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71 9 Investigating Fatal Suspected Poisonings INTRODUCTION Veterinary staff may encounter situations where they are asked to investigate cause of death of a companion animal that was apparently healthy when observed last but was later found dead by the owner. In many such situations, the animal may have had clinical signs that went unno- ticed by the owner, or the animal may not have been observed during the time of illness. Investigating sudden death in dogs and cats in the absence of clinical signs can be quite challenging. The definition of sudden death in terms of time may vary from person to person. For the purpose of this discussion, sudden, unattended, or unexplained death is defined as death occurring in an apparently healthy animal within a 12- to 24-hour period with no premonitory clinical signs or with minimal clini- cal signs (Casteel and Turk 2002). The purpose of this chapter is to outline the approach to take in the inves- tigation of sudden death and to provide some common toxicologic rule-outs that should be included for inves- tigating sudden acute unattended death in dogs and cats (Table 9.1). CAUSES OF SUDDEN DEATH A list of common causes of acute sudden death is available for large animals. However, for small animals, limited information is available on this topic. Animal poisoning (accidental or malicious) in dogs, according to one 10-year retrospective study, is the second most cause of sudden death in dogs after heart diseases (Table 9.2) (Olsen and Allen 2000). In cats, however, poisoning has not been listed as a cause of acute sudden death (Table 9.3) (Olsen and Allen 2001). Investigation of sudden death in a dog or a cat is no different than investigation of any other disease condition. Nontoxicologic rule-outs including infectious, metabolic, nutritional, physical, and miscellaneous causes must be considered along with poisoning when investigating sudden death in a pet. It is important to realize that the effects of a toxicant on the body are dose-dependent. Many of the toxicants listed in the rule-out list from Table 9.1 may not be expected to cause acute sudden death with small exposures. However, the list includes the most common/likely toxicants that possess the potential to cause acute sudden death with the right amount (dose) of exposure. The reader is encouraged to review more detail about a particular topic or agent listed in this text once a reasonable cause of death has been narrowed down. DIAGNOSTIC APPROACH History The investigation of acute sudden death involves close cooperation between client, veterinary staff, and diagnos- tic laboratory personnel. A complete and thorough case history is essential for such investigations. A good case history can help expedite the process of putting together all the pieces and eliminate several unnecessary steps early. Obtaining a recent case history from the client may Small Animal Toxicology Essentials, First Edition. Edited by Robert H. Poppenga, Sharon Gwaltney-Brant. © 2011 John Wiley and Sons, Inc. Published 2011 by John Wiley and Sons, Inc. Safdar A. Khan

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71

9 Investigating Fatal Suspected Poisonings

INTRODUCTION

Veterinary staff may encounter situations where they are asked to investigate cause of death of a companion animal that was apparently healthy when observed last but was later found dead by the owner. In many such situations, the animal may have had clinical signs that went unno-ticed by the owner, or the animal may not have been observed during the time of illness. Investigating sudden death in dogs and cats in the absence of clinical signs can be quite challenging. The defi nition of sudden death in terms of time may vary from person to person. For the purpose of this discussion, sudden, unattended, or unexplained death is defi ned as death occurring in an apparently healthy animal within a 12 - to 24 - hour period with no premonitory clinical signs or with minimal clini-cal signs (Casteel and Turk 2002 ). The purpose of this chapter is to outline the approach to take in the inves-tigation of sudden death and to provide some common toxicologic rule - outs that should be included for inves-tigating sudden acute unattended death in dogs and cats (Table 9.1 ).

CAUSES OF SUDDEN DEATH

A list of common causes of acute sudden death is available for large animals. However, for small animals, limited information is available on this topic. Animal poisoning (accidental or malicious) in dogs, according to one 10 - year retrospective study, is the second most cause of sudden death in dogs after heart diseases (Table 9.2 ) (Olsen and Allen 2000 ).

In cats, however, poisoning has not been listed as a cause of acute sudden death (Table 9.3 ) (Olsen and Allen 2001 ).

