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Review Article

The Changing Role of Monitored Anesthesia Care in the Ambulatory Setting

Sa Rego, Monica M. MD; Watcha, Mehernoor F. MD; White, Paul F. PhD, MD, FANZCA

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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
Table 1:
Definitions Proposed by the American Dental Association Council on Dental Education

The 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
Table 2:
Surgical Procedures That Can be Performed Under Sedation/Analgesia

In 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
Table 3:
Recommended Doses of Commonly Used Sedative and Analgesic Drugs During MACa

Sedative-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
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 elimination half-life (8-10 h) [111]. The duration of nalmefene's reversal of fentanyl-induced respiratory depression is dose-dependent [112]. The following side effects have been observed after the use of nalmefene: light-headedness, drowsiness, dizziness, mental fatigue, hypertension, tachycardia, and pulmonary edema [113-115]. The recommended dose of nalmefene is 0.25 micro g/kg administered every 2-5 min to a total dose of 1 micro g/kg [116].

Use of Drug Combinations

It is a common practice to use combinations of drugs for sedation and analgesia. The combination of meperidine (Demerol[registered sign]; Sanofi Winthrop Pharmaceutical, New York, NY) 2 mg/kg, promethazine (Phenergan[registered sign]; Wyeth-Ayerst Laboratories, Philadelphia, PA) 1 mg/kg, and chlorpromazine (Thorazine[registered sign]; Smith-Kline Beecham Pharmaceutical, Philadelphia, PA) 1 mg/kg has been used frequently in children and is known as a "lytic cocktail" or "DPT." Although the combination can produce profound sedation and analgesia, the effects are long-lasting (with "sleep" times of 4.7 +/- 2.4 h and a "return to normal" of 19 +/- 15 h) [18,117]. The prolonged recovery time has lead to recommendations that the use of this combination be abandoned [18,117]. With the availability of improved sedative and analgesic drugs (e.g., midazolam, fentanyl, remifentanil, and propofol), physicians now have the ability of titrating the sedative/analgesic medication to achieve the desired clinical end points, thereby allowing for a more rapid recovery.

Monk et al. [118] compared the efficacy and safety of ketamine (20-50 micro g [center dot] kg-1 [center dot] min-1) and alfentanil (0.5-2.0 micro g [center dot] kg-1 [center dot] min-1) infusions when administered in combination with midazolam (4-9 mg in the alfentanil group and 4-14 mg in the ketamine group) during ESWL procedures. Although use of ketamine was associated with superior intraoperative cardiorespiratory stability, a higher number of disruptive movements were noted in the ketamine group, contributing to inadequate stone fragmentation. In addition, discharge times were prolonged in the ketamine group (161 +/- 31 vs 142 +/- 42 min). Finally, more patients in the alfentanil group rated the anesthetic technique as excellent (96% vs 70% for ketamine). Compared with fentanyl (1.5 micro g/kg)-propofol (50 micro g [center dot] kg-1 [center dot] min-1), the midazolam (0.05 mg/kg)-alfentanil (1.0 micro g [center dot] kg-1 [center dot] min-1) combination produced more effective intraoperative amnesia, with similar recovery times, stone fragmentation, and patient satisfaction, but slower respiratory rates and a higher incidence of transient decreases in oxygen saturation (<90%) during the ESWL procedures [54].

For the sedative component of MAC, midazolam, 1-3 mg IV, followed by a titrated propofol infusion, 10-100 micro g [center dot] kg-1 [center dot] min-1, provides excellent sedation, anxiolysis, and amnesia without significantly prolonging recovery times compared with propofol alone [56]. For the analgesic component, a simple approach is to administer an analgesic dose of fentanyl, 25-50 micro g IV, or alfentanil, 250-500 micro g IV, 3-5 min before injection of the local anesthetic solution and small intermittent bolus doses (fentanyl, 25 micro g IV, or alfentanil, 250 micro g IV) for transient pain not responding to supplemental local anesthetic infiltration. Smaller dose recommendations should be administered to elderly outpatients undergoing MAC (e.g., midazolam 0.5-1.0 mg IV, fentanyl 12.5 micro g, alfentanil 125 micro g).

