HIGH IMPACT BUNDLE: Electroencephalogram (EEG) Correlates of Infant Spinal Anesthesia

Spinal anesthesia is a powerful alternative to general anesthesia in infants undergoing infraumbilical procedures, with advantageous physiological properties unique to the first year of life¹. Clinicians have long observed and leveraged the beneficial attributes of infant spinal anesthesia to confer greater cardiorespiratory stability compared to general anesthesia. Successful administration of spinal anesthesia avoids intraoperative hypotension², the need for airway instrumentation, and reduces the incidence of early postoperative apnea³. Infant spinal anesthesia has also been shown to have operational benefits including shorter operating room and recovery unit times⁴ as well as lower pain scores in some institutions⁵. A common observation in pediatric patients after administration of plain intrathecal bupivacaine is a clinically striking decreased state of arousal and reduced level of consciousness resembling “sleep” without the administration of any sedative-hypnotic agents¹. The mechanism by which bupivacaine causes motor and sensory blockade is known to be via antagonism of sodium channels at the level of the spinal cord. However, less is known about what accounts for the effect of spinal anesthesia on wakefulness, and whether the associated sedation classically observed in very young children reflects an anesthetized state, a sleep state, or some combination of both.

Prior research in the adult population has demonstrated that epidural and spinal anesthesia are associated with increased levels of sedation^6,7 and decreased anesthetic requirements^8,9. Clinical researchers have sought to measure these clinical effects with studies demonstrating a reduction in bispectral index (BIS) values¹⁰ or patient state index (PSI) values¹¹ following spinal anesthesia. However, other studies did not find a significant difference in BIS values despite observed differences in levels of alertness or sedation¹². Fundamentally, researchers have sought to obtain a readout able to more precisely quantify the effect of spinal anesthesia to induce sedation and reduce anesthetic requirements by using scalp electroencephalogram (EEG) recordings to measure underlying changes in voltage potentials in the brain. In this way, the EEG might measure the depth of anesthesia in order to better “explain” the clinical effects observed. A limitation of BIS and PSI is that they are processed EEG algorithms that may not account for neurodevelopmental age differences, interindividual pharmacodynamic differences, or the unique mechanisms of neuraxial anesthesia that could account for sedation. To our knowledge, EEG patterns in adults during spinal anesthesia, outside of BIS and PSI, have not been described in the literature.

Similarly, the effects of spinal anesthesia on the EEG in infants have not been well-studied. Preliminary work in infants examined EEG correlates of spinal anesthesia using EEG-derived depth-of-anesthesia monitors. Hermanns et al. obtained EEG correlates of spinal anesthesia in a cohort of 20 preterm infants using the BIS monitor¹³. After administration of 1 mg/kg of 0.5% hyperbaric bupivacaine with 10 μg/kg epinephrine, BIS levels were reduced, with a decrease in spectral power. Disma et al. studied 12 infants receiving 1 mg/kg 0.5% levobupivacaine using the Cerebral State Index (CSI)¹⁴. They observed a reduction in the CSI of all infants accompanied by findings consistent with burst suppression, a pattern of decreased voltage. This pioneering work obtaining neurophysiological correlates of infant spinal anesthesia inspired other investigators to build on this research. The mechanism of the sedation observed with spinal anesthesia has been hypothesized to be due to a decrease in afferent input to the reticular activating system, rather than rostral spread of local anesthetics. Of note, Holman and Puglia highlighted a case series of 4 infants with loss of corneal and eyelash reflexes after spinal anesthesia with 0.5% bupivacaine suggesting an effect on brainstem reflexes despite the lack of general anesthesia¹⁵. Corneal reflexes may be modulated by the reticular activating system as well as by natural sleep, suggesting the loss of corneal reflexes in these patients could be directly related to sleep¹⁵. The absence of the corneal reflex in younger infants could also reflect neurological pathways that are not yet fully mature, with full-term infants developing the tactile corneal reflex over the first 12 weeks of life¹⁶. Whitaker et al. obtained unprocessed EEGs in the International 10–20 System in a pilot cohort of 12 infants receiving spinal anesthesia¹. All patients received 1 mg/kg of 0.5% bupivacaine (maximum 5 mg), with 4 infants receiving 1 mcg/kg of intrathecal clonidine. All infants developed a sedated state, with EEG findings most commonly demonstrating an initial voltage attenuation and background slowing, followed by the appearance of sleep spindle complexes (12–14 Hz) distributed in frontal and central leads, suggestive of physiologic Stage 2, non-rapid eye movement (NREM) sleep (Figure 1). No burst suppression patterns were observed.

Figure 1.

Density spectral array demonstrating transition from the awake state to stage 2 of sleep over an 8 min period. The density of spectral power is color coded for percentage of total power as a function of frequency. Sleep spindles (12–14 Hz) are denoted by the asterisks and faint yellow density measures.

