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Rational selection of preanesthetic medication for oral surgical patients
Anesthesiology
Rational selection of preanesthetic medication for oral surgical patients Elem& K. Zsigmd, ANESTHESIA
RESEARCH
M.D., Pittsburgh, LABORATORY,
Pa.
ALLEGHENY
GENERAL
HOSPITAL
T
he importance of psychic management of the surgical patient before and after a surgical procedure has long been recognized, but the complex and often paradoxical actions of the drugs used in this management has continued to pose a pharmacologic dilemma, requiring further evaluation of preanesthetic medication.* The trends, goals, and obstacles of preanesthetic medication are presented in Table I. The objectives of premeditation are focused on the goals of smooth induction and good maintenance of anesthesia without adverse effects.l Complications may be avoided by the induction of a preoperative state of tranquility rather than stupor, leaving the patient oriented and cooperative. The objective is to assure a smooth induction of anesthesia and postoperative freedom from emergence delirium, confusion, and excitement.z There are, however, some obstacles to the achievement of these goals. The potential depressant effect of some agents commonly used for preanesthetic medication presents a problem, since these agents induce a state of sedation that is more profound than the desired tranquilization. This problem, which is basic to the narcotics and barbiturates, extends also to the phenothiazine congeners.1-3 This class of tranquilizers depressesthe brain stem arousal mechanism and may result in unpredictable adverse psychic effects.415 Side effects of all these drugs may be respiratory and circulatory depression, confusion, disorientation, and excitement. Othere complications linked to the use of narcotics and barbiturates include allergic reactions, nausea, and vomiting.? Barbiturates and phenothiazines often cause prolongation of anesthesia, an effect that the narcotics share.lo * Other potential side effects associated with the use of phenothiazine are the appearance of extrapyramidal motor symptoms and hepatic and hematopoietic systemic toxicity.‘j Over a period of 8 years, we have observed approximately 10,000 patients who underwent various surgical procedures in which the tranquilizer hydroxy457
458
Zsigmond
Table
I
OS., OX & 0.1’. October, 1968
Goals Preoperattie Calm and cooperative patient to facilitate smooth and uncomplicated induction Operative Maintenance of anesthesia with no complicating influence from premeditation Postoperative Uncomplicated and rapid recovery from anesthesia with relative freedom from pain and confusion, reduced incidence of nausea and vomiting
Obstacles Circulatory depression Respiratory depression Confusion Disorientation Excitement Prolongation of anesthesia Nausea Vomiting Extrapyramidal motor symptoms Allergic reactions
Sequelae Preoperative Comatose, stuporous or apprehensive, agitated, and uncooperative patients complicate anesthetic induction Operative Frequent anesthetic complications, potentiation, prolongation, severe depression, and hypotension Postoperative Delayed recovery,. emergence dellrmm, nausea, and vomiting
zine hydrochloride (Vistaril, Atarax) was used as premeditation for anesthesia and oral surgery.6 Since a number of reports in the literature have noted a definite superiority of hydroxyzine over other tranquilizers for preanesthetic medication,7-12 a double-blind evaluation of the drug’s effect on predelivery anxiety in obstetrical patients was also conducted.13 These studies revealed that hydroxyzine hydrochloride, alone or in combination with narcotics, most closely approximated the goals of preanesthetic medication. Hydroxyzine hydrochloride produced tranquility without adverse effects on respiration, since the Apgar scores13p I4 used in obstetrics to assessthe vitality of the newborn were not altered by this drug. Further studies conducted on the ventilation in human volunteers also substantiated hydroxyzine’s lack of respiratory depressant effectI MATERI,AL
AND
METtiODS
Five hundred and thirty-two patients who underwent either full-mouth extraction with alveolectomy or extraction of multiple impacted third molars were selected at random. All patients were in physical state No. 1 (American Society of Anesthesiologists classification) and were free of organic disease. The distribution of patients as to age, weight, height, pulse and respiratory rates, and blood pressure was the same in the three study groups. Therefore, a valid statistical evaluation can be made from this homogeneous group. It was anticipated that patients selected would fit the requirements for a homogeneous group, since both the surgical procedures and the physical conditions of these persons were identical. Premeditation
The patients were grouped into three categories : Group I-243 patients received 0.8 mg. meperidine per kilogram of body weight in combination with 0.007 mg./kg. atropine intramuscularly.
