Monitored anesthesia care (MAC) has evolved from an era in which anesthesiologists were asked to be available on a "stand-by" basis to provide monitoring and sedation during palliative surgical procedures in high-risk patients deemed "too sick for a general anesthetic" to the practice of a unique form of intravenous (IV) sedation-analgesia combined with local anesthesia. The classic example of anesthesia stand-by was a case involving a patient with multiple organ failure undergoing tracheostomy, for which the anesthesiologist would be available to monitor the patient's vital signs and provide sedation and analgesia with small bolus doses of diazepam and morphine, respectively. The technique of combining local anesthetics and parenteral drugs for sedation-analgesia was subsequently extended to cases in which the procedure itself was relatively minor but excessive patient anxiety resulted in less than optimal cooperation (e.g., pediatric patients undergoing dental procedures). The combination of local anesthetics and IV anesthetic drugs for sedation and analgesia has been particularly well suited for outpatients undergoing less invasive procedures known as minimally invasive ("key hole") surgery. With technological advances in fiberoptics and lasers, procedures that previously could only be performed with large surgical incisions and that were associated with major physiological (autonomic) responses are now performed with small incisions and decreased tissue injury. Many of these procedures can be performed on an outpatient basis using local anesthetic techniques combined with newer, more rapid, and shorter-acting IV drugs to provide anxiolysis, sedation, and supplemental analgesia. In contrast to the usual "light" level of sedation administered by nonanesthesiologists, when an anesthesia practitioner monitors a patient receiving local anesthesia and/or administers sedative-analgesic medications to patients undergoing diagnostic or therapeutic procedures, the technique is known as MAC. In this review, the conceptual basis for MAC is described. In addition, the specific role of sedative-hypnotic, amnestic, and analgesic drugs during MAC will be discussed. Finally, studies comparing the use of MAC with general and regional anesthetic techniques are reviewed. Conscious Sedation Versus MAC The term "conscious sedation" was introduced by the American Dental Association to describe the care of patients requiring sedative/analgesic drugs during dental procedures (Table 1). However, the term is imprecise and has been misused by many practitioners. As originally defined, patients undergoing conscious sedation must be capable of rationally responding to commands and maintaining airway reflexes [1,2]. Because the drugs commonly used to achieve this state of consciousness produce dose-dependent central nervous system (CNS) depression, conscious sedation lies on a continuum from minimal sedation (i.e., an awake, relaxed state) to profound, deep sedation (i.e., an unconscious or hypnotic state) or general anesthesia (i.e., lack of movement in response to painful stimuli). The term conscious sedation implies that the level of vigilance required for monitoring those patients is less than that for general anesthesia. The rapidity with which a patient can move from a minimally depressed state of conscious sedation to general anesthesia, and variations in individual patient responses to the same dose of a sedative or analgesic drug, makes careful monitoring of the patient's vital signs an essential feature of clinical management. The marked variation in individual patient responses to a given dose of an anesthetic drug has led the ASA to avoid the use of the term conscious sedation in their Practice Guidelines for Sedation and Analgesia by Non-Anesthesiologists [3]. The ASA prefers the term "sedation/analgesia" and has recommended that all patients receiving this technique be monitored by a designated individual who is primarily responsible for administration of sedative and analgesic drugs and monitoring the patient's vital signs.Table 1: Definitions Proposed by the American Dental Association Council on Dental EducationThe policy of the ASA states that the same standard of care should be provided by an anesthesia practitioner during MAC as for general or regional anesthesia [4]. Therefore, the provisions of MAC should include a preoperative evaluation, prescription of an anesthetic care plan, the continuous presence of a member of the anesthesia care team with the proximate presence, and immediate availability of an anesthesiologist for the management of emergencies. The standards of monitoring include the usual cardiovascular and respiratory monitoring required for general anesthesia (e.g., electrocardiogram, blood pressure cuff, pulse oximeter, end-tidal carbon dioxide [CO2]). In addition to patient monitoring, the anesthesia provider should be ready to administer oxygen, IV sedatives, tranquilizers, opioid and nonopioid analgesics, beta-blockers, vasopressors, bronchodilators, antihypertensives, or other pharmacological therapy so that the desired level of sedation, amnesia, anxiolysis, and analgesia can be achieved without compromising cardiorespiratory function or delaying recovery. Use of Local Anesthetics During MAC Local anesthetics may be administered by local infiltration, topical anesthesia, IV regional anesthesia, or peripheral nerve blocks during MAC (Table 2) [5,6]. The advantages of using local anesthesia include residual postoperative analgesia with the use of long-acting local anesthetic and avoidance of the side effects associated with general and regional anesthesia [7,8]. However, the injection of local anesthetic solutions is uncomfortable, especially when multiple injections are required. Traction on deep structures, as well as the need for patients to remain immobile for prolonged periods of time, can be associated with significant discomfort. Finally, many patients find the operating room (OR) environment and the idea of being awake during surgery anxiety-provoking. For these reasons, local anesthetic techniques are usually combined with IV drugs to provide anxiolysis, sedation, and supplemental analgesia [9].Table 2: Surgical Procedures That Can be Performed Under Sedation/AnalgesiaIn addition, there may be some economic advantages associated with operations performed under local anesthesia with IV sedation compared with general or regional anesthesia. Outpatient urologic and orthopedic procedures performed under local anesthesia can significantly decrease the overall costs of these operations [10-14]. For inguinal herniorrhaphy, local anesthesia offers advantages over both general and regional anesthesia with respect to the recovery profile [15,16]. Malhotra et al. [17] described a local anesthetic technique for lithotripsy involving a combination of local infiltration and intercostal nerve blocks. Hand and foot procedures performed using peripheral nerve block techniques are allegedly associated with a decreased incidence of postoperative pain and emesis.1 (1) Allen HW, Mulroy MF, Fundis K, Carpenter RL. Regional versus propofol general anesthesia for outpatient hand surgery [abstract]. Anesthesiology 1993;79:A1. Specific areas in which local sedation techniques are useful for pediatric outpatients include the emergency department (for suturing lacerations and reducing closed fractures), procedures in oncology clinics (e.g., bone marrow biopsies, lumbar punctures), gastrointestinal (GI) endoscopy suites, radiological image scanners, cardiac catheterization laboratories, and dental offices. Although verbal reassurance, distraction techniques, and play therapy can help in gaining the cooperation of the child, pharmacologic interventions are often required to alleviate anxiety, pain, and discomfort, particularly if immobilization is required for the satisfactory completion of the procedure [18]. Choice of Drugs A wide variety of centrally active IV and inhaled drugs have been used during MAC, including barbiturates, benzodiazepines, ketamine, propofol, opioid and nonopioid analgesics, alpha2-agonists, and nitrous oxide (N2 O) (Table 3). Drug administration typically occurs during the pre- or intraoperative periods, with drugs from two or more pharmacologic groups often being combined. However, careful titration of the drug(s) to achieve the desired clinical effect(s) and to avoid hemodynamic and respiratory depression may be more important than the choice of any individual drug.Table 3: Recommended Doses of Commonly Used Sedative and Analgesic Drugs During MACaSedative-Hypnotics Barbiturates. The barbiturate compounds have been used for sedation during MAC [19] and regional anesthesia [20]. Methohexital provides excellent intraoperative sedation with a rapid recovery when administered by either intermittent bolus injections (10-20 mg) or as a variable-rate infusion (0.1%-0.2% solution) [9]. Adverse effects reported with subhypnotic (sedative) doses of barbiturates include pain on injection, paradoxical excitement, antianalgesic effects, nausea and vomiting, hiccoughing, and excessive postoperative drowsiness [21-24]. Residual sedation seems to be greater with methohexital than with propofol [25,26]. However, a recent publication showed no statistical significant difference in the recovery times when comparing infusions of methohexital (40 micro g [center dot] kg-1 [center dot] min-1) or propofol (50 micro g [center dot] kg-1 [center dot] min-1) during a MAC technique [27]. These authors also found a higher incidence of pain on injection in the propofol infusion group (46% vs 9% in the methohexital group). Therefore, methohexital may be a safe alternative to midazolam and propofol for sedation during MAC. Rectal methohexital (10-30 mg/kg) has been widely used in children, with sedation lasting for 45-60 min in the absence of stimulation [28]. However, erratic rectal absorption and the potential for loss