Avramov et al. [85] evaluated the safety and efficacy of remifentanil infusion alone and in combination with different bolus doses of midazolam. Midazolam produced a dose-dependent increase in the level of sedation, as well as loss of consciousness and enhanced remifentanil-induced respiratory depression. Remifentanil alone did not provide adequate sedation or patient comfort in this outpatient population. These investigators recommended midazolam 2-4 mg IV in combination with remifentanil 0.05-0.1 micro g [center dot] kg-1 [center dot] min-1 for sedation and analgesia during MAC [85]. However, in outpatients premedicated with midazolam 2 mg IV, an infusion of propofol (25-50 micro g [center dot] kg-1 [center dot] min-1) in combination with remifentanil (12.5- to 25-micro g bolus injections or an infusion of 0.025-0.15 micro g [center dot] kg-1 [center dot] min-1) represents an even more controllable and efficacious approach to providing MAC [70,86]. Using the sedative and antiemetic effects of propofol in combination with the analgesic effects of remifentanil should decrease the sedative and analgesic requirement, as well as minimize the perioperative side effects. Further investigations are necessary to clarify the potential interactions of remifentanil with propofol when used for MAC in the ambulatory setting.

Patient-Controlled Sedation and Analgesia

Because the degree of sedation desired during MAC, as well as the level of stimulation and discomfort during ambulatory surgical procedures, varies widely among patients, patient-controlled techniques are useful alternatives to physician-controlled drug administration [119,120]. Park and Watkins [121] found that patient-controlled administration of a fixed-dose combination of midazolam (0.5 mg) and fentanyl (25 micro g), with a lockout interval of 5 min between doses, was as safe and effective as anesthesiologist-controlled drug administration. However, Cork et al. [122] found that patients were more sedated at the end of the procedures when they self-administered their sedative drugs using a patient-controlled sedation (PCS) system compared with anesthetist-controlled sedation. Osborne et al. [123] reported that patient satisfaction with patient-controlled administration of propofol was higher than with physician-controlled sedation with midazolam and fentanyl. When patients used propofol, alfentanil, or midazolam via a patient-controlled analgesia (PCA) device as part of a MAC technique, no differences were found in the degree of patient satisfaction [124]. However, propofol was associated with the highest incidence of pain on injection, midazolam produced more intra- and postoperative amnesia, and alfentanil was associated with more postoperative nausea and vomiting [124].

In comparing the efficacy of PCA with physician-controlled analgesia with alfentanil in patients undergoing ESWL, Kortis et al. [125] reported that the PCA patients received 31% less alfentanil than the control group. Although the pain scores were higher in the PCA group, most patients reported minimal pain. However, Zelcer et al. [120] described comparable patient comfort and satisfaction during vaginal ovum pickup procedures when comparing alfentanil administered using a PCA device with physician-controlled administration. The primary advantage of PCA over physician-controlled drug administration is that it allows the patient to become an active participant in the medication process, which produces a positive psychological effect that may be more important in increasing patient satisfaction than the specific drug or dose regimen used [126].

Complications and Recovery Profiles

Adverse outcomes are still common after general anesthesia in the ambulatory setting [127-129]. Although most practitioners consider local anesthesia to be safer than general or regional anesthesia, Muir et al. [130] found only minor differences in postoperative morbidity when comparing local and general anesthesia for young outpatients undergoing oral surgery. Serious complications associated with local sedation techniques for dental surgery were initially reported in a British study [131]. Although the overall mortality rate was only 1 in 152,000, one third of the deaths occurred in association with local sedation. Most sedation deaths occurred when operator-administered anesthetics were used (e.g., by oral surgeons), and the most common precipitating causes included respiratory obstruction, hypoxia, or cardiovascular collapse secondary to arrhythmias [132]. Pierce [133] reported that most sedation accidents resulting in severe brain damage (or death) were preventable by proper use of available monitoring techniques.

