Lidocaine as a Supplement to General Anesthesia for Extraction of Third Molars: Serum Levels J. Scaramelia DDS, G. D. Allen MD, W. M. Goebel DDS MSD, and D. Donaldson BDS FDS RCS MDS

The supplementation of outpatient general anesthesia for oral surgery with local anesthesia is in part an attempt to decrease nociceptive reflexes and thus lower the amount of general anesthetic required (1). In addition a measure of post-operative pain relief is provided. Because of the need for speed during outpatient general anesthesia the local anesthetic is usually administered more rapidly than in the conscious patient. This, together with the lack of feedback as to the effectiveness of the local anesthetic which is achieved in the conscious patient, may cause the placement of the local anesthetic to be less accurate. In some oral surgery techniques under general anesthesia all four oral quadrants are injected simultaneously with the supplementary local anesthetic. It was considered possible that in such circumstances the circulating level of serum lidocaine could reach levels which could produce central effects, and thus contribute to the depth of general anesthesia (2). Serum levels of lidocaine have been studied following the use oflidocaine for general surgical procedures (3) and dentistry (4). General anesthesia could influence the uptake and distribution of the local anesthetic during oral surgery and toxic levels of circulating serum lidocaine be approached. It was determined to study serum levels of circulating lidocaine during a technique of routine oral surgery general anesthesia. In addition as it has been suggested that serum levels of methohexital could be used as an index of recovery (5), the serum levels of methohexital on recovery were measured. (Editor's Comment:) This paper raises a significant question as to whether local anesthesia may also serve as a central supplement to general anesthesia. Lidocaine has been shown by others to have an effect which enhances the minimum alveolar concentration (MAC). Because of the clinical nature of this study, the authors found it extremely difficult to control variations in the length ofprocedures and, of course, dosage. Limitations imposed by Human Subjeu. Protection Committee, compromised the number of samples obtained. Mindful of these problems, subsequent studies are being designed to provide more definitive data. Other investigators are encouraged to react to the hypothesis posed by the authors.) From the Division of Biological Dental Sciences and The Departmenit of Anesthesia, Center for the Health Sciences, University of California at Los Angeles

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Method Ten patients presenting for surgical removal of third molars under outpatient general anesthesia were studied. After having obtained a fully informed consent, the patient was seated in the semi-supine position in the dental chair, and a control venous sample obtained. The technique followed throughouit the procedure was to start an intravenous infuision with dextrose-saline and, following the placement of suitable monitors to administer glycopyrrolate 0.2mg, diazepam 10mg and fentanyl 0.05 mg intravenously. After placement of a mouth prop the patient was induced with 1% methohexital to the level of loss of lash reflex. An oropharangeal partition was placed and all four quadrants of the mouth were anesthetized using lidocaine 2% with epinephrine 1:100,000. The total dose of lidocaine varied from 144 to 252 mg dependent upon the surgeon's assessment of the surgical requirement. Supplementary doses of methohexital 20 mg were administered and supplementation with 10 liters of nitrous oxide-oxygen in the ratio of 7:3 was continued throughouit the procedure. Control cubital fossa venous blood samples were withdrawn initially and then subsequent to the administration of glycopyrollate, diazepam and fentanyl, two minutes after the administration of methohexital, 2 minutes after the administration of the local anesthetic, seven minutes after the administration of the local anesthetic, on completion of the surgery, and when the patient was judged to be recovered. The determination of recovery was made with the use of Bender face-hand test (6), response to questioning of place and time, and a negative 'Rhomberg" sign which were considered to imply street fitness. The samples were analyzed by gas chromatography for serum lidocaine levels (7) and the final sample for methohexital levels by gas chromatography developed for multiple drug evaluations (8). Results Of the 10 patients participating in this study the results from only six patients could be compared, the others being unsuitable because ofthe use ofadditional drugs or problems with obtaining samples at appropriate times. The mean dose of lidocaine administered was 3.16 mg/kg, dependent upon the estimated difficulty of the surgery. The circulating levels oflidocaine ANESTHESIA PROGRESS

indicate great individual variation tunrelated to the dose or to the weight of the patient (Table I). The

Table I Serum Lidocaine Levels /ug/ml Mean (2 x S.D.) Range +2 min 1.07 (1.1) .5 - 2.01 +7 min 1.15 (.42) .79 - 1.46 End 1.03 (.48) .79 - 1.41 .85 (.46) .73 - 1.12 Recovery Dosage 3.16 mg/kg 1.9 - 4.2 (144 - 252 mg) Table 1: The levels of serutim lidocaine and twice tbe standaird deviation, togetler witbi the individual ranges ar-e notes. Tbe administer-ed dosage of lidocaine on a weigbt basis is given.

operating time ranged from 14 to 60 minuites and thirty mintutes elapsed fiom the end of suirgery before all the patients met the three criter-ia set for recovery. As with the local anesthetic the total dosage and the blood levels of metholhexital did not appear related (Table II). Table II Methohexital Levels Total Dosage mg/kg 2 6.1 3.7 3.4 3.9 3.9 Blood Seruim Level at Recover ypg/ml 1.9 2.2 1.5 0 0 .8 Table 2: The high levels of methohexital at recovery may indicate late r-elease of metbobexital from tbe body stor-es.

