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Presumptive Benzocaine-Induced Methemoglobinemia in aSlender-Tailed Meerkat (Suricata Suricatta)Author(s): Zoltan S. Gyimesi, D.V.M. and Roy B. Burns, D.V.M.Source: Journal of Zoo and Wildlife Medicine, 40(2):389-392. 2009.Published By: American Association of Zoo VeterinariansDOI: http://dx.doi.org/10.1638/2008-0158.1URL: http://www.bioone.org/doi/full/10.1638/2008-0158.1

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PRESUMPTIVE BENZOCAINE-INDUCED METHEMOGLOBINEMIA

IN A SLENDER-TAILED MEERKAT (SURICATA SURICATTA)

Zoltan S. Gyimesi, D.V.M., and Roy B. Burns, D.V.M.

Abstract: An 8-yr-old castrated male slender-tailed meerkat (Suricata suricatta) was anesthetized for physical

examination and dental prophylaxis. To facilitate intubation, two short bursts of benzocaine spray were applied

topically to the glottis. Shortly thereafter, the meerkat developed a muddy, blue-gray mucous membrane color and

low oxygen saturation readings measured via pulse oximetry. Despite positive pressure ventilation and treatment

with doxapram, the cyanosis and hypoxemia did not improve. Blood collected during the procedure was noticeably

dark brown and a clinical diagnosis of methemoglobinemia was made. Because of persistent cyanosis and

prolonged recovery, the meerkat was anesthetized a second time to facilitate treatment for methemoglobinemia via

a slow intravenous bolus of methylene blue and subcutaneously administered dextrose. Within 20 min, the tongue

and gingival color normalized. This is the first report of methemoglobinemia in this species. Although it is

commonly used in small animal practice and in humans undergoing certain endoscopic procedures, and present in

numerous over-the-counter preparations, the risk of topical benzocaine inducing methemoglobinemia is well

described. Administration of topical benzocaine in all mammalian species, particularly small patients, should be

done with caution. If it is utilized in zoo practice, clinicians are encouraged to administer benzocaine judiciously to

avoid accidental overdose, and be familiar with the signs of methemoglobinemia and its treatment.

Key words: Benzocaine, Herpestidae, methemoglobinemia, methylene blue, slender-tailed meerkat, Suricata

suricatta.

BRIEF COMMUNICATION

An 8-yr-old, 1.26 kg, castrated male slender-

tailed meerkat (Suricata suricatta) was anesthe-

tized for physical examination and dental pro-

phylaxis. The meerkat was administered a dose of

ketamine HCl (KetaVedTM, Phoenix Scientific,

Inc., St. Joseph, Missouri 64503, USA; 15.9 mg/

kg i.m.), followed immediately by isoflurane

(IsothesiaTM, Butler Animal Health Supply,

Dublin, Ohio 43017, USA; 3% during induction,

0.5–2.0% during maintenance) via mask. To

facilitate intubation with a 2.5-mm endotracheal

tube, two short bursts of a topical anesthetic

spray containing 14% benzocaine, 2.0% butam-

ben, and 2.0% tetracaine HCl (CetacaineH,

Cetylite Industries, Inc., Pennsauken, New Jersey

08110, USA) were applied to the glottis.

Following intubation, the meerkat began

breath-holding and, shortly thereafter, the meer-

kat developed a muddy, blue-gray mucous

membrane color and low oxygen saturation

readings measured via pulse oximetry (50–70%

on multiple locations: tongue, cheek, foot).

Because of the clinical signs, positive pressure

ventilation with isoflurane and oxygen was

administered, delivering 4–6 breaths/min. A dose

of doxapram HCl (RespiramTM, Modern Veter-

inary Therapeutics, LLC, Miami, Florida 33157,

USA; 3.2 mg/kg i.m.) was given and the percent-

age of isoflurane being delivered to maintain

anesthesia was reduced. Despite these measures,

cyanosis and hypoxemia persisted. Routine blood

collection revealed grossly dark, brown blood.

The remaining examination, whole body radio-

graphs, vaccinations, and dental prophylaxis

were expedited because of the anesthetic compli-

cations.

The total anesthesia time was 53 min. Recov-

ery was prolonged and following extubation,

moist respiratory sounds were audible. Cyanosis

persisted and aspiration during the procedure,

pulmonary edema, and/or laryngeal trauma

related to intubation were considered possible

differentials for the moist respiratory sounds. The

meerkat was treated empirically with dexameth-

asone (Dexaject, Phoenix Scientific, Inc.; 1.1 mg/

kg i.m.), furosemide (Furoject, Butler Animal

Health Supply; 4.0 mg/kg i.m.), and penicillin G

benzathine/procaine (DurapenTM, IVX Animal

Health, Inc., Fort Dodge, Iowa 50501, USA;

59,524 U/kg s.c.) and placed in an oxygen

chamber. Thoracic radiographs obtained during

the procedure were interpreted as normal. A

complete blood count revealed a low normal

packed cell volume (PCV) (32%; reference range5

5 41 6 6.2%). No hemolysis was present and a

blood smear evaluation revealed no Heinz bodies.

