Sedation-Analgesia During Local and Regional Anesthesia

During local and regional anesthesia, it is a common practice to administer both sedative and analgesic medications to enhance patient comfort during the operation. Use of local anesthetic infiltration and peripheral nerve blocks (PNBs) techniques in combination with intravenous (IV) sedative-hypnotic and analgesic drugs is commonly referred to as monitored anesthesia care (MAC).

Author: Paul F. White, PhD, MD, FANZCA

Affiliation: Professor and McDermott Chair of Anesthesiology, Department of Anesthesiology & Pain Management, UT Southwestern Medical Center, Dallas, TX

For: Regional Anesthesia: Principles & Practice. Admir Hadzic, MD (Editor)

During local and regional anesthesia, it is a common practice to administer both sedative and analgesic medications to enhance patient comfort during the operation. Use of local anesthetic infiltration and peripheral nerve blocks (PNBs) techniques in combination with intravenous (IV) sedative-hypnotic and analgesic drugs is commonly referred to as monitored anesthesia care (MAC). In many centers around the world, over 50% of all ambulatory (day-surgery) procedures are performed utilizing these techniques (Table 1).1 When patients undergo surgical procedures under local anesthesia with IV sedation-analgesia in the operating room (OR), the old terminology used to describe the care of these patients was “conscious sedation.” As the term implies, conscious sedation was a minimally-depressed level of consciousness that retained the patient’s ability to maintain an airway independently and continuously, and to respond appropriately to physical stimulation and verbal commands. The American Society of Anesthesiologists (ASA) avoids this term in their Practice Guidelines for Sedation and Analgesia by Non-anesthesiologists2 because it is imprecise and instead refers to this practice of anesthesia as MAC.

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Figure 1: The dose-dependent spectrum of central nervous system depression produced by sedative-hypnotic drugs. MAC=monitored anesthesia care; LOC=loss of consciousness and LPR=loss of protective reflexes1

According to the ASA,2 MAC is the term used when an anesthesiologist monitors a patient receiving local anesthesia alone or administers anesthetic drugs to patients undergoing diagnostic or therapeutic procedures with or without local anesthesia. The ASA defines MAC “as instances in which an anesthesiologist has been called upon to provide specific anesthesia services to a particular patient undergoing a planned procedure in connection with which a patient receives local anesthesia or, in some cases, no anesthesia at all. In such a case, the anesthesiologist is providing specific services to the patient, is in control of his or her vital signs, and is available to administer anesthetics or provide other medical care as appropriate.” The standard of care for patients receiving MAC should be the same as for patients undergoing general anesthesia or central neuroaxis blockade, and should include a complete preoperative assessment, intraoperative monitoring, and postoperative in the recovery room prior to discharge.

Vigilant monitoring is required because patients may rapidly progress from a “light” level of sedation to “deep” sedation and ultimately, unconsciousness (Fig. 1).1 As a result, patients may be at risk for airway obstruction, oxygen desaturation, and even aspiration.3 Therefore, supplemental oxygen is commonly administered with end-expiratory CO2 monitoring for assessing ventilatory rate, presence of airway obstruction and apnea.4 Although cerebral monitoring (e.g., EEG bispectral index) has been used successfully to assess the sedative effects of both midazolam5 and propofol6 during procedures performed using local anesthesia and PNBs, the confounding effects of the surgical stimulus and patient discomfort on the cerebral index can make it difficult to interpret the findings.7 In addition, background noise in the OR can effect the cerebral index at “light” levels of sedation.8 Nevertheless, some investigators have suggested that the BIS is useful for monitoring the central nervous system during surgery under local or regional anesthesia with IV sedation.9

A wide variety of pharmacologic agents are commonly administered during administration of local anesthesia or PNBs, as well as during surgical procedures under local anesthesia (or PNBs) to produce sedation, analgesia, and anxiolysis, while optimizing the surgical conditions and insuring cardiorespiratory stability and a rapid recovery of cognitive functioning without untoward side effects (Table 2).10 Systemic opioid and non-opioid analgesics are used to reduce discomfort associated with injection of local anesthetics and prolonged immobilization, as well as procedural related pain which is not amendable to local anesthesia (e.g., endoscopy).

