Influenza in the Emergency Department: 2020 Update (Pharmacology CME)

Table of Contents

 

Patients presenting to the ED with “influenza-like illness” (cough, sore throat, fever) are typical in the fall and winter. How can you tell whether a patient might have influenza and infect others with a potentially dangerous strain? Are the guidelines the same in the spring and summer?

How do symptoms of influenza differ between adults and children?

What are the patient groups that are at high risk for complications from influenza?

When does rapid influenza diagnostic testing reduce costs and improve care, and when is it unnecessary?

Does the prevalence of influenza in the community affect whether or not you should order testing?

When is antiviral medication indicated?

Which antiviral should be prescribed, and why?

What about the new antiviral drug on the market, baloxavir marboxil?

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Influenza Epidemiology
   1. Types of Outbreaks
   2. Seasonality and Transmission
6. Classification of Influenza Viruses
   1. Antigen Variations
7. Influenza Pathophysiology
   1. Influenza Vaccination
   2. The 2019-2020 Influenza Epidemic
8. Differential Diagnosis
9. Prehospital Care
10. Emergency Department Evaluation
11. Diagnostic Studies
12. Treatment
    1. The Neuraminidase Inhibitors
       1. Oseltamivir
       2. Zanamivir
       3. Peramivir
    2. The Adamantane Derivatives
    3. Baloxavir Marboxil
    4. Antiviral Resistance
    5. Chemoprophylaxis for Influenza
13. Antiviral Use in Pregnant Patients
14. Controversies and Cutting Edge
    1. Efficacy of Treatment With Antiviral Medications
15. Disposition
16. Summary
17. Time- and Cost-Effective Strategies
18. Risk Management Pitfalls for Managing Influenza in the Emergency Department
19. Case Conclusions
20. Clinical Pathways
    1. Clinical Pathway for Managing a Patient Who Presents to the ED With an Influenza-Like Illness
    2. Clinical Pathway for Managing a Patient Who Presents to the ED With an Influenza-like Illness When There is Low Regional Prevalence of Disease
21. Tables and Figures
    1. Table 1. Influenza Pandemics Over the Past 100 Years
    2. Table 2. Online Resources for Evaluation/Management of Influenza
    3. Table 3. Most Frequent Clinical Symptoms of Seasonal Influenza, by Age Group
    4. Table 4. Complications Associated With Influenza Infection in Adults
    5. Table 5. Clinical Considerations of Testing  When Influenza Prevalence Is Low
    6. Table 6. Clinical Considerations of Testing  When Influenza Prevalence Is High
    7. Table 7. Antiviral Treatment Recommendations from the Centers for Disease Control and Prevention
    8. Table 8. CDC Recommendations for Antiviral Medications for Treatment and Chemoprophylaxis of Influenza
    9. Figure 1. Schematic Diagram of an Influenza Virion
    10. Figure 2. Influenza Cases and Virus Strains, 2010-2017
    11. Figure 3. Effectiveness of Seasonal Influenza Vaccines From the 2005-2019 Flu Seasons
    12. Figure 4. Estimated United States Influenza Disease Burden, By Season (2010-2019)
    13. Figure 5. Year-to-Date Influenza Estimates, October 1, 2019 through February 15, 2020
22. References

Abstract

Emergency clinicians must be aware of current diagnostic and therapeutic recommendations for influenza and the resources available to guide management. This comprehensive review outlines the classification of these viruses, their pathophysiology, the identification of high-risk patients, and the importance of influenza vaccination. Seasonal variations of influenza are discussed, as well as the rationale for limiting testing during periods of high prevalence. Differences between strains of influenza are discussed, as well as the challenges in achieving optimal vaccine effectiveness. Recommendations for use of the currently available oral, intranasal, and intravenous antiviral treatments are provided, as well as utilizing shared decision-making with patients regarding risks and benefits of treatment.

Case Presentations

A 20-month-old boy presents to the ED with a cough and fever for 3 days. He has no past medical history, and his routine vaccinations are up-to-date. His parents say he has been eating less than usual; however, his urine output is normal, and he has had no vomiting or diarrhea. Vital signs are: temperature, 39.6˚C (103.2°F); heart rate, 156 beats/min; respiratory rate, 32 breaths/ min; and oxygen saturation, 100% on room air. He is well-appearing, although his left tympanic membrane is erythematous and bulging, with apparent middle-ear purulence. You make the diagnosis of otitis media in the setting of a presumed viral upper respiratory infection. While preparing the discharge papers, you consider the many patients you’ve seen during the current flu epidemic and wonder whether treatment for influenza would be appropriate . . .

Your next patient is a 32-year-old man with the same chief complaints: cough and fever. His maximum temperature over the past 5 days was 40˚C (103.9°F). He has been taking over-the-counter cold remedies without relief, and today he is markedly short of breath. The patient has no regular primary care provider and has no significant past medical history. His initial vital signs are: temperature, 39.2˚C (102.5°F); heart rate, 118 beats/min; respiratory rate, 28 breaths/min; blood pressure, 134/78 mm Hg; and oxygen saturation, 88% on room air. On examination, he appears uncomfortable, with notable tachypnea. The oropharynx is clear and the neck supple. Crackles are noted in the right lower lung field, without any wheezing. The abdomen is soft and nontender. The patient is given oxygen via face mask, with an improvement in saturation to 100%. Chest x-ray reveals a right lower lobar pneumonia with a small pleural effusion. You start IV antibiotics and request an inpatient bed, as he is hypoxic with his pneumonia. You wonder whether influenza testing is indicated, and if so, what type of test, and how reliable would it be?

