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Double-blind comparison of nalbuphine and meperidine in combination with diazepam for intravenous conscious sedation in oral surgery outpatients
Double-blind comparison of nalbuphine and meperidine in combination with diazepam for intravenous conscious sedation in oral surgery outpatients Edward A. Dolan, D.D.S.,* William J. Murray, M.D., Ph.D.,** and Michelle P. Ruddy, R.N.,*** Durham, N.C. DUKE
UNIVERSITY
MEDICAL
CENTER
Nalbuphine and meperidine were compared as analgesic components of intravenous conscious sedation a double-blind, prospective trial of 47 patients undergoing elective oral surgery. Subjects were evaluated for pain intensity, pain relief, anxiety, sedation, recall, and vital signs at systematic observation points intraoperatively and postoperatively. At the conclusion of surgery 83% of patients who had received nalbuphine and 88% of patients treated with meperidine indicated complete pain relief. One observed adverse reaction was attributed to meperidine and another to the sedative component diazepam. No statistically significant differences were observed between nalbuphine and meperidine treatments.
in
(ORAL SURC ORAL MED ORAL PATHOL 1988;66:536-9)
S
ince adults are fearful of general dental procedures,’ higher levels of anxiety are probable among those requiring oral surgical manipulations. Thus pharmacologic strategies to manage apprehension and pain during oral surgery offer a model to study clinical techniques and to evaluate analgesics. A significant advance has been the implementation of intravenous conscious sedation. This concept of using sedative-analgesic mixtures first gained wide attention more than three decades ago with the use of meperidine, hyoscine, and pentobarbital.2 Since that time the regimen has evolved as benzodiazepines, and additional synthetic opioids have become available. There has also been significant interest in narcotic agonist-antagonist drugs as substitutes for the pure agonist opioids. As such pentazocine has been used in dentistry ,3 but it is not popular in the United States, possibly because of risks of psychotomimetic reactions4 and respiratory depression.5Nal-
Supported by a research grant from Du Pont Pharmaceuticals of Wilmington, Del. Presented in part at the 88th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, Orlando, Fla., March 25-28, 1987. *Assistant Professor, Division of Oral and Maxillofacial Surgery. **Professor, Department of Anesthesiology. ***Medical Research Analyst, Department of Anesthesiology.
536
buphine is another parenteral agonist-antagonist analgesic that has a low abuse potential,6 a general safety profile that includes minimal effects on cardiovascular function’, * and a “ceiling” beyond which respiratory depression does not significantly worsen with further doses of drug.9 To assess the potential value of nalbuphine in intravenous conscious sedation, a double-blind study was conducted in which oral surgery outpatients received either nalbuphine or meperidine in combination with diazepam before infiltration of a local anesthetic. PATIENTS
AND METHODS
After institutional review board approval, 47 informed, consenting oral surgery outpatients, 20 to 52 years of age (American Society of Anesthesiologists status I or II), were entered into this protocol. No patients were pregnant or lactating females; suffered from pain unrelated to the presenting oral surgery condition; had a history of liver dysfunction, psychiatric disorders, or drug abuse; or had known hypersensitivity to local anesthetics, diazepam, nalbuphine, or meperidine. Subjects were asked to avoid analgesics, antiinflammatory medications, sedatives, or other central nervous system-active agents for at least 6 hours before the surgical procedure. Study medications packaged in identical 2 ml syringes (containing either 20 mg of nalbuphine
Nalbuphine
Volume 66 Number 5
Table
versus meperidine in conscious sedation
537
1. Rating scales
Pain intensity* Pain relief? Level of anxiety? Degree of recall* Patient cooperationt Degree of sedation?
patient
0
I
None None Unchanged None No None (awake)
Mild Incomplete Decreased Partial Yes Slight (sleepy)
*Defined
by direct
tDefined
by surgeon/observer.
