Table of Contents

 

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Etiology And Pathophysiology
6. Differential Diagnosis
   1. Local Infections
   2. Systemic Infections
7. Prehospital Care
8. Emergency Department Evaluation
   1. History
   2. Physical Examination
9. Diagnostic Studies
   1. Blood Culture
   2. Complete Blood Count
   3. C-Reactive Protein
   4. Polymerase Chain Reaction
   5. Other Laboratory Testing
   6. Imaging Studies
10. Treatment
    1. Initial Resuscitation
11. Special Circumstances
12. Controversies And Cutting Edge
    1. Procalcitonin And Other Serum Biomarkers
13. Disposition
14. Summary
15. Risk Management Pitfalls For Pediatric Patients With A Central Venous Catheter Presenting With Fever Or Suspected Infection
16. Time- And Cost-Effective Strategies
17. Case Conclusions
18. Clinical Pathway For Management Of Fever Or Suspected Infection In Pediatric Patients With A Central Venous Catheter
19. Tables
    1. Table 1. Types Of Central Venous Catheters
    2. Table 2. Common Organisms Causing Infection In Patients With Central Venous Catheters
    3. Table 3. Types Of Systemic Infections
    4. Table 4. Differential Diagnosis For Fever In Patients With A Central Venous Catheter
20. References

Abstract

The use of indwelling central venous catheters is essential for pediatric patients who require hemodialysis, parenteral nutrition, chemotherapy, or other medications. Fever is a common chief complaint in the emergency department, and fever in a patient with a central venous catheter may be related to a common cause of fever, or it may be due to a catheter-associated bloodstream infection. Catheter-associated bloodstream infections may also lead to additional complications such as sepsis, septic shock, or septic complications including suppurative thrombophlebitis, endocarditis, osteomyelitis, septic emboli, and abscesses. Early resuscitation as well as timely and appropriate antibiotic therapy have been shown to improve outcomes. This issue focuses on the approach to fever in pediatric patients with central venous catheters and the management and disposition of patients with possible catheter-associated bloodstream infections.

Case Presentations

An 8-year-old boy with a history of standard-risk acute lymphoblastic leukemia presents to the ED with a fever. He has a port central line and is currently undergoing the delayed intensification phase of chemotherapy. He last received chemotherapy 1 day prior to presentation. He also reports a headache and a cough. Upon examination, he is febrile to 39.2ºC, with a heart rate of 120 beats/min and blood pressure of 108/60 mm Hg. He is breathing comfortably and has an oxygen saturation of 99% on room air. You consider what initial laboratory workup you might need…

A 4-year-old girl with a history of gastroschisis requiring intestinal resection that resulted in short gut syndrome presents with a history of fever, vomiting, and diarrhea. She is dependent upon total parenteral nutrition, which is delivered through a Broviac® catheter. She has a history of multiple previous line infections, including a recent MRSA line infection. On examination, her temperature is 38.2°C, and she has a heart rate of 105 beats/min and blood pressure of 100/55 mm Hg. You wonder what initial laboratory testing and imaging you should consider, and what the appropriate disposition for this patient should be…

Introduction

Fever is a common chief complaint of pediatric patients presenting to the emergency department (ED), and patients with a central venous catheter (CVC) may also have common causes of fever similar to children without pre-existing medical conditions. While these common causes of fever may occur in patients with CVCs, it is imperative that emergency clinicians investigate all episodes of fever for catheter-associated bloodstream infections (CA-BSI), and initiate prompt and appropriate antibiotic therapy if catheter-associated infection is suspected.

The use of an indwelling CVC is essential in pediatric patients who require hemodialysis, parenteral nutrition, frequent blood draws, frequent blood product transfusions, or long-term intravenous medications (such as antibiotics or chemotherapeutics). Although essential to the treatment of these patients, there are several complications that may arise with the ongoing use of CVCs. In addition to catheter dysfunction, thrombosis, and embolization, patients with a CVC may also experience infection at the insertion site, the tunneled portion of the catheter, the subcutaneous pocket of a totally implanted intravascular device (a pocket infection), or within the catheter itself. The indwelling catheter provides a portal of entry for bacteria (and other organisms), and renders these patients susceptible to the development of a CA-BSI and the potential for progression to overwhelming infection and sepsis.

The rapid recognition and triage of these patients, with subsequent initiation of antibiotics and resuscitative measures, has been studied extensively and has been shown to improve outcomes in febrile neutropenic patients with indwelling central catheters.¹ The time to antibiotic therapy has been consistently used as a quality-of-care measure in this patient population.^1,2 Although less-studied in other pediatric populations relying on CVCs, a regular complication in these patients remains the occurrence of CA-BSI. Sepsis syndrome remains a leading cause of morbidity and mortality in pediatric patients, and the Surviving Sepsis Campaign (www.survivingsepsis.org) recommends initiation of empiric antibiotic therapy within 1 hour of the recognition of severe sepsis or septic shock in both adult and pediatric patients.

