Fluid resuscitation in the early management of septic shock

What are the current guidelines for fluid resuscitation in the early management of patients with septic shock?

Waleed Alhazzani: Once you suspect sepsis or recognize that the patient is septic and tachycardic or hypotensive, then the first step is to establish an intravenous (IV) access and give them fluids – [that is a] part of the resuscitation process. The usual thinking in the past, years ago was, “Should we give crystalloids or colloids?” However, this mentality has changed over the years because we know colloids can be many things. They could be starches, for example, could be albumin, or gelatins, and they are completely different in terms of composition, in terms of effect and clinical outcomes as well. I will talk about that in a second. The other category is crystalloids, which again could be divided into balanced crystalloids or saline products, and they both have their own consequences and their own impact on outcomes of the patient.

The Surviving Sepsis Campaign Guidelines extensively reviewed the literature in this area, and we made recommendations for clinicians on what fluid choices to make and the amount of fluid to give as a guidance. However, we all have to remember that these are only guidelines and in specific situations things may be different.

What the guidelines recommend at the moment is to start resuscitation with crystalloids. We are talking about saline or balanced crystalloids like Ringer lactate. That is over albumin, because early resuscitation with albumin or saline really does not make much difference. [When it comes to] the cumulative effect of giving too much fluid, then you might see some difference with supplementing albumin with crystalloids versus giving just crystalloids alone. What the guidelines recommend is to give around 30 mL/kg fluid challenge for any patients who are suspected to have sepsis and hypovolemia. Again, this comes mostly from expert consensus and from the amount of fluid given in the major trials in the field. I am talking about the ProCESS (Protocolized Care for Early Septic Shock), ARISE (Australasian Resuscitation in Sepsis Evaluation), and ProMISe (Protocolised Management in Sepsis) trials. They were published in the last 3 years, and they used on average anywhere between 1 to 2.5 L of fluid resuscitation for those patients. I am talking about the fluid challenge.

Once you give the patient your fluid challenge in the beginning with crystalloids, ongoing resuscitation is a different story, and the guidelines suggest supplementing albumin with crystalloids when you reach a substantial amount of fluid required. However, it remains vague – what do we mean by a substantial amount of fluid? It is left open to the clinician’s judgement, but ideally, in these trials the amount of fluid given in the first 6 hours was anywhere between 4 to 5 L on average. If you are giving 12 L of fluid, you know you are far off the chart. If you are giving 2 L, for example, over 6 hours, you know you are far below where you should be.

Again, it remains unclear whether there is a benefit or an impact on mortality when you look at fluids like balanced crystalloids or normal saline. The main worry is the chloride content. We know from observational studies that hyperchloremia could have an impact on acute kidney injury. However, there are no head-to-head trials looking at crystalloids or subcomponent of crystalloids. Therefore, we have to make inferences from indirect evidence. And the indirect evidence, which is at best of low quality, suggests that maybe balanced crystalloids are superior to normal saline. However, this should not result in practice change. It should be at best hypothesis-generating, and more trials are needed to help guide future resuscitation.

One last thing I want to mention is that starches are harmful, and we know we have at least moderate- to high-quality data suggesting that starches may increase the risk of death and increase the risk of acute kidney injury in septic patients in acute resuscitation. We should avoid it at all cost.