Background: Fluid resuscitation with crystalloid is one of the most basic initial management approaches to adult and pediatric patients with severe sepsis and septic shock. However, which fluid should we be giving, and does it matter? Should we give an unbalanced, chloride rich solution such as normal saline or a balanced, chloride restrictive fluid, such as lactated ringers, Plasma-Lyte, or Normasol? Interestingly, the 2016 Surviving Sepsis Guidelines, added resuscitation with balanced fluids into the guidelines, although a weak recommendation with low quality of evidence.
This recommendation was based on some growing adult data, albeit retrospective, showing that resuscitation strategies using normal saline may be harmful and associated with increased risk of AKI (1), need for CRRT (1) and increased mortality (2-3). The effects of balanced fluids however, have not been studied in the resuscitation of children in severe sepsis and septic shock.
A balanced fluid is a fluid that closely resembles the plasma’s electrolyte concentration and its strong ion difference (SID). The SID is the main driving force of our bodies’ acid-base balance and can be calculated by taking the difference between a patient’s serum sodium and chloride levels. Normally patients have a plasma SID close to 40 mEq/L (Serum Na=140mEq/L – Serum Chloride=100 mEq/L). Giving a fluid like normal saline with a SID=0mEq/L will decrease the patients serum SID and cause a metabolic acidosis. Giving a fluid with a SID greater than 40 mEq/L will increase a patients plasma SID and cause a metabolic alkalosis.
Is there an association between the use of balanced solutions for resuscitation in pediatric sepsis management and improved outcomes when compared to unbalanced solutions?
What They Did:
- Observational cohort review of prospectively collected data
- A large data base consisting of over 43 standalone children’s hospitals for 2004-2012 was analyzed
- 36,908 pediatric patients (0-18 years old) who met inclusion criteria for severe sepsis or septic shock based on ICD-9 coding.
- Patients who were resuscitated with balanced fluids only at 24 hours (n=2,398) and 72 hours (n=1641) were compared to those who received unbalanced fluids only at 24 hours & 72 hours using propensity matching.
- Primary Outcome: In-hospital mortality
- Secondary Outcomes:
- Development of AKI
- Need for continuous renal replacement therapy (CRRT)
- Hospital length of stay
- PICU length of stay
- Vasoactive infusion days
Propensity-Matched Outcomes for 72-Hour Fluid Groups
- Patient centered outcomes
- Examines a therapy common to all pediatric septic patients
- Data prospectively collected over a long period of time (2004-2012)
- Multi-centered study
- Large pediatric data base – Pediatric Health Information System (PHIS): Database of 43 different children’s hospitals in the USA
- Observational cohort study: Prospectively looks at exposure over time (balanced vs. unbalanced fluid) and development of an outcome (mortality, AKI, CRRT use…ect)
- The study did use Propensity Matching, a technique used in observational studies to control for cofounders (RCT’s use randomization to control for cofounders, an advantage compared to observational trials)
- There were clinically important factors that were unable to be determined in a retrospective analysis of patient data, such as the total fluid volume received (seen in previous pediatric studies to be an independent risk factor for mortality)
- Definition of severe sepsis and septic shock were based on ICD-9 codes rather than Goldstein Criteria (4) (modified adult SIRS criteria used in children), so Severe Sepsis &/or Septic Shock may have been under represented in the cohorts
- AKI was defined by ICD-9 codes rather than creatinine changes and/or urine output, which again may have underrepresented the prevalence of AKI in the cohorts
- The overall mortality in both cohorts decreased from 21% in 2004 to 12% in 2012 and the amount of patients who received balanced fluid only, decreased from 10.9% in 2004 to 3.4% in 2012
- The authors stated regarding the above findings, that, “these findings make it difficult to ascribe mortality differences from balanced fluids alone”.
- Not surprisingly, it appears that the resuscitative fluid of choice in many children’s hospital’s around the US for pediatric severe sepsis and septic shock is normal saline.
- This was the first study examining the effects of balanced versus unbalanced fluids in pediatric sepsis, and it demonstrated a modest, but significant difference in mortality.
- There was an association with balanced fluids and decreased incidence of the development of acute kidney injury and shortening of vasoactive infusion days.
- Balanced fluids have been recently recommended in adult sepsis and septic shock guidelines, and now there is prospectively collected data from a large pediatric database showing a mortality benefit in severe sepsis and septic shock.
“In this retrospective analysis carried out by propensity matching, exclusive use of balanced fluids in pediatric severe sepsis patients for the first 72 hours of resuscitation was associated with improved survival, decreased prevalence of acute kidney injury, and shorter duration of vasoactive infusions when compared with exclusive use of unbalanced fluids.”
Clinical Bottom Line:
Taking into consideration the adult data, as well as this study, it appears that balanced fluids are safe, physiologic, and inexpensive compared to normal saline. In pediatric severe sepsis and septic shock, resuscitation with balanced fluids should be strongly considered.
Special Guest Contributor
Frank J. Lodeserto MD
Adult & Pediatric Critical Care
Geisinger Medical Center
Janet Weis Children’s Hospital
- 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; 308:1566–1572. PMID: 23073953
- Neyra JA, Canepa-Escaro F, Li X, et al; Acute Kidney Injury in Critical Illness Study Group: Association of Hyperchloremia with Hospital Mortality in Critically ill Septic Patients. Crit Care Med 2015; 43:1938–1944. PMID: 26154934
- Raghunathan K, Shaw A, Nathanson B, et al: Association Between the Choice of IV Crystalloid and In-Hospital Mortality Among Critically ill Adults with Sepsis. Crit Care Med 2014; 42:1585–1591. PMID: 24674927
- Goldstein B, Giroir B, Randolph A, et al: International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction In Pediatrics. Pediatr Crit Care Med 2005; 6:2–8. PMID: 15636651