A startling episode with an inconsolable, hallucinating two year old highlights a rare ocular emergency.
A startling episode with an inconsolable, hallucinating two year old highlights a rare ocular emergency.
A two year-old normally healthy female arrives with her mother to the emergency department with the complaint of inconsolable crying. Shortly prior to this, she was examined in the ophthalmologist’s office and received a mydriatic during her ocular exam. About five minutes after the drops had been administered, the child began crying, initially rubbing her eyes, then progressing to whole body writhing and loud screaming. Her tearful mother described her child’s behavior as quite uncharacteristic. While having her vitals taken the child continually yelled for “Mickey Mouse”. Her heart rate was 190 beats/min; blood pressure 140/90 mmHg, respiratory rate was 40 breaths/min with a pulse oximetry reading of 98%. The mother repeatedly told staff her daughter’s skin felt “hot”.
Anticholinergic Toxicity
Inhibition of acetylcholine neurotransmission at its centrally nicotinic and muscarinic, and peripherally muscarinic receptor sites results in a constellation of symptoms that define the anticholinergic toxidrome. Loss of the inhibitory effects of the parasympathetic neurotransmitter system results in a relative imbalance of sympathetic activity and activation of the “fight or flight” response. Patients might present with tachycardia, hypertension and hyperthermia. They may also display dilated pupils, urinary retention, and decreased bowel activity. If the offending agent penetrates the blood brain barrier the victim will become agitated, could hallucinate, experience seizure, or if untreated, hastily decline into coma. To help remember signs and symptoms the anticholinergic syndrome is often taught using the following mnemonic: Red as a beet (cutaneous vasodilation), Dry as a bone (anhidrosis), Hot as a hare (hyperthermia), Mad as a hatter (psychosis/agitation), Blind as a bat (nonreactive mydriasis), and Stuffed as a pipe (ileus and urinary retention).
Differentiation of the anticholinergic toxidrome from that of the sympathetic toxidrome can be clinically difficult, as both typically cause similar symptoms. However, recall that the sweat glands, while sympathetically innervated, utilize muscarinic receptors to signal for increased perspiration. Consequently, while sympathomimetics such as cocaine will typically cause increased sweating, anticholinergics will block the function of sweat glands and cause anhidrosis. As a result, in the absence of a clear clinical picture pointing to a specific exposure, one can use this physical finding to differentiate these syndromes.
Treatment
The mainstay of anticholinergic poisoning is aggressive supportive care with intravenous fluids, active cooling if significantly hyperthermic, and control of agitation with benzodiazepines. However, the effects of anticholinergic toxicity may be emergently reversed by focusing on increasing the relative activity of acetylcholine. This is accomplished by providing medications that inhibit acetylcholinesterase, the enzyme responsible for ACh degradation in the synaptic cleft. Medications such as physostigmine (Anti- delirium®), pyridostigmine, neostigmine, and edrophonium all act in this manner. However, physostigmine, a tertiary amine acetylcholinesterase inhibitor, is the preferred agent due to its reversible inhibition, favorable pharmacokinetics, and ability to cross the blood-brain-barrier.
The practitioner must exercise caution when administering this agent. Over-zealous delivery can lead to a surge of parasympathetic activity by increasing acetylcholine activity beyond the body’s safe capacity. The result would include symptoms of cholinergic toxicity (e.g. bradycardia, increased secretions, bronchospasm, and even cardiovascular collapse). In addition, physostigmine is contraindicated in patients with anticholinergic excess as a result of an overdose of a tricyclic antidepressant due to the possibility of sudden cardiac collapse. TCA toxicity also manifests QRS interval widen- ing as a consequence of its sodium-channel blocking properties, so a pre-administration EKG may be beneficial in patients manifesting anticholinergic effects from an unknown agent.
Quick Facts
It has been reported that children with blond hair and blue eyes are more susceptible to these rare adverse systemic effects. Such was the case with the child in this case.
Ocular Drops Causing Potential Systemic Toxicity in Children
- Anticholinergics (cyclopentolate)
- B-Blockers (timolol)
- Alpha-2 receptor agonists (brimonidine)
- Alpha1-adrenergic receptor agonists (phenylephrine)
Case Outcome
The child was showing systemic effects from the mydriatic agent cyclopentolate (brand names include Cyclogyl®, Cylate®, and Pentolair®) Her pulse and respiratory rate, high blood pressure, and psychosis with hallucinations warranted reversal therapy. Physostigmine was administered at 0.02 mg/kg in a single, slow IV push dose. Within several minutes the child’s heart rate, blood pressure and respiratory rate normalized. Her general restlessness abated, she quieted, and began to respond to her parents with normal recognition.
A conversation between the emergency physician and hospital pharmacist determined the appropriate observation time. The decision was made based on the pharmacokinetics, particularly the peak plasma activity of each medication in the quantities administered. The child remained under observation for ninety minutes, a conservative estimate, and was then discharged. She required no additional medications. The mother was instructed to avoid similar eye drops in the future. While toxicity from ophthalmologic preparations is rare, cases like this show that it can indeed occur and should be on the emergency physician’s radar.
Ben Feinzimer, DO
Timothy Meehan, MD, MPH
Timothy Erickson, MD
REFERENCES
Beaver, K. M. & Gavin, T. J. (1998). Treatment of acute anticholinergic poisoning with physostigmine. America Journal of Emergency Medicine. Volume 16, 505.
Derinoz, O. & Emeksiz, H. C. (2012). Use of physostigmine for cyclopentolate overdose in an infant. Pediatrics, Volume 130, 703.
Fraunfelder, F. T. & Meyer, S. M. (1987). Systemic Reactions to Ophthalmic Drug Preparations. Medical Toxicology and Adverse Drug Experience, Volume 2 (4), 287-293.
Lexi-Comp OnlineTM , Pediatric & Neonatal Lexi-Drugs OnlineTM , Hudson, Ohio: Lexi-Comp, Inc.; January 29, 2011
Richmond, M. & Seger, D. (1985). Central anticholinergic syndrome in a child: a case report. Journal of Emergency Medicine. Volume 3, 453.