Authors: Parisa Mirmoghtadaee ( Department of Clinical Pharmacy and Pharmacy Practice, Isfahan University of Medical Sciences, Isfahan Iran. )
Ali Mohammad Sabzghabaee ( 1 Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan Iran. )
Mahdi Bagheri ( Pharmacy Student, Student\'s Research Committee, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan Iran. )
Rasool Soltani ( Department of Clinical Pharmacy and Pharmacy Practice, Isfahan University of Medical Sciences, Isfahan Iran. )
Objective: This study aims to explore the knowledge of a randomly selected cohort of Iranian general practitioners (GPs) on the topic of acetaminophen dosing for fever in children.
Methods: In this cross-sectional study, which was conducted in March 2011 in Isfahan (Iran) 515 GPs who were practicing general family medicine were sent a self-administered 10-item questionnaire about the usage of acetaminophen for fever in pediatric patients. Questions were designed to evaluate the knowledge of GPs on acetaminophen dosing amount and interval for fever in children and were formatted as multiple choice answers. The questionnaire were face and content validated and checked for reliability before the study (Croanbach\\\'s alpha=0.75) in two separate sample sets of the same population.
Results: 51.5% of questionnaires were returned and analyzed. 41.9% of the physicians gave doses different from the recommended dose (10-15 mg/kg every 4 hours). Only 23.8% of the physicians suggested true maximal daily dose of acetaminophen. 65.7% of the responders usually or always gave prescriptions for antipyretics and 8.7% did not routinely give parents instructions on the dosing of antipyretics.
Conclusions: We found that some GPs do not strictly adhere to the dosing guidelines of acetaminophen, so intense clinical courses of pharmacology and rational usage of drugs and other relevant educational programs for medical students and practitioners seems to be necessary for the sake of safety of pediatric patients in Iran.
Keywords: Acetaminophen, Paracetamol, General Practitioners, Fever, Rational use of Drugs (JPMA 62: S-55; 2012).
Acetaminophen, a commonly used over-the-counter drug, is on access of general population which leads to the high incidence of overdose in the pediatric population.1,2 In 2006, 140000 poisoning cases involving acetaminophen were reported to the American Association of Poison Control Centers.3 Acetaminophen is a safe and effective drug4,5 but some problems including giving a wrong dose of medication by health care providers and parents6 and not to receive dosing instructions from physicians7 may resulted in incorrect doses of acetaminophen. Although it has a wide margin of safety at therapeutic doses, a single dose of acetaminophen 150 mg / kg in children, has the potential to cause severe hepatocellular damage.8 Association of repeated over dose prescription and liver toxicity was reported in several studies.9-17
In Iran general practitioners (GPs) visit pediatric patients routinely in early stages of many febrile diseases in community health centers and medical clinics. In this study we evaluated current knowledge of community-based general practitioners regarding acetaminophen usage and dosing issues for fever in pediatric patients.
In this cross-sectional study, which was conducted in March 2011 in Isfahan Province (Iran) 515 randomly selected GPs who were practicing general family medicine were sent a questionnaire. These physicians were chosen disregarding to their age and graduation dates and were from both genders. We did a literature review using "Acetaminophen", "Paracetamol", "Drug Utilization Evaluation" and "dosing method" as key words through PubMed, Ovid® and Elsevier® for assessing the questionnaire of similar studies. The results were discussed in 3 meeting sessions of academic experts of the fields who were Pediatrician, Clinical Pharmacist, Pharmacologist and Family Medicine practitioner. In this way, we prepared a pre-questionnaire for data collection written 10-item.
The validity and reliability of this pre-questionnaire were evaluated in December 2010, analyzed separately and involved different subjects. For the sake of face-validity, the pre-questionnaire was distributed between 25 university professors, medical students and pharmacy students and their comments for the clearness of the sentences and phrases were taken to effect. Content validity of our research tool was performed by 5 medical/ pharmacotherapy experts who were different from the group who primarily constructed the pre-questionnaire.
Reliability of this pre-questionnaire was determined using test-retest method. A sample of GPs (n = 61) was recruited from a monthly continuing education meeting which was held in the same city, at Isfahan University of Medical Sciences (Test-1). They have filled in the pre-questionnaire after a lecture which was not related to drug usage in children and acetaminophen\\\'s drug information. They did this for the second time one month later at the same place (Test-2). Physicians who had not done both tests (in two separate times with the time interval of one month) were excluded (n=11). The test-retest reliability coefficient of our questionnaire was calculated by comparing the results of these two tests using SPSS (Cronbach\\\'s alpha= 0.75).