Serum chemistries revealed elevated blood urea

From the Louisville Zoological Garden, 1100 Trevi-

lian Way, Louisville, Kentucky 40213, USA. Corre-

spondence should be directed to Dr. Gyimesi (zoli.

gyimesi@louisvilleky.gov).

Journal of Zoo and Wildlife Medicine 40(2): 389–392, 2009

Copyright 2009 by American Association of Zoo Veterinarians

389

nitrogen (53 mg/dL; reference range5 5 25 6

7 mg/dL) and high normal creatinine (1.4 mg/dL;

reference range5 5 0.9 6 0.3 mg/dL). Urinalysis

revealed well-concentrated (sp. gr. 5 1.049),

acidic (pH 5 6.5) urine, proteinuria (300 mg/

dL), and an unremarkable sediment. Aside from

the dark, brown color of the blood and prerenal

azotemia, the laboratory results from the proce-

dure were considered unremarkable. One to two

hours later, the meerkat was still lethargic in the

oxygen chamber and cyanosis persisted. An

episode of vomiting was observed, and when

ambulating, the meerkat would walk in an

uncoordinated manner and bump into the walls

of the chamber. Despite oxygen support and

empirical treatment, clinically, the meerkat did

not improve.

The brown coloration of the blood and

persistent cyanosis unresponsive to ventilation

and oxygen support led to a presumptive diagnosis

of methemoglobinemia. A vial of 1% methylene

blue (American Regent, Inc., Shirley, New York

11967, USA) was acquired from a local human

hospital. The meerkat was anesthetized a second

time with isoflurane via mask and 1.3 mg of

methylene blue (1 mg/kg) diluted in 2.5 ml of

0.9% saline was administered as a slow intrave-

nous bolus in a cephalic vein over 7 min. In

addition, 60 ml of 5% dextrose (Hospira, Inc.,

Lake Forest, Illinois 60045, USA) was adminis-

tered subcutaneously and the meerkat was recov-

ered and placed back into the oxygen chamber.

The total anesthesia time for this second event was

13 min. On a subsequent recheck exam under

manual restraint, within 20 min of methylene blue

administration, the meerkat was more alert and its

mucous membrane color was pink and interpreted

as normal. The meerkat was crated and discharged

from the zoo hospital.

The following day the meerkat was lethargic

and inactive. Recheck examination via manual

restraint revealed normal mucous membrane

color and capillary refill time. Differentials

considered for the lethargy included potential

adverse effects related to methylene blue therapy

(Heinz body anemia, other red cell morphologic

changes, methemoglobinemia, and decreased

erythrocyte life span), tissue damage from pro-

longed hypoxemia, or exhaustion from the

clinical events the day prior. The meerkat was

induced with isoflurane via mask as before. A

physical examination revealed no new findings.

Blood was collected and appeared grossly nor-

mal. The meerkat was administered subcutaneous

fluids (lactated Ringer’s solution, Hospira, Inc.;

120 ml) and recovered routinely. The PCV

remained low normal (34%; reference range5 5

41 6 6.2%) and red blood cell morphology was

interpreted as normal. The meerkat’s attitude and

activity normalized by the following day and

thereafter.

Methemoglobin develops when the iron in

hemoglobin is oxidized from the oxygen-carrying

ferrous state (Fe2+) to the ferric state (Fe3+).

Methemoglobin cannot bind and transport oxy-

gen, and when levels get high enough, can lead to

cyanosis and tissue hypoxemia. In healthy adult

humans and animals, methemoglobin accounts

for less than 3% of total hemoglobin.7–10,12

Methemoglobinemia is a relatively uncommon,

but potentially fatal, hemoglobinopathy. It may

be an inherited disorder, or, more commonly,

acquired as a result of drug or chemical exposure.

A long list of medications and chemicals are

reported to cause methemoglobinemia, including

certain herbicides and pesticides, acetaminophen,

antimalarials (chloroquine and primaquine), sul-

fonamides, nitrates and nitrites, and local anes-

thetics (benzocaine, lidocaine, prilocaine, and

procaine).7,10,12 Of the local anesthetics, benzo-

caine is a powerful oxidizing agent and most

commonly implicated with methemoglobinemia.9

Benzocaine sprays are commonly used during

certain human medical procedures to topically

anesthetize mucous membranes in order to help

obtund the pharyngeal and tracheal reflexes.

