1. Fospropofol for sedation
Chris More, SRNA
Jeff Varga, SRNA

2. Properties Water soluble prodrug of propofol Sedative/hypnotic agent
Indications:
MAC/sedation in adults undergoing diagnostic or therapeutic procedures

3. 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
Pharmacologically inactive phosphate prodrug of propofol, hydrolyzed by alkaline phosphatases to liberate propofol.
Exerts its effect through the potentiation of the GABA receptor
Fospropofol disodium 1.86mg is the molar equivalent of propofol 1mg
In comparison to the rapid rise and fall in plasma propofol concentrations observed after administration of propofol lipid emulsion, fospropofol disodium produces a smooth and gradual increase and decrease in therapeutic plasma propofol concentrations

4. Dosing Initial dose: 6.5mg/kg Supplemental dose: 1.5mg/kg
Onset: 40 seconds
Peak effect: 3-15 minutes
Duration: 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
Because of the high variability between patients in the rate of conversion of fospropofol into propofol, its difficult to anticipate the peak effect and duration of this drug
This can cause providers to stack doses and get an over anesthetized patient, requiring airway or hemodynamic intervention
Studies show re-dosing should occur no sooner than every 4 minutes
Modified dosing for patients over 65 years old, or those with severe systemic disease ASA 3-4

5. Advantages Less pain at injection site
Less hyperlipidemia with long term administration
Reduced risk of bacteremia

6. Disadvantages Paresthesia in perianal and perineal areas Pruritis
Hypoxemia and hypotension
Currently no research on cost analysis comparing fospropofol, propofol, versed
Paresthesias
(burning, stinging, or tingling
sensations) generally occurred in
the perianal and perineal regions
and were usually described as mild
to moderate in intensity, were transient
and self-limited, generally
occurred within 5 minutes after
administration of the initial dose,
and typically lasted 1 to 2 minutes

7. 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)

8. 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 < ). 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).

9. 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
Hypotension occurred during the dosing and recovery periods of the procedure but was considered to be related to fospropofol in only three of these patients. The hypotension resolved with treatment of atropine (n = 1), ephedrine (n = 1), and normal saline (n = 1). One case of hypotension occurred after administration of propofol in a patient not adequately sedated with fospropofol. Concurrently with hypotension, one patient experienced bradycardia, which resolved with atropine. Hypoxemia (less than one min) was reported in one patient (the hysteroscopy patient described above) and was managed with airway assistance (chin lift and verbal stimulation). No patient experienced apnea on the day of the procedure.
The need for alternative sedative medications during the procedure was also low (4.9% of pts)

10. Summary Safe Effective for minor surgical procedures
Requires patience!
Further research needed
Experiences?

11. 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:
Garnock-Jones, K. P., & Scott, L. J. (2010). Fospropofol. Drugs , 70 (4),
Leslie, J. B. (2010). Fospropofol (lusedra) may be an alternative to propofol for monitored anesthesia. Anesthesia patient safety foundation newsletter , 25 (2),
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 , (fospropofol) [online]. Available from URL: