Caleigh Curran, PharmD, BCPS, BCCCP
Critical Care Pharmacist
North Shore Medical Center
Salem, Massachusetts
Disclosure information not submitted.
George Abdallah, PharmD, BCCCP, BCCP
Clinical Pharmacist IV - Critical Care
Beth Israel Deaconess Medical Center, United States
Disclosure information not submitted.
Title: The Use of Phenobarbital in ECMO
Case Report Body:
Introduction: A high prevalence of critically ill patients have difficulty obtaining an appropriate level of sedation. Additional challenges may arise in patients requiring extracorporeal membrane oxygenation (ECMO). The utility of phenobarbital, a barbiturate sedative hypnotic that produces sedation through GABAA receptor agonism, in adult ECMO patients has yet to be described within the literature.
Description: A 46-year-old male (95 kg) with asthma, hyperlipidemia and recently diagnosed COVID19, was admitted to the ICU for acute hypoxic respiratory failure and subsequently initiated on VV ECMO. By day 13, his sedation regimen consisted of the following: hydromorphone 12 mg/hr, midazolam 15 mg/hr, ketamine 1.4 mg/kg/hr and dexmedetomidine 1.4 mcg/kg/min, along with oral diazepam 15 mg every 6 hours. Propofol use was limited because of hypertriglyceridemia. Despite this, he was dyschronous with the ventilator. A recommendation was made to use phenobarbital. The patient was loaded with 10 mg/kg using ideal body weight (IBW), followed by 1 mg/kg twice daily. At steady state, a serum level was checked and resulted at 10.8 ug/mL. Simultaneously, the patient was more synchronous and did not require any escalation in sedation. Following a decompensatory event, a repeat bolus of 5 mg/kg IBW was given, followed by a 2 mg/kg twice daily regimen. A second steady state level was checked and resulted at 16.7 ug/mL.
Discussion: This case highlights the potential role for phenobarbital in ECMO patients refractory to conventional sedation, and sheds light on pharmacokinetic (PK) considerations. Phenobarbital is a relatively lipophilic drug with a LogP value of 1.47 and limited protein binding (48% protein bound). Given this PK profile, we anticipated that the degree of sequestration in the ECMO circuit would be low. We performed therapeutic drug monitoring and obtained serum levels at steady state and compared the findings to non-ECMO patients. Although no optimal phenobarbital level for sedation has been defined, extrapolation from therapeutic levels for epilepsy (15-40 ug/mL) was made. Based on our results, we concluded that limited drug sequestration occurred within the circuit and no dosing adjustment may be needed. The standard dose may be similar to non-ECMO patients and should be guided by therapeutic drug monitoring.