Investigation of sudden death in a dog or a cat is no different than investigation of any other disease condition. Nontoxicologic rule - outs including infectious, metabolic, nutritional, physical, and miscellaneous causes must be considered along with poisoning when investigating sudden death in a pet.

It is important to realize that the effects of a toxicant on the body are dose - dependent. Many of the toxicants listed in the rule - out list from Table 9.1 may not be expected to cause acute sudden death with small exposures. However, the list includes the most common/likely toxicants that possess the potential to cause acute sudden death with the right amount (dose) of exposure. The reader is encouraged to review more detail about a particular topic or agent listed in this text once a reasonable cause of death has been narrowed down.

DIAGNOSTIC APPROACH

History

The investigation of acute sudden death involves close cooperation between client, veterinary staff, and diagnos-tic laboratory personnel. A complete and thorough case history is essential for such investigations. A good case history can help expedite the process of putting together all the pieces and eliminate several unnecessary steps early. Obtaining a recent case history from the client may

Small Animal Toxicology Essentials, First Edition. Edited by Robert H. Poppenga, Sharon Gwaltney-Brant.© 2011 John Wiley and Sons, Inc. Published 2011 by John Wiley and Sons, Inc.

Safdar A. Khan

72

Table 9.1. Common toxicants that can cause sudden death in dogs and cats

Agent Comments

5 - Flurouracil Topically used anticancer medication; seizures, vomiting, cardiac arrhythmias; acute death possible with large ingestion

5 - hydroxytryptophan (5 - HTP) Used as OTC sleep aid and antidepressant; seizures, hyperthermia; acute death with large ingestions possible

Acetaminophen Death due to methemoglobinemia within hours with large ingestion; cats more sensitive

Albuterol Prescription bronchodilator for asthma; acute death with large ingestion possible; cardiac arrhythmias, hypokalemia

Amphetamines Recreational or human prescription; hyperthermia, hyperactivity, circling, hypertension, tachyarrhythmias; acute death with large ingestion possible

Anticoagulant rodenticides Internal bleeding 3 – 5 days postingestion; acute death due to pulmonary hemorrhage possible

Antidepressants Common human prescription medications; acute death possible with large ingestion; CNS and cardiac effects

Arsenic Toxicosis uncommon; watery diarrhea, abdominal pain, shock, acute death possible

Baclofen Prescription drug; coma, hypothermia, respiratory depression; death with large ingestion

Barbiturates Common anticonvulsant, accidental ingestion of large doses; farm dogs eating fl esh/carcass of animals euthanized by barbiturates; coma, hypothermia, and death

Blue - green algae History of drinking from a lake/pond; algae on the muzzle; collapse, shock, seizures, liver failure, death

Botulism Acute death rare; ingestion of preformed toxins from eating a carcass; progressive weakness, paralysis, death

Brunfelsia spp ingestion Strychnine - like signs (seizures, rigidity); dogs attracted to fruit/seed pods/fl owers; acute death possible with large ingestion

Bufo toad Common in Florida and other Southern states; acute collapse, salivation, cardiac arrhythmias, seizures, death

Caffeine Ingestion of chocolate or caffeine pills; acute death with large ingestion possible; vomiting, CNS signs, cardiac arrhythmias

Carbon monoxide Uncommon; bright red mucous membranes Cardiac glycosides - containing plants Acute death uncommon; evidence of plant ingestion Castor beans Acute death unlikely; only possible if several seeds have been ingested Cocaine Recreational drug; acute death possible Ethylene glycol Acute death with large ingestions possible; cats more sensitive Garbage poisoning History of eating garbage; acute death possible with some Salmonella,

E. coli toxins; vomiting, progressive shock and death Hepatotoxic mushrooms Vomiting, diarrhea, abdominal pain, shock, liver failure, death Hops (used for beer fl avoring) Malignant hyperthermia - like syndrome in dogs; acute death possible Ionophores (e.g., monensin, lasalocid) Eating cattle feed; farm dog; acute death with large ingestion (premix)

possible Iron Multivitamins; large ingestions, acute death uncommon, vomiting,

shock, liver damage Isoniazid ingestion Antituberculosis drug; seizures, acute death possible

