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Anesthetic Failures – Current Etiologies

Hargraves – Endodontic Topics Vol.2; Reader





  1. Anatomic variations/Accessory innervation

  2. Acute tachyphylaxis – reduced responsiveness due to repeated injection

  3. Effect of Inflammation on local tissues (pH) -  pH = less base form

  4. Effect of Inflammation on blood flow – vasodilation/inc vasc. perm.

  5. Effect of Inflammation on peripheral nociceptors - Peripheral sensitization

    1. Gold; Wells2-3x Inc in Nav1.8, 1.9 channelsTTX resistant – resistant to Lidocaine (Roy) – Neuronal plasticity

    2. Fouad – 6x Inc in TTX resistant Na channels in SIP cases

    3. Byers – Neuropeptides (SP/CGRP)  fibroblasts  NGF  Nerve sprouting =  Nociceptor field

  6. Effect of Inflammation on central nociceptors – Central sensitization -neuroplasticity(sprouting/unmasking) following afferent C fiber barrage

  7. Psychological/Anxiety factors

Reasons for local anesthetic failures

  1. Anatomic variations/accessory inervation

  2. Acute Tachyphylaxis – reduced responsiveness due to repeated injections

  3. Effect of inflammation on pH –  pH, less base form to cross barrier

  4. Effect of inflammation on blood flow – vasodilation/increased vascular permeability – carries away LA faster

  5. Effect of inflammation on peripheral nociceptors – Nerve sprouting (Byers) and  TTX-resistant Na channels (2-3x - 6x Na channels) (Gold, Wells, Fouad) which are resistant to Lidocaine (Roy)

  6. Effect of inflammation on Central sensitization – exaggerated CNS response to even gentle peripheral stimuli due to central neuroplasticity

  7. Psychological factors – anxiety reduces pain threshold

Approaches for managing failures:

  1. Reader – Supplemental LA: B infiltration, Intraosseous, PDL, Intrapulpal

  2. Hargreaves – Adjunctive drugs: NSAIDs (reduced PGE2 decreases nociceptor sensitization and decreases TTX-R Na channel activity)


How do you manage a Local Anesthetic Overdose?

Finder & Moore 2002 DCNA

  1. LA Toxicity –

    1. Initial symptoms - Tremors, muscle twitching and convulsions

    2. Later findings Respiratory depression, lethargy and loss of consciousness.

    3. Final findings – Cardiovascular depression and hypoxia secondary to respiratory depression can rapidly produce serious outcomes including cardiovascular collapse, brain damage and death.

  2. Vasoconstrictor Overdose –

    1. Initial signs - Palpitations, increase heart rate and elevated BP

    2. Anxiety, nervousness and fear are often found as well

    3. Severe overdose - Arrythmia, stroke and MI are possible

Prevention: Good technique, watch for drug interactions, avoid high doses, get good medical history



How do you manage a Local Anesthetic Overdose? Continued


  1. Management from Little & Falace

    1. Protect patient during convulsive phase, consider IV Valium (Diazepam)

    2. Monitor and record vitals (BP, Pulse)

    3. Supportive therapy

      1. Supine position

      2. O2 10 L/min, Monitor O2 with Pulse Oximeter

      3. Maintain BP

      4. Treat Bradycardia w/ IV Atropine 0.4 mg

      5. EMS

    4. CPR if unconscious


Haas 2002 DCNA – Recommended Emergency drugs: O2, Epi Pen, Nitro, Injectable antihistamines (diphenhydramine or chlorpheniramine), albuterol, aspirin, oral carbohydrates, and corticosteroids.

