expert guidance in developing institutional algorithms for...

Expert Guidance in Developing Institutional Algorithms for Snake Envenomation Management

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To participate in this activity, visit www.theheart.org/spotlight/venom or at www.medscape.org/spotlight/venom

Target AudienceThis activity is intended for emergency department physicians, hospitalists, family practice providers, nurses, pharmacists, and other healthcare professionals involved in the treatment of patients with crotaline envenomation.

GoalSignificant variations on the management of snake envenomation exist in the United States. This program provides an update on the use of a new algorithm for the management of crotaline envenomation, including initial assessment, the decision to initiate antivenom therapy, and application of and monitoring response to antivenom therapy.

Learning Objectives •Identifyclinicalmanifestationsofcrotalineenvenomationandappropriatepatientsforantivenomtherapy

•Developanalgorithmfortheuseofantivenomtherapy,includinginitialdosing,monitoring,andassessmentofresponse

•Reviewstrategiestodeterminedischargecriteriaanddischargeplanningfollowingantivenomtherapy

Credits Available Physicians - maximum of 0.5 AMA PRA Category 1 CreditTM; Nurses - 0.5 ANCC Contact Hours (0.5 contact hours are in the area of pharmacology); Pharmacists - 0.5 Knowledge-based ACPE credit (0.05 CEUs)

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Medscape designates this continuing education activity for 0.5 contact hour(s) (0.05 CEUs) (Universal Activity Number 0461-0000-13-004-H01-P)

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CME Released 03/12/2013 Valid for credit through 03/12/2014


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Authors and Disclosures

As an organization accredited by the ACCME, Medscape, LLC, requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines “relevant finan-cial relationships” as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food andDrugAdministration,atfirstmentionandwhereappropriateinthecontent.

Eric J. Lavonas, MDAssociateDirector,RockyMountainPoison&DrugCenter;Chair,Pharmacy&TherapeuticsCommittee,DenverHealth&HospitalAuthority; Associate Professor, DepartmentofEmergencyMedicine,UniversityofColoradoSchoolofMedicine,Denver,Colorado

EricJ.Lavonas,MD,hasdisclosedthefollowingrelevantfinancialrelationships:Servedasanadvisororconsultantfor:Reckitt-BenckiserPharmaceuticalsReceivedgrantsforclinicalresearchfrom:BTGInternational,Inc.;EndoPharmaceuticals;JanssenScientificAffairs;McNeilConsumerHealthCare;Reckitt-BenckiserPharmaceuticals

DrLavonasdoesnotintendtodiscussoff-labelusesofdrugs,mechanicaldevices,biologics,ordiagnosticsapprovedbytheFDAfor use in the United States.

DrLavonasdoesnotintendtodiscussinvestigationaldrugs,mechanicaldevices,biologics,ordiagnosticsnot approvedbytheFDAfor use in the United States.

Brent R. Fox, PharmDClinicalPharmacySpecialist,TexasHealth-HarrisMethodistFortWorthHospital,FortWorth,Texas

BrentR.Fox,PharmD,hasdisclosedthefollowingrelevantfinancialrelationships:Served as a speaker or a member of a speakers bureau for: BTG International, Inc.

DrFoxdoesnotintendtodiscussoff-labelusesofdrugs,mechanicaldevices,biologics,ordiagnosticsapprovedbytheFDAforusein the United States.

DrFoxdoesnotintendtodiscussinvestigationaldrugs,mechanicaldevices,biologics,ordiagnosticsnot approvedbytheFDAforuse in the United States.

Anne-Michelle Ruha, MDDirector,MedicalToxicologyFellowship;ClinicalAssistantProfessorofEmergencyMedicine,UniversityofArizonaCollegeofMedi-cine, Phoenix, Arizona

Anne-MichelleRuha,MD,hasdisclosedthefollowingrelevantfinancialrelationships:Served as an advisor or consultant for: BTG International, Inc.Served as a speaker or a member of a speakers bureau for: BTG International, Inc.

DrRuhadoesnotintendtodiscussoff-labelusesofdrugs,mechanicaldevices,biologics,ordiagnosticsapprovedbytheFDAforuse in the United States.

DrRuhadoesnotintendtodiscussinvestigationaldrugs,mechanicaldevices,biologics,ordiagnosticsnot approvedbytheFDAfor use in the United States.