To further expand on these findings, Santa Cruz et al. obtained frontal EEG recordings in 34 infants with a median age of 11.5 weeks postmenstrual age (PMA) undergoing spinal anesthesia with 1 mg/kg of 0.5% bupivacaine with or without 1 mcg/kg of intrathecal clonidine, at the discretion of the anesthesiologist¹⁷. EEG findings consisted predominantly of slow oscillations (Figure 2). The spectrograms were visually scored for episodes of EEG discontinuity (a pattern of low voltage defined as less than 25 μvolts lasting for 2 seconds or greater) and sleep spindle activity. The authors made a distinction between gestational age, postmenstrual age, and chronological age in their analysis of EEG discontinuity and sleep spindle development, which is important because these findings vary depending on the stage of neurodevelopment of the infant^18,19. The authors described age-dependent changes in the presence of EEG discontinuities (Figure 3) and sleep spindles (Figure 4) in infants under spinal anesthesia, which appeared to correspond to developmental changes in the natural sleep EEG of infants. The first transition in EEG dynamics occurred in neonates, in which the probability of discontinuities decreased to zero with increasing gestational age. These discontinuities were more likely to be observed in premature infants, who are known to exhibit discontinuous patterns of activity on their EEG during physiologic sleep^18,19. Of note, EEG discontinuity is distinct from burst suppression, and frequently is not differentiated from burst suppression in the EEG-derived depth-of-anesthesia monitors. While the previous study by Disma and colleagues noted an increase in burst suppression in infants under spinal anesthesia¹⁴, it is possible that this calculated index may have been identifying EEG discontinuities as opposed to burst suppression. This is an important distinction, as EEG discontinuities can be observed in healthy preterm and term neonates up to 46 weeks PMA and are characterized by bursts of high amplitude EEG activity alternating with low amplitude (<25–50 μV) EEG activity¹⁹. In contrast, burst suppression is considered a severe disruption of EEG continuity that is characterized by bursts of EEG activity with abnormal features alternating with prolonged periods of abnormally low amplitude (<5 μV) EEG activity¹⁹ and is often associated with poor neurologic outcomes²⁰. The second transition in EEG dynamics was related to spindle activity under anesthesia. Spindle oscillations were absent in neonates and appeared at approximately 49 weeks postmenstrual age, similar to the time when sleep spindles are observed during brain development^18,19. Overall, these findings by Santa Cruz et al. are consistent with previous work showing the EEG following infant spinal anesthesia was characterized by the appearance of spindles and background slowing, suggestive of a sleep-like state^1,17.

Figure 2.

Spectrogram and time domain waveform of an 11-week-old premature infant (33 week gestational age) under spinal anesthesia. The spectrogram shows a dominant low-frequency (slow/delta: 0.1–4 Hz) activity. A corresponding 10-second EEG trace recorded at minute 26 featuring slow-delta oscillations is shown.

Figure 3.

Spectrogram and time-domain waveform of an 11-week-old premature infant (26 week gestational age) under spinal anesthesia. The spectrogram shows an alternating pattern of burst events lasting a few seconds followed by periods of discontinuity of variable duration and amplitude. A corresponding 10-second EEG trace recorded at minute 44 shows alternating discontinuity events and high-frequency bursts.

Figure 4.

Spectrogram and time-domain waveform of a 20-week-old infant (38 week gestational age) under spinal anesthesia. The spectrogram shows spindles (10–15 Hz oscillations) and slow-delta oscillation (0.1–4 Hz). A corresponding 10-second EEG trace recorded at minute 31 shows slow waves and spindles (red underlines).

Lastly, infants receiving intrathecal clonidine as an adjunct to spinal anesthesia have been observed to have a higher incidence of hiccups and mild airway obstruction compared to infants receiving bupivacaine alone, perhaps suggesting higher levels of blockade²¹. These airway events did not, however, result in an increased rate of conversion to general anesthesia or a longer recovery period²¹. Alpha-2 agonists, like clonidine and dexmedetomidine, have also been associated with slow oscillations with spindles²². Given these observations, studies are ongoing to investigate whether the addition of intrathecal clonidine as an adjunct to spinal anesthesia resulted in a potentially deeper level of sedation, with associated differences in sleep spindle characteristics observable in the EEG. Preliminary data suggest that the use of adjunctive intrathecal clonidine at a dose of 1 mcg/kg does not substantially alter the EEG properties of infants during spinal anesthesia, demonstrating that while clonidine prolongs spinal anesthetic duration, there does not appear to be identifiable differences in EEG features.

In conclusion, findings from studies to date seem to indicate that the apparent sedative state observed in infants following spinal anesthesia is most consistent with natural sleep. This sedative state is likely promoted by a shift in the balance between and sleep and wakefulness, influenced by a decrease in ascending afferent inputs to reticulo-thalamo-cortical pathways and an immature general arousal and attention system in infants²³. Specifically, the EEG correlates of infant spinal anesthesia consist of: (1) global slowing in the background frequency of EEG waveforms¹⁷; (2) low voltage (or discontinuous) EEG patterns in the youngest of infants, which may account for the burst suppression detected by BIS and CSI^13,14; and (3) the appearance of sleep spindles in older infants consistent with age-related observations from sleep literature^1,17. No epileptiform or other abnormal findings have been reported²⁴. Future research could further investigate EEG sleep spindle architecture and incorporate other approaches to sleep spindle detection²⁵.