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Local anaesthesia for the 21st

Century – an update

BSDHT Liverpool ACC 10th November 2012

Dr Nigel D RobbReader in Restorative

Dentistry

Traditional local anaesthetics

• Lidocaine • Prilocaine• Mepivacaine

New Local Anaesthetics and Equipment

• Articaine• Phentolamine

mesylate(OraVerse)

• Computer controlled delivery systems

( )• Oraqix

Importance of local anaesthesia in dentistry

The severe pain caused by diseases of teeth and jaw is a sign of the importance of

these parts of the body.

Local anaesthesia is an invaluable good for a

dentist. It is his commitment to have a very good command of it in all

scientific and technical aspects.

Guido Fischer 1911

Use of vasoconstrictors

I read about the possibility to produce an extract of the adrenal gland of animals which constricts

blood vessels.

A few days later I got a small amount of this extract, mixed it up with cocaine and injected it

into my forearm.

Immediately I knew that this was the dawn of a new period of

local anaesthesia.Heinrich Braun 1900

concentration 1: 600.000

The brilliant Formula The brilliant Formula 1904 1904

++ ++ ==Local

Anaesthesia

Drug DeliverySystem

Technique Outcome++ ++ ==

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Choice of local anaesthetic agent

• Lidocaine (2%) and epinephrine (1:80 000)– Gold standard in UK

Active in 2 3 mins (infiltration)– Active in 2-3 mins (infiltration)

– Duration 45-60 mins

– Max dose 4.4mg/kg up to 300mg maximum

Role of lidocaine

• First choice local anaesthetic in UK clinical practice

• Currently routine choice

Prilocaine 3% + 0.03 IU felypression

• 2.2ml cartridges• 30mg prilocaine and 0.54g felypressin / ml• Maximum safe dose

of prilocaine 6mg/kg up to maximum ofof prilocaine 6mg/kg up to maximum of 400mg

• 1/10th rule does not apply maximum 6 cartridges

Role of prilocaine and felypressin

• Use when epinephrine best avoided– Allergy to reducing agent

– Acute coronary syndromes• Unstable angina• Unstable angina

• Refractory arrythmias

– Concurrent use of cocaine or other illicit stimulants

Felypressin and ischaemic heart disease

• Can cause coronary artery constriction

• Limit dose to 3 cartridges in patients with ischaemic heart diseasewith ischaemic heart disease

Mepivacaine 3% or 2% +1:100 000 epinephrine

• 2.2ml cartridges• 30mg or 20mg mepivacaine and

10g epinephrine per mlM d 4 4 /k t i• Max dose 4.4mg/kg up to maximum of 300mg

• 1/10th rule for 2% not for 3% - up to 6.8 cartridges for 2%, but only 4.5 cartridges for 3%

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Role of mepivacaine

• Use plain solution when epinephrine contraindicated– Better for blocks than infiltrations

2% with epinephrine comparable• 2% with epinephrine comparable with lidocaine, but slightly shorter duration of action

Articaine HCL

1974

Choice of local anaesthetic agent

• Articaine (4%) with adrenaline epinephrine (1:100 000 or 1:200 000)

Advantages of short half life (30mins)– Advantages of short half life (30mins)

– Use serially toxicity less likely

– Now emerging evidence of improved efficacy / diffusing power etc

– Maximum dose 7mg/kg

Articaine

• Marketed for improved diffusing properties

• Makes IAN Blocks obsolete“ h i t t ti d• “…… has intense penetrating and spreading powers. Infiltration is possible in the mandible eliminating the need for mandibular block.”

Articaine

“Xylocaine has intense penetrating and spreading powers. Infiltration is possible in the mandible eliminating the need for mandibular block.”Bremer et al, 1948

Difficult to demonstrate

Recent studies show articaine more effective in buccal infiltration next to molars and upper lateral incisors

Articaine

• This review supports the argument that articaine compared with lidocaine provides a higher rate of success with comparable safety tosuccess with comparable safety to lidocaine when used for infiltrations or blocks

• Causes slightly more post injection pain

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Articaine

• Rcommendation that 4% articaine (+ 1:100 000 epinephrine) to replace lidocaine (+ 1:100 000 epinephrine)

Non surgical paraesthesias???

