Prime the Pump: A Failed Paradigm in Sepsis

Why is “prime the pump”, dying?

  • It’s now accepted that sepsis has more to do with vasodilation, and less to do with vascular permeability. Administering a vasopressor turns unstressed volume into stressed volume and improves venous return, thereby improving venous return.
  • Administration of large volumes of fluid is associated with increased mortality.
  • Not every patient will respond to fluid administration with an increase in cardiac output.
  • The fluid does not remain in the vascular space.

Consider this excerpt from Byrne et. al.

The current acceptance of the therapy is based in part on long history and familiarity with its use in the resuscitation of other forms of shock, as well as on an incomplete and incorrect understanding of the pathophysiology of sepsis. Recently, the safety of intravenous fluids in patients with sepsis has been called into question with both prospective and observational data suggesting improved outcomes with less fluid or no fluid. The current evidence for the continued use of fluid resuscitation for sepsis remains contentious with no prospective evidence demonstrating benefit to fluid resuscitation as a therapy in isolation.

How much fluid do we give in septic shock, and when do we start a vasopressor?

“Just the right amount”, and as soon as it’s evident the patient isn’t or WON’T respond to fluid administration.

Practically speaking, there’s not a novel method of determining fluid responsiveness in the field. Use clinical gestalt and the physical exam (are the knees cold or warm, how’s the mental status?) to determine the need and the patients response to a fluid bolus. Blood pressure is a static measure, and not great for determining fluid responsiveness. Give a marginal fluid bolus and start early pressor therapy to maintain a MAP>65 mmHg.

An interesting, possible way for Prehospital Providers to determine fluid responsiveness:

You can test for fluid responsiveness without giving a drop of fluid by using ETCO2 and Passive Leg Raise, but it might not be ready for prime time.

What should be the first line vasopressor for vasodilatory shock?

Norepinephrine if you have it, but Epinephrine is fine, and may be preferred in select cases:

Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial: 

There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.

A comparison of epinephrine and norepinephrine in critically ill patients:

Despite the development of potential drug-related effects with epinephrine, there was no difference in the achievement of a MAP goal between epinephrine and norepinephrine in a heterogenous population of ICU patients.

Using a pump is the preferred method for administering vasopressors. Don’t have a pump but want to give Epi?

Versatility of Epinephrine Complete


Want more? Check out Paul Marik’s talk on Early Goal Directed Therapy:


Now for the Podcast:





Owyang, C., & Meyers, C. (2016). Is Passive Leg Raise an Accurate Diagnostic Method for Assessing Fluid Responsiveness in Adults? Annals of Emergency Medicine. https://doi.org/10.1016/j.annemergmed.2015.11.025
Monnet, X., & Teboul, J. L. (2015). Passive leg raising: Five rules, not a drop of fluid! Critical Care, 19(1). https://doi.org/10.1186/s13054-014-0708-5
Benomar, B., Ouattara, A., Estagnasie, P., Brusset, A., & Squara, P. (2012). Fluid responsiveness predicted by noninvasive Bioreactance-based passive leg raise test. In Applied Physiology in Intensive Care Medicine 1: Physiological Notes – Technical Notes – Seminal Studies in Intensive Care, Third Edition (pp. 235–241). https://doi.org/10.1007/978-3-642-28270-6_43
Andrews, B., Semler, M. W., Muchemwa, L., Kelly, P., Lakhi, S., Heimburger, D. C., … Bernard, G. R. (2017). Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: A randomized clinical trial. JAMA – Journal of the American Medical Association, 318(13), 1233–1240. https://doi.org/10.1001/jama.2017.10913
Maitland, K., Kiguli, S., Opoka, R. O., Engoru, C., Olupot-Olupot, P., Akech, S. O., … Gibb, D. M. (2011). Mortality after Fluid Bolus in African Children with Severe Infection. New England Journal of Medicine, 364(26), 2483–2495. https://doi.org/10.1056/NEJMoa1101549
Krenn, L., & Karth, D. G. (2011). Essential lessons in cardiogenic shock: Epinephrine versus norepinephrine/dobutamine. Critical Care Medicine, 39(3), 583–584. https://doi.org/10.1097/CCM.0b013e318208e381
Myburgh, J. A., Higgins, A., Jovanovska, A., Lipman, J., Ramakrishnan, N., & Santamaria, J. (2008). A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Medicine, 34(12), 2226–2234. https://doi.org/10.1007/s00134-008-1219-0
Annane, D., Vignon, P., Renault, A., Bollaert, P. E., Charpentier, C., Martin, C., … Bellissant, E. (2007). Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet, 370(9588), 676–684. https://doi.org/10.1016/S0140-6736(07)61344-0
Marik, P. E. (2011). Surviving sepsis: going beyond the guidelines. Annals of Intensive Care, 1(1), 17. https://doi.org/10.1186/2110-5820-1-17
Byrne, L., & Van Haren, F. (2017). Fluid resuscitation in human sepsis: Time to rewrite history? Annals of Intensive Care. https://doi.org/10.1186/s13613-016-0231-8
Marik, P., & Bellomo, R. (2016). A rational approach to fluid therapy in sepsis. British Journal of Anaesthesia. https://doi.org/10.1093/bja/aev349
Durairaj, L., & Schmidt, G. A. (2008). Fluid therapy in resuscitated sepsis: Less is more. Chest. https://doi.org/10.1378/chest.07-1496

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