Rattlesnake Envenoming Therapies - VETgirl

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Rattlesnake Envenoming Therapies

For The Small Animal Veterinarian

Raegan J. Wells, DVM, MS, DACVECC

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INTRODUCTION

Justine A. Lee, DVM, DACVECC, DABT

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INTRODUCTION Garret Pachtinger, VMD, DACVECC

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INTRODUCTION

Raegan J. Wells, DVM, MS, DACVECC

Disclosures No financial disclosures

Previous unpaid scientific collaboration with Veteria

Personal fascination with snake venom and pathophysiology of envenomation

Overview •  Brief review of rattlesnake envenomation pathophysiology

•  Antivenom 101

•  Antivenom options for the small animal veterinarian

•  Other rattlesnake envenomation therapies

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Venom

• Enzymes " Hyaluronidase & collagenase

•  Tissue destruction " Proteases

•  Necrosis/coagulopathy " Phospholipases

•  Cytotoxicity

• Peptides that can act as toxins to many systems " Neurotoxins " Cardiotoxins " Nephrotoxins

Local Tissue Injury "  ↑ capillary permeability

"  Endothelial cell swelling & rupture

"  Tissue edema, ecchymosis & necrosis

"  Loss of the vascular basement membrane

"  Myonecrosis

"  Can become systemic = SIRS/SEPSIS/MODS

Coagulopathy "  Fibrinolysins

•  Defibrinogenation = hemorrhage

"  Fibrinogen clotting enzymes

"  Thrombin-like enzymes o Do not activate XIII = small, friable blood clots

"  Anticoagulants

"  Platelet function inhibition

"  Vascular damage

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Green = native plasma Red = venom 1:10 + plasma Black = venom + plasma

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Venom Induced Coagulopathy (VIC) Does not start as a consumptive coagulopathy

aka, this is not disseminated intravascular coagulation

Coagulation factors are not being consumed, rather they are inhibited by the venom

Venom is also impairing platelet function, vessel wall function, and can impact fibrinolysis

May be direct fibrinolysins, or may enhance native fibrinolysis

Treatment is aimed at neutralizing the venom Plasma is not indicated to treat rattlesnake envenomation

Original Study Journal of Veterinary Emergency and Critical Care 24(2) 2014, pp 144–153doi: 10.1111/vec.12139

Thromboelastographic evaluationof hemostatic function in dogs treatedfor crotalid snake envenomationRobert A. Armentano, DVM, DACVIM; Carsten Bandt, DVM, DACVECC; Michael Schaer, DVM,DACVIM, DACVECC; John Pritchett, DVM and Andre Shih, DVM, DACVAA

Abstract

Objective – To characterize the overall hemostatic changes in dogs envenomated by crotaline snakes via kaolin-activated thromboelastography (TEG), and to determine any prognostic/monitoring value from a TEG tracingon presentation, as well as during treatment with antivenom therapy.Design – Prospective observational, cohort study.Setting – University teaching hospital and primary emergency hospital.Animals – Thirty-eight dogs envenomated by crotaline snakes.Interventions – TEG tracings were evaluated on presentation to the hospital (pre) as well as immediatelyfollowing (post) and 12 hours (12 h post) after antivenom treatment, if administered.Measurements and Main Results – At presentation, data were available for 38 dogs envenomated by crotalinesnakes. Twenty dogs were in Group 1 (Antivenin [Crotalidae] Polyvalent antivenom), 12 dogs were in Group2 (Antivipmyn antivenom), and 6 dogs in Group 3 that were not treated with antivenom. The average numberof vials administered to group 1 and 2 were equal at 2.2. On presentation, based on a G value < TEG referencerange, 15/38 (39%) of the dogs had hypocoagulable TEG tracings. There was a significant increase in G and MAvalue from the pre and 12 hour post measurement (P = 0.0001 and 0.0003, respectively), as well as from the postto 12 hour post measurement (P = 0.003 and, 0.014, respectively). During the study, 5 of 38 dogs died (13%) andof the dogs that died, 4/5 (80%) had angle and MA equal to zero on presentation. A decreased G and MA weresignificantly associated with mortality (P = 0.02 and 0.04, respectively).Conclusions – A hypocoagulable TEG tracing, particularly a decreased G value and MA, is associated with anincreased mortality in crotaline snake envenomation. G and MA also demonstrate a significant increase overtreatment time.

(J Vet Emerg Crit Care 2014; 24(2): 144–153) doi: 10.1111/vec.12139

Keywords: coagulopathy, snake bite, TEG

Abbreviations

ACP Antivenin (Crotalidae) PolyvalentACT activated clotting timeaPTT activated partial thromboplastin time

From the University of Florida Small Animal Hospital, Small Animal Clin-ical Sciences, Gainesville, FL 32610 (Armentano, Bandt, Schaer, Shih) andAffiliated Pet Emergency Services, Gainesville, FL 32607 (Pritchett).

The authors declare no conflict of interests.

Funding for this project was provided by Boehringer-Ingelheim.

Presented as an abstract at the International Veterinary Emergency and Crit-ical Care Symposium, Nashville, TN, September 16, 2011.

Address correspondence and offprint requests toDr. Bandt, University of Florida Small Animal Hospital, Small Ani-mal Clinical Sciences, 2015 SW 16th Avenue, Gainesville, FL 32610.Email: [email protected] March 19, 2012; Accepted November 10, 2013.

PLT platelet countPT prothrombin timeSSS snakebite severity scoreTEG thromboelastography

Introduction

Pit viper snake (family Crotalidae) envenomation in dogsis a common emergency within certain regions of theUnited States, particularly in the southeast, southern,and western regions.1 Most crotaline snake enveno-mations typically cause severe swelling, pain, hema-tologic abnormalities, hypotension, and occasionallyneurologic impairment depending on the particularspecies of snake. A numerically graded snakebite sever-ity score (SSS) has been validated in people to evaluate

144 C⃝ Veterinary Emergency and Critical Care Society 2014


Thromboelastographic evaluationof hemostatic function in dogs treatedfor crotalid snake envenomationRobert A. Armentano, DVM, DACVIM; Carsten Bandt, DVM, DACVECC; Michael Schaer, DVM,DACVIM, DACVECC; John Pritchett, DVM and Andre Shih, DVM, DACVAA