Chapter 9 / Investigating Fatal Suspected Poisonings 73

Agent Comments

Lidocaine and other local anesthetics Uncommon toxicosis; CNS, and cardiovascular effects Metaldehyde Used mostly as slug bait; seizures, hyperthermia, acute death with

large ingestion possible Moldy food ingestion (tremorgenic

mycotoxins) History of ingestion of moldy food; seizures, hyperthermia, vomiting,

acute death possible Nicotine Acute death with large ingestion possible; GI, CNS and cardiac effects Organochlorine type pesticides Lindane, eldrin, dieldrin; use not common anymore; cats more

sensitive; seizures, tremors, and acute death Organophosphates/Carbamate insecticides Some highly toxic OPs/carbamates like methomyl, aldicarb (tres

pasitos), disulfoton; usually SLUD signs present; acute rapid death possible

Paint ball ingestion (glycols) Ingestion of large amounts; acute death not common, seizures due to hypernatremia possible

Pseudoephedrine OTC decongestant; amphetamine - like signs; acute death with large overdose possible

Pyrethrins/pyrethroids (permethrin in cats) Cats more sensitive to concentrated products; tremors, seizures, death Sago palm Acute death unlikely; only possible if several seeds have been

ingested; seizures, liver failure Salt (sodium chloride) Homemade play - dough ingestion; some use for inducing emesis;

seizures, hypernatremia, death possible Smoke inhalation History of pet trapped in the house during fi re Snake bite Mohave rattle snake, eastern rattle snake; acute death possible Strychnine Used as a rodenticide bait; rapid onset, seizures, hyperthermia, rigidity,

death, rapid onset rigor mortis Tetrodotoxins Acute death rare; ingestion of dried puffer fi sh, pet salamander;

paresis, respiratory failure, death Water intoxication History of being on the beach/swimming; hyponateremia,

hypochloremia, polydipsia Xylitol ingestion Acute death due to severe hypoglycemia possible; acute liver failure

possible 1 – 3 days after ingestion Zinc phosphide Available as gopher bait; vomiting, CNS effects; acute death with large

ingestion possible

Table 9.1. Continued

sometimes be diffi cult, especially in situations where the animal was unsupervised immediately prior to death. Clients may be too distraught to have good recollection of recent events, and it is not uncommon for them to focus on one particular event (e.g., herbicide recently applied to lawn) as the potential cause of death. Patient and tactful questioning is paramount to getting a history that is as accurate as possible.

Important historical questions must include animal sig-nalment (breed, sex, weight, and age); previous medical history, vaccination history, and any medications the pet was taking; information regarding other animals present

in the household; timeline of death (i.e., when the pet was last seen alive, where and when the pet was found dead); where pet had been in the hours/days prior to death (e.g., traveling, beach, park, neighbors, pet sitter, party); evi-dence of clinical signs (e.g., vomiting, diarrhea, seizure); number of affected animals (i.e., any other sick animals in the household); information about the animal ’ s environ-ment (indoor vs. outdoor, free - roaming vs. fenced), loca-tion (urban vs. rural), time of the year (summer vs. winter); recent renovations, construction or updates; availability of recreational drugs (amphetamines, cocaine) or human medications in the animal ’ s environment (antidepressants,

74 Section 1 / Fundamentals of Veterinary Clinical Toxicology

Table 9.2. Underlying causes of sudden and unexpected deaths in 151 dogs as reported in the literature

General Cause of Death Number of Cases

% of Total

Heart disease 33 21.9 Toxicosis 25 16.6 Gastrointestinal disease 20 13.2 Trauma 19 12.6 Hemorrhage not associated

with trauma 10 6.6

Malnutrition or dehydration 8 5.5 Respiratory disease 6 4.0 Urogenital disease 5 3.3 Central nervous system disease 2 1.3 Peritonitis 2 1.3 Pancreatic disease 2 1.3 Undetermined 19 12.6 Total 151 100

Source : Olsen and Allen 2000 .

