Propofol vs Dexmedetomidine

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1 Propofol vs Dexmedetomidine A highlight of similarities & differences Lama Nazer, PharmD, BCPS Critical Care Clinical Pharmacy Specialist King Hussein Cancer Center

2 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

3 Pharmacology Pharmacologic Properties Sedative Propofol (Diprivan ) Sedative Dexmedetomidine (Precedex ) Mechanism of Action Not well-known Stimulates GABA-receptors Alpha-2 agonist

4 Pharmacology Pharmacologic Properties Sedative Propofol (Diprivan ) Dexmedetomidine (Precedex ) Sedative Analgesic effects Mechanism of Action Not well-known Stimulates GABA-receptors Alpha-2 agonist

5 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.

6 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

7 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 hours

8 Pharmacokinetics Propofol Diprivan Package Insert, Fresenius, Feb 2014

9 Pharmacokinetics Dexmedetomidine Lirola T, et al. Pharmacokinetics of prolonged infusion of high dose dexmedetomidine in critically ill patients. Critical Care 2011.

10 Efficacy

11 Efficacy Medical & Surgical ICU patients Within the first 72 hrs of ICU and expected sedation need 24 hrs

12 Efficacy Dexmedetomidine Standard Therapy (propofol or midazolam) Target RASS achieved, % time 64% 63% P=NS

13 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)

14 Efficacy

15 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.

16 Efficacy-PRODEX Study % time at target sedation

17 Efficacy-PRODEX Study Total dose of rescue sedation % time at target sedation Dexmedetomidine was not inferior to propofol in maintaining light-moderate sedation.

18 Efficacy-PRODEX STUDY

19 Efficacy: Clinical Outcomes Mechanical Ventilation ICU Length of stay Delirium Mortality

20 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

21 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

22 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 JOD for 200 mcg vial* 148 JOD per day *Cost based on JFDA pricing *Cost based on JFDA pricing

23 Indirect Cost Mechanical Ventilation ICU Length of stay Delirium Mortality

24 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.

25 Thank You

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