local anesthetics - Hamad Medical Corporation

SRPS 10(18) Pt 2, 2007TABLE 2Characteristics of Ester and Amide Local Anesthetics(Reprinted with permission from Schecter WP, Swisher JL: Local anesthesia in surgical practice. Curr Probl Surg Jan 2000:10-66.)The proportion of uncharged base to charged cationdepends upon the pH of the solution and the pKa of thecompound. A decrease in pH will shift the equilibriumtoward the “inactive” charged cation form and result inrelatively more cation present than “active” base. Onthe other hand, a rise in pH changes the equilibrium infavor of the active free base form. Local anesthetics withhigh pKa’s of 7.6–7.8, like lidocaine and etidocaine, showrelatively rapid onset at normal tissue pH of 7.4 becauseapproximately 35% of the drugs are in the active baseforms. By comparison, bupivacaine and tetracaine, withpKa’s between 8.1 and 8.9, are 80% to 95% cation at normaltissue pH of 7.4, and their onset of action is muchslower. 21Alkalinization of a local anesthetic with sodiumbicarbonate speeds the drug’s onset and enhances its8

SRPS 10 (18) Pt 2, 2007effect. 22 In the presence of infection and inflammation,local anesthetics may fail. Inflammation leads to a moreacidic tissue environment, which causes local anestheticagents to exist in largely inactive cationic forms and limitstheir local anesthetic effects. 23DiffusabilityThe speed of onset of a local anesthetic is affected by thediffusion rate of the compound through tissues otherthan nerve. For example, procaine and chloroprocainehave similar pKa and onset times in vitro, but in livingtissue chloroprocaine acts more quickly than procainebecause it diffuses faster through nonneural tissue.Another example is lidocaine, which in the laboratory issimilar to prilocaine in pKa value and onset of action butwhich clinically has much faster anesthetic effect due toits higher diffusability.Intrinsic Vasodilator ActivityAll local anesthetics except cocaine exhibit a vasoactiveeffect on vascular smooth muscle. At very lowconcentrations they cause vasoconstriction, but at clinicallyrelevant concentrations local anesthetics tend tobe vasodilatory. Vasodilation will promote removal oflocal anesthetic molecules from the site of action,thereby decreasing the intensity of block and durationof action. Epinephrine added to the local anestheticsolution counters these effects and prolongs durationof action.Clinical FactorsPharmacokinetics is the fate of drugs in the body over aperiod of time, including the processes of absorption,distribution, localization in tissues, biotransformation,and excretion. The pharmacokinetics of a local anestheticare affected by body weight, general health, andconcurrent medical disorders or therapies.DosageThe mass of local anesthetic (ie, the number of milligramsadministered) influences the onset, depth of block, andduration of action—for example, 20mL of 1% lidocaine isequivalent to 10mL of 2% lidocaine in its effect. In theepidural space, however, a higher volume of drug isassociated with increased dermatomal spread.Addition of VasoconstrictorEpinephrine is frequently added to local anesthetic solutionsfor its vasoconstrictive, hemostatic effect and toprolong lidocaine analgesia by decreasing the rate ofabsorption. This has the effect of decreasing the rate atwhich local anesthetic molecules leave the site of actionto be absorbed into the systemic circulation; thus thelocal anesthetic activity is more profound, with a longerduration of action, and the potential for systemic toxicityis lessened.Effective vasoconstriction can be achieved with as littleas 1:800,000 epinephrine added to the local anestheticsolution. 24 However, this mixture is unstable after a fewhours, must be mixed by hand, and requires a longerpostinjection interval for maximum effect. Commercialsolutions of 1:100,000 and 1:200,000 epinephrine are commonlyused because they are readily available.Epinephrine use is not without risk. Cardiacarrhythmias are a concern in persons who have predisposingintrinsic heart disease or when epinephrine isadministered concomitantly with agents that sensitizethe myocardium (eg, halothane). Epinephrine may precipitatea hypertensive crisis in patients who havehypertension or hyperthyroidism. High concentrationsof epinephrine may produce local tissue necrosis or triggerrebound hyperemia, resulting in bleeding orhematoma as the effect resolves. At dilutions of 1:200,000,epinephrine is detrimental to the survival of delayedskin flaps. 25,26Epinephrine 1:1,000,000 is commonly added to wettingsolution during liposuction, 27 and patients may beexposed to total doses of epinephrine >5–10mg duringcases involving large volumes of lipoaspirate and infiltration.Epinephrine toxicity may play a role in some ofthe deaths associated with liposuction, although this isdifficult to prove at autopsy for the following reasons: 1)postmortem metabolism; 2) the ultra short half-life ofepinephrine (T½ = 2min); 3) difficulty distinguishingendogenous from exogenous epinephrine; and 4) unclearsource because epinephrine is often administered duringattempts at resuscitation.9

