Epidural or spinal opioids

Epidural opioids

Epidural or spinal opioids allow reduce the concentration of local anesthetic, thus reducing muscle weakness associated with their use, as well as improve the quality of the block. Intrathecal morphine is used for prolonged analgesia after cesarean section.

As discussed previously, opioids, in particular pethidine (meperidine), are widely used in laboring patients. When given by intramuscular injection they are not very effective for relieving pain and may cause some unpleasant side-effects, such as pruritis (itch), nausea and vomiting, constipation and dizziness. However, opioids can also be administered with local anesthetics for epidural or spinal block, and in obstetric anesthesia their use in this way is invaluable.

When given epidurally opioids diffuse into the cerebrospinal fluid and bind with opioid receptors in the spinal cord. As the result the transmission of painful stimuli is modified and clinically pain intensity is reduced. Similarly to the kinetics of other drugs administered epidurally, considerable amount of opioids absorbed into the blood, and only a small proportion – about ten percent – gets into the CFS. Still, the total dose of opioid in epidural is significantly smaller than that required to produce meaningful pain relief by intramuscular injection. Opioids are also commonly used in spinal anesthesia for cesarean section, at doses considerably smaller than in epidural block. In that case no absorption of opioid occurs and there are side-effects typical for opioid drugs are virtually non-existent.

The effects of neuraxial opioids vary according to a particular drug. In the context of neuraxial use opioids are divided into lipid soluble and water soluble. The most used water soluble opioid is morphine, lipid soluble – fentanyl and sufentanyl. This quality of opioid determines its behavior in the cerebrospinal fluid.

When lipid soluble fentanyl is given epidurally part of it diffuses through the dura and into the CSF. Anatomical structures of and around the spinal cord are rich in lipids, fentanyl binds to them and is effectively eliminated from the CSF. The onset of action is quick and the duration of action of neuraxial fentanyl is relatively short, about half hour. Neuraxial morphine, on the other hand, behaves differently. First of all, it takes longer for the effect to take place. But most importantly, morphine does not bind to the spinal cord structures and stays in the CSF. Because of this the analgesic effect of morphine is prolonged, up to twenty four hours and even longer. However, SCF slowly circulates within the subdural space towards the brain, taking morphine administered earlier with it. At the junction of the spinal cord and the brain is the medulla oblongata, or simply medulla, part of the central nervous system responsible for many important functions. It contains respiratory center that determines the rate and depth of breathing, in response to the content of carbon dioxide in the arterial blood. Direct action of morphine contained in the CSF has inhibitory effect on the respiratory center and may cause depression of breathing or, in severe cases, respiratory arrest. The degree of respiratory depression is dose dependent and also depends on the sensitivity of a particular patient to opioids.

Most reports of respiratory depression with intrathecal and epidural morphine are associated with relatively high doses of this drug, standard for clinical practice several decades ago. Later research however demonstrated that though lower doses result in slightly less efficient pain relief, they cause considerably fewer side-effects and complications.

Respiratory depression caused by neuraxial morphine is also easily treated with opioid antagonist naloxone. The dose of naloxone necessary to alleviate respiratory depression is lower than the dose that leads to the reversal of analgesia, and when this drug is be given in small increments respiratory problems are corrected and pain relief is preserved.

Small amounts of morphine – 75 to 100 microgram – are commonly used in spinal anesthesia for caesarean section, and this considerably reduces pain after the operation. Reduced pain leads to the reduced use of opioids for analgesia, with consequent reduction of possible side-effects.

In labor epidurals the effects of morphine are not beneficial, and lipid soluble opioids such as fentanyl or sufentanyl are used instead.

The effect of adding of opioids to local anesthetic mixture used for labor epidural if two fold. First, opioids improve the quality of pain relief by local anesthetics. Second, they allow to reduce the concentration of local anesthetics. This reduces undesirable side-effects, such as drop in blood pressure and muscle weakness that potentially can interfere with the second stage of labor.

The most popular local anaesthetic-opioid combination is the mixure of 0.2% ropivacaine with fentanyl at concentrations between 1 and 4 microgram per milliliter. These mixtures are pre-manufactured which eliminates errors during preparing the drugs. Ropivacaine is less toxic local anesthetic than previously used bupivacaine and has the least effect on muscle strength. Added fentanyl further reduces potential side-effects by allowing further reduction of the concentration of ropivacaine, to the point that some institutions practice the technique of “walking epidural”. To achieve this the amount of fentanyl is increased while the dose of ropivacaine is reduced to the minimum, thus preserving muscle strength to such degree that the woman can walk around the labor ward. Preservation of the ability to remain vertical may counteract prolongation of labor that may be caused by epidural.

Neuraxial opioids have their set of side-effects. Most common is pruritis, or itch. In most cases it is mild and well tolerated. In more severe cases it can be treated by small doses of naloxone. Nausea and/or vomiting are very rare with opioids administered in doses currently used in labor epidurals. Sedation and urinary retention are other potential side-effects of neuraxial opioids.

Potentially the most serious side-effect is respiratory depression, though it is very rare with opioids are used in epidural doses. It happens mostly when morphine is used, but has also been documented with other opioids. Respiratory depression is exceptionally uncommon with intrathecal morphine at doses below 200 microgram. When labor epidural is continued for prolonged period of time it is theoretically possible for fentanyl to accumulate and cause respiratory depression. Every patient with labor epidural is monitored for possible side-effects, and respiratory depression typically develops over a period of time. If respiratory rate starts decreasing epidural is stopped and the anesthetist called to assess the situation. In more serious cases naloxone is given to the patient. However, this scenario is unlikely, as the doses of fentanyl used currently in practice are low. Normally epidural infusion is given at the rate of about ten milliliters per hour. If the mixture contains 2 ug/ml of fentanyl, the hourly dose of this opioid will be 20 microgram. For comparison, the doses of fentanyl used during general anesthesia are in hundreds of micrograms. Spinal dose of fentanyl used for cesarean section is between 15 and 25 ug.

While discussing neuraxial opioids it is necessary to mention unique properties of pethidine. Until recently this drug was popular in labor wards for relieving pain in labor, though in recent years it has earned bad reputation due to its metabolite norpethidine that in some patients may cause seizures. Pethidine has very distinct pharmacological quality: in addition to its ability to bind to opioid receptors it affects electro-physiological conduction of the nerve tissue by blocking sodium receptors and acts as the local anesthetic. This property makes it possible to use pethidine as the sole drug for spinal or epidural anesthesia. It also causes side-effects typical for local anesthetics, such as reduction in blood pressure and motor block. In some places it is still used for this purpose.

As already mentioned, neuraxial morphine is generally not used in for labor analgesia. In some situations however the use of intrathecal morphine may be beneficial. The analgesic effect of small amount of spinal morphine in combination with very small dose of local anesthetic may last several hours, though both the duration and the degree of pain relief are variable. For patients who are well progressed in labor the effect may last long enough to provide pain relief until the baby is born. Recent study indicates that about sixty percent of women in labor who receive spinal block in this fashion get satisfactory pain relief for their childbirth. Single shot spinal does not require close monitoring of the patients, and this method – though not optimal – may be suitable for places with limited healthcare resources.

The standard of current practice of labor epidural is the use of low concentration of ropivacaine in combination with low dose fentanyl, though other combinations have been tested and used in some institutions. At the end of the day the precise composition of epidural mixture is less important than the principles it is based on: achievement of maximal analgesia with lowest incidence of side-effects.



Dr. Eugene Smetannikov is a practicing anesthesiologist with the interest in obstetric anesthesia. He is the author of the most comprehensive book on the subject, The Truth About Labor Epidural