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Continuous infusion of methohexital and alfentanil hydrochloride for general anesthesia in outpatient third molar surgery
J Oral Maxillofac
Surg
47~233-237. 1989
Continuous Infusion of Methohexital and Alfentanil Hydrochloride for General Anesthesia in Outpatient Third Molar Surgery MICHAEL T. DACHOWSKI, DMD,* ROBERT KALAYJIAN, MD,t JOHN C. ANGELILLO, DDS, MD,* AND EDWARD A. DOLAN, DDS§ Three anesthetic techniques were compared in this study: 1) Intermittent BrevitaP boluses supplemented with fentanyl and midazolam all titrated to patient movement, 2) constant infusion of BrevitaP supplemented with fentanyl and midazolam all delivered in calculated mg/kg doses based on total body weight, and 3) constant infusion of methohexital (BrevitaP) and alfentanil (Alfentam) supplemented by midazolam (Versed@), droperidol, and glycopyrolate (RobinuP) delivered in calculated mg/kg doses based on lean body mass. Nitrous oxide was delivered in all cases via nasal mask in a 30% to 50% concentration. The mean total dose of BrevitaP in group 1 (intermittent BrevitaP bolus) was 0.17 mg/kg/min (SD = O-07), group 2 (Brevitalm infusion) was 0.23 mg/kg/min (SD = 0.06), and group 3 (alfentanil/Brevital@ infusion) was 0.12 mg/kg/min (SD = 0.07). Mean total dose of alfentanil in group 3 equaled 1.58 mcg/kg/min (SD = 0.73). In group 1, 94% of the patients experienced moderate to severe movement intraoperatively. Twenty-three percent of the patients in group 2, and only 7% of group 3 exhibited moderate to severe movement. Emergence in group 3 averaged 4.5 minutes (SD = 1.6). Three patients (7%) in group 3 had postoperative nausea. Additional subjective findings in group 3 included easier airway maintenance during administration of the anesthetic, lack of unpleasant emergence phenomena such as crying, and prompt readiness for discharge. It was concluded that continuous alfentanil and BrevitaP infusion satisfied the objectives of safety, stability, predictability, and rapid recovery, while improving operating conditions (less patient movement) when compared with more traditional anesthetic techniques.
Introduction Received from Duke University Medical Center, Durham, North Carolina. * Resident, Division of Oral and Maxillofacial Surgery. t Assistant Professor, Department of Anesthesia. $ Associate Professor and Chief, Division of Oral and Maxillofacial Surgery. § Assistant Professor, Division of Oral and Maxillofacial Surgery. Address correspondence and reprint requests to Dr Dachowski: Division of Oral and Maxillofacial Surgery, Duke University Medical Center, Box 2945, Durham, NC 27710. 0 1989 American
Association
of Oral and Maxillofacial
In recent years, increased attention has been directed toward administration of general anesthesia in the dental office. Usually, it is the oral and maxillofacial surgeon, with the support of a trained office staff, who delivers this service in the outpatient, office-based setting. With the advent of shorter-acting, higher-potency intravenous (IV) medications, many of these anesthetics are of the “deep sedation” type. When accompanied with local anesthesia, sedation is usually enough to adequately manage the anxious patient while complet-
Sur-
geons 0278-2391/89/4703-0003$3.00/0
233
234
METHOHEXITAL
ing surgery. In these cases the patient remains conscious and breathing with laryngeal reflexes intact. Many times, though, the patient must be unconscious for surgery to be effectively and efficiently completed. ’ Over the past several decades, barbiturates have become popular because of their anesthetic inductive properties, the relative hemodynamic stability they produce, and their short duration of action. methohexital (BrevitaP, Eli Lilly and Company, Indianapolis) is most preferred because of its extremely short duration of action as well as its shorter elimination half-life when compared with the other short-acting barbiturate, thiopental.’ The general anesthetic effect may be potentiated by other sedative medications that may have been infused in the presurgical stages. In many practices, Brevital is administered in intermittant IV boluses, as a 1% to 2% solution, in doses sufficient to produce amnesia and unconsciousness. By repeating small doses of Brevital, a relatively stable level of general anesthesia is produced. Inherent to this technique is movement of the patient. As an indicator of need for additional Brevital, at times this movement interrupts the case until the next dose of Brevital takes effect.394 This “roller coaster” type of anesthesia can lead to a longer procedure and considerable accumulation of barbiturate that can prolong recovery. One solution is a constant infusion of Brevital to reduce these widely fluctuating levels of anesthesia. Another aspect to a pure Brevital technique for general anesthesia is the frequency of unpleasant emergence phenomena in which patients wake up crying uncontrollably or very angry.5 This result is probably related to providing amnesia with minimal or inadequate analgesia. To reduce these unpleasant experiences, other medications can be titrated prior to administration of the Brevital. These include narcotics such as demerol, fentanyl, and morphine, and/or tranquilizers such as the benzodiaz-