Methemoglobinemia
Wilburn-Goo & Lloyd 1999 JADA


  1. Caused by metabolite of Prilocaine (MRD=4mg/lb) & Benzocaine – Met-hemoglobin (selective affinity for O2)

  2. Symptoms occur 1-3 hrs after treatment

    1. Cyanosis without respiratory distress when met-Hgb reach 10-20%

    2. Vomiting and headache have been described

    3. Dyspnea, seizures, coma and death at levels higher than 20%

  3. Patients at increased risk

    1. Heart disease

    2. Anemia

    3. G6PD deficiency

    4. Children < 2yo

    5. Elderly

Allergic Reactions to local anesthetics

Esters (benzocaine) – yes, Amides (Lido, Mepivicaine, Articaine) – no



  1. Appearance –

    1. Urticaria - Hives

    2. Erythema/Edema – Redness/swelling

    3. Itching

    4. Angioedema & Respiratory depression (more severe reaction)

    5. Anaphylactic reaction




  1. Sulfite antioxidant (EPI preservative) – allergic reaction – Asthmatics

    1. Asthma-like signs of tachypnea, wheezing, bronchospasm, dyspnea, tachycardia, dizziness, and weakness

    2. Severe flushing, general urticaria, angioedema, tingling, purities, rhinitis, conjunctivitis, dysphasia, nausea, and diarrhea

    3. No sulfite reaction in dental practice has ever been documented


0.3-0.5 mL 1:1000 Epi Subcutaneous, 50-100 mg IV Diphenhydramine, O2

Local anesthetics
Maximum Dosages:

  1. Lidocaine: 4.4 mg/kg

  2. Prilocaine: 4.4 mg/kg

  3. Articaine: 7.0 mg/kg


Finder/Moore – Rule of 25 = 1 carp anesthetic for every 25 lbs of weight
Normal Pulp vs. Irreversible Pulpitis

IAN B Success (1st Molar)

Normal Pulp: 43-60% Success (Vreedland/Reader, McLean/Reader)



Irreversible Pulpitis: 25-33% Success (Nusstein, Reisman/Reader, Aggarwal)

An Update on local anesthetics in dentistry

Hass 2002 J Can Dent Association:


  1. Metabolism of Amide LA occurs in the liver. Reduced hepatic function does not increase duration of anesthesia, but predisposes the patient to toxic effects. Use reduced dosages!




  1. Methemoglobinemia is associated with prilocaine and benzocaine




  1. Articaine & Prilocaine (4%) are associated with increased paresthesia




  1. Malignant hyperthermia occurs with exposure to inhalation anesthetics (succinylcholine, volatile anesthetics), not local anesthetics




  1. Lidocaine and prilocaine are pregnancy cat. B; others are C (Mep)




  1. 7 mg/kg is max lido dose. (4.4mg/kg is conservative)

Trigeminal Nerve Injury associated with Local Anesthetics
Pogrel - Mechanisms of neurosensory disturbance (NSD):

  1. Mechanical injury – penetrating neural sheath with needle

  2. Mechanical injury – intraneural hemorrhage, granulation tissue, scar formation

  3. Neurotoxicity – axonal degeneration



Hillerup

  1. 4% Septocaine is most common anesthetic involved in NSDs (neurosensory disturbances) – 60/96 NSDs reported over 12 yr period in Denmark

  2. Mechanism of injury – Neurotoxicity of 4% Solution – Axonal degeneration. Not mechanical due to under representation of other solutions.


Contraindications to Epinephrine


  1. Untreated Congestive Heart Failure

  2. Uncontrolled HTN (180/110 or >)

  3. Severe Recalcitrant Arrythmias

  4. Digoxin – Anti-Arrythmia/CHF drug

  5. Unstable Angina

  6. Recent MI (within 6 months)

  7. Recent CABG (within 3 months)

  8. Recent Stroke (within 6 months)

  9. Uncontrolled Hyperthryoidism (Grave’s disease, Pituitary adenoma)

  10. Pheochromocytoma – adrenal tumor EPI/NorEPI

  11. Sickle Cell Anemia (limit 2 carps in surgery) – vasoconstrictionCrisis

  12. Severe Asthmatics – possible sulfite allergy – no reported incidents

  13. Sulfite Allergy

  14. Recent Cocaine or Methamphetamine use (within 48 hrs)

  15. PRONJ – Post-radiation osteonecrosis of jaw; >6000 cGy radiation

Limitations for Epinephrine (limit to 2 carps)


  1. Stable Angina, Non recalcitrant Arrythmias

  2. Controlled HTN

  3. Previous MI > 6 months

  4. Previous Stroke > 6 months

  5. Beta blockers (non selective) – Propranolol, Timolol, Nadolol, Cartelol, Sotalol, Penbutol – unopposed alpha stimulation (HTN, bradycardia)