Abstract

Objective – To characterize the overall hemostatic changes in dogs envenomated by crotaline snakes via kaolin-activated thromboelastography (TEG), and to determine any prognostic/monitoring value from a TEG tracingon presentation, as well as during treatment with antivenom therapy.Design – Prospective observational, cohort study.Setting – University teaching hospital and primary emergency hospital.Animals – Thirty-eight dogs envenomated by crotaline snakes.Interventions – TEG tracings were evaluated on presentation to the hospital (pre) as well as immediatelyfollowing (post) and 12 hours (12 h post) after antivenom treatment, if administered.Measurements and Main Results – At presentation, data were available for 38 dogs envenomated by crotalinesnakes. Twenty dogs were in Group 1 (Antivenin [Crotalidae] Polyvalent antivenom), 12 dogs were in Group2 (Antivipmyn antivenom), and 6 dogs in Group 3 that were not treated with antivenom. The average numberof vials administered to group 1 and 2 were equal at 2.2. On presentation, based on a G value < TEG referencerange, 15/38 (39%) of the dogs had hypocoagulable TEG tracings. There was a significant increase in G and MAvalue from the pre and 12 hour post measurement (P = 0.0001 and 0.0003, respectively), as well as from the postto 12 hour post measurement (P = 0.003 and, 0.014, respectively). During the study, 5 of 38 dogs died (13%) andof the dogs that died, 4/5 (80%) had angle and MA equal to zero on presentation. A decreased G and MA weresignificantly associated with mortality (P = 0.02 and 0.04, respectively).Conclusions – A hypocoagulable TEG tracing, particularly a decreased G value and MA, is associated with anincreased mortality in crotaline snake envenomation. G and MA also demonstrate a significant increase overtreatment time.


Keywords: coagulopathy, snake bite, TEG

Abbreviations

ACP Antivenin (Crotalidae) PolyvalentACT activated clotting timeaPTT activated partial thromboplastin time

From the University of Florida Small Animal Hospital, Small Animal Clin-ical Sciences, Gainesville, FL 32610 (Armentano, Bandt, Schaer, Shih) andAffiliated Pet Emergency Services, Gainesville, FL 32607 (Pritchett).


Funding for this project was provided by Boehringer-Ingelheim.

Presented as an abstract at the International Veterinary Emergency and Crit-ical Care Symposium, Nashville, TN, September 16, 2011.

Address correspondence and offprint requests toDr. Bandt, University of Florida Small Animal Hospital, Small Ani-mal Clinical Sciences, 2015 SW 16th Avenue, Gainesville, FL 32610.Email: [email protected] March 19, 2012; Accepted November 10, 2013.

PLT platelet countPT prothrombin timeSSS snakebite severity scoreTEG thromboelastography

Introduction

Pit viper snake (family Crotalidae) envenomation in dogsis a common emergency within certain regions of theUnited States, particularly in the southeast, southern,and western regions.1 Most crotaline snake enveno-mations typically cause severe swelling, pain, hema-tologic abnormalities, hypotension, and occasionallyneurologic impairment depending on the particularspecies of snake. A numerically graded snakebite sever-ity score (SSS) has been validated in people to evaluate


Polyvalent ACP (IgG) = 20 F(ab’)2 = 12 No antivenom = 6

13% mortality (5/38 died)

3/5 – C. adamentus 1/5 – A. piscivorus 1 – unknown species

Hypocoagulable whole blood tracing significantly associated with mortality

14/38 were hyperfibrinolytic

Mojave Toxins? C. Scutulatus Responsible for neurological complications Types

" Mojave venom A •  Presynaptic neurotoxin

•  Paresis/paralysis •  Phospholipase activity

" Mojave venom B •  Proteolytic enzymes

Documented in Southern Pacific Rattlesnakes (C. helleri) Isolated in Prairie Rattlesnake (C. viridis) venom

Also myotoxin A Neurotoxins possible in all species May or may not exhibit classic swelling and pain

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Common Clinical Signs

"  Puncture wounds Head Distal extremity

"  Regional swelling and pain Tracheostomy may be necessary

"  Tachycardia, hypotension, arrhythmias

"  Neurological abnormalities Obtundation Seizures Diffuse neuromuscular weakness


Myocardial injury in dogs with snakeenvenomation and its relation to systemicinflammationRebecca Langhorn, DVM; Frida Persson, DVM; Bjorn Ablad, DVM; Amelia Goddard, BVSc(Hons),MMedVet; Johan P. Schoeman, BVSc, MMedVet, PhD; Jakob L. Willesen, DVM, PhD; Inge Tarnow,DVM, PhD and Mads Kjelgaard-Hansen, DVM, PhD

Abstract

Objective – To investigate the presence of myocardial injury in dogs hospitalized for snake envenomation andto examine its relationship with systemic inflammation.Design – Prospective case-control study.Setting – University teaching hospital and small animal referral hospital.Animals – Dogs naturally envenomed by the European viper (Vipera berus; n = 24), African puff adder (Bitisarietans; n = 5), or snouted cobra (Naja annulifera; n = 9).Interventions – Blood was collected from dogs envenomed by V. berus at admission, 12–24 hours postadmission,and 5–10 days postadmission. Blood was collected from dogs envenomed by B. arietans or N. annulifera atadmission, and 12, 24, and 36 hours postadmission.Measurements and Main Results – Concentrations of cardiac troponin I (cTnI), a marker of myocardial injury,and C-reactive protein (CRP), a marker of systemic inflammation, were measured in each blood sample. Evidenceof myocardial injury was found in 58% of dogs envenomed by V. berus at one or more time points. A significantcorrelation between cTnI and CRP concentrations was found at all time points. Evidence of myocardial injurywas found in 80% of dogs envenomed by B. arietans at one or more time points; however, no correlation was foundbetween cTnI and CRP concentrations. Evidence of myocardial injury was found in 67% of dogs envenomedby N. annulifera at one or more time points. A significant correlation between cTnI and CRP concentrations wasfound at admission, but not at other time points.Conclusions – Myocardial injury frequently occurred in dogs with snake envenomation. While the degree ofsystemic inflammation was significantly correlated with degree of myocardial injury in V. berus envenomation atall time points, this was not the case in dogs envenomed by N. annulifera or B. arietans. This could be due to differ-ences in the toxic substances of the snake venoms or to differences in the cytokines induced by the venom toxins.


Keywords: biomarker, cardiac troponin I, companion animals, toxins

Introduction

In many countries, snake envenomation poses ahealthrisk to both people and animals. The type of snake,

From the Department of Veterinary Clinical and Animal Sciences, Univer-sity of Copenhagen, Frederiksberg, Denmark (Langhorn, Persson, Willesen,Kjelgaard-Hansen); The Blue Star Animal Hospital, Gothenburg, Sweden(Ablad); Department of Companion Animal Clinical Sciences, Universityof Pretoria, Pretoria, South Africa (Goddard, Schoeman); and Chr. HansenA/S, Horsholm, Denmark (Tarnow).

