Drugs Used for Parenteral Sedation in Dental Prac'dce Raymond A

Anesth Prog 35:199-205 1988

Drugs Used for Parenteral Sedation in Dental Prac'dce Raymond A. Dionne, DDS, PhD,* and Helen C. Gift, PhDt *Neurobiology and Anesthesiology Branch, Intramural Program, and tDisease Prevention and Health Promotion Branch, Epidemiology Program, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland

The relative efficacy and safety of drugs and supplemented with intravenous sedation combinations used clinically in dentistry as consisting of a benzodiazepine and an opioid or a premedicants to alleviate patient apprehension barbiturate. are largely unsubstantiated. To evaluate the efficacy and safety of agents used for parenteral sedation through controlled clinical trials, it is first necessary to identify which drugs, doses, and routes of administration are actually used in practice. A survey instrument was developed to characterize the drugs used for The control of pain and anxiety is an essential part of clinically dental practice. Many strategies are used to achieve anesthesia and sedation by dentists with this goal, including psychologic approaches, local anes- advanced training in pain control. A random thetics, and and individu- sample of 500 dentists who frequently use sedatives general anesthetics, in was selected ally or in combination. The choice of the modality for a anesthesia and sedation practice particular situation is based on the training, knowledge, from the Fellows of the American Dental Society and experience of the dentist, the medical status of the of Anesthesiology. The first mailing was followed patient, and the psychologic and dental needs of the by a second mailing to nonrespondents after 30 1,2 days. The respondents report a variety of patient. General and sedative are parenteral sedation techniques in combination anesthesia procedures used with local anesthesia (the response categories are widely for dentistry in the United States and Canada, as not mutually exclusive): nitrous oxide (64%), well as in other countries. Accurate information, how- intravenous conscious sedation (59%), ever, regarding the number of cases performed is not intravenous "deep" sedation (47%), and available or is based on limited data.1,3 The data that do outpatient general anesthesia (27%). Drugs most exist indicate that a wide variety of drugs, doses, and commonly reported for intravenous sedation routes of administration currently are used clinically in include diazepam, methohexital, midazolam, and dentistry as premedicants to alleviate patient appre- combinations of these drugs with narcotics. A hension.2 Ideally, drugs administered should be selective total of 82 distinct drugs and combinations was in accomplishing the therapeutic objective with few, if reported for intravenous sedation and anesthesia. any, effects on other functions. In reality, this happens Oral premedication and intramuscular sedation only if the drugs used, their routes of administration, and are rarely used by this group. Most general dosage are carefully controlled. anesthesia reported is done on an outpatient The drug classes used for sedation or general anesthe- basis in private practice. These results indicate sia in the dental office include benzodiazepines, barbi- that a wide variety of drugs is employed for turates, opioid analgesics, antihistamines, phenothiazines, parenteral sedation in dental practice, but the and alcohols, as well as nitrous oxide and oxygen. Drugs most common practice among dentists with such as the ultrashort-acting barbiturates and the disso- advanced training in anesthesia is local anesthesia ciative agent ketamine in low dosage produce sedation but are generally recognized as general anesthetics. Virtually all routes of drug administration are used in the Received May 13, 1988; accepted for publication June 17, 1988. dental office including oral, inhalational, submucosal, Address correspondence to Dr. Raymond A. Dionne, National intramuscular, intravenous, and rectal.1 Evidence to date Institute of Dental Research, NIH, Building 10, Room 3C-442, 9000 suggests that inhalational and intravenous techniques Rockville Pike, Bethesda, MD 20896 appear to be the most popular, and that opioids, ben- © 1988 by the American Dental Society of Anesthesiology ISSN 0003-3006/88/$3.50