The finalized questionnaire was including demographic variables of the participants, years elapsed from graduation (10 years and less or more than 10 years), location of medical graduation and the rank of it (1st class, 2nd class and 3rd class according to the classification criteria of the Iranian Ministry of Health and Medical Education), and questions about acetaminophen prescribing including the recommended dose of acetaminophen, the minimal allowed interval between two administration, the maximum allowed dose in a day for a child, and points about patient counseling for acetaminophen prescription.
The Ethics Committee of the Isfahan University of Medical Sciences approved the study protocol. All medical participants were requested to return the filled questionnaire then data was analyzed using SPSS software v.12. Descriptive analysis was done and independent T test was used to compare means for quantitative variables.
51 percent of the questionnaires were returned. The mean age of the responders was 42.04 ± 10.02 years and they were mostly (67.5 %) graduated from Isfahan University of Medical Sciences. The demographic features of the study population are presented in Table-1.
The frequency of correct answers to questions regarding acetaminophen prescription by physicians is presented in Table 2.
When asked on the recommended dose of acetaminophen for a 3-year-old child with fever, (21.7%) of the medical doctors gave lower doses than the recommended dose and (20.1%) of them gave more doses than the recommended dose. 65.7% of the responders usually or always give prescriptions for antipyretics and (8.7%) do not routinely give parents instructions on the dosing of antipyretics. There was not a Significant correlation between the time of graduation and the pattern of prescription of Acetaminophen (p=0.25), but there was a significant correlation between genders (p=0.032) and the pattern of prescribing of acetaminophen was more promising in female GPs.
Fever is still a common reason for which parents seek emergency departments, health care centers and clinics.18-20 In Iran general physicians visit the children in health care centers and many emergency departments. Our study showed that nearly half of the studied physicians prescribed antipyretics incorrectly. Others used subtheraputic or supratheraputic doses. About one fourth of the studied GPs were aware of the correct maximal doses of Acetaminophen. In a similar study among US physicians, 76% of them were aware of maximum doses of acetaminophen21 which may shows that Iranian GPs need to have more effective continuing education programs. Although due to the especial metabolism pathways of acetaminophen, young children may be less susceptible to the toxicity of the acute ingestion of acetaminophen than adults,22 some studies showed hepatic cell injury due to repeated supratheraputic doses.10-15 In addition using low doses decreased acetaminophen efficacy. In this study although we considered 38.5ºC as a point to start acetaminophen prescribing, more than 70 percent of physicians answered this item incorrectly. Early administer of acetaminophen may increase the risk of acetaminophen overdose. To prevent health problems related to acetaminophen, improving the knowledge of health care providers such as physicians, clinical nurses and parents is necessary. Many studies showed that parents misused acetaminophen to lower the child\\\'s body temperature. As Physicians are the most frequent source of information for fever, enhanced levels of continuing medical education and studies to evaluate these interventions might help to increase their knowledge. Emphasis on acetaminophen dosage and its indications, other factors which predispose toxicity such as co-ingestion of other OTC containing acetaminophen and other effective drugs on liver metabolism seems to be essentials. In addition, written and verbal instructions have important roles in medication education for parent especially for poor literacy individuals.7 It seems that the curriculum for medical students needs to be enriched for clinical pharmacology issues. Acetaminophen is only a simple probe drug which is prescribed frequently and is supposed to be well-known for any physician. We are not sure about the knowledge of GPs on less frequently used drugs and this may cause a real concern despite the limitations for our study. More effective and interactive courses on clinical pharmacology for medical students and the same item for continuing education session for graduated are highly recommended.
The limitations for our study were the low response rate of participants which limited the power of generalization for the results and also recall bias.
Authors would like to acknowledge all of general practitioners who participated in this study. The protocol of this study was designed in the Student\\\'s Research Committee of the School of Pharmacy and Pharmaceutical Sciences was financially supported by the vice-chancellery of Research and Technology at Isfahan University of Medical Sciences.
Conflict of Interest:
Authors declare no conflict of interest.
