A Jadon, S Parida, S Chakraborty, A Panda
buprenorphine, epidural opioid, naloxone, ponv
A Jadon, S Parida, S Chakraborty, A Panda. Epidural naloxone to prevent Buprenorphine induced PONV. The Internet Journal of Anesthesiology. 2007 Volume 16 Number 2.
Epidural infusion of local analgesic and opioid are commonly used for postoperative pain relief. This combination gives excellent anlgesia but nausea and vomiting remains a major concern. Low dose epidural naloxone prevents PONV induced by spinal opioids like morphine, fentanyl and sufentanil. However, it is not known that epidural naloxone administration prevents PONV induced by epidural buprenorphine. We have reported three of our cases of major abdominal operation in which lowdose epidural infusion of naloxone releived the symptom of buprenorphine induced severe PONV and improved the quality of analgesia.
Epidural buprenorphine is an effective analgesic but PONV is very common undesirable side effect 5. Buprenorphine and other opioid drugs cause PONV by action on MOR (µ opioid receptor) present in the brain and gastro intestinal tract 6., Buprenorphine is a semi-synthetic opioid with agonistic activity at the MOP-receptor and antagonistic properties at the KOP-receptor. Human studies show that buprenorphine behavior is typical of MOP-receptor agonists, with respect to its intended effect (potent and long-lasting analgesia) and side-effects (e.g. it causes sedation, nausea, delayed gastric emptying ) but a
Naloxone is an opiate receptor antagonist has been used through intravenous and epidural route to counter opioid induced side effects like itching, nausea vomiting, decreased intestinal motility and respiratory depression. By titration of naloxone doses it is possible that, only side effects (PONV, itching, respiratory depression etc.) are controlled and opioid analgesia is retained 348.
The possible mechanism include, (a) low dose naloxone may enhance release of endogenous opioid peptides by blocking presyneptic autoinhibition of encephalin release9 and, (b) low dose naloxone directly and comptetively antagonize the Gs protein-coupled excitatory opioid receptor that are responsible for the hyperalgesia occasionally reported with opioid administration without attenuating inhibitory Gi/Go-coupled opioid receptors mediating analgesia 10. Whether similar mechanism also active with co-administration of naloxone and buprenorphine is not documented however, experimental studies have shown the efficacy of intrathecal naloxone to couneract effects of buprenorphine administered intrathecally 11. We used infusion of naloxone after initial bolus instead of only bolus because it is better to infuse naloxone continuously as it has half life of 55 minutes and intermittent administration will result in fluctuation of concentration 12. There was no previous guideline available for epidural dose of naloxone to prevent PONV with buprenorphine. We have used an average dose of 0.20-0.27 µg/ kg/hr, considering that, this will be low dose as similar dose has been used to prevent sufentanil induced PONV 4. Regarding safety of naloxone for spinal use, various experimental and clinical studies have shown that naloxone not only safe for spinal use rather it is neuroprotective 13.
So far clinically reduction in nausea, vomiting and analgesia enhancing effect with low dose naloxone have been noticed only with pure mu agonist like morphine, fentanyl and sufentanil. In present report, we have observed that similar effects were seen when naloxone interacted with partial mu agonist buprenorphine, as all three patients responded in similar and predicted manner. Symptoms of PONV were controlled and quality of analgesia improved.
Pharmacology of buprenorphine is very complex and still poorly understood. This case report highlights the possibilities that, epidural administration of naloxone may help in management of epidural buprenorphine induced PONV and may enhance analgesic effect of epiduraly administerd buprenorphine. However to prove this hypothesis, a large RCT along with receptor binding analysis studies are required.
We noticed improvement in pain score with relief of nausea and vomiting when low dose naloxone used epiduraly to control buprenorphine-induced nausea and vomiting. However, with only three cases observed, further detail study is required to reach any conclusion.
Dr. Ashok Jadon, MD, DNB 44, Beldih Lake Flats, Dhatkidih Jamshedpur-831001 Jharkhand (India) Phone: 0657-2228483, Mobile: 9431179528 E-mail: firstname.lastname@example.org