Patient-controlled analgesia (PCA) is a delivery system with which patients self-administer predetermined doses of analgesic medication to relieve their pain. Since its introduction in the early 1980s, the daily management of postoperative pain has been extensively optimised. The use of PCA in hospitals has been increasing because of its proven advantages over conventional intramuscular injections. These include improved pain relief, greater patient satisfaction, less sedation and fewer postoperative complications. All PCA modes contain the following variables: initial loading dose, demand dose, lockout interval, background infusion rate and 1-hour or 4-hour limits. Morphine is the most studied and most commonly used intravenous drug for PCA. In spite of the fact that it is the 'first choice' for PCA, other opioids have been successfully used for this option. The most observed adverse effects of opioid-based PCA are nausea and vomiting, pruritus, respiratory depression, sedation, confusion and urinary retention. Although intravenous PCA is the most studied route of PCA, alternative routes have extensively been described in the literature. PCA by means of peridural catheters and peripheral nerve catheters are the most studied. Recently, transdermal PCA has been described. The use of peripheral or neuraxial nerve blocks is recommended to avoid the so called opioid tolerance observed with the intravenous administration of opioids. Numerous studies have shown the superiority of epidural PCA to intravenous PCA. The beneficial postoperative effects of epidural analgesia are more apparent for high-risk patients or those undergoing higher risk procedures. PCA with peripheral nerve catheters results in increased postoperative analgesia and satisfaction for surgery on upper and lower extremities. Serious complications occur rarely with these catheters. With the introduction of an Acute Pain Service, management of postoperative pain can be improved. This will also help to minimise adverse effects related to PCA and to avoid lethal mishaps.

Patient-Controlled Analgesia in the Management of Postoperative Pain

Uncertainty about the clinical significance of tolerance to opioid analgesia has important and diverse implications. Although understanding of the characteristics and mechanisms of experimental tolerance has grown, the clinical correlates and ramifications of these findings remain ambiguous to practitioners prescribing long-term opioid therapy to patients for the treatment of malignant and non-malignant pain. In this review I shall discuss clinical aspects of tolerance and the associated phenomena of dependence, withdrawal and addiction to opioids as they apply to the practice of clinicians who manage patients with chronic malignant and non-malignant pain.

Opioid tolerance: the clinical perspective

Opioidergic and dopaminergic modulation of respiration.

Electroacupuncture (EA) is used in traditional Chinese medicine to treat arrhythmias, hypertension and myocardial ischemia. Our previous work suggests that the inhibitory effect of EA on the pressor reflex induced by bradykinin (BK) applied to the gallbladder is due, in part, to the activation of opioid receptors, most likely located in the rostral ventrolateral medulla (rVLM). However, specific opioid receptor subtypes, and hence the neurotransmitters. responsible for this inhibition are unknown. Therefore, in anesthetized cats, BK (10 microg/ml) was applied to the gallbladder to induce transient reflex increases in arterial blood pressure (BP). EA (1-2 mA, 5 Hz, 0.5 ms pulses) was delivered through acupuncture needles inserted bilaterally into Neiguan and Jianshi acupoints on forelimbs, overlying the median nerves. EA attenuated the BK-induced pressor response by 39%. Opioid receptor subtype antagonists or agonists were microinjected unilaterally into the rVLM. The mu- and delta-receptor antagonists CTOP and ICI 174,864, respectively, significantly attenuated the EA-induced inhibition for at least 30 min. The K-receptor antagonist (nor-BNI) was less effective and was shorter acting. Like EA, microinjection of mu- and delta-opioid agonists, DAGO and DADLE, respectively, into the rVLM significantly decreased the pressor responses. In contrast, the kappa-opioid agonist, U50,488, failed to alter the BK-induced pressor response. We conclude that a significant portion of inhibition of the gallbladder pressor response by EA is related to activation of mu- and delta-opioid receptors in the rVLM. The endogenous neurotransmitters for mu- and delta-opioid receptors, beta-endorphins and enkephalins, in the rVLM, therefore appear to play a role in the EA-related modulation of cardiovascular reflex responses. Conversely, dynorphin is less likely to be involved in this response.

Rostral ventrolateral medullary opioid receptor subtypes in the inhibitory effect of electroacupuncture on reflex autonomic response in cats

Pruritus occurs frequently following opioid use, particularly after neuraxial administration. Although not life threatening, pruritus is discomforting and may decrease patient satisfaction. Even though the mechanism of opioid-induced pruritus is not yet fully understood, there is increasing evidence of the important role played by μ opioid receptors. Animal experiments pointing to the role of the μ opioid receptor and the efficacy of μ opioid receptor antagonists for opioid adverse effect prophylaxis and treatment have been replicated in several studies. Serotonin and dopamine D2 receptors, prostaglandins and spinal inhibitory pathways may also be involved in the genesis of pruritus.

T. Siener

Papers

Opioid-Agonists and -Antagonists, Opioid-Receptors

[Opioid agonists and antagonists, opioid receptors].