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Side Effects of Intrathecal and Epidural Opioids

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Side Effects of Intrathecal and Epidural Opioids 891 Review Article Side effects of intrathe- Mark A. Chancy MD cal and epidural opioids The purpose of this article is to review the literature on the condaires classiques sont le prurit, les nausdes et les vomis- side effects of intrathecal and epidural opioids. English-language sements, la rktention urinaire et ia ddpression respiratoire; ce articles were identified through a MEDLINE search and ne sont toutefois pas les seuls effets secondaires rapport~s. La through review of the bibliographies of identified articles. With plupart ddpendent de la dose et sont plus frrquents lorsque the increasing utilization of intrathecal and epidural opioids le morphinique est administr~ par la voie sous-arachno~dienne. in humans during the 1980s, a wide variety of clinically relevant Les effets second_aires surviennent moins souvent chez lea pa- side effects have been reported. The four classic side effects tients exposds de fafon chronique ~ des morphiniques sous- are pruritus, nausea and vomiting, urinary retention, and res- arachnoi'diens, 6piduraux ou systdmiques. Quelquevuns des ef- piratory depression. Numerous other side effects have also been fets secondaires rrsultent .de l'interaction de r~cepteurs morphi- described. Most side effects are dose-dependent and may be niques sprcifiques mais pas tous. Les auteurs concluent que more common if the opioid is administered intrathecaily. Side Hntroduction des morphiniques sous-arachno?diens et dpidu- effects are less common in patients chronically exposed to either raux reprrsente la pere~e la plus importante des deux dernib.res intrathecal, epidural, or systemic opioids. Some side effects are drcennies dans le domaine du traitement de la douleur. Ce- mediated via interaction with specific opioid receptors while pendant, des effets secondaires multiples de nature non- others are not. It is concluded that the introduction of intrath- nociceptive sont susceptiblea de survenir. Tous lea mkdecins ecal and epidural opioids marks one of the most important utilisateurs de morphinique sous-arachnoMiens et ~piduraux breakthroughs in pain management in the last two decades. doivent connattre ces effets secondaires qui sont mineurs pour However, a wide variety of clinically relevant non-nociceptive la plupart, alors que d'autres sont potentiellement idtaux. side effects may occur. All physicians utilizing intrathecal and epidural opioids must be aware of these side effects, for while most are minor, others are potentially lethal. Pure antinoeiception without side effects has long been an elusive goal. In the 1970s, the discovery of highly spe- Ce travail constitue un survol de la litt$rature portant sur les cific opioid receptors in the central nervous system, in effets secondaires des morphiniques sous-arachnogdiens et ~pi- particular their existence in the spinal cord, created new durau:c. Les articles en langue anglaise ont ~t~ identifids grace enthusiasm for the possible realization of this goal. Sub- ?: une recherche sur Medline et une revue des bibliographies sequent demonstration that small amounts of intrathecal des articles trouv$s de cette fafon. Avec l'utilisation croissante or epidural opioids produced profound antinociception des morphiniques sous-arachno~diens et ~piduraux d$but6e only heightened enthusiasm. However, with increasing clans les anr~es 80, on a d~crit avec pertinence une grande universal application of the technique in humans in the varidt6 d'effets secondaires convaincants. I_~ quatres effets se- 1980s, a wide variety of clinically relevant non-nocieeptive side effects have been reported, t,2 Because of the profound antinociception obtained and despite the non-nociceptive Key words side effects, spinal application of opioids remains very ANALGESIA: postoperative; popular and effective in the treatment of many pain states. ANALGESIA: morphine, fentanyl, sufentanil. Opioids are perhaps the oldest and most studied of From the Department of Anesthesiology, Foster G. MeGaw drugs. Opium use, for its euphoric effects, can be traced Hospital, Loyola University Medical Center, 2160 South First back over 4000 yr and its respiratory depressant effects Avenue, Maywood, Illinois 60153. were first noted approximately 600 yr ago. It was not Address correspondence to: Dr. Mark A. Chaney, until 1971, however, that highly specific opioid receptors Department of Anesthesiology, Foster G. MeGaw Hospital, were discovered. 3 In 1973, opioid receptors were localized Loyola University Medical Center, 2160 South First Avenue, in mammalian brain 4 and in 1976 they were found to Maywood, Illinois 60153. exist in primate spinal cord. s Also in 1976, Yaksh and Acceptedfor publication 9th June, 1995. Rudy first demonstrated the effectiveness of intrathecal CAN J ANAESTH 1995 / 42:I0 / ppS91-903 892 CANADIAN JOURNAL OF ANAESTHESIA opioids in abolishing experimental pain in an animal TABLE I Side effects of intratheeal and epidural opioids model. 