2015 Dr. Stanley F. Malamed
Transcription
2015 Dr. Stanley F. Malamed
Local Anesthesia © 2015 2014 Dr. Stanley F. Malamed © 2013 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved PAIN © 2015 Dr. Stanley F. Malamed All Rights Reserved 1 © 2015 Dr. Stanley F. Malamed All Rights Reserved 2 PAIN The greatest fear dental patients have is FEAR of PAIN © 2015 Dr. Stanley F. Malamed All Rights Reserved 3 © 2015 Dr. Stanley F. Malamed All Rights Reserved 4 Painless Injections How Dentists Are Judged By Patients How important - to the patient is pain-free dental treatment? © 2015 Dr. Stanley F. Malamed All Rights Reserved 5 2. Does not hurt 1. A painless injection de St. Georges J. Dentistry Today 23(8): 96-99, August 2004 © 2015 2014 Dr. Stanley F. Malamed All2013 Rights Reserved © Dr. Stanley F. Malamed All Rights Reserved 6 LOCAL ANESTHETICS are the SAFEST and MOST EFFECTIVE drugs in medicine for the PREVENTION & MANAGEMENT of pain LOCAL ANESTHETICS are the only drugs that actually PREVENT PAIN © 2015 Dr. Stanley F. Malamed © 2014 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved 7 © 2014 Dr. Stanley F. Malamed © 2014 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved 8 © 2015 Dr. Stanley F. Malamed All Rights Reserved 9 Cocaine Tetracaine 10 AMIDES ESTERS Procaine © 2015 Dr. Stanley F. Malamed All Rights Reserved 1948 Articaine Stanley F. Malamed, DDS Bupivacaine Dentist Anesthesiologist Emeritus Professor of Dentistry Ostrow School of Dentistry of U.S.C. Los Angeles, CA, USA Lidocaine Benzocaine Mepivacaine Chloroprocaine Prilocaine Propoxycaine © 2015 Dr. Stanley F. Malamed All Rights Reserved 11 © 2015 Dr. Stanley F. Malamed All Rights Reserved 12 Local anesthetics What Local Anesthetics are available in (Dentistry) Articaine Dentistry Worldwide? Bupivacaine Lidocaine Mepivacaine Prilocaine © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 17 18 What Local Anesthetics Local anesthetics are available in (Spain) Articaine SPAIN? Bupivacaine Lidocaine Mepivacaine © 2015 Dr. Stanley F. Malamed All Rights Reserved 19 © 2015 Dr. Stanley F. Malamed All Rights Reserved 20 Local Anesthetics by EXPECTED duration of PULPAL anesthesia By MARKET SHARE SPAIN USA Articaine Lidocaine Lidocaine Articaine Mepivacaine Mepivacaine Bupivacaine Prilocaine Normal Distribution Curve BellShaped Curve Bupivacaine © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 21 22 Local Anesthetics by EXPECTED duration of PULPAL anesthesia • Cocaine Mepivacaine 3%, Prilocaine 4% Intermediate-duration (~60 minutes) • • Blood flow through area is INCREASED Short-duration (~30 minutes) • • All injectable local anesthetics are VASODILATORS Articaine 4%, Lidocaine 2%, Mepivacaine 2%, Prilocaine 3% or 4% (all with vasoconstrictor) Long-duration (>90 minutes) • Bupivacaine 0.5% (with vasoconstrictor) 23 LA diffuses OUT of AREA more rapidly © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 24 ESPAÑA Short - Duration LAs A SPAIN PLAIN LAs provide a SHORT-DURATION of NOT AS PROFOUND anesthesia ~ 30 minutes Mepivacaine 3% No vasoconstrictor © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 2014 Dr. Stanley F. Malamed ©All 2013 Rights Dr. Stanley Reserved F. Malamed All Rights Reserved 25 26 Short - duration LAs To increase DURATION, and to increase DEPTH, of anesthesia, Drug Onset (textbook) Mepivacaine 3 - 5 min 3% Pulpal Soft Tissue 20 - 40 min 2 - 3 hours infiltration - NB ESPAÑA a VASOCONSTRICTOR is added to the LA solution USA Worldwide Epinephrine Levonordefrin Epinephrine Norepinephrine Felypressin SPAIN A © 2015 Dr. Stanley F. Malamed All Rights Reserved 27 © 2015 2014 Dr. Stanley F. Malamed ©All 2013 Rights Dr. Stanley Reserved F. Malamed All Rights Reserved 28 ESPAÑA Intermediate - Duration LAs A SPAIN ~ 60 minutes Articaine 4% + vasoconstrictor Lidocaine 2% + vasoconstrictor Mepivacaine 2% + vasoconstrictor Through addition of a vasoconstrictor, the ensuing BLOOD LEVEL of the local anesthetic is significantly decreased, making the LA drug SAFER by minimizing risk of overdose (toxic reaction) Epinephrine © 2015 Dr. Stanley F. Malamed All Rights Reserved • © 2015 2014 Dr. Stanley F. Malamed All Rights Reserved 29 30 Local Anesthetic Blood Levels Local Anesthetics by EXPECTED duration of PULPAL anesthesia MEPIVACAINE Intermediate-duration (~60 minutes) • 5 mg/kg - NO epinephrine - PEAK LEVEL 1.2 ug/mL • • • 5 mg/kg - Epi 1:200,000 - PEAK LEVEL 0.7 ug/mL LIDOCAINE • 400 mg - NO epinephrine - PEAK LEVEL 2.0 ug/mL • 400 mg - Epi 1:200,000 - PEAK LEVEL 1.0 ug/mL Articaine 4%, Lidocaine 2%, Mepivacaine 2%, Prilocaine 4% (all with vasoconstrictor) Approximately 90% of all local anesthetics used by North American dentists are intermediate-duration drugs © 2015 Dr. Stanley F. Malamed All Rights Reserved 31 © 2015 Dr. Stanley F. Malamed All Rights Reserved 32 Long - Duration LAs Long - duration LAs > 90 minutes Drug Bupivacaine Bupivacaine 0.5% 0.5% + vasoconstrictor ESPAÑA SPAIN A Epi 1:200k Onset (textbook) Pulpal Soft Tissue 6 -10 min 60 - 180 infiltration - NB up to 12 hours (up to 7 hours) ESPAÑA SPAIN A © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 33 34 SELECTION CRITERIA Lidocaine for LOCAL ANESTHETICS 1st AMIDE local anesthetic Introduced 1948 Astra Pharmaceuticals (SWEDEN) © 2015 Dr. Stanley F. Malamed All Rights Reserved 35 © 2015 Dr. Stanley F. Malamed All Rights Reserved 36 Lidocaine 2% with vasoconstrictor Lidocaine with epinephrine Intermediate - Duration LA 1: 50,000 1: 80,000* 1:100,000 1:200,000 1:300,000 • Duration of pulpal anesthesia = ~60 minutes • Duration of soft tissue anesthesia = ~3 - 5 hours © 2015 Dr. Stanley F. Malamed All Rights Reserved 37 © 2015 Dr. Stanley F. Malamed All Rights Reserved 38 Lidocaine 2% with vasoconstrictor • Indicated for: • Dental therapy of approximately 45 - 60 minute duration • Depth of pulpal anesthesia usually adequate for pulpallyinvolved teeth • Pediatric patients (< 30 kg) when treating one or more quadrants Mepivacaine © 2015 Dr. Stanley F. Malamed All Rights Reserved 39 © 2015 Dr. Stanley F. Malamed All Rights Reserved 40 Mepivacaine 3% No vasoconstrictor Mepivacaine 3% No vasoconstrictor Short - Duration LA Mepivacaine 2% With vasoconstrictor • Duration of pulpal anesthesia (infiltration) = ~20 minutes • Duration of pulpal anesthesia (nerve block) = ~40 minutes • Duration of soft tissue anesthesia = ~2 - 3 hours © 2015 Dr. Stanley F. Malamed All Rights Reserved 41 © 2015 Dr. Stanley F. Malamed All Rights Reserved 42 Mepivacaine 3% No vasoconstrictor • Indicated for: • Dental therapy of SHORT duration (~30 minutes) • Depth of pulpal anesthesia MAY NOT be adequate for pulpally-involved teeth • Pediatric patients (< 30 kg) when treating one quadrant only Mepivacaine with epinephrine 1:100,000 © 2015 Dr. Stanley F. Malamed All Rights Reserved 43 © 2015 Dr. Stanley F. Malamed All Rights Reserved 44 Mepivacaine 2% with vasoconstrictor Mepivacaine 2% with vasoconstrictor • Intermediate - Duration LA • Duration of pulpal anesthesia = ~60 minutes • Duration of soft tissue anesthesia = ~3 - 5 hours Indicated for: • Dental therapy of approximately 45 - 60 minute duration • Depth of pulpal anesthesia usually adequate for pulpallyinvolved teeth • Pediatric patients (< 30 kg) when treating one or more quadrants © 2015 Dr. Stanley F. Malamed All Rights Reserved 45 © 2015 Dr. Stanley F. Malamed All Rights Reserved 46 Bupivacaine Bupivacaine 0.5% with epinephrine 1:200,000 © 2015 Dr. Stanley F. Malamed All Rights Reserved 47 © 2015 