Hydroxocobalamin for Vasodilatory Hypotension in Shock: A Systematic Review With Meta-Analysis for Comparison to Methylene Blue.

Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.

Analysis of Wholesale Drug Acquisition and Laboratory Assessment Costs Between Heparin Compared With Bivalirudin-Based Systemic Anticoagulation Strategies in Adult Extracorporeal Membrane Oxygenation.

OBJECTIVES: To assess the wholistic costs of systemic anticoagulation delivery in heparin versus bivalirudin-based maintenance of adult patients supported on extracorporeal membrane oxygenation (ECMO). DESIGN: Single-center retrospective cohort study. SETTING: Large academic ECMO center. PATIENTS: Adults on ECMO receiving heparin or bivalirudin for primary maintenance systemic anticoagulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electronic data were abstracted from a database maintained by our ECMO center, which transitioned to a preferred bivalirudin-based anticoagulation management in 2017. The pretransition group consisted of 126 patients (123 heparin and three bivalirudin), whereas the posttransition group included 275 patients (82 heparin and 193 bivalirudin). Drug costs were estimated using the wholesale acquisition cost, and laboratory assays costs were estimated using reimbursement fee schedules. Cost data were normalized to the duration of the ECMO run and reported in U.S. Dollar per ECMO day. Following the practice change, bivalirudin patients were less likely to receive AT supplementation (31.0 vs 12.4%; p < 0.0001) and had fewer coagulation assays ordered (6.1 vs 5.4 per ECMO day; p = 0.0004). After the transition, there was a dramatic decrease in costs related to AT assay assessments ($11.78 [interquartile range {IQR}, $9.48-$13.09] vs $1.03 [IQR, $0-$5.75]; p < 0.0001) and AT supplementation ($0 [IQR, $0-$312.82] vs $0 [IQR, $0-$0]; p < 0.0001) per ECMO day. Unadjusted survival at 28 days was higher posttransition (64.3 vs 74.9%; p = 0.0286). CONCLUSIONS: Antithrombin assays and supplementation compromise a significant proportion of heparin-based anticoagulation costs in ECMO patients and is substantially reduced when a bivalirudin-based anticoagulation strategy is deployed. A favorable association exists between the aggregate cost of administration of bivalirudin compared with heparin-based systemic anticoagulation in adults supported on ECMO driven by reductions in antithrombin activity assessments and the cost of antithrombin replacement.

Sodium-glucose cotransporter 2 inhibitors for treatment of diabetes mellitus after kidney transplantation.

INTRODUCTION: Diabetes mellitus in kidney transplant recipients is a risk factor for cardiovascular events and premature death. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly used in nontransplant populations to improve diabetes control and cardiovascular and renal benefits. Limited literature exists regarding the safety and efficacy of these agents in renal transplant recipients. METHODS: We retrospectively reviewed all kidney transplant recipients within our health system who were prescribed a SGLT2i after transplantation for diabetes. The safety, tolerability, and effectiveness of SGLT2i were analyzed. RESULTS: Thirty-nine kidney transplant recipients were initiated on SGLT2i therapy, twenty-seven of which remained on therapy for at least 1 year. Ten (25%) patients experienced an adverse event while on a SGLT2i, with urinary tract infections (UTI) being the most common. Seventeen patients (43%) discontinued the SGLT2i at the time of chart review, most commonly due to cost and kidney function decline. The median [IQR] hemoglobin A1c (HbA1c) at SGLT2i initiation of 8.4% [7.8-9.2] decreased to 7.5% [6.8-8.0%] after 3 months and 7.5% [6.5-7.9] after 12 months. No meaningful change in kidney function or tacrolimus exposure was observed. CONCLUSION: SGLT2i may be a safe and effective treatment for diabetes in kidney transplant recipients. Cost is a barrier to SGLT2i therapy, and UTIs were the most frequently encountered adverse events in this cohort. More studies are needed to understand the safety profile and determine the effect of SGLT2i on diabetes-related comorbidities among kidney transplant recipients.

Hemostatic Management in Extracorporeal Membrane Oxygenation.

The use of extracorporeal membrane oxygenation (ECMO) for acute cardiac and/or respiratory failure has grown exponentially in the past several decades. Systemic anticoagulation is a fundamental element of caring for ECMO patients. Hemostatic management during ECMO walks a fine line to balance the risk of safe and effective anticoagulant delivery to mitigate thromboembolic complications and minimizing hemorrhagic sequelae. This review discusses the pharmacology, monitoring parameters, and special considerations for anticoagulation in patients requiring ECMO.