A survey by the Federated Ambulatory Surgery Association [134] found higher overall complication rates after ambulatory surgery with combined local anesthesia and IV sedation (1:106) compared with general (1:120), regional (1:277), or local anesthesia alone (1:268). The length of the operative procedure was another important determinant of morbidity after ambulatory surgery. For procedures lasting less than 1 h, the incidence of perioperative complications was 1:155; this ratio increased to 1:35 for procedures lasting longer than 3 h. In this survey, outpatients with preexisting cardiovascular diseases were also reported to be at increased risk of postoperative complications. However, a more recent epidemiologic study at the Mayo Clinic by Warner et al. [135] revealed that the overall risk of major morbidity and mortality for outpatients undergoing ambulatory surgery did not differ from that of a similar age-matched population not undergoing an ambulatory procedure.

The risk of adverse drug reactions increases when combinations of sedative and analgesic drugs are administered during local anesthesia. The potential for compromising the respiratory system results from depression of esophageal and laryngeal reflexes, upper airway obstruction, and depression of central hypercarbic and hypoxic ventilatory responses [136-138]. Interestingly, when sedative drugs are administered by carefully titrated infusions (versus intermittent bolus doses), the respiratory depressant effects can be minimized [99]. However, with the rapid, short-acting opioid analgesic remifentanil, Sa Rego et al. [86] reported that the infusion group received a larger total dose of remifentanil than the bolus group, which contributed to greater depression of the ventilatory drive. Mora et al. [102] found that 5 of 10 patients administered an average diazepam dose of 0.97 +/- 0.34 mg/min developed depressed hypoxic responsiveness, and that only 1 of the 5 patients had complete reversal of ventilatory depression after flumazenil administration. Bailey et al. [139] reported no significant respiratory depressant effect after midazolam (0.05 mg/kg IV). However, fentanyl (2 micro g/kg IV) produced transient hypoxemia in 50% of the subjects and significantly depressed the ventilatory response to CO2. Furthermore, the combination of midazolam and fentanyl increased the incidence of both hypoxemia (11 of 12 subjects) and apnea (6 of 12 subjects) [139]. In a clinical investigation, the incidence of hypoxemia with a propofol-fentanyl combination was found to be significantly lower than that with midazolam and alfentanil [54]. Because more than 40% of patients breathing room air during local anesthesia with sedation/analgesia for oral surgery experienced clinically significant oxygen desaturation [140], supplemental oxygen, which can be delivered through a nasal canula with an end-tidal CO2 port to assess ventilatory rate, is always recommended when IV adjuvants are used during local anesthesia. However, there is still a risk of hypoventilation (hypercarbia) despite the administration of supplemental oxygen.

Monitoring During MAC

Concerns regarding the safety of sedation practices were raised by reports of increased mortality and morbidity in dental offices and reports of misadventures during sedation for diagnostic procedures (e.g., GI endoscopy) by nonanesthesiologists. In response to these reports, the American Academy of Pediatrics (AAP) developed guidelines for monitoring and managing pediatric patients during and after sedation [141]. In these guidelines, emphasis was placed on accident prevention and human factor issues to prevent situations in which no one was specifically assigned to monitor the patient and in which attention was directed more to the performance of the procedure than observing patient response to the sedative/analgesic drugs [142,143]. The AAP guidelines for deep sedation (but not for conscious sedation) insist that an additional individual who is not assisting in the performance of the procedure be available to administer drugs and monitor the child. Maxwell and Yaster [144] claim that some practitioners attempt to circumvent this requirement by referring to all sedation techniques as conscious sedation. In 1996, the ASA published its guidelines for sedation/analgesia by nonanesthesiologists [3]. These guidelines were written for nonanesthesiologists and state that the individual administering the sedative/analgesic medications should have previous experience with the drugs they are using and be familiar with the patient's medical history. For elective procedures, an appropriate period of fasting should be undertaken because there is always the possibility of loss of airway reflexes if the patient inadvertently becomes deeply sedated [18].

The ASA has specified that the standards for basic monitoring during MAC by anesthesiologists are the same as those for general anesthesia. These include evaluations of oxygenation, ventilation, circulation, and body temperature, and the continuous presence of qualified anesthesia personnel [4]. The Joint Commission on Accreditation of Health Care Organizations (JCAHCO) [145] has insisted that the same standards of care that apply for general and regional anesthesia be provided during sedation techniques in all areas of an institution. Because anesthesiologists have the most expertise in sedation/analgesia techniques, they should have a critical role in approving institutional policies and procedures for sedation/analgesia.