SRPS 10(18) Pt 2, 2007Site of InjectionSpinal anesthesia is associated with a rapid onset andrelatively short duration of action. In contrast, regionaltechniques such as a brachial plexus block typicallyhave a slow onset and long duration of action, perhapsbecause of the large volumes of anesthetic solutionused. 28AdditivesCombining local anesthetics with other agents has beensuggested to speed the onset of the block by lowering theintracellular pH to increase the proportion of cationsand trap them in the axoplasm. Though early studieswere promising, 29 later trials failed to demonstrate anadvantage. 30On the other side of the cell membrane, sodium bicarbonatehas been added to increase the pH of the solution,which would then increase the amount of drug in theuncharged base form, promote diffusion across the nervemembrane, and decrease the latency. This has been demonstratedto be clinically effective in brachial plexusblock. 31,32CompoundingMixtures of local anesthetic agents take advantage of certainqualities of each drug. For example, chloroprocaine,lidocaine, or mepivacaine, all of which have rapid onsetof action, could be combined with tetracaine orbupivacaine to increase the duration of action of thesolution. 33 Compounding also allows single-dose injectionfor epidural or caudal block in cases where a continuoustechnique would be mandatory if a single agentwere to be used.The toxicity of a mixture is no greater than that of itsindividual components. 34,35 When short-acting agents—present in the serum early—are combined with longactingagents, their effect on excitable membranes neverexceeds the toxic threshold.Mixtures of ester- and amide-type local anestheticscapitalize on different routes of disposition, meaning thatlarger volumes of each drug can be administered perdose. To date there are no studies of any possible toxicityof these combinations.AbsorptionAbsorption depends on vascularity at the injection site:The more vascular the site of local anesthetic infiltration,the greater the absorption rate. Lidocaine andbupivacaine are absorbed faster from the highly vascularepidural space than from poorly perfused subcutaneoustissue.The rate of systemic absorption is controlled by theextent of local binding. The peak concentration is ultimatelylower and is reached after a longer period of timefor lipophilic drugs compared to hydrophilic drugs. 36Systemic ToxicityLocal anesthetics vary considerably in their potentialfor causing systemic toxic reactions. In clinical practice,the systemic toxic responses to local anesthetic drugsmay result from unintentional intravascular injectionof an appropriate dose (Table 3) or from excessive dosing.Toxicity secondary to extravascular administrationis related to the pharmacokinetic properties of thedrug. 5 TABLE 3Recommended Maximum Doses of Local Anesthetics(Reprinted with permission from Schecter WP, Swisher JL: Localanesthesia in surgical practice. Curr Probl Surg Jan 2000:10-66.)CNS ToxicityMost toxic reactions involve the central nervous system.Local anesthetic-induced cardiovascular depressionoccurs infrequently but tends to be serious and difficultto manage. There is a biphasic response to elevatedlevels of local anesthetic in the CNS. Initially there is anexcitatory phase resulting from blockage of inhibitory pathwaysin the amygdala that manifests as muscle twitching,first in the face and distal extremities, that progressesto tremors and ultimately to generalized tonic-clonic10

SRPS 10 (18) Pt 2, 2007convulsion. As the anesthetic levels in the CNS rise, adepressive phase ensues, evidenced by drowsiness, unconsciousness,and respiratory arrest. 37 Occasionally theexcitatory phase may be skipped, as seen with directinjection of local anesthetic into the carotid or vertebralartery and immediate rise of drug level in the brain,especially when sedatives have been administered.Hypercapnea increases cerebral blood flow anddecreases protein binding, with the result that a higheramount of free drug will be available in the brain. Acidosiswill increase the cationic form of local anestheticand theoretically lessen diffusion across the cell membrane,yet it potentiates toxicity. In fact, one of the keyelements of treatment is to control ventilation and bringabout respiratory alkalosis.Cardiovascular ToxicityThe cardiovascular system is more resistant than thecentral nervous system to the effect of local anesthetics,and CNS manifestations are typically seen first, at lowerblood levels of the drug. In the cardiovascular system,local anesthetics affect both conduction pathways andcontractility of the heart and blood vessels. 37 The ratioof blood levels required to produce irreversible cardiovascularcollapse to blood levels required to elicit convulsionsis the CC/CNS ratio. In adult sheep, this ratio islower for bupivacaine than for the less lipid-solublelidocaine (2.7 vs 7.0). 38 In other words, early warningsigns of CNS toxicity from bupivacaine occur at muchlower blood levels and, if recognized and treated appropriately,cardiovascular collapse can be averted.In 1979, Albright 39 demonstrated the correlationbetween cardiovascular toxicity and the longer-acting,highly lipid-soluble local anesthetics bupivacaine andetidocaine. Of 49 fatal cases, 43% involved bupivacaine.The FDA subsequently warned against the use of 0.75%bupivacaine in obstetrical practice. Since this time, therehas been a decrease in the incidence of severe cardiactoxicity.High concentrations of local anesthetic in the CNS mayalso contribute to local anesthetic toxicity in the cardiovascularsystem. Direct application of local anestheticswithin vasomotor and cardioactive regions of themedulla may lead to hypotension, bradycardia, and ventriculararrhythmias. 40 Despite sharing the same site ofaction at the medulla, bupivacaine is 2–4X more potentthan lidocaine in producing cardiovascular effects in rats.The arrhythmias can be terminated by midazolamadministration. 41Most incidents of cardiac toxicity from bupivacainehave been in pregnant women, 37 mirroring the results inpregnant ewes. 38 This increased susceptibility to cardiovasculartoxicity in pregnancy is not seen with otheragents. 37Prevention of Systemic ToxicityAuletta and Grekin 42 recommend several practical stepsto prevent systemic toxicity during local anestheticadministration, as follows:• Use the lowest dose necessary to induce anesthesia.• Before reinjecting an area, allow sufficient time forthe anesthetic to work, particularly when using anagent with long onset of action.• Avoid intravenous infusion by exercising carefultechnique and by aspirating before injection.• Use epinephrine unless contraindicated.• Employ nerve blocks when possible.• When anesthetizing a large area, use the lowesteffective concentration of anesthetic.Careful technique with attention to appropriate dosageguidelines will go a long way to preventing localanesthetic toxicity. Nevertheless, unrecognized intravascularinjections can still occur despite negative aspirationtests. Some authors recommend the use of a testdose containing epinephrine for detecting intravascularinjection, but not in pregnant patients. ECG monitoringis a useful indicator of bupivacaine toxicity. An increasein the blood concentration of bupivacaine is associatedwith decreased R wave amplitude and increased QRScomplex. Despite significantly decreased cardiac outputof up to 40%, the blood pressure is maintained and cannotbe used as a sign of impending toxicity. 43Treatment of Toxic ReactionsThe treatment of seizures induced by local anestheticsincludes placing the patient in the recovery position;delivering oxygen by face mask; maintaining the air-11