6 In 1979, initial reports of intrathecal 7 and epi- Pruritus dural s use of morphine in humans appeared in the lit- Nausea and vomiting erature. Urinary retention Intrathecal and epidural opioids produce profound seg- Respiratory depression mental antinociception in doses much smaller than would Mental status changes be required for comparable antinociception if adminis- Central nervoussystem excitation Hyperalgesia tered systemically. Antinociception may be prolonged; Herpes simplex labialis virus reactivation when morphine is utilized, it may persist for days fol- Neonatal morbidity lowing a single injection. 9 Unlike the response to local Sexual dysfunction anaesthetics, there is no motor, sensory, or autonomic Ocular dysfunction blockade. Paralysis and hypotension, therefore, are ab- Gastrointestinaldysfunction Thcrmoregulatorydysfunction sent. Another critical advantage over local anaesthetics Water retention is the availability of a specific opioid receptor antagonist, Cardiac dysrhythmia naloxone. Hair loss Neurotoxicity Phmnacokinefics of intmthecal and epidural opioids Anaphylaxis Side effects of intrathecal and epidural opioids are caused by presence of the drug in either cerebmspinal fluid or blood. Therefore, following administration of intrathecal and epidural opioids, side effects will be profoundly af- for elimination. Zs The terminal elimination half-life of fected by their pharmacokinetic behaviour. Fentanyl and morphine in cerebrospinal fluid is similar to that in sufentanil are, respectively, approximately 800 and 1600 plasma, two to four hours. 10,17 times as lipid-soluble as morphine. When administered Epidural administration of opioids also produces con- intrathecally or epiduraUy, therefore, morphine will ex- siderable cerebrospinal fluid concentrations of drug. hibit slower onset and longer duration of antinociception Penetration of the dura is considerably influenced by li- and a higher incidence of some side effects. pophilicity, but molecular weight may also play an im- Intratheeal administration of opioids immediately pro- portant role. 19 Following epidural administration, cere- duces high cerebrospinal fluid concentrations of drug that brospinal fluid concentrations of fentanyl peak in 10 to are dose-dependent.~~ Vascular reabsorption of opioids 20 rain 2~ while sufentanil concentrations peak in about following intrathecal administration does occur to some six minutes. 21 In contrast, cerebrospinal fluid concentra- degree, but is clinically irrelevant, n-13 Fentanyl and su- tions of morphine, following epidural administration, fentanil penetrate the spinal cord quickly, leaving little peak in one to four hours. ~,z3 Furthermore, only about drug to ascend cephalad in cerebrospinal fluid. In con- 3% of the dose of morphine administered epidurally Wast, morphine penetrates the spinal cord slowly, allowing crosses the dura to enter cerebrospinal fluid.Z~ The epi- considerable amounts of drug to ascend cephalad in cere- dural space contains an extensive venous plexus. There- brospinal fluid. Following lumbar intrathecal morphine fore, vascular reabsorption following epidural administra- administration, appreciable cervical cerebrospinal fluid tion of opioids is extensive. Epidural administration of eoneentrations occur one to five hours after injection, morphine, fentanyl, or sufentanil produces opioid blood while cervical cerebrospinal fluid concentrations of a concentrations that are similar to an intramuscular in- highly lipophilic opioids, similarly administered, are min- jection of an equivalent dose. Following epidural admin- imal. 14.15 The underlying cause of ascension of morphine istration, fentanyl blood concentrations peak at about five is bulk flow of eerebrospinal fluid. Cerebrospinal fluid to ten minutes ~;-s while sufentanll blood concentrations ascends in a cephalad direction from the lumbar region, peak even faster. =3~6 In contrast, blood concentrations of reaching the cisterna magna by one or two hours and morphine following epidural administration peak at about the fourth and lateral ventricles by three to six hours. 16 10 to 15 mill. ~7;s Although coughing, sneezing, or straining can affect movement of cerebrospinal fluid, body position does Side effects of intratheezd and epidural opioids not. 16 Highly lipophilic opioids are removed from cere- Side effects of intrathecal and epidural opioids are listed brospinal fluid rapidly secondary to vascular reabsorption in Table I. The four classic side effects are pruritus, nan- and spinal cord penetration. 17 In contrast, morphine per- sea and vomiting, urinary
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