- Email: [email protected]
Phenol as an adjuvant anesthetic for tympanostomy tube insertion
International Journal of Pediatric Otorhinolaryngology, 21 (1991) 51-58 Elsetier Science Publishers B.V.
PEDOT
51
00690
Phenol as an adjuvant anesthetic for tympanostomy tube insertion Peter W. Orobello Jr. r, Robert I. Park I, Randall C.Wetzel Laura J. Belcher r and Robert M. Naclerio ’
2,
’ Diwion of Pediatric Otolaryngologv, Department of Otolaryngology - Head and Neck Surgery and the ’ Department of Anesthesiology and Critical Care Medicine of The Johns Hopkins University School of Medicine, Baltimore, MD (U.S.A.) (Received 30 July 1990) (Accepted 21 October 1990)
Key words: Tympanostomy
tube; Anesthesia;
Phenol;
Pain
Abstract
The use of inhalational anesthesia for insertion of tympanostomy tubes in children provides no postoperative pain relief. Our retrospective analysis of children following tympanostomy tube insertion previously had shown significant postoperative elevations of blood pressure and heart rate in over 70% of cases. These changes, along with behavioral findings and complaints of discomfort, are suggestive of pain. Phenol has been used in adults for local anesthesia during tympanostomy tube insertion. This study determined prospectively whether pain occurred postoperatively and whether phenol placed on the tympanic membrane just prior to myringotomy would reduce postoperative pain in children, as measured by behavioral and physiologic parameters. Results of a double-blind, randomized trial in 46 children showed that both the phenol-treated and the control groups demonstrated significant elevations in pain scores postoperatively (P = O.OOOl),which then slowly diminished to baseline by 45 min to one hour. The phenol group had consistently higher pain scores than the non-phenol group (P -C0.001). Possible reasons for these findings are discussed.
Introduction
Most otolaryngologists believe that children experience pain after tympanostomy tube insertion. In a retrospective analysis, we found that following tympanostomy Correspondence: R.M. Naclerio, MD 21205, U.S.A.
Carnegie
490, The Johns Hopkins
Hospital,
600 N. Wolfe St., Baltimore,
52
tube insertion children showed significant elevations in heart rate and blood pressure in over 70% of cases. Suggesting significant discomfort, this occurred with use of inhalational anesthesia, which provides relief of pain intraoperatively but not postoperatively. In adults undergoing tympanostomy tube insertion, phenol has been effective as a local anesthetic [5]. Although a burning sensation is felt immediately upon placement of the phenol, anesthesia quickly ensues, allowing painless myringotomy and recovery. The purpose of this study was to determine whether children experienced pain after myringotomy and whether topical anesthesia of the tympanic membrane with phenol during general anesthesia would reduce postoperative pain, as measured by behavioral and physiologic parameters.
Materials and methods
Forty-six children between 7 months and 6 years of age who only required myringotomy and tympanostomy tube placement for persistent otitis media with effusion were randomized into two groups after induction of anesthesia. One group received topical phenol (90%) on the tympanic membrane just prior to myringotomy, and the other group received no topical analgesia. Inhalational anesthesia and surgical techniques were otherwise the same for both groups (see details below). Excluded from the study were cases in which trauma to the ear canal occurred or anesthesia time exceeded 20 min. No premeditation was given prior to induction of anesthesia with oxygen, nitrous oxide and halothane (l-4%), standard practice at our institution. Ventilation was provided by mask alone, and patients received no intravenous catheters, and, hence, no intravenous supplementation of anesthesia. Intraoperatively, blood pressure and heart rate were recorded serially (Dynamap). Records were kept to indicate the adequacy of anesthesia and the hemodynamic response to surgical stimuli. The surgical technique consisted of gently cleaning the ear canal of cerumen with a curette, placing the phenol on the anterior inferior quadrant of the tympanic membrane (in the phenol-treated group), performing the myringotomy over the site of the phenol, suctioning the middle ear dry, and placing a type 1 Paparella tube followed by Cortisporin Otic Suspension in the ear canal. The non-phenol-treated group received the same procedure with the exception of the phenol placement. All measurements of postoperative pain were made by the same observer, who was unaware of treatment. Scoring of pain was based upon a current clinically accepted method in children [1,2]. Heart rate, blood pressure, crying, movement, vomiting, agitation, posturing, verbalization of pain, and requirements for pain medication were measured on a 3 point scale (Table I). The pain scores were recorded preoperatively, immediately postoperatively, and every 15 min for one hour. A total score was calculated by adding the 9 individual scores. Statistical analysis was performed using a split-plot repeated measures analysis of variance [7]. P values were calculated between phenol- and non-phenol-treated
53 TABLE
I
Physiologic and behavioral parameters
of pain scoring system Score
Heart rate: % change above baseline > 10% > 20% > 30% Blood pressure: % change above baseline > 10% > 20% > 30% Crying Silent, comfortable Consolable Unconsolable, screaming Movement Resting Restless Thrashing vomiting None 1-3 times > 3 times Agitation Sleeping Mild Hysterical Posture Normal Guarding head Holding ears Verbalization of pain None When asked and localized Spontaneously Analgesia None Non-narcotic Narcotic
2 0
1 2 0
1 2 0
1 2 0
1 2 0
1 2 0
1 2
groups and within groups over the duration of the experiments. Least significant differences (P -c0.05) were then calculated [3] between phenol and non-phenol groups as well as pre- and postoperative results within groups for each parameter of pain analyzed. To determine whether the pain score postoperatively reflected differences in preoperative agitation (i.e. do children who cry preoperatively before induction show a higher ‘pain’ score upon awakening), linear regression analysis between preoperative and each of the 5 postoperative data was done.
