Inhaled lidocaine for equine asthma

Background information

Equine asthma is a commonly encountered clinical presentation in equine veterinary medicine and can be challenging to manage due to the multi-factorial approach required for optimal control of symptoms. Possible side effects of systemic medication need to be considered. With an ageing population of horses and ponies under our veterinary care and a high proportion of them being overweight, the impact of underlying endocrinopathies such as pars pituitary intermedia dysfunction (PPID) and/or equine metabolic syndrome, in conjunction with glucocorticoid medication should not be underestimated. Some clinicians also have concerns regarding impaired wound healing and immune system effects when using systemic glucocorticoids. Inhaled medication has become more mainstream in recent years thanks to ergonomic advancements in the equipment available for meter-dosed inhaler administration and nebulisation of liquid medication (e.g. the AeroHippus® and Flexineb® E3 system). However, some owners still have reservations about inhaled glucocorticoid use in horses or ponies with metabolic disease as low-level systemic glucocorticoid absorption may still occur, and they may wish to consider alternative therapies, such as inhaled lidocaine for equine asthma treatment.

Common clinical symptoms of equine asthma

Increased respiratory rate and effort – even at rest
Coughing (sometimes only observed during exercise or upon increased exertion)
Exercise intolerance / poor performance
Increased mucus production from airways (typically white mucoid discharge)
A ‘heave’ line (external abdominal oblique muscle hypertrophy on either side of the abdomen)
In poorly controlled or severe cases, episodes of respiratory distress

Why consider lidocaine as an inhaled medication?

Lidocaine has been shown to have a positive effect on asthma symptoms in both human and feline patients, decreasing coughing in human asthma patients, and decreasing airway hyperreactivity in a feline asthma model. Equine asthma shares pathophysiological mechanisms with human asthma – hence why this common respiratory condition is now considered best referred to as ‘equine asthma’, rather than chronic obstructive pulmonary disorder (COPD), or recurrent airway obstruction (RAO).

What’s new in equine asthma?

A recent pilot study by Mahalingam-Dhingra (2022) published in the Canadian Journal of Veterinary Research looked to investigate the feasibility, safety and efficacy of using inhaled lidocaine via a Flexineb® nebuliser as an alternative treatment for equine asthma. A budesonide treatment group was included in the study to provide a known and validated treatment option as a point of reference; however, the aim of the study was not to prove a difference in efficacy between the two treatments.

Study design

Study design – double-blind, randomised, controlled clinical trial – subsequently re-designed as a pilot study.
16 pleasure/companion horses met the inclusion criteria – all of these had history and clinical signs consistent with equine asthma – diagnosis was confirmed based on clinical score, lung function testing and respiratory secretion cytology.
Of 19 horses assessed for eligibility, one horse was excluded due to significant upper airway tract abnormality on endoscopy (soft palate displacement) and two were excluded due to their fractious nature and therefore inability to perform the respiratory testing.
Physical examination, peripheral blood differential analysis, serum amyloid A (SAA) measurement, an abbreviated exercise test and upper airway endoscopy were performed to rule out other cases of exercise intolerance.
Only 13 horses completed the study – two horses in the placebo nebulised saline group were excluded due to severe exacerbation of disease and the placebo trial stopped early – one further case was excluded before allocation to a treatment group because the initial disease was too severe to conduct pulmonary function testing or bronchoalveolar lavage (BAL)
Horses were not given glucocorticoids or antihistamines in the 14 days prior to the start of the study, nor aerosolised bronchodilators in the 48hrs before the start of the study.
Owners were asked to keep management consistent during the two-week study period i.e. no changes to bedding, feed or turnout location/times.
A 23-point clinical scoring system (including respiratory rate, nostril-flaring, nasal discharge, auscultation findings and coughing) was used as an indication of the clinical severity of asthma and pulmonary resistance in horses recruited for the study.
Upper airway endoscopy was used to assess laryngeal function and mucus grade (score 0-4).
Spirometry was performed to measure tidal volume, minute ventilation, peak inspiratory and expiratory flow rates, and inspiratory/expiratory times.
Non-invasive forced oscillatory mechanics (FOM) were used to measure total respiratory system resistance.
Changes in respiratory system resistance were used as a measure of the effects of histamine bronchoprovocation (performed in horses with a low level of respiratory resistance) or bronchodilator challenge (performed in horses if respiratory resistance was elevated)
A dose-response curve was generated to determine the histamine dose required to reach a 75% increase in total respiratory system resistance (or until the horse displayed clinical reaction to histamine administration i.e. increased respiratory rate/effort or coughing).
For the bronchodilator challenge, total respiratory system resistance was measured 15 minutes post-albuterol administration via an AeroHippus®
In 11/13 horses, respiratory secretions were assessed using BAL fluid cytology at the start and end of the study i.e. on day 0 and day 14. 2/13 horses who did not tolerate the BAL procedure had endoscopic-guided tracheal aspirates performed instead.
Owners were taught how to use the Flexineb system to deliver aerosolised medication q12 hours for 14 days – either 1mg/kg lidocaine, or 1.0ug/kg budesonide – both diluted to a total volume of 20ml using 0.9% sterile saline.
Owners were instructed to fast horses for 45 minutes after nebulisation to avoid any potential dysphagia (choke) associated with local laryngeal/pharyngeal anaesthetic effects.
Remote check-ins by email, telephone or text were completed every one to two days.
At 14 days, horses returned as outpatients to the hospital for repeat clinical evaluation.

