ANESTH ANALG 1990;71 :42S-6
423
Clinical Reports Local Anesthetic Serum Concentrations After Penile Nerve Block in Children Michel Sfez, MD, Yann Le Mapihan, Helene Dreux-Boucard, MD
MD,
Xavier Mazoit,
Key Words: ANESTHESIA, PEDIATRIC. ANESTHETIC TECHNIQUES, REGroNAL-penile block. ANESTHETICS, LOCAL-bupivacaine, lidocaine. Regional anesthesia provides adequate postoperative analgesia in children undergoing circumcision (1,2). Because caudal anesthesia can lead to local anesthetic serum concentrations close to levels considered to be in the toxic range (3,4), penile block may be the safer regional technique as the drug dosage used is very low (2,5,6), although serum levels of local anesthetics have not been determined. In addition, there is no agreement on the proper drug and dosage to use in order to provide the most rapid onset and longest duration of analgesia with the lowest peak serum concentration of local anesthetics. A mixture of lidocaine and bupivacaine may reduce the time of onset of analgesia without reducing its duration (7), although it might enhance the risk of toxicity due to each individual drug (8-10). The aim of this study was therefore to assess the duration of analgesia and to determine the timecourse of serum concentrations of lidocaine and bupivacaine used in combination as well as of bupivacaine alone when used in children undergoing circumcision with general anesthesia supplemented by penile block.
Supported in part by grants from Roger Bellon Laboratoires. Received from the Departments of Anesthesiology, HBpital Jean Verdier, Bondy, France, and HBpital Robert Ballanger, Villepinte, France. Accepted for publication May 24, 1990. Address correspondence to Dr. Sfez, MD, C.C.B.B. 105, Avenue Victor Hugo, 92100 Boulogne Billancourt, France. 01990 by the International Anesthesia Research Society
MD,
and
Patients and Methods Patients The study was approved by the local ethical committee and informed consent was obtained from the parents. Twelve boys, ASA physical status I, aged 3-11 yr, weighing 13-34 kg, were randomly assigned to have penile blocks performed while anesthetized with halothane-nitrous oxide-oxygen using 0.25% bupivacaine alone (group 1, n = 6) or 1% lidocaine plus 0.25% bupivacaine (group 2, n = 6). In group 2, the mixture of local anesthetics was obtained by mixing equal volumes of each drug.
Anesthetic Technique Halothane (up to 2%) was given in 50% nitrous oxide and 50% oxygen, through a face mask in an open circuit. Once the children were anesthetized, a short 22-gauge indwelling catheter was placed in a forearm vein for blood sampling, and penile block was then performed. A bilateral approach, modified from the technique described by Kirya and Werhmann (5) was used. On each side, a paramedian injection of 0.1 mLlkg of anesthetic solution was performed after the needle penetrated Bucks fascia and aspiration was negative for blood. Patients therefore were given 0.5 mgikg bupivacaine in group 1 and 0.25 mg/kg bupivacaine with 1 mglkg lidocaine in group 2. No additional intraoperative or postoperative analgesic was given until children complained of pain.
Clinical Assessment The postoperative pain-free period was defined as the time between termination of general anesthesia
424
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ANESTH ANALG 1990;71:42>6
Table 1. Demographic Data and Pharmacokinetics of Local Anesthetics C,,
Patient No. Group 1 1 2 3 4 5 6
Mean SD
Group 2 7 8 9 10 11 12 Mean SD
Age (yr) 10.5 4.5 4.5 4 5 5.5 5.55 2.5
3 4.5 5.5 10.8 7.2 4 5.84 2.84
Weight (kg)
bupivacaine (FgimL)
T,,,,
bupivacaine (min)
C,,
lidocaine bg/mL)
T,,
lidocaine (min)
31 19 13 20 23 18
0.35 0.13 0.26 0.32 0.35 0.21
30 30 20 20 20 20
20.7 6.0
0.27 0.09"
23 5
13 21 18 33.5 22.5 20
0.07 0.06 0.06 0.09 0.16 0.09
30 25 5 30 60 10
0.31 0.39 0.23 0.40 0.38 0.47
30 20 10 20 60 20
21.3 6.8
0.09 0.04'
27 19
0.36 0.08
27 18
Age, weight, and bupivacaine T,, are not significantly different in groups 1 and 2. is not significantly different for lidocaine and bupivacaine in group 2 . Bupivacaine, ,C , is significantly lower in group 2 than in group 1. "Statistical significance between groups: P < 0.001.
