section epub:type=”chapter” id=”c0110″ role=”doc-chapter”> Cecil B. Drain; John M. Edwards, III Opioid intravenous (IV) anesthetics constitute a major portion of the clinical anesthesia process. These drugs enhance the effectiveness of the inhalation anesthetics. More specifically, the opioids meet much of the analgesic portion of the anesthesia process. Opioids are used to manage acute and chronic pain and are administered for general inhalation anesthesia, total intravenous anesthesia (TIVA), sedation, and pain relief during regional anesthesia; therefore, implications for the perianesthesia nursing care of the surgical patient are profound. With a detailed understanding of the major opioids used in the perianesthesia period, the perianesthesia nurse will be able to make informed decisions with regard to the anticipated outcome of administered opioids. opioid agonist; opioid anesthetic agents; opioid antagonist; postanesthesia care unit Opioid intravenous (IV) anesthetics constitute a major portion of the clinical anesthesia process. These drugs enhance the effectiveness of the inhalation anesthetics. More specifically, the opioids meet much of the analgesic portion of the anesthesia process. The addition of the opioids to the medications used for general anesthesia can reduce the concentration of inhaled anesthetics, and, as a result, a safer anesthetic can be administered to the patient. Because opioids are used to manage acute and chronic pain and are administered for general inhalation anesthesia, total intravenous anesthesia (TIVA), sedation, and pain relief during regional anesthesia, the implications for the perianesthesia nursing care of the surgical patient are profound. The immediate postanesthesia phase is when the patient is most vulnerable to complications (see Chapter 29).1 Many medications 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 various opioid agents optimize patient outcomes. In addition, the reduction of pain in the PACU is a primary focus of care in the perianesthesia phase. In addition to assessing pain, the perianesthesia nurse must also evaluate the preoperative, intraoperative, and postanesthesia phase of the surgical patient. Because all pain-reducing medications must be considered during the pain assessment in the PACU, the mixed-action or agonist-antagonist combination drugs are presented in this chapter. With a detailed understanding of the major opioids used in the perianesthesia period provided, the PACU nurse will be able to make excellent informed decisions with regard to the anticipated outcome of the patient of pain reduction and comfort. Definitions Agonist A drug with a specific cellular or receptor affinity that produces a predictable response. Antagonist A drug that exerts an opposite action to that of another or competes for the same receptor site or sites. Breakthrough Pain A transient increase in the intensity of pain from a baseline pain level no greater than moderate. Dysphoria A disorder of affect or paradoxical reaction to medication characterized by discomfort, anxiety, and dissatisfaction; it often occurs with administration of pure mu opioids. Endogenous Originating inside the body. Endorphins Opioid peptides produced in the body composed of many amino acid (protein) substances that attach to opioid receptors in the central nervous system (CNS) and the peripheral nervous system for reduction of pain. Exogenous Originating outside the body. Fixed Chest Syndrome Rigidity of the diaphragmatic and intercostal muscles. Miosis Excessive constriction of the pupil of the eye. Mydriasis Dilation of the pupil of the eye. Opiate Receptor Receptors that are transmembrane proteins that bind to endogenous opioid neuropeptides and exogenous morphine and similar compounds. They are designated mu, kappa, and delta subtypes of the opiate receptor. Opioid A drug that contains opium or a derivative of opium along with semisynthetic or synthetic drugs that have opium-like properties. Piloerection Erection of the hairs of the skin. Spasmolytic Stoppage of muscle group contractions. Total Intravenous Anesthesia (TIVA) Techniques of anesthesia in which a combination of medications are given solely IV in the absence of any inhalational agent including nitrous oxide. Opioids are substances, either natural or synthetic, administered into the body (exogenous) or produced by the body (endogenous) that bind to specific receptors to produce morphine-like or opioid agonist effects by activating the body’s pain-modulating system. The endogenous opioids include endorphins, enkephalins, dynorphins, and endomorphins. 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.2 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.2,3 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 brainstem 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).2,3 The receptors are also described by an international nomenclature scheme, International Union of Basic and Clinical Pharmacology (IUPHAR), as MOP, KOP, and DOP (mu, kappa, and delta opioid peptide).2 The existence of subtypes such as mu-1 and mu-2 have been proposed, but no distinct gene codes are available.2 The mu receptors are primarily responsible for the production of supraspinal analgesia effects with stimulation. Activation of the mu receptors results in analgesia, hypoventilation, bradycardia, physical dependence, euphoria, and ileus. The mu receptors are activated by morphine and fentanyl. Other characteristics of the mu receptors are summarized in Table 22.1. Fig. 22.1 shows the pharmacodynamic effects of fentanyl and its analogs.2 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 (κ) opioid receptors. The delta (δ) opioid receptors, when stimulated, serve to modulate the activity of the μ 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.2,3 From Nagelhout JJ, Elisa S. Nurse anesthesia. 