PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial

Abstract

Background/aims Despite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock. Methods The Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under “exception from informed consent” in the USA or “deferred consent” in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed. Discussion PRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings. Trial registration PRoMPT BOLUS was first registered at ClinicalTrials.gov (NCT04102371) on September 25, 2019. Enrollment started on August 25, 2020.

Comparison of balanced crystalloid versus normal saline for fluid resuscitation in the early stages of acute severe pancreatitis: study protocol for a randomized controlled trial

“…Besides, it is unrealistic to set a 100% complete grouping solution. So we de ne a well adherence as receipt of ≥80% of total randomly assigned solution referenced to a paediatric sepsis study [29]. Our study aims to nd a predominant balanced crystalloid uid better than normal saline used in SAP for supplemental treatment.…”

Fluid bolus therapy in pediatric sepsis: a narrative review

“…Finally, a recent observational study of 99 pediatric sepsis found a decrease in acute kidney injury, need for renal replacement therapy and hospital length of stay with balanced crystalloids [ 48 ]. Thus, the debate is not over and the results of an ongoing international RCT with anticipated enrollment of 8,800 children with septic shock are eagerly awaited [ 49 ], especially as two recent large RCTs in adults ICUs did not report improved survival with balanced crystalloids [ 50 , 51 ].…”

Dysnatremia in children, why is it so hard to stay normal?

“…8 Thus, it remains to be seen if balanced solutions are superior to NS in pediatric intensive care settings. 9 A large portion of the documented pediatric dysnatermia cases is iatrogenic and related to fluid composition. 10 Consequently, it is not unreasonable to assume that the amount of fluid given is equally important as the choice of fluid.…”