Managing opioid side – effects in clinical practice

Alain Borgeat

Orthopedic University Hospital Balgrist, Zurich, Switzerland

Pain is probably the most widely experienced and yet the last effectively contained affliction suffered by mankind. Opioid analgesics have a selective action on neurotransmission at various sites in the central nervous system.
They have little or no effect on peripheral nociceptive pathways or impulse conduction in primary afferent neurons. Experimental evidence suggests that they reduce both presynaptic and postsynaptic effects on central neurotransmission. Opioids decrease the release of substance P by producing presynaptic inhibition of small amyelinated C fibres in the dorsal columns of the spinal cord. In addition, at postsynaptic sites in the central nervous system, opioids decrease spontaneous activity by inducing hyperpolarization and thus increasing the threshold for excitation.¹

Effects and most adverse effects of opioids are mediated by specific opioid receptors; three major types have been identified as mu (u). Kappa (k) and delta (s). The vast majority of the opioids used in postoperative pain treatment are dealing with the mu receptor (mu 1 and mu 2).

The most frequent observed side effects in the postoperative period are nausea and vomiting (PONV), decreased gastrointestinal mobility, urinary retention and sedation. The occurrence of pruritus and hyperalgesia, although less frequent, are other troublesome effects.

1.      Nausea and Vomiting (PONV)
Large studies have shown that the incidence of PONV is around 25%.² The simplified risk score by Apfel et al.³ identifies four principal factors: female gender, non-smoking status, history of PONV and / or motion sickness and postoperative opioids. The need of postoperative opioids is a major risk factor. Roberts et al (4) clearly demonstrated that PONV are strongly influenced by postoperative opioid use in a dose – related manner. The authors were able to show that halving of the opioid dose results in a reduction of 6.0% in postoperative vomiting.
Management
The first stop is to recognize patients at high risks. For these it is important to keep the perioperative risk low, avoiding inhalation agents, nitrous oxide and anticholinesterase drugs (5). Performance of regional blocks and use of postoperative NSAIDs and paracetamol will decrease the need of postoperative opioids. PONV prophylaxis should be considered in patients classified, Apfel IV. Effective treatment of PONV includes 5-HT3 receptor antagonists, low dose droperidol and / or TCI with propofol at an effect site concentration between 0.5 – 0.8ug/ml.^3-6

2.      Decreased gastrointestinal mobility.
Opioid gastrointestinal toxicity is due to an increased tone of the small and large intestine, disorganization of peristalsis with decreased mobility, spasm of sphincters, decrease in gastric secretions, pancreatic juice and bile, increased water absorption, and intestinal content consolidation. Interestingly, tolerance does not develop to this effect.⁷
Management
The best way to reduce opioid gastrointestinal toxicity is to use any means which will reduce opioid need. The addition of NSAIDs and paracetamol is highly recommended. The use of an epidural with local anesthetics is the best way to prevent or to treat opioid induced gastrointestinal side - effects.

3.      Urinary retention
Systemic opioids may cause dysuria and urinary retention due to increased spasm of the sphincter and decreased detrusor tone.⁷ Urinary retention occurs in 15 to 70% of patients following epidural or intrathecal opioids.⁸
Management
It is mandatory to recognize patient and type of surgery at risk for this complication. It is wise for this group to place a urinary catheter prophylactically.
As soon as urinary retention occurred, the only effective treatment is catheterization.

Opioids are potent and often used analgesic in the postoperative period. To assure the success of postoperative analgesia it is important to anticipate the occurrence of side – effects. Patients at risk for opioid – induced side effects, type of surgery prone to exacerbate their occurrence should be early recognized in order to take the necessary measures to reduce their incidence and severity.⁹

References

            1.         Schug SA, Garrett WR, Gillespie G: Opioid and non-opioid analgesics. Best Pract Res Clin Anaesthesiol 2003; 17: 91-110

            2.         Wheeler M, Oderda GM, Ashburn MA, Lipman AG: Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain 2002; 3: 159-80

            3.         Apfel CC, Roewer N, Korttila K: How to study postoperative nausea and vomiting. Acta Anaesthesiol Scand 2002; 46: 921-8

            4.         Roberts GW, Bekker TB, Carlsen HH, Moffatt CH, Slattery PJ, McClure AF: Postoperative nausea and vomiting are strongly influenced by postoperative opioid use in a dose-related manner. Anesth Analg 2005; 101: 1343-8

            5.         Tramer MR: A rational approach to the control of postoperative nausea and vomiting: evidence from systematic reviews. Part II. Recommendations for prevention and treatment, and research agenda. Acta Anaesthesiol Scand 2001; 45: 14-9

            6.         Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N: A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004; 350: 2441-51

            7.         Schug SA, Zech D, Grond S: Adverse effects of systemic opioid analgesics. Drug Saf 1992; 7: 200-13

            8.         Chaney MA: Side effects of intrathecal and epidural opioids. Can J Anaesth 1995; 42: 891-903

            9.         Dolin SJ, Cashman JN: Tolerability of acute postoperative pain management: nausea, vomiting, sedation, pruritis, and urinary retention. Evidence from published data. Br J Anaesth 2005; 95: 584-91