How Effective is Paracetamol Compared with Ibuprofen in Reducing Fever in Children?
Statement of Intent
Research evidence plays a crucial role in ensuring quality of care and patient safety. Therefore, nurses are charged with examining the evidence supporting a particular clinical topic and appraising the evidence underpinning it. This paper will discuss the process of translating research evidence into clinical practice and discuss the factors that may hinder the implementation of best practices. Specifically, this paper will compare the effectiveness of paracetamol with ibuprofen in reducing fever in children. Also, the paper will discuss the importance of evidence-based practice in nursing. A literature search to find the relevant studies will be conducted using the databases CINAHL and MEDLINE. The identified studies will be critiqued using Coughlan et al. (2007) quantitative critiquing tool, focusing on the five aspects of Mellynk and Fineout-Overhalt’s (2011) stages of critical evaluation to critique the studies simultaneously. Furthermore, the paper will discuss the implementation to practice using the different change theories.
Evidence-based Practice
According to Sackett, Straus, Richardson, Rosenberg, and Haynes (2000) defined evidence-based practice (EBP) is the “conscientious use of current best evidence in making decisions about patient care.” The Academy of Medical-Surgical Nursing [AMSN] (2017) views EBP as “a problem-solving approach to clinical practice and administrative issues.” The AMSN (2017) further states that the approach encompasses three components. First, it involves a systematic search for and critical evaluation of the most appropriate evidence to address a daunting clinical issue (Seeman, 2001). The second component of EBP is an individual’s own clinical proficiency, and lastly, the patient’s values and preferences (Melnyk & Fineout-Overhault, 2014). EBP is a technique that enables the practitioner to evaluate research, practice guidelines, and other relevant information resources documenting high-quality results in order to use them in clinical practice (Gray, 2004). Thus, it represents a means to achieve top-notch patient care by integrating the best existing evidence to direct nurses in caring for patients to improve their outcomes. Essentially, it helps health providers solve healthcare problems by adapting evaluative and qualitative strategies.
Overview of the Topic
Relevance of the Research Question
Nurses need to compare interventions in order to inform their practice and provide the best intervention available. In this light, they need to know which antipyretic agent, between paracetamol and ibuprofen is the best for treating fever in children, which is the most prevalent condition in the world. In the UK, especially in England, a steep increase in scarlet fever was reported since the start of the cold season back in September 2015. Based on Public Health England (2016) that was the third season consecutively that the scarlet fever has shown a significant increase. Specifically, 6157 cases had been reported since the start of the season in September 2015, with about 600 cases being reported every week with further increases expected as the season approached its peak in late March and mid-April (Public Health England, 2016). According to a BBC news reporter, Dominic Howell, the cases of scarlet fever in the UK, especially Wales and England, had increased to the highest levels since the 1960s with a high of 17,586 cases in 2015. This latest incidence rivals that of 1967 when 19,305 cases were reported in 1967. This fever affects mostly children younger than 10 years old. Worth noting, the cases had steeply increased from 4,642 cases in 2013 to 15,625 in 2014, constituting a 236% increase. This incident has been a cause for alarm to the public health stakeholders. Thus, fever is currently the most prevalent condition among children under 10 years in the UK.
According to Dr. Chris Williams (cited in Howell, 2016), cases of scarlet fever reduced by 10% to 1,234 from 1,374 in 2015, which was high relative to 190 cases in 2013. In Scotland, the latest data indicated an increase in the cases through the early part of 2016 with the levels matching those of 2015 levels. England reported the highest level of 6,157 in March 2016 an increase of 7% from the previous level. Conversely, the cases had decreased from 625 cases in 2014 to 363 in 2015, representing a 41% decrease. However, the cases were still higher than the 199 cases in 2013 (Howell, 2016). Clinicians, parents, and guardians all use antipyretic agents to treat fever in conjunction with other classes of drugs, such as antibiotics.
According to the Medicines and Healthcare Products Regulatory Agency (MHRA) (n.d.), paracetamol is the most widely used treatment for pain and fever in not only adults but also children aged 2 months and older. It is also used for reducing post-vaccination fever in babies aged between 2 and 3 months old. In particular, MHRA (n.d.) states that approximately 84% of children in the United Kingdom are given the antipyretic agent by the age of 6 months.
