Failure of combination oral oseltamivir and inhaled zanamivir antiviral treatment in ventilator- and ECMO-treated critically ill patients with pandemic influenza A (H1N1)v

Scand J Infect Dis. 2011 Jul;43(6-7):495-503. doi: 10.3109/00365548.2011.556144. Epub 2011 Feb 10.

Abstract

Objective: The objective of this study was to describe the clinical course of severe and complicated pandemic (H1N1)v infection treated with oral oseltamivir and inhaled zanamivir in a series of intensive care patients.

Methods: We investigated a case series of patients with respiratory failure and a positive (H1N1)v real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Treatment consisted of oseltamivir tablets 75 mg × 4 daily in a nasogastric tube plus zanamivir intravenous (i.v.) solution 25 mg × 4 daily as inhalation. Ventilator inspiratory plateau airway pressure in the ventilator was kept below 30 cmH₂O, PaO₂ above 8 kPa and pH above 7.30. If this could not be achieved, inhalational nitric oxide (NO) was added or extracorporeal membrane oxygenation (ECMO) was initiated.

Results: Twenty-one patients were admitted, with a median age of 50 y (range 6-69 y). Five patients (23.8%) died in the intensive care unit (ICU) and 1 patient died 2 weeks after ICU discharge. Nine patients received ECMO treatment, of whom 3 died during ECMO (33.3%; 3/9) and 1 at 2 weeks after. The mortality in patients not receiving ECMO treatment was 16.6% (2/12). Sixteen patients (76%) were influenza PCR-positive on day 7 after the start of antiviral treatment. Irreversible presumed lung fibrosis complicated with pneumothorax was common. A high Murray score at admission was significantly associated with a fatal outcome.

Conclusions: The mortality in these patients was high despite combined antiviral treatment with oseltamivir and zanamivir. Patients shed virus for a long time despite intensive therapy. Optimal management of patients with bilateral pneumonia and respiratory failure caused by (H1N1)v still needs to be determined.

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Child
  • Critical Illness
  • Drug Therapy, Combination / methods
  • Extracorporeal Membrane Oxygenation*
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / isolation & purification*
  • Influenza, Human / drug therapy*
  • Influenza, Human / mortality
  • Influenza, Human / virology
  • Male
  • Middle Aged
  • Oseltamivir / administration & dosage*
  • Respiration, Artificial*
  • Time Factors
  • Treatment Failure
  • Virus Shedding
  • Zanamivir / administration & dosage*

Substances

  • Antiviral Agents
  • Oseltamivir
  • Zanamivir