms, as well as possible decline in forced expiratory volume in the first second of expiration (FEV1), warrant the use of long-acting bronchodilators. For patients with frequent exacerbations with or without consistent symptoms, inhaled corticosteroids should be considered in addition to a long-acting beta2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) and may even consist of “triple therapy” with all three agents with more severe disease. Phosphodiesterase-4 inhibitors may be an option in patients with frequent exacerbations and symptoms of chronic bronchitis. In addition to a variety of novel ultra-LABAs, LAMAs and combination bronchodilator and inhaled corticosteroid (ICS) therapies, other bronchodilators with a variety of mechanisms are also being considered, to expand therapeutic options for the treatment of COPD. With more than 50 new medications in the pipeline for the treatment of COPD, optimal management will continue to evolve and grow more complex as benefits of therapy are balanced with the limitations and needs of each patient.

Intracerebral hemorrhage secondary to a warfarin-metronidazole interaction

Abstract Background: Rifampin is a potent inducer of both cytochrome P-450 oxidative enzymes and the P-glycoprotein transport system. Among numerous well documented, clinically significant interactions, examples include warfarin, oral contraceptives, itraconazole, digoxin, verapamil, simvastatin, and human immunodeficiency virus-related protease inhibitors. Rifabutin reduces serum concentrations of antiretroviral agents, but less so than rifampin. Rifapentine is also an inducer of drug metabolism. Methods: A literature search of English language journals from 2008 to March 2012 was completed using several databases, including PubMed, EMBASE, and SCOPUS. Search terms included rifampin, rifabutin, rifapentine AND drug interactions. Findings: Examples of clinically relevant interactions with rifampin demonstrated by recent reports include posaconazole, voriconazole, oxycodone, risperidone, mirodenafil, and ebastine. Conclusions: To avoid a reduced therapeutic response, therapeutic failure, or toxic reactions when rifampin, rifabutin, or rifapentine are added to or discontinued from medication regimens, clinicians need to be aware of these interactions. Recent studies have indicated that other transporter systems play a role in these drug interactions. As reports of rifampin drug interactions continue to grow, this review is a reminder to clinicians to be vigilant.

Evaluation of glycemic control following discontinuation of an intensive insulin protocol

This study was conducted to identify current practice in provision of enteral nutrition (EN) and to determine effects of early enteral nutrition (EEN) on length of stay in the medical intensive care unit (ICU). In this prospective, observational study, medical ICU patients were evaluated to determine their candidacy for EEN. If patients were candidates for EN and expected to remain nothing-by-mouth for 48 hours, they were classified as receiving EEN (within 24 hours of admission) or delayed EN. Thirty-six patients were candidates for EEN. Eighteen received EEN and 18 received delayed EN. In the delayed group, the median time to start of EN was 2.1 +/- 4.8 days. Median ICU length of stay was 4.7 +/- 3.5 days in the EEN group compared with 8.5 +/- 8.3 days in the delayed group. Although hospital length of stay was shorter in the EEN group, this was not statistically significant (10.4 +/- 6.9 vs 16.9 +/- 11.5 days). Time on the ventilator was significantly shorter in the EEN group vs delayed (n = 30, 3.0 +/- 4.2 vs 6.0 +/- 9.2 days). The incidence of new pneumonia was lower in the EEN group (5.5% vs 44%), but no difference was found in the incidence of bacteremia. Hospital mortality was lower in the EEN group (1 vs 7 deaths). Given its association with numerous benefits, EEN within 24 hours of admission should be encouraged and implemented by clinicians in medical ICU patients, but additional research is needed.

Acute inhalant-induced neurotoxicity with delayed recovery

We describe the case of a patient in whom anticonvulsant hypersensitivity syndrome developed during treatment with phenytoin and progressed when therapy was changed to phenobarbital. Although therapeutic options remain controversial, corticosteroids and IV immunoglobulin were used in our patient. The patient had a complete recovery, suggesting the potential benefit of corticosteroids and IV immunoglobulin for anticonvulsant hypersensitivity syndrome.

An evaluation of peak expiratory flow monitoring: a comparison of sitting versus standing measurements.

BACKGROUND It has been >25 years since the interaction between warfarin and metronidazole was last reported in the literature. The current case report represents the first documentation of this interaction associated with intracerebral hemorrhage. CASE SUMMARY We present a case of a 78-year-old white woman started on metronidazole (250 mg every 8 hours for 5 days) and levofloxacin (500 mg QD for 6 days) for an upper respiratory tract infection after visiting a walk-in clinic. The patient did not notify any of the health care professionals involved that she was on concomitant warfarin therapy, which had been stable over the last 3 months. Her warfarin dose was 7 mg daily, and her most recent international normalized ratio (INR) reading was 2.5. Nine days after her clinic visit, the patient was admitted to the hospital for a profuse nosebleed with an INR of 8.0 and was found to have an intraparenchymal hemorrhage of the left occipital lobe. The Naranjo adverse drug reaction probability scale indicated that the association with metronidazole was probable and the association with levofloxacin was possible (scores of 7 and 4, respectively). After a 1-week hospital stay, she was discharged. CONCLUSIONS This adverse event is highly suggestive of a drug interaction caused primarily by metronidazole, which produces an increase in S-warfarin concentrations. Treatment provided by health care providers who were not familiar with the patient and the use of a different pharmacy (where the pharmacist was unaware of her current medications) likely contributed to the event.