Article: Therapeutic Drug Monitoring in ECMO Patients

Extracorporeal membrane oxygenation (ECMO) provides prolonged cardiac and respiratory support for patients with a life-threatening illness that stops their heart or lungs from working properly. It is increasingly used in intensive care units (ICU) for treating patients, but the nature of the technique carries a risk of bacterial infections and sepsis.

A lot of antibiotics are now being given for patients to combat any infections during ECMO. Many of the antibiotic treatments – especially beta-lactams – have been found to be more effective when they are administered continuously. However, if these drugs are not measured regularly, then patients are at risk of being underdosed and are unlikely to meet the minimum inhibitory concentration (MIC) because many of the dosage models are based on healthy patients and not the typical ICU patient.

A study has recently been published using an HPLC assay* from Chromsystems for therapeutic drug monitoring (TDM) of antibiotic drugs to measure the dosage levels of both ECMO and non-ECMO patients.

Five drug dose regimes were analysed during this trial – piperacillin, linezolid, ceftazidime, and meropenem in high dose and regular dose regimens. Pre-specified dosage targets were not met for a standard dose regimen of piperacillin, linezolid and meropenem in a significant number of patients, 48%, 35% and 6% respectively. This result highlights the need for TDM with clinically ill patients on ECMO support.

The study also found that piperacillin and meropenem had significantly lower antibiotic serum concentrations for ECMO patients compared to the non-ECMO counterparts, highlighting the need for greater monitoring of ECMO patients. The reason for this may be that small molecule drugs can be sequestered during ECMO, thereby reducing their blood concentration, hence the need for drug monitoring. Throughout the study, patients with ECMO treatment had a much higher mortality and renal failure rate than non-ECMO patients despite their younger age. While not all deaths can be attributed to low antibiotic therapeutic levels, low levels increase the risk of infection and sepsis occurring – something which is common in ECMO patients.

The results of the study demonstrate that while antibiotics can be used for successfully treating ECMO patients, TDM should be carried out. This is particularly true for piperacillin, standard dose meropenem and linezolid. TDM allows clinicians to identify and rectify any potential underdosing, as some of these drugs are particularly susceptible to underdosing.

The implementation of TDM to these administered drugs enables their dose regimen to be monitored and adjusted based on their analysed levels, enabling the drug to reach the required therapeutic levels to combat the infection of ECMO patients in ICU settings.

This study showed how easy it is to underdose certain antibiotic drugs (especially piperacillin and linezolid) in ECMO settings and highlights the need for therapeutic drug monitoring (TDM) for ensuring that patients are not underdosed. The specific nature of the study should not take away the need for TDM in all ICU patients.

This study confirms the general notion on how easy it is to underdose certain antibiotic drugs in ICU, whilst highlighting the need for therapeutic drug monitoring (TDM) to ensure that patients are not being underdosed. Commercial CE-IVD solutions are available for TDM that are accurate and affordable even for smaller laboratories.

Kühn, D., Metz, C., Seiler, F. et al. Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study. Crit Care, 24, 664 (2020). https://doi.org/10.1186/s13054-020-03397-1

* This assay is not available in all countries. Please ask your local representative for more information.