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anesth prog 39 187 193 1992 briefreviews vasoconstrictors in local anesthesia for dentsty allen l sisk dds department of oral and maxillofacial surgery medical college of georgia school of dentistry ...

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           Anesth Prog 39:187-193 1992
                                                                                                                               BRIEFREVIEWS
           Vasoconstrictors in Local Anesthesia for Dentsty
                                                                                                                                Allen L. Sisk, DDS
                                                                                                        Department of Oral and Maxillofacial Surgery,
                                                                                                      Medical College of Georgia School of Dentistry,
                                                                                                                                        Augusta, Georgia
               Addition of a vasoconstrictor to a local anesthetic                     tion has several potentially beneficial effects. It may de-
               may have several beneficial effects: a decrease in                      crease the peak plasma concentration of the local anes-
               the peak plasma concentration of the local                              thetic agent,1'2 increase the duration of anesthesia and
               anesthetic agent, increase in the duration and the                      improve its quality,3'4 decrease the minimum concentra-
               quality of anesthesia, reduction of the minimum                         tion of local anesthetic agent needed for nerve block,5-7
               concentration of anesthetic needed for nerve                            and reduce blood loss during surgical procedures.8'9 The
               block, and decrease of blood loss during surgical                       only vasoconstrictors marketed in the US in combination
               procedures. The addition of a vasoconstrictor to a                      with local anesthetics are epinephrine, levonordefrin, and
               local anesthetic may also have detrimental effects.                     norepinephrine; all are sympathomimetic amines. The
               A review of the literature indicates that                               following discussion will primarily concern epinephrine,
               vasoconstrictor concentrations in local anesthetics                     the best studied and most widely used vasoconstrictor.
               marketed for dental use in the United States are                        The other vasoconstrictors used in local anesthetics in the
               not always optimal to achieve the purposes for                          US, namely levonordefrin and norepinephrine, have not
               which they are added. In most cases, a reduced                          been examined extensively and will be only briefly men-
               concentration of vasoconstrictor could achieve the                      tioned.
               same goal as the marketed higher concentration,                            Epinephrine produces its vasoconstrictor effects by
               with less side-effect liability.                                        binding to and stimulating both a1-, and a2-adrenergic
                                                                                       receptors located in walls of arterioles. Epinephrine also
                                                                                       has /32-adrenergic activity and may cause vasodilation in
                                                                                       tissues, such as skeletal muscle, which have a predomi-
                                                                                       nance of /32-adrenergic receptors. In tissues that have
              A 11 local anesthetics currently available for dental use                approximately equal numbers of a and ,8 receptors, the
                    in the United States (US) have                                     ,/ effects of epinephrine will normally predominate due
           and increase blood flow in the tissuesvasodilating activity                 to greater sensitivity of the /3 receptors to epinephrine. At
           injected. Increased blood flow at the into which they are                   the low systemic concentrations normally associated with
                      increased                         site of injection may          dental anesthesia, epinephrine can increase heart rate
           promote                 blood concentrations of the anesthetic              (a 81-adrenergic effect), cardiac output, and peripheral
           agent, with greater likelihood of overdose reactions. In-                   vasodilation. Local anesthetics with epinephrine marketed
           creased blood flow may also result in a shorter duration                    for dental use in the US contain either 1: 50,000 (0.02
           of anesthetic action; the degree to which the anesthetic                    mg/mL), 1: 100,000 (0.01 mg/mL), or 1:200,000
           action is shortened clinically also depends upon other                      (0.005 mg/mL) concentrations of the vasoconstrictor.
           specific factors, such as tissue binding of the drug. If the                When epinephrine is administered intravenously, it has a
           purpose of the local anesthetic injection is to allow a soft                half-life of 1 to 3 min.