epines, diazepam and midazolam, and phenergan and droperidol, to name a few.’ Determining the cause of prolonged recovery or other anesthetic complications with a technique such as this is difficult due to the number of drugs used and the imprecise dosing. Conversely, the seasoned surgeon/ anesthetist who uses this technique would exclaim that the predictability with which the primary agent, the barbiturate, acts is reassuring. This style of anesthetic practice was used over the years at our institution with satisfactory results. However, we were always somewhat dissatisfied with the intermittent patient movement as well as what appeared to be significant patient variability in anesthetic requirements and recovery time. At one point in our experience, the constant infusion of Brevital provided some improvement of the surgical conditions (reduced patient movement), but slow recovery and unpleasant emergence were still a problem. We hypothesized that if a greater degree of analgesia could be provided, undesirable patient movement and emergence phenomena could be reduced. Narcotics would be the logical choice. With the introduction of alfentanil, a powerful, short-acting, analgesic appropriate for continuous infusion was available.5-‘0 As shown in Table 1, alfentanil is significantly different from other commonly used narcotics.” The most significant difference is a high percentage of un-ionized drug at normal pH resulting in a more rapid uptake through membranes and, therefore, more rapid onset of action. A small volume of distribution and an elimination half-life (tl/2 B) one-half that of the other narcotics results in rapid redistribution of the drug and a more rapid total body elimination. These characteristics make it the most useful narcotic for short procedures in which rapid recovery is desirable. These characteristics also make the drug particularly useful for continuous IV infusion. It was also hypothesized that if dosing of all med-
Table 1.
Comparative
AND ALFENTANIL
HYDROCHLORIDE
Table of Narcotics
pKa Percent Un-ionized at pH 7.4 Octanal: water partition coefficient Percentage bound to plasma proteins t1/2 7~(min) U/2 ci t1/2 p (hr) Vdcc (L/kg) Vdss (L/kg) Clearance (mL/min)
Morphine
Demerol
Fentanyl
Alfentanil
8 23 1.4 30 0.9-2.4 10-20 2-4 0.1-0.4 3-5 10-20
8.5
8.4
6.5 90 145 92 l-3 5-20 1-2 0.1-0.3 0.5-1.0 3-8
Abbreviations: t1/2 7~,rapid distribution half-life; t1/2a, slow distribution half-life; Vdcc, volume of distribution (central compartment); Vdss, volume of distribution (steady state).
DACHOWSKI
ET AL
235
ications was more rigorously controlled, a more consistent blood level and physiological response to pharmacological agents by all the patients could be achieved. One step toward this would be to calculate medication dosage on an actual metabolic mass, the lean body mass (LBM), thus narrowing the differences between patients and producing a more consistent response to anesthesia and recovery from anesthesia in the patient population as a whole.‘2q’3 Strict principles of pharmacokinetics were applied to all patients, using many of the concepts recently described in the literature concerned with constant infusion kinetics such as “plasma efflux. “‘2,‘4-‘7 To this end, a data base on a personal computer was developed. This data base system also was used to calculate each patient’s LBM and the precise doses of all medications according to that figure. Intraoperative and postoperative data also were entered into the data base, thereby affording the ability for ongoing analysis of quality and effectiveness of our anesthetic technique. Method
All patients were to have multiple extractions of impacted third molars with IV general anesthesia without endotracheal intubation. The decision to use general anesthesia was based on preoperative assessment of the patient’s anxiety as well as the degree of expected surgical difficulty. All of the patients were classified as American Society of Anesthesiologists (ASA) 1 or 2. Patients were instructed to fast after midnight on the day of their anesthesia and surgery. Each anesthetic was delivered with the patient seated in a traditional dental chair in the Oral and Maxillofacial Surgery Clinic. Agents were delivered by a surgeon/anesthetist who monitored the patient and maintained the airway. Monitors included precordial stethoscope, noninvasive blood pressure machine (Dinamapm, Critikon, Inc, Tampa, FL), ECG, and pulse oximeter. A complete anesthetic record was kept for each case. A staff anesthesiologist was in attendance for all cases. In group 1, agents were administered based on approximations of dose based on the patient’s body weight. The supplemental agents, fentanyl and midazolam, were titrated to sedative effect on each patient prior to administration of the Brevital. Data were retrospectively entered into the later implemented data base collection program. Patients’ data in groups 2 and 3 were prospectively entered into a data base computer program (Microsoft Works, Microsoft Cot-p, Redmond, WA, with a Macintosh SE computer, Apple Computer, Inc., Cupertino, CA). From these data, microgram-