,T
and the time the children started to cry or to complain of pain. Pain was assessed only during the first eight postoperative hours. This assessment of the incidence of postoperative analgesia, also used by parents and nurses to determine when pain required the administration of analgesics, has been previously used to compare different analgesic techniques for circumcision (2).
Assay In each patient, 2 mL of venous blood was taken immediately before and 5, 10, 20, 30, 60, 90, and 120 min after the injection of the local anesthetic solution. The blood sample was allowed to clot and then was centrifuged. Serum was stored at -20°C until local anesthetic concentrations were determined using a gas chromatograph with a specific nitrogen detector. Etidocaine was used as internal standard, and a single extraction in toluene was performed (11).Sensitivity of the assay was 0.01 pg/mL for bupivacaine and 0.05 pglmL for lidocaine. The within-day coefficient of variation was less than 12% at 30 ngimL and less than 5% at 200 ng/mL for both drugs.
Statistics Kruskrall-Wallis and Mann-Whitney tests were used when appropriate. The incidence of pain in the two
groups was compared using a 2 test with Yates' correction. A value of P < 0.05 was considered to be statistically significant.
Results No complications of penile block were observed. Both groups were of similar age and weight (Table 1).In no patients did serum concentrations of local anesthetic reach levels generally considered to be in the toxic range (12,13) (Table 1). The patterns of serum concentrations of bupivacaine as a function of time were significantly different in the two groups (Figure 1;P < 0.001) but time to peak concentration (Tmax)did not significantly differ (23 t 5 min in group 1and 27 ? 19 min in group 2, mean ? SD). Mean serum bupivacaine concentrations were 2.5-6 times higher in group 1. The mean maximal bupivacaine serum concentration (Cmax)was three times higher in group 1 than in group 2 (P < 0.001). In group 2, T,, was similar for lidocaine (27 -+ 19 min) and bupivacaine (27 ? 18 min). During the first eight postoperative hours, the incidence of pain was the same in the two groups: two of six patients. The duration of the pain-free period did not differ significantly in the two groups: 6.7 -+ 1.7 h (group 1) and 7.4 +- 1.0 h (group 2).
CLINICAL REPORTS
ANESTH ANALG 1990:71:42>6
03
-
0,4
-
0,3
-
0,2
-
A
.
425
EIl
3 to
0
2
E w
0
z 0
0
5
3
E
0,1
w
v)
0,o
--
0
20
40
I
1
1
60
80
100
Discussion Penile block is a safe and efficient method for providing postcircumcision analgesia (1,2,5,6). In the two groups of the present study, the duration of the pain-free period postoperatively was greater than previously reported with 0.5% bupivacaine (2). This was achieved using very low drug dosage, making the block still safer, as indicated by serum concentrations of local anesthetics. The serum concentrations of local anesthetics were lower than levels generally considered to be in the toxic range: 1 . 6 4 pg/mL for bupivacaine and 5-10 pg/mL for lidocaine (11,12). Furthermore, in most patients, bupivacaine serum concentrations were lower than unbound drug concentrations reported as toxic (14). We therefore chose not to determine the bupivacaine free fraction. The reduction of the risk of toxicity associated with local anesthetics that we observed is partly related to the low dosage of local anesthetics used, as bupivlevels in group 1 were proportionally acaine C,, lower than reported during caudal block, where dosages used are generaIly five times greater (4). The addition of lidocaine to bupivacaine enhances the safety of penile block because bupivacaine serum concentrations are reduced. But they were reduced more than expected when the amount of bupivacaine injected was halved by mixing equal volumes of lidocaine and bupivacaine: mean serum concentrations in group 2 were consistently less than one-half
120
140
Time (min)
Figure 1. Serum local anesthetic concentrations as a function of time after injection. Mean serum concentrations of local anesthetics are represented with their standard deviation: group 1 bupivacaine only (m); group 2 lidocaine (0) plus bupivacaine (+). Serum bupivacaine levels were significantly lower in group 2 than in group 1 at each time ( P < 0.001). In group 2, time-course of serum levels of bupivacaine and lidocaine differ significantly from each other (P < 0.001).
