Pupil Size and IV anaesthetics in clinical practice
Luc Barvais
Department of Anaesthesia.
Erasme Hospital, 808 route de Lennik, 1070, Anderlecht, Belgium
Tel: + 32 2 5553919 ; Fax : + 32 2 5554363 ; E-mail address:
Introduction
Estimation of the µ-agonist opioid effect during anaesthesia is often based upon different imprecise clinical measurements such as arterial pressure and heart rate variations, tear formation, sweating and movement. The sympathetic response can be obscured by
b-adrenergic blocking agents and EEG derived data such as the BIS index is not affected by low opioid concentrations (1). Moreover, movement is abolished in paralysed patients. During general anaesthesia, pupillary changes to light or to a painful stimulus are rarely explored because of the lack of a convenient and accurate method to record pupillary activity in the operating room. Recently, new accurate and easy to use pupillometers have been marketed which allow measurement of the pupils size without any influence to the light reflex. So the interest of pupil size and reactivity has to be revisited.
Pupil innervation
Pupil size is determined by smooth muscles in the iris that are innervated by the two divisions of the autonomic system (2) and is determined by the equilibrium between the sympathetic and parasympathetic divisions of the autonomic system.
The parasympathetic system (cholinergic innervation) of the iris originates exclusively in the midbrain (Edinger Westphall nucleus), innervates the circular fibers of the iris and has a pupil constrictive action.
Sympathetic outflow begins in the posterolateral area of the hypothalamus. First-order preganglionic neurons descend uncrossed through the tegmentum of the midbrain and pons and terminate in the intermediolateral cell column at the C8 to T2 cord level. Second-order preganglionic fibers exit the cord primarily with the first ventral thoracic root and enter the paravertebral sympathetic chain. The second-order neuron takes a circuitous course through the posterosuperior aspect of the chest and ascends in the neck in relationship to the carotid system. The fibers ascend without synapsing through the inferior and middle cervical ganglia, and terminate in the superior cervical ganglion at the base of the skull. Third-order neurons originate in the superior cervical ganglion and are distributed to the face with branches of the external carotid artery and to the orbit via the ophthalmic artery and ophthalmic division of the trigeminal nerve. This polysynaptic sympathetic system, mediated by alpha-1 adrenergic receptors, innervates the radicular fibers of the iris muscles and dilates the pupil.
Noxious stimulation dilates the pupil in both unanaesthetized and anaesthetised humans and is mediated primarily by the sympathetic system in the awake state. However, during desflurane anaesthesia, pupil dilation to a noxious stimulus appears to involve either inhibition of the pupilloconstrictor nucleus located in the central pathway as high as the rostral mesencephalon, or a previously undescribed noncholinergic, nonadrenergic synapse at neuromuscular junctions within the iris (3).
General anaesthetics and IV drugs used during anaesthesia
The halogenated agents (halothane, isoflurane, sevoflurane, desflurane), the catecholamines and atropine provoke mydriasis (4, 5). Propofol, thiopentone, lidocaine and the muscle relaxants do not alter pupil reactivity (6, 7). The neuroleptic and opioid drugs have a pupilloconstriction effect. During isoflurane anaesthesia, alfentanil did not diminish the light reflex but produced a substantial dose-dependant depression of pupil dilation after a noxious stimulus. Larson and colleagues have demonstrated that alfentanil does not diminish the light reflex but blocks the reflex pupil dilation in response to noxious stimulation and reported a good correlation between plasma alfentanil concentration and magnitude of pupil dilation (8). Dilation was reduced to 50% of control values at alfentanil concentrations around 20 ng.ml-1, and was almost abolished at concentrations approaching 100 ng.ml-1 (8). Larson and colleagues have also demonstrated that pupil dilation is a more sensitive measure of noxious stimulation than the commonly used variables of arterial pressure and heart rate during isoflurane and propofol anaesthesia (4).
The relationship between the effect site concentration (Ce) of remifentanil and the pupil diameter and reactivity in response to a standard noxious stimulation has been evaluated (9). Pupil dilation to a tetanic stimulus of 100 Hz during 10 seconds (T100) decreased progressively and a correlation between pupil dilation to T100 and remifentanil Ce from 0 to 5 ng.ml-1 was found (R² = 0.68). The authors concluded that during propofol TCI in healthy patients, the decrease of pupil dilation to a painful stimulus was a better measurement of the progressive increase of remifentanil Ce up to 5 ng.ml-1 than haemodynamic or BIS measurements.
The effect of dopamine D2 receptor antagonists, such as chlorpromazine and haloperidol, on pupil size in awake subjects suggests that these drugs might also alter pupillary reflex dilation and pupil size during general anesthesia.. Metoclopramide produced a small decrease in pupil diameter and transiently depressed reflex dilation, whereas droperidol decreased pupil size and depressed reflex dilation throughout the study period (10). Ondansetron had no effect on pupil diameter or reflex dilation (10). The authors concluded that when pupillary diameter measurements are used to gauge opioid levels during experimental conditions or during surgical anesthesia, antiemetic medication acting on the dopamine D2 receptor should be avoided. Moreover, miosis is often considered as an effect of opioid administration during general anesthesia, but other drugs, such as antiemetics might produce a similar effect on the pupil (10).
The effects of intravenous lidocaine on the magnitude and duration of reflex pupillary dilation had also been evaluated in six volunteers anesthetized with desflurane 3.5-6.0% (11). Intravenous lidocaine was administered to a plasma concentration of 5.3 +/- 1.5 micrograms/ml. When the plasma concentrations were stable, a 5-second tetanic electrical stimulus was applied. Lidocaine did not significantly alter the pupillary response to electrical stimulation.
Epidural anaesthesia
The hypothesis that pupillary dilation in response to noxious stimulation would predict the level of sensory block achieved during combined epidural/general anesthesia has also been tested in volunteers and patients (12). A twofold increase in pupil size following electrical stimulation in volunteers and an increase in pupil size exceeding 50% in patients were considered the predicted block level. After general anesthesia was discontinued, observers blinded to the pupillary measurements independently determined the actual epidural block level using pain in response to a pinprick as the criterion. The level predicted by pupillary responses was within two dermatomal segments of the actual level and never differed by more than four dermatomes. The authors conclude that dilation of the pupil in response to electrical stimulation is an accurate test of the sensory block level during combined epidural/general anesthesia (12). The influence of typical plasma lidocaine concentrations observed during epidural anesthesia are unlikely to prevent the use of pupillary responses to evaluate sensory block level (11).
Conclusions
If pupil size cannot help the anaesthesiologist to evaluate the depth of analgesia, the pupil reflex dilation in response to a standard noxious stimulus could help the anaesthesiologist to quantify the level of epidural or opioid analgesia during general anaesthesia. However, the relation between pupil reflex dilation to a noxious stimulus and the opioid concentration is limited because no pupil dilation is observed at very high opioid concentrations. Consequently, pupil dilation to a noxious stimulus could only be a sensitive measure of low or moderate opioid analgesia in the daily clinical practice. In the future, the relationship between pupil reactivity and adequacy of preoperative and postoperative analgesia must be studied on a larger scale. Moreover, other studies are required to evaluate the relationship between pupil reflex dilation and analgesia in some particular clinical conditions such as in elderly patients or patients tolerant to opioids.
References