  6. Hepatic disease -  Hepatic function =  L.A. toxic effects -drugs/anesthetics

  7. Tricyclic Antidepressant (TCA) – Amitryptiline, Doxepine

  8. Monoamine Oxidase Inhibitor (MAOI) – Phenelzine, Tranylcypromine

  9. Alpha adernergic blockers (non selective) – Chlorpromazine, Haloperidol, Clozapine

  10. Anti-adrenergics – Guanethidine, Guanadrel

  11. Levothyroxine (Synthroid)

  12. Epilepsy/Seizures – Gabapentin (Neurontin), PreGabalin (Lyrica)

  13. COMT Inhibitors (Parkinson’s) – Levodopa, Entacapone, Tolcapone

Does accessory innervation affect anesthesia?
Frommer 1972 JADAmylohyoid nerve occasionally innervates mandibular molars. 30% of the population have separate canals for the mylohyoid nerve.
Walton 1988 JADA5% of maxillary 1st molars have innervation from both the PSA and the MSA.
Topical Anesthesia
Nusstein/Beck 2003 - Compared 20% topical benzocaine w/ no topical for pain of needle insertion: NSD for IAN B or Max. Post. Infilatration, Maxillary Lat. Infiltration was significantly less painful with topical use
Martin/Ramsay 1994 – 20% topical benzocaine, maxillary infiltrations – psychological effect of topical anesthetic responsible for success

Anesthetic Techniques: Gow Gates (V3 Block)

  1. Malamed OOO 1981 – Textbook pg 237 – Better success rates 95%, decreased positive aspirations 2%, fewer post injection problem however longer onset 5-10 min vs 3-5min IANB

    1. Technique: anesthetized V3 – target – lat side of condylar neck

      1. Dry & apply topical for 1 minute

      2. 25 gauge needle (long)

      3. Insertion – mucous membrane on line from intertragic notch to corner of mouth, distal to max 2nd molar at height of mesiolingual cusp max 2nd molar.

      4. Slowly advance needle until bone is contacted (average depth 25mm) withdraw 1mm & aspirate (if positive it is usually the internal max artery, aim higher & repeat)

      5. Deposit 1.8cc over 60-90 seconds, may use up to 3ml

      6. Use rubber block 1-2 minutes for diffusion

      7. Return to upright and wait 5 minutes (due to diameter of nerve or greater distance to nerve trunk)

Anesthetic Techniques: Akinosi (closed mouth)

Also known at the closed mouth mandibular block or Vazirani-Akinosi Block

  1. Malamed Textbook pg 242 – Indications for Akinosi technique are Trismus or inability to see landmarks for IANB (large tongue), lower aspiration rate (10%), successful for bifid alveolar nerve.

    1. Technique: anesthetize same as IANB, target – medial lingual border of ramus (above IANB below Gow Gates)

      1. Dry & apply topical for 1 minute

      2. 25 gauge needle (long)

      3. Insertion – turn bevel of needle toward midline (deflects needle toward ramus) soft tissue overlying medial border of ramus directly adjacent to max. tuberosity at the height of the mucogingival junction adjacent to the max 3rd molar.

      4. Advance needle 25mm (ave) from tuberosity, aspirate, deliver 1.8ml over 60 sec., wait 5 min. (motor nerve effect will reduce trismus)

Anesthetic Techniques: Incisive

  1. Nist/Reader JOE 1992 – Incisive block alone - No pulpal effects

  2. Malamed Textbook Page 249 – “Pulpal, buccal soft tissue and bone anesthesia is readily obtained” with the Incisive nerve block. Lingual tissue is not anesthetized.

    1. Technique: no need to enter target mental foramen (traumatic)

      1. Dry & apply topical for 1 minute

      2. 25 gauge (short)

      3. Insertion – orient bevel toward the bone- have pt partially close, locate mental foramen (see x-ray), enter tissue at canine or 1st bi directing needle toward MF (approx 5-6mm), aspirate, deposit 0.6ml over 20 secs.

      4. Maintain gentle finger pressure over site to increase volume of solution entering MF (intra or extra orally) for 2 minutes.

