The PRoMPT BOLUS trial (Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis) is the largest randomized controlled trial to date comparing balanced crystalloids to 0.9% normal saline in children with septic shock. The primary outcome showed no significant difference in major adverse kidney events at 30 days between the two groups.  The secondary outcome showed  no significant difference in 30 or 90 day mortality.

Additional Information

PRoMPT BOLUS was a pragmatic, open-label, multicenter RCT conducted across 47 emergency departments in five countries. Children aged 2 months to <18 years with suspected septic shock and abnormal perfusion were randomized to receive either balanced fluid (lactated Ringer's or PlasmaLyte) or 0.9% saline for up to 48 hours. 

Primary Outcome

The primary endpoint was a major adverse kidney event (MAKE) within 30 days — a composite of death, new renal-replacement therapy, or persistent kidney dysfunction. Among 8,482 patients analyzed:

Balanced fluid group: 137/4,073 (3.4%) experienced a MAKE event

0.9% saline group: 124/4,068 (3.0%) experienced a MAKE event

Risk ratio: 1.10 (95% CI, 0.88–1.40; P = 0.85) — no significant difference

Secondary Outcomes

No differences were observed in any secondary effectiveness endpoint:

30-day mortality: 1.0% vs. 0.9% (RR 1.07; 95% CI, 0.70–1.64)

90-day mortality: 2.3% vs. 2.1% (RR 1.07; 95% CI, 0.80–1.42)

New renal-replacement therapy: 0.6% vs. 0.7% (RR 0.84; 95% CI, 0.50–1.42)

Hospital-free days at 28 days: median 23 in both groups

While the primary outcome was neutral, balanced fluids demonstrated more normal lab values:

Hyperchloremia (Cl >110 mEq/L): 31.4% vs. 49.0% (RR 0.64; P < 0.001)

Hypernatremia (Na >155 mmol/L): 1.8% vs. 3.1% (RR 0.60; P = 0.003)

Hyperlactatemia (lactate >4 mmol/L): 19.8% vs. 16.7% (RR 1.18; P = 0.04) — slightly higher in the balanced fluid group, likely reflecting the lactate content in LR

No differences were seen in thrombosis, cerebral edema, hyperkalemia, or hypercalcemia between groups

References

Balamuth F, Weiss SL, Long E, Thompson GC, Artis AS, Campos AB, Borland ML, Dalziel SR, Yock-Corrales A, Singh R, Williams A, Mickiewicz B, Hickey CP, Fitzgerald JC, Laskin BL, Hickey RW, Eckerle M, Alqurashi W, Alpern E, Ambroggio L, Badawy M, Baumer-Mouradian S, Berthelot S, Clukies LD, Craig S, Curtis SJ, Davis AL, Duffy S, Eisenberg MA, Emsley JG, Festekjian A, George S, Green R, Gripp KE, Jain PG, Jani S, Joubert GI, Judge P, Kam A, Kochar A, Koutroulis I, Kwok MY, Lane RD, Lithgow A, Lloyd J, Mansour K, McManemy JK, Morris C, Phillips N, Rao A, Rogers A, Sehgal A, Shayan Y, Silverman J, Tan E, Uspal NG, Vance C, Whyte E, Huang J, Freedman SB, Babl FE, Kuppermann N; PRoMPT BOLUS Investigators of the PECARN, PERC, and PREDICT Networks. Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock. N Engl J Med. 2026 Apr 24:10.1056/NEJMoa2601969. doi: 10.1056/NEJMoa2601969. Epub ahead of print. PMID: 42028918; PMCID: PMC13134814.