Opioid Induced Hyperalgesia

Controversy: whether or not intraoperative opiates are indicated when general anesthesia can be maintained by other means (volatile anesthetics, propofol, lidocaine, ketamine, dexmedetomidine, etc.). On one hand, opiates clearly have MAC-reducing effects. On the other hand, one could argue that analgesics are unnecessary during general anesthesia as these patients should have no awareness or memory. The majority of data deals with remifentanil, and it is questionable whether or not these data represent a class effect or are specific to remifentanil

Data Suggestive of Hyperalgesia:

A single dose of fentanyl with induction can increase the incidence of PONV, increase post-operative opioid consumption, and delay PACU discharge [Sukhani R. Anesth Analg 83: 975, 1996; FREE Full-text at Anesthesia & Analgesia]

A study of 50 abdominal surgery patients randomized to 0.5 MAC desflurane vs. remifentanil (average 0.3 ucg/kg/min) or remifentanil at 0.1 ucg/kg/min plus desflurane titrated to autonomic response. Postoperative pain scores were worse for the high-dose group, and need 59 mg morphine in 24 hrs (as opposed to 32 mg in the low-dose group, p < 0.01) [Guignard B et. al. Anesthesiology 93: 409, 2000]

A study of 20 patients undergoing off-pump CABG with standard propofol/fentanyl anesthesia randomized them to receive either remifentanil at 0.1 ucg/kg/min versus placebo. At one hour post-operatively, the remifentanil group required 8.39 mg morphine, as compared to 3.29 mg in the placebo group (p < 0.01), however this difference resolved by 12 hours [Rauf K et. al. Br J Anaesth 95: 611, 2005]

A study of 30 adolescents with scoliosis randomized them to continuous remifentanil vs. intermittent morphine boluses during scoliosis surgery. All patients were placed on a morphine PCA post-operatively. At 24 hours, the remifentanil group had consumed 30% more opiates than the intraoperative morphine group, although there were no differences in pain or sedation scores, thus the increased morphine consumption, while statistically significant, may not be clinically significant [Crawford MW et. al. Anesth Analg 102: 1662, 2006; FREE Full-text at Anesthesia & Analgesia]

Data Against Hyperalgesia: A multicenter, prospective, randomized study of 245 patients undergoing urologic or general surgery with remifentanil-based anesthesia were randomized to morphine at 0.15 mg/kg versus 0.25 mg/kg 30 minutes before the end of surgery. The high-dose group required less post-operative morphine in the PACU (0.10 mg/kg, versus 0.1 mg/kg, p < 0.01), but also had three episodes of respiratory depression. This study does not adequately address the issue of hyperalgesia as the time period for which pain scores and opiate consumption were measured (ie in the PACU) is well within the expected period of efficacy for the morphine given 30 minutes prior to closing [Fletcher D et. al. Anesth Analg 90: 666, 2000; FREE Full-text at Anesthesia & Analgesia]

A study of 60 elective open gynecological surgery patients randomized them to remifentanil (mean 0.24 ucg/kg/min) vs. sevoflurane-based (mean 1.75% inspired) anesthesia. All patients received a PCA post-operatively. The remifentanil group used 28.0 mg (versus 28.6 mg in the sevoflurane group, NS) at 24 hours. Pain scores were similar [Cortínez LI et. al Br J Anaesth 87: 866, 2001]

A study of 60 adults undergoing open colorectal surgery randomized them to either remifentanil (0.17 ucg/kg/min) versus 70% nitrous oxide during isoflurane anesthesia. Morphine was titrated to effect in the PACU, then a PCA was started. The median visual analog pain score was worse in the remifentanil group on arrival to the PACU (3 vs 1, p < 0.05), however there was no difference in pain scores at 5, 10, and 15 minutes, and no difference in morphine consumption, sedation scores, or PONV [Lee LH et. al. Anesthesiology 102: 398, 2005].