7th ed. St. Louis, MO: Elsevier; 2023. Front view of human with head turned to one side shows pharmacodynamics effects of opioid with labels (clockwise) as follows: Supraspinal analgesia, miosis, cough suppression, bradycardia, pruritus, delayed gastric emptying, ileus and constipation, urinary retention, depressed cellular immunity, muscle rigidity, increased biliary pressure, ventilatory depression, vasodilation, spinal analgesia, nausea and vomiting, and sedation and euphoria. Opioids or narcotics are used often in anesthesia practice. 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 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 (Demerol) was discovered in 1939 by Eisleb and Schaumann. 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. Meperidine’s popularity as an analgesic was the misconception that its use would result in less biliary tract spasm than morphine.4 This opioid may slow the rate of respiration, but the rate generally returns to normal within 15 minutes after IV 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 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, a metabolite that has some analgesic effects, but, more importantly, it lowers the seizure threshold and can induce CNS excitability. Since the early 2000s, meperidine use has declined, with many hospital formularies removing or restricting its use. Meperidine is rarely used as an analgesic, but low doses (12.5–25 mg IV) have been used to treat shivering in postoperative patients after general or spinal anesthesia.4 Morphine, one of the oldest known drugs, is used as an opioid IV anesthetic agent and for pain management. Alkaloid morphine is from the phenanthrene class of opium. The exact mechanism of action of morphine is unknown. In humans, it produces analgesia, drowsiness, changes in mood, and mental clouding. The analgesic effect can become profound before the other effects become severe and can persist after many of the side effects have almost disappeared. With direct effect on the respiratory center, morphine depresses respiratory rate, tidal volume, and minute volume. Maximal respiratory depression occurs within 7 minutes after IV injection of the drug and 30 minutes after intramuscular (IM) administration, although IM administration of opioids is discouraged. After therapeutic doses of morphine, the sensitivity of the respiratory center begins to return to normal in 2 or 3 hours, but the minute volume does not return to a preinjection level until 4 or 5 hours have passed. The greatest advantage of morphine is the remarkable cardiovascular stability that accompanies its use. It has no major effect on blood pressure, heart rate, or heart rhythm—even in toxic doses—as long as hypoxia is avoided. Morphine does, however, decrease the capacity of the cardiovascular system to adjust to gravitational shifts. This effect is important to remember because orthostatic hypotension and syncope can easily occur in a patient whose care necessitates a position change. This phenomenon is primarily the result of the peripheral vasodilator effect of morphine. Therefore, a position change for a patient who has received morphine should be accomplished slowly with constant monitoring of the patient’s vital signs. Morphine can cause nausea and vomiting, especially in ambulatory patients, because of its direct stimulation of the chemoreceptor trigger zone. The emetic effect of morphine can be counteracted with opioid antagonists and phenothiazine derivatives such as prochlorperazine (Compazine), dexmedetomidine (Precedex), or the 5-HT3 receptor antagonist ondansetron (Zofran). Histamine release has been noted with morphine, and morphine also causes profound constriction of the pupils, stimulation of the visceral smooth muscles, and spasm of the sphincter of Oddi.2–5 Morphine is detoxified by conjugation with glucuronic acid. About 90% is excreted by the kidneys, and 7% to 10% is excreted in the feces via the bile.2 It is important to reduce morphine doses in patients with severely altered renal clearance issues, the elderly, or to consider use of alternative opioids.2,4 In the PACU, morphine is an excellent drug for the control of postoperative pain. When given IV, this drug has a peak analgesic effect in approximately 20 minutes with a duration of approximately 2 hours. Methadone was introduced in the late 1930s in Germany and the 1940s in the United States. This drug’s original intent was to help treat chronic pain, opioid abstinence syndromes, and heroin addiction. It has seen a resurgence in popularity for clinical use in the perioperative setting to manage surgical pain. Methadone is a unique opioid agonist that has a long half-life. It is a potent mu opioid receptor agonist with the most prolonged elimination half-life of any opioid used clinically, 24–36 hours.6 In addition to its