Camphor ingestion in a 10-year-old male.

Abstract: A 10-year-old male with a history of oppositional defiant disorder and attention deficit disorder suffered from mental status changes, nausea, vomiting and tremulousness after intentional ingestion of three over-the-counter cold remedy transdermal patches. Each patch contained approximately 100 mg of camphor. While in the hospital, the patient was treated supportively, with IV fluids and careful monitoring. Before discharge, it was noted that the patient had improved significantly and pediatric neurology documented that the initial presenting symptoms were consistent with camphor toxicity. Our case is unique from other pediatric case reports in the literature because this was an intentional overdose with a specific over-the-counter transdermal product. Education should be given to caregivers regarding appropriate storage of all prescription and over-the-counter medications, household cleaning materials and other potentially toxic chemicals, especially when there are children in the area. Healthcare providers should be aware of the variety of over-the-counter products containing camphor, the complications of overdose, and available treatment strategies.

Key Words: camphor, ingestion, toxicity, pediatric

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Ingestion of toxic substances is a leading cause of emergency room visits for pediatric patients. Most of these exposures are unintentional and may be related to the attractiveness of color or appearance of the agent or container, making it easier for children to believe it is a food source. The following case discusses the evaluation and treatment of a pediatric patient who presented after intentional exposure to a large amount of camphor in an over-the-counter cold product.

Case Report

A 10-year-old male presented to the emergency room with symptoms of lethargy, nausea, vomiting and rigors. He also complained of neck pain and stiffness at the time of admission. The history taken from his grandparent guardians included ingestion of over-the-counter cold remedy transdermal patches approximately 24 hours previously. The patient eventually admitted to opening and chewing three patches. These type of patches are generally applied to the chest or throat of a patient suffering from a common cold to allow the vapors to reach the nose and mouth. Emergency personnel retrieved the three opened packages with missing patches. The patches were found to be Triaminic Cherry Menthol Vapor Patches. Each patch was found to contain 4.7% camphor (95.37 mg) as well as 2.6% menthol as active ingredients. His grandparents noted a history of the child eating "anything and everything," and it was noted by healthcare providers that the picture of cherries on the outside of the box may have contributed to the patient's confusion.

The patient's medical history included behavioral issues and attention-deficit hyperactivity disorder (ADHD). The patient was currently being followed by a mental health specialist and was taking clonidine 0.1 mg four times a day, methylphenidate 40 mg every day and valproic acid 125 mg four times a day before admission. At arrival at the hospital, the patient had a temperature of 99[degrees]F, a heart rate of 102 and oxygen saturation of 100%. The key abnormal findings on physical examination were tremulousness, hyperreflexia, clonus and pain on flexion of his neck. Laboratory parameters were all within normal limits, except for a blood glucose level of 198 mg/dL and positive urine ketones. The patient's glucose and test for urine ketones were subsequently found to be within the normal range. It was determined that the initially elevated readings for these tests were likely the result of the patient's vomiting and overall stress response, rather than a cause of the underlying problem (ie, diabetic ketoacidosis). Since the patient did have an equivocal Brudzinski sign, a spinal tap was performed with negative corresponding results. A blood lead level test was also ordered which ruled out lead toxicity. The patient's thyroid function was also found to be normal. The child remained lethargic during the first hours of admission and was placed in the Pediatric Intensive Care Unit for observation for the initial 24 hours. He was treated conservatively, with IV fluids. All outpatient medications were held. No attempt to induce vomiting was made. The patient was transferred from the Intensive Care Unit to the floor as he became more responsive and his tremulousness and clonus became less apparent. The remainder of the hospital course was uneventful and he continued to gain strength and mental alertness until discharge on day 4. Upon discharge, the guardians were educated on the importance of keeping medications, cleaners and other substances locked away and out of the reach of the patient. According to outpatient electronic medical records, the patient continues to show no long-term ill effects and is otherwise doing well.

