Editorials

Fever Without Source in Infants and Young Children--A Hot Potato?

WILLIAM F. MISER, M.D., M.A.
Ohio State University College of Medicine and Public Health
Columbus, Ohio

Although fever is common in infants and young children three to 36 months of age, its management remains challenging and controversial. In this issue of American Family Physician,¹ Luszczak provides an update of the 1993 practice guideline on the management of febrile infants and young children, which was developed by an expert panel of senior academic pediatricians.²

In the first two years of life, children have an average of four to six acute febrile episodes, with medical care being sought for two thirds of these children.^2,3 Most have a temperature lower than 39°C (102.2°F) and a viral infection or an obvious bacterial origin for the fever.⁴ The challenge in management involves determining which of the 20 percent of children with no obvious source for their fever have occult bacteremia and will subsequently develop a serious bacterial illness.⁵

Various important issues were not addressed in Luszczak's article.¹ Fever phobia (an exaggerated fear of fever) exists equally among parents and health care professionals. Results of several studies^6,7 have documented the anxiety parents experience when their young child develops a fever. Despite evidence showing that a temperature elevation up to 40°C (104°F) has a number of beneficial effects, including improved host defenses and increased susceptibility of bacteria to these defenses,⁸ many nurses and physicians are overly concerned about rare potential complications and often needlessly prescribe antipyretics.^9,10

In addition, physicians often assume that parents are able to manage their febrile child at home. However, recent evidence challenges this assumption. In one study of 92 caregivers of young children,¹¹ fewer than one third could accurately measure their child's temperature and treat the fever appropriately. In another study,¹² more than one half of infants younger than one year received an incorrect dose of antipyretic. Many instruction labels for commonly used antipyretics include language that surpasses the reading comprehension of one half of the parents in the United States.¹³ Furthermore, the common practice of using a tepid sponge bath to reduce fever offers little advantage over antipyretics and may cause the child more discomfort.^14,15 Finally, the frequently recommended practice of alternating doses of acetaminophen with ibuprofen has never been studied; in fact, this practice may lead to parental confusion and overdosing of medication.¹⁶ Clearly, education on the management of fever is needed for health care professionals and parents.

Surveys of family physicians, pediatricians and emergency medicine physicians demonstrate significant variability in approaches to the evaluation and management of infants and young children who have a fever with no apparent locus of infection.¹⁷ One reason for this variability is that most research in this area has been performed in urban pediatric emergency departments--not in physicians' offices where most of these children are initially seen. A number of the tests recommended for the initial assessment of febrile infants and young children (e.g., white blood cell count, chest radiograph) may not be readily available in many medical offices.¹⁸ Thus, physicians must decide either to follow the guidelines and send infants and young children with fever to the emergency department, or to modify their approach based on what can be done in the office.

As noted in Luszczak's article,¹ the initial approach to the febrile infant or young child involves a careful history, observation of the patient's state of well-being and a detailed physical examination. About one in five children younger than three years of age will have a fever without source. Of these children who have a temperature of 39°C (102.2°F), 2 to 5 percent will have occult bacteremia, and of these, 10 percent may develop a serious bacterial illness (e.g., meningitis or pneumonia) if untreated.^19,5

Physicians must make a series of crucial decisions when treating infants and young children who have a fever without source¹⁸: Should tests be performed to identify those who have occult bacterial infections? If no locus of bacterial infection is found, should antibiotics be given empirically? If the choice is to empirically treat with antibiotics, should oral or parenteral therapy be used, or should a broad-spectrum or narrow-spectrum antibiotic be used, and how long should treatment last? Should the patient be treated as an outpatient or in a hospital? If the patient is not hospitalized, what follow-up should be arranged? The 1993 practice guideline was developed to help physicians make these decisions.

