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