Download Infusion of a lipid emulsion to treat lidocaine intoxication in a cat

SMALL ANIMALS/
EXOTIC
Infusion of a lipid emulsion
to treat lidocaine intoxication in a cat
Taylor Q. O’Brien, dvm; Stuart C. Clark-Price, dvm, ms, dacvim, dacva;
Erika E. Evans, dvm; Renata Di Fazio, dvm; Maureen A. McMichael, dvm, dacvecc
Case Description—A 5-year-old castrated male domestic shorthair cat was examined because of presumptive lidocaine intoxication. Thirty minutes earlier, the cat had received an
SC injection of approximately 140 mg of lidocaine hydrochloride (20 mg/kg [9.1 mg/lb]) to
facilitate closure of a wound on the left pelvic limb.
Clinical Findings—Initial physical examination revealed severe lethargy and respiratory distress; erratic, poor-quality pulses with severe hypotension; and pulmonary edema.
Treatment and Outcome—Initial supportive treatment included administration of oxygen
and IV administration of lactated Ringer’s solution. Additional treatment with a 20% lipid
emulsion (1.5 mL/kg [0.68 mL/lb], IV) delivered over a 30-minute period resulted in dramatic
improvement in cardiovascular and behavioral variables. No adverse effects from lipid emulsion were detected on routine hematologic evaluation, thoracic radiography, or computed
tomography.
Clinical Relevance—IV administration of a lipid emulsion was used in the treatment of
lidocaine intoxication in a cat. Rapid infusion of a lipid emulsion may be a therapeutic option
for veterinary patients with toxicosis attributable to local anesthetics or other lipid-soluble
drugs. (J Am Vet Med Assoc 2010;237:1455–1458)
A
5-year-old 6.8-kg (15.0-lb) castrated male domestic shorthair cat was examined at the Small Animal
Emergency Service of the University of Illinois Veterinary Teaching Hospital because of severe lethargy and
respiratory distress. Thirty minutes before admission,
the cat had received an SC injection of approximately
140 mg of lidocaine hydrochloride (20 mg/kg [9.1 mg/
lb]) to aid debridement and repair of a 5-cm circumferential wound on the lateral aspect of the proximal
portion of the left pelvic limb.
Physical examination revealed that the cat was severely lethargic, unresponsive to stimuli, and unable to
support itself in sternal recumbency. Rectal temperature
was 38.3°C (101.0°F). The cat had an irregular pulse
rate that varied from 60 to 200 beats/min; a rapid, gasping, open-mouth breathing pattern; dark red mucous
membranes; and a prolonged capillary refill time of
> 3 seconds. Pulse quality was poor. Thoracic auscultation revealed an irregular heart rhythm consistent with
the pulse findings and bilateral crackles throughout all
lung fields. An attempt was made to measure systolic
blood pressure via Doppler oscillometry, but it was unsuccessful. Venous blood samples were collected for a
CBC, serum biochemical analysis, and venous blood
gas analysis. An attempt was made to obtain an arterial
sample for blood gas analysis, but it was unsuccessful.
Results of the CBC revealed leukopenia (3.87 X 103
cells/µL; reference range, 5.50 X 103 cells/µL to 19.50
From the Department of Veterinary Clinical Medicine, College of
Veterinary Medicine, University of Illinois, Urbana, IL 61802. Dr.
O’Brien’s present address is Animal Emergency and Referral Center,
1810 Skokie Blvd, Northbrook, IL 60062. Dr. O’Brien was a fourthyear veterinary student at the time of this report.
Address correspondence to Dr. Clark-Price ([email protected]).
JAVMA, Vol 237, No. 12, December 15, 2010
X 103 cells/µL) and lymphopenia (0.66 X 103 cells/µL;
reference range, 1.70 X 103 cells/µL to 7.00 X 103 cells/µL).
Results of the serum biochemical analysis revealed
hypokalemia (3.54 mmol/L; reference range, 3.7 to
4.91 mmol/L), hypocalcemia (1.10 mmol/L; reference
range, 1.17 to 1.37 mmol/L), hypernatremia (152.2
mmol/L; reference range, 144 to 152 mmol/L), and hyperchloremia (121.4 mmol/L; reference range, 110.04
to 117.96 mmol/L). Venous blood gas analysis revealed
a mild decrease in bicarbonate concentration (16.6
mmol/L; reference range, 17.08 to 24.64 mmol/L);
however, pH, partial pressure of oxygen (venous), partial pressure of carbon dioxide (venous), and lactate
concentration were all within the respective reference
ranges. On the basis of the medical history and clinical
signs, a presumptive diagnosis of acute intoxication
attributable to a local anesthetic was made.