of those in group 1. Furthermore, in group 2 the bupivacaine concentration versus time curve was flatter than in group 1, suggesting that bupivacaine absorption was altered by mixing it with lidocaine. As a consequence, mean bupivacaine C,, levels in group 2 were a third of those in group 1. Cumulative bupivacaine absorption could not, however, be assessed in the two groups because the area under the concentration-time curve could not be extrapolated to infinity because of the limited number of blood samples taken. Assuming that local anesthetic absorption does not depend on whether the site of injection was the caudal or penile as suggested by bupivacaine absorption parameters (4), it is likely that lidocaine absorption is also altered by the addition of bupivacaine. Indeed, even though the C,, levels of lidocaine were reduced in proportion to the reduction of the amount of lidocaine injected, the T,, level for lidocaine was greater with penile block in this study than during caudal block as reported by others (3). It is likely that each local anesthetic in the mixture
426
CLINICAL REPORTS
ANESTH ANALG 1990;71:42?--6
we used altered the absorption of the other. Mechanisms involved in such alterations have not yet been adequately investigated. Because absorption of local anesthetics depends on the mass action law, it is likely that alteration of dosage and concentration of a given local anesthetic can change its absorption characteristics (12). Thus, lowering the dosage and concentration of bupivacaine in group 2 decreased its Whether this limitation is absorption rate and C,,. proportional to the reduction of drug dosage and concentration has not been determined, so that no conclusion can be drawn on the low ratio of mean bupivacaine concentrations between groups 1 and 2 in the present study. It is also possible that intrinsic vasoactive properties of each individual drug may interfere with drug absorption because the latter also depends on regional blood flow (15). Aps and Reynolds have reported that, after intradermal administration, 0.25% bupivacaine induces local vasodilatation (16), whereas under the same conditions 0.570 lidocaine and 0.125% bupivacaine alone induce either vasodilatation or vasoconstriction (16). Unfortunately, the effects of the mixture of the two local anesthetics on vasoactivity have not been investigated. Nevertheless, it is likely that unpredictable vasoactive effects of 0.5% lidocaine and 0.125% bupivacaine account for the greater variability of bupivacaine T,,,, in group 2. In the present study, the duration of postoperative analgesia provided by penile block was longer than previously reported with 0.5% bupivacaine (2). This is probably a consequence of delayed drug absorption, associated with reduction in both dosage and concentration of bupivacaine used. The lack of difference in the duration of analgesia between our two groups of patients may be due to the fact that differences in local vasomotor activity of the two anesthetic solutions used are counteracted by the effect of drug concentration, as suggested by Aps and Reynolds (16). In conclusion, the use of low dosage of local anesthetics for penile block increases the duration of postoperative analgesia with an increased safety margin as shown by low serum drug concentrations. Safety of the block is increased when a mixture of 1% lidocaine and 0.25% bupivacaine is used because bupivacaine C,,,, is thus reduced more than expected
due simply to reduction in amount of bupivacaine injected.
