A Case for Ketofol in the Pediatric ED

Imagine it’s a warm day in June when an 18-month old male with a complicated facial laceration involving the oral mucosa from a dog bite presents to your emergency department (ED). His parents are requesting that his lacerations be repaired by a plastic surgeon.   You recognize their concern and are happy to oblige. You want to ensure the best outcome so you decide to do procedural sedation for the repair. You reach for your handy dandy procedural sedation hammer Ketamine. However, while your patient has obviously achieved a dissociative state, he seems to be periodically moving and tongue thrusting. Your consultant is not very pleased at that thought of attempting a delicate repair on a moving child. What can be done?

 

Ketamine

Ketamine is a dissociative anesthetic that has been increasing in popularity as an ED procedural sedation agent since the 1990s1-3. Ketamine is best utilized for short painful procedures such as orthopedic reduction, abscess drainage, laceration repair or burn debridement. A common loading dose of ketamine for the pediatric patient is 1.5 mg/kg – 2mg/kg if given IV. Subsequent doses of 0.5 mg/kg – 1 mg/kg of ketamine can be given to maintain a dissociative state. Intravenous ketamine should be administered slowly over 30-60 seconds to avoid respiratory depression and apnea that has been associated with rapid administration. Ketamine can also be given IM if a procedure is short and an IV unnecessary or if the patient is unable to safety cooperate with IV placement. IM ketamine dosing is generally 4 mg/kg – 5 mg/kg. IM ketamine has been associated with increased rates of vomiting. A recent review of literature suggests that Ketamine is widely utilized, consistently effective for procedural sedation and has a low risk of adverse events when administered by an experienced clinician5. On the con side, Ketamine has a relatively long recovery time with one study citing an average of 64 minutes4.

 

Propofol

There are a few studies that examine the use of propofol in the pediatric ED primarily for non painful procedures or in conjunction with opiates for painful procedures. Propofol is a short acting non-opioid, non-barbiturate sedative hypnotic agent that has been gaining momentum outside the operating room. Propofol is contraindicated in patients with egg or soy allergies.

Current guidelines favor an induction dose of 1 mg/kg over 1-2 minutes with repeated aliquots of 0.5 mg/kg over 30-60 seconds until a relatively motionless state is achieved. Key benefits of propofol are its anti-emetic properties and its shorter recovery time and sedation time compared to similar sedatives 6-8. Important side effects of propfol are respiratory depression and hypotension. Propofol can be painful when injected which is why some studies suggest injecting a small amount of lidocaine into the vein 9.

 

Ketofol

The combination of ketamine and propofol, aka “ketofol,” was initially described in the surgical setting in the early 1990s. Ketofol has an advantage over ketamine alone with literature showing improved airway preservation, decreased vomiting and decreased need for opioids The combination also maintains more stable cardiovascular profile with fewer incidence of hypotension compared to propofol alone2. While no standard dosing regime has been established several articles use a 1:1 ratio2,10-11. Some institutions prefer a 0.5 mg/kg dose of ketamine followed by a 1mg/kg dose of propofol for induction. Ketofol has also been consistently associated with a high patient and physician satisfaction level. There are no systematic reviews of ketofol and most of current reported literature comes in the form of case series.

 

An Argument for Ketofol in Complex Lacerations

 Now that we have reviewed some of the literature let’s return to our patient. When selecting an appropriate sedative, the practitioner must keep in mind the desired sedation depth, duration of procedure, how painful the procedure is and individual patient characteristics.   Additionally, an agent’s efficacy and safety profile compared to other medications must be considered 5.   Because of its unique pharmacological properties, ketamine does not display a dose dependent continuum like other analgesia agents.   Once a patient reaches dissociative threshold additional does of ketamine does not enhance or deepen the sedation3. Complex facial lacerations especially those involving intraoral or perioral repair provide a large stimuli load. I have found in these incidences that a dissociative state does not confer stillness especially in the toddler age. Why not just use propofol alone you might ask?   Sedation with propofol alone in children requires total dosing between 2.8 to 3.5 mg/kg to achieve the desired level of sedation 10,12. The rate of adverse airway events with propofol are known to be dose-dependent. While larger studies are needed, one case series showed that the use of ketofol reduced the amount of propofol needed to achieve the desired level of sedation in pediatric patients13.   I therefore argue that when faced with a complex facial laceration in a younger patient, one should consider ketofol.   With a better safety profile, faster recovery time and a high patient and provider level of satisfaction, ketofol may just be the shiny new hammer my tool belt.

 

Article By:

Katharine Long, MD

Pediatric Emergency Fellow

The Children’s Hospital of Philadelphia

 

References:

  1. Melendez E, Bachur R. Serious adverse events during procedure sedation with ketamine. Pediatr Emerg Care. 2009;25:325-328.
  2. Alletag MJ, Auerbach MA and Baum CR. Ketamine, Propofol, and Ketofol Use for Pediatric Sedation. Pediatr Emerg Care. 2012;28(12):1391-1395.
  3. Green SM, Roback MG, Kennedy RM et al Clinical Practice Guideline for Emergency Department Ketamine Dissociated Sedation: 2011 Update. Ann of Emerg Med. 2011;57(5):449-461.
  4. Sherwin TS, Green SM, Khan A, et al Does adjunctive midazolam reduce recover agitation after ketamine sedation for pediatric procedures? A randomized double-blind, placebo-controlled trial Ann Emerg Med. 2000; 35:229-238.
  5. Hartling L, Milne A, Foise M et al. what Works and What’s Safe in Pediatric Emergency Procedural Sedation: An Overview of Reviews.   Acad Emerg Med. 2016; 23:519-530.
  6. Migita RT, Klein EJ, Garrison MM. Sedation and analgesia for pediatric fracture reduction in the emergency department: a systematic review. Arch Pediatr Adolesc Med. 2006;160:46-51.
  7. National Clinical Guidelines Centre (UK). NICE Clinical Guidelines, No 112. Sedation in Children and Young People: Sedation for Diagnostic and Therapeutic Procedures in Children and Young People. London: Royal College of Physicians (UK), 2010.
  8. Pershad J & Godambe SA. Propofol for Procedural Sedation in the Pediatric Emergency Department. J Emerg Med. 2004; 27(1): 11-14.
  9. Jalota L, Kalira V, George E et al. Prevention of pain on injection of propofol: systematic review and meta-analysis. BMJ. 2011; 342:d1110.
  10. Anderson JL, Junkins E, Pribble C et al. Capnography and depth of sedation during propofol sedation in children. Ann Emerg Med. 2007;49:9-13
  11. Green SM Andolfatto G, Krauss B. Ketofol for procedural sedation? Pro and con. Ann Emerg Med. 2011;57:444-448.
  12. Guenther E, Pribble CG, Junkins EP Jr et al. Propofol sedation by emergency physicians for elective pediatric outpatient procedures. Ann Emerg Med. 2003;42:783-791.
  13. Mourad M, El-Hamamsy M, Anware M et al. Low dose ketamine reduces sedative doses of propofol during ambulatory transesophageal echocardiography. Egypt J Anaes. 2004:20:41-46.
  14. Shavit I, Bar-Yaakov N, Grossman L et al. Sedation for Children with Intraoral Injuries in the Emergency Department: A Case-Control Study. Pediatr Emerg Car 2014;30:805-807.

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