54
Results
Mean total scores showed significant increases in both phenol and control groups post-operatively. The phenol group (Fig. 1) showed significant differences at all postoperative times (P = 0.0001). In every case, the postoperative mean total pain score was higher for the phenol-treated patients than for the non-phenol-treated patients. Figure 2 depicts the 7 behavioral parameters used to define pain in children. When comparing the phenol- and non-phenol-treated groups, differences were noted in agitation, posturing and pain verbalization scores (Table II). Again, where differences are significant, the phenol-treated patients’ scores were higher. When examining the changes within each group, significant differences were demonstrated in all parameters except vomiting. For crying, movement, agitation, posturing and pain verbalization, the immediate postoperative scores were greater than the preoperative scores. These gradually returned towards baseline over the next 45 min to one hour. In both phenol- and non-phenol-treated groups, there was a postoperative change in behavioral parameters suggestive of pain. In addition to the preoperative and timed postoperative measurements for pulse and blood pressure, additional intraoperative measurements were recorded. The purpose of this was to detect adequacy of inhalation anesthesia by monitoring these physiologic parameters following myringotomy. Adequate intraoperative anesthesia was accomplished (Fig. 3). Heart rate was different between phenol- and non-phenol-treated groups (P = 0.045). Blood pressure showed significant differences between groups preoperatively; and, when absolute blood pressures were compared, no significant differences were noted between groups. However, when the changes in blood pressure were analyzed, significant differences were noted (P = 0.002) between phenol- and non-phenol-treated children. * :
6-
5
5-
f2
.f
4-
h %
3-
z I-
2-
0
Phenol
0
No Phenol
s S' o-
I 8 E a
5 0, 2 ki a
1 15
1 30
I 45
60
Time (minutes)
Fig. 1. Total pain score comparing phenol- and non-phenol-treated patients. * Indicates significant differences between groups at P < 0.05. (bars = S.E.M.)
statistically
55
a) g
1
x
.-P
;”
a
s
dr
0
Phenol
0
No Phenol
Time (minutes)
e)
a‘
5
d
h f
Time (minutes)
Time (minutes)
Fig. 2. Individual behavorial indicators of postoperative pain in children in phenol- and non-phenoltreated patients. Mean scores of (a) crying, (b) movement, (c) vomiting, (d) agitation, (e) posturing, (f) * Indicates statistically significant differences pain verbalization and (g) requirement for analgesia. between groups at P -z 0.05. (bars = S.E.M.)
Phenol had a significant effect on how patients responded were noted for the total score, the changes in blood pressure (interaction term, Table II). For crying, movement, agitation ters, however, the phenol curves appear simply to be shifted
to surgery. Differences and pain verbalization and posturing parameupwards.