References 1. Lunn JW. Postoperative pain after circumcision. Anaesthesia 1979;34:552-4. 2. Tree-Trakarn T, Pirayavaraporn S. Postoperative pain relief for circumcision in children: comparison among morphine, nerve block and topical analgesia. Anesthesiology 1985;62:519-22. 3. Ecoffey C, Desparmet J, Berdeaux A, Maury M, Giudicelli JF, Saint-Maurice C. Pliarmacokinetics of lignocaine in children following caudal anaesthesia. Br J Anaesth 1984;56:1399402. 4. Ecoffey C, Desparmet J, Berdeaux A, Maury M, Giudicelli JF, Saint-Maurice C. Bupivacaine in children: pharmacokinetics following caudal anesthesia. Anesthesiology 1985;63:447-8. 5. Kirya C, Werhmann MW Jr. Neonatal circumcision and penile dorsal nerve block-a painless procedure. J Pediatrics 1978;92: 99&1000. 6. Carlsson P, Svensson J. The duration of pain relief after penile block to boys undergoing circumcision. Acta Anaesthesiol Scand 1984;28:432-4. 7. Magee DA, Seet PT, Holland AJC. Epidural anaesthesia with mixtures of bupivacaine and lignocaine. Can Anaesth Soc J 1983;30:174-8. 8. Goolkasian DL, Slaughter RL, Edwards DJ, Lalka D. Displacement of lidocaine from serum alpha 1 acid glycoprotein binding sites by basic drugs. Eur J Clin Pharmacol 1983;25:41%7. 9. Dirkes WE, Gregg RV, Raj PP, Coyle DE, Denson DD. Clinical significance of drug displacement interactions between amide local anesthetics. Anesthesiology 1985;63:A210. 10. McNamara PJ, Slaughter RL, Pieper JA, Wigman MG, Lalka D. Factors influencing serum protein binding of lidocaine in humans. Anesth Analg 1981;60:395-400, 11. Coyle DE, Denson DD. Simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine and methadone. Ther Drug Monit 1986;8:9&101. 12. Tucker GT, Mather LE. Absorption and disposition of local anesthetics: pharmacokinetics. In: Cousins MJ, Bridenbaugh PO, eds. Neural blockade in clinical anesthesia and management of pain. Philadelphia: JB Lippincott, 1980:4585. 13. Reynolds F. A comparison of the potential toxicity of bupivacaine, lignocaine and meyivacaine during epidural blockade for surgery. Br J Anaesth 1971;43:567-72. 14. Denson DD, Myers JA, Hartrick CT, Pither CP, Coyle DE, Raj PP. The relationship between free bupivacaine concentration and central nervous system toxicity. Anesthesiology 1984;61: A211. 15. Tucker GT. Absorption and disposition of local anesthetics in relation to regional blood flow changes. In: Van Kleef JW et al., eds. Current concepts in regional anaesthesia. Boston and the Hague: Martinus Nijhoff, 1984:192. 16. Aps C, Reynolds F. The effect of concentration on vasoactivity of bupivacaine and lignocaine. Br J Anaesth 1976;48:1171-4.
423
Clinical Reports Local Anesthetic Serum Concentrations After Penile Nerve Block in Children Michel Sfez, MD, Yann Le Mapihan, Helene Dreux-Boucard, MD
MD,
Xavier Mazoit,
Key Words: ANESTHESIA, PEDIATRIC. ANESTHETIC TECHNIQUES, REGroNAL-penile block. ANESTHETICS, LOCAL-bupivacaine, lidocaine. Regional anesthesia provides adequate postoperative analgesia in children undergoing circumcision (1,2). Because caudal anesthesia can lead to local anesthetic serum concentrations close to levels considered to be in the toxic range (3,4), penile block may be the safer regional technique as the drug dosage used is very low (2,5,6), although serum levels of local anesthetics have not been determined. In addition, there is no agreement on the proper drug and dosage to use in order to provide the most rapid onset and longest duration of analgesia with the lowest peak serum concentration of local anesthetics. A mixture of lidocaine and bupivacaine may reduce the time of onset of analgesia without reducing its duration (7), although it might enhance the risk of toxicity due to each individual drug (8-10). The aim of this study was therefore to assess the duration of analgesia and to determine the timecourse of serum concentrations of lidocaine and bupivacaine used in combination as well as of bupivacaine alone when used in children undergoing circumcision with general anesthesia supplemented by penile block.
Supported in part by grants from Roger Bellon Laboratoires. Received from the Departments of Anesthesiology, HBpital Jean Verdier, Bondy, France, and HBpital Robert Ballanger, Villepinte, France. Accepted for publication May 24, 1990. Address correspondence to Dr. Sfez, MD, C.C.B.B. 105, Avenue Victor Hugo, 92100 Boulogne Billancourt, France. 01990 by the International Anesthesia Research Society
MD,
and
Patients and Methods Patients The study was approved by the local ethical committee and informed consent was obtained from the parents. Twelve boys, ASA physical status I, aged 3-11 yr, weighing 13-34 kg, were randomly assigned to have penile blocks performed while anesthetized with halothane-nitrous oxide-oxygen using 0.25% bupivacaine alone (group 1, n = 6) or 1% lidocaine plus 0.25% bupivacaine (group 2, n = 6). In group 2, the mixture of local anesthetics was obtained by mixing equal volumes of each drug.