199 200 Drugs Used for Parenteral Sedation in Dental Practcce Anesth Prog 35:199-205 1988 zodiazepines, and ultrashort-acting barbiturates are the drugs as well as the usual dosage. Open-ended sections most popular drug groups.3 of the questionnaire permitted respondents to describe The relative efficacy and safety of these drugs and other specific drugs or combinations used for these combinations, however, are largely unsubstantiated. Cur- purposes. The survey was pretested twice at professional rent dosage guidelines for drugs used singly are based on meetings. minimal data, and dosage guidelines for use of multiple The questionnaire was mailed to a random sample of drugs are virtually nonexistent.4 Despite the record of 500 of the approximately 1500 Fellows of the American safety that has been asserted by the dental profession, Dental Society of Anesthesiology (ADSA). After a period many questions have been raised regarding the 1) appro- of 30 days, nonrespondents were sent a second ques- priate safe and effective use of sedation and general tionnaire. Telephone calls were made to clarify any anesthesia, 2) indications and contraindications for the discrepant responses. Two hundred sixty-four usable use of the techniques in different age groups, 3) appro- responses were received by the cutoff date using this priate agents to be used to provide the greatest margin of approach, a response rate of 53%. safety, and 4) proper management and monitoring of the Fellows of the ADSA must have graduated from an patient.1 accredited dental school and completed one of the Selection and clinical use of anesthesia or sedation is following: continuous, full-time participation for 1 or predicated on a rational evaluation of which drugs or more years of residency in an acceptable anesthesiology techniques are suited to the patient and practitioner. In program; continuous, full-time participation for 3 or more fact, however, the literature upon which such an evalu- years of residency in an acceptable oral and maxillofacial ation might be made is incomplete, leaving the practi- surgery program; continuous participation for 2 or more tioner to make a decision for care without adequate years in a half-time acceptable anesthesiology residency evidence.5 program; or part-time participation in an acceptable The debate over these issues led to the NIH-supported anesthesiology residency program (with specific require- Consensus Development Conference on Anesthesia and ments). Successful completion of an oral examination Sedation held in April 1985. Although the Consensus administered by a panel of ADSA examiners is required Statement concluded that appropriate use of anesthesia for certification. In more than 40 states, dentists who use and sedation in dentistry has a "remarkable record of anesthetics are required to have training equivalent to safety," it was noted that there was not sufficient and being Fellows in the American Dental Society of Anesthe- reliable 1) evidence on the patterns of use of these drugs, siology. 2) esfimates of morbidity and mortality, and 3) evalu- Over two-thirds of the Fellows are oral and maxillofa- ations based on well-controlled, randomized, double- cial surgeons. Of the remainder, most are general practi- blind clinical trials and risk/benefit analysis of drugs used tioners and periodontists. Thus, the results provide a singly or in combination.1 description of use of parenteral sedation in a select group No recent major surveys on current use of anesthetic of dentists, those most likely to be trained to use anesthe- and sedative techniques have been conducted.6 The sia and parenteral sedation. The results are not meant to study reported here was conducted to address one of the describe the use of anesthesia in the general practice of gaps in information-the extent of use, dosage patterns, dentistry, but the use patterns of those who most fre- and routes of administration of these drugs. The identifi- quently use and are most qualified to use parenteral cation of the drugs, doses, and routes of administration sedation. actually used in practice is a prerequisite to the evaluation of the efficacy and safety of drugs. These results will assist in identifying agents and combinations for prospective RESULTS clinical trials of the safety and efficacy of sedative drug regimens in dentistry. Results are presented as percentage distributions, medi- ans, and ranges. In the case of the open-ended questions, the results are presented as counts or qualitative descrip- METHODS tions. Given the wide range of reported use, these summaries appear to provide the most meaningful de- A four-page questionnaire was developed to gather scriptions of the results. information on the use of parenteral sedation in the clinical practice of dentistry. The most common drugs and combinations used for intravenous (IV) sedation, oral Types of Anesthetic Procedures Used premedication, intramuscular (IM) sedation, and general in Dental Practice anesthesia were listed. The respondents were asked to A broad spectrum of pain control modalities are used by indicate the number of patients receiving these specific the respondents; the response categories are not mutu- Anesth Prog 35:199-205 1988 Dionne and Gift 201

