Effect of Combined Dexmedetomidine and Sevoflurane Sedation on Sleep Homeostasis in Sprague Dawley Rat
Authors: Fracz Zuzanna , Groenhout Trent , Liu Tiecheng , Mashour George A. , Pal Dinesh 
Published: May 2022

Background

The effect of continuous long‐term administration of sedative‐hypnotics ‐ as occurs in the intensive and perioperative care ‐ on sleep homeostasis is not completely understood. Ongoing studies in our laboratory have shown that sedation produced by continuous infusion (8 h) of dexmedetomidine (DEX, 0.5‐1.0 μg/kg/min) increased wake state (WAKE), decreased slow‐wave sleep (SWS) and reduced rapid eye movement sleep (REMS) in the post‐sedation period, while sedation with continuous (8 h) sevoflurane (SEVO, 2.5‐3.0%) administration did not affect WAKE or SWS but increased post‐sedation REMS [1]. In the current study, to investigate the possibility of a synergistic effect of DEX and SEVO on sleep homeostasis, we maintained the rats on sedation (8 h) produced by simultaneous administration of DEX and SEVO and quantified the effect on post‐sedation sleep‐wake states (48 h).

Methods

Adult male and female Sprague Dawley rats (n=4) were surgically prepared for sleep‐wake recordings and a catheter was chronically positioned in the jugular vein for DEX or lactated Ringer’s (control) infusion. Each rat received 8 h of continuous (10:00 am – 6:00 pm) combined administration of SEVO (0.5‐1.0%) and intravenous DEX (0.1 ug/kg/min), and lactated Ringer’s on a different day with inter‐experiment interval of at least 5‐7 days. The SEVO and DEX concentrations were titrated to maintain loss of righting reflex, which is a surrogate for loss of consciousness in rodents. Post‐sedation sleep‐wake data were recorded for 48 h and manually scored in 4 s epochs into WAKE, SWS, and REMS.

Results

The total time (in minutes) spent in WAKE during the first 12 h post‐sedation period was comparable to that observed after lactated Ringer’s infusion (mean ± standard deviation: 87.78 ± 13.58 after lactated Ringer’s vs 98.59 ± 11.71 after sedation). Similar trend was observed for SWS (mean ± standard deviation: 65.95 ± 10.37 after lactated Ringer’s vs 75.08 ± 12.60 after sedation) while REMS was reduced by 78.68% during the first 12 h post‐sedation period as compared to that observed after lactated Ringer’s infusion (mean ± standard deviation: 25.36 ± 6.715 after lactated Ringer’s vs 5.41 ± 3.30 after sedation). The time spent in WAKE, SWS, and REMS during the remaining 36 h of post‐sedation period was comparable to that after lactated Ringer’s infusion. Compared to the individual administration of DEX and SEVO, as reported previously from our lab [1], combined administration of SEVO and DEX in the current study required 5‐10 times less dose to maintain the loss of righting reflex.

Conclusion

The effect of combined sedation with SEVO and DEX are distinct from the effects after individual administration of these sedatives, suggesting minimal interruption of sleep homeostatic processes leading to a sleep profile that more closely mirrors the natural sleep‐wake states.

References

Parkar A, Liu T, Fryzel A, Groenhout T, Mashour GA and Pal D (2020) Effect of prolonged sedation with dexmedetomidine, midazolam, propofol, or sevoflurane on sleep homeostasis in rat. J Neurosurgical Anesthesiology, Vol 32, No 4, Page 403, Abstract no SNACC‐387.