Anesthetic Technique Halothane (up to 2%) was given in 50% nitrous oxide and 50% oxygen, through a face mask in an open circuit. Once the children were anesthetized, a short 22-gauge indwelling catheter was placed in a forearm vein for blood sampling, and penile block was then performed. A bilateral approach, modified from the technique described by Kirya and Werhmann (5) was used. On each side, a paramedian injection of 0.1 mLlkg of anesthetic solution was performed after the needle penetrated Bucks fascia and aspiration was negative for blood. Patients therefore were given 0.5 mgikg bupivacaine in group 1 and 0.25 mg/kg bupivacaine with 1 mglkg lidocaine in group 2. No additional intraoperative or postoperative analgesic was given until children complained of pain.
Clinical Assessment The postoperative pain-free period was defined as the time between termination of general anesthesia
424
CLINICAL REPORTS
ANESTH ANALG 1990;71:42>6
Table 1. Demographic Data and Pharmacokinetics of Local Anesthetics C,,
Patient No. Group 1 1 2 3 4 5 6
Mean SD
Group 2 7 8 9 10 11 12 Mean SD
Age (yr) 10.5 4.5 4.5 4 5 5.5 5.55 2.5
3 4.5 5.5 10.8 7.2 4 5.84 2.84
Weight (kg)
bupivacaine (FgimL)
T,,,,
bupivacaine (min)
C,,
lidocaine bg/mL)
T,,
lidocaine (min)
31 19 13 20 23 18
0.35 0.13 0.26 0.32 0.35 0.21
30 30 20 20 20 20
20.7 6.0
0.27 0.09"
23 5
13 21 18 33.5 22.5 20
0.07 0.06 0.06 0.09 0.16 0.09
30 25 5 30 60 10
0.31 0.39 0.23 0.40 0.38 0.47
30 20 10 20 60 20
21.3 6.8
0.09 0.04'
27 19
0.36 0.08
27 18
Age, weight, and bupivacaine T,, are not significantly different in groups 1 and 2. is not significantly different for lidocaine and bupivacaine in group 2 . Bupivacaine, ,C , is significantly lower in group 2 than in group 1. "Statistical significance between groups: P < 0.001.
,T
and the time the children started to cry or to complain of pain. Pain was assessed only during the first eight postoperative hours. This assessment of the incidence of postoperative analgesia, also used by parents and nurses to determine when pain required the administration of analgesics, has been previously used to compare different analgesic techniques for circumcision (2).
Assay In each patient, 2 mL of venous blood was taken immediately before and 5, 10, 20, 30, 60, 90, and 120 min after the injection of the local anesthetic solution. The blood sample was allowed to clot and then was centrifuged. Serum was stored at -20°C until local anesthetic concentrations were determined using a gas chromatograph with a specific nitrogen detector. Etidocaine was used as internal standard, and a single extraction in toluene was performed (11).Sensitivity of the assay was 0.01 pg/mL for bupivacaine and 0.05 pglmL for lidocaine. The within-day coefficient of variation was less than 12% at 30 ngimL and less than 5% at 200 ng/mL for both drugs.
Statistics Kruskrall-Wallis and Mann-Whitney tests were used when appropriate. The incidence of pain in the two
groups was compared using a 2 test with Yates' correction. A value of P < 0.05 was considered to be statistically significant.
Results No complications of penile block were observed. Both groups were of similar age and weight (Table 1).In no patients did serum concentrations of local anesthetic reach levels generally considered to be in the toxic range (12,13) (Table 1). The patterns of serum concentrations of bupivacaine as a function of time were significantly different in the two groups (Figure 1;P < 0.001) but time to peak concentration (Tmax)did not significantly differ (23 t 5 min in group 1and 27 ? 19 min in group 2, mean ? SD). Mean serum bupivacaine concentrations were 2.5-6 times higher in group 1. The mean maximal bupivacaine serum concentration (Cmax)was three times higher in group 1 than in group 2 (P < 0.001). In group 2, T,, was similar for lidocaine (27 -+ 19 min) and bupivacaine (27 ? 18 min). During the first eight postoperative hours, the incidence of pain was the same in the two groups: two of six patients. The duration of the pain-free period did not differ significantly in the two groups: 6.7 -+ 1.7 h (group 1) and 7.4 +- 1.0 h (group 2).