Table
II. Demographic patient data
Severe Complete
Moderate (verbal stimulus to awaken)
Severe (painful stimulus to awaken)
Surgery (min) + SEM
Sex (M/F)
Nalbuphine Meperidine between
Moderate Adequate Increased Total
questioning.
Treared groups
No dii?erences
3
2
11/13 10113 groups
are statistically
significant
27.1 * 1.5 28.5 f 1.6
69.5 k 3.0 71.5 t 2.6
43.5 k 4.2 46.4 f 4.6
(I, 5 0.05).
hydrochioride or 30 mg of meperidine hydrochloride) were randomly assigned. Patients, surgeon, and observer were “blinded.” Medication code numbers were assigned in blocks of 10. Except for the local anesthetic, all medications were administered via a peripheral intravenous infusion of 5% dextrose in 0.225% saline. Incremental dosesof diazepam were titrated at a rate of 2.5 mg every 45 to 60 secondsto achieve the desired degree of tranquilization; maximum dose permitted was 20 mg. After the effects of diazepam had been assessed, 20 mg of nalbuphine or 50 mg of meperidine was administered over 3 minutes. After a regional injection of 2% lidocaine hydrochloride with 1: 100,000 epinephrine was given, surgery was initiated. One additional dose of study medication (20 mg of nalbuphine or 50 mg of meperidine) was allowed if the operation was prolonged or if analgesia was inadequate. Administration of any other medications required the patient’s withdrawal from the study. Table I shows the rating scales for recording observations for an individual patient. The same surgeon and observer studied each patient. Pain intensity, level of anxiety, degree of sedation, and vital signs were documented preoperatively, at 5minute intervals during surgery, and every 15 minutes during a recovery period of at least 1 hour. Pain relief, degree of recall, and patient cooperation were determined after surgery. Adverse reactions were reported for duration, severity, and probability of cause by the study medication. Results were considered statistically significant when tests yielded two-tailed p values of 0.05 or less,
A paired t test was used to assesshomogeneity of the treatment groups for demographic variables and to evaluate changes in vital signs. Fisher’s exact test was utilized for analysis of categoric data, efficacy parameters, and the comprehensive evaluations. RESULTS
No significant differences between the groups were detected on the basis of demographic variables depicted in Table II. Also, there were no significant differences between treatment groups with respect to surgical difficulty (Table III). Five nalbuphine- and seven meperidine-treated patients underwent routine extractions with bone cutting; impacted teeth were removed in 14 nalbuphine- and 11 meperidinetreated patients. Twenty-three of the 24 nalbuphine- and 21 of the 23 meperidine-treated patients successfully completed the protocol; 3 of the 24 nalbuphine- and 2 of the 23 meperidine-treated patients received an allowed second dose of study medication; 1 of the 24 nalbuphine- and 2 of the 23 meperidine-treated patients were excluded from analyses because they had received additional diazepam after administration of study medication. Table IV shows mean total drug dosages for patients who completed the protocol. Table V shows changes from baseline to end of surgery for pain intensity, pain relief, sedation, anxiety, and recall. At baseline every patient was rated as having “no pain” and “no sedation.” There were no significant differences between the nalbuphine- and meperidine-treated groups for any of the
538
Dolan et al.
Table
III. Distribution
Oral Surg November 1988
of surgical difficulty
in treated
groups Nalbuphine ! ~~-
I Meperidine
3 (13%‘) 2 (8’%)
7 (30%) 0 (0%)
3 (13%) 4 (17%) 6 (25%) 1 (4%) 0 (0%) 5 (21%)
2 3 3 2 I 5
Routine extractions Bone cutting---minimum Bone cutting---extensive Impactions Soft tissue Partial bone Vertical Mesioangular Horizontal Not recorded No differences
Table
IV.