Two noteworthy developments have occurred since the practice guideline was first published. Urinary tract infection is now known to be among the most common occult bacterial sources of fever in children younger than three years of age.^4,5 Because the risk of renal damage is greatest in this age group, the American Academy of Pediatrics recently released a practice guideline on the diagnosis, treatment and evaluation of urinary tract infections in febrile infants and young children.²⁰ The combination of a urine dipstick test and microscopic examination of a centrifuged sample appears to be the best way to screen for urinary tract infection. Controversy exists concerning the best method for obtaining a urine sample for culture when this screen is abnormal. Bag-collected urine samples are associated with a false-positive rate as high as 87 percent,⁴ but the recommended approach of transurethral bladder catheterization or suprapubic bladder aspiration may not be easily performed by most office-based physicians.

With the introduction of routine vaccination, Haemophilus influenzae type b disease in infants and children has nearly been eradicated in the United States. Results of several studies^21,22 indicate that most cases of occult bacteremia are now caused by Streptococcus pneumoniae infection, which often resolves spontaneously without treatment. A recent meta-analysis²¹ of S. pneumoniae occult bacteremia suggests that 2,910 children with fevers of 39°C and higher would have to be treated with oral antibiotics to prevent one case of meningitis. Assuming that an adverse outcome (death or neurologic disability) occurs in 33 percent of children with meningitis, 6,570 children would have to be treated to prevent a single adverse outcome. Consequently, some investigators²³ advocate that empiric antibiotic therapy not be given. Furthermore, other investigators⁵ believe that the introduction of a conjugate S. pneumoniae vaccine will make the practice guideline on fever in infants and young children obsolete within the next one to two years.

In the meantime, family physicians faced with febrile children three to 36 months of age should individualize therapy. It is impossible to eliminate all risk in medical practice. As pointed out in one recent article,²⁴ one must choose between being a "risk-minimizer" (which potentially eliminates adverse sequelae from occult infections--and liability risk), and a "test-minimizer" (which, for the sake of practicality, increases the risk of missing an occult infection).²⁴ For physicians who are risk-minimizers, the modified guideline presented in this issue can serve as a useful starting point.

REFERENCES

1. Luszczak M. Evaluation and management of infants and young children with fever. Am Fam Physician 2001;64:1219-26.
2. Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH, Powell KR, et al. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Pediatrics 1993;92:1-12.
3. McCarthy PL. Fever. Pediatr Rev 1998;19:401-7.
4. Slater M, Krug SE. Evaluation of the infant with fever without source: an evidence based approach. Emerg Med Clin North Am 1999;17:97-126.
5. Baraff LJ. Management of fever without source in infants and children. Ann Emerg Med 2000;36: 602-14.
6. Parkinson GW, Gordon KE, Camfield CS, Fitzpatrick EA. Anxiety in parents of young febrile children in a pediatric emergency department: why is it elevated? Clin Pediatr 1999;38:219-26.
7. Blumenthal I. What parents think of fever. Fam Pract 1998;15:513-8.
8. Styrt B, Sugarman B. Antipyresis and fever. Arch Intern Med 1990;150:1589-97.
9. May A, Bauchner H. Fever phobia: the pediatrician's contribution. Pediatrics 1992;90:851-4.
10. Poirier MP, Davis PH, Gonzales-delRey JA, Monroe KW. Pediatric emergency department nurses' perspectives on fever in children. Pediatr Emerg Care 2000;16:9-12.
11. Porter RS, Wenger FG. Diagnosis and treatment of pediatric fever by caretakers. J Emerg Med 2000; 19:1-4.
12. Li SF, Lacher B, Crain EF. Acetaminophen and ibuprofen dosing by parents. Pediatr Emerg Care 2000;16:394-7.
13. Heubi JE, Bien JP. Acetaminophen use in children: more is not better. J Pediatr 1997;130:175-7.
14. Purssell E. Physical treatment of fever. Arch Dis Child 2000;82:238-9.
15. Sharber J. The efficacy of tepid sponge bathing to reduce fever in young children. Am J Emerg Med 1997;15:188-92.
16. Mayoral CE, Marino RV, Rosenfeld W, Greensher J. Alternating antipyretics: is this an alternative? Pediatrics 2000;105:1009-12.
17. Baker MD. Evaluation and management of infants with fever. Pediatr Clin North Am 1999;46:1061-72.
18. Kramer MS, Shapiro ED. Management of the young febrile child: a commentary on recent practice guidelines. Pediatrics 1997;100:128-34.
19. Lee GM, Harper MB. Risk of bacteremia for febrile young children in the post-Haemophilus influenzae type b era. Arch Pediatr Adolesc Med 1998;152: 624-8.
20. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection. Pediatrics 1999;103:843-52.
21. Rothrock SG, Harper MB, Green SM, Clark MC, Bachur R, McIlmail DP, et al. Do oral antibiotics prevent meningitis and serious bacterial infections in children with Streptococcus pneumoniae occult bacteremia? A meta-analysis. Pediatrics 1997;99: 438-44.
22. Alpern ER, Alessandrini EA, Bell LM, Shaw KN, McGowan KL. Occult bacteremia from a pediatric emergency department: current prevalence, time to detection, and outcome. Pediatrics 2000;106:505-11.
23. Stamos JK, Shulman ST. Abandoning empirical antibiotics for febrile children. Lancet 1997;350:84.
24. Green SM, Rothrock SG. Evaluation styles for well-appearing febrile children: Are you a "risk-minimizer" or a "test-minimizer"? Ann Emerg Med 1999;33:211-4.