• “Thus there is an urgent need for further studies focused on the neurotoxicity of local anaesthetics with specific focus on articaine 4%with specific focus on articaine 4%. Until factual information is available, a preference for other formulations to 4% articaine may be justified, especially for mandibular block anaesthesia.”– Hillerup and Jensen, 2006

Non surgical paraesthesias???

• “Regarding articaine, the conclusion is the safety profile of the drug has not changed since its launch (1998). Thus no medical evidence exists toThus, no medical evidence exists to prohibit the use of articaine…”– Pharmacovigilance Working Party of

EU, 2006

Non surgical paraesthesias???

• Study of 53 patients (1/1/2003-31/12/2005– Symptoms 9/12 after injection– 35% lidocaine– 30% articaine– 30% prilocaine

• On the figures….we do not see a disproportionate involvement from articaine– Pogrel, 2007. Danish Medicines

Agency, 2008

Non surgical paraesthesias???

• Study of referrals in Denmark appears to implicate articaine– Some bias – non returning patients

classified as “potentially permanentclassified as potentially permanent damage”

– Fall in referrals after 2005 no real reason given

– Doesn’t quote Pogrel 2007

Practical advice

• There is no restriction on use of articaine for inferior alveolar nerve blocks

• In UK defence organisations will• In UK defence organisations will support you if you use it

• In UK defence organisations will support you if you don’t use it

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Plasma concentration of tritium labeled epinephrine after intra oral injections in

volunteers

20 % partial

Regional Anaesthesia

1994

intra vasal injections

Up to 80 fold increase of epinephrine

levels

70.000.000 administrations/year• 90 % Articaine 4 %:

– Epinephrine 1:100.000 (~ 45 %)– Epinephrine 1:200.000 (~ 55 %)

Local Anaesthesia in Germany

6,1

3,1

0

1

2

3

4

5

6

7

Articaine 200 ( n = 664 ) Articaine 100 ( n = 547 )

%

p p ( )

• Side effects: 4,5 %

Anesth Prog, 1997 p = 0,0411

Aspiration

A vital step when injecting dental anaesthetic

Why?

• Deposition of any anaesthetic into a blood vessel can result in systemic disturbances. 

• Deposition of any anaesthetic into a blood vessel causes the solution to dissipates around the body; anaesthesia reduced

Aspiration technique

Basic principle:To create a negative pressure in the cartridge ‐ liquid from the tissue at the deposition site is sucked upBefore injecting :1. Insert the needle

2. Aspirate by pulling plunger back, check for blood in 

Standard Self-Aspirating

cartridge, if so reposition the needle and try again. DON’T INJECT UNLESS NEGATIVE! 

Aspiration can be performed actively or passively with standard cartridges or passively with self‐aspirating cartridges.

Manual

Manual Aspiration  ‐ Standard Cartridges

Standard dental cartridges have a solid bung ‐pierced by a barb or hook on the syringe plunger.

Aspiration by manually pulling back the plunger to create negative pressure

DISADVANTAGE: Risk of the needle moving during aspiration ‐ risk of false negative

Passive Aspiration System ‐DENTSPLY Self‐Aspirating Cartridges

Mechanism of the DENTSPLY Self‐Aspirating Cartridges (Astra type)

• Self – aspirating is a more reliable than manual aspiration• No active movement from operator required

• Self‐aspiration cartridges have specially adapted bung, needing different syringe plunger

• Thin centre of the bung distended when pressure exerted.

