Ken Miller MD PhD

Objectives

· Define the symptom complex associated with influenza and its age-related variations.

· Identify the mode of transmission of the influenza virus.

· Define antigenic drift and antigenic shift and their importance in influenza prevention strategies.

· Identify age-related complications of influenza.

· Briefly review symptoms and management of dehydration, febrile seizures and respiratory distress in children.

· Identify some of the strategies for managing acute dyspnea when some combination of CHF, COPD and pneumonia are possible but the diagnosis is unclear.

· Review options for prevention and treatment of influenza among health care providers.

1999's influenza incidence seemed to be higher than in 1998, but not as bad as1997. It’s a good time to review some of the complications of influenza in certain patient populations as well as some of the related seasonal infectious diseases that are encountered in routine EMS operations. The influenza season also effects firefighter wellbeing. There are several new drugs available against influenza and a new vaccine that may become available before our next influenza season. We’ll review influenza, its complications, its prevention in firefighters & healthcare workers as well as other significant seasonal infectious diseases.

Influenza

If you haven’t had it yet, here’s what you’re missing. Influenza is characterized by a febrile illness with upper respiratory symptoms, headache and muscle aches. The exact nature of the symptoms depends somewhat on the age of the patient. Adults tend to have the most common symptoms of fever, cough, runny nose and sore throat, headache, chills, muscle aches and fatigue. Although no symptom complex is diagnostic of influenza, this is the most common presentation. Notably, children tend to have a slightly different symptom complex. Children still have fever, cough and runny nose but they tend to have a higher incidence of vomiting and diarrhea. Children may also have a non-specific febrile illness or may present with croup or bronchitis just like the many other respiratory viruses that occur during the same season as influenza. This will become important when we talk about complications of influenza and EMS interventions. The elderly tend to have fewer and more vague symptoms like just fever and cough but are at risk for more complications. Only laboratory tests for the virus can confirm the causative agent as influenza, but these are rarely done in non-hospitalized patients. In otherwise healthy persons these symptoms are self-limiting and resolve within a week or so. Cough and fatigue may persist longer, sometimes several weeks.

Influenza virus is spread from person to person by respiratory aerosols created by sneezing, coughing or talking. Respiratory aerosols or secretions on the hands can also transmit the virus when the hand contacts the nose or mouth. The virus lives and replicates in the respiratory mucosa. The incubation period for influenza is short, 1-4 days. This makes it very easy for infected persons to transmit the virus to others. Virus shedding is the process of virus particles appearing in secretions, in this case respiratory secretions, and is the time interval during which transmission to other persons is possible.

In influenza, peak virus shedding occurs from about one day before symptom onset to about 3 days afterwards. This would be the period of maximum transmissibility from an infected person to an uninfected person.

There are two forms of influenza that infect humans: Influenza A and Influenza B. Influenza B tends to cause more mild clinical disease. During the cold and flu season cooler weather keeps people in closer contact facilitating respiratory droplet and aerosol transmission. The reason these viruses cause recurrent problems has to do with the way the virus protects itself from our body defenses. These properties are antigenic drift and antigenic shift. An antigen is a chemical structural component that stimulates the production of antibodies. These antibodies then neutralize the antigen and prevent or minimize the effect of the antigen on the body. Sometimes these antigen-antibody reactions cause clinical symptoms of allergy like urticaria (the raised, red, blanching, itchy rash), bronchospasm or the shock state of anaphylaxis. These are the extremes of antigen-antibody reactions. Antigen-antibody reactions usually are protective and occur without producing any symptoms at all. There are two antigenic components of the influenza virus (a hemagglutinin and a neuraminidase, if you feel the need to know). Antibodies are produced to these two components. Changes in these antigens from one season to another will prevent last season’s antibodies from being effective. Small changes in these antigens are called antigenic drift. The nature of the antigens drifts just enough to be unrecognizable to the antibodies produced to a previous influenza virus. This is why vaccination against influenza must be done annually. As long as the antigenic drift matches the antigens in the vaccine the body will have produced antibodies from the vaccine to neutralize the virus. Occasionally, and fortunately infrequently, a major change in the antigens on the Influenza A virus occurs. This antigenic shift results in a virus different from those seen in previous years with no immunity in humans. This results in large epidemics or even worldwide pandemics and usually occurs when influenza viruses that normally infect birds or pigs are transmitted to humans. This happened in this century in 1918, 1957, 1968 and 1977.

