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Predicted values of propofol EC50 and sevoflurane concentration for insertion of laryngeal mask ClassicTM and ProSealTM
British Journal of Anaesthesia 92 (2): 242±5 (2004)
DOI: 10.1093/bja/aeh032
Predicted values of propofol EC50 and sevo¯urane concentration for insertion of laryngeal mask ClassicTM and ProSealTM M. Kodaka*, Y. Okamoto, K. Koyama and H. Miyao Department of Anesthesiology, Saitama Medical Center, Saitama Medical School, 1981, Tsujido-cho, Kamoda, Kawagoe, Saitama 350±8550, Japan *Corresponding author. E-mail:[email protected]
Methods. Seventy-six elective female patients (aged 20±60 yr and ASA I±II) were randomly assigned to one of four groups. Either a PLMA or a CLMA was inserted using either propofol target controlled infusion or sevo¯urane. Both propofol and sevo¯urane targets were determined with a modi®ed Dixon's up-and-down method. After equilibration between the predetermined blood and effect site concentrations, which had been held steady for more than 10 min, LMA insertion was attempted without neuromuscular block. Results. The predicted EC50CLMA and EC50PLMA for propofol were 3.14 (0.33) and 4.32 (0.67) mg ml±1. E¢CLMA and E¢PLMA of sevo¯urane (mean (SD)) were 2.36 (0.22) and 2.82 (0.45)% (P<0.01 and 0.05, respectively). Conclusions. The estimated concentration of propofol and the sevo¯urane concentration needed to allow insertion of the ProSealTM are respectively 38 and 20% greater than those needed for insertion of the Classic LMA. Br J Anaesth 2004; 92: 242±5 Keywords: anaesthetics i.v., propofol; anaesthetics volatile, sevo¯urane; equipment, ProSealTM Accepted for publication: September 6, 2003
A newly developed laryngeal mask airway, the ProSealÔ (PLMA: Laryngeal Mask Company, Henley-on-Thames, UK), has a modi®ed cuff to improve the seal and a drainage tube to provide access to the oesophagus.1 With a stylet, the PLMA is more rigid than the laryngeal mask airway ClassicÔ (CLMA). The design allows higher airway pressure and facilitates passing an orogastric tube.2 Firstattempt success of PLMA insertion is less than for the CLMA after i.v. propofol in a dose of 2±3 mg kg±1,3 indicating that more anaesthetic is needed for insertion of the PLMA. We tested for differences in the predicted concentration of propofol and end-tidal concentration of sevo¯urane for insertion of the PLMA and the CLMA (EC50PLMA, EC50CLMA, E¢PLMA and E¢CLMA).
Patients and methods After approval of the ethics committee of Saitama Medical School and with written informed consent, we enrolled 76 female surgical patients, ASA class I±II, aged 20±60 years. We did not recruit patients if they were taking analgesic medication or if they had a body mass index >30 kg m±2, cervical spine disease, a known dif®cult airway (Mallampati grade III or IV), a mouth opening less than 2.5 cm, symptoms of upper respiratory tract disease, or if they were at risk of aspiration (non-fasted, gastro-oesophageal disease). We also excluded patients who were unable to lie supine. All the patients were about to have minor gynaecological surgery. They were given midazolam 2 mg
Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2004
Downloaded from http://bja.oxfordjournals.org/ at University of Waterloo on March 13, 2015
Background. A new laryngeal mask airway, the ProSealÔ (PLMA), is said to be more dif®cult to insert than the laryngeal mask airway ClassicÔ (CLMA) using propofol anaesthesia. Therefore, we expected a greater dose of propofol and sevo¯urane to be required to insert the PLMA compared with the CLMA. We determined the effective concentration 50% (EC50) of propofol and end-tidal sevo¯urane to allow insertion of the PLMA and the CLMA.