opioid agonist effect, methadone is a potent N-methyl-D-aspartate (NMDA) receptor agonist. This property allows methadone to potentially reduce opioid tolerance, hyperalgesia, and chronic postsurgical pain. Lastly, methadone inhibits the neurotransmitters serotonin and norepinephrine reuptake, which can potentially provide mood elevation in the perioperative period. This synthetic opioid agonist’s actions resemble those of morphine; side effects include depression of ventilation, miosis, constipation, and biliary tract spasm. Clinically, the sedative and euphoric actions of methadone appear to be less than those produced by morphine.5 Two distinct dosing regimens for methadone exist. When smaller doses are given (5–10 mg), methadone acts like other short-acting opioids with a duration of action approximating 3–4 hours.6 When larger doses are given (≥ 20 mg), a longer analgesic duration of action occurs with an effect of up to 35 hours.6 The larger dose has shown benefit for surgical procedures that have higher postoperative pain levels (major spine, thoracic).6 Dosing of 20 mg IV at the induction of the anesthetic seems to be most beneficial. This timing of the dose allows for a prolonged analgesic benefit with minimal risk of postoperative respiratory depression. In the PACU, additional doses of methadone can be carefully titrated to treat surgical pain. When doses of 3–5 mg are given, 20 minutes should be allowed between dose titration.6 Methadone, given via the IV route, has a rapid onset of effect with an analgesic benefit noted within 4 minutes and the peak respiratory depressant effect occurring 8–10 minutes after administration.6 Lastly, a naloxone infusion may be required if methadone-induced respiratory depression is noted. Hydromorphone (Dilaudid), which is a derivative of morphine, was developed in Germany in the 1920s and released to the mass market in the late 1920s. The drug can be administered IV, IM, rectally, or orally. The drug profile with regard to its analgesia and side effects is similar to morphine. Hydromorphone is recommended for patients in renal failure because of its virtual lack of active metabolites after its breakdown in the liver. It has a high solubility, a rapid onset of action, and appears to have less troublesome side effects and dependence liability profile compared with morphine. Because of its high lipid solubility, hydromorphone can be administered via epidural or spinal route for a wide area of anesthesia. Hydromorphone, like all opioids, is a CNS depressant and has actions and side effects similar to morphine. Its depressant effects can be enhanced with beta blockers and alcohol. The duration of action of this drug is approximately 3 to 4 hours, with a peak action in approximately 8–20 minutes with IV administration.4 Hydromorphone is more potent than morphine, and care should be given to prevent inadvertent overdose. Janssen and colleagues 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.7 Fentanyl (Sublimaze) appeared to be of special interest. Fentanyl is approximately 80 to 125 times more potent than morphine and has a rapid IV onset of action of 1 to 5 minutes and a peak effect within 5 to 15 minutes.4 The analgesia lasts 20 to 40 minutes when administered IV. 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 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 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 recycles 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.8 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.3 Fentanyl shares with most other opioids a profound respiratory depressant effect, even to the point of apnea. Rapid IV 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 IV route. Should this syndrome occur, IV subclinical administration of succinylcholine (15–25 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. Sufentanil is an analog of fentanyl and is approximately fivefold to sevenfold more potent than 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, 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 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 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).3 Alfentanil is another analog 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.3 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 further the lethal dose is 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.9,10 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 is a selective mu-opioid agonist that has an analgesic potency almost equal to fentanyl and is 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, and its effects disappear within 4 minutes.3 The remifentanil anesthetic technique is excellent for suppression of the stress response and allows for excellent depression of neurologic responses. Regarding the immediate postanesthesia period, remifentanil is better than most IV opioid drugs with regard to residual effects because it has a rapid recovery and less risk of postoperative respiratory depression. Remifentanil is the most common opiate drug used in TIVA. The most common TIVA technique consists of the administration of propofol with or without remifentanil. When receiving a patient who has received TIVA with a combination of remifentanil and propofol, a synergistic effect can occur in which a lower dose of each drug can be used to achieve a desired effect, resulting in the patient having stable hemodynamic parameters and a rapid emergence in the PACU. If remifentanil is used in the PACU, the patient should be monitored closely because of risks for adverse effects and have ready access to an anesthesia provider.4 Because of its brief half-life, a long-acting analgesia should be given before the end of surgery. The PACU nurse should assess the patient carefully for pain.11 Remifentanil is administered via IV infusion with an infusion pump and should never be administered via IV bolus. The drug can produce the fixed chest syndrome and can also cause nausea and vomiting, respiratory depression, and mild to moderate depression of heart rate and blood pressure. 