Rational selection of preanesthetic medication
Volume 26 Number 4
459
II. Rating scales for evaluation of the effect of drug combinations on preoperative anxiety
Table
Attitude Agitated Excited Normal Relaxed Depressed Awakmess Alert Awake Drowsy Tendency to sleep Asleep Bodily movements Extreme Much Moderate Little None
5 4 3 2 1
Tall&g Extremely talkative Moderately talkative Normal response to questions Little response to questions No voluntary response
: 3 2 1
Eyelid position Wide open Open Tendency to close eyes Marked tendency to close eyes Closed eyelids
5 4 3 T
Eyelid movements Extreme Much Moderate Little None
5 4 i: 1 5 4 3 T 5 4 i 1
II-82 patients received 0.8 mg./kg. meperidine in combination with 1.4 mg./kg. of secobarbital or pentobarbital and 0.007 mg./kg. of atropine. Group III-207 patients received 0.8 mg./kg. meperidine or 0.008 mg./kg. oxymorphone in combination with 1 mg./kg. hydroxyzine and atropine 0.007 mg./kg. The dosage of meperidine in each study group was kept intentionally as constant as possible in order to eliminate narcotic potentiation of anesthesia that would be reflected in differences in maintenance requirements (Table III). The addition of atropine was deemed necessary, since previous studies indicated neither antisialogogue nor parasympatholytic effects of hydroxyzine in clinical trials1 Furthermore, a reduction in the normal dose of meperidine was possible, since previous studies indicated that hydroxyzine potentiated the effect of analgesics.1l *I 1o-*2The drugs were given by deep intramuscular injection into the gluteal muscles of the buttock at least 90 minutes prior to the induction of 8nesthesia.l” Group
Anesthetic
agents
Induction of anesthesia was accomplished by the intravenous injection of an average of 0.4 to 0.5 mg/kg. of thiopental in a 2.5 per cent solution, followed by the administration of oxygen by face mask at a flow rate of 5 liters per minute. As soon as the eyelid reflex disappeared and the pulse rate became stabilized, an intravenous infusion of 0.2 per cent solution of succinylcholine dichloride (Anectine, Quelicine) was started and continued until the patient’s jaw became relaxed and the patient became apneic. In all patients a thin-walled rubber (King) endotracheal tube (internal diameter, 7 to 8 mm.) was inserted by the nasal route under direct laryngoscopy. Anesthesia was maintained with a flow of 3.5 liters of nitrous oxide and 1.5 liters of oxygen per minute and intermittent dosesof thiopental.
OS., O.M. & O.P. October, 1968
460 Zsigmond Experimental
design
to permit
objective
evaluation
of the data
In order to exclude bias, an objective scoring system was designed and used for the evaluation of preoperative tranquility, as shown in Table II. The questionnaire originally designed by Carpenter and associates” was modified to simplify the evaluation. This coding sheet was used to evaluate patients before the administration of premeditation, at the time of induction of anesthesia, and in the recovery room. The adequacy of the premeditation at the induction of anesthesia was also assessedby the anesthesiologist. The effects of premed&&ion on the course of anesthesia and on the incidence of pre- and postanesthetic complications were assessedby an IBM coding sheet specifically designed by the author for this purpose. RESULTS
A comparison of three types of medication, as presented in Fig. 1, demonstrates the greater effectiveness of the combination of hydroxyzine with meperidine over that of barbiturates with meperidine. It also can be observed in Fig. 1 that the scores recorded in the recovery room were influenced primarily by the residual effect of anesthesia, since this evaluation was made 20 minutes after the arrival of patients when the blood level of anesthetic agents might have altered the normal body physiology and psychic responses. Table III indicates that neither drug combination had any effect on the thiopental or succinylcholine requirement as expressed in milligrams per minute per 70 kg. Table IV demonstrates that the incidence of complications following
MU’ERIDINE WITH HYDROXYZINE MEPERIDINE WITH BARBITURATES ‘-: :-J
r-3
;
I--I,
Effects
of various
premedioations
,
' II!
;I
on the preoperative
SCORES IN RECOVERY ROOM
1 '
anxiety
in oral
surgical
Volume 26 Number 4
Rat&ma1 selection
of preanesthetic medication
461
administration of the hydroxyzine-narcotic combination was considerably less than that resulting from the others. It is interesting to note in the table that in three patients ventilatory depression was caused by the administration of large dosesof succinylcholine chloride; this was substantiated by a nerve stimulator. The influence of different premeditations on the time required for recoveryroom care can best be compared by considering the duration of anesthesia as a common denominator. Fig. 2 shows the duration of recovery-room care required for each group of patients as compared to the duration of anesthesia. The patients receiving meperidine alone or in combination with barbiturates required recovery-room care for a period twice as long as the duration of anesthesia and surgery. In contrast, patients given hydroxyzine in combination with meperidine or oxymorphone required recovery-room care for a period only slightly in excess of the duration of anesthesia and surgery. Fig. 2 also shows that these differences are real, for the duration of anesthesia and surgery was similar in all three study groups. DISCUSSION
The results of this study on oral surgical patients substantiate claims that hydroxyzine hydrochloride]-* 3*4l lo, l3 has no adverse effect on respiratory or circulatory stability. In another series of thirty-five patients (twenty-eight healthy volunteers and seven patients with obstructive lung disease), tidal volume, respiratory rate, and oxygen uptake were determined before and 30, 60, and 90 minutes after the intramuscular administration of 1.5 mg./kg. hydroxyzine. In addition, arterial pH, carbon dioxide pressure, oxygen pressure, and oxygen saturation were determined in thirty normal subjects after the intravenous administration of 1.5 mg./kg. hydroxyzine. I5 The results indicated no significant depression of ventilation after either the intramuscular or intravenous injection of 1.5 mg./kg. hydroxyzine. These doseswere 50 to 100 per cent higher than the recommended intramuscular doses of hydroxyzine for routine clinical use. Since the absorption of a drug after intramuscular injection takes longer and Table III. The effect of preoperative medication on the thiopental and
succinylcholine dose requirements
Preoperative melioation’ (&rug ccmbimcthn) Meperidine
Dose (w./70 kg.) 57.1
Meperidine and secobarbitd Meperidine and pentobarbital
58.2 99.1 58.2 96.4
Numberof
piktiats 243 82
MeDeridine and 59.5 lijd.ro+ne 70.3 Hydroxyzine and 70.3 207 oxymorphone 0.59 ‘Premeditation included atropine, 0.007 mg./kg.