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Susie Smith, RN, BSN, PHNEmergencyDepartmentNurse,LomaLindaUniversityMedicalCenter;LomaLinda,California;Founder,VenomRNEducationalConsulting,RanchoCucamonga,California

SusieSmith,RN,BSN,PHN,hasdisclosedthefollowingrelevantfinancialrelationships:Served as an advisor or consultant for: BTG International, Inc.Served as a speaker or a member of a speakers bureau for: BTG International, Inc.

Caroline M. Padbury, B.PharmGroupScientificDirector,Medscape,LLC

Disclosure:CarolineM.Padbury,B.Pharm,hasdisclosednorelevantfinancialrelationships.

Fernando L. Martin, MDScientificDirector,Medscape,LLC

Disclosure:FernandoL.Martin,MD,hasdisclosednorelevantfinancialrelationships.

Content ReviewerNafeez Zawahir, MDCMEClinicalDirector,Medscape,LLC

Disclosure:NafeezZawahir,MD,hasdisclosednorelevantfinancialrelationships.

Nurse PlannerLaurie E. Scudder, DNP, NPNursePlanner,ContinuingProfessionalEducationDepartment,Medscape,LLC;ClinicalAssistantProfessor,SchoolofNursingandAlliedHealth,GeorgeWashingtonUniversity,Washington,DC Disclosure:LaurieE.Scudder,DNP,NP,hasdisclosednorelevantfinancialrelationships.

Peer ReviewerThis activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.

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Editor’s Note: This program discusses the management of crotaline snakebites in the United States, specifically rattlesnakes, cottonmouths, and copperheads. The information and treatments discussed are relevant for US audiences only. An example of an order set, nursing checklist, treatment orders, and discharge instructions are available for download. Please note these are provided as examples only and should be adapted as required

Eric J. Lavonas, MD:Hello,IamDr.EricLavonas.IamassociatedirectoroftheRockyMountainPoisonandDrugCenterandassociateprofessorofemergencymedicineattheUniversityofColoradoSchoolofMedicineinDenver,Colorado.

Welcometothisprogramtitled“ExpertGuidanceinDevelopingInstitutionalAlgorithmsforSnakeEnvenomationManagement.”

JoiningmetodayisDrAnne-MichelleRuha,directorofthemedicaltoxicologyfellowshipatBannerGoodSamaritanMedicalCenter and clinical assistant professor of emergency medicine at the University of Arizona College of Medicine in Phoenix, Arizona. WelcomeMichelle.

Anne-Michelle Ruha, MD: Thank you.

Dr Lavonas: Susie Smith is an emergency department nurse at Loma Linda University Medical Center in Loma Linda, California. SusieisalsofounderofVenomRNEducationalConsultinginCalifornia.WelcomeSusie.

Susie Smith, MSN, RN, PHN: Thank you.

Dr Lavonas: DrBrentFoxisaclinicalpharmacyspecialistatthedepartmentofpharmacyservicesatTexasHealthHarrisMethodistHospitalFortWorthinFortWorth,Texas.Welcome.

Brent R. Fox, PharmD: Thank you.

Dr Lavonas: The goals of our program today are to identify the clinical manifestations of crotaline snake envenomation and appropriate patients for antivenom therapy; to help you develop an algorithm for the use of antivenom therapy, including initial dosing, monitoring, and assessment of response; and to review strategies to determine discharge criteria and discharge planning, post envenomation therapy.

a snake and have a very rapid onset of loss of consciousness and cardiovascular collapse. Obviously these are the most life-threatening bites, and often what we see is hypotension. Some patients may have hemorrhage, and another not uncommon effect with this would be angioedema, or airway swelling.


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Patientcareisateamactivityandeveryteamneedsagameplan.Wehaveprovidedatemplatestandardordersetforyou.Pleasepause the presentation now, download the document, and fill in the details as we go along. At the end of the presentation, you will have created a standard order set that you can use in your own institution.

Wearegoingtotalkaboutpitvipersnakebites.Iwantedtomakethescopeoftheprogramclear.Pitvipersnakesarerattlesnakes,copperheads,andcottonmouthsnakes.Wearenotgoingtobedealingwithcoralsnakebitesorbitesofsnakesthatarenotnativeto the United States.

IwouldliketostartwithDrRuha.Pleasetalktousabouttheclinicaleffectsofasnakebite.Whathappenstoourpatientswhenthey are bitten by a pit viper?

