V 20TH ANNIVERSARY
12 December 1999
CE Refereed Peer Review
FOCAL POINT
★Acute ethylene glycol (EG)
intoxication, characterized by
hyperosmolality, high anion gap
metabolic acidosis, and acute
renal failure, is a medical
emergency that requires rapid
diagnosis and early, aggressive
therapy.
KEY FACTS
■ Measurement of serum
osmolality and calculation of the
osmolal and anion gaps may aid
in diagnosis.
■ Ethanol therapy is associated
with central nervous system and
respiratory depression as well as
exacerbation of EG-induced
hyperosmolality and osmotic
diuresis.
■ 4-Methylpyrazole is the treatment
of choice for dogs but not cats.
■ Intensive monitoring and
aggressive use of intravenous
fluids and sodium bicarbonate
are essential in the management
of acute EG intoxication.
■ The use of peritoneal dialysis
may allow cats and dogs to
recover from acute renal failure
secondary to EG intoxication.
Vol. 21, No.
Acute Ethylene Glycol
Intoxication. Part II.
Diagnosis, Treatment, Prognosis,
and Prevention*
Tufts University
Alison R. Gaynor, DVM
Nishi Dhupa, BVM, MRCVS
ABSTRACT: Acute ethylene glycol (EG) intoxication is a rapidly progressive, life-threatening
emergency with a complex pathophysiology—the key features of which include hyperosmolali-
ty, high anion gap metabolic acidosis, and acute oliguric renal failure. Rapid diagnosis is critical
and requires a strong index of suspicion and often repeat analyses. Antidotal therapy is based
on preventing biotransformation of EG to its toxic metabolites; however, intensive physiologic
monitoring and aggressive use of intravenous fluids and sodium bicarbonate are also essential
components of treatment. Despite advances in our understanding of the pathophysiology and
therapy of EG intoxication, most animals are presented already in oliguric renal failure and may
require hemodialysis or peritoneal dialysis to survive the effects of this intoxication.
A
cute ethylene glycol (EG) intoxication is a rapidly progressive medical
emergency characterized by hyperosmolality, profound high anion gap
metabolic acidosis, and acute oliguric renal failure. Although EG itself
causes central nervous system (CNS) depression, serum hyperosmolality, and os-
motic diuresis, most of the toxic effects are caused by the products of its
metabolism after initial conversion by hepatic alcohol dehydrogenase (ADH;
Figure 1). Glycolate in particular has been shown to be primarily responsible for
the severe metabolic acidosis that develops and is thought to be the most likely
major mediator of toxicity; however, the mechanism of renal tubular epithelial
necrosis remains poorly understood. The pathophysiology, clinical stages, and
clinicopathologic findings of acute EG toxicosis were reviewed in Part I of this
two-part presentation. This article discusses the diagnosis, current treatment rec-
ommendations, prognosis, and prevention of this devastating intoxication.
DIAGNOSIS
Early, rapid diagnosis of EG intoxication is critical because the prognosis for recov-
ery is inversely related to the time elapsed between ingestion and initiation of thera-
py.1 Clinicians must maintain a high index of suspicion because a history of inges-
*Part I of this two-part presentation appeared in the November 1999 (Vol. 21, No. 11)
issue of Compendium.
Compendium December 1999 20TH ANNIVERSARY Small Animal/Exotics