Table 9.3. Underlying causes of sudden and unexpected deaths in 79 cats as reported in the literature

General Cause of Death Number of Cases

% of Total

Trauma 31 39.2 Heart disease 16 20.3 Intestinal disease 6 7.6 Respiratory disease 5 6.3 Urinary tract disease 4 5.1 Feline leukemia virus –

related disease 3 3.8

Menengioencephlitis 1 1.3 Hepatic necrosis 1 1.3 Sepsis 1 1.3 Hemorrhage not associated

with trauma 1 1.3

Undetermined 10 12.7 Total 79 100.2 a

Source : Olsen and Allen 2001 . a Exceeds 100 due to rounding.

painkillers, stimulants, nutritional supplements, overnight visitors taking prescription medications); the presence of insecticides, fl ea/tick control products, herbicides, or rodenticides in the house or yard; recent visits by pest control or lawn care companies; and information about presence of indoor or outdoor plants and lawn/garden fer-tilizers or chemicals) (Cote and Khan 2005 ). Information about disputes involving the neighbors, coworkers, family members, or others may help determine if the death could be malicious.

Sample Collection

The best way to investigate acute sudden death is by having a complete necropsy (gross and histopathologic examination) performed, preferably by a board certifi ed veterinary pathologist (Volmer and Meerdink 2002 ). After obtaining an initial history, multiple digital pictures of the dead animal with any lesions (hemorrhage, mucous mem-brane color, broken skin/bones etc.) along with incriminat-ing agent (if any) and surrounding environment (plants, chewed - up container, bait, feed, water etc.) should be taken. Stringent written documentation and chain of custody protocols should be followed for all potential medicolegal cases; if necessary, contact local animal control or law enforcement for details on securing poten-tial legal evidence. For shipment to a diagnostic labora-tory, triple - bag the dead animal and ship it to a diagnostic

laboratory on ice or dry ice through an express mail. Inform the diagnostic laboratory about the shipment before shipping. Avoid shipping over the weekends or holidays. Talk to the shipping carrier before shipping the animal to discuss packaging and labeling requirements.

Unfortunately, in many situations the options for a com-plete necropsy may not be feasible due to economics, animal size, or shipment constraints. In such circum-stances, appropriate postmortem samples should be obtained from the animal and the environment. Collection of inappropriate type or amount of samples, and inade-quate preservation techniques are some of the most common errors that hinder investigation by diagnostic laboratories. To avoid cross - contamination, all samples should be collected in separate containers, properly labeled with the patient ’ s and owner ’ s name, and dated. For his-topathologic examination, a full set of tissues from all major organ systems should be cut 4 – 5 mm thick and placed in 10% formalin.

Most toxicologic analyses require frozen or refrigerated samples. Important samples for toxicologic investigations include liver, kidney, stomach contents, urine, abdominal fat, brain, heart clot blood and serum, hair, feed, water, or suspected bait (if available). The preferred anticoagulant for storage of whole blood is EDTA, although heparin is also acceptable in some case. Whole blood, serum, or urine

Chapter 9 / Investigating Fatal Suspected Poisonings 75

detail sample submission requirements. Discuss cost, turn-around time, limitations of analytical methods if any, and interpretations of results with the diagnostic toxicologist if needed. The latter is especially important, because with modern analytical equipment it is possible to detect a wide variety of compounds at levels far below those that would have clinical signifi cance. The toxicologist can assist in determining whether the levels found are consistent with a toxicosis.

CONCLUSION

The sudden death of a companion animal can be an emo-tionally challenging time for animal owners and veterinary staff. It is important that the veterinary staff understand the steps that need to be taken to investigate the cause of death so that the right questions can be answered and the appro-priate samples are collected.

samples should be refrigerated or chilled until analyzed. The amount of samples should be reasonable. Generally, the larger the amount, the better it may be. You can always discard the excessive amount or extra samples later if not needed. Larger amounts can allow the toxicologist to repeat an analysis, test for additional potential toxicants, and confi rm the results with a different method if neces-sary. An entire set of samples must be collected for toxi-cologic analysis even when the diagnosis may be obvious or apparent (Casteel and Turk 2002 ; Volmer and Meerdink 2002 ).

