Opioids epidural

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 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). 

Infumorph The recommended initial epidural dose in patients who are not tolerant to opioids range from 3.5 to 7.5 mg/day. The usual starting dose for continuous epidural infusion, based upon limited data in patients who have some degree of opioid tolerance, is 4.5 to 10 mg/day. The dose requirements may increase significantly during treatment, frequently to 20 to 30 mg/day. 

Epidural and intrathecal opioids are widely used for postoperative and obstetric analgesia. In contrast to local anaesthetics, spinal opioids cause minimal sympathetic efferent and motor blockade. Pethidine, which has local anaesthetic activity, can produce sensory and motor blockade. Because remifentanil is formulated with glycine as a vehicle, it should not be used epidurally or intrathecally, since glycine is neurotoxic. 

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. 

Because epidural opioids are usually ineffective in controlling pain during the final stages of labour they are commonly combined with a low concentration of a local anaesthetic, e.g. 0.125% bupivacaine. There has been speculation that epidural opioids may reactivate herpes simplex in pregnant patients. The aetiology is unclear. Herpes simplex after delivery is potentially dangerous because of the risk of herpes encephalitis in the infant. Spinal opioids should therefore be avoided in the parturient with a history of recurrent herpes simplex. 

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. 

Because of their direct action on the superficial neurons of the spinal cord dorsal horn, opioids can also be used as regional analgesics by administration into the epidural or subarachnoid spaces of the spinal column. A number of studies have demonstrated that long-lasting analgesia with minimal adverse effects can be achieved by epidural administration of... 

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. 

Clinical use Ropivacaine is used for local infiltrations such as field block (0.75 % solution) and for nerve block (0.75 %) up to 300 mg and for epidural anesthesia (0.75 and 1.0 %) up to 200 mg. When used for labour analgesia, epidural doses up to 40 mg are recommended. A combination of opioids is often administered via the epidural route for postoperative analgesia. 

Consistent with these hypotheses is the finding that continuous infusion of the opioid into the epidural or intrathecal space provides optimal pain relief postoper-atively or in chronic, intractable pain.2 40 83 Continuous infusion is associated with certain side effects, especially nausea and constipation, as well as the potential for disruption of the drug delivery system.24 57 77 Problems with tolerance have also been reported during continuous administration,27 but it is somewhat controversial whether tolerance really develops when these drugs are used appropriately in the clinical management of pain (see section on Concepts of Addiction, Tolerance, and Physical Dependence ). Hence, the benefit-to-risk ratio for continuous epidural or intrathecal infusion is often acceptable in patients with severe pain. This method of opioid administration continues to gain acceptance.24 57... 

Werawatganon T, Charuluxanun S. Patient controlled intravenous opioid analgesia versus continuous epidural analgesia for pain after intra-abdominal surgery. Cochrane Database Syst Rev. 2005 CD004088. 

Small quantities of opiate injected intrathecally or epidurally produce segmental analgesia. This observation led to the clinical use of spinal and epidural opiates during surgical procedures and for the relief of postoperative and chronic pain. As with local anesthesia, analgesia is confined to sensory nerves that enter the spinal cord dorsal horn in the vicinity of the injection. Presynaptic opioid receptors inhibit the release of substance P and other neurotransmitters from primary afferents, whereas postsynaptic opioid receptors decrease the activity of certain dorsal horn neurons in the spinothalamic tracts. 

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. 

Opioid analgesics can also be used at low doses by the epidural and spinal routes of administration to produce excellent postoperative analgesia. 

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