The immediate postanesthesia phase is when the patient is most vulnerable to complications (see Chapter 29).¹ Many drugs that have residual anesthetic effects well into the postanesthesia period are used in modern anesthesia care. These agents include the potent inhaled agents, muscle relaxants, benzodiazepines, and opioids. Respiratory depression is the most common adverse event in the postanesthesia care unit (PACU); therefore the use and understanding of the various opioid agents optimize patient outcomes. In addition, the reduction of pain in the PACU is one of the primary focuses of care in the perianesthesia phase. In addition to assessing pain, the perianesthesia nurse must take into the evaluation of pain the preoperative, intraoperative, and postanesthesia phase of the surgical patient. Because all pain-reducing drugs must be taken into account during the pain assessment in the PACU, the mixed action or agonist-antagonist combination drugs are presented in this chapter. With a detailed description of the major opioids used in the perianesthesia period provided, the PACU nurse will be able to make excellent informed decisions in regard to the anticipated outcome of the patient of pain reduction and comfort.

Concept of opioids and opioid receptors

Opioids are the substances, either natural or synthetic, that are administered into the body (exogenous) and bind to specific receptors to produce a morphine-like or opioid agonist effect. The endogenous opioids are the endorphins. The endorphins, which are produced in the body, attach to the opioid receptors in the central nervous system (CNS) to activate the body’s pain modulating system. The term opioid is used because of the multitude of synthetic drugs with morphine-like actions; with the advent of receptor physiology, opioid has replaced the term narcotic, which is derived from the Greek word for “stupor” and usually refers to both the production of the morphine-like effects and the physical dependence.²

The naturally occurring alkaloids of opium are divided into two classes: phenanthrene and benzylisoquinoline. The principal phenanthrene series of drugs includes morphine, codeine, and thebaine. Papaverine and noscapine, which lack opioid activity, represent the benzylisoquinoline alkaloids of opium.³

The synthetic opioids have been produced with the modification of the chemical structure of the phenanthrene class of drugs. Drugs such as fentanyl (Sublimaze) and meperidine (Demerol) are examples of synthetic opioids.²^,⁴

The identification of specific opioid receptors has enhanced the understanding of the agonist and antagonist actions of this category of drugs. The opioid receptors are located in the CNS, principally in the brain stem and spinal cord. These receptors have been determined by the pharmacologic effect they produce when stimulated by a specific agonist along with how the effect is blocked by a specific antagonist. The three major categories of opioid receptors are the mu (μ), delta (δ), and kappa (κ).⁴^,⁵

The mu receptors are mainly responsible for the production of supraspinal analgesia effects with stimulation. These receptors are further divided into mu-1 and mu-2 types. Activation of the mu-1 receptors results in analgesia; when the mu-2 receptors are stimulated, hypoventilation, bradycardia, physical dependence, euphoria, and ileus can result. The mu receptors are activated by morphine, fentanyl, and meperidine. The drug that is specific to the mu-1 receptor is meptazinol, which is supraspinal in regard to analgesia; the mu-2 receptor analgesia occurs at the spinal level. Other characteristics of the mu-1 and mu-2 receptors are summarized in Table 22-1. Stimulation of the kappa receptors results in spinal analgesia, dysphoria, hallucinations, hypertonia, tachycardia, tachypnea, mydriasis, sedation, and miosis, with little effect on ventilation. The drugs that possess both opioid agonist and antagonist activities, such as nalbuphine (Nubain), have their principal action on the kappa opioid receptors. The delta opioid receptors, when stimulated, serve to modulate the activity of the mu receptors and cause depression and urinary retention. The drug naloxone (Narcan) attaches to all the opioid receptors and thus serves as an antagonist to all the opioid agonists (see Table 22-1).²^,⁴

Table 22-1 Characteristics of Various Opioid Receptors

Opioids

Opioids, or narcotics, are used often in anesthesia practice. They are usually used in the nitrous-opioid (balanced) techniques, which involve the use of an opioid, nitrous oxide, and oxygen, with or without a muscle relaxant, and propofol for induction.