per-kilogram doses of the selected agents were produced from the LBM calculation. The following formula was used to calculate LBM: Male LBM = [ 1.1 x weight (kg])] - [128 x [weight [kg]/height (cm)]*]; Female LBM = [1.07 x weight (kg])] [I48 x [weight [kg]/height (cm)]*]. Every patient, therefore, received individualized and precisely calculated amounts of anesthetic agents in hope of producing more predictable results. In group 2, fentanyl and midazolam were initially administered at 1.5 t&kg (LBM in kg) and 30 kg/kg, respectively. The Brevital bolus dose was 0.7 mg/ kg, and the infusion rate was 150 pg/kg. A Travenol infusion pump (Travenol Labs, Hookseh, NH) was used for infusion of the Brevital. In group 3, glycopyrrolate was administered at a fixed dose of 0.2 mg and droperidol was administered at 20 &kg. The dose of midazolam was reduced to 15 t&kg. The initial alfentanil bolus was 10 t&kg; a second bolus of 5 &kg was delivered at the discretion of the surgeon/anesthetist based upon the clinical level of anesthesia and respiratory rate. The alfentanil infusion was maintained at 0.75 pg/kg/min. Approximately one to three minutes after the alfentanil bolus, a 0.4 mglkg bolus of Brevital was given to induce anesthesia. Occasionally, a 0.2 mg/kg bolus of Brevital was given at the discretion of the surgeon/anesthetist based on the patient’s response to stimulation. The Brevital infusion rate was maintained at 80 pg/kg/min. Both Brevital and alfentanil were delivered by Bard (C.R. Bard, Inc., North Reading, MA) alfentanil infusion pumps. In addition, the Infusa-Plate@ (Kalayjian Enterprises, Long Beach, CA) system was implemented for utilization of the Bard pump for Brevital delivery. In each group, patients were preoxygenated with 70% oxygen and 30% nitrous oxide delivered through nasal mask for three to five minutes. After induction, nitrous oxide was delivered through the nasal mask at 30% to 50% concentrations with oxygen. Parameters that were measured and compared included total dose of the infused agents, total time of the case, emergence time, and amount of distracting movement by the patient. In addition, intraoperative and postoperative complications were recorded. These included problems with airway management , nausea, and vomiting. Results
Review of the demographic data in Table 2 indicates no significant difference between the groups. There were 16 patients in group 1, 13 in group 2, and 42 in group 3. This variability in number of patients
236 Table 2.
METHOHEXITAL
AND ALFENTANIL
HYDROCHLORIDE
Demographics and Length of Anesthetic
Group
No. of Cases
Age lyrsl
Height (cm)
Weight (kg)
Male
Female
LBM (kg)
Length of Procedure (mm)
I
16 13 42
25.30 2 6.5 19.10 2 4.8 26.10 2 9.0
169.19 i 10.9 166.85 _t 9.6 170.14 ” 11.4
64.50 + 12.6 59.20 & 8.8 64.60 * 11.9
44% 23% 33%
56% 77% 66%
49.79 i 9.6 45.90 2 7.8 49.43 * 9.5
25.75 + 12.7 19.80 * 10.1 23.16 ‘- 11.0
2 3
Values are given as the mean 2 SD.
in each group reflects the evolutionary nature of the project. As is apparent in Table 3, the patients in group 3 required less Brevital (0.12 mg/kg/min) than those of group 1 (0.17 mg/kg/min) or group 2 (0.23 mg/ kg/min), but the difference between groups 1 and 3 was not significant. In group 3, total alfentanil averaged 1.58 t.&kg/min (SD = 0.73). Inherent to the technique in group 3 was a predictable period of apnea, lasting from 30 seconds to one minute, which occurred shortly after the initial Brevital bolus. In three cases this period of apnea was treated by administering 100% oxygen by face mask and briefly suspending the infusions. If respiratory rate decreased below six to eight breaths per minute, the infusion rate of the alfentanil was decreased. None of the patients in the alfentanil group required intubation, or assisted or positive-pressure ventilation. The oxygen saturation was >90% in all cases. The overall incidence of airway complications was minimal. In group 2 there was one case of laryngospasm that was treated with positivepressure ventilation. The degree of patient movement decreased significantly as the anesthetic technique evolved from group 1 through group 3. Moderate to severe movement was exhibited in 94% of the group 1 patients (Table 4). Patients in group 2 had moderate to severe movement 23% of the time, whereas only 7% of the patients in group 3 demonstrated this degree of movement. Time to eye opening was measured only in group 3 (Fig 1). This represented the time from discontinuation of Brevital, alfentanil, and nitrous oxide to eye opening in response to verbal request in a normal tone of voice. The average of 4.6 minutes (SD Table 3.
