Post-Mortem Findings in 54 Cases of Anesthetic Associated Death in Cats From Two Spay Eneuter Programs in New York State
Post-Mortem Findings in 54 Cases of Anesthetic Associated Death in Cats From Two Spay Eneuter Programs in New York State
Post-Mortem Findings in 54 Cases of Anesthetic Associated Death in Cats From Two Spay Eneuter Programs in New York State
doi:10.1016/j.jfms.2011.07.021
1
Department of Anatomic Anesthetic-associated death (AAD) in cats is infrequent, but occurs far more
Pathology, College of Veterinary frequently than in people. Post-mortem investigations of AAD in cats are
Medicine, Cornell University, uncommon, and results only sporadically published. Here we report the
Ithaca, NY 14853, United States findings in 54 cases of AAD in cats. Significant gross and/or microscopic
2
Animal Health Services, ASPCA, pre-existing disease, including pulmonary, cardiac, and systemic disease, was
1717 South Philo Road, Suite 36, detected in 33% of cases. Pulmonary disease was most frequently diagnosed
Urbana, IL 61802, United States (24% of cases), and included cases of Aelurostrongylus abstrusus infection (9% of
3
Animal Health Services, ASPCA, cases). Heart disease, including two cases of hypertrophic cardiomyopathy, was
PO Box 1144, Orchard Park, NY less frequent (11% of cases). Four percent died from surgical complications.
14127, United States No significant gross or microscopic disease was detected in 63% of cases.
4
Upstate Veterinary Specialties, 222 Additional studies are needed to determine if these findings are representative
Troy Schenectady Road, Albany, of AAD in cats in other geographic areas or with access to veterinary care. This
NY 12210, United States study demonstrates that post-mortem investigation of AADs is an important and
5
Shelter Outreach Services, 78 worthwhile endeavor.
Dodge Road, Ithaca, NY 14850,
United States
Date accepted: 19 July 2011 Ó 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
A
nesthetic-associated death (AAD) has been cats that die unexpectedly perioperatively often have
variably defined as death occurring within hypertrophic cardiomyopathy (HCM), no data exist
24 or 48 h of anesthetic administration, or to support this statement. The lack of studies cannot
at any time, so long as the cause of death is relatable be blamed on lack of AAD cases, for although
to anesthesia.1e5 In human pathology, AAD investiga- AADs in day-to-day veterinary practice are relatively
tions are often legally mandated. These investigations, rare events, the AAD rate for cats is approximately
in combination with studies of anesthesia-associated 2.4 per 1000 procedures.4 Although comparisons of
mortality risk, have been credited with making anes- mortality data between humans and cats must be
thesia safer for people over the past 70 years, reducing done cautiously, due to differences in patient popula-
the AAD rate in the US from roughly one per 1000 tions and different disease severity profiles, the anes-
procedures to one per 100,000 procedures.6 thetic death rate for cats is roughly an order of
Post-mortem investigations of animals with AAD magnitude greater than that of people.9
are uncommon, with few, sporadic reports of findings The purpose of post-mortem AAD investigation in
on a small number of cases.7,8 Because there have been veterinary medicine is to determine the cause of
no systematic investigations to examine the lesions, death, primarily by ruling in or out surgical complica-
diseases, or mechanisms of AADs in veterinary med- tion or concurrent disease complicated by anesthesia.
icine, there is minimal information available on the There are no known pathognomonic or even typical
nature and frequency of lesions in animals that expe- gross or histopathologic findings for anesthesia-re-
rience AAD. For instance, although it is an adage that lated deaths. As a result, post-mortem investigations
of AADs are likely to be either informative (ie, surgi-
cal complication or disease discovered) or neutral
*Corresponding author. E-mail: jag56@cornell.edu (ie, no disease discovered).
1098-612X/11/120959+08 $36.00/0 Ó 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.
960 JA Gerdin et al
High quality, high volume spayeneuter organiza- by the HQHVSNOs included: owned cats from
tions (HQHVSNOs) are surgical initiatives that per- low-income households, cats in shelters, unowned
form sterilization of large numbers of dogs and cats, cats with regular human supervision and/or interac-
and which meet or exceed established veterinary tion (stray cat colonies, barn cats, etc), and un-
medical guidelines of care.10 Investigating AADs in owned trapped feral cats. A variety of anesthetic
cats served by HQHVSNOs offer a unique opportu- drugs, used in varying combinations at varying dos-
nity to study the pathologic findings in cases of ages, were used by the programs over the course of
AAD. Firstly, these programs perform the same surgi- the study period.
