|Year : 2016 | Volume
| Issue : 2 | Page : 39-41
Case series of Cyclogyl-induced delirium in elderly
Kalpana Sharma1, Tarun Sood1, Mandeep Tomar1, Anuj Sharma2
1 Department of Ophthalmology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
2 Department of Ophthalmology, RPGMC, Tanda, Himachal Pradesh, India
|Date of Web Publication||17-Jan-2017|
Eye Surgeon, Civil Hospital, Sarkaghat, Himachal Pradesh
Source of Support: None, Conflict of Interest: None
Cyclopentolate is an anticholinergic, antimuscarinic tertiary amine which has been widely used as a topical cycloplegic and mydriatic agent by ophthalmologists. Systemic absorption of the drug can occur transconjunctivally or through nasolacrimal duct through highly vascular nasal mucosa. This can lead to central anticholinergic syndrome which includes restlessness, hallucination, psychosis, hyperactivity, seizures, incoherent speech, and ataxia. We report a case series of three patients developing central nervous system toxicity following instillation of cyclopentolate. This article lays stress on the judicious use of this drug and outlines the steps that can be taken to reduce systemic absorption and toxicity include using the lowest available concentration of the drug.
Keywords: Antimuscarinic action, central anticholinergic syndrome, cyclopentolate, pupillary dilator
|How to cite this article:|
Sharma K, Sood T, Tomar M, Sharma A. Case series of Cyclogyl-induced delirium in elderly. Sudanese J Ophthalmol 2016;8:39-41
| Introduction|| |
Central anticholinergic syndrome (CAS) was first described by Longo in 1966. Systemic absorption of the drug can occur transconjunctivally or through nasolacrimal duct through highly vascular nasal mucosa. The syndrome may consist of agitation including seizures, restlessness, hallucinations and disorientation, or of signs of depression such as stupor, coma, and respiratory depression.  The estimated frequency of this syndrome varies between 1% and 11.2%.  The syndrome may be induced by anticholinergic drugs such as atropine or scopolamine but has also been observed after administration of opiates, benzodiazepines, phenothiazines, ketamine, cimetidine, etomidate, propofol, nitrous oxide, and volatile anesthetics. 
Patients undergoing cataract surgery in hospital for various reasons are given eyedrops often for cycloplegia and mydriasis to facilitate adequate papillary dilatation. The agents commonly used are 10% phenylephrine eyedrops to dilate the pupils and cyclopentolate in the form of 0.5% or 1% eyedrops to paralyze the iris temporarily.
We hereby intend to describe case series of three patients who had acute central nervous system (CNS) manifestation following instillation of cyclopentolate.
An 83-year-old female planned for cataract surgery was preoperatively screened for systemic diseases involving cardiovascular system and CNS. She was started on topical tropicamide, cyclopentolate, and ketorolac drops every 15 min preoperatively. The patient got restless and agitated. He developed irrelevant talks and turned disoriented to surroundings.
A 76-year-old male preoperatively screened for systemic diseases was planned for cataract surgery. He started feeling uncomfortable and could not recognize the attendants. Meanwhile, he started behaving abnormally with delusions and hallucinations. He had drowsiness, agitation, hallucinations, and was jerkily moving all extremities. All eyedrops in our ward were applied by an experienced nurse under ophthalmologist supervision.
Another 86-year-old female, immediately after the second instillation, the patient reported drowsiness, dizziness, nausea, and fatigue. Ten minutes later, stimulatory CNS symptoms in the form of restlessness, cheerfulness, and a 20 min-long roar of laughter were observed, interrupted by a new sedative phase.
All the cases had been planned toward the end of the operation theatre (OT) list which emphasize on dose-dependent side effect of cyclopentolate. The OT had to be deferred in all the cases. These patients were again systemically examined.