Discussion

Camphor was originally obtained by distillation of the bark from the camphor tree, Cinnamomum camphora. Today, it is produced synthetically from turpentine oil. Camphor is highly lipophilic, which accounts for its rapid movement across mucous membranes and its large volume of distribution. After absorption, camphor is oxidized to camphorol, which is then conjugated to the glucuronide form. Active metabolites are stored in fat deposits and ultimately excreted in the urine. (1) Camphor has been used topically to relieve pain, and treat warts, cold sores, hemorrhoids and osteoarthritis and is a common ingredient in a wide variety of over-the-counter topical products. It has been shown to be safe when used topically in low concentrations for short periods of time. Concentrations ranging from 0.1 to 11% seem to be safe for short-term topical use on intact skin. (2,3) However, camphor is likely unsafe when used topically on broken or injured skin, as it can result in systemic absorption and toxicity. (2) Since 1983, the Food and Drug Administration (FDA) has regulated that over-the-counter products may not contain concentrations of camphor which exceed 11%. (4) Camphor is unsafe when used orally, especially in children. Ingestion of camphor can cause significant toxicity, including death. (5) Although oral preparations of camphor (camphorated oil) are no longer available in the United States, there are many common commercially available products which contain camphor as an active ingredient (Table). Because alternative agents exist for all of the currently approved uses of camphor, the benefits of using such a product containing this substance must be weighed against the risks. For example, hydrocortisone can be used as a topical antipruritic, multiple oral agents containing dextromethorphan are available for antitussive effects and agents containing benzocaine/tetracaine can be used for topical analgesic effects. While no product is without risk or side effects, these alternatives have been shown to be less likely to cause toxicity (inadvertent or not) compared with a known toxin such as camphor, especially in children. Symptoms of camphor toxicity occur rapidly (as early as 5-15 min after ingestion) and include nausea and vomiting, oral and intestinal burning, and a feeling of warmth and headache. These symptoms may progress to confusion, vertigo, excitement, restlessness, delirium, hallucinations, tremors, and/or convulsions. Other adverse effects that may occur after oral ingestion include tachycardia, visual disturbances, urinary retention, albuminuria and elevations of liver enzymes. The final stage of toxicity often results in depression and sometimes coma. Death can occur from respiratory failure or status epilepticus. (6-8) While adults may recover after ingesting as much as 42 g of camphor, as little as 2 g is often enough to produce clinically significant toxic effects. In children, ingestion of as little as 700 to 1000 mg of camphor has been fatal. (9) In those who survive, clinical toxicity typically resolves within 24 hours, although residual findings may persist for days or weeks.

There is no antidote for camphor toxicity and treatment is largely supportive, involving airway management and seizure control. Seizures in adults and children can usually be managed with the use of benzodiazepines and/or barbiturates. Ipecac syrup should be avoided because of the risk of aspiration. Although there is no clear evidence of efficacy, gastric lavage and/or activated charcoal have been used in some individuals with varying results. Hemoperfusion has not been shown to improve the clinical outcome in these patients. (10) Unfortunately, data from the American Association of Poison Control Centers (AAPCC) demonstrate that camphor continues to be a source of pediatric exposures. In 2001, the AAPCC reported approximately 8500 exposures and these numbers have remained stable over the past few years. (11) Our literature search (MEDLINE; 1966 to present) did reveal other pediatric case reports; however, they all differ in the type of product, route of absorption and amount of camphor ingested. (10,12-28) In addition, the majority of these cases involved unintentional overdose and included camphorated oil, which is no longer available. Ours was a unique case of a complicated child with an intentional oral ingestion of three Triaminic Cherry Menthol Vapor patches. The signs and symptoms were consistent with this form of toxicity. Although we were initially concerned with the elevated blood glucose level and ketonuria, the history and symptoms were consistent with camphor ingestion and the blood glucose level returned to normal.

It should be noted that in June 2006, Novartis Consumer Health voluntarily recalled their Triaminic Vapor Patches (both mentholated cherry and menthol-scented versions) from the market, after it was documented that a child suffered a seizure after chewing on one of the patches. Novartis has also admitted to receiving multiple other complaints regarding ingestion of the patches; however, they have not specified how many reports have been received altogether. The recall is being conducted with the knowledge of the Food and Drug Administration (FDA). (29) We believe that this adds further relevance and timeliness to our case report and the importance of carefully monitoring any available product that contains camphor.

Conclusion

Every pharmacologically active agent has risks and benefits and most can potentially cause toxicity, depending upon dose and route of administration. In the case of camphor, the risks of toxicity seem to outweigh any pharmacologic benefits, especially considering the fact that many alternative therapies exist. In our patient, the history of present illness and classic symptoms of nausea, vomiting, mental status changes and tremors made it clear that this was a case of camphor toxicity. Lay persons, especially those individuals caring for children, need to be educated on the proper storage of potentially toxic substances, including both prescription and over-the-counter products. In addition, healthcare providers should be aware of the many products on the market that contain camphor and recommend these products judiciously based upon the still large number of toxicities that occur each year.

References

1. Robertson JS, Hussain M. Metabolism of camphors and related compounds. Biochem J 1969;113:57-65.

2. Allen LV, Kroon LA, et al. Handbook of Nonprescription Drugs. 12th ed. Washington. DC, APhA Publications, 2000.

3. Cohen M, Wolfe R, Mai T, et al. A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee. J Rheumatol 2003;30:523-528.

4. United States Food and Drug Administration. Proposed rules: external analgesic drug products for over-the-counter human use; tentative final monograph. Fed Reg 1983;48:5852-5869.

5. McGuffin M, Hobbs C, Upton R, et al, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, CRC Press, 1997.

6. Ellenhorn MJ. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, Williams & Wilkins, 1997.

7. Geller RJ, Spyker DA, Garrettson LK, et al. Camphor toxicity: development of a triage strategy. Vet Hum Toxicol 1984;26 (Suppl 2):8-10.

8. American Academy of Pediatrics. Committee on Drugs. Camphor: who needs it? Pediatrics 1978;62:404-406.

9. American Academy of Pediatrics Policy Statement. Camphor Revisited: Focus on Toxicity (RE9422). Pediatrics 1994;94:127-128. Available at: http://www.aap.org/policy/00300.html. Accessed June 1, 2006.