Propofol EC50 and sevo¯urane
Table 1 Patient characteristics. Values are mean (SD) Agent
Propofol
Sevo¯urane
Group
CLMA
PLMA
CLMA
PLMA
No. of patients Age (yr) Weight (kg) Height (cm)
20 40 (13) 51.6 (7.7) 156.5(5.7)
20 43 (13) 50.2 (5.4) 155.1 (5.6)
18 42 (9) 55.2 (7.9) 157.7 (5.0)
18 43 (9) 54.1 (8.7) 157.5 (3.7)
for ProSealTM
SpO2, FIO2 and end-tidal carbon dioxide (FE¢CO2) were also monitored breath by breath using a multiple monitoring system (BP-508; Nippon Colin Co, Aichi, Japan). Predetermined propofol blood and effect site concentrations were held constant for at least 10 min. For sevo¯urane, predetermined end-tidal concentrations were maintained for more than 10 min before insertion of the device. Insertion of either device (size 3), in the de¯ated state, was attempted by an anaesthetist who had no knowledge of agent concentration. Neuromuscular blocking drugs were not given. The CLMA was inserted without an introducer and the PLMA was inserted using an introducer stylet. Responses by the patient to LMA insertion were classi®ed as either `movement' or `no movement' by the surgeons, who were also unaware of the anaesthetic concentration. Movement was de®ned as bucking or gross purposeful muscular movement within 1 min of LMA insertion. Propofol concentrations (starting with 4 mg ml±1 for predicted EC50) were chosen by a modi®cation of Dixon's up-and-down method6 7 (with 0.5 mg ml±1 as the step size). A single measurement was obtained from each patient. If the patient in the propofol group reacted with movement, the propofol concentration for the next patient was increased by 0.5 mg ml±1; if there was no movement, it was decreased by 0.5 mg ml±1. In the sevo¯urane group, the starting end-tidal concentration was 2.5% and the step size of increase/ decrease was also 0.5%. One trial for each patient was performed and a decision was made to increase or decrease the dose based on the patient's response, i.e. dif®culty of LMA insertion because of dif®culty in opening the mouth, or if the patient gagged or
Fig. 1 Responses in each group with a modi®ed Dixon's up-and-down method.
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i.m. before surgery. The patients were randomly assigned into one of four groups using a computer-randomized table: CLMA insertion and ProSealÔ (PLMA) insertion, with either propofol or sevo¯urane, respectively. Before giving propofol, we gave lidocaine 2%, 1 mg kg±1 to reduce pain in the vein. The propofol infusion was controlled by computer to obtain a stable effect site concentration. We used TCI software incorporating the standard DiprifusorÔ pharmacokinetic model, introduced by Gepts and colleagues4 and later modi®ed by Marsh and colleagues,5 controlling an infusion syringe driver (Graseby 3500; SIMS Graseby, Watford, UK). In the sevo¯urane groups, anaesthesia was induced with sevo¯urane up to 5% in oxygen via facemask with fresh gas ¯ow at 6 litres min±1. After loss of consciousness, the inspired concentration of sevo¯urane was changed to obtain a predetermined end-tidal concentration. The depth of anaesthesia was monitored with the bispectral index (BIS; A-1050, Version 3.4; Aspect Medical Systems, Newton, MA, USA) every 15 s. Blood pressure and heart rate were measured non-invasively every minute. Inhaled and exhaled concentrations of sevo¯urane,
E¢
Kodaka et al.
Results The groups were well matched for age, weight and height (Table 1). Dose±response data obtained by Dixon's up-anddown method are shown in Fig. 1. The predicted EC50PLMA and E¢PLMA were greater than those for the Classic CLMA (P<0.01 and <0.05, respectively). The BIS values for CLMA and PLMA were signi®cantly different with propofol (Table 2). In contrast, there were no differences in the sevo¯urane group. BIS values were not signi®cantly different before and after insertion, within each group. Circulatory values were not different between the groups (data not shown), and there was no signi®cant change with time between groups. No patient reported recall of events during LMA insertion or surgery. In six patients (two in the sevo¯urane with PLMA group, four in the propofol with PLMA group), we exchanged the LMA for a larger one because a large leak prevented adequate ventilation. A sore throat was reported the next day by three, two, Table 2 Values for EC50 and E¢ calculated from Fig. 1. Mean (SD), 95% con®dence interval (CI) and BIS values at different times in the four groups. Median (25±75% range). Comparison of PLMA vs CLMA: *P<0.05 and **P <0.01 Propofol CLMA
Sevo¯urane PLMA
CLMA
PLMA
EC50 (mg ml±1)/MAC (%) 3.14 (0.33) 4.32 (0.67)** 2.36 (0.22) 2.82 (0.45)* (CI) (2.88±3.40) (3.70±4.94) (2.19±2.53) (2.41±3.24) BIS Before induction 1 min before LMA insertion 1 min after LMA insertion
97 (95±98) 56 (39±61) 61.5 (47±69)
94 (92±96) 34* (31±38) 36* (33.0±45)
97 (92±97) 39.0 (33.8±54.0) 52 (41.0±66)
97 (95±97) 38.0 (34.0±43.5) 49 (38±60)
seven and ®ve patients in the sevo¯urane with CLMA, propofol with CLMA, sevo¯urane with PLMA, and propofol with PLMA groups, respectively. All recovered from their symptoms in a few days.
