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© 1999 International Anesthesia Research Society
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Abstract |
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We designed this study to test the hypothesis that methohexital is a cost-effective alternative to propofol for sedation during local anesthesia. Sixty consenting women undergoing breast biopsy procedures under local anesthesia were randomly assigned to receive an infusion of either propofol (50 µg · kg-1 · min-1) or methohexital (40 µg · kg-1 · min-1). The sedative infusion rate was titrated to maintain an observer’s assessment of alertness/sedation (OAA/S) score of 3 (with 1 = awake/alert to 5 = asleep). Fentanyl 25 µg IV was administered as a "rescue" analgesic during the operation. We assessed the level of sedation (OAA/S score), vital signs, time to achieve an OAA/S score of 3 at the onset and a score of 1 after discontinuing the infusion, discharge times, perioperative side effects, and patient satisfaction. The direct cost of methohexital was lower than that of propofol, based on the milligram dosage infused during the operation. The sedative onset (to achieve an OAA/S score of 3) and the recovery (to return to an OAA/S score of 1) times, as well as discharge times, did not differ between the two groups. Patients receiving methohexital had a significantly lower incidence of pain on initial injection compared with those receiving propofol (10% vs 23%). Because the use of methohexital (29.4 ± 2.7 µg · kg-1 · min-1) for sedation during breast biopsy procedures has a similar efficacy and recovery profile to that of propofol (36.8 ± 15.9 µg · kg-1 · min-1) and is less costly based on the amount infused, it seems to be a cost-effective alternative to propofol for sedation during local anesthesia. However, when the cost of the drug infused and drug wasted was calculated, there was no difference in the overall drug cost.
Implications: When administered to maintain a stable level of sedation during local anesthesia, methohexital is an acceptable alternative to propofol. However, the overall drug costs were similar with the two drugs.
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Introduction |
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IV sedative and analgesic medications are useful adjuvants during local anesthesia because the operating room is an anxiety-provoking environment, positioning for surgery can be uncomfortable, injection of local anesthetic solutions is often painful, and spontaneous movements by an inadequately (or excessively) sedated patient can interfere with the operation (1).
Midazolam, a water-soluble benzodiazepine, has been the most widely used IV adjuvant during monitored anesthesia care (MAC) (1). However, propofol, a rapid and short-acting IV sedative-hypnotic, has become an increasingly popular alternative to midazolam for sedation during MAC because of its more favorable early recovery profile (2,3). Methohexital is also a rapid and short-acting IV sedative-hypnotic that has been widely used for both anesthesia and sedation in the ambulatory setting (4–7). Small-dose infusions of both propofol and methohexital can provide titratable intraoperative sedation, with a prompt recovery from the central nervous system (CNS) depressant effects (2,5). Because the intermittent bolus administration of sedative drugs during procedures performed under local anesthesia can produce varying levels of sedation and significant respiratory depression (8), continuous IV infusions of sedative and analgesic drugs have become increasingly popular (2,3,9,10).
The cost-efficacy of methohexital and propofol has not been directly compared with respect to intraoperative sedation, recovery profiles, and pharmacoeconomics when administered as part of a MAC technique. The purpose of this study was to compare the direct (drug) and indirect (recovery profiles) costs of using methohexital and propofol infusions to produce a stable level of intraoperative sedation during local anesthesia as part of a MAC technique.
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Methods |
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After institutional review board approval and written, informed consent, 60 women scheduled to undergo breast biopsy procedures under local anesthesia participated in this clinical investigation. Patients were randomly assigned to receive either a propofol or methohexital infusion for sedation during the operation, according to a single-blinded protocol design. Exclusion criteria included age <18 yr; a positive pregnancy test, a history of allergic reaction to any of the study medications; a history of neurological impairment or inability to understand the psychological assessment tools; clinically significant cardiovascular, pulmonary, renal, or hepatic disease; morbid obesity (>50% above ideal body weight); or a history of porphyria.
Preoperatively, standardized psychological tests were performed by the patient. We used 100-mm visual analog scales (VAS) to determine the pretreatment level of sedation (0 = wide awake to 100 = asleep) and anxiety (0 = calm to 100 = extremely anxious). A digit symbol substitution test (DSST) was used to assess the baseline level of cognitive function. The sedation level was also assessed by the investigator (MMS) using the observer’s assessment of alertness/sedation (OAA/S) scale, with 1 = wide-awake and alert to 5 = asleep and/or unarousable. After completing the preoperative VAS, DSST, and OAA/S assessments, patients were taken to the operating room, where baseline measurements of hemodynamic (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure, and heart rate [HR]) and respiratory (oxygen saturation [SpO2], respiratory rate [RR], and end-expiratory carbon dioxide [EECO2]) variables were obtained. The EECO2 values were obtained through a CO2 sampling nasal cannula to determine the RR and to estimate PETCO2 (11). An IV line was inserted into the dorsum of the patient’s hand for infusion of the study drugs.
