Pharmacologic rationale for anesthetic agents in ambulatory practice

Pharmacologic Rationale for Anesthetic Agents in Ambulatory Practice JOHN J. NAGELHOUT, MICHAEL J. BOYTIM,

PhD, CRNA MN, CRNA

Patients undergoing surgery in the ambulatory setting require anesthetic agents that expedite postoperative recovery, minimize adverse side effects, and contribute to patient satisfaction. The newer anesthetic agents that are currently used in today’s practice offer the flexibility needed to provide anesthesia care for a wide variety of diagnostic and therapeutic procedures performed on an outpatient basis. It is important for the perianesthesia nurse to be familiar with the anesthetic agents used in the operating room to fully understand the influence of these drugs on the patient’s recovery process. The role of the perianesthesia nurse is vital in assessing the residual effects of the anesthetic agents and instituting proper nursing interventions during the patient’s postanesthesia experience. This article focuses on the rationale for the use of a variety of anesthetic and related agents necessary for the provision of ambulatory anesthesia. The commonly used agents used in ambulatory anesthesia care and their influences on the continuum of care is reviewed. © 2001 by American Society of PeriAnesthesia Nurses.

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HARMACOLOGIC knowledge of currently used anesthetic agents assists the practitioner in developing the most appropriate anesthetic plan for ambulatory surgical practice. Over the last 3 decades, ambulatory surgery has increased exponentially to encompass a broad spectrum of procedures. Concurrently, the patient now deemed acceptable for outpatient surgery has also grown. Broad groups of patients (eg, elderly or unhealthy) are no longer being excluded from having their surgery and being sent home on the same day. These patients require an anesthetic tailored to their individual needs and the requirements of the surgical procedure, yet it must also be an anesthetic designed to promote a safe and expeditious recovery. Today, approximately 70% of all elective surgeries are performed on an outpatient basis, and that figure is expected to continue to grow well within this century. This rapid growth in ambulatory surgery has been made possible with the development of short-acting, titratable anesthetic agents and less invasive surgical procedures

(eg, laparoscopy). Rapid, short-acting anesthetic agents, analgesics, and muscle relaxants decrease the recovery process; this allows for more extensive procedures that were traditionally performed on an inpatient basis to now move to the ambulatory surgical setting. In this era of cost containment, an ideal ambulatory anesthetic is one that would be safely administered without sacrificing quality but would minimize consumer or third party expense. An ideal anesthetic used in ambulatory surgery

John J. Nagelhout, PhD, CRNA, is the Director and Michael J. Boytim, MN, CRNA, is the Assistant Director at Kaiser Permanente School of Anesthesia, California State University Fullerton, Pasadena, CA. Address correspondence to John J. Nagelhout, PhD, CRNA, Director, Kaiser Permanente School of Anesthesia, California State University Fullerton, 100 South Los Robles, Suite 550, Pasadena, CA 91188. © 2001 by American Society of PeriAnesthesia Nurses. 1089-9472/01/1606-0005$35.00/0 doi:10.1053/jpan.2001.28750

Journal of PeriAnesthesia Nursing, Vol 16, No 6 (December), 2001: pp 371-378

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is one that (1) renders rapid patient unconsciousness, (2) is technically easy to administer, (3) is maintained with a controlled duration of action, and (4) is readily titratable to patient response or surgical intervention. In addition, these anesthetic agents should undergo rapid predictable elimination, produce no toxic metabolites or side effects, possess a high therapeutic safety index, be tolerated by all patient populations, and promote rapid recovery. The cost-benefit ratio is also an increasing consideration in contemporary medical practice; the benefits derived from the use of a particular drug should outweigh the cost of the drug. This article reviews the rationale for the use of commonly administered pharmacologic agents in ambulatory practice. PREOPERATIVE ANESTHETIC AGENTS