Discussion This study is the ®rst to determine the propofol EC50 predicted and end-tidal sevo¯urane concentration required for insertion of the ProSealÔ and Classic LMA. The values for propofol and sevo¯urane were 38% and 20% greater for the PLMA than for the CLMA. We previously found that the predicted concentration of propofol for classic LMA insertion was 3.24 mg ml±1 when premedication was not used, which is slightly greater than in this study9 (3.14 mg ml±1). This is probably because midazolam 2 mg was given in the present study. Previous studies10±12 have reported the success rate for LMA insertion with TCI target values between 6 and 8 mg ml±1, with or without premedication. The greater concentrations provided good conditions for insertion of the LMA. However, in all these studies the device was inserted within a few minutes of starting the propofol infusion, so there would be limited equilibration between target and effect site. Their study designs are quite different from ours. Two studies13 14 reported the EC50 of propofol for LMA insertion using TCI infusions. Casati and colleagues13 reported the EC50 of propofol for LMA placement to be 4.3 mg ml±1, but did not state the time given for equilibration, and allowed more than one attempt if necessary in each patient, by increasing the target until satisfactory insertion was achieved. Higuchi and colleagues14 found the effective median measured propofol concentration for LMA insertion was 8.7 mg ml±1. This value is 2.8 times higher than that of our study. An explanation for this large difference could be the gender, because they studied men. A second possibility is giving lidocaine, since this can reduce the re¯ex response to LMA insertion during propofol induction15. Thirdly, we used premedication, with midazolam 2 mg. In addition, we used a size 3 LMA for all patients, although a size 4 would have been better in several cases. Finally, actual measured values after induction of anaesthesia are often underestimated by prediction software.16 Tanaka and colleagues17 found the end-tidal sevo¯urane for insertion of the Classic LMA was 2.0% for both young and elderly patients. The value we found was 2.38%. The difference could have been caused by age or by the time from equilibration to insertion (20 min) and the number of attempts (one to three) for each patient in each study. Because brain equilibration with arterial sevo¯urane is >90% complete in 4±8 min,18 a different effect site partial pressure is unlikely. Our ®ndings support studies2 3 which showed that the PLMA needs more attempts and a longer time for insertion than the CLMA. The semi-rigid distal end of the drain tube at the leading edge of the ProSealÔ and the
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coughed. If adequate ventilation was not obtained because of a leak, the mask was changed for a larger size. Values of EC50 and E¢ were determined by calculating the midpoint concentration after at least seven crossover points were obtained in each subgroup. As a result, 20 and 18 patients for each anaesthetic were used to determine propofol EC50 and E¢ sevo¯urane. These values were obtained by calculating the mean values for crossover midpoint in each group. The standard deviation (SD) of EC50 or E¢ was the SD of the crossover midpoint of each group.6±8 We compared BIS values, pulse and blood pressure 5 min before induction and 1 min before and after attempted insertion, whether the insertion was successful or not. Patients were asked after surgery if they had any recall of event, and about sore throat. Predicted EC50 and sevo¯urane E¢ were compared by Student's t-test. Heart rate, arterial pressure and BIS data changes were compared by repeated measures ANOVA, within either the propofol or the sevo¯urane group. P<0.05 was considered signi®cant.