Table 1. Types of Anesthetic Procedures Used in Practice, Percent Who Used, and Number of Patients per Month Median Number of Range of Patient Percent Using Patient Visits per Month Visits (2 SD) Local Anesthesia Alone 94 40 0-240 Local Anesthesia and Nitrous Oxide 68 2 0-78 Local Anesthesia and Oral Sedation 11 0 0-3 Local Anesthesia, Nitrous Oxide, and Oral Sedation 14 0 0-6 Local Anesthesia and IM Sedation 4 0 0-3 Local Anesthesia and IM Sedation and Nitrous Oxide 5 0 0-2 Nitrous Oxide Alone 14 0 0-4 IV Sedation ("Conscious Sedation") 53 1 0-80 "Deep" IV Sedation 44 0 0-92 "Deep" IV Sedation and Nitrous Oxide 43 0 0-80 Outpatient General Anesthesia and Local Anesthesia 57 2 0-165 Inpatient General Anesthesia and Local Anesthesia 40 0 0-18 n = 264. ally exclusive (Table 1). For all procedures reported, the Benzodiazepines, such as diazepam and midazolam, range of the number of patients receiving these drugs were the most commonly employed agents (Table 2). indicates wide variation. A few dentists reported very high Barbiturates, primarily methohexital, were the next most use, but most dentists reported no or few patients. Local commonly employed agents. Opioids were not com- anesthesia alone was the most frequently used method, monly used alone as an IV premedicant. with 94% of all respondents reporting using it with one or The three most common drug combinations were used more patients per month. Local anesthesia alone was by approximately one-third of the respondents with one administered to a median of 40 patients per month, but or more patients per month (Table 2). The combination its use varied widely, with a range of 0-240 patients per of a benzodiazepine, a narcotic, and a barbiturate was month reported. The combination of local anesthesia and used widely, as were the combinations of a benzodia- nitrous oxide was also common, with 68% of the survey zepine plus a narcotic and a benzodiazepine plus a sample reporting using this combination with one or barbiturate. more patients. The diversity of specific drugs used clinically for IV A variety of intravenously administered sedative and sedation is illustrated in Tables 3 and 4. Diazepam and anesthetic drug regimens enjoy widespread use among midazolam were the most commonly reported single the survey respondents. Light IV sedation, commonly agents used for this purpose. These two benzodiazepines referred to as conscious sedation, is used by approxi- are being used in combination with a variety of opioid mately half of the respondents on one or more patients agents, as well as other agents such as nitrous oxide and per month. A similar percentage also use IV sedation in atropine. As can be seen in Table 3, meperidine and combination with nitrous oxide. fentanyl are the most frequently reported opioids in So-called deep sedation is used by 44% of the respon- combination with a benzodiazepine. Combinations of dents on one or more patients per month, often in diazepam or midazolam with methohexital are also com- combination with nitrous oxide. Also, outpatient and monly reported, occasionally with nitrous oxide. inpatient anesthesia are still widely used by this group of A variety of combinations were reported in which practitioners in combination with local anesthesia. either diazepam or midazolam is used with an opioid, A small portion (2%-7%) of respondents indicated usually meperidine or fentanyl, and a barbiturate, pre- that they used other, unspecified pharmacologic and nonpharmacologic methods; not enough information was provided to evaluate these responses. Table 2. Drug Classes Used for Intravenous Sedation Percent Using Intravenous Sedation Used Alone Benzodiazepines 52 The most comprehensive data were obtained from the Barbiturates 22 section of the questionnaire on IV sedation. The respon- Narcotics 4 dents were asked to provide patient visit and dosage Most Common Combinations information on commonly used drugs and combinations. Benzodiazepine, Opioid, and Barbiturate 35 Additionally, they indicated other specific drugs or com- Benzodiazepine and Opioid 34 Benzodiazepine and Barbiturate 32 binations that they used, but that were not listed. 202 Drugs Used for Parenteral Sedation in Dental Practice Anesth Prog 35:199-205 1988