           tissue or osseous surgical procedure to be performed,                          Levonordefrin and norepinephrine, like epinephrine,
           increased local blood flow may resultin increased intraop-                  are direct-acting sympathomimetic amines; their actions
           erative bleeding and complicate the performance of the                      are directly exerted on adrenergic receptors. Levonor-
           surgical procedure.                                                         defrin and especially norepinephrine have qualitatively
              Addition of a vasoconstrictor to a local anesthetic solu-                less /32 activity than epinephrine. Levonordefrin is sup-
                                                                                       plied for dental use in the US only in a 1: 20,000
                                                                                       (0.05 mg/mL) concentration. The 1: 20,000 solution of
           Received April 20, 1992; accepted for publication December 18, 1992.        levonordefrin is believed to have about the same clinical
             Address correspondence to Dr. Allen L. Sisk, Department ofOral and        activity and cardiovascular side-effect liability as an equal
           Maxillofacial Surgery, Medical College of Georgia School of Dentistry,      volume of 1: 100,000 epinephrine10; however, data
           Augusta, GA 30912-1270.                                                     from one animal study suggest that inadvertent intravas-
           C 1992 by the American Dental Society of Anesthesiology                                                               ISSN 0003-3006/92/$6.00
                                                                                 187
                188 Vasoconstrictors Review
                                                                                                                   Anesth Prog 39:187-193 1992
               cular injection of 1: 20,000 levonordefrin might cause               traoral  injection   of  1.8 mL of 2% lidocaine with
               greater stress on the cardiovascular system than the                 1: 100,000 epinephrine (18 ug of epinephrine), Tolas
               standard concentration of epinephrine." Norepinephrine               and coworkers'7 found plasma epinephrine concentra-
               is supplied for dental use in a 1: 30,000 (0.033 mg/mL)              tions to be 240 + 69 pg/mL (mean + SD) compared to a
               strength.                                                            baseline level of 98 + 38 pg/mL. When lidocaine without
                                                                                    vasoconstrictor was injected, plasma epinephrine did not
               POTENTIAL BENEFITS                                                   differ significantly from baseline. In the healthy subjects
                                                                                    in this study, heart rate, mean arterial pressure, and rate-
                                                                                    pressure product were not significantly different from
               While it is generally accepted that addition of a vasocon-           baseline after epinephrine injection. Cioffi et al,18 in a
               strictor will retard local anesthetic absorption into the sys-       study of hemodynamic and plasma catecholamine re-
               temic circulation,12 not all studies have demonstrated de-           sponses to amalgam restoration ofa single tooth with local
               layed local anesthetic absorption. Goebel et al'3 studied            anesthesia (also 1.8 mL of 2% lidocaine with 1: 100,000
               peakplasmaconcentrations oflocalanesthetics aftermax-                epinephrine), found plasma epinephrine to increase
               illary supraperiosteal infiltration of 1.8 mL of 2% lidocaine        from a baseline of 28 + 8 pg/mL to 105 + 28 pg/mL 5
               with 1: 100,000 epinephrine or the same volume of 2%                 (mean + SE) min after injection. Heart rate increased in
               lidocaine without vasoconstrictor. These investigators               parallel with the plasma epinephrine concentration, but
               found that addition of 1: 100,000 epinephrine did not                mean arterial pressure was unaltered. Chernow et al'9
               significantly alter the peak plasma concentration of lido-           found a transient increase in heart rate for 2 min after
               caine. Even if local anesthetic absorption is retarded, it is        inferior alveolar nerve block with epinephrine-containing
               not absolutely certain that this will provide an additional          local anesthetic. Eight min afterinjection, plasma epineph-
               margin of safety. The vasoconstrictor is also absorbed into          rine levels were 3.5 times greater than preinjection control
               the systemic circulation, and its presence could conceiv-            without significant hemodynamic response.
               ably lower the threshold of the central nervous system or               Twostudiesinwhich54,gofepinephrinewasadminis-
               cardiovascular system to the local anesthetic agent.                 tered demonstrated significant cardiovascular system
                  Although adding epinephrine or other vasoconstricting             changes.20'21 In these studies, the use of 5.4 mL of 2%
               agents to local anesthetics usually will increase the dura-          lidocaine with 1: 100,000 epinephrine for unilateral max-
               tion of anesthetic action, this is not true for all local anes-      illary and mandibular third molar extractions resulted in
               thetic drugs in all concentrations. Keesling and Hinds'4             plasma epinephrine titers 5 min after injection that were
               studied the depth and duration of local anesthesia with              approximately five times greater than baseline. Both heart
               lidocaine combined with various strengths of epinephrine.            rate and systolic blood pressure were significantly in-
               Epinephrine concentrations of 1: 250,000 to 1: 300,000               creased. Plasma epinephrine, blood pressure, and heart
               were as effective in prolonging the duration of lidocaine            rate were not significantly increased when 2% lidocaine
               as was 1: 50,000 epinephrine. Gangarosa and Halik3 also              without vasoconstrictor was used for third molar extrac-
               studied the effects of epinephrine concentration on lido-            tions on the opposite sides. Knoll-Kohler et al,22 in a study
               caine local anesthesia, and found 1: 300,000 epinephrine             of cardiovascular and serum catecholamine responses to
               to be as effective on depth and duration of anesthesia               third molar removal with local anesthesia, found that an
               and degree of hemostasis as 1: 100,000 epinephrine.                  increase in circulating epinephrine concentrations to more
               Kennedyetal,15 in a report ofthe cardiorespiratory effects           than six times the previously reported threshold for blood
               of epinephrine in local anesthesia, stated that increasing           pressure increase23 did not cause significant hemody-
               the concentration of epinephrine above 1: 200,000 does               namic changes. A tentative conclusion that may be
               notincrease the duration ofa local anesthetic block. How-            reached from these studies is that, in healthy patients,
               ever, Cowan,16 using a minimum dosage technique, re-                 administration of the dose of epinephrine found in one
               ported that the duration of anesthesia increased as epi-             standard cartridge of 2% lidocaine with 1: 100,000 epi-
               nephrine concentration was raised to 1: 100,000 from                 nephrine results very quickly in plasma epinephrine two
               1: 200,000.                                                          times greater than baseline. This increase is not associated
                                                                                    with any biologically significant cardiovascular change.
