Epidural morphine

Bozkurt P. The analgesic efficacy and neuroendocrine response in paediatric patients treated with two analgesic techniques using morphine-epidural and patient-controlled analgesia. Paediatr Anaesth 2002 12(3) 248-54. 

This type of pain management is used for postoperative pain, labor pain, and cancer pain. The most serious adverse reaction associated with the administration of narcotics by the epidural route is respiratory depression. The patient may also experience sedation, confusion, nausea, pruritus, or urinary retention. Fentanyl is increasingly used as an alternative to morphine sulfate because patients experience fewer adverse reactions. 

Sufentanil, fentanyl, remifentanil, alfentanil, and morphine sulfate should be administered only by those specifically trained in the use of IV and epidural anesthetics Oxygen, resusdtative, and intubation equipment should be readily available. 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Epidural analgesia is frequently used for lower extremity procedures and pain (e.g., knee surgery, labor pain, and some abdominal procedures). Intermittent bolus or continuous infusion of preservative-free opioids (morphine, hydromorphone, or fentanyl) and local anesthetics (bupivacaine) may be used for epidural analgesia. Opiates given by this route may cause pruritus that is relieved by naloxone. Adverse effects including respiratory depression, hypotension, and urinary retention may occur. When epidural routes are used in narcotic-dependent patients, systemic analgesics must also be used to prevent withdrawal since the opioid is not absorbed and remains in the epidural space. Doses of opioids used in epidural analgesia are 10 times less than intravenous doses, and intrathecal doses are 10 times less than epidural doses (i.e., 10 mg of IV morphine is equivalent to 1 mg epidural morphine and 0.1 mg of intrathecally administered morphine).45... 

Morphine may be administered orally, intravenously, or epidurally. An advantage of epidural administration is that it provides effective analgesia while minimizing the central depressant effects associated with systemic administration. The mechanism of action with the epidural route of administration involves opioid receptors on the cell bodies of first-order sensory neurons in the dorsal root ganglia as well as their axon terminals in the dorsal hom. Stimulation of these receptors inhibits release of substance P and interrupts transmission of the pain signal to the second-order sensory neuron. 

The IV or IM administration of parenteral narcotics (meperidine, morphine, fentanyl) is commonly used to treat the pain associated with labor. Compared to epidural analgesia, parenteral opioids are associated with lower rates of oxytocin augmentation, shorter stages of labor, and fewer instrumental deliveries. 

Morphine is often the choice in this category (1) multiple products available (2) multiple route of administration options, such as oral, rectal. IM. SC. IV. epidural, and intrathecal and (3) a known eqiipotency between these routes that allows a much easier transition. 

Morphine can be given orally or parenterally, as well as epidurally or intrathecally in the spinal cord. The opioids heroin and fentanyl are highly Upo-phiUc, allowing rapid entry into the 01S. Because of its high potency, fentanyl is suitable for transdermal deUvery (A). 

Limit epidural or intrathecal administration of morphine to the lumbar area. 

Epidural/Intrathecal administration Limit epidural or intrathecal administration of preservative-free morphine and sufentanil to the lumbar area. Intrathecal use has been associated with a higher incidence of respiratory depression than epidural use. Asthma and other respiratory conditions The use of bisulfites is contraindicated in asthmatic patients. Bisulfites and morphine may potentiate each other, preventing use by causing severe adverse reactions. Use with extreme caution in patients having an acute asthmatic attack, bronchial asthma, chronic obstructive pulmonary disease or cor pulmonale, a substantially decreased respiratory reserve, and preexisting respiratory depression, hypoxia, or hypercapnia. Even usual therapeutic doses of narcotics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Reserve use for those whose conditions require endotracheal intubation and respiratory support or control of ventilation. In these patients, consider alternative nonopioid analgesics, and employ only under careful medical supervision at the lowest effective dose. 

When used via the epidural route, the site for injection must be free of infection. In addition, the use of corticosteroids by the patient should be halted for at least 2 weeks prior to the insertion of the catheter to prevent infection, since morphine increases the immunosuppressive effects of the steroids. 

Zakowski M.I., S. Ramanathan, and H. Turndorf (1993). A 2-dose epidural morphine regimen in cesarean-section patients—pharmacokinetic profile. Acta Anaesthesiologica Scandinavica 37 584—589. 

After epidural injection, an opioid may transfer into the cerebrospinal fluid (CSF), into the blood or bind to epidural fat, the extent depending on their lipophilicity. After epidural administration, morphine passes slowly into the CSF. Sufentanil, which is highly lipid soluble, can be detected in the plasma within 2-5 minutes after epidural injection and part of the analgesic effect of the more lipid soluble opioids may be due to a supraspinal action amplifying the direct spinal action. Epidural fentanyl and sufentanil produce a more consistent and intense analgesia than morphine, with a faster onset. Flowever, the duration is short but this can be overcome by giving them by continuous epidural infusions. 

