Toxicology Reports 1 (2014) 1026–1028

Contents lists available at ScienceDirect

Toxicology Reports
journal homepage: www.elsevier.com/locate/toxrep

Case report

Acute permethrin neurotoxicity: Variable presentations, high

index of suspicion
Bonny Drago a , Namrata S. Shah b , Samir H. Shah c,∗
a
Department of Pediatrics, State University of New York at Stony Brook, New York, NY 11790, USA
b
Department of Pediatric Neurology, Le Bonheur Children’s Hospital and The University of Tennessee Health Science Center, Memphis,
TN 38103, USA
c
Department of Pediatric Critical Care Medicine, Le Bonheur Children’s Hospital and The University of Tennessee Health Science Center,
Memphis, TN 38103, USA

a r t i c l e i n f o a b s t r a c t

Article history: Permethrin is a synthetic Type I pyrethroidal neurotoxic pesticide that has been responsi-
Received 11 July 2014 ble for accidental animal deaths. Despite its widespread use, there are no published case
Received in revised form 6 September 2014 reports on pediatric intensive care unit admissions due to permethrin exposure. We report
Accepted 10 September 2014
the unusual and varied presentations of permethrin toxicity in three siblings presenting to a
Available online 20 September 2014
tertiary care pediatric intensive care unit (PICU). While there is no standard clinical diagnos-
tic test for permethrin, accurate diagnosis was obtained by rapidly analyzing the offending
Keywords:
agent. In the absence of a known antidote for permethrin, supportive management was
Permethrin
initiated and resulted in a favorable outcome for all three siblings.
Toxicology
Neurological presentations © 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under
the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

1. Background reports of pediatric intensive care unit (PICU) admissions

with good outcomes.
Permethrin is a synthetic Type I pyrethroidal pesticide
that is commonly used worldwide on crops. It is highly toxic
to animals, particularly fish and cats. It is primarily a neu- 2. Patient presentations
rotoxin and its main mechanism of action is axonal sodium
channel depolarization causing repetitive nerve impulses We describe the following case summaries of three
[1]. At relatively high concentrations, pyrethroids can act siblings who presented simultaneously to the PICU with
on gamma-aminobutyric acid (GABA)-gated chloride chan- varied clinical symptoms resulting from what was ini-
nels, which may be responsible for the seizures seen with tially suspected to be organophosphate poisoning. All three
severe Type II poisoning [2]. Despite its widespread use, patients were originally exposed to an unknown sub-
there are few recorded cases of human toxicity and fewer stance used to bathe a puppy. They initially presented to
an outside medical facility following the exposure, which
included both topical contact and ingestion. It is unknown
how much of the substance was found at the location where
exposure occurred. After sampling by the local Fire Depart-
∗ Corresponding author at: Department of Pediatrics, Division of Pedi-
ment of the substance found on a trampoline, emergent
atric Critical Care Medicine, University of Tennessee Health Sciences
Center, 50 North Dunlap Street, Suite 346R, Memphis, TN 38103, USA.
analysis of the unknown substance identified it as per-
Tel.: +1 901 287 6303. methrin. Subsequently, the patients were diagnosed with
E-mail address: sshah7@uthsc.edu (S.H. Shah). acute permethrin poisoning.

http://dx.doi.org/10.1016/j.toxrep.2014.09.007
2214-7500/© 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/3.0/).
 B. Drago et al. / Toxicology Reports 1 (2014) 1026–1028 1027