Measurement of serum osmo-

HO-CH2-CH2-OH lality, if available, and calcula-
Lactate Ethylene glycol tion of the osmolal gap may be
NAD+
helpful diagnostic aids early in
Alcohol
dehydrogenase the course of intoxication be-
cause serum hyperosmolality
NADH
parallels (and is caused by) in-
Pyruvate HO-CH2-C O
H creasing serum EG concentra-
Glycoaldehyde tions.2–7 Osmolality is a measure
NAD+
Citric acid cycle Glucose of the total number of solute
Aldehyde
dehydrogenase particles per weight of a solvent;
Glyoxal sodium and potassium salts, urea,
NADH
and glucose are the osmotically
HO-CH2-C O active compounds that con-
OH
Glycolate tribute to extracellular fluid os-
molality in normal animals. 8
Normal serum osmolality in
dogs and cats is roughly 280 to
310 mOsm/kg,1,2 although ref-
O C-C O α-Hydroxy, β-ketoadipate erence ranges vary among spe-
H OH c tor cies and laboratories.8 Evalua-
ine cofa
Glyoxylate Thia
m tion of the osmolal gap (i.e., the
Pyrid difference between measured
oxine
cofac
tor Glycine and calculated osmolality) is
helpful in detecting an in-
Benzoate
creased amount of an abnormal
O O Hippurate osmotically active solute (i.e.,
C-C EG) in the blood. Numerous
HO OH
formulas are available for calcu-
Oxalate lating serum osmolality; those
that work well with one set of
Figure 1—Ethylene glycol metabolic pathways. Solid arrows indicate the quantitatively most instruments may not work well
important steps; broken arrows indicate postulated metabolic pathways. Pathways may vary in other laboratories.9 We prefer
according to species.
to use the following formula10:

tion is often unavailable, and clinical signs are relatively
nonspecific and may mimic other disease syndromes.
There are, however, a few key features that may aid in
more rapid diagnosis. As discussed in Part I, clinical signs
of depression, vomiting, ataxia, polyuria, polydipsia, and
tachypnea in combination with hyperosmolality, metabol-
ic acidosis with an elevated anion gap (AG), isosthenuria,
and calcium oxalate monohydrate or dihydrate crystalluria
are early findings in dogs and cats with acute EG intoxica-
tion. EG intoxication must also be considered in any ani-
mal presenting with signs of acute renal failure. Laboratory
testing should ideally include a complete serum chemistry
profile, urinalysis, arterial or venous blood gas determina-
tions, and preferably determination of ionized calcium
concentrations. Because the time of appearance of certain
of these key features, such as calcium oxalate crystalluria,
may vary among individuals, the importance of repeat
analyses cannot be overemphasized.
Calculated osmolality (mOsm/kg) =
2(Na+ + K+) + (BUN ÷ 2.8) + (Glucose ÷ 18)
There is a significant correlation between serum EG
concentrations and the osmolal gap,4,5 such that the
serum EG concentration in dogs may be estimated by
multiplying the osmolal gap by a factor of 6.2.5 Clini-
cians must keep in mind that serum osmolality and the
osmolal gap may not be elevated if animals are present-
ed later in the course of intoxication (after most or all
of the serum EG has been metabolized) or if animals
have ingested small quantities of EG.
Another useful diagnostic aid is determination of the
AG, which is used to help characterize clinical causes of
metabolic acidosis. The AG is calculated as follows:
AG (mEq/L) = (Na+ + K+) – (Cl– + HCO3–)
Because positive and negative charges in the blood