Sedative-hypnotic drugs are also commonly used to make procedures more tolerable for patients by reducing anxiety and providing an appropriate degree of intraoperative sedation and amnesia. During longer surgical procedures, patients may become restless, bored, or uncomfortable when forced to remain immobile. Therefore, sedative-hypnotic drugs, as well as non-pharmacologic approaches (e.g., music), may prove beneficial because they allow patients to rest during the operation. Patients’ anxiety can be reduced by using benzodiazepines, as well as by good preoperative communication, keeping the patient warm and covered, and allowing the patient to listen to relaxing music during the procedure. This article will discuss the commonly used adjunctive techniques to enhance patient comfort during local and regional anesthesia.

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Many different sedative-analgesic drugs have been used for premedication (including barbiturates, benzodiazepines, opioid analgesics and alpha-2 agonists) (Table 3).10 Midazolam remains the most popular premedicant because of its predictable sedative, anxiolytic and amnestic properties unrespective of the route of administration (i.e., oral, topical, or parenteral).11-14 In addition, a wide variety of drug delivery systems such as intermittent boluses, variable-rate infusions, target-controlled infusions, as well as patient-controlled sedation-analgesia techniques have been utilized during procedures under local and regional anesthesia.15,16

Although benzodiazepines (e.g., diazepam, midazolam) were formerly the most popular sedatives for “conscious sedation,”17,18 their use has declined with the introduction of more titratable IV sedative-hypnotics (e.g., methohexital, etomidate, propofol) and analgesics (e.g., alfentanil, remifentanil).15,19 Methohexital, a shorter-acting barbiturate than thiopental, was the IV sedative-hypnotic of choice prior to the introduction of propofol. Etomidate, a popular IV induction agent for cardiovascular surgery, can be administered by continuous infusion (5-20 mcg•kg-1•min-1) and may be particularly useful for sedation of elderly patients and those with significant underlying cardiac disease due to its minimal cardiovascular depressant properties. However, when combined with opioid analgesics, etomidate is associated with an increased risk of postoperative nausea and vomiting (PONV).

Propofol, the IV sedative-hypnotic of choice at the present time, has been found to be equivalent to both midazolam and methohexital for providing adequate sedation and amnesia during superficial procedures under local anesthesia and PNBs.20-23 Importantly, compared to other available sedative-hypnotic drugs, use of propofol is associated with less residual postoperative sedation, amnesia, and nausea and vomiting, as well as ease of fast-tracking (i.e., bypassing the PACU), leading to a reduced recovery time to a “home readiness” state. Although use of the benzodiazepine antagonist, flumazenil, reduces the residual sedative-amnestic effects of midazolam, and allows the early recovery profile after midazolam sedation to compare favorably to propofol.24 However, the short duration of action of the reversal drug can lead to varying degrees of resedation in the postdischarge period.

The most popular sedative technique consists of a small dose of midazolam (1-2 mg) for premedication (or induction of sedation), and propofol (0.5-0.75 mg/kg followed by a variable-rate infusion at 25-100 µg/kg/min).20,25 Methohexital has also been used successfully during MAC by intermittent boluses (10–20 mg) or as a variable-rate infusion (20-60 µg•kg-1•min-1).19,26 Although residual sedation appears to be somewhat greater with methohexital than propofol, there were no differences in the recovery times to ambulating and discharge home when comparing infusions of methohexital (40 µg/kg/min) and propofol (50 µg/kg/min) during a MAC technique.26 In addition, there was a significantly higher incidence of pain on injection in the propofol infusion group. Therefore, methohexital remains a cost-effective alternative to propofol for sedation during MAC despite the fact it is less convenient to use because it has to be reconstituted. Careful titration of these IV anesthetics is essential to maintain the desired level of sedation while avoid ventilatory depression during surgery, and ensuring a prompt recovery of cognitive functioning after surgery.

