Recommendations to use vasoconstrictors in dentistry and ......médecine buccale chirurgie buccale page 1 VOL. 9, N° 2 2003 Working group Carlos Madrid ( O d o n t o l o g i s t e

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Working groupCarlos Madrid ( O d o n t o l o g i s t e , Toulouse), Rapporteur

Bruno Courtois (Odontologiste, Toulouse)

M a rc Vi ronneau (Anesthésiste Réanimateur, To u l o u s e )

Reading groupJacques Bayssière (Odontologiste, Montpellier)

Jean Pierre Bernard (Stomatologiste, Genève)

Jean Loup Coudert (Odontologiste, Lyon)

Damien Duran (Odontologiste, Toulouse)

Ahmed Feki (Odontologiste, Strasbourg)

Jean Christophe Fricain (Odontologiste, Bordeaux)

Patrick Girard (Odontologiste, Paris)

Jean Claude Harnet (Odontologiste, Strasbourg)

Jacques Jeandot (Stomatologiste, Bordeaux)

Benoît Lefèvre (Odontologiste, Reims)

Dan Longrois (Anesthésiste-Réanimateur, Nancy)

Louis Maman (Odontologiste, Paris)

Gilbert de Mello (Odontologiste, Rennes)

Guillaume Penel (Odontologiste, Lille)

François Prédine-Hug (Odontologiste, Brest)

Yvon Roche (Odontologiste, Paris)

Jacky Samson (Stomatologiste, Genève)

Jacques Henri Torres (Stomatologiste, Montpellier)

Daniel Viennet (Odontologiste, Nancy)

GENERAL METHODOLOGY

These recommendations on the use of vaso-constrictors in odonto-stomatology were wor-ked out by a working group at the end of ananalysis of the scientific literature and collectionof the opinion of the members of the French-speaking Society of Oral Medicine and OralSurgery at a scientific meeting in Metz on May23, 2002. The text was then submitted to a rea-ding group before being definitively adopted. The members of the reading and workinggroups were designated by the French-spea-king Society of Oral Medicine and Oral Surgery.The working group was chaired by a rapporteurwho compiled the final document before propo-sing it and discussing it with the working groupthen submitting it to the reading panel. A syste-matic library search was carried out by interro-gation of the Medline data bank. This bibliogra-phy obtained by automation was supplementedby a manual research. The members of the wor-king group and the reading group transmittedarticles. The lists of references quoted in thealready identified articles were consulted.

Recommendations to use vasoconstrictors in dentistry and Oral surgery

SOCIÉTÉ FRANCOPHONE DE MÉDECINE BUCCALE ET DE CHIRURGIE BUCCALE

www.societechirbuc.com

Recommendations

Secrétariat : Christine Gueutier — Buroscope • 4, rue de Bray • Z.I. Sud Est • 35510 Cesson-Sévigné • Tél. 02.99.22.84.84 • Fax 02.99.22.84.80 • Adresse e-mail: [email protected]

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Société Francophone de Médecine Buccale et de Chirurgie Buccale

The rapporteur with the working group usedreading grids intended to assess the methodo-logical quality and the level of scientific evi-dence of these documents. The documentsw e re classified according to these grids invarious categories. On the basis of this literaturereview, the working group proposed recommen-dations whenever possible. Those were basedeither on a scientific level of evidence, or, in theabsence of evidence, on a professional agree-ment collected at the time of the scientific mee-ting of the French-speaking Society of OralMedicine and Oral Surgery on May 23, 2002.The bibliography obtained was almost comple-tely used so that the working group did notconsider it useful to separate selective biblio-graphy and complementary bibliography. Onthe other hand the totality of the bibliographyobtained was classified analytically accordingto the level of evidence (LoE) based on the fol-lowing classification (US Agency for HealthCare Policy and Research):

Grades A, B or C are assigned to the recom-mendations according to the level of evidenceof the respective bibliography:

Strategy of the documentary research The automated research was based on the fol-lowing key words:- local anaesthesia- general anaesthesia- vasoconstrictors- noradrenalineadrenaline- levonordefrin- corbadrine The preceding key words were cross with:- dentistry- maxillofacial surgery- side effects- adverse effects- special patients

Selected questions• What is the place of vasoconstrictors in odonto-stomatology?– Are vasoconstrictors necessary in odonto-sto-matologic anaesthesia?– Can vasoconstrictors be useful in odonto-sto-matologic practice other than in associationwith a local anaesthetic substance?– Can vasoconstrictors be associated withgeneral anaesthetics during general anaesthe-sia in odonto-stomatology? • How to choose the vasoconstrictive mole-cule in odonto-stomatology?– Which are the advantages and disadvantagesof adrenaline compared to noradrenaline? – Which is the interest of other substances? • What are the indications of vasoconstrictorsin odonto-stomatology? • Which dose of vasoconstrictors should beused in odonto-stomatologic anaesthesia?• Which are the drug interactions of the vaso-constrictors used in odonto-stomatologicanaesthesia? • Which are the pathologies which contraindi-cate the use of vasoconstrictors in odonto-stomatology? • Do physiological states contraindicate theuse of vasoconstrictors in odonto-stomatolo-gic anaesthesia?

Level I a: Meta-analysis evidence from randomised controlled trials (RCT)

Level I b : Evidence from at least one RCT

Level II a : Evidence from a non-randomisedcontrolled study

Level II b : Evidence from another well definedexperimental study

Level III : Evidence from a well defined descrip -tive experimental study (this includescomparative studies, cohort studies,and the study of case controls)

Level IV : Opinion of experts or clinical expe-rience

Grade A : Based on level of evidence I

Grade B : Based on level of evidence II or III

Grade C : Based on level of evidence IV


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RECOMMENDATIONS

1. Injection technique1. The injection of an anaesthetic solution withor without vasoconstrictor must always be car-ried out slowly (1 ml per minute) and in fractioneddoses in order to supervise the possible signs ofa noxious effect of the injection. When the injec-tion takes place in a well vascularised territory, anegative aspiration test is a pre requisite to theinjection of the anaesthetic solution with orwithout vasoconstrictor. The smallest eff e c t i v edose is always recommended. [Grade C]

Indications2. The association of a vasoconstrictor with ananaesthetic solution in local odonto-stomatolo-gic anaesthesia by infiltration is indicatedbecause the vasoconstrictor decreases theintravascular passage of the injected solutionand thus ensures an increase in duration anddepth of the anaesthesia while reducing thesystemic effects of the solution. [Grade A]

3. It does not appear possible to conclude for-mally as for the harmlessness of retractioncords soaked with vasoconstrictor used in den-tal prosthetics. Evaluations based on the animalseem to show that haemodynamic changes areinconstant. The literature reports one seriousaccident in the human. [GradeB]

4 . Local haemostasis techniques by usingvasoconstrictors, pure or mixed with anaesthe-tic or astringent substances, have not beeninvestigated in publications presenting a satis-factory level of evidence. Thus they are empiri-cal. Although largely diffused, they have not ledto the publication of an accident or an incidentin connection with vasoconstrictors. [Grade C]

5 . The use of an anaesthetic solution containinga vasoconstrictor as a means of decreasing thebleeding and of lowering the threshold of analge-sia among patients operated in oral surg e r yunder general anaesthesia contributes to

d e c rease the sympathetic nerve response to thes u rgical aggression and to decrease the depth ofthe necessary general anaesthesia. [Grade B]

Choice of the molecule 6. A d renaline is industrially and medically theleader of the vasoconstrictors used alone or inassociation with a local anaesthetic in odonto-s t o m a t o l o g y. It has the broadest casuistrywhich confirms a great safety of this molecule.Non-catecholamine derivatives have not showntheir superiority to date even among patientslikely to badly tolerate catecholamines.[ G r a d e B ]

Indications according to the anaes-thetic technique 7. The use of a vasoconstrictor in the tech-niques of intrapulpal, intraligamentary and intra-septal anaesthesia is not essential but conside-rably improves the success rate, the durationand the depth of the anaesthesia obtained. Ifthe injection is carried out under adequateconditions, the local lesions directly ascribableto the vasoconstrictor are negligible and rever-sible. The systemic effects of these injectionsexist but are generally much lower than thoseobserved in infiltration anaesthesias. [Grade A]

8 . The use of a vasoconstrictor in local anaes-thesia techniques (para-apical, anaesthesia ofthe lingual nerve, anaesthesia of the buccalnerve) is not essential, but appre c i a b l yi m p roves the success rate, the duration andthe depth of the anaesthesia obtained.[Grade C]

9. The addition of a vasoconstrictor to theanaesthetic solution is not essential for theanaesthesia of the lower alveolar nerve at themandibular foramina. The addition of adre n a l i n ei n c reases the duration of the anaesthesia butdoes not seem to have a decisive effect on theincidence of failures. The results concerning thesuccess rate of the anaesthesia are contradic-t o r y. Taking into account the relation whichexists between the success rate and the volume

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of injected solution, the addition of a vasocons-trictor could be considered in the prevention ofthe systemic effects of the local anaesthetic.[ G r a d eC ]

Dosage of the vasoconstrictor 10. The results are contradictory about theideal dosage of adrenaline in 2% lidocaine solu-tions. The 1/200000 solution gives a sufficientduration of action for the majority of odonto-stomatologic acts. For 4% articaine and 2%mepivacaine, 1/200000 solutions should bepreferred in the absence of a significant diffe-rence in the performances with the 1/100000solution and because they are probably tolera-ted better. [Grade A]

Drug interactions 11. The attitude towards patients under tricy-clic antidepressants must be to avoid noradre-naline in association with local anaesthetics andto inject reduced amounts of local anaestheticsassociated with 1/200000 adrenaline. In prac-tice the amount injected should be one the thirdof the total amount of that of the normal subject.[GradeC]

1 2 . Patients under cardio-selective beta-bloc-kers can receive local anaesthesias with vaso-constrictor (1/200000 adrenaline). Amongpatients receiving non-selective beta-blockers, itis recommended to use anaesthetic solutionswith the lowest dose of vasoconstrictor.[ G r a d eC ]

13. Volatile halogenous general anaestheticsshould not be used with adrenaline. The litera-ture encourages prudence as for the use of alocal anaesthetic with adrenaline in the event ofassociation of thiopental + halothane duringgeneral anaesthesia. [Grade C]

14. Vasoconstrictors will be proscribed at least24 hours after the consumption of cocaine toallow the elimination of the drug and its activemetabolites. [Grade C]

15. No accident has been reported as for theadministration of a local anaesthetic with adre-naline among patients under antipsychoticdrugs or alpha-blockers. The risk of interactionbetween these substances is theoretical at theusual doses in odonto-stomatologic anaesthe-sia. [Grade C]

16. There is no contra-indication in the admi-nistration of a local anaesthetic with adrenalinein patients under selective MAOI. [Grade C]