between
groups
are stntiatically
significant
V. Pain, sedation. anxiety, and recall of treatment groups at end of surgery ,
Table
Nuibuphirw
Pain intensity None Mild Moderate Pain relief Adequate Complete Sedation Slight Moderate Anxiety Unchanged Decreased Increased Recall Partial Total
(9%) (13%) (13%) (9%) (4%) (22%)
(p 5 0.05)
Mean total drug doses
Nalbuphine
Meperidine
Note
that
evaluation
Nalbuphine Meperidine Diazepam Local anesthetic* *2W
Lidocaine
hydrochloride
0.33 mg/kg
are not recorded
0.78 mg/kg 9.6 mg 7.9 ml
9.6 mg 8.4 ml with
I : 100.000
the
epinephrine.
cited parameters. None of the patients in either treatment group was rated as uncooperative. All vital signs were within normal limits and not statistically different between treatment groups at any intraoperative or postoperative period, but several statistically significant blood pressure and pulse rate changes within groups did occur. However, no statistical observation had clinical importance. One meperidine-treated patient developed a severe headache at completion of the surgical procedure; the headache resolved in approximately 1 hour. Another patient who experienced a hysterical reaction after IO mg of diazepam and 50 mg of meperidine responded to treatment with physostigmine and promethazine. No adverse reactions were observed in the nalbuphine-treated group. DISCUSSION
In this series of patients nalbuphine and meperidine provided similar analgesia and sedation. Differences observed were not statistically significant. At the end of surgery 83% of patients who had received nalbuphine and 86% of patients who had been treated with meperidine described the relief of pain afforded by their study medication as complete. Total operation recall occurred in 22% of nalbu-
statistically
number
was added
12 (57%) 5 (24%) 4 (19%)
4 (17%) 19 (83%)
3 (14%) 18 (86%)
I2 (52%) (48%)
11 (55%) 9 (45%) 7 (41%)
9 (47%) 9 (47%) 1 (5%)
10 (57%) 0 (0%)
10 (48%)
18 (78%) 5 (22%) for
anxiety
to protocol
Meperidinr
9 (39%) 8 (35%) 6 (26%)
I I
for one meperidine
significant
/
1 I (52%)
is less than after
study patient.
other
ratings
was in progress. No
between-group
because Sedation values
thk data are
(p 5 0.05).
phine- versus 52% of meperidine-treated patients, but these differences did not reach statistical significance. Both study drugs exhibited good safety profiles at the dosesused. There were few significant changesin vital signs and no differences between the groups. Those statistically significant changes in blood pressure and pulse rate were not considered clinically important. The modest blood pressure effects of meperidine do differ from the oral surgery findings of Oikarinen,” who observed much larger reductions of systolic and diastolic blood pressure after administration of similar doses of meperidine but higher doses of diazepam. Meperidine-treated patients experienced the only notable side effects-a headache that responded to additional analgesia and a hysterical reaction. Since the latter is occasionally encountered with diazepam, that medication is considered the probable cause of the adverse reaction. Major proposed advantages of nalbuphine over certain opioid analgesics include hemodynamic stability in the therapeutic dosage range7,’ and a low propensity to produce clinically significant respiratory depression, even with repeated doses.9Rhodes” found nalbuphine to be more cost-effective than meperidine in oral surgery because of a longer recovery room stay and consequent greater nursing care requirement with meperidine. Also, nalbuphine
Volume 66 Number 5
Nalbuphine
and meperidine were recently shown to have similar analgesic properties in the removal of impacted third mo1ars.12 In conclusion, this blinded study successfully employed conscious sedation to manage pain and apprehension during oral surgery. It also commends the agonist-antagonist nalbuphine as an analgesic component by demonstrating no clinical or statistical difference in analgesic and sedative performance compared to meperidine. The authors express their thanks to Mrs. Sharon M. Murry for her secretarial assistance. REFERENCES
1. Gatchel RJ, Ingersoll
BD, Bowman L, Robertson MC, Walker C. The prevalence of dental fear and avoidance: a recent survey study. J Am Dent Assoc 1983;107:609-10. 2. Jorgensen NB, Hayden J Jr. Sedation, local and general anesthesia in dentistry. 3rd ed. Philadelphia: Lea and Febiger, 1980:25-55. 3. Brown PR, Main DM, Wood N. Intravenous sedation in dentistry. A study of 55 cases using pentazocine and diazepam. Br Dent J 1975;139:59-60. 4. Dundee JW. Psychotomimetic effect of n-ally1 opiates used as premeditation. In: Payne JP; Burt RA, Janzen R, K&de! WD, Herz A, Steichele C, eds. Pain, basic principles-pharmacology-therapy. London: Churchill-Livingstone, 1972:346-7.
