Comparison of fluid resuscitation weight-based dosing strategies in obese patients with severe sepsis.

OBJECTIVE: This study aims to compare the composite outcome of progression to septic shock between 30 mL/kg/ideal body weight (IBW) versus 30 mL/kg/non-IBW fluid resuscitation dosing strategies in obese patients with severe sepsis. METHODS: We retrospectively evaluated obese patients admitted to an academic tertiary care center for the management of severe sepsis. Patients were included if they had a fluid bolus order placed using the sepsis order set between Oct 2018 and Sept 2019. The primary objective was the composite of progression to septic shock, defined as either persistent hypotension within 3 h after the conclusion of the 30 mL/kg fluid bolus administration or the initiation of vasopressor(s) within 6 h of the bolus administration. RESULTS: Of 72 included patients, 49 (68%) were resuscitated using an IBW-based and 23 (32%) using a non-IBW-based dosing strategy. There were similar rates of progression to septic shock in the IBW and non-IBW groups (18% vs. 26%; p = 0.54). Median ICU and hospital LOS in the IBW group versus non-IBW group were (0 [IQR 0] vs. 0 [IQR 0 to 4] days; p = 0.13) and (6 [IQR 3 to 10] vs. 8 [IQR 5 to 12] days; p = 0.07), respectively. In-hospital mortality rates were similar between the groups. CONCLUSIONS: Our study results suggest that in obese septic patients, fluid administration using an IBW-dosing strategy did not affect the progression to septic shock.

Heparin vs bivalirudin anticoagulation for extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) induces hemostatic alterations that may contribute to hematological complications. Unfractionated heparin (UFH) is the mainstay antithrombotic in ECMO and depends on antithrombin III (AT III) to exhibit its actions. However, it bears the risk for heparin-induced thrombocytopenia. Bivalirudin is a direct thrombin inhibitor and is inherently not dependent on AT III. AIM OF THE STUDY: To assess the efficacy and safety profiles of UFH compared with bivalirudin during ECMO support. METHODS: We retrospectively reviewed 52 adult patients who were supported by ECMO from 1 January 2013 to 1 September 2018. Among them, 33 received UFH and 19 received bivalirudin. We analyzed their 7-day rate of composite thrombotic, bleeding, and mortality episodes while on anticoagulation. RESULTS: There were no statistical differences in the 7-day rate of composite thrombosis (33.3% vs 26.3%; P = 0.60), major bleeding (18.2% vs 5.3%; P = .24), 30-day mortality, (42.4% vs 26.3%; P = .37), or in-hospital mortality (45.5% vs 36.8%; P = .58). The percentage of time activated partial thromboplastin time (aPTT) was within the therapeutic range was higher with bivalirudin (50% vs 85.7%; P = .007). CONCLUSIONS: This study suggests that UFH and bivalirudin are associated with similar rates of thrombosis, major bleeding, and mortality events in patients supported by ECMO. However, it was observed that bivalirudin consistently maintained aPTT within the therapeutic range in comparison to UFH.

Bivalirudin resistance in a patient on veno-venous extracorporeal membrane oxygenation with a therapeutic response to argatroban.

A 48-year-old male patient requiring extracorporeal membrane oxygenation (ECMO) support for hypoxaemic respiratory failure failed to achieve therapeutic anticoagulation with bivalirudin after continuous dose escalations, and continued to have recurrent fibrin stranding in the circuit over a 6-day course of treatment. Suspecting bivalirudin resistance, the patient was transitioned to argatroban and achieved a therapeutic response in less than 24 hours. The case describes the challenges of anticoagulation in ECMO supported patients. The interplay between bivalirudin metabolism, renal replacement therapy, and immunological effects leading to a heparin-like-effect, inflammatory mediators, and thrombotic burdens may all impact the clinical effect during bivalirudin therapy. The structural biochemistry of thrombin and bivalirudin likely plays a role in the presented patient's successful response to argatroban. Bivalirudin may fail at achieving therapeutic anticoagulation in patients with genetic thrombin mutations or structural defects that alter the binding pockets at the thrombin exosites.