of consciousness and apnea with this route of administration emphasizes the need for careful monitoring [18]. Pentobarbital (5-7 mg/kg IV or intramuscularly) is used by many radiologists for sedating children undergoing interventional procedures because of the low risk of respiratory depression when the drug is used alone [29,30]. However, when used in combination with other sedative or opioid drugs, there is a marked increase in the incidence of airway obstruction and hypoxemia [18]. Benzodiazepines. Benzodiazepines are the most widely used sedative drugs during MAC because they combine anxiolysis with varying degrees of amnesia and sedation. Although diazepam is the prototypic benzodiazepine, it has a long elimination half-life (24-48 h), and its active metabolites make it less desirable in the outpatient setting. The original formulation of diazepam (Valium[registered sign]; Roche Laboratories, Nutley, NJ) contains propylene glycol, and its parenteral administration is associated with a high incidence of pain on injection, as well as venoirritation and phlebitis [31]. However, the newer lipid-based formulation of diazepam (Dizac[registered sign]; Ohmeda, Liberty Corner, NJ) is associated with a lower incidence of venoirritation [32]. Midazolam, a rapid and relatively short-acting benzodiazepine, is more widely used because it is associated with less pain on injection and venous irritation [33], and it produces more profound amnesia than diazepam [33-35]. The time required to achieve a peak CNS effect with midazolam (2-4 min) may lead to cumulative effects (oversedation) when repeated bolus doses are administered over a short time interval. When midazolam is administered as an infusion (loading dose of 0.025-0.05 mg/kg followed by a maintenance infusion of 1-2 micro g [center dot] kg-1 [center dot] min-1), it provides a titratable level of sedation during local anesthesia [16]. White et al. [33] noted a similar spectrum of CNS activity with midazolam (0.05-0.15 mg/kg IV) and diazepam (0.1-0.3 mg/kg IV). However, the slope of the dose-response curve for sedation was much steeper with midazolam compared with diazepam (Figure 1), which suggests that midazolam possesses a smaller margin of safety and greater need for careful titration to achieve the desired clinical end point without untoward side effects [33]. Although clinical recovery characteristics were similar for diazepam and midazolam when used as adjuvants to ketamine, the incidence of amnesia and overall patient acceptance was significantly higher with midazolam [33].Figure 1: Relationship between the sedation score (2 = awake/relaxed to 6 = asleep/unarousable) and the initial dose of midazolam or diazepam (mg/kg). Values represent mean values +/- SEM. Reproduced with the permission of the publisher [33].Magni et al. [36] also found a higher patient preference for midazolam (versus diazepam) during upper GI endoscopy. In most studies, midazolam provided more profound perioperative amnesia, anxiolysis, and sedation [36,37]. Although full recovery from the CNS effects of midazolam is generally more rapid than diazepam, large doses of midazolam (0.2 mg/kg) can result in prolonged postoperative sedation [38]. Although midazolam provided more effective intraoperative sedation and amnesia than methohexital or propofol, it was associated with a slower recovery of psychomotor function [16,20]. The use of midazolam for sedation of children outside the OR is increasing in popularity [39]. In comparative studies, parents of children undergoing bone marrow biopsy procedures preferred midazolam to fentanyl for sedation [40]. Recent studies have suggested that the combination of oral midazolam, 0.5 mg/kg, and low concentrations of inhaled N2 O for sedation/analgesia is associated with only mild ventilatory depression in children; however, progression from conscious to deep sedation occurs with N2 O concentrations exceeding 30% [41]. Ketamine. Ketamine is a water-soluble phencyclidine derivative that produces a "dissociative" sedative/anesthetic state [42]. Clinical observations suggest that ketamine-induced analgesia can outlast its anesthetic effects and occurs even at subanesthetic doses. In patients undergoing intercostal nerve block procedures, ketamine produced more optimal clinical conditions and higher patient acceptance than diazepam or a droperidol-fentanyl combination [43]. Furthermore, the use of a diazepam-ketamine combination was not associated with any more side effects or a greater need for postoperative care than an unpremedicated control group undergoing similar nerve block procedures [44]. Small-dose ketamine (0.25-0.75 mg/kg) combined with either diazepam or midazolam has been administered before injection of local anesthetics in out patients undergoing cosmetic surgical procedures [44]. Use of ketamine alone is associated with an incidence of psychic disturbances that varies from 5% to 30% [42]. Benzodiazepines seem to be the most effective