Primary indications for the use of premedication in ambulatory surgery include the following: anxiolysis, sedation, analgesia, amnesia, antisialagogue, vagolysis, and the prevention of postoperative nausea and vomiting (PONV) and pulmonary aspiration of gastric contents. However, sedative premedication is not routinely used in many ambulatory surgical settings in the United States because of the concern that these drugs will prolong the recovery period.1 Most prospective studies, however, found inconclusive evidence regarding prolonged recovery time in ambulatory surgery after the routine use of premedication.4,5 The correct choice of premedication may actually decrease the recovery phase because of the decreased intraoperative anesthetic requirements. Commonly

used preoperative sedative agents and adjunctive drugs are listed in Table 1. Anxiolytics and Sedatives When used properly, anxiolytic and sedativehypnotic drugs allay anxiety while reducing the overall anesthetic requirements, thereby decreasing the recovery period. Both barbiturates and benzodiazepines have been traditionally used as premedicant drugs. Barbiturates, however, are rarely used in the ambulatory setting because of their propensity to prolong recovery time. Benzodiazepines. Midazolam is the most commonly used benzodiazepine preoperatively because of its relatively short elimination half-life and lack of significant side effects, which contribute to rapid recovery.6 It is water soluble with an elimination half-life of 2.5 hours, which increases to 6 hours in the elderly. The drug’s dose should be decreased with increasing age.7 Oral midazolam is reported to be highly effective in both adults and children at a dose of 0.5 mg/kg.8 Increasing the dose of midazolam above 0.5 mg/kg orally only increases the incidence of adverse side effects (eg, increased sedation, loss of balance and head control, blurred vision, dysphoric reactions).9 Diazepam has historically been used as the benzodiazepine of choice for preoperative anxiolysis. Because of its long duration of action and elimination half-life, it is not routinely used in ambulatory surgery. Its metabolite, desmethyldiazepam, has pharmacologic properties similar to the parent drug, thus prolonging recovery time, which makes it undesirable for short procedures.

Table 1. Preoperative Anesthetics and Pharmacologic Agents Drug

Midazolam Diazepam Opioids NSAIDs Droperidol Chlorpromazine Dolasetron Granisetron Ondansetron Ranitidine Sodium citrate Metoclopramide

Action

Short-acting, retrograde amnesia Long-acting, active metabolite lends to residual sedative effect May cause prolonged recovery, PONV, respiratory depression Moderate, postoperative pain control without opioid side effects High doses may result in sedation and delayed recovery; therefore use lowest effective dose to control PONV Associated with hypotension, and significant sedation Effective in treatment of PONV; little sedation, most effective if administered at end of surgery Effective in treatment of PONV; little sedation, most effective if administered at end of surgery Effective in treatment of PONV; little sedation, most effective if administered at end of surgery More potent than cimetidine with fewer side effects; increases gastric pH and decreases gastric volume Increases gastric pH Increases lower esophageal sphincter tone, increases gastric emptying

Abbreviation: PONV, postoperative nausea and vomiting.

ANESTHETIC AGENTS IN AMBULATORY PRACTICE Flumazenil (0.2 mg over 15 seconds; repeat at 60-second intervals until desired effect is seen or a maximum dosage of 1 mg) is the first benzodiazepine antagonist available for clinical use. Its primary indication is for reversal of the prolonged sedative effects of midazolam in the ambulatory setting.10 The routine use of flumazenil in ambulatory care is not indicated; rather, it should be administered based on the need to reverse excessive drowsiness associated with midazolam. Analgesics Opioids. The effectiveness of opioids for relieving anxiety is controversial. Routine use of opioid analgesics for premedication is not warranted unless the patient is experiencing pain. Use of opioids in premedication can increase the incidence of PONV, decrease respirations, and may cause pruritis, which may result in delay in discharge after ambulatory surgery. Intravenous opioids are best when given just before the induction of general anesthesia to control hypertensive responses often associated with endotracheal intubation and to decrease surgical stress. If reduction of anxiety is the primary goal, it is better achieved with a benzodiazepine such as midazolam. Oral transmucosal fentanyl (10 ␮g/kg) has been used preoperatively in children to reduce anxiety and increase sedation, but it is associated with a high incidence of pruritis and PONV.11 Nonopioids. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proven as valuable adjunct drugs because of their long-acting, opioidlike actions.12 NSAIDs (eg, ketorolac, ibuprofen) can facilitate early recovery, decrease opioid usage along with its adverse side effects, and result in faster discharge times from Phase II.3 Although NSAIDs may reduce or eliminate the need for postoperative opioid analgesics, these drugs have a ceiling analgesic effect and may be less efficacious than opioid compounds for controlling acute postoperative pain.11 PREVENTION OF POSTOPERATIVE VOMITING

