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Mechanism of pupillary reflex dilation in awake volunteers and in organ donors.

BACKGROUND: The mechanism of reflex pupillary dilation was investigated in eight patients who were declared brain dead after rupture of intracranial vascular malformations and in eight awake volunteers. The authors hypothesized that the reflex was primarily a spinal sympathetic reflex that would be blocked by topical application of the alpha1-adrenergic blocking agent dapiprazole and that it would be present in organ donors with intact spinal reflexes and no history of hypoxia. METHODS: In volunteers, pupil size was measured with an infrared pupillometer while brief painful electric stimuli were delivered to the finger. Pain was assessed with a visual analog scale and adjusted with each volunteer to equal 3 on a visual analog scale of 0-10. Subjects were studied before and after topical application of the alpha1-adrenergic antagonist dapiprazole. In organ donors, the authors measured pupil size after high-intensity tetanic electric stimulation and in dapiprazole-blocked and -unblocked pupils after surgically induced nociception. RESULTS: In volunteers, the pupil dilated 0.43 +/- 0.23 mm after nociceptive stimuli. Dapiprazole eyedrops blocked this dilation, confirming that the reflex in awake humans is primarily a sympathetic reflex. Baseline diameters were 5.7 +/- 0.5 mm before dapiprazole and 4.1 +/- 0.9 mm after dapiprazole. In organ donors, a tetanic electric current failed to dilate the pupil, whereas the skin incision dilated the pupil 0.4 +/- 0.4 mm, but this dilation was not blocked by dapiprazole. CONCLUSION: The authors conclude that pupillary reflex dilation, as it is clinically performed in awake subjects by stimulating somatic nociceptors, is a sympathetic reflex. Because it is not present in organ donors, the neural pathway must require a supraspinal component for completion.

Adult↗

Latency of pupillary reflex dilation during general anesthesia.

Areas of insensibility produced by neuraxial anesthesia or peripheral nerve blocks can be detected during general anesthesia by failure of noxious stimulation to trigger pupillary reflex dilation. We examined the latency of pupillary reflex dilation and the effect of fentanyl on the latency of reflex dilation during anesthesia in nine volunteers. We hypothesized that the reflex was generated by slowly conducting C nociceptive fibers and would be significantly delayed if a distal dermatome (L(4)) was stimulated compared with a proximal dermatome (C(5)). We also hypothesized that fentanyl would prolong the latency and alter the shape of the reflex. After induction of general anesthesia, pupillary reflex dilation was measured with an infrared pupillometer every 5 min after stimulations of the L(4) and C(5) dermatomes. Fentanyl (3 microg/kg) was then given intravenously. Pupillary reflex dilation latencies were calculated by examining each individual measurement. After 3 h, naloxone (400 microg) was given intravenously; anesthesia was then discontinued. Pupillary reflex dilation had a long latency and consisted of distinct early and late phases. No differences were found between latencies of reflex dilation after simulation of L(4) and C(5) dermatomes either before or after fentanyl administration. Fentanyl at high concentrations essentially eliminated pupillary reflex dilation; but over the 180-min observation period, first early and then late dilation returned. Fentanyl produced a small increase in the latency of the initial early dilation. We conclude that pupillary reflex dilation during anesthesia is not initiated by slowly conducting C fibers and that fentanyl depresses the reflex in a stereotypical manner.

Adult↗

On the difficulties encountered when establishing the correct diagnosis of disturbances in the pupillary reflexes.

It is always difficult to interpret abnormalities in pupillary reflexes when a patient who has suffered injuries to the upper part of the face is unconscious. Nevertheless, thorough examination of pupillary reflexes can provide vital information about possible damage to the central nervous system. Decisions about treatment of and prognosis for patients with multiple injuries can be made more accurately when the status of the nerves supplying the eye are taken into account. Anatomical and physiological relationships of pupillary reflexes and oculomotor reactions in a patient with multiple injuries are discussed.

Adult↗

Assessment of thoracic epidural analgesia during general anesthesia using pupillary reflex dilation: a preliminary study.