CLINICAL SIGNS ■ SERUM OSMOLALITY ■ ANION GAP

Small Animal/Exotics 20TH ANNIVERSARY Compendium December 1999

must be in balance, there is erol and metaldehyde (snail

no true AG. As indicated by
this formula, the calculated
AG is mainly caused by un-
measured serum anions, con-
sisting of negatively charged
proteins (primarily albumin)
and such inorganic acids as
phosphate and sulfate. 8,11
The addition of an organic
acid (an unmeasured anion;
in this case, primarily glyco-
late) to the body results in
a metabolic acidosis with a
normal chloride level and an Figure 2—Ultrasonographic appearance of a kidney in a dog as 4 to 6 hours after inges-
increased AG. For cats and with anuric renal failure secondary to ethylene glycol intoxi- tion.15,16 With increasing time
dogs, “normal” AGs are ap- cation. (Courtesy of Dr. D. Penninck, Tufts University School and dose of EG, progressive
of Veterinary Medicine)
proximately 15 to 25 mEq/L,
although this also varies
among laboratories and species.8 An elevated AG may
not be evident very early in the course of EG intoxica-
tion. In addition, the AG may appear normal in intoxi-
cated animals that are concurrently receiving potassium
bromide therapy because bromide is not distinguished
12
from chloride in some assays.
Analysis of serum or urine concentrations of EG by
gas chromatography is the most specific diagnostic test
for intoxication; however, such tests are expensive and
are not always readily available, even in human hospi-
tals.12 Laboratory testing for glycolate would also be use- or confirm a diagnosis of EG intoxication.
ful, especially because it can be detected 3 to 60 hours
after ingestion in dogs13 and for at least 72 hours in
cats.3 However, no tests for glycolate are currently avail-
able at most medical centers or reference laboratories.
A commercial test kit (Allelic Biosystems Ethylene
Glycol Test Kit, PRN Pharmacal, Inc., Pensacola, FL)
that appears to accurately measure blood EG concentra-
tions of 50 mg/dl or greater is available for use in dogs
with EG intoxication; results are available within 30
minutes. The test kit, based on an enzymatic assay, is
most useful 1 to 12 hours after ingestion but may help
document exposure for up to 24 hours. After 24 hours,
most EG will have been metabolized. The test kit is not
sensitive enough for use in cats and may yield negative
results despite the ingestion of a lethal dose of EG. Al-
though the test kit has never been validated, it appears to
be reliable and accurate.a Blood samples for testing
should be drawn before initiation of any therapy because
false-positive results may occur with propylene glycol (an
additive in many anticonvulsants [e.g., diazepam] and
other medications, including activated charcoal). Glyc-
a
Personal communication: Chew DJ, The Ohio State Univer-
sity, 1998.
bait) will also cause false-
positive results.
Because antifreeze often con-
tains sodium fluorescein to de-
tect radiator leaks, a Wood’s
lamp may be used to help de-
tect fluorescence in urine or
gastric contents.14 Renal ul-
trasonography, although not
pathognomonic, may also
contribute to earlier diagnosis.
Increased renal cortical echo-
genicity may be seen as early
cortical and medullary hy-
perechogenicity occur; at
later stages, relatively hypoechoic areas appear at the
corticomedullary junction and central medullary region
(Figure 2). This “halo sign” is associated with the devel-
opment of anuria, and its presence warrants a grave
prognosis.15,16
For cats and dogs presented in oliguric renal failure, a
renal biopsy is usually diagnostic for EG intoxication.
Acute tubular necrosis with calcium oxalate crystals
within disrupted renal tubules is often seen.17–19 Renal
histopathology can also be used postmortem to make
TREATMENT
The goals of treatment for EG intoxication include
preventing absorption, increasing excretion of both the
parent compound and its toxic metabolites, and pre-
venting additional metabolism of EG. Because EG tox-
icosis develops rapidly, treatment must be initiated
quickly and aggressively. If EG ingestion is known to
have occurred within 1 to 2 hours, vomiting may be in-
duced. However, clinicians must consider the risk of as-
piration in depressed animals. Gastric lavage and/or as-
piration may also be helpful if performed within 1 to 2
hours of ingestion. The use of activated charcoal is
widely advocated, although it may be of little use be-
cause EG is not significantly adsorbed by charcoal.20
Specific Therapy
The cornerstone of specific therapy involves prevent-
ing the metabolism of EG to its toxic metabolites by
inhibiting ADH, the enzyme responsible for the initial
reaction in the EG metabolic pathway (Figure 1). The
findings that the minimum lethal dose of EG in labora-
tory animals was increased if the animals were given