PONV is problematic in ambulatory surgery because it may delay Phase II discharge, result in unanticipated hospital admission, and reduce patient satisfaction. Certain anesthetic and nonanesthetic factors place the patient at risk for PONV. Conditions that predispose the patient to developing PONV include obesity, female gender,

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pregnancy, the type of surgery (ie, emergency, ophthalmic, middle ear, abdominal, laparoscopic procedures), early age, menstruation, certain anesthetic agents (eg, opioid, inhalation agents), uncontrolled pain, history of PONV or motion sickness, and anxiety.13 A combination of medications that target the various neurotransmitters (eg, acetylcholine, dopamine, histamine, opiate, serotonin) that have an impact on PONV may be required to successfully treat patients.14 Routine use of these drugs prophylactically is recommended only in high-risk patients because the incidence of PONV is actually low (18% to 28% in adults) and the newer antinausea medications are costly, and when the risk of side effects of the older medications is increased. Butyrophenones Droperidol is a neuroleptic drug with antiemetic properties that are a result of its antagonist effects on dopamine receptors. Use of droperidol includes the prevention and treatment of PONV. Lower doses (10 to 20 ␮g/kg) seem to be as effective as higher doses, and recovery after anesthesia is not delayed.15 Large doses (eg, 50 ␮g/kg) may result in dyskinesia, restlessness, and dysphoria, which may last up to 24 hours. The lowest effective dose of droperidol is recommended to limit these adverse side effects. Phenothiazines Chlorpromazine and promethazine have antiemetic properties that result from their ability to block dopamine receptors in the chemotactic trigger zone. Both drugs can produce hypotension, significant sedation, extrapyramidal effects, and restlessness, which can prolong recovery phase. Serotonin Antagonists Ondansetron is a drug that is a 5-HT3-receptor antagonist used in the treatment and prevention of PONV and is popular in the ambulatory surgery setting.16 As the original serotonin antagonist, ondansetron is administered in an effective dose of 4 mg intravenously and has a half-life of 3.5 hours. It is not associated with the sedative and extrapyramidal effects that are occasionally associated with the other previously mentioned antiemetic agents. The primary side effects include transient headache, diarrhea, or constipation. The cost of the drug often prohibits routine use. As the price of serotonin antagonists come down, their justification and

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usage will increase. Ondansetron should be given at the end of surgery because it has been shown to be most effective when administered at this time.17 Two other serotonin agonist antiemetics are available. Dolasetron can be given as a 100-mg tablet preoperatively, or as a 12.5-mg intravenous injection at the end of the surgical procedure. Granisetron can be given orally at a dose of 1 to 2 mg or 20 to 40 ␮g/kg, intravenously.

Antacids Sodium citrate is a nonparticulate antacid that increases gastric pH. The usual dose of 30 mL, orally, may additionally raise gastric volume and should be administered with a gastrokinetic agent such as metoclopramide. Disadvantages include an unpleasant taste and variability in duration of action. It should be restricted to high-risk patient populations such as those who are diabetic, morbidly obese, or pregnant.

Dexamethasone Dexamethasone is effective in reducing the incidence of PONV when administered either alone or in combination with additional antiemetic agents. An intravenous dose of 5 to 10 mg or 170 ␮g/kg of dexamethasone has been shown to be effective in the adult patient (150 ␮g/kg intravenously in children).18-20 Adverse side effects from a single dose of dexamethasone have not been documented.