CLINICAL REPORTS
ANESTH ANALG 1990:71:42>6
03
-
0,4
-
0,3
-
0,2
-
A
.
425
EIl
3 to
0
2
E w
0
z 0
0
5
3
E
0,1
w
v)
0,o
--
0
20
40
I
1
1
60
80
100
Discussion Penile block is a safe and efficient method for providing postcircumcision analgesia (1,2,5,6). In the two groups of the present study, the duration of the pain-free period postoperatively was greater than previously reported with 0.5% bupivacaine (2). This was achieved using very low drug dosage, making the block still safer, as indicated by serum concentrations of local anesthetics. The serum concentrations of local anesthetics were lower than levels generally considered to be in the toxic range: 1 . 6 4 pg/mL for bupivacaine and 5-10 pg/mL for lidocaine (11,12). Furthermore, in most patients, bupivacaine serum concentrations were lower than unbound drug concentrations reported as toxic (14). We therefore chose not to determine the bupivacaine free fraction. The reduction of the risk of toxicity associated with local anesthetics that we observed is partly related to the low dosage of local anesthetics used, as bupivlevels in group 1 were proportionally acaine C,, lower than reported during caudal block, where dosages used are generaIly five times greater (4). The addition of lidocaine to bupivacaine enhances the safety of penile block because bupivacaine serum concentrations are reduced. But they were reduced more than expected when the amount of bupivacaine injected was halved by mixing equal volumes of lidocaine and bupivacaine: mean serum concentrations in group 2 were consistently less than one-half
120
140
Time (min)
Figure 1. Serum local anesthetic concentrations as a function of time after injection. Mean serum concentrations of local anesthetics are represented with their standard deviation: group 1 bupivacaine only (m); group 2 lidocaine (0) plus bupivacaine (+). Serum bupivacaine levels were significantly lower in group 2 than in group 1 at each time ( P < 0.001). In group 2, time-course of serum levels of bupivacaine and lidocaine differ significantly from each other (P < 0.001).
of those in group 1. Furthermore, in group 2 the bupivacaine concentration versus time curve was flatter than in group 1, suggesting that bupivacaine absorption was altered by mixing it with lidocaine. As a consequence, mean bupivacaine C,, levels in group 2 were a third of those in group 1. Cumulative bupivacaine absorption could not, however, be assessed in the two groups because the area under the concentration-time curve could not be extrapolated to infinity because of the limited number of blood samples taken. Assuming that local anesthetic absorption does not depend on whether the site of injection was the caudal or penile as suggested by bupivacaine absorption parameters (4), it is likely that lidocaine absorption is also altered by the addition of bupivacaine. Indeed, even though the C,, levels of lidocaine were reduced in proportion to the reduction of the amount of lidocaine injected, the T,, level for lidocaine was greater with penile block in this study than during caudal block as reported by others (3). It is likely that each local anesthetic in the mixture
426
CLINICAL REPORTS
ANESTH ANALG 1990;71:42?--6
we used altered the absorption of the other. Mechanisms involved in such alterations have not yet been adequately investigated. Because absorption of local anesthetics depends on the mass action law, it is likely that alteration of dosage and concentration of a given local anesthetic can change its absorption characteristics (12). Thus, lowering the dosage and concentration of bupivacaine in group 2 decreased its Whether this limitation is absorption rate and C,,. proportional to the reduction of drug dosage and concentration has not been determined, so that no conclusion can be drawn on the low ratio of mean bupivacaine concentrations between groups 1 and 2 in the present study. It is also possible that intrinsic vasoactive properties of each individual drug may interfere with drug absorption because the latter also depends on regional blood flow (15). Aps and Reynolds have reported that, after intradermal administration, 0.25% bupivacaine induces local vasodilatation (16), whereas under the same conditions 0.570 lidocaine and 0.125% bupivacaine alone induce either vasodilatation or vasoconstriction (16). Unfortunately, the effects of the mixture of the two local anesthetics on vasoactivity have not been investigated. Nevertheless, it is likely that unpredictable vasoactive effects of 0.5% lidocaine and 0.125% bupivacaine account for the greater variability of bupivacaine T,,,, in group 2. In the present study, the duration of postoperative analgesia provided by penile block was longer than previously reported with 0.5% bupivacaine (2). This is probably a consequence of delayed drug absorption, associated with reduction in both dosage and concentration of bupivacaine used. The lack of difference in the duration of analgesia between our two groups of patients may be due to the fact that differences in local vasomotor activity of the two anesthetic solutions used are counteracted by the effect of drug concentration, as suggested by Aps and Reynolds (16). In conclusion, the use of low dosage of local anesthetics for penile block increases the duration of postoperative analgesia with an increased safety margin as shown by low serum drug concentrations. Safety of the block is increased when a mixture of 1% lidocaine and 0.25% bupivacaine is used because bupivacaine C,,,, is thus reduced more than expected
due simply to reduction in amount of bupivacaine injected.