Complications of Influenza

We can’t fix influenza. However, fire service EMS may be called on to manage the complications of influenza. The best way to look at this problem is by age group.

We mentioned that children tend to have somewhat more gastrointestinal symptoms with influenza along with the respiratory symptoms compared to adults. As with any illness in a child that causes vomiting and diarrhea the biggest risk is dehydration. Signs of dehydration can be subtle. Hypotension is a very late sign indicating extreme dehydration or sepsis. Tachycardia is also an unreliable sign because it may be a result of fever or crying. Capillary refill can be helpful. It should be brisk (less than 2-3 seconds) in the skin of the forehead, lip or at the nailbed. Skin tenting may follow moderate dehydration when skin is gently pinched between the thumb and index finger. Normally the skin relaxes back quickly. Mental status is probably the most sensitive but also most subtle sign of clinically significant dehydration. In older verbal children, as in adults, mental status can be assessed using the Glasgow Coma Scale. In younger preverbal children more subtle behavioral changes become important. Absence of appropriate stranger anxiety, crying and evasive maneuvers from the examiner all suggest a reduced level of alertness. The crying vigorous child is a good sign. Weak or absent crying and indifference are bad signs.

Febrile seizures are certainly possible as with any other febrile viral illness. Toweling off with a wet towel and fanning for evaporative heat loss is the most efficient cooling measure. A single brief seizure with a fairly rapid return to normal mental status is typical of uncomplicated febrile seizures. Persistent or recurring seizures will require supplemental oxygen by mask or blow-by, airway suction if needed to keep the airway clear, IV access if possible and either IV or IM midazolam (Versed). The dose is 0.1mg/kg IV up to 5mg or 0.2mg/kg IM up to 10mg. The additional advantage of IV access is that a saline fluid bolus of 20ml/kg can also be given to address the insensible fluid losses of sustained high fever and the reduced oral intake of fluids during illness.

A rare complication in children and young adults is Reye’s Syndrome. This syndrome is characterized by rapidly progressive mental status changes after seeming improvement from a viral syndrome like influenza or varicella (chicken pox). The cause of the syndrome is unknown but is associated with the use of salicylates (like aspirin) for fever control. Cerebral edema causes vomiting, altered mental status, decorticate or decerebrate posturing and seizures. Liver dysfunction is also part of this syndrome. Prehospital management would be oxygenation and ventilation as needed, slight head-up position, IV access if possible, and IV or IM midazolam (Versed) to control seizures.