Critical Appraisal Of The Literature

Risk Management Pitfalls For Pediatric Patients With A Central Venous Catheter Presenting With Fever Or Suspected Infection

1. “The patient was well-appearing in triage, so she didn’t need to be seen immediately.”
   All patients with a CVC presenting with fever should be evaluated upon arrival. In the setting of a CR-BSI, a patient’s clinical examination can change precipitously. Patients presenting with unstable vital signs should be triaged and evaluated immediately by an emergency clinician.
2. “The patient was tachycardic with fever, but he had a normal blood pressure, so we didn’t initially provide any fluid resuscitation.”
   In pediatric patients, hypotension is not required for a patient to meet the criteria for septic shock, and this is often a late finding. A patient with evidence of hemodynamic changes without hypotension is considered to be in compensated shock. Fluid resuscitation should be initiated promptly with the goal of reversing hemodynamic abnormalities such as tachycardia and hypotension, and normalizing urine output, mental status, and capillary refill time.
3. “We were having difficulty accessing the patient’s port, and the parents refused a peripheral blood culture, so the patient didn’t receive antibiotics for almost 2 hours.”
   It is recommended that blood cultures be drawn prior to the patient’s receiving antibiotics. However, since prompt antibiotic therapy has been shown to improve outcomes in neutropenic and critically ill patients, obtaining cultures should not significantly delay antibiotic therapy.
4. “We started antibiotic therapy within the first hour, but didn’t realize that the patient had a history of a previous infection with a multidrug-resistant organism.”
   Timely and appropriate antibiotic therapy has been shown to improve outcomes in pediatric sepsis patients. It is important to consider each patient’s infection history and cover for resistant organisms if the patient has a history of a previous drug-resistant infection.
5. “The patient had a CVC and presented with fever, so blood cultures were drawn from 1 of 2 catheter lumens and empiric antibiotics were started 2 days ago. Even though the patient was still febrile after 48 hours, the culture results were negative, so we discontinued antibiotics.”
   A single culture from 1 lumen of the CVC has been shown in several studies to fail to diagnose bacteremia in some patients. Cultures should be drawn from the catheter and a peripheral vein or from all catheter lumens if a peripheral culture cannot be obtained. In the setting of a negative initial culture, repeat cultures should be obtained, and antibiotics should not be discontinued if clinical suspicion for bacteremia remains high.
6. “All patients with evidence of local catheter site infections should receive systemic antibiotic therapy.”
   When there is evidence of local catheter site infection, topical antibiotics may be sufficient if blood culture results are negative and there is no clinical concern for systemic infection.
7. “The patient has a CVC and is febrile. He is also complaining of abdominal discomfort. We drew blood cultures and started antibiotics prior to admitting him to the general pediatric service.”
   The presence of a CVC does not mean that the source of the patient’s fever is always the catheter. In this case, a thorough examination would have revealed right lower quadrant tenderness and guarding, and prompted further evaluation for intra-abdominal pathology.
8. “The patient remained hypotensive after receiving a total of 60 mL/kg of normal saline in the first hour in addition to antibiotics. Dopamine was initiated; however, we had to titrate up on the dose due to persistent hypotension.”
   In patients with fluid refractory shock after appropriate resuscitation, inotropes should be started. If shock persists after the initiation of inotropic support with the appropriate escalation to additional inotropes as needed, hydrocortisone should be considered. Additional considerations include correcting electrolyte abnormalities and administering blood products if anemia or thrombocytopenia are present.
9. “An oncology patient with a port presented with a reported history of fever. We obtained a blood culture and CBC with differential and determined that the patient was not neutropenic. We gave him a dose of ceftriaxone and told him to follow up with his oncologist as needed.”
   Well-appearing, nonneutropenic patients with a CVC may not require admission to the hospital when presenting with fever. However, proper follow-up is essential. It is necessary to be in communication with the patient’s primary care service (ie, oncology) and ensure that there is timely follow-up of the cultures drawn. Furthermore, it should be confirmed that the patient will be able to return to the hospital in the event of a positive culture or clinical deterioration.
10. “The patient’s blood culture grew coagulase-negative staphylococci at 20 hours, and he was called back into the ED. He is well-appearing now, so we did not start antibiotics.”
    Coagulase-negative Staphylococcus is a common skin micro-organism that is often a contaminant in blood cultures. However, it can also be pathogenic in these patients, and it cannot be determined to be a contaminant if only 1 blood culture is drawn and found to be positive. Treatment should be continued until an additional blood culture can be drawn and determined to be negative.

Tables

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study will be included in bold type following the references, where available. The most informative references cited in this paper, as determined by the author, will be noted by an asterisk (*) next to the number of the reference.

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2. Jobson M, Sandrof M, Valeriote T, et al Decreasing time to antibiotics in febrile patients with central lines in the emergency department. Pediatrics. 2015;135(1):e187-e195. (Quality improvement study)
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33. Silverstein DM, Moylan K. Cause and outcome of central venous catheter infections in paediatric haemodialysis patients. Nephrol Dial Transplant. 2010;25(10):3332-3337. (Retrospective review; 39 patients)
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36. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control. 2011;39(4 Suppl 1):S1-S34. (Practice guidelines)
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51. Andreola B, Bressan S, Callegaro S, et al. Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department. Pediatr Infect Dis J. 2007;26(8):672-677. (Prospective study; 408 children)
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