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Dr Ruha: The most common clinical effect is swelling, which can vary from minimal to very severe. It can involve an entire extremity or even extend into the torso and cause swelling throughout the entire body.

In addition to swelling, we often see ecchymosis and sometimes over the first 24 hours, patients will develop hemorrhagic bullae around the bite site. This most often occurs when patients have a bite to a digit, but sometimes you can see these bullae elsewhere. If you were to debride the bullae, the tissue underneath usually looks healthy. However, extensive bullae around the digit or circumferential can signify underlying deep tissue necrosis.

The second most common effect of crotaline snake envenomation is hematologic toxicity. Coagulopathy and thrombocytopenia are what we usually see, and this is much more common following rattlesnake envenomation than with copperhead or cottonmouth bites. The nice thing is that despite severe hematologic toxicity in some patients, we almost never see bleeding.


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Thelast2majorcategoriesofclinicaleffectswouldbeneurotoxicityandsystemictoxicity.NeurotoxicityiswellknowntooccurafterbitesfromtheMojaverattlesnake.However,severalotherrattlesnakespeciescancauseneurotoxicity.Intheworstcasescenario, that would result in respiratory failure from muscle weakness, necessitating intubation and mechanical ventilation. However,patientsmayjustexperienceparesthesiasorfasciculations.

Probably the least common, but the most severe effect of snake envenomation, is systemic toxicity. Some people will be bitten by a snake and have a very rapid onset of loss of consciousness and cardiovascular collapse. Obviously these are the most life-threatening bites, and often what we see is hypotension. Some patients may have hemorrhage, and another not uncommon effect with this would be angioedema, or airway swelling.

Dr Lavonas: So Susie, what do we do for initial management?

Ms Smith: Inassessmentandinitialmanagement,twointravenous(IV)linesshouldbeestablishedintheunaffectedextremity,ifpossible.WewanttomakesurethatwegiveanIVfluidbolusandbecautiousinthegeriatricandthepediatricpatient.Tourniquets or constricting bands should be removed as soon as possible. No ice should be applied in this situation.

Poison control should be contacted as soon as possible if there is no toxicologist or local expert available. The number is 1-800-222-1222, and ask to speak to the toxicologist on call.

The extremity should be elevated as soon as possible.

The initial laboratory tests are complete blood count (CBC), prothrombin time (PT), partial prothrombin time (PTT), fibrinogen test when available, and blood type and screen if the patient has severe envenomation or severe bleeding. It is most important to watch the progression of swelling. Swelling and tenderness are measured and marked with a permanent marker.

In the initial period, measurements are taken every 15 to 20 minutes and then as needed, maybe every 1 to 2 hours.

Dr Lavonas: That is a lot about initial assessment and supportive care, but what about specific therapy? Michelle, can you talk to us about antivenom?

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Dr Ruha: Antivenom usually refers to a biologic product that is used to reverse the effects of venom in humans. For crotaline snakebiteintheUnitedStatesthereisoneFDA-approvedantivenom.[1] This is made from the blood of sheep that have been hyperimmunized with the venom from several species of native pit vipers. The antibodies are then obtained from that blood of the animal and concentrated, and the fragment antigen-binding (Fab) portions are mixed together. These portions counteract the effects of venom in the body; they bind to the venom antigens and neutralize them.

Indications for treatment with antivenom following pit viper envenomation are: progressive swelling following the bite; hematologic toxicity, including thrombocytopenia or coagulopathy; neurotoxicity; and systemic toxicity.

The people who probably should not receive antivenom are those who have very minimal envenomation, possibly localized swelling around the bite site that is really not progressing. Of course, anyone who has a dry bite or no venom effect also should not receive antivenom.

Antivenom is indicated probably in most patients with rattlesnake envenomation, but far fewer patients with copperhead or cottonmouth envenomation require treatment with antivenom. In fact, clinicians who treat patients with copperhead bites often will reserve antivenom for those who have really severe extremity swelling or bites around the head or neck area that might pose a risk of airway obstruction.

Dr Lavonas: Thank you. Brent, you’re our pharmacy specialist. Tell us how you mix antivenom and how it is given.