EG TEST KIT ■ RENAL ULTRASONOGRAPHY ■ TREATMENT GOALS

Compendium December 1999 20TH ANNIVERSARY Small Animal/Exotics

ethanol simultaneously21 and sion.7 A study in cats, how-

that ethanol is a competitive
Suggested Protocols for Specific Therapy of
ever, suggested that blood
inhibitor of ADH with a Ethylene Glycol Intoxication in Dogs and Cats ethanol levels above 60
higher affinity than that of mg/dl are needed for effica-
a
EG22 led to the first success- Ethanol cy.29 Determination of blood
ful therapy of EG intoxica- Dogs: ethanol concentrations is
tion using ethanol in hu- 20% Ethanol1: not readily available in most
mans23 and subsequently in 5.5 ml/kg IV every 4 hr for five treatments, then veterinary hospitals.
dogs24,25 and cats.26 Best re- For years, alternative treat-
every 6 hr for four treatments
sults are achieved when etha- ments for EG intoxication
nol therapy is initiated early or
have been investigated in an
in the course of intoxication, Same total dose given CRI
attempt to avoid the inherent
before much of the EG has 7 disadvantages of ethanol
30% Ethanol (low-dose protocol) :
been metabolized (see Sug- therapy. Pyrazole and some
gested Protocols for Specific 1.31 ml/kg slow IV bolus, followed by 0.42
of its derivatives, particularly
Therapy of Ethylene Glycol ml/kg/hr for 48 hr 4-methylpyrazole (4-MP;
Intoxication in Dogs and or Antizol-VetTM and AntizolTM
Cats).1,24–26,28 Prolonged treat- 300 mg/kg slow IV bolus, followed by 100 [fomepizole], Orphan Medi-
ment is usually necessary be- mg/kg/hr CRI cal, Minnetonka, MN), have
cause ethanol therapy will been shown to markedly in-
increase the effective half-life Cats: hibit the activity of ADH in
of EG.3,4,7 20% Ethanol27: vitro33 and in vivo in both
Ethanol itself will cause animals4,6,34–36 and humans.37,38
5.0 ml/kg IV every 6 hr for five treatments, then
severe CNS and respiratory Although pyrazole is associ-
depression, usually necessi- every 8 hr for four treatments
ated with hepatotoxicity and
tating intensive monitoring or
bone-marrow toxicity,36 4-
and supportive therapy; this Same total dose given CRI MP has been shown to be a
is particularly true with inter- 6,17 strong competitive inhibitor of
mittent administration4,24,25,28 4-Methylpyrazole (50 mg/ml) ADH that is safe and effec-
and in cats.3,26,29 Ethanol also Dogs: tive in intoxicated dogs4,6,17,30,36
exacerbates EG-induced serum Initial loading dose: 20 mg/kg IVb and humans37,38 and does not
hyperosmolality and osmot- At 12 hours: 15 mg/kg IV induce CNS depression, hy-
ic diuresis.1,3,6,30 In animals At 24 hours: 15 mg/kg IV perosmolality, or osmotic di-
that respond to therapy, pe- c uresis. 4-MP has a slower
At 36 hours: 5 mg/kg IV
riods of ethanol-induced rate of elimination compared
CNS depression may become a50% Ethanol [100 proof] contains 393 mg ethanol/ml. with ethanol20 and therefore
progressively shorter.26,28 Be- bSlow IV infusion over 15 to 30 min. has a longer duration of ac-
cause bolus infusions of eth- cIf the dog is not recovered and there is suspicion of tion and a more practical
anol are associated with a high remaining unmetabolized ethylene glycol, continue to dosing schedule (see Suggest-
risk of respiratory arrest, 29 administer 5 mg/kg IV every 12 hr. ed Protocols for Specific
CRI = continuous-rate infusion; IV = intravenous.
administration as a continu- Therapy of Ethylene Glycol
ous infusion (see Suggested Intoxication in Dogs and
Protocols for Specific Therapy of Ethylene Glycol In- Cats).
toxication in Dogs and Cats) may be safer. In human Most dogs treated with 4-MP within 8 hours of EG
intoxication, maintaining blood ethanol concentrations ingestion have a favorable outcome.6 Adverse clinical
at 100 mg/dl is usually recommended for efficacy.20,31,32 signs (tachypnea, gagging, salivating, trembling) have
This requires frequent adjustments in infusion rates be- been reported in only one dog after repeated adminis-
cause ethanol itself is rapidly metabolized. The amount tration; these signs resolved with discontinuation of 4-
of ethanol required will also vary depending on the in- MP.17 Other potential advantages of 4-MP over ethanol
dividual and the amount of EG ingested.20 Alternative- include shorter hospitalization times and perhaps less
ly, a low-dose ethanol infusion protocol in which blood intensive monitoring.17 4-MP has been approved for
ethanol levels are maintained at 50 mg/dl has been used use in EG intoxication in dogs in the United States for
successfully in dogs and causes less severe CNS depres- several years; although it has been considered the treat-