OBJECTIVE: Pupillary reflex dilation (PRD) secondary to noxious stimulation accurately predicts sensory block during combined lumbar epidural/general anesthesia. Therefore, the adequacy of PRD-guided thoracic epidural infusion during general anesthesia for thoracotomy was studied. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Thirteen patients undergoing thoracotomy. INTERVENTIONS: An epidural catheter was placed at the T3-T4 level with initial infusion rate of 5 mL/h of ropivacaine 0.5%. Propofol/remifentanil target-controlled infusion was used for induction and maintenance of general anesthesia. Remifentanil effect site concentration was maintained constant at 0.5 ng/mL during surgery. By using a portable pupillometer, PRD secondary to tetanic stimulation of the C8, T2, and T4 segments were evaluated. Ropivacaine flow rate was adapted half hourly, according to PRD testing and a predefined algorithm. At the end of surgery, PRD was tested in the 3 investigated segments, and general anesthesia was stopped. After emergence, these zones were tested for their sensitivity to cold. Pain was evaluated by using the visual analog scale. RESULTS: Pain scores were <3 of 10 in 84.6% of the patients. Mean PRD was 0.9 +/- 0.6 mm in unblocked levels versus 0.2 +/- 0.5 mm in blocked segments (p = 0.02). PRD >or= 0.5 mm was predictive of incomplete block (sensitivity 76%, specificity 79%, and positive predictive value 86%). PRD >or= 1 mm was highly predictive of inadequate block (sensitivity 73%, specificity 91%, and positive predictive value 94%). CONCLUSION: PRD-guided continuous thoracic epidural analgesia under low-dose remifentanil/propofol anesthesia is feasible and ensures good postoperative analgesia.

Amides↗

Alfentanil blocks reflex pupillary dilation in response to noxious stimulation but does not diminish the light reflex.

BACKGROUND: Estimation of the mu-agonist opioid effect in anesthetized and paralyzed patients is often imprecise and can be obscured by concomitant administration of drugs that affect the sympathetic nervous system, such as beta-adrenergic blocking agents. As an alternative to hemodynamic measures of opioid effect, the authors tested the hypothesis that the pupillary light reflex or pupillary reflex dilation correlated with alfentanil concentrations during isoflurane anesthesia. METHODS: Six volunteers were anesthetized on 4 days with 0.8% isoflurane. Alfentanil was administered intravenously to target total plasma concentrations of 0, 25, 50, and 100 ng/ml. A 5-s tetanic electrical stimulus was applied to the skin. Pupil size and the pupillary light reflex were recorded before and after alfentanil administration, and before and for 8 min after the stimulus. RESULTS: Alfentanil exponentially impaired reflex pupillary dilation, decreasing the maximum response amplitude from 5 mm at 0 ng/ml, to 2.3 mm at 25 ng/ml, to 1.0 mm at 50 ng/ml, and finally to 0.2 mm at 100 ng/ml. In contrast, only the highest concentration of alfentanil depressed the dilation of the pupil in the first 2 s after the stimulus. Alfentanil administration had no effect on the pupillary light reflex. CONCLUSIONS: Dilation of the pupil in response to a noxious stimulus is a measure of opioid effect in isoflurane-anesthetized volunteers. In contrast, the pupillary light reflex is unaffected by alfentanil during isoflurane anesthesia. These data suggest that stimulus-induced pupillary dilation may be used to evaluate the analgesic component of a combined volatile and opioid anesthetic.

Adult↗

Chronic cerebral hypoperfusion: loss of pupillary reflex, visual impairment and retinal neurodegeneration.

