Pharmacotherapy
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Review Meta Analysis Comparative Study
Comparative effectiveness of low-molecular-weight heparins versus other anticoagulants in major orthopedic surgery: a systematic review and meta-analysis.
To evaluate the comparative efficacy and safety of low-molecular-weight heparins (LMWHs) versus other anticoagulants as venous thromboembolism prophylaxis in major orthopedic surgery. ⋯ According to moderate-to-high strength of evidence, LMWH prophylaxis provides additional benefits with less harm compared with UFH. With predominantly moderate strength of evidence, the balance of benefits to harms for factor Xa inhibitors or DTIs compared with LMWHs seems favorable. With predominantly low-to-moderate strength of evidence, the known benefits in total DVT and distal DVT with LMWHs versus VKAs may not be sufficient to counteract the increased risk of bleeding.
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The average weight of adults in the United States has increased by 25 pounds (11 kg) over the past 50 years, with a marginal change in height. Drugs are generally dosed according to one of three approaches: fixed dosing, weight-based dosing, or body surface area-based dosing. Dosing based on body weight or body surface area assumes that drug pharmacokinetic parameters increase in proportion with increasing body size. ⋯ These dosing strategies are more likely to result in drug overexposure (weight-based approach) or underexposure (body surface area-based approach) among obese patients. Alternate weight descriptors such as ideal body weight, adjusted body weight, fat-free weight, and lean body weight are used to prevent drug overexposure with weight-based dosing, but their benefits and limitations must be understood. Reappraisal of the drug dosing paradigm is needed in this era of rising obesity; however, until drug-specific reviews can be performed, clinical studies must include patients at the extremes of the weight continuum to ensure applicable dose extrapolation for body size.
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Despite numerous pharmacologic and nonpharmacologic treatment strategies, heart failure remains a complex, progressive disorder with significant morbidity and mortality. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and β-blockers have been used as routine treatment options for heart failure for the majority of patients with left ventricular systolic dysfunction who tolerate these agents. Mineralocorticoid receptor antagonists (MRAs) have also demonstrated significant benefits in the treatment of heart failure, which include a reduction in sudden cardiac death and ventricular remodeling; however, these agents have not been recommended for most patients with heart failure. ⋯ Based on more recent evidence, it is likely that future recommendations and guidelines will further expand the use of MRAs to patients with mild heart failure as well. These agents have the potential to be recommended nearly as universally as ACE inhibitors and β-blockers because of the potential to reduce mortality and hospital admissions for heart failure. The risk of hyperkalemia should be carefully assessed when using these drugs; nonetheless, new strategies being developed may reduce the occurrence of hyperkalemia as well.
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To examine the effect of the drug interaction between clopidogrel and proton pump inhibitors (PPIs) on the risk of an adverse cardiovascular event. ⋯ Concurrent use of clopidogrel plus a PPI was associated with a significant increase in risk of an adverse cardiovascular event in patients with ACS. Large randomized studies are needed to confirm this finding. Until then, clinicians should prescribe the concurrent use of these two drugs cautiously.
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Opioid-related adverse drug events (ORADEs) can have a significant impact on patient recovery after surgery. This review investigates the impact of two ORADEs, respiratory depression and postoperative ileus (POI), on clinical and economic outcomes. Opioid-induced ventilatory impairment is a potentially serious ORADE that can result in apnea and even death. ⋯ Data from a retrospective analysis show that a daily hydromorphone dose of 2 mg/day markedly increases the risk of POI. In addition, although the incidence of POI is reduced in patients who undergo laparoscopic surgery or hand-assisted laparoscopic surgery compared with open surgery, the reduction of POI can potentially be negated by excessive opioid use. Therefore, multimodal, opioid-sparing strategies should be explored and used to reduce severe ORADEs and improve outcomes in the surgical setting.