ETHANOL THERAPY ■ BLOOD ETHANOL LEVELS ■ 4-METHYLPYRAZOLE

Small Animal/Exotics 20TH ANNIVERSARY Compendium December 1999

TABLE I
Suggested Protocols for Supportive Therapy of Ethylene Glycol Intoxication in Dogs and Catsa
Therapy Purpose Parameters Monitored

IV crystalloid fluids
Sodium bicarbonate
Amount needed (mEq) = 0.3 ×
weight (kg) × base deficit/L (1⁄4
to 1⁄3 given slow IV bolus, the
remainder as a CRI over 4–6 hr)
or
6.2 mEq/kg IV every 4–6 hr
10% Calcium gluconate
0.5–1.5 ml/kg slow IV bolus
(+/– 5–15 mg/kg/hr CRI)
and/or
Diazepam
Warming, turning, ophthalmic
lubrication; oxygen, ventilation;
colloids, pressors; gastrointestinal
protectants; avoidance of
aspiration
a
See text for details.
CRI = continuous-rate infusion; IV = intravenous.
Restore deficits and perfusion;
supply fluid for maintenance and
ongoing losses; maintain diuresis
Correct metabolic acidosis
Control seizure activity, tetany,
twitching
Additional therapy as needed
Hematocrit and total plasma solids;
body weight; urine output; heart rate;
mucous membrane color, capillary refill
time; central venous pressures;
electrolytes
Arterial and/or venous blood gases;
serum bicarbonate concentrations;
total carbon dioxide; urine pH
Electrocardiogram/bradycardia;
seizures, twitching; serum and/or
ionized calcium concentrations
Arterial blood gases, hemoglobin
saturation (pulse oximetry), end-tidal
carbon dioxide; arterial blood pressure,
electrocardiogram; mentation/level of
consciousness; body temperature

ment of choice for EG-intoxicated humans in France
since 1990,39 it was not approved for human use in the
United States until late 1997.39
Although 4-MP is currently the treatment of choice
in dogs, its use in cats cannot be recommended because
it has been shown to be effective only if given concur-
rent with EG.3 As evidenced by this and by the lower
minimum lethal dose of EG and the earlier develop-
ment of crystalluria and azotemia in cats,3 it is apparent
that considerable species differences exist in the
metabolism of EG and the efficacy of various ADH in-
hibitors. Postulated reasons include a more rapid rate of
EG metabolism in cats3 and differences in the substrate
specificity of ADH33 and/or the pathways of EG bio-
transformation.40 Another proposed explanation is that
feline renal tubular epithelium may be more sensitive
to the cytotoxic effects of EG metabolites.3
Other 4-substituted pyrazoles may be better in-
hibitors of ADH in cats and could possibly be useful.
Alkyldiols, such as 1,3-butanediol and 1,2-propanediol
(propylene glycol), are also substrates for ADH, are
considered relatively nontoxic, and have been used or
evaluated for use as food additives.20 1,3-Butanediol has
been shown to be efficacious in the treatment of EG in-
toxication in dogs4,41,42; however, to our knowledge, no
studies have been reported that evaluate the use of
pyrazoles or 1,3-butanediol in cats. It is unlikely that
further studies will be performed because of the efficacy
and commercial development of 4-MP. Ethanol, al-
though not optimal, remains the recommended therapy
for EG intoxication in cats.
Supportive Therapy
Intensive physiologic monitoring and frequent
reevaluation are necessary in the management of EG-
intoxicated animals; patient status can change rapidly
throughout the course of treatment. Animals that pre-
sent or become severely obtunded or comatose may re-
quire endotracheal intubation and ventilation in addi-
tion to hemodynamic support. Aspiration is a serious
risk in these patients and must be avoided. Recumbent
animals may need periodic turning to prevent conges-