Dose reqzuirements (mg./mim/70 kg.) I”hiopental Swin.ylaholine YIB(MIF 19.6 16.9 3.8 3.3 18.4
19.5
3.7
3.1
16.0
15.8
3.5
3.7
462
Zsigmond
OS., O.M. & O.P. October, 1968
Table IV. The influence of preanesthetic medication on the
occurre~m
of
complications preoperatively and postoperatively
Qpe of
complication Hypotenaion Hypertension Tachycardia Arrhythmia Ventilatory depression Coughing Laryngospasm Vomiting Excessive salivation Excessive bleeding Allergic reactions Excitement, agitation Delayed return of consciousIlWS Over-all complications *Ventilatory
ilfcperidine p&e
with atro($443)
Preoperative (per cen;t)
Postoperativa (per cent)
Mepn-idine awl seoobarbital or pentobarbital with a#tropine (88) PostoperaPreopera,tive tive (per cent) (per cent)
1.6 0.4 -
6.2 2.9 0:4
3.7 1.2 -
0.4 -
03 0.4 1.7
1.2
2:4
-
0.8
-
1.2
-
3.7
-
1.2
0.8
0.4 0.4
-
0.8
3.2
18.5
depression resulted
4.9 -
Hydroxyzk~ cvnd atropine with meperidine or oxymorph.ane (207) Yostopera-
Preoperative (per cent) 0.5 -
6.1
0.5 015 -. 1.5s 0.5
-
-
tive (per cent)
0.5
-
2.4
-
0.5
-
-
1.0
12.1
0.5
5.0
from overdose of suocinylcholine.
the blood levels attained a,re lower than after intravenous injection of the identical dose, it is unlikely that patients who showed no change after intravenous injection of 1.5 mg./kg. would develop respiratory depression after either the intramuscular or intravenous injection of lower doses (0.7 to 1.0 mg./kg.) of hydroxyzine hydrochloride for preanesthetic medication. In a previous study,13 it was found that the circulatory stability of fifty patients undergoing hemorrhoidectomy under spinal anesthesia was remarkably well maintained after the intramuscular administration of 1 mg./kg. hydroxyzine hydrochloride. No orthostatic hypotension resulted when the patient was changed from the recumbent to the upright position before induction of the spinal anesthesia; this was in contrast to the marked drop in blood pressure routinely observed after the combination of barbiturates or phenothiazines with narcotics.13 Hydroxyzine hydrochloride as assessedin this report proved to be an effective and safe tranquilizer for the relief of preoperative anxiety prior to oral surgery. Hypotension, hypertension, respiratory depression, arrhythmia, excitement, agitation, prolongation of anesthesia, excessive salivation, vomiting, excessive bleeding, and allergic reaction were leas frequent with hydroxyzine hydrochloride in combination with meperidine or oxymorphone as compared to narcotics alone or in combination with barbiturates. This reduced incidence of complications when
Rational
Volume 26 Number 4
90 -
B
MINUTES DURATION OF ANESTHESIA
-
selection of preanesth.etic medication
0
100 c--
PERCENT
-
463
220
DURATION OF RECOVERY ROOM CARE
Fig. S. Duration of recovery-room care as compared with duration of anesthesia.
