Fospropofol for sedation
Chris More, SRNAJeff Varga, SRNA
Properties
• Water soluble prodrug of propofol
• Sedative/hypnotic agent
• Indications:– MAC/sedation in adults
undergoing diagnostic or therapeutic procedures
Pharmacology
• Pharmacologically inactive• Hydrolyzed to propofol• GABA-ergic• Fospropofol 1.86mg = Propofol 1mg• Sedation-hypnotic effects
indistinguishable from propofol except: – More gradual onset– Longer duration
Dosing
• Initial dose: 6.5mg/kg– Onset: 40 seconds– Peak effect: 3-15 minutes– Duration: 20-45 minutes
• Supplemental dose: 1.5mg/kg– Frequency: 4 minutes
• Modified Dosing (>65yo or ASA 3-4):– Initial: 5mg/kg– Supplemental: 1mg/kg every 4 minutes
Advantages
• Less pain at injection site
• Less hyperlipidemia with long term administration
• Reduced risk of bacteremia
Disadvantages
• Paresthesia in perianal and perineal areas
• Pruritis
• Hypoxemia and hypotension
• Currently no research on cost analysis comparing fospropofol, propofol, versed
Research
• Sedation for Colonoscopy (Cohen et al.)– 314 patients >18 years (ASA I-III) were randomized to receive
fospropofol 2 mg/kg, fospropofol 6.5- mg/kg, or midazolam 0.02 mg/kg, after pretreatment with intravenous fentanyl 50 mcg
– Results• Sedation success was higher in the fospropofol 6.5 mg/kg
versus 2 mg/kg group (87% vs. 26%; P<0.001) and was 69% in the midazolam group
• Patients in the 6.5-mg/kg group were significantly less likely to remember being awake during the procedure (51% vs. 100% in the 2-mg/kg group, P<0.001; 60% for the midazolam group)
Research
• Sedation for Bronchoscopy (Silvestri et al.)– 252 patients, 150 were randomized to receive 6.5 mg/kg
fospropofol; 102 were randomized to receive 2 mg/kg fospropofol
– Results• Sedation success rates were 88.7% and 27.5%, respectively (p <
0.0001). Treatment success (91.3% vs 41.2%, respectively; p < 0.001), willingness to be treated again (94.6% vs 78.2%, respectively; p < 0.001), and absence of procedural recall (83.3% vs 55.4%, respectively; p < 0.001) were significantly better with the administration of 6.5 mg/kg fospropofol
• median time to full alertness was slightly longer for the 6.5 mg/kg dose (5.5 vs 3.0 min, respectively).
Research – Safety Evaluation• Sedation for minor surgical procedures (Gan et al.)
– 123 patients ≥18 years (ASA I-IV)
– Arthroscopy, AV shunt placement, bunionectomy, D & C, EGD, lithotripsy, TEE, and ureteroscopy.
• Pretreatment with fentanyl 50 μg• Initial bolus dose of fospropofol 6.5 mg/kg• Supplemental doses of 1.63 mg/kg• Procedural duration 4 mins – 45 mins
– Results• Need for alternative sedative medications during the procedure low (4.9% of pts)• Adverse events:
– Paresthesia (n = 77, 62.6%)– Pruritus (n = 34, 27.6%)– Hypotension (n = 4, 3.25%)– Bradycardia (n = 1, 0.8%)– Hypoxemia (n = 1, 0.8%)
• Fospropofol at an initial dose of 6.5 mg/kg is easily titrated to a target level of sedation for brief diagnostic and therapeutic procedures, and is associated with an acceptable safety and tolerability profile
Summary
• Safe
• Effective for minor surgical procedures
• Requires patience!
• Further research needed
• Experiences?
References• Cohen, L.B., Cattau, E., Goetsch, A., et al. A random, double-blind, phase 3 study of fospropofol
disodium for sedation during colonoscopy. Journal of Clinical Gastroenterology, 2010;44:345–353
• Gan, T.J., Berry, B.D., Ekman, E.F., et al. Safety evaluation of fospropofol for sedation during minor surgical procedures. Journal of clinical anesthesia, 2010;22:260-270
• Garnock-Jones, K. P., & Scott, L. J. (2010). Fospropofol. Drugs , 70 (4), 469-477
• Leslie, J. B. (2010). Fospropofol (lusedra) may be an alternative to propofol for monitored anesthesia. Anesthesia patient safety foundation newsletter , 25 (2), 21-44.
• Silvestri GA, Vincent BD, Wahidi MM, et al. A phase 3, randomized, double-blind study to assess the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy. Chest 2009 Jan; 135 (1): 41-7
• US FDA. Center for drug evaluation and research summary review for application number 22-244, (fospropofol) [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022244s000_SumR.pdf