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Lauren Igneri
Critical care pharmacist and proud Rutgers University graduate. Enjoys rock climbing, cycling, travel, and lively discussions on the finer points of pharmacokinetics and critical care over a beer with friends.
The Pre-brief
- Extracorporeal membrane oxygenation (ECMO) provides mechanical support for the treatment of cardiac or respiratory failure.
- Highly protein bound and lipophilic drugs are sequestered by the ECMO circuit resulting in altered drug absorption. Therefore, higher than usual doses may be required to achieve desired effects.
- Ex vivo models demonstrate substantial drug loss in post-oxygenator blood at 24 hours with midazolam and fentanyl: 50% and 70% loss within 1 hour of ECMO run and 87% and 97% loss at 24 hours, respectively.2
- In general, obese patients are not well represented in PK studies. They may have higher dose requirements of lipophilic drugs secondary to increased Vd from increased adipose tissue.
The Debrief:
- The majority of commonly used sedatives (propofol, midazolam, dexmedetomidine) and analgesics (fentanyl) are highly protein-bound and may be prone to ECMO circuit sequestration. In contrast, hydromorphone and ketamine exhibit low protein binding properties and may be less susceptible to circuit loss.
- A recent study demonstrated a significant increase in delirium-free and coma-free days with hydromorphone vs. fentanyl use in ECMO at 7 and 14 days. Additionally, those treated with hydromorphone had reduced opioid requirements compared to fentanyl which may be attributable to low-protein binding
- Another study evaluating obese (BMI≥30) vs. non-obese (BMI <30) patients requiring ECMO did not find a difference in opioid and midazolam requirements between groups. However, obese patients had lower median RASS scores at days 6 and 7, potentially indicating drug accumulation of highly lipophilic medications.
References:
- Dzierba AL, Abrams D, Brodie D. Medicating patients during extracorporeal membrane oxygenation: the evidence is building. Crit Care. 2017; 66:1-7.
- Shekar K, Roberts JA, Mcdonald CI, et al. Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care. 2012; 16(5):R194.
- Verkerk BS, Dzierba AL, Muir J, et al. Opioid and benzodiazepine requirements in obese adult patients receiving extracorporeal membrane oxygenation. Ann Pharmacother. 2020; 54(2):144-50.
- Landolf KM, Rivosecchi RM, Gomez H, et al. Comparison of hydromophone versus fentanyl-based sedation in extracorporeal membrane oxygenation: a propensity-matched analysis. Pharmacotherapy. 2020 May;40(5):389-397.
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