CASE REPORTS
Methocarbamol CRI for Symptomatic Treatment of Pyrethroid Intoxication: A Report of Three Cases William E. Draper, DVM*, Luiz Bolfer, DVM, Emily Cottam, DVM, Maureen McMichael, DVM, Thomas Schubert, DVM
ABSTRACT Pyrethroids are popular for use in companion animals due to their relatively low mammalian toxicity and efficacy against arthropods. Nonetheless, pyrethroid intoxication has been reported in cats and dogs, and cats appear to be more susceptible due to difficulty in biotransformation and excretion of pyrethroids. Pyrethroid intoxications are generally due to either the improper use or accidental ingestion of approved products. Methocarbamol, given as intermittent injections, is a common first-line treatment choice for the tremors associated with pyrethroid intoxication. Two cats and one dog were treated with a methocarbamol continuous rate infusion (CRI) for pyrethroid intoxication. Clinical signs of toxicity resolved within a few hr in all three cases, with no adverse drug effects. A methocarbamol CRI can be considered in animals presenting with pyrethroid intoxication. (J Am Anim Hosp Assoc 2013; 49:---–---. DOI 10.5326/JAAHA-MS-5835)
Introduction
delayed for up to 72 hr postexposure.3,7,9 Symptomatic treatment
Pyrethrum is a combination of six natural insecticidal esters
regimens are based on control of the muscle tremors and/or
called pyrethrins. Pyrethrins are naturally occurring compounds
seizures, supportive care, and decontamination.5,10 Traditionally,
derived from a combination of insecticidal esters (pyrethrins,
it is recommended to control the muscle tremors with IV boluses
cinerins, and jasmolins) that are isolated from the flowers of
of methocarbamol, a centrally acting muscle relaxant, and to treat
Chrysanthemum cinerariaefolium and related species.
1,2
Pyre-
seizures with IV diazepam and/or barbiturates.
thrins are poisons that act on the nervous system. Products
In this report, three cases of pyrethroid toxicity successfully
containing 45–65% permethrin intended for use in dogs only
treated with methocarbamol using a continuous rate infusion
are particularly concerning. Pets may be adversely affected after
(CRI) technique are described. To the authors’ knowledge, there
either oral ingestion or by topical application of such concen-
have not been any studies previously published regarding the use
trated products.1,3,4
of a methocarbamol CRI in animals presenting with pyrethroid
The clinical signs most commonly reported with pyrethroid
intoxication.
toxicity in the veterinary literature include hypersalivation, muscle tremors/fasciculations, hyperthermia, hyperesthesia, ataxia, hy-
Case Report
perexcitability, mydriasis, and seizures.3,5–8 The onset of clinical
The two cats described in the following section were treated at
signs is usually within a few hr of exposure, with some being
the College of Veterinary Medicine, University of Illinois between
From the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL (W.D., T.S.); and Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL (L.B., E.C., M.M).
CRI continuous rate infusion; ICU intensive care unit; PO per os *W. Draper’s present affiliation is VCA Animal Specialty Center of South Carolina, Columbia, SC.
Correspondence:
[email protected] (W.D.)
ª 2013 by American Animal Hospital Association
JAAHA.ORG
1
February 2009 and March 2009. The dog described below presented
information, the cat was then bathed with soap and given an IV
in June 2010 to the University of Florida’s College of Veterinary
bolus of methocarbamolf at a dose of 89.3 mg/kg. The tremors
Medicine. Before transfer to the authors’ institution and/or clinical
were reduced shortly after that treatment. The cat was then
service all three animals were treated with diazepam, and two of them
placed on IV lactated Ringer’s solutiong (2.7 mL/kg/hr) and
were treated with phenobarbital. Both of those treatments achieved
a methocarbamol CRI (8.8 mg/kg/hr). After a few hr, the muscle
only minimal control of muscle tremors. All three patients responded
tremors had ceased. After 8 hr, the methocarbamol CRI was de-
well to methocarbamol IV boluses, and a complete resolution of
creased to 4.7 mg/kg/hr for an additional 4 hr, and minimal
muscle tremors was achieved after starting a methocarbamol CRI.