SPECIES DIFFERENCES ■ ALKLYDIOLS ■ INTENSIVE MONITORING

Small Animal/Exotics
tion and may require ophthalmic lubrication; thermal
support is usually necessary as well.
Aggressive intravenous (IV) crystalloid fluid therapy
is essential in the treatment of EG intoxication (Table
I). High infusion rates are usually required to combat
the severe dehydration and hypoperfusion secondary to
EG- (and ethanol-) induced osmotic diuresis and other
ongoing losses, such as vomiting. Improved tissue per-
fusion will also help correct metabolic acidosis and help
promote renal excretion of EG and its toxic metabo-
lites.1,3,43,44 If possible, maintaining the animal in a state
of diuresis is important because renal excretion of un-
metabolized EG is a major route for its elimina-
tion4,40,43–45 and depends on free water excretion.46
Aseptic placement and maintenance of an indwelling
urinary catheter attached to a closed sterile collection
system is important for monitoring urine output. Early
in the course of intoxication, this will help ensure con-
tinued diuresis and delivery of adequate volumes of IV
fluids. Careful monitoring of urine output will also aid
in the detection and management of oliguria and will
determine the reduced volumes of IV fluids required
during this period of limited urine production. Olig-
uria is defined as a urine output of less than 1 to 2
ml/kg/hour in a volume-expanded animal.47 Monitor-
ing central venous pressures, particularly in animals
Raise the Standard of Practice at Your Hospital with
STANDARDS of CARE
ENDIU
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ENDIU
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C O M P E N D I U M ’ S
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EMERGENCY AND CRITICAL CARE MEDICINE®
Feline Hepatic Lipidosis
Sharon A. Center, DVM, DACVIM
Professor, Internal Medicine
College of Veterinary Medicine
Cornell University
H
epatic lipidosis (HL) is the most common cause of jaundice in cats
in North America. It develops primarily in obese cats that have
recently been anorectic. By definition, HL occurs when >50% of
hepatocytes accumulate excessive triglycerides (TGs), resulting in severe cell
vacuolation, cholestasis, and liver dysfunction. Left untreated, HL progresses
to metabolic dysregulation and death. Although HL was initially considered
an idiopathic disorder, it is now known to more commonly occur secondary
to other disease conditions.
DIAGNOSTIC CRITERIA
Historical Information
■ Age/gender/breed
predispositions. None.
■ Other historical considerations.
• Most commonly noted in
indoor, obese cats; most cats
have been anorectic for several
days or longer.
• On presentation, many have
lost at least 25% of pre-illness
body mass.
• Reclusiveness, affection, and
lethargy are typical owner
observations.
• Jaundiced mucous membranes,
nonpigmented skin or sclera, and
hyperbilirubinuria may be noted.
• Ptyalism, vomiting, diarrhea, or
Articles with this symbol provide
standards for canine patients.
Articles with this symbol provide
standards for feline patients.
Articles with both symbols cover canine
and feline topics.
STANDARDS of CARE: EMERGENCY AND CRITICAL CARE MEDICINE
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EMERGENCY AND CRITICAL CARE MEDICINE
constipation may occur as part of
primary disease, but these signs are
highly variable among cats.
Physical Examination
Findings
■ Unkempt and in poor condition,
jaundice, and weakness.
■ May have ptyalism without
provocation or on oropharyngeal
examination.
■ Variable dehydration attributed
to anorexia, vomiting, and
diarrhea.
■ Head and neck ventroflexion.
■ Cats show some signs
consistent with severe hepatic
encephalopathy (HE), such as
lethargy, collapse, obtundation,
and seizure activity.
■ Abdominal palpation discloses
nonpainful hepatomegaly.
■ Bleeding tendencies may be
evidenced by bruising around
venipuncture, palpation, or
ultrasound probe sites.
1
20TH ANNIVERSARY Compendium December 1999
with underlying cardiopulmonary disease or that are
becoming oliguric, is also recommended.
Early and aggressive use of sodium bicarbonate is an-
other essential component of therapy in EG intoxica-
tion, especially to help fully correct the initial excess of
acids, particularly glycolate.34,48,49 The dose of sodium
bicarbonate is controversial and, if possible, should be