Sample Submission

A concise history of events should be submitted to the diagnostic laboratory along with your request for analyses. For a completed necropsy or toxicologic analysis an accredited diagnostic laboratory should be utilized when-ever possible. Most laboratories now have websites that

1. A client brings a dead adult male cat into the hospital. What is the fi rst step in dealing with this case? a. Collect samples for toxicology. b. Perform a necropsy. c. Obtain a history. d. Take radiographs. e. Draw some blood for a chemistry profi le.

2. The client says that the cat was a stray that she and several neighbors had been feeding for several months. One neighbor had taken the cat to be neu-tered and vaccinated 2 months ago, and the cat appeared generally healthy. The client had fed the cat last night and he seemed fi ne; this morning he was lying dead on her porch. The client called the neigh-bors who were helping to feed the cat; no one saw anything out of the ordinary in the past 24 hours, and none had administered medication or fl ea control to the cat within the past week. The client is suspicious that the cat has been maliciously poisoned and wants to know why the cat died. A cursory external exam of the shows no lesions or evidence of why the cat may have died. What is the next step? a. Collect samples for toxicology. b. Perform a necropsy. c. Take radiographs. d. Draw some blood for a chemistry profi le.

3. A necropsy is performed and samples are taken for histopathology. Additional samples are collected for toxicology, but are kept at the clinic pending the results of the necropsy and histopathology. What is the preferred means of storage of these samples until they are ready to be submitted to the toxicology laboratory? a. Frozen b. Refrigerated c. Fixed in 10% buffered formalin solution d. a and b e. a, b, and c

4. The necropsy and histopathology on the cat were highly suggestive of ethylene glycol (antifreeze) toxi-cosis. What is the next step? a. Call the diagnostic laboratory to determine which

sample(s) to submit for ethylene glycol. b. Call animal control to report a malicious

poisoning. c. Call the neighbors to see whether they suspect

anyone of poisoning the cat. 5. The toxicologic analysis of the submitted samples

confi rmed the presence of ethylene glycol in the cat ’ s stomach contents, fat, and kidney. Is this proof that the cat was maliciously poisoned? Why or why not?

CHAPTER 9 STUDY QUESTIONS

Continued

76 Section 1 / Fundamentals of Veterinary Clinical Toxicology

— — — . 2001 . Causes of sudden and unexpected death in cats: A 10 - year retrospective study . Canadian Veterinary Journal 42 : 61 – 62 .

Volmer P.A. , Meerdink G.L. 2002 . Diagnostic toxicology for the small animal practitioner . Veterinary Clinics of North America Small Animal 32 : 357 – 365 .

ANSWERS

1.c. Obtain a history to determine the most appropriate course of investigation.

2.b. A necropsy holds the best chance of determining why the cat died.

3.d. Samples for toxicology can be stored either refrig-erated or frozen prior to submitting to the laboratory.

4.a. Determine which samples to submit and have them analyzed by the diagnostic laboratory.

5. No. Without a witnessed exposure it is not pos-sible to say for sure whether the exposure was malicious or accidental.

REFERENCES

Casteel S.W. , Turk J.R. 2002 . Collapse/sudden death . In Large Animal Internal Medicine , 3rd edition , edited by B.P. Smith , pp. 246 – 253 . St. Louis: Mosby - Elsevier.

Cote E. , Khan S.A. 2005 . Intoxication versus acute, non - toxicologic illness: Differentiating the two . Ettinger and Feldman ’ s Text Book of Veterinary Internal Medicine , 6th edition , pp. 242 – 245 . St. Louis : Elsevier - Saunders .

Olsen T.F. , Allen A.L. 2000 . Causes of sudden and unex-pected death in dogs: A 10 - year retrospective study . Cana-dian Veterinary Journal 41 : 873 – 875 .