Unilateral mydriasis secondary to ipratropium bromide in a critically ill patient.

Unilateral dilated pupil in a critical patient under sedation is an important clinical sign that requires prompt evaluation. An exhaustive assessment must be performed, including neurological examination and imaging tests, and pharmacological causes must be ruled out. We describe a case of unilateral fixed dilated pupil secondary to the administration of a nebulized cholinergic antagonist, ipratropium bromide, in an unconscious patient.

INTRODUCTION

Unilateral dilated pupil in a critical patient under sedation is an important clinical sign that requires prompt evaluation. The differential diagnosis includes compression of the third cranial nerve, Adie's pupil, tentorial herniation, and meningeal irritation and inflammation. Pharmacological causes (anesthetic and decongestive agents and recreational drugs) must be ruled out in order to avoid unnecessary tests. There are some reports in the literature on anisocoria caused by the local action of ipratropium due to its effects antagonizing acetylcholine at the cholinergic receptors located in the eye.[12]

CASE REPORT

A 36-year-old male patient was admitted to intensive care unit due to acute severe asthma that required intubation and positive pressure ventilation. He was obese and asthmatic since childhood and cigarette smoker of a pack a day for the last 15 years. He was sedated with midazolam and morphine hydrochloride at usual doses. He received nebulized ipratropium bromide and endovenous salbutamol, developing mydriasis in the left eye on the fourth day of the treatment. The left pupil was insensitive to the light and measured 6 mm in diameter, in opposition to the right pupil that was 2 mm and sensitive to the light. Computerized cranial tomography was ordered to rule out cerebrovascular event and revealed no cerebral or vascular structural pathology. The sedation was withdrawn on the fifth day after admission, and we verified that the patient was conscious, orientated, and cooperative. He was able to move all four extremities equally, and there was no loss of vision. In order to make a differential diagnosis, a pilocarpine eye drop test was performed, showing no effect after its administration in the midriatic eye, indicating a possible role of a pharmacological muscarinic blockade. Ipratropium bromide was stopped, and the diameter of the midriatic pupil was normal 48 h after the suspension of the treatment without any sequela. Salbutamol treatment was continued. No other pharmacological agents with sympathomimetic effects (catecholamine or cocaine) were administered during his stay in the intensive care unit, and an analysis of recreational drugs in the urine performed at admission was negative.

DISCUSSION

Different physiopathologic abnormalities can lead to anisocoria and an exhaustive assessment must be performed, including neurological examination and imaging tests. Areflexic unilateral mydriasis in a patient without any neurological deficit or systemic disease forces the physician to rule out pharmacological causes. Unilateral mydriasis can be seen in several intoxications, and in practice the exposition to mydriatic substances is a common cause. Zeiter et al described the existence of unilateral mydriasis in habitual crack smokers (crack eye)[3] and the role of decongestive (oxymetazoline) and anesthetic agents have been broadly discussed.[4-6] Recreational drugs (e.g., ecstasy) can release monoamine neurotransmitters enhancing the inhibition of the uptake of serotonin that can produce mydriasis in susceptible individuals.[6] In our patient, urine tests of recreational drugs were negative at admission and structural damage was ruled out with tomography. Pilocarpine eye-drop test has shown to be useful in differential diagnosis of unilateral mydriasis. Pilocarpine should constrict the neurologically dilated pupil and the normal one by acting on the muscarinic receptors of the iris sphincter. It will have no miotic effect on a pupil dilated due to muscarinic receptor blockade.[7] If ipratropium bromide (a quaternary anticholinergic agent that produces bronchodilation in asthmatic patients slower than beta 2 inhaled agents) is administered blocking the cholinergic stimulation of sphincter muscle, the constriction does not occur.[89] In our case, the recuperation of the normal pupil diameter after the suspension of ipratropium excludes the role of the other medication able to cause unilateral mydriasis (salbutamol). Nevertheless, the long duration of the episode (48 h) could be explained with the possible interaction between beta-adrenergic agonists and muscarinic antagonists in iris sphincter relaxation, as seen in vitro in previous reports.[10]

CONCLUSIONS

In conclusion, unilateral mydriasis in an unconscious patient is an important clinical sign and a differential diagnosis must be quickly performed in order to rule out structural and pharmacological causes. Size of the pupil and its reaction to light can help identify the problem and a pilocarpine eye-drop test can be useful in order to avoid unnecessary tests but a complete assessment must be performed. Physicians should keep in mind that cholinergic antagonists agents administered via nebulizers can cause this unusual effect by its local action.