ARTICAINE June 2014

Home , Articaine

ARTICAINE June 2014

1 Today’s Menu

Part 2: Articaine HCl: Just the Facts

2 Articaine HCl

3 Articaine HCl

4%! Availability epi 1:100k epi 1:200k

Mg /cartridge 72

MRTD 3.2 mg/lb! 7.0 mg/kg! (USA) Absolute max = n/a

4 Articaine HCl

Onset 2 - 3 min (textbook)

Duration! 60 min (pulpal)

Duration! 3 - 5 hrs (soft tissue)

5 Articaine HCl

1976 Germany

1985 Canada

2000 USA

2005 Australia

6 Articaine HCl

Germany (2012) . . . 97% of ALL LAs used in dentistry*

USA (2009) . . . 41% of ALL LAs used in dentistry

Australia (2012) . . . 70% of dentists use articaine**

7 Why do doctors LIKE articaine?

Anecdotal comments from dentists: “It works faster” “It works better” “I don’t miss as often” “Hard to get ‘numb’ patients are easier to numb with articaine”

8 The SCIENCE of Articaine HCl

Since 1973 there have been more than 200 papers published in the dental / medical literature on articaine HCl

9 The SCIENCE of Articaine HCl

Articaine has been compared to lidocaine, mepivacaine and prilocaine Virtually ALL studies have demonstrated that articaine is AS SAFE and AS EFFECTIVE as the drug it which it was compared.

10 The SCIENCE of Articaine HCl 1999 - Three identical randomized, double-blind, parallel group, active controlled, multicenter Phase 3 clinical trials

Safety & efﬁcacy of articaine HCl for USA Food & Drug Administration (FDA) approval

Patients aged 4 - 79 years

JADA 2000 . . . Efﬁcacy of articaine HCl

JADA 2001 . . . Safety of articaine HCl

Pediatric Dentistry 2001 . . . Safety & efﬁcacy in pediatric dentistry

11 The SCIENCE of Articaine HCl 1999 - Three identical randomized, double-blind, parallel group, active controlled, multicenter Phase 3 clinical trials

Safety & efﬁcacy of articaine HCl for USA Food & Drug Administration (FDA) approval

Because of the Haas 1995 paper we were asked to actively pursue possible post-operative complications (e.g. paresthesia).

All patients were contacted 24-hours and 7-days following their treatment and presented with a list of potential signs & symptoms

12 29 sites in the USA & UK

13 Efﬁcacy of articaine: a new amide local anesthetic

CONCLUSIONS

Four percent articaine with epinephrine 1:100,000 is a safe and effective local anesthetic for use in clinical dentistry. In this investigation consisting of three randomized, double-blind trials, we found articaine to be well tolerated in 882 subjects, and that it provided clinically effective pain relief during most dental procedures. Furthermore, we observed no signiﬁcant difference in pain relief between subjects in the 4 percent articaine with epinephrine 1:100,000 group and those in the 2 percent lidocaine with epinephrine 1:100,000 group.

14 Efﬁcacy of articaine: a new amide local anesthetic

CONCLUSIONS

For 4 percent articaine with epinephrine 1:100,000, time to onset of anesthesia and duration of anesthesia are appropriate for clinical use and are comparable to those observed for other commercially available local anesthetics. Articaine can be used effectively in both adults and children.

16 Safety of articaine: a new amide local anesthetic

CONCLUSIONS:

The incidence of complications (including paresthesia) was equal for both of the tested local anesthetics, lidocaine & articaine.

17 FDA-approved to age 4 years

18 The SCIENCE of Articaine HCl

Virtually ALL studies have demonstrated that articaine is AS SAFE and AS EFFECTIVE as the drug it which it was compared. WHY? Because local anesthetics are VERY EFFECTIVE drugs

19 Before Articaine HCl Pre-2005 (Australia) Pre-2000 (USA)

Lidocaine + epinephrine Mepivacaine + epinephrine Prilocaine + epinephrineUSA Prilocaine + felypressin Australia

20 Before Lidocaine HCl Pre-1948

Procaine + epinephrine Tetracaine + epinephrine

21 Procaine HCl

♥ Procaine HCl

♥ Remains the most well-known local anesthetic in the world by its proprietary name: NOVOCAIN.