The cat was admitted to the intensive care unit for
treatment. Supportive treatment (administration of oxygen via a facemask) was initiated. Attempts were made
to place catheters in a jugular and cephalic vein, but
ultimately they were unsuccessful. Thirty minutes after
admission (15 minutes after instituting oxygen administration), the cat was less lethargic and able to remain
in sternal recumbency without support but remained
unable to support its head. Pulse quality had improved.
A catheter was placed in a medial saphenous vein. Systolic blood pressure was measured (190 mm Hg). The
cat was placed in an oxygen cage (fraction of inspired
oxygen, 40%), and lactated Ringer’s solution was administered at a rate of 80 mL/kg/d (36.4 mg/lb/d).
At that time, the cat received an IV infusion of a
20% lipid emulsiona for specific treatment of lidocaine
toxicosis. A dose (3 mL/kg [1.4 mL/lb]) delivered over a
Scientific Reports
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EXOTIC
30-minute period was selected for treatment; this treatment was extrapolated from a case report for a human.1
However, because of concerns about fluid overload and
lack of reports on the use of this treatment in cats, the
treatment was reduced to infusion of a 20% lipid emulsion (1.5 mL/kg [0.68 mL/lb]) over a 30-minute period
with a second equivalent dose to be administered over
an additional 30-minute period, if necessary. Fifteen
minutes after initiation of the lipid emulsion, the cat
was more responsive to stimuli (ie, could be more easily aroused) and was able to hold its head up without
assistance. At the conclusion of the infusion, the cat
appeared to be aware of its surroundings and began
grooming behaviors; therefore, the second infusion of
the lipid emulsion was not administered. The cat was
kept in the oxygen cage overnight; it was continuously
monitored for any decline in mental status, including
seizure activity.
The following morning, the cat appeared to be
bright, alert, and responsive. Physical examination
findings were within anticipated limits. The oxygen
concentration in the cage was gradually reduced over a
2-hour period until the cat was breathing only room air;
no adverse effects were observed. Results of a CBC and
serum biochemical analysis revealed no abnormalities.
Additionally, because of concerns about oxidative damage to the cat’s RBCs resulting from lidocaine intoxication, the methemoglobin concentration was measured.
However, the methemoglobin concentration was within the reference range (0.3%; reference range, < 1%).
Thoracic radiography and computed tomography
were performed to assess pulmonary edema or pulmonary lipid deposition. Results revealed clear lung fields;
however, there was an incidental finding of spondylosis
deformans at T11-12.
Blood samples obtained at admission and again
the following morning were submitted for determination of plasma lidocaine concentration. The value was
6.3 µg/mL for the pretreatment sample, and lidocaine was
not detected in the posttreatment sample. Therapeutic and
toxic concentrations of plasma lidocaine have not been
determined for cats; however, the reported2 range for
antiarrhythmic treatment in humans is 2 to 5 µg/mL,
with signs attributable to toxic effects evident at plasma
concentrations of 5 to 10 µg of lidocaine/mL.
The wound on the pelvic limb of the cat was
cleaned and bandaged, and buprenorphine (0.02 mg/kg
[0.009 mg/lb], IV) was administered for analgesia. The
cat was discharged to the owner with instructions for
continued care of the wound. Two days later, the owner
reported that the cat was doing well with no residual
effects from the lidocaine intoxication.
Discussion
Lidocaine is one of the most commonly used local
anesthetics in human and veterinary medicine. It exerts
local anesthetic effects by reversibly binding to sodium
channels and preventing impulse conduction through
nervous tissue.3 Lidocaine has a rapid onset of action
with a duration of 60 to 120 minutes, which makes it
suitable for use in procedures for which a short duration of action is desired.2 Lidocaine can also be administered IV as a treatment for ventricular arrhythmias, to
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Scientific Reports provide systemic analgesia, and to reduce the minimum
alveolar concentration of inhalant anesthetics needed
for anesthesia.4–6 Mepivacaine and bupivacaine are other local anesthetics that have been used in veterinary
medicine. Both have a longer duration of action than
does lidocaine, with the effects of mepivacaine lasting
90 to 180 minutes and the effects of bupivacaine lasting
240 to 480 minutes.7
Similar to other local anesthetics, toxic effects of
lidocaine are related to excessive plasma and tissue
concentrations. Some of the more serious toxic effects
result from effects on the CNS and the cardiovascular
system. Clinically, these can be evident as lethargy, unconsciousness, coma, convulsions, seizures, hypotension, bradycardia, and cardiovascular collapse and can
result in death.2 Several of these signs were observed in
the cat described here. At admission, the cat was lethargic, and severe hypotension was evident as an inability
to obtain an initial blood pressure measurement and
difficulty in inserting a catheter in a vein.