Respiratory complications are common. In children these may be croup, bronchitis, bronchiolitis, pneumonia or bronchospasm. In adults and the elderly these may be bronchitis, pneumonia or worsening of pre-existing CHF, COPD or asthma. In all these age groups the emergency condition would be respiratory failure or hypoxia. Hypoxia will be evident by a pulse oximeter reading of 95% hemoglobin saturation or below. Serious hypoxia will be a pulse oximeter reading in the 80’s or below. Respiratory distress may be seen by tachypnea, tachycardia, and accessory muscle use in children and adults. Accessory muscles of respiration are the neck (sternocleidomastoid and scalene) muscles and the shoulder and chest (pectoralis major and minor) muscles. These muscles assist the intercostal muscles with rib and chest expansion to augment lung tidal volume. That’s why in the extreme case the patient will be sitting straight upright, head and neck held up and anchoring the hands or arms on something stationary (the tripod position). Anchoring the arms helps transfer the force of the shoulder muscles to the chest. In children, nasal flaring and intercostal and subclavicular retractions will also indicate increased respiratory effort. Any of these signs would indicate the need for supplemental oxygen by nasal cannula or nonrebreather mask. Croup may improve with aerosolized saline. The narrowing of the upper airway from mucosal swelling in croup results in stridor. Usually stridor is evident only during coughing episodes. More severe cases of croup may have stridor at rest during otherwise quiet breathing, use of accessory muscles of respiration and even hypoxia by pulse oximetry. These patients will need further in hospital care possibly including aerosolized epinephrine and steroids. Pneumonia can present with signs of respiratory distress, wheezing from bronchospasm, hypoxia by pulse oximetry and even sepsis in severe cases. Occasionally there is a case of primary influenza pneumonia but this is unusual. These patients can be quite ill. More commonly a respiratory viral pneumonia or a secondary bacterial pneumonia can follow influenza. The very young and the very old are at highest risk of acquiring pneumonia and its complications. Wheezing should respond to aerosolized albuterol. Even in the absence of wheezing, albuterol may be helpful in the setting of clinical pneumonia with hypoxia by pulse oximetry. Bronchodilators like albuterol may improve oxygenation and help the patient cough up secretions.

Lung infections can worsen underlying congestive heart failure or other lung diseases like emphysema, chronic bronchitis and asthma. This can create a very difficult field clinical assessment. Sometimes the physical exam will be helpful. If the patient has a history and medications for CHF but now has a recent fever, productive cough, dyspnea, and pronounced crackles at the base of one lung then the likelihood of pneumonia is high and specific field treatment for CHF is probably not necessary. However, a patient with a history and medications for CHF and COPD now with worsening cough and dyspnea with no fever but with diffuse bilateral crackles is a different problem. Cough can be an early sign of subclinical bronchospasm or respiratory secretion accumulation from any cause. Diffuse bilateral crackles are also nonspecific. These symptoms and signs could represent worsening CHF, COPD or developing pneumonia (especially a viral pneumonia). Field treatment for pneumonia is supplemental oxygen, and possibly IV fluids for dehydration associated with fever and reduced oral fluid intake. Albuterol may be helpful for wheezing or significant hypoxia. Of course IV fluids would be contraindicated in CHF. Vasodilators like nitroglycerine and morphine may be helpful for CHF but may cause hypotension in the dehydrated pneumonia or COPD patient. Sedation from morphine may worsen the hypoxia from pneumonia and COPD without the benefit of unloading the heart like it does in CHF. So the wrong therapy for the wrong disease can be potentially harmful.

One solution to this dilemma is to start the decision making process by considering the severity of the patient’s symptoms. If the patient is quite stable with no hypoxia by pulse oximeter, no dysrhythmia and reasonably normal vital signs then supplemental oxygen and position of comfort may be the only therapy needed. Nonemergent treatments can await chest x-ray to help determine the most probable diagnosis. For moderate dyspnea albuterol aerosol alone may be both safe and helpful in relief of subjective symptoms when the diagnosis is unclear. The challenge comes when the patient has severe dyspnea, hypoxia by pulse oximetry and other abnormal vital signs. In the acutely dyspneic patient who could have any combination of CHF, COPD or pneumonia, albuterol aerosols are still a safe and potentially effective initial intervention along with initial supplemental oxygen and position of comfort. Here IV access is desirable in case further deterioration occurs. If the patient remains normotensive or hypertensive then it is probably safer to avoid IV fluid boluses and morphine when the diagnosis is unclear. Instead, sublingual nitroglycerine is probably the safest and potentially effective intervention when CHF is considered to be a likely contributor to the acute dyspnea. Things get a little more complicated when the patient is hypotensive. In the patient with CHF, COPD and now possibly pneumonia, hypotension may represent pulmonary edema with cardiogenic shock, sepsis or hypovolemia from dehydration. If acute dyspnea with hypoxia by pulse oximetry and diffuse bilateral crackles are still part of the picture along with hypotension then supplemental oxygen, albuterol aerosols, supine position or position of comfort and IV access would remain initial interventions. Careful IV saline boluses of 250-500 cc with re-evaluation after each bolus and dopamine for refractory hypotension would be the next line therapies. Expeditious transport to the emergency department should be occurring simultaneously or close behind.