SRPS 10(18) Pt 2, 2007way; and ventilatory support if necessary. Hyperventilationmay increase the seizure threshold. Intravenousadministration of 5–10mg of diazepam is recommendedto control seizures 37,44–46 (Table 4).Allergic ReactionsAllergic reactions to local anesthetics are more commonwith ester-type local anesthetics than with amide-classcompounds. The metabolic product of ester local anestheticsis para-aminobenzoic (PABA), which is highlyallergenic. When an allergic response to an amide localanesthetic occurs, it is usually due to preservatives suchas methylparabens and metabisulfite. 47 Symptoms oftype 1 reactions include pruritus, urticaria, erythema,facial swelling, nausea, vomiting, abdominal cramps anddiarrhea, coughing, wheezing, dyspnea, cyanosis, andlaryngeal edema. Recommended treatment for mildallergic reactions consists of administration of epinephrine0.3–0.5mg subcutaneously every 20–30 minutes. Foranaphylaxis, epinephrine 0.5mg (5mL in 1:10,000 solution)intravenously repeated every 5–10 minutes is thetreatment of choice. It is essential to maintain thepatient’s airway and deliver oxygen. 48COCAINECocaine is the only local anesthetic that produces bothnerve block and vasoconstriction, yet its dangerous sideeffectsand abuse potential confine its use primarily totopical analgesia of the upper respiratory tract. 49 Theduration of anesthesia is 30 minutes and the maximumsafe dose is 200mg.In 1930, a morphine-cocaine elixir was introduced asan analgesic post thoracotomy at the Brompton Hospitalin London. Forty-some years later, “Brompton’s cocktail”was standardized in the British PharmaceuticalCodex as consisting of 10mg diamorphine hydrochloride,10mg cocaine hydrochloride, 1.25mL 90% ethylalcohol, 2.5mL syrup, and 10mL chloroform water. 50 TheBrompton formula was used for pain relief of terminallyill patients until very recently.Cocaine is usually excluded from the “euphoriant elixirs”today because it was found to cause restlessnessand confusion. 51LIDOCAINEThe potential for toxic reactions from lidocaine is theoreticallyless with increasing body weight. Obesepatients can accommodate higher volumes of the drugbecause of greater absorption by the tissue mass.Lidocaine is extensively bound to alpha-1 acid glycoprotein,a plasma protein that is also an acute phasereactant. Increases in alpha-1 acid glycoprotein concentrationare seen after acute myocardial infarction, withcorresponding decreases in free lidocaine in the plasmaand total plasma lidocaine clearance. Patients withaltered hepatic blood flow, eg, from congestive heart failureand hypotension, have reduced metabolism oflidocaine and may be at greater risk of toxic reactions.Lidocaine metabolism may be faster or slower in thepresence of drugs that induce or inhibit cytochrome P-450 CYP3A4 isoenzyme. The clinician must be aware ofother medications the patient is taking to avert unwelcomeinteractions with lidocaine. 52 In addition, 5% ormore of surgical patients use herbal remedies, some ofwhich—garlic, ginseng, ginkgo biloba, and echinacea, forexample—are metabolically active and may reducelidocaine elimination. St John’s wort, another commonlyavailable herbal remedy, is a P-450 CYP3A4 inducer andtherefore enhances lidocaine metabolism.TABLE 4Management of Local Anesthetic and Epinephrine Overdose Reactions(Reprinted with permission from Koerner KR, Taylor SE: Emergencies associated with local anesthetics. Dentistry Today; Oct 2000:72-79.)12