♥ Procaine was the 1st local anesthetic to be marketed in glass dental cartridges (1922)

22 Procaine HCl

Procaine

Onset - 6-10 min

Duration - 2-3 hrs

Duration - 20-30 min Allergy YES, rare Rare from Overdose “too much”

23 Procaine HCl Lidocaine HCl

Procaine Lidocaine

Onset - 6-10 min 3-5 min

Duration - 2-3 hrs 3-5 hrs

Duration - 20-30 min 60 min

Allergy YES, rare Exceedingly rare Rare from More likely from ‘too Overdose “too much” much’

24 So, What, if any, are the clinical advantages of articaine HCl compared with the other amide LAs?

25 Articaine HCl Advantages 1. More lipid-soluble Diffuses through soft & hard tissues better Palatal anesthesia with buccal inﬁltration Mandibular anesthesia in adults via inﬁltration

26 Maxillary Inﬁltration

Articaine Articaine More lipid-soluble

Flared palatal roots Palatal soft tissue

27 Articaine HCl by Mandibular Inﬁltration in Adults

Mandibular inﬁltration

28 Articaine HCl Advantages

2. Elimination half-life of 27 minutes (162 min = 2:42) Lidocaine, mepivacaine, prilocaine ~ 90 minutes (540 min = 9 hrs)

29 Articaine HCl Advantages

3. Pregnancy EliminationAll other amide local anesthetics half-life Betaof half-life 27 ~90minutes minutes + ARTICAINE Beta half-life 27 minutes

30 Articaine HCl Advantages 4. EliminationNursing half-life All other local anesthetics USA FDA Pumpof & 27 discard minutes for 9 hours* ARTICAINE USA FDA Pump & discard for 4 hours*

31 Articaine HCl Advantages 5. PediatricsElimination - preferred half-life LA Decreased risk of overdose Eliminationof 27 half-lifeminutes of 27 minutes

32 Articaine HCl Advantages

Articaine is the LEAST LIKELY anesthetic to induce an overdose caused by administration of too many cartridges

33 Articaine HCl Advantages

6. Endodontics (infected / inﬂammed teeth) Greater lipid-solubility Thiophene ring = articaine Benzene ring = other LAs

34 Articaine HCl Advantages

7. ‘Hard to ‘numb’ patients (anecdotal)

35 Articaine HCl Advantages 1. More lipid-soluble Diffuses through soft& hard tissues better Palatal anesthesia with buccal infiltration Mandibular anesthesia in adults via infiltration 2. Elimination half-life of 27 minutes (162 min = 2:42) Lidocaine, mepivacaine, prilocaine ~ 90 minutes (540 min = 9 hrs) 3. Pregnancy - preferred LA 4. Nursing - ‘Pump & dump’ for 4 hours (FDA) Lidocaine, mepivacaine, prilocaine P&D for 9 hours 5. Pediatrics - Lesser risk of OD 6. Endodontics (infected/inflammed teeth) 7. ‘Hard to ‘numb’ patients (anecdotal) © 2014 Dr. Stanley F. Malamed! All Rights Reserved

36 Articaine 4% Epinephrine 1:100,000 or 200,000

• Should I use articaine 4% with 1:100,000 or 1:200,000 100,000 epineprine?

200,000

37 Articaine 4% Epinephrine 1:100,000 or 200,000

• Less epinephrine is, of course, better for the patient, therefore MY 100,000 RECOMMENDATION is the use of articaine 4% with 1:200,000 epinephrine for optimal depth and duration of pain control

200,000

38 So, Malamed, you think articaine’s a great drug, but . . .

40 A basic truism regarding ANATOMY: Everybody is different

We teach ‘normal’ anatomy: Insert the needle here Advance 25 mms Aspirate Deposit the drug We HOPE the nerve is in the area

41 A basic truism regarding INJECTIONS: Once a needle penetrates the skin or mucous membrane, every injection is BLIND

42 A basic truism regarding LOCAL ANESTHETICS: LAs are chemicals that interrupt nerve conduction (producing anesthesia) transiently (hopefully)

43 Another truism regarding LOCAL ANESTHETICS

ALL LAs are neurotoxic (they can damage nerves)

44 A basic truism regarding PARESTHESIA:

Paresthesia has existed ever since injections were ﬁrst administered

45 Articaine and Paresthesia

46 Canada

Articaine introduced in Canada in 1983

47 Haas, D A. Lennon, D.

A 21 year retrospective study of reports of paresthesia following local anesthetic administration.

