ihearttriangles

5+ Year Member
Jul 29, 2010
78
18
PNW
Status
Resident [Any Field]
Obviously, the situation with Ebola in West Africa is utterly tragic. And I don't want to downplay the badness of this state of affairs but is anyone else seeing the opportunity for sepsis research here? I mean, this seems like an amazing opportunity to further our knowledge of resuscitation in sepsis akin to how traumatology gets advanced during war. I really hope that once things get a little more stabilized that research will begin in earnest.

Also, from everything I can gather via news sources, and granted this is not super reliable, patients are currently not receiving any intravenous fluid resuscitation. Patients are isolated and given PO fluids and that is about the extent of their "resuscitation." Am I missing something here? Most patients are dying of dehydration/MOD and it would seem prudent to give them some IV fluids. Are there no IVFs, no one to start them, or do the treating docs just have a different approach?
 
  • Like
Reactions: Michele Stagnaro

jdh71

Grim Optimist.
10+ Year Member
Dec 14, 2006
68,151
48,071
Last House on the Block, USA
Status
Attending Physician
Obviously, the situation with Ebola in West Africa is utterly tragic. And I don't want to downplay the badness of this state of affairs but is anyone else seeing the opportunity for sepsis research here? I mean, this seems like an amazing opportunity to further our knowledge of resuscitation in sepsis akin to how traumatology gets advanced during war. I really hope that once things get a little more stabilized that research will begin in earnest.

Also, from everything I can gather via news sources, and granted this is not super reliable, patients are currently not receiving any intravenous fluid resuscitation. Patients are isolated and given PO fluids and that is about the extent of their "resuscitation." Am I missing something here? Most patients are dying of dehydration/MOD and it would seem prudent to give them some IV fluids. Are there no IVFs, no one to start them, or do the treating docs just have a different approach?
Bro. This is WEST Africa. That's resuscitation over there.
 
  • Like
Reactions: ihearttriangles
Oct 5, 2014
1
0
http://www.bmj.com/content/349/bmj.g4997/rr/763229

An interesting perspective on Ebola published as a Rapid Response to an article in BMJ in August:

The current outbreak of Ebola virus in Guinea, Liberia, and Sierra Leone remains an enormous public health concern for the management, treatment and containment of this deadly disease. At the time of this letter, the Ebola virus has been attributed to an outbreak of more than 1300 documented or suspected infections with mortality estimated between 50-75%.1 Ebola is noted to be a type of hemorrhagic fever virus, which frequently results in disseminated intravascular coagulopathy (DIC) through massive overproduction of tissue factor. Active fibrinolysis of cross-linked fibrin has been demonstrated within 24 hours of challenge with viral exposure by measurement of elevated D-dimer.2,3 Treatment is currently aimed at supportive care as new therapies, including humanized monoclonal antibodies, are developed and tested.

It is possible to anticipate that this massive overproduction of tissue factor could initially develop into a prothrombotic state resulting in overproduction of thrombin and subsequent activation of Factors V and VIII. As the coagulopathy progresses through increased thrombin production, factor consumption, and dysregulation of fibrinolysis a bleeding diathesis results. DIC results from dysregulated hemostasis; consumption of coagulation constituents with a loss of appropriate feedback mechanisms further drives the process.

Should we consider initiating treatment with low dose heparin or low-molecular weight heparin in prophylactic doses at time of suspected exposure to counteract or block tissue factor release as a form of post-exposure prophylaxis? While this may not be able to treat the underlying illness, it may potentially result in decreased thrombin production through increasing antithrombin affinity for the overproduced thrombin, partial inhibition of Factor Xa and aid endothelial release of tissue factor pathway inhibitor (TFPI). While it may seem counterintuitive to provide someone at risk for bleeding with anticoagulation, this strategy is already considered in prothrombotic states of DIC prior to development of a bleeding diathesis.4-6 It is possible if dysregulated hemostasis is controlled at the point of the prothrombotic state that the bleeding diathesis may be avoided.7

While clearly there is no single targeted therapy that would resolve DIC induced from Ebola infection currently available, this strategy would be both cost effective and easy to administer. If adequate inhibition of thrombin production did not occur and the affected person progressed to a bleeding diathesis, heparin therapy, with a short half-life, could be stopped. However, administration of heparin during non-prothrombotic states of DIC with global factor consumption occurring could result in significant bleeding morbidity and mortality. For this reason, cautious consideration of treatment would be best warranted as post-exposure or at onset of symptoms and only prior to development of a bleeding diathesis. Other potential treatment options would also be available including recombinant tissue factor pathway inhibitor (rTFPI) or anti-tissue factor monoclonal antibodies. These treatments, however, may be prohibitive from a cost or accessibility standpoint.

While this remains speculative and certainly with significant controversy, it does provide justification for further investigation to all treatments of a disease with up to 90% mortality until more successful ones are available. Blockage of the prothrombotic state could inhibit progression to a bleeding diathesis but aggressive treatment in the form of supportive care would still be needed for other disease-associated symptoms. Opinions on the matter are likely to be strong as well as polarizing. However, at the expense of controversy, ongoing discussion is likely beneficial. Continued treatment strategies that are cost effective and can be made available worldwide should be in foresight of a potential pandemic and not hindsight.

Peter J. Miller, MD
[email protected]

References:
1. Outbreak of Ebola in Guinea, Liberia, and Sierra Leone. Vol. 2014: Centers for Disease Control and Prevention; 2014.
2. Geisbert TW, Young HA, Jahrling PB, et al. Pathogenesis of Ebola hemorrhagic fever in primate models: evidence that hemorrhage is not a direct effect of virus-induced cytolysis of endothelial cells. Am J Pathol. 2003;163(6):2371-2382.
3. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis. 2003;188(11):1618-1629.
4. Wada H, Asakura H, Okamoto K, et al. Expert consensus for the treatment of disseminated intravascular coagulation in Japan. Thromb Res. 2010;125(1):6-11.
5. Di Nisio M, Baudo F, Cosmi B, et al. Diagnosis and treatment of disseminated intravascular coagulation: guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res. 2012;129(5):e177-184.
6. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009;145(1):24-33.
7. Pernerstorfer T, Hollenstein U, Hansen J, et al. Heparin blunts endotoxin-induced coagulation activation. Circulation. 1999;100(25):2485-2490.

Competing interests: No competing interests

24 August 2014
Peter Miller
Physician
Wake Forest Baptist Medical Center
Wake Forest Baptist Health. Attention Dr. Peter Miller. Dept. of Anesthesiology Medical Center Blvd Winston-Salem, NC 27157-1009