The University of Copenhagen financially supported the study through anunrestricted grant to Rebecca Langhorn.


Offprints will not be available from the authors.

Address correspondence and reprint requests toDr. Rebecca Langhorn, Department of Veterinary Clinical and AnimalSciences, University of Copenhagen, Groennegaardsvej 3, Ground floor,DK-1870 Frederiksberg C, Denmark. Email: [email protected] January 7, 2013; Accepted October 29, 2013.

Abbreviations

CRP C-reactive proteincTnI cardiac troponin IVPC ventricular premature complex

amount of venom injected, and site of envenomation allinfluence the initial hazard and the progression of theintoxication.1–3 In some cases, only a local reaction occurswith edema and tissue necrosis,4 but often the toxic insultprogresses to a systemic reaction that may lead to spe-cific or multiple organ dysfunction and death.5–7 Snakevenoms are known to contain a complex mixture oftoxins. Some are proteolytic, causing tissue destruction



Myocardial injury in dogs with snakeenvenomation and its relation to systemicinflammationRebecca Langhorn, DVM; Frida Persson, DVM; Bjorn Ablad, DVM; Amelia Goddard, BVSc(Hons),MMedVet; Johan P. Schoeman, BVSc, MMedVet, PhD; Jakob L. Willesen, DVM, PhD; Inge Tarnow,DVM, PhD and Mads Kjelgaard-Hansen, DVM, PhD

Abstract

Objective – To investigate the presence of myocardial injury in dogs hospitalized for snake envenomation andto examine its relationship with systemic inflammation.Design – Prospective case-control study.Setting – University teaching hospital and small animal referral hospital.Animals – Dogs naturally envenomed by the European viper (Vipera berus; n = 24), African puff adder (Bitisarietans; n = 5), or snouted cobra (Naja annulifera; n = 9).Interventions – Blood was collected from dogs envenomed by V. berus at admission, 12–24 hours postadmission,and 5–10 days postadmission. Blood was collected from dogs envenomed by B. arietans or N. annulifera atadmission, and 12, 24, and 36 hours postadmission.Measurements and Main Results – Concentrations of cardiac troponin I (cTnI), a marker of myocardial injury,and C-reactive protein (CRP), a marker of systemic inflammation, were measured in each blood sample. Evidenceof myocardial injury was found in 58% of dogs envenomed by V. berus at one or more time points. A significantcorrelation between cTnI and CRP concentrations was found at all time points. Evidence of myocardial injurywas found in 80% of dogs envenomed by B. arietans at one or more time points; however, no correlation was foundbetween cTnI and CRP concentrations. Evidence of myocardial injury was found in 67% of dogs envenomedby N. annulifera at one or more time points. A significant correlation between cTnI and CRP concentrations wasfound at admission, but not at other time points.Conclusions – Myocardial injury frequently occurred in dogs with snake envenomation. While the degree ofsystemic inflammation was significantly correlated with degree of myocardial injury in V. berus envenomation atall time points, this was not the case in dogs envenomed by N. annulifera or B. arietans. This could be due to differ-ences in the toxic substances of the snake venoms or to differences in the cytokines induced by the venom toxins.


Keywords: biomarker, cardiac troponin I, companion animals, toxins

Introduction

In many countries, snake envenomation poses ahealthrisk to both people and animals. The type of snake,

From the Department of Veterinary Clinical and Animal Sciences, Univer-sity of Copenhagen, Frederiksberg, Denmark (Langhorn, Persson, Willesen,Kjelgaard-Hansen); The Blue Star Animal Hospital, Gothenburg, Sweden(Ablad); Department of Companion Animal Clinical Sciences, Universityof Pretoria, Pretoria, South Africa (Goddard, Schoeman); and Chr. HansenA/S, Horsholm, Denmark (Tarnow).

The University of Copenhagen financially supported the study through anunrestricted grant to Rebecca Langhorn.


Offprints will not be available from the authors.

Address correspondence and reprint requests toDr. Rebecca Langhorn, Department of Veterinary Clinical and AnimalSciences, University of Copenhagen, Groennegaardsvej 3, Ground floor,DK-1870 Frederiksberg C, Denmark. Email: [email protected] January 7, 2013; Accepted October 29, 2013.

Abbreviations

CRP C-reactive proteincTnI cardiac troponin IVPC ventricular premature complex

amount of venom injected, and site of envenomation allinfluence the initial hazard and the progression of theintoxication.1–3 In some cases, only a local reaction occurswith edema and tissue necrosis,4 but often the toxic insultprogresses to a systemic reaction that may lead to spe-cific or multiple organ dysfunction and death.5–7 Snakevenoms are known to contain a complex mixture oftoxins. Some are proteolytic, causing tissue destruction


Confirmed Mojave RSE to Tongue

Day 1 post 1 vial Venom Vet™

Day 2 1 additional vial AV given Veteria (Mexico) F(ab’)2

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Neuromuscular

Antivenom •  First developed in the late 1800s

•  Immune response to venom created in host animal

•  Purified antibodies infused into patient to neutralize venom

•  Veterinary specific antivenoms regulated by U.S.D.A.

•  Human antivenoms regulated by F.D.A.

Venom is collected

Animals (horses or sheep) are hyperimmunized to produce neutralizing antibodies against the venom(s).

Antibodies are harvested from blood and purified Enzyme digestion utilized to fragment IgG molecules

Antibodies are used to make final product

Antivenom Production

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Pit Viper Antivenoms in Veterinary Medicine "  Crotalidae Polyvalent

Whole IgG (Equine) o Boreinger Ingleheim®

"  Crotalidae Polyvalent Immune Fab (Ovine) o CroFab®

"  VenomVet™ (Equine) o MT Venom, LLC, Argentina

"  Crotalidae Polyvalent Immune F(ab’)2 (Equine) •  Veteria, Mexico

Antivenoms IgG Antivenin

(crotalidae)

Boehringer Ingelheim (Fort Dodge)

USDA approved for veterinary medicine Equine origin

Fab CroFab® Not approved for veterinary medicine FDA Approved for human medicine Ovine origin