tremors were noted. The cat was discharged on the same day with minimal tremors and was prescribed methocarbamol (45 mg/kg
Case 1
per os [PO] q 8 hr for 2 days). No muscle tremors were present at
A 3 yr old castrated male domestic shorthair weighing 5.6 kg
a follow-up appointment 3 days after discharge.
presented to the University of Illinois Veterinary Teaching Hospital in lateral recumbency and with severe, generalized,
Case 2
muscle tremors after being found in a ditch by the owners’
A 2 yr old spayed female domestic longhair weighing 4.6 kg
neighbors in the morning. The neighbors were not able to
presented to the University of Illinois’ Veterinary Teaching Hos-
contact the owners at the time of presentation to collect more
pital with generalized tremors that started approximately 12 hr
information about the cat’s history. On physical examination,
after the owner applied one tube of flea medication labeled for
a mild tachypnea was noted. Due to the severity of the muscle
dogs containing imidacloprid (8.8%), permethrin (44.0%), and
tremors, a full neurologic examination and evaluation for ap-
pyripoxyfen (0.44%)e. The cat had been bathed and treated with
propriate mentation were not possible. The remaining vital
an unknown dose of diazepam administered rectally by the re-
parameters were within normal limits (Table 1). Given the
ferring veterinarian. Physical exam findings at the time of referral
clinical presentation and inability to obtain additional historic
included a mild tachypnea (Table 1). Blood was submitted for
information, seizures and possible head trauma were initially
packed cell volume and total solids, and a hand-held glucometer
suspected. An IV catheter was placed, and the cat was treated
revealed hypoglycemia (Table 1). Diazepam (1 mg/kg) was ad-
a
b
with IV diazepam (1 mg/kg) followed by phenobarbital (6 mg/kg
ministered rectally at the time of presentation. An IV catheter was
IV), which did not reduce the clinical signs. The cat was ad-
placed, and the cat was started on 2.5% dextroseh in lactated
ministered 25% mannitolc (10 mL IV slowly over 20 min) and
Ringer solution at a rate of 3.2 mL/kg/hr. Methocarbamol was
was maintained on flow-by oxygen at 2 L/min via a face mask.
administered (43.5 mg/kg) as an IV bolus, followed by a CRI
A packed cell volume, total plasma protein, and blood gas
(11.6 mg/kg/hr). During the first day of hospitalization, the cat
analysisd was performed, and no major abnormalities were
had muscle tremors only when aroused. No muscle tremors
identified (Table 1). The owners were eventually contacted, and
were observed on the second day of hospitalization, so the
they stated that the cat was healthy and normal before they left
methocarbamol CRI was discontinued over 4 hr, and the cat
for work that morning. Because of a flea infestation, the owners
was switched to oral methocarbamol (54 mg/kg PO q 12 hr for
had applied their dog’s flea prevention, which contained imid-
3 days following discharge). The owner reported no muscle
e
tremors after discharge during follow-up contact several days after
acloprid (8.8%), permethrin (44.0%), and pyripoxyfen
(0.44%), on the cat early that morning. Based on that
the incident.
TABLE 1 Summary of Vital Parameters and Blood Work in the Three Described Cases Body temperature (8C)
Heart rate (beats/min)
Respiratory rate (breaths/min)
PCV* (41–55%)
TS (6.0–7.4 g/dL)
Na1 (144–151 mmol/L)
K1 (3.7–4.91 mmol/L)
Cl2 (110–117 mmol/L)
iCa11 (1.1–1.5 mmol/L)
1
38.4
186
44
30
6.5
154.4
3.15
125.6
2 3
38.5 37.2
200 118
52 28
39 42
7.7 6.5
N/A 151
N/A 3.65
N/A 115
Case
* Reference ranges and units are provided in parentheses. BUN, blood urea nitrogen; Cl, chloride; iCa; ionized Ca; K, potassium; N/A, not available; PCV, packed cell volume; TS, total solids.
