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Oxycodone for management of postoperative visceral pain

12 Aug 2020

Despite the armamentarium of analgesics available today, management of postoperative pain remains suboptimal, with many patients still reporting moderate-to-severe pain after surgery. Postoperative pain is associated with delays in discharge and unexpected hospital admissions. Postoperative visceral pain, in particular, is a major clinical concern as treatment with classical µ-opioid agonists such as morphine is often associated with toxicity and tolerability issues. This article summarizes the key points and evidence from two clinical papers investigating the efficacy of oxycodone (OxyContin®, OxyNorm®, Mundipharma) vs morphine in the management of postoperative visceral pain, as well as the mechanism-of-action and benefits of oxycodone.

Pharmacological profile of oxycodone and its role in visceral pain

Oxycodone is a semisynthetic opioid with agonist activity at the µ, κ and δ receptors. [Clin Transl Oncol 2007;9:298-307] It has been used safely and effectively for postoperative pain management following diverse types of surgery, including but not limited to facial surgery, breast surgery, abdominal surgery and urological procedures. [J Pain Res 2016;9:25-36]

Oxycodone is generally known to cause less nausea and pruritus, and fewer hallucinations than morphine, which acts primarily on the µ-opioid receptors within the central nervous system (CNS). [Clin Transl Oncol 2007;9:298-307] Based on animal models, it has been proposed that oxycodone has an effect on the κ-opioid receptors, which are believed to play an important role in antinociception in visceral pain. [Pain 1997;73:151-157; Eur J Pharmacol 2005;524:75-79; J Pharmacol Exp Ther 1998;285:707-715; EMBO J 1998;17:886-897; Motil 2004;16:383-394]

Oxycodone may be superior to morphine at attenuating visceral pain

A study in 24 healthy volunteers was carried out to test the hypothesis that experimental pain would be modulated differently in different tissues by morphine and oxycodone, and that this modulation would vary with stimulation modality. [Pain 2006;123:28-36] According to the investigators, experimental pain models are advantageous for the evaluation of analgesic effects as confounding factors such as sedation, nausea and general malaise would pose difficulties in clinical evaluation.

Opioid-naïve volunteers were randomized to receive oral morphine (30 mg), oxycodone (15 mg) or placebo, and subjected to mechanical, thermal and electrical pain stimulation tests in the skin, muscles and viscera.

Compared with placebo, oxycodone and morphine were found to attenuate induced pain to the same extent in skin and muscles. However, the visceral pain models demonstrated superior analgesic effect with oxycodone vs morphine and placebo for both thermal (p<0.001) and mechanical stimulation (p<0.05) of the oesophagus. (Figure 1)

MUN-063mo_01

While the use of an inert placebo was a key limitation of this first-in-human study that investigated the effect of morphine and strong opioids on visceral pain, this was done as the study’s main objective was to evaluate the tissue-differential effect of the opioid analgesics, the investigators explained.

While further studies are required to better understand the effect of κ-agonists on visceral pain, it was concluded that the results support the clinical experience that oxycodone, with its distinct pharmacological profile vs morphine, could have a better analgesic profile in visceral pain.

Oxycodone: A potent, long-lasting & opioid-sparing analgesic in postoperative visceral pain 

Another study compared the analgesic potency, pain scores and side effects of oxycodone vs morphine in a clinical model of postoperative visceral pain. The study’s participants were women scheduled for laparoscopic supracervical hysterectomy or total laparoscopic hysterectomy. The patients received intravenous oxycodone or morphine before the end of surgery, and then continued with patient-controlled analgesia for 24 hours postoperatively. [Anesth Analg 2009;109:1279-1283]

Results showed significantly lower accumulated 24-hour consumption of oxycodone vs morphine (13.3 ± 10.4 mg vs 22.0 ± 13.1 mg; p=0.001). (Figure 2) The visual analogue scores (VAS) at rest and during coughing were significantly lower in the oxycodone group at 30 minutes and 1 hour after surgery, and overall postoperative sedation level was also significantly lower in the oxycodone vs morphine group (p=0.006). No significant differences were observed in the side effects of nausea, vomiting or itching between the groups.

MUN-063mo_02

Importantly, the investigators also observed a significantly longer time to the first patient-controlled analgesia (PCA) oxycodone request following a standardized dose of oxycodone vs morphine before the end of surgery. “This may indicate that oxycodone has a longer-acting effect or is more potent,” they suggested.

The lower VAS scores in the oxycodone group are also an indication of oxycodone’s faster onset of action compared with morphine, which is generally considered to be a slower-acting drug, they added.

“Our results support the findings in experimental studies in humans, demonstrating that oxycodone is more potent than morphine in the treatment of visceral pain,” they concluded. They noted that this may be explained by oxycodone’s κ-opioid receptor agonist properties, but highlighted the need for more studies to better understand this phenomenon.

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