Pathologies contraindicating vaso-constrictors associated with a localanaesthetic 17. Pheochromocytoma constitutes an abso-lute contraindication to the administration ofvasoconstrictors. Patients suffering from thispathology must be dealt with in a hospital whichdisposes of a reanimation structure when alocal anaesthesia with or without vasoconstric-tor is necessary. [GradeC]

18. It appears desirable to avoid the associa-tion of vasoconstrictors with a local anaestheticduring conservative treatment and even moreso during non-conservative treatment on boneirradiated beyond 40 Gy. [Grade A]

19. Intra-osseous injections of local anaesthe-tic with adrenaline must be avoided amongpatients presenting with arrhythmia. [Grade A]

Pathologies which do not contraindi-cate vasoconstrictors associatedwith a local anaesthetic 2 0 . Stabilised hyper- and hypothyro i dpatients do not have major disorders whenthey are subjected to corrective tre a t m e n tand put in the presence of catecholamines.Although the theoretical risk of thyro x i n e -a d renaline potentiation is serious, no clinicalcase has been reported. [Grade C]

21. Vasoconstrictors associated with an anaes-thetic solution are not contraindicated in a


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hypertensive subject stabilised by an antihyper-tension treatment. [Grade A]

22. In the event of unstable blood pressureassociated with other elements burdening theprognosis, treatment implying a local anaesthe-sia with vasoconstrictor will have to be carriedout under monitoring in a hospital disposing ofa reanimation unit. [Grade C]

23. In auricular fibrillations stabilised by ade-quate treatment, the control of stress and thetherapeutic heart rate is essential and the use oflocal anaesthetics with vasoconstrictor is indi-cated. [Grade C]

24. Patients under digoxin and those sufferingfrom atrio-ventricular arrhythmias must be trea-ted under monitoring in a hospital disposing ofa reanimation unit when a local anaesthesiawith or without vasoconstrictor is necessary.[Grade C]

25. Vasoconstrictors associated with an anaes-thetic solution are not contraindicated in stabili-sed coronary cardiopathies. [Grade C]

26. Vasoconstrictors associated with an anaes-thetic solution are not contraindicated in asth-matic subjects in order to control pain and avoidstress which is probably the principal source ofasthma attack at the dental practice. In theevent of cortico-dependent asthma, the resortto an anaesthetic without vasoconstrictor andthus without bisulphite is indicated. [Grade C]

27. Vasoconstrictors associated with an anaes-thetic solution are not contraindicated amongpatients having presented previous and cured

viral or toxic hepatic injury. In the event of evo-lutionary severe attack, the evaluation of thehepatic function is important. The total quantityinjected may have to be reduced and intervalsbetween the injections increased, without beingdetrimental to the use of an associated vaso-constrictor. [Grade C]

28. Vasoconstrictors associated with an anaes-thetic solution are not contraindicated amongstabilised type I or II diabetic patients. In theevent of non-stabilised and unstable diabetes,with brutal passage from hypo- to hyperglycae-mia, the quantities of local anaesthetic withvasoconstrictor will be reduced in order to takethe hyperglycaemic character of adrenaline intoaccount. [Grade C]

Physiological states and vasocons-trictors 2 9 . Vasoconstrictors associated with ananaesthetic solution are not contraindicatedduring pregnancy and lactation. The usualamounts can be used. [Grade C]

30. Vasoconstrictors associated with an anaes-thetic solution are not contraindicated in chil-dren beyond six months. The total amount oflocal anaesthetic with or without vasoconstric-tor usually used in the healthy adult should bedivided by 3 below 15 kg and 2 between 15 and40 kg. [Grade C]

31. Vasoconstrictors associated with a localanaesthetic are not contraindicated in theelderly. The total amount of anaesthetic with orwithout vasoconstrictor should be adapted tothe metabolic state of the considered subject.[Grade C]

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ARGUMENTATION

1. 1. Vasoconstrictors in odonto-sto-matology

A d re n e rgic vasoconstrictors are among the mosta d m i n i s t e red therapeutic substances in odonto-s t o m a t o l o g y. Their use in association with ananaesthetic substance started in 1904 whenHeinrich Braun (1903) a reputed German specia-list in local anaesthesia developed an adre n a l i n e -p rocaine solution rapidly marketed by Hoechstunder the Novocaine brand® which was to domi-nate the market for 50 years (Yagiela, 1995[ L o E IV]). Vasoconstrictors are also re s p o n s i b l efor more drug interactions than the majority ofother drug substances specific to the odonto-stomatologist (Yagiela, 1999 [LoE IV]). Adre n a l i n eand the other sympathomimetic amine deriva-tives are injected routinely in association withlocal anaesthetics (LA) for pain control, or usedalone on gingival retraction cords and in injec-table or topic solutions intended for local blee-ding contro l .

1.1. 1.1. Are vasoconstrictors necessary instomatologic anaesthesia? The advantages of vasoconstrictors in odonto-stomatologic anaesthesia are universally reco-gnized by the scientific community and theprincipal handbooks of odonto-stomatologiclocal anaesthesia [LoE IV] refer to them asscientific evidence (Davies and Lefkowitz, 1981;Malamed, 1997; Berini and Gay, 1997; Gaudyand Arreto, 1999).It is generally admitted that, whatever the pathof injection, the bio-disponiblity of amino-amideLA is total. After injection, part of the dosereaches its target while another fraction passesinto the systemic circulation. The passagethrough the endothelial vascular barrier is easytaking into account the good liposolubility ofLA. An important capillary density, a local bloodflow and a high blood/tissue division coefficientare as many factors increasing the systemicresorbtion which are found in the majority of tar-get territories of local anaesthesia of the oralcavity. Various pharmacological interventions

and in particular the addition of vasoconstric-tors to the LA solution can modify the systemicresorbtion appreciably although it also varieswith the effect of the LA itself upon local vascu-larisation (Viel and coll, 1997 [LoE IV];Ackermann and coll, 1988 [LoE III]; Myers andHeckmann, 1989 [LoE IIb]).The vasoconstrictor thus acts initially like a sub-stance likely to slow down the speed of absorp-tion of the anaesthetic solution at the point ofinjection (Fink and coll, 1978 [LoE IIb]; Jage,1993 [LoE IV]). The reduction in systemicresorbtion is related to the local action of vaso-constrictors (adrenaline being selected as areference) by stimulation of the alpha1 recep-tors of the smooth muscle of the peripheral ves-sels. The consequence of this action is a reduc-tion in tissue perfusion which results in localischaemia of the tissues (Allwood and coll, 1963[Not classified]).This ischaemia also relates to the vasa nervo-rum which supply the axons of sensitive nervefibres concerned by the local anaesthesia; asignificant reduction of the metabolism of thenerve cells then arises and thus of the transmis-sion of the nerve impulse which leads to a dee-pening of the anaesthesia and an increase in itsduration.The effect of the vasoconstrictor also comprisesa facilitating action on the penetration of the LAin nerve fibres by direct stimulation of anti-noci-ceptive adrenergic receptors. Such an actionwas demonstrated during peridural and intra-thecal injections. (Bromage and coll, 1983[LoE IIb]; Yaksh and Reddy, 1981 [LoE Ib]). Fromthe clinical point of view, the reduction of thespeed of absorption leads to two positiveresults known for a long time:(1) An increase in the duration of the anaesthe-sia (Jage, 1993 [LoE IV]);(2) (2) A reduction of the plasmatic peak of LA,which has, itself, two beneficial consequences:reduction in systemic toxicity and consequen-tially the possibility of increasing the amountinjected. Covino and Vassallo (1976) [LoE V ]thus reported that the addition of adre n a l i n emade it possible to increase by 200% the dura-tion of a lidocaine 0,5% anaesthesia while

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d e c reasing the plasmatic peak by 50%. Thebehaviour of other LA tested is similar.Let us note however that one of the unexpectedside effects of vasoconstrictors, when they areassociated with LA, is to slow down the induc-tion time of the anaesthesia. Falaiye and Rood(1990) [LoE IIa] thus showed that the addition ofadrenaline to a solution of lidocaine appreciablydelayed the induction time of a deep anaesthe-sia appreciated with pulp-testing. This sideeffect would be dependent at the same time ona barrier effect of the vasoconstrictor towardsthe anaesthetic solution which it would block onthe site of injection, at a distance of the targe-ted nerve fibre, and on an acidifying effect of thevasoconstrictor on the medium which is favou-rable to maintaining the anaesthetic in its inac-tive non-ionised form.The association of a vasoconstrictor with ananaesthetic solution in odonto-stomatology isthus indicated because the vasoconstrictordecreases the plasmatic resorbtion of the injec-ted mixture and thus ensures an increase in theduration and depth of the anaesthesia whilereducing the systemic effects of the solution.

1.2. Can vasoconstrictors be useful in sto-matologic practice other than in associationwith a local anaesthetic substance? Two fields of odonto-stomatology call uponvasoconstrictors other than anaesthesia: • on the one hand prosthetics: retraction cordsintended to push back the gingiva below prepa-rations of enamel and/or dentine at the time oftaking impressions (Pallasch, 1998 [LoE IV]);• on the other hand: oral surgery and in particu-lar endodontic surgery where among other solu-tions the injection of vasoconstrictors or the ins-tallation of supports containing them isrecommended to limit bleeding at the centre ofthe surgical zone (Syngcuk and Sivakami, 1997[LoE IV]).