In an effort to enhance patient comfort, both opioid and non-opioid analgesics have been used to supplement the sedative hypnotics.27-31 Although fentanyl remains the most commonly used opioid analgesic, remifentanil has become increasingly popular because its faster onset and recovery characteristics may minimize the potential for adverse drug interactions in the postoperative period. However, careful titration is necessary when remifentanil is combined with midazolam and propofol to avoid ventilatory depression and apnea.30-35 Of interest, some investigators have suggested that remifentanil fails to improve the quality of propofol sedation36 A variety of nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, ketorolac, piritramide, celecoxib) may also prove useful in preventing pain and discomfort which is refractory to local anesthetics.37-40 However, with effective local anesthesia, the addition of an NSAID provides only minimal intraoperative improvement in the local analgesic effect.27,38,41

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Opioid analgesics are routinely administered to alleviate the discomfort associated with injection of the local anesthetic solution, and to treat pain not amenable to local anesthesia.28 In addition, the concomitant use of opioid analgesics reduces the sedative-hypnotic dosage requirement and thereby minimizes residual sedation. Avramov et al29 first described the combined use of alfentanil (0.3–0.4 µg/kg/min) and propofol (25, 50, or 75 µg/kg/min) infusions for MAC. Compared to the opioid alone, concomitant use of propofol significantly reduced the alfentanil dosage requirement (30–50%) and the incidence of PONV. Comparing alfentanil (0.25 µg/kg/min) and remifentanil (0.05 µg/kg/min) infusions when administered as an adjuvant to propofol, Dilger et al30 reported that the remifentanil group required fewer “rescue” doses of local anesthetic during MAC for breast surgery.

An infusion of remifentanil, 0.05 to 0.15 µg/kg/min, can provide adequate sedation and analgesia during minor surgical procedures performed with the patient under local anesthesia when administered in combination with small doses of midazolam.31,32 Sá Rêgo et al35 compared the use of intermittent remifentanil boluses (25 µg) vs a continuous variable-rate infusion (0.025–0.15 µg/kg/min) when administered to patients receiving a MAC technique involving midazolam (2 mg) and propofol (25–50 µg/kg/min). Patient comfort was higher during the procedure when remifentanil was administered by a variable-rate infusion. However, the patients receiving the propofol-remifentanil infusion also experienced a higher incidence of desaturation (30% vs 0%) compared with those receiving small intermittent boluses of remifentanil during a propofol infusion.

In direct comparisons of remifentanil and propofol administered by continuous infusion after premedication with midazolam, there was a decreased level of intraoperative sedation and a greater degree of respiratory depression with remifentanil (versus propofol) administration.33,34 Therefore, remifentanil infusions must be carefully titrated to avoid excessive respiratory depression in the presence of midazolam and/or propofol. Using remifentanil in combination with local anesthetics obviates the disadvantage associated with the minimal residual analgesia when remifentanil is used during painful procedures. Unfortunately, even the short-acting opioid analgesic remifentanil can increase PONV and the need for routine antiemetic prophylaxis.42

Given the increased risk of ventilatory depression when opioid analgesics are combined with sedative-hypnotics, a variety of non-opioid analgesics have been evaluated during MAC. Ketorolac, a potent, parenterally-active NSAID, has been used both as an analgesic supplement to propofol sedation during local anesthesia.27,37-39 Use of ketorolac was associated with a lower incidence of pruritus, nausea, and vomiting than fentanyl. However, when used with propofol sedation, ketorolac-treated patients required higher intraoperative doses of propofol and more supplemental opioid analgesia compared with fentanyl.27,37 Piritramide, 0.05 mg/kg IV, prior to PNBs can reduce pain perception and the endocrine stress response during cataract surgery.40

Low-dose ketamine (0.25–0.75 mg/kg) combined with either midazolam or propofol has also been administered before injection of local anesthetics in outpatients undergoing a variety of surgical procedures.18,43-47 Ketamine has the advantage over opioid analgesics of producing less ventilatory depression and PONV, while providing better intraoperative analgesia than the NSAIDs, when combined with propofol as part of a MAC technique. Importantly, both midazolam and propofol are highly effectively in attenuating the dysphoric and psychomimetic side effects associated with ketamine administration.18,45,46 When used for sedation during local anesthesia, newer formulations of propofol may reduce pain on injection (e.g., propofol-MCT/LCT,48 a propofol prodrug called Aquavan)49 and the risk of hyperlipidemia (e.g., Ampofol) during prolonged sedation.50