56
TABLE II Analysis of variance P values between phenol and non-phenol-treated of the experiments, and interaction terms
Total score Heart rate Change in heart rate Blood pressure Change in blood pressure Crying Movement Vomiting Agitation Posturing Pain verbalization Analgesia
Within
Interaction
O.cQOl
0.0001
0.0045
0.0450
0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0775 0.0001 0.0001 0.0001 0.0297
0.4816 0.3823 0.0522 0.0001 0.9383 0.2686 0.8835 0.8895 0.1399 0.0151 0.7018
0.7236 0.8457 0.0024 0.0703 0.0813 0.4934 0.0025 o.cQO9 0.0056 0.2440
z
E
0
Phenol
0
No Phenol
‘0 ; 2
groups, within groups over the duration
” ;I
f
8 2
C
2 ? 0,
15
30
45
60
Time (minutes)
d
b)
8
;
5
tj 2
z
N
%
z"
6
z
E B u
nz
15
30
45
60
Time (minutes)
Fig. 3. Heart rate (a) and blood pressure (b) in phenol- and non-phenol-treated patients (myr = time of myringotomy). * Indicates statistically significant differences between groups at P c 0.05. (bars = S.E.M.)
TABLE
III
Correlation coefficients comparing preoperative and postoperatwe pain scores in all patients Preop Preop Preop Preop Preop
vs vs vs vs vs
recovery room 15 min postop 30 min postop 45 min postop 60 min postop
0.089 0.086 0.026 -0.159 -0.121
Table III lists the correlation coefficients for each of the 5 preoperative and postoperative comparisons. No significant correlations existed between agitation prior to induction and postoperative pain scores. Hence, it does not appear that agitated children before anesthesia were necessarily the ones who awoke with high pain scores.
These data demonstrate that tympanostomy tube insertion is associated with physiologic and behavioral responses as well as complaints of discomfort, indicative of pain. The purpose of this study was to demonstrate a possible means of diminishing postoperative pain following tympanostomy tube insertion. The application of phenol on the tympanic membrane accomplished the opposite effect. Instead of providing prolonged topical anesthesia, it appears that the phenol actually induced more pain, presumably from its irritative effects. The scores in Fig. 1 show that the total pain level started at a higher level immediately postoperatively, but the slope of decline was the same in both groups, indicating that the initial discomfort was greater but was not sustained. Whether discomfort was decreased in treated children after the first hour was not studied. Phenol, also known as carbolic acid, is an aromatic hydrocarbon derived from coal tar. When used in high concentrations, phenol causes protein denaturation and coagulation of surface keratin, which in turn forms a protective eschar preventing further absorption of phenol [6]. This coagulation necrosis results in local devascularization and destruction of nerve endings, thereby providing local anesthesia. Thus, the method by which this anesthesia is produced may be responsible for the increased ‘pain’ scores in those patients receiving topical phenol application on their tympanic membranes. Although toxic effects of phenol have been reported following chemical face peels [4] and include cardiac and central nervous system stimulation (followed later by cardiac and CNS depression), the absorption of phenol in these 50% solutions applied to a large surface area is much higher than would be expected from the minute amount applied to the myringotomy sites. Nevertheless, this effect cannot be excluded completely. Even without phenol, the physiologic scores, behavioral scores, and actual complaints of discomfort indicate that rnyringotomy and tympanostomy tube inser-
58
tion do result in postoperative pain. This was evident immediately upon awakening and subsided over the next 45 min to 1 h. The scoring system presented here thus provides a means of quantifying postoperative pain in children following this procedure and can be used for evaluating other means of diminishing postoperative pain.
Conclusions
This study demonstrates that myringotomy and tympanostomy tube insertion results in behavioral and physiologic changes, indicative of pain. The intraoperative application of phenol to the tympanic membrane prior to myringotomy during inhalation anesthesia provided no postoperative analgesia.
References 1 Aldrete, J.A. and Krouhk, D., Postanesthetic recovery score, Anesth. Analg., 49 (1970) 924-933. 2 Hannallah, R.S., Broadman, L.M., Belman, A.B., Abramowitz, M.D. and Epstein, B.S., Comparison of caudal and ilio-inguinal/ihohypogastric nerve blocks for control of postorchiectomy pain in pediatric ambulatory surgery, Anesthesiology, 66 (1987) 832-834. 3 Kirk, R.E., Split plot-factoral design: design with group treatment confounding. In Experimental Design Procedures for the Behavioral Sciences, 2nd edn., Brooks Cole Publishing Co., Pacific Grove, CA, 1982, 489 pp. 4 Litton, C., Szachowicz, E.H. and Trinidad, G.P., Present day status of chemical face peel, Aesth. Plast. Surg., 10 (1986) l-7. 5 Neisskopf, A., Phenol anesthesia for myringotomy, Laryngoscope, 93 (1983) 114. 6 Rothman, S., The principles of percutaneous absorption, J. Lab. Med., 28 (1943) 1305-1309. 7 Statview 512+ program for the Apple Macintosh computer, 1988.