1.2.1. Vasoconstrictors on gingival retractioncordsStudies concerning the toxicity of gingivalretraction cords impregnated with a vasoactivesubstance (in practice 8% racemic adrenaline)

are contradictory by divergence of the toxicolo-gical and pharmacokinetic results.For 3 cm of cord Malamed (1997) [LoE IV]reports values varying from 225,5 to 661 µg ofracemic adrenaline which actually represents113 to 330 µg of the pharmacologically active L-form. Such a quantity is equivalent according toPallasch (1998) [LoE IV] to 3,13 to 9,16 car-tridges of 2 ml of anaesthetic solution with1/100000 adrenaline.Studies in the dog concerning tolerance sho-wed spectacular rises in heart rate and bloodpressure after placing cords. The plasmatic rateof adrenaline was measured in one patient pas-sing from 15 pg.ml -1 to 316 pg.ml-1 after placingcords and this without a haemodynamic effect.Houston and coll (1970) [LoE IIb] took interest inthe possible haemodynamic effects of thesecords. They use a badly defined protocol on9 subjects. Their results relate to blood pressureand heart rate at various times during impres-sion-taking. They show negligible haemodyna-mic variations.Other re s e a rch highlights a significant diff e re n c ein systemic resorbtion according to whether thegingival epithelium is intact or whether there isactive gingivitis or that it is deteriorated by ap rosthetic preparation: an intact crevicular epi-thelium seems to constitute an effective barrieragainst the plasmatic passage of adre n a l i n e .It should be noted finally that the various proto-cols are not easily comparable: duration of pla-cing of the cords varying from 30 to120 minutes, variable number of teeth concer-ned, size of the cords and variable doses, nondiscrimination of the quantities absorbed byplasma, the gingival fluid and saliva.Pallasch thus proposes to retain some rulesconcerning the specifications of research on thetolerance of the cords impregnated with race-mic adrenaline: (1) level of adrenaline indeedpresent on the cord; (2) duration of the presenceof the cord in the sulcus; (3) state of the sulcus;(4) number of teeth concerned; (5) dilution bysaliva and the gingival fluid; (6) metabolism ofracemic adrenaline by catechol-O-methyltrans-ferases ; (7) local vasoconstriction induced bya d renaline as a factor decreasing its own


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absorption; (8) gingival traumatism during theplacing of the cords; (9) individual sensitivity ofthe patient to even tiny variations of the circula-ting level of vasoconstrictor.In the absence of concordant research, it doesnot appear possible to conclude as for harm-lessness of the retraction cords used in dentalprosthetics. Evaluations in the animal seem toshow that the haemodynamic variations areinconstant, and that their symptomatic charac-ter is dependent either on the sensitivity of thesubject, or on the experimental conditions. Theliterature reports only one serious incident in thehuman (Hilley, 1984) [Not classified: clinicalcase] related to halothane-adrenaline interac-tion.

1.2.2. Vasoconstrictors used for surgicalhaemostasisAnaesthetic substances associated with highamounts of vasoconstrictors have been usedwith the only aim of controlling local bleeding bya broad infiltration of the operational site beforeincision (Gutman, 1993 [LoE IV]). The suppor-ters of these techniques nevertheless observethat, on the one hand, it is often difficult to injectnear the apexes without infiltrating skeletalmuscle fibres which are rich in adrenergic beta2receptors which are responsible for vasodilationrather than vasoconstriction (Milam andGiovannitti, 1984 [LoE IV]); in addition, that thisper operative vasoconstriction is generally follo-wed by vasodilation by reactive hyperaemia:indeed, progressively with the resorbtion of thevasoconstrictor, the latter reaches a concentra-tion on the surgical site which does not ensurestimulation of the alpha adrenergic receptorsany more. The blood flow quickly finds its nor-mal course then, by rebound phenomenon, gra-dually reaches a flow higher than normal bybeta adrenergic reaction: this phenomenon isrelated to the local hypoxia of the tissues and tothe acidosis caused by the prolonged vaso-constriction. When this local hyperaemia settlesin, the complementary LA injections with vaso-constrictor are without effect (Gutman, 1993;Gutman and Harrison, 1994 [LoE IV]; Syngcukand Sivakami, 1997 [LoE IV]).

A d renaline, noradrenaline, phenyl-adre n a l i n ewere used alone in the control of local bleedingin endodontic surgery. Sommer (1962) [LoE IV]was the first to use various solutions: 1/1000and 1/500 racemic adrenaline, 1/100 phenyl-adrenaline and 1/200 noradrenaline, the supportalways being gauze; Ingle (1965) [LoE IV] pro-posed to fill the osseous cavity with gauze satu-rated with a solution of 2% racemic adrenalineduring 4 minutes. Grossman (1970) [LoE IV]recommends the use of salivary rolls of cottonsoaked with 1/100000 adrenaline and also pro-poses the use of cotton pellets impregnatedwith a solution of 1,5 % racemic adrenaline.Only the quantities of adrenaline present on thepellets could be evaluated, the other techniquesnot offering any standardisation. Besner (1972)[LoE IIb] could thus show that on n° 2 pelletsone finds on average 1,15 mg of racemic adre-naline in the form of hydrochloride. The applica-tion of a n° 2 pellet during 4 minutes did notcause a variation of the heart rate in the seriesof Besner, which the author allots to the localvasoconstriction caused by adrenaline andwhich would lead to very weak and very slowabsorption of the adrenaline itself.Let us note that besides pellets impregnatedwith adrenaline alone, there also exists on themarket pellets impregnated at the same timewith adrenaline and astringent substances suchas zinc phenol sulphonate and ferric sulphate.These specialities have not been tested in theliterature and are not marketed in France to theknowledge of the working group. The local hae-mostasis techniques by use of vasoconstric-tors, pure or mixed with anaesthetic or astrin-gent substances have not been investigated inpublications presenting a satisfactory level ofevidence. They are thus empirical. Althoughbroadly diffused, they have not led to the publi-cation of an accident or incident in connectionwith vasoconstrictors.

1.3. Can vasoconstrictors be associated withgeneral anaesthetics (GA) during generalanaesthesia in odonto-stomatology?The use of LA solutions associated with a vaso-constrictor for infiltration of the operative field

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during general anaesthesia has often beenrecommended as a means of haemostasis inoral and maxillofacial surgery (Cantaloube andcoll, 1991 [LoE IV]). It is a comfortable and bac-teriologically safe alternative compared to mani-pulations intended to manufacture an extempo-raneous serum containing adrenaline. Theserum containing adrenaline is classically com-posed of 0,9% sodium chloride; the vasocons-trictive action being obtained by addition of0,025% adrenaline in solution or 0,25 mg percartridge of 1 ml of serum. Under these condi-tions, the usual amount of adrenaline not to beexceeded would be of 0,01 mg.kg-1 of weight ofthe patient.The use of a LA as a vector of the vasoconstric-tor in addition to the advantages of handlingmentioned above lowers the threshold of anal-gesia, increases the quality of per and post ope-rational control of pain as demonstrated byEngquist and coll (1977) [LoE IIa], Hosoda andcoll (1991) [LoE Ib], Yuge and coll (1995)[LoE IV], for the peridural anaesthesia and espe-cially Mamiya and coll (1997) [LoE Ib] in oral sur-gery. Cantaloube recommends either 1% lido-caine hydrochloride with 1/100000 adrenalineor 2% with 1/80 000 adrenaline or articaine with1 / 2 0 0 000 adrenaline or mepivacaine with1/100000 noradrenaline for these infiltrations.Tordoff and coll (1996) [LoE Ib] sought to knowif the use of a loco-regional anaesthesia beforeincision under general anaesthesia for the extra-ction of lower third molars decreased post-ope-rative pain. In 36 patients they injected thesame quantity of anaesthetic solution of 2%lidocaine with 1/200000 adrenaline on one sideand a saline solution on the other. Injectionswere also made around the extracted teeth.Post-operative pain was evaluated by an analo-gical visual scale. No significant diff e re n c ea p p e a red between the physiological salinesolution injected and the anaesthetic.Mamiya and coll (1997) [LoE Ib] practised thefollowing experiment on a group of 28 ASA 1patients having to undergo a bilateral sagittalmandibular osteotomy: the 28 patients weredivided into 4 groups. Groups 1 and 2 did notreceive a loco-regional mandibular anaesthesia

and differed by an increasing level of the depthof the general anaesthesia by inhalation asquantified by minimal alveolar concentration(MAC: minimum alveolar concentration) passingfrom 1,3 MAC to 1,6 MAC. For groups 3 and 4the patients underwent in addition to a bilateralloco-regional mandibular anaesthesia, a generalanaesthesia by inhalation respectively 1,0 MACand 1,3 MAC. It should be noted that the LAwere identical in the two groups receiving theregional anaesthesia: 4 ml of 0,5% mepiva-caine. In both groups 3 and 4, a different vaso-constrictive solution was locally infiltrated(group 3: 8 ml of 1% lidocaine containing 10µg.ml-1 of adrenaline; group 4: 8 ml of 3% pro-pitocaine containing 0,03 U l . m l- 1 of felypre s-sine). The general anaesthesia was carried outwith the following general anaesthetics: induc-tion by thiopental (4 mg.kg-1) then maintenanceby isoflurane and a 40% mixture of nitrogenprotoxide and oxygen. Controls of the haemo-dynamic effects of the surgery were as follows:blood pressure and heart rate. The sympatheticnerve response was evaluated by dosing theplasmatic noradrenaline. Measures started atthe 4th minute after local infiltration and wererepeated at various significant surgical times.The results show very significant differencesbetween the groups with and without loco-regional anaesthesia. No significant differencewas observed between groups 3 and 4. Thesame results are observed as for the plasmaticnoradrenaline rates which are significantly lowerin the groups with loco-regional anaesthesia.The authors thus conclude that loco-re g i o n a lanaesthetic infiltrations associated with theanaesthetic infiltration of a solution containing avasoconstrictor in the operative site contribute,on the one hand, to decrease and prevent theauto-immune endocrine sympathetic nerve re s-ponse to the surgical aggression which is at theorigin of a great part of the post-operative pain,on the other hand, to decrease the depth of thegeneral anaesthesia necessary to the interventioncarried out.A similar experiment was undertaken bySantoro and Marsicano (1998) [LoE IIb], with adifferent goal: to check the generated haemo-


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dynamic modifications, this time, by injection ofadrenaline while making the stress factors ofcoma vigil inoperative by general anaesthesia.The authors infiltrated 7 patients under generalanaesthesia with 4 ml of a solution of 2% mepi-vacaine with 1/100000 adrenaline at the mandi-bular foramen. The patients were subjected tovery different interventions in oral or maxillofa-cial surgery. The authors noted the variations ofheart rate and blood pressure at various signifi-cant phases of the intervention. The authorsconclude from a very debatable protocol thatthe variations of rhythm and heart rate observedat the time of a LA infiltration with vasoconstric-tor under general anaesthesia are lower thanthose observed under local anaesthesia in thecoma vigil. The use of an anaesthetic solutioncontaining a vasoconstrictor as a means ofdecreasing bleeding and of lowering the thre-shold of analgesia among patients operated inoral surgery under general anaesthesia is apractice commonly reported in the literature.Recent experiments undertaken under periduraland block anaesthesia of the mandibular nerveshow that this practice contributes to decreasethe sympathetic nerve response to the surgicalaggression and to decrease the depth of thegeneral anaesthesia necessary.A restriction must be made with halogenousvolatile GA (halothane) which should not beused with adrenaline. Indeed halogenous GAcause a potentiation of the depressor effects ofcatecholamines on the speed of conduction ofPurkinje fibres in the cardiac autonomous sys-tem (Camara and coll, 2001 [LoE IIb]).