= 1.6 minutes) was very predictable as evidenced by the narrow range for the group (95% between 1.4 and 7.8 minutes). All were oriented to person, place, and day, and were able to stand within two minutes from eye opening. Subjectively, the group 3 patients had better tone of the oro-facial musculature and the tongue during the anesthetic, improving the ease of airway management. None of the patients in group 3 had an unpleasant emergence from their anesthetic, and only three patients (7%) in this group experienced nausea or vomiting in the recovery period. Discussion Operative conditions in outpatient third molar surgery with general anesthesia in nonintubated patients were greatly improved by the simultaneous continuous infusion of Brevital and alfentanil. This was primarily demonstrated by decreased intraoperative movement. Additionally, increased myofacial tonus, predictable period of emergence, and lack of unpleasant emergence phenomena resulted. With the addition of alfentanil in this fashion, less Brevital was required than that infused while supplemented with fentanyl and midazolam. The dose of alfenatanil used in this investigation was within the low range of the recommended general anesthesia continuous infusion dose, 0.5 to 3.0 l.J_glkglmin.i8 Because of the respiratory depression often associated with potent narcotics such as alfentanil, preoxygenation was necessary. Pulse oximetry and vigilant airway monitoring were required with this technique of anesthetic administration. Recovery and emergence were rapid, very predictable, and pleasant. Patients were found ready for discharge in less than one hour from termination of anesthesia.
Brevital Totals Mean Total Dose of Brevital
Group
(ms)
1 2 3
210.2 t 122.7 200.1 f 88.2 112.5 ? 47.9
Values are given as the mean 2 SD.
(m&kg/min) 0.17 ? 0.07 0.23 ? 0.06 0.12 + 0.07
Table 4. Degree of Movements and Percentage of Occurrence Group
None
Mild
Moderate
1 2 3
0 54 57
6 23 36
75 23 7
Severe 19 0 0
237
DACHOWSKI ET AL
20
1
3.
4.
5. 6. 7.
8.
0
0
2
4 6 8 TIME(MIN.)
10
9.
FIGURE 1. Time to eye-opening.
10.
Using the computer and a data base to operatively calculate all doses of medication and for prospective analysis of patient outcome improved the precision of drug dosing and formed the basis of evaluation of this new anesthetic technique. This model will be used in the future to modify the technique as indicated by our analysis of data. This model will also facilitate evaluation of new drugs or techniques that are incorporated in our practice. We feel that computer technology contributes invaluable quality and safety to our practice and that its use should be considered by all practitioners.
11. 12.
13.
14.
15.
16.
References 1. National Institutes of Health: Consensus development statement on anesthesia and sedation in the dental office. J Am Dent Assoc 390, 1985 2. Thornton JA: Recent Advances in Anesthesia and Analge-
17.
18.
sia, General Anesthesia and Sedation for Dentistry. New York, Churchill-Livingston, 1979, pp 117-137 Wise CC, Robinson JS, Heath MJ, et al: Physiological responses to intermittent methohexitone for conservative dentistry. Br Med J 2:540, 1969 Mann PE, Matt SD, Dixon R, et al: A minimal increment methohexitone technique in conservative dentistry. Anesthesia 26:3, 1970 Cookson RF, Niemegeers CJE, Vanden Bussche G: The development of alfentanil. Br J Anaesth 55: 147S, 1983 Hull CJ: The Pharmacokinetics of alfentanil in man. Br J Anaesth 55:1578, 1983 Hull CJ, Jacobson L: A clinical trial of alfentanil as an adjuvant for short anaesthetic procedures. Br J Anaesth 55:1738, 1983 Kay B, Venkataraman P: Recovery after fentanyl and alfentanil in anaesthesia for minor surgery. Br J Anaesth 5531698, 1983 O’Connor M, Escarpa A, Prys-Roberts C: Ventilatory depression during and after infusion of alfentanil in man. Br J Anaesth 55:217S, 1983 Reitz JA, Howie MB, Hoffer L, et al: The pharmacokinetics of alfentanil in gynecologic surgical patients. J Clin Pharmacol 26:60, 1986 Miller RD: Anesthesia. New York, Churchill-Livingston, 1986, pp 778-782 Crankshaw DP, Boyd MD, Bjorksten AR: Plasma drug efflux-A new approach to optimization of drug infusion for constant blood concentration of thiopental and methohexital. Anesthesiology 67:32, 1987 Crankshaw DP, Edwards NE, Blackman GL, et al: Evaluation of infusion regimens for thiopentone as a primary anaesthetic agent. Eur J Clin Pharmacol28:543, 1985 Prys-Roberts C, Sear JW, Low JM, et al: Hemodynamic and hepatic effects of methohexital infusion during nitrous oxide anesthesia in humans. Anesth Analg 62:317, 1983 McMurray TJ, Robinson FP, Dundee JW, et al: A method for producing constant plasma concentrations of drugs: Application to methohexitone. Br J Anaesth 58:1085, 1986 Crankshaw DP, Boyd MD, Bjorksten AR: An iterative approach to optimization of barbiturate infusions for constant plasma concentration. Anesthesiology 65:A558, 1986 Crankshaw DP: Hypnotics in infusion anaesthesia-With particular reference to thiopentone. Anaesth Intens Care 1590, 1987 Alfenta Manufacturers’ Recommendations per insert.
