George Abdallah, PharmD, BCCCP, BCCP
Clinical Pharmacist IV - Critical Care
Beth Israel Deaconess Medical Center, United States
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Title: A Case of Paralytic Tachyphylaxis and ECMO
Case Report Body:
Introduction: Critically ill adult patients requiring extracorporeal membrane oxygenation (ECMO) with prolonged paralytic exposure may develop potential tachyphylaxis. This phenomenon has yet to be described within the ECMO literature.
Description: A 49-year-old male (70 kg) with hyperlipidemia and recently diagnosed COVID19, was admitted to the ICU for acute respiratory distress syndrome, intubated and paralyzed, and subsequently initiated on VV ECMO. By day 20, his sedation and paralytic regimen consisted of the following: hydromorphone 6 mg/hr, midazolam 12 mg/hr, phenobarbital IV 120 mg twice daily, and cisatracurium 12 mcg/kg/min, which was gradually increased from 5 mcg/kg/min from the previous 7 days. Propofol use was limited because of hypertriglyceridemia. Despite this, he was dyschronous with the ventilator and had 4/4 twitches on a train of four (TOF), with stable hemodynamics. A recommendation was made to stop cisatracurium and switch to rocuronium given concern for paralytic tachyphylaxis. The cisatracurium drip was stopped and the patient was loaded with a 1.2 mg/kg (85 mg) rocuronium bolus using total body weight (TBW), followed by an 8 mcg/kg/min infusion. After 24 hours of use, the patient was more synchronous, had 0/4 twitches on a TOF, and did not require any escalation in the rocuronium infusion rate. This effect persisted for several days thereafter.
Discussion: This case highlights the phenomenon of paralytic tachyphylaxis in the ECMO population and sheds light on pharmacokinetic (PK) considerations. While the specific mechanism of resistance is not clearly understood, case reports in non-ECMO patients suggest that the likelihood of tachyphylaxis increases with high doses (>12 mcg/kg/min) and prolonged use ( > 7 days). Management included stopping the initial paralytic and switching to an alternative agent. Rocuronium is a hydrophilic drug with limited protein binding. Given this PK profile, we anticipated that the degree of sequestration in the ECMO circuit would be relatively low. Following our experience, we concluded that the switch to rocuronium was safe and effective in minimizing tachyphylaxis. Dosing of rocuronium may be similar to non-ECMO patients and should be guided by ventilator synchrony and TOF monitoring.