Current Practice and Pitfalls of Select Biomarkers in the Emergency Care of Children

Table of Contents

 

About This Issue

Appropriate incorporation of biomarkers into clinical decision-making can potentially improve management by minimizing unnecessary procedures and tests without sacrificing patient safety. This issue reviews the known literature on 4 biomarkers: lactate (lactic acid), C-reactive protein (CRP), ferritin, and procalcitonin (PCT). The performance characteristics of these biomarkers is discussed in 3 clinical scenarios: potential bacterial meningitis, common bacterial infections, and appendicitis. You will learn:

Features of an ideal biomarker

Characteristics of the 4 biomarkers, including where the biomarker is primarily produced, onset time, and peak time

The limitations of these biomarkers in common clinical scenarios

Recommendations for which biomarkers can assist in diagnosing or ruling out certain pediatric illnesses

Settings in which these biomarkers should not be applied

1. About This Issue
2. Abstract
3. Case Presentations
4. Introduction
5. Critical Appraisal of the Literature
6. Pathophysiology
   1. Lactate
   2. C-Reactive Protein
   3. Ferritin
   4. Procalcitonin
7. Emergency Department Evaluation
8. Use of Select Biomarkers for Specific Conditions
   1. Meningitis
      1. Introduction
      2. Lactate for Meningitis
         • Analysis of the Evidence of Lactate for Meningitis
      3. C-Reactive Protein for Meningitis
         • Analysis of the Evidence of C-Reactive Protein for Meningitis
      4. Ferritin for Meningitis
         • Analysis of the Evidence of Ferritin for Meningitis
      5. Procalcitonin for Meningitis
         • Analysis of the Evidence of Procalcitonin for Meningitis
      6. Summary of Recommendations for the Use of Select Biomarkers for Meningitis
   2. Bacterial Infections
      1. Introduction
      2. Lactate for Bacterial Infections
         • Analysis of the Evidence of Lactate for Bacterial Infections
      3. C-Reactive Protein for Bacterial Infections
         • Analysis of the Evidence of C-Reactive Protein for Bacterial Infections
      4. Ferritin for Bacterial Infections
      5. Procalcitonin for Bacterial Infections
         • Analysis of the Evidence of Procalcitonin for Bacterial Infections
           • The Step-by-Step Approach
           • Infants
      6. Summary of Recommendations for the Use of Select Biomarkers for Bacterial Infections
   3. Appendicitis
      1. Introduction
      2. Lactate for Appendicitis
      3. C-Reactive Protein for Appendicitis
         • Analysis of the Evidence of C-Reactive Protein for Appendicitis
      4. Ferritin for Appendicitis
      5. Procalcitonin for Appendicitis
         • Analysis of the Evidence of Procalcitonin for Appendicitis
      6. Summary of Recommendations for the Use of Select Biomarkers for Appendicitis
9. Special Considerations
10. Controversies and Cutting Edge
11. Summary
    1. Meningitis
    2. Bacterial Infection
    3. Appendicitis
12. Time- and Cost-Effective Strategies
13. Risk Management Pitfalls When Using Select Biomarkers for the Emergency Care of Children
14. Case Conclusions
15. Tables and Appendices
16. References

Abstract

Specific biomarker levels can help differentiate children who require emergent medical interventions, such as procedures, surgeries, or antibiotics, from those who may not. Appropriate application of biomarkers after a thorough history and physical examination can potentially improve cost-effective management by minimizing unnecessary procedures and tests without sacrificing patient safety. This issue reviews the literature regarding 4 biomarkers: lactate, C-reactive protein, ferritin, and procalcitonin. Evidence-based recommendations are made for the clinical evaluation of bacterial meningitis, common infections, and appendicitis.

Case Presentations

A 10-year-old boy is brought in for stomach pain that started last night…

• The boy’s mom says he has been complaining of “tummy pain” since before he went to bed last night, and he has been walking “hunched over.” The boy tells you that the pain started at his belly button and has now moved down into his lower abdomen. When you question him, he says that he is hungry, and he denies nausea.
• On examination, the boy does not have a fever, and his vital signs are stable. The boy is lying comfortably on the bed. His heart and lung examinations are normal. His abdomen is mildly tender between the umbilicus and right lower quadrant but not specifically at McBurney’s point. There is no rebound or guarding. He has a positive obturator sign and negative psoas and Rovsing signs. The genitourinary examination is benign.
• As you walk away, you think: Does this patient have acute appendicitis? What additional blood tests might change suspicion for acute appendicitis? If an ultrasound is inconclusive, is a CT of the abdomen warranted?