Obtaining Evidence
The question that was used to obtain evidence was how paracetamol compares with ibuprofen in treating fever among young children in the UK. A Pico grid was used to search for literature on the topic. The population used was children aged 10 years and younger, the intervention was paracetamol and ibuprofen as counter intervention and the outcome was fever or temperature. The databases used were CINAHL and MEDLINE because they archive peer-reviewed journals, such that the information from these data are valid and reliable. The limits used were peer-reviewed full-text articles from 2007 to the present. The inclusion criteria were the term “children” and a time limit of 2007 and 2017. The exclusion criteria were neonates and adults, and articles older than 2007.
Data
The hierarchy of evidence is a guide to the type of evidence that is more probable to offer dependable answers to the clinical question. According to Melnyk, and Fineout-OVerhault (2011), for questions about intervention, the hierarchy of evidence ranks quantitative research designs as the leading in terms of confidence level regarding the reliability of answers to the questions posed than those studies with lower confidence levels, such as descriptive studies. Based on the hierarchy of evidence level, the systematic review of multiple randomized controlled trials ranks first, then the randomized controlled trials followed by non-randomized trials (Mullen & Streiner, 2004). Case-controlled studies and cross-sectional surveys rank third. Then non-experimental studies come fourth. Expert opinion and views of peers rank fifth and sixth, respectively, in the ranking of confidence levels of the answer to the intervention question (“Chapter 2: What is evidence and evidence-based practice?”, n.d.).
A randomized controlled trial is the best research design for providing information concerning cause and effect (Couglan, Cronin & Ryan, 2007). However, on its own, an RCT is less reliable in giving an answer to the clinical question than a systematic review of multiple RCTs about a common research question. Melynk and colleagues (2014) assert that the higher the ranking of a methodology of a research study, the more likely that its results are objective and the more confidence clinicians should have concerning the intervention producing identical outcomes for the patients under their care.
My search yielded a number of research studies and reviews on the topic. However, I avoided review studies because they just compare research studies done on a topic and do not involve the methodology used to collect data and the sample used. Therefore, the reviewer cannot be able to establish the validity and subsequent generalizability of the data. The data I obtained from mixed types of research. Some data obtained are from random controlled trials, such as the research by Khalil, Hahn, Chumpitazi, Rock, Kaelin, and Macias (2017). The data was from a hospitalized sample derived from a random assignment of the sample into intervention and counter-intervention groups. One group was given ibuprofen as an injection and the other acetaminophen. Also, data corresponding to randomized children subjects was used (Autret-Leca, Gibb, & Goulder, 2007). The intervention used in this study was paracetamol and the counter intervention was ibuprofen. The subjects were aged between 3 months and 12 years old. Other data were obtained from a study by Jayawardena and Kellstein (2016) that used subjects aged between 6 months and 11 years who had a fever. The interventions and counter interventions used were acetaminophen (paracetamol) suspension and ibuprofen suspension. Yet, data was also obtained from a randomized, blinded, three-arm trial that used children aged from 6 months to 6 years old who had a fever (Hay, 2008). Finally, data were obtained from a randomized, double-blind, parallel-group trial that used 464 participants aged from 6 to 36 months old (Sarell, Wielunsky, & Cohen, 2006).