Gastrokinetic Agents Metoclopramide is a dopamine antagonist that increases lower esophageal sphincter tone, increases gastric emptying, and may be effective in alleviating PONV. It is often used in combination with an H2 receptor blocker to further decrease the risk of pulmonary aspiration. Metoclopramide, 0.1 to 0.2 mg/kg intravenously, has a short duration of action and is often given before and at the end of surgery.

PREVENTION OF ASPIRATION PNEUMONITIS

The incidence of pulmonary aspiration of gastric contents is very low in elective ambulatory surgical patients with no specific risk factors. Routine prophylaxis for aspiration pneumonitis is not recommended for the otherwise low-risk patient. Prophylactic medications for the prevention of pulmonary aspiration of gastric contents should be used on ambulatory surgery patients that have predisposing factors such as pregnancy, hiatal hernia, morbid obesity, insulin-dependent diabetes mellitus, or inpatients undergoing emergency procedures. Histamine (H2) Receptor Antagonists Cimetidine and ranitidine antagonize the action of histamine on H2 receptors, causing a decrease in gastric volume by decreasing gastric acid secretion and increasing gastric pH. Cimetidine is more cost effective but can cause confusion, interfere with drug metabolism, and cause hypotension if administered quickly. Cimetidine’s effect on gastric pH begins in 1 to 1.5 hours and lasts for 3 hours. Ranitidine is 4 to 6 times more potent than cimetidine and exhibits fewer side effects. Newer agents, famotidine (20 mg intravenous, adult) and nizatidine, are similar to ranitidine but possess a longer duration of effect.

INTRAVENOUS ANESTHETIC DRUGS

Rapid-acting, intravenous anesthetic agents possessing minimal adverse side effects (eg, prolonged sedative action or PONV) are used for the induction of anesthesia for ambulatory surgery (Table 2). Barbiturates The prototype barbiturate agent is thiopental (3 to 6 mg/kg intravenously). It has a rapid onset and short duration of action. This drug has the ability to impair fine motor skills for several hours. Methohexital may have a shorter awakening time, but it is often associated with loss of fine motor skills up to 6 hours after surgery. It is often associated with a higher incidence of pain on injection, involuntary muscle movements, and hiccoughing.21 Table 2. Intravenous Anesthetic Agents Drug

Recovery Profile

Thiopental Methohexital Etomidate Ketamine Propofol

Immediate Rapid Immediate Immediate Rapid

Side Effects

Drowsiness Hiccoughing Myoclonus, PONV Emergence reactions Pain on injection

Abbreviation: PONV, postoperative nausea and vomiting.

ANESTHETIC AGENTS IN AMBULATORY PRACTICE Etomidate Recovery tends to be faster with etomidate than thiopental and methohexital when used at an induction dose of 0.2 to 0.3 mg/kg intravenously. Side effects include pain on injection, PONV, myoclonic movements, and transient adrenal steroid suppression. It is best used in patients in whom hemodynamic stability is compromised; thus, the indications for its use in the ambulatory setting are limited. Ketamine Ketamine is often not favored in ambulatory surgery because of its prominent psychomimetic effects and the incidence of PONV. Premedication with midazolam (0.05 to 0.1 mg/kg intravenously) decreases the psychologic-induced reactions. Oftentimes, an antisialagogue such as glycopyrrolate (5 ␮g/kg intravenously) is administered to reduce increased oral secretions caused by ketamine. Propofol Propofol has a metabolic clearance 10 times faster than any other anesthetic induction agent, which has a profound effect on postoperative recovery.22 Even though the cost of propofol is higher than other agents, its use may contribute to significant savings. Faster recovery can yield substantial savings in nursing hours. Propofol is associated with less PONV than the other induction agents, which results in a decreased use of antiemetic agents.23 For propofol to be useful as an antiemetic, a continuous infusion is needed because of its rapid clearance. Pain on intravenous injection may occur, but it is often reduced if lidocaine (40 mg intravenously) is given before the propofol injection.