Dr. Stanley F. Malamed All Rights Reserved 48 Bupivacaine 0.5% with vasoconstrictor Bupivacaine 0.5% with vasoconstrictor • Not indicated for: • Long - Duration LA Rarely indicated for administration to children (long duration soft tissue anesthesia = increased risk of self-inflicted soft tissue injury) • Duration of pulpal anesthesia = >90 minutes (nerve block) • Duration of soft tissue anesthesia = ~5 - 12 hours © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 49 50 Bupivacaine 0.5% with vasoconstrictor Endodontics Post-surgical pain control • Pre-surgical NSAID po 1 hr. prior to appointment Indicated for: LA of choice for surgery • Dental therapy of > 2 hour duration • Post-surgical pain control Articaine, Lidocaine, Mepivacaine Long-acting LA at end of surgery just prior to discharge of patient Bupivacaine NSAID on timed basis (q4,6,8h) for xx days Post-surgical telephone call early evening © 2015 Dr. Stanley F. Malamed All Rights Reserved 51 © 2015 Dr. Stanley F. Malamed All Rights Reserved 52 Articaine 4% with epinephrine Articaine 1:100,000 1:200,000 • • Synthesized in Germany 1969 Introduced Germany 1976 1st & only Local anesthetic designed for dentistry © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 53 54 Articaine 4% Epinephrine 1:100,000 & 200,000 0 1:100,00 Articaine 4% Epinephrine 1:100,000 & 200,000 • 1:200,000 • Duration of pulpal anesthesia (infiltration) = 60 minutes • Duration of pulpal anesthesia (nerve block) = 60 minutes • Duration of soft tissue anesthesia = 3 - 5 hours Indicated for: • Dental therapy of approximately 60 minute duration • Depth of pulpal anesthesia usually adequate for pulpallyinvolved teeth • Pediatric patients (< 30 kg) when treating one or more quadrants 1:100,000 © 2015 Dr. Stanley F. Malamed All Rights Reserved 55 1:200,000 © 2015 Dr. Stanley F. Malamed All Rights Reserved 56 Articaine 4% Epinephrine 1:100,000 & 200,000 • Pregnancy Indicated for: 1:100,000 • Pregnant patients* • Nursing mothers* • Mandibular infiltration in adult patients* & Nursing 00 1:200,0 © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 57 58 Pregnancy USA FDA Basic rules: 1st trimester . . . NO ELECTIVE DENTAL CARE Greater risk of spontaneous abortion & fetal malformation Pregnancy classification Definition A [Generally considered safe] Controlled studies show no risk in 1st trimester; no evidence of 2nd or 3rd trimester risk; risk of fetal harm remote B [Caution advised] Animal studies show no risk or adverse fetal effects but controlled human 1st trimester studies not available/do not confirm; no evidence of 2nd or 3rd trimester risk; fetal harm possible but unlikely; see package insert for drugspecific recommendations C [Weigh risk/benefit] Animal studies show adverse fetal effect(s) but no controlled human studies OR no animal or human studies; weigh possible fetal risk vs. maternal benefit; see package insert for drug-specific recommendations C/D/D [Weigh risk/benefit] Category C in 1st trimester but positive evidence of human fetal risk in 2nd and 3rd trimester; maternal benefit may outweigh fetal risk in serious or life-threatening situations; see package insert for drug-specific recommendations 2nd trimester & early 3rd trimester . . . DENTAL CARE, if necessary late 3rd trimester . . . DENTAL CARE only if absolutely necessary D X © 2015 Dr. Stanley F. Malamed All Rights Reserved 59 [Weigh risk/benefit] Positive evidence of human fetal risk; maternal benefit may outweigh fetal risk in serious or life-threatening situations; see package insert for drug-specific recommendations [Contraindicated] Positive evidence of serious fetal abnormalities in animals, humans, or both; fetal risks clearly outweigh maternal benefit© 2015 Dr. Stanley F. Malamed All Rights Reserved 60 Nursing Drug Lactation category Definition S Safe for nursing infant; medication usually compatible with breast-feeding S? Safety in nursing infants unknown; inadequate literature available S* Potential for significant effects on nursing infants; medication should be given with caution NS Not safe for nursing infants; medication contraindicated or requires cessation of breast-feeding Pregnancy classification Nursing When using articaine, nursing mothers may choose to pump and discard breast milk for approximately 4 hours (based on plasma half life) following an injection of articaine (to minimize infant ingestion) and then resume breastfeeding. Articaine C Bupivacaine C Lidocaine B Mepivacaine C S? S S? Prilocaine B Safety unknown – exercise caution Epinephrine C *NS LA concentrations - OK *Large doses, such as in ACLS USA FDA USA FDA © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 61 62 Articaine 4% Epinephrine 1:100,000 & 200,000 Articaine 4% Epinephrine 1:100,000 & 200,000 • Should I use articaine 4% with 1:100,000 or 1:200,000 epineprine for PAIN CONTROL? • Though BOTH epinephrine concentrations are SAFE in most patients, the lesser concentration (1:200,000) is preferred as there is NO clinical difference in either the DEPTH or DURATION of PAIN • PAIN CONTROL 1:100,000 • 00 1:200,0 CONTROL. Therefore, logically, the 1:200,000 epinephrine concentration would be preferred for PAIN CONTROL © 2015 Dr. Stanley F. Malamed All Rights Reserved 63 1:200,000 © 2015 Dr. Stanley F. Malamed All Rights Reserved 64 Articaine 4% Epinephrine 1:100,000 & 200,000 • Should I use articaine 4% with 1:100,000 or 1:200,000 epineprine for HEMOSTASIS? 0 1:100,00 Local Anesthetics by EXPECTED duration of PULPAL anesthesia • • • • For HEMOSTASIS during surgical procedures, small volumes of 1:100,000 epinephrine infiltrated is recommended. 65 End session #1 Short-duration (~30 minutes) Mepivacaine 3% Intermediate-duration (~60 minutes) • Articaine 4%, Lidocaine 2%, Mepivacaine 2%, (all with vasoconstrictor) • Long-duration (>90 minutes) • Bupivacaine 0.5% (with vasoconstrictor) © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 66 INJECTION TECHNIQUES and the DENTAL SPECIALTIES © 2015 Dr. Stanley F. Malamed All Rights Reserved 67 68 LOCAL ANESTHETICS are the SAFEST and MOST EFFECTIVE drugs in medicine for the PREVENTION & MANAGEMENT of pain INJECTION TECHNIQUES © 2015 Dr. Stanley F. Malamed All Rights Reserved 69 © 2015 Dr. Stanley F. Malamed © 2014 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved 70 LOCAL ANESTHETICS are the only drugs that actually PREVENT PAIN © 2015 Dr. Stanley F. Malamed © 2014 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved 71 Depositing LA anywhere along the IA nerve will produce pain control © 2015 Dr. Stanley F. Malamed All Rights Reserved 72 Deposit a Local Anesthetic Close to a Nerve and It WILL Produce Pain Control Depositing LA anywhere along the IA nerve will produce pain control © 2015 Dr. Stanley F. Malamed © 2014 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 73 74 N = 121 So, when problems achieving clinically adequate pain control occur . . . Where do they happen? Tooth group Often Sometimes Rarely Very Rarely Never Maxillary Incisors 1 3 17 37 3 Maxillary Canines 1 2 23 42 53 Maxillary Premolars 1 8 29 40 43 Maxillary Molars 1 19 31 41 29 Mandibular Incisors 4 6 17 39 55 Mandibular Canines 4 10 23 39 45 Mandibular Premolars 8 29 18 41 25 Mandibular Molars 20 47 32 21 1 © 2015 Dr. Stanley F. Malamed All Rights Reserved 75 © 2015 Dr. Stanley F. Malamed All Rights Reserved 76 N = 121 Tooth group Often Sometimes Rarely Very Rarely Never Maxillary Incisors 1 3 17 37 3 Maxillary Canines 1 2 23 42 53 Maxillary Premolars 1 8 29 40 43 Maxillary