Empirical dose reductions of VTE prophylaxis are infrequently used in underweight, critically ill patients. Further studies need to be conducted that assess the safety and efficacy of reduced-dose VTE prophylactic regimens in this population to determine if acceptable efficacy can be achieved, with lower risks of bleeding.

the FDA labeling for this product indicated "no data inform the use in patients with creatinine clearance <15 mL/min or on dialysis."This previous cautious recommendation regarding the lack of data seems to be a prudent treatment of clinical data where patients with either a serum creatinine of 2.5 mg/dL or estimated creatinine clearance of less than 25 mL/min were excluded. 2,3 As such, very little insight into the efficacy and safety of this agent in patients with severe renal insufficiency is available in these populations.This nuance is important because 27% of apixaban is eliminated as unchanged drug in the urine. 1 One single-dose pharmacokinetic study among 8 patients was used to assess the response of apixaban with dialysis, which indicated an increase in drug exposure via an area under the curve increase of 36%. 1,4 This study provides no insight into the effect of subsequent, multiple doses and the extent of drug accumulation but did indicate that dialysis only removed 14% of the drug.Using this information, the package labeling for apixaban was changed to the following: "the recommended dose for nonvalvular atrial fibrillation patients with end-stage renal disease (ESRD) maintained on hemodialysis is 5 mg twice daily. Reduce dose to 2.5 mg twice daily if one of the following patient characteristics (age ≥80 years or body weight ≤60 kg) is present." 1 Apixaban is now also indicated for the treatment of deep-vein thrombosis (DVT), pulmonary embolism (PE), and the reduction of the risk of recurrence of DVT and PE. In this same patient population, the package labeling states that there is no dose adjustment required for these indications. 1 Together, these recommendations represent the use of full-dose apixaban in many patients undergoing dialysis and are made with no evidence regarding the clinical impact or safety of continued use of this agent.The use of anticoagulants in patients undergoing dialysis despite unclear dosing guidance can be tantalizing, as was demonstrated in one study where the use of enoxaparin or eptifibatide was present in 22% in a cohort of dialysis patients with acute coronary syndromes. 5 Furthermore, use of these agents was associated with an increase in both mortality and bleeding events. Lessons from this retrospective evaluation should be taken into account in this new clinical controversy.Without a doubt, an easy-to-use, safe, effective therapy for patients with severe renal impairment and dialysis are needed. We ask that the desire for such an agent not supersede the evidence in patients with renal impairment, especially among agents with narrow therapeutic indices or unclear monitoring and unreliable reversal.We agree with other expert bodies that among patients with severe renal impairment, warfarin remains the agent of choice and ask that other clinicians exercise caution before recommending or prescribing apixaban for patients with severe renal impairment or those requiring dialysis.

Current practice does not reflect dose reductions for neurologically injured, underweight patients. Caution should be considered when using increased doses of UFH in neurologically injured patients that are underweight and/or may be exposed to >150 units/kg/day of UFH. Continued assessment of VTE prophylaxis is needed to confirm these findings.

Background: Thiazide diuretics are often utilized to overcome loop diuretic resistance when treating acute decompensated heart failure (ADHF). In addition to a large cost advantage, several pharmacokinetic advantages exist when administering oral metolazone (MTZ) compared with intravenous (IV) chlorothiazide (CTZ), yet many providers are reluctant to utilize an oral formulation to treat ADHF. The purpose of this study was to compare the increase in 24-hour total urine output (UOP) after adding MTZ or CTZ to IV loop diuretics (LD) in patients with heart failure with reduced ejection fraction (HFrEF). Methods and Results: From September 2013 to August 2016, 1002 patients admitted for ADHF received either MTZ or CTZ in addition to LD. Patients were excluded for heart failure with preserved ejection fraction (HFpEF) (n = 469), <24-hour LD or UOP data prior to drug initiation (n = 129), or low dose MTZ/CTZ (n = 91). A total of 168 patients were included with 64% receiving CTZ. No significant difference was observed between the increase in 24-hour total UOP after MTZ or CTZ initiation (1458 [514, 2401] mL vs 1820 [890, 2750] mL, P = .251). Conclusions: Both MTZ and CTZ similarly increased UOP when utilized as an adjunct to IV LD. These results suggest that while thiazide agents can substantially increase UOP in ADHF patients with HFrEF, MTZ and CTZ have comparable effects.

Background: Adjunctive vasopressin use in septic shock reduces catecholamine requirements and is associated with a lower incidence of new-onset arrhythmias (NOAs). The association of vasopressin timing on NOA development is ill-described. Objective: To determine whether early administration of vasopressin was associated with a lower incidence of NOA in septic shock patients. Methods: A retrospective analysis of intensive care unit (ICU) patients at a large, academic medical center. Septic shock patients who required vasopressin and norepinephrine were eligible for inclusion. Patients were excluded for receipt of other vasoactive agents, history of cardiac arrhythmias, or outside hospital admission. Early vasopressin was defined as receipt within 6 hours of septic shock onset. The primary outcome was incidence of NOA. Results: In total, 436 patients, 220 (50.4%) in the early and 216 (49.6%) in the late vasopressin group, were included. Early vasopressin was not associated with a lower incidence of NOA compared with late vasopressin (9% vs 7%, median absolute difference [95% confidence interval, CI]: −2.1 [−7.2, 3.0], P = 0.41). Early vasopressin patients were observed to have shorter shock duration (2 vs 4 days, median absolute difference [95% CI]: 2 [1, 2], P < 0.001), and ICU length of stay (6 vs 7 days, median absolute difference [95% CI]: 1 [0, 2], P = 0.02). Conclusions and Relevance: Early vasopressin use was not associated with a lower incidence of NOA. Additional studies are needed to elucidate the effect of vasopressin timing on NOA and other clinical outcomes.