Question 19

College Answer

1) Hypotension a feature of sepsis

2) Hypotension –multifactorial – leaky capillaries, vasoplegia, myocardial dysfunction, NO,
adrenergic failure

3) Fluid resuscitation can only treat one component of sepsis.

4) Current guidelines for the acute management of severe sepsis in pediatric and adult patients place prime importance on early, rapid, and substantial infusion of intravenous fluids. The immediate aim is to correct a possible fluid responsive hypodynamic circulation. Beyond this, the common assumption is that expansion of effective circulating volume will attenuate hypotension, distress) and clinical evidence of impaired peripheral perfusion.

5) Evidence that +ve fluid balance associated with worse outcomes in sepsis (SOAP study) and ALI

6) FEAST study – first RCT- compared albumin, saline and no fluid resus – Mortality at 48 hrs clearly higher in the fluid resuscitation groups. Caveats – paediatric study, 48 hr end point, no ICU package.

7) In adults – a post hoc analysis of the SAFE study showed that adminstration of albumin as
compared to saline reduced the risk of death in severe sepsis.

8) Other points to mention are – fluid should include blood products to a target Hb and
conservative rather than liberal approach in presence of ALI. End points of fluid resuscitation
are difficult

Summary statement: Fluid resuscitation is clearly indicated to treat acute hypotensive episodes. Beyond that, an assessment of causes of ongoing hypotension in sepsis must be evaluated for and treated. Robust RCTs in adults are lacking but use of albumin is preferred to saline

Discussion

The topic of fluid resusicitation in sepsis enjoys a more detailed discussion in the Required Reading section.

Let us first deconstruct the college answer.

Points 1 and 2 set the mood, so to speak. there is no mention of the fluid resuscitation studies here, merely a backdrop as to why it may be neccessary.

Point 3 mentions that fluid resuscitation only treats one component of sepsis, restoring an adequate effective intravascular volume.

Point 4 sensibly repeats the Surviving Sepsis dogma ("early, rapid, and substantial infusion of intravenous fluids") but then degenerates somewhat. The circulation in sepsis is generaly held to be hyperdynamic. Volume restoration (pouring water into an ever-enlarging leaky bucket) is an early goal of management insofar as it allows organ perfusion to continue unimpaired even as the vessels dilate abominably, and third space losses increase.

Point 5 refers to the SOAP study, which found that a positive fluid balance was a strong predictor for death from sepsis in the ICU. The odds ratio of mortality in Europe increased by 1.1 for every added litre of cumulative fluid balance in the first 72 hours.

Point 6 adds the FEAST study which also questions the use of fluid boluses in sepsis. In order to appease the proponents of wet intensive care, the savvy candidate will mention study limitations (such as the absence of ICU facilities for it to run in, the relative mildness of the septic shock, the prevalence of malaria in the population group, and the difficulty generaising these findings to an adult population).

Point 7 raises the recent meta-analysis of albumin as a resuscitation fluid for patients with sepsis. Delaney et al (2011)  found that albumin is better than saline. One may argue that almost any sterile isotonic fluid would be better than saline. Moreover, this meta-analysis compared albumin to "control fluid" which was hydroxyethyl starch or gelofusine in 14 of the 17 analysed studies. Thus, albumin is better than starch. I thank Luke (you know who you are) for pointing out that albumin is also better than cyanide. So, hardly a convincing victory for albumin in 2011. Most recently, the ALBIOS investigators also found no outcome difference among the "mildly septic" shock patients, though perhaps with some subtle benefits among the group with severe illness.

Point 8 returns to Surviving Sepsis guidelines to mention the maintenance of hematocrit above 0.30 with blood products, as well as mentioning the value of conservative fluid management in ALI.

Lastly, the use of "balanced" crystalloids in the resuscitation of sepsis has recently (in 2014) been shown to improve mortality. In fact, "Mortality was progressively lower among patients receiving larger proportions of balanced fluids".

Overall, the successful candidate would have ranted at length about the SOAP, SAFE and FEAST trials, before coming to the conclusion that fluid resuscitation is mandatory, careful, guided by end-points, and that albumin is preferred to saline.

Thus, a model answer would look like this:

Introduction:

• Fluid resuscitation has been the traditional starting point in the resuscitation of sepsis
• The choice of fluids and the required volume remain topics of debate

Rationale:

• Fluid resuscitation maintains intravascular volume and organ perfusion pressure
• Fluid resuscitation maintains preload, ensuring an adequate cardiac output
• Fluid resuscitation improves microvascular perfusion and thus tissue oxygen delivery
• Haemodilution decreases blood viscosity, which may also improve microcirculatory flow

Evidence:

• Recent evidence regarding the choice of fluids (SAFE, ALBIOS) has demonstrated the non-inferiority of crystalloid as compared to colloid in terms of mortality; however, haemodynamic goals appear to be achieved faster with human albumin.
• There is some argument (on the basis of subgroup analysis) that albumin use may be associated with increased survival in sepsis.
• There is a strong argument against fluid over-resuscitation, and it is known that every 1 L of positive fluid balance at day 3 after admission is associated with an increase in mortality.

Summary

• Fluid resuscitation is an important part of the resuscitation of sepsis
• It should be guided by dynamic markers of fluid responsiveness
• It should be guided by haemodynamic goals and surrogate markers of tissue perfusion (eg.lactate)
• Its use should be curtailed to prevent excessively positive fluid balance

An excellent resource for this topic are the chapters in Oh's Manual dealing with severe sepsis (ch 61, by A Raffaele de Gaudio) and with the immunocompromised host (ch 59, by Steve Wesselingh and Martyn A H French).

 

An older, yet similarly respectable source is Shoemaker (2005); Chapter 155 (Infections in the immunocompromised patient) by Andrew Githaiga, Magdaline Ndirangu and David L. Paterson covers this topic with great detail.

 

The Surviving Sepsis Campaign has these published guidelines to peruse.

 

Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344-53.

 

Maitland K, et al and the FEAST Trial Group. Mortality after Fluid Bolus in African Children with Severe Infection. N Engl J Med. 2011 May 26.

 

Delaney, Anthony P., Arina Dan, John McCaffrey, and Simon Finfer. "The role of albumin as a resuscitation fluid for patients with sepsis: A systematic review and meta-analysis*." Critical care medicine 39, no. 2 (2011): 386-391.

 

Raghunathan, Karthik, et al. "Association Between the Choice of IV Crystalloid and In-Hospital Mortality Among Critically Ill Adults With Sepsis." Critical care medicine (2014).

 

Caironi, Pietro, et al. "Albumin replacement in patients with severe sepsis or septic shock." New England Journal of Medicine 370.15 (2014): 1412-1421.