All patients received midazolam 2 mg IV for preanesthetic medication. Supplemental oxygen 4 L/min was administered via nasal prongs with a CO2 sampling port. The study drug solutions were prepared using standard 200-mg ampules of propofol or 500-mg vials of methohexital. The methohexital was diluted with 50 mL of the patient’s IV fluid. According to the random treatment group assignment, an infusion of either methohexital (40 µg · kg-1 · min-1) or propofol (50 µg · kg-1 · min-1) was initiated immediately after obtaining the baseline vital signs. No lidocaine was administered through the IV catheter before initiating the study drug infusion. The initial study drug infusion rate was continued until patients achieved an OAA/S level of 3 (i.e., resting comfortably with their eyes closed but responsive to voice commands). The infusion rate was later varied to maintain an OAA/S level of 3. Fentanyl 25 µg IV was administered 3–5 min before injection of the local anesthetic solution. Moderate to severe pain during the procedure was treated with supplemental injections of the local anesthetic solution, and mild pain was treated by administering supplemental fentanyl 25 µg IV as needed.
Vital signs and OAA/S scores were recorded at 5-min intervals throughout the maintenance period. The sedative infusion was discontinued when the surgical drapes were removed. The total dosages of the sedative and analgesic medications administered during the operation were recorded. The time required for the patients to return to an OAA/S score of 1 after discontinuing the sedative infusion was recorded. The patients were transferred directly to the phase II recovery area in the day surgery unit (DSU). The OAA/S assessment, as well as the VAS and DSST, were repeated 15, 30, and 60 min after discontinuing the sedative infusion. Times to ambulation and achieving discharge criteria (home-readiness), as well as actual discharge times, were recorded. Home-readiness was defined as the time at which the patient was able to stand up and walk unaided without experiencing symptoms of drowsiness, dizziness, orthostatic hypotension, nausea, vomiting, or moderate-severe pain. These assessments during the recovery period were performed by the blinded observer (YI).
Perioperative side effects (e.g., pain on injection, desaturation [SpO2 <90%], excessive sedation [OAA/S >4], flushing, hiccoughing, involuntary muscle movement, nausea and vomiting) were also noted. Pain on injection of the study drug was treated with 2 mL of lidocaine 1% IV. A global assessment of the quality of sedation and recovery was performed by both the patient and the blinded observer at the time of discharge, using a scale from 1 = poor to 5 = excellent. Before discharge, all patients were given a nonopioid analgesic (e.g., acetaminophen, ibuprofen) and were encouraged to take a repeat dose every 4–6 h to provide analgesia after discharge.
The drug cost calculation was based on the milligrams of study drug infused and reflects the actual amount administered to each individual patient. The total drug cost was based on the amount actually infused plus the amount of drug wasted for each individual patient. In the methohexital group, the cost based on amount used plus wastage was the same for each patient because a new vial of methohexital (500 mg) had to be opened for each patient. The cost calculations were based on the cost per vial of propofol 200 mg ($12.56) and methohexital 500 mg ($16.00) at the University of Texas Southwestern Medical Center, Dallas, TX.
A power analysis suggested that a sample size of 30 patients per group should be adequate to detect a 30% reduction in the time for the patients to meet the criteria for discharge home (home-readiness) with a power of 0.9 (
= 0.05). Data were analyzed by using a two-sample t-test and the 
2 test. Temporal changes in the VAS and DSST recovery tests, as well as the vital signs, were evaluated using repeated-measures analysis of variance. Data are presented as mean values ± SD (percentages), with P values <0.05 considered statistically significant.
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Results |
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The demographic and clinical data are summarized in Table 1. The two study groups were comparable with respect to age, ASA physical status, duration of sedation, and duration of surgery. The total study drug dosages, the average infusion rate required to maintain an OAA/S score of 3, the total fentanyl dosage, the volume of local anesthetic solution injected, and the cost of the study medication based on the actual amount used and wasted are summarized in Table 2. Although there was a significant decrease in drug cost with methohexital based on the actual amount (milligrams) of drug administered, comparing the cost based on the amount of drug used and wasted per case revealed no significant difference between the two sedative drugs.
