Ketamine Versus Co-administration of Ketamine and Propofol for Procedural Sedation in a Pediatric Emergency Department

Brief Summary

Official Title: “Comparison of Ketamine Versus Co-Administration of Ketamine and Propofol for Procedural Sedation in a Pediatric Emergency Department”

The purpose of this study is to compare the effectiveness of the co-administration of intravenous ketamine and propofol to intravenous ketamine as a single agent for procedural sedation in the pediatric emergency department. The investigators hypothesize that patients receiving co-administration of ketamine and propofol will have a lower rate of adverse events, compared to patients receiving ketamine for procedural sedation.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment
  • Study Primary Completion Date: June 2013

Detailed Clinical Trial Description

Procedural sedation and analgesia (PSA) is a frequent occurrence in pediatric emergency departments. The goals of PSA include maximizing analgesia and amnesia, and minimizing adverse events while ensuring stable cardiopulmonary function. For decades, ketamine has been the main pharmacologic agent used for pediatric PSA. Numerous studies support the use of ketamine for sedation, amnesia, and analgesia on children undergoing painful procedures in the emergency department setting. Research has continually shown ketamine to cause emergence phenomenon, laryngospasm and vomiting.

Propofol is a sedative-hypnotic widely used for procedural sedation in adult emergency departments. The advantages of propofol include rapid onset, with quick and predictable recovery time, and antiemetic effects. Disadvantages include dose-dependent hypotension, bradycardia, respiratory depression, as well as pain with injection. In addition, propofol does not provide any analgesia.

Ketamine and propofol administered together have been successfully utilized in a variety of settings, including dermatologic, cardiovascular, and interventional radiological procedures in children. The co-administration of ketamine and propofol has been shown to preserve sedation while minimizing the respective adverse events. When used in combination, doses administered of each can be reduced, while producing a more stable hemodynamic and respiratory profile. Furthermore, this combination may reduce the frequency of emergence reactions, vomiting, and the pain of propofol injection.

To date, there are no randomized controlled trials evaluating the co-administration of ketamine and propofol versus ketamine monotherapy for PSA in the Pediatric Emergency Department.

Interventions Used in this Clinical Trial

  • Drug: Ketamine
    • 1.0 milligrams/kilogram (mg/kg) ketamine with additional doses of 0.5 mg/kg ketamine as needed (maximum single dose based on 100 kilogram (kg) person)
  • Drug: Ketamine Co-administered with Propofol
    • 0.5 mg/kg ketamine and 0.5 mg/kg propofol with additional doses of 0.25 mg/kg ketamine and 0.25 mg/kg propofol as needed (maximum single dose based on 100 kg person)

Arms, Groups and Cohorts in this Clinical Trial

  • Active Comparator: Ketamine Alone
  • Experimental: Ketamine Co-Administered with Propofol

Outcome Measures for this Clinical Trial

Primary Measures

  • Frequency of Adverse Events
    • Time Frame: From enrollment through completion of follow-up, up to 7 days
      Safety Issue?: Yes

Secondary Measures

  • Recovery Time
    • Time Frame: Once Vancouver Sedation Recovery Scale Score reaches 18 or greater, on average less than 1 hour
      Safety Issue?: No
  • Efficacy of Sedation
    • Time Frame: After procedure is completed, on average less than 1 hour
      Safety Issue?: No
  • Levels of Ketamine and Propofol in the blood measured in nanograms per milliliter (ml)
    • Time Frame: Baseline
      Safety Issue?: No
  • Putative functional polymorphisms in genes that influence inter-individual variability in ketamine and propofol pharmacokinetics
    • Time Frame: Baseline
      Safety Issue?: No
  • Parent satisfaction
    • Time Frame: Once Vancouver Sedation Recovery Scale Score reaches 18 or greater, on average less than 1 hour
      Safety Issue?: No
  • Patient Satisfaction
    • Time Frame: Once Vancouver Sedation Recovery Scale Score reaches 18 or greater, on average less than 1 hour
      Safety Issue?: No
  • Physician Performing Procedure Satisfaction
    • Time Frame: After procedure is completed, on average less than 1 hour
      Safety Issue?: No
  • Nurse Satisfaction
    • Time Frame: After procedure is completed, on average less than 1 hour
      Safety Issue?: No
  • Levels of Ketamine and Propofol in the blood measured in nanograms per ml
    • Time Frame: 5 minutes
      Safety Issue?: No
  • Levels of Ketamine and Propofol in the blood measured in nanograms per ml
    • Time Frame: 15 minutes
      Safety Issue?: No
  • Levels of Ketamine and Propofol in the blood measured in nanograms per ml
    • Time Frame: 30 minutes
      Safety Issue?: No
  • Levels of Ketamine and Propofol in the blood measured in nanograms per ml
    • Time Frame: 60 minutes
      Safety Issue?: No
  • Putative functional polymorphisms in genes that influence inter-individual variability in ketamine and propofol pharmacokinetics
    • Time Frame: 5 minutes
      Safety Issue?: No
  • Putative functional polymorphisms in genes that influence inter-individual variability in ketamine and propofol pharmacokinetics
    • Time Frame: 15 minutes
      Safety Issue?: No
  • Putative functional polymorphisms in genes that influence inter-individual variability in ketamine and propofol pharmacokinetics
    • Time Frame: 30 minutes
      Safety Issue?: No
  • Putative functional polymorphisms in genes that influence inter-individual variability in ketamine and propofol pharmacokinetics
    • Time Frame: 60 minutes
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