Surg
47~233-237. 1989
Continuous Infusion of Methohexital and Alfentanil Hydrochloride for General Anesthesia in Outpatient Third Molar Surgery MICHAEL T. DACHOWSKI, DMD,* ROBERT KALAYJIAN, MD,t JOHN C. ANGELILLO, DDS, MD,* AND EDWARD A. DOLAN, DDS§ Three anesthetic techniques were compared in this study: 1) Intermittent BrevitaP boluses supplemented with fentanyl and midazolam all titrated to patient movement, 2) constant infusion of BrevitaP supplemented with fentanyl and midazolam all delivered in calculated mg/kg doses based on total body weight, and 3) constant infusion of methohexital (BrevitaP) and alfentanil (Alfentam) supplemented by midazolam (Versed@), droperidol, and glycopyrolate (RobinuP) delivered in calculated mg/kg doses based on lean body mass. Nitrous oxide was delivered in all cases via nasal mask in a 30% to 50% concentration. The mean total dose of BrevitaP in group 1 (intermittent BrevitaP bolus) was 0.17 mg/kg/min (SD = O-07), group 2 (Brevitalm infusion) was 0.23 mg/kg/min (SD = 0.06), and group 3 (alfentanil/Brevital@ infusion) was 0.12 mg/kg/min (SD = 0.07). Mean total dose of alfentanil in group 3 equaled 1.58 mcg/kg/min (SD = 0.73). In group 1, 94% of the patients experienced moderate to severe movement intraoperatively. Twenty-three percent of the patients in group 2, and only 7% of group 3 exhibited moderate to severe movement. Emergence in group 3 averaged 4.5 minutes (SD = 1.6). Three patients (7%) in group 3 had postoperative nausea. Additional subjective findings in group 3 included easier airway maintenance during administration of the anesthetic, lack of unpleasant emergence phenomena such as crying, and prompt readiness for discharge. It was concluded that continuous alfentanil and BrevitaP infusion satisfied the objectives of safety, stability, predictability, and rapid recovery, while improving operating conditions (less patient movement) when compared with more traditional anesthetic techniques.
Introduction Received from Duke University Medical Center, Durham, North Carolina. * Resident, Division of Oral and Maxillofacial Surgery. t Assistant Professor, Department of Anesthesia. $ Associate Professor and Chief, Division of Oral and Maxillofacial Surgery. § Assistant Professor, Division of Oral and Maxillofacial Surgery. Address correspondence and reprint requests to Dr Dachowski: Division of Oral and Maxillofacial Surgery, Duke University Medical Center, Box 2945, Durham, NC 27710. 0 1989 American
Association
of Oral and Maxillofacial
In recent years, increased attention has been directed toward administration of general anesthesia in the dental office. Usually, it is the oral and maxillofacial surgeon, with the support of a trained office staff, who delivers this service in the outpatient, office-based setting. With the advent of shorter-acting, higher-potency intravenous (IV) medications, many of these anesthetics are of the “deep sedation” type. When accompanied with local anesthesia, sedation is usually enough to adequately manage the anxious patient while complet-
Sur-
geons 0278-2391/89/4703-0003$3.00/0
233
234
METHOHEXITAL
ing surgery. In these cases the patient remains conscious and breathing with laryngeal reflexes intact. Many times, though, the patient must be unconscious for surgery to be effectively and efficiently completed. ’ Over the past several decades, barbiturates have become popular because of their anesthetic inductive properties, the relative hemodynamic stability they produce, and their short duration of action. methohexital (BrevitaP, Eli Lilly and Company, Indianapolis) is most preferred because of its extremely short duration of action as well as its shorter elimination half-life when compared with the other short-acting barbiturate, thiopental.’ The general anesthetic effect may be potentiated by other sedative medications that may have been infused in the presurgical stages. In many practices, Brevital is administered in intermittant IV boluses, as a 1% to 2% solution, in doses sufficient to produce amnesia and unconsciousness. By repeating small doses of Brevital, a relatively stable level of general anesthesia is produced. Inherent to this technique is movement of the patient. As an indicator of need for additional Brevital, at times this movement interrupts the case until the next dose of Brevital takes effect.394 This “roller coaster” type of anesthesia can lead to a longer procedure and considerable accumulation of barbiturate that can prolong recovery. One solution is a constant infusion of Brevital to reduce these widely fluctuating levels of anesthesia. Another aspect to a pure Brevital technique for general anesthesia is the frequency of unpleasant emergence phenomena in which patients wake up crying uncontrollably or very angry.5 This result is probably related to providing amnesia with minimal or inadequate analgesia. To reduce these unpleasant experiences, other medications can be titrated prior to administration of the Brevital. These include narcotics such as demerol, fentanyl, and morphine, and/or tranquilizers such as the benzodiaz-