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Dr Fox: Whenthedecisionismadetogiveantivenom,theorderneedstobeprocessedimmediately.Itdoestakesometimeto prepare this product for delivery to the patient. The approved dose for achieving initial control is 4 to 6 vials, and each vial is reconstituted with 18 mL of normal saline. The total dosage is then made up to 250 mL in normal saline.

This is administered to the patient slowly at first at a rate of 25 to 50 mL per hour for the first 10 minutes. If there is no reaction or hypersensitivity in the patient, the rate can be increased to 250 mL per hour to complete the bag. At that point in time, we assess the patient to make sure they are tolerating it throughout the entire infusion.

Dr Lavonas:Acutehypersensitivityreactionshappeninabout5%ofpatientstreatedwithantivenom.Whatdoyoudo?

Dr Fox:Firstwestoptheinfusionoftheantivenom.Wehaveproductsthatweneedtopotentiallytreatthepatientforhypersensitivity reaction close by. These anaphylactoid or anaphylactic reactions, however you want to quantify them, are treated the same way.

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WenormallystartwithgivingabolusofIVfluid,usuallynormalsaline.Wethengiveepinephrine;diphenhydramine,anantihistamine;andanH2--receptorantagonist,suchasfamotidineorranitidine,orevencimetidine.Wealsoassessthepatientaftertreatmenttoseeifwecancontinuetheantivenomtherapyatthatpoint.Wedonotnecessarilystoptheinfusionofantivenomandnottreatthepatientanylonger.Wetreatthereactionandreassessthepatienttoseeiftheyneedtocontinuewith therapy or if, at this point in time, the risk is outweighing the benefit.

Dr Lavonas: A key point is that antivenom reactions are uncommon, but when they do happen it does not necessarily mean that the patient has to forego antivenom therapy entirely. It is a great time for people to call the poison center and speak with a regional expert.

Whatshouldbeontheordersetsofar?

Dr Fox: On the order set now we have our initial assessment of the patient. That is key in the beginning, outlining that in your order set, what we are looking for, how to measure that in the patient.

Next,weconductlaboratorytests.Whatlaboratoryvaluesdowewanttoassessandatwhattiming?Wethenalsoobtainphysicalmeasurementsofthepatient.Wewanttooutlineexactlywhereweneedtomeasurethesepatientsandwhatwearelookingfor -- how swelling or edema is progressing. Also we need to include all the information on the order set about the antivenom itself; how we dose it, where we need to start, and when we need to repeat it. The more information we can get on there the better, because it helps us keep it concise and to the point of where we need to treat these patients.

Dr Lavonas: Our patient has been stabilized and received antivenom, if indicated. So, Susie, now what?


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Ms Smith: The most important part is initial control, which is defined as the cessation of the progression of swelling and tenderness,andthatpainisundercontrol.Weensurethatbywatchingthemeasurementsandseeingifthecoagulopathiesaretrending toward normal. If the coagulopathies are trending toward normal and there is cessation of swelling, we say that we have initial control. Then maintenance dosing can commence. If initial control has not been achieved, additional doses of antivenom may need to be given.

Dr Lavonas:Whatismaintenancetherapy,andwhogetsit?

Dr Ruha: Maintenancetherapyisdosesofantivenomthatareprovidedroutinelyafterinitialcontrolisachieved.TheFDArecommendation is that patients are given 2 vials of antivenom every 6 hours for a total of 3 doses after initial control. This would allow treatment for another 18 hours and another 6 vials after control.

The idea behind maintenance is that it will decrease the incidence of recurrent local swelling in the hours after the control is achieved, and also decrease the incidence of recurrent or late hematologic toxicities, such as thrombocytopenia and coagulopathy, that develop or recur after they had initially improved.

Maintenance dosing is not completely effective in preventing these toxicities, but it may decrease their incidence. Not all clinicians administer maintenance dosing despite the recommendation, and it is not entirely clear if all patients and all patient populations, such as those with copperhead bites, need it.

However, if clinicians decide not to give maintenance dosing they do monitor patients very carefully with repeat clinical examinations for the first 24 hours after control. Then they will give additional doses as necessary if symptoms develop, such as recurrent swelling or a worsening trend in laboratory studies.

Dr Lavonas: Iagreewithyoucompletely.WhenIworkedinthesoutheasternUnitedStates,wherewetreatedmostlycopperheadbites,wetypicallydidnotgivemaintenancetherapy.Workingoutwestwherewehaveallrattlesnakebites,wetypicallydo,buteither way that clinical vigilance of going back and reassessing your patients and keeping a close eye on laboratory trends is really the key to good patient care.

