Propofol vs Dexmedetomidine A highlight of similarities & differences Lama Nazer, PharmD, BCPS Critical Care Clinical Pharmacy Specialist King Hussein Cancer Center
Outline Highlight similarities and differences between propofol & dexmedetomidine in: Pharmacology and Pharmacokinetics Efficacy Safety profile Cost This presentation only be a highlight! Focus on the sedation in mechanically ventilated patients
Pharmacology Pharmacologic Properties Sedative Propofol (Diprivan ) Sedative Dexmedetomidine (Precedex ) Mechanism of Action Not well-known Stimulates GABA-receptors Alpha-2 agonist
Pharmacology Pharmacologic Properties Sedative Propofol (Diprivan ) Dexmedetomidine (Precedex ) Sedative Analgesic effects Mechanism of Action Not well-known Stimulates GABA-receptors Alpha-2 agonist
Pharmacology Pharmacologic Properties Sedative Propofol (Diprivan ) Dexmedetomidine (Precedex ) Sedative Analgesic properties Mechanism of Action Not well-known Stimulates GABA-receptors Alpha-2 agonist Indications Sedation in mechanically ventilated patients Sedation in mechanically ventilated patients, not to exceed 24 hrs Sedation of non-intubated patients.
Pharmacokinetics Propofol (Diprivan ) Dexmedetomidine (Precedex ) Onset of action < 1 mintue 5-10 minutes Metabolism Hepatic (inactive metabolites) Hepatic (inactive metabolites) Clearance Kidney Kidney Half-life 4 hours 2 hours
Pharmacokinetics: Long-Term Infusions Propofol (Diprivan ) Dexmedetomidine (Precedex ) Onset of action < 1 minute 5-10 minute Metabolism Hepatic (inactive metabolites) Hepatic (inactive metabolites) Clearance Kidney Kidney Half -life 4 hours 2 hours 1-3 days 2.9-4.4 hours
Pharmacokinetics Propofol Diprivan Package Insert, Fresenius, Feb 2014
Pharmacokinetics Dexmedetomidine Lirola T, et al. Pharmacokinetics of prolonged infusion of high dose dexmedetomidine in critically ill patients. Critical Care 2011.
Efficacy
Efficacy Medical & Surgical ICU patients Within the first 72 hrs of ICU and expected sedation need 24 hrs
Efficacy Dexmedetomidine Standard Therapy (propofol or midazolam) Target RASS achieved, % time 64% 63% P=NS
Efficacy Dexmedetomidine Standard Therapy (propofol or midazolam) Target RASS achieved, % time 64% 63% P=NS Target RASS 0 to -3, %time (light to moderate sedation) 74% 64% P=NS Target RASS -4, % time (deep sedation) 42% 62% (P=0.006)
Efficacy
Efficacy-PRODEX Study Objective: to determine the efficacy of dexmedetomidine, compared to propofol in maintaining sedation in MV patients and on the duration of MV. Multicenter, randomized, double-blinded. Inclusion: adult ICU patients receiving mechanical ventilation who needed light to moderate sedation >24 hrs.
Efficacy-PRODEX Study % time at target sedation
Efficacy-PRODEX Study Total dose of rescue sedation % time at target sedation Dexmedetomidine was not inferior to propofol in maintaining light-moderate sedation.
Efficacy-PRODEX STUDY
Efficacy: Clinical Outcomes Mechanical Ventilation ICU Length of stay Delirium Mortality
Safety Propofol (Diprivan ) Dexmedetomidine (Precedex ) Respiratory depression Triglyceride/ pancreatitis Propofol-infusion syndrome (cardiac failure, rhabdomyolysis, metabolic acidosis, renal failure) Not reported Not reported Not reported
Safety Propofol (Diprivan ) Dexmedetomidine (Precedex ) Respiratory depression Triglyceride/ pancreatitis Propofol-infusion syndrome Hemodynamic changes Hypotension Bradycardia Not reported Not reported Not reported Hemodynamic changes Hypotension Bradycardia
Cost Propofol (Diprivan ) 50 mcg/kg/min Dexmedetomidine (Precedex ) 0.7 mcg/kg/hr 3.7 JOD for 1% 20 ml propofol* 90 JOD per day 24.61 JOD for 200 mcg vial* 148 JOD per day *Cost based on JFDA pricing *Cost based on JFDA pricing
Indirect Cost Mechanical Ventilation ICU Length of stay Delirium Mortality
Summary Dexmedetomidine is a sedative with analgesic properties. The PK of dexmedotomidine & propofol change with prolonged use. Dexmedetomidine is not-inferior to propofol for light-moderate sedation. The impact of dexmedetomidine on clinical outcomes is unclear: time on mechanical ventilation, ICU length of stay, delirium Safety: hemodynamic adverse effects have been reported with both drugs. The direct cost associated with dexmedetomidine is higher than propofol.
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