Electroencephalographic patterns in a mechanically ventilated cat with permethrin intoxication

Abstract

Case summary

A 1-year-old male castrated domestic shorthair cat was presented in a condition of status epilepticus following incidental permethrin spot-on administration by its owner. General anaesthesia and mechanical positive pressure control ventilation were necessary to control the epileptic seizures and a progressive condition of hypoventilation. The cat was managed with an intravenous constant rate infusion of midazolam, propofol and ketamine associated with a low-dose intravenous lipid emulsion. A condition of non-convulsive status epilepticus was detected by serial continuous electroencephalogram (cEEG) monitoring. Initial cEEG showed paroxysmal epileptiform discharges; thus, antiseizure treatment with phenobarbital was added and a bolus of hypertonic saline solution was administered to treat suspected intracranial hypertension. A second cEEG performed 24 h later showed the presence of rare spikes and a burst-suppression pattern, so the decision was made to discontinue propofol. A third cEEG, 72 h post-hospitalisation, showed a normal encephalographic pattern; therefore, anaesthetic drugs were progressively tapered, and the patient was extubated. Five days after admission the cat was discharged on phenobarbital treatment, which was gradually tapered during the following months.

Relevance and novel information

This is the first reported case to describe cEEG monitoring during hospitalisation for feline permethrin intoxication. cEEG should be encouraged in cats with altered mental status that have previously suffered cluster seizures or status epilepticus, which could guide clinicians in the choice of antiseizure drugs.

Introduction

Permethrin, a fat-soluble synthetic pyrethroid insecticide, is a potent neurotoxicant in cats. Permethrin interferes with the axonal sodium gates found in the cell membrane of excitable cells, preventing normal depolarisation and leading to repetitive firing.¹ Acting primarily on the central nervous system (CNS), clinical signs are characterised by tremors and muscle fasciculations at one end of the scale, up to seizures and coma at the other.² After dermal decontamination, supportive care for permethrin toxicosis in cats includes the administration of intravenous (IV) fluids, IV intralipid emulsion (ILE), and symptomatic treatment of muscle tremors and seizures.^1,3–5

Monitoring seizures and CNS activity in hospitalised patients can be challenging. Epileptic brain activity may not be phenotypically evident, especially in the anaesthetised or heavily sedated patient, resulting in a non-convulsive seizure or in non-convulsive status epilepticus (NCSE).⁶ Continuous electroencephalography (cEEG) allows for non-invasive recording of epileptic activity through the detection of three different patterns of increasing frequency and duration: spikes, sharp waves and polyspike. Therefore, cEEG is essential in detecting possible epileptic brain activity and allowing for modification of antiseizure therapy in hospitalised patients.

To the best of our knowledge, a specific description of a cEEG findings in cats treated in an intensive care unit for permethrin intoxication has not been reported in the literature. The aim of this case report was to describe the cEEG findings demonstrating NCSE in a cat with permethrin toxicosis, and to demonstrate the usefulness of cEEG in the decision-making process.

Case description

A 1-year-old male castrated domestic shorthair cat weighing 4.8 kg was presented to the emergency service in a condition of status epilepticus (SE) lasting approximately 12 h, following the accidental administration of a spot-on solution for the treatment and prevention of tick and flea infestation in dogs weighing 40–60 kg (fipronil 402 mg and permethrin 3600 mg [Effitix; Virbac]). On presentation, the cat was recumbent with tonic-clonic seizures and continuous generalised tremors, rapid shallow breathing and miotic pupils. Additional clinical findings were unremarkable.