2
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49:3 May/Jun 2013
BUN (9.1–24 mg/dl.5)
Glucose (77–192 mg/dL)
1.12
36
N/A
N/A 1.20
N/A 24
62 135
Methocarbamol CRI for Pyrethroid Intoxication
Case 3
function. Methocarbamol has a greater effect in the spinal cord
A 5 yr old castrated male miniature schnauzer weighing 8.2 kg
compared with the brain. This is displayed in its ability to protect
presented for tremors and generalized ataxia that started ap-
against the convulsant effects of strychnine (a spinal cord stim-
proximately 4 hr after the owner witnessed him licking a flea and
ulant), but not pentylenetetrazol (a stimulant that produces ex-
tick preventative containing cyphenothrin (40%) and pyriproxyfen
citation in the central nervous system rostral to the foramen
(2%) off of another animal residing in the household. The physical
magnum).11 Methocarbamol, given as intermittent injections, is
examination showed severe whole-body tremors and generalized
often a first-line treatment for the control of increased muscular
ataxia. Vital parameters were unremarkable (Table 1). A venous
activity associated with pyrethroid intoxication.1,5,10 To the authors’
i
j
blood sample was submitted for blood gas analysis , which revealed
knowledge, methocarbamol has not been used as a CRI in humans,
no abnormalities (Table 1). The dog was bathed to remove any
dogs, or cats; therefore, specific information regarding pharma-
possible dermal contamination and was monitored throughout
codynamics and pharmacokinetics of a CRI are lacking at this
the day. The muscle tremors increased, and diazepam (0.3 mg/kg)
point. At clinically relevant doses, methocarbamol reportedly
and methocarbamol (61 mg/kg) were administered PO 10 hr after
prolongs the refractory period of skeletal muscle by a direct action
admission. No resolution of the tremors was noted. An IV cath-
on the fibers.12 That same study showed that diazepam did not
eter was placed, and 0.9% NaClk was started 12 hr after admission
have that direct effect on the muscles.12 That additional mecha-
at a rate of 3.7 mL/kg/hr. Diazepam (0.5 mg/kg IV), midazolaml
nism could also be helpful in controlling the spasms related to
(0.2 mg/kg IV), and methocarbamol (50 mg/kg IV) were given as
pyrethroid intoxication.
boluses q 4 hr starting 12 hr after admission. Resolution of the
The dose of methocarbamol used by the authors was based on
tremors was noted shortly after the boluses, but the resolution was
the published maximum safe dose of 330 mg/kg/day. The initial
described as short-lived by the attending technicians in the in-
bolus of methocarbamol administered to the patient was sub-
tensive care unit (ICU). Three phenobarbital boluses (2 mg/kg
tracted from the total daily dose, and the remainder was ad-
IV) were administered overnight as well. The tremors were still
ministered as a CRI. The CRI can be administered either as the
quite severe 22 hr after admission. At that time, methocarbamol
drug alone on a syringe pump (as described in case 3) or as the drug
was administered as a 12.2 mg/kg bolus. Immediately after that
added to a fluid bag (e.g., methocarbamol added to 240 mL of 0.9%
bolus, a 12.2 mg/kg/hr methocarbamol CRI was maintained for
NaCl) and given as a CRI (10 mL/hr to start, then tapered as
4 hr. After 4 hr the rate was reduced to 9.1 mg/kg/hr for 10 hr,
necessary) as described in cases 1 and 2. The decision of when to
3mg/kg/hr for 7 hr, and then stopped. Oral methocarbamol
taper, and by how much, is dependent on the clinician and patient.