F(ab’)2 VenomVet™

Veteria

USDA Approved, equine origin

Pending USDA approval, equine origin

Antibody Comparisons

IgG

Fab

150 kDa

50 kDa Fc portion removed

• Fc portion removed • Rapid elimination (~35X of IgG) • Risk of re-envenomation

• Longer ½ life than Fab and F(ab’)2

F(ab’)2 110 kDa (dimer) Fc portion removed

• Fc portion removed • Longer ½ life than Fab • Larger volume distribution than IgG

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Whole IgG- Veterinary Boeringer Ingelheim

USDA approved antivenom

•  Equine origin Acute and delayed reactions reported

•  Higher incidence than with fragmented (Fab) antivenoms •  Examples

•  20 dogs #no reaction reported1 •  2/218 # acute reaction13 •  1/31 dogs # acute reaction4 •  One case report of a delayed reaction14

•  23/95 (24%) cats # acute reaction7

Crotalidae polyvalent immune Fab (Ovine) antivenom

•  Crofab®

"  All dogs received at least one vial (n=115) "  6/115 acute reactions "  6/115 intermediate reactions

"  83% overall survival

Recommend 1.25 vials OPCA to stabilize or reverse signs of envenomation

Original Study

A randomizedmulticenter trial of Crotalidaepolyvalent immune Fab antivenom for the treatmentof rattlesnake envenomation in dogsMichael E. Peterson, DVM, MS; Michael Matz, DVM, DACVIM; Karen Seibold, DVM, DAVECC;Signe Plunkett, DVM; Scott Johnson, DVM, DACVECC and Kevin Fitzgerald, DVM, PhD, DABVP

Abstract

Objective – To determine clinical efficacy of the Crotalidae polyvalent immune Fab (ovine) antivenom (OPCA)against progressive crotalid envenomation in the dog as reflected in stabilization or improvement of snakebiteseverity scores (SSS). Additionally, due to the potential decreased half-life of the Fab antibodies in dogs wecompared SSS between dogs receiving 2 different dosing regimes.Design – Prospective, clinical trial.Setting – Five veterinary emergency and critical care facilities.Animals – One hundred and fifteen client-owned Crotalid (rattlesnake) snake bitten dogs in whom worseningof the envenomation syndrome was observed before OPCA treatment.Interventions – In a multicenter randomized clinical trial a single dose (1 vial) of OPCA alone was comparedwith 2 doses (1/2 vial each) administered 6 hours apart. Standard supportive care was provided in all cases.Measurements and Main Results – Data were available for 115 patients, 9 of which were fatalities. Allpatients’ clinical condition was documented with a standardized SSS system accounting for each major bodysystem. Each fatality received maximum severity scores of 20. The mean severity score of the 115 patientsdecreased from 4.19 to 3.29 points and there was no difference between the 2 treatment groups. The meanseverity score of the 107 patients without fatalities decreased from 4.16 to 2.15. Antivenin-related acutereactions occurred in 6 dogs (6%), and no serum sickness occurred within the 95 cases contacted at the 2-weekposttreatment follow-up.Conclusions – In the first randomized trial in dogs of antivenin in the United States, OPCA effectivelystabilized or terminated venom effects. There were no statistical differences detected between treatmentgroups within the study time frame.

(J Vet Emerg Crit Care 2011; 21(4): 335–345) doi: 10.1111/j.1476-4431.2011.00643.x

Keywords: dogs, efficacy trial, pit viper, postexposure therapy, snakebite

[Correction added after online publication 16 MAY 2011: Dr. Signe Plunkett’s name has been corrected.]

Introduction

In North America the venomous snakes known as pitvipers include 26 subspecies of rattlesnakes (Crotalusspp.), 3 subspecies of pigmy rattlesnakes (Sistrurus mili-aris), 3 subspecies of massassauga (Sistrurus catenatus),

5 subspecies of copperheads (Agkistrodon contortrix),and 3 subspecies of cottonmouth water moccasins(Agkistrodon piscivorus). It is estimated that 7,000–8,000rattlesnake bites occur per year in people in the UnitedStates.1 In 1999, the University of Arizona’s Poison andDrug Information Center managed 57 human rattle-snake bite cases in Tucson, AZ.2 In a veterinary surveyconducted by Johnston and Schmidt,3 466 dogs werepresented for rattlesnake bites to veterinary practices inthe Tucson area during the months of June, July, andAugust 1998, with only a 41% survey response rate.

The only proven, definitive treatment against anLD100 of pit viper venom in rats is IV administration ofantivenom (antivenom crotalidae polyvalenta [ACP]).4

The mortality rate in the United States for people

Address correspondence and reprint requests toDr. Michael E. Peterson, Reid Veterinary Hospital, 933 SW Queen Ave,Albany, OR 97321, USA.Email: [email protected] February 17, 2010; Accepted April 12, 2011.

From the Reid Veterinary Hospital, Albany, OR 97321 (Peterson); VeterinarySpecialty Center of Tucson, Tucson, AZ 85704 (Matz); Animal Urgent Careand Specialty Group, Escondido, CA 92025 (Seibold); Animal HealthServices, Cave Creek, AZ 85331 (Plunkett); Emergency Animal Hospital ofNorthwest Austin, Austin, TX 78759 (Johnson); and VCA Alameda EastVeterinary Hospital, Denver, CO 80247 (Fitzgerald).

Journal of Veterinary Emergencyand Critical Care 21(4) 2011, pp 335–345doi:10.1111/j.1476-4431.2011.00643.x

& Veterinary Emergency and Critical Care Society 2011 335

Original Study

A randomizedmulticenter trial of Crotalidaepolyvalent immune Fab antivenom for the treatmentof rattlesnake envenomation in dogsMichael E. Peterson, DVM, MS; Michael Matz, DVM, DACVIM; Karen Seibold, DVM, DAVECC;Signe Plunkett, DVM; Scott Johnson, DVM, DACVECC and Kevin Fitzgerald, DVM, PhD, DABVP

Abstract

Objective – To determine clinical efficacy of the Crotalidae polyvalent immune Fab (ovine) antivenom (OPCA)against progressive crotalid envenomation in the dog as reflected in stabilization or improvement of snakebiteseverity scores (SSS). Additionally, due to the potential decreased half-life of the Fab antibodies in dogs wecompared SSS between dogs receiving 2 different dosing regimes.Design – Prospective, clinical trial.Setting – Five veterinary emergency and critical care facilities.Animals – One hundred and fifteen client-owned Crotalid (rattlesnake) snake bitten dogs in whom worseningof the envenomation syndrome was observed before OPCA treatment.Interventions – In a multicenter randomized clinical trial a single dose (1 vial) of OPCA alone was comparedwith 2 doses (1/2 vial each) administered 6 hours apart. Standard supportive care was provided in all cases.Measurements and Main Results – Data were available for 115 patients, 9 of which were fatalities. Allpatients’ clinical condition was documented with a standardized SSS system accounting for each major bodysystem. Each fatality received maximum severity scores of 20. The mean severity score of the 115 patientsdecreased from 4.19 to 3.29 points and there was no difference between the 2 treatment groups. The meanseverity score of the 107 patients without fatalities decreased from 4.16 to 2.15. Antivenin-related acutereactions occurred in 6 dogs (6%), and no serum sickness occurred within the 95 cases contacted at the 2-weekposttreatment follow-up.Conclusions – In the first randomized trial in dogs of antivenin in the United States, OPCA effectivelystabilized or terminated venom effects. There were no statistical differences detected between treatmentgroups within the study time frame.