      5. Wait 3-5 minutes to begin treatment.


Compare different anesthetic studies

IAN B:


  1. Aggarwal 2012 – 1 vs. 2 carps 2% Lidocaine w/1:200,000 epi – Symp. Irreversible Pulpitis, Success: 1 carp: 26%, 2 carps: 54% (Stat. Sig.)




  1. Fowler/Reader 2013 – Retrospective. 1 vs. 2 carps 2% Lidocaine w/1:100,000 epi – Symp. Irreversible Pulpitis, Success: 1 carp: 28%, 2 carps: 39% (NSD)




  1. Vreeland/Reader – Compared 1 carp 2% Lido w/1:100k epi vs. 2 carps 2% Lido w/1:200k epi vs. 1 carp 4% Lido w/1:100k epi, Vital pulps. NSD in degree or duration of anesthesia. Molars = 43-60% Success




  1. McLean/Reader JOE 1993 – Compared 4% Prilocaine, 3% Mepivicaine and 2% Lidocaine w/ 1:100,000 epi. Vital pulps. NSD in onset, success or failure between any of the 3 solutions used. Molars = 43-57% Success



Compare different anesthetic studies

B Infiltration supplemental to IAN B:

  1. Aggarwal 2012 – B/L Infiltration (2 carps) supplemental to IAN B – Sym. Irreversible Pulpitis, Success: No Inf.: 33%, 2% Lido w/1:200,000 epi: 47%, 4% Articaine w/1:200,000 epi: 67%

  2. Matthews/Reader 2009 B infiltration supplemental to Failed IAN B – Sym. Irreversible Pulpitis, 4% Septocaine w/1:100k epi, Success: 58%

  3. Haase 2008 –B infiltration supplemental to IAN B – Normal Pulp, Success: 4% Septocaine w/1:100k epi - 88%, 2% Lidocaine w/1:100k epi – 71%

Maxillary Infiltration (normal pulp):

  1. Evans/Reader 2008 – 2% Lidocaine w/1:100k epi vs. 4% Articaine w/1:100k epi (1 carp) – B Infiltration Max Laterals/1st Molars: Max Laterals: L: 62%, A: 88% (Sig. Difference), 1st Molars: L: 73%, A: 78% (NSD)

  2. Guglielmo/Reader 2011 –2% Lidocaine w/1:100k epi – B inf (1.8 mL) + L inf (0.5 mL) vs. B inf (1.8 mL) only. Success: NSD. Duration: B only – 21 mins, B+L – 57 mins

  3. Mikesell – 2 carps vs. 1 carp 2% lido w/ epi – Inc duration lat, 1st pm, 1st m

Compare different anesthetic studies

Mandibular Infiltration:

Anterior:

  1. Nuzum/Reader 2010- Normal pulp - 4% Articaine w/1:100k epi – B inf (1.8 mL) + L inf (1.8 mL) vs. B inf (1.8 mL) only. Success: B+L – 98%, B only – 76%, Duration: B+L improved duration 4th-58th minute


Supplemental Buccal (Symptomatic Irreversible pulpitis)

  1. Aggarwal – IAN B only (2% Lido w/1:200 k epi): 33%, vs. IAN B + B/L infiltration (2% Lido w/1:200k epi): 47%, vs. IAN B + B/L infiltration (4% Septocaine w/1:200 k epi): 67%

  2. Matthews/Reader 2009 – IAN B only (2% Lido w/1:100k epi): 33%, IAN B + Supplemental B infiltration (4% Septo w/1:100k epi): 58%


Gow Gates vs. Akinosi vs. IAN B:

  1. Goldberg/ReaderNo difference in anesthetic success of IAN vs. Gow Gates vs. Akinosi. Faster onset of pulpal anesthesia with IAN B.

Intraosseous Anesthesia

Reader 1997, 1999 OOO; JADA 1999; JOE 199




  1. Nusstein/Reader – Irreversible Pulpitis, IAN B only 19% success, Intraosseous Stabident (2% Lidocaine w/1:100k epi): 90% success (Mandibular Molars), 88% Overall




  1. Coggins/Reader 1996 – Stabident + 2% Lido w/1:100,000 epi – Primary injection technique - 75-93% success (Max/Mand teeth)




  1. Dunbar/Reader 1996 – Stabident + 2% Lido w/1:100,000 epi – Supplemental to IAN B – 98% success




  1. Reisman/Reader 1997 – Irreversible Pulpitis (Mand. Posterior), IANB only 25% success. Intraosseous injection (3% mepivacaine w/o epi): 1st Injection: 80% success, 2nd Injection 98% success.