Managing Pain at the End of Life

ALAN B. DOUGLASS, M.D.
Middlesex Hospital Family Practice Residency Program
Middletown, Connecticut

As a patient nears the end of life, treatment goals change from measures aimed at prolonging life via cure or remission of disease to the provision of palliative care. Palliative care focuses on maximizing the quality of the patient's remaining life by relieving suffering through the control of pain and other symptoms. The provision of palliative care during this challenging period has recently become a major theme of medicine in the United States.

An extensive body of literature on the assessment and management of pain is now available. Medical schools are revamping their curricula to include this important area, and several major initiatives, including the American Medical Association's landmark Education for Physicians on End-of-Life Care Project (EPEC),¹ are helping practicing physicians improve their skills. The Joint Commission on the Accreditation of Health Care Organizations has made the assessment of pain management in hospitalized patients a major priority in 2001.²

Such efforts may reverse earlier trends, which showed that patients were receiving inadequate pain relief. In one study,³ 67 percent of patients with metastatic cancer reported significant daily pain, and 42 percent were not provided with adequate analgesia.³ In the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT),⁴ 40 percent of patients reported having serious pain during the last three days of life.

Pain is defined by the International Association for the Study of Pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of that damage."⁵ Pain, which can be acute or chronic, or a mixture of the two, profoundly affects quality of life. While physiologically triggered, pain is mediated by a patient's subjective perceptions and is therefore uniquely perceived by each individual.

In this issue of American Family Physician, Miller and associates⁶ provide information on the pharmacologic management of pain syndromes. This information will be useful to anyone who provides care for patients who experience pain. Of particular value is the emphasis on nonopioid adjuvant therapies for neuropathic and somatic pain. Use of these frequently neglected medications often results in improved pain control, with fewer and less severe side effects than occur with high-dose opioids.

Nonetheless, opioids remain the mainstay of pain control in the terminally ill. As the authors of the article⁶ mention in their introduction, the World Health Organization (WHO) step model⁷ is the standard approach to pain management in patients who are approaching the end of life. When properly implemented, this program has been proved to relieve pain in more than 90 percent of patients.⁸

In the WHO model,⁷ nonopioids are used first, followed by combination products containing weak opioids and, finally, strong opioids such as morphine. Adjuvant therapies are considered at every level. A common error that physicians make in using the step model is not moving to the strong opioids of step 3 soon enough. An earlier shift avoids the distressingly common problem of excessive intake of potentially toxic co-analgesics such as acetaminophen, particularly in frail, elderly patients with impaired hepatic function. An earlier shift also facilitates appropriate use of breakthrough dosing with pure opioids, as described later in the article.⁶

