Impact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model

Guillaume Poliquin, Duane Funk, Shane Jones, Kaylie Tran, Charlene Ranadheera, Mable Hagan, Kevin Tierney, Allen Grolla, Amrinder Dhaliwal, Alexander Bello, Anders Leung, Cory Nakamura, Darwyn Kobasa, Darryl Falzarano, Lauren Garnett, Hugues Fausther Bovendo, Heinz Feldmann, Murray Kesselman, Gregory Hansen, Jason GrenGeorge Risi, Mia Biondi, Todd Mortimer, Trina Racine, Yvon Deschambault, Sam Aminian, Jocelyn Edmonds, Ray Sourette, Mark Allan, Lauren Rondeau, Sharron Hadder, Christy Press, Christine DeGraff, Stephanie Kucas, Bradley W.M. Cook, B. J. Hancock, Anand Kumar, Reeni Soni, Darryl Schantz, Jarrid McKitrick, Bryce Warner, Bryan D. Griffin, Xiangguo Qiu, Gary P. Kobinger, Dave Safronetz, Derek Stein, Todd Cutts, James Kenny, Geoff Soule, Robert Kozak, Steven Theriault, Liam Menec, Robert Vendramelli, Sean Higgins, Guodong Liu, Niaz Md Rahim, Samantha Kasloff, Angela Sloan, Shihua He, Nikesh Tailor, Michael Gray, James E. Strong

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: There are currently limited data for the use of specific antiviral therapies for the treatment of Ebola virus disease (EVD). While there is anecdotal evidence that supportive care may be effective, there is a paucity of direct experimental data to demonstrate a role for supportive care in EVD. We studied the impact of ICU-level supportive care interventions including fluid resuscitation, vasoactive medications, blood transfusion, hydrocortisone, and ventilator support on the pathophysiology of EVD in rhesus macaques infected with a universally lethal dose of Ebola virus strain Makona C07. Methods: Four NHPs were infected with a universally lethal dose Ebola virus strain Makona, in accordance with the gold standard lethal Ebola NHP challenge model. Following infection, the following therapeutic interventions were employed: continuous bedside supportive care, ventilator support, judicious fluid resuscitation, vasoactive medications, blood transfusion, and hydrocortisone as needed to treat cardiovascular compromise. A range of physiological parameters were continuously monitored to gage any response to the interventions. Results: All four NHPs developed EVD and demonstrated a similar clinical course. All animals reached a terminal endpoint, which occurred at an average time of 166.5 ± 14.8 h post-infection. Fluid administration may have temporarily blunted a rise in lactate, but the effect was short lived. Vasoactive medications resulted in short-lived improvements in mean arterial pressure. Blood transfusion and hydrocortisone did not appear to have a significant positive impact on the course of the disease. Conclusions: The model employed for this study is reflective of an intramuscular infection in humans (e.g., needle stick) and is highly lethal to NHPs. Using this model, we found that the animals developed progressive severe organ dysfunction and profound shock preceding death. While the overall impact of supportive care on the observed pathophysiology was limited, we did observe some time-dependent positive responses. Since this model is highly lethal, it does not reflect the full spectrum of human EVD. Our findings support the need for continued development of animal models that replicate the spectrum of human disease as well as ongoing development of anti-Ebola therapies to complement supportive care.

Original languageEnglish (US)
Article number54
JournalIntensive Care Medicine Experimental
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

Keywords

  • Ebola
  • Fluid
  • Hydrocortisone
  • NHP
  • Pathophysiology
  • Supportive care
  • Vasoactives
  • Ventilatory support

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology (medical)
  • Emergency Medicine

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