The essential characteristics of monitoring techniques for outpatient MAC are that they be not only effective, but also simple to apply, noninvasive, and economical [146]. The pulse oximeter has become an invaluable monitor because it fulfills all of these criteria. The monitoring guidelines of the AAP and ASA regarding the routine use of pulse oximetry to assess oxygenation during sedation are based on studies establishing the superiority of pulse oximetry over visual inspection of mucous membranes and nail beds in detecting oxygen desaturation [147]. The initial opposition to the routine use of these devices outside the OR has disappeared as nonanesthesiologists have become more familiar with their clinical use. However, desaturation after sedation is a late event, and the inadequacy of ventilation should be detected and corrective measures instituted when the oxygen saturation value decreases below 90%. Unfortunately, impedance plethysmography may fail to detect airway obstruction, and the measurement of exhaled carbon dioxide can be difficult in nonintubated patients. Thus, the vigilance of the observer responsible for monitoring the patient receiving sedation/analgesia remains the best protection against adverse respiratory events. As with other types of anesthesia, the optimal level of patient care during MAC is achieved by meticulous attention to detail [148].

Methods Used to Assess the Level of Sedation

A wide variety of objective clinical scoring systems has been developed to reduce individual observer bias and to provide a more consistent method for monitoring temporal changes in the level of sedation during MAC [149]. The most commonly used methods for assessing the level of sedation include:

1. The Ramsay scale, an objective scoring system that was originally used to quantitate the level of drug-induced sedation and measure patient responsiveness and drowsiness in the intensive care unit [150]. Unfortunately, it is difficult to quantify the degree of agitation and oversedation using this scale.

2. The observer's assessment of alertness/sedation (OAA/S) scale was developed to quantify the CNS effects of benzodiazepines [151]. The OAA/S score is based on assessments in four separate categories: responsiveness, speech, facial expression, and ocular appearance. To correlate a greater degree of sedation with a higher OAA/S score, the original 5-point OAA/S scoring system is usually reversed (with a score of 1 corresponding to an awake and alert state and 5 representing profound sedation). The OAA/S scale provides a higher discriminatory power of the different levels of sedation. The scale has also been validated against the Digit Symbol Substitution Test (DSST), a sensitive measure of cognitive and psychomotor impairment produced by sedative-hypnotic drugs [152]. The major disadvantages of these methods of CNS assessment are that the patients must be stimulated to perform the testing procedure during the operation, the patients' cooperation is required, and they are subject to testing fatigue.

3. The sedation visual analog scale (VAS) has also been used to quantify the level of sedation during MAC [16,48,55]. A 100-mm VAS for sedation is anchored at one end with the adjective "awake and alert" and at the opposite end by "asleep." Although this assessment tool also requires that the patients be stimulated for the testing procedure, it requires minimal patient cooperation. Smith et al. [55] demonstrated a good correlation between VAS sedation scores assessed simultaneously by the patient and by an independent observer during fixed-rate propofol infusions (Figure 2).

Figure 2
Figure 2:
Mean (+/- SEM) sedation visual analog scale scores during propofol infusion recorded by the patients (A) and a blinded observer (B): before propofol infusion (Time 0); at 15-, 30-, 45-, and 60-min intervals during sedation; and on arrival in the postanesthesia care unit (PACU). Groups 1-4 received propofol boluses of 0.2, 0.4, 0.5, or 0.7 mg/kg IV, respectively. Subsequently, a constant-rate propofol infusion of 8, 17, 33, or 67 micro g [center dot] kg-1 [center dot] min-1 was administered to Groups 1-4, respectively. [square bullet, filled] = Group 1, [square, open] = Group 2, [round bullet, filled] = Group 3, [circle, open] = Group 4. *P < 0.05 from Group 1. dagger P < 0.05 from 15-min value in the same group. Reproduced with the permission of the publisher [55].