cal procedures on large numbers of cats. Together, the All post-mortem investigations were conducted by
two programs in this study spay or neuter more than the Section of Anatomic Pathology. A complete nec-
25,000 cats per year. The surgeries are planned, non- ropsy, following standard procedures, was performed
emergency, elective procedures. Also, cats presented within 12e48 h of receiving the body.11 Bodies were
to these clinics are ostensibly in good health, with received both fresh and frozen. In all cases, a full set
an assessed or assumed (in the case of cats unable to of tissues were collected and fixed in 10% formalin.
be physically examined) to be of American Society The tissues processed for histology were dependent
of Anesthesiologists (ASA) Physical Status Scale Class upon the gross findings in the case. In nearly all cases,
I or II (Table 1). This degree of standardization reduces histologic examination of major organs, including the
or eliminates variables such as surgical procedure, heart, lung, brain, liver and kidneys, plus any lesions,
urgency of procedure, monitoring methods and was performed in addition to the gross inspection. In
equipment, and general health status, variables which rare cases, histology was not performed as the cause
have been shown to correlate with risk of anesthetic of death was conclusively determined from the gross
death in animals.4 The rates of AADs in these two inspection (ie, hemoabdomen) or initial histologic
HQHVSNOs are generally low, at 0.8 and 1.6 per evaluation. In some cases, additional special stains
1000 procedures (LA and MS, personal communica- and immunohistochemistry were performed in order
tion); due to varying anesthetic protocols and proce- to confirm or refute the differential diagnosis (eg, pan-
dures as well as underlying health issues, AAD rates leukopenia, HCM, etc). The presence or absence of
likely vary in different practice settings. Finally, inves- significant disease, defined as pre-existing natural dis-
tigating AADs in this population of cats could also ease that would have increased anesthetic risk of
yield important information about the health status death, was determined by the pathologist in charge
of cats with limited or no veterinary care. of the case. At the end of the study period, all submis-
sion information, final necropsy reports, and all histo-
logic sections were reviewed by one of the authors
Materials and methods (JG). Rare discrepancies between the initial interpreta-
A retrospective study of post-mortem investigations tion and those based on review (JG) were resolved by
of AAD in domestic cats from HQHVSNOs was con- a third evaluation (SPM) to arrive at a consensus
ducted at Cornell College of Veterinary Medicine. diagnosis.
Cases of AAD were defined as death within 24 h of re-
ceiving anesthetic agents. Cases of AAD were submit-
ted from two HQHVSNOs. One, operating in central
Results
upstate New York (CNY), submitted cases between At the end of the study period, 56 cases had been sub-
May 2009 and December 2010. The other, in the mitted for necropsy by two HQHVSNOs. In two of
greater New York City (NYC) area, submitted cases these cases, the cats died 6 or more days after anesthe-
between February 2009 and August 2010. Cats served sia and surgery. These cases, in which the cause of
death was determined to be septic peritonitis and
panleukopenia (feline parvovirus), respectively, were
excluded.
Table 1. ASA Physical Status Scale (http://www. In total, 54 cases met the inclusion criteria for the
asahq.org/clinical/physicalstatus.htm). study, including 33 females and 21 males. Both popu-
Patient characteristics lations of cases of AADs were composed primarily of
young adult cats weighing approximately 3 kg
Class I Normal, healthy (Table 2). From the CNY group, two cases were un-
Class II Mild systemic disease owned cats, three cases were owned cats, and seven
Class III Severe systemic disease cases were not specified. From the NYC group, 33
Class IV Severe systemic disease that is cases were unowned cats, and nine cases were owned
a constant threat to life cats.
Class V Moribund patient; not expected to Fifty-two cases submitted were of cats that went into
survive without surgery cardiopulmonary arrest, within a period of minutes to
24 h, from the time of premedication administration.
Class VI, not applicable to veterinary medicine, is not
Of the cats that arrested, two were resuscitated but
included.
euthanased a short time later, due to persistent
Post-mortem findings in 54 cases of anesthetic associated death in cats 961
Hepatic lesions were noted only in three cases, and Cats eliminate the infection after approximately
only by histologic examination. All three cases dem- 5 months and cannot be re-infected.17 Clinical disease
onstrated multifocal random hepatitis. In one case, in infected cats is rarely reported, but can include
toxoplasmosis was suspected as myocarditis was coughing, dyspnea, bronchopneumonia, and in rare
also noted. In the other two cases of hepatitis, small cases, spontaneous pneumothorax. The gold standard
foci of neutrophils with hepatocyte loss, along with for diagnosis is a Baerman fecal examination.18 In this
hepatic extramedullary hematopoiesis, were the only study, a majority of the cats diagnosed post-mortem
lesions noted. These lesions were not considered ex- with A abstrusus came from the CNY area; this may re-
tensive enough to have contributed significantly to flect differences in food sources available, with greater
death. access to paratenic hosts in more rural areas.