• When force stopped the bung returns to usual shape ‐negative pressure (aspiration)  

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Self‐aspirating mechanism (Astra type)

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Other aspirating systems

Phentolamine mesylate (OraVerse)

• Nonselective -adrenergic blocking drug

• First therapeutic agent for reversal of soft tissue anaesthesiasoft-tissue anaesthesia

• Median lip recovery times reduced by 75 - 85 minutes

• Clinical use viewed favourably by dentists and patients

• No serious adverse events reported

Percentage of patients reporting normal sensation 30 mins post PM

injection

Arch PM ShamMax 26.7 1.7Mand 17.2 0.8

Tavares et al, J Am Dent Assoc 2008

Phentolamine mesylate (OraVerse)

• Costs $10-12 (£6.20 – 7.40) per 1.7ml cartridge

• Prohibitive for routine use at present

1853 1904 1999 130 years1897

The delivery systemsThe delivery systems

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Application of new technologyApplication of new technology

The Wand - 1997The Wand - 1997 CC Syringe - 2001CC Syringe - 2001

The WANDThe WAND

Disposable handpiece

Microprocessor

Foot control

Precision needle control pen grip

Speed of Delivery

Flow Rate?Flow Rate?

• Direct positive correlation between pressure and pain exists in dentistry.

• Pressure direct positive correlation with flow-rate.

Clinical Relevance

• To decrease pain and anxiety of local anesthetic injection use pressure less then 306 mmHg (6 psi) in movable mucosa.

A Correlation exists:

“Tissue Type” and “Exit-pressure”

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Pulpal

Palatal

Labial/Buccal

AMSA AMSA -- anaesthetized anaesthetized areaarea

Williams WP (1999)Williams WP (1999)Williams WP (1999)Williams WP (1999)

Single injection for multiple teeth

Crosses midline

Single injection for multiple teeth

Crosses midline

PP--ASA ASA -- advantagesadvantages

Reduced dosage of anaesthetic

No unwanted soft tissue anaesthesia

Reduced dosage of anaesthetic

No unwanted soft tissue anaesthesia

Pulpal

Palatal

Labial

PP--ASAASA -- anaesthetised areaanaesthetised area

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Petzer (2001)

STA - SystemSingle Tooth Anesthesia

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The Formula 2008The Formula 2008

++ ++ ==Local

Anaesthesia

Drug DeliverySystem

Anatomy Outcome++ ++ ==

“Innovation Defines Our Future”“Innovation Defines Our Future”

====Local

Anaesthesia++++ ++++

What is Oraqix®?

• Oraqix® 25/25 mg per g Periodontal Gel (2.5% lidocaine, 2.5% prilocaine)

• Same active ingredients as EMLA®

– 2.5% lidocaine; 2.5% prilocaine

• Anaesthetic drugs in Xylocaine® and Citanest®• Anaesthetic drugs in Xylocaine and Citanest , respectively

– White cream for skin anaesthesia

• Pre canulation

– Not licensed for dental use

What is Oraqix®?

• Oraqix®

– Contained in a clear liquid

– Still 2.5% lidocaine; 2.5% prilocaine

A liquid that sets as a gel at body– A liquid that sets as a gel at body temperature

– Oraqix® is a POM (Prescription Only Medicine)

Oraqix®

• Licensed indications– Oraqix® is a non-injectable dental local

anaesthetic indicated in adults for localised anaesthesia in periodontal ppockets for diagnostic and treatment procedures such as probing, scaling and/or root planing

How do we use it?

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What is in the box?

