Demographic and Clinical Characteristics of Theophylline Exposures between 1993 and 2011

Year 2014, Volume: 31 Issue: 4, 322 - 327, 01.10.2014

Nil Hocaoğlu Burç Aydın Yeşim Tunçok Şule Kalkan Engin Yıldıztepe , Başak Bayram

Abstract

Background: Acute and chronic exposure to theophylline can cause
serious signs and symptoms of poisoning. Additionally, with a narrow
therapeutic range, toxicity could be observed even with therapeutic
doses of theophylline. Epidemiological data on theophylline
exposures in our country are extremely limited. The results of our
study may improve the clinical management of theophylline poisoning
in our country and elsewhere.
Aims: To present aetiological and demographic features, clinical
findings and treatment attempts with regard to theophylline exposures
reported to Dokuz Eylül University Drug and Poison Information
Center (DPIC), between 1993 and 2011.
Study Design: Descriptive study.
Methods: The data regarding demographics, date, time, type of exposure,
route of and reason for exposure, signs and symptoms upon
admission, clinical management and outcome were retrospectively
evaluated.
Results: The DPIC recorded 88,562 poisoning calls between 1993
and 2011; 354 (0.4%) of them were due to theophylline exposure.
The mean age of all cases was 24.1±15.4 (range between 1 month and
90 years). Females dominated all age groups (72.6%, 257 females).
Intentional exposure was significantly higher in women than in men
(88.2% vs. 68.2% for all age groups; p<0.001 for children; p<0.001
for adults; p<0.001 for all age groups). While 60.5% of the cases
had no symptoms, severe signs of toxicity were present in 1.9% of
theophylline exposure cases during the telephone inquiry. Signs and
symptoms were found to be significantly more prevalent in adults than
in children (p<0.01). The serum theophylline level was regarded as
toxic in 74% (65 toxic levels) of theophylline measured cases. Clinical
signs and symptoms were found to be significantly prevalent in cases
with toxic theophylline levels (p<0.001). The rate of gastrointestinal
decontamination procedures was higher than that of recommended
gastrointestinal decontamination procedures by DPIC (83% and 66%,
respectively). There were two fatalities (4.6%) associated with chronic
theophylline toxicity and theophylline overdose in an acute setting for
suicide (a 90 year-old and 25 year-old, respectively).
Conclusion: Although most of the theophylline exposure cases had
no symptoms, some reported serious signs and symptoms of poisoning
such as hypokalaemia, tachycardia and hyperglycaemia. DPICs
have an important role in the management of theophylline exposure
without unnecessary gastrointestinal decontamination procedures

Keywords

Exposure, Drug and Poison Information Center, poisoning, retrospective, theophylline

References

• 1. Barnes PJ. Theophylline: New perspectives for an old drug. Am J Respir Crit Care Med 2003;167:813-8.[CrossRef]
• 2. Henderson-Smart DJ, De Paoli AG. Methylxanthine treatment for apnoea in preterm infants. Cochrane Database Syst Rev 2010;12:CD000140.
• 3. Sessler CN. Theophylline toxicity: Clinical features of 116 consecutive cases. Am J Med 1990;88:567-76.[CrossRef]
• 4. Shannon M. Life-threatening events after theophylline overdose: A 10-year prospective analysis. Arch Intern Med 1999;159:989-94. [CrossRef]
• 5. Persson HE, Sjöberg GK, Haines JA, Pronczuk de Garbino J. Poisoning severity score. Grading of acute poisoning. J Toxicol Clin Toxicol 1998;36:205-13.[CrossRef]
• 6. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2009 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 27th Annual Report. Clin Toxicol (Phila) 2010;48:979-1178.[CrossRef]
• 7. McCoubrie D, Murray L, Daly FF, Little M. Toxicology case of the month: Ingestion of two unidentified tablets by a toddler. Emerg Med J 2006;23:718-20.[CrossRef]
• 8. Schiff GD, Hegde HK, LaCloche L, Hryhorczuk DO. Inpatient theophylline toxicity: Preventable factors. Ann Intern Med 1991;114:748-53. [CrossRef]
• 9. Mokhlesi B, Leikin JB, Murray P, Corbridge TC. Adult toxicology in critical care: Part II: specific poisonings. Chest 2003;123:897-922. [CrossRef]
• 10. Klasco RK (Ed): POISINDEX® System. Thomson Reuters, Greenwood Village, Colorado (Vol. 153 expires 09/2012).
• 11. Parr MJ, Anaes FC, Day AC, Kletchko SL, Crone PD, Rankin AP. Theophylline poisoning - A review of 64 cases. Intens Care Med 1990;16:394-98.[CrossRef]
• 12. Shannon M, Lovejoy FH Jr. Effect of acute versus chronic intoxication on clinical features of theophylline poisoning in children. J Pediatr 1992;121:125-30.[CrossRef]
• 13. Tufekci IB, Curgunlu A, Sirin F. Characteristics of acute adult poisoning cases admitted to a university hospital in Istanbul. Hum Exp Toxicol 2004;23:347-51.[CrossRef]
• 14. Andıran N, Sarikayalar F. Pattern of acute poisonings in childhood in Ankara: What has changed in twenty years? Turk J Pediatr 2004;46:147- 52.
• 15. Afshari R, Majdzadeh R, Balali-Mood M. Pattern of acute poisonings in Mashhad, Iran 1993-2000. J Toxicol Clin Toxicol 2004;42:965-75. [CrossRef]
• 16. Antoniou T, Gomes T, Mamdani MM, Juurlink DN. Ciprofloxacin-induced theophylline toxicity: A population-based study. Eur J Clin Pharmacol 2011;67:521-6.[CrossRef]
• 17. Hines LE, Murphy JE. Potentially harmful drug-drug interactions in the elderly: A review. Am J Geriatr Pharmacother 2011;9:364-77. [CrossRef]
• 18. Doughty C, Walker A, Brenchley J. Herbal mind altering substances: an unknown quantity? Emerg Med J 2004;21:253-5.[CrossRef]
• 19. Self TH, Chafin CC, Soberman JE. Effect of disease states on theophylline serum concentrations: are we still vigilant? Am J Med Sci 2000;319:177-82.[CrossRef]
• 20. Ozkose Z, Ayoglu F. Etiological and demographical characteristics of acute adult poisoning in Ankara, Turkey. Hum Exp Toxicol 1999;18: 614-8.[CrossRef]
• 21. Goksu S, Yildirim C, Kocoglu H, Tutak A, Oner U. Characteristics of acute adult poisoning in Gaziantep, Turkey. J Toxicol Clin Toxicol 2002;40:833-7.[CrossRef]
• 22. Hocaoglu N, Kalkan S, Akgun A, Capar S, Tuncok Y. A retrospective evaluation of analgesic exposures from İzmir, Turkey. Hum Exp Toxicol 2007;26:629-36.[CrossRef]
• 23. American Academy of Clinical Toxicology/European Association of Poisons Centres and Clinical Toxicologists. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol 1999;37:731-51.[CrossRef]
• 24. Chyka PA, Seger D, Krenzelok EP, Vale JA; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005;43:61-87.[CrossRef]
• 25. Vale JA, Kulig K; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 2004;42:933-43.
• 26. Rogers JJ, Heard K. Does age matter? Comparing case fatality rates for selected poisonings reported to U.S. poison centers. Clin Toxicol (Phila) 2007;45:705-8.[CrossRef