Balanced Crystalloids versus Saline in Critically ill adults
Although normal saline is the most commonly administered intravenous fluid its use has been associated with hyperchloremic metabolic acidosis, acute kidney injury and death. In several observational studies, crystalloids with compositions more similar to plasma (lactated Ringer’s or Plasma-Lyte A) have been shown to have lower rates of acute kidney injury, need for renal replacement therapy or death. The authors of this study set out to determine if the use of balanced crystalloids improved these outcomes for critically ill adults when compared with the use normal saline.
This was a pragmatic, unblended, cluster randomized, multiple crossover trial conducted at five ICUs at Vanderbilt University Medical Center between June 1 2015 and April 30 2017.
– All adults admitted to a participating ICU were enrolled
– Each month the participating ICUs were assigned to use either balanced crystalloids or saline for any intravenous administration of isotonic crystalloid
– Patients in the saline group received 0.9% sodium chloride whereas patients in the balanced-crystalloids group received either lactated Ringer’s or plasma-lyte A
– Relative contraindications to the use of balanced crystalloids included hyperkalemia or brain injury
– Trial was coordinated with the emergency department and operating room so that patients would receive the same type of fluid throughout all of their care
– Predetermined they would need 14,000 patients enrolled in order to provide a power of 90% at a type 1 error rate of 0.05 to detect a relative difference of 12% (absolute difference of 1.9 percentage points)
– Intention to treat analysis
Primary outcome: proportion of patients who met one or more criteria for a major adverse kidney event within 30 days, death, new receipt of renal-replacement therapy, or persistent renal dyfunction (final inpatient creatinine value >200% of the baseline) at hospital discharge or 30 days after enrollment (whichever came first)
– Determined a baseline creatinine level by looking at levels during the year before hospitalization
– Patients who had renal-replacement prior to the study were ineligible for the new renal replacement therapy or persistent renal dysfunction outcome but could qualify for the primary outcome if they died in the hospital
Secondary clinical outcomes:
– In-hospital death before ICU discharge or at 30 or 60 days
– ICU-free days
– Ventilator-free days
– Vasopressor-free days
– Days alive and free of renal-replacement therapy during the 28 days after enrollment
Secondary renal outcomes:
– New receipt of renal-placement therapy
– Persistent renal dysfunction
– Acute kidney injury of stage 2 or higher as defied in the Kidney Disease: Improving Global Outcomes criteria for creatinine level
– Highest creatinine during hospital stay
– Change from baseline to the highest creatinine level
– Final creatinine level prior to hospital discharge
– Baseline characteristics equal between groups (15,802 patients enrolled with mean age 58% and 57.6% were men; 1/3 mechanically ventilated and ¼ on vasopressors)
– Median volume of balanced crystalloids given was 1000 ml and the median volume of normal saline given was 1020 ml
– Only 426 patients (5.4%) in the balanced-crystalloid group and 343 in the normal saline group (4.4%) received any volume of unassigned crystalloid
– Fewer patients in the balanced-crystalloids group had a plasma chloride concentration greater than 110 mmol per liter (24.5% vs 35.6%) or a plasma bicarbonate concentration less than 20 mmol per liter (35.2% vs 42.1%)
– 1139 patients (14.3%) in the balanced crystalloid group and 1211 patients (15.4%) in the saline group had a major adverse kidney event
– Among septic patients, 30-day in hospital mortality was 25.2% with balanced crystalloids versus 29.4% with saline
– 818 patients (10.3%) in the balanced saline group died before hospital discharge and within 30 days of ICU discharge as compared to 875 (11.1%) in the saline group
– 189 patients (2.5%) in the balanced-crystalloid group and 220 patients (2.9%) in the saline group received new renal-replacement therapy
– Highest stage of acute kidney injury and the incidence of persistent renal dysfunction did not differ significantly between the groups
– In this trial the use of balanced crystalloids rather than saline resulted in an absolute difference of 1.1 percentage points in favor of balanced crystalloids in the primary outcome. This is consistent with the findings of the SALT-ED trial conducted in non-critically ill patients.
– Authors state that if these findings were applied to a wider group of patients there could be significant improvements in the risk of AKI, need for dialysis or death. The use of balanced crystalloids rather than saline might prevent 1 patient among every 94 patients admitted to the ICU from needing new renal-replacement therapy, persistent renal dysfunction, or death.
– These differences appear greater for patients with sepsis and patients who received larger doses of isotonic crystalloid (dose-dependent)
– Concern that the relative hypotonicity of balanced crystalloids may increased intracranial pressure in patients with brain injury à findings not generalizable to this group
– Strengths: large sample size, critically ill patients, delivery of assigned crystalloids early in patient care
– Limitations: conducted at a single academic center, non-blinded to clinicians giving fluids (clinicians decision to initiate renal-replacement therapy may be susceptible to treatment bias), evaluated lactated Ringers and plasma-lyte A together
Author’s conclusion: For critically ill patients, intravenous administration of balanced crystalloids rather than saline had a favorable effect on the composite outcome of death, new renal-replacement therapy or persistent renal dysfunction.
Bottom line: Consider using LR instead of NS for intravenous fluid repletion in critically ill patients!