The effects of opioids generally last well into the PACU phase, and every perianesthesia nurse should have a good knowledge of the pharmacologic actions of each opioid that is administered to the patient in the perioperative phase of the surgical experience.

The administration of opioids in the perioperative period is not without the concern of overdose. The major signs of overdose with opioids are miosis, hypoventilation, and coma. If the patient becomes severely hypoxemic, mydriasis can occur. Airway obstruction is a strong possibility because the skeletal muscles become flaccid. Hypotension and seizures can also occur. The treatment for an opioid overdose is mechanical ventilation and the slow titration of naloxone. Consideration must always be given to the fact that some patients who become overdosed with an opioid may indeed be already physically dependent. Naloxone can precipitate an acute withdrawal syndrome.²

Meperidine hydrochloride

Meperidine (Demerol) was discovered in 1939 by Eisleb and Schauman. Because it is chemically similar to atropine, it was originally introduced as an antispasmodic agent and was not used as an opioid anesthetic agent until 1947. The main action of this drug is similar to morphine; it stimulates the subcortical mu receptors, which results in an analgesic effect. Meperidine is approximately one tenth as potent as morphine and has a duration of action of 2 to 4 hours. The onset of analgesia is prompt (10 minutes) after subcutaneous or intramuscular administration. All pain, especially visceral, gastrointestinal, and urinary tract, is satisfactorily relieved. This drug causes less biliary tract spasm than morphine; however, in comparison with codeine, meperidine causes greater biliary tract spasm. It produces some sleepiness but causes little euphoria or amnesia. Meperidine increases the sensitivity of the labyrinthine apparatus of the ear, which explains the dizziness, nausea, and vomiting that sometimes occur in ambulatory patients.²^,⁴

This opioid may slow the rate of respiration, but the rate generally returns to normal within 15 minutes after intravenous injection. The tidal volume is not changed appreciably. In equivalent analgesic doses, meperidine depresses respiration to a greater extent than does morphine. Some authors have noted that meperidine can release histamine from the tissues. Occasionally, urticarial wheals form over the veins where meperidine has been injected. The usual treatment is discontinuation of the use of meperidine and, if the reaction is severe, administration of diphenhydramine (Benadryl). Diphenhydramine further sedates the patient, however, and should be administered only if truly warranted.

Meperidine in therapeutic doses does not cause any significant untoward effects on the cardiovascular system. When this drug is administered intravenously, it usually causes a transient increase in heart rate. With intramuscular administration, no significant change in heart rate is observed. One of the major concerns with this drug is orthostatic hypotension, probably caused by meperidine’s interference with the compensatory sympathetic nervous system reflex. After administration of meperidine, a patient should be repositioned slowly in a “staged” approach to avoid any possibility of hypotension.

Meperidine is generally metabolized in the liver; less than 5% is excreted unchanged by the kidneys. However, because of a toxic metabolite of meperidine, patients who are administered this drug may have seizures.² Meperidine is partially metabolized to normeperidine which has some analgesic effects, but more importantly, lowers the seizure threshold and can induce CNS excitability. Meperidine probably should not be administered to elderly patients because renal dysfunction may occur and less tolerance to normeperidine.

Because of its spasmolytic effect, meperidine is the drug of choice for biliary duct, distal colon, and rectal surgery. It offers the advantages of little interference with the physiologic compensatory mechanisms, low toxicity, smooth and rapid recovery, prolonged postoperative analgesia, excellent cardiac stability in patients at poor risk, and ease of detoxification and excretion.²^,⁴^,⁵ Meperidine is used most often with procedures now, and not typically for long-term pain management because of the effects of normeperidine over time.