SRPS 10 (18) Pt 2, 200714. Ritchie JM: Voltage-gated cation and anion channels inmammalian Schwann cells and astrocytes. J Physiol (Paris)82(4):248, 1987.15. Butterworth JF 4th, Strichartz GR: Molecular mechanisms oflocal anesthesia: a review. Anesthesiology 72(4):711, 1990.16. Perlia X, Buchi J: Physico-chemical properties and localanesthetic activity in the cinchocaine series. Boll Chim Farm101:497, 1962.17. De Jong RH: Local Anesthetics. St Louis, Mosby-Year Book,1994.18. Lund PC, Cwik JC, Pagdanganan RT: Etidocaine – a new longactinganesthetic agent: a clinical evaluation. Anesth Analg52(3):482, 1973.19. Courtney KR, Kendig JJ, Cohen EN: Frequency-dependentconduction block: the role of nerve impulse pattern in localanesthetic potency. Anesthesiology 48(2):111, 1978.20. Setnikar I: Ionization of bases with limited solubility. Investigationof substances with local anesthetic activity. J PharmSci 55(11):1190, 1966.21. Covino BG: Physiology and pharmacology of local anestheticagents. Anesth Prog 4:98, 1981.22. Rud J: Local anesthetics. An electrophysiological investigationof local anesthesia of peripheral nerves, with specialreference to xylocaine. Acta Physiol Scand Suppl 51(178):1,1961.23. Brown RD: The failure of local anesthesia in acute inflammation—somerecent concepts. Br Dent J 151:47, 1981.24. Siegel RJ, Vistnes LM, Iverson RE: Effective hemostasis withless epinephrine. An experimental and clinical study. PlastReconstr Surg 51:129, 1973.25. Reinisch J, Myers B: The effect of local anesthesia with epinephrineon skin flap survival. Plast Reconstr Surg 54:324, 1974.26. Wu G, Calamel PM, Shedd DP: The hazards of injecting localanesthetic solutions with epinephrine in flaps. Plast ReconstrSurg 62:396, 1978.27. Burk RW 3rd, Guzman-Stein G, Vasconez LO: Lidocaine andepinephrine levels in tumescent technique liposuction. PlastReconstr Surg 97(7):1379, 1996.28. Yan AC, Newman RD: Bupivacaine-induced seizures andventricular fibrillation in a 13-year-old girl undergoing wounddebridement. Pediatr Emerg Care 14(5):354, 1998.29. Bromage PR: Improved conduction blockade in surgery andobstetrics: carbonated local anesthetics. Can Med Assoc J97(23):1377, Dec 2 1967.30. Morison DH: A double-blind comparison of carbonatedlidocaine and lidocaine hydrochloride in epidural anaesthesia.Can Anaesth Soc J 28(4):387, 1981.31. Fulling PD, Peterfreund RA: Alkalinization and precipitationcharacteristics of 0.2% ropivacaine. Reg Anesth Pain Med25(5):518, 2000.32. Tetzlaff JE, Yoon HJ, O’Hara J, et al: Alkalinization ofmepivacaine accelerates onset of interscalene block forshoulder surgery. Reg Anesth 15(5):242, 1990.33. Moore DC et al: Does compounding of local anestheticagents increase their toxicity in humans? Anesth Analg51:579, 1972.34. De Jong RH, Bonin JD: Mixtures of local anesthetics are nomore toxic than the parent drugs. Anesthesiology 54:177, 1981.35. Kennedy KS, Cave RH: Anaphylactic reaction to lidocaine.Arch Otolaryngol Head Neck Surg 112:671, 1986.36. Taka GT, Mayfair LE: Physicochemical properties: absorptionand disposition of local anesthetic agents. In: CousinsMJ, Britton PO (eds), Neural Blockade in Clinical Anesthesiaand Management of Pain, 2nd ed. Philadelphia, JB Lippincott,1988, pp 47-110.37. Englesson S, Grevsten S: The influence of acid-base changeson central nervous system toxicity of local anaestheticagents. I and II. Acta Anaesthesiol Scand 18(2):79, 1974.38. Morishima HO, Pedersen H, Finster M, et al: Bupivacainetoxicity in pregnant and nonpregnant ewes. Anesthesiology63:134, 1985.39. Albright GA: Cardiac arrest following regional anesthesiawith etidocaine or bupivacaine. Anesthesiology 51:285, 1979.40. Thomas RD, Behbehani MM, Coyle DE, et al: Cardiovasculartoxicity of local anesthetics: an alternative hypothesis.Anesth Analg 65:444, 1986.41. Bernards CM, Artru AA: Effect of intracerebroventricularpicrotoxin and muscimol on intravenous bupivacaine toxicity.Evidence supporting central nervous system involvementin bupivacaine cardiovascular toxicity. Anesthesiology78:902, 1993.42. Grekin RC, Auletta MJ: Local anesthesia in dermatologicsurgery. J Am Acad Dermatol 19(4):599, 1988.43. Nystrom EU, Heavner JE, Buffington CW: Blood pressure ismaintained despite profound myocardial depression duringacute bupivacaine overdose in pigs. Anesth Analg 88(5):1143,1999.44. De Jong RH, Heavner JE: Local anesthetic seizure prevention:diazepam versus pentobarbital. Anesthesiology 36(5):449, 1972.45. Sawaki K, Ohno K, Miyamoto K, et al: Effects of anticonvulsantson local anaesthetic-induced neurotoxicity in rats. PharmacolToxicol 86(2):59, 2000.46. Koerner KR, Taylor SE: Emergencies associated with localanesthetics. Dent Today 19(10):72, 2000.47. Campbell JR, Maestrello CL, Campbell RL: Allergic responseto metabisulfite in lidocaine anesthetic solution. Anesth Prog48(1):21, Winter 2001.48. Malamed SF: Allergy and toxic reactions to local anesthetics.Dent Today 22(4):114, 118, 2003.49. Hashisaki GT, Johns ME: Cocaine applications inotorhinolaryngologic anesthesia. Contemp Anesth Pract9:31, 1987.50. Noorily AD, Noorily SH, Otto RA: Cocaine, lidocaine,tetracaine: which is best for topical nasal anesthesia? AnesthAnalg 81(4):724, 1995.51. Kaiko RF, Kanner R, Foley KM, et al: Cocaine and morphineinteraction in acute and chronic cancer pain. Pain 31(1):35, 1987.52. Kenkel JM, Lipschitz AH, Shepherd G, et al: Pharmacokineticsand safety of lidocaine and monoethylglycinexylidide inliposuction: a microdialysis study. Plast Reconstr Surg114(2):516, 2004.53. Klein JA: The tumescent technique. Anesthesia and modifiedliposuction technique. Dermatol Clin 8(3):425, 1990.54. McClure JH: Ropivacaine. Br J Anaesth 76(2):300, 1996.55. Geiser RR, Venkateswaren P, Cheek TG, et al: Comparisonof 0.25% ropivacaine and bupivacaine for epidural analgesiafor labor and vaginal delivery. J Clin Anesth 9(7):564, 1997.56. Knudsen K, Beckman Suurkula M, Blomberg S, et al: Centralnervous and cardiovascular effects of i.v. infusions ofropivacaine, bupivacaine and placebo in volunteers. Br JAnaesth 78(5):507, 1997.15