The two cats diagnosed with postoperative he- A abstrusus infection in cats results in granulomatous
moabdomen were both were female, and all ligatures pneumonia. A combination of eggs, L1 larvae and mac-
were in place. Additional evidence of a bleeding di- rophages fill alveoli, reducing available surface area for
athesis, such as significant hemorrhage or petechia- gas exchange (Fig 2). A abstrusus infection also results in
tion in other locations (body wall, skin, mucous hypertrophy and hyperplasia of the tunica muscularis
membranes) was not noted. of pulmonary arteries and smooth muscle hypertrophy
None of the 54 cases included in the study had sig- throughout the lung.19 In one study of experimental in-
nificant gross or histologic evidence of renal disease. fection, these changes were shown to persist for over
a year.20 Hypertrophy and hyperplasia of the smooth
muscle of pulmonary arteries is also induced by
Discussion Dirofilaria immitis infection in cats, and has been shown
Our results demonstrate that post-mortem investiga- to result in pulmonary hypertension.21 Although pul-
tions of animals with AAD can yield important infor- monary hypertension has not been conclusively dem-
mation about occult infectious and idiopathic disease, onstrated in cats with A abstrusus, it is reasonable to
especially lung, heart, and systemic infections. suspect it occurs, based on the similarity of vascular
Although this study was limited to cats with minimal changes. No gross or histologic evidence of right ven-
access to veterinary care, including feral cats, the find- tricular free wall hypertrophy, a sequelae of chronic
ing of a high frequency of occult pulmonary disease pulmonary hypertension, was noted in any of the cases
also has implications for surgical candidates that are of A abstrusus infection; however, the relationships be-
recently adopted stray cats or owned cats that spend tween the duration and degree of pulmonary hyperten-
a large percentage of time outdoors. sion and effect on the right ventricular free wall
thickness is not well characterized in cats.
In people with pulmonary hypertension, anesthetic
A abstrusus and anesthesia
drug-induced decreases in heart rate and/or systemic
The high frequency of cases of A abstrusus was unex- blood pressure result in a sudden drop in pulmonary
pected. The reported prevalence of infection rates of perfusion, and an attendant decrease in the volume of
A abstrusus in domestic cats varies widely among blood returned to the left ventricle.22 Similarly, when
studies (1e22%), due to differences in the studies’ sedated or anesthetized, cats infected with A abstrusus
geographic area, methods of detection, and the nature may no longer be able to compensate for decreased
of the populations studied e owned versus stray gas exchange surface area and (presumed) pulmonary
cats.14 Some studies suggest that stray cats have hypertension, resulting in a precipitous drop in blood
higher rates of infection.14,15 Interestingly, an equal oxygen saturation and decreased left ventricular fill-
number of owned and feral cats were diagnosed ing. With lung perfusion and ventilation significantly
post-mortem with A abstrusus infection in this study. compromised, these cats would rapidly succumb to
A abstrusus is a metastrongyloid nematode parasite a combination of hypoxia and systemic hypotension,
with worldwide distribution. Adult worms reside in culminating in cardiovascular collapse and arrest.
the terminal bronchioles of cats, the definitive host. Unfortunately, the prevalence of A abstrusus in the
Females lay eggs which molt into first stage larvae populations studied is unknown, as is the percentage
(L1) in alveoli. These L1 larvae are then coughed up of cats infected with A abstrusus that survived anesthe-
and eliminated through the feces, which contaminate sia and surgery. Disease prevalence investigations into
the environment and infect gastropods (snails and this population of cats could help clarify the role of
slugs), the intermediate host. After molting to the this parasite in AADs.