               SYSTEMIC UPTAKE AND CARDIOVASCULAR                                   Administration of three standard cartridges of the same
               EFFECTS                                                              local anesthetic/vasoconstrictor combination is associated
                                                                                    with a fivefold increase in plasma epinephrine; significant
               Several studies have looked at the systemic responses to             cardiovascular system changes may occur, but are not
               administration of catecholamines in doses associated with            consistently associated with this dose.
               local anesthetic injections for dentistry. Five min after in-          It is reported that the threshold plasma epinephrine
                                                                                    level for an increase in blood pressure is 50 to 100 pg/
          Anesth Prog 39:187-193 1992                                                                                              Sisk  189
          mL, the threshold foran increase in systolic blood pressure          volume and decreased afterload and mean arterial pres-
          is 75 to 125 pg/mL, and the threshold for a decreased                sure. These hemodynamic changes were more severe in
          diastolic blood pressure is 150 to 200 pg/mL.23 However,             older patients.
          the study from which these threshold values were deter-                Barkin and Middleton26 used electrocardiogram (ECG)
          mined used only six healthy subjects. As mentioned pre-              monitoringin 225 patients undergoing oralsurgical proce-
          viously, the mean maximum circulating epinephrine con-               dures with local anesthetic only (2% lidocaine with
          centrations after administration of 18 ,ug of epinephrine            1: 100,000 epinephrine). Thirty-six patients (16%) were
          were from 105 to 240 pg/mL, and the maximum plasma                   noted to have either preoperative or intraoperative dys-
          epinephrine reported after 54 ,ug of epinephrine was                 rhythmias. No distinction was made between a dysrhyth-
          302 + 142 pg/mL (mean + SD).21 The cardiovascular                    mia detected before local anesthetic/vasoconstrictor injec-
          changes that should have occurred based upon threshold               tion, and those occurring after injection, but the overall
          values did not occur with 18 ,tg of epinephrine, but were            incidence of dysrhythmia was sufficient that the authors
          seen when 54 ,ug was administered.                                   recommended routine precordial stethoscope or ECG
                                                                               monitoring of all patients receiving local anesthetics.
                                                                                 Anargumentfrequently heard forthe inclusion ofvaso-
          ADVERSE EFFECTS                                                      constrictors in local anesthetic solutions is that the amount
                                                                               of endogenousepinephrine released in response to inade-
          Unfortunately, the effects of vasoconstrictors are not al-           quate anesthesia or stress is much greater than that which
          ways beneficial. The cardiac excitatory action of epineph-           reaches the circulation from a dental injection. Many re-
          rine, which is desired in the management of medical emer-            cent studies, using lidocaine with epinephrine as experi-
          gencies such as anaphylaxis, may be detrimental to a                 mental treatment and lidocaine without epinephrine as
          patient with reduced cardiovascular system reserve. An-              control, have not supported this argument.18,20.21.27 These
          gina or myocardial infarction could conceivably result if            studies have used standard dental injections, usually su-
          the patient's cardiovascular system is unable to respond             praperiosteal infiltration, posterior superior alveolar nerve
          to the demands caused by actions of the vasoconstrictor.             block, and inferior alveolar nerve block. Studies of an
          Epinephrine may indirectly cause central nervous system              alternative injection technique, the periodontal ligament
          excitation, as well have effects on metabolism and bron-             injection, have also demonstrated significant effects on the
          chial and gastrointestinal smooth muscle. Signs and symp-            cardiovascular system despite its use of reduced volumes
          toms of vasoconstrictor toxicity include hypertension,               when compared to standard techniques.28 Since the peri-
          tachycardia, tremors, headache, palpitations, and cardiac            odontal ligament injection is essentially an intraosseous
          dysrhythmias.                                                        injection,29 Smith and Pashley feel that the high pressures
             While vasoconstrictors administered with local anes-              developed duringthese injections may force solutions into
          thetics may have minimal effects on healthy patients, they           capillaries and venules so rapidly that the technique may
          may cause significant changes in patients with hyperten-             mimic an intravascular injection.30 Vasoconstrictors in-
          sion, heart disease, hypokalemia, and other medical con-             jected with the local anesthetic are rapidly absorbed into
          ditions, and may interact with other drugs that a patient            the circulation, regardless of the type of dental injection,
          may be taking or receiving as part of the anesthetic man-            and may cause significant cardiovascular system changes
          agement. Most studies of the systemic effects of vasocon-            within minutes of the time of injection.