drugs in attenuating the psychomimetic actions of ketamine. However, large doses of benzodiazepines may be required (e.g., midazolam 5-15 mg) and can result in prolonged recovery times after ambulatory procedures. Propofol. Propofol is a rapid and short-acting IV anesthetic with an excellent recovery profile. At propofol infusion rates of 2.3-5.6 mg [center dot] kg-1 [center dot] h-1, patients undergoing lower limb surgery under spinal anesthesia were asleep but would arouse with verbal commands [45]. Patients were completely awake within 4 min after terminating the propofol infusion and rapidly became clearheaded with a "strong desire of food." Small-dose propofol infusions have also been used as adjuvants to local infiltration anesthesia in patients undergoing central venous catheter placement [46], oral surgery [47], and superficial surgical procedures (e.g., breast biopsy and herniorrhaphy) [16,48]. In comparing propofol and midazolam infusions for sedation during procedures performed under local anesthesia, loading doses of 69 +/- 23 mg and 4.2 +/- 1.4 mg, followed by maintenance infusion rates of 61.7 +/- 16.7 micro g [center dot] kg-1 [center dot] min-1 and 2.0 +/- 1.1 micro g [center dot] kg-1 [center dot] min-1, respectively, were used [16]. Use of propofol was associated with a more rapid recovery of cognitive function and less postoperative sedation, drowsiness, confusion, clumsiness, and amnesia than midazolam. Both early and intermediate recovery have been found to be superior after propofol sedation compared with midazolam [16,46] and diazepam [47], even when the benzodiazepine antagonist flumazenil was administered [49]. Compared with midazolam and methohexital, propofol was associated with the lowest incidence of awareness during injection of the local anesthetic for retro- and peribulbar blocks and also resulted in more satisfactory sedation during the remainder of the procedure [50]. Propofol also decreases intraocular pressure and reduces the incidence of postoperative emesis [51]. Several studies suggest that subhypnotic doses of propofol possess specific antiemetic properties [51-53], an important benefit in the outpatient setting. Because subhypnotic doses of propofol are associated with minimal intraoperative amnesia [54,55], a small dose of midazolam (2 mg IV) has been found to be beneficial in enhancing propofol-induced sedation, amnesia, and anxiolysis without delaying recovery [56]. Use of a propofol infusion, 72 micro g [center dot] kg-1 [center dot] min-1, during upper GI endoscopic procedures was associated with good patient cooperation, effective amnesia, and a rapid recovery profile [57]. Lebovic et al. [58] used propofol (0.5-mg/kg boluses) for sedation during cardiac catheterization and noted significantly shorter recovery times compared with children receiving ketamine (2-mg/kg bolus, followed by a continuous infusion of 2 mg [center dot] kg-1 [center dot] h-1). Propofol has also been used successfully during diagnostic outpatient transesophageal echocardiography in children with complex congenital heart conditions [59], for radiofrequency ablation of aberrant cardiac conduction tracts [60], transcatheter closure of ventricular septal defects [61], and noncardiac surgery in children with heart defects [61-63]. Frankville et al. [64] recommended a propofol loading dose of 2 mg/kg followed by a maintenance infusion of 100 micro g [center dot] kg-1 [center dot] min-1 for children undergoing magnetic resonance imaging scans. Propofol seems to have a very low incidence of perioperative side effects when used in sedative doses [65]. Pain on injection is the most common side effect, followed by excitatory phenomena or involuntary movements. Sedative doses of propofol have minimal depressant effects on tidal volume and minute ventilation, with end-tidal CO2 tension and arterial blood gas values remaining unchanged [66]. However, larger doses of propofol can depress the hypoxic ventilatory response [67] and cause more frequent and longer apnea than barbiturates [68], which suggests that supplemental oxygen (O2) should be available. Although small-dose propofol infusions (<50 micro g [center dot] kg-1 [center dot] min-1) have minimal cardiorespiratory depressant effects, it has been recommended that they only be administered by personnel trained in the use of drugs with the potential for producing apnea and/or airway obstruction (Diprivan[registered sign] package insert; ICI-Stuart Pharmaceuticals, Wilmington, DE). Analgesic Drugs Opioid and nonopioid analgesics have been used as adjuvants during local anesthesia to decrease the pain associated with the injection of local anesthetics, as well as the discomfort related to nonincisional factors (e.g., back pain secondary to lying on a hard OR table, or pressure and traction on deep tissues not rendered insensitive by the local anesthetic solutions) [69]. Opioid Analgesics. Opioids can be used as the sole supplement to local