Eye movements under general anaesthesia have always generated great interest. In 1848 Snow12 defined the concept of anesthetic depth and defined the cessation of voluntary eye movement and inclination of eyes in up-gaze as the point of sufficient anesthetic depth. Using the degree of etherization, Guedel 13 described the various stages of anaesthesia. Stages 1 and 2 relate to the induction of anaesthesia and stage 3 corresponds to the stage of ‘surgical anaesthesia’ the ideal state for most surgeries which he further divided into 4 planes. During plane 1 there is somatic relaxation, loss of blink reflex but marked roving movement of eyeballs and this plane ends as eyeball movement cesses. Plane 2 is characterized by fixed eyeballs (eccentric eye position) and loss of a corneal reflex. In deeper planes (3 and 4) pupillary reflex is lost, pupils are dilated and extraocular muscles became flaccid.
Eccentric eye positioning under general anaesthesia is not uncommon. Though few studies have described up-gaze eccentric eye-positioning under general anesthesia, there is paucity in literature regarding eccentric down positioning of eyes.4,5,6,14 Few of the studies describing eye positioning under general anesthesia encountered down positioning of eyes.4,6,14 Power et al in his study observed final eye position in downward direcion under different depths of general anesthesia14 in few patients but their number, depth of general anaesthesia, and down-scoring of eye position were never described. In his study of 32 patients, Chung et al6 encountered elevation of the eyes in 83%, and down-shoot of eyes was noted in 2%. Down-shoot eye movement was seen at BIS values less than 35. They also studied the relationship between fixed eccentric eye elevation and depth of anaesthesia during surgery and scored the vertical position of each eye on an ordinal scale from − 2 to + 6, according to its height in relation to the medial canthus.6 Only one child (2%) out of 32 children developed downward drift.6 To our knowledge no study has ever studied the down-rolling of eyes preceded by up-rolling and compared it with the increase or decrease of anesthetic concentration and their corresponding MAC values. Also, no study has described scoring of eccentric down-rolling of eyes up-to inferior fornix and has discussed the entity in detail.
In our case series, this tonic downward movement was seen in pediatric cases (< 2 years) under sevoflurane general anaesthesia without muscle relaxant when attempts were made to rapidly deepen/optimize the plane of anaesthesia (on surgeon’s request to centralize eye position from eccentric positioning in up-gaze) or at the beginning of surgery. Under all occasions, at the time eccentric fixation of eyes in downgaze, and adequately deeper plane of anaesthesia was found as demonstrated by the higher value of MAC in all cases (Table 1). The lower value of BIS (in case1) corroborated the finding of the prior studies4,6 though values of BIS in children infants and young children do not indicate a similar concentration of sevoflurane like adults.15 Down-movement of eyes to eccentric position towards inferior fornix was fast but the return of down-movement was smooth and gradual lasting over few minutes till the depth of anaesthesia was comparatively lightened by decreasing the flow of sevoflurane and eye reached to the central position. Its occurrence made surgeons abandon the procedure till the time it lasted. It appeared to have resulted from a tonic contraction of the inferior rectus of both eyes as it was difficult to manually rotate the eyes and carry the procedure. All cases had symmetric down-rolling (Fig. 4) except case 6 in which asymmetry was evident (Fig. 3). Though we could not understand the exact reason we suspected asymmetric dissociated vertical deviation in the child to alter the eye position.
The nerve impulses that generate the motor discharge in the form of a saccade originate as two types: burst neurons and tonic neurons.16 High-frequency bursts of action potentials beginning before the commencement of the saccade and ending just before the eye movement are produced by burst neurons whereas tonic neurons discharge at regular intervals to hold the eye in the new eccentric position. In our case series, the hypo-tropic movement appeared both as a result of pulse firing which caused the eye to achieve rapid saccade velocity in downgaze and tonic firing which held the eye in the downward eccentric position till the anaesthesia was lightened.
Most authors have described eccentric positioning of eyes under GA in upgaze.4,5,6,12 Power et al while studying the depth of anaesthesia in young adults via sevoflurane induction compared eye signs with EEG polysomnography and showed that, the deepest level of sleep was reached on an average 3 minutes before the onset of eccentric ocular positioning thereby suggesting that eccentric eye movements may occur even when a patient appears satisfactorily anesthetized.14 Rossiter reported an incidence of 8% which increased up-to 18% without the use of muscle relaxants.5 Higher incidence of up-gaze eccentric movement (34.4%) in Kook’s study was due to an extended duration of the measurement period, including the time of emergence from anaesthesia4 as upward eye positioning is more commonly seen at the end of surgery when anaesthesia is lightened. Few authors quantified eye position related to the depth of anesthesia using BIS and found a shallower level of anaesthesia to be associated with a higher BIS value and a higher eye position.4,6 In our case series also upward drifting of the eyeball was seen under lighter planes of anesthesia during eye manipulation during surgery as demonstrated by lower MAC values (mean 1.03±0.10) in 4 patients in which upward drift was seen during surgery. High BIS value (55) recorded in case1 corroborated the findings of the prior studies.4,6
Inhalational agents are known to cause a dose-dependent suppression of reflexes and movements.1 Complete lack of electrical discharge in the extraocular muscles occurs only during deep sleep or deep anaesthesia.1 Presence of electrical activity in one of the extraocular muscles occurs over its opposing muscle in the lighter plane of anaesthesia and probable causation has been discussed in the literature by many researchers. Rossiter et al reasoned intense and sustained contraction of superior rectus (SR) behind the eccentric upward eye position.5 Harrad and Stoddart17 suggested that Bell’s phenomenon, a natural protective reflex, in which the globe rolls up in response to any noxious stimuli in the form of pressure on the globe or any manipulation of the eyeball may explain this upward eccentric eye position.18,19 This occurs both in the awake state and with lighter planes of anaesthesia (though the patient is not awake) which may explain the entity. The exact neural mechanism is unknown but involves brainstem pathways between the seventh cranial nerve nucleus in the pons and the third cranial nerve nuclear complex in the rostral midbrain. Hiraoka et al have suggested that the mesencephalic reticular nucleus may play an important role in integrating these two patterns of movement (bilateral lid closure and upward movement of both eyes).20 Bell's reflex is also extinguished with deep planes of anaesthesia such that the eye remains in the neutral gaze.16, 17 And this upward drift in cases 2, 3, and 4 prompted the anesthetist to increase the depth of anesthesia to make the eyes return from the upward position following which down-rolling was encountered.