Patient #1 is a five-year-old previously healthy female less than her siblings, as she presented with symptoms of
who, along with her siblings, had bathed a puppy, poured vomiting and stomach cramps. Her total length of stay in
the unknown chemical on a trampoline, then played with it the hospital was two days, with one day in the ICU. She
and possibly ingested some of it. Eight hours following sus- never demonstrated central nervous system effects, pupil-
pected ingestion, she presented to an outside Emergency lary changes or increased secretions. Her laboratory data
Department (ED) with symptoms of increased lacrima- were within normal limits. The puppy, unfortunately, was
tion, salivation, bronchorrhea, vomiting, stomach cramps, reported to have died from this exposure.
and significant respiratory depression and altered mental
status. She was intubated, volume-resuscitated and admin- 3. Discussion
istered two doses of 1 mg atropine, then transferred to
the PICU at our facility. Upon admission, she manifested This is the first report of a set of children simul-
symptoms of excessive secretions and pinpoint pupils. taneously presenting with permethrin toxicity with
Hence, she was given two further doses of 1 mg atropine differing clinical spectra with successful outcomes. Lack of
with no therapeutic response. The patient continued to standard management response to previously suspected
be comatose with no response to anticholinergic manage- organophosphate poisoning prompted a rapid analysis of
ment; hence, the chemical found at the site of exposure was the offending toxin, confirming the toxin as permethrin
emergently analyzed and determined to be permethrin and in these three cases. Unfortunately, bodily fluid analysis
not organophosphate, as initially suspected. was not performed. However, the substance was chem-
The existing literature was reviewed, poison control was ically analyzed and a diagnosis of permethrin poisoning
contacted again and further treatment was discussed as was made. It would have been useful if red blood cell
being mainly supportive. Continuous bedside electroen- acetylcholinesterase (RBC-AChE) could have been used as
cephalogram (EEG) monitoring was performed because a confirmatory test for toxicity resulting from exposure
of the potential for permethrin to cause subclinical sta- to organophosphorus compounds, specifically in ICU man-
tus epilepticus. Subsequently, benzodiazepine therapy was agement of these patients [3]; however, that test was
initiated. The patient remained comatose and on mechan- unavailable in our geographical area.
ical ventilation with poor deep tendon reflexes, muscle Review of existing literature reveals a paucity of cases
weakness, pinpoint pupils, increased secretions and diar- of human toxicity with permethrin. It appears to be par-
rhea, and elevated body temperature for one week. Head ticularly rare in children and the presentations may be
computed tomography (CT) and magnetic resonance imag- variable; however, in vivo, permethrin is almost five times
ing (MRI) scans were reported as negative. She was started more acutely toxic to eight-day-old rats than to adult rats.
on gabapentin for possible paresthesia, a known associa- Based on in vivo experiments, it is possible that children
tion with permethrin toxicity. After eight days, the patient may be more sensitive to permethrin than adults [4]. A
was extubated after demonstrating improved responsive- study performed at an Ohio daycare center to analyze path-
ness, normal pupils, and decreased secretions. ways of exposure to permethrin in children concluded that
Patient #2 is a six-year-old female with similar exposure children are exposed to low levels from several sources
history. As this patient was related to Patient #1, diag- and through several routes; however, the exposure did not
nosis was made again based on the chief complaint and result in symptoms of apparent toxicity [5]. Based on these
history of present illness, suspected ingestion of perme- studies in combination with our patient presentations,
thrin. Her initial presentation was not as severe as her it is suspected that lower levels of exposure to perme-
sister’s, and did not require intubation at the outside ED. thrin can likely cause either none or minor side effects,
She received one dose of atropine and was transferred whereas exposure to higher doses of permethrin can
to the PICU for observation. After a few hours, her men- lead to worsened symptoms. In addition, the detection of
tal status deteriorated and she was intubated to protect urinary metabolites, cis- and trans-3-(2,2-dichlorovinyl)-
her airway from excessive secretions. Unlike Patient #1, 2,2-dimethylcyclopropane-1-carboxylic acids, have been
she also demonstrated signs of aspiration pneumonitis and previously used in suspected permethrin toxicity cases,
abnormal motor movements. Her course was otherwise however, they were not tested for in these patients, as the
similar with high fever, pinpoint pupils, altered mental sta- tests are not available in our geographical area [6].
tus, muscle weakness, profuse secretions and diarrhea. Her A review of 48 cases of acute ingestion-related
movements were random, non-purposeful, and very diffi- poisoning with pyrethroids in Taiwan revealed that
cult to control despite sedation. She responded to a low, gastrointestinal tract signs and symptoms were most com-
defasciculating dose of pancuronium with an improvement mon, found in 73% of cases [7]. Pulmonary abnormalities
of her movements. However, she had the longest ICU course were found in 29% of cases, including aspiration pneumoni-
and remained mechanically ventilated for 12 days. tis and pulmonary edema [7], as evident in our second case.
Patient #3 is an eight-year-old female who ingested the Central nervous system involvement, as demonstrated in
same chemical as the two siblings previously presented. the first case described here, was found in 33% cases and
Again, the chemical ingested was sampled by the local Fire included confusion, coma and seizures [7].
Department and subsequently tested and identified as per- The biodegradation of synthetic pyrethroidal com-
methrin. However, this patient possibly did not have the pounds has been extensively studied [8–10]. Permethrin
same level of exposure as her siblings, as she had tried is a synthetic Type I pyrethroid with a high selectivity for
to wash the permethrin off the puppy after the other sib- insects. It has four isomers with 1R cis-permethrin being
lings had doused it. It is suspected that this patient ingested the most insecticidal active isomer [11]. Pyrethroids kill
1028 B. Drago et al. / Toxicology Reports 1 (2014) 1026–1028