• Supplied in 1.7g Glass cartridges– Box of 20 cartridges

– Each cartridge is supplied with a blunt tip applicator

• Each cartridge– 42.5mg lidocaine

– 42.5mg prilocaine

Cartridges

• The air-bubble is larger than in injectable local anaesthetics, and does not pose a risk as Oraqix® is not injected

Cartridges

• Oraqix® should be a liquid when administered. If it has gelled, cool until becomes a liquid again. Visible air bubble moves when tilting cartridge

Cartidges

• Not labelled “sterile”• Manufactured

aseptically, like injectable anaesthetics– Cartridge can be

disinfected with 60% ethanol or 60-70% isopropanol wipes

Unassembled Dispenser Inserting Cartridge

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Bending Applicator Tip

• Can be bent to aid access• Bend using tip cover• Do not bend at hubDo not bend at hub

Ready for use

Application

• Depress paddle to dispense liquid

ApplicationApplication

Position of tip of applicator

• Applicator tip in gingival crevice / periodontal pocket

• Inject and move jround tooth

Timings

• Effective in 30 seconds,

• Duration 20 minutes– Sufficient in one

cartridge to ca t dge toanaesthetise one quadrant

– Can be site specific • Apply to two or three

sites at a time

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Maximum dose

• Maximum dose is 5 cartridges in one treatment session

• Maximum dose cumulative if usedcumulative if used with injectable local anaesthetics

Scaling Showing RemovalScaling Showing Removal

Clinical Studies: Safety

• 10 patients– At least 16 teeth with pockets 4mm

– Application of Oraqix® to all teeth (18-28) 0.9-3.5g

– SRP on 3 teeth.

• Maximum plasma levels detected 20 40 min after• Maximum plasma levels detected 20-40 min after application– Lidocaine (99-266 ng/ml)

– Prilocaine (46-118 ng/ml)

• Initial signs of CNS-toxicity at 5000 ng/ml• Plasma levels of lidocaine and prilocaine after application of 

Oraqix®, a new intrapocket anesthetic, in patients with advanced periodontitis

Friskopp J & Huledal G, J Clin Periodontol 2001

Clinical Studies: Duration and Onset

• 30 patients

– Oraqix® applied and left for 30 seconds, 2 minutes and 5 minutes

– SRP on 2-3 teeth

• Pain assessment with Visual Analogue Scale (VAS; 100mm)Pain assessment with Visual Analogue Scale (VAS; 100mm) and Verbal Rating Scale (VRS; 5 levels)

• Duration of anaesthesia probing using “normal force” 5 minutes intervals until sensation returned or 30 minutes after end of SRP

• Evaluation of side effects by follow-up phone call 24-48 hours after SRP

The anesthetic onset and duration of a new lidocaine/prilocain gel intra‐pocket anesthetic (Oraqix®) for periodontal scaling/root planing.  Friskopp J et al., J Clin Periodontol 2001

Clinical Studies: Duration and Onset Results

• Visula Analogue ScaleTime VAS (median) Duration (mean)30 sec 7.5 mm 18.1 minutes2 min 28.5 mm 17.3 minutes5 min 15.5 mm 19.9 minutes

• VRS– no patient severe or very severe pain– no significant differences between groups

• Conclusion

– Oraqix® provides anaesthesia after 30 seconds

– Duration of action 17-20 minutes

Clinical Studies: Efficacy

• 122 patients at 8 centres Oraqix® or placebo - 30 seconds - 2 minutes, SRP on one quadrant.

• Patient discomfort

– second application of gel

• Discomfort continuedDiscomfort continued

– classed as in need of a rescue anaesthesia (Injection)

• Measurements– Pain assessment Visual Analogue Scale (VAS; 100mm) and

Verbal Rating Scale (VRS; 5 levels)

– Need of a rescue anaesthesia

Intrapocket Anesthesia for Scaling and Root Planing: Results of a Double‐Blind Multicenter Trial Using Lidocain Prilocaine Dental Gel

Jeffcoat MK et al., J Periodontol 2001

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Clinical Studies: Efficacy Results

• VAS– Oraqix®: 7 mm

– Placebo: 17 mm (median)

– VAS significant reduction in reported pain. Mean reduction 8mm compared to placebogroup (p < 0.0005, Hodges-Lehmann estimate)

• VRS– Oraqix®: 90% of patients no pain or mild pain– Placebo: 64% of patients no pain or mild pain