Inclusion Criteria

  • Ages > 3 years and < 21 years
  • American Society of Anesthesiologists (ASA) class I or II
  • Fracture or dislocation requiring reduction under procedural sedation with ketamine as deemed by the attending emergency medicine physician
  • Parent/Legal Guardian or Patient (if 18 years of age or older) has already given verbal consent for procedural sedation as part of standard care for their condition

Exclusion Criteria

  • Hypertension (Blood Pressure > 95th percentile for age)
  • Glaucoma or acute globe injury
  • Increased intracranial pressure or central nervous system mass lesion
  • Porphyria
  • Previous allergic reaction to ketamine
  • Previous allergic reaction to Propofol or its components including soybean oil, glycerol, egg lecithin, and disodium edentate
  • Disorders of lipid metabolism including primary hyperlipoproteinemia, diabetic hyperlipemia, or pancreatitis
  • Mitochondrial myopathies or disorders of electron transport
  • Pregnancy
  • Parent, guardian or patient unwilling/unable to provide informed consent/assent

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 3 Years

Maximum Age for this Clinical Trial: 21 Years

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • University of Colorado, Denver
  • Collaborator
    • Colorado Clinical & Translational Sciences Institute
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Lalit Bajaj, MD, MPH, Principal Investigator, University of Colorado, Denver
    • Keith Weisz, MD, Principal Investigator, University of Colorado, Denver

References

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Wathen JE, Roback MG, Mackenzie T, Bothner JP. Does midazolam alter the clinical effects of intravenous ketamine sedation in children? A double-blind, randomized, controlled, emergency department trial. Ann Emerg Med. 2000 Dec;36(6):579-88.

Akin A, Esmaoglu A, Guler G, Demircioglu R, Narin N, Boyaci A. Propofol and propofol-ketamine in pediatric patients undergoing cardiac catheterization. Pediatr Cardiol. 2005 Sep-Oct;26(5):553-7.

Akin A, Esmaoglu A, Tosun Z, Gulcu N, Aydogan H, Boyaci A. Comparison of propofol with propofol-ketamine combination in pediatric patients undergoing auditory brainstem response testing. Int J Pediatr Otorhinolaryngol. 2005 Nov;69(11):1541-5. Epub 2005 Jun 3.

Akin A, Guler G, Esmaoglu A, Bedirli N, Boyaci A. A comparison of fentanyl-propofol with a ketamine-propofol combination for sedation during endometrial biopsy. J Clin Anesth. 2005 May;17(3):187-90.

Barbi E, Marchetti F, Gerarduzzi T, Neri E, Gagliardo A, Sarti A, Ventura A. Pretreatment with intravenous ketamine reduces propofol injection pain. Paediatr Anaesth. 2003 Nov;13(9):764-8.

Sharieff GQ, Trocinski DR, Kanegaye JT, Fisher B, Harley JR. Ketamine-propofol combination sedation for fracture reduction in the pediatric emergency department. Pediatr Emerg Care. 2007 Dec;23(12):881-4.

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 Jan;49(1):23-30. Epub 2006 Oct 23.

Cravero JP, Beach ML, Blike GT, Gallagher SM, Hertzog JH; Pediatric Sedation Research Consortium. The incidence and nature of adverse events during pediatric sedation/anesthesia with propofol for procedures outside the operating room: a report from the Pediatric Sedation Research Consortium. Anesth Analg. 2009 Mar;108(3):795-804.

American Academy of Pediatrics; American Academy of Pediatric Dentistry; Coté CJ, Wilson S; Work Group on Sedation. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: an update. Pediatrics. 2006 Dec;118(6):2587-602.

Bhatt M, Kennedy RM, Osmond MH, Krauss B, McAllister JD, Ansermino JM, Evered LM, Roback MG; Consensus Panel on Sedation Research of Pediatric Emergency Research Canada (PERC) and the Pediatric Emergency Care Applied Research Network (PECARN). Consensus-based recommendations for standardizing terminology and reporting adverse events for emergency department procedural sedation and analgesia in children. Ann Emerg Med. 2009 Apr;53(4):426-435.e4. Epub 2008 Nov 20.

Macnab AJ, Levine M, Glick N, Phillips N, Susak L, Elliott M. The Vancouver sedative recovery scale for children: validation and reliability of scoring based on videotaped instruction. Can J Anaesth. 1994 Oct;41(10):913-8.

Bieri D, Reeve RA, Champion GD, Addicoat L, Ziegler JB. The Faces Pain Scale for the self-assessment of the severity of pain experienced by children: development, initial validation, and preliminary investigation for ratio scale properties. Pain. 1990 May;41(2):139-50.

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