third larval stage (L3) in intermediate hosts, L3 larvae
are infective for cats, but L3 larvae are also carried by
Other lesions
paratenic hosts: birds, rodents, frogs and lizards. L3
larvae ingested by cats migrate from the intestine to The proportional mortality ratio of HCM within the
the lung, and develop into adult (L5) worms. Eggs AAD study group was 4% (2/54). The small number
are deposited in cats’ lungs 25 days after infection; of cases would seem to contradict the adage that
however, it takes 40 days for L1 larvae to develop AADs are often due to HCM. The etiology of the
and pass in the feces where they can be detected.16 four cases of lymphocytic myocarditis is unknown,
964 JA Gerdin et al
and although toxoplasmosis was often suspected in endotracheal intubation, biochemical derangements
these and other cases, tachyzooites were not detected such as respiratory acidosis secondary to hypoventila-
using immunohistochemical stains. However, the tion, and cardiac conduction abnormalities. It is impor-
small size of the infective form of Toxoplasma gondii, ta- tant to note that proving death due to drug-specific side
chyzooites, measure approximately 5 2 mm, which effects or anesthetic overdose, using post-mortem toxi-
makes identification challenging in the majority of cological analysis, is currently not feasible in veterinary
toxoplasmosis cases. Only a few of the tiny T gondii medicine.
tachyzooites are needed to incite significant inflamma- Cases of AAD with occult disease were diagnosed
tion however, and so the absence of organisms in his- as ‘AAD with [disease entity],’ because it is the an-
tologic section does not conclusively rule out this esthetic effects in combination with the disease
differential diagnosis. Additional diagnostic tech- state(s) that precipitate death. Complicating dis-
niques such as polymerase chain reaction (PCR) eases considered significant should be limited to
would have been more sensitive for detection of those body systems which are affected by or have
T gondii organisms had cost not been a constraint in a profound effect upon anesthesia, including the re-
this study. Differential diagnoses for primary lympho- spiratory system, cardiovascular system, nervous
cytic myocarditis in cats also includes Bartonella hense- system, and renal and hepatic (drug-metabolizing)
lae, a wide variety of systemic infectious agents may systems. Systemic disease states, including both in-
spread to the heart. Myocarditis may also be seen in fectious and non-infectious diseases (neoplastic, id-
association with cardiomyopathy, although no other iopathic, etc), also have the potential to have
evidence of cardiomyopathy was seen in the four a profound impact on anesthesia and risk, as re-
cases of lymphocytic myocarditis. flected in the ASA Physical Status Scale. Only in
In the two cases of hepatitis with small foci of neu- those cases where the patient could be expected to
trophilic infiltration and hepatocyte loss and extrame- die regardless of anesthesia, can the anesthetic set-
dullary hematopoiesis, an acute bacterial shower from ting of the death potentially be disregarded.2
portal blood was suspected, as was infection with Using standardized terminology in pathology re-
Mycoplasma haemofelis. However, neither case had ad- ports for cases of AADs will more clearly reflect the
ditional histologic changes, such as icterus, splenic he- nature and circumstances of the death, and allow eas-
mosiderosis, or lymphadenopathy, to support ier identification of these cases and compilation of
a diagnosis of M haemofelis. data, so that population-based studies of risk factors
Finding cases of panleukopenia in this population for AAD can be conducted in the future.
of young, largely unvaccinated cats were unsurpris-
ing. Clearly, more studies of cats with AAD need to Study limitations
be investigated to determine if the population studied
here is representative of AADs of owned cats with The amount of case-related information recorded in
regular veterinary care. Cornell’s necropsy data varied widely, in large part
Both cases of hemoabdomen were diagnosed in fe- due to the open-ended nature of the necropsy submis-
males, and no other evidence of a bleeding diathesis sion form. Unfortunately, the variability of informa-
was noted at necropsy. As all ligatures were in place, tion submitted and protocols employed during the
we suspect that an ovarian or uterine artery retracted study period limited the comparisons that could be
proximal to the level of the ligature, effectively releas- made regarding anesthetic drugs administered, doses,
ing the artery from ligation. Alternatively, ligatures and relationship to sex, age, weight, time to arrest, etc.
may not have adequately constricted the artery. Towards the end of the study, a standard list of infor-
mation, useful from clinical, anesthesiologic, and
Cases without gross or histologic findings pathologic perspectives in cases of AAD, was devel-
oped (Table 3).
