Background: Chronic exposure to dexamethasone is associated with resistance to non-depolarizing neuromuscular blocking agents. Previous studies have reported that chronic dexamethasone treatment induced alteration and upregulation in immature subunits of nicotinic acetyl-choline receptor in diaphragm of rats. However there was no previous report about the effect of chronic exposure to dexamethasone on sugammadex (SGX) reversal in rat diaphragm.

Methods: Male Sprague‑Dawley rats (7-8 week-old; 202 to 271 g) were randomized to receive a daily intraperitoneal injection of dexamethasone (500 µg/kg) in dexamethasone group or same amount of saline (0.9% NaCl) in control for 14 days. At 1,3,7 days after the last dexamethasone (group D1,D3,D7) (given the withdrawal time) or 1 day after saline (C), the rats were anesthetized. The hemi-diaphragm with attached phrenic nerve intact was immediately obtained. 
After the elicited twitch tension by phrenic nerve had been stabilized, Train-of-four (TOF) was determined. Rocuronium 250 µg was then applied to the organ bath. Following stabilization, TOF was again determined with repetitive administration of cumulative dose of Rocuronium 250 µg. 
After complete block (T1 height <5%), SGX twice as much as rocuronium-equimolar dose was applied. Recovery profiles (time to TOFratio[TOFR]>0.9, recovery index) were observed. 

Results: There was no significant difference between groups in diaphragm size and weight. Dose-response curve of rocuronium in group D1 was shifted to right compared to group C (p < 0.05), but curves in D3, D7 groups were not significantly different. IC50 in group D1 is significantly larger than group C.
Recovery time to TOFR > 0.9 and recovery index were 12.8 ± 4.9, 15.0 ± 7.1, 10.2 ± 3.3, 10.1 ± 3.8 and 5.36 ± 1.9, 5.8 ± 3.3, 3.8 ± 1.3, 3.12 ± 1.2 (min) in group C and group D1, D3, D7 respectively. It was not statistically significant in time to TOFR > 0.9, but recovery index in group D7 were significantly shorter than group C and D1. 

Conclusions: Chronic exposure to dexamethasone causes resistance of the rat diaphragm to rocuronium. Furthermore, the pharmacodynamics change in dexamethasone treatment was recovered in 3 days after withdrawal (in 7-8 week-old rats). TOFR > 0.9 when reversed with SGX was not affected by dexamethasone administration, however the recovery index in group D7 was shorter than group C and D1. 
The chronic exposure to dexamethasone seemed not effect on sugammadex (SGX) reversal in rat diaphragm.



09 / Effect of chronic exposure to dexamethasone and its withdrawal on rocuronium-induced neuromuscular block and sugammadex reversal in in vitro study of rats