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Ketofol USE in the ED. By Carmen Lau Pharmacy Year 4 December 27 th , 2013. Procedural sedation and analgesia (PSA). Definition: A technique of administering sedatives w/ or w/o analgesics to induce a state that allows for unpleasant procedures, also referred to as conscious sedation

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ketofol use in the ed

Ketofol USE in the ED

By Carmen Lau

Pharmacy Year 4

December 27th, 2013

procedural sedation and analgesia psa
Procedural sedation and analgesia (PSA)

Definition: A technique of administering sedatives w/ or w/o analgesics to induce a state that allows for unpleasant procedures, also referred to as conscious sedation

Procedures

  • Setting fractures
  • Draining abscesses
  • Reducing dislocations
  • Endoscopy
  • Cardioversion
  • TEE and other imaging
procedural sedation and analgesia psa1
Procedural sedation and analgesia (PSA)
  • The ideal drug
    • Easily titrated
    • Rapid onset
    • Brief duration of action
    • Provides adequate sedation and analgesia
    • Minimal respiratory and hemodynamic effects
propofol use in psa
Propofol use in PSA

Pro’s

  • Rapid onset, short duration of action, antiemetic effects

Con’s

  • Use limited to dose-dependent respiratory depression and hypotension
  • Lack of analgesic effect: often co-administered with opioids but the combination increases likelihood of adverse airway events
ketamine in psa
Ketamine in PSA

Pro’s

  • Preservation of airway reflexes
  • CV and respiratory stimulation
  • Analgesia

Con’s

  • Longer recovery time
  • Recovery agitation and vomiting
better together
Better together?

Physically compatible when mixed in a single polypropylene syringe and stable at room temperature with exposure to light

the case
The case

23yo 60kg F is brought to the ED with a dislocated left shoulder after a MVC. The physician decides to use ketofol for the procedure and asks you, the pharmacist, for help dosing the medication. How are you going to prepare this medication?

Chem 7: Na 139, K 4.2, Cl 109, CO2 22, BUN 30, SCr 0.70, Glu 126

CBC: pending

VS: HR 98, RR 22, Temp 37.6, BP 122/88

the case cont
The case cont.

23yo 60kg F is brought to the ED with a dislocated left shoulder. The physician decides to use ketofol for the procedure.

Chem 7: Na 139, K 4.2, Cl 109, CO2 22, BUN 30, SCr 0.70, Glu 126

CBC: pending

VS: HR 98, RR 22, Temp 37.6, BP 122/88

You start to prepare ketofol at a 1:1 mixture of ketamine 10mg/ml and propofol 10mg/ml in a 10ml syringe. How much are you going to draw up, and how is the physician supposed to administer it?

administration
Administration

Approach 1 (Andolfatto et al.)

  • Initial dose= 0.375mg/kg of each ketamine and propofoladministered during 15-30sec
  • Every minute thereafter, the physician assesses the pt’s level of sedation and administers 0.188mg/kg of each drug if needed until sedation

Approach 2

  • Administer 1-3ml aliquots of 1:1 ketamine 10mg/ml and propofol 10mg/ml at the physician’s discretion
how to gauge sedation
How to gauge sedation?
  • Physician assessment
    • Loss of lid reflexes, verbal response, tactile stimuli
  • Ramsay Sedation Scale <5
  • Bispectral index (BIS)
    • Neurophysiological monitoring device that analyzes a pt’s electroencephalogram
    • Mostly used to assess deep anesthesia but is now studied in the ED
the case cont1
The case cont.

23yo 60kg F is brought to the ED with a dislocated left shoulder. The physician decides to use ketofol for the procedure.

Chem 7: Na 139, K 4.2, Cl 109, CO2 22, BUN 30, SCr 0.70, Glu 126

CBC: pending

VS: HR 98, RR 22, Temp 37.6, BP 122/88

  • You mix 30mg (3ml) of ketamine and 30mg (3ml) of propofol in a syringe
  • The physician gives 3ml of the mixture (0.25mg/kg of each drug) initially, followed in 1min by the remainder 3ml
  • Adequate sedation was not reaches, so more ketofol was prepared and the physician gives another 3ml
the case cont2
The case cont.
  • A total of 9ml of the 1:1 mixture was administered
    • 9ml= 45mg of each drug
    • 45mg/60kg= 0.75mg/kg of each drug

Remember that the median dose for the Willman et al. ketofol case series was 0.75mg/kg!!!

the case cont3
The case cont.

