Fospropofol for sedation

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Fospropofol for sedation
Chris More, SRNA Jeff Varga, SRNA
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Properties

• Water soluble prodrug of propofol
• Sedative/hypnotic agent
• Indications
• MAC/sedation in adults undergoing diagnostic or
  therapeutic procedures

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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

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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 (gt65yo or ASA 3-4)
• Initial 5mg/kg
• Supplemental 1mg/kg every 4 minutes

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Advantages

• Less pain at injection site
• Less hyperlipidemia with long term administration
• Reduced risk of bacteremia

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Disadvantages

• Paresthesia in perianal and perineal areas
• Pruritis
• Hypoxemia and hypotension
• Currently no research on cost analysis comparing
  fospropofol, propofol, versed

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Research

• Sedation for Colonoscopy (Cohen et al.)
• 314 patients gt18 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
  Plt0.001) 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, Plt0.001 60 for the midazolam group)

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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 lt 0.0001). Treatment success
  (91.3 vs 41.2, respectively p lt 0.001),
  willingness to be treated again (94.6 vs 78.2,
  respectively p lt 0.001), and absence of
  procedural recall (83.3 vs 55.4, respectively
  p lt 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).

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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

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Summary

• Safe
• Effective for minor surgical procedures
• Requires patience!
• Further research needed
• Experiences?

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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, 201044345353
• 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, 201022260-270
• 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