10. Koppel C, Martens F, Schirop T. Hemoperfusion in acute camphor poisoning. Intensive Care Med 1988;14:431-433.

11. Litovitz TL, Klein-Schwartz W, Rodgers GC, et al. 2001 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2002;20:391-452.

12. Rampini SK, Schneemann M, Rentsch K, et al. Camphor intoxication after cao gio (coin rubbing). JAMA 2002;288:45.

13. Emery DP, Corban JG. Camphor toxicity. J Paediatr Child Health 1999;35:105-106.

14. Rabl W, Katzgraber F, Steinlechner M. Camphor ingestion for abortion (case report). Forensic Sci Int 1997 89:137-140.

15. Lahoud CA, March JA, Proctor DD. Campho-Phenique ingestion: an intentional overdose. South Med J 1997;90:647-648.

16. Gouin S, Patel H. Unusual cause of seizure. Pediatr Emer Care 1996;12:298-300.

17. Theis JG, Koren G. Camphorated oil: still endangering the lives of Canadian children. CMAJ 1995;152:1821-1824.

18. Gibson DE, Moore GP, Pfaff JA. Camphor ingestion. Am J Emerg Med 1989;7:41-43.

19. Jimenez JF, Brown AL, Arnold WC, et al. Chronic camphor ingestion mimicking Reye's syndrome. Gastroenterology 1983;84:394-398.

20. Mascie-Taylor BH, Widdop B, Davison AM. Camphor intoxication treated by charcoal haemoperfusion. Postgrad Med J 1981;57:725-726.

21. Camphor. South Med J 1980;73:769.

22. Reid FM. Accidental camphor ingestion. JACEP 1979;8:339-340.

23. Kopelman R, Miller S, Kelly R, et al. Camphor intoxication treated by resin hemoperfusion. JAMA 1979;241:727-728.

24. Antman E, Jacob G, Volpe B, et al. Camphor overdosage. Therapeutic considerations. N Y State J Med 1978;78:896-897.

25. Trestrail JH, Spartz ME. Camphorated and castor oil confusion and its toxic results. Clin Toxicol 1977;11:151-158.

26. Skoglund RR, Ware LL, Schanberger JE. Prolonged seizures due to contact and inhalation exposure to camphor. A case report. Clin Pediatr 1977;16:901-902.

27. Phelan WJ. Camphor poisoning: over-the-counter dangers. Pediatrics 1976;57:428-431.

28. Weiss J, Catalano P. Camphorated oil intoxication during pregnancy. Pediatrics 1973;52:713-4.

29. Food and Drug Administration website. Available at: http://www.fda.gov/cder/drug/advisory/triaminic.htm. Accessed July 5, 2006.

Life is like a blanket too short. You pull it up and your toes rebel,
you yank it down and shivers meander about your shoulder; but cheerful
folks manage to draw their knees up and pass a very comfortable night.
--Marion Howard

Kelly R. Ragucci, PharmD, FCCP, BCPS, CDE, Philip R. Trangmar, MD, Jefferson G. Bigby, PharmD, and Todd D. Detar, MD

From the Department of Pharmacy and Clinical Sciences/Family Medicine, Medical University of South Carolina, Charleston, SC.

Reprint requests to Kelly R. Ragucci, PharmD, FCCP, BCPS, Associate Professor, Pharmacy and Clinical Sciences/Family Medicine, Pharmacy Residency Program Director, Family Medicine, Medical University of South Carolina, 295 Calhoun Street, PO Box 250192, Charleston, SC 29425. Email: [e-mail]

Accepted July 25, 2006.

RELATED ARTICLE: Key Points

* Camphor ingestion continues to be a source of pediatric exposure and as little as 700-1000 mg may produce clinically significant toxic effects, including death.

* Symptoms such as nausea, vomiting, oral and intestinal burning, feeling of warmth and headache occur rapidly. There is no antidote for camphor toxicity and treatment is largely supportive.

* Guardians must be educated on the proper storage of potentially toxic substances and healthcare providers need to be aware of the many over-the-counter products that may pose a danger.

Table. Examples of common commercially available products containing
camphor

Product                               Percent camphor

Chapstick Medicated/Blistex Ointment   1%
Minit-Rub Cream                        2.3%
Chapstick Cold Sore Therapy            3%
Anbesol Cold Sore Therapy Ointment     3%
Orajel Cold Sore Medication            3%
Flexall Plus Gel                       3.1%
Heet Lotion/Spray                      3%/3.6%
BenGay Ultrastrength                   4%
Triaminic Vapor Patch                  4.7% (now recalled)
TheraFlu Vapor Stick                   4.8%
Vick's VapoRub Ointment/Cream          4.8%/5.2%
Soltice Quick Rub Cream                5.1%
Vick's VapoSteam Liquid                6.2%
Mentholatum Ointment                   9%
Campho-Phenique Liquid/Gel            10.8%