May 2002

Dear Readers: Here's the Article for this Month:

Name of article:

INTRAVENOUS METHADONE IN THE MANAGEMENT OF CHRONIC CANCER PAIN

Safe and effective starting doses when substituting Methadone for Fentanyl

Author(s): Santiago-Palma J, Khojainova N, Kornick C, Fischberg DJ, Primavera LH, Payne R, Manfredi P.

Reference: Cancer 2001; 92: 1919-25

Abstract:

Opioid rotation (i.e. the switching from one opioid to another) is considered to be one of the therapeutical approaches to manage adverse effects and/or to improve analgesia in patients with cancer-related pain.

Retrospective and prospective studies have indicated the switching modalities and the starting doses of methadone when rotating from morphine and hydromorphone; no data are available regarding rotation between fentanyl and methadone.

A prospective study was carried out for 4 days on 18 cancer patients with pain who underwent opioid rotation from intravenous (IV) patient-controlled analgesia (PCA) with fentanyl to IV-PCA with methadone. The reasons of switching were uncontrolled pain associated with sedation (12 patients) or confusion (6 patients). Inadequate pain control was defined as pain intensity of 5 or more on a 0-10 verbal numerical scale. Sedation was defined as a subjective feeling of sleepiness rated by the patients using a 0-3 point verbal numerical scale (0=no sedation, 3=severe sedation). Confusion was defined as a deficit in orientation , attention, recall and ability to perform simple calculations.

The initial hourly infusion rate of methadone was calculated based on the previous hourly infusion rate of fentanyl. A conversion ratio of 25 mcg/h of fentanyl to 0.1 mg/h of methadone was used to estimate the initial dose of methadone in all patients (0.25 ratio between fentanyl and methadone). Self-administered bolus doses of IV methadone equal to 50-100% of the hourly infusion rate were allowed every 20 minutes and additional boluses of 100-200% of the hourly infusion rate every 60 minutes.

Satisfactory pain control was achieved in 16 patients (88.8%). The mean pain score decreased from 8.1 to 4.8 on Day 1 after the switch (p<0.001) and to 3.22 on Day 4. Fourteen patients rated analgesic treatment satisfactory 24 hours after the switch, two patients on Day 2 and 1 patient on Day 3. One patient reported no pain control and was treated with epidural opioids.

None of the patients experienced toxicity from methadone.

Before switching in 12 patients mean sedation score was 1.5 and it progressively decreased till 0.16 on Day 4 (p= 0.001). Five out of the 6 patients who presented confusion during fentanyl treatment improved subjectively and objectively 2 days after the switch . In one patient the confusion worsened and he died of bacterial sepsis.

Regarding the dose of IV methadone necessary to control pain, there was a 10% increase in the median hourly infusion dose of methadone from Day 1 to Day 2; after Day 2 the median hourly infusion dose of methadone was the same. The median total methadone 24-h dose decreased from 64.45 mg on Day 1 to 54 mg on Day 4.

If the final mean hourly infusion dose of methadone were used to calculate the initial hourly infusion rate, a conversion of 25 mcg/h of fentanyl for 0.125 mg/h of methadone would result.

WHY I SELECTED THIS PAPER

Opioid switching is increasingly used in clinical practice. To do this, it is necessary to know what the dose ratio is between the different opioids. This study supplies data which till today was missing i.e. the safe and effective starting dose of IV methadone when switching from IV fentanyl. Furthermore , this study gives another clinical indication regarding the improvement of pain control and the reduction of symptoms such as confusion and sedation when switching to methadone.

Regards,

Carla Ripamonti, MD
Member of the Board of Directors, IAHPC