General and neurological examination did not reveal any abnormality. Laboratory studies consisted of a complete blood count, electrolytes, blood urea nitrogen, creatinine, hepatic enzymes, coagulation studies, urine test, and all results were within normal levels. Chest X-ray was unremarkable. Psychiatrist's opinion revealed normal consciousness and orientation, delusion of persecution, visual hallucination, impaired judgment, and lack of insight. Based on the above findings, drug-induced psychosis was suspected. Thereafter, the eyedrops were withdrawn, and patient's behavior reverted to normal within 48 h.
| Discussion|| |
Acetylcholine and acetylcholine receptors are widely distributed in the brain. Acetylcholine is important in regulating many functions including the sleep-wake cycle, memory, alertness, orientation, and analgesia. An absolute or relative reduction in cholinergic activity in the CNS can result in anticholinergic syndrome. Because of the ubiquitous presence and diverse functions of acetylcholine in the CNS, anticholinergic syndrome can manifest with a variety of signs and symptoms. Central manifestations can include CNS excitation or depression. These can include convulsions, excitation, hallucinations, disorientation, hyperpyrexia, hyperalgesia, ataxia, mental impairment, sedation, and coma. ,,
When instilled topically in the eye, it is well absorbed, both into the eye and systemically. This is because both the conjunctiva and nasal mucus membranes are good drug-absorbing surfaces and eyedrops pass readily through the nasolacrimal duct into the nose. Systemic absorption also occurs through the conjunctiva, the nasolacrimal duct, the oropharynx, the digestive system, and the skin. , In our case, cyclopentolate eyedrops can be absorbed by capillary and reached to brain through angulus venosus of deep cerebral veins and cavernous sinuses. This direct accessibility to brain may improve CAS in our case.
Steps that can be taken to reduce systemic absorption and toxicity include using the lowest available concentration of the drug, not exceeding recommended number of drops (instill one drop of 0.5% or 1% in eye, followed by one drop of 0.5% or 1% after 5 min, if necessary), occluding the lacrimal passage after topical administration, and blotting away excess drops after administration. Gentle and quiet eyelid closure for 3 min after drug instillation. Decreasing dimensions of the eye dropper tip, employing drug suspensions instead of drug solutions along with the use of a preceding local anesthetic such as proparacaine to enhance the effect of drugs by increasing transcorneal absorption may be utilized.
The precise epidemiologic profile of the occurrence of cognitive and/or behavior changes in patients treated with anticholinergic agents remains unknown, especially due to inherent biases and confounding factors in each population studied including treatment regimens, age group, underlying pathology, and so on.  However, advanced age, lower Mini-Mental State Examination scores, bereavement, and loneliness are generally accepted potential risk factors for such events in the elderly. ,
Systemic toxicity induced by the ocular administration of cyclopentolate is similar to that produced by atropine, except that cerebellar dysfunction and visual and tactile hallucinations are more constant and striking features of cyclopentolate toxicity. This is not surprising because cyclopentolate is structurally similar to atropine but contains a dimethylated side group (-N-[CH 3]2) also found in some tranquilizers and hallucinogenic drugs. Seizures and acute psychosis induced by cyclopentolate are especially prominent in children ,,,,,,,,, and the elderly. ,, The psychosis is characterized by disorientation, dysarthria, ataxia, hallucinations, and retrograde amnesia. This seems to indicate that CNS immaturity or aging is necessary for its potent psychotomimetic action to become manifest. In addition, ocularly instilled cyclopentolate is rapidly absorbed in adults and children. ,, The peripheral signs and symptoms of cyclopentolate toxicity are variable and frequently are absent.
Toxic reactions to cyclopentolate are dose dependent and are more likely to occur with the 2% solution than with repeated doses of 1% solution. The onset of cyclopentolate toxicity occurs within 20-30 min of drug instillation, and although usually transient (subsiding in 4-6 h), the symptoms can last 12-24 h.
Limited quantitative data on the systemic absorption of drugs after conjunctival instillation indicate that 30% to 80% of a retained topically applied dose enters the general circulation.  If systemic absorption averages 50% of the instilled medication, the systemic dose can be dangerously large.
| Conclusion|| |
The present case series highlights the important CNS side effect of a topically administered cyclopentolate. One should be aware of all adverse effects of the drugs while prescribing routinely so that optimum treatment can be given. The medical and paramedical staff should use the drug in the prescribed dose and methods to minimize systemic absorption. There should be judicious use of this drug as a dose-dependent side effect is warranted in the cases to be operated late in operating list.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Jones LW, Hodes DT. Possible allergic reactions to cyclopentolate hydrochloride: Case reports with literature review of uses and adverse reactions. Ophthalmic Physiol Opt 1991;11:16-21.