The dosages of local anesthetics that cause CNS
toxicosis are less than the dosages that cause signs of
cardiovascular toxicosis.7 The reported plasma concentration of lidocaine in humans at which signs of CNS
toxicosis are apparent is 5 to 10 µg/mL, whereas plasma
concentrations > 25 µg/mL are associated with cardiovascular toxicosis.2 Lidocaine intoxication of the CNS
often manifests initially as twitching and weakness of
skeletal muscles and progresses to drowsiness and then
seizures. In severe cases, CNS depression and coma
can follow seizures. There is evidence that the plasma
concentration at which CNS toxicosis develops may be
more a function of the rate of administration and subsequent increase in the plasma concentration, rather than
a function of the total amount of drug administered.8
Cardiovascular effects of toxic dosages of lidocaine
may be evident as refractory hypotension from direct
vasodilatory effects on vascular smooth muscle and
reduced cardiac output from myocardial depression.2
Electrocardiographic findings from local anesthetic–induced cardiovascular toxicosis include a prolonged PR
interval and widening of the QRS complex.2
Lidocaine and other local anesthetics generate methemoglobin, which typically comprises < 1% of the total blood hemoglobin content, from oxidation of hemoglobin, thereby potentially reducing the ability of RBCs
to carry oxygen. Heinz bodies, which can result in RBC
lysis, can also form as a result of oxidative damage to
RBCs from toxic concentrations of local anesthetics.7
In domestic cats, lidocaine is commonly used to
provide local analgesia and anesthesia for routine procedures, such as dental extractions, onychectomy,
wound debridment, and epidural anesthesia.7 Although
relatively free of adverse effects when proper dosages
are used, excessive or IV administration of lidocaine
can result in toxic effects similar to those seen in human patients. These toxic effects can develop as the
dosage of lidocaine approaches 6 mg/kg (2.7 mg/lb)
in cats. Seizure activity can be elicited in cats via IV
administration of lidocaine at a dosage of 11.7 ± 4.6
mg/kg (5.3 ± 2.1 mg/lb).9 Therefore, it is recommended
that the dosage of lidocaine used for local anesthesia
in cats should not exceed 3 to 4 mg/kg (1.4 to 1.8 mg/
lb).10 The cat described here received an approximate
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JAVMA, Vol 237, No. 12, December 15, 2010
to cyclic antidepressants, verapamil, β-adrenoceptor
blockers, and clomipramine.21,24–26 A lipid emulsion has
been used to treat moxidectin toxicosis in a puppy.27
Treatment with a lipid emulsion is not without potential complications. These emulsions can promote
bacterial growth, which requires that aseptic procedures
be used during administration to prevent contamination and possible sepsis. Intravenous administration
of a lipid emulsion may cause immunosuppression
through immune-cell dysfunction.28 Other potential effects include phlebitis, thrombosis, hypertriglyceridemia, and hepatic lipidosis.28
The dosage of a 20% lipid infusion has varied in
human clinical case reports. The dosage used in the cat
described here was extrapolated from a single human
case report1 in which the authors reported success with
a dosage of 3 mL/kg. In the cat of our case report, dramatic clinical response was achieved with a dosage of
1.5 mL/kg delivered over a 30-minute period, and at
least in this cat, administration of an additional 1.5 mL/
kg dose was not necessary. After resolution of the condition in the cat reported here, a review of the use of
lipid emulsion as a treatment for lidocaine intoxication
in humans was published.21 The authors of that report
made a recommendation for administration of a 20%
lipid emulsion at a dosage of 1.5 mL/kg at infusion rates
of 0.25 to 0.5 mL/kg/min (0.11 to 0.23 mL/lb/min),
which could be repeated up to 3 times. On the basis of
the findings in the cat described here, this recommendation may also be applicable to veterinary patients.
It is important to mention that although lidocaine
was not detected in the second plasma sample obtained
from the cat described here, this may not have been a
result of the use of the lipid emulsion. The half-life of lidocaine in cats is approximately 1.7 hours,29 and a lack
of lidocaine in the second sample was most likely the
result of typical elimination of the drug.
The present case report confirmed the IV administration of a lipid emulsion for treatment of local anesthetic–induced toxicosis in a veterinary patient. The
authors recognize the limitations of this report in that
it represents only a single cat and that findings were
based on subjective assessment of the cat. Further investigation into the use of lipid emulsions for the treatment of toxicosis attributable to local anesthetics is
warranted. In this cat, no adverse effects from the lipid
infusion were detected. Additionally, rapid infusion of
a lipid emulsion may be a treatment option for patients
with toxicosis attributable to other lipid-soluble drugs.
a.
Liposyn II, Hospira Inc, Lake Forest, Ill.
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