based on determination of serial serum bicarbonate
concentrations using the following formula50:
Amount of HCO3– needed (mEq) =
0.3 × Weight (kg) × Base deficit/L
If determination of serum bicarbonate concentra-
tions is unavailable, one recommendation is to use
sodium bicarbonate at a dose of 6.2 mEq/kg every 4 to
6 hours based on the fact that the average serum bicar-
bonate concentration in intoxicated cats and dogs is 8.5
mEq/L.1 Ideally, serum bicarbonate levels should be
monitored every 4 to 6 hours; at least 30 minutes must
elapse after an infusion of sodium bicarbonate is com-
pleted before its clinical effect can be determined.51
Monitoring urine pH may also be helpful. The aim of
therapy should be to increase the animal’s pH to 7.2 to
reduce the risk of life-threatening hemodynamic com-
plications. Bicarbonate therapy may also enhance renal
excretion of glycolate by “ion trapping.”49,52 Potential
complications of sodium bicarbonate therapy include
(1) volume overload and exacerbation of hyperosmolal-
ity due to administered sodium, (2) tetany from de-
creased serum ionized calcium concentrations sec-
ondary to increased binding of calcium to plasma
proteins, (3) paradoxical CNS acidosis as hyperventila-
tion decreases and carbon dioxide diffuses into cere-
brospinal fluid, and (4) hypokalemia secondary to in-
tracellular movement of potassium.50
...An exciting new publication Treatment of seizures or tetany is occasionally re-
quired in EG-intoxicated animals; if so, 10% calcium
from the trusted publishers of
■ Other abnormalities may be
Compendium. gluconate may be given very slowly at a dose of 0.5 to
1.5 ml/kg IV (to effect) with concurrent electrocardio-
found depending on the primary
disease.
Laboratory Findings
■ CBC.
• Poikilocytosis (i.e., irregular
RBC shapes) is common.
• A mild nonregenerative anemia
accompanies primary
Expert help fast in a graphic monitoring.53 To maintain calcium levels, sub-
practical and readable format
underlying chronic
inflammatory disorders.
sequent continuous IV infusion (5 to 15 mg/kg/hour)
• Hemolytic anemia may
be severe and related to
hypophosphatemia or Heinz
body formation at presentation
and/or during treatment.
• Leukogram reflects underlying
may be necessary.53 If this is ineffective, more conven-
disorders; HL is not a reactive
Each monthly* issue
process (no necrosis,
inflammation, fibrosis).
• Icteric plasma.
■ Biochemistry.
tional anticonvulsants (e.g., diazepam) may be neces-
• Hyperbilirubinemia.
• ↑↑↑ALP, ↑↑ALT, ↑↑AST,
normal or mildly ↑γGT.
Discordance between
ALP–γGT is an important
is peer-reviewed
diagnostic feature. The ↑γGT
sary. Calcium gluconate should not be used to treat
indicates necroinflammatory
VOLUME 2 • NUMBER 10
OCTOBER 2000
In each article you will find:
INSIDE THIS ISSUE:
Peer-Reviewed Articles on
HEPATIC DISORDERS
hypocalcemia per se because this may increase the pre-
■ Danger signs
1 Feline Hepatic Lipidosis
6 Congenital Portosystemic Shunts
cipitation of calcium oxalate in body tissues.20 Calcium
10 Correction
■ Guidelines
■ Step-by-step tips should not be administered in solutions containing bi-
carbonate or lactate because of formation of calcium
Standards of Care: Emergency salts.53
and Critical Care Medicine. Other suggested therapy for EG intoxication includes
Concise. Authoritative. Cur-
rent. No general practice should the use of thiamine and pyridoxine to shunt the
be without it. metabolism of glyoxylate to α-hydroxy, β-ketoadipate
and glycine, respectively, and away from oxalate (Figure
CRYSTALLOID FLUID THERAPY ■ OLIGURIA
Compendium December 1999 20TH ANNIVERSARY
1).31,43,49 Although often advocated in human EG intox-
ication, their use is controversial because of a lack of ex-
perimental or clinical data supporting any beneficial ef-
fects and the potential of pyridoxine to cause peripheral
sensory neuropathies.20 Furthermore, therapy to reduce
oxalate levels may not sufficiently block toxicity if other
metabolites, particularly glycolate, are responsible for
the adverse effects of EG intoxication.
For animals that are presented in oliguric renal fail-
ure, although most of the EG will already have been
metabolized, there may still be some small benefit to
trying 4-MP or ethanol. More importantly, reestablish-
ment of diuresis should be attempted with the judi-
cious use of IV crystalloids, mannitol, furosemide, and