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There was no difference between the two drug groups with respect to the time required to achieve an OAA/S score of 3 at the beginning of the surgical procedure. Similarly, there were no statistically significant differences in the time until the OAA/S score returned to 1, to ambulate unassisted, to be judged fit for discharge (home-readiness), and to actual discharge after surgery (Table 3). A higher incidence of pain during the injection of the study medication was reported in the patients receiving propofol (23% vs 10%). There were no differences in the incidence of perioperative side effects, including transient oxygen desaturation
90% (3% vs 3%), nausea (10% vs 3%), or vomiting (7% vs 3%). We did not observe any cases of hiccups, coughing, or laryngospasm. The requirement for antiemetic medication before discharge (10% vs 7%) did not differ between the propofol and methohexital groups. None of the patients required antiemetic drugs to treat nausea and/or vomiting after discharge.
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Intraoperatively, there was no significant difference in HR values between the two treatment groups or compared with their respective baseline values (Fig. 1A). The SBP values were significantly lower in the propofol group 10 and 20 min after starting the study drug infusion compared with those in the methohexital group (Fig. 1B). DBP values were also lower in the propofol (versus methohexital) group 10, 15, and 20 min after starting the infusion (Fig. 1B). All blood pressure values were significantly decreased compared with baseline values in both groups from 10 min after starting the study drug infusions until the end of the operation.
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P 
= SBP methohexital, • = SPB propofol, 
= DPB methohexital, 
= DPB propofol.The RR and EECO2 values were similar in the two study groups (Fig. 2). Compared with the baseline values, the RR was decreased in the methohexital group 20 min after initiating the infusion until the end of the procedure (Fig. 2A). In the propofol group, the RR was decreased only 40 and 45 min after starting the infusion compared with the baseline value. Compared with baseline values, the EECO2 values were increased in both drug groups 20 min after starting the infusion until the end of the procedure (Fig. 2B).
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There were no differences in the level of sedation (OAA/S scores) between the two study groups during the procedure (Fig. 3A). In both groups, the OAA/S score was maintained at a level of 3 throughout the surgical procedure. Similarly, there were no significant differences between the two groups with respect to the sedation and anxiety VAS scores during the recovery period. The postoperative performance on the DSST was also similar in the two treatment groups (Fig. 3B). Finally, there were no significant differences between the two groups with respect to the global assessments of sedation and recovery as performed by the blinded investigator and the patients.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Ambulatory surgery requires anesthetic drugs and techniques that provide adequate intraoperative conditions with a rapid recovery and minimal side effects (12). The use of IV sedation during local anesthesia can increase the patient’s acceptance of local anesthetic-based techniques by providing anxiolysis and amnesia during the surgical procedure (1). The use of a continuous, variable-rate IV infusion for administering rapid and short-acting sedative drugs can improve the practitioner’s ability to titrate these drugs, decrease the number of interventions by the anesthesiologist, and provide for a more rapid recovery of cognitive function (9,10,13).
Methohexital was a popular drug for the induction and maintenance of anesthesia in the ambulatory setting before the widespread availability of propofol (14,15). Early studies comparing these two sedative medications for the maintenance of general anesthesia suggested that the use of propofol was associated with a more rapid recovery and fewer postoperative side effects, nausea and vomiting in particular (4). In the current investigation, recovery from the residual sedative effects was equally rapid with both drugs. The results of the DSST, a cognitive function test that involves hand-eye coordination skills, as well as ability to recall multiple pairings of digits and symbols, suggest that return to baseline was similar with both drugs. Other investigators also failed to find any difference between the recovery profiles of propofol and methohexital when these drugs were administered by repeated bolus injections for sedation during regional anesthesia (16). Meyers et al. (17) compared propofol and methohexital administered as intermittent bolus injections for "deep" sedation of patients undergoing the removal of impacted wisdom teeth under local anesthesia. These authors concluded that the patients sedated with propofol recovered more rapidly than those sedated with methohexital. However, the difference in the recovery profiles was based on a difference in the Trieger dot test (a less sensitive psychomotor test than the DSST), which was performed at only one time point after the procedure. Jessop et al. (6) also reported a shorter recovery time when a propofol infusion was compared with a methohexital infusion for "light" general anesthesia during spinal anesthesia. However, induction doses of the sedative-hypnotic drugs were administered and the maintenance infusions were titrated to maintain an unconscious state during the operation. The pharmacokinetics of methohexital suggest that accumulation occurs when doses >600 mg are administered (14). Similarly, Apfelbaum et al. (18) reported prolonged times to awakening when the total dose of propofol exceeded 8 mg/kg during the maintenance period. It seems that when these drugs are infused for sedation (OAA/S <4), recovery profiles after propofol and methohexital are equivalent. However, when used for deep levels of sedation (i.e., light anesthesia), recovery may favor propofol over methohexital.