Benzocaine is also present in many over-the-

counter products such as oral analgesic gels,

throat lozenges, hemorrhoid preparations, vaginal

creams, and first aid sprays for children. Benzo-

caine-induced clinical methemoglobinemia has

been reported in humans,3,6,9–16 dogs,4 cats,7 and

sheep,8 and was first recognized in 1950.1 Methe-

moglobinemia from benzocaine has also been

experimentally induced in several laboratory

animal species (rats, mice, ferrets, rhesus monkeys,

cynomolgus monkeys, owl monkeys, rabbits, and

miniature pigs), following topical application to

the mucous membranes.2 The exact mechanism of

action is unclear but appears to involve direct

oxidation of the iron in hemoglobin.12

Whether this is an idiosyncratic hypersensitiv-

ity reaction in certain individuals or strictly dose-

related is also not clear.7,14 Factors that appear to

predispose to acquired methemoglobinemia in-

clude an excessive dose, a break in the normal

mucosal barrier (ulceration or inflammation

present, which may increase systemic absorp-

tion), age (human cases appear to occur more

commonly in infants and the elderly), preexisting

390 JOURNAL OF ZOO AND WILDLIFE MEDICINE

condition (anemia, sepsis), and the concomitant

use of other drugs known to cause methemoglo-

binemia.3,4,6,12 In human infant studies, it appears

that 15–25 mg/kg of benzocaine is capable of

inducing methemoglobinemia and cyanosis.11,15 In

one study in cats, approximate doses of 1.4–

2.1 mg/kg of benzocaine resulted in clinical

methemoglobinemia in 2 of 7 cats tested.7 The

meerkat in this report received an estimated 0.2–

0.4 ml of benzocaine topically, equivalent to 28–

56 mg (22–44 mg/kg). The benzocaine product

used in this report is recommended to be applied

for 1 sec or less. Spray in excess of 2 sec is

considered contraindicated. The relatively high

dose administered to the mucous membranes

may have been the primary contributor to

inducing methemoglobinemia in this patient.

The presence of brown blood is highly

suggestive of methemoglobinemia; however a

definitive diagnosis is established with co-oxim-

etry. Co-oximetry not only measures the percent-

age of methemoglobin in whole blood, but can

also differentiate between oxyhemoglobin, deox-

yhemoglobin, and carboxyhemoglobin.9,16 In hu-

mans, treatment is indicated when the methemo-

globin level is 30% or greater.3,11 Co-oximetry was

not performed in this case because of logistics,

because an insufficient blood volume was collect-

ed and a laboratory able to run the specialized

test was not identified in a timely manner. The

oxygen saturation readings obtained via pulse

oximetry (SpO2) in this case were likely spurious,

because methemoglobinemia is reported to force

SpO2 towards 85%, regardless of the true arterial

hemoglobin oxygen saturation (SaO2).9,10,13,16 A

presumptive diagnosis of methemoglobinemia

was made in this meerkat based on the history

of benzocaine exposure, distinctive brown blood

color, cyanosis that did not respond to ventila-

tion or supplemental oxygen, and the rapid

response to methylene blue treatment.

Treatment in cases of acquired methemoglobi-

nemia typically involves supportive care and

intravenous administration of methylene blue at

1–2 mg/kg. Methylene blue dye acts as an electron

donor, and its metabolic product effectively reduces

methemoglobin back to hemoglobin.4,10 This meer-

kat was also administered dextrose subcutaneously,

as glucose must be present in adequate levels for

methylene blue therapy to be effective.16

Benzocaine continues to be utilized in many

settings despite the numerous reports in the

literature on the methemoglobinemia side effect.

In humans, the incidence is still relatively low.

This is the first report of methemoglobinemia in a

meerkat. Administration of topical benzocaine in

all mammalian species, particularly small pa-

tients, should be done with caution. If benzocaine

is utilized in zoo practice, clinicians are encour-

aged to administer it judiciously to avoid

accidental overdose, and to be familiar with the

signs of methemoglobinemia and its treatment.

Acknowledgments: The authors thank Cathe-

rine Smolinski and Virginia Crossett for technical

assistance, and the pharmacy at Norton Audu-

bon Hospital for promptly supplying the vial of

methylene blue.

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GYIMESI AND BURNS—METHEMOGLOBINEMIA IN A MEERKAT 391

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Received for publication 29 August 2008

392 JOURNAL OF ZOO AND WILDLIFE MEDICINE