Objectives: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. Design: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. Setting: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). Patients: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. Interventions: None. Measurements and Main Results: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851–5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 μg/min norepinephrine equivalents (3.4–18.1 μg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 μg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16–1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. Conclusions: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). We aimed to characterize the burden of CRRT filter clotting in COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing. Multi-center study of consecutive patients with COVID-19 receiving CRRT. Primary outcome was CRRT filter loss. Sixty-five patients were analyzed, including 17 using an anti-factor Xa protocol to guide systemic heparin dosing. Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 [2.5, 33.5] h. There was no difference in first or second filter loss between the anti-Xa protocol and standard of care anticoagulation groups, however fewer patients lost their third filter in the protocolized group (55% vs. 93%) resulting in a longer median third filter survival time (24 [15.1, 54.2] vs. 17.3 [9.5, 35.1] h, p = 0.04). The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is reasonable approach to anticoagulation in this population.

Background: Continuous renal replacement therapy (CRRT) is commonly employed in the intensive care unit (ICU), though there are no guidelines around the transition between CRRT and intermittent hemodialysis (iHD). Accelerated venovenous hemofiltration (AVVH) is a modality utilizing higher hemofiltration rates (4–5 L/h) with shorter session durations (8–10 h) to “accelerate” the clearance and volume removal that normally is spread out over a 24-h period in CRRT. We examined AVVH as a transition therapy between CRRT and iHD, with the aim of decreasing time on CRRT and providing a more graduated transition for hemodynamically unstable patients requiring RRT. Methods: Retrospective cohort study describing the clinical outcomes and quality initiative experience of the integration of AVVH into the CRRT program at an academic tertiary care center. Outcomes of interest included mortality, ICU length of stay and readmission rates, and technical characteristics of treatments. Results: In total, 97 patients received a total of 298 AVVH treatments (3.1 ± 3.3 treatments per patient). Totally, 271/298 (91%) treatments were completed successfully. During an average treatment time of 9.5 ± 1.6 h with 4.2 ± 0.5 L/h ­replacement fluid rate, urea reduction ratio was 23 ± 26% per 10-h treatment, and net ultrafiltration volume was 2.4 ± 1.3 L/treatment. Inpatient mortality was 32%, mean total hospital length of stay was 54 ± 47 days. Sixty-four out of 97 (66%) patients recovered renal function by discharge. Among those who transferred out of the ICU, 7/62 (11%) patients required readmission to the ICU after developing hypotension on iHD. Conclusion: AVVH can serve as a transition therapy between CRRT and iHD in the ICU and has the potential to decrease total time on CRRT, improve patient mobility, and sustain low ICU readmission rates. Future study is needed to analyze the implications on resource use and cost of this modality.

Current fluconazole dosing strategies can be described using either standardized doses (800 or 400 mg) or as weight-based dosing recommendations (12 mg/kg loading dose followed by 6 mg/kg maintenance dose). The ideal method of fluconazole dosing is still unclear for certain patient populations, such as those receiving renal replacement therapy or the morbidly obese. We describe a 48-year-old man with a body mass index of 84 kg/m(2) who was receiving continuous venovenous hemofiltration (CVVH) and was treated with fluconazole by using a weight-based dose determined by lean body weight, infused at a rate of 200 mg/hour. Blood samples were collected at hour 0 (i.e., ~24 hrs after the loading dose was administered) and at 3.5, 6.8, and 11.3 hours after the start of the 600-mg maintenance dose, infused over 3 hours. Pharmacokinetic parameters calculated were maximum serum concentration 9.64 mg/L, minimum serum concentration 5.98 mg/L, area under the serum concentration-time curve from 0-24 hours (AUC0-24 ) 184.75 mg/L•hour, elimination rate constant 0.0199 hour(-1) , elimination half-life 34.8 hours, and total body clearance 3.25 L/hour. Our data, when combined with previously published literature, do not support using a linear dose-to-AUC approximation to estimate drug dosing needs in the critically ill patient population receiving CVVH. In addition, our results suggest that morbidly obese patients are able to achieve pharmacodynamic goals defined as an AUC:MIC ratio higher than 25 by using a lean body weight for fluconazole dosing calculations.