PEDOT
51
00690
Phenol as an adjuvant anesthetic for tympanostomy tube insertion Peter W. Orobello Jr. r, Robert I. Park I, Randall C.Wetzel Laura J. Belcher r and Robert M. Naclerio ’
2,
’ Diwion of Pediatric Otolaryngologv, Department of Otolaryngology - Head and Neck Surgery and the ’ Department of Anesthesiology and Critical Care Medicine of The Johns Hopkins University School of Medicine, Baltimore, MD (U.S.A.) (Received 30 July 1990) (Accepted 21 October 1990)
Key words: Tympanostomy
tube; Anesthesia;
Phenol;
Pain
Abstract
The use of inhalational anesthesia for insertion of tympanostomy tubes in children provides no postoperative pain relief. Our retrospective analysis of children following tympanostomy tube insertion previously had shown significant postoperative elevations of blood pressure and heart rate in over 70% of cases. These changes, along with behavioral findings and complaints of discomfort, are suggestive of pain. Phenol has been used in adults for local anesthesia during tympanostomy tube insertion. This study determined prospectively whether pain occurred postoperatively and whether phenol placed on the tympanic membrane just prior to myringotomy would reduce postoperative pain in children, as measured by behavioral and physiologic parameters. Results of a double-blind, randomized trial in 46 children showed that both the phenol-treated and the control groups demonstrated significant elevations in pain scores postoperatively (P = O.OOOl),which then slowly diminished to baseline by 45 min to one hour. The phenol group had consistently higher pain scores than the non-phenol group (P -C0.001). Possible reasons for these findings are discussed.
Introduction
Most otolaryngologists believe that children experience pain after tympanostomy tube insertion. In a retrospective analysis, we found that following tympanostomy Correspondence: R.M. Naclerio, MD 21205, U.S.A.
Carnegie
490, The Johns Hopkins
Hospital,
600 N. Wolfe St., Baltimore,
52
tube insertion children showed significant elevations in heart rate and blood pressure in over 70% of cases. Suggesting significant discomfort, this occurred with use of inhalational anesthesia, which provides relief of pain intraoperatively but not postoperatively. In adults undergoing tympanostomy tube insertion, phenol has been effective as a local anesthetic [5]. Although a burning sensation is felt immediately upon placement of the phenol, anesthesia quickly ensues, allowing painless myringotomy and recovery. The purpose of this study was to determine whether children experienced pain after myringotomy and whether topical anesthesia of the tympanic membrane with phenol during general anesthesia would reduce postoperative pain, as measured by behavioral and physiologic parameters.
Materials and methods
Forty-six children between 7 months and 6 years of age who only required myringotomy and tympanostomy tube placement for persistent otitis media with effusion were randomized into two groups after induction of anesthesia. One group received topical phenol (90%) on the tympanic membrane just prior to myringotomy, and the other group received no topical analgesia. Inhalational anesthesia and surgical techniques were otherwise the same for both groups (see details below). Excluded from the study were cases in which trauma to the ear canal occurred or anesthesia time exceeded 20 min. No premeditation was given prior to induction of anesthesia with oxygen, nitrous oxide and halothane (l-4%), standard practice at our institution. Ventilation was provided by mask alone, and patients received no intravenous catheters, and, hence, no intravenous supplementation of anesthesia. Intraoperatively, blood pressure and heart rate were recorded serially (Dynamap). Records were kept to indicate the adequacy of anesthesia and the hemodynamic response to surgical stimuli. The surgical technique consisted of gently cleaning the ear canal of cerumen with a curette, placing the phenol on the anterior inferior quadrant of the tympanic membrane (in the phenol-treated group), performing the myringotomy over the site of the phenol, suctioning the middle ear dry, and placing a type 1 Paparella tube followed by Cortisporin Otic Suspension in the ear canal. The non-phenol-treated group received the same procedure with the exception of the phenol placement. All measurements of postoperative pain were made by the same observer, who was unaware of treatment. Scoring of pain was based upon a current clinically accepted method in children [1,2]. Heart rate, blood pressure, crying, movement, vomiting, agitation, posturing, verbalization of pain, and requirements for pain medication were measured on a 3 point scale (Table I). The pain scores were recorded preoperatively, immediately postoperatively, and every 15 min for one hour. A total score was calculated by adding the 9 individual scores. Statistical analysis was performed using a split-plot repeated measures analysis of variance [7]. P values were calculated between phenol- and non-phenol-treated
53 TABLE
I
Physiologic and behavioral parameters
of pain scoring system Score
Heart rate: % change above baseline > 10% > 20% > 30% Blood pressure: % change above baseline > 10% > 20% > 30% Crying Silent, comfortable Consolable Unconsolable, screaming Movement Resting Restless Thrashing vomiting None 1-3 times > 3 times Agitation Sleeping Mild Hysterical Posture Normal Guarding head Holding ears Verbalization of pain None When asked and localized Spontaneously Analgesia None Non-narcotic Narcotic
2 0
1 2 0
1 2 0
1 2 0
1 2 0
1 2 0
1 2
groups and within groups over the duration of the experiments. Least significant differences (P -c0.05) were then calculated [3] between phenol and non-phenol groups as well as pre- and postoperative results within groups for each parameter of pain analyzed. To determine whether the pain score postoperatively reflected differences in preoperative agitation (i.e. do children who cry preoperatively before induction show a higher ‘pain’ score upon awakening), linear regression analysis between preoperative and each of the 5 postoperative data was done.