Whatdoyoudoifthepatienthasrecurrentswellingorarecurrentorlatedropinthecoagulopathies?

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Dr Ruha: Once you have finished the maintenance dosing and you finished administering antivenom, as far as you know, you measure PT, fibrinogen, and platelets every day until the patient is discharged. If you do have a worsening trend in laboratory values you may need to give more antivenom.

Ifpatientsaredoingwell--thereisnoworseningintheirlaboratorytrends,theynolongerrequireIVpainmedications,andtheycan function independently or with assistance from family at home -- they can be discharged.

However, you really do need to be careful and monitor them closely as outpatients for potential late hematologic toxicity. It is recommended that patients undergo laboratory evaluation usually comprising PT, fibrinogen, and platelet count 2 to 3 days after the last antivenom dose and again 5 to 7 days after the last antivenom dose; so, usually twice after discharge from the hospital. If late hematologic toxicity is detected, it is recommended that you call a poison center and talk to a toxicologist or local snakebite expert about whether your patient requires retreatment with antivenom.

Not all patients with recurrent hematologic toxicity require retreatment, but many do, especially those who may have evidence of bleeding,riskfactorsforbleeding,ormaybejusthavereallysevere,isolatedthrombocytopenia.Therearealotoffactorsthatneedto be considered, which is why it is a good idea at that point to talk to an expert.

Dr Lavonas: Thanks. Susie, speaking of talking to an expert, we want to make our patients experts in self-care when they go home.Whatshouldwebetellingthem?


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Ms Smith: Planningfordischargeatthetimeofadmissionisessential.Weshouldstartprovidinginformationwhentheyareadmitted, such as that the limb should be elevated whenever possible, especially when they are in the hospital and when they go home.

They should follow their pain medication criteria; they should have opiate analgesics and no nonsteroidal anti-inflammatory drugs (NSAIDs).ItisessentialtoadvisepatientsthattheymustnottakeMotrin®,Aleve®,oraspirinbecauseofbleedingcomplications.They should be advised that if they have any bleeding complications at home -- such as any easy bruising, if they bleed when they brush their teeth -- or if they have any weakness, they should contact their health care provider or go to the emergency department(ED)immediately.Theyshouldnottakepartincontactsportsorhaveanydentalworkdonefor2weeksaftertheirsnakebite. If they have a snakebite to the lower limb they should be on crutches or told not to bear weight as directed by the clinician that is in charge.

Also,theymustfollowupwiththeirlaboratorystudiesasdirectedbytheirprovider,asDrRuhasaid,at2to3daysand5to7days,to make sure they are not having any abnormal trends in their coagulopathies. Of course, if they have any difficulties at all -- any weakness,bleeding,orbruising--theyshouldfollowupwiththeirproviderorreturntotheEDimmediately.

Dr Lavonas:Whataboutserumsickness?Weknowthat8%or10%ofantivenom-treatedpatientswillgetserumsickness.Whatshould they do for that?

Susie Smith: Serum sickness is due to the antivenom and not due to the venom of the snake. They need to know that serum sicknesswillhappeninapercentageofpatients,andiftheyhaveanyfever,jointpain,feelingalmostliketheyhavetheflu,theyneedtofollowupwiththeirproviderorreturntotheEDtogettreatment.

Dr Lavonas: The good news, in my experience, is that serum sickness with the new modern antivenom is much less common and much less serious than with the older products and easily treated with antihistamine and steroids when it does develop.

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Whatshouldbeonthatordersetnow?

Dr Fox: Wearenowwrappingupourorderset.ThepatienthastransitionedoutoftheED,possiblytotheintensivecareunit(ICU)ormaybeeventothefloor,sothisis12tomaybe24hoursaftertheyhavebeenbitten.Wearenowmonitoringthemcloselyfordischarge or retreatment, if needed.

However, we are going to look at measurements as outlined on your order set to determine exactly how you want this to be done and at what times. Also, we mentioned maintenance therapy. You should at least mention on your order set whether you want to routinely do that or give criteria as to when it should be done. Once again, you need to very clearly identify which laboratory tests you want to have repeated and at what times. Finally, make a clear indication when the provider should be recalled if recurrence is imminent in this patient, and whether it is systemic or local, because we need to catch these things as quickly as we can.