Molars 1 19 31 41 29 Mandibular Incisors 4 6 17 39 55 Mandibular Canines 4 10 23 39 45 Mandibular Premolars, Canine, and Incisors, 31% Mandibular Premolars 8 29 18 41 25 can be easily accomplished 55% Mandibular Molars 20 47 32 21 1 16% Anesthesia of © 2015 Dr. Stanley F. Malamed All Rights Reserved 77 © 2015 Dr. Stanley F. Malamed All Rights Reserved 78 Incisive NB Incisive NB aka Mental NB aka Mental NB (incorrectly) Needle: 27 gauge short Insertion: MB fold at or anterior to mental foramen Target: Mental nerve as it exits mental foramen Volume: 0.6 mL Aspiration: 5.7% Insert needle in buccal fold and advance towards mental foramen Aspirate Deposit 0.6 mL outside foramen © 2015 Dr. Stanley F. Malamed All Rights Reserved 79 (incorrectly) © 2015 Dr. Stanley F. Malamed All Rights Reserved 80 Incisive NB aka Mental NB (incorrectly) Apply finger pressure for 2 minutes Video Vas = 0 -2 © 2015 Dr. Stanley F. Malamed All Rights Reserved 81 © 2015 Dr. Stanley F. Malamed All Rights Reserved 82 The limited success rate for the IANB has led to the development of alternative techniques: Gow-Gates Mandibular Nerve Block Vazirani - Akinosi (closed mouth) Mandibular Nerve Block Periodontal ligament injection (intraligamentary) Intraosseous anesthesia So, now we’re left with those ‘darned’ mandibular molars! Articaine HCl via buccal infiltration Buffered local anesthetics © 2015 Dr. Stanley F. Malamed All Rights Reserved 83 © 2015 Dr. Stanley F. Malamed All Rights Reserved 84 Mandibular anesthesia A dentist will administer approximately 30,000 IANBs in the course of a 20-year career Pogrel MA, Thamby S. Permanent nerve involvement resulting from inferior alveolar nerve blocks The traditional ‘Mandibular Block’ has the LOWEST success rate of all major nerve blocks in the human body JADA 2000;131:901-907 © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 85 86 Mandibular anesthesia Mandibular anesthesia Bone is TOO thick Lack of consistent anatomy THE problem with mandibular anesthesia, in the adult, is the density of the cortical plate of bone. It precludes the successful administration of supraperiosteal anesthesia © 2015 Dr. Stanley F. Malamed All Rights Reserved 87 A second problem with mandibular anesthesia, in the adult, is the lack of consistent landmarks © 2015 Dr. Stanley F. Malamed All Rights Reserved 88 Inferior Alveolar NB N = 121 Tooth group Often Sometimes Rarely Very Rarely Never Mandibular Incisors 4 6 17 39 55 Mandibular Canines 4 10 23 39 45 “Mandibular NB” Inferior Dental Block The ‘HALSTED Approach’ 55% Mandibular Premolars 8 29 18 41 25 Mandibular Molars 20 47 32 21 1 © 2015 Dr. Stanley F. Malamed All Rights Reserved 89 © 2015 Dr. Stanley F. Malamed All Rights Reserved 90 Inferior Alveolar NB “Mandibular NB” Inferior Dental Block Needle: 25- or 27- gauge long Insertion: soft tissue on medial border of mandibular ramus Target: IA nerve on lingual aspect Immediately following completion of IANB . . . of ramus prior to entering mandibular foramen Volume: 1.5 mL Aspiration: 10% - 15% © 2015 Dr. Stanley F. Malamed All Rights Reserved 91 © 2015 Dr. Stanley F. Malamed All Rights Reserved 92 Buccal NB “Long” Buccal Needle: 25- or 27- gauge long Insertion: mucus membrane distal and buccal to last mandibular molar Target: buccal nerve passing over border of ramus Volume: 0.3 mL Aspiration: 0.7% VAS = 3 -8 Video © 2015 Dr. Stanley F. Malamed All Rights Reserved 93 © 2015 Dr. Stanley F. Malamed All Rights Reserved 94 Following completion of IANB & Buccal NBs . . . Seat patient comfortably upright Speeds onset of anesthesia Video © 2015 Dr. Stanley F. Malamed All Rights Reserved 95 © 2015 Dr. Stanley F. Malamed All Rights Reserved 96 Inferior Alveolar NB “Mandibular NB” Inferior Dental Block The most common reason for missing the IANB is depositing LA solution too low. (BELOW the mandibular foramen) Inferior Alveolar Nerve Block A little higher is a little better The ‘nerve’ is gone! The traditional IANB deposits LA at the LOWEST part if the IAN © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 97 98 Inferior Alveolar NB Inferior Alveolar NB “Mandibular NB” Inferior Dental Block “Mandibular NB” Inferior Dental Block Disadvantages 1. 2. 3. 4. Advantages 1. More extensive profound pulpal anesthesia • Multiple preparations Slower onset of pulpal anesthesia Limited success Not indicated for limited treatment Prolonged duration of soft tissue anesthesia • Lip & tongue • Self-inflicted soft tissue injury © 2015 Dr. Stanley F. Malamed All Rights Reserved 99 © 2015 Dr. Stanley F. Malamed All Rights Reserved 100 The limited success of the IANB has led to the development of alternative techniques: JADA September 2011 Gow-Gates Mandibular Nerve Block Vazirani - Akinosi (closed mouth) Mandibular Nerve Block Is the ‘Mandibular Block’ Passé? Periodontal ligament injection (intraligamentary) Intraosseous anesthesia Articaine HCl via buccal infiltration © 2013 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 101 102 JADA September 2011 So the question is: Is the INFERIOR ALVEOLAR NERVE BLOCK Passé ? © 2015 Dr. Stanley F. Malamed All Rights Reserved 103 © 2015 Dr. Stanley F. Malamed ©All 2013 Rights Dr. Stanley Reserved F. Malamed All Rights Reserved 104 JADA September 2011 1973 . . . Gow-Gates Mandibular Nerve Block © 2015 Dr. Stanley F. Malamed ©All 2013 Rights Dr. Stanley Reserved F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 105 106 George Albert Edward Gow-Gates Gow-Gates Mandibular Nerve Block 1910 - 2001 If a little higher is a little better, a lot higher is a lot better The Gow-Gates technique deposits LA at the HIGHEST area George Gow-Gates @ Westmeade Dental Hospital, 1993 The Gow-Gates technique is the only true MANDIBULAR NB © 2015 Dr. Stanley F. Malamed All Rights Reserved 107 © 2015 Dr. Stanley F. Malamed All Rights Reserved 108 Gow-Gates Mandibular Nerve Block Advantages 2003 1. Higher success rate . . . once you learn it 2. Lower aspiration rate 3. Complete anesthesia of quadrant Video © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 109 110 Gow-Gates Mandibular Nerve Block Vazirani SJ. Closed mouth mandibular nerve block: a new technique. Dr. Sunder VAZIRANI Dent Dig 66:10-3, 1960. Disadvantages Dr. Oyekunle J. AKINOSI 1. Learning curve . . . “once you learn it” © 2015 Dr. Stanley F. Malamed All Rights Reserved 111 © 2015 Dr. Stanley F. Malamed All Rights Reserved 112 Vazirani-Akinosi Nerve Block © 2015 Dr. Stanley F. Malamed All Rights Reserved 113 © 2015 Dr. Stanley F. Malamed All Rights Reserved 114 Akinosi-Vazirani Mandibular NB Vazirani-Akinosi Mandibular NB Advantages 1. “Successful” when trismus is present Video © 2015 Dr. Stanley F. Malamed All Rights Reserved 115 © 2015 Dr. Stanley F. Malamed All Rights Reserved 116 Akinosi-Vazirani Mandibular NB Vazirani-Akinosi Mandibular NB Gow-Gates Mandibular Nerve Block Vazirani-Akinosi Nerve Block Disadvantages Inferior Alveolar Nerve Block 1. No bone contact so have to ‘guesstimate’ depth of penetration Depositing LA anywhere along the IA nerve will produce pain control © 2015 Dr. Stanley F. Malamed All Rights Reserved 117 © 2015 Dr. Stanley F. Malamed All Rights Reserved 118 JADA September 2011 1980’s Periodontal Ligament Injection, Intraosseous & Intraseptal (Crestal) © 2015 Dr. Stanley F. Malamed All Rights Reserved 119 © 2014 Dr. Stanley F. Malamed All Rights Reserved 120 Periodontal Ligament Injection (PDL) 27 gauge short needle Place interproximally SLOWLY deposit 0.2 mL per root Video © 2015 Dr. Stanley F. Malamed All Rights Reserved 121 122 Nusstein J, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the supplemental intraosseous injection of 2% lidocaine with 1:100,000 epinephrine in irreversible pulpitis. J Endodont 24(7):487-491, 1998 1980’s . . . Intraosseous Anesthesia (IO) 88% successful mandibular molars Parente SA, Anderson RW, Herman WW, Kimbrough WF, Weller RN. Anesthetic efficacy of the supplemental intraosseous injection for teeth with irreversible pulpitis. J Endodont 24(12):826-828, 1998 Leonard M, J Amer Dent Assoc October 103(4): 571-575, 1981 91% successful mandibular molars 123 124 X-Tip Stabident Video © 2015 Dr. Stanley F. Malamed All Rights Reserved Use a gentle “pecking” motion to penetrate the cortical plate. 