Table 3. Specific Benzodiazepine Combinations Reported for Intravenous Sedation Number of Respondents Benzodiazepine Alone Diazepam 71 Midazolam 75 Benzodiazepine Plus Opioid Combinations Diazepam or Midazolam + Meperidine 54 Diazepam or Midazolam + Fentanyl 29 Diazepam or Midazolam + Fentanyl + Nitrous Oxide 6 Diazepam or Midazolam + Butorphanol 6 Diazepam or Midazolam + Pentazocine 3 Diazepam or Midazolam + Atropine 2 Diazepam or Midazolam + Atropine + Nitrous Oxide 1 Benzodiazepine Plus Barbiturate Combinations Diazepam or Midazolam + Methohexital 67 Diazepam or Midazolam + Methohexital + Nitrous Oxide 5 Midazolam + Thiopental 1 Benzodiazepine + Opioid + Barbiturate Combinations Diazepam or Midazolam + Fentanyl + Methohexital 27 Diazepam or Midazolam + Meperidine + Methohexital 20 Diazepam or Midazolam + Butorphanol + Methohexital 8 Diazepam or Midazolam + Pentazocine + Methohexital 6 Diazepam or Midazolam + Meperidine + Methohexital + Atropine 2 Diazepam or Midazolam + Meperidine + Methohexital + Pentobarbital 2 Diazepam + Meperidine + Methohexital + Nitrous Oxide 2 Diazepam + Butorphanol + Methohexital + Atropine 2 Diazepam + Alphaprodine + Methohexital 1 Diazepam + Midazolam + Methohexital + Pentobarbital 1 Diazepam + Fentanyl + Thiopental 1 Midazolam + Fentanyl + Methohexital + Nitrous Oxide 1 Midazolam + Meperidine + Methohexital + Droperidol 1 Midazolam + Meperidine + Methohexital + Pentobarbital + Droperidol 1 Midazolam + Meperidine + Thiopental 1 Midazolam + Butorphanol + Methohexital + Ketamine 1 Midazolam + Butorphanol + Methohexital + Nitrous Oxide 1 Midazolam + Lorazepam + Butorphanol + Methohexital 1

Table 4. Specific Barbiturate and Opioid Combinations Reported for Intravenous Sedation Number of Respondents Barbiturates and Barbiturate Combinations Methohexital Alone 45 Methohexital + Nitrous Oxide 1 Secobarbital + Methohexital + Atropine 1 Secobarbital + Methohexital + Meperidine 1 Pentobarbital + Nitrous Oxide 1 Pentobarbital + Meperidine + Perchlorperazine 1 Pentobarbital + Meperidine + Scopolamine 1 Opioids and Opioid Combinations Meperidine Alone 6 Meperidine + Methohexital 3 Butorphanol Alone 2 Meperidine + Pentobarbital + Scopolamine ("Jorgensen") 2 Meperidine + Atropine 1 Meperidine + Promethazine 1 Fentanyl Alone 1 Fentanyl + Methohexital 1 Alphaprodine Alone 1 Pentazocine Alone 1 Anesth Prog 35:199-205 1988 Dionne and Gift 203

Table 5. Drugs or Combinations Used for Intravenous Sedation, Percent Who Used, Patients per Month, and Usual Dosage Median Number of Percent Using Patient Visits Range of Patient Median Dosage (n = 264) (n = 264) Visits (2 SD) (mg) Midazolam (Versed) Alone 35 0 0-40 5 Diazepam (Valium) Alone 38 0 0-60 10 Methohexital (Brevital) Alone 23 0 0-80 88 Diazepam (Valium) Plus Meperidine (Demerol) 23 0 0-50 10/50 Diazepam (Valium) Plus Fentanyl (Sublimaze) 14 0 0-20 10/0.1 Diazepam (Valium) Plus Methohexital (Brevital) 34 0 0-125 10/50 Diazepam (Valium) Plus Fentanyl (Sublimaze) 10 0 0-65 10/0.1/80 Plus Methohexital (Brevital)