Keywords: dogs, efficacy trial, pit viper, postexposure therapy, snakebite

[Correction added after online publication 16 MAY 2011: Dr. Signe Plunkett’s name has been corrected.]

Introduction

In North America the venomous snakes known as pitvipers include 26 subspecies of rattlesnakes (Crotalusspp.), 3 subspecies of pigmy rattlesnakes (Sistrurus mili-aris), 3 subspecies of massassauga (Sistrurus catenatus),

5 subspecies of copperheads (Agkistrodon contortrix),and 3 subspecies of cottonmouth water moccasins(Agkistrodon piscivorus). It is estimated that 7,000–8,000rattlesnake bites occur per year in people in the UnitedStates.1 In 1999, the University of Arizona’s Poison andDrug Information Center managed 57 human rattle-snake bite cases in Tucson, AZ.2 In a veterinary surveyconducted by Johnston and Schmidt,3 466 dogs werepresented for rattlesnake bites to veterinary practices inthe Tucson area during the months of June, July, andAugust 1998, with only a 41% survey response rate.

The only proven, definitive treatment against anLD100 of pit viper venom in rats is IV administration ofantivenom (antivenom crotalidae polyvalenta [ACP]).4

The mortality rate in the United States for people

Address correspondence and reprint requests toDr. Michael E. Peterson, Reid Veterinary Hospital, 933 SW Queen Ave,Albany, OR 97321, USA.Email: [email protected] February 17, 2010; Accepted April 12, 2011.

From the Reid Veterinary Hospital, Albany, OR 97321 (Peterson); VeterinarySpecialty Center of Tucson, Tucson, AZ 85704 (Matz); Animal Urgent Careand Specialty Group, Escondido, CA 92025 (Seibold); Animal HealthServices, Cave Creek, AZ 85331 (Plunkett); Emergency Animal Hospital ofNorthwest Austin, Austin, TX 78759 (Johnson); and VCA Alameda EastVeterinary Hospital, Denver, CO 80247 (Fitzgerald).

Journal of Veterinary Emergencyand Critical Care 21(4) 2011, pp 335–345doi:10.1111/j.1476-4431.2011.00643.x

& Veterinary Emergency and Critical Care Society 2011 335

Veterinary F(ab’)2 Pit Viper Antivenom Veteria

Format and Attributes

20mL injection vial; room temperature storage Sterile lyophilized contents – rapid dissolution 3 year shelf life

Composition F(ab’)2 neutralizing antibody fragments Equine derived Venom used for production - Crotalus durissus, C. oreganus, C. o. helleri, C. adamanteus, C. scutulatus, C. atrox, C. horridus, Agkistrodon contortix, A. piscivorus, and Bothrops asper

Cross Neutralization

Neutralizes all common North American Pit Vipers

(in development

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60 healthy dogs

Administered 3 or 6 vials in under 1 hour

3 vial group (n = 30)

•  No reactions 6 vial group (n = 30)

•  Mild, self-limiting facial edema (n=3) •  Vomit (n =1)

No severe adverse events or alterations in CBC

Brief Clinical Communication Journal of Veterinary Emergency and Critical Care 21(5) 2011, pp 565–569doi: 10.1111/j.1476-4431.2011.00678.x

Clinical safety evaluation of F(ab′)2 antivenom(Crotalus durissus – Bothrops asper)administration in dogsCraig Woods, DVM, MS, MBA and David Young, DVM, PhD, DACVS

Abstract

Background – Antivenoms consisting of selective antigen binding antibody fragments, or F(ab′)2, are becomingmore popular in human and veterinary medicine, owing to their preferred kinetics, tissue distribution, andremoval of the Fc binding portion of IgG. Consequences of antivenom administration can include acute anddelayed reactions, dependent, in part, on the antivenom’s donor source, purity, and composition. This studyevaluated an equine-derived polyvalent F(ab′)2 pit viper antivenom in healthy dogs of various size, age, andbreed under controlled conditions. Dogs were allocated into 6 treatment groups (n = 10 per group) based onweight (3 weight groups) and dose (2 dose groups) and administered F(ab′)2 antivenom over 1 hour by IVinfusion. Dogs were observed for adverse events at 3, 6, 12, and 24 hours after administration and blood wascollected for CBC and serum biochemistry before and at 24 hours postadministration.Key Findings – No abnormalities were noted in the 3-vial group. In the 6-vial group, 3 dogs developed mildself-limiting edema around the head or neck, suggestive of a type 1 hypersensitivity, while another dog vomitedand developed mild hypocalcemia at 24 hours, reflecting a 13% reaction rate at high doses. However, no dogsexhibited clinical signs of hypocalcemia or had any severe adverse events. CBC remained normal in all groups.Significance – This study demonstrated that the polyvalent F(ab′)2 pit viper antivenom is well tolerated in dogsgiven large doses in a short period of time.


Keywords: antidote, antivenins, snake bite, viper venoms

Introduction

Envenomation often necessitates the immediate admin-istration of antivenom to reduce morbidity and mortality.In people, complications from antivenom administrationinclude anaphylaxis, delayed hypersensitivity, serumsickness, and the formation of immune complexes.1 Indogs, whole IgG antivenom has been documented tocause acute and delayed hypersensitivity reactions2 withacute adverse events occurring in up to 7% of dogs re-ceiving whole IgG crotalidae antivenom.3 Recent interestin the development of F(ab′)2 antivenoms has centered

From Animal Health Consulting, LLC, Prescott, AZ (Woods), and YoungVeterinary Research Services, Turlock, CA (Young).

Funding for this study was provided by BioVeteria Life Sciences, LLC,Prescott, AZ 86301.