2. Choosing the vasoconstrictivemolecule in odonto-stomatology

2.1. Adrenaline versus noradrenalineAdrenaline and the closely related adrenergicamines cause vasoconstriction by stimulatingspecific membrane receptors of the cells of thesmooth muscles of the vessels.Two principal types of adrenergic alpha1 andalpha2 receptors can initiate vasoconstriction.A n a t o m i c a l l y, alpha1 receptors are located

close to the sympathetic nerves which innervatethe vessels whereas alpha2 receptors are disse-minated in order to respond more easily to cir-culating catecholamines. The cascade of eventswhich go from the stimulation of the receptor tovasoconstriction is now well established(Ruffolo and coll, 1991 [LoE IV]).The adre n e rgic receptors are connected toeffector enzymes and ionic channels by G pro-teins, i.e. polypeptides which bind guanosinetriphosphate when these receptors are stimula-ted by adrenaline. The activation of the G pro-teins bound to alpha1 a d re n e rgic re c e p t o r scauses the opening of the calcic channels of theplasma membrane and the stimulation of aphospholipase C. The calcium ions then pene-trate into the cell and activate a kinase from thelight chain of the calmodulin-dependent myo-sin. It is this which, in turn, initiates the muscu-lar contraction. During this time, the hydrolysisof certain components of the cellular membraneby the phospholipase C leads to the formationof diacylglycerol and inositol triphosphate.These second messengers induce contractionby facilitating the release of intracellular calciumreserves and by maintaining the activation ofthe protein kinase C which contributes to themetabolic support of the contraction.Stimulation of the alpha2 receptors by vaso-constrictors also opens calcium channels byactivation of the G proteins. Moreover adenyl-cyclase is inhibited by a specific inhibiting Gprotein. The adrenergic beta2 receptors acti-vate, on the contrary, adenylcyclase and conse-quently cause vasodilation. Beta2 receptors arew i d e s p read in the vessels of the skeletalmuscles and in certain internal organs, they arerare in mucous membranes and the skin.Noradrenaline shares with adrenaline the capa-city to stimulate alpha1 and alpha2 receptorsbut it does not interact with beta2 receptors sothat the only direct effect of noradrenaline onvessels is to favour their constriction. This purely alpha-adrenergic character was ini-tially taken advantage of by the industry asproof of specificity of this catecholamine. Infact, the affinity of noradrenaline for alphareceptors is less than that of adrenaline which

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implies the use of more important noradrenalinedoses to obtain the same vasoconstriction(Knoll Kohler, 1988 [LoE IV]).N o r a d renaline is thus approximately 4 times lessvasoconstrictive locally than adrenaline. The fir s tconsequence is a shorter action by faster plas-matic absorption. An intravascular injection ofn o r a d renaline has more severe consequencesthan that of adrenaline: rise in the systolic bloodp re s s u re (> 200 mm Hg), increase of 75 to 80%of the average blood pre s s u re and increase inm y o c a rdial oxygen consumption (Boakes, 1972and 1973 [LoE IV]) which makes it a diffic u l tmolecule to handle in patients suffering fro mm y o c a rdial ischaemia. The absence of action ofn o r a d renaline on beta2 receptors produces ani n c rease in peripheral vascular re s i s t a n c e swhich largely explains its toxicity. More o v e rn o r a d renaline has a severe and paradoxical bra-d y c a rdic action as it is active on the card i a cb e t a1 receptors, it should cause in all logic anacceleration of the heart rate. In fact, noradre n a-line could also cause a re flex stimulation of theaortic and carotid baro receptors in response toa rise in the diastolic and systolic pre s s u res andlead to brutal bradycardia (Berini and Gay, 1997[LoE IV]). The duration of the rise in blood pre s-s u re consecutive to a noradrenaline injection is4 minutes and that of the bradycardic effect is1 5 minutes (Knoll Kohler, 1988 [LoE IV]).Anaesthetic solutions containing an associationof adrenaline and noradrenaline have been mar-keted. Although no specific study has beenpublished on this subject, the opinion of the lite-rature is unfavourable asserting that the benefi-cial effects of these associations are not higherthan those of adrenaline alone whereas theyadd the disadvantages of noradrenaline (Jage,1993 [LoE IV], Berini and Gay, 1997 [LoE IV]).

2.2. Other vasoconstrictors Facing the risks identified with catecholamines,the re s e a rchers and the industrialists thought ofusing non-catechol vasoconstrictive substancesderived from a natural hormone secreted by thepost-pituitary gland: vasopre s s i n .Felypressine (phenyl alanine 2-lysin-vasopres-sin 8) is the leader of the synthetic analogues of

vasopressin, it has its local vasoconstrictivecharacteristics without having its powerful diu-retic effects nor the vasoconstrictive effects onthe coronary arteries (approximately one third ofthe coronary action of vasopressin) (Goldmanand coll, 1971 [LoE IIb]).It does not seem to act on blood pressure noron the central nervous system (Von Tsakiris andBultmann, 1961).Recent well documented research (Sunada andcoll, 1996 [LoE IIa]) relativises the systemicadvantages of felypressine which was regardedat a time as the vasoconstrictor of choice inpatients with a history of myocardial ischaemia(Johnson and Widrich, 1977 [LoE Ib]). In thisarticle, the myocardial effects of various solu-tions of 2% propitocaine associated with dosesvarying from 0 (re f e rence group) to + 0,25 IU.ml- 1

of felypressine are compared in 26 patients suf-fering from essential hypertension. The resultsshow that the systolic pressure is increased inthe groups with high doses of felypressine com-pared to the reference but that all the groupshave a rise in diastolic pressure compared tothe reference.Even if myocardial ischaemia is not highlightedformally because of experimental skews, theauthors observe a reduction of the myocardialcontractility in the 3 groups with the highestdoses of felypressine. They conclude by recommending a dose of0,18 IU of felypressine in patients with essentialhypertension which corresponds to 6 ml of 3%propitocaine with 0,03 IU of felypressine.Volpato (1999) [LoE Ib] shows that with a highdose in the animal, the toxicity of adrenaline andfelypressine are comparable but that adrenalinewould have a “protective” effect as for the onsetof convulsions when it is associated with lido-caine.Shanks (1963) [LoE III] showed that the effectsof the interaction of felypressine with haloge-nous general anaesthetics are close to those ofadrenaline. Roberts and Sowray (1987) [LoE IV]recommend not to use felypressine in pregnantwomen because of a possible inhibitory actionon placental circulation by interfering with ute-rine tonicity.


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Ornipressin (POR-8) is another synthetic ana-logue of vasopressin which has local vasocons-trictive properties. It was at one time describedas the vasoconstrictor of choice in infiltration ofthe operative field but severe complications(Kleemann and coll, 1986 [LoE IV]; Cantaloube,1991 [LoE IV]) showed its powerful constrictoreffect on the coronary arteries and led it to beabandoned.Mixed with a LA ornipressin has much lowerperformances than adrenaline: it takes approxi-mately 10 minutes to obtain its maximum vaso-constrictor effect (Jage, 1993 [NdP IV]) whichcomplicates its use.Corbadrine is still found in association withaptocaine, a LA having known a renaissancerecently because of a good tolerance in somehepatic porphyries. Corbadrine is an alpha-methyl noradrenaline much less toxic than nora-drenaline itself. Nevertheless its vasoconstric-tive activity is much weaker. Doses 10 timeshigher than that of noradrenaline have to begiven to obtain a comparable effect. Moreover,this synthetic substance is slowly eliminatedwhich prolongs its action which can constitutean obstacle. This prolongation of the duration ofaction is related to the presence of a methylgroup which prevents the degradation of corba-drine by mono-oxydase (Jacquot and coll 1978[LoE IV]).Adrenaline is industrially and medically the lea-der of vasoconstrictors used alone or in asso-ciation with LA in odonto-stomatology. It hasthe broadest casuistry which confirms the greatsafety of this molecule. The non catechol deri-vatives have not shown their superiority to dateeven among patients likely to badly toleratecatecholamines.

3. Indications of vasoconstrictors inodonto-stomatology

The characteristics of vasoconstrictors associa-ted with LA solutions have been reminded inthis work and justify the very broad use of theseassociations in infiltration anaesthesias inodonto-stomatology. The working group ques-

tioned two anatomically opposed anaesthetictechniques for which the use of vasoconstric-tors poses different problems. They are: on theone hand local anaesthesias known as intrapul-pal, intraseptal, intradiploic and intraligamen-tary anaesthesia; on the other hand loco-regio-nal anaesthesias at the mandibular foramenwhich are carried out in a richly vascularisedterritory as well on the arterial level as on thevenous level which raises the risk of endovas-cular injection of an anaesthetic substancecontaining adrenaline.

3.1. Do vasoconstrictors have to be used atthe time of intrapulpal, intraseptal, intradi-ploic and intraligamentary anaesthesias? These anaesthesias have in common the factthat the anaesthetic solution is infiltrated in ananatomically closed space where diffusion willbe minimal so that the quantity injected will below and that the addition of a vasoconstrictorcould appear useless even harmful because ofthe aggressiveness of the local vasoconstrictionit causes on the tissues (Madrid and coll, LoE[NdP IV]).Intra-osseous or intradiploic anaesthesia hasbeen the subject of many studies aiming at stu-dying in particular the contribution of thesetechniques as a complement of the loco-regio-nal techniques of anaesthesia of the mandibularnerve at the mandibular foramen. Reitz and coll(1998) [LoE Ib] tested 0,9 ml of a solution of 2%lidocaine with 1/100000 adrenaline in intra-osseous injections in the region of the 2ndmolar, 1st molar and 2nd premolar in 38 sub-jects. Guglielmo and coll (1999) [LoE Ib] follo-wed a strictly identical protocol with a solutionof 2% mepivacaine containing 1/20000 levo-nordefrine in 40 subjects. In both cases no localcomplication was reported by the authors withthe use of a vasoconstrictor in intra-osseousinjections. Dunbar and coll (1996) [LoE Ib] andCoggins (1996) [LoE IIa] have, as for them,noted inflammation and suppuration at thepoint of injection but in both cases the authorsaccuse the injection technique and not the pos-sible effect of the vasoconstrictor.

