use morphine instead of fentanyl for ECMO sedation

A common issue in the management of patients receiving ECMO is drug sequestration within the ECMO circuit. This unique pharmacodynamic feature of ECMO leads to an increased volume of distribution, which in turn leads to decreased concentration of the administered drugs within the patient’s plasma. This sequestration has the greatest effect on lipophilic drugs, which can adhere to the circuit tubing, and protein-bound drugs, which are retained within the membrane oxygenator.

Observational studies suggest that patients receiving ECMO receive higher doses of analgesic and sedative agents as compared with other critically ill patients. While this observation has multiple causes and explanations, one likely and important contributor is the sequestration of drugs used for analgesia and sedation within the ECMO circuit. Studies that measure drug clearance in ex-vivo ECMO models provide evidence about which drugs are affected by circuit sequestration. In these studies, morphine is not meaningfully sequestered, while fentanyl, midazolam, and dexmedetomidine all demonstrate major reduction in concentration across the ECMO circuit. These experimental findings are compatible with the known properties of the drugs, with fentanyl and midazolam both being highly lipophilic, while morphine is not. Dexmedetomidine is both lipophilic and highly protein bound, which, again, is consistent with findings that it is highly sequestered within ECMO circuits.

Despite these mechanistic insights, the optimal approach to analgesia and sedation in the context of ECMO remains a matter of investigation. Whether tolerating higher doses of lipophilic medications or using alternate agents is associated with better outcomes in patients supported with ECMO remains unknown. While morphine may not be sequestered within ECMO circuits, it also has an active metabolite with potential for causing prolonged effects and oversedation in the setting of acute kidney injury. Morphine has also been associated with greater histamine release compared with other opioids, which may lead to hypotension, pruritus, and bronchospasm.123456

Footnotes

  1. SEEK Questionnaires ↩

  2. Dean M. Opioids in renal failure and dialysis patients. J Pain Symptom Manage. 2004;28(5):497-504. PubMed ↩

  3. Dzierba AL, Abrams D, Brodie D. Medicating patients during extracorporeal membrane oxygenation: the evidence is building. Crit Care. 2017;21(1):66. PubMed ↩

  4. Lemaitre F, Hasni N, Leprince P, et al. Propofol, midazolam, vancomycin and cyclosporine therapeutic drug monitoring in extracorporeal membrane oxygenation circuits primed with whole human blood. Crit Care. 2015;19(1):40. PubMed ↩

  5. 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. PubMed ↩

  6. Wagner D, Pasko D, Phillips K, Waldvogel J, Annich G. In vitro clearance of dexmedetomidine in extracorporeal membrane oxygenation. Perfusion. 2013;28(1):40-46. PubMed ↩