SGEM#368: Just A Normal Saline Day in the ICU – The PLUS Study

Date: June 12th, 2022

Reference: Finfer et al. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. NEJM 2022.

Guest Skeptic: Dr. Aaron Skolnik is an Assistant Professor of Emergency Medicine at the Mayo Clinic Alix School of Medicine and Consultant in the Department of Critical Care Medicine at Mayo Clinic Arizona.  He is board certified in Emergency Medicine, Medical Toxicology, Addiction Medicine, Internal Medicine-Critical Care, and Neurocritical Care.  Aaron is a full-time multidisciplinary intensivist.  He is the Medical Director of Respiratory Care for Mayo Clinic Arizona and is most proud of his position as medical student clerkship director for critical care.

Case: A 62-year-old man is brought in by EMS from home with lethargy and hypotension.  Chest x-ray is clear, labs are remarkable for a leukocytosis of 16,000 with left shift; exam is notable for left flank pain and costovertebral tenderness.  Straight catheter urinalysis is grossly cloudy, and pyuria is present on microscopy.  Blood pressure is 85/50 mmHg.  You wonder which IV fluid should you order?

Background:  There has been a longstanding debate about which intravenous fluid is the best for volume resuscitating critically ill patients.  We’ve known for some time that albumin is bad for injured brains, and that hydroxyethyl starch solutions have been associated with kidney injury and mortality.  Since then that debate has broadly centered on the choice between what we will call “abnormal saline” (0.9% sodium chloride), and balanced crystalloid solutions, meaning those with a chloride composition closer to plasma such as lactated ringer’s or Plasma Lyte 148.

Early work suggested potential harm from 0.9% saline, that may be partly driven by kidney injury associated with the administration of high-chloride content IV fluids.

In the last few years, the pendulum has swung back and forth.  Two large, cluster-randomized trials (SMARTand SALT-ED) showed a small benefit to the use of balanced crystalloids in preventing a composite outcome of Major Adverse Kidney Events within 30 days (aka MAKE-30).

Then, the BaSICS trial (a multicentred RCT done in 75 Brazilian ICUs) came along and compared saline to Plasma-Lyte at what the authors deemed slow and fast infusion rates.  We reviewed that last time on SGEM#347. There was no interaction between fluid type or rate of infusion with the primary outcome of 90-day survival.  Among 19 secondary outcomes, which should only be considered hypothesis generating, SOFA scores and neuro SOFA scores at day seven were worse in the balanced crystalloid group.

Now we have the PLUS trial, from Australia and New Zealand to add to the medical literature on this issue.

Clinical Question: Is the 90-day mortality in critically ill adult patients lower with the use of Plasma-Lyte 148, a balanced crystalloid solution, for fluid resuscitation and therapy, than with the use of normal saline?

Reference:  Finfer et al. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. NEJM 2022.

* Population: Patients 18 years or older, admitted to 53 ANZ ICUs over 38 months, whom the treating clinician deemed to need fluid resuscitation and were expected to be in the ICU on three consecutive days.

Exclusions: Patients with specific ICU fluid requirements, those who received disqualifying fluid prior to enrollment (> 500 mL in the ICU),