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Replogue and coll (1998) [LoE Ib] has, as forhim, established the superiority of an intra-osseous injection of 2% lidocaine with1 / 1 0 0 000 adrenaline compared to a solution of3% mepivacaine without vasoconstrictor duringthe anaesthesia of the 1st mandibular molarwhich does seem to indicate an interest in theuse of vasoconstrictors since mepivacaine ispractically neutral as for vasodilation evenslightly vasoconstrictive. These results arec o n c o rdant with those of Petrikas (1990) [LoE I I I ]who studied on 22 subjects the efficiency of asolution of lidocaine with and without adre n a l i n eduring a series of intraseptal injections: heconcluded that the addition of adre n a l i n ei m p roves the depth of the anaesthesia, its suc-cess rate and its duration, contributes to the pul-pal dissemination of the anaesthesia and doesnot increase the local noxious eff e c t s .For intraligamentary anaesthesia, the researchof Tagger and coll (1994) [LoE Ib] clearly sho-wed that the anaesthesia results more fromintra-osseous diffusion than from direct diffu-sion to the apex so that the remarks made forthe intra-osseous techniques should apply tothe intraligamentary techniques. In fact, thework of Gray and coll (1990) [LoE IIa] showed atthe same time the absence of noxious effects ofvasoconstrictors associated with an anaesthe-tic solution injected into the ligament (lidocaine+ adrenaline or prilocaine + felypressine) andthe marked superiority of the success rates withvasoconstrictors compared to LA alone.The work of Walton (1982) [LoE IIb] and of Galiliand coll (1984) [LoE IIb] show a complete re c o-very of the periodontal ligament after 8 to1 5 days of healing in the monkey having under-gone intraligamentary injections of solutionscomprising a vasoconstrictor. Tsirlis and coll(1992) [LoE IIa] showed in a study group of3 0 5mandibular tooth extractions that the fre-quency of dry socket after intraligamentaryanaesthesia was not increased compared to are f e rence group with a conventional anaesthesia.Mc Lean and coll (1992) [LoE Ib] showed thesuperiority of a solution of bupivacaine with1/200 000 adrenaline over a solution of lido-caine with 1/100 000 adrenaline.

Finally in a methodologically rigorous study,Handler and Albers (1987) [LoE IIb] comparedthe use of 4 different solutions during intraliga-mentary anaesthesias: 2% lidocaine, 2% lido-caine with 1/50000 adrenaline, 2% lidocainewith 1/100000 adrenaline and finally 1/100000adrenaline alone. Their surprising results showthat contrary to what is usually reported, there isno relation of proportionality between theamount of adrenaline present in the solutionand the duration of the anaesthesia measuredwith the pulp tester. There is no difference bet-ween the 4 solutions as for the frequency ofsuccess of the anaesthesia. The anaesthesia isalso obtained with the solution of adrenalinealone which the authors explain by the fact thatthe anaesthesia in this case would be related tothe pressure and not to the pharmacologicalaction of the vasoconstrictor. The use of a vaso-constrictor in intrapulpal, intraseptal, intradi-ploic and intraligamentary anaesthesia tech-niques is not essential but considerablyimproves the frequency, the duration and thedepth of the anaesthesia obtained. If the injec-tion is carried out under adequate conditions:c o n t rolled pre s s u re, slow injection, smallvolumes – 0,2 ml on average per dental root,(Handler and Albers, 1987) [LoE IIb] – the locallesions directly ascribable to the vasoconstric-tor are negligible and reversible.Systemic effects of these injections exist butare generally much lower than those observedin anaesthesias by infiltration.

3.2. Do vasoconstrictors have to be usedduring loco-regional anaesthesias of themandibular nerve?For a long time the risk of an intravascular injec-tion of an anaesthetic solution with adre n a l i n ewas suggested as an argument in favour of thep roscription of the use of a vasoconstrictor inthe anaesthesia technique at the mandibularforamen (Gaudy and Aretto, 1999) [LoE IV]). Thisa rgument is opposed to the consensual feelingin the profession that the success rate of thel o c o - regional mandibular anaesthesia is re l a t e dto the presence and the dose of the vasocons-t r i c t o r. The literature does not confirm this


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i m p ression. Keesling and Hinds (1963) [LoE Ib]c o m p a red 5 solutions of 2% lidocaine containingrespectively 1/50 000, 1/250 000, 1/750 0 0 0 ,1 / 10 0 00 0 0 a d renaline and without adre n a l i n efor anaesthesia at the mandibular foramen. Theauthors report a success rate with the pulp tes-ter of 87,5% for an average duration of anaes-thesia of 44 ±5,7 minutes for lidocaine withouta d renaline. To be compared for example with asuccess rate of 96% and an average duration of6 6 , 9 ±8,7 minutes for the 1/750 000 solution.T h e re does not seem to be a significant diff e-rence between the solutions with 1/50000 and1 / 2 5 0000, neither for the success rates, nor forthe duration of the anaesthesia.Mac Lean and coll (1993) [LoE Ib] thus showedby testing on 30 subjects 3 anaesthetic solutions(2% lidocaine with 1/100000 adrenaline, 4% pri-locaine alone and 3% mepivacaine alone) thatt h e re was no significant diff e rence in the suc-cess rates of the anaesthesia at the mandibularforamen controlled with the pulp tester.Dagher and coll (1997) [LoE IIa] tested 3 solu-tions of 2% lidocaine with re s p e c t i v e l y1 / 5 00 0 0 , 1 / 8 0 000 and 1/100 000 adre n a l i n e .A c c o rding to the methodology of Mac Lean(1993) out of 30 subjects in good health, the3 solutions appear equivalent as for the successrate, the rate of failure and the frequency of theanaesthesia. Malamed (1997) [LoE IV] re c o m-mends the block anaesthesia of the alveolarnerve with vasoconstrictor only if a pro l o n g e dduration of the anaesthesia is re q u i re d .Knoll-Kohler and Fortsch (1992) [LoE Ib] tested,on 10 students, two solutions of 2% lidocainewithout adrenaline, one with a pH of 3,5, theother with a pH of 6,8, and three solutions of 2%lidocaine with 1/50000, 1/100000 and 1/2000 0 0a d renaline. According to these authors lidocainewithout adrenaline whatever the pH shows ahigh rate of failures and a lower duration. Theaddition of 1/100000 or 1/200 000 adre n a l i n ei m p roves the success rate and the duration ofthe anaesthesia but does not make the latencytime vary. These results are in agreement withthose of Kabambe and coll (1982) [LoE Ib] whoobserve, by comparing a solution of lidocainewith and without adrenaline, a failure in more

than half of their subjects during anaesthesia ofthe lower alveolar nerve.The addition of a vasoconstrictor to the anaes-thetic solution is not essential for anaesthesia ofthe lower alveolar nerve at the mandibular fora-men. The addition of adrenaline increases theduration of the anaesthesia but does not seemto have a decisive effect on the success rate.The results concerning the success rate of theanaesthesia are contradictory. Taking intoaccount the relation which exists between thesuccess rate and the volume of solution injected( Vreeland, 1989) [LoE IIb], the addition of a vaso-constrictor could prove to be judicious in thep revention of the systemic effects of LA.Another argument called upon to dispute theuse of a vasoconstrictor in loco-regional anaes-thesia of the mandibular nerve is the fact that thevasoconstrictor could lengthen the duration ofthe labio-mental anaesthesia and consequentlyfavour wounds by lip biting which constitute oneof the most frequent adverse effects of theseinjections (Wahl, 2000). In fact, re s e a rch hasshown that only the pulpal anaesthesia is leng-thened during loco-regional anaesthesias of themandibular nerve with vasoconstrictor and notthe labio-mental anaesthesia (Hersh andHermann, 1995 [Not classified: clinical case];Yaguiela, 1985 [LoE Ib]).

4. Dose of vasoconstrictors inodonto-stomatologic anaesthesia

There does not exist a definitively conclusivework concerning the ideal dose of adrenaline inLA. Fink (1978) [LoE IIb] showed that the dura-tion of the local anaesthesia (all techniquestaken into account) was directly dependent onthe amount of adrenaline present in the solut i o n :the duration obtained for a solution of 1% lido-caine with 1/50000 adrenaline is 210 m i n u t e s ,160 minutes with 1/100000 and 130 minuteswith 1/200 000. Taking into account the averageduration of dental acts, Himuro and coll (1989)p ropose to replace lidocaine with 1/80000 bylidocaine with 1/200 000 after a comparative teston only 6 volunteers. Since 1967, Gangaro s a

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and Halik [LoE Ib] showed that the solution oflidocaine with 1/100000 or with 1/300000 wereequivalent for the speed of onset and the effi-cacy evaluated according to the experience of agroup of 17 dental surgeons in a prospectivedouble blinded series of 542 patients. Withregard to the duration of the anaesthesia, whichis believed since Braun (1924) [LoE III] to bedose-dependent; the results of the same studyshow a negligible gain in terms of duration whilepassing from the anaesthetic solution with1 / 3 0 0 000 adrenaline to the solution with1 / 1 0 0 000 adrenaline. Knoll-Kohler (1992)[LoE Ib] after studying 10volunteers affirms thatonly lidocaine with 1/100000 gives constantresults. Obviously, the dosing of adre n a l i n emust be adapted to the characteristics of the LAmolecule. In addition to lidocaine, carticaineand articaine are also available and marketedwith 1/100000 and 1/200000 adrenaline.Vahatalo and coll (1993) [LoE Ib] tested 2% lido-caine with 1/80000 adrenaline and 4% articainewith 1/200000 adrenaline for latency time andduration of the anaesthesia controlled with thepulp tester. There was no statistically significantdifference between the two groups which wouldmake it possible to choose the molecule contai-ning the lowest dose of adrenaline.Knoll-Kohler and coll (1992) [LoE Ib] compared4% articaine with 1/100000 and the solutionwith 1/200000 during the extraction of a 3rdmandibular molar by measuring the variationsof heart rate, the concentration of cyclic AMPand the level of noradrenaline. These parame-ters were correlated to the plasmatic levels ofadrenaline as a reference of endogenous secre-tion. The resorbtion of adrenaline from the siteof injection appeared to be dose-dependentwhich should have made the authors lean infavour of the solution with 1/200000 adrenaline.In fact, in earlier research, Knoll-Kohler (1991)[LoE Ib] estimated that the risk of cardiovascu-lar accident was all the more high as the opera-tional gesture was prolonged and that the doseof adrenaline was low.This result is disputed by the work ofDaublander and coll (1997) [LoE III] who notethat the sympathomimetic side effects of the LA

injections with vasoconstrictor are significantlymore important in their retrospective series ofmore than 2700 subjects for the solution of arti-caine with 1/100000 in comparison with thesolution of articaine with 1/200000. Jage (1993)[LoE IV] estimates that the best concentration inthe healthy patient is (all molecules taken intoaccount) 1/100000 to 1/200000 knowing thatthe individual maximum dose is 0,25 mg. On theother hand in the patient presenting a vascularpathology the obligatory concentration wouldbe 1/200000. Let us recall that for 1 ml ofanaesthetic solution a solution with1/1000accounts for 1 000µg of adrenalinewhile a solution with 1/200 000 contains 5µg ofadrenaline.For mepivacaine Berling’s re s e a rch (1958)[LoE IIb] shows an absence of statistically signi-ficant difference between the 2% solutions withrespectively 1/100000 and 1/200000 adrena-line for the success rate and the duration of thepulpal anaesthesia.Work is still contradictory concerning the idealdose of adrenaline in 2% solutions of lidocaine.The solution with 1/200000 gives more thantwo hours of anaesthesia which represents asufficient duration for the immense majority ofall odonto-stomatologic acts. For 4% articaineand 2% mepivacaine, 1/200 000 solutionsshould be preferred in the absence of significantdifference in performance with the 1/100000solution.Finally the work of Jorkjend and Skoglung(2000) [LoE Ib] clearly shows:• On the one hand that the increase in thevolume of adrenaline and local anaestheticsolution injected can have an adverse effectwhich is the increase in post-operative painwithout counterparts in terms of duration orquality of the anaesthesia;• On the other hand that the increase in thedose of adrenaline in the anaesthetic solutionalso significantly increases post-operativepain by rising the level of cyclic AMP in gingi-val tissues which enhances the accumulationof noxious substances or pro-algesic media-t o r s .