epines, diazepam and midazolam, and phenergan and droperidol, to name a few.’ Determining the cause of prolonged recovery or other anesthetic complications with a technique such as this is difficult due to the number of drugs used and the imprecise dosing. Conversely, the seasoned surgeon/ anesthetist who uses this technique would exclaim that the predictability with which the primary agent, the barbiturate, acts is reassuring. This style of anesthetic practice was used over the years at our institution with satisfactory results. However, we were always somewhat dissatisfied with the intermittent patient movement as well as what appeared to be significant patient variability in anesthetic requirements and recovery time. At one point in our experience, the constant infusion of Brevital provided some improvement of the surgical conditions (reduced patient movement), but slow recovery and unpleasant emergence were still a problem. We hypothesized that if a greater degree of analgesia could be provided, undesirable patient movement and emergence phenomena could be reduced. Narcotics would be the logical choice. With the introduction of alfentanil, a powerful, short-acting, analgesic appropriate for continuous infusion was available.5-‘0 As shown in Table 1, alfentanil is significantly different from other commonly used narcotics.” The most significant difference is a high percentage of un-ionized drug at normal pH resulting in a more rapid uptake through membranes and, therefore, more rapid onset of action. A small volume of distribution and an elimination half-life (tl/2 B) one-half that of the other narcotics results in rapid redistribution of the drug and a more rapid total body elimination. These characteristics make it the most useful narcotic for short procedures in which rapid recovery is desirable. These characteristics also make the drug particularly useful for continuous IV infusion. It was also hypothesized that if dosing of all med-
Table 1.
Comparative
AND ALFENTANIL
HYDROCHLORIDE
Table of Narcotics
pKa Percent Un-ionized at pH 7.4 Octanal: water partition coefficient Percentage bound to plasma proteins t1/2 7~(min) U/2 ci t1/2 p (hr) Vdcc (L/kg) Vdss (L/kg) Clearance (mL/min)
Morphine
Demerol
Fentanyl
Alfentanil
8 23 1.4 30 0.9-2.4 10-20 2-4 0.1-0.4 3-5 10-20
8.5
8.4
6.5 90 145 92 l-3 5-20 1-2 0.1-0.3 0.5-1.0 3-8
Abbreviations: t1/2 7~,rapid distribution half-life; t1/2a, slow distribution half-life; Vdcc, volume of distribution (central compartment); Vdss, volume of distribution (steady state).
DACHOWSKI
ET AL
235
ications was more rigorously controlled, a more consistent blood level and physiological response to pharmacological agents by all the patients could be achieved. One step toward this would be to calculate medication dosage on an actual metabolic mass, the lean body mass (LBM), thus narrowing the differences between patients and producing a more consistent response to anesthesia and recovery from anesthesia in the patient population as a whole.‘2q’3 Strict principles of pharmacokinetics were applied to all patients, using many of the concepts recently described in the literature concerned with constant infusion kinetics such as “plasma efflux. “‘2,‘4-‘7 To this end, a data base on a personal computer was developed. This data base system also was used to calculate each patient’s LBM and the precise doses of all medications according to that figure. Intraoperative and postoperative data also were entered into the data base, thereby affording the ability for ongoing analysis of quality and effectiveness of our anesthetic technique. Method
All patients were to have multiple extractions of impacted third molars with IV general anesthesia without endotracheal intubation. The decision to use general anesthesia was based on preoperative assessment of the patient’s anxiety as well as the degree of expected surgical difficulty. All of the patients were classified as American Society of Anesthesiologists (ASA) 1 or 2. Patients were instructed to fast after midnight on the day of their anesthesia and surgery. Each anesthetic was delivered with the patient seated in a traditional dental chair in the Oral and Maxillofacial Surgery Clinic. Agents were delivered by a surgeon/anesthetist who monitored the patient and maintained the airway. Monitors included precordial stethoscope, noninvasive blood pressure machine (Dinamapm, Critikon, Inc, Tampa, FL), ECG, and pulse oximeter. A complete anesthetic record was kept for each case. A staff anesthesiologist was in attendance for all cases. In group 1, agents were administered based on approximations of dose based on the patient’s body weight. The supplemental agents, fentanyl and midazolam, were titrated to sedative effect on each patient prior to administration of the Brevital. Data were retrospectively entered into the later implemented data base collection program. Patients’ data in groups 2 and 3 were prospectively entered into a data base computer program (Microsoft Works, Microsoft Cot-p, Redmond, WA, with a Macintosh SE computer, Apple Computer, Inc., Cupertino, CA). From these data, microgram-