Introduction

During the 1918–1919 influenza pandemic, approximately one-third of the world’s population was infected and approximately 50 million people died.¹ At that time, influenza pandemics were not new occurrences, but their mortality and morbidity had not been well documented and the causative organisms had not been identified. Fifty years later, it was estimated that the 1968 “Hong Kong” influenza pandemic (H3N2) caused between 1 and 4 million deaths worldwide. Despite advances in diagnostic and treatment strategies, mortality from influenza continues to increase, with over 30,000 deaths annually in the United States, partly related to the aging of the population.² With globalization, the need to contain regional influenza outbreaks has assumed more urgency to prevent an emerging pandemic. The emergency department (ED) plays a key role in disease outbreaks, since containment of a potential epidemic relies on early and rapid identification, treatment, and—in some cases—prophylaxis.

The medical costs and lost wages from influenza are substantial. According to the United States Centers for Disease Control and Prevention (CDC), influenza epidemics cost $10.4 billion per year in direct medical expenses and an additional $16.3 billion in lost earnings annually in the United States.^3,4 An influenza epidemic is responsible for 3.1 million hospitalized days, and 31.4 million outpatient visits annually (during the epidemic), with a total economic burden of $87.1 billion in the United States alone.⁴

This supplement to Emergency Medicine Practice presents an update to the 2018 review, based on a critical appraisal of the most current literature on influenza. Recent studies on clinical presentation, diagnosis, and treatment are reviewed, and recommendations on the evaluation and management of patients with suspected symptoms of influenza are provided. 2020 updates are highlighted in blue.

This update also includes an overview addendum on the emerging COVID-19 (novel coronavirus outbreak of 2019-2020), along with resources for up-to-date information on this novel virus outbreak.

Critical Appraisal of the Literature

PubMed, ISI Web of Knowledge, and the Cochrane Database of Systematic Reviews resources from 2012 to 2020 were accessed using the keywords: emergency department, epidemic, pandemic, influenza, novel H1N1, and H3N2. The CDC⁵ and the World Health Organization (WHO)⁶ websites were accessed. Guidelines from the American College of Emergency Physicians (ACEP),⁷ the Infectious Diseases Society of America (IDSA),⁸ and the American Academy of Pediatrics (AAP)⁹ were also reviewed. References from the literature were searched to identify additional content.

Influenza Epidemiology

Although precise data for influenza-related illness and sequelae are difficult to obtain, up to 20% of the United States population has been estimated to be infected with the influenza virus during the winter season.² Influenza disproportionately affects young children and elderly persons, and influenza deaths have increased substantially in the last 2 decades, in part due to the aging of the population.² Annual mortality in the United States from influenza typically ranges from 12,000 to 56,000 deaths; 140,000 to 710,000 patients are hospitalized each year; and 9.2 to 35.6 million patients present for treatment.^4,10

Morbidity and mortality from influenza can vary depending on a given population’s immunity to previous strains.¹¹ Historically, mortality from seasonal outbreaks disproportionately affects the elderly, with up to 90% of deaths occurring in people aged 65 years and older. In the pandemic of 2009, more significant outbreaks of disease were seen in the younger population, who had no (or weaker) immunity.^11,12

Risk Management Pitfalls for Managing Influenza in the Emergency Department

2. “The patient had an infiltrate on chest x-ray, so bacterial pneumonia appeared to be the clear diagnosis.”

Numerous secondary complications can stem from a primary influenza infection. When addressing and treating these complications, do not overlook the possibility of a primary influenza infection and the need for medical management. In certain clinical situations, treatment with antiviral medications as well as antibacterial medications may be indicated.

5. “My patient is pregnant and has influenza. The side-effect profile of antiviral medications concerns me, so I feel better treating her with supportive care.”

Pregnancy is a risk factor for a more severe disease course during an influenza infection. Initial CDC epidemiologic data from the last 10 influenza seasons indicate that some of the highest rates of morbidity and mortality are among pregnant women, which confirms the necessity of antivirals in this population.

7. “Flu is everywhere. I don’t have the time to consult the CDC website. I will just give oseltamivir to my patient and be done with it.”

Even in times of epidemic influenza infection, numerous strains can be circulating at a given time within a particular region. In past epidemics, there have been reports of influenza strains resistant to oseltamivir. Thus, without knowing the prevalence of local strains, one might mistakenly choose an antiviral agent that will prove less effective on those strains. Treatment with more than 1 agent may even be indicated in some regions until more formal strain-specific diagnostic testing can be undertaken. Since certain medications are effective against only influenza type A, the local prevalence of any type B influenza should be determined in order to select the appropriate drug therapy.

Tables and Figures

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 is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

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