At the time of the data collection, Dr. Craig Woods was a paid consultant toBioVeteria Life Sciences, LLC.

Address correspondence and reprint requests to Dr. Craig Woods, AnimalHealth Consulting, LLC, 1042 Willow Creek Rd, A101-430 Prescott, AZ 86301,USA.Email: [email protected] February 02, 2011; Accepted August 04, 2011.

on overcoming the limitations of whole IgG or Fab an-tivenom preparations. F(ab′)2 antivenoms have been de-veloped for envenomation from snakes (eg, pit vipers,cobra) and scorpions.4–6 Enzymatic cleavage and purifi-cation can remove the fragment crystallizable (Fc) por-tion from the final product, which reduces the activationof complement and anti-immunoglobulin response as-sociated with Fc binding.7 Recent studies using F(ab′)2

antivenom preparations support their safety profiles inpeople8, 9 but the safety profile in dogs is currently un-known and is the basis for this study.

The polyvalent F(ab′)2 pit viper antivenom used in thisstudy cross-protects against all common North Ameri-can pit viper venoms and has been previously assessedfor canine safety under field conditions.10 It was previ-ously administered to 74 dogs that were naturally en-venomated by North American pit vipers, with no doc-umented associated adverse events in dogs receiving 4vials.a The objectives of the current study were to deter-mine, in healthy dogs, (1) if acute toxicity develops indogs administered large doses in a short period of time,(2) the specific signs associated with adverse events,

C⃝ Veterinary Emergency and Critical Care Society 2011 565

Canine Field Efficacy And Safety Evaluation Of F(ab’)2 Antivenom

• 74 dogs o 4 vials F(ab’)2 antivenom administered

IV o No placebo o One death – intra-ocular envenomation

•  Significant improvement in clinical scores o Pain, extension of pain, ecchymosis,

discharge, swelling, extension of swelling, and sum of scores.

• Significant , rapid normalization of hematology o PT, PTT, platelets, echinocytosis

• No adverse events reported

Data presented IVECCS 2010, abstract session

Venom Levels In Dogs Treated With F(ab’)2 Antivenom

• Venom levels (ng/mL) were examined in dogs (n=55) at baseline, immediately after F(ab’)2 antivenom administration, and at 3, 6, 12, and 24 hrs after presentation.

Woods, Seibold and Wells. Abstracts, J. Toxicon 60 (2012) 296 Data presented at Venom Week 2012, oral abstract

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274 Cases Of Rattlesnake Envenomation In Dogs from Maricopa County, AZ 237 treated with Veteria F(ab’)2 antivenom

24 treated with ACP

12 received both

4 patients died, 4 were euthanized

274 Cases Of Rattlesnake Envenomation In Dogs from Maricopa County, AZ Overall survival > 97%

5/8 of the nonsurvivors received glucocorticoids Only 8% of survivors received glucocorticoids

15/274 had a history of rattlesnake vaccine No survival advantage 96% unvaccinated survived, 93% vaccinated survived

66/274 (24%) received antibiotics

Length of stay significantly (P<0.001) longer in dogs with bites to head and extremety combined

Lower body weight was associated with significantly (p<0.001) higher number of vials administered

274 Cases Of Rattlesnake Envenomation In Dogs from Maricopa County, AZ Preliminary conclusions….. F(ab’)2 antivenom (Veteria Labs, Mexico) safe, low rate of hypersensitivity reaction (0.7%)

1 vial sufficient to mitigate clinical signs in most dogs Survival advantage not appreciated with the following interventions: "  Rattlesnake vaccination "  Glucocorticoid administration "  Antibiotic administration

Bites to combination head and extremity more severe Dogs > 10 years of age have more severe clinical signs

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Venom Vet™

Format and Attributes

10ml injection vial, Sterile liquid contents 3 year shelf life

Composition F(ab’)2 neutralizing antibody fragments Equine derived Venoms used in production - Crotalus durissus, C. C. simus, Lachesis muta, Bothrops asper, B alternatus, B diporus,

Cross Neutralization

Labeled to neutralize all common North American Pit Vipers

(in development

Venom Vet™ - evidence IVECCS 2014 Abstract Session

n=23 (canine) mean dose = 4.39 vials **1 dog received 16 vials, caution in interpretation 1 dog experienced anaphylaxis, 1 dog had urticaria All dogs had reduction of modified SSS

Data from USDA approval process n = 36 (canine) 0 deaths in treated patients Significant reduction in modified snakebite severity score (p<0.05)

Bandt, C, Bulfer, L, Schaer, M, Buckley, G. Clinical safety evaluation of F(ab)2 antivenom for treatment of crotalidae envenomation in dogs. Abstracts IVECCS 2014

Venom Vet™

"  USDA approved for veterinary use, April 2014 "  Instituto Biológico Argentino S.A.I.C. Instituto Nacional de Microbiología.

Antibothropico tetravalente

"  Peer review literature and abstracts "  Abstract session, IVECCS 2014

"  F(ab’)2 antivenom, polyvalent, produced in Argentina – equine origin

"  No reconstitution required, liquid – ready for injection

"  Not labeled for cats or horses "  Has been used without known adverse events in both species

"  Equine clinical trials happening now – expect label change by Fall, 2015

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Veteria F(ab’)2 "  Peer review literature and abstracts

"  Pashmakova M, Bishop M, Black D, Bernhard C, Johnson S, Mensack S, Wells R, Barr J. Multi-center evaluation of the administration of crotalid antivenom in cats: 115 cases (2000-2011). J Am Vet Med Assoc 2013;243(4):520-525

"  Woods C and Young D. Clinical safety evaluation of F(ab’)2 antivenom administration in dogs. J Vet Emerg Crit Care 2011;21(5):565-9.

"  Wells R and C Woods. F(ab)2 antivenom treatment: a retrospective analysis of 180 rattlesnake envenomations in dogs. Oral Abstract. IVECCS 2013.

"  Seibold K, Woods C and Wells R. F(ab’)2 antivenom in dogs envenomated by pit vipers. Toxicon 2012:60:Abstract nr 295.

"  Woods C, Seibold K and Wells R. Crotalidae venom levels in dogs before and after administration of F(ab’)2 antivenom. Toxicon 2012:60:Abstract nr 296.

"  K Seibold, C Woods, R Wells, M Lagutchik, S Johnson, A Reniker, M Kaelble, M Clare, D Bordelon, B Vasilopulos. Neutralizing effects of F(ab’)2 antivenom on serum pit viper venom levels in dogs. Oral Abstract. IVECCS 2011.

