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Machines that help machines to help patients: optimising antimicrobial dosing in patients receiving extracorporeal membrane oxygenation and renal replacement therapy using dosing software.

ABSTRACT: Intensive care unit (ICU) patients with end-organ failure will require specialised machines or extracorporeal therapies to support the failing organs that would otherwise lead to death. ICU patients with severe acute kidney injury may require renal replacement therapy (RRT) to remove fluid and wastes from the body, and patients with severe cardiorespiratory failure will require extracorporeal membrane oxygenation (ECMO) to maintain adequate oxygen delivery whilst the underlying pathology is evaluated and managed. The presence of ECMO and RRT machines can further augment the existing pharmacokinetic (PK) alterations during critical illness. Significant changes in the apparent volume of distribution (V_d) and drug clearance (CL) for many important drugs have been reported during ECMO and RRT. Conventional antimicrobial dosing regimens rarely consider the impact of these changes and consequently, are unlikely to achieve effective antimicrobial exposures in critically ill patients receiving ECMO and/or RRT. Therefore, an in-depth understanding on potential PK changes during ECMO and/or RRT is required to inform antimicrobial dosing strategies in patients receiving ECMO and/or RRT. In this narrative review, we aim to discuss the potential impact of ECMO and RRT on the PK of antimicrobials and antimicrobial dosing requirements whilst receiving these extracorporeal therapies. The potential benefits of therapeutic drug monitoring (TDM) and dosing software to facilitate antimicrobial therapy for critically ill patients receiving ECMO and/or RRT are also reviewed and highlighted.

SUBMITTER: Roberts JA

PROVIDER: S-EPMC9467945 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Machines that help machines to help patients: optimising antimicrobial dosing in patients receiving extracorporeal membrane oxygenation and renal replacement therapy using dosing software.

Roberts Jason A JA Bellomo Rinaldo R Cotta Menino O MO Koch Birgit C P BCP Lyster Haifa H Ostermann Marlies M Roger Claire C Shekar Kiran K Watt Kevin K Abdul-Aziz Mohd H MH

Intensive care medicine 20220823 10

Intensive care unit (ICU) patients with end-organ failure will require specialised machines or extracorporeal therapies to support the failing organs that would otherwise lead to death. ICU patients with severe acute kidney injury may require renal replacement therapy (RRT) to remove fluid and wastes from the body, and patients with severe cardiorespiratory failure will require extracorporeal membrane oxygenation (ECMO) to maintain adequate oxygen delivery whilst the underlying pathology is eval ...[more]

PMID: 35997793

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Project description:BackgroundDespite the surge in use of extracorporeal membrane oxygenation (ECMO) in the adult intensive care unit, little guidance is available on the appropriate dosing of antimicrobials in this setting. Ceftriaxone is an antimicrobial with a high affinity to plasma protein, a property identified in the literature as susceptible to sequestration into extracorporeal circuits and hypothesised to require dosage adjustments in this setting.ObjectiveThe aim of this study was to describe the pharmacokinetics of ceftriaxone and identify the best dosing regimen for critically ill adult patients receiving ECMO.MethodsSerial blood samples were taken from patients receiving both ECMO and ceftriaxone. Total and unbound drug concentrations were measured in plasma by chromatographic assay and analysed using a population pharmacokinetic approach with Pmetrics®. Dosing simulations were performed to identify the optimal dosing strategy: 60 and 100% of time with free (unbound) drug concentration exceeding the minimum inhibitory concentration (fT>MIC).ResultsIn total, 14 patients were enrolled, of which three were receiving renal replacement therapy (RRT). Total and unbound ceftriaxone was best described in a two-compartment model with total body weight, serum albumin concentrations, creatinine clearance (CrCL), and the presence of RRT included as significant predictors of pharmacokinetics. Patients not on RRT generated a mean renal clearance of 0.90 L/h, non-renal clearance of 0.33 L/h, and central volume of distribution of 7.94 L. Patients on RRT exhibited a mean total clearance of 1.18 L/h. ECMO variables were not significant predictors of ceftriaxone pharmacokinetics. Steady-state dosing simulations found that dosages of 1 g every 12 h and 2 g every 24 h achieved >90% probabilities of target attainment in patients with CrCL of 0 mL/min with RRT and 30 and 100 mL/min and various serum albumin concentrations (17 and 26 g/L).ConclusionsDosing recommendations for critically ill adult patients not on ECMO appear to be sufficient for patients on ECMO. Patients exhibiting augmented renal clearance (> 130 mL/min) or treatment of less susceptible pathogens may require higher doses, which requires further investigation.

Project description:BackgroundThere are limited data regarding prolonged extracorporeal membrane oxygenation (ECMO) support, despite increase in ECMO use and duration in patients with respiratory failure. The objective of this study was to investigate the outcomes of severe acute respiratory failure patients supported with prolonged ECMO for more than 28 days.MethodsBetween January 2012 and December 2015, all consecutive adult patients with severe acute respiratory failure who underwent ECMO for respiratory support at 16 tertiary or university-affiliated hospitals in South Korea were enrolled retrospectively. The patients were divided into two groups: short-term group defined as ECMO for ⩽28 days and long-term group defined as ECMO for more than 28 days. In-hospital and 6-month mortalities were compared between the two groups.ResultsA total of 487 patients received ECMO support for acute respiratory failure during the study period, and the median support duration was 8 days (4-20 days). Of these patients, 411 (84.4%) received ECMO support for ⩽28 days (short-term group), and 76 (15.6%) received support for more than 28 days (long-term group). The proportion of acute exacerbation of interstitial lung disease as a cause of respiratory failure was higher in the long-term group than in the short-term group (22.4% versus 7.5%, p < 0.001), and the duration of mechanical ventilation before ECMO was longer (4 days versus 1 day, p < 0.001). The hospital mortality rate (60.8% versus 69.7%, p = 0.141) and the 6-month mortality rate (66.2% versus 74.0%, p = 0.196) were not different between the two groups. ECMO support longer than 28 days was not associated with hospital mortality in univariable and multivariable analyses.ConclusionsShort- and long-term survival rates among patients receiving ECMO support for more than 28 days for severe acute respiratory failure were not worse than those among patients receiving ECMO for 28 days or less.

Dataset Information

Machines that help machines to help patients: optimising antimicrobial dosing in patients receiving extracorporeal membrane oxygenation and renal replacement therapy using dosing software.

Publications

Machines that help machines to help patients: optimising antimicrobial dosing in patients receiving extracorporeal membrane oxygenation and renal replacement therapy using dosing software.

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