anesthetics; however, they do not produce reliable sedation in the absence of ventilatory depression [70]. Fentanyl, the most commonly used opioid during MAC, has an onset time of 3-5 min and a duration of effect of 45-60 min when administered in doses of 50-100 micro g IV. However, even small doses of fentanyl (25-50 micro g) can cause respiratory depression when combined with sedative drugs [71]. Fentanyl, 1 micro g/kg IV, has been used to sedate children undergoing repair of minor lacerations [18,72]. Fentanyl is also available in a sucrose base for oral transmucosal administration (Oralet[registered sign]; Abbott Laboratories, Chicago, IL). Although this opioid preparation is readily accepted by children and is effective for procedure-related pain [73], its use is associated with typical opioid-related side effects, including emesis, pruritus, and respiratory depression. Alfentanil, a more rapid and shorter-acting analog of fentanyl, may be given by intermittent boluses during the injection of local anesthetics or by continuous infusion to provide a stable level of analgesia [74]. White et al. [75] reported fewer perioperative side effects when alfentanil was administered as a continuous titrated infusion compared with intermittent bolus injections. An equianalgesic dose of alfentanil is associated with a shorter duration of respiratory depression than fentanyl [75] and similar or shorter recovery times in the outpatient setting [76,77]. The use of alfentanil and midazolam has been reported to provide highly satisfactory conditions for immersion extracorporeal shock wave lithotripsy (ESWL) [54]. Avramov and White [78] recently described the combined use of alfentanil (0.3-0.4 micro g [center dot] kg-1 [center dot] min-1) and propofol (25, 50, or 75 micro g [center dot] kg-1 [center dot] min-1) infusions for MAC. Concomitant use of propofol significantly reduced the opioid dose requirement (30%-50%) and the incidence of postoperative nausea and vomiting (0%-17% vs 33%) when compared with an alfentanil infusion alone. Alfentanil has also been found useful for sedating young children undergoing cardiac catheterization [79]. Remifentanil, a potent, rapid-acting micro-selective opioid analgesic, is rapidly metabolized by nonspecific tissue esterases [80-82]. Remifentanil is unique among the currently available opioid analgesics because of its extremely short context-sensitive half-time (3-5 min), which is largely independent of the duration of infusion [80,83]. Although remifentanil is capable of producing all the usual opioid-related side effects, its rapid elimination may reduce the duration of these undesirable effects [84]. A recent study suggests that an infusion of remifentanil, 0.05-0.15 micro g [center dot] kg-1 [center dot] min-1, can provide adequate sedation and analgesia during minor surgical procedures performed under local anesthesia in combination with midazolam 2-8 mg [85]. Sa Rego et al. [86] compared the use of intermittent remifentanil boluses (25 micro g) versus a continuous variable-rate infusion (0.025-0.15 micro g [center dot] kg-1 [center dot] min-1) when administered to patients undergoing ESWL under a MAC technique involving midazolam (2 mg) and propofol (25-50 micro g [center dot] kg-1 [center dot] min-1). These authors reported greater overall patient comfort during the procedure when remifentanil was administered by infusion. However, the patients experienced a higher incidence of desaturation (30% vs 0%) compared with those receiving intermittent boluses of remifentanil. Therefore, the remifentanil infusion must be carefully titrated to avoid excessive respiratory depression [86]. Although the short duration of residual analgesia is a potential disadvantage of remifentanil after painful procedures, its use in combination with local anesthetics may obviate this problem. Nonsteroidal Antiinflammatory Drugs. Concerns regarding opioid-related side effects have stimulated a search for potent analgesics devoid of these untoward effects. The nonsteroidal antiinflammatory drugs (NSAIDs) have become increasingly popular in the perioperative management of pain because they do not produce opioid-related side effects [87,88]. Ketorolac, a potent, parenterally active NSAID, has been used both as a sole supplement and as an adjunct to propofol sedation during local anesthesia. Use of ketorolac is associated with a decreased incidence of pruritus, nausea, and vomiting compared with fentanyl [48,69,89]. However, when used during propofol sedation, ketorolac-treated patients required larger intraoperative doses of propofol and more supplemental opioid analgesia compared with fentanyl-treated patients [69]. Similarly, in patients undergoing ESWL procedures with a MAC technique, the administration of diclofenac was associated with only a marginal reduction in the opioid analgesic requirement [90]. However, the use of ketorolac with patient-controlled fentanyl administration resulted in improved pain control