54
Results
Mean total scores showed significant increases in both phenol and control groups post-operatively. The phenol group (Fig. 1) showed significant differences at all postoperative times (P = 0.0001). In every case, the postoperative mean total pain score was higher for the phenol-treated patients than for the non-phenol-treated patients. Figure 2 depicts the 7 behavioral parameters used to define pain in children. When comparing the phenol- and non-phenol-treated groups, differences were noted in agitation, posturing and pain verbalization scores (Table II). Again, where differences are significant, the phenol-treated patients’ scores were higher. When examining the changes within each group, significant differences were demonstrated in all parameters except vomiting. For crying, movement, agitation, posturing and pain verbalization, the immediate postoperative scores were greater than the preoperative scores. These gradually returned towards baseline over the next 45 min to one hour. In both phenol- and non-phenol-treated groups, there was a postoperative change in behavioral parameters suggestive of pain. In addition to the preoperative and timed postoperative measurements for pulse and blood pressure, additional intraoperative measurements were recorded. The purpose of this was to detect adequacy of inhalation anesthesia by monitoring these physiologic parameters following myringotomy. Adequate intraoperative anesthesia was accomplished (Fig. 3). Heart rate was different between phenol- and non-phenol-treated groups (P = 0.045). Blood pressure showed significant differences between groups preoperatively; and, when absolute blood pressures were compared, no significant differences were noted between groups. However, when the changes in blood pressure were analyzed, significant differences were noted (P = 0.002) between phenol- and non-phenol-treated children. * :
6-
5
5-
f2
.f
4-
h %
3-
z I-
2-
0
Phenol
0
No Phenol
s S' o-
I 8 E a
5 0, 2 ki a
1 15
1 30
I 45
60
Time (minutes)
Fig. 1. Total pain score comparing phenol- and non-phenol-treated patients. * Indicates significant differences between groups at P < 0.05. (bars = S.E.M.)
statistically
55
a) g
1
x
.-P
;”
a
s
dr
0
Phenol
0
No Phenol
Time (minutes)
e)
a‘
5
d
h f
Time (minutes)
Time (minutes)
Fig. 2. Individual behavorial indicators of postoperative pain in children in phenol- and non-phenoltreated patients. Mean scores of (a) crying, (b) movement, (c) vomiting, (d) agitation, (e) posturing, (f) * Indicates statistically significant differences pain verbalization and (g) requirement for analgesia. between groups at P -z 0.05. (bars = S.E.M.)
Phenol had a significant effect on how patients responded were noted for the total score, the changes in blood pressure (interaction term, Table II). For crying, movement, agitation ters, however, the phenol curves appear simply to be shifted
to surgery. Differences and pain verbalization and posturing parameupwards.
