Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT05581901 |
Other study ID # |
SHS-An-2-2022 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
January 12, 2023 |
Est. completion date |
April 4, 2023 |
Study information
Verified date |
April 2023 |
Source |
University of Southern Denmark |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Postoperative analgesic treatment needs to be improved. Numerous studies suggest that a
single dose of Methadone given during surgery significantly ameliorates postoperative pain
and reduces postoperative opioid consumption. Perioperative methadone is already used in
isolated cases such as patients with chronic pain or patients with high morphine tolerance.
However, it is not routinely used in the elderly and fragile, and there is insufficient
reliable evidence on this treatment and population. Further investigation is highly relevant
and necessary.
Description:
A multimodal approach and the use of peripheral nerve blocks have improved the treatment of
postoperative pain. However, supplemental opioids are predominantly necessary and often
continued for months or years after surgery. In fact, continued use of opioids after surgery
is an increasing challenge. Consequently, patients undergoing surgery are at risk of
experiencing side effects and developing physical as well as psychological addiction to
opioids. The most common opioid-related side effects include obstipation, nausea, itchy skin,
dry mouth, vertigo, and sedation. The means to decrease the need for opioids in the
postoperative phase are in high demand, and therefore the investigation of perioperative
Methadone is highly relevant. Methadone is a lipophilic opioid agonist with a large
distribution volume and a very long elimination half-life of 15 - 60 hours. It is also an
N-methyl D-aspartate (NMDA) receptor antagonist, which attenuates opioid-induced tolerance
and hyperalgesia. Furthermore, Methadone inhibits the reuptake of Serotonin and Noradrenalin,
which could positively affect the experience of pain in the postoperative phase. Methadone is
mostly excreted through the bile and can, therefore, even be used in patients with reduced
kidney function. Methadone's analgesic effects occur only eight minutes after intravenous
administration. In most studies, methadone is given perioperatively in dosages of 0.10-0.30
mg/kg and is commenced at the induction of anaesthesia or the initiation of surgery. Studies
investigating the optimal dosage and time for administration found that patients receiving
methadone after the procedure needed twice as much opioid pain medication on postoperative
day one compared to patients receiving methadone at anaesthetic induction. These studies also
indicate that using smaller dosages such as 5-10 mg, the analgesic duration is only 3-4
hours, whereas doses of 20 mg or more have a clinical effect closely related to the
elimination half-life of 15-60 hours without any increased risk for respiratory depression.
The aim of this study is to determine the optimal dose of methadone for a future randomized
controlled trial (RCT). The objective is to investigate whether doses greater than 0.10 mg/kg
are tolerated with no increased risk to respiratory depression, side effects, or prolonged
stay in the post-anaesthesia care units (PACU).