The implications in cases without gross or histologic Also, although AAD was defined as death within
findings are limited. What can be said conclusively 24 h of receiving anesthesia, postoperative monitoring
is that death occurred in association with anesthesia, of all cats for a full 24 h could not be guaranteed, even
and no gross or histologic evidence of significant, though it is recommended by the HQHVSNOs to care-
complicating disease was detected. Ultimately, these takers that cats be monitored for 48 h postoperatively
cases are best labeled as ‘AAD of unknown etiology’. prior to release. Both HQHVSNOs have phone numbers
Note that this categorization only specifies the cir- available to call if caretakers had questions or problems,
cumstances of the death, and is not the same as or however. Therefore, cats that died or were euthanased
tantamount to concluding that death was solely or within 24 h were likely completely reported.
primarily due to anesthesia. Finally, variation among pathologists is always
All parties involved in an AAD investigation should a concern in retrospective pathology studies. In this
be aware that many fatal anesthetic complications can- study, differences were minimized by strict adherence
not be detected by post-mortem investigations. These to the necropsy protocol and collection of a complete,
include mechanical causes of death such as upper air- standardized set of tissues, although the tissues exam-
way occlusion by the soft palate or improper ined histologically varied among pathologists and
Post-mortem findings in 54 cases of anesthetic associated death in cats 965
Table 3. Recommended submission information for cases of AAD. The type of arrest can be essential in
establishing the mechanism and cause of death.3 The percentage of oxygen in the lungs at the time of
death can have a profound impact upon the gross appearance at the time of necropsy and affect inter-
pretation (artifact or true lesion). Similarly, cardiopulmonary resuscitation (CPR) efforts, including drug
administration, may result in post-mortem artifacts.
Recommended submission information for cases of AAD
Signalment Time arrest was noted
Presenting complaint Type of arrest: respiratory or cardiopulmonary
ASA Physical Status Scale category/significant Oxygen content inspired/delivered at time of death
physical exam findings (based on information (room air, 100% O2, etc)
available prior to anesthesia)
Purpose of anesthesia/sedation (exam, surgery, CPR attempted (Y/N)
other procedure, etc)
Pre-anesthetic medications: drugs, doses, routes, CPR drugs/reversal agents administered
and times given (dose and route)
Induction drugs: drugs, doses, routes, and times given Oxygen content delivered during CPR
(room air, 100% O2, etc)
Maintenance drugs: list drugs, doses, routes, Duration of CPR
and times given
Endotracheal intubation (Y/N) Body handling since time of death
(refrigeration, freezing, thawing, etc)
cases handled by the same pathologist. While having 3. Lienhart A, Auroy Y, Pequignot F, et al. Survey of
all necropsies performed by an individual pathologist anesthesia-related mortality in France. Anesthesiology
may decrease variability, review by multiple patholo- 2006; 105: 1087e97.
gists decreases the risk of a systematic bias in 4. Brodbelt DC, Pfeiffer DU, Young LE, Wood JL. Risk
factors for anaesthetic-related death in cats: results
interpretation.
from the confidential enquiry into perioperative small
animal fatalities (CEPSAF). Br J Anaesth 2007; 99:
617e23.
Conclusion 5. Start RD, Cross SS. Acp. Best practice no 155. Pathologi-
We hope that this is the first in a series of studies of cal investigation of deaths following surgery, anaesthe-
the lesions and diseases that contribute to AADs in sia, and medical procedures. J Clin Pathol 1999; 52:
640e52.
cats, as well as other veterinary species. It is important
6. Li G, Warner M, Lang BH, Huang L, Sun LS. Epidemiol-
for clinicians to be aware of the utility of the necropsy ogy of anesthesia-related mortality in the United States,
in AAD investigation, both as a means to discover 1999e2005. Anesthesiology 2009; 110: 759e65.
more information on an individual case-basis, and as 7. Dyson DH, Maxie MG, Schnurr D. Morbidity and mor-
a contribution to the effort to make anesthesia safer tality associated with anesthetic management in small
for all veterinary species. animal veterinary practice in Ontario. J Am Anim Hosp
Assoc 1998; 34: 325e35.
8. Scott KC, Levy JK, Crawford PC. Characteristics of free-
roaming cats evaluated in a trap-neuter-return program.
Acknowledgements J Am Vet Med Assoc 2002; 221: 1136e8.
Funding for post-mortem investigations was provided 9. Brodbelt MA. Feline anesthetic deaths in veterinary
in part by a grant from Pfizer Animal Health. Pfizer practice. Top Companion Anim Med 2010; 25: 189e94.
Animal Health had no role in the study design, collec- 10. Looney AL, Bohling MW, Bushby PA, Howe LM, Griffin
B, Levy JK. The Association of Shelter Veterinarians vet-
tion, analysis or interpretation of data, or in the writ-
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manuscript for publication. 11. King. The necropsy book. 5th edn. Ithaca, NY: Charles
Louis Davis Foundation, 2007.
13. Liu S, Peterson ME, Fox PR. Hypertrophic cardiomyop-
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