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While generally associated with mild infections, seasonal influenza can have serious complications beyond its well-known respiratory manifestations, which claim up to 650,000 lives annually world-wide. Accumulating data suggest that cardiovascular effects also account for significant influenza-related morbidity and mortality. These include , which is often asymptomatic and can be fatal in otherwise healthy patients, particularly with early presentation.

The Case

A 14-year-old female presents to your family practice with a high fever of 39°C and flu-like symptoms. Otherwise, she is in good health. You prescribe ibuprofen to relieve the fever. Her temperature returns to normal (35°C) by the following day.

That morning, however, she develops referred pain to the abdomen and pain in both legs. She has no skin rash or neck stiffness. Over the course of the day, her abdominal pain worsens. Late that afternoon, her parents contact emergency medical services. Before their arrival 30 minutes later, she begins to have difficulty breathing and develops tachypnea.

On assessment by paramedics, the patient describes referred pain to the abdomen. They note tachycardia (200 beats/min) and 60% peripheral oxygen saturation.

Treatment and Outcome

Before paramedics are able to take her blood pressure, the patient loses consciousness and goes into cardiac arrest. Use of cardiac massage and automated external defibrillation are not successful.

Emergency physicians arrive and proceed to intubate and ventilate the patient, and administer epinephrine (15 mg intravenously and 3 mg intratracheally), norepinephrine (1 μg/kg/min) and bicarbonates. The team performs cardiopulmonary resuscitation. After 1 hour, the patient has not responded and is pronounced dead at 8:30 p.m., just over 24 hours after her visit to your office related to her initial fever and flu-like symptoms.

Case Follow-up

Medical findings on autopsy included the following:

• Nasopharyngeal and throat specimens were positive for A (H3N2) influenza, of the 3C.2a clade, the most frequent of the circulating H3N2 strains, but negative for other respiratory viruses
• Myocardial tissue, pericardial fluid, and cerebrospinal fluid were negative for influenza virus
• Evidence of nascent influenza pneumonia was detected
• Pericardium in tension and significant pericardial effusion postmortem (160 mL) were observed

Microscopic findings included:

• Interstitial edema with an abundant mononuclear inflammatory infiltrate
• Multiple foci sources of myocardial necrosis with contraction bands in both ventricles and the septum
• Lymphocytic inflammatory infiltrate in the epicardium
• Indicated pericarditis (Figure).
• Congestive lung walls with a lymphoplasmacytic inflammatory infiltrate
• Hemorrhagic alveolar edema in right lung infiltrate

Illustration of the cardiac tissue, postmortem histopathological examination (Hemalin Phloxin Safran coloration; 400.) Inflammatory infiltrate with myocardic necrosis is shown in one field of cardiac tissue (solid arrow); multifocal lesions with myocardic edema are shown (dashed arrows).

Supporting evidence for this hypothesis includes abdominal referred pain, tachypnea, tachycardia, rapid cardiac arrest, autopsy evidence of significant pericardial effusion, and no arrhythmia requiring external electrical shock.

Discussion

Pediatric myocarditis is an important cause of acute cardiovascular death – early diagnosis and aggressive treatment are necessary to save the patient.

While enteroviruses, especially group B coxsackieviruses, are the most common viral causes of myopericarditis, influenza infection is associated with a wide range of cardiac complications. These from mild pericarditis to relatively rare cases of debilitating and potentially fatal inflammatory cardiomyopathy.

Cardiac effects typically develop 4 to 9 days following onset of flu symptoms, and may include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat.

Although often not clinically evident, myocardial involvement in influenza infections is reported to range from 0% to 11% -- the precise prevalence of cardiac manifestations of influenza is unknown due to wide variations in presentation. Fulminant myocarditis in seasonal influenza patients has a reported mortality rate of about 25%.

Importantly, while influenza viruses account for 2% to 10% of all viral agents detected in myocardial tissues, influenza may not be detected in many biopsies of patients, despite having directly invaded the myocardium.

Cardiovascular complications associated with influenza infection are not fully understood – coagulopathy, an increase in inflammatory cytokines, and temporary endothelial dysfunction may be involved.

Antiviral treatment should be administered as early as possible for patients with confirmed or suspected influenza who have a severe, complicated, or progressive illness, or those at risk for serious influenza-related complications.

Importantly, influenza vaccination of high-risk patients has been shown to decrease cardiovascular mortality during influenza outbreaks.

Limitations

Due to the rapid deterioration of the patient's condition, interpretation of this case report is limited by the lack of assessment of biochemical parameters, cytokines, and echocardiographic findings, the latter of which might have identified systolic dysfunction with an impaired left ventricular function.

Conclusion

Physicians treating young patients with influenza infection should be aware of the rare potential for pericardial effusion myopericarditis, despite having no known risk factors. Respiratory distress and unstable hemodynamics are often the only signs of a rapidly deteriorating cardiac status.