Methadone analgesia in the critically ill

The use of methadone to facilitate opioid weaning in pediatric critical care patients: a systematic review of the literature and meta‐analysis

“…This results in a long, variable terminal half‐life, with a broad range—7–65 h in healthy patients. Therefore, dose adjustments also take a long time to reach steady state and demonstrate clinical effect and may be less predictable in critically ill patients . The use of a loading regimen in our reviewed studies varied, but the benefits of a loading regimen are supported by the study examining different doses utilized in different phases of treatment and by pharmacologic data estimating that a minimum starting dose of 0.2 mg·kg −1 q8 h is required to ‘load’ to a therapeutic methadone level (to achieve pain relief) in 36 h .…”

Methadone in Pain Management: A Systematic Review

“…Methadone elicits its analgesic effects largely through agonistic binding at the m-opioid receptor, and to a lesser degree through antagonistic binding at the Nmethyl-D-aspartate (NMDA) receptor and inhibition of serotonin reuptake. 16 Evidence suggests that antagonism at the NMDA receptor is responsible for the modulation of neuropathic pain and may prevent the remodeling of pain pathways that results in the chronification of pain. 16 Figure 1.…”

“…16 Evidence suggests that antagonism at the NMDA receptor is responsible for the modulation of neuropathic pain and may prevent the remodeling of pain pathways that results in the chronification of pain. 16 Figure 1. Chemical structure of methadone.…”

“…Following oral administration, methadone has a bioavailability of 70% to 80%, with less than 10% of the dose being removed in the first pass effect. 5,16 The analgesic effect begins within 30 minutes after administration of the drug and lasts for 4 to 6 hours. 5 Methadone binds to plasma proteins in circulation; most predominantly, a 1 -acid glycoprotein.…”

“…This accounts for the wide variation in half-life, recorded as a range from 2 to 65 hours. 5, 16,17 Methadone is metabolized into inactive molecules by the liver CYP450 enzyme and the intestinal CYP3A4/ CYP2D6 enzymes, before elimination in the feces or urine. 5 Since methadone undergoes hepatic, renal, and intestinal metabolism, it can be safely administered to patients with chronic liver disease or renal impairment.…”