Editor-Guedel used ocular signs as part of his classic description of the four stages of ether anaesthesia in 1937. These were deemed to be relevant clinical tools when ether, cyclopropane, and chloroform were in use, but with newer drugs and advanced monitoring, the eye signs gradually faded into obscurity.We report a case of off-label use of dexmedetomidine with bupivacaine for epidural anaesthesia that led to deep sedation and bilateral miosis.A 62-yr-old female patient, ASA I, was to undergo vaginal hysterectomy. Under strict asepsis, an 18 G epidural catheter was placed in the L3 -4 space. A test dose of 3 ml of 2% lidocaine with epinephrine 5 mg ml 21 was given after which 12 ml of 0.5% bupivacaine with dexmedetomidine 1 mg kg 21 was administered through the epidural catheter. After an initial increase to 190/110 mm Hg, arterial pressure decreased to 90/40 mm Hg and heart rate to 46 beats min 21 over the next 5 min. The patient was breathing normally with 99% oxygen saturation but was deeply sedated and was not responding even to painful stimulus (Ramsay score 6). Rapid infusion of i.v. fluids was started and i.v. atropine 0.6 mg was given. Oxygen was delivered by a facemask and a quick re-check was done to exclude any medication error. The pupils were pinpoint in ambient light and a possibility of pontine haemorrhage was also considered. However, the patient started to stabilize gradually and the sedation score improved to 3 after 30 min. The sensory block was adequate and the surgery could be performed as planned. The rest of the perioperative period was uneventful without any neurological sequelae.While a plethora of information exists about the clinical effects of dexmedetomidine in the anaesthesia journals, little has been said about its effects on the pupils. We examined the current medical literature for its mechanism of action and the effect on reflex pupillary reaction in humans. 1 -4 The regulation of sedation, autonomic function, and pupillary reaction are all inter-related and controlled centrally at the locus coeruleus (LC) due to stimulation of presynaptic a 2Aadrenergic receptors by dexmedetomidine. The LC is the largest group of noradrenergic neurones in the central nervous system and gives rise to fibres innervating most structures of the neuraxis. Any pharmacological alteration to this neuronal circuitry would affect the activity at the LC and clinically result in changes in the level of sedation, heart rate, arterial pressure, and pupil size.There is a biphasic response with dexmedetomidine, with an initial transient sympathomimetic action (peripheral postsynaptic action leading to hypertension) followed by a persistent sympatholytic effect (hypotension and bradycardia). The central sympatholytic action also causes a reduction in pupil diameter due to attenuation of the activity of the coeruleo-spinal pathway and reduction in noradrenergically mediated inhibition of the Edinger-Westphal nucleus. This action is known to predominate in comparison with the peripheral post-synaptic a 2 -adr...