4. The most common neurophysiologic techniques for monitoring the depth of sedation involve the use of electroencephalogram (EEG), a noninvasive, objective, and continuous measure of brain function that has been shown to correlate with the depth of sedation [153]. Because sedative and analgesic drugs alter the EEG in a drug-specific fashion [153,154], interpretation of EEG changes can be difficult when drug combinations are used. The interpretation of EEG changes has been simplified by using computerized EEG analysis (e.g., power bands [a, b, d and q], frequency variables [95% spectral edge frequency and median frequency], and interfrequency phase-coupling numbers [bispectral (BIS) index]). Recent studies with the EEG-BIS index suggest that the BIS value correlates best with the depth of sedation [155]. (3) Liu et al. [156,157] demonstrated that the EEG-BIS index correlates with the depth of both midazolam- and propofol-induced sedation as validated using the OAA/S rating scale (Figure 3). As the depth of sedation increases with either midazolam or propofol, there are consistent and predictable decreases in the EEG-BIS index, with recovery following a similar pattern. These preliminary data suggest that anesthesiologists may be able to improve the titration of sedative-hypnotic drugs during MAC by using the EEG-BIS monitor as an adjunct to the clinical assessment of CNS depression.

(3) Sebel P, Rampil I, Cork R. Bispectral analysis for monitoring anesthesia: a multicenter study [abstract]. Anesthesiology 1993;79:A178.

Figure 3
Figure 3:
Electroencephalogram (EEG) bispectral index as a function of the level of propofol (A) and midazolam (B) induced sedation during the onset and recovery phases. Observer assessment of alertness/sedation scale (OAA/S) score: 5 = awake/alert to 1 = deeply sedated. The values are either mean or individual (scatter plot). Reproduced with the permission of the publisher[156,157].

Cost Comparisons of MAC Versus General and Regional Anesthesia

With the recent growth in managed care, global and capitation fees and payments for health care services are increasingly becoming "fixed" regardless of the resources consumed to provide a given service. One of the consequences of this change in health care financing has been a much-needed scrutiny of surgical costs, with an emphasis on reducing expenditures in areas of high-resource utilization (e.g., OR suites, recovery areas). Anesthetic costs are a highly visible target for hospital administrators, and practicing anesthesiologists have begun to examine the value of anesthetic drugs and techniques with the aim of maintaining the current high standard of patient care within the limits of tight fiscal constraints (i.e., value-based anesthesia care) [158]. Unfortunately, many OR managers have adopted the overly simplistic view that drugs with the lowest acquisition prices are preferred, an approach known as "cost minimization." In comparing the cost for each treatment strategy, it is also important to consider the personnel costs required to provide the service, as well as the costs of managing side effects.

At the present time, there are limited data available comparing the costs associated with general anesthesia, regional anesthesia, and MAC [159,160]. In a nonrandomized, retrospective study of 248 surgical procedures performed in a teaching hospital in France, the total cost (i.e., drugs and personnel) of a general anesthetic was 2.5 times higher than the cost of a local anesthetic-based technique. However, this difference could be explained in part by differences in the complexity and duration of the surgical procedures, as well as in the severity of the patients' underlying illness [159]. Although Dexter and Tinker [160] noted an apparent relationship between the anesthetic technique and time to discharge from the recovery room, they cautioned that retrospective data from patients undergoing different types of surgery "should not be used to conclude that using MAC would decrease time to discharge and thus save money." It is important that data on the effect of anesthetic techniques on costs be collected prospectively after a large number of patients undergoing similar operations are randomized to different anesthetic regimens (e.g., general versus regional versus MAC). Unfortunately, no such data are available, even though a number of outpatient procedures (e.g., inguinal herniorrhaphy, tubal sterilization, arthroscopy, ESWL) can be performed with either a general, regional, or MAC technique.

The inadequacy of cost data in healthy patients precludes definitive conclusions regarding the relative cost-effectiveness of any given anesthetic technique. Based on retrospective, nonrandomized, and/or uncontrolled data, several authors have suggested that MAC techniques are more cost-effective than either general or regional anesthetic techniques because of decreased complication rates and less time spent in the more labor-intensive areas (e.g., the OR and the postanesthesia care unit). The low incidence of side effects and the ability to routinely transfer patients directly from the OR to the Phase II step-down unit should contribute to decreased costs with MAC techniques. In addition, the residual analgesia provided by the local anesthetic could contribute to an earlier discharge after ambulatory surgery. However, if institutional policies mandate a minimal period of observation after surgery, the economic benefits associated with MAC may be limited.