J. Canadian Dental Association 61(4):319-20, 323-6, 329-30, 1995 Apr

48 Haas, D A. Lennon, D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995

Overall incidence of paresthesia (all LAs) = 1:785,000 2% and 3% LAs = 1:1,250,000 4% prilocaine = 1:588,235 4% articaine = 1:440,529

49 Haas, D A. Lennon, D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995

70.6% involve LINGUAL nerve

50 Haas, D A. Lennon, D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 Apr

This was NOT a scientiﬁc study:

1. Duration of paresthesia was NOT documented

2. In > 30% of incidents the LA used was not identiﬁed

3. The reports of paresthesia did not include cases where the LA might have been used for surgical procedures

**** Surgery is THE most common cause of paresthesia

51 Haas, D A. Lennon, D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 Apr

4. The gauge and length of the needle used was documented in only 26% of the reviewed cases (n = 143)

5. The injection technique used during each incident was not identiﬁed

6. It was a review of voluntary reports reviewed by the Provincial Insurance Commission.

7. Conclusions are quite subjective.

52 Haas, D A. Lennon, D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 Apr

Yet this paper has taken on a life of its own . . . has become THE most cited paper purporting to demonstrate that 4% LAs are associated with a higher risk of paresthesia

Virtually all papers reporting increased risk of paresthesia from articaine ultimately use this paper as their initial source.

53 The DANISH experience Articaine introduced in Denmark in 2001

54 The DANISH experience Articaine introduced in Denmark in 2001

Prof. S. Hillerup 2006 IJOMS

55 77% Lingual N.

57 The DANISH experience

2004 . . . Danish Dental Association recommended that articaine not be used by inferior alveolar nerve block

Sales of articaine declined signiﬁcantly

58 Pharmacovigilance Working Party of the European Union

EU equivalent to Canada’s TGA Australia’s TGA and the USA’s FDA

59 Konklusioner på vurdering af bivirkninger ved lokalbedøvelsesmidler brugt til tandbehandling http://www.laegemiddelstyrelsen.dk/1024/visLSArtikel.asp?artikelID=9578

Lægemiddelstyrelsens netsteder:

English Min side Nyheder Publikationer Links Kontakt Sitemap Søg

Forside > Bivirkninger > Meddelelser om bivirkninger >

Meddelelser om bivirkninger Konklusioner på vurdering af bivirkninger ved lokalbedøvelsesmidler brugt til tandbehandling Indberetning af bivirkninger hos Produktresumé for Septanest® mennesker EU´s Bivirkningskomité har på et møde d. 17. oktober 2006 igen vurderet forekomst af Produktresumé for Septocaine® Indberetning af bivirkninger hos dyr bivirkninger, især mistanke om nerveskader (paræstesier, føleforstyrrelser), ved brug af lokalbedøvelsesmidler anvendt i forbindelse med tandbehandling. Produktresumé for Ubistesin® Indberetning af bivirkninger ved Produktresumé for Ubistesin Forte® kliniske forsøg Vurderingen er en opfølgning på en undersøgelse, der indledtes i 2005. Undersøgelsen blev sat i værk, fordi der i Danmark var rejst mistanke om, at ét af lokalbedøvelsesmidlerne, articain, Folder om indberetning indebar øget risiko for nerveskader, set i forhold til risikoen ved anvendelse af andre lokalbedøvelsesmidler (mepivacain, prilocain, lidocain). Bivirkningsrådet Undersøgelsen er foretaget i tæt samarbejde med indehaveren af markedsføringstilladelsen for Septanest® og Septocain® og risiko Sikkerhedsopdatering lægemidlerne Septanest® og Septocain®. I undersøgelsen indgår de samlede internationale for føleforstyrrelser erfaringer indhentet fra 57 lande. Det anslås at ca. 100 millioner patienter årligt behandles med EudraVigilance articain. Undersøgelse af bivirkninger ved bedøvelsesmidler ved tandbehandling Undersøgelsen omfatter en gennemgang af eksperimentelle studier samt af kliniske forsøg med raske frivillige samt patienter. Gennemgangen omfatter de almindeligst anvendte lokalbedøvelsesmidler og altså ikke kun articain. Endvidere er samtlige bivirkningsrapporter indsamlet på verdensplan gennemgået.