The alpha2-agonists reduce central sympathetic outflow and have been shown to produce both anxiolysis and sedation.10 Kumar et al51 demonstrated that oral clonidine (300 µg) provided effective anxiolysis for elderly patients undergoing ophthalmic surgery under local anesthesia, and also decreased the incidence of intraoperative hypertension and tachycardia. Dexmedetomidine, a more selective and potent alpha2-agonist, significantly decreased anxiety levels and reduced the requirements for supplemental opioid analgesic medications when given before IV regional anesthesia for hand surgery.52 When comparing dexmedetomidine with midazolam for sedation, Aho et al53 described a faster recovery from sedation when dexmedetomidine was followed by reversal with the specific alpha2-antagonist atipamezole. Unfortunately, the midazolam-treated patients did not receive the reversal drug flumazenil. In the early studies, administration of dexmedetomidine during local anesthesia was associated with severe bradycardia. However, more recent studies54,55 involving lower dosages have been associated with good intraoperative hemodynamic stability and reduced patient discomfort during local anesthesia compared to midazolam and propofol.

Other non-opioid analgesics which may be useful adjuvants to local anesthesia in the future include novel compounds like gabapentin and pregabalin,56-58 as well as adenosine59 and compounds which can elevate levels of this endogenous compound. For example, pregabalin (300 mg) produced a significantly longer duration of analgesia than ibuprofen (400 mg) after oral surgery under local anesthesia.57 Although lacking any intrinsic analgesic properties, dexamethasone has been found to facilitate an earlier discharge after MAC independent of its well-known antiemetic properties.60 Perhaps one of the most intriguing new analgesic compounds in development is capsaicin (ALGRX 4975) for injection, as well as a gel formulation for intraoperative topical applications. Although capsaicin causes transient discomfort on administration, it can produce prolonged analgesia by producing localized degradation of the C-neuron endings. Topical treatment with capsaicin may offer other clinical advantages over existing analgesic drugs used to prevent postoperative pain in combination with local anesthetics (e.g., by reducing tissue swelling).61

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Several investigators have evaluated the use of patient-controlled sedation-analgesia.62-67 Although self-administration of midazolam and propofol can be an effective alternative to MAC in selected patients, careful monitoring is required to optimize surgical conditions and patient safety.62 Osborne et al65 reported that patient-controlled sedation with propofol and was preferred by the patients over a standard propofol infusion during MAC. Regardless, many patients prefer to have an expert in charge of sedative-analgesic drug administration during surgery.62 Interestingly, patient-controlled sedation requirements were similar for cataract surgery under topical and retrobulbar anesthesia.66 Use of intraoperative patient-controlled analgesia with potent opioids can produce significant ventilatory depression when patients are also receiving sedative-hypnotic drugs.62 However, a recent study suggested patient-controlled remifentanil administration in combination with midazolam sedation is “a safe and reliable” method in conjunction with local anesthesia for oral surgery.67

Subanesthetic concentrations of inhaled anesthetics (e.g., N2O, 30–50% in oxygen or sevoflurane 0.3-0.6% inspired) can also be used to supplement local and regional anesthesia.68,69 However, this technique may not offered any significant advantages over IV midazolam77 or propofol.78 The primary concerns in using inhaled anesthetics relates to the ease which the patient can drift into an unconscious state and/or develop upper airway obstruction, as well as the issue of operating room (OR) air pollution. Therefore, volatile anesthetics are rarely used and N2O is only used to supplement inadequate local anesthesia or PNBs not well-controlled by potent opioid analgesics.

Finally, non-pharmacologic therapies like music,70,71 electroanalgesia72,73 and hypothesis74 may also prove to be useful in enhancing patient comfort and in reducing the sedative and analgesic requirements during surgical procedures under local anesthesia in the future. If effective, these non-pharmacologic approaches have the potential of reducing drug-related side effects and adverse drug interactions during the perioperative period (Table 6).75

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Due to the presence of an anesthesia provider during MAC, the cost is obviously higher compared to OR nurse-administered “conscious sedation.” Although some studies have suggested that patient outcomes are comparable with conscious sedation and MAC,76 these findings have been seriously questioned because of flaws in the study design.77 Although so-called “unmonitored” local anesthesia can be used as an alternative to MAC for minor surgical procedures,78 most patients (and surgeons) prefer the presence of an anesthesia provider to insure optimal sedation and analgesia during surgery under local anesthesia.79 From a cost-benefit perspective, local anesthesia and PNBs with or without sedation offer significant advantages in addition to reduced costs compared to general and central neuroaxis anesthesia.79 Compared to general anesthesia, one study found that when MAC was used for assisted reproductive procedures the patients’ experienced improved pregnancy rates.80

