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Opioid-induced hyperalgesia or opioid-withdrawal hyperalgesia?

Tzabazis, A. Z.*; Koppert, W.*

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European Journal of Anaesthesiology: September 2007 - Volume 24 - Issue 9 - p 811-812
doi: 10.1017/S0265021507000506


We read with interest the letter by Dumont and colleagues [1]. They present a case of a 62-yr-old male undergoing revascularization of the right femoral artery who, due to chronic pain from his vascular disease, received daily fentanyl-patch (75 μg h−1), tramadol 150 mg, paracetamol 3 g and amitriptyline 50 mg preoperatively. During anaesthesia, he received in total 6.3 mg remifentanil over 5 h of surgery followed by 2 g proparacetamol and 10 mg piritramide for postoperative analgesia. He complained of intense pain upon arrival in the ICU, and 2 mg of morphine intravenously increased the pain. Another 2 mg of morphine induced a similar result. The pain was managed with ketamine, and the authors concluded that this case was a good example of opioid-induced hyperalgesia. Furthermore, they suggested that remifentanil in association with ketamine was useful in patients pretreated with opioids.

One possibility for this patient's pain in the postoperative period - and in our view the most likely one - however is not discussed, namely opioid-withdrawal hyperalgesia. Postoperative analgesia in patients who receive opioids for chronic pain is undoubtedly a challenge for anaesthesiologists and pain therapists. In clinical practice, chronic pain patients receiving strong opioids preoperatively show high inter-individual variability and sometimes extremely high postoperative demand for opioids. Depending on the chronic opioid dose, total cumulative doses of 30-45 mg piritramide within the first 1-2 h are common in these patients. These observations are in accordance with Rapp and colleagues [2], who found a more than three-fold (135.8 vs. 42.8 mg) increase in opioid demand in the first 24 h after surgery in patients with preoperative opioid consumption as compared with opioid-naïve patients.

In addition, we feel that postoperative analgesia is much more difficult to handle in chronic pain patients receiving remifentanil as sole opioid intraoperatively as compared with those receiving long-acting μ-opioid agonists like fentanyl or sufentanil. Irrespective of the fact whether this patient's fentanyl patch was removed before surgery or not, we feel that the administration of 10 mg piritramide and 4 mg morphine for postoperative analgesia in this patient was simply not enough to provide sufficient analgesia.

It has been shown that enhanced pain sensations after cessation of a remifentanil infusion are due to an acute withdrawal response, which cannot be modulated by N-methyl-d-aspartic acid receptor antagonists [3,4]. Therefore, we think that the therapeutic effect of ketamine observed by Dumont and colleagues is most likely due to its direct analgesic or hypnotic effect and not based on the reversal of pronociceptive mechanisms induced by remifentanil. The increasing evidence for opioid-induced hyperalgesia should not lead to a restricted use of opioids in the perioperative period, especially not in patients who have a history of chronic opioid administration.


1. Dumont H, Guntz E, Sosnowski M, Talla G. Opioid-induced hyperalgesia. Eur J Anaesthesiol 2007; 24(2): 205-207.
2. Rapp SE, Ready LB, Nessly ML. Acute pain management in patients with prior opioid consumption: a case-controlled retrospective review. Pain 1995; 61(2): 195-201.
3. Koppert W, Sittl R, Scheuber K, Alsheimer M, Schmelz M, Schuttler J. Differential modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by S-ketamine and clonidine in humans. Anesthesiology 2003; 99: 152-159.
4. Koppert W, Angst M, Alsheimer M et al. Naloxone provokes similar pain facilitation as observed after short-term infusion of remifentanil in humans. Pain 2003; 106(1-2): 91-99.
© 2007 European Society of Anaesthesiology