Critique of the Studies
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Headings/Authors |
Khalil et al. 2017 |
Autret-Leca et al., 2007 |
Jayawardena and Kellstein 2016 |
Hay, et al., 2008 |
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Research design and approach |
Randomized assignment of patients to either ibuprofen or acetaminophen. The study drugs were administered at four-hour intervals after the first dose for 5 days |
The participants were randomized into either ibuprofen or paracetamol. The first dose was administered using a double-dummy method. Subsequent doses were administered by a subject’s parents open-label for three days. At the end of the double-blind, and open-label periods, parents were requested to give the rating of the drug’s efficacy and indicate whether they would give their children the drug to treat fever or opt for a different one. |
Two double-blinded single-dose, randomized, parallel-controlled trials were conducted. Studies were combined for post hoc analyses of efficacy and side effects endpoints. |
Children were followed up from January 2005 to May 2007 after they were recruited. All NHS organisations giving primary care services were asked to help with the recruitment among other healthcare organizations. The participants were followed up at 24 and 48 hours and at day 5. The participants were randomly assigned to three trial arms of paracetamol combined with ibuprofen, ibuprofen alone, and paracetamol alone. Parent and research nurses were blinded to treatment allocation by the use of identically matched placebo drugs. |
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Sampling strategy and selection of subjects |
The sample was recruited from hospitalized pediatric patients aged 16 years and younger from 14 hospitals in the U.S. The inclusion criteria were 16 years of age and younger presenting with body temperatures of 101.00 F or higher. The exclusion criteria were inadequate intravenous access, history of allergy to any component of IV-ibuprofen or related products, lactating or pregnancy, use of other antipyretic drugs within 2 hours of dosing, a participant in another study, fever associated with malignant hypothermia. |
The sample was selected from patients aged between 3 months to 12 years receiving outpatient treatments, and who indicate at least 38.50 C with an upper limit of 40.50 C. Patients who are hypersensitive to any of the interventions were excluded from the study. |
The sample was chosen from children aged between 6 months and 11 years weighing between 13 and 95 lb and indicated the first onset of fever at least 2 hours before enrolment to the study. Exclusion criteria included dehydration, malnourishment, or severe debilitation. Also, children below the 5th percentile or above the 95th percentile in weight were excluded. Those who received any medication or investigational drugs were also excluded. Further exclusion criteria included hypersensitivity to APAP, IBU, aspirin, or any other NSAIDs, history of febrile seizures, bronchospatic condition, urtricaria and hives, chronic renal disorder, blood coagulation defect, anaemia, hepatic disease, or metabolic disease. |
Children aged 6 months to 6 years presented temperatures of at least 37.80 C and a maximum of 41.00 C due to ailments that can be cared for at home. The participants were selected from 4515 contacts, but 3477 were ruled out due to insufficient fever. 882 candidates were excluded due to the reluctance of the parents to participate in the study. 156 children were enrolled in the study. Over 90% of the participants experienced discomfort, reduce activity, abnormal sleep, and abnormal appetite. The mean of minutes without fever within the first four hours was 219 for the paracetamol arm, 211 for the ibuprofen arm, and 202 for paracetamol with the ibuprofen arm. Children receiving paracetamol and ibuprofen had more time without fever than those in the other two arms. Faster fever clearance was reported in the combined arm than in the paracetamol arm but the same as ibuprofen. |
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Data collection technique and instruments |
Blood samples were drawn for drug analysis. Ibuprofen and its metabolites were extracted from 0.025mL aliquots of plasma. A mass spectrometry detector was used to detect the drug and its metabolites. Changes in temperature were assessed for each patient during the first 30, 60, and 240 minutes of treatment. The outcome of temperature change after the first 30, 60, and 240 minutes of dose administration were assessed using ANCOVA, and the change in temperature versus time was compared using ANOVA. Two-sided t-test was used to detect the difference of 0.50C between the area under the curve 0 to 2 hours for ibuprofen and acetaminophen groups. The treatment with intravenous ibuprofen resulted in a greater reduction in temperature than acetaminophen. The difference between the groups was evident at 30 minutes post-dose and maintained for four hours. Also, more patients who received ibuprofen reached an afebrile temperature than patients who received acetaminophen. However, the time taken to reach an afebrile temperature was not different. Side effects were reported in 54 subjects of the 100. The number of subjects who experienced adverse events was almost the same. |
Tympanic thermometry was used to collect data because of the recommendation by the Ethics Committee for the suitability of its use for babies and young children. The temperatures of the subjects were taken 30 minutes after the first dose and were subsequent measurements followed after 2, 3, 4, 5, 6, 7, and 8 hours. The parents recorded the temperature reading and the time taken in a diary. |
Oral or rectal temperatures were recorded using B-D Digital Fever Thermometer at baseline and then at 15, 30, and 45 minutes after the first dose, and then at 1,2,3,4,5,6,7, and 8 hours subsequently. The time-weighted sum temperature difference (TWSTDs) were collected from baseline through 8 hours. |