The shoulder reduction was successful and the physician thanks you for your help. BP only dropped to 114/80 during the procedure. The patient will be discharged in about 1 hour after she recovers.

The physician really likes ketofol, but wonders how it compares to other PSA agents. You tell him that…

ketofol vs p ropofol case series
Ketofol vs Propofol Case Series
  • Phillips et al. 2010
    • Prospective randomized case series of 28 patients >21yo
    • Propofol 0.5-1.5mg/kg vs. ketofol 0.75mg/kg
    • Measured procedural success, BIS score, adverse effects, recovery time, and VS
  • Results
  • Smaller % decline in SBP with ketofol (1.6% vs 12.5%)
  • Smaller difference between baseline and goal sedation BIS score with ketofol (18.78 vs 34.64)
  • Lower mean propofol dose with ketofol (92.5mg vs 177.27mg)
  • No respiratory depression in either group
ketofol vs propofol recap
Ketofol vs Propofol Recap
  • SBP
    • Less SBP % decrease with ketofol
  • Respiratory Depression
    • Similar if not fewer incidence of adverse respiratory events with ketofol
  • Sedation depth
    • Greater consistency based on Ramsay Scale and Colorado Behavioral Numerical Pain Scale with ketofol
  • Satisfaction score
    • Similar if not higher with ketofol
  • Mean propofol dose
    • Conflicting data, with most studies indicating less propofol required with ketofol
are the benefits clinically relevant
Are the benefits clinically relevant?
  • Safe sedation can be achieved with just propofol
    • Induced hypotension is usually transient and self limiting
    • Using “extra” propofol doesn’t necessarily mean lengthened recovery time
    • No compelling evidence showing that ketofol greatly reduces respiratory depression compared to propofol
  • Ketamine works well alone if dissociative sedation is desired
  • Added complexity of administering 2 drugs and having to anticipate the side effects of both
  • It does not make sense pharmacokinetically to mix an ultrashort acting medication with another that isn’t
conclusion
Conclusion
  • Ketofol provides adequate procedural sedation and analgesia
  • Ketofol is safe and effective: recovery times are short and adverse events are limited
  • Compared to other PSA agents, ketofol may have ↓ hypotension, ↓ respiratory depression, ↑ sedation quality, and ↑ patient satisfaction
  • It is still not certain whether ketofol offers clinically relevant benefits over either agent alone
questions
Questions?

Unrelated fun fact: Photofrin is a drug that requires lasers!!!

references
References

Baker SN and Weant KA. Procedural Sedation and Analgesia in the Emergency Department. J Pharm Pract. 2011; 24(2): 189-195.

Green SM, Andolfatto G, Krauss B. Ketofol for Procedural Sedation? Pro and Con. Ann Emerg Med. 2011; 57(5): 444-448.

Willman EV, Andolfatto G. A Prospective Evaluation of “Ketofol” (Ketamine/Propofol Combination) for Procedural Sedation and Analgesia in the Emergency Department. Ann Emerg Med. 2007; 49(1): 23-30.

Andolfatto G, Willman E. A Prospective Case Series of Single-syringe Ketamine-Propofol (Ketofol) for Emergency Department Procedural Sedation and Analgesia in Adults. AcadEmerg Med. 2011; 18: 237-245.

Phillips W, Anderson A, Rosengreen M, et al. Propofol Versus Propofol/Ketamine for Brief Painful Procedures in the Emergency Department: Clinical and Bispectral Index Scale Comparison. J Pain Palliat Care Pharmacother. 2010; 24: 349-355.

Andolfatto G, Abu-Laban RB, Zed PJ, et al. Ketamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia: A Randomized Double-Blind Trial. 2012; 59: 504-512.

Nejati, A. Moharari S, Ashraf H, et al. Ketamine/Propofol Versus Midazolam/Fentanyl for Procedural Sedation and Analgesia in the Emergency Department: A Randomized, Prospective, Double-blind Trial. AcadEmerg Med. 2011; 18: 800-806.