small doses of a combination of specific drugs, patients can recover more quickly with fewer side effects, less discomfort, and be ready for rapid discharge.24,25 Inhalation Anesthetics The 3 most popular gas anesthetics are isoflurane, desflurane, and sevoflurane, which are frequently supplemented with nitrous oxide.26,27 Older drugs, such as halothane, are rapidly becoming obsolete because the newer agents offer a minimum of toxicity and rapid induction and emergence (Table 3). The potent inhalation anesthetics provide the foundation for the maintenance of unconsciousness and memory loss during the surgery. Administration via the inhalation route allows for titration to meet surgical needs and rapid recovery. Recovery from desflurane and sevoflurane is more rapid than isoflurane; however, all 3 allow for a reestablishment of consciousness within approximately 15 minutes after their cessation.28 Serious morbidity is rare, and because these Table 3. Drugs Commonly Used for Anesthesia Maintenance Drug

Isoflurane Desflurane Sevoflurane

Fentanyl Alfentanil Sufentanil Remifentanil

ANESTHESIA MAINTENANCE

When a patient is under anesthesia, what is achieved is a drug-induced anesthesia or loss of consciousness, amnesia, and analgesia that refers to loss of pain and muscle relaxation. In years past, this effect was produced with high doses of potent inhalation anesthetics usually given alone. Although effective, recovery could take up to 24 hours. In modern practice, this goal is attained with small amounts of a combination of inhalation anesthetics, intravenous opioids, and the judicious use of shorter-acting muscle relaxants. By using

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Ketorolac Succinylcholine Mivacurium Rocuronium Atracurium Cisatracurium

Vecuronium

Comments

Most widely used inhalation anesthetic worldwide Most rapid acting and fastest recovery of all inhalation anesthetics Newest inhalation anesthetic; especially popular in pediatrics for inhalation inductions Most common anesthetic opioid Short-acting opioid; use is diminishing because of cost Most potent opioid; rarely used for ambulatory surgery Administered by infusion; effects dissipate 5 to 10 minutes after discontinuation of the infusion Nonsteroidal inflammatory for postoperative analgesia Ultrashort-acting depolarizing muscle relaxant used for intubation Short-acting muscle relaxant; associated with histamine release Intermediate-acting muscle relaxant Intermediate-acting muscle relaxant; associated with histamine release Isomer of atracurium; intermediateacting muscle relaxant, no histamine release Intermediate-acting muscle relaxant

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drugs are given under direct minute-by-minute observation, adjustments can be made as appropriate. Intravenous Opioids Surgery requires a high intensity of analgesia to render the patient pain free. This is accomplished with the use of high-potency, rapid-acting, shortduration opioids such as fentanyl, sufentanil, alfentanil, and remifentanil.29,30 A comparison of some of their pharmacologic properties is given in Table 3. The opioids allow lower concentrations of the inhalation anesthetics to be administered, thus allowing a faster recovery.31 The ideal opioid technique is to titrate the dose so that some residual analgesia without respiratory depression is maintained into the recovery period, and antagonists such as naloxone are not required. Unfortunately, the opioids increase the incidence of nausea and vomiting, which may be problematic during the recovery period.32,33 Fentanyl is the standard opioid used during anesthesia. Although the duration of all drugs is dose dependant, the amounts given during ambulatory procedures generally last from 45 to 90 minutes. Alfentanil is similar to fentanyl and offers no appreciable advantages. This fact, along with higher cost, accounts for its minimal use. Sufentanil, the most potent opioid marketed, is generally reserved for specialized longer procedures that are not commonly performed in an ambulatory setting. Remifentanil, the newest anesthetic opioid, is given by continuous infusion because of rapid metabolism.34 The drug’s effects dissipate within 10 minutes after discontinuation.35 When remifentanil is used, the patient will have minimal residual analgesia and may require supplementation with additional pain medication in the PACU.36 The primary concern during postanesthesia recovery with regard to opiates is respiratory depression. Administration of any drug with depressant properties during anesthesia recovery must be undertaken with caution because additive effects may be anticipated. As previously noted, the NSAID, ketorolac, provides excellent postoperative analgesia without respiratory depression and is a useful alternative to the use of opioids.37 Intravenous Muscle Relaxants A large number of muscle relaxants are available; however, only the shorter-acting agents are used in ambulatory anesthesia. The commonly

