Clinical Presentation, Consecutive Measurements of Serum Butyryl-Cholinesterase Activity and Treatment of a Dog Intoxicated by Anticholinesterase and Presented Acute Cholinergic Crisis Followed by Intermediate Syndrome. Case Report and Review of the Literature

Abstract

The article describes the clinical signs, laboratory findings, including consecutive serum butyryl-cholinesterase (sBuChE) activity measurements, treatment and outcome of a dog diagnosed with intermediate syndrome (IMS) of organophosphate intoxication. A 2-year old neutered female mixed-breed dog was presented with acute cholinergic crisis (ACC) due to  anticholinesterase intoxication. sBuChE activity upon admission was markedly low [382 U/L; reference interval, (RI) 2,660-11,00 U/L]. The dog was treated with atropine sulfate, diphenhydramine, 2-pyridine aldoxime-methyl-chloride and supportive care. The  muscarinic signs resolved, but 24 hrs post-admission the dog sustained a grand-mal seizure and developed quadriparalysis and severe weakness, including respiratory muscle weakness, necessitating positive pressure mechanical ventilation (PPMV). The dog recovered slowly, presenting signs of ventroflexion, front limb muscle weakness and absent swallow reflex of several days, which gradually improved. During ventilation sBuChE activity was 2735 U/L,
and later on during hospitalization, remained mildly less than the RI. The dog was discharged on day 8 of hospitalization. IMS has previously been diagnosed based on the history of a previous case of ACC, with deterioration to classic IMS clinical signs, requiring PPMV. Interestingly, sBuChE was within or mildly below RI during the course of the IMS, which highlighted the possibility of a diagnosis of IMS in face of normal sBuChE activity. The authors conclude that IMS should be suspected in dogs showing cranial nerve, respiratory, neck and proximal limb muscle weakness or paralysis, especially in face of prior ACC, but even in the absence of preceding ACC signs.

Keywords: Organophosphate; Carbamates; Canine; Positive Pressure Ventilation, Ventroflexion.

Introduction

Organophosphates are commonly used in agriculture, industry and home environmental pest control, and as chemical warfare agents (1-3). Organophosphate intoxication induces several neurological syndromes, including acute cholinergic crisis (ACC; type-1 syndrome) (1, 4-6),
intermediate syndrome (IMS; type-2 syndrome) (7, 8) and organophosphate-induced delayed polyneuropathy (OPIDP), myopathy and central nervous system (CNS) impairment (9, 19). Cases of organophosphate intoxication in humans, describing signs of ambulation difficulty,
ataxia and muscle weakness have been recorded during the 1960’s and 1970’s, and were then categorized as intoxication “type-2 signs” (11), and later termed IMS (12). Since then, IMS has been reported extensively in humans, with only few reports in animals (13-19). IMS presented as paralysis, occurring 7 to 96 hours post-ACC, but before the typical onset time of OPIDP. It was clinically characterized by muscular weakness, predominantly of proximal limb muscles, neck flexors, muscles innervated by motor cranial nerves or respiratory muscles (7, 8, 12-14). IMS was also characterized by prolonged cholinesterase inhibition (7, 8, 20-24).
Herein, we describe a dog that sustained ACC, which later developed to IMS, requiring positive pressure mechanical ventilation (PPMV). Interestingly, serum butyrylcholinesterase activity (sBuChE) normalized during the IMS period, although no clinical improvement was noted.

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