A case report published Online First and in a future edition of The Lancet documents the case of a 22-year-old woman who survived a serious case of swine-flu. She was treated with the unlicensed intravenous form of relenza, in combination with high-dose corticosteroids. Her immune system was impaired due to recent chemotherapy. The article is the work of Dr Michael Kidd and Dr Mervyn Singer, University College London Hospitals NHS Foundation Trust, London, UK, and colleagues.
The woman had received chemotherapy as part of treatment for Hodgkin’s disease. She was referred on the 8 of July 2009 to the Intensive Care Unit (ICU) at the University College Hospital. She had laboratory-confirmed H1N1 infection, increasing shortness of breath, build-up of fluid in both lungs. Her condition was not responding either to tamiflu (75mg twice daily) or broad-spectrum antimicrobials. Her progressive deterioration indicated she needed artificial ventilation from the third day of her ICU admission. Since she did not appear to be absorbing the tamiflu, this was switched to nebulised relenza for ICU days 6 to13. However this had no noticeable clinical benefit. High levels of H1N1 RNA were detected on the tenth day in ICU. Increasing the relenza dose for ICU days 13 to16 did not improve her clinical state.
She remained critically ill with severe respiratory failure. For that reason, doctors decided on day 16 to begin treatment using unlicensed intravenous relenza provided by GlaxoSmithKline. Permission for the treatment was granted by the hospital and a close relative. Treatment with the corticosteroid methylprednisolone was also started to treat the lung inflammation. The patient’s condition improved within 48 hours. H1N1 viral load had decreased over 100-fold by ICU day 21. She was extubated the same day. She then was discharged back to the ward after 24 days in ICU. Inhaled relenza was sustained as a precaution due to her immunocompromised state.
The authors explain: “Since her inflamed, atelectatic lungs were probably impeding adequate drug absorption, and clinical improvement was not forthcoming, we decided to use intravenous (unlicensed) zanamivir. High dosing achieves effective respiratory epithelial concentrations and is well-tolerated. Our patient progressively recovered with no drug related side-effects.”
Atelectatic lungs have numerous small areas of collapse filled with fluid and possibly dead material.
Generally, deaths due to pandemic H1N1 influenza are associated to severe respiratory failure, or acute respiratory distress syndrome (ARDS). The authors point out that persistent high level H1N1 replication may drive ongoing lung inflammation. In this case, the intravenous relenza and high-dose corticosteroids may possibly have worked together. However, this may be considered controversial. In addition, high-dose corticosteroids are not recommended in swine influenza treatment guidelines. The authors mention: “However, controlled trials are lacking and a rationale does exist for the use of corticosteroids in ARDS.”
They write in conclusion: “Although this is a single case report and direct cause and effect cannot be confirmed, the improvement in clinical status following intravenous relenza encourages prompt further investigation, both alone and in combination with high-dose methylprednisolone.”
“H1N1 pneumonitis treated with intravenous zanamivir”
I Michael Kidd, Jim Down, Eleni Nastouli, Rob Shulman, Paul R Grant, David CJ Howell, Mervyn Singer
Written by Stephanie Brunner (B.A.)