NAGELHOUT AND BOYTIM used drugs are listed in Table 3. Rapacuronium, a newly released short-acting relaxant, has recently been withdrawn voluntarily from the market because of many cases of severe bronchospasm and several unexplained deaths.38 The muscle relaxants have no central nervous system anesthetic effects, but they assist the surgeon in provision of a proper surgical environment when an operation requires entering major body cavities. A serious principal complication after anesthesia is residual muscle weakness after the administration of muscle relaxants. This may lead to respiratory difficulty, as well as an increased risk of aspiration. The use of the shorter-acting neuromuscular blockers helps minimize, but does not completely remove, this risk. Despite the use of nerve stimulators to gauge dosing and reversal agents to antagonize their effects, proper muscle recovery is one of the most important nursing observations after surgery. Clinical signs to look for that indicate return of adequate muscle strength include the following: normal respiratory rate and a tidal volume of at least 5 mL/kg, sustained headlift for 5 seconds or leglift in young children, sustained strong hand grip and jaw clench on a tongue blade or plastic airway, ability to open eyes widely, and ability to stick out the tongue. Table 4. Common Adverse Outcomes in the Postanesthesia Period Excessive pain Nausea, vomiting Shivering/hypothermia Drowsiness/sleepiness Cardiovascular complications Hypertension Hypotension Dysrhythmias Myocardial infarction Respiratory complications Laryngospasm/stridor Airway obstruction Hypoventilation Oxyhemoglobin desaturation Pulmonary aspiration of gastric contents Sore throat Excessive bleeding Dizziness Headache Data from Marley RA: Outpatient anesthesia, in Nagelhout JJ, Zaglaniczny KL (eds): Nurse Anesthesia (ed 2). Philadelphia, PA, Saunders, 2001, pp 848-876; and Litwack K: Postanesthesia recovery, in Nagelhout JJ, Zaglaniczny KL (eds): Nurse Anesthesia (ed 2). Philadelphia, PA, Saunders, 2001, pp 1177-1190.

ANESTHETIC AGENTS IN AMBULATORY PRACTICE The primary route of metabolism and elimination among the relaxants varies; however, certain patient subtypes should be observed for possible prolonged effects. These subtypes include the very young or elderly, patients with renal or hepatic disease and/or multiorgan failure, and patients undergoing more extensive surgeries.

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when necessary.39 The PACU staff is the frontline provider for detection of and intervention in all possible adverse consequences after surgery and anesthesia. The most common adverse outcomes that occur in the postanesthesia time frame, which are familiar to any practicing perianesthesia nurse, are listed in Table 4.40,41

POSTOPERATIVE CONSIDERATIONS

SUMMARY

Initial recovery from an anesthetic occurs in the operating room. Patient awakening is accomplished by stopping anesthetic gas administration and allowing time for the gas to be eliminated via breathing. The opioids are titrated, therefore they are generally wearing off by the end of the procedure, although opioid antagonists such as naloxone are occasionally necessary to ensure adequate recovery. The muscle relaxants are usually reversed with drugs such as neostigmine or edrophonium. Establishing early consciousness and recovering airway reflexes, breathing, and stabilizing vital signs are the responsibility of the anesthesia provider. On arrival to the PACU, nursing care is standard regardless of the specific anesthetic drug administered. This includes observation of basic vital functions and pain control and interventions

Modern anesthesia practice has evolved as better drugs have been introduced, technological advances in monitoring have become commonplace, and a more thorough understanding of disease management has been developed. Surgery and anesthesia are performed for procedures in the ambulatory setting that would have been unthinkable a few years ago. Diagnostic and therapeutic procedures will continue to move to an outpatient setting as systems are developed to provide optimum surgical, anesthetic, and nursing care. Similar advances in safety and patient satisfaction are expected in the years to come as physicians, nurses, and other health care professionals contribute their unique expertise and work together as a team to improve patient care.