Med hensyn til articain er konklusionen, at der ikke er sket afgørende ændringer i dette lægemiddels sikkerhedsprofil siden tidspunktet for påbegyndelse af markedsføringen (1988). Der er således intet grundlag for at afvige fra at bruge articain efter de gældende retningslinier, som fremgår af produktresumeet.

Konklusionen er endvidere at

alle lokalbedøvelsesmidler kan forårsage nerveskade (er neurotoksiske). o Forekomsten20 af føleforstyrrelser Octoberforekommer tilsyneladende med lidt større hyppighed 2006 efter anvendelse af articain og prilocain. Set i forhold til antallet af behandlede patienter er føleforstyrrelserne imidlertid sjældent forekommende. Eksempelvis anslås forekomsten af føleforstyrrelser ved anvendelse af articain at være et tilfælde pr. 4.5 millioner behandlede patienter. nerveskader kan have flere årsager o mekanisk forårsaget skade ved nåleindstikket o direkte toksisk påvirkning af lægemidlet o utilstrækkelig ilttilførsel til nerven der er ikke umiddelbart behov for yderligere eksperimentelle undersøgelser eller kliniske forsøg der bør gøres en indsats for yderligere at mindske forekomsten af nerveskader o Indehaveren af markedsføringstilladelsen har fremsat forslag til, hvorledes risikoen for nerveskader kan nedsættes yderligere; forslaget indebærer bl.a. undervisningstilbud for tandlæger, forbedret information i produktresumeet samt øget rapportering i en periode til myndighederne.

I Danmark er følgende lokalbedøvelsesmidler med indhold af articain markedsført: Septanest®, Septocaine®, Ubistesin® og Ubistesin Forte® (se link til produktresumeer for de fire lægemidler i faktaboksen øverst til højre på siden).

Yderligere oplysninger kan fås ved henvendelse til overlæge Doris I. Stenver, Forbrugersikkerhed, tlf. 44 88 92 47, mobil 22 46 09 79.

Sidst opdateret d. 27.11.2006

1 of 1 27/11/06 07:28 Pharmacovigilance Committee of the European Union

Regarding articaine, the conclusion is that safety proﬁle of the drug has not signiﬁcantly evolved since its initial launch (1998). Thus, no medical evidence exists to prohibit the use of articaine according to the current guidelines listed the summary of product characteristics.

61 Pharmacovigilance Committee of the European Union

All local anaesthetics may cause nerve injury (they are neurotoxic in nature). The occurrence of sensory impairment is apparently slightly more frequent following the use of articaine and prilocaine. However, considering the number of patients treated, sensory impairments rarely occur. For example, the incidence of sensory impairment following the use of articaine is estimated to be 1 case in 4.8 million treated patients.

Nerve injuries may result from several incidents: Mechanical injury due to needle insertion Direct toxicity from the drug Neural ischaemia

There is no need for new experimental studies or clinical trials

62 The DANISH experience

Danish Medicines Agency (Laegemiddel Styrelsen) - 25 October 2011

The Danish Medicines Agency's database of side effects contain 160 reports on adverse reactions from articaine that occurred from 2001-2005. The adverse reactions are mainly sensory impairment and nerve damage.

63 Danish Medicines Agency (Laegemiddel Styrelsen) 25 October 2011

Since 2005, we have seen a drop in the number of reports of new adverse reactions.

Up until 1 October 2011, we have received 2 reports on suspected adverse reactions from articaine which occurred in 2011. In both cases, the patients have experienced sensory impairment after treatment with articaine.

64 The DANISH experience

Danish Medicines Agency (Laegemiddel Styrelsen) 25 October 2011

2001 - 2005 . . . 160 reported cases The2005 - 2011Weber . . . 2 reported Effect cases

65 The AMERICAN experience Articaine introduced in USA in 2000

66 2010

67 FDA Adverse Event Reporting System (AERS)

Average number of adverse reports received by the FDA is currently over 400,000/year…

“For the 159 of the 248 cases (of dental paresthesia) for which no procedure was listed, we assumed that they involved nonsurgical dentistry.”