Propofol EC50 and sevo¯urane
References 1 Brain AIJ, Verghese C, Strube PJ. The LMA `ProSeal': a laryngeal mask with an oesophageal vent. Br J Anaesth 2000; 84: 650±4 2 Cook TM, Nolan JP, Verghese C, et al. Randomized crossover comparison of the ProSeal with the classic laryngeal mask airway in unparalysed anaesthesia patients. Br J Anaesth 2002; 88: 527± 33 3 Brimacombe J, Keller C, Fullekrug B, et al. A multicenter study comparing the ProSeal and Classic laryngeal mask airway in anesthetized, nonparalyzed patients. Anesthesiology 2002; 96: 289±95
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for ProSealTM
4 Gepts E, Camu F, Cockshott ID, Douglas EJ. Disposition of propofol administered as constant rate intravenous infusion in humans. Anesth Analg 1987; 66: 1256±63 5 Marsh B, White M, Morton N, Kenny GNC. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67: 41±8 6 Dixon WJ. Quantal response to variable experimentation: the up-and-down method. In: McArthur JW, Colton T, eds. Statistics in Endocrinology. Cambridge: MIT Press, 1967; 251±64 7 Dixon WJ. Staircase bioassay: the up-and-down method. Neurosci Biobehav Rev 1991; 15: 47±50 8 Taguchi M, Watanabe S, Asakura N, Inomata S. End-tidal sevo¯urane concentrations for laryngeal mask airway insertion and for tracheal intubation in children. Anesthesiology 1994; 81: 628±31 9 Kodaka M, Handa F, Miyao H. Nitrous oxide reduced the propofol Cp50 of propofol for laryngeal mask insertion. Anaesthesia 2002; 57: 956±9 10 Tayler N, Kenny GNC. Requirements for target-controlled infusion of propofol to insert the laryngeal mask airway. Anaesthesia 1998; 53: 222±6 11 Smith I, Thwaites AJ. Target-controlled propofol vs. sevo¯urane: a double-blind, randomized comparison in day-case anaesthesia. Anaesthesia 1999; 54: 745±52 12 Baik HJ, Kim JH, Lee CH. Laryngeal mask insertion during targetcontrolled infusion of propofol. J Clin Anesth 2001; 13: 175±81 13 Casati A, Fanelli G, Casaletti E, et al. The target plasma concentration of propofol required to place laryngeal mask versus cuffed oropharyngeal airway. Anesth Analg 1999; 88: 917± 20 14 Higuchi H, Adachi Y, Arimura S, Nitahara K, Satoh T. Oral clonidine premedication reduces the EC50 of propofol concentration for laryngeal mask airway insertion in male patients. Acta Anaesthesiol Scand 2002; 46: 372±7 15 Stoneham MD, Bree SE, Sneyd JR. Facilitation of laryngeal mask insertion. Effect of lignocaine given intravenously before induction with propofol. Anaesthesia 1995; 50: 464±6 16 Swinhoe CF, Peacok JE, Glen JB, Reilly CS. Evaluation of the predictive performance of a `Diprifusor' TCI system. Anaesthesia 1998; 53 (Suppl. 1): 61±7 17 Tanaka M, Watanabe S, Nishikawa M. Minimum alveolar sevo¯urane concentrations required for insertion of the cuffed oropharyngeal airway and the laryngeal mask airway: a comparative study. Anaesthesia 1999; 54: 1155±60 18 Eager II EI. Uptake and Distribution. In: Miller RD, ed. Anesthesia, Vol. 1, 5th edn. NY: Churchill Livingstone, 2000; 74±95 19 Howath A, Brimacombe J, Keller C. Gum-elastic bougie-guided insertion of the ProSeal laryngeal mask airway: a new technique. Anaesth Intensive Care 2002; 30: 624±7 20 Brimacombe J, Keller C, Boehler M, Puhringer F. Positive pressure ventilation with the ProSeal versus Classic laryngeal mask airway: a randomized, crossover study of healthy female patients. Anesth Analg 2001; 93: 1351±3 21 Sebel PS, Lang E, Rampil IJ, et al. A multicenter study of bispectral electroencephalogram analysis for monitoring anesthetic effect. Anesth Analg 1997; 84: 891±9
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use of an introducer makes the PLMA more rigid than the CLMA. The PLMA can be inserted without the stylet or with a gum elastic bougie,19 and the difference in insertion technique might explain the difference in the success rate of insertion and the estimate of EC50/E¢ sevo¯urane that we found. In our study, anaesthetists who had used the CLMA for more than 2 yr and the PLMA in more than 50 cases took part. The patients in our study were smaller than those reported in the study by Brimacombe and colleagues20 and half of our patients were suitable for size 3 LMA. We inserted just one size 3 for all of the patients, which could have made the EC50 lower. In six patients with a PLMA we needed to exchange the LMA for a bigger one. We did not have to change any Classic LMA devices because most of the patients in this group were breathing spontaneously. Table 2 shows that BIS values with PLMA insertion during propofol anaesthesia were less than those for CLMA insertion. This difference was not seen with sevo¯urane. Propofol decreases BIS values21 in a dose-related way, but we did not see an effect for sevo¯urane despite the fact that sevo¯urane concentration for PLMA insertion was also greater than for CLMA insertion. Sebel and colleagues21 studied the relative effects of propofol, iso¯urane and opioids on BIS in relation to the probability of movement at induction. The BIS value of iso¯urane was greater than that of propofol in relation to the probability of movement, and it is likely that a similar effect exists for sevo¯urane. We found no adverse effects during the induction of anaesthesia in the middle-aged female patients we studied. However, in older or less ®t patients a greater dose of anaesthetic agent could have adverse effects, and in such patients a classical LMA would allow less anaesthetic and could avoid circulatory effects, if the other features of the PLMA were not required. In conclusion, we found that more anaesthesia is needed for insertion of the ProSealTM laryngeal mask airway, particularly when propofol is used.
