Chertow: Influenza, coming soon to an ICU near you!

Clinical Pearls

• Influenza virus is a SS RNA virus with surface glycoproteins, HA (hemagglutinin) and NA (neuraminidase)
  • Antigens are made to combat the flu by targeting the HA and NA groups
    • Antigenic “drift”: the change year to year in the HA groups leading to less immunological protection year to year and a need for new immunizations
    •  18 HA + 11 NA subtypes, a combination leads to nomenclature and flu types (H1N1, H5N1….)
      • Nearly all found in birds, some in other species of animals (pigs, etc.) as a reservoir
        • Pigs and birds are “mixing vessels” that lead to new strains
    • Vaccines are recommended for all persons ≥ 6 months of age
      • Recent technology has made them well matched for all circulating strains (including H1N1)
        • Influenza B is always a guess, no data showing which will surface
• Risk factors for severe disease:
  • >65 yo, <5yo 
  • Obesity, BMI>40
  • Pre-existing Resp/Cardiac/Neuro conditions
  • Immune suppression
  • Pregnancy
• Sialic acids on respiratory epithelium are the preferred binding surface for influenza virions
  • Neuraminidase works to make a binding location on influenza- can be targeted for inhibition and thus limit influenza’s virulence
• Influenza predisposes to secondary bacterial damage by damaging epithelial airway linings
  • Starts with bronchiolitis → sloughing of epithelial layer→ necrotic debris
    • Fills alveoli with proteinaceous materials and inflammatory cells
  • Exposes binding sites on the basement membrane, increases bacterial adherence, and immune cell dysfunction
  • Increases morbidity and mortality overall (~death in 7 days)
  • Bacterial co-infection diagnosis is often delayed or inaccurate as testing is difficult
    • Clinical judgement predominates
• Diagnosis: Rapid antigen tests insensitive (50-70%)
  • Molecular testing = Gold standard
  • Collect nasopharyngeal swab/aspirate or a BAL
    • Synthetic NOT cotton swab (will interfere with the assay)
    • Collected w/in 7 days of symptom onset (or longer if its a BAL)
• Neuraminidase inhibitors (NAI)
  • 5 metaanalyses, 2 Cochrane reviews- Mixed reviews
    • In 2014 Munthiri et al.  showed that Neuraminidase inhibitors given earlier led to decreased mortality

• Based on this study we are now treating empirically, especially if early in the course.
• ICU recommendations:
  • NAI:
    • Oseltamivir 75mg PO BID (90-95% successful at viral treatment)
    • Peramivir IV x 5 days for those unable to tolerate enteral route
    • Zanamivir IV for those with Oseltamivir resistance (need to contact health officials!)
  • Antibiotics
    • Cover for CAP and MRSA PNA (reduces mortality)
  • Adjunct therapy
    • No benefits for rescue modalities for refractory hypoxia
    • No benefits for immune modulation (ex: statins)
    • Steroids may be harmful