Anisocoria - is it always sinister?

INTRODUCTION

Acute anisocoria suggests impending neurologic emergency unless proven otherwise. Sinister causes include tumor, hemorrhage while benign causes are physiological, pharmacological, trauma or congenital abnormalities. Determining the cause is challenging in critical ventilated patients having altered sensorium leading to multiple cross consultations and costly evaluations which would be appropriate if raised intracranial pressure is confirmed after ruling out other reasons of unilateral dilated pupil, sparing the patient unnecessary expense.^1,2

Intensive care unit (ICU) patients with bronchospasm are treated with nebulized salbutamol and ipratropium bromide, causing mydriasis with inadvertent ocular instillation. Failure of the dilated pupil to constrict with 1% of Pilocarpine confirms the diagnosis. We report a case of nebulized ipratropium bromide-induced anisocoria to draw clinicians’ attention to possible benign anticholinergic systemic side effect of inhaled ipratropium bromide.^3,4

CASE REPORT

An 11-year-old boy with childhood asthma on preventers was admitted to pediatric intensive care unit (PICU) with life threating exacerbation of asthma and started on bronchodilator nebulization (salbutamol, ipratropium bromide), IV steroids, IV magnesium sulphate, IV aminophylline, s/c adrenaline and high flow nasal cannula (HFNC) under continuous monitoring. Since admission, his sensorium remained normal. On day 3, his pupils were found to be unequal; right measuring 5 mm sluggishly reacting to light and left measuring 3 mm reacting to light (Figure 1). History was negative for headache, vomiting, altered sensorium, fever, double vision and eye drops instillation. As his neurological examination was normal with no evidence of papilledema or raised intracranial pressure (ICP), anisocoria was postulated to be induced by accidental exposure to nebulized ipratropium.

Management and outcome

Ipratropium was stopped and he was closely monitored with a plan for imaging in case of worsening. However, anisocoria improved and by 24 hours child’s pupils were equal in size.

DISCUSSION

Anisocoria is cautionary of an imminent neurologic emergency. Acute unilateral mydriasis implies fatal conditions like tumor compression, intracranial hypertension with impending uncal herniation.

Benign anisocoria is seen in one-fifth of individuals with a normal light reaction.⁵ Benign pharmacological anisocoria develops from mucosal absorption of drugs after the topical use of eye drops (atropine, scopolamine hydrobromide, amphetamines, serotonergic medications, cyclopentolate) or nebulized use of drugs (ipratropium bromide). Systemic medications cause bilateral mydriasis whereas eye drops or inhaled anticholinergics cause unilateral mydriasis.

Ipratropium bromide, an atropine derivative and a direct antagonist at muscarinic cholinergic receptors of bronchial smooth muscles causes bronchodilation but has unintended anticholinergic effects like mydriasis, cycloplegia, blurred vision, dry mucous membranes, dry eyes, tachycardia, decreased gastric emptying, urinary retention and rarely acute glaucoma.²

Ipratropium bromide induced anisocoria was first reported in 1986 by Samaniego and Newman.²

Usually, children are seated on parents’ lap, who holds the mask and places it on the face of the child with the right hand. While this prevents a tight seal, it often results in the drugs having more contact with the left eye resulting in anisocoria mimicking an acute neurological condition. Aerosol inhalation has a maximum effect up to one hour after administration with half-life of six to eight hours. The anisocoria usually resolves within 48 hours of removal of the agent but may last for 3 weeks. Recommendation is to use fitting mask well placed on the face with eyes closed during nebulizer drug therapy and thorough ophthalmological examination before discharge. In case of anisocoria, inform and observe for 8 hours.^3,6 Failure of the dilated pupil to constrict after instillation of 1% of pilocarpine confirms the diagnosis of ipratropium induced anisocoria from trauma or nerve damage.^1,4

CONCLUSION

In summary, benign causes like ipratropium bromide should be considered as a cause for unilateral fixed dilated pupil in patients on nebulisations when features of raised intracranial pressure are absent. With a proper history, detailed physical examination and close monitoring unnecessary investigations like computed tomography (CT), magnetic resonance imaging (MRI) and electroencephalography (EEG) can be avoided.

Recommendations

Detailed history, physical examination and knowledge of causes of anisocoria can avoid unnecessary cross references and non-emergent invasive studies.

Common medications used in ICU can have uncommon adverse effects like anisocoria and masks should be adjusted well before administration of nebulization.

Medication induced anisocoria should be suspected in a patient with a normal sensorium.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

1. 1. Pejic R, Klaric B. Transient anisocoria in a patient treated with nebulized Ipratropium bromide. Am J Ophthalmol Case Rep. 2017;7:11-3.
2. 2. Bisquerra RA, Botz GH, Nates JL. Ipratropium-bromide-induced acute anisocoria in the intensive care setting due to ill-fitting face masks. Respir Care. 2005;50:1662-4.
3. 3. Derinoz-Guleryuz O, Fidanci Đ, Men-Atmaca Y. Nebulized Ipratropium Bromide-induced Anisocoria: Why Is Anisocoria Observed? Iran J Allergy Asthma Immunol. 2021;20:125-8.
4. 4. Eustace N, Gardiner C, Eustace P, Marsh B. Nebulised Ipratropium Causing a Unilateral Fixed Dilated Pupil in the Critically Ill Patient: A Report of Two Cases. Crit Care Resusc. 2004;6:268-70.
5. 5. Moeller JJ, Maxner CE. The dilated pupil: An update. Curr Neurol Neurosci Rep. 2007;7:417-22.
6. 6. Wehbe E, Antoun SA, Moussa J, Nassif I. Transient Anisocoria Caused by Aerosolized Ipratropium Bromide Exposure from an Ill-Fitting Face Mask. J Neuroophthalmol. 2008;28:236-37.