hydroxyzine is combined with narcotics may be explained by the antiemetic, antiadrenaline, bronchodilator, antihistaminic, and potent tranquilizing effect of hydroxyzine hydrochloride, Since the completion of these studies, the narcotics have been omitted from preanesthetic medication. Hydroxyzine hydrochloride alone gave adequate preoperative tranquility in patients without pain. At present, we employ narcotics in preanesthetic medication solely for the relief of pain. As was formerly suggested by oral surgeons,1ohydroxyzine hydrochloride is one of the most suitable tranquilizers for oral surgical patients. Its advantage over other tranquilizers is further emphasized by the fact that phenothiazines commonly produce drowsiness6 On the contrary, patients may receive an oral dose of hydroxyzine prior to office dental procedures and may be allowed to return home immediately after recovery from anesthesia with lesser risk of impaired driving ability than after barbiturates. Since completion of the study, 25 to 50 mg. capsules of hydroxyzine pamoate have been given routinely for preoperative medication to a wide variety of patients with severely impaired cariorespiratory function scheduled for of&e dental procedures, and there have been no untoward effects. SUMMARY
Evaluation of 532 oral surgical patients who received either meperidine alone, meperidine in combination with secobarbital or phenobarbital, or meperidine or oxymorphone in combination with hydroxyzine demonstrated the following : 1. Hydroxyzine hydrochloride in combination with narcotics was superior to narcotics alone or in combination with barbiturates as a premedication for oral surgical procedures, when evaluated in a doubleblind study with the aid of an objective scoring system.
444 Zsigmond
O.S., OX & O.P. October, 1968
2. IBM evaluation of the anesthetic records denmnstrated t,hat, hydroxyzine in combination with meperidine and oxymorphone had not altered thiopental or succinylcholine requirements for anesthesia.. It did not appear to alter the course elf anesthesia adversely in any other way. 3. The incidence of complications prior to and after oral surgery was markedly reduced by the combination of hydroxyzine with meperidine or oxymorphone, as compared to the use of meperidine alone or in combination with barbiturates. 4. Because of the reduced incidence of complications, the duration of recovery-room care in patients who received hydroxyzine in combination with narcotics was shortened. The results substantiate the clinical impression formed during the past 8 years, from the observat,ion of about 10,000 surgical patients in this department, that hydroxyzine in combination with narcotics was superior to meperidine or its combination with ba,rbiturates for preanesthetic medication of oral surgical patients. A grant Department,
for the study of Pfizer Laboratories,
hydroxyzinehydrochloride(Vistaril)
was given by the Medical
New York, N. Y.
REFERENCES
1. Dobkin, A. B.: Sedatives, Analgesics, Antidotes and Their Interaction: A Review, Canad. Anaesth. Sot. J. 11: 252-279. 1964. Is Important, Scientific Exhibit, 2. Grady, R. W., and Rich, A: L.: Proper Premeditation Medical Society of the State of Alabama, Tuscaloosa, Ala., April 27-29, 1961. Drugs in Clinical Anesthesia; a Review, Canad. 3. Dobkin, A. B.: Efficacy of Ataractic Anaesth. Sot. J. 5: 177-208, 1958. 4. Carpenter, F. A., Steinhaus, J. E., Sessions, G. P., Stein, 5. D., and Thompson, W. R.: Methods of Evaluation of Preanesthetic Drugs, Scientific Exhibit, Southern Medical Association, St. Louis! MO., Oct. 30, 1960. J.: Pre-medication-An Old Idea and New Drugs, J. A. M. A. 171: 1086-1089, 5. Adriani, 1959. Hazards of 6. Eckenhoff, J. E., Helrich, M., Hege, M. J. D., and Jones, R. E.: Respiratory Opiates and Other Narcotic Analgesics, Surg. Gynec. & Obst. 101: 701-708, 1955. T. H.: The Pharmacologic Basis for the 7. Zsigmond, E. K., Patterson, R. L., and Porritt, Selection of a Preanesthetic Medication-A Pharmacological Dilemma? Scientific Exhibit, American Dental Association, Dallas, Texas, Nov. 13-17, 1966. Report on the Use of Hydroxyzine Hydro8. Grady, R. W., and Rich, A. L.: A Preliminary chloride (Vistaril) as a Pre-medicant for Surgical Patients, J. M. A. Alabama 29: 377380, 1960. a Neuropsychic Regulator for Pre-medication 9. Bozza, M. L., and Ghezzi, R.: Hydroxyzine in Neurosurgery, Minerva anestesiol. 22: 308-306, 1956. as an Adjunct to Local Anesthesia, J. S. California D. A. 10. Abramson, A. S.: Hydroxyzine 26: 26, 1958. Analgesia and Neonatal Response, 11. Benson, C., and Benson, R. C.: Hydroxyzine-Meperidine Am. J. Obst. & Gynec. 84: 37-43, 1962. of Parenteral Hydroxyzine for Pre12. Grady, R. W., and Rich, A. L.: Clinical Evaluation operative Medication, South. M. J. 54: 766768, 1961. Evaluation of Hydroxyzine Hydro13. Zsigmond, E. K., and Patterson, R. L.: Double-Blind chloride in Obstetrical Anesthesia, Anesth. & Analg. 46: 275280, 1967. of 14. Apgar, V., Holaday, D. A., James, L. S., Weisbrot, I. M., and Berrien, C.: Evaluation the Newborn Infant; Second Report, J. A. M. A. 168: 1985,1958. and Blood Gas Studies on the Respira15. Zsigmond, E. K., and Shively, J. G.: Spirometric tory Effects of Hydroxyzine Hydrochloride in Human Volunteers, J. New Drugs 6: 128, 1966.