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5. Drug interactions

Vasoconstrictors used in association with LAbut also as topic or injectable haemostaticagents and finally on gingival retraction cordshave the potential to interact with a broadvariety of drugs (Hansten, 1981) [LoE IV].Local reactions go as far as local ischaemia andnecrosis (Yagiela, 1999; Damm and Fantasia,1992). They are related to the relative overdoseby saturation of the tissues with the vasocons-trictor and with too rapid injections (Meechan,1998) Most of the systemic reactionsare of short duration mainly because of therapid inactivation of the vasoconstrictors oncethat they are absorbed in the blood flow(Yaguiela, 1999) [LoE IV]. Nevertheless seriouslesions or even the death of the patient canresult from fibrillation of medicamentous origin,a myocardial infarction or a cerebro-vascularaccident (Hilley, 1984; Okada, 1989; Massalha,1996) [Not classified: clinical cases].

5.1. Tricyclic antidepressantsThey are gradually replaced by selective inhibi-tors of the recapture of serotonin, neverthelessthey remain used among patients who are into-lerant or resistant to these new drugs. Tricyclicantidepressants block the active recapture ofbiogenic amine neurotransmitters (catechola-mines and serotonins) by the nervous termina-tions where they were released. The result is apotentiation of the concerned neurotransmit-ters: the adrenergic vasoconstrictors but espe-cially noradrenaline are prone to the same phe-nomenon of recapture. Tricyclic antidepressantsblock the muscarinic and alpha1 adrenergicreceptors and depress the myocardium whatcan in turn modify the cardiovascular responseto vasoconstrictors.According to Boakes and coll (1972) [LoE IV] outof 15 case of patients having presented severedisorders with noradrenaline, 5 took tricyclicantidepressants.Such accidents can occur for injections of2,5 cartridges of 1/100000 adrenaline (Perssonand Siwers, 1975) [LoE IV]. Cawson and coll(1983) [LoE IV] drew aside the possibility of cli-

nically significant interactions between tricyclicantidepressants and LA containing adrenaline.Actually if the theoretical risk is high the clinicalsigns are rare. Several factors contribute to it:– the competition between the vasoconstrictor(a adrenergic) and vasodilator (ß2 adrenergic)effect leads to a compensation of the haemody-namic variations at the usual doses in odonto-stomatology;– the prescription of these drugs is often doneon a long term basis which causes a desensiti-sation to adre n e rgic vasoconstrictors andconsequently a reduction in the risk of interac-tion (Moyer and coll,1979) [LoE Ib].The attitude toward patients under tricyclic anti-depressants must be to avoid noradrenaline inassociation with LA and to inject measureddoses of LA associated with 1/100 000 or1/200000 adrenaline. In practice the amountinjected should be one third of the maximumamount in the normal subject (Yaguiela, 1999[LoE IV]).

5.2. Monoamine oxydase inhibitorsThe only selective inhibitors still used do notpresent an interaction with adrenaline. Studiesrepeated in human subjects and the animal didnot show any significant interaction with thedoses used in odonto-stomatology (Boakes andcoll, 1973 [LoE IV]; Wong and coll, 1980 [LoEIb]).

5.3. Beta-blockers Although broncho- and vasoconstrictor effectscan theoretically appear when taking cardio- orbeta1 selective beta-blockers (which are thuslikely to cause asthma attacks), there does notexist any incident described among patients inwhom beta-blockers, cardio-selective drugsand adrenaline anaesthetic solutions wereassociated (Pallash, 1998 [LoE IV]).Thus it is mainly non cardio-selective beta-bloc-kers that competitively block the stimulation ofthe beta1 and beta2 receptors by endogenouscatecholamines which are the cause. They alsoblock the activation of the beta receptors byexogenous catecholamines. It is mainly uponthe beta2 receptors that the beta-blockers act

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by transforming adrenaline into an exclusivelyalpha-adrenergic drug. The consequences arean increase in peripheral resistances and,directly in connection with the dose, an increasein blood pressure and a deceleration of theheart rate which can lead to major and welldocumented accidents (Hansbrough and Near,1980; Foster and Aston, 1983 [Not classified:clinical cases]).This risk must be moderated for non cardio-selective beta-blockers with an intrinsic sympa-thomimetic activity (ISA) for which the partialbeta-agonist activity leads to a limitation of thebradycardia and vasoconstrictor effect. Let usnote that beneficial local effects have been des-cribed for beta-blockers like lengthening of theduration of the pulpal anaesthesia and soft tis-sues (Zhang, 1999 [LoE Ib]).The precautions will include a split and slowinjection of LA containing no more than1/100000 adrenaline after negative aspiration.

5.4. General anaestheticsWe have discussed the possible interactionswith halogenous derivatives. The mechanism bywhich GA potentiate the arythmogenous effectsof catecholamines are unknown. It is probably asimultaneous stimulation of the alpha1 and betareceptors. Adrenaline is in turn able to activatethe two types of receptors and to generaterhythm disorders during general anaesthesia(Hayashi, 1993 [LoE Ib]).Thiopental is also able to exaggerate the aryth-mogenous potential of adrenergic substances.As thiopental is often used during induction withhalogenous derivatives, its interaction was ini-tially under estimated.When thiopental is used alone, a dose of adre-naline of 2 µg.kg-1 will be allowed in per-opera-tive injection under general anaesthesia. Thisdose will be 1 µg.kg-1 if the thiopental is asso-ciated with halothane (Christensen and coll,1993 [LoE IV]). One death has been reportedunder halothane, due to an interaction with aretractor cord containing racemic adrenaline(Hilley and coll, 1984 [Not classified: clinicalcase ]).

5.5. Cocaine Animal experiments and human cases havegiven proof of the interaction of cocaine withadrenergic vasoconstrictors. (Lathers and coll,1988) [Not classified: clinical case]. Severaldeaths whose study is well documented,appear in the literature (Chiu, 1986) [Not classi-fied: clinical case]. The mechanism is a facilita-tor effect of cocaine on the release of adrener-gic neurotransmitters and the intensification ofpostsynaptic responses to adrenaline-like sub-stances. The blocking of muscarinic cardiacreceptors and the central deterioration of thevegetative nervous system can more o v e rcontribute to worsen the reactions to the injec-tion of vasoconstrictors.No dental treatment should be carried out inpatients under the effects of narc o t i c s .Vasoconstrictors will be proscribed for at least24 hours after the consumption of cocaine toallow the elimination of the drug and its activemetabolites.

5.6. Antipsychotic drugs and alpha-blockersThese drugs (chlorpromazine, thioridazine, ris-peridone) have as a side effect blocking of thealpha-adrenergic receptors and thus causingorthostatic hypotension reactions. In the eventof overdose, the plasmatic passage of adrena-line would be worsening since only beta2 recep-tors would be activated leading to vasodilation.It is in fact a strictly theoretical risk: no seriouslydocumented accident has been reported withthe doses used in odonto-stomatology.

5.7. Guanethidine Being a substance inhibiting the release of nora-d renaline at the terminal sympathetic nervefib res, it is used in the treatment of severe arte-rial hypertension: used over a long period it couldcause a multiplication of adre n e rgic receptors ora decrease in their sensitivity threshold. This risk is theoretical for a rare drug.

5.8. Adrenergic anorecticsThese are sympathomimetic drugs that affectthe metabolism of catecholamines and are che-mically similar to amphetamines. These drugs


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increase the adrenergic neurotransmission andstimulate the central nervous system, their ano-rectic activity follows from this stimulation of theSNC.Their effects can be potentiated by the conco-mitant use of vasoconstrictive substances. It isthe case of mazindol for which the FDA and themanufacturer recommend caution before usewith vasoconstrictors (Wynn, 1997 [LoE IV]).

6. Does there exist pathologiescontraindicating vasoconstrictors?

One must keep in mind that 45% of the patientspresenting at a dental practice have one ormore intercurrent pathologies with the oralpathology and that 20% of them present a car-diovascular pathology. Daublander and coll(1997) [LoE III] estimate in their series at 0,07%the risk of a serious accident in connection witha local anaesthesia at the dental surgery whichis comparable with the incidence of seriouscomplications of general anaesthesia (0,05%).But these figures must be balanced by the sta-tus of the patient. Thus the side effects obser-ved under dental local anaesthesia concern5,7% of the patients presenting risks against3,5% of the healthy patients. These figures areto be put in relation with those of general anaes-thesia for which the side effects affect 12,3% ofASA 1 patients and 34,9% of ASA III and IVpatients. Daublander shows clearly that thefound side effects are independent of theanaesthetic molecule used (articaine, lidocaineor mepivacaine) and of the presence or not ofan associated vasoconstrictor but ratherdepend on the dose employed.Local anaesthesia with vasoconstrictor is thus,in odonto-stomatology, a very safe techniquewhose contraindications appear to be largelyexaggerated.

6.1. HyperthyroidismHyperthyroidism can result from a disease orfollow from a chronic overdose in thyroxine.H y p e r t h y roidism will result in card i o v a s c u l a rdisorders which reproduce the effects of an

overdose in adrenaline: tachycardia and otherarrhythmias, widening of the amplitude of thepulse, myocardial ischaemia... It was believedfor a long time that adrenaline and noradrena-line took part in the disorders of hyperthyroi-dism in a synergistic manner to that of thy-roxine; It is not the case: in hyperthyroidism, thehaemodynamic responses to the action of adre-naline and noradrenaline are not fundamentallychanged. (Yaguiela, 1999 [LoE IV]).Recent studies (Johnson, 1995 [LoE Ib]) haveshown that hyper- and hypothyroid patients donot present major disorders when they are sub-jected to corrective treatment and put in thepresence of catecholamines before the begin-ning of this treatment. Although the theoreticalrisk of thyro x i n e - a d renaline potentiation isserious, no clinical cases have been reported.