Fentanyl

Janssen and colleagues ⁸ introduced a series of highly potent meperidine derivatives that were found to render the patient free of pain without affecting certain areas in the CNS. Fentanyl (Sublimaze) appeared to be of special interest. In regard to analgesic properties, fentanyl is approximately 80- to 125-fold more potent as morphine and has a rapid onset of action of 5 to 6 minutes and a peak effect within 5 to 15 minutes. The analgesia lasts 20 to 40 minutes when administered intravenously. Via the intramuscular route, the onset of action is 7 to 15 minutes; the analgesia usually lasts 1 to 2 hours. When fentanyl is administered as a single bolus, 75% of the drug undergoes first-pass pulmonary uptake. That is, the lungs serve as a large storage site and this nonrespiratory function of the lung (see Chapter 12) limits the amount of fentanyl that actually reaches the systemic circulation. If the patient receives multiple doses of fentanyl via single injections or infusion, the first-pass pulmonary uptake mechanism becomes saturated and the patient has a prolonged emergence because of increased duration of the drug. Consequently, during the admission of the patient to the PACU, the postanesthesia nurse must determine the frequency and amount of intraoperative fentanyl administration. Patients who have received a significant amount of fentanyl via infusion or via titration should be continuously monitored for persistent or recurrent respiratory depression. In addition, fentanyl has been implicated in what is called a delayed-onset respiratory depression. In some patients, a secondary peak of the drug concentration in the plasma occurs approximately 45 minutes after the apparent recovery from the drug. This syndrome can occur when some of the fentanyl becomes sequestered in the gastric fluid and then can become recycled into the plasma in approximately 45 minutes. Therefore, in the PACU, all patients who have received fentanyl should be continuously monitored for respiratory depression for at least 1 hour from the time of admission to the unit.²

Fentanyl can be administered during surgery at three different dose ranges, depending on the type of surgery and the desired effect. For example, the low-dose range of 2 to 20 mcg/kg attenuates moderately stressful stimuli. The moderate dose range is 20 to 50 mcg/kg and strongly obtunds the stress response. The megadose range of as much as 150 mcg/kg blocks the stress response and is particularly valuable when protection of the myocardium is critical.⁴

Fentanyl shares with most other opioids a profound respiratory depressant effect, even to the point of apnea. Rapid intravenous injection can provoke bronchial constriction and resistance to ventilation caused by rigidity of the diaphragmatic and intercostal muscles. This is commonly called the fixed chest syndrome, which can occur when any potent opioid analgesic is administered too rapidly via the intravenous route. Should this syndrome occur, intravenous subclinical administration of succinylcholine (15 to 25 mg) relieves the rigidity of the chest wall muscles. When succinylcholine is administered for this purpose, the perianesthesia nurse should be prepared to ventilate the patient’s lungs until the skeletal muscle relaxant properties of succinylcholine subside.

Fentanyl, unlike most opioids, has little or no hypotensive effects and usually does not cause nausea and vomiting. Because of its vagotonic effect, it may cause bradycardia, which can be relieved with atropine or glycopyrrolate. Fentanyl can be reversed with the opioid antagonist naloxone, which also reverses analgesia. Should fentanyl be reversed with naloxone in the PACU, the perianesthesia nurse should continue to monitor the patient for the possible return of respiratory depression, because the duration of the respiratory depression produced by the fentanyl may be longer than the duration of action of naloxone.

Fentanyl can be used alone in a nitrous-opioid technique. It also is used in the PACU in the form of a low-dose intravenous drip for pain relief; however, fentanyl is usually given slowly intravenously in the PACU for breakthrough pain (see Table 22-2 for helpful calculation of milligram to microgram dosage information).

Table 22-2 Example of Conversion of Dosage Calculations from Milligrams to Micrograms

MILLIGRAMS	MICROGRAMS	MILLILITERS OF FENTANYL
0.025	25	0.5
0.05	50	1.0
0.10	100	2.0
0.15	150	3.0
0.20	200	4.0
0.25	250	4.5
0.50	500	10.0
1.00	1000	20.0