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and vomiting after dexamethasone versus droperidol following outpatient laparoscopy with a propofol-based general anesthetic. Acta Anaesthesiol Scand 42:637-642, 1998 19. Splinter WM, Roberts DJ: Dexamethasone decreases vomiting by children after tonsillectomy. Anesth Analg 83:913916, 1996 20. Liu K, Hsu CC, Chia YY: Effect of dexamethasone on postoperative emesis and pain. Br J Anaesth 80:85-86, 1998 21. Sun R, Skrivanek G, Stool L, et al: Use of methohexital for induction of outpatient anesthesia. Anesth Analg 84:S29, 1997 (abstr) 22. Smith I, White PF, Nathanson M, et al: Propofol. An update on its clinical use. Anesthesiology 81:1005-1043, 1994 23. Korttila K: Recovery from propofol: Does it really make a difference? J Clin Anesth 5:443-446, 1993 24. Eger EI, White PF, Bogetz MS: Clinical and economic factors important to anaesthetic choice for day-case surgery. Pharmacoeconomics 17:245-262, 2000 25. Brennan LJ: Modern day-case anaesthesia for children. Br J Anaesth 83:91-103, 1999 26. Tarazi EM, Philip BK: A comparison of recovery after sevoflurane or desflurane in ambulatory anesthesia. J Clin Anesth 10:272-277, 1998 27. Mahmoud NA, Rose DJ, Laurence AS: Desflurane or sevoflurane for gynaecological day-case anaesthesia with spontaneous respiration? Anaesthesia 56:171-174, 2001 28. Behne M, Wilke HJ, Lischke V: Recovery and pharmacokinetic parameters of desflurane, sevoflurane, and isoflurane in patients undergoing urologic procedures. J Clin Anesth 11:460-465, 1999 29. Minto CF, Power I: New opioid analgesics: An update. Int Anesthesiol Clin 35: 49-65, 1997 30. Davis PJ, Finkel JC, Orr RJ, et al: A randomized, double-blinded study of remifentanil versus fentanyl for tonsil-

NAGELHOUT AND BOYTIM lectomy and adenoidectomy surgery in pediatric ambulatory surgical patients. Anesth Analg 90:863-871, 2000 31. Song D, White PF: Remifentanil as an adjuvant during desflurane anesthesia facilitates early recovery after ambulatory surgery. J Clin Anesth 11:364-367, 1999 32. Langevin S, Lessard MR, Trepanier CA, et al: Alfentanil causes less postoperative nausea and vomiting than equipotent doses of fentanyl or sufentanil in outpatients. Anesthesiology 91:1666-1673, 1999 33. Anderson BJ, Ralph CJ, Stewart AW, et al: The doseeffect relationship for morphine and vomiting after day-stay tonsillectomy in children. Anaesth Intensive Care 28:155-160, 2000 34. Roscow CE: An overview of remifentanil. Anesth Analg 89:S1-S3, 1999 (suppl 4) 35. Mackey JJ, Parker SD, Nass CM, et al: Effectiveness of remifentanil versus traditional fentanyl-based anesthetic in high-risk outpatient surgery. J Clin Anesth 12:427-432, 2000 36. Larsen B, Seitz A, Larsen R: Recovery of cognitive function after remifentanil-propofol anesthesia: A comparison with desflurane and sevoflurane anesthesia. Anesth Analg 90: 168-174, 2000 37. Tarkkila P, Saarnivaara L: Ketoprofen, diclofenac or ketorolac for pain after tonsillectomy in adults? Br J Anaesth 82:56-60, 1999 38. US Food and Drug Administration: Rapacuronium, voluntary market withdrawal. FDA Medwatch March 27, 2001 39. Feeley TW: Postanesthesia care of the outpatient. Int Anesthesiol Clin 32:127-144, 1994 40. Marshall SI, Chung F: Discharge criteria and complications after ambulatory surgery. Anesth Analg 88:508-517, 1999 41. Chung F, Mezei G: Adverse outcomes in ambulatory anesthesia. Can J Anaesth 46:R18-R34, 1999 (part 2)