Discussion If the commonly accepted toxic level of lidocaine is 5 )g/ml(9) then this stuidy indicates that the techniquie of anesthltizing all fouir quiadrants with lidocaine in dosages uip to 4.2 mg/kg does not produice toxic blood levels. Even serulm levels in excess of twice the standard deviation wotuld not produice such toxic blood levels althouighi levels as low as 1.5 uig/ml have been reported as being toxic (10). However, in the presence of diazepam and nitrous oxide the toxic thleslhold for lidocaine has been shown_to be el (11) While the serulm levels of lidocaine may not be toxic, the central effect of the lidocaine muist be considered. The suipplementation of nitrouis oxide-oxygen with thiobarbitturate and lidocaine has been shown to produice a level of anesthesia suiitable for suirgery (12) althouiglh the 475 mgs of lidocaine uised exceeds that uised in normal dental cases. Seruim lidocaine levels of 3.2 uig/ml (range 2.9 to 3.5 uig/ml) do however reduice the anesthetic requirement for general anesthesia (13) while level ;aslow as 1 ..5ng/ml are sufficient to control cardiac alrythmias (14). While suich levels were not revealed in this sttudy it is possible that the time restriction on ouir sampling and the few samples taken resuilted in missing the peak serulm levels (15,16). In dentistry, levels of anesthesia as deep as the minimuim anesthetic concentr-ation MAC are not normally achieved becauise of the brevity of the procedurie and SEPTEMBER-OCTOBER 1979

since total body movement need not be entirely abolished. It is conceivable then that, in addition to acting locally as suiggested (1), the cential effect oftie lidocaine mav deepen the anesthetic level or indeed combine with the effect of druigs uised in sedative techniquies to approach levels of general anesthesia. The levels of seruim methohexital deter-mined at the time of dischar-ge of the patient, show great variability. The levels do not correlate with total dose, duiration or weight of patient and, in this stuidy, the levels did not correlate with street fitness. This wouild suiggest that either recircuilation prior to metabolism has occuirred (17) or that acuite tolerance had developed (18). The small nuimber of patients stuidied pirecluide any conclulsion in this r-egard. We wish to thank F. Randall Ph.D., for developing the gas chromatography techniquie allowing muiltiple simuiltaneotus druig evaluations. REFERENCES 1. Crile G W: The kinetic theory of shock and its prevention thr-ough anoci-association Lancet 185:7, 1913.

2. DeJong R H: Phtysiology and pharmacology of local anesthesia Charles C Thomas Springfield Illinois 1970 p. 158. 3. Bromage P R and Robson J G: Concentrations of lignocaine in the blood after intravenous, intr-amuiscuilar-, epiduri-al and endotr-acheal administr-ation Anaesth 16:461, 1961. 4. Cannell H and Beckett A H: Perio-oral injections of local anesthetic into defined sites Brit Dent J 141:48. 1976. 5. Wynn R L Lovelace G E O'Reilly J E Gontv A A: Rapid sensitive gas chlomatographic quiantitation of methohexital in plasma or

oral stur-gery otutpatients Anes Prog 25:92, 1978. Per-ceptuial patter-ns duri-ing recovery fiom general anesthesia J Neurlol Neurlosurlg Psychiat 14:316,

6. Jaffe J and Bender M B:

1951. 7. Tuicker G T:

Plhar-macokinetic aspects of intravenous regional anestlhesia Anesthes 34:538, 1971. 8. Randall F: Per-sonal commuinication 1978. 9. Jorfeldt L Lofstr-om B Per-now B Per-sson B Wahr-en J and Widman B: The effect of local anesthetics on the central circullation and r-espir-ation in man and dog Acta Anaesth Scand 12:153, 1968. 10. Foldes F F Davidson G M Duincalf D Kuiwabara S: The intravenouis toxicity of local anesthetic agents in man Clin Pharmacol Ther 6:328, 1965. 11. DeJong R H Heavner J E and DeOliveira L F: Effects of nitrouis oxide on the lidocaine seizurle threshold and diazepam protection Anesthes 37:299, 1972. 12. Steinhauis J E Howland D E: Intravenously administered lidocaine as a suipplement to nitr-ouis oxide -thiobarbiturate anesthesia Anestlh and Analg 37-40, 1958. 13. Hines R S Jr DiFazio C A and Buri-ney R G: Effects of lidocaine on the anesthetic requirements of nitrouis oxide and halothalne Anesthes 47:437, 1977. 14. Fehmer-s M C 0 Duinning A J: Intr-amuiscuilar and or ally administered lidocaine in the treatment of ventricular arrythmias in actute myocardial infarction Am J Cardiol 29:514, 1972. 15. Goebel W Allen G D and Randall F: Circullating serutim levels of mepivacaine after dental injection Anes Prog 25:52, 1978. 16. Schnider S M and Way E L: Plasma levels of lidocaine (XylocaineR) in mother and newborn following obstetrical conduiction anesthesia: Clinical application Anesthes 29:951, 1968. 17. Suinshine I Whitwam J G Fike W W Finkle B and LeBeai J:Distribution and excretion of methohexitone in man Brit J Anaesth 38:23, 1966. 18. Duindee J W Pr-ice H L Dripps R D: Acuite toler ance to thiopentone in man Brit J Anaesth 28:344, 1956.

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Lidocaine as a supplement to general anesthesia for extraction of third molars: serum levels.

Lidocaine as a Supplement to General Anesthesia for Extraction of Third Molars: Serum Levels J. Scaramelia DDS, G. D. Allen MD, W. M. Goebel DDS MSD,...
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