68 Mepivacaine 1:623,112,900

Lidocaine 1:181,076,673

Bupivacaine 1:124,286,050

OVERALL 1:13,800,970

Articaine 1:4,159,848

69 USA Ontario - 1993

Mepivacaine 1:623,112,900 1:1,125,000

Lidocaine 1:181,076,673 1:1,125,000

Bupivacaine 1:124,286,050

OVERALL 1: 13,800,970 1: 785,000

(2.27:1,000,000) Articaine 1: 4,159,848 1: 440,529

70 Annual risk of being struck by lightning (USA) = 1:750,000

71 Anaphylaxis to penicillin = 1:50,000

72 Risk of paresthesia following mandibular implant = 37%

Long term neuropathy = 13%

73 92.7% involve LINGUAL nerve

74 FDA - AERS website

75 U.S. FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH OFFICE OF POST-MARKETING DRUG RISK ASSESSMENT revised 9 January 2009 AERS data do have limitations.

First there is no certainty that the reported event was actually due to the product . . .

FDA does not require that a causal relationship between the product and event be proven . . .

Furthermore, FDA does not receive all adverse event reports that occur with a product.

Estimated ~10% of all ADRs are reported

76 U.S. FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH OFFICE OF POST-MARKETING DRUG RISK ASSESSMENT revised 9 January 2009

Many factors can inﬂuence whether or not an event will be reported, such as the time a product has been marketed (Weber Effect) and publicity about an event.

77 U.S. FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH OFFICE OF POST-MARKETING DRUG RISK ASSESSMENT revised 9 January 2009

Therefore, AERS cannot be used to calculate the incidence of an adverse event in the US population

78 the WEBER effect

Dr JCP Weber

Epidemiology of adverse reactions to nonsteroidal antiinﬂammatory drugs.

Rainsford KD, Velo GP, eds. Advances in inﬂammation research. Vol. 6. New York: Raven Press, 1984: 1-7.

79 the WEBER effect

The Weber Effect is an epidemiologic phenomenon which states that the number of reported adverse reactions for a drug rises until about the middle to end of the 2nd year of marketing, peaks, and then steadily declines despite steadily increasing prescribing rates.

80 the WEBER effect

81 Weber Effect

82 Hillerup paper

Publicity

Negative EU report

Positive

83 The Australian experience Articaine introduced in Australia in 2005

84 ARTICAINE HCL ARTICAINE HCL

>70% use articaine ARTICAINE HCL ARTICAINE

85 Australian Dental Journal 56:348-351, 2011 5 case reports

86 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011

Electric shock sensation

Lingual nerve involvement

4% LA

Restorative dentistry

87 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011

Lingual nerve involvement 4% LA Restorative dentistry

88 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011

Mental nerve involvement 4% LA Restorative dentistry

89 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011

Electric shock sensation

Lingual nerve involvement

4% LA

Restorative dentistry

90 Kingon A, Sambrook P, Goss A. Australian Dent J 56:348-351, 2011

Lingual nerve involvement 3% LA Restorative dentistry

91 4 of 5 cases involve LINGUAL NERVE 2 cases experienced ‘electric shock’

92 Professor Dr. Stanley F. Malamed In my opinion . . . If paresthesia involves the distribution of the inferior alveolar and/or mental nerves . . . Possible etiologies: Direct needle trauma LA neurotoxicity Edema

93 Professor Dr. Stanley F. Malamed

However, IF it’s the lingual nerve . . .

It’s MECHANICAL

Not chemical

94 Paresthesia in dentistry

> 95% of reported cases occur in the MANDIBLE

Of these the overwhelming percentage involve only the lingual nerve

95 Paresthesia in dentistry

Is rarely observed in the maxilla < 5% Yet 1/2 of all dental care is in the upper arch

96 Paresthesia in dentistry

Is rarely (no reported cases) observed following:

Gow-Gates mandibular nerve block

Vazirani-Akinosi mandibular nerve block

No lingual nerve in area

Only occasionally following mental/incisive nerve block

97 Paresthesia and 4% Anesthetics

Articaine is used in medicine:

Ophthalmology

Orthopedic surgery

Arthroscopic, hand, foot

Plastic and reconstructive surgery

98 Paresthesia and 4% Anesthetics

Articaine is used in medicine:

NO reports of paresthesia from articaine following use in medicine

99 Paresthesia and 4% Anesthetics

Question: Is it possible that articaine is so speciﬁcally neurotoxic that it only affects nerves within the mouth and more speciﬁcally the lingual nerve?