Clinical Studies: Efficacy Results

• Rescue anaesthesia– Oraqix®: 11% of patients (7 of 63)– Placebo: 17% of patients (10 of 59)– Trend noted: higher efficacy in deeper pockets

with more pronounced inflammationwith more pronounced inflammation

Clinical Studies: Efficacy in “Pain Sensitive

Patients”• 85 patients at 4 centres, VAS scores on probing greater

than 30, Oraqix® or placebo for 30-45 seconds, SRP on one quadrant

• If the patient had any discomfort– second application of gel

• If discomfort continued– classed as in need of a rescue anaesthesia (Injection)

• Measurements– Pain assessment with VAS 100 mm

– Pain assessment with VRS (5 levels)

– Need of a rescue anaesthesia

Intrapocket Anesthesia for Scaling and Root Planing in Pain‐Sensitive Patients

Magnusson I et al., J Periodontol 2003

Clinical Studies: Efficacy in “Pain Sensitive Patients” Results

• VAS– Oraqix®: 11 mm

– Placebo: 27 mm

– The VAS significant reduction in reported pain. Mean reduction of 10 mm vs placebo-group (p < 0.004, Hodges-Lehmann estimate)

– Results similar between centres

• VRS (p=0.003)– Oraqix®: 70% of the patients reported no pain or mild

pain– Placebo: 48% of the patients reported no pain or mild

pain

Clinical Studies: Efficacy in “Pain Sensitive Patients” Results

• Rescue anaesthesia– Oraqix®: 5% of the patients (2 of 43)– Placebo: 17% of the patients (7 of 42)– Trend noted: higher efficacy in deeper pockets with more

pronounced inflammation

Clinical Studies: Oraqix® vs Infiltration

Anaesthesia• 175 patients, 8 centres

– Oraqix® vs. Xylocaine® 2% with Adrenaline

• Two treatment visits one week apart – 2 quadrants one side Oraqix®q q

– 2 quadrants other side injection

• Apple Newton® Message Pad for evaluation by the patients

Patient evaluation of a novel non‐injectable anesthetic gel – a multicenter crossover study comparing the gel with infiltration anesthesia during scaling and root planing van Steenberge D et al., J Periodontol 2004

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Clinical Studies: Oraqix® vs Infiltration Anaesthesia Results

Gel (n=157) Injection (n=157)

Satisfactory anaesthesia duringSRP?

(patient opinion)

Gel (n=157) Injection (n=157)

Very satisfactory 34% 51%

Satisfactory 45% 45%

Not completelysatisfactory

17% 4%

Unsatisfactory 3% 0

Preference of patients70 % (110 of 157) patients preferred Oraqix®

22 % (35 of 157) patients preferred the injection8 % (12 of 157) patients had no preference

Clinical Studies: Oraqix® vs Infiltration Anaesthesia Results

Gel (n=110) Injection (n=35)

Reason for Patient Preference

Less pain 19 80

Less discomfortafterwards

22 23

Less numbness 70

Absence of injection 35

Less apprehension re feeling pain

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Clinical Studies: Oraqix® vs Infiltration Anaesthesia Results

Gel injection

Ability to perform adequate treatment (investigator’s opinion)

Very satisfactory 42% 83%

Satisfactory 34% 17%

Not completely satisfactory

20% 0

Unsatisfactory 4% 0

Review of Findings

• Flexible use– Local, quadrant, arch,

• Safe in clinical use• Rapid onset (30 seconds) • Acceptable duration ~20 minutes• Can be reapplied

Review of Findings

• Good pain elimination• Good patient comfort

– No injection

N t ti ft ti– No post operative soft tissue anaesthesia

• 70% of the patients preferred Oraqix® to conventional anaesthesia

• Improved compliance with SRP treatments

Summary

• Treat local with respect• Reflective practice• Patients appreciate efficacy

– Dislike postoperative numbness and injections

• Use LA appropriately and effectively

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Thank you for your kind attention