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

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dc.contributor.authorPoliquin, Guillaume
dc.contributor.authorFunk, Duane
dc.contributor.authorJones, Shane
dc.contributor.authorTran, Kaylie
dc.contributor.authorRanadheera, Charlene
dc.contributor.authorHagan, Mable
dc.contributor.authorTierney, Kevin
dc.contributor.authorGrolla, Allen
dc.contributor.authorDhaliwal, Amrinder
dc.contributor.authorBello, Alexander
dc.contributor.authorLeung, Anders
dc.contributor.authorNakamura, Cory
dc.contributor.authorKobasa, Darwyn
dc.contributor.authorFalzarano, Darryl
dc.contributor.authorGarnett, Lauren
dc.contributor.authorBovendo, Hugues F
dc.contributor.authorFeldmann, Heinz
dc.contributor.authorKesselman, Murray
dc.contributor.authorHansen, Gregory
dc.contributor.authorGren, Jason
dc.contributor.authorRisi, George
dc.contributor.authorBiondi, Mia
dc.contributor.authorMortimer, Todd
dc.contributor.authorRacine, Trina
dc.contributor.authorDeschambault, Yvon
dc.contributor.authorAminian, Sam
dc.contributor.authorEdmonds, Jocelyn
dc.contributor.authorSourette, Ray
dc.contributor.authorAllan, Mark
dc.contributor.authorRondeau, Lauren
dc.contributor.authorHadder, Sharron
dc.contributor.authorPress, Christy
dc.contributor.authorDeGraff, Christine
dc.contributor.authorKucas, Stephanie
dc.contributor.authorCook, Bradley W M
dc.contributor.authorHancock, B. J
dc.contributor.authorKumar, Anand
dc.contributor.authorSoni, Reeni
dc.contributor.authorSchantz, Darryl
dc.contributor.authorMcKitrick, Jarrid
dc.contributor.authorWarner, Bryce
dc.contributor.authorGriffin, Bryan D
dc.contributor.authorQiu, Xiangguo
dc.contributor.authorKobinger, Gary P
dc.contributor.authorSafronetz, Dave
dc.contributor.authorStein, Derek
dc.contributor.authorCutts, Todd
dc.contributor.authorKenny, James
dc.contributor.authorSoule, Geoff
dc.contributor.authorKozak, Robert
dc.contributor.authorTheriault, Steven
dc.contributor.authorMenec, Liam
dc.contributor.authorVendramelli, Robert
dc.contributor.authorHiggins, Sean
dc.contributor.authorLiu, Guodong
dc.contributor.authorRahim, Niaz M
dc.contributor.authorKasloff, Samantha
dc.contributor.authorSloan, Angela
dc.contributor.authorHe, Shihua
dc.contributor.authorTailor, Nikesh
dc.contributor.authorGray, Michael
dc.contributor.authorStrong, James E
dc.date.accessioned2019-10-01T06:07:08Z
dc.date.issued2019-09-13
dc.date.updated2019-10-01T06:07:08Z
dc.description.abstractAbstract 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.
dc.identifier.citationIntensive Care Medicine Experimental. 2019 Sep 13;7(1):54
dc.identifier.urihttps://doi.org/10.1186/s40635-019-0268-8
dc.identifier.urihttp://hdl.handle.net/1993/34317
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderThe Author(s).
dc.titleImpact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model
dc.typeJournal Article
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