Low Dose Ketamine Study on Opioid Tolerance and Hyperalgesia

Study Overview
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Brief Summary
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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.

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

Conditions
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Idiopathic Scoliosis, Spondylolisthesis

Intervention / Treatment
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* Drug: Ketamine
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is 10 to 18 years of age The subject's American Society of Anesthesiologists physical status is ASA 1, 2 or 3 (see appendix I) The subject is scheduled for elective posterior spinal fusion and instrumentation. The subject's parent/legally authorized guardian has given written informed consent to participate Exclusion Criteria: The subject has a history or a family (parent or sibling) history of malignant hyperthermia The subject is pregnant or nursing. The subject has known significant renal disorders determined by medical history, physical examination or laboratory tests The subject has a known or suspected allergy to morphine, remifentanil or ketamine The subject is an ASA classification of 4 or greater (See Appendix I) The subject is scheduled for a surgical sub-procedure (i.e. anterior spinal fusion) The subject is unable to self-administer morphine using patient-controlled analgesia (PCA) pump The subject had a recent opioid exposure (within 1 month of surgery) The subject is obese (body mass index >30kg/m2) The subject is planned for elective postoperative ventilation The subject has a known ocular disease not permitting pupillometric examination The subject has used any investigation products in the past 30 days

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Normal Saline<br>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<br>* 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<br>* Other names: 0.90% NaCl;|
| Active Comparator: Ketamine<br>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<br>* 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<br>* Other names: Ketanest, Ketaset, and Ketalar;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid tolerance, hyperalgesia, scoliosis, pupillometry