In women undergoing laparoscopic tubal sterilization with a MAC technique, the anesthetic drug costs were found to be significantly reduced compared to general anesthesia (US $21 vs $46, respectively).81 The MAC technique was also associated with less time in the OR, a higher degree of alertness on the evening of the day of surgery, as well as decreased postoperative pain (33% vs 80%) and sore throats (3% vs 70%), contributing to a significant reduction in the overall perioperative costs. Patel et al82 reported that the use of MAC sedation resulted in a 6-7 min decrease in the OR exit time compared to general anesthesia with desflurane, contributing to enhanced turnover of cases. Similarly, comparative studies involving general endotracheal anesthesia, central neuroaxial blockade, and MAC techniques for inguinal herniorrhaphy (Table 4)83 and anorectal (Table 5)84 procedures have consistently found improved recovery profiles, decreased side effects, greater patient satisfaction, and reduced anesthetic costs with MAC.83-85 More recent studies86-88 involving outpatients undergoing orthopedic procedures have also found superior recovery profiles with PNB compared to general anesthesia, contributing to a more favorable cost-benefit profile. The application of topical local anesthetic techniques have also offered significant advantages for outpatients undergoing ophthalmologic (e.g., cataract)66 and plastic (e.g., facial laser resurfacing) surgery procedures.89 The impact of the anesthetic technique on cost and recovery time is an increasingly important consideration in today’s clinical practice environment because of the heavy emphasis on “fast-tracking” recovery processes.

In summary, the use of local (infiltration) or regional anesthesia with IV sedation-analgesia is the anesthetic technique of choice for providing cost-effective anesthetic care for patients undergoing superficial (non-cavitary) surgical procedures (Table 8).1,90 The most important factors in achieving the desired clinical outcome and highest patient satisfaction are achieving effective local analgesia and carefully titrating intravenous sedative and analgesic medications to avoid ventilatory depression and to insure a prompt recovery of cognitive functioning following surgery. The recommended loading and maintenance doses of the most commonly used IV selective-analgesic drugs are summarized in table 7.90

In conclusion, use of sedation-analgesia techniques in combination with local anesthesia and regional anesthesia achieve the best outcome for the patient at the lowest cost to the health care system. When properly applied, the use of MAC techniques can provide excellent operating conditions while optimizing patient comfort and safety during the operation, and insuring a prompt resumption of normal activities of daily living after surgery.

