Balanced crystalloids vs saline for critically ill patients

Another trial was conducted in parallel. Saline against LR or another branded BC (PlasmaLyte) in the ED (SALT-ED) compared BC with saline among 13,347 non-critically ill adults treated with IVF in the ED (Self WH, et al. N Engl J Med. 2018;378[9]:829). Like the SMART trial, the SALT-ED trial found a 1% absolute reduction in the risk of death, new dialysis, or renal dysfunction lasting to hospital discharge favoring BC.

The SMART and SALT-ED trials have important limitations. They were conducted at a single academic center, and treating clinicians were not blinded to the assigned fluid. The key outcome was a composite of death, new dialysis, and renal dysfunction lasting to hospital discharge – and the trials were not powered to show differences in each of the individual components of the composite.

Despite these limitations, we now have data from two trials enrolling nearly 30,000 acutely ill patients suggesting that BC may result in better clinical outcomes than saline for acutely ill adults. For clinicians who were already using primarily BC solutions, these results will reinforce their current practice. For clinicians whose default IVF has been saline, these new findings raise challenging questions. Prior to these trials, the ICU in which I practice had always used primarily saline. Some of the questions we faced in considering how to apply the results of the SMART and SALT-ED trials to our practice included:

1. Recent data suggest BC may produce better clinical outcomes than saline for acutely ill adults. Are there any data that saline may produce better clinical outcomes than BC? Currently, there are not.

2. Cost is an important consideration in critical care, are BC more expensive than saline? The cost to produce saline and BC is similar. At our hospital, the cost for a 1L bag of saline, LR, and another branded BC (PlasmaLyte A ) is the exactly the same.

3. Is there a specific population for whom BC might have important adverse effects? Because some BC are hypotonic, the safety of administration of BC to patients with elevated intracranial pressure (e.g., traumatic brain injury) is unknown.

4. Are there practical considerations to using BC in the ICU? Compatibility with medications can pose a challenge. For example, the calcium in LR may be incompatible with ceftriaxone infusion. Although BC are compatible with many of the medication infusions used in the ICU for which testing has been performed, less data on compatibility exist for BC than for saline.

5. Are BC as readily available as saline? The three companies that make the majority of IVF used in the United States produce both saline and BC. Recent damage to production facilities has contributed to shortages in the supply of all of them. Over the long term, however, saline and BC are similar in their availability to hospital pharmacies.

After discussing each of these considerations with our ICU physicians and nurses, consultants, and pharmacists, our ICU collectively decided to switch from using primarily saline to BC. This involved (1) our pharmacy team stocking the medication dispensing cabinets in the ICU with 90% LR and 10% saline; and (2) making BC rather than saline the default in order sets within our electronic order entry system. Based on the results of the SMART trial, making the change from saline to BC might be expected to prevent around 100 deaths in our ICU each year.

Many questions regarding the effect of IV crystalloid solutions on clinical outcomes for critically ill adults remain unanswered. The mechanism by which BC may produce better clinical outcomes than saline is uncertain. Whether acetate-containing BC (eg, PlasmaLyte) produced better outcomes than non-acetate-containing BC (eg, LR) is unknown. The safety and efficacy of BC for specific subgroups of patients (eg, those with hyperkalemia) requires further study. Two ongoing trials comparing BC to saline among critically ill adults are expected to finish in 2021 and may provide additional insights into the best approach to IVF management for critically ill adults. An ongoing pilot trial comparing LR to other branded BC (Plasmalyte/Normosol )may inform the choice between BC.

In summary, IVF administration is ubiquitous in critical care. For decades, much of that fluid has been saline. BC are similar to saline in availability and cost. Two large trials now demonstrate better patient outcomes with BC compared with saline. These data challenge ICU providers, pharmacies, and hospital systems primarily using saline to evaluate the available data, their current IVF prescribing practices, and the logistical barriers to change, to determine whether there are legitimate reasons to continue using saline, or whether the time has come to make BC the first-line fluid therapy for acutely ill adults.

Dr. Semler is with the Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine –Vanderbilt University Medical Center, Nashville, Tennessee.