Side effects and complications tend to be higher with the intrathecal than the epidural route. A common side effect is pruritus, the incidence of which is higher with intrathecal than with epidural administration. It is dose-dependent, with an incidence of about 10% after epidural morphine 5 mg. The risk of severe, distressing itching is about 1%. Pruritus may be related to cephalad spread of morphine... 

Therapeutic doses of the opioid analgesics produce flushing and warming of the skin accompanied sometimes by sweating and itching CNS effects and peripheral histamine release may be responsible for these reactions. Opioid-induced pruritus and occasionally urticaria appear more frequently when opioid analgesics are administered parenterally. In addition, when opioids such as morphine are administered to the neuraxis by the spinal or epidural route, their usefulness may be limited by intense pruritus over the lips and torso. 

Dosages and routes of administration Morphine is available in different salt forms but the hydrochloride and sulfate (Vermeire and Remon, 1999) are used preferentially. The compound can be administered by the oral, parenteral or intraspinal route. Oral application is preferred for chronic pain treatment and various slow release forms have been developed to reduce the administration frequency to 2-3 times per day (Bourke et al., 2000). Parenteral morphine is used in intravenous or intramuscular doses of 10 mg, mostly for postoperative pain and self-administration devices are available for patient-controlled analgesia (PCA). Morphine is additionally used for intraspinal (epidural or intrathecal) administration. Morphine is absorbed reasonably well in the lower gastrointestinal tract and can be given as suppositories. 

Medico-technical instruments such as infusion pumps can be used in PCA (patient-controlled analgesia, Fig. 1) to provide patient-orientated and therapy as required, e.g. with morphine injection solutions. Depending on the patients perception of pain, they may add small doses of analgesics to the basic infusion by means of an electrically controlled infusion pump. The physician specifies the basic dose, which is infused independent of patient demands, the boluses that can be demanded, an hourly maximum dose and a refractory time that cannot be reduced between two doses. The infusion may be given intravenously, subcutaneously, epidurally or intraspinally. 

Glynn, C., Dawson, D., Sanders, R. A double blind comparison between epidural morphine and epidural clonidine in patients with chronic non cancer pain, Pain 1988, 34, 123-128. 

Motsch, J., Graber, E., Ludwig, K. Addition ofclonidine enhances postoperative pain analgesia from epidural morphine a double blind study, Anesthesiology 1990, 73, 1067-1073. 

Clinical use The indications for levobupivacaine include wound infiltration (0.25 % solution), nerve conduction block (0.25 - 0.5 %), spinal analgesia (0.5 %) and epidural anesthesia (0.5 to 0.75 %). For labour analgesia, lower concentrations of levobupivacaine are recommended when administered as epidural injection (0.125 to 0.25 % up to 25 mg) or infusion (0.25 %). The maximum dose for ilioinguinal or iliohypogastric block in children is 1.25 mg/kg/side (0.25 to 0.5 % solutions). For postoperative pain management, levobupivacaine can be applied epidurally in combination with the opioids fentanyl or morphine or with the a2-agonist clonidine. 

Asano, T., Dohi, S., lida, H. Antinociceptive action of epidural KATP channel openers via interaction with morphine and an a2-adrenergic agonist in rats, Anesthesia and Analgesia 2000, 90, 1146-1151. 

Pereira et al. (1993) evaluated postoperative pain relief and incidence of side-effects of the combination of epidural morphine (0.5 mg) and sublingual nifedipine (10 mg). In this double-blind, placebo-controlled study 36 women were submitted to elective operations (hysterectomy and colpoperineoplasty). The nifedipine-treated group showed a significant drop in blood pressure which was controlled by rehydration. The results indicate that epidural morphine-induced postoperative pain relief may be enhanced by systemic administration of nifedipine with easily controlled side-effects. 

Pereira, I.T., Prado, W.A., Dos Reis, M.P. Enhancement of the epidural morphine-induced analgesia by systemic nifedipine, Pain, 1993, 53, 341-355. 

Morphine sulfate Depodur SkyePharma/Endo Labs Epidural... 

Fentanyl is primarily used alone, but sometimes it is combined with other opiates such as Licodaine, Bupiva-caine, or morphine in epidural administration or in some I Vs. However, one of the more appealing virtues of fentanyl is that, unlike other opioids, it has a very mild effect on the emetic trigger zone of the medulla. For this reason, patients have less nausea and no vomiting when fentanyl is used. With other drugs, such as morphine, this unwanted side effect can be intense. Fentanyl also does not cause the release of histamine, which makes it safer for the cardiovascular system than morphine. 

Fentanyl Sublimaze , Duragesic 0.01-0.1 mg per hour 30-125 times more potent than morphine-, can be given via skin patch also used as an epidural during childbirth... 

Morphine Kadian , MS Contin , Oramorph 10-30 mg every 4 hours More effective when given intravenously than orally-, can also be used as an epidural during childbirth... 

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