High call volume times with lots of patients sick with similar symptoms can be a somewhat high-risk time for missing complications. Be alert for complications like these and think each patient through before making triage decisions.

Firefighter Wellbeing

The influenza season can be tough on fire service personnel as well. Increased sick call, working with mild to moderate symptoms of various viral illnesses and constant exposure to ill patients with a transmissible disease are all part of the season. Hospital emergency department saturation and associated longer transport times and logistics add to the stress of the job.

Annual vaccination remains the only effective means of preventing influenza. Occasionally antigenic drift occurs different from that predicted by the vaccine designers and limited immunity results. This however is not usual. Because of the potential repeated exposures of firefighters to ill patients, annual vaccination will help prevent primary influenza infection in our personnel and reduce the rate of transmission of the disease within fire stations and home to the family. Other general vaccination guidelines against influenza from the Centers for Disease Control and Prevention include individuals who would be at increased risk of complications of influenza: older than 65, chronic illnesses, lung or cardiovascular disease, immunosupression and women who will be in the second or third trimester of pregnancy during the influenza season. The influenza vaccine is produced in eggs so persons with known egg protein allergy should not receive the vaccine. Vaccination generally confers immunity in 60-90% of children and adults, and somewhat less in the elderly. The current influenza vaccine is an inactivated injected vaccine. In the foreseeable future a new vaccine may be approved. This vaccine is a live attenuated vaccine that is administered intranasally. This route produces more antibodies in the respiratory tract where the virus makes first contact with the body and should result in a more immediate antibody response following exposure to the virus from an infected person.

There are some antiviral drugs available against influenza. Amantadine (Symmetrel) and rimantadine (Flumadine) have been available for some time but are effective only against Influenza A. Both must be administered within 48 hours of symptom onset to have an effect and even then they simply shorten the course of the disease by a few days. They are not curative. Rimantadine has a better safety profile than amantadine. They can be used to prevent illness in unvaccinated persons too, but must be taken throughout the influenza season while new cases are still occurring. There is drug resistance to these antiviral drugs among Influenza A viruses.

Two new antiviral drugs effective against both Influenza A and B have become available and the FDA has approved one for use in the US. Zanamivir (Relenza) is available as an inhaled powder in the US for treatment of influenza. Oseltamivir (Tamiflu) is an oral antiviral drug just very recently approved for use in the US. They too must be administered within 36 hours of the onset of symptoms to be effective in shortening the duration of illness. They are also not curative. Like the others they can be used to prevent illness in unvaccinated persons but neither drug is currently approved for prophylactic use nor are they yet approved for use in children. Since zanamivir is new it is unlikely to be covered by healthcare plans yet. The wholesale cost of zanamivir and its Diskhaler for 5 days of treatment is approximately $45.

Otherwise treatment of uncomplicated influenza is symptomatic: fever control with Tylenol or Motrin (which also works for the muscle aches and headache), oral fluid hydration, cough suppressant and decongestant. Keep in mind that over-the-counter medicines can have drug-drug interactions with prescribed medicines and may have contraindications in certain medical conditions. Read the label and talk to your doctor.

References

Cox, NJ, Subbarao, K, Influenza, Lancet 1999; 354(9186): 1277.

Cox, NJ, Fukuda, K, Influenza, Infectious Disease Clinics of North America 1998, 12(1): 27.

Webster, RG, Influenza: An Emerging Disease, Emerging Infectious Diseases 1998, 4(1):1.

Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices, Morbidity and Mortality Weekly Report 1999; 48(RR-4): 1.

Brammer, L, Arden, N, Regnery, H, Schmeltz, L, Fukuda, K, Cox, N, Chapter 5: Influenza, www.cdc.gov/nip/publications/manuals/wpd/influenza.