dominantly methohexital. As can be seen in Table 3, Intramuscular Sedation these three-drug combinations are occasionally supple- Three percent of the respondents indicated the use of IM mented with nitrous oxide or atropine. sedation. Diazepam and ketamine were the most fre- Methohexital alone enjoys widespread use under the quently reported, with 4% using each of these with one guise of IV sedation, although it is possible that the division between deep sedation and general anesthesia or more patients per month. Less than 2% of the respondents reported use of meperidine or other agents becomes indistinct with the IV administration of a drug for IM sedation with one or more patients per month. that is normally thought of as a general anesthetic (Table 4). Narcotics are infrequently used alone, but are occasionally combined with barbiturates or the antisialogogue General Anesthesia atropine for sedation (Table 4). Other drugs, both alone and in combination, were Fifty-two percent of the respondents reported using reported in a seemingly endless series of permutations. general anesthesia with one or more patients, the great There was a total, for all IV sedation, of 82 distinct drugs majority with fewer than 10 patients per month (Table 6). or combinations of drugs reported by the sample. Methohexital alone, inhalation anesthetics alone, and Drugs used for IV sedation that were of interest for methohexital plus nitrous oxide were the most commonly further clinical trials were listed on the questionnaire, so reported drugs (23%, 25%, and 19%, respectively) used more specific data could be obtained (Table 5). Less than for general anesthesia with one or more patients per two-fifths of the respondents reported using any of these month. specified drugs or combinations with one or more pa- Those dentists who reported any use of general tients per month. As would be expected, given the data anesthesia were asked if they both administered the reviewed earlier, most dentists do not use the drugs, anesthesia and performed the procedures (Table 6). resulting in a median of zero, but a few dentists report a Seventy-three percent of those respondents who use large number of patients receiving the therapy. For general anesthesia indicated that they did both. The example, diazepam plus methohexital is used on as many remainder indicated that the procedure and anesthesia as 125 patients per month in at least one practice. were done by separate individuals. The respondents in Similarly, there is a range of dosages being provided to this case indicated that they usually did one or the other. those patients who receive the drugs. For those respondent dentists who were not doing the anesthesia, it was being done by another dentist, a nurse anesthetist or registered nurse, or an anesthesiologist. Oral Premedication Six percent of the respondents indicated the use of oral Table 6. General Anesthesia Use premedication. Diazepam was the most frequently re- Use General Anesthesia with Some Patients ported, with 13% using it with one or more patients per (n = 264) 52% month. Less than 5% of the respondents indicated use of If General Anesthesia is Used (n = 213) chloral hydrate, hydroxyzine, promethazine, lorazepam, Administers Anesthesia and Performs Procedure 64% meperidine, diphenhydramine, pentobarbital, or other Procedure and Anesthesia Done by agents as oral premedicants with one or more patients Different Individuals* 36% per month. * eg, D.D.S., nurse anesthetist/R.N., anesthesiologist. 204 Drugs Used for Parenteral Sedation in Dental Practice Anesth Prog 35:199-205 1988

Table 7. Where General Anesthesia is Done Among Those Who Use General Anesthesia Administers Anesthesia and Administers Anesthesia or Location Total* (%) Performs Procedurest (%) Performs Procedures* (%) Private Practice 66 81 40 Outpatient Surgery 5 3 10 Hospital 23 12 41 Dental School 5 3 8 Other 1 1 1 * n = 213. t n = 135. t n = 72.