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• Sa Rego MM, Watcha MF, White PF: The changing role of monitored anesthesia care in the ambulatory setting. Anesth Analg 85:1020, 1997.
• American Society of Anesthesiologists: Position on Monitored Anesthesia Care. Directory of Members. Park Ridge, Illinois, American Society of Anesthesiologists, 1997, p 413.
• Smith I, White PF: Use of intravenous adjuvants during local and regional anesthesia. Curr Rev Clin Anesth 12: 145-52, 1992.
• Soto RG, Fu ES, Vila H Jr, Miguel RV: Capnography accurately detects apnea during monitored anesthesia care. Anesth Analg 99: 379-82, 2004.
• Liu J, Singh H, White PF: EEG bispectral analysis predicts the depth of midazolam-induced sedation. Anesthesiology 1996; 84: 64-9.
• Liu J, Singh H, White PF: Electroencephalographic bispectral index correlates with intraoperative recall and depth of propofol-induced sedation. Anesth Analg 1997; 84: 185-9.
• Sakai T, Matsuki A, White PF, Giesecke AH: Use of an EEG-bispectral closed-loop system for administering propofol. Acta Anaesthesiol Scand 44: 1007-10, 2000.
• Kim DW, Kil HY, White PF: The effect of noise on the bispectral index during propofol sedation. Anesth Analg 93: 1170-3, 2001.
• Buyukkocak U, Ozcan S, Daphan C, et al: A comparison of four intravenous sedation techniques and bispectral index monitoring in sinonasal surgery. Anaesth Intensive Care 31: 164-71, 2003.
• White PF: Perioperative Drug Manual, Elsevier/Saunders Publishers, Philadelphia, 2005
• van Vlymen JJ, Sa Rego MM, White PF: Benzodiazepine premedication: Can it improve outcome in patients undergoing breast biopsy procedures? Anesthesiology 90: 740-7, 1999
• al-Rakaf H, Bello LL, Turkustani A, Adenubi JO: Intra-nasal midazolam in conscious sedation of young paediatric dental patients. Int J Paediatr Dent 11: 33-40, 2001.
• Cote CJ, Cohen IT, Suresh S, et al: A comparison of three doses of a commercially prepared oral midazolam syrup in children. Anesth Analg 94: 37-43, 2002.
• Habib NE, Mandour NM, Balmer HG. Effect of midazolam on anxiety level and pain perception in cataract surgery with topical anesthesia. J Cataract Refract Surg 30: 437-43, 2004.
• White PF: Clinical uses of intravenous anesthetic and analgesic infusions. Anesth Analg 68: 161-71, 1989.
• Newson C, Joshi GP, Victory R et al: Comparison of propofol administration techniques for sedation during monitored anesthesia care. Anesth Analg 81:486-91, 1995.
• Hegarty JE, Dundee JW: Sequelae after the intravenous injection of three benzodiapepines – diazepam, lorazepam, and flunitrazepam. Br Med J 2: 1384-5, 1977.
• White PF, Vasconez LO, Mathes SA, et al: Comparison of midazolam and diazepam for sedation during plastic surgery. J Plast Reconstr Surg 81: 703-12, 1988.
• Urquhart ML, White PF: Comparison of sedative infusions during regional anesthesia – methohexital, etomidate, and midazolam. Anesth Analg 68: 249-54, 1989.
• White PF, Negus JB: Sedative infusions during local and regional anesthesia: A comparison of midazolam and propofol. J Clin Anesth 3:32, 1991.
• Pratila MG, Fischer ME, Alagesan R et al: Propofol vs midazolam for monitored sedation: A comparison of intraoperative and recovery parameters. J Clin Anesth 5:268, 1993.
• Smith I, Monk TG, White PF, Ding Y: Propofol infusion during regional anesthesia: sedative, amnestic, and anxiolytic properties. Anesth Analg 79: 313-9, 1994.
• Ferrari LR, Donlon JV: A comparison of propofol, midazolam, and methohexital for sedation during retrobulbar and peribulbar block. J Clin Anesth 4: 93-6, 1992.
• Ghouri AF, Ramirez Ruiz MA, White PF: Effect of flumazenil on recovery after midazolam and propofol sedation. Anesthesiology 81: 333-9, 1994.
• Taylor E, Ghouri AF, White PF: Midazolam in combination with propofol for sedation during local anesthesia. J Clin Anesth 4:213, 1992.
• Sá Rêgo MM, Inagaki Y, White PF: The cost-effectiveness of methohexital versus propofol for sedation during monitored anesthesia care. Anesth Analg 88: 723-8, 1999.
• Ramirez-Ruiz M, Smith I, White PF: Use of analgesics during propofol sedation: a comparison of ketorolac, dezocine, and fentanyl. J Clin Anesth; 7: 481-5, 1995.
• Gesztesi Z, Sa Rego MM, White PF: The comparative effectiveness of fentanyl and its newer analogs during extracorporeal shock wave lithotripsy under monitored anesthesia care. Anesth Analg 90: 567-70, 2000.