When physicians are wrestling with challenging pain management problems, it is easy to become focused on the technicalities of drug dosing and to miss seeing some of the larger issues that are affecting patients and their quality of life. The following approaches may help avoid some of the more common pitfalls:

1. Develop a systematic, comprehensive approach to pain assessment in each patient at every encounter. The most important rule is to listen to patients--and believe them! The history and physical examination should focus on assessing the frequently multiple causes of the patient's pain. Disease status, quality of life and prognosis must always be considered. After a plan has been developed, it must be reassessed frequently, as the patient's situation often changes rapidly.
2. Constantly remind yourself that pain does not usually emanate from a single source, and that all pain is not physical in origin. The concept of "total pain" recognizes that terminally ill patients also suffer pain from emotional sources such as depression or anxiety, family stresses, social problems and spiritual fears.⁹ A health care system that seldom works as well or as smoothly as anyone would like can be a constant stressor for all patients. Good pain control will seldom be achieved unless all areas are systematically addressed.
3. Remember that it is unrealistic to expect a single person to provide complete, optimal care at the end of life. High-quality care is usually best delivered through an interdisciplinary team in which the skills and perspectives of the various members are complementary. The modern hospice movement provides a valuable model for the delivery of carefully integrated, coordinated care.

Although pain management at the end of life is seldom perfect, a systematic, thorough and comprehensive approach to care can result in reasonable pain control and substantially improved quality of life in most patients. Key physician skills include effective pain assessment strategies, appropriate use of opioids and adjuvant pain therapies, attention to nonphysiologic sources of pain, coordination with a strong interdisciplinary care team, appropriate follow-up and, above all, careful listening. In the words of an anonymous 16th century physician, "Cure sometimes, relieve often, but comfort always."

REFERENCES

1. EPEC: education for physicians on end-of-life care. Institute for Ethics at the American Medical Association. Chicago: EPEC Project, The Robert Wood Johnson Foundation, 1999.
2. Comprehensive accreditation manual for hospitals: the official handbook. Hospital accreditation manual. Oakbrook Terrace, Ill.: Joint Commission on Accreditation of Healthcare Organization, 2000.
3. Cleeland CS, Gonin R, Hatfield AK, Edmonson JH, Blum RH, Stewart JA, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994;330:592-6.
4. McCarthy EP, Phillips RS, Zhong Z, Drews RE, Lynn J. Dying with cancer: patients' function, symptoms, and care preferences as death approaches. J Am Geriatr Soc 2000;48(5 suppl):S110-21.
5. Mersky H, Bogduk N, eds. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms/prepared by the Task Force on Taxonomy of the International Association for the Study of Pain. 2d ed. Seattle: IASP, 1994:222.
6. Miller KE, Miller MM, Jolley MR. Challenges in pain management at the end of life. Am Fam Physician 2001;64:1227-34.
7. Stjernsward J. WHO cancer pain relief programme. Cancer Surv 1988;7:195-208.
8. Zech DF, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Pain 1995;63:65-76.
9. Saunders CM, ed. The management of terminal disease. London: Edward Arnold, 1978:194-5.

William F. Miser, M.D., M.A., is associate professor and residency program director in the Department of Family Medicine at Ohio State University College of Medicine and Public Health, Columbus.

Address correspondence to William F. Miser, M.D., M.A., Department of Family Medicine, Ohio State University College of Medicine and Public Health, 2231 N. High St., Columbus, OH 43201 (e-mail: miser.6@osu.edu).

Alan B. Douglass, M.D., is assistant director of the Middlesex Hospital Family Practice Residency Program, Middletown, Conn.

Address correspondence to Alan B. Douglass, M.D., 90 S. Main, Middletown, CT 06457.

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