          strictors in local anesthetic solutions are carried out in
          healthy patient populations. Abraham-Inpijn and others24
          recorded changes in blood pressure, heart rate, and the              DRUG INTERACTIONS
          electrocardiogram during and after tooth extraction under
          local anesthesia for both normotensive and hypertensive              Significant drug interactions may occur between vasocon-
          (preoperative systolic blood pressure -160 mm Hg, or                 strictors injected with local anesthetic agents and either
          diastolic blood pressure - 95 mm Hg) patients. Thirty-               tricyclic antidepressants or /3 blockers. Tricyclic antide-
          eight of 40 patients received 2% lidocaine with 1: 80,000            pressants inhibit the neuronal uptake of catecholamines,
          epinephrine. Both groups showed a statistically significant          resulting in increased concentrations of catecholamines
          increase in blood pressure, but the hypertensive patients            at the sympathetic neuroeffector junction. Yagiela et al31
          experienced greater increases. Also noted was a 7.5%                 found that the cardiopulmonary response to epinephrine
          incidence of potentially dangerous cardiac dysrhythmias              was not significantly affected in tricyclic antidepressant-
          in the hypertensive group. In a study of catecholamine               treated dogs if the dose of epinephrine was less than 0.67
          effects on cardiovascular function Kiyomitsu et a125 found           mg/kg. From these data a maximum limit of 0.05 mg of
          thatthe addition of 1: 80,000 epinephrine to2% lidocaine             exogenous epinephrine was proposed for the patient on
          resulted in increased cardiac output, heart rate, and stroke         tricyclic antidepressants. Yagiela et al reported that the
                                      Review
               190 Vasoconstrictors                                                                             Anesth Prog 39:187-193 1992
               action of epinephrine was increased in dogs concurrently           tentiation of lidocaine toxicity by epinephrine could be
               administered the tricyclic antidepressant desiprimine two          due to either epinephrine-induced effects on the cardio-
               to four times and that the potency of levonordefrin and            vascular system, which alter the distribution of lidocaine,
               norepinephrine was increased seven to eightfold in these           or a lidocaine-epinephrine interaction that directly en-
               experimental animals.31                                            hances central nervous system or cardiovascular system
                 Beta blockers inhibit the vasodilation of arterioles by          toxicity.
               sympathomimetic drugs. This a-receptor blockade will
               allowthe vasoconstricting a-adrenergic effects ofepineph-
               rine to predominate, since compensatory vasodilation               HEMOSTASIS
               cannotoccur. Administration ofepinephrine oreven levo-
               nordefrin to a patient who is f8 blocked may result in a           Vasoconstrictors are added to local anesthetic solutions
               significant increase of blood pressure.32 The more cardio-         to provide hemostasis at surgical sites. A 1: 50,000 con-
               selective (,81) the blocker is the less chance there is for        centration of epinephrine is sometimes used for this pur-
               this interaction to occur.33                                       pose, although many studies have shown that this is not
                 It is unclear whether inclusion of a vasoconstrictor in          the concentration of epinephrine that provides optimal
               the local anesthetic solution alters the response to the           vasoconstriction balanced with potential for cardiovascu-
               local anesthetic agent if inadvertent intravascular injection      lar system toxicity. For example, studies of epinephrine's
               occurs. Since epinephrine is used in the treatment of local        effects on cutaneous blood flow have indicated that no
               anesthetic-induced cardiovascular collapse, it has been            measurable difference exists between equal volumes of
               suggested that epinephrine-containing local anesthetic so-         1: 50,000, 1: 100,000, and 1: 200,000 solutions.40 Har-
               lutions are safer than the local anesthetic alone. Moore           rington and Carpenter,41 in a study using a laser Doppler
               andScurlock hypothesized that added epinephrine would              device to follow dynamic changes in skin perfusion after
               counteract local anesthetic cardiovascular toxicity.34 Ber-        infiltration of 1% lidocaine with graded concentrations of
               nards et al,35 in a study to determine whether 1: 200,000          epinephrine, found that the lidocaine alone caused an
               epinephrine altered bupivacaine toxicity, administered             increase in local blood flow of two to three times base-
               bupivacaine with or without epinephrine intravenously to           line. Five min after infiltration of 1% lidocaine plus
               pigs until cardiovascular collapse occurred. Epinephrine           epinephrine      (1: 50,000,     1:100,000,       1:200,000
               had no effect on the dose of bupivacaine that caused               1: 400,000), the vasodilating effect of lidocaine was effec-
               cardiovascular collapse or the ability to resuscitate the          tively counterbalanced by each of these concentrations.