Sufentanil

Sufentanil is an analogue of fentanyl and is approximately fivefold to sevenfold more potent as fentanyl. Anesthesia with sufentanil can be induced more rapidly, with basically the same technique as that used for fentanyl, without an increase in the incidence rate of chest wall rigidity. However, sufentanil can produce chest wall rigidity; therefore if it is administered in the PACU, equipment for administration of oxygen with positive pressure and the skeletal muscle relaxant succinylcholine should be on hand. The incidence rate of hypertension with sufentanil is lower than with comparable doses of fentanyl. Bradycardia is infrequently seen in patients who receive sufentanil, and when high-dose sufentanil is used in combination with nitrous oxide-oxygen, the mean arterial pressure and cardiac output may be decreased. The recovery time from sufentanil from the time of injection is about the same as with fentanyl, because sufentanil is rapidly eliminated from tissue storage sites; consequently, the duration of action of sufentanil is about the same as with fentanyl. In addition, the incidence rates of postoperative hypertension, the need for vasoactive agents, and the requirements for postoperative analgesics are generally reduced in patients who are administered moderate or high doses of sufentanil in comparison with patients given inhalation agents. Of particular interest to the perianesthesia nurse is that sufentanil has an additive effect that is seen in patients who receive barbiturates, tranquilizers, other opioids, general anesthetics, or other CNS depressants. This effect is especially true of benzodiazepines because they can potentiate a profound hypotensive action. Therefore, when sufentanil is combined with any of these drugs, particular attention should be paid to any signs of decreased respiratory drive, increased airway resistance, or hypotension. Immediate countermeasures include maintenance of a patent airway with proper positioning of the patient, placement of an oral airway or endotracheal tube, and administration of oxygen. If indicated, naloxone should be used as a specific antidote for management of the respiratory depression. The duration of respiratory depression after overdose with sufentanil may be longer than the duration of action of the naloxone. Consequently, the patient should be constantly observed for the recurrence of respiratory depression, even after the initial successful treatment with naloxone. Hypotension can be treated with reversal with naloxone; however, fluids and vasopressors may be indicated (see Chapter 11).⁴

Alfentanil

Alfentanil is another analogue of fentanyl that is approximately one tenth as potent and has approximately one third the duration of action of fentanyl. The onset of action of this drug occurs in 1 or 2 minutes, and the duration of action is 20 to 30 minutes. Alfentanil appears to have significant advantages over currently available opioid anesthetics. For example, it has no cumulative drug effects, and once the infusion of alfentanil is terminated, the emergence time is predictable. Alfentanil, like fentanyl, produces minimal hemodynamic effects and offers a high therapeutic index. In fact, the therapeutic index for alfentanil is higher than those of fentanyl and other opioids. A therapeutic index is the ratio of the lethal dose to the effective dose; the higher the therapeutic index, the farther the lethal dose from the dose used for the desired effect. More specifically, the therapeutic index of fentanyl is 270, which means that it is approximately four times safer than morphine. The therapeutic index of alfentanil is approximately 2.5 times more favorable than that of fentanyl.⁹^–¹¹

Alfentanil, in addition to its place in the operating room, may also have important uses in the PACU. Its rapid onset and brief duration of action make it advantageous for the immediate pain relief needs of PACU patients. As previously stated, the drug has approximately one third the potency of fentanyl, but its onset of action is at least three times faster; its duration is one third that of fentanyl, and it has a high therapeutic index, which makes alfentanil well suited for pain relief in the immediate postoperative period. The drug produces few cardiovascular effects and thus should be of great value in preventing dangerous reflexes, such as tachycardia during intubation. Clinical observation indicates that the recovery time for this drug is extremely rapid. Therefore patients who receive this drug during surgery most likely have pain early in the immediate postoperative period, and the appropriate analgesic should be administered.

Remifentanil

Remifentanil is a selective mu opioid agonist that has an analgesic potency almost equal to fentanyl and twentyfold more potent than alfentanil. This drug has some excellent pharmacologic properties in that it is brief in action, titratable, and noncumulative; it lacks histamine release; and it has a rapid recovery after the discontinuation of the drug. The onset of this drug is within 1 minute. When the drug is discontinued, it is metabolized quickly; its effects disappear within 4 minutes. The remifentanil anesthetic technique is excellent for suppression of the stress response and allows for excellent depression of neurologic responses. In regard to the immediate postanesthesia period, remifentanil is better than most intravenous opioid drugs in regard to residual effects because it has a rapid recovery and less risk of postoperative respiratory depression.

