Is the literature inconclusive about the harm from HES? We think….Yes!

recent editorial discusses the thorny issue of fluid resuscitation.

Notably, there is still no consensus about the major aspects of fluid resuscitation. It’s the usual rigmarole we face….no clarity about when to start and stop fluids, how to guide them or even how much to give.

The bulk of the research has been focused on comparing the type of fluid used. Despite this, the well-established and seemingly insoluble (excuse the pun), crystalloid vs colloid conflict persists to this day. You can attend meeting after meeting in a vane effort to come back with the perfect ‘one size fits all’, recipe for your patients. It NEVER happens!

We all know there are practises that just work, and without them, we would be lost to help our patients. Nowadays they have to be backed by hard evidence…otherwise they are chucked out as ancient voodoo!!

IV fluids is definitely one of those entities, and one we will focus on repeatedly over the next month. We all know that resuscitative IV fluid therapy saves lives in hypovolaemic shock, despite no formal proof from RCTs. The question of which to use etc. is not discussed here.

However, the issue is more nuanced than simply giving IV fluids in shock. The amount of fluid given and fluid balance itself has been found to influence morbidity & mortality. A positive fluid balance within the first 24hrs possibly improves survival….but may also do harm.

Even the timing of fluid therapy relative to the different stages of resuscitation, as outlined in the ‘four phases’ model of fluid resuscitation, has the potential to profoundly effect response and eventual outcome.

The ‘four phases’ model describes the initial two phases of ‘rescue’ and ‘optimisation’ that require robust fluid therapy to treat life-threatening shock. The subsequent two phases of ‘stabilisation’ and ‘de-escalation’ are characterised by judicious use of fluids, amounting to ongoing maintenance.

Recent trials on hydroxyethyl starch (HES) [VISEP, 6S, CHEST] are undermined by a number of shortcomings:

  1. Huge variability in fluid therapy protocols
  2. Subjective (not objective) indications for fluid resuscitation
  3. Huge variation in clinical judgement
  4. Unreliable static haemodynamic parameters (e.g. CVP)
  5. Delayed enrolment of patients
  6. >24hrs after onset of severe sepsis, likely to have completed rescue & optimisation phases

It is likely that fluids were given when not required, as suggested by observed data indicating haemodynamic stability. Logically, the likelihood for harm would be greater in these circumstances, as patients were overrated, received higher than normal volumes and thus suffered amplified effects of any individual fluid and it’s ‘toxicity profile’.

The CRISTAL trial did actually investigate the effect of crystalloid vs colloid in the initial rescue and optimization phases. Accordingly, shocked patients were included. In this study, the protocol involved giving HES on ICU days 0-2 (the median cumulative amount of HAS over 7 days was only 1500ml). We think this is more likely to reflect ‘rational resuscitation reality’. In the end however, there was yet again no difference in 28-day mortality and, interestingly, lower 90-day mortality in the colloid group. So the possibility here is that there is possibly some benefit to using low dose colloid EARLY.

Even peri-operatively, trials & meta-analyses with modern HES solutions have revealed no harmful effect.

The crux of the matter – more attention needs to be placed on how fluid therapy is performed rather than what is infused, for future trials to be meaningful.


Written by Dr Richard Pertwee.

Edited by Dr Jonny Wilkinson.


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