Rational selection of preanesthetic medication for oral surgical patients Elem& K. Zsigmd, ANESTHESIA
RESEARCH
M.D., Pittsburgh, LABORATORY,
Pa.
ALLEGHENY
GENERAL
HOSPITAL
T
he importance of psychic management of the surgical patient before and after a surgical procedure has long been recognized, but the complex and often paradoxical actions of the drugs used in this management has continued to pose a pharmacologic dilemma, requiring further evaluation of preanesthetic medication.* The trends, goals, and obstacles of preanesthetic medication are presented in Table I. The objectives of premeditation are focused on the goals of smooth induction and good maintenance of anesthesia without adverse effects.l Complications may be avoided by the induction of a preoperative state of tranquility rather than stupor, leaving the patient oriented and cooperative. The objective is to assure a smooth induction of anesthesia and postoperative freedom from emergence delirium, confusion, and excitement.z There are, however, some obstacles to the achievement of these goals. The potential depressant effect of some agents commonly used for preanesthetic medication presents a problem, since these agents induce a state of sedation that is more profound than the desired tranquilization. This problem, which is basic to the narcotics and barbiturates, extends also to the phenothiazine congeners.1-3 This class of tranquilizers depressesthe brain stem arousal mechanism and may result in unpredictable adverse psychic effects.415 Side effects of all these drugs may be respiratory and circulatory depression, confusion, disorientation, and excitement. Othere complications linked to the use of narcotics and barbiturates include allergic reactions, nausea, and vomiting.? Barbiturates and phenothiazines often cause prolongation of anesthesia, an effect that the narcotics share.lo * Other potential side effects associated with the use of phenothiazine are the appearance of extrapyramidal motor symptoms and hepatic and hematopoietic systemic toxicity.‘j Over a period of 8 years, we have observed approximately 10,000 patients who underwent various surgical procedures in which the tranquilizer hydroxy457
458
Zsigmond
Table
I
OS., OX & 0.1’. October, 1968
Goals Preoperattie Calm and cooperative patient to facilitate smooth and uncomplicated induction Operative Maintenance of anesthesia with no complicating influence from premeditation Postoperative Uncomplicated and rapid recovery from anesthesia with relative freedom from pain and confusion, reduced incidence of nausea and vomiting
Obstacles Circulatory depression Respiratory depression Confusion Disorientation Excitement Prolongation of anesthesia Nausea Vomiting Extrapyramidal motor symptoms Allergic reactions
Sequelae Preoperative Comatose, stuporous or apprehensive, agitated, and uncooperative patients complicate anesthetic induction Operative Frequent anesthetic complications, potentiation, prolongation, severe depression, and hypotension Postoperative Delayed recovery,. emergence dellrmm, nausea, and vomiting
zine hydrochloride (Vistaril, Atarax) was used as premeditation for anesthesia and oral surgery.6 Since a number of reports in the literature have noted a definite superiority of hydroxyzine over other tranquilizers for preanesthetic medication,7-12 a double-blind evaluation of the drug’s effect on predelivery anxiety in obstetrical patients was also conducted.13 These studies revealed that hydroxyzine hydrochloride, alone or in combination with narcotics, most closely approximated the goals of preanesthetic medication. Hydroxyzine hydrochloride produced tranquility without adverse effects on respiration, since the Apgar scores13p I4 used in obstetrics to assessthe vitality of the newborn were not altered by this drug. Further studies conducted on the ventilation in human volunteers also substantiated hydroxyzine’s lack of respiratory depressant effectI MATERI,AL
AND
METtiODS
Five hundred and thirty-two patients who underwent either full-mouth extraction with alveolectomy or extraction of multiple impacted third molars were selected at random. All patients were in physical state No. 1 (American Society of Anesthesiologists classification) and were free of organic disease. The distribution of patients as to age, weight, height, pulse and respiratory rates, and blood pressure was the same in the three study groups. Therefore, a valid statistical evaluation can be made from this homogeneous group. It was anticipated that patients selected would fit the requirements for a homogeneous group, since both the surgical procedures and the physical conditions of these persons were identical. Premeditation
The patients were grouped into three categories : Group I-243 patients received 0.8 mg. meperidine per kilogram of body weight in combination with 0.007 mg./kg. atropine intramuscularly.