Most (66%) general anesthesia is done in private clinical practices of dentists certified as Fellows of the practice (Table 7). A hospital is the next most frequently ADSA. The vast majority of dentists other than oral reported location for general anesthesia (23%). Further surgeons have little formal training in parenteral sedation examination shows that respondents who report that they and general anesthesia and are, thus, unlikely to use administer general anesthesia as well as perform the these drugs as frequently. Further research is needed to procedure themselves are doing much more anesthesia in characterize the uses of sedation by general dentists and private practice (81%), whereas those who report assis- specialists other than oral surgeons. Justification for tance with the anesthesia perform the procedure about anesthesia and sedation in dentistry is based on surveys equally in private practice and in the hospital (40% and of dental anxiety among patients8'9 and clinical observa- 41%, respectively). tions of anxious patients who are difficult to treat. Previ- ous reports have indicated that a clinician's preference for one sedative technique over another is largely based on DISCUSSION how well the patient cooperated during the procedure, whereas patients often cannot differentiate between It is clear that there is a wide variety of drugs and treatments in term of anxiety reduction, analgesia, or combinations being used in dental practice under the amnesia.10"1 Given the potential differences in safety umbrella of parenteral sedation, particularly IV sedation. among the wide variety of drugs and combinations Unfortunately, it has been repeatedly emphasized in the reported by the sample, further research should attempt literature that there is a dearth of scientifically acceptable to characterize the relation between the patient's need for evidence to support the use of even the most commonly anxiety reduction and the drug therapy selected. employed drugs such as diazepam and midazolam. The relatively small number of respondents in this study (n = 264) identified 82 different drugs and combinations in ACKNOWLEDGMENT use for IV sedation. Surveying a larger sample likely would reveal an even higher number of drugs and This project was supported in part by a grant from the combinations. It is unlikely that scientific evidence, in the Anesthesia Research Foundation of the American Dental form of prospective clinical trials, exists to support the Society of Anesthesiology. clinical use of such a wide variety of agents. Most general anesthesia is provided in private practice, parficularly by those who report administering the gen- REFERENCES eral anesthesia as well as performing the procedure themselves. The controversial pracfice of a single opera- 1. Anesthesia and Sedation in the Dental Office. National tor-anesthetist appears to be persisting despite the higher Institutes of Health Consensus Development Conference State- mortality attributed to this practice.7 Asserfions of the ment, Vol. 5, No. 5, 1985. safety of the single operator-anesthetist, however, are 2. Houpt M: Pharmacological methods, issues, and direc- based largely on self-report surveys commissioned to tions in behavioral management. Anesth Prog 33:25-28, 1986. 3. Jastak JT: Pharmacological methods and research issues document the safety of this anesthefic practice. Prospec- in the management of the adult patient. Anesth Prog 33:14-16, tive data from a large, representative sample including 1986. private pracfitioners is needed to provide convincing 4. Goodson JM: Evaluation of dose-response data to de- evidence of the safety of this widespread, but controver- rive maximum recommended dosage. In: Dionne RA, Laskin sial, practice. DM, eds., Anesthesia and Sedation in the Dental Office, New The data collected from this survey are based on the York, Elsevier, 1986, pp. 47-56. Anesth Prog 35:199-205 1988 Dionne and Gift 205

5. Yagiela JA. Preoperative preparation and anesthetic 8. Gatchel RJ, Ingersoll BD, Bowman L, Robertson C, selection. In: Dionne RA, Laskin DM, eds., Anesthesia and Walker C: The prevalence of dental fear and avoidance: A Sedation in the Dental Office, New York, Elsevier, 1986, pp. recent survey study. J Am Dent Assoc 107:609-610, 1983. 91-102. 9. Gale E: Fears of the dental situation. J Dent Res 6. Driscoll EJ: Historical perspective of dental anesthesia 51:964-966, 1972. and sedation: In: Dionne RA, Laskin DM, eds., Anesthesia and 10. Dionne RA, Driscoll EJ, Gelfman SS, Sweet JB, Butler Sedation in the Dental Office, New York, Elsevier, 1986, pp. DD, Wirdzek PR: Cardiovascular and respiratory responses to 1-6. intravenous diazapam, fentanyl and methohexital in dental 7. Coplans MD, Green RA: Mortality and morbidity studies. outpatients. J Oral Surg 39:343-349, 1981. In: Coplans MD, Green RA, eds., Anaesthesia and Sedation in 11. Dionne RA: Differential pharmacology of drugs used for Dentistry. Amsterdam, Elsevier, 1983, pp. 131-147. intravenous premedication. J Dent Res 63:842-847, 1984.