"  F(ab’)2 antivenom, polyvalent, produced in Mexico – Equine origin

"  USDA approval – additional clinical efficacy trials planned Not available for purchase at this time

"  Company based out of Mexico City Partnerships and collaboration with human medicine Significant progress in global toxinology research

Venoms Neutralized

Potency Spec DL50Neut/vial

Batch 1 Veteria DL50 Neut/vial

Batch 2 Veteria DL50 Neut/vial

Bothrops asper* >780 2790.7 3005 C. durissus * >790 1051.1 1080.2 C. helleri >790 1350 1290.3 C. adamanteus >790 975.2 1020.5 C. scutulatus A >790 1130.4 1125.4 C. scutulatus B >790 1105 1230.5

A. bilineatus >350 490.6 500.4 A. contortrix >300 387.3 390.3

A. piscivorous >300 420.5 410.1

Veteria F(ab’)2 Antivenom Neutralizes the following venoms

Manuscript in preparations Antivenom effectiveness is measured based upon neutralization, not mg per vial

Procedure for administration – F(ab’)2 1-2 vials quickly depending on clinical signs

Dilute antivenom (if lyophilized) in sterile, 0.9% NaCl, LRS, Plyte Administer as quickly as possible

•  Begin slowly (~1mL/kg/min) x 10 minutes •  ↑to get remainder in within 30 minutes •  Label instructions are available as well

Monitor for signs of reaction •  Body temperature, facial edema, hives

Do not pre-treat with diphenhydramine or steroids

Consider CRI of 1-2 vials over 4-6 hours if reenvenomation occurs, or protracted clinical signs

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Veteria Venom Vet™

Liquid suspension ready for administration

Equine Plasma?

“Snakebite Protein Support”

Pooled plasma from horses vaccinated against C. atrox, C. adamentus, C. viridis, C. scutulatus

Website claims cheaper, 4mL/kg dose recommended

Unknown dose of antibodies

All other proteins are included

I do not recommend use in species other than equine at this time

6/6 dogs developed lymphadenopathy

Vaccination "  What is the

rationale? "  What is the

evidence?

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Natural Vaccination "  Antibodies

following natural envenomation in humans documented from days to years

"  Duration of immunity unpredictable

ELISA to measure antivenom in naturally exposed VS vaccinated horses

Vaccinates – 3 vaccines, 30 days apart

28% of horses did not respond to vaccine

•  50% had decreasing titers after last vaccine Natural exposure ! higher titers

**titers based on cell culture and mouse inoculation model designed by manufacturer of vaccine (unpublished)**

Antibody Responses to Natural Rattlesnake Envenomation and aRattlesnake Toxoid Vaccine in Horses

Lyndi L. Gilliam,a Robert C. Carmichael,a* Todd C. Holbrook,a Jennifer M. Taylor,b Charlotte L. Ownby,c Dianne McFarlane,d

Mark E. Paytone

Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, USAa; Hygieia Biological Laboratories,Woodland, California, USAb; Office of the Vice President for Research and Technology Transfer, Oklahoma State University, Stillwater, Oklahoma, USAc; Department ofPhysiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, USAd; Department of Statistics, Oklahoma State University,Stillwater, Oklahoma, USAe

Antivenom antibody titers following administration of rattlesnake venom for antivenom production in horses are well docu-mented; however, antivenom antibody titers following natural rattlesnake envenomation in horses are not. Antibody titers pro-duced in response to the commercially available rattlesnake venom vaccine are also not published. Our study objectives were tomeasure antivenom antibody titers in rattlesnake-bitten horses and compare them to titers in horses vaccinated with the rattle-snake venom vaccine. Additionally, titers were compared in pregnant versus nonpregnant horses to assess the affect of preg-nancy on vaccine response and were measured pre- and postsuckle in foals of vaccinated mares to detect passive transfer of vac-cine immunoglobulins. Blood samples were collected from16 rattlesnake-bitten horses. Thirty-six horses (11 pregnant mares, 12nonpregnant mares, 13 geldings) were vaccinated using a Crotalus atrox venom toxoid vaccine. Blood was collected before ad-ministering each vaccination and 30 days following the third vaccination. Blood was collected from foals of vaccinated marespre- and postsuckle. All serum was assayed for anti-Crotalus atrox venom antibodies using an enzyme-linked immunosorbentassay (ELISA). Rattlesnake-bitten horses had higher (P ! 0.001) titers than vaccinated horses. There was no significant differ-ence between titers in vaccinated pregnant versus nonpregnant horses. One mare had a positive titer at foaling, and the foals hadpositive postsuckle titers. Antivenom antibody titer development was variable following natural envenomation and vaccination,and vaccine-induced titers were lower than natural envenomation titers. Further studies are required to determine if natural orvaccine antivenom antibody titers reduce the effects of envenomation.

Antibody titers are frequently measured in horses used for theproduction of various antivenoms (1). Little is known, how-

ever, about antivenom antibody titers produced in horses follow-ing natural rattlesnake envenomation or following vaccinationwith the commercially available rattlesnake venom toxoid vac-cine. Information is not available on the duration that antivenomantibody titers persist following natural envenomation andwhether or not they protect horses against the adverse effects ofvenom in subsequent envenomations (2). Clinical signs, labora-tory responses, and clinical outcomes following natural rattle-snake envenomation vary in horses, and it is unknown whetherdiffering immune responses play a part in this variability (3–5). Inmice, it has been shown that circulating antivenom antibodiespresent at the time of, or shortly after, experimental envenoma-tion are effective at decreasing the toxic effects of venom (6). Inpeople bitten by the king cobra, there is evidence that the humoralimmune response to repeated envenomations is greater, more ef-fective at neutralizing venom effects, and longer lasting than thatof a single envenomation (7). Following natural envenomation,the persistence of circulating antibodies is highly variable in peo-ple and has been reported to be anywhere from 81 days after a puffadder bite (Bitis arietans) (8) to 8 weeks following a king cobra bite(Ophiophagus hannah) (7). Antibodies have persisted for 40 yearsin a patient after being bitten by a black-necked spitting cobra(Naja nigricollis) (9). Because people bitten multiple times oftenhave more mild venom effects, vaccination against venom haslong been attempted (10, 11). However, snake venoms seem tomake poor immunogens, and the duration of immunity is unpre-dictable (10, 12, 13).

The purpose of this study was to examine the immunologicresponse to natural rattlesnake envenomation by measuringvenom antibody titers in horses bitten by rattlesnakes. Subse-quently, we sought to compare immune response to natural en-venomation with that stimulated by a commercial rattlesnaketoxoid vaccine. The immunologic response to vaccination in late-gestation mares and colostral transfer of antivenom antibodies infoals were also investigated.

