The Production, Efficacy, and Safety of Machine-Generated Bicarbonate Solution for Continuous Venovenous Hemodialysis (CVVHD): The Cleveland Clinic Method.

RATIONALE & OBJECTIVE: Since 1994, the Nephrology and Hypertension Department at the Cleveland Clinic has prepared and used bicarbonate-based solution for continuous venovenous hemodialysis (CVVHD) using a standard volumetric hemodialysis machine rather than purchasing from a commercial vendor. This report describes the process of producing Cleveland Clinic UltraPure Solution (CCUPS), quality and safety monitoring, economic costs, and clinical outcomes. STUDY DESIGN: Retrospective study. SETTING & PARTICIPANTS: CVVHD experience at Cleveland Clinic, focusing on dialysate production, institutional factors, and patients requiring continuous kidney replacement therapy. Production is shown at www.youtube.com/watch?v=WGQgephMEwA. OUTCOMES: Feasibility, safety , and cost. RESULTS: Of 6,426 patients treated between 2011 and 2019 with continuous kidney replacement therapy, 59% were men, 71% were White, 40% had diabetes mellitus, and 74% presented with acute kidney injury. 98% of patients were treated with CVVHD using CCUPS, while the remaining 2% were treated with either continuous venovenous hemofiltration or continuous venovenous hemodiafiltration using commercial solution. The prescribed and delivered effluent doses were 24.8 (IQR) versus 20.7 mL/kg/h (IQR), respectively. CCUPS was as effective in restoring electrolyte and serum bicarbonate levels and reducing phosphate, creatinine, and serum urea nitrogen levels as compared with packaged commercial solution over a 3-day period following initiation of dialysis, with a comparable effluent dose. Among those with acute kidney injury, mortality was similar to that predicted with the 60-day acute kidney injury predicted mortality score (r = 0.997; CI: 0.989-0.999). At our institution, the cost of production for 1 L of CCUPS is $0.67, which is considerably less than the cost of commercially purchased fluid. LIMITATIONS: Observational design without a rigorous control group. CONCLUSIONS: CVVHD using locally generated dialysate is safe and cost-effective.

Cefiderocol in Critically Ill Patients with Multi-Drug Resistant Pathogens: Real-Life Data on Pharmacokinetics and Microbiological Surveillance.

Cefiderocol is a new siderophore-cephalosporin for the treatment of multi-drug resistant Gram-negative pathogens. As a reserve agent, it will and should be used primarily in critically ill patients in the upcoming years. Due to the novelty of the substance little data on the pharmacokinetics in critically ill patients with septic shock and renal failure (including continuous renal replacement therapy and cytokine adsorber therapy) is available. We performed therapeutic drug monitoring in a cohort of five patients treated with cefiderocol, to improve the knowledge on pharmacokinetics in this vulnerable patient population. As expected for a cephalosporin with predominantly renal elimination the maintenance dose could be reduced in patients with renal impairment or on continuous renal replacement therapy. The manufacturer's dosing instructions were sufficient to achieve a drug level well above the MIC. However, the addition of a cytokine adsorber might reduce serum levels substantially, so that in this context therapeutic drug monitoring and dose adjustment are recommended.