Kulka PJ, Toker H, Heim J, Joist A, Jakschik J. Suspected central anticholinergic syndrome in a 6-week-old infant. Anesth Analg 2004;99:1376-8.
Demayo AP, Reidenberg MM. Grand mal seizure in a child 30 minutes after Cyclogyl (cyclopentolate hydrochloride) and 10% Neo-Synephrine (phenylephrine hydrochloride) eye drops were instilled. Pediatrics 2004;113:e499-500.
Brown DV, Heller F, Barkin R. Anticholinergic syndrome after anesthesia: A case report and review. Am J Ther 2004;11:144-53.
Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning, 2 nd
ed. Matthew J. Ellenhorn, Seth Schonwald, Gary Ordog, and Jonathan Wasserberger. Baltimore, MD: Williams and Wilkins; 1997. p. 2047.
Lim DL, Batilando M, Rajadurai VS. Transient paralytic ileus following the use of cyclopentolate-phenylephrine eye drops during screening for retinopathy of prematurity. J Paediatr Child Health 2003;39:318-20.
Mirshahi A, Kohnen T. Acute psychotic reaction caused by topical cyclopentolate use for cycloplegic refraction before refractive surgery: Case report and review of the literature. J Cataract Refract Surg 2003;29:1026-30.
Simcoe CW. Cyclopentolate (Cyclogyl) toxicity. The report of a case. Arch Ophthalmol 1962;67:406-8.
Beswick JA. Psychosis from cyclopentolate. Am J Ophthalmol 1962;53:879-81.
Binkhorst RD, Weinstein GW, Baretz RM, Clahane AC. Psychotic reaction induced by cyclopentolate (Cyclogyl). Am J Ophthalmol 1963;55:1243-5.
Adcock EIII. Cyclopentolate (Cyclogyl) toxicity in pediatric patients. J Pediatr 1971;79:127-9.
Kennerdal JS, Wucher FP. Cyclopentolate associated with two cases of grand mal seizure. Arch Ophthalmol 1972;87:634-5.
Bauer CR, Trepanier-Trottier MC, Stern L. Systemic cyclopentolate (Cyclogyl) toxicity in the newborn infant. J Pediatr 1973;82:501-5.
Khurana AK, Ahluwalia BK, Rajan C, Vohra AK. Acute psychosis associated with topical cyclopentolate hydrochloride. Am J Ophthalmol 1988;105:91.
Kellner V, Esser J. Acute psychosis caused by poisoning with cyclopentolate. Klin Monatsbl Augenheilkd 1989;194:458-61.
Hanson RM, West C, Fitzgerald DA, Martin F, Brown J, Kilham HA. Seizures associated with 1% cyclopentolate eyedrops. J Pediat Child Health 1990;26:196-7.
Mwanza JC. Cyclopentolate and grand-mal seizures. Bull Soc Belge Ophtalmol 1999;273:17-8.
Mark HH. Psychotogenic properties of cyclopentolateJAMA 1963;186:430.
Carpenter WT. Precipitous mental deterioration following cycloplegia with 0.2% cyclopentolate HCl. Arch Ophthalmol 1967;78:445-7.
Awan KJ. Adverse systemic reactions of topical cyclopentolate hydrochloride. Ann Ophthalmol 1976;8:695-8.
Kaila T, Huupponen R, Salminen L, Iisalo E. Systemic absorption of ophthalmic cyclopentolate. Am J Ophthalmol 1989;107:563-4.
Lahdes K, Huupponen R, Kaila T, Ali-Melkkilä T, Salminen L, Saari M. Systemic absorption of ocular cyclopentolate in children. Ger J Ophthalmol 1992;1:16-8.
Lahdes K, Huupponen R, Kaila T, Monti D, Saettone MF, Salminen L. Plasma concentration and ocular effects of cyclopentolate after ocular application of three formulations. Br J Clin Pharmacol 1993;35:479-83.