101 Pogrel MA, Thamby S. Permanent nerve involvement resulting from inferior alveolar nerve blocks JADA 2000;131:901-907 Prior to articaine’s introduction in the USA

Estimates PERMANENT nerve damage at 1:26,762 Inferior Alveolar Nerve Block’s

102 Pogrel MA, Thamby S. Permanent nerve involvement resulting from inferior alveolar nerve blocks JADA 2000;131:901-907 Prior to articaine’s introduction in the USA

“It is reasonable to suggest that during a career, each dentist may encounter at least one patient with an inferior alveolar nerve block resulting in permanent nerve involvement” “The mechanisms are unknown and there is no known prevention or treatment”

103 Pogrel MA CDAJ 35(4):271-273, 2007

104 Pogrel MA J. Calif Dent Assoc 35(4):271-273, 2007

Study covered 1 January 2003 through 31 December 2005

U. California San Francisco School of Dentistry n = 57 All NON-surgical

‘We were aware of the discussion in dental circles as to the use of articaine for inferior alveolar nerve blocks, and are aware of recommendations suggesting that it not be used for IANBs.

This was the predominant reason for submitting this paper at this time.”

105 Pogrel MA J. Calif Dent Assoc 35(4):271-273, 2007

Study covered 1 January 2003 through 31 December 2005

U. California San Francisco School of Dentistry n = 57 All NON-surgical

ALL patients evaluated Dental records reviewed Treating dentists consulted Needle, type of injection(s), drug used and treatment known for ALL 57

106 If all LAs were equally neurotoxic the % of cases of paresthesia would be equal to the drugs % market share

50% of market share = 50% of cases of paresthesia 25% of market share = 25% of cases of paresthesia Ratio should be 1.0

% Cases of paresthesia % Market share

107 Approximate share Ratio Anesthetic # of cases (%) of LA market in (1.0 = USA expected)

Lidocaine HCl 20 (35%) 54% 0.64

Prilocaine HCl 17 (29.8%) 6% 4.96

Pogrel MA Articaine HCl 17 (29.8%) 25% 1.19 J Calif Dent Assoc Articaine HCl + 35(4):271-273, 2007 1 (1.75%) Lidocaine HCl Lidocaine HCl + 1 (1.75%) Prilocaine HCl Bupivacaine HCl 1 (1.75%)

108 Pogrel MA J Calif Dent Assoc 35(4):271-273, 2007

“Therefore, using our previous assumption that approximately half of all local anesthetic used is for inferior alveolar nerve blocks, then on the ﬁgures we have generated from our clinic we do not see disproportionate nerve involvement from articaine”

109 Pogrel MA J. Calif Dent Assoc 40:795-797, 2012 (October)

110 Pogrel MA J. Calif Dent Assoc 40:795-797, 2012 (October) N = 38 January 2006 - December 2011 Articaine is still causing Carbocaine: 11% of cases with permanent inferior alveolar a market share of 5% and lingual nerve damage (36%), which is proportionate to its market share (37%) Prilocaine: However, by causing 26% of all cases seen since 2005 with a local market share of only Lidocaine: The number of cases 8% is somewhat disproportionate caused by lidocaine, on the to its market share other hand, appears to be only around 50% of its market share

111 Pogrel MA J. Calif Dent Assoc 40:795-797, 2012 (October) N = 38 January 2006 - December 2011

Ratio (1.0 = expected)

Lidocaine 0.5

Articaine 0.97

Mepivacaine 2.2

Prilocaine 3.25

112 2007 2011

Lidocaine 0.64 0.5

Articaine 1.19 0.97

Mepivacaine 2.2

Prilocaine 4.96 3.25

113 The German experience Articaine introduced in Germany in 1976

114 The German experience

Synthesized articaine (carticaine) in 1973 - as a DENTAL LA

Introduced into dentistry in 1976

2010 . . . 97% of LA used in German dentistry is articaine

Deutscher Dentalmarkt Jahresbericht (DDM) 2010 (German Dental Market Annual Report 2010) GfK HealthCare, Nuremberg, Germany

115 The German experience

Dr. Wolfgang Jakob

Dr. Monika Daublander

E-mail (1 February 2012):

“. . . the problem of neurosensory disturbances was never a big issue in the German speaking Countries.”