SRPS 10(18) Pt 2, 200757. Stewart J, Kellett N, Castro D: The central nervous system andcardiovascular effects of levobupivacaine and ropivacainein healthy volunteers. Anesth Analg 97(2):412, 2002.58. Ladd LA, Chang DH, Wilson KA, et al: Effects of CNS sitedirectedcarotid arterial infusions of bupivacaine,levobupivacaine, and ropivacaine in sheep. Anesthesiology97(2):418, 2002.59. Shafer A, White PF, Urquhart ML, Doze VA: Outpatientpremedication: use of midazolam and opioid analgesics.Anesthesiology 71(4):495, 1989.60. Baker TJ, Gordon HL: Midazolam (Versed) in ambulatorysurgery. Plast Reconstr Surg 82(2):244, 1988.61. White PF, Vasconez LO, Mathes SA, et al: Comparison ofmidazolam and diazepam for sedation during plastic surgery.Plast Reconstr Surg 81(5):703, 1988.62. Schneider M, Datta S, Strichartz G: A preferential inhibitionof impulses in C-fibers of the rabbit vagus nerve by veratridine,an activator of sodium channels. Anesthesiology74(2):270, 1991.63. Son SL, Wong K, Strichartz G: Antagonism by local anestheticsof sodium channel activators in the presence of scorpiontoxins: two mechanisms for competitive inhibition. Cell MolNeurobiol 24(4):565, 2004.64. Kuzma PJ, Kline MD, Calkins MD, Staats PS: Progress in thedevelopment of ultra-long-acting local anesthetics. RegAnesth 22(6):543, 1997.65. Scurlock JE, Curtis BM: Tetraethylammonium derivatives:ultralong-acting local anesthetics? Anesthesiology 54(4):265,1981.66. Narahashi T: Nerve membrane ionic channels as the targetof toxicants. Arch Toxicol Suppl 9:3, 1986.CARDIOPULMONARY RESUSCITATIONAND ADVANCED CARDIAC LIFE SUPPORTIntroductionCardiac arrest is defined as the sudden and unexpectedcessation of myocardial contractility for a period of 60seconds. 1 About 1000 Americans experience cardiacarrest daily. 2 The most common cause of cardiac arrestis heart-related in adults and of respiratory origin inchildren. Respiratory arrest can result from a numberof causes, including near-drowning, stroke, foreign bodyairway obstruction, smoke inhalation, epiglotitis, drugoverdose, electrocution, suffocation, myocardial infarction,lightning strike, or coma. In cardiac arrest, the bloodceases to flow and vital organs are deprived of oxygen.Regardless of the cause of arrest, asphyxia is the proximatecause of sudden death. The key to resuscitation isto reverse asphyxia by transporting oxygen to tissues,reoxygenating the myocardium, and restoring myocardialcontractility.The technique of cardiopulmonary resuscitation wasdescribed by Kouwenhoven, Jude, and Knickerbocker in1960. 3 There is little question that early intervention isvital for survival in cardiorespiratory arrest. Whenbasic life support is instituted within 1 minute of arrest,there is a 99% chance of surviving 24 hours. When lifesupport does not begin for 10 minutes or more afterarrest, the likelihood of survival plummets to approximately1 in 10,000. 4There is some controversy regarding the mechanismfor restoring blood flow during cardiopulmonary resuscitation(CPR). There are two basic theories. One theoryholds that the heart is compressed between the sternumand the thoracic spine, forcing blood out of the heartduring closed cardiac massage. 5–7 A second theory isthat chest compressions cause a general intrathoracicpressure increase—a “thoracic pump”—and that bloodflow is not in fact dependent on ventricular compression.8 During chest compression the increase in intrathoracicpressure is transmitted as increased intravascularpressures that are differentially transmitted peripherallyas a result of venous valve closure.Indications and Contraindications to CPRThe goal of medical interventions such as CPR is to preservelife, restore health, relieve suffering, and limit disability.Unique to CPR is the reversal of clinical deathand the fact that CPR is initiated without a physician’sorder.CPR may not be in the patient’s best interest. 9,10 Withlimited resources, resuscitation may be a burden onmedical infrastructure, though many would argue thatconcerns about the costs of prolonged ICU care shouldnot be part of the decision whether to administer CPR.Clearly, CPR should not be used to prolong the lives ofterminal patients.All patients admitted to a medical or surgical facilityshould be asked to sign advance directives—living wills,do not resuscitate (DNR) orders, or durable powers ofattorney (DPA)—to guide caregivers in the event the16