125 126 Intraosseous Anesthesia (IO) DISADVANTAGES Highly vascular region ADVANTAGES Relatively comfortable X-Tip LA OD Single or multiple tooth anesthesia Vasopressor “shakes” No lip / tongue Can’t locate hole with needle use 1:200k or plain Video © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 127 128 Intraseptal (Crestal) Anesthesia Intraseptal (Crestal) Anesthesia J Dent Res Dent Clin Dent Prospect. Winter 2011 5(1): 17-22, 2011 © 2015 Dr. Stanley F. Malamed All Rights Reserved 129 7.00 3.30 +/- 0.67 Duration 23.10 32.10 +/- 2.13 Pain Intraseptal (Crestal) Anesthesia IANB +/- 0.71 Onset © 2015 Dr. Stanley F. Malamed All Rights Reserved 130 Intraseptal (Crestal) Anesthesia Crestal J Dent Res Dent Clin Dent Prospect. Winter 2011 5(1): 17-22, 2011 +/- 2.02 1.54 3.44 +/- 0.18 +/- 0.22 <0.001 <0.05 <0.001 mL 1.99 mL Volume 0.4 +/- 2.07 J Dent Res Dent Clin Dent Prospect. Winter 2011 5(1): 17-22, 2011 131 © 2015 Dr. Stanley F. Malamed All Rights Reserved J Dent Res Dent Clin Dent Prospect. Winter 2011 5(1): 17-22, 2011 132 © 2015 Dr. Stanley F. Malamed All Rights Reserved Local Anesthesia & DENTAL SPECIALTIES Pediatric Dentistry © 2015 Dr. Stanley F. Malamed All Rights Reserved 133 © 2015 Dr. Stanley F. Malamed All Rights Reserved 134 Pediatric Dentistry Considerations (1) Local anesthetic dosage Seizure starts (overdose, toxic reaction) (2) Self-inflicted soft tissue injury (residual soft tissue anesthesia) Local anesthetic dosage (3) Technique © 2015 Dr. Stanley F. Malamed All Rights Reserved 135 (overdose, toxic reaction) 136 Maximum Recommended Therapeutic Dosages Drug Mg/kg Absolute maximum Articaine HCl 7 n/a Bupivacaine HCl *** 90 Lidocaine HCl 7 500 Mepivacaine HCl 6.6 400 Prilocaine HCl 8 600 Self-inflicted soft tissue injury © 2015 Dr. Stanley F. Malamed All Rights Reserved 137 138 13% of pediatric patients receiving IANB suffer post-treatment traumatic injury to soft tissues. Age % with soft tissue trauma < 4 years 18% 4 - 7 years 16% 8 - 11 years 13% 12+ 7% Self-inflicted soft tissue injury Tongue / lips most common Children, handicapped adults Advise parent / guardian Select appropriate LA Select appropriate technique PDL, IO College C, Feigal R, Wandera A, Strange M. Bilateral versus unilateral mandibular block anesthesia in a pediatric population. Pediatr Dent. 22(6):453-457, 2000. © 2015 Dr. Stanley F. Malamed Local anesthesia reversal agent: phentolamine mesylate (Oraverse) © 2015 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved 139 140 Phentolamine mesylate PM is a vasodilator Increases blood flow into area of LA deposition Technique Speeds up discussion of LA out of injection site Minimal increase in LA blood level © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 141 142 Pediatric Dentistry Pediatric Dentistry Needle Maxillary Short needle appropriate until anatomy dictates long needle Volume All 1º teeth anesthetized by infiltration 1st permanent molar may be difficult ASA NB for all 1º teeth Lesser volumes of LA required Technique Technique © 2015 Dr. Stanley F. Malamed All Rights Reserved 143 © 2015 Dr. Stanley F. Malamed All Rights Reserved 144 Pediatric Dentistry Periodontology Mandibular Infiltration OK for 1º mandibular teeth Incisive nb for ALL 1º teeth in mandible 0.45 mL Try to avoid long-duration LA’s Technique IANB not required Foramen lower in child © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 145 146 Periodontology Periodontology Considerations Hemostasis To achieve hemostasis the vasopressor must be injected into the surgical site Infiltration, not nerve block for hemostasis (1) Hemostasis (2) Post-surgical pain control 1:50k and 1:100k provide clinically adequate hemostasis 1:200k does NOT provide clinically adequate hemostasis © 2015 Dr. Stanley F. Malamed All Rights Reserved 147 © 2015 Dr. Stanley F. Malamed All Rights Reserved 148 Periodontology Post-surgical pain control Pre-surgical NSAID po 1 hr. prior to appointment Endodontics LA of choice for surgery Articaine, Lidocaine, Mepivacaine Long-acting LA at end of surgery just prior to discharge of patient Bupivacaine NSAID on timed basis (q4,6,8h) for xx days Post-surgical telephone call early evening © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 149 150 Endodontics Endodontics Considerations Fear of dentistry Effects of inflammation on LA (1) Fear of dentistry (2) The dilemma of the “Hot” mandibular molar (3) Post-surgical pain control © 2015 Dr. Stanley F. Malamed All Rights Reserved 151 r ide s n Co s on ati Effects of infection on LA Long-term pain (chronic) Co ns id er at io ns Recently acute pain Fear of dentistry 152 © 2015 Dr. Stanley F. Malamed All Rights Reserved The scared dental patient OVERREACTS to incoming sensory stimulation, be it visual, auditory, proprioceptive, or nociceptive © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 153 154 Routes of Drug Administration The goal of sedation is DISTRACTION Oral sedation Inhalation sedation N2O – O2 To take the patients mind off of what is happening to them whilst in the dental chair Intravenous sedation Intranasal sedation © 2015 Dr. Stanley F. Malamed All Rights Reserved 155 © 2015 Dr. Stanley F. Malamed All Rights Reserved 156 The Herman Ostrow School of Dentistry of U.S.C. The overall percentage of medical emergencies occurring within the postdoctoral ENDODONTICS clinic is significantly higher than expected. Most result from either the patients FEAR of dentistry and/or to the INABILITY TO OBTAIN PROFOUND ANESTHESIA when extirpating the pulpal tissues. © 2015 Dr. Stanley F. Malamed All Rights Reserved Deal with the FEAR first then PAIN will be a minor problem Milgrom P, Weinstein P, Kleinknecht R, Getz T Treating fearful dental patients, Reston 1980 © 2015 Dr. Stanley F. Malamed All Rights Reserved 157 158 Endodontics The Dilemma of the Infected mandibular molars ‘Hot’ Mandibular Molar Effects of inflammation on LA Effects of infection on LA Long-term pain (chronic) Recently acute pain © 2015 Dr. Stanley F. Malamed All Rights Reserved 159 Stanley F. Malamed, D.D.S. Dentist Anesthesiologist Emeritus Professor of Anesthesia & Medicine Ostrow School of Dentistry of U.S.C. © 2014 2013 Dr. Stanley F. Malamed All Rights Reserved 160 Endodontic “Tricks” N = 121 Dental pathology Almost always Average Caries - - 17 46 58 Deep Caries - 2 34 56 29 Chronic Pulpitis 1 4 44 42 30 84% Exacerbated Chronic Pulpitis 2 22 60 30 7 89% Acute Pulpitis 2 26 61 26 6 Often Sometimes Rarely Never Assume all is ‘good’ 1. Inferior alveolar nerve block a. Preferably buffered local anesthetic (lidocaine or articaine) + epinephrine 2. Supplement IANB with articaine infiltration in buccal fold of tooth to be treated Consider SEDATION - N2O-02 preferred If necessary: 3. Intraosseous