Only a few randomized trials of general anesthesia versus MAC have been published in the peer-reviewed medical literature. Bordahl et al. [7] reported a decreased use of drugs and disposable anesthetic supplies in women undergoing laparoscopic tubal sterilization with a midazolam (0.05 mg/kg)-alfentanil (0.01 mg/kg) MAC technique compared with a propofol-alfentanil-atracurium general anesthetic technique ($21 vs $46). The MAC technique was associated with less time in the operating room (30 +/- 4 vs 34 +/- 1 min), a higher "awakeness" score on the evening of the day of surgery (4.3 +/- 1.4 vs 3.6 +/- 1.4), and decreased postoperative pain (33% vs 80%) and sore throats (3% vs 70%), contributing to a reduction in perioperative costs [7]. Petersen et al. [161] confirmed these findings and added that the incidence of emesis was also higher after general anesthesia (19% vs 14%). Finally, Patel et al. [162] reported that the use of IV sedation resulted in a 6- to 7-min decrease in the OR exit time compared with general anesthesia, contributing to a significant cost saving as a result of enhanced "turnover" of the cases.

In comparing costs of general and local anesthesia for inguinal herniorrhaphy from the perspective of the health insurance company, Behnia et al. [163] reported a decreased cost with local anesthesia because of the elimination of fees for anesthesia services, and decreased recovery room costs because of reductions in the need for analgesic and antiemetic drugs. Sedative regimens combined with local anesthesia have also proved to be highly successful for cataract surgery [164].

Many of these preliminary studies can be criticized for: (a) using hospital charges and not true costs, (b) having small group sizes that fail to detect rare but potentially life-threatening complications that consume a considerable amount of resources, (c) failure to prospectively randomize patients to different anesthetic techniques, and (d) failure to ensure homogeneity of the comparative techniques [163]. The use of charges as a substitute for costs leads to an overestimate of resource consumption by an anesthesia department compared with other hospital departments because the cost to charge ratio is lower for anesthesia services [165].

United States Medicare Policy on MAC Anesthesia

In the United States, a new Medicare policy on MAC anesthesia reimbursement has recently been published in the Medicare Newsletter (Medicare Part B Newsletter. No. 149, March 21, 1997). This new policy denies payment for anesthesia services for a long list of procedures commonly performed under MAC ("Category B" surgeries-procedures for which anesthetists or anesthesiologists are generally not needed) unless Medicare determines that the "anesthesia service is reasonable and medically necessary." This rule implies that one or more of the conditions or situations found in the diagnostic (ICD-9-CM) codes that support medical necessity be present, otherwise it will not be possible for the anesthesiologist to bill for the MAC services. Furthermore, the policy states that the presence of an underlying condition alone, as reported by an ICD-9-CM code, may not be sufficient evidence that MAC is necessary. The medical condition must be "significant enough" to support the need to provide MAC (e.g., patient requires chronic medications or is currently symptomatic). The presence of a stable, treatable medical condition is not necessarily sufficient in and of itself. This ruling means that an ASA physical status I, II, and maybe even III, outpatient who is undergoing one of the procedures in Category B (e.g., breast biopsy, partial mastectomy, circumcision, prostate biopsy, eye surgery) may not be allowed to have an anesthesiologist if the surgeon (or patient) decides that a MAC technique is the most appropriate anesthetic choice for the particular procedure.

Interestingly, this policy may well result in increased overall surgical costs. First, the surgeons will have to deal with the performance of the surgical procedure while at the same time managing the patient's intraoperative comfort, thereby increasing the duration of surgery. Second, many surgeons will request that the patient receive a general (or regional) anesthetic technique even though a MAC technique may be more appropriate for the surgical procedure, thereby increasing the time in the postanesthesia recovery unit and/or day surgery unit. Finally, if this policy is not reversed, it will also interfere with the anesthesiologists' medical decision-making process by limiting their ability to determine the most appropriate anesthetic for a particular patient and surgical procedure. The potential implications of the proposed Medicare legislation on the future use of MAC techniques in the ambulatory setting are great.