versus meperidine in conscious sedation
539
5. Engineer S, Jennett S. Respiratory depression following single and repeated doses of pentazocine and pethidine. Br J Anaesth 1972;44:795-802. 6. Jasinski DR. Mansky PA. Evaluation of nalbuphine for abuse potential. Clin Pharmacol Ther 1972;13:78-90. 7. Lee G, Low RI, Amsterdam EA, DeMaria AN, Huber PW, Mason DT. Hemodynamic effects of morphine and nalbuphine in acute myocardial infarction. Clin Pharmacol Ther 198 1;29:576-8 1. 8. Lake CL, Duckworth EN, DiFazio CA, Durbin CG, Magruder MR. Cardiovascular effects of nalbuphine in patients with coronary or valvular heart disease. Anesthesiology 1982; 57:498-503. 9. Romagnoli
A, Keats AS. Ceiling effect for respiratory depression by nalbuphine. Clin Pharmacol Ther 1980;27:478-85. IO. Oikarinen VJ. Intravenous diazepam-pethidine premedication in oral surgery. Proc Finn Dent Sot 1976;72:143-51. I I. Rhodes RA. A cost analysis of nalbuphine versus meperdine used in oral surgery procedures. Clin Ther 1986;8:415-9. 12. Scott RF. A double-blind comparison of nalbuphine and meperidine hydrochloride as intravenous analgesics in combination with diazepam for oral surgery outpatients. J Oral Maxillofac Surg 1987;45:473-6. Reprint requests to: Dr. Edward Dolan Division of Oral and Maxillofacial Box 2955 Duke University Medical Center Durham, NC 27710.
Surgery
UNIVERSITY
MEDICAL
CENTER
Nalbuphine and meperidine were compared as analgesic components of intravenous conscious sedation a double-blind, prospective trial of 47 patients undergoing elective oral surgery. Subjects were evaluated for pain intensity, pain relief, anxiety, sedation, recall, and vital signs at systematic observation points intraoperatively and postoperatively. At the conclusion of surgery 83% of patients who had received nalbuphine and 88% of patients treated with meperidine indicated complete pain relief. One observed adverse reaction was attributed to meperidine and another to the sedative component diazepam. No statistically significant differences were observed between nalbuphine and meperidine treatments.
in
(ORAL SURC ORAL MED ORAL PATHOL 1988;66:536-9)
S
ince adults are fearful of general dental procedures,’ higher levels of anxiety are probable among those requiring oral surgical manipulations. Thus pharmacologic strategies to manage apprehension and pain during oral surgery offer a model to study clinical techniques and to evaluate analgesics. A significant advance has been the implementation of intravenous conscious sedation. This concept of using sedative-analgesic mixtures first gained wide attention more than three decades ago with the use of meperidine, hyoscine, and pentobarbital.2 Since that time the regimen has evolved as benzodiazepines, and additional synthetic opioids have become available. There has also been significant interest in narcotic agonist-antagonist drugs as substitutes for the pure agonist opioids. As such pentazocine has been used in dentistry ,3 but it is not popular in the United States, possibly because of risks of psychotomimetic reactions4 and respiratory depression.5Nal-
Supported by a research grant from Du Pont Pharmaceuticals of Wilmington, Del. Presented in part at the 88th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, Orlando, Fla., March 25-28, 1987. *Assistant Professor, Division of Oral and Maxillofacial Surgery. **Professor, Department of Anesthesiology. ***Medical Research Analyst, Department of Anesthesiology.