Intraosseous Anesthesia

Reader 1997, 1999 OOO; JADA 1999; JOE 1998 –




  1. Replogle/Reader 1999 Cardiovascular effects of 2% Lidocaine w/1:100k epi vs. 3% Mepivicaine w/o epi: 2% Lido - 67% of patients experienced  HR (23-24 bpm) for ~ 4 mins, 3% MepNo  HR. No sig. difference in BP between the 2 groups. Transient  HR.




  1. Nusstein/Reader - Overall, the supplemental intraosseous inj was found to be 88% successful in gaining pulpal anesthesia for endodontic therapy. In posterior teeth diagnosed with irreversible pulpitis, the supplemental intraosseous injection of 2% Lidocaine w/1:100k epi was successful when conventional therapies failed.




  1. Anderson 1998 JOE – Stabident IOI was an effective supplemental anesthetic technique in 89%. More success in mandible than maxilla. (91% vs 67%)

PDL injection
Kim 1986 JOE – PDL is effective, painful, affects adjacent teeth, and doesn’t work via pressure. Pulpal blood flow is decreased when vasoconstrictor is used; don’t use for operative dentistry. Vasoconstriction is mechanism of action.
Walton 1986 JOE – PDL is primarily intraosseous and required backpressure. Anesthetic spreads through cribiform plate. It is safe to the periodontium and pulp when used with operative procedures. Can’t be used for differential diagnosis - anesthetizes adjacent teeth. Widespread distribution. Supplemental only.
Torabinejad & Peters et al OOO 1993 – PDL inj has no long-term deleterious effects on pulps of human premolars.
Reader 1988 JOE – 2% Lido w/1:100,000 epi is preferred for PDL and was more effective than anesthetic w/out epi. Average pulpal anesthesia = 20 min.
Do additional measures increase success of IAN?

Pre-op admin of Pain meds

  1. Simpson/Reader – NO – 800 mg Ibu+1000 mg Aceto did NOT inc success of IAN B in Symptomatic Irreversible Pulpitis pts

  2. Oleson/Reader – NO – 800 mg Ibu alone did NOT inc success of IAN B in Symptomatic Irreversible Pulpitis pts

  3. Parirokh – YES – 600 mg Ibu or Indomethacin DID Inc success of IAN B in Symptomatic Irreversible Pulpitis pts (78%, 72%, 32%)

Pre-op admin of Steroids

  1. Shahi JOE 2013 – YES – 0.5 mg Dextramethasone admin 1 hour prior to IAN B in Asymptomatic Irreversible Pulpitis pts Inc success of IAN B vs placebo

Pre-op admin of Benzodiazepines

  1. Khademi JOE 2012 – NO – 0.5 mg Alprazolam (Xanax) 1 hr prior did NOT inc success (53% vs. 40%) of IAN B in Sym Irrev. Pulpitis pts

Pre-op admin of N2O

  1. Stanley/Reader – YES – Sym Irrev. Pulpitis pts admin 5 mins N2O prior to IAN B and procedure – Success of IAN B: w/ N2O: 50%, w/o N2O: 28%

What about Oraverse?

Oraverse = Phentolamine Mesylate



MOA: Reversible non-selective alpha adrenergic antagonist, Vasodilation due to 1 blockade


  1. Fowler/Reader 2011 – Reversal of soft tissue anesthesia following admin of phentolamine in asymptomatic endodontic patients post IAN B and Maxillary Infiltrations. Statistically significant decreases in time for return of normal lip sensation: Maxillary – 88 min decrease, Mandibular – 47 min decrease.




  1. Elmore/Reader 2013 – Reversal of soft tissue anesthesia in normal patients following admin of phentolamine 30 min or 60 min post IAN block. Phentolamine significantly reduced duration of both pulpal and soft tissue anesthesia. 30 min post IAN admin was 24 mins faster (75 mins vs. 90-100 mins) for reversal effect than 60 mins post IAN admin


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