and decreased opioid requirements compared with fentanyl alone.2 Although the use of ketorolac as an intraoperative adjuvant may be useful in the ambulatory setting, its cost-effectiveness during MAC techniques needs to be studied in future clinical investigations [91]. (2) McCallion CF, McCallion J, Shulman MS. The effect of ketorolac on fentanyl PCA requirements in patients undergoing lithotripsy [abstract]. Anesth Analg 1993;76:S253. alpha2-Agonists alpha2-Agonists reduce central sympathetic outflow and have been shown to produce anxiolysis and sedation [92,93]. Kumar et al. [93] demonstrated that oral clonidine (300 micro g) provides effective anxiolysis for elderly patients undergoing ophthalmic surgery under local anesthesia and also decreases the incidence of intraoperative hypertension and tachycardia. Dexmedetomidine, a more selective and potent alpha2-agonist, significantly decreases anxiety levels and reduces the requirements for supplemental analgesic medications when given before IV regional anesthesia for hand surgery [94]. When comparing dexmedetomidine with midazolam for sedation, Aho et al. [95] described a faster recovery from sedation when using dexmedetomidine, followed by reversal with the specific antagonist atipamezole. However, the administration of dexmedetomidine has been associated with bradycardia, which may limit its usefulness during MAC [94,96]. Antagonist Drugs Flumazenil. Flumazenil, a 1,4-imidazobenzodiazepine that is structurally related to midazolam, acts at the GABAA receptor complex to competitively antagonize the central effects of benzodiazepines [97]. It is more effective in reversing benzodiazepine-induced sedation and amnesia than respiratory depression [98,99]. Clinical studies involving outpatients undergoing dental surgery, endoscopic procedures, and minor ambulatory surgery have reported that flumazenil facilitates early recovery without producing adverse side effects when given in small incremental doses of 0.2 mg IV [100-102]. Ghouri et al. [49] noted that the administration of flumazenil, 1 mg IV, at the end of surgery decreased the time to ambulation and discharge in patients who received large doses of midazolam (10.9 +/- 4.2 mg IV) during local anesthesia. The similar intraoperative conditions and early recovery profiles suggest that the use of a midazolamflumazenil combination or a propofol infusion are equally acceptable during MAC [49]. However, the additional cost and relatively short duration of its reversal effect (<90 min) has led many practitioners to question the value of routinely administering flumazenil in the outpatient setting. Flumazenil should only be used to treat persistent excessive sedation after the MAC procedure [49]. Although there are only a few reported cases of clinically significant resedation after conscious sedation with midazolam followed by flumazenil, a subsequent increase in the level of sedation after discharge is not uncommon [49,103]. The varying definitions of resedation make it difficult to determine the actual incidence after reversal of conscious sedation with midazolam followed by flumazenil [103]. Nalbuphine. Nalbuphine is an agonist-antagonist opioid with an onset time of 5-10 min, a duration of 3-6 h, and an elimination half-life of 5 h [104,105]. Garfield et al. [106] described the use of nalbuphine compared with fentanyl in ambulatory gynecologic patients. These authors noted a higher incidence of postoperative sedation, nausea, and psychological side effects (e.g., dreaming and postoperative anxiety) in patients receiving nalbuphine. Sury and Cole [107] described the use of nalbuphine with midazolam compared with midazolam alone for sedation of outpatients undergoing fiberoptic bronchoscopy and found increased patient comfort, as well as an increased incidence of nausea, dizziness, and prolonged recovery times, with the concomitant use of nalbuphine. These findings suggest that the use of nalbuphine may be problematic in the outpatient setting. Naloxone. Naloxone is an opioid receptor antagonist with a rapid onset and short duration of effect and an elimination half-life of 1-1.5 h [108]. Although naloxone, 0.5-2.0 mg IV, rapidly restores adequate ventilation in patients receiving excessive doses of opioids analgesics [109,110], recurrence of respiratory depression can occur [108]. In addition, reversal of opioid-induced ventilatory depression may also be associated with reversal of residual analgesia [109]. When decreased plasma levels of short-acting opioids are anticipated after a bolus dose or on diminution (or discontinuation) of a continuous infusion, it may be possible to avoid the administration of naloxone by supplying supplemental oxygen and assisting ventilation for a short time until adequate spontaneous ventilation is reestablished. Nalmefene. Nalmefene, a newer opioid antagonist that is structurally similar to naloxone, possesses a more prolonged duration of action because of its longer eliminati