536
buphine is another parenteral agonist-antagonist analgesic that has a low abuse potential,6 a general safety profile that includes minimal effects on cardiovascular function’, * and a “ceiling” beyond which respiratory depression does not significantly worsen with further doses of drug.9 To assess the potential value of nalbuphine in intravenous conscious sedation, a double-blind study was conducted in which oral surgery outpatients received either nalbuphine or meperidine in combination with diazepam before infiltration of a local anesthetic. PATIENTS
AND METHODS
After institutional review board approval, 47 informed, consenting oral surgery outpatients, 20 to 52 years of age (American Society of Anesthesiologists status I or II), were entered into this protocol. No patients were pregnant or lactating females; suffered from pain unrelated to the presenting oral surgery condition; had a history of liver dysfunction, psychiatric disorders, or drug abuse; or had known hypersensitivity to local anesthetics, diazepam, nalbuphine, or meperidine. Subjects were asked to avoid analgesics, antiinflammatory medications, sedatives, or other central nervous system-active agents for at least 6 hours before the surgical procedure. Study medications packaged in identical 2 ml syringes (containing either 20 mg of nalbuphine
Nalbuphine
Volume 66 Number 5
Table
versus meperidine in conscious sedation
537
1. Rating scales
Pain intensity* Pain relief? Level of anxiety? Degree of recall* Patient cooperationt Degree of sedation?
patient
0
I
None None Unchanged None No None (awake)
Mild Incomplete Decreased Partial Yes Slight (sleepy)
*Defined
by direct
tDefined
by surgeon/observer.
Table
II. Demographic patient data
Severe Complete
Moderate (verbal stimulus to awaken)
Severe (painful stimulus to awaken)
Surgery (min) + SEM
Sex (M/F)
Nalbuphine Meperidine between
Moderate Adequate Increased Total
questioning.
Treared groups
No dii?erences
3
2
11/13 10113 groups
are statistically
significant
27.1 * 1.5 28.5 f 1.6
69.5 k 3.0 71.5 t 2.6
43.5 k 4.2 46.4 f 4.6
(I, 5 0.05).
hydrochioride or 30 mg of meperidine hydrochloride) were randomly assigned. Patients, surgeon, and observer were “blinded.” Medication code numbers were assigned in blocks of 10. Except for the local anesthetic, all medications were administered via a peripheral intravenous infusion of 5% dextrose in 0.225% saline. Incremental dosesof diazepam were titrated at a rate of 2.5 mg every 45 to 60 secondsto achieve the desired degree of tranquilization; maximum dose permitted was 20 mg. After the effects of diazepam had been assessed, 20 mg of nalbuphine or 50 mg of meperidine was administered over 3 minutes. After a regional injection of 2% lidocaine hydrochloride with 1: 100,000 epinephrine was given, surgery was initiated. One additional dose of study medication (20 mg of nalbuphine or 50 mg of meperidine) was allowed if the operation was prolonged or if analgesia was inadequate. Administration of any other medications required the patient’s withdrawal from the study. Table I shows the rating scales for recording observations for an individual patient. The same surgeon and observer studied each patient. Pain intensity, level of anxiety, degree of sedation, and vital signs were documented preoperatively, at 5minute intervals during surgery, and every 15 minutes during a recovery period of at least 1 hour. Pain relief, degree of recall, and patient cooperation were determined after surgery. Adverse reactions were reported for duration, severity, and probability of cause by the study medication. Results were considered statistically significant when tests yielded two-tailed p values of 0.05 or less,
A paired t test was used to assesshomogeneity of the treatment groups for demographic variables and to evaluate changes in vital signs. Fisher’s exact test was utilized for analysis of categoric data, efficacy parameters, and the comprehensive evaluations. RESULTS
No significant differences between the groups were detected on the basis of demographic variables depicted in Table II. Also, there were no significant differences between treatment groups with respect to surgical difficulty (Table III). Five nalbuphine- and seven meperidine-treated patients underwent routine extractions with bone cutting; impacted teeth were removed in 14 nalbuphine- and 11 meperidinetreated patients. Twenty-three of the 24 nalbuphine- and 21 of the 23 meperidine-treated patients successfully completed the protocol; 3 of the 24 nalbuphine- and 2 of the 23 meperidine-treated patients received an allowed second dose of study medication; 1 of the 24 nalbuphine- and 2 of the 23 meperidine-treated patients were excluded from analyses because they had received additional diazepam after administration of study medication. Table IV shows mean total drug dosages for patients who completed the protocol. Table V shows changes from baseline to end of surgery for pain intensity, pain relief, sedation, anxiety, and recall. At baseline every patient was rated as having “no pain” and “no sedation.” There were no significant differences between the nalbuphine- and meperidine-treated groups for any of the
538
Dolan et al.