SRPS 10 (18) Pt 2, 2007patient becomes seriously ill or permanently unconscious.Unlike living wills, a DPA lets patients choosewhom they would appoint to make medical decisionsfor them if they become incapacitated.There is no way to predict whether resuscitationattempts will be futile. 11 The medical literature supportsattempted resuscitation for all patients except when• attempts to perform resuscitation place the rescuerat risk of physical injury• there is a DNR order or a valid surrogate declinesresuscitation• the patient shows signs of irreversible arrest: rigormortis, dependent lividity, decapitation• no benefit can be expected from resuscitation becausephysiologic processes have deteriorated despite maximaltherapy—eg, cardiogenic shock, septic shock• newborn infants have birth weight

SRPS 10(18) Pt 2, 2007sensor followed by an esophageal detector device (EDD)if no color change is seen. 26In 2000, the American Heart Association updated itsguidelines for cardiopulmonary resuscitation, whichnow call for 100 chest compressions per minute and 2breaths for every 15 chest compressions. These guidelinesapply whether one or two workers are performingCPR. The victim should be in the horizontal supineposition on a firm surface to optimize the effect of compressionson the lower half of the sternum. Of note, theAHA now recommends that lay rescuers do not checkthe pulse before beginning CPR because of the low sensitivityof this test in a lay rescuer’s hands. 27Most adults with sudden, witnessed, nontraumaticcardiac arrest are found to be in ventricular fibrillation. 22Early CPR prevents the ventricular fibrillation fromdeteriorating to asystole, may increase the chance of successfuldefibrillation, contributes to preservation of heartand brain function, and improves survival. Earlydefibrillation is the most important determinant of survivalfor adult victims of cardiac arrest. Survival fromcardiac arrest caused by ventricular fibrillation declines7–10% for each minute without defibrillation.Public access defibrillation (PAD) programs strive tomake automated external defibrillators ubiquitous anduniversally available. Police officers, firefighters, flightattendants, and other lay persons have been trained inthe use of AEDs, and resuscitation rates as high as 49%have been achieved. 20Active compression-decompression CPR is associatedwith increased 24-hour survival rates 28–33 but less clearlywith long-term survival. 34,35 In patients with high-riskcardiac arrhythmias (tachyarrhythmias), simple coughingcan prolong consciousness for sustained periods andcan even lead to resolution of the arrhythmia and restorationof normal cardiac rhythm. 36The interposed abdominal compression (IAC-CPR)technique 37–42 has been proposed to improve cardiac outputduring CPR. During standard CPR, systolic arterialpressures of 60–80mmHg can be obtained, but diastolicpressures tend to be low. Total blood flow is only 20–35% of normal and coronary perfusion pressure is often

SRPS 10 (18) Pt 2, 2007external defibrillator is an extremely useful device tohave in your office.3) In offices where surgical procedures are regularly performed,an arrangement should be in place for the transferof a critically ill patient to an appropriate nearbyfacility. In other words, you must establish a relationshipwith your local emergency room, ambulance service,and hospital ER before starting to do surgeries inyour office.CPR in ChildrenMost cases of cardiopulmonary arrest in infants andchildren under 8 are caused by airway or ventilationproblems. 43 The resuscitation priority therefore changesto restore breathing by a trained rescuer, 44 rather thanto call the EMS for defibrillator assistance.Clearing the AirwayThe tongue is the most common cause of airway obstructionin the unresponsive victim. Because the tongue isattached to the lower jaw, when you move the lowerjaw forward you will lift the tongue away from the backof the throat and open the airway. If there is no evidenceof head or neck trauma, use the head tilt–chin liftmaneuver (Fig 1) to move the tongue out of the way.Remove any foreign material from the mouth with ahooked index finger while keeping the forehead tiltedback and the jaw forward.Bag-mask ventilation is more effective than manualbreathing but requires more skill and should be usedonly by trained personnel. Training should focus onselection of an appropriately sized mask and bag,opening the airway and securing the mask to the face,delivering adequate ventilation, and assessing theeffectiveness of ventilation. Regardless of the size ofthe bag-mask system, the rescuer should use only theforce and tidal volume necessary to cause the chest torise visibly. 44Figure 1. Head tilt–chin lift maneuver lifts the tongue out of theway to help relieve airway obstruction. (Reprinted with permissionfrom Guidelines 2000 for Cardiopulmonary Resuscitation andEmergency Cardiovascular Care: International Consensus on Science.Part 3: Adult Basic Life Support. Circulation 102(8) Suppl:I122-I159, 22 August 2000.)consensus is that neonates should receive 90 compressionsper minute instead of 120, with a 3:1 ratio of compressionsto ventilations. Chest compressions shouldbegin when the heart rate drops below 60 per minute.Positive pressure ventilation and 100% oxygen shouldalways be given, preferably by endotracheal tube andalways before trying any drug therapy. 45 When endotrachealintubation is not possible, mouth-to-mouthand-nosebreathing is considered most effective in infantsand children under 1 year of age 44,46–48 (Fig 2).Chest compression in small children can be performedeither by depressing the sternum with two fingers whilethe child is supine or by opposing the thumbs againstthe sternum with the hands wrapped around the child’schest. Circumferential compression improves arterialand coronary perfusion pressures and is preferred bymost authors. 45,49,50 In pediatric CPR, a child’s bonesshould be considered a noncompressible venous plexus.CPR TechniquesLeuthner, Jansen, and Hageman 45 review guidelines forCPR in newborns. Although children do require morechest compressions per minute than adult patients, theDrug TherapyIn a comprehensive review of the pharmacology of pediatricresuscitation, Zaritsky 51 recommends low-doseepinephrine (0.01mg/kg) and reserves calcium, atropine,19