This drug should probably not be used in the PACU; however, if the drug is administered in the PACU, it should be administered only by an anesthesia provider who is experienced in the administration of the drug. Some of the adverse effects of the drug may accompany its administration.¹^,¹²^,¹³

Remifentanil is given via intravenous infusion with an infusion pump and should never be administered via intravenous bolus. The drug can produce the fixed chest syndrome and can also cause nausea and vomiting, respiratory depression, and mild-to-moderate depression of the heart rate and blood pressure.

Partial agonist-antagonist drugs

The partial agonist-antagonist drugs represent a category of drugs that have a primary opioid effect by using the competitive antagonist properties on the mu opioid receptor and an agonist at the kappa and sigma receptors, all leading to providing analgesia. This category of drugs has a low addiction potential, providing mild to moderate pain relief.

Pentazocine

Pentazocine (Fortral, Talwin), an opioid agonist and antagonist analgesic, was first synthesized in 1959. The drug has significant activity and a low addiction potential. It is approximately one third as potent as morphine when given intramuscularly. Its advantage over morphine is that it can be given orally. Pentazocine can be used before and after surgery for the relief of pain from abdominal, cardiac, genitourinary, orthopedic, neurologic, and gynecologic surgery. The observed side effects of this drug include sedation, dizziness, nausea, and vomiting, but these occur infrequently.

Studies of the relative potency of this drug indicate that 30 mg of pentazocine is analgesically equivalent to 10 mg of morphine and 75 mg of meperidine. Pentazocine has been established to relieve severe pain and is approximately twofold to fourfold less potent than morphine when administered parenterally.²^,⁴^,¹⁴^–¹⁶

Pentazocine can be used in the nitrous-opioid technique. The respiratory depression produced by pentazocine is potentiated when general anesthetics are used concomitantly. Pentazocine produces an increase in systolic blood pressure and does not appear to have depressant effects on cardiac output. The drug should be used with caution in patients with renal or hepatic impairment. Pentazocine depresses the respiratory system in a manner comparable with morphine in equivalent analgesic doses. Tolerance to the analgesic effect of the drug does not appear to develop as it does with other opioids. Because pentazocine is an opioid antagonist at the mu receptors, administration of this drug to a patient who depends on opiates can induce abrupt withdrawal symptoms.

The onset of analgesic activity of pentazocine is approximately 2 or 3 minutes when it is given intravenously and 15 to 20 minutes when given intramuscularly. The duration of action is approximately 3 hours. When given orally, the drug is approximately one third as potent as when it is given intramuscularly.²^,¹³

Butorphanol

Butorphanol is a synthetic analgesic that is chemically related to the nalorphine-cyclazocine series with both opioid and antagonist properties. More specifically, it serves as an agonist at the kappa and sigma opioid receptors. In regard to its analgesic potency, it is approximately fivefold more potent than morphine, thirtyfold more potent than meperidine, and twentyfold more potent than pentazocine. Butorphanol can produce sedation, nausea, and respiratory depression. The respiratory depression is plateaulike in that 2 mg of butorphanol depresses respiration to a degree equal to 10 mg of morphine. The magnitude of respiratory depression with butorphanol is not appreciably increased at doses of 4 mg. The duration of the respiratory depression is dose related and is reversible with naloxone. Intravenous administration of butorphanol can produce increased pulmonary artery pressure, pulmonary wedge pressure, left-ventricular end-diastolic pressure, systemic arterial pressure, and pulmonary vascular resistance. Consequently, this drug increases the workload of the heart, especially in the pulmonary circuit. Because of its antagonist properties, butorphanol is not recommended for patients who are physically dependent on opioids, because butorphanol can precipitate withdrawal symptoms in those patients. See Table 22-3 for an overview of the clinical pharmacology of butorphanol.⁴