The time without fever was recorded within the first 4 hours and the ratio of participants reported as being normal on the discomfort scale at 48 hours. Secondary outcomes were measured at three-time points. The time to temperatures first falling below 37.20 C was recorded within the first 24 hours. Fever-associated symptoms and temperature were recorded at 48 hours and day 5. The time without fever was measured using a data logger connected to an axillary temperature probe. Parents completed symptoms diaries with assistance from the research nurses |
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Data analysis and results |
The area under a curve was used to determine the change in temperature using the linear trapezoidal rule. ANOVA was used to assess the primary efficacy variable between the treatment groups. |
Various statistical methods were used to analyze data. ANCOVA was used to analyze the endpoints using age and temperature as covariates. Comparison between the treatments was evaluated at a two-sided α of 0.5. A 95% confidence interval (CI) for the difference between the two treatments was computed from the fitted model. The participants presented the same baseline characteristics without any clinically relevant differences. No statistically significant divergence was found in the primary endpoint or in any of the objective secondary endpoints. |
Two-way ANOVA with baseline and treatment temperatures stratum was used to analyse maximum temperature variance, and temperature differences from baseline at each time point, and to analyze the TWSTDs. Conchran-Mantel-Haenszel test was used to classify treatment failures while the Cox proportional hazards regressional model was used to analyze time to treatment failure, time to temperature control, and duration of temperature control. Kaplan was also used to estimate the time to treatment failure, duration of control, and time to onset of temperature control. |
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Ethical considerations |
The study was approved by the Institution Review Board (IRB). It was performed under the investigational new drug application consistent with the Helsonki Declaration. |
The study was performed consistent with the Declaration of Helsinki and in compliance with The International Conference on Harmonization, Good Clinical Practice (GCP) and regulatory requirements. |
Approval of the Arkansas Institutional Review Board (AIRB) for study 1 and of the Western Institutional Review Board for study 2 were obtained. Consent was obtained from parents and participants. |
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Translation into Practice
Traditionally, paracetamol has widely been used in the UK as the first-line drug for treating fever. However, other antipyretic agents especially ibuprofen have gained popularity in use for treating fever in children and adults. Patients and care providers have differed in preference for either antipyretic. Research studies have been conducted to compare the efficacy of paracetamol with ibuprofen. Thus, this review of the research results will help clarify the situation and inform healthcare practice. The evidence will determine which antipyretic is superior to the other in terms of the time required to restore the body temperature within the normal limit. From the above evaluation of evidence on the selected RCTs, ibuprofen is superior to paracetamol in the treatment of fever among children, whereas a combination of the two is better than either drug administered alone. Therefore, a combined formulation of the two should be the primary prescription for treating fever in children. In case of the absence of a combined formulation, ibuprofen should be the preferred medication over paracetamol.
A number of change theories can be used to inform this situation. According to Lewin’s (1958) theory of change, the change process has three basic phases: the unfreezing phase, the moving phase, and finally the refreezing phase. The unfreezing step describes the occurrence of the motivation for change, that is, when practitioners realize that change is necessary. The second step, moving, involves planning the change and reviewing consensus. The refreezing phase denotes integrating and establishing change, stabilizing into a new equilibrium.
Importantly, change should not be suddenly imposed on practitioners but each process should be initiated in a constructed way. The assessment of the current practice, along with the need to switch from paracetamol to a combined formulation of ibuprofen and paracetamol or ibuprofen alone should be engaged by the change champion with the help of a steering group specially appointed to develop principles into practice. In addition, teamwork should be developed to mobilize groups and individuals to commit to actualize and sustaining change (Broome, 1998).
The major barriers to implementing evidence-based practice are resistance and lack of resources to facilitate change. Based on Houser and Oman (2010) some common barriers to implementing evidence are limitations in evidence-based practice systems, human factors, and organizational factors. Limitations in evidence-based practice entail an overwhelming amount of information on the topic in the literature. Sometimes conflicting findings serve to confound practitioners (Sackett, Rosenberg, Gray, Haynes, & Richardson, 1996). The most significant barriers include a lack of knowledge about EBP and a lack of skills in appraising research studies (Houser & Oman, 2010).
Conclusion
Evidence-based practice has become the mantra of practicing medicine in the post-modern world, especially in developed countries. In the United Kingdom, concerns about the best antipyretic agent to use to treat fever have emerged. A review of research findings of studies considered reliable comparing paracetamol and ibuprofen showed that the letter is a more efficacious antipyretic agent than the latter. RCTs are considered the best research studies to analyze for evidence regarding the clinical question of interest. Developing a clinical question has emerged as an important step in searching for evidence. Reliable databases provide the right materials to conduct the research review. Despite the revelation of the research studies considered, implementing this evidence is often challenging because of human barriers as well as organizational barriers.
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