All authors contributed the idea of research, design of study, data analysis and manuscript preparation. MB did the data collection as well.
1. Rowden AK, Norvell J, Eldridge DL, Kirk MA. Acetaminophen poisoning. Clin Lab Med 2006; 26: 49-65.
2. Yaman H, Isbilir S, Cakir E, Uysal B. Current issues with paracetamol induced toxicity. J Experimental and Integrative Med 2011; 1: 165-6.
3. Bronstein AC, Spyker DA, Cantilena LR Jr,Green J, Rumack BH, Heard SE. 2006 Annual Report of the American Association of Poison Control Centers National Poison Data System (NPDS). Clin Toxicol (Phila) 2007; 45: 815-917.
4. Lavonas Ej Fau - Reynolds, K.M, et al, Therapeutic acetaminophen is not associated with liver injury in children: a systematic review. Altern Med Rev 2009; 14: pp 322-3.
5. Kozer E, et al, Repeated supratherapeutic doses of paracetamol in children-a literature review and suggested clinical approach. Acta Pædiatrica 2006; 95: pp 1165-71.
6. Simon Hk Fau - Weinkle DA, DA. Weinkle, Over-the-counter medications. Do parents give what they intend to give? Arch Pediatr Adolesc Med 1997; 151: pp 654-6.
7. Kozer E Fau - Barr, J, et al, A prospective study of multiple supratherapeutic acetaminophen doses in febrile children. Vet Hum Toxicol 2002; 44: pp 106-9.
8. Rumack Bh Fau - Matthew H, H. Matthew, Acetaminophen poisoning and toxicity. Pediatrics 1975; 55: pp 871-6. 4-7.
9. Cranswick N, coghlan D. Paracetamol efficacy and safety. in children: the first 40 years. American Journal of Theraputics 2000; 7: 135-41.
10. Heubi Je Fau - Barbacci, M.B., H.J. Barbacci Mb Fau - Zimmerman, and H.J. Zimmerman, Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children. J Pediatr 1998; 132: pp 22-7.
11. Chang M, Chen Y, Chang S, Smith G. Knowledge of using acetaminophen syrup and comprehension of written medication instruction among caregivers with febrile children. J Clin Nurs 2011; 21: 42-51.
12. Miles Fk Fau - Kamath R, et al. Accidental paracetamol overdosing and fulminant hepatic failure in children. Med J Aust 1999; 171: pp 472-5.
13. Pershad J Fau - Nichols M, W. Nichols M Fau - King, W. King. "The silent killer": chronic acetaminophen toxicity in a toddler. Pediatr Emerg Care 1999; 15: pp 43-6.
14. Alhelail Ma Fau - Hoppe JA, et al. Clinical course of repeated supratherapeutic ingestion of acetaminophen. Clin Toxicol (Phila) 2011; 49: pp 108-12.
15. Daly Ff Fau - O\\\'Malley GF, et al. Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. Ann Emerg Med 2004; 44: pp 393-8.
16. Henretig Fm Fau - Selbst SM, et al. Repeated acetaminophen overdosing. Causing hepatotoxicity in children. Clinical reports and literature review. Clin Pediatr (Phila) 1989; 28: pp 525-8.
17. Blake Kv Fau - Bailey D, et al. Death of a child associated with multiple overdoses of acetaminophen. Clin Pharm 1988; 7: pp 391-7.
18. Alomar M Fau - Alenazi F, N. Alenazi F Fau - Alruwaili, N. Alruwaili. Accuracy of acetaminophen dosing in children by caregivers in Saudi Arabia. Ann Saudi Med 2011; 31: pp 513-7.
19. Crocetti M Fau - Moghbeli N, J Moghbeli N Fau - Serwint, J Serwint. Fever phobia revisited: have parental misconceptions about fever changed in 20 years? Pediatrics 2001; 107: pp 1241-6.
20. Al-Nouri L Fau - Basheer K, K. Basheer. Mothers\\\' perceptions of fever in children. J Trop Pediatr 2006; 52: pp 113-6.
21. Hornsby LB, Przybylowicz J, Andrus M, Starr J. Survey of physician knowledge and counseling practices regarding acetaminophen. J Patient Saf 2010; 6: 216-20.
22. Kearns GL. Acetaminophen poisoning in children: treat early and long enough. J Pediatr 2002; 140: 495-8.