Table 22-3 Comparison of Five Analgesics that Use Morphine as Drug with Primary Opioid Effects

Nalbuphine

Nalbuphine (Nubain) is a potent analgesic with opioid agonist and antagonist actions. It is chemically related to oxymorphone and naloxone. This drug is an antagonist at the mu receptors, a partial agonist at the kappa receptors, and an agonist at the sigma receptors. Nalbuphine is as potent as morphine and approximately threefold more potent as pentazocine on a milligram basis. At a dose of 10 mg/kg, nalbuphine causes the same degree of respiratory depression as does 10 mg of morphine. At higher doses, nalbuphine exhibits the same plateau effect as butorphanol (i.e., respiratory depression is not increased appreciably with higher doses). The respiratory depression produced by nalbuphine can be reversed with naloxone. Nalbuphine does not appear to increase the workload of the heart or to decrease cardiovascular stability. This drug has a lower abuse potential than does morphine; however, if it is given to a patient who is physically dependent on opioids, withdrawal symptoms may appear. Signs of withdrawal include abdominal cramps, nausea and vomiting, lacrimation, rhinorrhea, anxiety, restlessness, elevation of temperature, and piloerection. If these symptoms appear after the injection of nalbuphine, the administration of small amounts of morphine can relieve the objective effects of the syndrome. See Table 22-3 for an overview of the clinical pharmacology of nalbuphine.⁴

Opioid antagonists

Opioid antagonists are used to reverse opioid-induced respiratory depression. An opioid antagonist, such as naloxone (Narcan), is a drug that completely antagonizes the effect of an opioid.

Naloxone

Naloxone (Narcan), a pure antagonist, reverses the depressant effects of opioids. More specifically, this drug antagonizes the opioid effects at the mu, kappa, and sigma receptors. This drug also reverses the analgesic effect of the opioid, which is important in assessing the patient’s respiratory effort. Naloxone should be titrated according to the patient’s response. Usually, 0.1 to 0.2 mg given slowly intravenously should be adequate for reversal. The onset of action of naloxone is 1 or 2 minutes. If after 3 to 5 minutes inadequate reversal has been achieved, naloxone administration may be repeated until reversal is complete. If the patient shows no sign of reversal, assessment of other pharmacologic agents administered is indicated. Drugs such as halothane, barbiturates, and muscle relaxants are not reversed with naloxone.

The duration of action of naloxone is 1 to 4 hours, depending on the route and amount of drug used. If long-acting opioids were used, the patient must be monitored for respiratory embarrassment after the administration of naloxone because the depressant activity of the opioid may return. If this phenomenon occurs, supplemental doses of naloxone can be used. The intramuscular route of administration has been shown to produce a longer lasting effect.

An excessive dose of naloxone can increase blood pressure, a finding that may be seen as a response to pain. Too rapid reversal can induce nausea, vomiting, diaphoresis, and tachycardia. During the reversal procedure, the vital signs should be monitored; naloxone should be used with caution in patients with cardiac irritability.⁴^,⁵

Naloxone does not produce respiratory depression as do other opioid antagonists. It also does not produce any significant side effects or pupillary constriction. Naloxone reverses natural or synthetic opioids and the opioid-antagonist analgesic pentazocine. Because reversal may precipitate an acute withdrawal syndrome, naloxone should be administered with great caution in patients who are physically dependent on opioids.

Nalmefene

Nalmefene (Revex) is similar in chemical structure to naloxone and is considered a long-acting opioid antagonist. It has a rather rapid onset of 2 to 5 minutes, with a duration of action of approximately 8 hours. Nalmefene, when given at the usual dose range, produces the same clinical effects as naloxone.

