Nebulized dexamethasone sodium phosphate in the treatment of horses with severe asthma

Abstract

Background: A study reported low systemic availability of injectable dexamethasone nebulized to healthy horses using the Flexineb mask. When used in horses with severe asthma and a different nebulizer, lack of efficacy and cortisol suppression were observed.Hypothesis: Nebulized dexamethasone is as effective as PO administration for the treatment of severe asthma in horses.Animals: Twelve horses with severe asthma from a research herd.Methods: Randomized clinical trial. Horses were divided into 2 groups and received 5 mg of dexamethasone sodium phosphate by nebulization using a Flexineb mask (NE, n = 6) or PO (OR, n = 6) q24h for 7 days. Lung function and serum cortisol concentrations were evaluated at baseline, after 4 days of treatment (D4) and 1 day after the last treatment (D8). Data were analyzed using linear mixed models with Benjamini-Hochberg adjustments.

A CONSORT‐guided, randomized controlled clinical trial of nebulized administration of dexamethasone and saline on lower airway cytokine mRNA expression in horses with moderate asthma

“…7 Studies in horses with severe asthma report a rapid significant decrease in serum cortisol concentration after 3 (reduction: 52.4 nmol/L [converted from 1.9 μg/dL]) 2 and 7 (reduction: 57.9 nmol/L [converted from 2.1 μg/dL] 2 ; 44.7 nmol/L 3 ) days of nebulized administration of dexamethasone (5 mg q24h). Consistent with these studies, 2,3 we observed a significant decrease in blood endogenous cortisol at Day 7 and Day 14 of 62 and 59 nmol/L respectively, and as expected, the magnitude of cortisol suppression was greater than that observed at the lower dose rate (5 mg).…”

“…The 15 mg daily dosage of dexamethasone administered via nebulization used in the present study was greater than described in 2 trials of horses with severe asthma trials 2,3 . The reason for this was the lack of improvement in lung mechanics reported with a dosage of 5 mg dexamethasone sodium phosphate nebulized once daily in horses with severe asthma in both previous studies 2,3 .…”

“…The 15 mg daily dosage of dexamethasone administered via nebulization used in the present study was greater than described in 2 trials of horses with severe asthma trials. 2,3 The reason for this was the lack of improvement in lung mechanics reported with a dosage of 5 mg dexamethasone sodium phosphate nebulized once daily in horses with severe asthma in both previous studies. 2,3 We hypothesized that a higher dose of nebulized administration of dexamethasone sodium phosphate (15 mg) would be effective at treating horses with a less severe phenotype of asthma; we also used the same commercial dexamethasone sodium phosphate product as previous studies in severe asthma.…”

“…Nebulization of injectable dexamethasone does not induce airway inflammation and has minimal systemic bioavailability in the healthy horse 1 . However, nebulized administration of dexamethasone (5 mg q24h) does not improve lung mechanics in horses with severe asthma, whereas significantly suppressing endogenous cortisol production 2,3 . Recruitment of inflammatory cells is driven through increased production of inflammatory mediators, associated with increased activity of transcription factors.…”

Clinical effects and pharmacokinetics of nebulized lidocaine in healthy horses

“…While this may have contributed to a dampened maximal urine lidocaine concentration in the 1–3 h post-nebulization, this is considered unlikely to have changed the duration that lidocaine and MEGX were detectable in urine, as xylazine requires 30–60 min to cause a significant increase in the rate of urine production ( 39 ), and urinary catheterization was completed within 10 min of xylazine administration. As drug deposition in the distal airways is impeded by modifications in breathing pattern, cough, bronchoconstriction, and airway secretions such as mucus often present in EA ( 40 ), investigation into drug delivery in clinically affected animals remains essential to ensure that therapeutic concentrations are achieved. However, the peak serum concentrations achieved in healthy horses here indicate that nebulized lidocaine dosages in excess of 1 mg/kg may be safely considered, if needed to achieve clinical efficacy.…”