per-kilogram doses of the selected agents were produced from the LBM calculation. The following formula was used to calculate LBM: Male LBM = [ 1.1 x weight (kg])] - [128 x [weight [kg]/height (cm)]*]; Female LBM = [1.07 x weight (kg])] [I48 x [weight [kg]/height (cm)]*]. Every patient, therefore, received individualized and precisely calculated amounts of anesthetic agents in hope of producing more predictable results. In group 2, fentanyl and midazolam were initially administered at 1.5 t&kg (LBM in kg) and 30 kg/kg, respectively. The Brevital bolus dose was 0.7 mg/ kg, and the infusion rate was 150 pg/kg. A Travenol infusion pump (Travenol Labs, Hookseh, NH) was used for infusion of the Brevital. In group 3, glycopyrrolate was administered at a fixed dose of 0.2 mg and droperidol was administered at 20 &kg. The dose of midazolam was reduced to 15 t&kg. The initial alfentanil bolus was 10 t&kg; a second bolus of 5 &kg was delivered at the discretion of the surgeon/anesthetist based upon the clinical level of anesthesia and respiratory rate. The alfentanil infusion was maintained at 0.75 pg/kg/min. Approximately one to three minutes after the alfentanil bolus, a 0.4 mglkg bolus of Brevital was given to induce anesthesia. Occasionally, a 0.2 mg/kg bolus of Brevital was given at the discretion of the surgeon/anesthetist based on the patient’s response to stimulation. The Brevital infusion rate was maintained at 80 pg/kg/min. Both Brevital and alfentanil were delivered by Bard (C.R. Bard, Inc., North Reading, MA) alfentanil infusion pumps. In addition, the Infusa-Plate@ (Kalayjian Enterprises, Long Beach, CA) system was implemented for utilization of the Bard pump for Brevital delivery. In each group, patients were preoxygenated with 70% oxygen and 30% nitrous oxide delivered through nasal mask for three to five minutes. After induction, nitrous oxide was delivered through the nasal mask at 30% to 50% concentrations with oxygen. Parameters that were measured and compared included total dose of the infused agents, total time of the case, emergence time, and amount of distracting movement by the patient. In addition, intraoperative and postoperative complications were recorded. These included problems with airway management , nausea, and vomiting. Results
Review of the demographic data in Table 2 indicates no significant difference between the groups. There were 16 patients in group 1, 13 in group 2, and 42 in group 3. This variability in number of patients
236 Table 2.
METHOHEXITAL
AND ALFENTANIL
HYDROCHLORIDE
Demographics and Length of Anesthetic
Group
No. of Cases
Age lyrsl
Height (cm)
Weight (kg)
Male
Female
LBM (kg)
Length of Procedure (mm)
I
16 13 42
25.30 2 6.5 19.10 2 4.8 26.10 2 9.0
169.19 i 10.9 166.85 _t 9.6 170.14 ” 11.4
64.50 + 12.6 59.20 & 8.8 64.60 * 11.9
44% 23% 33%
56% 77% 66%
49.79 i 9.6 45.90 2 7.8 49.43 * 9.5
25.75 + 12.7 19.80 * 10.1 23.16 ‘- 11.0
2 3
Values are given as the mean 2 SD.
in each group reflects the evolutionary nature of the project. As is apparent in Table 3, the patients in group 3 required less Brevital (0.12 mg/kg/min) than those of group 1 (0.17 mg/kg/min) or group 2 (0.23 mg/ kg/min), but the difference between groups 1 and 3 was not significant. In group 3, total alfentanil averaged 1.58 t.&kg/min (SD = 0.73). Inherent to the technique in group 3 was a predictable period of apnea, lasting from 30 seconds to one minute, which occurred shortly after the initial Brevital bolus. In three cases this period of apnea was treated by administering 100% oxygen by face mask and briefly suspending the infusions. If respiratory rate decreased below six to eight breaths per minute, the infusion rate of the alfentanil was decreased. None of the patients in the alfentanil group required intubation, or assisted or positive-pressure ventilation. The oxygen saturation was >90% in all cases. The overall incidence of airway complications was minimal. In group 2 there was one case of laryngospasm that was treated with positivepressure ventilation. The degree of patient movement decreased significantly as the anesthetic technique evolved from group 1 through group 3. Moderate to severe movement was exhibited in 94% of the group 1 patients (Table 4). Patients in group 2 had moderate to severe movement 23% of the time, whereas only 7% of the patients in group 3 demonstrated this degree of movement. Time to eye opening was measured only in group 3 (Fig 1). This represented the time from discontinuation of Brevital, alfentanil, and nitrous oxide to eye opening in response to verbal request in a normal tone of voice. The average of 4.6 minutes (SD Table 3.
