The Paper That Made Me Rename Normal Saline
It's 2am, the department is humming, one of my patients has soft blood pressure, and I turn to the nurse and ask her to hang a litre of fluid. She turns back: "Sure — you want NS or LR?"
It's one of my favourite questions in Emergency Medicine. Because the answer used to be automatic for me — drilled in during medical school in Australia — and it took one paper to dismantle that reflex completely. That paper is SALT-ED.
The paper, in PICO
Title. Balanced Crystalloids versus Saline in Noncritically Ill Adults. Self WH et al. New England Journal of Medicine, 2018.
Population. 13,347 adults who received ≥500 mL of intravenous crystalloid in the Vanderbilt Emergency Department and were subsequently admitted outside the ICU.
Intervention. A pragmatic, cluster-randomised, multiple-crossover design: for one calendar month, the entire ED was stocked with balanced crystalloids (mostly lactated Ringer's); the next month, the entire department flipped to normal saline. Sixteen months in total.
Comparator. Normal saline (0.9% NaCl), the default crystalloid in most US emergency departments.
Outcomes. Primary — hospital-free days to day 28. Secondary — major adverse kidney events at 30 days (a composite of death, new renal-replacement therapy, or persistent renal dysfunction defined as creatinine ≥200% of baseline), AKI stage 2 or higher, and in-hospital death.
The results
The primary outcome — hospital-free days — showed no difference. Median 25 days in each group. Adjusted odds ratio 0.98 (95% CI 0.92–1.04), P=0.41.
But the secondary outcome is where the story sits. Major adverse kidney events at 30 days occurred in 4.7% of the balanced-crystalloid group versus 5.6% of the saline group. Adjusted odds ratio 0.82 (95% CI 0.70–0.95), P=0.01. Absolute risk reduction of 0.9 percentage points. Number needed to treat: 111.
Hyperchloremia and acidemia were both more common after saline, and those differences persisted for days into the hospitalisation. The biochemistry lined up with the predicted mechanism — supraphysiologic chloride load, hyperchloremic metabolic acidosis, worsened renal outcomes — making the story internally consistent.
Critical appraisal — what's good, what's not
Strengths. Enormous sample size for a single-centre trial. A pragmatic crossover design that achieved 88% adherence to assigned fluid while preserving external validity. Mechanism, biochemistry, and clinical outcome all pointed in the same direction. And the companion ICU trial — SMART, published in the same issue of NEJM — showed the same direction of effect in critically ill adults, giving us replication in a parallel population.
Limitations. Single centre (Vanderbilt, an academic tertiary referral hospital). The population was about 78% white, which is a real generalisability constraint. The only statistically significant secondary outcome was a composite, which some critics have called "signal boosting." My pushback: the elements of the composite — death, new dialysis, persistent renal dysfunction — are exactly the outcomes patients care about. Stacking them isn't gaming the p-value; it's measuring a coherent renal-injury phenotype. The trial only controlled fluid in the ED; once patients hit the ward, all bets were off. And the design was unblinded by necessity, although it's hard to see how that would systematically favour balanced fluids.
How should this modify your practice?
Post-SALT-ED, my default is essentially this: if a patient needs IV crystalloid in the ED, the answer is lactated Ringer's. Full stop. If you end up giving saline — and there are reasons to — keep it modest. I try not to exceed a litre unless there's a hard indication.
The hard indications I keep on a short mental list:
• Traumatic brain injury or hyponatremia — saline's higher sodium concentration is helpful when you want a slightly hypertonic effect.
• Drug compatibility issues — ceftriaxone is calcium-incompatible and shouldn't be co-infused with LR. The fix isn't to switch all your fluids to saline; it's to put in a second line for the antibiotic. Don't let one drug bully you out of best-evidence fluids.
Outside those scenarios, default to balanced. It costs the same. It's stocked the same. It's administered the same. The only thing that changes is which bag the nurse grabs.
And here's the joke that came out of this entire literature, the one I've now told to every resident, attending, and unfortunate dinner companion in the last eight years: I don't call it normal saline anymore. I call it ABNORMAL saline. Because a supraphysiologic chloride load is, by definition, not normal.
Author
Dr Adrian Cois, MD
Assistant Professor, Emergency Medicine | @dr_cois
No financial conflicts to disclose for this episode.
Extend yourself
• Primary article: Self WH, Semler MW, Wanderer JP, et al. Balanced Crystalloids versus Saline in Noncritically Ill Adults. NEJM 2018;378(9):819-828. doi:10.1056/NEJMoa1711586
• Companion ICU trial (SMART): Semler MW et al. NEJM 2018;378(9):829-839. doi:10.1056/NEJMoa1711584
• The Bottom Line summary: https://www.thebottomline.org.uk/summaries/icm/salt-em/
• 2 Minute Medicine summary: https://www.2minutemedicine.com/salt-ed-normal-saline-versus-balanced-crystalloids-in-noncriticaly-ill-adults/
References (AMA)
1. Self WH, Semler MW, Wanderer JP, et al. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018;378(9):819-828. doi:10.1056/NEJMoa1711586
2. Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018;378(9):829-839. doi:10.1056/NEJMoa1711584
3. Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013;369:1243-1251.
4. Yunos NM, Bellomo R, Hegarty C, et al. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012;308(15):1566-1572.