Rational selection of preanesthetic medication
Volume 26 Number 4
459
II. Rating scales for evaluation of the effect of drug combinations on preoperative anxiety
Table
Attitude Agitated Excited Normal Relaxed Depressed Awakmess Alert Awake Drowsy Tendency to sleep Asleep Bodily movements Extreme Much Moderate Little None
5 4 3 2 1
Tall&g Extremely talkative Moderately talkative Normal response to questions Little response to questions No voluntary response
: 3 2 1
Eyelid position Wide open Open Tendency to close eyes Marked tendency to close eyes Closed eyelids
5 4 3 T
Eyelid movements Extreme Much Moderate Little None
5 4 i: 1 5 4 3 T 5 4 i 1
II-82 patients received 0.8 mg./kg. meperidine in combination with 1.4 mg./kg. of secobarbital or pentobarbital and 0.007 mg./kg. of atropine. Group III-207 patients received 0.8 mg./kg. meperidine or 0.008 mg./kg. oxymorphone in combination with 1 mg./kg. hydroxyzine and atropine 0.007 mg./kg. The dosage of meperidine in each study group was kept intentionally as constant as possible in order to eliminate narcotic potentiation of anesthesia that would be reflected in differences in maintenance requirements (Table III). The addition of atropine was deemed necessary, since previous studies indicated neither antisialogogue nor parasympatholytic effects of hydroxyzine in clinical trials1 Furthermore, a reduction in the normal dose of meperidine was possible, since previous studies indicated that hydroxyzine potentiated the effect of analgesics.1l *I 1o-*2The drugs were given by deep intramuscular injection into the gluteal muscles of the buttock at least 90 minutes prior to the induction of 8nesthesia.l” Group
Anesthetic
agents
Induction of anesthesia was accomplished by the intravenous injection of an average of 0.4 to 0.5 mg/kg. of thiopental in a 2.5 per cent solution, followed by the administration of oxygen by face mask at a flow rate of 5 liters per minute. As soon as the eyelid reflex disappeared and the pulse rate became stabilized, an intravenous infusion of 0.2 per cent solution of succinylcholine dichloride (Anectine, Quelicine) was started and continued until the patient’s jaw became relaxed and the patient became apneic. In all patients a thin-walled rubber (King) endotracheal tube (internal diameter, 7 to 8 mm.) was inserted by the nasal route under direct laryngoscopy. Anesthesia was maintained with a flow of 3.5 liters of nitrous oxide and 1.5 liters of oxygen per minute and intermittent dosesof thiopental.
OS., O.M. & O.P. October, 1968
460 Zsigmond Experimental
design
to permit
objective
evaluation
of the data
In order to exclude bias, an objective scoring system was designed and used for the evaluation of preoperative tranquility, as shown in Table II. The questionnaire originally designed by Carpenter and associates” was modified to simplify the evaluation. This coding sheet was used to evaluate patients before the administration of premeditation, at the time of induction of anesthesia, and in the recovery room. The adequacy of the premeditation at the induction of anesthesia was also assessedby the anesthesiologist. The effects of premed&&ion on the course of anesthesia and on the incidence of pre- and postanesthetic complications were assessedby an IBM coding sheet specifically designed by the author for this purpose. RESULTS
A comparison of three types of medication, as presented in Fig. 1, demonstrates the greater effectiveness of the combination of hydroxyzine with meperidine over that of barbiturates with meperidine. It also can be observed in Fig. 1 that the scores recorded in the recovery room were influenced primarily by the residual effect of anesthesia, since this evaluation was made 20 minutes after the arrival of patients when the blood level of anesthetic agents might have altered the normal body physiology and psychic responses. Table III indicates that neither drug combination had any effect on the thiopental or succinylcholine requirement as expressed in milligrams per minute per 70 kg. Table IV demonstrates that the incidence of complications following
MU’ERIDINE WITH HYDROXYZINE MEPERIDINE WITH BARBITURATES ‘-: :-J
r-3
;
I--I,
Effects
of various
premedioations
,
' II!
;I
on the preoperative
SCORES IN RECOVERY ROOM
1 '
anxiety
in oral
surgical
Volume 26 Number 4
Rat&ma1 selection
of preanesthetic medication
461
administration of the hydroxyzine-narcotic combination was considerably less than that resulting from the others. It is interesting to note in the table that in three patients ventilatory depression was caused by the administration of large dosesof succinylcholine chloride; this was substantiated by a nerve stimulator. The influence of different premeditations on the time required for recoveryroom care can best be compared by considering the duration of anesthesia as a common denominator. Fig. 2 shows the duration of recovery-room care required for each group of patients as compared to the duration of anesthesia. The patients receiving meperidine alone or in combination with barbiturates required recovery-room care for a period twice as long as the duration of anesthesia and surgery. In contrast, patients given hydroxyzine in combination with meperidine or oxymorphone required recovery-room care for a period only slightly in excess of the duration of anesthesia and surgery. Fig. 2 also shows that these differences are real, for the duration of anesthesia and surgery was similar in all three study groups. DISCUSSION
The results of this study on oral surgical patients substantiate claims that hydroxyzine hydrochloride]-* 3*4l lo, l3 has no adverse effect on respiratory or circulatory stability. In another series of thirty-five patients (twenty-eight healthy volunteers and seven patients with obstructive lung disease), tidal volume, respiratory rate, and oxygen uptake were determined before and 30, 60, and 90 minutes after the intramuscular administration of 1.5 mg./kg. hydroxyzine. In addition, arterial pH, carbon dioxide pressure, oxygen pressure, and oxygen saturation were determined in thirty normal subjects after the intravenous administration of 1.5 mg./kg. hydroxyzine. I5 The results indicated no significant depression of ventilation after either the intramuscular or intravenous injection of 1.5 mg./kg. hydroxyzine. These doseswere 50 to 100 per cent higher than the recommended intramuscular doses of hydroxyzine for routine clinical use. Since the absorption of a drug after intramuscular injection takes longer and Table III. The effect of preoperative medication on the thiopental and
succinylcholine dose requirements
Preoperative melioation’ (&rug ccmbimcthn) Meperidine
Dose (w./70 kg.) 57.1
Meperidine and secobarbitd Meperidine and pentobarbital
58.2 99.1 58.2 96.4
Numberof
piktiats 243 82
MeDeridine and 59.5 lijd.ro+ne 70.3 Hydroxyzine and 70.3 207 oxymorphone 0.59 ‘Premeditation included atropine, 0.007 mg./kg.
