Prospective Study of the Multisite Spread of a Medication Safety Intervention: Factors Common to Hospitals With Improved Outcomes.

Context and implementation approaches can impede the spread of patient safety interventions. The objective of this article is to characterize factors associated with improved outcomes among 9 hospitals implementing a medication safety intervention. Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a pharmacist-driven intervention that led to a sustained reduction in nephrotoxic medication-associated acute kidney injury (NTMx-AKI) at 1 hospital. Using qualitative comparative analysis, the team prospectively assessed the association between context and implementation factors and NTMx-AKI reduction during NINJA spread to 9 hospitals. Five hospitals reduced NTMx-AKI. These 5 had either (1) a pharmacist champion and >2 pharmacists working on NINJA (Scon 1.0, Scov 0.8) or (2) a nephrologist-implementing NINJA with minimal competing organizational priorities (Scon 1.0, Scov 0.2). Interviews identified ways NINJA team leaders obtained pharmacist support or successfully implemented without that support. In conclusion, these findings have implications for future spread of NINJA and suggest an approach to study spread of safety interventions more broadly.

Nephrotoxin-Related Acute Kidney Injury and Predicting High-Risk Medication Combinations in the Hospitalized Child.

BACKGROUND: In the hospitalized patient, nephrotoxin exposure is one potentially modifiable risk factor for acute kidney injury (AKI). Clinical decision support based on nephrotoxin ordering was developed at our hospital to assist inpatient providers with the prevention or mitigation of nephrotoxin-related AKI. The initial decision support algorithm (Algorithm 1) was modified in order to align with a national AKI collaborative (Algorithm 2). OBJECTIVE: Our first aim was to determine the impact of this alignment on the sensitivity and specificity of our nephrotoxin-related AKI detection system. Second, if the system efficacy was found to be suboptimal, we then sought to develop an improved model. DESIGN: A retrospective cohort study in hospitalized patients between December 1, 2013 and November 30, 2015 (N = 14,779) was conducted. INTERVENTIONS: With the goal of increasing nephrotoxin-related AKI detection sensitivity, a novel model based on the identification of combinations of high-risk medications was developed. RESULTS: Application of the algorithms to our nephrotoxin use and AKI data resulted in sensitivities of 46.9% (Algorithm 1) and 43.3% (Algorithm 2, P = .22) and specificities of 73.6% and 89.3%, respectively (P < .001). Our novel AKI detection model was able to deliver a sensitivity of 74% and a specificity of 70%. CONCLUSIONS: Modifications to our AKI detection system by adopting Algorithm 2, which included an expanded list of nephrotoxins and equally weighting each medication, did not improve our nephrotoxin-related AKI detection. It did improve our system's specificity. Sensitivity increased by >50% when we applied a novel algorithm based on observed data with identification of key medication combinations.

Recombinant activated factor VII effectively reverses the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin ex vivo as measured using thromboelastography.

Bleeding is the major adverse reaction to anticoagulants, leading to significant morbidity and even mortality. Protamine is a specific antidote for heparin yet is only partially effective for enoxaparin, and the activated factor X inhibitor fondaparinux and the direct thrombin inhibitors argatroban and bivalirudin lack specific antidotes. We evaluated the ability of recombinant activated factor VII (rFVIIa), a general hemostatic agent, to reverse the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin, as measured by thromboelastography. Whole-blood samples containing each test anticoagulant, with or without rFVIIa 1.5-4.5 microg/ml, were prepared ex vivo (n >or= 48, each anticoagulant) and analyzed by thromboelastography. The thromboelastography parameters of clot initiation, propagation, rigidity and elasticity were compared for the ex-vivo samples for each anticoagulant. The reversal ability of rFVIIa was also assessed using the standard clinical assay used to monitor each anticoagulant. Thromboelastography was performed on blood from eight stably anticoagulated patients, with and without exogenous rFVIIa. For each anticoagulant, rFVIIa significantly improved and, in some cases, completely normalized all thromboelastography parameters (P < 0.001). rFVIIa significantly (P < 0.01) decreased the activated partial thromboplastin time for argatroban-containing, bivalirudin-containing, or heparin-containing blood yet did not affect the anti-activated factor X levels for enoxaparin-containing or fondaparinux-containing blood. By thromboelastography, rFVIIa exerted generally similar reversal effects on the anticoagulated patient samples as on the ex-vivo samples. In conclusion, rFVIIa effectively reverses the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin, and should be considered for patients with excessive bleeding associated with these anticoagulants.

Differential effects of direct thrombin inhibitors and antithrombin-dependent anticoagulants on the dynamics of clot formation.

New anticoagulants, including the direct thrombin inhibitors (DTIs) and fondaparinux, are increasingly replacing unfractionated heparin and enoxaparin. We examined the effects of argatroban (n = 60), bivalirudin (n = 44), heparin (n = 14), enoxaparin (n = 22), and fondaparinux (n = 24) on clot formation utilizing thromboelastography. Blood samples containing anticoagulants at clinically relevant concentrations were prepared ex vivo and analyzed using kaolin or tissue factor activation. Thromboelastography parameters of clot initiation (R), clot propagation (K and angle), clot rigidity (maximum amplitude) and clot elasticity (G) were compared between anticoagulants. Thromboelastography was also performed on blood from eight patients receiving anticoagulants. Each anticoagulant exerted significant concentration-dependent effects on R, K and angle. Only heparin, enoxaparin, and fondaparinux significantly affected maximum amplitude and G. Significant differences existed for all parameters between heparin and each anticoagulant and between fondaparinux and each DTI (P < 0.001), and for angle, maximum amplitude, and G between enoxaparin and each DTI (P < 0.008). Thromboelastography responses in ex-vivo samples and patient samples were comparable. In conclusion, whereas argatroban, bivalirudin, heparin, enoxaparin and fondaparinux each delay clot formation, the DTIs do not alter clot rigidity or elasticity. The reduced bleeding reported with DTIs versus heparin may relate to the fact that clots form with normal rigidity and elasticity.

Argatroban as an alternative to heparin in extracorporeal membrane oxygenation circuits.

We investigated the anticoagulant effects of argatroban, a direct thrombin inhibitor, versus heparin in extracorporeal membrane oxygenation (ECMO) circuits. Three sham circuits were prepared according to our hospital's standard practice and run for six hours simultaneously. Two circuits were anticoagulated with argatroban (one with heparin in the wet prime and one without). One circuit had heparin in the initial prime and was then anticoagulated with heparin. We measured thrombin generation (prothrombin fragment 1+2, D-dimer and thrombin-antithrombin complexes), activated clotting times (ACTs) and partial thromboplastin times (aPTTs), and monitored thrombus formation using thromboelastography. ACTs were >1000 s in each circuit throughout assessment. No clot initiation was detected by thromboelastography. Thrombin generation was decreased in circuits anticoagulated with argatroban versus heparin, despite aPTTs being less prolonged. These results suggest that argatroban may be more efficacious than heparin for anticoagulation in ECMO. Additional studies are warranted to further evaluate argatroban in this setting.