The BaSICS trial: Normal saline has been fine all along

Do you have strong opinions about normal saline? If so, you might need a hobby, but also this paper is for you. The BaSICS trial is a massive RCT with more than 10,000 patients comparing normal saline to a balanced crystalloid IV fluid.

The paper

Zampieri FG, Machado FR, et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA. 2021 Aug 10. doi: 10.1001/jama.2021.11684. PMID: 34375394 [free full text]

The Methods

This is a multicenter double blind RCT from 75 ICUs in Brazil.

Patients

They included patients being admitted to the ICU and requiring fluid expansion (per the attending physician), and who had at least 1 risk factor for acute kidney injury (older than 65 years, hypotension, sepsis, mechanical or noninvasive ventilation for at least 12 hours, oliguria, elevated creatinine, cirrhosis, or acute liver failure).

They excluded patients expected to require renal replacement therapy, with a serum sodium less than 120 mmol/L or greater than 160 mmol/L, those who were expected to die within 24 hours, receiving palliative care, and those with suspected or confirmed brain death. 

Intervention

Balanced IV solution (Plasma-Lyte-148) for all fluids.

Comparison

Normal saline for all IV fluids.

Unlike some prior trials, the fluids were provided in identical 500 mL bags, and so the trial was properly blinded. Decisions about fluid management were left to the treating physician.

Outcome

The primary outcome was 90 day survival. 

The Results

They randomized 11,052 patients, but because consent was done after randomization, the actual trial dataset is 10,520 patients (which is slightly shy of their target sample size of 11,000). The mean age was 61 and 44% were women. About half were admitted to the ICU after elective surgery, 60% were hypotensive or on vasopressors, and 45% required mechanical ventilation.

Groups received a median of 1.5 L of IV fluids in the first 24 hours and 4 L of fluid in their first 3 days (3 L of which was study fluid, as patients received an average of a 1 L IV bolus before being enrolled in the study). 

There was no change in the primary outcome of all cause mortality: 26% versus 27%, adjusted HR, 0.97 [95% CI, 0.90-1.05]; P = 0.47.

There was no change in the key secondary outcomes of need for dialysis (1% vs 1%) or kidney injury (27% vs 27%).

There was a statistically significant finding in a subgroup: 90 day mortality was a lot higher with balanced fluids in patients with traumatic brain injury (21% versus 31%, p=0.02), but the numbers were relatively small, the confidence intervals wide, and I don’t believe they adjusted their statistics for multiple comparisons.

My thoughts

This is an 11,000 patient trial of IV fluids! And the methods were excellent. The biggest limitation is probably that the initial fluids in the emergency department or operating room were not controlled, which allowed some cross contamination between the groups. However, this is an excellent trial overall, with very believable results. 

No trial is perfect, but I think the limitations of this trial are very minor, especially when compared to the SMART and SALT-ED trials, which were touted as game-changing by many (although I strongly disagreed). The overall amount of IV fluid prescribed is not huge, but 4 L over 72 hours is reasonable by modern ICU standards. When compared to the average of 1 L of IV fluids given in the SMART trial, these patients were absolutely drowning. I think we need to be aware that these results may not apply to patients we are flooding with 15 L of IV fluids, but unless you are working in a cholera ward somewhere, is anyone really giving that much fluid anymore?

This trial only looked at Plasma-Lyte. There could be differences between this fluid and other balanced solutions, and I imagine we will hear a lot about that, but I would want to see some evidence of a real clinical difference before making clinical decisions based on that theory.

Of note, this trial also looked at the rate of fluid administration, which was published in a second paper. (Zampieri 2021 #2) I think that topic is less controversial, so decided not to discuss it in full, but it is worth nothing that there also was no difference between giving your IV fluid boluses at a rate of 999 mL/hr and 333 mL/hour, so I will continue to bolus rapidly when I think boluses are indicated. 

People got really excited about the SMART and SALT-ED trials, but they were trials with very imperfect methodology and mixed results. I imagine people will nitpick many aspects of the BaSICS trial, but I would ask whether they applied the same degree of skepticism to the previous trials. It is reasonable to state that BaSICS does not provide us with perfect information (as no trial does), but we need to be honest about what the existing evidence says if we are going to reject the results of BaSICS. Before BaSICS, the highest quality trial we had was SPLIT, and it also showed no harm from normal saline. Although there are some physiological reasons to think saline could be harmful, physiologic reasoning loses most of its value in the face of a very well done 10,000 patient RCT.

Of course, there is no compelling reason to choose normal saline, and there is nothing wrong with a balanced solution. If the existing standard of care was Ringer’s lactate, and normal saline was being marketed as a brand new fluid, there is definitely nothing to convince us to change over to normal saline. (Although, there are a few practical reasons to use saline, such as drug and blood product compatibility.) However, some people talk as if hanging a bag of saline is equivalent to putting a gun to a patient’s head, and those people are clearly wrong.

Bottom line

This is the best and largest study of normal saline and balanced IV fluids to date, and it is pretty clear that normal saline is as safe as the balanced fluid. (Whether providing either IV fluid to these patients is beneficial is a completely different question.) Continue to use whatever is easiest for your team. I still almost always use saline myself.

Other FOAMed

EMCrit Wee – Breaking News on Fluid Choice and Rate – The BaSICS Trial

The SALT-ED trial

The SPLIT trial

The SMART trial

References

Zampieri FG, Machado FR, et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA. 2021 Aug 10. doi: 10.1001/jama.2021.11684. PMID: 34375394

Zampieri FG, Machado FR, Biondi RS, et al. Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients JAMA. 2021;