Study validity

Strengths:

Consolidated Standards of Reporting Trials (CONSORT) guidelines were followed for recruiting cases, conducting the study and analysing results.
Data were normally distributed, and the statistical methods chosen appear to be appropriate to the study design.
No recall bias was present, as this was a prospective study.
Reporting was clear – all horses were accounted for, and a comprehensive methodology was outlined with sufficient detail for the study to be repeatable.
The paper has a high level of authority due to the publishing journal (Canadian Journal of Veterinary Research) and therefore should provide good quality evidence.

Weaknesses

Initially, horses were randomly assigned to a treatment group – either nebulised lidocaine or saline. However, two horses in the saline control group had severe exacerbation of clinical signs, so were removed from the study and the placebo trial had to be stopped early – at this point the study was re-designed as a pilot study of nebulised lidocaine alongside nebulised budesonide.
The study is low down in the hierarchy of evidence due to being re-designed as a pilot study.
Case numbers in the budesonide group were too small to draw statistical comparisons between lidocaine and budesonide groups – statistics are therefore largely descriptive only.
The only analyses carried out were within treatment groups pre- and post-treatment.
Detection bias was present and owner-assessed respiratory scoring had to be dropped from the study, as owners were able to determine which treatment group their horse was in by tasting the solution to be placed in the nebuliser and experiencing tongue numbness if their horse was in the lidocaine group – this was an unexpected complication of treatment being conducted in the home environment.

Study findings

No adverse effects to a twice daily 1mg/kg dose of inhaled 4% preservative-free lidocaine were noted over the 14-day treatment period.
Clients reported administration of nebulised lidocaine was well-accepted by their horses.
In most cases, a relatively short period of approximately 15-20 minutes was required for the nebulisation of 20mls of medication via the Flexineb system.
Occasional coughing during nebulisation of lidocaine and budesonide was observed.
Occasional technical difficulties with the Flexineb device resulted in one missed dose and one delayed dose in the lidocaine treatment group.
No incidents of dysphagia were reported – although owners were not uniformly compliant with withholding feed for 45 minutes post-nebulisation.
There was a significant decrease in clinical respiratory scores in both lidocaine and budesonide groups.
BAL neutrophil percentage and tracheal mucus score decreased significantly in the lidocaine treatment group only, but overall improvements in lung function were not seen.
In the budesonide group, decreases in respiratory rate and resistance were observed.
Two horses in each treatment group demonstrated a 25% reduction in total respiratory system resistance with the albuterol bronchodilation challenge.

Conclusions and clinical relevance

Although at first glance the findings of this pilot study appear encouraging in terms of nebulised lidocaine as an alternative treatment option for equine asthma, very small case numbers mean that conclusions regarding feasibility and safety should be interpreted with caution. Conclusions regarding the efficacy of nebulised lidocaine should not be drawn, however, these initial results do suggest inhaled lidocaine may still be a potential alternative treatment in patients where glucocorticoids are contraindicated, but that detailed further investigation is needed.

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