Table
III. Distribution
Oral Surg November 1988
of surgical difficulty
in treated
groups Nalbuphine ! ~~-
I Meperidine
3 (13%‘) 2 (8’%)
7 (30%) 0 (0%)
3 (13%) 4 (17%) 6 (25%) 1 (4%) 0 (0%) 5 (21%)
2 3 3 2 I 5
Routine extractions Bone cutting---minimum Bone cutting---extensive Impactions Soft tissue Partial bone Vertical Mesioangular Horizontal Not recorded No differences
Table
IV.
between
groups
are stntiatically
significant
V. Pain, sedation. anxiety, and recall of treatment groups at end of surgery ,
Table
Nuibuphirw
Pain intensity None Mild Moderate Pain relief Adequate Complete Sedation Slight Moderate Anxiety Unchanged Decreased Increased Recall Partial Total
(9%) (13%) (13%) (9%) (4%) (22%)
(p 5 0.05)
Mean total drug doses
Nalbuphine
Meperidine
Note
that
evaluation
Nalbuphine Meperidine Diazepam Local anesthetic* *2W
Lidocaine
hydrochloride
0.33 mg/kg
are not recorded
0.78 mg/kg 9.6 mg 7.9 ml
9.6 mg 8.4 ml with
I : 100.000
the
epinephrine.
cited parameters. None of the patients in either treatment group was rated as uncooperative. All vital signs were within normal limits and not statistically different between treatment groups at any intraoperative or postoperative period, but several statistically significant blood pressure and pulse rate changes within groups did occur. However, no statistical observation had clinical importance. One meperidine-treated patient developed a severe headache at completion of the surgical procedure; the headache resolved in approximately 1 hour. Another patient who experienced a hysterical reaction after IO mg of diazepam and 50 mg of meperidine responded to treatment with physostigmine and promethazine. No adverse reactions were observed in the nalbuphine-treated group. DISCUSSION
In this series of patients nalbuphine and meperidine provided similar analgesia and sedation. Differences observed were not statistically significant. At the end of surgery 83% of patients who had received nalbuphine and 86% of patients who had been treated with meperidine described the relief of pain afforded by their study medication as complete. Total operation recall occurred in 22% of nalbu-
statistically
number
was added
12 (57%) 5 (24%) 4 (19%)
4 (17%) 19 (83%)
3 (14%) 18 (86%)
I2 (52%) (48%)
11 (55%) 9 (45%) 7 (41%)
9 (47%) 9 (47%) 1 (5%)
10 (57%) 0 (0%)
10 (48%)
18 (78%) 5 (22%) for
anxiety
to protocol
Meperidinr
9 (39%) 8 (35%) 6 (26%)
I I
for one meperidine
significant
/
1 I (52%)
is less than after
study patient.
other
ratings
was in progress. No
between-group
because Sedation values
thk data are
(p 5 0.05).