(Portions of these data were presented at the 2011 ACVIMForum in Denver, CO.)

MATERIALS AND METHODSStudy population and data collection. This was a prospective observa-tional study, including two distinct populations of horses. Sixteen horsesthat presented to participating veterinary clinics with a clinical diagnosisof rattlesnake bite were enrolled in the study. Areas where these horsesresided when bitten were the Texas Panhandle (13), western Oklahoma(1), southeast Oklahoma (1), and central Oklahoma (1). The most com-mon snakes in the area of the Texas panhandle and western Oklahoma

Received 2 January 2013 Returned for modification 14 January 2013Accepted 11 March 2013

Published ahead of print 20 March 2013

Address correspondence to Lyndi L. Gilliam, [email protected].

* Present address: Robert C. Carmichael, Carter Animal Hospital, Thayne,Wyoming, USA.

Copyright © 2013, American Society for Microbiology. All Rights Reserved.

doi:10.1128/CVI.00004-13

732 cvi.asm.org Clinical and Vaccine Immunology p. 732–737 May 2013 Volume 20 Number 5

on September 4, 2013 by CO

LARADO STATE UNIV

http://cvi.asm.org/

Downloaded from

I do not recommend the rattlesnake vaccine – no evidence of protection in dogs

Consider rattlesnake aversion training if high risk patient

Wound Laser Light Amplification by Stimulated Emission of Radiation

Anecdotal reduction in swelling

" Low Level Recommended " No more than TID

recommended

No peer review literature published at this time in veterinary patients

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Antibiotics – The Rationale Most common bacteria isolated from crotalid mouths

" Pseudomonas " Proteus " Clostridium " Bacteroides

Previous human studies recommended antimicrobial therapy based on studies of oral flora

Newer studies failed to document any morbidity or survival benefit with prophylactic antibiotics

Antibiotics?

Lack of value in human and veterinary medicine for RSE

Consider guidelines for responsible antimicrobial use

No documented case reports of tetanus in any veterinary or human literature secondary to snake envenomation

Humans and horses are significantly more susceptible to tetanus

Antibiotics – the veterinary evidence Manuscript in press (Journal Vet Emerg Crit Care)

A Carr, et al

"  Prospective observational study in So. California "  n = 102, canine "  No antibiotics administered "  Each patient followed for evidence of infection "  Avg. length of stay 24 hours "  Incidence of infection low (0.01%, 1/102) "  Overall mortality rate low (0.03%, 3/105)

•  2 upper airway obstruction •  1 direct arterial envenomation

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Glucocorticoids No longer considered standard of care Multiple publications demonstrating lack of survival or morbidity advantage What about upper airway swelling?

" More antivenom STAT! " These patients typically need a tracheostomy

" Steroids unlikely to prevent this need " Glucocorticoid and surgical wound in hospital

" Increased risk of surgical site infection

NSAIDS Not recommended Platelet inhibition

May exacerbate coagulopathy Risk of kidney injury

Rattlesnake Envenoming – Summary Treatment Analgesia •  Opioids are a safe option Antivenom

•  F(ab’)2 Antivenom or Polyvalent ACP •  Some cases stabilize without antivenom

IV fluids •  Crystalloids, use synthetic colloids with caution **coagulopathy and risk of kidney injury**

Antibiotics only in select cases •  E.g., documented infections, severe distal extremity wounds •  Monotherapy against likely opportunistic pathogens pending culture/sensitivity

•  E.g., Cefazolin,Ampicillin Monitor coagulation times, PCV/TS, monitor for hemolysis Monitor for arrhythmias Prioritize renal perfusion Avoid NSAIDs Avoid plasma – will not treat coagulopathy

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Summary- Overall Regarding Antivenoms Rattlesnake envenoming can be a serious clinical problem

Low mortality overall

Antivenom administration improves morbidity

F(ab’)2 is safe and clinically effective in dogs

RTLR™ is not antivenom, not recommended for non equine patients

VenomVet™ USDA approved for pit viper envenomation in veterinary patients

Clinical efficacy in Eastern Diamondback envenomation

Anecdotal efficacy in AZ

Boreinger Ingelheim(ACP) remains available, is USDA approved

FAQs - RSE Can I give multiple types of antivenom to a patient?

Yes

The animal was vaccinated, does this mean they do not need antivenom?

Vaccination does not eliminate the need for antivenom We used to treat these with steroids and Benadryl and the dogs survived, why should I give antivenom?

The newer F(ab’)2 antivenoms are safe and effective, minimize morbidity and likely shorten time to recovery. Cost may be justified by less time in hospital and less need for other interventions.

FAQs - RSE I’ve heard that the fragmented (Fab) antivenoms don’t last long and need more frequent re-dosing, why should I bother?

The Fab monomer antivenom (Crofab™) does have an extremely short T1/2 and requires frequent re-dosing. The F(ab’)2 antivenoms have a longer T1/2 than the monomer variations, but in most cases a single vial is sufficient. The two fragmented antivenoms discussed in this webinar should not require more frequent dosing based upon antivenom composition.

If overall mortality of rattlesnake bite is low, why bother giving antivenom?

Antivenom improves clinical scores, reducing patient suffering and may decrease length of stay.

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Common Treatment Plan

IV fluid therapy •  Shock and maintenance to perfuse kidneys

Analgesia •  Opioid CRI, multimodal may be required

Antivenom •  1-2 vials rapid, repeat if clinical signs do not improve or

worsen. Consider CRI (1-2 vial over 6 hours, continuous) for refractory or recurrent clinical signs


Baseline labs •  PCV/TS, venous blood gas/lytes, blood smear/CBC

(platelet estimate), PT/PTT or whole blood clotting time (does blood clot in tube?)

Hospitalization and monitoring •  24 hours ideal, continuous EKG ideal, blood pressure,

urine output, pain scores, serial coags/platelet est. (repeat 1 hour post antivenom if possible, then in 12-24 hours), PCV/TS (monitor for hemolysis)


Discharge •  24 hours if stable for at least 12 hours, sometimes

finances dictate sooner

Recheck •  PCV/TS 24-48 hours after discharge to monitor for

delayed hemolysis

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Treated with multiple vials ACP antivenom, still unable to walk – severe myopathy

Immediately following rapid infusion of F(ab’)2 antivenom - Veteria

1 hour following F(ab’)2 antivenom - Veteria

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