E¢
DOI: 10.1093/bja/aeh032
Predicted values of propofol EC50 and sevo¯urane concentration for insertion of laryngeal mask ClassicTM and ProSealTM M. Kodaka*, Y. Okamoto, K. Koyama and H. Miyao Department of Anesthesiology, Saitama Medical Center, Saitama Medical School, 1981, Tsujido-cho, Kamoda, Kawagoe, Saitama 350±8550, Japan *Corresponding author. E-mail:[email protected]
Methods. Seventy-six elective female patients (aged 20±60 yr and ASA I±II) were randomly assigned to one of four groups. Either a PLMA or a CLMA was inserted using either propofol target controlled infusion or sevo¯urane. Both propofol and sevo¯urane targets were determined with a modi®ed Dixon's up-and-down method. After equilibration between the predetermined blood and effect site concentrations, which had been held steady for more than 10 min, LMA insertion was attempted without neuromuscular block. Results. The predicted EC50CLMA and EC50PLMA for propofol were 3.14 (0.33) and 4.32 (0.67) mg ml±1. E¢CLMA and E¢PLMA of sevo¯urane (mean (SD)) were 2.36 (0.22) and 2.82 (0.45)% (P<0.01 and 0.05, respectively). Conclusions. The estimated concentration of propofol and the sevo¯urane concentration needed to allow insertion of the ProSealTM are respectively 38 and 20% greater than those needed for insertion of the Classic LMA. Br J Anaesth 2004; 92: 242±5 Keywords: anaesthetics i.v., propofol; anaesthetics volatile, sevo¯urane; equipment, ProSealTM Accepted for publication: September 6, 2003
A newly developed laryngeal mask airway, the ProSealÔ (PLMA: Laryngeal Mask Company, Henley-on-Thames, UK), has a modi®ed cuff to improve the seal and a drainage tube to provide access to the oesophagus.1 With a stylet, the PLMA is more rigid than the laryngeal mask airway ClassicÔ (CLMA). The design allows higher airway pressure and facilitates passing an orogastric tube.2 Firstattempt success of PLMA insertion is less than for the CLMA after i.v. propofol in a dose of 2±3 mg kg±1,3 indicating that more anaesthetic is needed for insertion of the PLMA. We tested for differences in the predicted concentration of propofol and end-tidal concentration of sevo¯urane for insertion of the PLMA and the CLMA (EC50PLMA, EC50CLMA, E¢PLMA and E¢CLMA).
Patients and methods After approval of the ethics committee of Saitama Medical School and with written informed consent, we enrolled 76 female surgical patients, ASA class I±II, aged 20±60 years. We did not recruit patients if they were taking analgesic medication or if they had a body mass index >30 kg m±2, cervical spine disease, a known dif®cult airway (Mallampati grade III or IV), a mouth opening less than 2.5 cm, symptoms of upper respiratory tract disease, or if they were at risk of aspiration (non-fasted, gastro-oesophageal disease). We also excluded patients who were unable to lie supine. All the patients were about to have minor gynaecological surgery. They were given midazolam 2 mg
Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2004
Downloaded from http://bja.oxfordjournals.org/ at University of Waterloo on March 13, 2015
Background. A new laryngeal mask airway, the ProSealÔ (PLMA), is said to be more dif®cult to insert than the laryngeal mask airway ClassicÔ (CLMA) using propofol anaesthesia. Therefore, we expected a greater dose of propofol and sevo¯urane to be required to insert the PLMA compared with the CLMA. We determined the effective concentration 50% (EC50) of propofol and end-tidal sevo¯urane to allow insertion of the PLMA and the CLMA.