The cat was initially treated with an IV bolus of midazolam 0.3 mg/kg (Midazolam; Hameln Pharmaceuticals). The lack of clinical improvement prompted the induction of a balanced general anaesthesia with propofol (2 mg/kg IV bolus followed by constant rate infusion [CRI] of 0.1–0.3 mg/kg/min [Proposure; Merial]), associated with midazolam (0.2–0.3 mg/kg/h CRI) and ketamine (1 mg/kg IV bolus and then a CRI of 0.3 mg/kg/h [Nimatek; Dechra]). Resolution of the tremors and tonic–clonic seizures was obtained. The patient was intubated and transferred to the intensive care unit (ICU), and was breathing spontaneously with supplemental oxygen. Because of persistent bilateral miosis and the suspicion of intracranial hypertension (IH), a bolus of hypertonic saline solution (NaCl 7.5%) was administered (4 ml/kg IV over 20 mins) without clinical improvement. The patient was washed with a gentle shampoo for dermal decontamination and a low-dose CRI of ILE (Intralipid 20%; Fresenius-Kabi) was initiated, as previously reported: 1.5 ml/kg IV bolus over 30 mins, then a second IV bolus of 0.25 ml/kg/min over 3 mins, followed by an infusion of 0.025 ml/kg/min given for 8 h.⁷ Bloodwork (blood gas analysis, haematology and biochemistry) was unremarkable.

In the next hour, the cat developed shallow and ineffective breathing associated with progressive respiratory acidosis (venous pH 7.23 [range 7.34–7.40]; partial venous CO₂ tension [PvCO₂] 60.4 mmHg [range 32.7–44.7]). Mechanical ventilation with a volume-controlled mode was subsequently initiated (Evita 4 Ventilator [Draeger]). The settings were as follows: fraction of inspired oxygen 30%; respiratory rate 16 breaths/min; positive end-expiratory pressure 5 cmH₂O; target tidal volume 8 ml/kg. End-tidal CO₂ was 35–37 mmHg and oxygen saturation was 98–100%. A venous blood gas run approximately 2 h after the initiation of mechanical ventilation showed normal pH and PvCO₂ values (venous pH 7.34 [range 7.34–7.40]; PvCO₂ 40.5 mmHg [range 32.7–44.7]). After discontinuation of ILE at the eighth hour of infusion, sporadic facial tremors and involuntary movements of the ears were evident, and levetiracetam (60 mg/kg initial IV bolus, followed by 40 mg/kg q8h [Levetiracetam; Keppra]) was administered for suspicion of focal seizure. Facial tremors and involuntary movements of the ears disappeared.

At 24 h post-hospitalisation, a first cEEG (EBNeuro) was carried out for 1 h and 5 mins, which showed paroxysmal epileptiform discharges (PEDs) such as spikes, mainly at the level of the right cerebral cortex (Figure 1). For these reasons, antiseizure treatment with phenobarbital (3 mg/kg q8h IM [Luminale; Bracco]) and another bolus of hypertonic saline solution was administered following the suspicion of IH.

Figure 1.

Continuous electroencephalography (cEEG) recording 24 h post-hospitalisation. Periodic epileptiform discharges are evident (red continuous arrow shows spike and red dotted arrow shows spike and wave). A monopolar montage was performed using 17 subcutaneously monopolar stainless steel disposable needle (length 12 mm; diameter 0.32 mm). The nomenclature for the positioning of the electrodes was in accordance with that described for the 10–20 international system of human electroencephalography (EEG), with odd numbers denoting the left side electrodes and even numbers for right side electrodes. The letter ‘Z’ defines the midline. The electrodes were positioned according to the following arrangement: frontal (F8, F4, Fz, F3 and F7); temporal (T6, T4, T5 and T3); parietal (P4, P3 and Pz); central (C4, C3 and Cz); and occipital (O1 and O2). The ground electrode was placed caudal to the occipital protuberance, while the reference electrode was placed on the bridge of the nose. Recording parameters included a time constant of 0.1 s and a high frequency filter set at 30 Hz; sensitivity was 2 µV/mm. A 50 Hz notch filter was used. Impedances below 5 kΩ were measured for all electrodes before performing cEEG

A second cEEG was performed 48 h post-hospitalisation, showing the presence of rare spikes and a burst-suppression pattern (BSP; Figure 2). Because of the finding of a BSP, propofol was discontinued.