Summary

The use of MAC techniques is increasing in popularity because recovery profiles seem to be improved compared with general and regional anesthesia [7,13,161]. The effective use of a MAC technique can provide highly acceptable patient comfort while optimizing intraoperative conditions. Patient cooperation, effective local anesthesia, and a gentle surgical technique are all essential elements for the successful application of a MAC technique. Although local anesthetic-based techniques are generally assumed to be safer than general or regional anesthesia, supplementation with potent sedative-hypnotic and analgesic drugs may result in significant depression of the central respiratory drive and/or transient upper airway obstruction. Therefore, the decision to use MAC in place of general or regional anesthesia should be made only after carefully assessing both patient and surgeon preferences, as well as any co-existing medical conditions (e.g., obesity, chronic obstructive pulmonary disease, cardiac disease). The use of carefully titrated infusions of rapid- and short-acting sedative and analgesic drugs seems to enhance patient comfort and safety during MAC. However, the need for vigilant monitoring, combined with supplemental oxygen administration and the availability of resuscitation equipment, are all essential elements for the safe practice of MAC.

The choice of a regimen of sedative/analgesic drugs for use during MAC should be based on the anticipated degree of pain associated with the procedure and the requirements for its successful completion. If the procedure is relatively pain-free and anxiolysis is the main consideration (e.g., during upper GI tract examinations), it may be justified to use only a benzodiazepine (e.g., midazolam). If the procedure is pain-free but patient immobility is essential for its success (e.g., radiation therapy), a small-dose propofol infusion should be added to the regimen and titrated to effect. If brief periods of pain are anticipated during the procedure (e.g., when local anesthetics are injected, with deep tissue dissection, painful manipulations), administration of a rapid, short-acting analgesic opioid is indicated. For procedures in which analgesia is provided by a regional anesthetic technique, a stable level of sedation can be easily achieved by a variable-rate infusion of propofol or methohexital. Thus, an effective regimen for MAC might include midazolam 1-3 mg IV, followed by propofol 25-100 micro g [center dot] kg-1 [center dot] min-1 or methohexital 20-60 micro g [center dot] kg-1 [center dot] min-1 in combination with intermittent boluses of fentanyl (25 micro g), sufentanil (5 micro g), alfentanil (250 micro g), or remifentanil (12.5 micro g) [56,86]. Alternatively, a basal infusion of alfentanil (0.5-1.0 micro g [center dot] kg-1 [center dot] min-1) or remifentanil (0.025-0.15 micro g [center dot] kg-1 [center dot] min-1) can be supplemented with small bolus doses of the analgesics. To avoid inadvertent overdoses in higher-risk outpatient populations (e.g., elderly, critically ill), it is important to administer small bolus doses when supplementation is necessary and to allow sufficient time between repeated doses to avoid cumulative effects. Careful titration to ensure adequate cardiorespiratory stability using variable-rate infusions of sedative and analgesic drugs will minimize the possibility of adverse side effects during MAC [166].

In conclusion, concerns regarding the effects of the increasing cost of health care on the medical decision-making process have led to a reexamination of anesthetic practices [167]. In general, the overall cost of a MAC technique is less than that of either general or regional anesthesia [7,163,168]. To realize the savings resulting from decreased time to discharge, reduced postoperative pain, and lower incidence of sore throats and emesis with MAC techniques [161,163,169,170], recovery procedures and discharge criteria will have to be modified (i.e., "fast-tracking" concept). Nursing policies that dictate mandatory minimal stays in the labor-intensive postanesthesia care unit will need to be changed to obtain the maximal benefit from the use of the newer, short-acting drugs during MAC. Fast-tracking in the ambulatory setting implies the direct transfer of all MAC patients from the OR to a Phase II recovery area and should save the institution money. If these benefits can be proven in prospectively conducted, randomized cost-benefit studies, the use of MAC techniques will continue to grow in the future.

The authors thank Dr. Patricia A. Kapur for her guidance and expert advice in the preparation of this review article.

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