Propofol EC50 and sevo¯urane
Table 1 Patient characteristics. Values are mean (SD) Agent
Propofol
Sevo¯urane
Group
CLMA
PLMA
CLMA
PLMA
No. of patients Age (yr) Weight (kg) Height (cm)
20 40 (13) 51.6 (7.7) 156.5(5.7)
20 43 (13) 50.2 (5.4) 155.1 (5.6)
18 42 (9) 55.2 (7.9) 157.7 (5.0)
18 43 (9) 54.1 (8.7) 157.5 (3.7)
for ProSealTM
SpO2, FIO2 and end-tidal carbon dioxide (FE¢CO2) were also monitored breath by breath using a multiple monitoring system (BP-508; Nippon Colin Co, Aichi, Japan). Predetermined propofol blood and effect site concentrations were held constant for at least 10 min. For sevo¯urane, predetermined end-tidal concentrations were maintained for more than 10 min before insertion of the device. Insertion of either device (size 3), in the de¯ated state, was attempted by an anaesthetist who had no knowledge of agent concentration. Neuromuscular blocking drugs were not given. The CLMA was inserted without an introducer and the PLMA was inserted using an introducer stylet. Responses by the patient to LMA insertion were classi®ed as either `movement' or `no movement' by the surgeons, who were also unaware of the anaesthetic concentration. Movement was de®ned as bucking or gross purposeful muscular movement within 1 min of LMA insertion. Propofol concentrations (starting with 4 mg ml±1 for predicted EC50) were chosen by a modi®cation of Dixon's up-and-down method6 7 (with 0.5 mg ml±1 as the step size). A single measurement was obtained from each patient. If the patient in the propofol group reacted with movement, the propofol concentration for the next patient was increased by 0.5 mg ml±1; if there was no movement, it was decreased by 0.5 mg ml±1. In the sevo¯urane group, the starting end-tidal concentration was 2.5% and the step size of increase/ decrease was also 0.5%. One trial for each patient was performed and a decision was made to increase or decrease the dose based on the patient's response, i.e. dif®culty of LMA insertion because of dif®culty in opening the mouth, or if the patient gagged or
Fig. 1 Responses in each group with a modi®ed Dixon's up-and-down method.
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i.m. before surgery. The patients were randomly assigned into one of four groups using a computer-randomized table: CLMA insertion and ProSealÔ (PLMA) insertion, with either propofol or sevo¯urane, respectively. Before giving propofol, we gave lidocaine 2%, 1 mg kg±1 to reduce pain in the vein. The propofol infusion was controlled by computer to obtain a stable effect site concentration. We used TCI software incorporating the standard DiprifusorÔ pharmacokinetic model, introduced by Gepts and colleagues4 and later modi®ed by Marsh and colleagues,5 controlling an infusion syringe driver (Graseby 3500; SIMS Graseby, Watford, UK). In the sevo¯urane groups, anaesthesia was induced with sevo¯urane up to 5% in oxygen via facemask with fresh gas ¯ow at 6 litres min±1. After loss of consciousness, the inspired concentration of sevo¯urane was changed to obtain a predetermined end-tidal concentration. The depth of anaesthesia was monitored with the bispectral index (BIS; A-1050, Version 3.4; Aspect Medical Systems, Newton, MA, USA) every 15 s. Blood pressure and heart rate were measured non-invasively every minute. Inhaled and exhaled concentrations of sevo¯urane,
E¢
Kodaka et al.
Results The groups were well matched for age, weight and height (Table 1). Dose±response data obtained by Dixon's up-anddown method are shown in Fig. 1. The predicted EC50PLMA and E¢PLMA were greater than those for the Classic CLMA (P<0.01 and <0.05, respectively). The BIS values for CLMA and PLMA were signi®cantly different with propofol (Table 2). In contrast, there were no differences in the sevo¯urane group. BIS values were not signi®cantly different before and after insertion, within each group. Circulatory values were not different between the groups (data not shown), and there was no signi®cant change with time between groups. No patient reported recall of events during LMA insertion or surgery. In six patients (two in the sevo¯urane with PLMA group, four in the propofol with PLMA group), we exchanged the LMA for a larger one because a large leak prevented adequate ventilation. A sore throat was reported the next day by three, two, Table 2 Values for EC50 and E¢ calculated from Fig. 1. Mean (SD), 95% con®dence interval (CI) and BIS values at different times in the four groups. Median (25±75% range). Comparison of PLMA vs CLMA: *P<0.05 and **P <0.01 Propofol CLMA
Sevo¯urane PLMA
CLMA
PLMA
EC50 (mg ml±1)/MAC (%) 3.14 (0.33) 4.32 (0.67)** 2.36 (0.22) 2.82 (0.45)* (CI) (2.88±3.40) (3.70±4.94) (2.19±2.53) (2.41±3.24) BIS Before induction 1 min before LMA insertion 1 min after LMA insertion
97 (95±98) 56 (39±61) 61.5 (47±69)
94 (92±96) 34* (31±38) 36* (33.0±45)
97 (92±97) 39.0 (33.8±54.0) 52 (41.0±66)
97 (95±97) 38.0 (34.0±43.5) 49 (38±60)
seven and ®ve patients in the sevo¯urane with CLMA, propofol with CLMA, sevo¯urane with PLMA, and propofol with PLMA groups, respectively. All recovered from their symptoms in a few days.