(61 mg/kg q 8 hr) was started at the same time as the 3 mg/kg/hr
The decision to use a CRI instead of multiple boluses is made for
CRI. The muscle tremors were controlled immediately after the
a number of reasons, including reduced stress on the patient
methocarbamol bolus, and no muscle tremors were observed after
(because the tremors rarely return), reduced need for the ICU staff
starting the methocarbamol CRI. The dog was monitored in the
to monitor for recurrence of tremors, and the routine need for less
ICU for the rest of the day and overnight. The dog was discharged
total medication when given as a CRI.
with oral methocarbamol (61 mg/kg PO q 8 hr for 8 days). When
Methocarbamol, given intermittently, is often considered
contacted the day after discharge, the owner reported no muscle
a first-line treatment of muscle tremors due to pyrethroid in-
tremors.
toxication. Although seizures are rarely a sequela of pyrethroid intoxication (and can be difficult to differentiate from severe
Discussion
tremors), a wide variety of pharmacologic treatments have been
This case series documents the use of methocarbamol as a CRI for
reported, including intermittent boluses of diazepam and phe-
control of muscle tremors due to pyrethroid toxicosis in two cats
nobarbital. Those drugs are sometimes followed by a CRI of either
and one dog. The prognosis for recovery from intoxication due to
a benzodiazepine (i.e., diazepam, midazolam) or propofol. Given
pyrethroids is good, presuming therapy is instituted early in the
a lack of historical information at the time of presentation for case
course of the disease. The majority of animals that receive prompt
1, the authors suspected seizures and possible head trauma. After
and aggressive treatment recover within 48–72 hr with few per-
collecting additional information, treatment with methocarbamol
manent sequelae.
1,2,5,9
was initiated, which controlled the muscle tremors when ad-
Methocarbamol is a propanediol, and this class of drug has its
ministered as an IV bolus followed by a CRI. In retrospect, all three
therapeutic value in abolishing abnormal muscle tone and in-
of the cases should have been treated with a methocarbamol bolus
voluntary movement without impairing normal neuromuscular
followed by a CRI immediately after presentation. It is likely that
JAAHA.ORG
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this would have controlled any tremors due to the pyrethroid intoxication, obviating the need for other medications with more
d e f
side effects.6
g
General supportive care for pyrethroid intoxication was
h
provided for all three cases described in this report, including
i
bathing the animals in a dilute solution of liquid dishwashing
j
detergent to help remove residual drug from the skin and coat,
k
maintenance of normothermia, IV fluid therapy to support cir-
l
Blood gas analysis; Nova Biomedical, Waltham, MA K9 Advantix; Bayer HealthCare, KA Methocarmabol; Baxter Healthcare Corp., Deerfield, IL Lactated Ringer’s solution; Hospira Inc., Lake Forest, IL Dextrose; Hospira Inc., Lake Forest, IL Sentry Pro XFC; Sergeant Pet Care Products Inc., Omaha, NE Blood gas analysis; Radiometer Medical ApS, Bronshoj, Denmark 0.9% NaCl; Abbott Laboratories, North Chicago, IL Midazolam; Hospira Inc., Lake Forest, IL
culation, and monitoring in the ICU. In this small case series, there did not appear to be any side effects associated with using a methocarbamol CRI, and all three patients had resolution of clinical signs. Because all three patients were treated with diazepam and/or phenobarbital, it is not entirely clear that the resolution was due to methocarbamol alone. When giving IV boluses of methocarbamol, the muscle tremors should become less intense but the action appears to be short lived. To avoid using multiple drugs that can cause side effects and promote little muscle relaxation effect (as was performed in the three cases described herein), a CRI of methocarbamol should be started immediately after the IV bolus. As described above, the methocarbamol CRIs were not initiated without an initial IV bolus.
Conclusion The use of methocarbamol as a CRI for pyrethroid intoxication appeared beneficial in this report; however, further studies regarding the pharmacology of methocarbamol (in general and as a CRI) and to examine the efficacy of methocarbamol for tremorogenic diseases are necessary. FOOTNOTES a Diazepam; Hospira Inc., Lake Forest, IL b Phenobarbitol; Baxter Healthcare, Corp., Deerfield, IL c Mannitol; Hospira Inc., Lake Forest, IL
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