               animals. Epinephrine, however, decreased the dose of               Concentrations of 1: 800,000 and 1: 1,600,000 were not
               bupivacaine that produced cardiac dysrhythmias and sei-            reliably effective at 5 and 10 min. Periodontal flap surgery
               zures, although the plasma concentration of bupivacaine            may be an exception, however, in that the 1: 50,000
               was identical in the two groups at onset of seizures. The          concentration might be superior to more dilute solutions
               authors felt that epinephrine produced a peripheral vaso-          of epinephrine. According to a study by Buckley et al,42
               constriction that resulted in a reduced volume of distribu-        blood loss with 2% lidocaine plus 1: 100,000 epinephrine
               tion and led to exposure of the central nervous system             injected locally for hemostasis is more than double that
               to a higher concentration of bupivacaine. In this model            when 2% lidocaine with 1: 50,000 epinephrine is used.
               of local anesthetic toxicity, epinephrine did not increase
               the margin of safety of the local anesthetic; it did not           Ropivacaine
               protect the animals against bupivacaine-induced cardio-
               vascular collapse; nor did it make the animals any easier          Ropivacaine, a new long-acting local anesthetic, has been
               to resuscitate after collapse. Other animal studies have           demonstratedto causevasoconstriction when used alone.
               shown that epinephrine may potentiate the lethality of             Kopacz et al43 evaluated both bupivacaine and ropiva-
               the local anesthetic when both drugs are administered              caine, with and without added epinephrine, for effects on
               intravascularly. Measurements ofradioactive-labeled lido-          local cutaneous blood flow after subcutaneous infiltration
               caine have shown that epinephrine promotes entry of                in pigs. Solutions of 0.25% and 0.75% ropivacaine re-
               local anesthetics into brain tissues due to a greater propor-      duced blood flow by 52% and 54%, respectively. Solu-
               tion of cardiac output being directed to the brain.36'37           tions of 0.25% bupivacaine increased blood flow by 90%,
               Kambam and associates,' in a survival study of rats after          and 0.75% bupivacaine increased blood flow by 82%.
               cardiotoxic doses of 0.5% bupivacaine with or without              Ropivacaine may prove to be a useful agent in dentistry.
               1: 200,000 epinephrine, found that the addition of epi-            If its vasoconstricting effect decreases its vascular uptake
               nephrine potentiated the cardiotoxic effects of bupiva-            and prolongs its action, ropivacaine could be used alone,
               caine. Yagiela,39 in a report conceming the influence of           thereby eliminating potential side effects from systemic
               epinephrine on lidocaine toxicity, postulated that the po-         absorption of epinephrine.
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...Anesth prog briefreviews vasoconstrictors in local anesthesia for dentsty allen l sisk dds department of oral and maxillofacial surgery medical college georgia school dentistry augusta addition a vasoconstrictor to anesthetic tion has several potentially beneficial effects it may de have decrease crease the peak plasma concentration anes thetic agent increase duration improve its quality minimum concentra reduction needed nerve block reduce blood loss during surgical procedures only marketed us combination with anesthetics are epinephrine levonordefrin also detrimental norepinephrine all sympathomimetic amines review literature indicates that following discussion will primarily concern concentrations best studied most widely used dental use united states other not always optimal achieve purposes namely which they added cases reduced been examined extensively be briefly men could tioned same goal as higher produces by less side effect liability binding stimulating both adrenergic recept...

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