Dose reqzuirements (mg./mim/70 kg.) I”hiopental Swin.ylaholine YIB(MIF 19.6 16.9 3.8 3.3 18.4
19.5
3.7
3.1
16.0
15.8
3.5
3.7
462
Zsigmond
OS., O.M. & O.P. October, 1968
Table IV. The influence of preanesthetic medication on the
occurre~m
of
complications preoperatively and postoperatively
Qpe of
complication Hypotenaion Hypertension Tachycardia Arrhythmia Ventilatory depression Coughing Laryngospasm Vomiting Excessive salivation Excessive bleeding Allergic reactions Excitement, agitation Delayed return of consciousIlWS Over-all complications *Ventilatory
ilfcperidine p&e
with atro($443)
Preoperative (per cen;t)
Postoperativa (per cent)
Mepn-idine awl seoobarbital or pentobarbital with a#tropine (88) PostoperaPreopera,tive tive (per cent) (per cent)
1.6 0.4 -
6.2 2.9 0:4
3.7 1.2 -
0.4 -
03 0.4 1.7
1.2
2:4
-
0.8
-
1.2
-
3.7
-
1.2
0.8
0.4 0.4
-
0.8
3.2
18.5
depression resulted
4.9 -
Hydroxyzk~ cvnd atropine with meperidine or oxymorph.ane (207) Yostopera-
Preoperative (per cent) 0.5 -
6.1
0.5 015 -. 1.5s 0.5
-
-
tive (per cent)
0.5
-
2.4
-
0.5
-
-
1.0
12.1
0.5
5.0
from overdose of suocinylcholine.
the blood levels attained a,re lower than after intravenous injection of the identical dose, it is unlikely that patients who showed no change after intravenous injection of 1.5 mg./kg. would develop respiratory depression after either the intramuscular or intravenous injection of lower doses (0.7 to 1.0 mg./kg.) of hydroxyzine hydrochloride for preanesthetic medication. In a previous study,13 it was found that the circulatory stability of fifty patients undergoing hemorrhoidectomy under spinal anesthesia was remarkably well maintained after the intramuscular administration of 1 mg./kg. hydroxyzine hydrochloride. No orthostatic hypotension resulted when the patient was changed from the recumbent to the upright position before induction of the spinal anesthesia; this was in contrast to the marked drop in blood pressure routinely observed after the combination of barbiturates or phenothiazines with narcotics.13 Hydroxyzine hydrochloride as assessedin this report proved to be an effective and safe tranquilizer for the relief of preoperative anxiety prior to oral surgery. Hypotension, hypertension, respiratory depression, arrhythmia, excitement, agitation, prolongation of anesthesia, excessive salivation, vomiting, excessive bleeding, and allergic reaction were leas frequent with hydroxyzine hydrochloride in combination with meperidine or oxymorphone as compared to narcotics alone or in combination with barbiturates. This reduced incidence of complications when
Rational
Volume 26 Number 4
90 -
B
MINUTES DURATION OF ANESTHESIA
-
selection of preanesth.etic medication
0
100 c--
PERCENT
-
463
220
DURATION OF RECOVERY ROOM CARE
Fig. S. Duration of recovery-room care as compared with duration of anesthesia.
hydroxyzine is combined with narcotics may be explained by the antiemetic, antiadrenaline, bronchodilator, antihistaminic, and potent tranquilizing effect of hydroxyzine hydrochloride, Since the completion of these studies, the narcotics have been omitted from preanesthetic medication. Hydroxyzine hydrochloride alone gave adequate preoperative tranquility in patients without pain. At present, we employ narcotics in preanesthetic medication solely for the relief of pain. As was formerly suggested by oral surgeons,1ohydroxyzine hydrochloride is one of the most suitable tranquilizers for oral surgical patients. Its advantage over other tranquilizers is further emphasized by the fact that phenothiazines commonly produce drowsiness6 On the contrary, patients may receive an oral dose of hydroxyzine prior to office dental procedures and may be allowed to return home immediately after recovery from anesthesia with lesser risk of impaired driving ability than after barbiturates. Since completion of the study, 25 to 50 mg. capsules of hydroxyzine pamoate have been given routinely for preoperative medication to a wide variety of patients with severely impaired cariorespiratory function scheduled for of&e dental procedures, and there have been no untoward effects. SUMMARY
Evaluation of 532 oral surgical patients who received either meperidine alone, meperidine in combination with secobarbital or phenobarbital, or meperidine or oxymorphone in combination with hydroxyzine demonstrated the following : 1. Hydroxyzine hydrochloride in combination with narcotics was superior to narcotics alone or in combination with barbiturates as a premedication for oral surgical procedures, when evaluated in a doubleblind study with the aid of an objective scoring system.