In the PACU, the dose of this drug for reversal of respiratory depression is 0.1 to 0.5 mcg/kg slowly titrated intravenously at 2- to 5-minute intervals. This drug should be titrated slowly with observation for a return of respiratory effort. When the patient has a return of the appropriate rate and volume of breathing, titration should be stopped and a constant vigilance of the rate and volume of respiration should be continued throughout the PACU stay. This drug should not be administered in a dose of more than 1.6 mcg because this does not elicit additional effects. As with naloxone, nalmefene should not be administered to a patient with opioid dependency. Both drugs should always be titrated slowly to all patients in case a patient is opioid dependent. If the PACU nurse is titrating these drugs and signs of acute opioid withdrawal are seen, titration should stop immediately.

Naltrexone

Naltrexone (Revia) is a pure mu and kappa, and to a lesser extent delta, opioid receptor antagonist; therefore its actions are similar to naloxone. This drug can produce sustained opioid antagonist activity for as long as 24 hours, with a peak action in 8 to 12 hours. This drug can only be administered orally and is used in opioid detoxification because it can facilitate withdrawal; once the patient has undergone complete detoxification, naltrexone can prevent relapses to opioids by blocking the euphoric effects of the opioid. In addition, note that naltrexone is used to treat alcohol dependence; therefore the same can be said in regard to titrating the drug slowly because it can also cause acute alcohol withdrawal.

Selected methods of opioid administration

Intrathecal and epidural routes of administration

For management of acute and chronic pain, the opioids can be administered via the subarachnoid or epidural space. The technique is called the neuraxial administration of opioids. This concept of pain relief is based on the fact that opioid receptors exist in the substantia gelatinosa on the dorsal horn of the spinal cord. More specifically, mu, kappa, and delta opioid receptors are located in the substantia gelatinosa. The pain relieved with the administration of neuraxial opioids is usually of the visceral as opposed to the somatic type. When the opioid is administered via the epidural space, it crosses the epidural space to the opioid receptors in the spinal cord. Consequently, the dose of the opioid, when administered into the epidural space, is usually 10 times the dose of the opioid if it were administered via the subarachnoid space.

When 0.1 to 0.2 mg of preservative-free morphine (Duramorph) is administered into the subarachnoid space (intrathecal), the maximum concentration is reached in 5 to 10 minutes, with a duration of 80 to 200 minutes. When 5 mg of morphine is administered into the epidural space in the lumbar region, analgesia can last for as long as 24 hours. The patient should obtain pain relief in 30 to 60 minutes after injection. If appropriate pain relief is not achieved, incremental doses of 1 to 2 mg can be administered. The maximum dose in a 24-hour period is 10 mg.⁵

After spinal surgery, epidural morphine administered with the continuous epidural technique has advantages and disadvantages. Its advantage is a profound degree of pain relief, especially for the first 12 to 18 postoperative hours. However, disadvantages are related to displacement of the epidural catheter and the length of action of the epidural morphine. If the epidural catheter becomes displaced and the morphine has been injected, only partial pain relief ensues. Because of the possibility of profound respiratory depression, opioids must be administered cautiously. In fact, a nonopioid drug such as ketorolac may be especially useful in this circumstance. Depending on the anticipated amount and length of pain, a patient-controlled analgesia (PCA) device can be started in the patient for an immediate result of pain resolution. In addition, the postanesthesia nurse can have a profound effect on reducing the pain threshold by repositioning and reassuring the patient. The new technology of apnea monitors or end-tidal carbon dioxide monitors can be useful in detecting hypoventilation or apnea that can be created by the opioid in this technique. Therefore the use of either monitor on patients who are receiving epidural morphine certainly aids the postanesthesia nurse in monitoring for respiratory dysfunction.⁴

Other opioids that can be administered epidurally are fentanyl and sufentanil.¹⁴ These drugs offer some advantages over morphine; they are more suited for continuous infusion techniques because of their rapid onset and short duration of action. Because they have such a rapid clearance from the cerebrospinal fluid, less chance exists for these drugs to spread toward the head (rostral spread). Rostral spread, which is associated more with morphine, has been shown to produce side effects such as nausea, pruritus, and the previously discussed delayed respiratory depression syndrome. Naloxone reverses this side effect; however, the analgesic effect also is reversed. In this instance, nalbuphine administration should be considered to reverse the respiratory depression and preserve some of the analgesia.