dopamine.47 (Interested readers are referred to this latter
reference for an excellent review of therapy of acute re-
nal failure.) If adequate diuresis cannot be established,
hemodialysis or peritoneal dialysis should be consid-
ered. The presence of intact tubular basement mem-
branes and evidence of tubular epithelial regeneration
on histologic examination of renal biopsy specimens in-
dicating potential reversibility19,54,55 may assist clinicians
in selecting candidates for dialysis.
Hemodialysis is commonly used in human EG intox-
ication not only to treat acute renal failure but also ear-
ly in the course of intoxication to rapidly and effectively
remove both EG and glycolate from the blood.32,44,49,52,56
Early use of this invasive and expensive procedure has
recently been questioned, however, because of the rapid
improvement seen with 4-MP therapy.20,38,57 Hemodial-
ysis has also been demonstrated to efficiently and rapid-
ly remove EG and glycolate from the circulation of
dogs,58 but the availability of this procedure in veteri-
nary medicine is currently limited.
Peritoneal dialysis is a reasonable alternative for in-
toxicated dogs and cats in oliguric or anuric renal fail-
ure and will also remove EG and glycolate from the cir-
culation.19,23,28,43 Although labor-intensive, peritoneal
dialysis may be life sustaining while providing time for
the kidneys to repair and resume function.19 Clinicians
should be aware that because ethanol and 4-MP are
also dialyzable, higher doses than those recommended
(see Suggested Protocols for Specific Therapy of Ethy-
lene Glycol Intoxication in Dogs and Cats) may be
necessary in animals undergoing either hemodialysis or
peritoneal dialysis.20,32 An excellent and thorough re-
view of peritoneal dialysis in veterinary medicine is
available for interested readers.59
PROGNOSIS
The prognosis will depend primarily on the amount
of EG ingested and the length of time between inges-
tion and initiation of therapy. Dogs treated with 4-MP
HEMODIALYSIS ■ PERITONEAL DIALYSIS ■ PUBLIC AWARENESS
Small Animal/Exotics
within 5 hours of EG ingestion have a good prognosis,
and most dogs will recover if treatment is begun by 8
hours after ingestion.6 The prognosis for cats is good if
ethanol therapy is initiated within 3 hours of EG inges-
tion.3,26 Most animals, however, are presented after the
onset of oliguric renal failure,1,17,30,60 and for these dogs
and cats, the prognosis is grave.17,60 Most cats and dogs
that receive dialysis and survive the acute renal failure
phase will eventually regain normal renal function, but
it may take as long as 1 year to regain the ability to ade-
quately concentrate urine; a few animals may remain
isosthenuric.6,17,30
PREVENTION
Continuing to increase public awareness about the
dangers of EG will help prevent exposure and may
prompt earlier presentation of intoxicated cats and
dogs. Despite the use of more prominent warning la-
bels on antifreeze products,61 the incidence of EG in-
toxication appears to be increasing.62 Antifreeze manu-
facturers and others whose products contain EG should
be encouraged to advertise the dangers of their prod-
ucts more widely and to provide methods for their dis-
posal. The addition of bittering agents to antifreeze and
other EG-containing products is another means of
minimizing accidental ingestion that is already prac-
ticed in some countries.63 A few antifreeze products
now contain propylene glycol rather than EG; although
no nephrotoxicity is associated with propylene glycol
ingestion, it does cause CNS depression, hyperosmolal-
ity and osmotic diuresis, D-lactic acidosis with an in-
creased AG, and (particularly in cats) Heinz-body
hemolytic anemia.64,65 Continued research into safe, ef-
fective antifreeze products must be encouraged.
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About the Authors
When this paper was submitted for publication, Drs. Gay-
nor and Dhupa were affiliated with the Department of Clin-
ical Sciences, School of Veterinary Medicine, Tufts Uni-
versity, North Grafton, Massachusetts. Dr. Dhupa is now
affiliated with Angell Memorial Animal Hospital, Boston,
Massachusetts. Both authors are Diplomates of the
American College of Veterinary Internal Medicine, and Dr.
Dhupa is also a Diplomate of the American College of
Veterinary Emergency and Critical Care.