444 Zsigmond
O.S., OX & O.P. October, 1968
2. IBM evaluation of the anesthetic records denmnstrated t,hat, hydroxyzine in combination with meperidine and oxymorphone had not altered thiopental or succinylcholine requirements for anesthesia.. It did not appear to alter the course elf anesthesia adversely in any other way. 3. The incidence of complications prior to and after oral surgery was markedly reduced by the combination of hydroxyzine with meperidine or oxymorphone, as compared to the use of meperidine alone or in combination with barbiturates. 4. Because of the reduced incidence of complications, the duration of recovery-room care in patients who received hydroxyzine in combination with narcotics was shortened. The results substantiate the clinical impression formed during the past 8 years, from the observat,ion of about 10,000 surgical patients in this department, that hydroxyzine in combination with narcotics was superior to meperidine or its combination with ba,rbiturates for preanesthetic medication of oral surgical patients. A grant Department,
for the study of Pfizer Laboratories,
hydroxyzinehydrochloride(Vistaril)
was given by the Medical
New York, N. Y.
REFERENCES
1. Dobkin, A. B.: Sedatives, Analgesics, Antidotes and Their Interaction: A Review, Canad. Anaesth. Sot. J. 11: 252-279. 1964. Is Important, Scientific Exhibit, 2. Grady, R. W., and Rich, A: L.: Proper Premeditation Medical Society of the State of Alabama, Tuscaloosa, Ala., April 27-29, 1961. Drugs in Clinical Anesthesia; a Review, Canad. 3. Dobkin, A. B.: Efficacy of Ataractic Anaesth. Sot. J. 5: 177-208, 1958. 4. Carpenter, F. A., Steinhaus, J. E., Sessions, G. P., Stein, 5. D., and Thompson, W. R.: Methods of Evaluation of Preanesthetic Drugs, Scientific Exhibit, Southern Medical Association, St. Louis! MO., Oct. 30, 1960. J.: Pre-medication-An Old Idea and New Drugs, J. A. M. A. 171: 1086-1089, 5. Adriani, 1959. Hazards of 6. Eckenhoff, J. E., Helrich, M., Hege, M. J. D., and Jones, R. E.: Respiratory Opiates and Other Narcotic Analgesics, Surg. Gynec. & Obst. 101: 701-708, 1955. T. H.: The Pharmacologic Basis for the 7. Zsigmond, E. K., Patterson, R. L., and Porritt, Selection of a Preanesthetic Medication-A Pharmacological Dilemma? Scientific Exhibit, American Dental Association, Dallas, Texas, Nov. 13-17, 1966. Report on the Use of Hydroxyzine Hydro8. Grady, R. W., and Rich, A. L.: A Preliminary chloride (Vistaril) as a Pre-medicant for Surgical Patients, J. M. A. Alabama 29: 377380, 1960. a Neuropsychic Regulator for Pre-medication 9. Bozza, M. L., and Ghezzi, R.: Hydroxyzine in Neurosurgery, Minerva anestesiol. 22: 308-306, 1956. as an Adjunct to Local Anesthesia, J. S. California D. A. 10. Abramson, A. S.: Hydroxyzine 26: 26, 1958. Analgesia and Neonatal Response, 11. Benson, C., and Benson, R. C.: Hydroxyzine-Meperidine Am. J. Obst. & Gynec. 84: 37-43, 1962. of Parenteral Hydroxyzine for Pre12. Grady, R. W., and Rich, A. L.: Clinical Evaluation operative Medication, South. M. J. 54: 766768, 1961. Evaluation of Hydroxyzine Hydro13. Zsigmond, E. K., and Patterson, R. L.: Double-Blind chloride in Obstetrical Anesthesia, Anesth. & Analg. 46: 275280, 1967. of 14. Apgar, V., Holaday, D. A., James, L. S., Weisbrot, I. M., and Berrien, C.: Evaluation the Newborn Infant; Second Report, J. A. M. A. 168: 1985,1958. and Blood Gas Studies on the Respira15. Zsigmond, E. K., and Shively, J. G.: Spirometric tory Effects of Hydroxyzine Hydrochloride in Human Volunteers, J. New Drugs 6: 128, 1966.