6.2. Hypertension Hypertension and its relationship with vaso-constrictors are the subject of an abundant lite-rature. It is now largely accepted that the plas-matic passage of the vasoconstrictor ispractically negligible in terms of cardiovasculareffect (increase in the heart rate and the bloodpressure) in comparison with endogenous cate-cholamine secretion in case of pain and stress.The totality of the debate on the cardiovascularchanges induced by the possible addition of avasoconstrictor to LA thus focuses on the eva-luation of the exogenous contribution (about20 µg.l-1) caused by the injection of a cartridgeas compared with the level of the plasmaticconcentration which is around 300 µg.l-1. If oneconsiders the physiological capacity to absorbsuch an exogenous contribution, certain welldocumented facts can be taken into account: atthe time of the childbirth without peridural thelabour pains can multiply the level of plasmaticadrenaline by a factor 4 to 6 (Bonica, 1999[LoE IV]); at the time of a dental extraction thestress alone without pain multiplies the plasma-tic adrenaline by a factor 10 or 20. The passageinto the blood at the time of the resorbtion of2,2 ml of lidocaine with 1/100000 adrenalinecauses only a doubling of the rate of plasmaticadrenaline (Tolas, 1982 [LoE IIa]).

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Chernow and coll (1983) [LoE Ib] compared theLA injection associated with adrenaline andwithout vasoconstrictor in 14 healthy subjectsfor variations in blood pressure, heart rate anddose of endogenous catecholamines. Theypoint out significant results after injection of thesolution with adrenaline for the rise in catecho-lamine concentration during 60 minutes afterinjection: the concentration passing fro m27+/ 4 pg.l-1 to 94+/-13 pg.l-1 in a 1:3 ratio. Thesame team (Cioffi, 1985 [LoE IIb]) reported anincrease in a 1:3,5 ratio in the concentration ofc i rculating catecholamines after anaesthesiawith adrenaline for conservative tre a t m e n t .These concentrations being divided by twofrom the very start of the treatment procedure(dental dam placement).In 1993, Lipp and coll [LoE Ib] tried to identify inthe increase of catecholamines which followsan anaesthetic injection the part which resultsfrom the exogenous contribution by the anaes-thetic solution with vasoconstrictor from thepart which results from the rise in endogenouscatecholamines related to stress due to the infil-tration and the global fear of the operational act.In order to do so the authors used an injectionof 4 % articaine with 20 µg of marked adrena-line. They observed a rise in the total adrenalineconcentration (exogenous and endogenous) 5to 10 times higher than in the reference grouptreated without anaesthesia. They also obser-ved two serum peaks of adrenaline: one5 minutes after the beginning of the injection,the other after the beginning of the dental treat-ment. The authors affirm that the increase intotal catecholamines is mainly the result of theexogenous contribution and explain the peakwhich marks the beginning of the treatment bythe increase in the rate of the plasmatic resorb-tion of the anaesthetic due to the inevitablemassage of the site of injection by the fingers ofthe operator.Niwa and coll (2000) [LoE Ib] in a particularlydetailed and sophisticated work establishedthat the infiltration of 3,6 ml of 2 % lidocainewith 1/80000 adrenaline was equivalent, interms of haemodynamic effects and plasmaticcatecholamine rates, to the perfusion of

10ng.kg.mn-1 of adrenaline alone. The plasma-tic catecholamine rate passing fro m52+/ 24pg.l-1 to 363 +/- 105 pg.l-1 for the anaes-thetic infiltration with adrenaline and fro m32+/ 18pg.l-1 to 214 +/- 69 pg.l-1 for the perfu-sion of 10 ng.kg.min-1, i.e. being multiplied by afactor 7.But if one could show a significant increase intotal catecholamines after LA injection withvasoconstrictor and even show the dominatings h a re of exogenous catecholamines in thisincrease, it is impossible to know with precisionthe cardiovascular repercussion of this increasebecause other additional factors make the inter-pretation of the results random. Thus, Di Angelisand Luepker (1983) [LoE IIa] showed that theonly fact of going to the dental surgeon’s for asimple check-up caused a rise in the bloodpressure of 4,5 mm Hg higher than that of acheck-up at the doctor’s. Work of Gortzack andcoll (1992) [LoE Ib] confirm these results andshow that there is no diff e rence betweennormo- and hypertensive subjects on this point.Many authors finally think that it is impossible toestablish proportionality between increase intotal catecholamines and card i o v a s c u l a re ffects, since if the majority observe thisincrease after LA injection with vasoconstrictor,they agree that they have not observed manifestclinical repercussions in healthy or hypertensivesubjects (Sack and Kleeman, 1992 [LoE IIa]).Cheraskin and coll (1958) [LoE Ib] have shownthat the main factor in the rise in blood pressuretook place in the waiting room and not duringthe operational phase. This rise in blood pres-sure was not significantly different betweenhypertensive and normotensive patients but itwas significantly reduced in the hypertensivesubjects who received a sedative premedica-tion 45 minutes before the time of the appoint-ment. This work thus clearly highlighted the roleof stress in comparison with the discrete role ofthe exogenous catecholamine injection at thetime of the LA.The same authors showed in later work(Cheraskin and Prasertsuntarasai, 1959 [LoEIb])that the phase of 5 to 10 minutes which followthe anaesthetic injection with or without adrena-


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line is marked by no significant change in bloodpressure or pulse, whether the patient is initiallynormo or hypertensive. They foresee the laterresults of Campbell (1996) [LoE IIb] by speci-fying that it is at the beginning and the end ofthe operational act itself that the most signifi-cant changes are observed.Their conclusion is that the use of a preopera-tive sedative and of a vasoconstrictor associa-ted with a LA in hypertensive subjects givessignificantly better results in terms of control ofthe blood pressure and pulse compared tohypertensive subjects who receive neither asedative nor a vasoconstrictor. This result is tobe put in relation with the work of Goldstein(1982) [LoE Ib] which shows that the haemody-namic variations observed are principally due tothe endogenous noradrenaline secretion underthe effect of the operational stress, secretionwell compensated by the administration of asedative premedication by diazepam.Meyer (1987) [LoE Ib] compared the variationsof blood pressure in 60 healthy subjects recei-ving for 30 of them a LA injection with adrena-line and for the 30 others a LA injection withoutvasoconstrictor. The results show that the bloodpressure of the patients of the group withoutvasoconstrictor are significantly worse, in termsof control of the blood pressure, than those ofthe group with vasoconstrictor. The author logi-cally explains these results by the bad quality ofthe anaesthesia obtained when the LA wasinjected alone and thus by the endogenouscatecholamine hypersecretion. It should benoted that in the two groups half of the subjectsunderwent only the anaesthesia while theothers were subjected to an anaesthesia follo-wed by a tooth extraction. In the group withoutv a s o c o n s t r i c t o r, those who underwent theextraction presented significant variations inblood pressure.Thus there is no contraindication to use of a LAassociated with adrenaline in particular for actsrequiring a prolonged and deep local anaesthe-sia in hypertensive subjects stabilized by anantihypertensive treatment.The maximum recommended dose is 0,04 mgin total which corresponds to 2 cartridges or

4 , 4 ml of LA with 1/100000 adre n a l i n e .(Budentz, 2000 [LoE IV]).For the great majority of stabilised hypertensivesubjects, it is possible to exceed this limit whiletaking into account the rules of overd o s e(Meechan, 1998 [LoE Ib]). In patients with non-stabilised blood pressure, one will be able tocontinue the anaesthesia beyond two cartridgeswith adrenaline with an anaesthetic withoutvasoconstrictor.Massalha and coll (1996) [Not classified: clinicalcase] report 2 cases of intracerebral haemor-rhages having resulted in the death of thepatient during dental care. We quote them torecall attention. They carry out a review of thel i t e r a t u re and put, like the majority of theauthors, these major hypertensive pushes lea-ding to death on the account of a hyperstimula-tion of the trigeminal nerve.Indeed, in addition to the sensitivity of the faceand the masticatory motricity, the trigeminal gan-glion, ensures the vasomotor innervation of allthe cerebral blood vessels (Moskowitz, 1984[LoE IV]). They conclude that there is a simulta-neous effect of this hyperstimulation and haemo-dynamic changes induced by the rise in theserum peak of catecholamines after anaestheticinjection. Their point of view is purely conjectural.In the event of unstable blood pressure asso-ciated with other elements burdening the pro-gnosis, the treatment will have to be carried outin a hospital disposing of a reanimation struc-ture and under vital function monitoring.

6.3. Rhythm disordersThe literature concerning the study of the varia-tions of the heart rate induced by the injectionof LA with vasoconstrictor is rich and often of avery good level of evidence (Meyer, 1987[LoEIb]; Montebugnoli, 1990 [LoE Ib]; Blinder,1996 [LoE IIb]; Campbell, 1996 [LoE Ilb];Replogue, 1999 [LoE Ib]).A very well documented work by Campbell andcoll (1996) [LoE IIb] allowed to study the varia-tions of the heart rate in a population of 40 old-aged subjects (20 re f e rence subjects and20subjects with arrhythmia (treated or not)) atvarious times of the intervention: preoperative,

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anaesthetic injection, per-operational, post-operative. The results made possible the down-fall of some common beliefs: (1) there was nos i g n i ficant diff e rence between the re f e re n c egroup and the arrhythmia group as for the onsetof an episode of benign arrhythmia (17 sub-jects); (2) the results show in a paradoxical waythat the rise in the heart rate is definitely lowerduring the anaesthetic injection compared tothe pre and per operational rise of the heartrate; (3) the authors show moreover that theinjection of an anaesthetic solution with vaso-constrictor is probably not implied in the epi-sodes of benign arrhythmia observed: theserum peak of the vasoconstrictor was reachedon average 5 minutes after the injection whe-reas the episodes of arrhythmia were after halfof the surgical time, i.e. well after the serumpeak of the vasoconstrictor.This work can be compared to the results ofBlinder and coll (1996) [LoE IIb] on the electro-c a rdiographic changes observed by Holtermonitoring among 40 cardiac patients followed-up 1 hour before an extraction under LA withoutvasoconstrictor and 23 hours afterwards. Theseresults show that 14 patients presented signifi-cant changes on the ECG and 12 of them pre-sented an arrhythmia although no vasoconstric-tor was present in the solution.Another result is that 12 of the 14 patientshaving presented a significant change on theECG were under digoxin, either for ischaemicaccidents or for auricular fibrillation. Theseresults seem to show the capacity of the anaes-thetic injection to cause alone, via the physiolo-gical and psychological stress which are asso-ciated to it and via the interaction of thepro-arrhythmogenic effects of LA, acute modifi-cations of the heart rate in a significant percen-tage of patients whether they have healthy car-diovascular functions or not (Malamed, 1996).The authors in agreement with StanleyMalamed [LoE IV] recommend the monitoring ofpatients under digoxin at the time of a localanaesthesia. The intra-osseous injections whichcause a more important rise in the heart rateand blood pre s s u re must be avoided(Chamberlain, 2000 [LoE IIb]). Replogue and

coll (1999) [LoE Ib] propose the use of a 3%solution of mepivacaine as an alternative to theinjection of a LA solution with adrenaline inthese patients.The rhythm disorders met in daily practice areessentially auricular fibrillations stabilised by anadapted treatment (Anguera Camos andBrugada Terradellas, 2000 [LoE IV]).Under these conditions the control of stress andthe therapeutic heart rate is essential and theuse of anaesthetics with vasoconstrictors isindicated. The dosing rules are the same asthose discussed previously.