Discussion This study is the ®rst to determine the propofol EC50 predicted and end-tidal sevo¯urane concentration required for insertion of the ProSealÔ and Classic LMA. The values for propofol and sevo¯urane were 38% and 20% greater for the PLMA than for the CLMA. We previously found that the predicted concentration of propofol for classic LMA insertion was 3.24 mg ml±1 when premedication was not used, which is slightly greater than in this study9 (3.14 mg ml±1). This is probably because midazolam 2 mg was given in the present study. Previous studies10±12 have reported the success rate for LMA insertion with TCI target values between 6 and 8 mg ml±1, with or without premedication. The greater concentrations provided good conditions for insertion of the LMA. However, in all these studies the device was inserted within a few minutes of starting the propofol infusion, so there would be limited equilibration between target and effect site. Their study designs are quite different from ours. Two studies13 14 reported the EC50 of propofol for LMA insertion using TCI infusions. Casati and colleagues13 reported the EC50 of propofol for LMA placement to be 4.3 mg ml±1, but did not state the time given for equilibration, and allowed more than one attempt if necessary in each patient, by increasing the target until satisfactory insertion was achieved. Higuchi and colleagues14 found the effective median measured propofol concentration for LMA insertion was 8.7 mg ml±1. This value is 2.8 times higher than that of our study. An explanation for this large difference could be the gender, because they studied men. A second possibility is giving lidocaine, since this can reduce the re¯ex response to LMA insertion during propofol induction15. Thirdly, we used premedication, with midazolam 2 mg. In addition, we used a size 3 LMA for all patients, although a size 4 would have been better in several cases. Finally, actual measured values after induction of anaesthesia are often underestimated by prediction software.16 Tanaka and colleagues17 found the end-tidal sevo¯urane for insertion of the Classic LMA was 2.0% for both young and elderly patients. The value we found was 2.38%. The difference could have been caused by age or by the time from equilibration to insertion (20 min) and the number of attempts (one to three) for each patient in each study. Because brain equilibration with arterial sevo¯urane is >90% complete in 4±8 min,18 a different effect site partial pressure is unlikely. Our ®ndings support studies2 3 which showed that the PLMA needs more attempts and a longer time for insertion than the CLMA. The semi-rigid distal end of the drain tube at the leading edge of the ProSealÔ and the
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coughed. If adequate ventilation was not obtained because of a leak, the mask was changed for a larger size. Values of EC50 and E¢ were determined by calculating the midpoint concentration after at least seven crossover points were obtained in each subgroup. As a result, 20 and 18 patients for each anaesthetic were used to determine propofol EC50 and E¢ sevo¯urane. These values were obtained by calculating the mean values for crossover midpoint in each group. The standard deviation (SD) of EC50 or E¢ was the SD of the crossover midpoint of each group.6±8 We compared BIS values, pulse and blood pressure 5 min before induction and 1 min before and after attempted insertion, whether the insertion was successful or not. Patients were asked after surgery if they had any recall of event, and about sore throat. Predicted EC50 and sevo¯urane E¢ were compared by Student's t-test. Heart rate, arterial pressure and BIS data changes were compared by repeated measures ANOVA, within either the propofol or the sevo¯urane group. P<0.05 was considered signi®cant.
Propofol EC50 and sevo¯urane
References 1 Brain AIJ, Verghese C, Strube PJ. The LMA `ProSeal': a laryngeal mask with an oesophageal vent. Br J Anaesth 2000; 84: 650±4 2 Cook TM, Nolan JP, Verghese C, et al. Randomized crossover comparison of the ProSeal with the classic laryngeal mask airway in unparalysed anaesthesia patients. Br J Anaesth 2002; 88: 527± 33 3 Brimacombe J, Keller C, Fullekrug B, et al. A multicenter study comparing the ProSeal and Classic laryngeal mask airway in anesthetized, nonparalyzed patients. Anesthesiology 2002; 96: 289±95