SRPS 10(18) Pt 2, 2007the only two interventions that unequivocally improvesurvival after cardiac arrest. Several drugs are advocatedto treat cardiac arrest, but despite very encouraginganimal data, none has been reliably proven to beeffective in humans.Figure 2. Mouth-to-mouth-and-nose breathing for small infantvictim of cardiac arrest. (Reprinted with permission fromGuidelines 2000 for Cardiopulmonary Resuscitation and EmergencyCardiovascular Care: International Consensus on Science. Part 9:Pediatric Basic Life Support. Circulation 102(8) Suppl:I253-I290, 22August 2000.)sodium bicarbonate, and bretyllium for specific indications.The drugs can be administered by peripheral IVinfusion, central IV infusion, endotracheally, orintraosseally. A central line can be dangerous becausethe torso of the small child is constantly moving, andmost clinicians prefer intraosseous drug administration.Drug delivery times by the intraosseous route are equalto or faster than those achieved by peripheral IV injection.37,51,52 According to Tibballs, 52 “all drugs andresuscitative fluids can be infused into the tibial bonemarrow using an intraosseous needle.” The currentlyrecommended doses of medications used for pediatricadvanced life support are listed in Table 1. Animal studies53 suggest that intraosseous dosages may need to belarger to achieve comparable hemodynamic effects, butconfirmation in humans is pending.ADVANCED CARDIAC LIFE SUPPORTPharmacologyBasic life support and rapid defibrillation for ventricularfibrillation or pulseless ventricular tachycardia areEpinephrine is the pharmacologic workhorse of CPR. 54–58Epinephrine has both α and β agonist activity. Its α adrenergiceffects prevent arterial collapse, increase peripheralvascular resistance, and improve coronary perfusionand cerebral blood flow. 59–62 The value and safety of the βadrenergic effects of epinephrine are controversial: Thepumping load of the heart and its oxygen consumptionare raised while the cardiac efficiency and subendocardialperfusion are reduced. In addition, epinephrine canexacerbate postresuscitation myocardial dysfunction. Therecommended dose in CPR is 1mg (10mL of 1:10,000 solution)administered every 3–5 minutes until circulation isrestored or CPR discontinued.Epinephrine may also be given by continuous infusionof 1μg/min (by adding 1mg to 250mL of normalsaline), increasing to 3–4μg/min until there is response.Continuous infusion epinephrine is given via a centralvenous line to ensure good bioavailability. Higher dosesof epinephrine do not improve long-term survival orneurologic outcomes from cardiac arrest.Vasopressin is a naturally occurring antidiuretic hormone(ADH). In high doses, vasopressin acts as anonadrenergic peripheral vasoconstrictor of skin,muscle, intestine, and fat by direct stimulation of the V 1receptors. Vasopressin is an effective vasopressor andcan be used as an alternative to epinephrine for treatmentof shock-refractory ventricular fibrillation. It producesless constriction of the coronary and cerebral vesselsthan epinephrine, has no β agonist activity, and doesnot trigger increased myocardial oxygen consumption.In asystole or pulseless electrical activity (PEA), vasopressinin a dose of 40 units IV push (2mL of 20U/mL) isrecommended.Atropine is a parasympathetic antagonist. It increasesheart rate, increases conduction rate, and has little effecton heart contractility. Atropine may restore normalheart rhythm in PEA, asystole or bradycardia. It is givenin a bolus dose of 0.5–1mg intravenously or endotracheallyevery 2–5 minutes, for a total dose of 2mg inadults.20