• Avramov MN, White PF: Use of alfentanil and propofol for outpatient monitored anesthesia care. Determining the optimal dosing regimen. Anesth Anlag 85: 566-72, 1997.
• Dilger JA, Sprung J, Maurer W, Tetzlaff J: Remifentanil provides better analgesia than alfentanil during breast biopsy surgery under monitored anesthesia care. Can J Anaesth 51: 20-4, 2004.
• Avramov MN, Smith I, White PF: Interactions between midazolam and remifentanil during monitored anesthesia care. Anesthesiology 85: 1283-9, 1996.
• Gold MI, Watkins WD, Sung YF, et al. Remifentanil versus remifentanil/midazolam for ambulatory surgery during monitored anesthesia care. Anesthesiology 87: 51-7, 1997.
• Smith I, Avramov MN, White PF: A comparison of propofol and remifentanil during monitored anesthesia care. J Clin Anesth 9: 148-54, 1997.
• Krenn H, Deusch E, Jellinek H, et al: Remifentanil or propofol for sedation during carotid endarterectomy under cervical plexus block. Br J Anaesth 89: 637-40, 2002.
• Sa Rego MM, Inagaki Y, White PF: Remifentanil administration during monitored anesthesia care: are intermittent boluses an effective alternative to a continuous infusion? Anesth Analg 88: 518-22, 1999.
• Moerman AT, Struys MM, Vereecke HE, et al: Remifentanil used to supplement propofol does not improve quality of sedation during spontaneous respiration. J Clin Anesth 16: 237-43, 2004.
• Bosek V, Smith DB, Cox C: Ketorolac or fentanyl to supplement local anesthesia? J Clin Anesth 4: 480-3, 1992.
• Coloma M, White PF. Huber PJ, et al: The effect of ketorolac on recovery after anorectal surgery: intravenous versus local administration. Anesth Analg 90: 1107-10, 2000.
• Place RJ, Coloma M, White PF, et al: Ketorolac improves recovery after outpatient anorectal surgery. Dis Colon Rectum 43: 804-8, 2000.
• Reinhardt S, Burkhardt U, Nestler A, Wiedemann R: Use of piritramide for analgesia and sedation during peribulbar nerve block for cataract surgery. Ophthalmologica 216: 256-60, 2002.
• Clerc S, Vuilleumier H, Frascarolo P, et al: Is the effect of inguinal field block with 0.5% bupivacaine on postoperative pain after hernia repair enhanced by addition of ketorolac or S(+) ketamine? Clin J Pain 21: 101-5, 2005
• Burmeister MA, Standl TG, Wintruff M, et al: Dolasetron prophylaxis reduces nausea and postanesthesia recovery time after remifentanil infusion during monitored anaesthesia care for extracorporeal shock wave lithotripsy. Br J Anaesth 90: 194-8, 2003.
• White PF: Use of ketamine for sedation and analgesia during injection of local anesthetics. Ann Plast Surg 15: 53-6, 1985.
• Blakeley KR, Klein KW, White PF, et al: A total intravenous anesthetic technique for outpatient facial laser resurfacing. Anesth Analg 1998; 87: 827-9.
• Monk TG, Rater JM, White PF: Comparison of alfentanil and ketamine infusions in combination with midazolam for outpatient lithotripsy. Anesthesiology 74:1023-8, 1991.
• Badrinath S, Avramov MN, Shadrick M, et al: The use of a ketamine-propofol combination during monitored anesthesia care. Anesth Analg 90: 858-62, 2000.
• Mortero RF, Clark LD, Tolan MM, et al: The effects of small-dose ketamine on propofol sedation: respiration, postoperative mood, perception, cognition, and pain. Anesth Analg 92: 1465-9, 2001.
• Adam S, van Bommel J, Pelka M, et al: Propofol-induced injection pain: comparison of a modified propofol emulsion to standard propofol with premixed lidocaine. Anesth Analg 99: 1076-9, 2004.
• Fechner J, Ihmsen H, Hatterscheid D, et al: Comparative pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 and propofol emulsion. Anesthesiology 101: 626-39, 2004.
• Song D, Hamza MA, White PF, et al: Comparison of a lower-lipid propofol emulsion with standard emulsion for sedation during monitored anesthesia care. Anesthesiology 100: 1072-5, 2004.
• Kumar A, Bose S, Bhattacharya A, et al: Oral clonidine premedication for elderly patients undergoing intraocular surgery. Acta Anaesthesiol Scand 36: 159-64, 1992.
• Jaakola ML: Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery. J Clin Anesth 6: 204-11, 1994.
• Aho MS, Erkola O, Kallio A, et al: Comparison of dexmedetomidine and midazolam sedation and antagonism of dexmedetomidine with atipamezole. J Clin Anesth 5: 194-203, 1993.
• Arain SR, Ebert TJ: The efficacy, side effects, and recovery characteristics of dexmedetomidine versus propofol when used for intraoperative sedation. Anesth Analg 95: 461-6, 2002.

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