6.4. Coronary cardiopathies These pathologies are frequently related to thetwo preceding ones and it appears obvious thatclose answers can be given, neverthelesstaking into account the extreme frequency ofthis pathology and the confusion which exists inour minds on their subject, as well in the gene-ral practitioners or specialists as in the dentalsurgeons, the working group made a point ofdevoting a specific paragraph to it.Episodic myocardial ischaemias during stableor unstable known coronary artery diseasefr.:coronaropathies??) pass clinically unpercei-ved in more than 2/3 of cases (Quyyumi andcoll, 1985 [LoE IIa]). Extra cardiac surgery, evenminor, is one of the identified sources of epi-sodes of myocardial ischaemia in known coro-nary patients (Deanfield, 1984 [LoE IIa]).Much work has shown that anomalies of the STsegment of the ECG translate episodes of myo-cardial ischaemia. In 1989, Vanderheyden andcoll [LoE Ib] studied these anomalies of the STsegment during periodontal treatment under LAwith a vasoconstrictor among known and trea-ted coronary patients, placed under monitoringin order to evaluate the anomalies of the STsegment in the immediate LA post injectionphase. They show that the use of a LA withvasoconstrictor does not cause any significantmodification of the ST segment taken as anindicator of myocardial ischaemia.The recommendations of the American DentalAssociation and American Heart Association(1964) specify that vasoconstrictors are not


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contraindicated in these diseases when a safeanaesthetic technique is used, when an aspira-tion test is practised and when the smallesteffective dose is used.

6.5. Asthma Vasoconstrictors associated with an anaesthe-tic solution can be used in asthmatic subjects inthe aim of controlling pain and of avoidingstress which is probably the principal source ofpassage to an asthma attack at the dental sur-gery.Besides adrenaline alone is used for its bron-cho-dilating properties in the treatment ofasthma and a recent systematic review reportslevel 3 and 4 clinical studies which confirm theabsence of adverse effects at the time of its use(Safdar and coll 2001 [LoE IV]). In the particularcase of cortico-dependant asthma (Bush andTaylor, 1986 [LoE IIb]; Perusse and coll 1992, 2[LoE IV]) the problem of the hypersensitivity tosulphites, conservative of the vasoconstrictor,can be posed. It seems however that 96% ofasthmatic subjects are not sensitive to themetabisulphite in question (Send, 1986).Besides Wahl (2000) pointed out that a meal atthe restaurant contains on average from 25 to200 mg of sulphite i.e. 27 times the amountcontained in a cartridge of lidocaine with1/100000 adrenaline (0,9 Mg). The recourse toan anaesthetic without vasoconstrictor andbisulphite however is indicated in the event ofcortico-dependent asthma.

6.6 Hepatic insufficiency Patients having presented a previous and curedviral or toxic hepatic attack may be treated likehealthy patients.In the event of evolutionary severe attack, theevaluation of the hepatic function is important.The total quantity injected can have to be redu-ced and the intervals between the injectionsincreased without detriment to the use of anassociated vasoconstrictor.

6.7. Diabetes Chez les patients diabétiques équilibrés detypeI ou II, l’utilisation de vasoconstricteurs est

indiquée. En cas de diabète déséquilibré etinstable, avec passage brutal de l’hypo à l’hy-perglycémie, les quantités d’AL avec vasocons-tricteur seront modérées de façon à tenircompte du caractère hyperglycémiant del’adrénaline (Meechan, 1996 [NdP Ib]).

6.8. PheochromocytomaIt is a tumour of the adrenal medulla or paraver-tebral sympathetic ganglion which causess e v e re hypertension because of the endoge-nous hypersecretion of adrenaline. Because ofthe risk of potentiation of cardiovascular disor-ders, p h e o c h romocytoma and all the tumoursof the adrenal medulla constitute an absolutecontraindication to the use of vasoconstric-tors (Kaufman and coll, 2002 [LoE IV]; Gaudyand Arreto, 1999 [LoE IV]; Perusse and coll, 1992[LoE IV]). The anaesthetic injection of a solutionwithout vasoconstrictor when it is necessary inthe patient suffering from pheochro m o c y t o m amust take place in a hospital and under vitalfunction monitoring taking into account the diffi-culties of per-operational stabilisation of theblood pre s s u re in these patients (Niruthisard andcoll, 2002 [LoE III]; Tanaka and coll, 1991 [LoEI I I ] ;Pratilas and Pratila, 1979 [LoEIV]).

6.9. Irradiated boneAny irradiation of the maxillofacial structures ina therapeutic aim, may it be in the form of bra-chy- or of teleradiotherapy, reduces the vascu-larisation of the bone so that the bone tissue isnot able to defend itself against aggressionsany more. Oedema followed by endothelialn e c rosis induces successively hyalinisation,fibrosis and thrombosis within the wall of theirradiated vessels. The vessels are obliteratedand the tissue hypoxia leads to the lysis of col-lagen then to degeneration of the bone medulla(Marx, 1983 [LoE III]). Osteoradionecrosis (ORN)or radio osteitis constitutes one of the majorcomplications of maxillofacial therapeutic irra-diations.It is easily understood that such a processwhich generally occurs for irradiations higherthan 60 Gy can be favoured by the local ischae-mia caused at the point of injection of a LA

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containing a vasoconstrictor. In the animal,Heiss and Grasser (1968) [LoE Ib] showedunder extreme experimental conditions thesignificant increase in the risk of ORN afterinjection of vasoconstrictor substances in irra-diated rat mandibles.Obviously there does not exist a comparableprotocol in the human. On the other hand,Maximiw and coll 1991 [LoE IIb] showed thatthe use of low doses of vasoconstrictors or LAsolutions without vasoconstrictor led to, for agroup of 449 extractions undertaken in a bonehaving received on average 50 Gy (values ran-ging from 25 to 84 Gy), a total absence of postextraction osteoradionecrosis and this after apost-extraction follow-up for 4,8 years on ave-rage.Although the mandible is a clearly identified riskfactor of post-extraction ORN, the total amountdelivered and the mode of irradiation (Curi andDib, 1997 [LoE III]) and that there is no evalua-tion in the human of the direct risk related to theuse of vasoconstrictors; it appears desirableto avoid the association of vasoconstrictorswith LA during conservative and especiallynon-conservative treatment on bone irradia-ted beyond 40 Gy.

7 Physiological states and vasocons-trictors

7.1. Pregnancy and breast-feedingAlthough vasoconstrictors (especially noradre-naline) have a potential for reducing the placen-tal perfusion, studies undertaken on this subjectdid not show any adverse effect of adrenalineon the foetus (Haas and coll, 2000 [LoE III]).Actually, the amounts of adrenaline used in themarketed local anaesthetic solutions are soweak that it is very improbable that they canaffect the uterine blood flow. As for breast-fee-ding the only data available is the opinion ofauthors. They confirm the possibility of usingvasoconstrictors in association with LA inwomen during breast-feeding (Gibbs andHawkins, 1994 [NdP IV]; Malamed, 1997[LoEIV).

7.2. ChildrenIn children, taking care of pain is done classi-cally by avoiding a systematic recourse to vaso-constrictors. This practice has no relationshipwith the toxic risk. It rises from the increase inthe severe risk of biting the labial area anaes-thetised for a long time after the end of thetreatment because of the lengthening of theduration of the anaesthesia in the presence of avasoconstrictor (Walh, 1997 [LoE IV]; Gaudyand Aretto, 1999 [LoE IV]). This concerns mainlythe loco-regional anaesthesia of the mandibularnerve and the danger of biting the lower lip.Hersh and Hermann (1995) [LoE Ib] neverthe-less showed that there was no significant diffe-rence in the duration of the labio-mental anaes-thesia after injection of mepivacaine withoutvasoconstrictor when one compares it with aninjection of lidocaine + adrenaline. According tothese authors, the recourse to an anaestheticwithout vasoconstrictor in the child is thuswithout interest and they recommend on thecontrary the use of lidocaine 2% with adrenalineup to a total amount of 4,4cartridges of 1,8 mlin a child of 25 kg against 2,8cartridges ofmepivacaine 3% without adrenaline.Let us note that Hersh and coll (1991) [Not clas-sified: clinical case] reported a mortal overdosein a 5 year old child weighing 16,4 kg and inwhom 5 cartridges of 1,8 ml of mepivacaine 3%without vasoconstrictor had been injected. There are various complex methods for calcula-ting the dose in the child depending on theamount of anaesthetic in the adult, and accor-ding to the body surface in relation to theweight. The different formulas of Clark andYoung lead to nearby results. The ADA and theFDA propose the conversion charts appearingin tables 1 and 2.Although in practice the problem seldom arises,the use of local anaesthetics and a vasocons-trictor in a child of less than 6 months iscontraindicated taking into account the lowmetabolic capacities which can lead to an over-dose or an accumulation of the free fraction.


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Table 1 : Child dose according to weight calculateda c c o rding to the usual amount in the adult.According to Berini and Gay, 1997.

Table 2 : Comparison of the total amounts recom-mended by the Food and Drug Administration in 2%lidocaine with adrenaline and mepivacaine in theadult and the child. According to Wahl, 1997.

7.3. The elderly The elderly are often the target of the variouspathologies which have already been reviewedin this report. It is moreover traditional to consi-der subjects beyond 70 years of age as suffe-ring from chronic renal insufficiency (after40years the glomerular filtration drops by 1 mlper minute and per annum) which forces us todecrease the total amounts by a third from 70 to80 years of age and by half beyond(Commissionnat and Rimet, 1992 [LoE IV]).

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BIBLIOGRAPHY

Weight of the child Fraction of the adult in kg dose

10 0,2715 0,3620 0,4825 0,5530 0,6235 0,6940 0,75

Mepivacaine Lidocaine 2%3% + adrenaline

Quantity of anaesthetic per 1,8 ml cartridge 54 mg 36 mg

Maximal number of cartridges per 24 hours 7,4 13,9for a 70 kg adult

Maximal number of cartridges per 24 hoursfor a 25 kg child 2,8 4,4

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Recommendations to use vasoconstrictors in dentistry and ......médecine buccale chirurgie buccale page 1 VOL. 9, N° 2 2003 Working group Carlos Madrid ( O d o n t o l o g i s t e