a. Distal to tooth being treated 4.Final choice: Intrapulpal injection © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 161 162 Endodontics Post-surgical pain control Pre-surgical NSAID po 1 hr. prior to appointment LA of choice for surgery Articaine, Lidocaine, Mepivacaine Long-acting LA at end of surgery just prior to discharge of patient Bupivacaine NSAID on timed basis (q4,6,8h) for xx days Local Anesthesia Considerations in Endodontic Treatment Bahcall, J. May 2012 163 Post-surgical telephone call early evening © 2015 Dr. Stanley F. Malamed All Rights Reserved 164 Oral & Maxillofacial Surgery Considerations Oral & Maxillofacial Surgery (1) Pain control (2) Post-surgical pain control © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 165 166 Oral & Maxillofacial Surgery Oral & Maxillofacial Surgery Pain control Post-surgical pain control Techniques Drugs Articaine Lidocaine Mepivacaine Bupivacaine Pre-surgical NSAID po 1 hr. prior to appointment Maxillary Mandibular Infiltration PSA MSA ASA AMSA V2 NB IANB Gow-Gates Vazirani-Akinosi Incisive LA of choice for surgery Articaine, Lidocaine, Mepivacaine Long-acting LA at end of surgery just prior to discharge of patient Bupivacaine NSAID on timed basis (q4,6,8h) for xx days Post-surgical telephone call early evening © 2015 Dr. Stanley F. Malamed All Rights Reserved 167 © 2015 Dr. Stanley F. Malamed All Rights Reserved 168 Is the ‘Mandibular’ Block Passé? So . . . Is the INFERIOR ALVEOLAR NERVE BLOCK Passé ? 169 Maybe NOT YET, but . . . you’ve got great options 170 Is the ‘Mandibular’ Block Passé? Options: Incisive (mental) nerve block Gow-Gates mandibular nerve block Akinosi-Vazirani nerve block PDL, Intraosseous, Intraseptal Articaine by mandibular infiltration Buffered lidocaine 171 End session #2 172 FUTURE TRENDS in PAIN CONTROL © 2015 Dr. Stanley F. Malamed All Rights Reserved 173 © 2015 Dr. Stanley F. Malamed All Rights Reserved 174 In my more than 40-year career teaching pain control in dentistry I have been involved with many, many “new” ideas and concepts seeking to improve pain control for dentists and their patients Periodontal Ligament Injection Intraosseous (IO) Electronic Dental Anesthesia (EDA) Computer Controlled Local Anesthetic Delivery (C-CLAD) Articaine Local Anesthesia Reversal Agent Buffered Local Anesthetics Nasal Local Anesthetic Mist Periodontal Ligament Injection Intraosseous (IO) Iontophoresis Electronic Dental Anesthesia (EDA) Computer Controlled Local Anesthetic Delivery (C-CLAD) Articaine HCl Local Anesthesia Reversal Agent (OraVerse® Phentolamine) Buffered Local Anesthetics (Onset®) Nasal Local Anesthetic Mist (Kovanest®) © 2015 Dr. Stanley F. Malamed All Rights Reserved 175 © 2015 Dr. Stanley F. Malamed All Rights Reserved 176 JADA September 2011 Articaine - Mandibular infiltration The LA ‘ON’ switch The LA ‘OFF’ switch Maxillary anesthesia without injection C-CLAD - (Dr. Mark Hochman) © 2015 Dr. Stanley F. Malamed All Rights Reserved 177 178 Articaine ARTICAINE 0 1:100,00 1:200,000 © 2015 Dr. Stanley F. Malamed All Rights Reserved 179 Ultracain Septocaine Artinibsa Articadent Vivacaine Septanest Alphacaine Zorcaine © 2015 Dr. Stanley F. Malamed All Rights Reserved 180 Articaine 4% Epinephrine 1:100,000 & 200,000 Articaine 4% with epinephrine 0 1:200,000 1:100,00 1:100,000 1:200,000 • • Synthesized in Germany 1969 Introduced Germany 1976 1st & only Local anesthetic designed for dentistry • Duration of pulpal anesthesia (infiltration) = 60 minutes • Duration of pulpal anesthesia (nerve block) = 60 minutes • Duration of soft tissue anesthesia = 3 - 5 hours © 2015 Dr. Stanley F. Malamed All Rights Reserved 181 © 2015 Dr. Stanley F. Malamed All Rights Reserved 182 Buccal infiltration ARTICAINE Articaine HCl by Mandibular Infiltration in Adults Mandibular infiltration John Meechan (UK) Al Reader (USA) © 2015 Dr. Stanley F. Malamed All Rights Reserved 183 © 2015 Dr. Stanley F. Malamed All Rights Reserved 184 Buccal infiltration ARTICAINE Pain Control Options 1. As sole injection by mandibular infiltration 2. As a supplement to lidocaine IANB Articaine as sole injection by mandibular buccal infiltration © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 185 186 Robertson D, Nusstein J, Reader A, Beck M, McCartney M. The anesthetic efficacy of articaine in buccal infiltration of mandibular posterior teeth. J Am Dent Assoc 138:1104-1112, 2007 2007 © 2015 Dr. Stanley F. Malamed All Rights Reserved 187 Design: N = 60 Infiltration mandibular buccal fold by #30 • Lidocaine 2% + epi 1:100K • Articaine 4% + epi 1:100K Randomized • At least 7 days apart • 60 on right side • 60 on left side 1.8 mL in 60 seconds 2007 © 2015 Dr. Stanley F. Malamed All Rights Reserved 188 JADA 138(8):1104-1112, 2007 EPT 1st 2nd 1st 2nd Teeth tested: and molar, and premolar Baseline • EPT @ 1 min = molars • EPT @ 2 min = premolars • EPT @ 3 min = Control (contralateral canine) • Repeated cycle every 3 minutes for 60 minutes Criteria for success: • No response to 2 or more consecutive 80uA tests • • 2007 © 2015 Dr. Stanley F. Malamed All Rights Reserved Pulp test every 3 min SUCCESS = 80/80 on 2 consecutive tests 2007 Mandibular 2nd Molar Mandibular 1st Molar Mandibular 2nd Premolar Mandibular 1st Premolar 189 Articaine Lidocaine 75% 87% 92% 86% 45% 57% p value for all: >.0001 67% 61% © 2015 Dr. Stanley F. Malamed All Rights Reserved 190 Results -2: Discussion -1: The onset of successful anesthesia was significantly faster for articaine than lidocaine for all 4 teeth tested 2007 © 2015 Dr. Stanley F. Malamed All Rights Reserved 191 2007 © 2015 Dr. Stanley F. Malamed All Rights Reserved 192 Discussion -2: Thiophene ring: JADA 138(8):1104-1112, 2007 > lipid solubility Lidocaine Benzene ring Articaine © 2015 Dr. Stanley F. Malamed All Rights Reserved 2007 193 © 2015 Dr. Stanley F. Malamed All Rights Reserved 194 Buccal infiltration ARTICAINE Comment 1. The research required articaine infiltration by tooth #30 (46) 2. In clinical situations you would logically infiltrate the articaine in the buccal fold adjacent to the tooth to be treated. © 2015 Dr. Stanley F. Malamed All Rights Reserved 195 Meechan JG, Ledvinka JI. Pulpal anaesthesia for mandibular central incisor teeth: a comparison of infiltration and intraligamentary injections. Int Endod J 35:629-634, 2002 2002 © 2015 Dr. Stanley F. Malamed All Rights Reserved 196 Meechan JG, Ledvinka JI. Pulpal anaesthesia for mandibular central incisor teeth: a comparison of infiltration and intraligamentary injections. Int Endod J 35:629-634, 2002 Meechan JG, Ledvinka JI. Pulpal anaesthesia for mandibular central incisor teeth: a comparison of infiltration and intraligamentary injections. Int Endod J 35:629-634, 2002 Design: Articaine 4% + epi 1:100K Lidocaine 2% + epi 1:80K Infiltration buccal fold by lateral incisor • 0.5 mL Infiltration buccal & lingual by lateral incisor • 0.5 mL per site EPT q 3 min for 45 minutes 2002 Results-1: Infiltration buccal fold by lateral incisor • 94% articaine; 70% lidocaine • Infiltration buccal & lingual by lateral incisor • 97% articaine; 88% lidocaine © 2015 Dr. Stanley F. Malamed All Rights Reserved 2002 Meechan JG, Ledvinka JI. Pulpal anaesthesia for mandibular central incisor teeth: a comparison of infiltration and intraligamentary injections. Int Endod J 35:629-634, 2002 197 © 2015 Dr. Stanley F. Malamed All Rights Reserved 198 Mandibular Incisors Meechan JG, Ledvinka JI. Pulpal anaesthesia for mandibular central incisor teeth: a comparison of infiltration and intraligamentary injections. Int Endod J 35:629-634, 2002 Articaine B&L Discussion: Articaine B Lidocaine B&L Lidocaine B © 2014 Dr. Stanley F. Malamed All Rights © 2015 Dr. Stanley Malamed ©F. 2013 Dr.Reserved Stanley F. Malamed All Rights Reserved All Rights Reserved 199 2002 © 2015 Dr. Stanley F. Malamed All Rights Reserved 200 Buccal Buccal infiltration infiltration -ARTICAINE ARTICAINE Buccal infiltration ARTICAINE Advantages 1. Profound pulpal anesthesia 2. 