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4 Gepts E, Camu F, Cockshott ID, Douglas EJ. Disposition of propofol administered as constant rate intravenous infusion in humans. Anesth Analg 1987; 66: 1256±63 5 Marsh B, White M, Morton N, Kenny GNC. Pharmacokinetic model driven infusion of propofol in children. Br J Anaesth 1991; 67: 41±8 6 Dixon WJ. Quantal response to variable experimentation: the up-and-down method. In: McArthur JW, Colton T, eds. Statistics in Endocrinology. Cambridge: MIT Press, 1967; 251±64 7 Dixon WJ. Staircase bioassay: the up-and-down method. Neurosci Biobehav Rev 1991; 15: 47±50 8 Taguchi M, Watanabe S, Asakura N, Inomata S. End-tidal sevo¯urane concentrations for laryngeal mask airway insertion and for tracheal intubation in children. Anesthesiology 1994; 81: 628±31 9 Kodaka M, Handa F, Miyao H. Nitrous oxide reduced the propofol Cp50 of propofol for laryngeal mask insertion. Anaesthesia 2002; 57: 956±9 10 Tayler N, Kenny GNC. Requirements for target-controlled infusion of propofol to insert the laryngeal mask airway. Anaesthesia 1998; 53: 222±6 11 Smith I, Thwaites AJ. Target-controlled propofol vs. sevo¯urane: a double-blind, randomized comparison in day-case anaesthesia. Anaesthesia 1999; 54: 745±52 12 Baik HJ, Kim JH, Lee CH. Laryngeal mask insertion during targetcontrolled infusion of propofol. J Clin Anesth 2001; 13: 175±81 13 Casati A, Fanelli G, Casaletti E, et al. The target plasma concentration of propofol required to place laryngeal mask versus cuffed oropharyngeal airway. Anesth Analg 1999; 88: 917± 20 14 Higuchi H, Adachi Y, Arimura S, Nitahara K, Satoh T. Oral clonidine premedication reduces the EC50 of propofol concentration for laryngeal mask airway insertion in male patients. Acta Anaesthesiol Scand 2002; 46: 372±7 15 Stoneham MD, Bree SE, Sneyd JR. Facilitation of laryngeal mask insertion. Effect of lignocaine given intravenously before induction with propofol. Anaesthesia 1995; 50: 464±6 16 Swinhoe CF, Peacok JE, Glen JB, Reilly CS. Evaluation of the predictive performance of a `Diprifusor' TCI system. Anaesthesia 1998; 53 (Suppl. 1): 61±7 17 Tanaka M, Watanabe S, Nishikawa M. Minimum alveolar sevo¯urane concentrations required for insertion of the cuffed oropharyngeal airway and the laryngeal mask airway: a comparative study. Anaesthesia 1999; 54: 1155±60 18 Eager II EI. Uptake and Distribution. In: Miller RD, ed. Anesthesia, Vol. 1, 5th edn. NY: Churchill Livingstone, 2000; 74±95 19 Howath A, Brimacombe J, Keller C. Gum-elastic bougie-guided insertion of the ProSeal laryngeal mask airway: a new technique. Anaesth Intensive Care 2002; 30: 624±7 20 Brimacombe J, Keller C, Boehler M, Puhringer F. Positive pressure ventilation with the ProSeal versus Classic laryngeal mask airway: a randomized, crossover study of healthy female patients. Anesth Analg 2001; 93: 1351±3 21 Sebel PS, Lang E, Rampil IJ, et al. A multicenter study of bispectral electroencephalogram analysis for monitoring anesthetic effect. Anesth Analg 1997; 84: 891±9
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use of an introducer makes the PLMA more rigid than the CLMA. The PLMA can be inserted without the stylet or with a gum elastic bougie,19 and the difference in insertion technique might explain the difference in the success rate of insertion and the estimate of EC50/E¢ sevo¯urane that we found. In our study, anaesthetists who had used the CLMA for more than 2 yr and the PLMA in more than 50 cases took part. The patients in our study were smaller than those reported in the study by Brimacombe and colleagues20 and half of our patients were suitable for size 3 LMA. We inserted just one size 3 for all of the patients, which could have made the EC50 lower. In six patients with a PLMA we needed to exchange the LMA for a bigger one. We did not have to change any Classic LMA devices because most of the patients in this group were breathing spontaneously. Table 2 shows that BIS values with PLMA insertion during propofol anaesthesia were less than those for CLMA insertion. This difference was not seen with sevo¯urane. Propofol decreases BIS values21 in a dose-related way, but we did not see an effect for sevo¯urane despite the fact that sevo¯urane concentration for PLMA insertion was also greater than for CLMA insertion. Sebel and colleagues21 studied the relative effects of propofol, iso¯urane and opioids on BIS in relation to the probability of movement at induction. The BIS value of iso¯urane was greater than that of propofol in relation to the probability of movement, and it is likely that a similar effect exists for sevo¯urane. We found no adverse effects during the induction of anaesthesia in the middle-aged female patients we studied. However, in older or less ®t patients a greater dose of anaesthetic agent could have adverse effects, and in such patients a classical LMA would allow less anaesthetic and could avoid circulatory effects, if the other features of the PLMA were not required. In conclusion, we found that more anaesthesia is needed for insertion of the ProSealTM laryngeal mask airway, particularly when propofol is used.
E¢