EEG Signature(s): Electroencephalogram (EEG) of Nitrous Oxide for Emergence

Nitrous oxide is an inhaled gas with anesthetic and analgesic effects. The anesthetic hypnotic effect of nitrous oxide is thought to be mediated through noncompetitive inhibition of the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptor that is crucial for excitatory neurotransmission in the central nervous system (CNS). Nitrous oxide, in combination with γ-aminobutyric acid type A (GABAA) receptor modulators, synergistically promotes amnesia and hypnosis. The analgesic effects of nitrous oxide occur supraspinally by engaging the endogenous opioid system within the periaqueductal gray matter (PAG) and the noradrenergic neurons in the locus coeruleus and brainstem.1

In surgical settings, halogenated ethers are often transitioned to nitrous oxide during closure to facilitate emergence. Nitrous oxide’s effects on EEG vary with concentration. When high concentrations of nitrous oxide (greater than 60% mixed with approximately 40% oxygen) are administered at high flow rates, there is swift uptake by the lungs, circulation, and brain. This rapid absorption leads to the emergence of slow-delta oscillations in the EEG.2 These oscillations are thought to be a consequence of nitrous oxide’s inhibitory effects on NMDA receptor-mediated excitatory transmissions in the brainstem, thalamus, and cortex.

In the clinical setting, when the halogenated ether is discontinued and nitrous oxide is introduced at concentrations exceeding 60%, large amplitude coherent delta waves appear for a period of 2-12 minutes. After this period, one observes a decrease in delta and theta activity and an increase in beta/gamma oscillations.2 The increase in low amplitude/high-frequency EEG is consistent with increased cortical activity.3,4,5 Furthermore, findings of heightened high beta (40–50 Hz) activity with lower nitrous oxide (i.e. 20-40%) concentrations suggest that at sub-anesthetic levels, nitrous oxide sustains a degree of CNS arousal and cognitive function (subjects remain cooperative and responsive on nitrous alone).6

In summary, nitrous oxide’s effect on the EEG is bidirectional, depending on the concentration: lower doses (20-40%) maintain beta and gamma activity conducive to mild sedation, while higher doses (>60%) initially induce slow-delta waves.

CASE 1: An 82-year-old male underwent implantation of an artificial urinary sphincter.

Primary anesthetic: Sevoflurane at age-adjusted 1.0 minimum alveolar concentration (M.A.C) and a dexmedetomidine infusion at 0.4 mcg/kg/hr actual body weight.
Emergence was facilitated with 50% nitrous oxide and 50% oxygen with 0.5% Sevoflurane.

In the spectrograms, time is listed on the x-axis, and frequencies are displayed on the y-axis. The power of the frequencies is indicated by colour on a decibel (dB) scale.  Red indicates higher power, with blue indicating lower/no power. For tracking brain states under anaesthesia, we utilize the frontal EEG.


Figure 1. Time 16:00 indicates the transition from sevoflurane to 50% nitrous oxide/0.5% ET sevoflurane; spectral analysis revealed a diminution of alpha band power. Concurrently, there was a significant decline in frequency power above 5 Hz, coupled with an increase in slow-delta power.  This pattern may be seen in many other situations: 1) higher dose of hypnotic; 2) pain7; 3) stage 3 sleep/high dose dexmedetomidine.  In this case, it is a typical EEG pattern seen with high dose nitrous oxide combined with sevoflurane and reflective of the hypno-sedative shift induced by nitrous oxide.

Figure 2. Raw EEG showing high amplitude delta activity with the transition from sevoflurane to nitrous oxide.

Figure 3. At 16:35, anesthetic vapors were discontinued. As the nitrous oxide concentration falls during emergence, there follows a decrease in delta power and a transition to the appearance of theta power during nitrous washout. With the concentration of nitrous oxide reduced below 50% and a reduction in sevoflurane dose, a distinct transition to beta oscillations was observed, typically associated with increased cortical activity.

Figure 4. Raw EEG demonstrating high beta oscillations.


Case 2: 25 year old undergoing a laparscopic appendectomy for acute appendicitis.

Primary anesthetic: Sevoflurane at age adjusted 1.0 M.A.C

Emergence was facilitated with 60% nitrous oxide and 40% oxygen.

Figure 5. Time 08:35 (spectrogram marked by a black rectangle) indicates the transition from sevoflurane to nitrous oxide.  Spectral analysis revealed a diminution of alpha band power, a significant decline in frequency power above 5 Hz, and an increase in slow-delta power.



  1. Sanders, R. D., Weimann, J., & Maze, M. (2008). Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology109(4), 707–722.
  2. Pavone, K. J., Akeju, O., Sampson, A. L., Ling, K., Purdon, P. L., & Brown, E. N. (2016). Nitrous oxide-induced slow and delta oscillations. Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology127(1), 556–564.
  3. Yamamura, T., Fukuda, M., Takeya, H., Goto, Y., & Furukawa, K. (1981). Fast oscillatory EEG activity induced by analgesic concentrations of nitrous oxide in man. Anesthesia and analgesia60(5), 283–288.
  4. Foster, B. L., & Liley, D. T. (2011). Nitrous oxide paradoxically modulates slow electroencephalogram oscillations: implications for anesthesia monitoring. Anesthesia and analgesia113(4), 758–765.
  5. Foster, B. L., & Liley, D. T. (2013). Effects of nitrous oxide sedation on resting electroencephalogram topography. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology124(2), 417–423.
  6. Rampil, I. J., Kim, J. S., Lenhardt, R., Negishi, C., & Sessler, D. I. (1998). Bispectral EEG index during nitrous oxide administration. Anesthesiology89(3), 671–677.
  7. García PS, Kreuzer M, Hight D, Sleigh JW. Effects of noxious stimulation on the electroencephalogram during general anaesthesia: a narrative review and approach to analgesic titration. Br J Anaesth. 2021 Feb;126(2):445-457. https://doi: 10.1016/j.bja.2020.10.036


Sagar Jolly

Sagar Jolly, MD

Clinical Fellow
University of Miami/Jackson Memorial Hospital