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There has been a ongoing debate over the choice of intravenous fluid in unwell patients. Here we look at the BaSICS and PLUS trials.

The battle is between 0.9% Saline and Balanced fluid. The arguments against 0.9% Saline is that it causes a hyperchloraemia, which can lead to acidaemia and acute kidney injury. Trials, some observational, some randomised but single center, have shown in favour of balanced fluids, however the evidence, is not definitive in terms of one fluid or another. 

At a recent EMCORE Conference we looked the evidence for the best fluid to use in sepsis. What can be said at this point is that 0.9% Saline is safe, especially if large volumes are not used.

BaSICS Trial

What they did

This was a randomised Clinical Trial in 75 ICU’s in Brazil. They randomised patients to balanced fluid (Plasma-Lyte 148) or 0.9% sodium chloride.

Blinding occurred in terms of type of fluid but not rate of fluid administration. There were two fluid rates of administration in both groups. A slower infusion rate of 333mls/hr and a higher rate of 999mls/hr.

Criteria for randomisation included:

  • Admitted to ICU and not expected to be discharged the next day
  • Need fluid expansion
  • Met at least one factor for AKI:
    • >65yo
    • Hypotension (MAP<65) or vasopressor used.
    • Sepsis
    • Mechanical or NIV ventilation
    • Oliguria or creatinine rise
    • Liver cirrhosis or liver failure

Exclusion criteria included 

  • Those with acute kidney injury requiring or expected to require renal replacement therapy
  • Severe electrolyte disturbances
  • Patients with expected death or those that were palliative.

N= 11052

Primary Outcome was 90-day survival

Secondary Outcomes included:

  • Need for renal replacement therapy within 90 days
  • Occurrence of acute kidney injury
  • SOFA Score at days 3 and 7
  • Number of days not requiring mechanical ventilation within 28 days.


Both groups received a median of 1.5L of fluid during the first day.

Patients did receive fluids before the study commenced ie., in the ED etc. The study commenced once they were admitted to ICU. This is a potential limitation of this study.

In terms of Primary Outcome, the was NO DIFFERENCE in fluid type or infusion speed in terms of 90-day survival.

In terms of Secondary Outcomes, there was NO DIFFERENCE in all except the SOFA Score (see below). That means that there was no difference in acute kidney injury, or need for renal replacement therapy.

There was a statistically significant difference in the SOFA Score in the two groups at 7 days, with 32.1% vs 26% for the saline group. 

In a subgroup analysis there was a statistically significant difference in patients with traumatic brain injury, and 90-day mortality, favouring Saline: 31.3% for balanced solution vs 21% for Saline solution.

What I take from this

Normal Saline is safe to use. I will still beware of using large volumes. In this study only 1.5L of fluid was given in the first 24 hours and 2.9 L at 72 hours.

PLUS Trial

What they did

This was a double-blind, randomised control trial in 53 ICUs in Australia and New Zealand.

Patients were eligible, if they were expected to be in ICU for 3 consecutive days.

They compared Plasma-Lyte 148 versus Saline.

Exclusion criteria included:

  • If they had specific fluid requirements
  • Had received disqualifying fluid resuscitation ie., >500ml (this was a change in study protocol)
  • Imminent risk of death
  • Life expectancy < 90 days
  • Had traumatic Brain injury
  • Were at risk of cerebral oedema.

Primary Outcome

Death from any cause within 90 days

Secondary Outcomes

  • Peak creatinine levels in the first 7 days
  • Maximum increase in creatinine level during ICU stay
  • Need for renal replacement therapy
  • Duration of treatment with vasoactive drugs
  • Duration of mechanical ventilation
  • Length of ICU stay

N= 5037


  • Median duration of treatment was 6 days.
  • Median volume of trial fluid was 3.9L (larger volume than the BaSICS Trial)

There was NO DIFFERENCE in 90 day mortality.

Although using saline did increase serum chloride levels and lowered pH, there was NO SIGNIFICANT effect on kidney function.

There was NO DIFFERENCE in secondary outcomes.

What I take from this

This was a good multicenter study that tested larger volumes of fluid, than previous studies, such as BaSICS or SMART.

There were some protocol violations and we are not sure of what fluids were given outside ICU.

Initially this study aimed to detect a 2.9% absolute reduction in 90 day mortality with 90% power. This was revised, due to research being affected by COVID to a 3.8% absolute difference. This meant that the patients required was reduced from 8800 to 5000.

What the study says to me is that Normal saline is safe to give. I would beware of large volumes.


0.9% Saline is safe, especially in appropriate volumes. I consider > 5L to be high volume. It may cause a hyperchloraemia and acidosis, but it does not lead to acute kidney injury in smaller amounts.


  1. Zampieri FG et al. Effect of Intravenous Fluid Treatment with Balanced Solution vs 0.9% Saline Solution on Mortality in Critically ill Patients. The BaSICS Randomised Clinical Trial.JAMA 2021;326:818-829
  2. Finfer S et al. Balanced Multielectrolyte Solution versus Saline in Critically ill Adults. NEJM 2022;386:615-826

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