56
TABLE II Analysis of variance P values between phenol and non-phenol-treated of the experiments, and interaction terms
Total score Heart rate Change in heart rate Blood pressure Change in blood pressure Crying Movement Vomiting Agitation Posturing Pain verbalization Analgesia
Within
Interaction
O.cQOl
0.0001
0.0045
0.0450
0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0775 0.0001 0.0001 0.0001 0.0297
0.4816 0.3823 0.0522 0.0001 0.9383 0.2686 0.8835 0.8895 0.1399 0.0151 0.7018
0.7236 0.8457 0.0024 0.0703 0.0813 0.4934 0.0025 o.cQO9 0.0056 0.2440
z
E
0
Phenol
0
No Phenol
‘0 ; 2
groups, within groups over the duration
” ;I
f
8 2
C
2 ? 0,
15
30
45
60
Time (minutes)
d
b)
8
;
5
tj 2
z
N
%
z"
6
z
E B u
nz
15
30
45
60
Time (minutes)
Fig. 3. Heart rate (a) and blood pressure (b) in phenol- and non-phenol-treated patients (myr = time of myringotomy). * Indicates statistically significant differences between groups at P c 0.05. (bars = S.E.M.)
TABLE
III
Correlation coefficients comparing preoperative and postoperatwe pain scores in all patients Preop Preop Preop Preop Preop
vs vs vs vs vs
recovery room 15 min postop 30 min postop 45 min postop 60 min postop
0.089 0.086 0.026 -0.159 -0.121
Table III lists the correlation coefficients for each of the 5 preoperative and postoperative comparisons. No significant correlations existed between agitation prior to induction and postoperative pain scores. Hence, it does not appear that agitated children before anesthesia were necessarily the ones who awoke with high pain scores.
These data demonstrate that tympanostomy tube insertion is associated with physiologic and behavioral responses as well as complaints of discomfort, indicative of pain. The purpose of this study was to demonstrate a possible means of diminishing postoperative pain following tympanostomy tube insertion. The application of phenol on the tympanic membrane accomplished the opposite effect. Instead of providing prolonged topical anesthesia, it appears that the phenol actually induced more pain, presumably from its irritative effects. The scores in Fig. 1 show that the total pain level started at a higher level immediately postoperatively, but the slope of decline was the same in both groups, indicating that the initial discomfort was greater but was not sustained. Whether discomfort was decreased in treated children after the first hour was not studied. Phenol, also known as carbolic acid, is an aromatic hydrocarbon derived from coal tar. When used in high concentrations, phenol causes protein denaturation and coagulation of surface keratin, which in turn forms a protective eschar preventing further absorption of phenol [6]. This coagulation necrosis results in local devascularization and destruction of nerve endings, thereby providing local anesthesia. Thus, the method by which this anesthesia is produced may be responsible for the increased ‘pain’ scores in those patients receiving topical phenol application on their tympanic membranes. Although toxic effects of phenol have been reported following chemical face peels [4] and include cardiac and central nervous system stimulation (followed later by cardiac and CNS depression), the absorption of phenol in these 50% solutions applied to a large surface area is much higher than would be expected from the minute amount applied to the myringotomy sites. Nevertheless, this effect cannot be excluded completely. Even without phenol, the physiologic scores, behavioral scores, and actual complaints of discomfort indicate that rnyringotomy and tympanostomy tube inser-
58
tion do result in postoperative pain. This was evident immediately upon awakening and subsided over the next 45 min to 1 h. The scoring system presented here thus provides a means of quantifying postoperative pain in children following this procedure and can be used for evaluating other means of diminishing postoperative pain.
Conclusions
This study demonstrates that myringotomy and tympanostomy tube insertion results in behavioral and physiologic changes, indicative of pain. The intraoperative application of phenol to the tympanic membrane prior to myringotomy during inhalation anesthesia provided no postoperative analgesia.
References 1 Aldrete, J.A. and Krouhk, D., Postanesthetic recovery score, Anesth. Analg., 49 (1970) 924-933. 2 Hannallah, R.S., Broadman, L.M., Belman, A.B., Abramowitz, M.D. and Epstein, B.S., Comparison of caudal and ilio-inguinal/ihohypogastric nerve blocks for control of postorchiectomy pain in pediatric ambulatory surgery, Anesthesiology, 66 (1987) 832-834. 3 Kirk, R.E., Split plot-factoral design: design with group treatment confounding. In Experimental Design Procedures for the Behavioral Sciences, 2nd edn., Brooks Cole Publishing Co., Pacific Grove, CA, 1982, 489 pp. 4 Litton, C., Szachowicz, E.H. and Trinidad, G.P., Present day status of chemical face peel, Aesth. Plast. Surg., 10 (1986) l-7. 5 Neisskopf, A., Phenol anesthesia for myringotomy, Laryngoscope, 93 (1983) 114. 6 Rothman, S., The principles of percutaneous absorption, J. Lab. Med., 28 (1943) 1305-1309. 7 Statview 512+ program for the Apple Macintosh computer, 1988.