References 1. Lunn JW. Postoperative pain after circumcision. Anaesthesia 1979;34:552-4. 2. Tree-Trakarn T, Pirayavaraporn S. Postoperative pain relief for circumcision in children: comparison among morphine, nerve block and topical analgesia. Anesthesiology 1985;62:519-22. 3. Ecoffey C, Desparmet J, Berdeaux A, Maury M, Giudicelli JF, Saint-Maurice C. Pliarmacokinetics of lignocaine in children following caudal anaesthesia. Br J Anaesth 1984;56:1399402. 4. Ecoffey C, Desparmet J, Berdeaux A, Maury M, Giudicelli JF, Saint-Maurice C. Bupivacaine in children: pharmacokinetics following caudal anesthesia. Anesthesiology 1985;63:447-8. 5. Kirya C, Werhmann MW Jr. Neonatal circumcision and penile dorsal nerve block-a painless procedure. J Pediatrics 1978;92: 99&1000. 6. Carlsson P, Svensson J. The duration of pain relief after penile block to boys undergoing circumcision. Acta Anaesthesiol Scand 1984;28:432-4. 7. Magee DA, Seet PT, Holland AJC. Epidural anaesthesia with mixtures of bupivacaine and lignocaine. Can Anaesth Soc J 1983;30:174-8. 8. Goolkasian DL, Slaughter RL, Edwards DJ, Lalka D. Displacement of lidocaine from serum alpha 1 acid glycoprotein binding sites by basic drugs. Eur J Clin Pharmacol 1983;25:41%7. 9. Dirkes WE, Gregg RV, Raj PP, Coyle DE, Denson DD. Clinical significance of drug displacement interactions between amide local anesthetics. Anesthesiology 1985;63:A210. 10. McNamara PJ, Slaughter RL, Pieper JA, Wigman MG, Lalka D. Factors influencing serum protein binding of lidocaine in humans. Anesth Analg 1981;60:395-400, 11. Coyle DE, Denson DD. Simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine and methadone. Ther Drug Monit 1986;8:9&101. 12. Tucker GT, Mather LE. Absorption and disposition of local anesthetics: pharmacokinetics. In: Cousins MJ, Bridenbaugh PO, eds. Neural blockade in clinical anesthesia and management of pain. Philadelphia: JB Lippincott, 1980:4585. 13. Reynolds F. A comparison of the potential toxicity of bupivacaine, lignocaine and meyivacaine during epidural blockade for surgery. Br J Anaesth 1971;43:567-72. 14. Denson DD, Myers JA, Hartrick CT, Pither CP, Coyle DE, Raj PP. The relationship between free bupivacaine concentration and central nervous system toxicity. Anesthesiology 1984;61: A211. 15. Tucker GT. Absorption and disposition of local anesthetics in relation to regional blood flow changes. In: Van Kleef JW et al., eds. Current concepts in regional anaesthesia. Boston and the Hague: Martinus Nijhoff, 1984:192. 16. Aps C, Reynolds F. The effect of concentration on vasoactivity of bupivacaine and lignocaine. Br J Anaesth 1976;48:1171-4.
