I’ll admit that my long term clinical practice has been to prefer balanced solutions (in my case Hartmans) over 0.9% saline in the management of the critically ill patient. It’s a topic we’ve blogged and podcasted on in the past, and on the basis of past evidence and on the pathophysiological arguments I’ve pretty much always prescribed Hartmans in preference to 0.9% saline unless there was a specific indication for saline.
Having said that, the evidence backing up my decision was hardly perfect and so it’s great to see a large randomised controlled trial that tackles this question regarding balanced solutions (albeit a different one to Hartmans). It’s published in JAMA and you can read the abstract below. As always we want you to read the full paper and come to your own conclusions.
What kind of trial is this?
It’s a randomised trial which is appropriate for a trial of a therapeutic intervention. Randomisation was done using a centralised computer based process and so should be relatively well protected against bias. Patients were randomised between the interventions (plasmalyte vs. saline) and rate of infusion.
The fluids were blinded to patients and staff, but obviously the rate of infusion was not.
Tell me about the patients.
The trial was conducted in 75 Brazilian ICUs. Patients were included if they needed a fluid expansion and were not expected to be discharged within 24 hours. They also had to be one of…
- Age over 65
- Invasive or non-invasive ventilation
- Early kidney dysfunction (but not already ineeding renal support)
- Liver cirrhosis
11052 patients were randomised and so this is a very large trial that should be able to pick up significant differences in outcome.
Patients were reasonably balanced between the study arms.
What about the interventions?
Patients were randomised to receive either balanced solution (plasmalyte) or 0.9% saline through the patient’s ICU stay (so the intention was that they stayed on the same fluid type for maintenance and for boluses). Patients were also secondarily randomised to the rate of infusion. The rates were either 333ml/hour or 999ml/hour (for when a bolus of fluid was administered).
What about the outcomes?
The primary outcome was survival at 90 days. Secondary outcomes included the need for renal replacement therapy, SOFA scores, kidney injury and days not requiring mechanical intervention.
All of these outcomes are reasonable and reflect not just patient focused outcomes such as mortality, but other important patient outcomes such as renal impairment which have been attributed to the chloride load in past studies.
Tell me about the results.
The headline figures suggest that there was no significant difference in terms of outcome between the two fluids, or the speed of administration.
90 day Mortality occurred in 1381/5230 (26.4%) of the balanced solution group vs. 1439/5290 in the saline group (adjusted HR, 0.97 [95% CI, 0.90-1.05]; P = .47
There was a total of 19 secondary outcomes. This is a large number of secondary analyses and so we should be cautious about drawing firm conclusions from them. Two of these analyses were significantly different. The SOFA score at day 7 was better for balanced solutions, as was the neurological score at day 7.
There was no statistically significant differences in the rate of infusion either.
The authors also performed a number of subgroup analyses (of which we should be even more wary). They noted an improvement for saline in traumatic brain injury but this should be seen to be hypothesis generating, although many people do use saline in this group of patients anyway.
So we should use Saline then?
The answer is it probably does not matter for the majority of the patients like the ones in the trial that we see. This is a large and pretty well conducted randomised controlled trial and in the absence of other data then that seems to be the conclusion. However, there will always be specific patients in whom you might make an individual decision to choose a specific fluid. For me I’ll probably continue to use balanced solutions on this basis for the majority of patients.
We should also be mindful that this is an ICU based trial with a specific patient group. Extrapolating the results to other settings and other patient groups is not without risk.
A counter argument would be that this trial and others may have a small benefit to balanced solutions. Although any benefit may be small, the sheer number of patients prescribed these drugs is so vast that even small benefits might be important. Previous trials have been inconclusive and/or contradictory or with different end points and so there may be more to learn on this topic. I expect to see a meta-analysis including this trial published somewhere soon (probably an update to the Cochrane review).
Finally there is the question of whether all balanced solutions are the same and clearly they are not. There are many significant differences and it may well be that one solution will perform differently to others. This trial looked at Plasmalyte (see supplementary materials).
It probably does not matter whether you choose balanced solutions or normal saline for the majority of patients who require volume expansion in an ICU setting.
Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients https://jamanetwork.com/journals/jama/article-abstract/2783039
Critical Care Reviews Livestream and links: Balanced Solution versus Saline in Intensive Care Study https://criticalcarereviews.com/livestream/basics
Buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children https://www.cochrane.org/CD012247/EMERG_buffered-solutions-versus-09-saline-resuscitation-critically-ill-adults-and-children
A balanced view of balanced solutions Bertrand Guidet, Neil Soni, Giorgio Della Rocca, Sibylle Kozek, Benoît Vallet, Djillali Annane & Mike James Critical Care volume 14, Article number: 325 (2010 https://ccforum.biomedcentral.com/articles/10.1186/cc9230