The causation of down-rolling has never been discussed. We hypothesize that the probable reason for such down-rolling movement could be due to temporary irritative effects in the central nervous system related to the used anesthetic agent as in all our observations eye movements altered as per the level of MAC. It is a norm to increase sevoflurane concentration for smooth intubation and it is lowered to a chosen value following intubation. And the causes of irritative effect can be two-fold though we need further research with prospective studies to investigate the same. First, it could be due to of sudden increase in sevoflurane concentration (higher MAC) and differential sensitivity of cortical and subcortical centers for different sevoflurane concentrations.21 Higher MAC means a higher level of an anesthetic agent within alveoli and, in turn, a higher level in the central nervous system. Mourisse and colleagues22 have demonstrated in adults that the blink reflex (brainstem function) was more sensitive to sevoflurane than BIS (forebrain function), To date, few available pediatric data have investigated the relative effect of anaesthesia on cortical and subcortical site controlling eye movements. The meso-diencephalic junction contains the rostral interstitial nucleus of the medial longitudinal fasciculus, the interstitial nucleus of Cajal, the mesencephalic reticular formation, and the posterior commissure, all of which are involved in premotor control of vertical eye movements.23 Forced downward gaze is common in the lesions affecting this area and presumably represents an imbalance in the vertical gaze plane.24 Downward deviation in our cases could be caused by a rapid increase in sevoflurane concentration and selective irritation of downgaze neurons in the midbrain. 25, 26 Its occurrence only in certain children can be explained by the varied sensitivity of different individuals and lower sensitivity of sevoflurane for some subcortical structures (i.e. mesencephalic control) in prepubertal children than older subjects.21 Its occurrence only on a certain occasion in the same child could be time interval and the deeper plane of anesthesia to which child was subjected during intubation and chosen value of MAC to which patient was stabilized before handing over the child to the ophthalmic surgeon for the procedure. It should be noted that though the mean MAC value in case8 when down-rolling was encountered before the start of the procedure was only 1.4 transient MAC values during the process of intubation was much higher (1.7) and as per the experience of authors it takes few minutes for the eyes to respond to increased or decreased sevoflurane concentration and eyes centration response comes when MAC level below their corresponding threshold is reached though further studies are needed to confirm the same
Another plausible reason could be due to transient drop in perfusion pressure below the lower limit in small children due to shortened autoregulation and vasodilatory effect of sevoflurane causing transient decreased cerebral blood flow (CBF) and irritative effect which get reversed on decreasing the concentration.27,28 Lower limits of autoregulation in sevoflurane anaesthesia is close to the baseline mean arterial pressure of young children.29 This hypothesis is supported by the finding that hypo-tropic movement in our cases was seen at or beyond 1.5 MAC as CBF in young children remain unaffected up-to 1.5 MAC value of sevoflurane.27,30 Its selective occurrence at one particular exposure out of multiple exposures/subjugations to general anesthesia (case1) probably point towards violation of narrow autoregulation limit when depth got deepened beyond the permissible limit for the child depending on hid individual sensitivity window at the time of particular exposure. The territory of the posterior circulation supplying mesencephalic-diencephalic junction, which contains structures important for vertical gaze and vergence could be an affected area that has been associated with tonic downward and inward movement30 as seen in our cases. Though rarely at higher concentration (5.3%) of sevoflurane, tonic-clonic movements have been described32 but the concentrations at which these hypo-tropic movements were seen in our cases, routinely and necessarily does not lead to cerebral ischemia in healthy children as thousands of sevoflurane inductions are performed every day in children, and neurologic complications are very rare. Eccentric movement of eyes on one occasion and not every time the same patient is taken under general anesthesia implies that the movement happened only when MAC level fell below or high beyond the narrow limit in the sensitive children.
This report aims to sensitize ophthalmologists regarding this sudden eye movement encountered under general anaesthesia and suggests the use of muscle relaxants in ophthalmic surgeries with critical steps like cataracts, squint, etc. Also, our case series highlight the importance of maintaining required depth of anaesthesia without fluctuation if GA given without muscle-relaxant for short procedures. We need further studies on the detailed evaluation of eccentric downgaze or hypo-tropic movement including eye movement tracking devices or recordings and its relationship with eccentric upward position and depth of anaesthesia (using BIS and MAC values). Also, via electro-oculographic records of eye movements, simultaneous EEG, and clinical observations we need to investigate the tonic force in the inferior rectus to understand the pathophysiology of these eye movements giving clue into ongoing sub-cortical processes. It will also be interesting to further study why certain children develop the extreme eccentricity of eyes in downgaze and if an anesthetic agent has a role in these movements. The entity also requires attention for further investigations regarding its relationship with the depth of anaesthesia and age of the child.