30 to 40 minute duration of pulpal anesthesia 3. Minimal accessory soft tissue anesthesia • Tongue Disadvantage I can’t think of any, unless it doesn’t work! © 2015 Dr. Stanley F. Malamed All Rights Reserved 201 © 2015 Dr. Stanley F. Malamed All Rights Reserved 202 Pain Control Options Articaine infiltration as a supplement to IANB © 2015 Dr. Stanley F. Malamed All Rights Reserved 203 Kanaa JM, Whitworth JM, Corbett IP, Meechan JG Articaine buccal infiltration enhances the effectiveness of lidocaine inferior alveolar nerve block. Int Endodont J 42:238-246, 2009 204 © 2015 Dr. Stanley F. Malamed All Rights Reserved Kanaa JM, Whitworth JM, Corbett IP, Meechan JG Articaine buccal infiltration enhances the effectiveness of lidocaine inferior alveolar nerve block. Int Endodont J 42:238-246, 2009 Articaine infiltration as a supplement to IANB 1st Molar 91.7% IANB’s at each of 2 visits = 2% lidocaine + epi 1:80K One visit = 4% articaine + epi 1:100K infiltration buccal fold 1st molar (2.0 mL) 55.6% One visit = ‘dummy injection’ buccal fold 1st molar Pulp test for 45 minutes © 2015 Dr. Stanley F. Malamed © 2013 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 205 206 Articaine infiltration as a supplement to IANB Articaine infiltration as a supplement to IANB 1st Premolar Lateral Incisor 88.9% 77.8% 66.7% 19.4% © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 207 208 The local anesthetic “ON SWITCH” Buffered Local Anesthetics Alkalinized Local Anesthetics © 2015 Dr. Stanley F. Malamed © 2013 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved 209 210 Intermediate - duration LAs - USA Drug How long does it take for pulpal anesthesia to develop? © 2015 Dr. Stanley F. Malamed All Rights Reserved 211 Lidocaine 2% Onset (textbook) Pulpal Soft Tissue Epi 1:50k, 1:100k 3 - 5 min 60 min 3 - 5 hours Mepivacaine Levonordefrin 1:20k 2% 3 - 5 min 60 min 3 - 5 hours Prilocaine 4% Epi 1:200k 3 - 5 min 60 min 3 - 8 hours Articaine 4% Epi 1:100k 1:200k 2 - 3 min 60 min 3 - 5 hours Epi = Epinephrine (Adrenalin) © 2015 Dr. Stanley F. Malamed All Rights Reserved 212 1980 Where do these numbers . . . Onset of anesthesia, Duration of pulpal anesthesia, Duration of soft tissue anesthesia 1st edition . . . come from? 1946 - 1973 © 2015 Dr. Stanley F. Malamed All Rights Reserved 213 © 2015 Dr. Stanley F. Malamed All Rights Reserved 214 Six-Hour Time Course for Pulpal Analgesia (EPT) IANB Second Premolar So the question is: The other 5% are anatomical misses 95% of patients will (eventually) get numb if given a 45-minute waiting period Why?does it REALLY take for How long pulpal anesthesia to develop? 45 minutes © 2015 Dr. Stanley F. Malamed All Rights Reserved 215 © 2015 Dr. Stanley F. Malamed All Rights Reserved 216 30-Minute Time Course for Pulpal Analgesia - Lidocaine IANBs Data from 28 PRP Studies - 1078 Subjects (1991 - 2008) IANB - Lido 28 peerreviewed trials 100%# #Kanaa#(2006)(m)(L)# #Nist#(1992)(m)(L)# 90%# #Chaney#(1991)(m)(L)# #Hinckley#(1991)(m)(L)# #McLean#(1993)(m)(L)# 80%# N = 1078 #Childers#(1996)(m)(L)# #Dagher#(1997)(m)(L)# #Goldberg#(2008)(m)(L)# 70%# #Goodman#(2006)(m)(L)# Infiltration - Lido #Hannan#(1999)(1m)(L)# 60%# 8 peer-reviewed trials #Hannan#(1999)(2m)(L)# #Steinkruger#(2006)(m)(L)# #Willet#(2008)(m)(L)# 50%# #Vreeland#(1989)(m)(L)# N = 416 The SPAGHETTI graph 40%# IANB - Articaine 5 peer-reviewed trials 30%# 20%# N = 222 10%# #Kanaa#(2006)(p)(L)# #Chaney#(1991)(p)(L)# #Hinckley#(1991)(m)(L)# #McLean#(1993)(p)(L)# #Dagher#(1997)(p)(L)# #Goldberg#(2008)(p)(L)# #Goodman#(2006)(p)(L)# #Hannan#(1999)(p)(L)# #Willet#(2008)(p)(L)# #Mikesell#(2005)(m)(L)# #Mikesell#(2005)(1p)(L)# #Mikesell#(2005)(1p)(L)# 0%# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# 30# © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 217 218 30-Minute Time Course for Pulpal Analgesia - Lidocaine IANBs 30 Minute Time Course for IANB Soft Tissue Analgesia (sharp dental explorer) Data from 28 PRP Studies - 1078 Subjects (1991 - 2008) 100%# Lai, et al, OOOOE, Vol 102, No 4, P 462-68 (2006) 100%# #Kanaa#(2006)(m)(L)# #Nist#(1992)(m)(L)# #Chaney#(1991)(m)(L)# 90%# 90%# #Hinckley#(1991)(m)(L)# #McLean#(1993)(m)(L)# 80%# 80%# #Childers#(1996)(m)(L)# #Dagher#(1997)(m)(L)# 70%# 70%# #Goodman#(2006)(m)(L)# Lidocaine#IANB#Mean# 70% #Goldberg#(2008)(m)(L)# #Hannan#(1999)(1m)(L)# #Hannan#(1999)(2m)(L)# 60%# 60%# #Steinkruger#(2006)(m)(L)# #Willet#(2008)(m)(L)# 50%# 50%# #Vreeland#(1989)(m)(L)# ‘MEAN’ 40%# 30%# 50% above 50% below 20%# 10%# #Kanaa#(2006)(p)(L)# #Chaney#(1991)(p)(L)# At 4 minutes: 70% soft tissue numb 25% pulpal anesthesia 40%# #Hinckley#(1991)(m)(L)# #McLean#(1993)(p)(L)# #Dagher#(1997)(p)(L)# 30%# #Goldberg#(2008)(p)(L)# #Goodman#(2006)(p)(L)# 25% 20%# #Hannan#(1999)(p)(L)# #Willet#(2008)(p)(L)# #Mikesell#(2005)(m)(L)# 10%# #Mikesell#(2005)(1p)(L)# Lai,#et#al,#so>#?ssue#v.#EPT# #Mikesell#(2005)(1p)(L)# Lidocaine#IANB#Mean# 0%# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# 0%# 30# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# © 2015 Dr. Stanley F. Malamed All Rights Reserved 219 20# 22# 24# 26# 28# 30# © 2015 Dr. Stanley F. Malamed All Rights Reserved 220 30 Minute Time Course for IANB Soft Tissue Analgesia (sharp dental explorer) 30 Minute Time Course for IANB Soft Tissue Analgesia (sharp dental explorer) Lai, et al, OOOOE, Vol 102, No 4, P 462-68 (2006) Lai, et al, OOOOE, Vol 102, No 4, P 462-68 (2006) 100%# 100%# 90%# 90%# 85% 85% 80%# 80%# Lidocaine#IANB#Mean# 70%# 70%# 60%# 60%# 50%# 50%# 40%# At 6 minutes: 85% soft tissue numb 40% pulpal anesthesia 40% 30%# 20%# 10%# OW! 70% Lidocaine#IANB#Mean# 40% 40%# 30%# Lai,#et#al,#so>#?ssue#v.#EPT# Lai,#et#al,#so>#?ssue#v.#EPT# 25% 20%# 10%# 0%# 0%# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# 0# 30# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# 30# © 2015 Dr. Stanley F. Malamed All Rights Reserved 221 222 Soft tissue anesthesia is NEVER a guaranteed sign of pulpal anesthesia © 2015 Dr. Stanley F. Malamed All Rights Reserved 223 © 2015 Dr. Stanley F. Malamed All Rights Reserved Is there a guarantee? The best* we have is using an electric pulp tester or Freezing spray (e.g. Endo-Ice) *Assumes no pulpal involvement 224 © 2015 Dr. Stanley F. Malamed All Rights Reserved 30-Minute Time Course for Pulpal Analgesia - Lidocaine IANBs 30-Minute Time Course for Pulpal Analgesia - Lidocaine IANBs Average for 28 PRP Studies - 1078 Subjects (1991 - 2008) with Lidocaine IANB Mean Average for 28 PRP Studies - 1078 Subjects (1991 - 2008) with Lidocaine IANB Mean 100%# 100%# Most doctors wait ~10 minutes 90%# 80%# 80%# 70%# 70%# N = 1078 Some doctors Many practitioners wait 15 minutes (67%) wait ~15 minutes 90%# N = 1078 60%# 50%# 60%# 50%# Lidocaine#IANB#Mean# Lidocaine#IANB#Mean# 40%# 40%# 20%# 10%# At 15 minutes: 67% pulpal anesthesia 30%# At 10 minutes: 60% pulpal anesthesia 30%# 20%# 10%# 0%# 0%# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# 30# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# 30# © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 