The Current Surviving Sepsis Campaign “recommends that, in the resuscitation from sepsis induced hypoperfusion, at least 30 mL/kg of IV crystalloid fluid be given within the first 3 hours” (with no exceptions) (STRONG RECOMMENDATION).

Do you support/agree with the above recommendation?  The answer is a Yes or No (NO conditional answers)

Results from the Surviving Sepsis Campaign Committee members

The number of “NO” votes exceeds the threshold of 20% established by the Guideline Rules and therefore this recommendation must be rejected.

Results from the Fluid Academy Survey

      NO=61%

Commentary:

The results of both surveys are not surprising. This recommendation has never been prospectively tested in a large RCT and has little supporting evidence. Imagine the American Heart Association (AHA) or the American Diabetes Association (ADA) making a STRONG RECOMMENDATION (which it then Federally mandated) regarding a therapeutic intervention which had never been tested. The medical community would reject such a recommendation out-of-hand and consider such a recommendation to be reckless.

The idea of giving large fluid boluses to patients with sepsis is illogical, is unphysiologic, is devoid of supporting clinical data and is likely harmful.  In the FINECE study which analyzed the use of fluid boluses (FB) in 2213 patients from 311 centers across 46 countries the median FB was 500 ml [IQR 500-999].[1] Almost all beside clinicians agree that the most effective approach to fluid resuscitation is to give a 500ml bolus of crystalloid and then for the clinician (at the bedside) to monitor the response. If the patient demonstrates no hemodynamic benefit; then it makes no sense to give more fluids- STOP. If the patient demonstrates a hemodynamic benefit, then the clinician may decide to cautiously give a second bolus. It has been claimed that in the Early Goal Directed Studies (EGDT) patients “received bags of crystalloid” prior to enrollment. It is however noteworthy that in the recent VANISH trial (conducted between 2013 and 2015) on average 1134ml fluid was administered in the 4 hours prior to enrollment and randomization to either vasopressin or norepinephrine. [2]

The idea of dosing a FB in an adult patient based on body weight is very ODD and without any scientific basis. Fluid boluses in the ICU, operating room, Emergency Room or field are almost never given in a “dosage” of ml/kg body weight.  Crystalloid solutions are usually provided in 1 L bags; less commonly in 500ml and 250ml bags. Consequently standard practice around the world is to provide a fluid boluses of 500ml (as demonstrated by the FENICE study). It would appear that the origin of dosing fluid by body weight comes from a small, observational study in 34 pediatric patients with septic shock published by Carcillo et al in 1991. [3] In this study, patients who received greater than 40mls/kg (n=9) were reported to have an improved survival.

According to Guytonion physiology the cardiac output (CO) and venous return (VR) are equal, and any parameter that determines VR will therefore also determine CO. An increase in venous return will result in an increase in cardiac output. In order for venous return to increase the pressure gradient for venous return must increase, i.e the increase in mean circulating filling pressure (MSFP) must be greater than the increase in CVP. [4]  In a dose titration study performed in post cardiac surgery patients, Cecconi et al demonstrated that a FB of about 300 ml is required to reliably increase MCFP.[5] In septic patients with an increased unstressed volume it is likely that a 500ml fluid bolus would achieve the same effect.

The physiologic effects of large FB’s have not been studied in contemporary medicine. In the healthy individuals the heart is able to regulate filling pressures (the CVP) by increasing the end-diastolic volume. However, septic patients frequently have diastolic dysfunction,[6] and a large fluid bolus likely exceed the hearts ability to compensate causing the CVP (and PCWP) to increase significantly and thereby preventing an increase in the gradient of venous return. Therefore a large fluid bolus may fail to increase CO (or produce a smaller increase) when compared to a smaller bolus. In addition, the increase in filling pressures are associated with serous hemodynamic consequences including pulmonary edema (high PCWP) and venous congestion (high CVP) leading to kidney and hepatic injury.[7] High filling pressure result in the release of naturetic peptides that have adverse hemodynamic effect (which include damage to the endothelial glycocalyx and inhibition of lymphatic drainage). Furthermore, the rapid increase in filling pressures may counteract the compensatory mechanism that occur in shock resulting in cardiovascular collapse; this is one of the mechanism that has been postulated to account for the increased mortality in the FEAST trial.[8]

Only two studies have been conducted to date which have explored the clinical outcome of patients with severe sepsis and/or septic shock randomized to receive large fluid boluses vs. standard of care. In the study by Andrews et al (Death by Fluids, Part 1) adult patients with septic shock were randomized to receive a 2L fluid bolus as compared to standard of care. In the FEAST study (Death by Fluids, Part 2) children with severe sepsis were randomized to a bolus of Saline or Albumin (40mls/kg) or no bolus.[12] In both studies the patients who received the large fluid boluses had a significantly higher mortality than the standard treatment group.

In summary, the results of both surveys and the scientific data speak for itself; large fluid boluses in patients with sepsis is unphysiologic and likely to increases the risk of death!

Moral/Medical Terrorrism

When you push your opinion(s) as if they are an (or the) absolute truth/facts or morals on others without acknowledging that what you are saying is your beliefs (and not generally supported) and when stating this is not pertinent to the subject at hand or to the point(s) made in which you are trying to support, you’re in turn: using strong emotions  to [unlawfully] change that person or persons’ morals/ideals/beliefs that governs their life (actions) through the use of moral [medical] terrorism – Legal Definition of Moral Terrorism

References

1. Cecconi M, Hofer C, Teboul JL et al. Fluid challenges in intensive care: THe FENICE study. A global inception cohort study. Intensive Care Med 2015; 41:1529-37.
2. Gordon AC, Mason AJ, Thirunavukkarasu N et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. The VANISH randomized clinical trial. JAMA 2016; 316:509-18.
3. Carcillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA 1991; 266:1242-45.
4. Cecconi M, Aya HD, Geisen M et al. Changes in the mean systemic filling pressure during a fluid challenge in postsurgical intensive care patients. Intensive Care Med 2013; 39:1299-305.
5. Aya HD, Rhodes A, Ster IC et al. Haemodynamic effect of different doses of fluids for a fluid challenge: a quasi-randomised controlled study. Crit Care Med 2017; 45:e161-e168.
6. Landesberg G, Gilon D, Meroz Y et al. Diastolic dysfunction and mortality in severe sepsis and septic shock. Eur Heart J 2012; 33:895-903.
7. Marik PE. Iatrogenic salt water drowning and the hazards of a high central venous pressure. Ann Intensive Care 2014; 4:21.
8. Maitland K, George EC, Evans JA et al. Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Medicine 2013; 11:68.

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Paul Marik

Intensivist, Researcher, Myth-Buster, Status Quo Destabilizer

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