Dr Lavonas: You raised a good point about setting of care as at some hospitals, snakebite patients are routinely taken care of in theICUorsometimesonthemedicalfloors.InmanyinstitutionswhereIhaveworked,thatisagreatuseforanEDobservationunit. I think it depends more on your institution almost than the patient, except for those who are critically ill.

Michelle,doyouwanttotalktousaboutsomepitfalls?Whatarethebigmistakestoavoidhere?


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Dr Ruha:Icanthinkof4things.Thefirstwouldbetobeverycarefulindiagnosingcompartmentsyndrome.Rattlesnakebitesdo have the potential to produce compartment syndrome, but it is really very, very rare. However, the clinical examination of a rattlesnake bite can look very much like compartment syndrome, so it is easy to make that mistake. Any time you are considering compartment syndrome, definitely measure intercompartmental pressures to document elevated pressure prior to doing a fasciotomy.Inthevastmajorityofsnake-bitecases,thepatientwillnotrequireafasciotomy.

The second thing I want to warn about is not to chase abnormal laboratory values with blood products. If you see severe thrombocytopenia or severe coagulopathy, we do not routinely treat with blood products in the absence of bleeding. Usually it responds very nicely to antivenom, and even if it does not respond to antivenom, if the patient is not bleeding, blood products still are not indicated. However, sometimes patients are bleeding and will require blood products, but you need to also give antivenom.

Dr Lavonas: I always think of this like a patient with idiopathic thrombocytopenic purpura (ITP), where if platelet counts are low, you treat the underlying cause. For that disease you would use steroids; for this disease you would use antivenom. Transfusion does not work, or at least does not have a lasting effect, unless you also address the underlying cause adequately. If you address the underlying cause, usually you do not need the transfusion.

Dr Ruha: That brings me to the next thing, which is chasing laboratory studies or other venom effects that do not seem to be responding to antivenom. There are patients very often who have clinical effects of the envenomation that seem to be resistant to antivenom treatment: one might be fasciculations.

Patients with neurotoxicities sometimes will have fasciculations that do not go away with the first few doses of antivenom. In such cases, it may not be worthwhile to continue giving antivenom. Similarly, there are patients who have very resistant thrombocytopenia. It is not the norm but it can happen. So if someone is given 1 or 2 doses of antivenom and they are not seeing a response, they should definitely call the poison center and talk to a toxicologist about whether further antivenom is indicated.

Also, we should have a low threshold for intubation in patients who have bites near the head and neck or who have angioedema. If there is any evidence of early airway swelling you may want to pursue intubation while you can, because patients can develop very rapid airway obstruction, and by the time you decide to intubate, it might be too late.

Dr Lavonas: Thanksverymuch.Iwouldliketothankmyfellowpanelists--DrMichelleRuha,MsSusieSmith,andDrBrentFox--fortakingthetimetohelpwiththistoday.Iwouldalsoliketothankyou,ourparticipants,foryourtimeandattention.Wehopeyou found this useful.

I want to stress again that if you find yourself in a dilemma and want to speak with an expert and do not have one in your own institution, you can always reach medical toxicologists through your regional poison center.

That number is 1-800-222-1222.

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References 1.Crofab®[packageinsert].WestConshohocken,PA:BTGInternational,Inc.

AbbreviationsCBC = complete blood count

CroFab®=CrotalidaePolyvalentImmuneFab(ovine)

ED=emergencydepartment

Fab = fragment antigen-binding

ICU = intensive care unit

ITP = idiopathic thrombocytopenic purpura

IV=intravenous

NSAIDs=nonsteroidalanti-inflammatorydrugs

PT = prothrombin time

PTT = partial thromboplastin time

DisclaimerThe educational activity presented above may involve simulated case-based scenarios. The patients depicted in these scenarios are fictitious and no association with any actual patient is intended or should be inferred.

The material presented here does not necessarily reflect the views of Medscape, LLC, or companies that support educational programming on medscape.org. These materials may discuss therapeutic products that have not been approved by the US Food andDrugAdministrationandoff-labelusesofapprovedproducts.Aqualifiedhealthcareprofessionalshouldbeconsultedbeforeusinganytherapeuticproductdiscussed.Readersshouldverifyallinformationanddatabeforetreatingpatientsoremployinganytherapies described in this educational activity.

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