The current results are consistent with previous studies that suggest that improved control of the central nervous system effects, decreased dosage requirements, and a more rapid recovery can be achieved when sedative-hypnotic drugs are administered by a continuous IV infusion titrated to the desired end point (9,19). Mackenzie and Grant (16) reported a methohexital dosage requirement of 90 µg · kg-1 · min-1 when methohexital was administered by intermittent bolus injections during regional anesthesia compared with an average infusion rate of only 29.4 µg · kg-1 · min-1 when the drug was administered by a titrated infusion during local anesthesia in the current study.
The most common side effects associated with propofol are pain on injection and transient cardiorespiratory depression (20). Although we observed a high incidence of pain on injection with propofol, this can be reduced if the IV catheter is inserted into larger veins and/or by pretreatment with IV lidocaine (20). Compared with previous anesthetic studies (21), the administration of methohexital by a small-dose infusion for sedation during local anesthesia was associated with a low incidence of pain on injection. In contrast to comparative general anesthesia studies (4,6), we found no difference in the incidence of perioperative nausea and vomiting after sedative infusions of methohexital and propofol. However, we did not assess emetic symptoms after the patient was discharged home. Although the intraoperative blood pressures were slightly lower in the propofol group, no clinically significant differences could be demonstrated between the two sedative groups. A reduction in the blood pressure values was found in both groups compared with their baseline values, but no episodes of hypotension (SBP <90 mm Hg) were noted. Similarly, no apneic (or bradypneic) episodes were observed during either the methohexital or propofol infusions.
Ideally, this study would have been performed in a double-blinded fashion. However, this was not possible because of the marked differences in the appearance of the two sedative-hypnotic solutions. To minimize investigator bias, comparable levels of sedation were achieved during the procedure with both study drugs, and objective testing was performed by a blinded observer to compare the recovery profiles in an unbiased manner. The initial study drug infusion rates were chosen based on a relative potency ratio for propofol to methohexital of 0.8 (4), which is similar to the potency ratio described by Mackenzie and Grant (16), Tucker et al. (8), and Schwilden et al. (22).
The cost of anesthetic drugs has become increasingly important in the current healthcare environment. Practitioners are being asked to provide the same high standard of care at a more reasonable cost (23). One of the approaches to cost minimization is the preferential use of older (generic), less expensive anesthetic drugs. However, anesthesiologists are often reluctant to return to older drugs because their recovery profiles may contribute to longer stays in the postanesthesia care unit (PACU) and/or DSU (24). This study suggests that methohexital is an acceptable alternative to propofol for sedation during MAC, as it did not interfere with the ability to fasttrack these patients (i.e., bypass the PACU) and to achieve an early discharge from the DSU. Although methohexital may be associated with an incremental cost reduction when used in place of propofol, this assumption is dependent on the amount of drug wastage. Because the policy in the hospital in which this investigation was conducted is that the methohexital vial (500 mg) be used for only one patient, there was no overall cost-savings when methohexital was used as an alternative to propofol. However, in institutions in which the 500-mg vial of methohexital can be diluted in the pharmacy and divided into smaller dosage units (100–200 mg), the drug cost associated with methohexital sedation could be significantly decreased.
In summary, a continuous variable-rate IV infusion of methohexital can achieve a stable level of sedation during local anesthesia and provide for a rapid recovery comparable to that of propofol. Given the similar efficacy and recovery profiles of these two sedative-hypnotics, the relative acquisition (direct) cost and wastage of these drugs may become a more important determinant in choosing the drug for the maintenance of sedation during MAC.
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References |
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- Sá Rêgo MM, Watcha MF, White PF. The changing role of monitored anesthesia care in the ambulatory setting. Anesth Analg 1997;85:1020–36.[Web of Science][Medline]
- White PF, Negus JB. Sedative infusions during local and regional anesthesia: a comparison of midazolam and propofol. J Clin Anesth 1991;3:32–9.[Medline]
- Pratila MG, Fischer ME, Alagesan R, et al. Propofol versus midazolam for monitored sedation: a comparison of intraoperative and recovery parameters. J Clin Anesth 1993;5:268–74.[Web of Science][Medline]
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Doze VA, Westphal LM, White PF. Comparison of propofol with methohexital for outpatient anesthesia. Anesth Analg 1986;65:1189–95.
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Urquhart ML, White PF. Comparison of sedative infusions during regional anesthesia—methohexital, etomidate, and midazolam. Anesth Analg 1989;68:249–54.
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Jessop E, Grounds RM, Morgan M, Lumley J. Comparison of infusions of propofol and methohexitone to provide light general anaesthesia during surgery with regional blockade. Br J Anaesth 1985;57:1173–7.
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