Minnesota Anesthesia Services

Sleep Quality After General Anesthesia

As more research reveals that anesthesia can significantly disrupt normal sleep patterns, sleep quality following general anesthesia has become an area of increasing clinical interest. Unlike natural sleep, general anesthesia alters neural activity through pharmacologic interventions, potentially interfering with the body’s circadian rhythms and homeostatic sleep mechanisms. Patients often report difficulty sleeping in the days following surgery, and a growing body of research concludes postoperative sleep disturbances are one of the many manifestations of postoperative brain dysfunction and can lead to postoperative fatigue, metabolic disorders, hypertension, and cerebrovascular and cardiovascular diseases.1 Sleep quality after anesthesia and surgery is also an important risk factor for delirium development, particularly in high-risk populations.2 Understanding sleep mechanisms under general anesthesia can improve clinical measures for preventing postoperative sleep disturbances.

Sleep includes 5 stages: stages 1-4 (non-rapid eye movement [NREM]) and stage 5 (rapid eye movement [REM]). Each sleep cycle will iterate between NREM, REM, and wake phases, with 3-5 sleep cycles per night. General anesthesia produces a state of unconsciousness that resembles NREM sleep in terms of brain activity. Research suggests general anesthetics target sleep-regulating brain regions in the hypothalamus—specifically, GABAergic neurons in its ventrolateral preoptic nucleus (VLPO)—to induce sedation and loss of consciousness. Anesthetic drugs such as propofol and thiopental enhance the activity of the inhibitory GABAergic neurons in this region.3 A 2019 study used c-Fos staining, ex vivo brain slice recoding, and in vivo multi-channel electrophysiology to identify a core ensemble of neurons in the hypothalamus. These neurons were most active in and around the supraoptic nucleus and were activated by anesthetic drugs like propofol, ketamine, isoflurane, dexmedetomidine, and clozapine.4

Experimental evidence suggests general anesthesia may also alter the molecular clock that relies on genes in the suprachiasmatic nucleus (SCN) of the hypothalamus. In 2016, researchers conducted an in vivo study on 72 mice, 14 of which were administered isoflurane. Murine subjects in the anesthesia group had significantly altered clock gene mRNA, particularly in genes such as Period (Per), Cryptochromes (Cry), Clock, and Bmal1.5 The SCN’s master clock controls the timing of sleep-wake cycles and the circadian rhythms of body temperature, melatonin secretion, and more.

There are a variety of risk factors associated with poorer sleep quality following general anesthesia, including age, surgical trauma, anesthetic mode, postoperative pain, postoperative complications, operating environment, and psychological factors. Patients with certain comorbidities (e.g., obstructive sleep apnea, Attention-deficit Hyperactive Disorder, polycystic ovarian syndrome) often are at greater risk of developing postoperative sleep disturbances.6 High-risk demographics, such as elderly patients, are more likely to have sleep disturbances due to their diminishing physiological reserves and increasing frailty. The duration and type of surgical procedure also directly correlates with the occurrence of postoperative sleep disturbances, likely due to the surgical trauma inflicted on patients.3

The interaction between general anesthesia and postoperative sleep quality is complex. General anesthetics interact with neural circuits involved in natural sleep regulation, especially within critical neural regions like the hypothalamus. They may disturb circadian rhythms and molecular clock gene expression, which can lead to postoperative sleep disturbances that not only impair patient recovery but also increase the risk of further complications such as delirium, cardiovascular events, and metabolic dysfunction. Studying the underlying neurobiological mechanisms and identifying patient risk factors are essential for developing targeted interventions for postoperative sleep disturbances.

References

  1. Horner, Richard L., and John H. Peever. “Brain Circuitry Controlling Sleep and Wakefulness.” CONTINUUM: Lifelong Learning in Neurology, 23(4), 2017, 955–972. https://doi.org/10.1212/CON.0000000000000495
  2. Fadayomi, Ayòtúndé B., et al. “A Systematic Review and Meta-Analysis Examining the Impact of Sleep Disturbance on Postoperative Delirium.” Critical Care Medicine, 46(12),  2018, 1204–1212. https://doi.org/10.1097/CCM.0000000000003400
  3. Luo, Man, et al. “Sleep Disturbances After General Anesthesia: Current Perspectives.” Frontiers in Neurology, 11, 2020. https://doi.org/10.3389/fneur.2020.00629
  4. Jiang-Xie, Li-Feng, et al. “A Common Neuroendocrine Substrate for Diverse General Anesthetics and Sleep.” Neuron, 102(5), 2019, 1053-1065.e4. https://doi.org/10.1016/j.neuron.2019.03.033
  5. Xia, Tianjiao, et al. “Murine Clock Gene Expression in the Suprachiasmatic Nuclei and Peripheral Blood Mononuclear Cells during the Daily Sleep-Wake Rhythm and after Isoflurane Anesthesia.” Sleep and Biological Rhythms, 13(4), 2015, 357–365. https://doi.org/10.1111/sbr.12126
  6. Auckley, Dennis, and Stavros Memtsoudis. “Unrecognized Obstructive Sleep Apnea and Postoperative Cardiovascular Complications: A Wake-up Call.” JAMA, 321(18), 2019, 1774. https://doi.org/10.1001/jama.2019.4781

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