= 1.6 minutes) was very predictable as evidenced by the narrow range for the group (95% between 1.4 and 7.8 minutes). All were oriented to person, place, and day, and were able to stand within two minutes from eye opening. Subjectively, the group 3 patients had better tone of the oro-facial musculature and the tongue during the anesthetic, improving the ease of airway management. None of the patients in group 3 had an unpleasant emergence from their anesthetic, and only three patients (7%) in this group experienced nausea or vomiting in the recovery period. Discussion Operative conditions in outpatient third molar surgery with general anesthesia in nonintubated patients were greatly improved by the simultaneous continuous infusion of Brevital and alfentanil. This was primarily demonstrated by decreased intraoperative movement. Additionally, increased myofacial tonus, predictable period of emergence, and lack of unpleasant emergence phenomena resulted. With the addition of alfentanil in this fashion, less Brevital was required than that infused while supplemented with fentanyl and midazolam. The dose of alfenatanil used in this investigation was within the low range of the recommended general anesthesia continuous infusion dose, 0.5 to 3.0 l.J_glkglmin.i8 Because of the respiratory depression often associated with potent narcotics such as alfentanil, preoxygenation was necessary. Pulse oximetry and vigilant airway monitoring were required with this technique of anesthetic administration. Recovery and emergence were rapid, very predictable, and pleasant. Patients were found ready for discharge in less than one hour from termination of anesthesia.
Brevital Totals Mean Total Dose of Brevital
Group
(ms)
1 2 3
210.2 t 122.7 200.1 f 88.2 112.5 ? 47.9
Values are given as the mean 2 SD.
(m&kg/min) 0.17 ? 0.07 0.23 ? 0.06 0.12 + 0.07
Table 4. Degree of Movements and Percentage of Occurrence Group
None
Mild
Moderate
1 2 3
0 54 57
6 23 36
75 23 7
Severe 19 0 0
237
DACHOWSKI ET AL
20
1
3.
4.
5. 6. 7.
8.
0
0
2
4 6 8 TIME(MIN.)
10
9.
FIGURE 1. Time to eye-opening.
10.
Using the computer and a data base to operatively calculate all doses of medication and for prospective analysis of patient outcome improved the precision of drug dosing and formed the basis of evaluation of this new anesthetic technique. This model will be used in the future to modify the technique as indicated by our analysis of data. This model will also facilitate evaluation of new drugs or techniques that are incorporated in our practice. We feel that computer technology contributes invaluable quality and safety to our practice and that its use should be considered by all practitioners.
11. 12.
13.
14.
15.
16.
References 1. National Institutes of Health: Consensus development statement on anesthesia and sedation in the dental office. J Am Dent Assoc 390, 1985 2. Thornton JA: Recent Advances in Anesthesia and Analge-
17.
18.
sia, General Anesthesia and Sedation for Dentistry. New York, Churchill-Livingston, 1979, pp 117-137 Wise CC, Robinson JS, Heath MJ, et al: Physiological responses to intermittent methohexitone for conservative dentistry. Br Med J 2:540, 1969 Mann PE, Matt SD, Dixon R, et al: A minimal increment methohexitone technique in conservative dentistry. Anesthesia 26:3, 1970 Cookson RF, Niemegeers CJE, Vanden Bussche G: The development of alfentanil. Br J Anaesth 55: 147S, 1983 Hull CJ: The Pharmacokinetics of alfentanil in man. Br J Anaesth 55:1578, 1983 Hull CJ, Jacobson L: A clinical trial of alfentanil as an adjuvant for short anaesthetic procedures. Br J Anaesth 55:1738, 1983 Kay B, Venkataraman P: Recovery after fentanyl and alfentanil in anaesthesia for minor surgery. Br J Anaesth 5531698, 1983 O’Connor M, Escarpa A, Prys-Roberts C: Ventilatory depression during and after infusion of alfentanil in man. Br J Anaesth 55:217S, 1983 Reitz JA, Howie MB, Hoffer L, et al: The pharmacokinetics of alfentanil in gynecologic surgical patients. J Clin Pharmacol 26:60, 1986 Miller RD: Anesthesia. New York, Churchill-Livingston, 1986, pp 778-782 Crankshaw DP, Boyd MD, Bjorksten AR: Plasma drug efflux-A new approach to optimization of drug infusion for constant blood concentration of thiopental and methohexital. Anesthesiology 67:32, 1987 Crankshaw DP, Edwards NE, Blackman GL, et al: Evaluation of infusion regimens for thiopentone as a primary anaesthetic agent. Eur J Clin Pharmacol28:543, 1985 Prys-Roberts C, Sear JW, Low JM, et al: Hemodynamic and hepatic effects of methohexital infusion during nitrous oxide anesthesia in humans. Anesth Analg 62:317, 1983 McMurray TJ, Robinson FP, Dundee JW, et al: A method for producing constant plasma concentrations of drugs: Application to methohexitone. Br J Anaesth 58:1085, 1986 Crankshaw DP, Boyd MD, Bjorksten AR: An iterative approach to optimization of barbiturate infusions for constant plasma concentration. Anesthesiology 65:A558, 1986 Crankshaw DP: Hypnotics in infusion anaesthesia-With particular reference to thiopentone. Anaesth Intens Care 1590, 1987 Alfenta Manufacturers’ Recommendations per insert.