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 (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 IM. 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 40 mg of pentazocine IM is analgesically equivalent to 10 mg of morphine. Pentazocine has been established to relieve severe pain and is approximately twofold to fourfold less potent than morphine when administered parenterally.3–4,11 The onset of analgesic activity of pentazocine is approximately 2 or 3 minutes when it is given IV and 15 to 20 minutes when given IM. The duration of action is approximately 3 hours. When given orally, the drug is approximately one-third as potent as when it is given IM.8,11 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 use of pentazocine is limited, however, due to a high incidence of postoperative nausea and vomiting, limited analgesia, and psychotomimetic effects.11 Butorphanol is a synthetic analgesic chemically related to the nalorphine-cyclazocine series with both opioid and antagonist properties. More specifically, it serves as an agonist at the kappa (κ) opioid receptor and a weak antagonist at the opioid mu receptor.3,11 With regard to its analgesic potency, it is approximately five- to eightfold more potent than morphine and twentyfold more potent than pentazocine. Butorphanol can produce sedation, nausea, and respiratory depression. The respiratory depression is plateau-like 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 reversible with naloxone. IV administration of butorphanol in patients with preexisting cardiac disease can produce increased pulmonary artery pressure, pulmonary wedge pressure, left ventricular end-diastolic pressure, systemic arterial pressure, and pulmonary vascular resistance.11 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 physically dependent on opioids because butorphanol can precipitate withdrawal symptoms in those patients. See Table 22.2 for an overview of the clinical pharmacology of butorphanol.4 Transnasal butorphanol can also be used for migraine headache and postoperative pain relief.3,11 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).2 The respiratory depression produced by nalbuphine can be reversed with naloxone. Nalbuphine does not appear to increase the workload of the heart or decrease cardiovascular stability. This drug has a lower abuse potential than does morphine; however, if it is given to a patient 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. Nalbuphine can also be used to reverse pruritus resulting from intrathecal or epidural morphine.3 See Table 22.2 for an overview of the clinical pharmacology of nalbuphine.3 Intramuscular injections of opioids are not recommended due to unpredictable absorption. Use of meperidine for acute pain is not recommended due to potential toxicity from accumulation of normeperidine. IV, Intravenous.
22: Opioid Intravenous Anesthetics
Abstract
Keywords
Concept of opioids and opioid receptors
Receptor
Effects
Mu Receptor
Kappa Receptor
Delta Receptor
Analgesia
Supraspinal, spinal
Supraspinal, spinal
Supraspinal, spinal; modulates mu receptor activity
Cardiovascular effects
Bradycardia
Respiratory effects
Depression
Possible depression
Depression
Central nervous system effects
Euphoria; sedation; prolactin release; mild hypothermia; catalepsy; indifference to environmental stimulus
Sedation; dysphoria; psychotomimetic reactions (hallucinations, delirium)
Pupil
Miosis
Miosis
Gastrointestinal effects
Inhibition of peristalsis; nausea, vomiting
Genitourinary effects
Urinary retention
Diuresis (inhibition of vasopressin release)
Urinary retention
Pruritus
Yes
Yes
Physical dependence
Yes
Low abuse potential
Yes
Antishivering
Yes
Opioids
Meperidine Hydrochloride
Morphine
Methadone
Hydromorphone
Fentanyl
Sufentanil
Alfentanil
Remifentanil
Partial Agonist-Antagonist Drugs
Pentazocine
Butorphanol
Nalbuphine
Morphine
Pentazocine
Butorphanol
Nalbuphine
Indication
Moderate to severe pain
Moderate to severe pain
Moderate to severe pain
Moderate to severe pain
Recommended IV dose (mg)
4–10
30
1
10
Time for onset of analgesia
Rapid IV
Rapid IV
Rapid IV
Rapid IV
Duration of analgesia (hours)
4
3–4
3–4
3–6
Respiratory depression
High
Occurs, but less than that with morphine
Occurs, but less than that with morphine
Occurs, but less than that with morphine
Cardiovascular effect
Decreases cardiac workload
Increases cardiac workload
Increases cardiac workload
Good cardiac stability
Abuse syndrome
High
Occurs; induces withdrawal syndrome
Occurs; induces withdrawal syndrome
Occurs; induces withdrawal syndrome
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