225 226 100%# IANB: Lidocaine + epinephrine #Kanaa#(2006)(m)(L)# #Nist#(1992)(m)(L)# 90%# #Chaney#(1991)(m)(L)# #Hinckley#(1991)(m)(L)# 80%# #McLean#(1993)(m)(L)# #Childers#(1996)(m)(L)# #Dagher#(1997)(m)(L)# 70%# #Goldberg#(2008)(m)(L)# #Goodman#(2006)(m)(L)# 60%# #Hannan#(1999)(1m)(L)# #Hannan#(1999)(2m)(L)# 50%# #Steinkruger#(2006)(m)(L)# #Willet#(2008)(m)(L)# #Vreeland#(1989)(m)(L)# 40%# #Kanaa#(2006)(p)(L)# #Chaney#(1991)(p)(L)# 30%# % clinically effective pulpal anesthesia #Hinckley#(1991)(m)(L)# #McLean#(1993)(p)(L)# 20%# #Dagher#(1997)(p)(L)# #Goldberg#(2008)(p)(L)# #Goodman#(2006)(p)(L)# 10%# #Hannan#(1999)(p)(L)# #Willet#(2008)(p)(L)# 0%# % • 25 at 4 minutes • 40% at 6 minutes 0# 60 at 10 minutes • 67% at 15 minutes • 95% at 45 minutes 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 26# 28# 30# with Articaine? © 2015 Dr. Stanley F. Malamed All Rights Reserved 227 24# Can we speed the onset of anesthesia . . . % • 2# © 2015 Dr. Stanley F. Malamed All Rights Reserved 228 30-Minute Time Course, Pulpal Analgesia, IANB, Why do doctors LIKE articaine? Lidocaine, Articaine 100%# 90%# 80%# Ar/caine#IANB#Mean# Anecdotal comments from dentists: 70%# N = 222 “It works better” Articaine “I don’t miss as often” Lidocaine “Hard to get ‘numb’ patients are easier to numb with articaine” N = 1078 60%# 50%# 40%# ARTICAINE + epinephrine 30%# 20%# 10%# “It works faster” Lidocaine#IANB#Mean# 0%# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# 30# © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 229 230 Can we speed the onset of anesthesia 100%# #Kanaa#(2006)(m)(L)# #Nist#(1992)(m)(L)# 90%# #Chaney#(1991)(m)(L)# #Hinckley#(1991)(m)(L)# 80%# #McLean#(1993)(m)(L)# #Childers#(1996)(m)(L)# #Dagher#(1997)(m)(L)# 70%# #Goldberg#(2008)(m)(L)# #Goodman#(2006)(m)(L)# 60%# #Hannan#(1999)(1m)(L)# #Hannan#(1999)(2m)(L)# 50%# #Steinkruger#(2006)(m)(L)# #Willet#(2008)(m)(L)# #Vreeland#(1989)(m)(L)# 40%# #Kanaa#(2006)(p)(L)# #Chaney#(1991)(p)(L)# 30%# #Hinckley#(1991)(m)(L)# #McLean#(1993)(p)(L)# 20%# #Goldberg#(2008)(p)(L)# with Articaine? NO 231 #Dagher#(1997)(p)(L)# #Goodman#(2006)(p)(L)# 10%# #Hannan#(1999)(p)(L)# #Willet#(2008)(p)(L)# 0%# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# 30# Can we speed the onset of anesthesia . . . by buffering the LA solution? © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 232 100%# 30-Minute Time Course, Pulpal Analgesia, IANB, Buffered Lidocaine #Kanaa#(2006)(m)(L)# #Nist#(1992)(m)(L)# 90%# Lidocaine, Articaine #Chaney#(1991)(m)(L)# 100%# #Hinckley#(1991)(m)(L)# 80%# #McLean#(1993)(m)(L)# #Childers#(1996)(m)(L)# #Dagher#(1997)(m)(L)# 70%# #Goldberg#(2008)(m)(L)# #Goodman#(2006)(m)(L)# 60%# 90%# #Hannan#(1999)(1m)(L)# #Hannan#(1999)(2m)(L)# 50%# #Steinkruger#(2006)(m)(L)# #Willet#(2008)(m)(L)# Ar/caine#IANB#Mean# #Vreeland#(1989)(m)(L)# 40%# #Kanaa#(2006)(p)(L)# 80%# #Chaney#(1991)(p)(L)# 30%# #Hinckley#(1991)(m)(L)# #McLean#(1993)(p)(L)# 20%# #Dagher#(1997)(p)(L)# #Goldberg#(2008)(p)(L)# #Goodman#(2006)(p)(L)# 10%# #Hannan#(1999)(p)(L)# 67% #Willet#(2008)(p)(L)# 0%# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# N = 18 30# Can we speed the onset of anesthesia . . . 70%# 60%# 50%# Lidocaine#IANB#Mean# 40%# 30%# by changing the pH of the LA solution? BUFFERED lidocaine + epinephrine 20%# 10%# #Buffered#Lido#IANB# 0%# 0# 2# 4# 6# 8# 10# 12# 14# 16# 18# 20# 22# 24# 26# 28# 30# © 2015 Dr. Stanley F. Malamed All Rights Reserved 233 © 2015 Dr. Stanley F. Malamed All Rights Reserved 234 Can we speed the onset of anesthesia The local anesthetic “ON SWITCH” by buffering the solution? YES 235 © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 236 Lidocaine Local anesthetics are INSOLUBLE in water. Mepivacaine Articaine Prilocaine Bupivacaine Hydrochloric acid is added to make the drug water-soluble © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 237 238 Mepivacaine HCl Let’s look at an anesthetic cartridge Lidocaine HCl We inject the acid-salt of the local anesthetic Bupivacaine HCl pH Articaine HCl Prilocaine HCl ‘Plain’ LA solution (mepivacaine 3%) = ~6.5 Vasoconstrictor LA solution = ~3.5 Lemon juice = 3.3 © 2015 Dr. Stanley F. Malamed All Rights Reserved 239 © 2015 Dr. Stanley F. Malamed All Rights Reserved 240 Let’s look at an anesthetic cartridge Let’s look at an anesthetic cartridge Lidocaine = RN + Hydrochloric acid = H The more acidic the solution the greater the number of H © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 241 242 H+ RN + So . . . inside the LA cartridge we have Some H attach to RN forming RNH + three things: RN + H and RNH © 2015 Dr. Stanley F. Malamed All Rights Reserved 243 + + © 2015 Dr. Stanley F. Malamed All Rights Reserved 244 RN is LIPID SOLUBLE and CAN cross the lipid-rich nerve membrane % Un-ionized (RN) LA pH Lidocaine Articaine Mepivacaine Bupivacaine pKa 7.9 pKa 7.8 pKa 7.6 pKa 8.1 0.004 0.005 0.008 0.003 RN 3.5 RN RN (with epi) RNH+ CANNOT cross the nerve membrane © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 245 246 pH 3.5 The body will SLOWLY buffer the anesthetic solution to a pH of 7.4 pH Lidocaine 7.4 24.03% 75.97% 0.004% 99.996% RN RNH+ pKa 7.9 (body pH) 3.5 (with epi) 45 minutes ? 45 minutes ? 3.4 © 2015 Dr. Stanley F. Malamed All Rights Reserved 247 pH 7.4 45 minutes ? 3.6 3.8 4 4.2 4.4 4.6 4.8 5 5.2 5.4 5.6 5.8 5.9 6 6.2 6.4 6.6 6.8 7 7.2 7.4 7.6 7.8 8 8.2 8.4 8.6 pH The human body is a magnificent buffering machine 248 © 2015 Dr. Stanley F. Malamed All Rights Reserved The Medical Profession & Local Anesthesia % Un-ionized (RN) LA 6000x increase in RN pH 7.4 Lidocaine pKa 7.9 Articaine Mepivacaine Bupivacaine pKa 7.8 pKa 7.6 pKa 8.1 24.03 28.47 38.69 16.63 3.83 4.77 7.36 2.45 0.004 0.005 0.008 0.003 Dermatology Plastics & Reconstructive Surgery Allergists (body pH) 6.5 (plain) 3.5 (with epi) © 2015 Dr. Stanley F. Malamed All Rights Reserved 249 Allows CO2 to Escape © 2015 Dr. Stanley F. Malamed All Rights Reserved 250 Medical use of Local Anesthetic Buffering BUFFERING with Sodium Bicarbonate Adsorbs active anesthetic Draws CO2 out of solution © 2015 Dr. Stanley F. Malamed All Rights Reserved 251 © 2015 Dr. Stanley F. Malamed All Rights Reserved 252 So, what has happened to make LA buffering a reality in dentistry? pH = 7.35 Stabilization BUFFERING of the Sodium Bicarbonate with NaBicarbonate Solution pH = 7.35 © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 253 254 Malamed SF, Hersh E, Poorsattar S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compendium 34:(spec issue #1):1-11, 2013 • • Summary • • Clinical Trial Data • • • Malamed SF, Hersh E, Poorsattar S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compendium 34:(spec issue #1):1-11, 2013 • Patients were appointed twice. Received IANB each time • At least 1 week between appointments Pulp tested mandibular premolar prior to start IANB administered • Traditional lidocaine + epi 1:100k (pH ~3.5) • Buffered lidocaine + epi 1:100k (pH 7.35) Timer started Endo-ice applied to premolar q20sec until no response Confirmed with EPT Onset of anesthesia when BOTH tests negative © 2015 Dr. Stanley F. Malamed All Rights Reserved 255 © 2015 Dr. Stanley F. Malamed All Rights Reserved 256 Injection Pain Reported by Participants 10 Standard Anesthetic 10 9 9 8 8 7 7 Buffered Anesthetic 6 6:37 Pain 10*cm* VAS 5 Average: 2.3 1:51 6 5 4 4 3 3 2 2 1 1 0 Average: 0.6 0 *******************6**************5****************4**************3****************2*************1************* * 258 (100mm VAS) ********************1****************2*****************3****************4******************5*******************6****** * No. of Participants at each 5mm pain interval No. of Participants at each 5mm pain interval © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 257 258 Clinical Data – Pain Free Injections Clinical Data – Patient Preference 50% 80% 44% 72% 38% 44% of buffered anesthetic patients experienced zero injection pain 72 % of patients rated buffered anesthetic as the more comfortable injection 25% 6% of traditional anesthetic patients 13% experienced zero injection pain 6% 60% 40% 20% 17% 11% 0% 0% No*Difference Control Malamed SF, Hersh E, Poorsattar S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compendium 34:(spec issue #1):1-11, 2013 Buffered Malamed SF, Hersh E, Poorsattar S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaine with epinephrine 1:100,000. Compendium 34:(spec issue #1):1-11, 2013 © 2015 Dr. Stanley F. Malamed All Rights Reserved 259 Control Buffered © 2015 Dr. Stanley F. Malamed All Rights Reserved 260 Clinical Data – Onset less than 2 minutes 80%$ 71%$ 70%$ 60%$ 50%$ 40%$ 30%$ 20%$ 12%$ 10%$ 0%$ Lidocaine$w/$Epi$ Buffered$Lidocaine$w/$Epi$ Malamed SF, Hersh E, Poorsattar S, Falkel M. Faster onset and more comfortable injection with alkalinized 2% lidocaineWhat%Percentage%of%Par.cipants%Achived%Pulpal% with epinephrine 1:100,000. Compendium 34:(spec issue #1):1-11, 2013 Anesthesia%in%Under%2%Minutes?% Video © 2015 Dr. Stanley F. Malamed All Rights Reserved 261 © 2013Dr. Dr. Stanley F. Malamed © 2015 Stanley F. Malamed All Rights Reserved All Rights Reserved 262 Buffering Lidocaine HCl Dr. Dawn Green Lidocaine 2% + epinephrine 1:100,000 = pH 3.5 BUFFERED Las Vegas, NV Lidocaine 1.75% + epi 1:125,000 + CO2 + NaHCO3 = pH 7.4 Video More dilute 6,000x more active ions to enter nerve © 2015 Dr. Stanley F. Malamed All Rights Reserved 263 © 2015 Dr. Stanley F. Malamed All Rights Reserved 264 Buffered Local Anesthetics When buffering is done properly the following advantages can be expected from the increase in pH: (1) More comfortable injection for patient pH of anesthetic 7.35 to 7.5 (2) More rapid onset on pulpal anesthesia (3) More profound anesthesia (4) Less post-injection soreness (5) No effect on duration of action (6) No increase in LA blood level (safety) The Mandibular anesthesia - IANB 1. Administer buffered lidocaine IANB 2. DO NOT LEAVE THE PATIENT !!! 3. You know if your block is successful in 2 minutes © 2015 Dr. Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved 265 The Onset® approach 266 Onset® approach The Mandibular anesthesia - IANB Onset® approach Maxillary anesthesia 4. Check for pulpal anesthesia: • EPT or Endo-Ice 5. In 2 minutes following IANB either begin tooth preparation or readminister LA Follow same procedure for maxillary teeth. Onset time is at least as rapid - if not faster following infiltration © 2015 Dr. Stanley F. Malamed All Rights Reserved 267 © 2015 Dr. Stanley F. Malamed All Rights Reserved 268 The local anesthetic “ON SWITCH” The local anesthetic “OFF SWITCH” © 2015 Dr. Stanley F. Malamed All Rights Reserved 269 © 2015 Dr. Stanley F. Malamed All Rights Reserved 270 Intranasal Drug Administration Intranasal Local Anesthesia in the Maxilla © 2015 Dr. Stanley F. Malamed All Rights Reserved 271 © 2015 Dr. Stanley F. Malamed All Rights Reserved 272 Intranasal Drug Administration Emergency medicine Pediatric grand mal status . . . Midazolam Pediatric sedation (dentistry) . . . Midazolam © 2015 Dr. Stanley F. Malamed All Rights Reserved Video Notice EMT place syringe in nose 273 274 Intranasal Local Anesthetic Mist Intranasal Local Anesthetic Mist © 2014 Dr. Stanley F. Malamed All Rights Reserved By late-2015, early 2016 (hopefully) in the USA we will be able to administer a local anesthetic intranasally to provide profound pulpal anesthesia from #4 to #13 Intranasal Local Anesthetic Mist 275 © 2015 Dr. Stanley F. Malamed All Rights Reserved (#1.1 to 1.5 and 2.1 to 2.5) 276 © 2015 Dr. Stanley F. Malamed All Rights Reserved Intranasal Local Anesthetic Mist Intranasal Local Anesthetic Mist Kovanest 3% Tetracaine Oxymetazoline Ester-type local anesthetic Commonly used by ENT surgeons Vasoconstrictor Has ‘track record’ as safe & effective IN Active ingredient in ‘Afrin’ & other nasal decongestants 2014 Dr. Stanley F. Malamed © 2015 © Rights 2013 Dr. Stanley F. Malamed All Reserved 2014 Dr. Stanley F. Malamed © 2015 © Rights 2013 Dr. Stanley F. Malamed All Reserved All Rights Reserved All Rights Reserved 277 278 Intranasal Local Anesthetic Mist Injectable (lidocaine + epi) Phase 2 clinical trial 94% success 1st molar to 1st molar 3% Tetracaine Oxymetazoline (active ingredient in Afrin nasal spray) Sprayed into R & L nares N = 48 © 2015 Dr. Stanley F. Malamed All Rights Reserved 279 © 2015 Dr. Stanley F. Malamed All Rights Reserved 280 Nasal Mist 84% success 1st molar to 1st molar 100% success Premolar to premolar Palate 16% failure on 1st molar JADA 143(8):872-880, 2012 © 2014 Stanley F. F. Malamed © 2015 Dr.Dr.Stanley Malamed Rights © All 2013 Dr. Reserved Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed © 2013 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved 281 All Rights Reserved 282 Whats’s New in Local Anesthesia Light-activated / Light-inactivated Local Anesthetic In the more distant future © 2015© 2014 Dr. Dr. Stanley F. Malamed Stanley F. Malamed All Rights Reserved © 2015 Dr.Reserved Stanley F. Malamed All Rights © 2015 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved 283 284 Optical control of painsensing neurons. QAQ selectively enters pain sensing neurons and silences their activity (top, green light). Illumination with violet light (bottom) quickly restores signal conduction Ultra Long-Acting Analgesia Neosaxitoxin © 2015© 2014 Dr. Dr. Stanley F. Malamed Stanley F. Malamed All Rights Reserved © 2015 Dr.Reserved Stanley F. Malamed All Rights © 2015© 2014 Dr. Dr. Stanley F. Malamed Stanley F. Malamed All Rights Reserved © 2015 Dr.Reserved Stanley F. Malamed All Rights All Rights Reserved 285 All Rights Reserved 286 Neosaxitoxin Over 1 week of analgesia (in rodents) without histologic or functional sequelae One of a group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs) Saxitoxin Tetrodotoxin © 2015© 2014 Dr. Dr. Stanley F. Malamed Stanley F. Malamed All Rights © 2015 Dr.Reserved Stanley F. Malamed All Rights Reserved © 2015© 2014 Dr. Dr. Stanley F. Malamed Stanley F. Malamed All Rights Reserved © 2015 Dr.Reserved Stanley F. Malamed All Rights All Rights Reserved 287 All Rights Reserved 288 20?? DRUGS Neosaxitoxin Saxitoxin Long-acting local ANESTHETIC Long-acting local ANALGESIC The ‘RED TIDE’ • Chile & Harvard © 2015© 2014 Dr. Dr. Stanley F. Malamed Stanley F. Malamed All Rights Reserved © 2015 Dr.Reserved Stanley F. Malamed All Rights © 2015© 2014 Dr. Dr. Stanley F. Malamed Stanley F. Malamed All Rights Reserved © 2015 Dr.Reserved Stanley F. Malamed All Rights All Rights Reserved 289 All Rights Reserved 290 Neosaxitoxin Over 1 week of analgesia (in rodents) without histologic or functional sequelae © 2015© 2014 Dr. Dr. Stanley F. Malamed Stanley F. Malamed All Rights © 2015 Dr.Reserved Stanley F. Malamed All Rights Reserved © 2015 Dr. Stanley F. Malamed All Rights Reserved All Rights Reserved 291 292 [email protected] Thank you for listening . . . © 2015 Dr. Stanley F. Malamed All Rights Reserved 293
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