Influence of Surgical-Level Propofol Anesthesia on Non-Rapid Eye Movement and Rapid Eye Movement Sleep in Aged Mice

Clinical studies indicate that sedation with propofol is associated with loss of rapid eye movement (REM) sleep, whereas animal experiments suggest that propofol anesthesia may be functionally equivalent to naturally occurring sleep. However, most preclinical studies of propofol's effects on sleep have used sedative doses in young animals, despite the frequent use of high doses in the operating room and the increased susceptibility of older individuals to sleep disturbances. Here, we investigated how surgical levels of propofol anesthesia affect sleep in aged mice. We hypothesized that anesthetic-dose propofol would significantly alter both the quantity and architecture of sleep in geriatric mice compared to baseline and vehicle-treated controls.

Eighteen- to twenty-month-old mice (N = 20) were implanted with frontal and parietal epidural electroencephalographic (EEG) electrodes and allowed a minimum recovery of 10 days. EEG recordings were obtained in three animal groups. After baseline EEG recordings (control group), mice were randomized to receive either intubation via a 22-gauge intravenous cannula and a propofol infusion titrated to EEG delta waves through a central catheter (propofol group) or an equivalent infused volume of intralipid (intralipid group). Non-rapid eye movement (NREM), REM sleep, wakefulness, and NREM stage III quantity; number and duration of sleep-wake bouts; burst suppression ratio and delta power were measured during continuous 24-hour EEG recordings and analyzed using one- and two-way repeated-measures analysis of variance.

Propofol mice exhibited increased wakefulness (820 ± 93.3 vs 658 ± 71.1 min; P < .001) and decreased NREM sleep (539 ± 93.3 vs 699 ± 64.2 min; P < .001) compared to controls. Early after propofol emergence, NREM stage III (15.7 ± 10.9 vs 52.0 ± 19.0 min; P = .0050), REM sleep (4.31 ± 2.81 vs 23.1 ± 8.26 min; P < .001), the number of REM bouts (13.9 ± 8.28 vs 32.0 ± 11.4; P = .0491), and their mean duration (14.9 ± 8.59 vs 41.9 ± 7.52 min; P < .001) were markedly decreased relative to controls.

Surgical-level propofol anesthesia differentially influenced NREM and REM sleep. Although propofol anesthesia satisfied NREM sleep homeostasis, delayed REM rebound during recovery was compatible with altered REM regulation.