Comparison of the Efficacy of Ketamine in Pediatric Patients With Idiopathic Scoliosis After Surgery

Study Overview
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Brief Summary
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Comparison of the Efficacy of ketamine measuring the total consumption of morphine in pediatric patients with idiopathic scoliosis

Detailed Description
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A randomized unicenter clinical trial, parallel, double-blind study, placebo-controlled group. Involve the participation of Pediatric patients, aged between 11 and 18 years, of both genders, diagnosed with idiopathic scoliosis and posterior spinal fusion surgery candidates included in the Anesthesia Physical Classification System (ASA) 1 or 2 classes. Both groups received remifentanil at doses of 0.3 mcg / Kg / min before surgical procedure and a bolus of 150 mcg / Kg of morphine hydrochloride, approximately 60 minutes before extubation, followed by PCA morphine hydrochloride administration. The patients in the experimental group are treated with a combination of ketamine, remifentanil hydrochloride and morphine while the control group will be treated with a combination of saline, remifentanil and morphine hydrochloride. Treatment of patients in the study is initiated during the induction of anesthesia and ends at the hospital discharge. The total duration of patient participation in the study is 6 months. During treatment the patients being admitted are monitored at regular intervals, at week 6, after the 3rd month and at 6 months post-intervention to assess the incidence of chronic pain. The entire study duration is approximately 24 months. The hypothesis of the study is that the combination of subanesthetic doses of ketamine to opioid drugs during the perioperative period reduces central sensitization processes, resulting in lower consumption of postoperative morphine with fewer adverse effects, postoperative faster recovery and less incidence of chronic pain. The post-operative analgesia is induced by the use of opioids or other analgesics associated with loco-regional techniques. The technique used in the investigators' center is the patient-controlled analgesia (PCA) with the administration of intravenous opioids. The association of ketamine to opioid treatment could reduce the consumption of these and can be useful in surgery. No clinical trials have been conducted in children with scoliosis, who underwent posterior lumbar fusion surgical procedure, evaluating the efficacy of post-operative association of ketamine to opioid drugs for both intra and post-operative periods.

Official Title
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Assessment of the Analgesic Efficacy and Tolerability of the Perioperative Association of the Ketamine With Opiates After Posterior Vertebral Fusion Surgery in Children With Idiopathic Scoliosis

Conditions
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Progressive Infantile Idiopathic Scoliosis

Intervention / Treatment
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* Drug: Ketamine Hydrochloride
* Other: Placebo
* Drug: Remifentanil
* Drug: Morphine hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both genders diagnosed with idiopathic scoliosis aged between 8 and 18 years old. Patients of both genders diagnosed with idiopathic scoliosis and candidates for vertebral fusion corrective surgery with instrumentation. Patients with ASA 1 or ASA 2. Patients and/or parents/tutors consent to participate in the clinical trial. Exclusion Criteria: Patients with chronic preoperative pain. Patients with addiction to narcotics. Patients with a history of allergy, contraindication or intolerance to the drugs used. Patients unable to understand the patient-controlled analgesia system. Patients with mental disorders. Reoperated patients. Patients requiring elective postoperative ventilation. Pregnant patients.

Ages Eligible for Study
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Minimum Age: 8 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine Hydrochloride<br>Received a combination of ketamine, remifentanil and morphine hydrochloride established by the following dosage regimen: KETAMINE HYDROCHLORIDE 0,5mg/Kg Intravenous bolus administered during the anesthetic induction, followed by 2 mcg / Kg / min of intravenous infusion during and after surgery until 72 hours postoperation during surgery remifentanil 0,3 mcg / kg / min. at the end of the operation morphine hydrochloride150 mcg / kg, PCA infusion postoperatively. | Drug: Ketamine Hydrochloride<br>* 50 mg/ml, IV (in the vein) during surgery operation, followed by IV ketamine hydrocloride perfusion 2mcg/Kg/min before and until 72 hours after operation Number of Cycles: until progression or unacceptable toxicity develops.<br>* Other names: KETOLAR 50 mg/ml;Drug: Remifentanil<br>* at doses of 0.3 mcg / kg / min during and until the end of the surgical operation<br>Drug: Morphine hydrochloride<br>* at the dose of 150 mcg / kg, 60 minutes before the extubation procedure and until 72 hours after operation by intravenous infusion<br>|
| Placebo Comparator: Placebo<br>Received a combination of physiological serum, remifentanil and morphine hydrochloride established by the following dosage regimen: 0,9 % physiological serum 0,5mg/Kg administered by an intravenous (IV) line during the anesthetic induction, followed by 2 mcg / Kg / min of intravenous infusion during and after surgery until 72 hours postoperation during surgery remifentanil 0.3 mcg / kg / min. at the end of the operation morphine hydrochloride150 mcg / kg, PCA infusion postoperatively. | Other: Placebo<br>* 50 mg/ml, IV (in the vein) during surgery operation, followed by IV placebo perfusion 2mcg/Kg/min before and until 72 hours after operation<br>* Other names: 0,9 % physiological serum;Drug: Remifentanil<br>* at doses of 0.3 mcg / kg / min during and until the end of the surgical operation<br>Drug: Morphine hydrochloride<br>* at the dose of 150 mcg / kg, 60 minutes before the extubation procedure and until 72 hours after operation by intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Consumption of Epidural Morphine at 72h Postoperatively | For the assessment of the related ketamine analgesic efficacy. Cumulative consumption of epidural morphine administered as loading dose, intraoperatively, of 0,3 mcg/kg/min until the surgery operation and 150mcg/Kg of Morphine hydrochloride 60min before extubation | in the first 72 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pain Scores (Visual Analogue Scale) | Pain scores at rest and on cough using a 10cm Visual Analogue Scale(0=no pain, 10=worst possible pain for the analgesic efficacy assessment of the association of Ketamine and opiates | in the first 72 hours after surgery. | 
| Rates of significant adverse events | To assess the tolerability of the association of ketamine and opiates | every 4 hours from the begin until the end of the surgical operation | 
| Time to oral tolerability | To assess the efficacy of the association of ketamine and opiates, measuring the time needed from the surgery for reaching the oral tolerability | up to 6 months from the end of the surgical operation | 
| Time to First Postoperative Ambulation | To assess the efficacy of the association of ketamine and opiates, measuring the time needed to being able to walk without assistance within the room or outside the room | up to 6 months from the end of the surgical operation | 
| Time to postoperative recovery | Post operation period needed for each patient from the end of the surgery until hospital discharge by counting each patient postoperative hospital night admissions | up to 6 months from the end of the surgical operation | 
| Change From Baseline in Pain by sensorial test using the Voy Frey filament | measure of the area of hyperalgesia of the inflamed skin and the length of the incision after 72 post surgery. The filaments is used to provide a range of forces to the skin of a test subject, in order to find the force at which the subject reacts because the sensation is painful. | in the first 72 hours post surgery | 
| Change From Baseline in Pain Scores (Visual Analogue Scale) | Assessment of pain at week 6 and chronic pain after 3 and 6 months post-surgery using the Visual Analogue Scale pain scale | at week 6 and after 3 and 6 months post surgery. | 
| Change From Baseline in neuropathic pain using Douleur Neuropathique en 4 Questions (DN4) questionnaire | The (DN4) questionnaire is a screening tool for neuropathic pain consisting of interview questions (DN4-interview) and physical tests. Two questions (I and II) were based on the interview of the patient and two questions (III and IV) were based on a standardized clinical examination | at week 6 and after 3 and 6 months post surgery. |