116 Dr. Wolfgang Jakob:

E-mail (1 February 2012): Beside the ongoing about articaine in Dänemark the problem of neurosensory disturbances was never a big issue in the German speaking countries. Hillerup reports 80 percent of all neurosensory after IANB with articaine in Europe. (Denmark = 5,6 million people; while the EU has a population of 501 million) © 2014 Dr. Stanley F. Malamed! All Rights Reserved

117 Dr. Wolfgang Jakob:

E-mail (1 February 2012):

Denmark . . . Population 5.6 million

EU ...... Population 501 million Denmark . . . 80% of all reports of neurosensory disturbance (Hillerup)

118 Journal of Dentistry April 2010 Volume 38, No. 4 307-317

119 Journal of Dentistry April 2010 Volume 38, No. 4 307-317

120 Conclusion: The results suggest that articaine is not toxic to the nervous structure and further studies are necessary to explain the possible relation between articaine injection and paresthesia.

121 So, why is it that the lingual nerve is primarily involved in cases of paresthesia?

122 Dr. Anthony Pogrel E-mail 2 February 2012 Malamed to Pogrel: Can you provide me with a summary of just why it appears that the lingual nerve is involved in this problem so much more so than others? How much LA does a dentist deposit to anesthetize the lingual nerve when doing the IANB? Very little, if any. So why do 'they' cast

123 Why LINGUAL nerve?

Dr. Pogrel’s reply: “I do think there is also a genuine difference in the incidence, and as you say, It is not due to the local anesthetic itself since the vast majority (volume) is deposited close to the inferior alveolar nerve and not the lingual nerve. If it was a neurotoxic phenomenon, you would expect the inferior alveolar nerve to be affected much more.”

124 Why LINGUAL nerve?

The fact that the lingual nerve is stretched when the mandible is open to an the inferior alveolar block probably does give it less opportunity to get out of the way and makes it much more likely that this phenomenon is traumatic.

125 “The Lingual Nerve is In the Way”

126 PerthPerth Sydney Adelaide Sydney Adelaide

127 Fascicle

Fascicle Fascicle Fascicle

Fascicle Fascicle

128 Pogrel, MA, Schmidt, BL, Sambajon, V, and Jordan, RCK Lingual Nerve Damage from Inferior Alveolar Nerve Blocks - A Possible Explanation, J Amer Dent Assoc 134, 195-199, 2003

The Inferior Alveolar Nerve usually had 5-7 fascicles whereas the Lingual Nerve in that area usually had around three but in the third of the cases was actually unifascicular in the area where the inferior alveolar nerve block was given.

129 Fascicle

Normal Damaged

130 Professor Dr. Stanley F. Malamed

IMO . . . IF it’s the distribution of the lingual nerve (loss of taste, paresthesia) . . .

It’s MECHANICAL

131 Haas, D A. Lennon, D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J. Canadian Dental Association). 61(4):319-20, 323-6, 329-30, 1995 Apr

70.6% involve LINGUAL nerve

132 Hillerup, 2006

133 Kingon, 2011

134 Garisto, 2010

92.7% involve LINGUAL nerve

135 % Author Country Year Lingual Haas, Canada 1995 70.6 Lennon

Hillerup Denmark 2006 77

Kingon, Australia 2011 80 Sambrook Garristo, USA 2010 92.7 Haas

136 So, what should YOU do?

137 Articaine has been claimed to be more effective, but there are reports of an increased risk of neurotoxicity, presenting as prolonged numbness in the areas of distribution, often with pain. This may be due to the high concentration of the solution rather than to the anesthetic itself.* Consequently, it is recommended that articaine should not be used for regional blocks (eg inferior alveolar).

138 Beneﬁt v. Risk

The doctor MUST always consider the BENEFIT to be gained from use of a procedure or drug versus the RISK involved in the procedure or drug.

ONLY when the beneﬁt to be gained CLEARLY OUTWEIGHS the risk should the procedure be done or the drug administered

139 ALL reports claiming an increased risk of paresthesia with articaine are ANECDOTAL

There is absolutely NO scientiﬁc evidence articaine has a greater risk of paresthesia than other LAs

142 [email protected]

Thank you for listening . . .

143