SRPS 10 (18) Pt 2, 2007Dopamine’s effect is dose dependent: a low dose of 0.5–2.0μg/kg/min causes dopaminergic effects, with dilationof renal, mesenteric, cerebral, and coronary arteries. Amedium dose of 2.0–10μg/kg/min produces a β-adrenergiceffect, with increased myocardial contractility, SAnode rate, and heart conduction. At high doses, dopamineproduces an α-adrenergic effect, increasing bloodpressure and systemic vascular resistance. Dopamine isused for bradyarrhythmias unresponsive to atropinewhen external heart pacing is unavailable, and to treathypotention in the presence of normovolemia.Norepinephrine has both α- and β-adrenergic effects.Norepinephrine is a peripheral vasoconstrictor and maybe a positive inotropic stimulator of the heart. Norepinephrineis used for patients with cardiogenic shock orsevere hypotension who are normovolemic. The recommendeddose is 2–12mg/min.Antiarrhythmic drugs such as amiodarone, lidocaine,procainamide, and bretyllium may be given as neededin CPR, but always after electrical countershock.Amiodarone blocks potassium channels and prolongs theduration of the action potential. It has additionalelectrophysiologic properties such as sodium and calciumchannel blockade and α- and β-adrenergic blockingaction. Amiodarone is effective in treating most ventricularand supraventricular tachyarrhythmias and isat least as effective as bretyllium in converting refractoryventricular arrhythmias, but is controversial inhigh-risk patients, long-term survival rates are no better,63 and amiodarone is now largely superseded bycardioverter-defibrillators. Amiodarone is typicallygiven as a 300mg intravenous bolus after the third electricalshock.Lidocaine given prophylactically to patients withacute myocardial infarction probably reduces the incidenceof ventricular fibrillation, but mortality rates areunchanged or possibly even higher. There is scant evidenceto support its use in refractory ventricular fibrillation,and has been replaced by amiodarone as the drugof choice for patients who remain in ventricular fibrillationor pulseless ventricular tachycardia after threeshocks. An initial dose of 1mg/kg is given intravenouslyor endotracheally, followed by titratable infusion untilit is no longer necessary.Procainamide suppresses atrial and ventriculararrhythmias. It is sometimes used for convertingsupraventricular arrhythmias to sinus rhythm. Procainamideis administered slowly because it may causehypotension and decreased tissue perfusion. After theloading dose is administered, 1–4mg/min may berequired up to a maximum dose of 20mg/min.Until a few years ago, bretyllium was used for the managementof ventricular fibrillation or tachycardia afterelectrical defibrillation. It is no longer recommended forthe ACLS toolbox because of a high incidence of adverseeffects and the ready availability of safer agents.Intravenous adenosine is the first-line therapy for paroxysmalsupraventricular tachycardia in adults andchildren. Adenosine is extensively used in all clinicalsettings. The initial dose is 6mg given by IV push, followedby saline flush. If the supraventricular tachycardiadoes not resolve within 2 minutes, a second 12mgdose may be given by IV push. A third and final 12mg IVdose may be required. Adenosine is thought to be safeand effective, though occasionally adverse reactionsoccur such as prolonged asystole or bradycardia, syncope,and seizures.Verapamil remains an extremely efficacious drug withwell-known side effects, including hypertension. Whenadenosine is not available, verapamil should be the nextline of treatment.Isoproterenol is a pure β-adrenergic agonist. It increasesmyocardial oxygen consumption, cardiac output, andmyocardial work, but may cause ischemia andarrhythmias in susceptible patients. Because of itsadverse-effect profile, isoproterenol should be a secondchoice for temporary control of bradycardia until apacemaker can be inserted. The recommended dose is0.5–10mg/min by IV infusion.Intramyocardial acidosis is best corrected by adequateventilation. In CPR/ACLS this means hyperventilationwith 100% oxygen. Sodium bicarbonate should not beused. Its breakdown product is CO 2, which raises thearterial pCO 2and adds to the burden of a recently resuscitatedheart. 58–65Calcium chloride is used for the treatment of acutehyperkalemia, hypocalcemia, calcium channel blockertoxicity, magnesium toxicity, and beta-blocker toxicity,not as a primary agent in cardiac resuscitation.21

SRPS 10 (18) Pt 2, 2007Outcome StudiesThe outcome of CPR/ACLS is determined to a large extentby the type of cardiac arrest. When the cause of the arrestis asystole or electromechanical dissociation, survival todischarge from hospital is less than 2%. When the causeis ventricular fibrillation, survival is usually 15–25%.The two primary predictors of outcome after cardiacarrest are ventricular fibrillation and the presence of awitness. Survival is much more likely if the cardiacrhythm is ventricular fibrillation. 66 Resuscitation is typicallyunsuccessful when there is a pulseless rhythm.Pulseless rhythms are simple manifestations of catastrophicevents such as cardiac rupture, rupture ofabdominal aortic aneurysm, global cardiac ischemia,pulmonary embolism, and respiratory arrest.Patients who arrest outside the hospital have significantlylower survival rates (4–10%) compared withpatients who arrest while hospitalized. For every minutethat passes from the time of collapse to defibrillation,there is a substantial decrease in survival. Age of thepatient is also a major determinant: patients youngerthan 70 who arrest in-hospital are successfully resuscitated20% of the time, whereas for patients older than 70survival is only 3.4%. 24,67Pepe et al 68 studied how several factors influencedsurvival rates after cardiac arrest. Despite IAC-CPR,vest compression, endotracheal intubation, pharmacologicmanipulation, and other innovations, only earlydefibrillation by electroshock was found to be of valuein increasing long-term survival. While most authorsbelieve that ACLS probably does improve the outcomein cardiac arrest, strong clinical data are lacking. 68AlgorithmsThe following flow charts should be studied and prominentlydisplayed in all environments where patientsgather.23

SRPS 10(18) Pt 2, 2007Algorithm 1. Comprehensive emergency cardiovascular care (ECC) algorithm. All cardiac arrest victims receive the same fourtreatments: CPR, tracheal intubation, vasoconstrictors, antiarrhythmics. (Reprinted with permission from Guidelines 2000 forCardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Part 6: Advanced CardiovascularLife Support. Sec 7: Algorithm Approach to ACLS Emergencies. Circulation 102(8) Suppl:I142-I157, 22 August 2000.)24

SRPS 10 (18) Pt 2, 2007Algorithm 2. Ventricular fibrillation/pulseless ventricular tachycardia algorithm. Note the recommendation for vasopressin asan adrenergic agent equivalent to epinephrine for VF/VT cardiac arrest. Vasopressin has a 10- to 20-minute half-life and doesnot duplicate the adverse effects of epinephrine. (Reprinted with permission from Guidelines 2000 for Cardiopulmonary Resuscitationand Emergency Cardiovascular Care: International Consensus on Science. Part 6: Advanced Cardiovascular Life Support. Sec 7: AlgorithmApproach to ACLS Emergencies. Circulation 102(8) Suppl:I142-I157, 22 August 2000.)25

SRPS 10(18) Pt 2, 2007Algorithm 3. Pulseless electrical activity algorithm. Vasopressin is not recommended in asystole or PEA. People in PEA canbe resuscitated only if a reversible cause of PEA is identified and treated appropriately. (Reprinted with permission from Guidelines2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Part 6: AdvancedCardiovascular Life Support. Sec 7: Algorithm Approach to ACLS Emergencies. Circulation 102(8) Suppl:I142-I157, 22 August 2000.)26

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