Adult rats underwent permanent bilateral occlusion of the common carotid arteries (2VO) to determine the effect of chronic cerebral ischemia on vision and retina. They were monitored post-surgically for the presence of the pupillary reflex to light. Some rats were tested for 6 months post-surgically on a radial arm maze task and then tested in another water-escape task which explicitly tested visual function. Another group of rats were tested post-surgically for 3 months on a task which simultaneously assessed visual and tactile discrimination ability. The thicknesses of the retinal sub-layers were then measured for some rats. Fourteen of the 25 rats that underwent 2VO lost the pupillary reflex. This seemed to occur within 5 days. Rats that lost the pupillary reflex but not rats whose reflex was intact, were impaired on all visually guided mazes. Tactile discrimination ability was unaffected. Only rats that lost the pupillary reflex showed reduced thickness of the retinal outer nuclear and plexiform layers, reduced cell density in the retinal ganglion cell layer and astrocytosis and degeneration of the optic tract. We conclude that 2VO can eliminate the pupillary reflex. Photoreceptors and retinal ganglion cells degenerate, but it is unclear if these are the cause(s) or result(s) of the loss of the pupillary reflex. These effects are accompanied by impairment of visually guided behavior. The possibility that visual system damage may also occur in acute ischemia merits further investigation.

Animals↗

Reflex pupillary dilatation in response to skin incision and alfentanil in children anaesthetized with sevoflurane: a more sensitive measure of noxious stimulation than the commonly used variables.

BACKGROUND: Estimation of analgesia in anaesthetized children is often imprecise, and consequently, anaesthesiologists commonly evaluate children's response to surgical stimulation by movement or haemodynamic changes. In adults reflex pupillary dilatation has been demonstrated to be a very sensitive measure of noxious stimulation, correlated with opioid concentrations. The autonomic nervous control changes with age, raising the hypothesis that mechanisms involved in pupillary autonomic functions regarding both sympathetic and parasympathetic components may also differ between adults and children. In this pilot study, we tested the hypothesis that the pupillary reflex dilatation might allow assessment of noxious stimulation and analgesic effect of alfentanil in children under sevoflurane anaesthesia, as an alternative to haemodynamic and bispectral measures. METHODS: After sevoflurane induction, 24 children were maintained in steady-state conditions at 1.5 MAC of sevoflurane in O(2)-N(2)O (50-50). An intense noxious stimulation was provided by standardized skin incision on the lower limb. A bolus of alfentanil (10 microg kg(-1)) was administered either 1 min (n=16) or 2 min (n=8) after skin incision. Haemodynamic values, bispectral index (BIS) and pupillary diameter (PD) were recorded just before stimulation and at 30-60 s intervals during 4 subsequent minutes. RESULTS: In all children PD increased significantly after noxious stimulation [+200 (40)%, at 60 s]. In contrast, mean heart rate and blood pressure increased only 11 (7)% and 10 (8)% respectively, 60 s after stimulation. BIS did not change significantly. In all children, alfentanil injection induced a rapid decrease of PD and restored pre-incision values in 2 min. CONCLUSION: PD is a more sensitive measure of noxious stimulation than the commonly used variables of heart rate, arterial blood pressure and BIS in children anaesthetized with sevoflurane.

Adolescent↗

Properties of the pupillary dilation produced by the humoral factor in the pupillary reflex dilation: an experimental study in the cat.

Physiopharmacological properties of the pupillary dilation produced by the humoral factor in the reflex pupillary dilation were studied in cats anesthetized with ketamine-HC1. Pupillary dilation produced by the humoral factor was separated from that produced by the neural mechanism, ie, sympathetic activation and parasympathetic inhibition, by atropinization of acutely sympathectomized pupil. To evoke the pupillary reflex dilation, the sciatic nerve was stimulated by using a bipolar electrode. The stimulus consisted of trains of 0.5 milliseconds duration rectangular pulses and was given for 5 seconds. The stimulus frequency was usually 50 Hz; high frequency stimuli were more effective to evoke pupillary dilation produced by the humoral factor. The pupillary dilation was recorded with an infrared pupillo-analyzing system. A long latency (about 6 seconds) and long peak latency (about 10 seconds) pupillary dilation was produced by the humoral factor. The threshold of pupillary dilation produced by the humoral factor was always higher than that produced by parasympathetic inhibition. The pupillary dilation produced by the humoral factor was not affected by local application and intravitreal injection of 10(-2) M propranolol-HC1 and 10(-2) M yohimbine-HC1. However, the dilation was markedly inhibited by intravitreal injection of 10(-2) M phenoxybenzamine-HC1 or local application of 10(-2) M bunazosin-HC1.

Animals↗