Low Dose Ketamine Study on Opioid Tolerance and Hyperalgesia (KPSF)

Modulation of μ Opioid Receptor Mediated Analgesia, Tolerance and Hyperalgesia in Children and Adolescents

The purpose of this study is to:

1. Establish whether ketamine can decrease opioid consumption and modulate the onset of opioid tolerance and prevent opioid-induced hyperalgesia in pediatric subjects, ages 10 years to 18 years, undergoing posterior spinal fusion and instrumentation.

Study Overview

• Status: Completed
• Conditions: Idiopathic Scoliosis; Spondylolisthesis
• Intervention / Treatment: Drug: Normal Saline; Drug: Ketamine

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject is 10 to 18 years of age
2. The subject's American Society of Anesthesiologists physical status is ASA 1, 2 or 3 (see appendix I)
3. The subject is scheduled for elective posterior spinal fusion and instrumentation.
4. The subject's parent/legally authorized guardian has given written informed consent to participate

Exclusion Criteria:

1. The subject has a history or a family (parent or sibling) history of malignant hyperthermia
2. The subject is pregnant or nursing.
3. The subject has known significant renal disorders determined by medical history, physical examination or laboratory tests
4. The subject has a known or suspected allergy to morphine, remifentanil or ketamine
5. The subject is an ASA classification of 4 or greater (See Appendix I)
6. The subject is scheduled for a surgical sub-procedure (i.e. anterior spinal fusion)
7. The subject is unable to self-administer morphine using patient-controlled analgesia (PCA) pump
8. The subject had a recent opioid exposure (within 1 month of surgery)
9. The subject is obese (body mass index >30kg/m2)
10. The subject is planned for elective postoperative ventilation
11. The subject has a known ocular disease not permitting pupillometric examination
12. The subject has used any investigation products in the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Normal Saline; Normal Saline given 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h	Drug: Normal Saline; Normal saline given 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h; Other Names: 0.90% NaCl
Active Comparator: Ketamine; ketamine 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h	Drug: Ketamine; ketamine 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h; Other Names: Ketanest, Ketaset, and Ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine Equivalent Consumption (mg/kg)	Morphine consumption (mg/kg) was measured over time in the Ketamine group and compared to the Control (saline) group. Values are for each 24 hour time period and displayed as hours post surgery.	at 24, 48, 72, 96 hours post operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sedation Score	Sedation scores 0 = completely awake; = sleepy but responds appropriately; = somnolent but arouses to light stimuli; = asleep but responsive to deeper physical stimuli; = asleep and not responsive to any stimuli Values are for each 24 hour time period and displayed as hours post surgery.	24, 48, 72, 96 hours post operatively
Pain Score at Rest	Patient volunteered response at rest, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery.	24, 48, 72, 96 hours post operatively
Pain Score During Cough.	Patient volunteered response during a cough, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery.	24, 48, 72, 96 hours post operatively

Collaborators and Investigators

• Sponsor: Julia Finkel
• Investigators: Principal Investigator: Pestieau Sophie, MD, Children's National Research Institute; Study Director: Finkel C Julie, MD, Children's National Research Institute

Publications and helpful links

General Publications

• Pestieau SR, Finkel JC, Junqueira MM, Cheng Y, Lovejoy JF, Wang J, Quezado Z. Prolonged perioperative infusion of low-dose ketamine does not alter opioid use after pediatric scoliosis surgery. Paediatr Anaesth. 2014 Jun;24(6):582-90. doi: 10.1111/pan.12417.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: February 25, 2011
• First Submitted That Met QC Criteria: March 28, 2011
• First Posted (Estimate): March 29, 2011

Study Record Updates

• Last Update Posted (Estimate): January 14, 2016
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: scoliosis; pupillometry; hyperalgesia; opioid tolerance
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Spinal Curvatures; Sensation Disorders; Somatosensory Disorders; Spondylolysis; Spondylosis; Scoliosis; Spondylolisthesis; Hyperalgesia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 4735