Ketamine and Hydromorphone for Patient Controlled Pain Relief in Children's Mucositis

The purpose of this observational pilot study is to evaluate the feasibility, efficacy and optimum ratio of a compounded mixture of HM-K administered parenterally by PCA in pediatric mucositis patients who have inadequate analgesia using conventional HM PCA.

An open-label study of 20 consecutive consenting/assenting subjects who meet the study criteria will be conducted. All patients who are eligible for the study will be approached for informed, written consent and subjects over age 7 will complete an assent form.

The subject will be examined by a pediatric oncology fellow/staff to determine the level of clinical severity of the mucositis using the Oral Mucositis Assessment Scale (OMAS) and World Health Organization Mucositis Scale.

A modified Colour Analogue Scale (mCAS) that was originally designed to evaluate pain intensity will be used to evaluate the self-report symptoms. The subject will then receive 24 hours of therapy using a compounded HM-K PCA solution.

Initial PCA prescription for the Background and Bolus will be set at the existing settings on the morning of recruitment as per the study entry criteria of minimum hourly use of 4 mcg/kg/hour of HM. The 1-hour Maximum will be set at 4 times the Background dose.

At 24 hours, the 24-hour HM and K consumption will be calculated. The subject will be re-examined by a pediatric oncology fellow/staff to determine the level of clinical severity of the mucositis and the self-report symptom evaluation questionnaire administered. Conventional Therapy of HM PCA will be restarted and at 24 hours, both the mucositis severity and the self-report symptom evaluation questionnaire administered. Descriptive summaries of the demographic data will be provided. The 24-hour HM utilization will be compared to the study entry-level utilization (24 hour period prior to recruitment). A 30% reduction in opioid use will be considered clinically important.A Symptom Index of Start Study Symptom Level - End Study Symptom Level / Start Study Symptom level will be calculated for each symptom including pain intensity. An Index of greater than or equal to 0.5 will be considered a positive outcome. Indexes at 0, 24 and 48 hours will be compared. A descriptive summary of the incidence and treatment of opioid-induced side effects at 0, 24 and 48 hours will be provided.

Ketamine Solution Concentrations

Solution 1 (low): HM 0.2 and K 0.2 mg/mL (1:1) - 20 mg/20 mg in 100 mL. Solution 2 (medium): HM 0.2 and K 0.6 mg/mL (1:3) - 20 mg/60 mg in 100 mL. Solution 3 (high): HM 0.2 and K 1 mg/mL (1:5) - 20 mg/100 mg in 100 mL.

The starting solution will be Solution 2 in a minimum dose 4 mcg/kg/hour of hydromorphone (HM) and 12 mcg/kg/hour of ketamine (K) (0.02 mL/kg/hour of solution.

"Add background": 4 mcg/kg/hour of Hydromorphone equivalent (0.02 mL/kg/hour of solution) may occur once as required after solution change criteria are met.

"Increase background": additional 4 mcg/kg/hour of Hydromorphone equivalent (0.02 mL/kg/hour of solution).

Repeat "Increase background": 4 mcg/kg/hour of Hydromorphone equivalent (0.02 mL/kg/hour of solution) may occur 3 hourly as required after solution change criteria are met.

"Decrease background": decrease by 4 mcg/kg/hour of Hydromorphone equivalent (0.02 mL/kg/hour of solution) may occur 3 hourly as required after solution change criteria are met.

"Stop background": Background is stopped so that only bolus dose remains. May occur when background has been reduced to 4 mcg/kg/hour of Hydromorphone for at least 3 hours or exceessive ADEs.

"D/C background: Discontinue background HM and only bolus remains.

"Stop Study (SS)": Converting the PCA to conventional HM therapy with any adjuvants required according to existing practice of Acute Pain Service. For compassionate reasons, if a patient/family expresses a with to remain on STudy Therapy, this will be accepted.

Once patient has ADEs and requires Solution 1, they may not re-start solution 2 or 3.