phine- versus 52% of meperidine-treated patients, but these differences did not reach statistical significance. Both study drugs exhibited good safety profiles at the dosesused. There were few significant changesin vital signs and no differences between the groups. Those statistically significant changes in blood pressure and pulse rate were not considered clinically important. The modest blood pressure effects of meperidine do differ from the oral surgery findings of Oikarinen,” who observed much larger reductions of systolic and diastolic blood pressure after administration of similar doses of meperidine but higher doses of diazepam. Meperidine-treated patients experienced the only notable side effects-a headache that responded to additional analgesia and a hysterical reaction. Since the latter is occasionally encountered with diazepam, that medication is considered the probable cause of the adverse reaction. Major proposed advantages of nalbuphine over certain opioid analgesics include hemodynamic stability in the therapeutic dosage range7,’ and a low propensity to produce clinically significant respiratory depression, even with repeated doses.9Rhodes” found nalbuphine to be more cost-effective than meperidine in oral surgery because of a longer recovery room stay and consequent greater nursing care requirement with meperidine. Also, nalbuphine
Volume 66 Number 5
Nalbuphine
and meperidine were recently shown to have similar analgesic properties in the removal of impacted third mo1ars.12 In conclusion, this blinded study successfully employed conscious sedation to manage pain and apprehension during oral surgery. It also commends the agonist-antagonist nalbuphine as an analgesic component by demonstrating no clinical or statistical difference in analgesic and sedative performance compared to meperidine. The authors express their thanks to Mrs. Sharon M. Murry for her secretarial assistance. REFERENCES
1. Gatchel RJ, Ingersoll
BD, Bowman L, Robertson MC, Walker C. The prevalence of dental fear and avoidance: a recent survey study. J Am Dent Assoc 1983;107:609-10. 2. Jorgensen NB, Hayden J Jr. Sedation, local and general anesthesia in dentistry. 3rd ed. Philadelphia: Lea and Febiger, 1980:25-55. 3. Brown PR, Main DM, Wood N. Intravenous sedation in dentistry. A study of 55 cases using pentazocine and diazepam. Br Dent J 1975;139:59-60. 4. Dundee JW. Psychotomimetic effect of n-ally1 opiates used as premeditation. In: Payne JP; Burt RA, Janzen R, K&de! WD, Herz A, Steichele C, eds. Pain, basic principles-pharmacology-therapy. London: Churchill-Livingstone, 1972:346-7.
versus meperidine in conscious sedation
539
5. Engineer S, Jennett S. Respiratory depression following single and repeated doses of pentazocine and pethidine. Br J Anaesth 1972;44:795-802. 6. Jasinski DR. Mansky PA. Evaluation of nalbuphine for abuse potential. Clin Pharmacol Ther 1972;13:78-90. 7. Lee G, Low RI, Amsterdam EA, DeMaria AN, Huber PW, Mason DT. Hemodynamic effects of morphine and nalbuphine in acute myocardial infarction. Clin Pharmacol Ther 198 1;29:576-8 1. 8. Lake CL, Duckworth EN, DiFazio CA, Durbin CG, Magruder MR. Cardiovascular effects of nalbuphine in patients with coronary or valvular heart disease. Anesthesiology 1982; 57:498-503. 9. Romagnoli
A, Keats AS. Ceiling effect for respiratory depression by nalbuphine. Clin Pharmacol Ther 1980;27:478-85. IO. Oikarinen VJ. Intravenous diazepam-pethidine premedication in oral surgery. Proc Finn Dent Sot 1976;72:143-51. I I. Rhodes RA. A cost analysis of nalbuphine versus meperdine used in oral surgery procedures. Clin Ther 1986;8:415-9. 12. Scott RF. A double-blind comparison of nalbuphine and meperidine hydrochloride as intravenous analgesics in combination with diazepam for oral surgery outpatients. J Oral Maxillofac Surg 1987;45:473-6. Reprint requests to: Dr. Edward Dolan Division of Oral and Maxillofacial Box 2955 Duke University Medical Center Durham, NC 27710.
Surgery