insects by strongly exciting their nervous systems. They Conflict of interest

make the nervous system hypersensitive to stimuli from
sensory organs. Permethrin-exposed nerves send a train of Authors have no conflicts of interest related to this arti-
impulses, instead of a single impulse, in response to a stim- cle. No funding was obtained for this study.
ulus. It does this by interacting with the voltage-dependent
sodium channels and produces a prolongation of inward Transparency document
sodium current, and hence the channels remain open much
longer, causing repetitive nerve impulses [11]. Permethrin The Transparency document associated with this article
has been shown in vitro and in vivo to increase acetylcholine can be found in the online version.
and acetylcholinesterase levels [12,13]. Monoamine oxi-
dase and ATPase enzymes are inhibited by permethrin Acknowledgment
[1,2,10]. It has been reported to inhibit the GABA recep-
tor, producing excitability and convulsions [2,11]. At high The authors would like to acknowledge the editorial
doses, neurotoxic symptoms can include tremors, incoor- assistance provided by Dr. Alina Nico West, Mrs. Andrea
dination, hyperactivity, paralysis, and hyperthermia [14]. Patters, and Ms. Pamela Cate.
Some other effects are irritation to the eyes and skin. It
is classified as a carcinogen and is a mutagen of human References
cell cultures [14]. The patients in this report were initially
treated with atropine, which had no effect. An expla- [1] B.K. Das, S.C. Mukherjee, Toxicity of cypermethrin in Labeo rohita fin-
gerlings: biochemical, enzymatic and haematological consequences,
nation for treatment failure could be that the atropine Comp. Biochem. Physiol. C: Toxicol. Pharmacol. 134 (2003) 109–121.
dose administered was not potent enough to overcome [2] S.M. Bradberry, S.A. Cage, A.T. Proudfoot, J.A. Vale, Poisoning due to
the permethrin toxin load. However, there is no liter- pyrethroids, Toxicol. Rev. 24 (2005) 93–106.
[3] M.L. Mortensen, Management of acute childhood poisonings caused
ature supporting treatment of permethrin toxicity with by selected insecticides and herbicides, Pediatr. Clin. N. Am. 33 (1986)
atropine. 421–445.
[4] F. Cantalamessa, Acute toxicity of two pyrethroids, permethrin, and
cypermethrin in neonatal and adult rats, Arch. Toxicol. 67 (1993)
4. Conclusion 510–513.
[5] M.K. Morgan, L.S. Sheldon, C.W. Croghan, P.A. Jones, J.C. Chuang, N.K.
Wilson, An observational study of 127 preschool children at their
Permethrin is a very common and highly effective pes-
homes and daycare centers in Ohio: environmental pathways to cis-
ticide widely used around the world; however, reports of and trans-permethrin exposure, Environ. Res. 104 (2007) 266–274.
toxicity in the pediatric literature are infrequent. The most [6] P. Panuwet, T. Prapamontol, S. Chantara, D.B. Barr, Urinary pesticide
metabolites in school students from northern Thailand, Int. J. Hyg.
common symptoms appear to be nausea and vomiting.
Environ. Health 212 (2009) 288–297.
Neurotoxicity appears to be most clinically significant. Per- [7] P.Y. Yang, J.L. Lin, A.H. Hall, T.C. Tsao, M.S. Chern, Acute ingestion
methrin toxicity may mimic organophosphate poisoning poisoning with insecticide formulations containing the pyrethroid
because of its cholinergic actions. Treatment for perme- permethrin, xylene, and surfactant: a review of 48 cases, J. Toxicol.
Clin. Toxicol. 40 (2002) 107–113.
thrin toxicity is mainly supportive, including protection of [8] J. Miyamoto, Degradation, metabolism and toxicity of synthetic
the airway due to the altered mental status and significant pyrethroids, Environ. Health Perspect. 14 (1976) 15–28.
secretions, and involves reversal of GABA receptor dysfunc- [9] F. He, Neurotoxic effects of insecticides – current and future research:
a review, Neurotoxicology 21 (2000) 829–835.
tion with benzodiazepines. Atropine is ineffective, and may [10] C.B. Breckenridge, L. Holden, N. Sturgess, M. Weiner, L. Sheets, D.
have the undesired side effect of reducing seizure thresh- Sargent, D.M. Soderlund, J.S. Choi, S. Symington, J.M. Clark, S. Burr,
old in these patients. Initial presentation of poisoning D. Ray, Evidence for a separate mechanism of toxicity for the Type I
and the Type II pyrethroid insecticides, Neurotoxicology 30 (Suppl.
with permethrins may mimic that seen with exposure to 1) (2009) S17–S31.
organophosphates and carbamates; however, rapid anal- [11] M.J. Wolansky, J.A. Harrill, Neurobehavioral toxicology of pyrethroid
ysis of the offending agent may assist with the accurate insecticides in adult animals: a critical review, Neurotoxicol. Teratol.
30 (2008) 55–78.
diagnosis. Thus, a high index of suspicion in patients
[12] J.T. Eells, P.A. Bandettini, P.A. Holman, J.M. Propp, Pyrethroid
presenting with cholinergic signs and neurotoxicity unre- insecticide-induced alterations in mammalian synaptic membrane
sponsive to standard management for organophosphate potential, J. Pharmacol. Exp. Ther. 262 (1992) 1173–1181.
[13] G.V. Rao, K.S. Rao, Modulation in acetylcholinesterase of rat brain by
poisons should suggest the possibility of permethrin tox-
pyrethroids in vivo and an in vitro kinetic study, J. Neurochem. 65
icity. Further investigation of this form of poisoning is (1995) 2259–2266.
recommended. [14] C. Cox, Permethrin, J. Pestic. Reform 18 (1998) 1.