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

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

Comparison of the Efficacy of ketamine measuring the total consumption of morphine in pediatric patients with idiopathic scoliosis

Study Overview

• Status: Completed
• Conditions: Progressive Infantile Idiopathic Scoliosis
• Intervention / Treatment: Drug: Ketamine Hydrochloride; Drug: Remifentanil; Drug: Morphine hydrochloride; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients of both genders diagnosed with idiopathic scoliosis aged between 8 and 18 years old.
2. Patients of both genders diagnosed with idiopathic scoliosis and candidates for vertebral fusion corrective surgery with instrumentation.
3. Patients with ASA 1 or ASA 2.
4. Patients and/or parents/tutors consent to participate in the clinical trial.

Exclusion Criteria:

1. Patients with chronic preoperative pain.
2. Patients with addiction to narcotics.
3. Patients with a history of allergy, contraindication or intolerance to the drugs used.
4. Patients unable to understand the patient-controlled analgesia system.
5. Patients with mental disorders.
6. Reoperated patients.
7. Patients requiring elective postoperative ventilation.
8. Pregnant patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine Hydrochloride; 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; 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.; Other Names: KETOLAR 50 mg/ml; Drug: Remifentanil; at doses of 0.3 mcg / kg / min during and until the end of the surgical operation; Drug: Morphine hydrochloride; at the dose of 150 mcg / kg, 60 minutes before the extubation procedure and until 72 hours after operation by intravenous infusion
Placebo Comparator: Placebo; 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.	Drug: Remifentanil; at doses of 0.3 mcg / kg / min during and until the end of the surgical operation; Drug: Morphine hydrochloride; at the dose of 150 mcg / kg, 60 minutes before the extubation procedure and until 72 hours after operation by intravenous infusion; Other: Placebo; 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; Other Names: 0,9 % physiological serum

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Fundació Sant Joan de Déu
• Collaborators: Instituto de Salud Carlos III
• Investigators: Principal Investigator: Marina Perelló Riera, MD, Hospital Sant Joan de Déu Servicio de Anestesiología, Reanimación y Tratamiento del Dolor

Publications and helpful links

General Publications

• Mao J. Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy. Pain. 2002 Dec;100(3):213-217. doi: 10.1016/S0304-3959(02)00422-0. No abstract available.
• Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000 Jun 9;288(5472):1765-9. doi: 10.1126/science.288.5472.1765.
• Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003 Nov;106(1-2):49-57. doi: 10.1016/s0304-3959(03)00276-8.
• Schmid RL, Sandler AN, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain. 1999 Aug;82(2):111-125. doi: 10.1016/S0304-3959(99)00044-5.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: September 28, 2015
• First Submitted That Met QC Criteria: October 7, 2015
• First Posted (Estimate): October 8, 2015

Study Record Updates

• Last Update Posted (Estimate): October 8, 2015
• Last Update Submitted That Met QC Criteria: October 7, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Spinal Curvatures; Scoliosis; 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; Analgesics, Opioid; Narcotics; Ketamine; Remifentanil; Morphine
• Other Study ID Numbers: FSJD-ESCOKETA-2010; 2011-000407-41 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No