A full-term 65-day-old girl is brought in for fever…

• The girl had a measured fever at home of 38.5°C. She has no significant past medical history. The mother denies the infant having difficulty breathing or malodorous urine. The girl has not received her 2-month immunizations yet. She is eating well and has no diarrhea.
• On examination, the girl's fontanelle is soft and nonbulging, and her neurologic examination is normal. Her lungs are clear, without tachypnea. Her abdomen is soft. You order bloodwork and go on to see the next patient.
• While awaiting the results, you think: Does this patient have a bacterial infection? Are there blood tests that can change your suspicion for a serious bacterial infection or meningitis? Does a lumbar puncture need to be performed?

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Risk Management Pitfalls When Using Select Biomarkers for the Emergency Care of Children

4. “It doesn’t matter what my history and physical exam are. I can just order these labs and be done with it.” Biomarkers are an adjunct to the emergency clinician’s data-gathering and decision-making processes—not a replacement. Details such as duration of symptoms should factor into the clinician’s assessment and clinical gestalt. Reassessment after obtaining reassuring biomarker results is also critical.

8. “If the PCT level comes back normal in my 8-year-old patient, it will mean that I don’t need to do a lumbar puncture—even though he’s got a fever and headache.” Biomarkers must be applied appropriately. A normal serum PCT can help differentiate bacterial from viral meningitis after an LP has been performed but it cannot exclude other etiologies of headache and neck pain. This statement is an inappropriate application of PCT in this clinical setting. PCT has not currently been found to predict the need for an LP in this age group.

9. “My pediatric patient had a normal WBC and a normal CRP, so I ruled out acute appendicitis.” While a normal WBC count and CRP may rule out appendicitis in adult patients, this is not true for the pediatric population. A normal WBC count and low CRP significantly decrease the posttest probability of acute appendicitis, but it does not entirely rule out the disease in children.

Tables and Appendices

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Key References

Following are the most informative references cited in this paper, as determined by the authors.

1. * Pantell RH, Roberts KB, Adams WG, et al. Evaluation and management of well-appearing febrile infants 8 to 60 days old. Pediatrics. 2021;148(2):e2021052228. (Clinical practice guideline) DOI: 10.1542/peds.2021-052228

30. * Šimundić AM. Measures of diagnostic accuracy: basic definitions. EJIFCC. 2008;19(4):203-211. (Review)

50. * Garcia S, Echevarri J, Arana-Arri E, et al. Outpatient management of children at low risk for bacterial meningitis. Emerg Med J. 2018;35(6):361-366. (Prospective; 182 patients) DOI: 10.1136/emermed-2017-206834

59. * Weiss SL, Peters MJ, Alhazzani W, et al. Surviving Sepsis Campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med. 2020;21(2):e52-e106. (International guidelines) DOI: 10.1097/PCC.0000000000002198

69. * Mintegi S, Bressan S, Gomez B, et al. Accuracy of a sequential approach to identify young febrile infants at low risk for invasive bacterial infection. Emerg Med J. 2014;31(e1):e19-e24. (Retrospective; 1123 patients) DOI: 10.1136/emermed-2013-202449

70. * Gomez B, Mintegi S, Bressan S, et al. Validation of the “Step-by-Step” approach in the management of young febrile infants. Pediatrics. 2016;138(2):e20154381. (Prospective; 2185 patients) DOI: 10.1542/peds.2015-4381

72. * Kuppermann N, Dayan PS, Levine DA, et al. A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections. JAMA Pediatr. 2019;173(4):342-351. (Retrospective derivation and prospective; 1821 patients) DOI: 10.1001/jamapediatrics.2018.5501

88. *Huckins DS, Simon HK, Copeland K, et al. A novel biomarker panel to rule out acute appendicitis in pediatric patients with abdominal pain. Am J Emerg Med. 2013;31(9):1368-1375. (Prospective; 503 patients) DOI: 10.1016/j.ajem.2013.06.016

107. *Williams R, Mackway-Jones K. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. White cell count and diagnosing appendicitis in children. Emerg Med J. 2002;19(5):428-429. (Review) DOI: 10.1136/emj.19.5.428

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Keywords: biomarker, serum biomarker, lactate, lactic acid, C-reactive protein, CRT, ferritin, procalcitonin, PCT, meningitis, bacterial meningitis, common infections, bacterial infection, invasive bacterial illness, serious bacterial infection, SBI, appendicitis