Figure 2.

Continuous electroencephalography recording during the second day. Burst suppression pattern characterised by beta and theta waves interspersed to period of isoelectric activity lasting a few seconds are present

At 72 h post-hospitalisation, a third cEEG showed normal cerebral activity and no spikes or BSP were detected (Figure 3). Anaesthetic drugs were progressively tapered, and the patient was weaned from ventilator support over the next 4 h. The cat recovered completely and was discharged 5 days after hospital admission with phenobarbital therapy, which was gradually tapered during the following months.

Figure 3.

Continuous electroencephalography recording 72 h post-hospitalisation. No pathological changes were found during 3 h of recording

Discussion

This case report describes NCSE in a cat with permethrin toxicosis managed in an ICU with standard treatments, low-dose ILE and mechanical ventilation. In particular, this case highlights how the use of antiseizure drugs may interrupt phenotypic epileptic manifestations but not those apparent on electroencephalography. However, cEEG can allow for modulation of the antiseizure therapy that is used to stop PEDs.

NCSE is a challenging neurological emergency characterised by persistent changes in mental status, with epileptiform activity seen only on cEEG monitoring, and subtle or no motor abnormalities.⁸ In the human and veterinary literature, cEEG recording during NCSE shows paroxysmal rhythmic activities.^6,9 In generalised NCSE, these activities are bilateral and often predominate in the anterior region. In focal NCSE, these activities are lateralised or asymmetric.⁹ Interestingly, in our case, PEDs were found mainly on the cerebral cortex of the parietal, temporal and occipital lobes.

In human medicine, despite treatment with antiseizure drugs, NCSE persists in 14–34.3% of patients with convulsive SE, potentially representing the end stage of refractory or inadequately treated convulsive SE.10 The mortality rate for NCSE as described in the human medicine literature is variable, and ranges from 30% to 65%.¹¹ Although there are no data available in veterinary medicine literature regarding the prevalence and mortality rate of NCSE, data reported in the human medicine literature should alert veterinary clinicians to the usefulness of cEEG in monitoring patients with SE.

Currently, there are no guidelines on the recording technique for cEEG in small animals. In our patient, an initial 17-channel monopolar montage was chosen. We considered this montage suitable for the study of the entire cerebral cortex.

On the second day of hospitalisation, a BSP was identified in our cat. A BSP arises from a variety of clinical and pathological conditions, generally portraying a state of profound brain inactivation.¹² BSP can occur in different pathological conditions such as cardiopulmonary arrest with secondary cerebral anoxia, trauma and space-occupying lesions in neonates with certain rare genetic or metabolic syndromes, or in the case of severe hypothermia.^13,14 This condition is characterised by a burst of theta or delta waves, or both (0.5–3.5 and 3.5–7.5 Hz), intermixed with faster waves of mixed alpha (7.5–12.5 Hz) and beta (12.5–30 Hz) waves, and an intervening period of isoelectric activity lasting for a few seconds.¹⁵ Owing to inactivity of the brain during a BSP, the pattern can be used to measure the level of coma. Persistence of this condition over time is often associated with poor prognosis. This pattern has been associated with a high dose of gamma-aminobutyric acid (GABA)ergic anaesthetic drugs (eg, propofol, barbiturates and benzodiazepines), and could be used to monitor depth of anesthesia.^16,17 In our patient, owing to the finding of a BSP, the propofol CRI was discontinued. The BSP resolved after a few minutes.

Conclusions

This case report describes the use of cEEG to diagnose and treat NCSE in a cat with a previous SE. The use of cEEG should be encouraged in patients with an altered mental status and previous intense epileptic seizures. Although the role of BSP is not yet clear, it could indicate the time when antiseizure drugs should be decreased during the treatment of patients with SE.