Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study

Weiss, Scott L.; Keele, Luke; Balamuth, Fran; Vendetti, Neika; Ross, Richard N.; Fitzgerald, Julie C.; Gerber, Jeffrey S.

doi:10.1016/j.jpeds.2016.11.075

Cited by 56 publications

(36 citation statements)

References 39 publications

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“…Rationale: Increasing evidence from observational studies and RCTs in adults suggests that resuscitation with crystalloid fluids containing high chloride concentrations (e.g., 0.9% saline) is associated with hyperchloremic acidosis, systemic inflammation, acute kidney injury (AKI), coagulopathy, and mortality when compared with resuscitation with more balanced/buffered crystalloids (e.g., lactated Ringer's, PlasmaLyte) [192]. Although no pediatric RCTs compare balanced/ buffered crystalloids to 0.9% saline, there are two large observational studies in children with sepsis [193,194]. They included a total of 30,532 children with sepsis, 2100 of whom received only balanced/buffered crystalloids for the first 72 h of hospital admission, and 28,432 who received 0.9% saline (Supplemental Table 5, Supplemental Digital Content 1, http://links .lww.com/ PCC/B139).…”

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“…They included a total of 30,532 children with sepsis, 2100 of whom received only balanced/buffered crystalloids for the first 72 h of hospital admission, and 28,432 who received 0.9% saline (Supplemental Table 5, Supplemental Digital Content 1, http://links .lww.com/ PCC/B139). These studies showed that use of balanced/ buffered crystalloids was associated with lower mortality (OR, 0.79; 95% CI, 0.65-0.95) but not AKI (OR, 0.98; 95% CI, 0.94-1.02) [193,194]. Indirect evidence from adult patients, including two large RCTs, also demonstrates benefit with balanced/buffered crystalloids over 0.9% saline, with adult patients who received larger volumes of fluid and those with sepsis exhibiting the greatest benefit [192,195].…”

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Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

et al. 2020

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Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those The Society of Critical Care Medicine guidelines are intended for general information only, are not medical advice, and do not replace professional advice, which should be sought for any medical condition. The full disclaimer for guidelines can be accessed at https ://www.sccm.org/Resea rch/Guide lines /Guide lines . panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. Conclusions:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research. S14 the group heads, panel members, and methodologists. Searches utilized ...

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Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

et al. 2020

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“…In a recent large matched cohort study on pediatric sepsis, LR resuscitation was not associated with reduced mortality, AKI, or dialysis even when matched by fluid volume and proportionate LR utilization ( 101 ). Mortality increased with larger fluid volumes and decreased with a greater proportion of fluid given as LR, but there were no differences between LR and NS groups after matching within volume quartiles, by proportionate LR utilization, or in the separate matched analysis of LR-only patients.…”

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Fluid Overload in Critically Ill Children

et al. 2018

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Background: A common practice in the management of critically ill patients is fluid resuscitation. An excessive administration of fluids can lead to an imbalance in fluid homeostasis and cause fluid overload (FO). In pediatric critical care patients, FO can lead to a multitude of adverse effects and increased risk of morbidity.Objectives: To review the literature highlighting impact of FO on a multitude of outcomes in critically-ill children, causative vs. associative relationship of FO with critical illness and current pediatric fluid management guidelines.Data Sources: A literature search was conducted using PubMed/Medline and Embase databases from the earliest available date until June 2017.Data Extraction: Two authors independently reviewed the titles and abstracts of all articles which were assessed for inclusion. The manuscripts of studies deemed relevant to the objectives of this review were then retrieved and associated reference lists hand-searched.Data Synthesis: Articles were segregated into various categories namely pathophysiology and sequelae of fluid overload, assessment techniques, epidemiology and fluid management. Each author reviewed the selected articles in categories assigned to them. All authors participated in the final review process.Conclusions: Recent evidence has purported a relationship between mortality and FO, which can be validated by prospective RCTs (randomized controlled trials). The current literature demonstrates that “clinically significant” degree of FO could be below 10%. The lack of a standardized method to assess FB (fluid balance) and a universal definition of FO are issues that need to be addressed. To date, the impact of early goal directed therapy and utility of hemodynamic parameters in predicting fluid responsiveness remains underexplored in pediatric resuscitation.

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“…The largest benefit was observed in adults with sepsis. However, no trial has compared the effectiveness of different crystalloid fluid types for resuscitation in children with sepsis, and the two largest observational pediatric studies reported conflicting results . Consequently, there is insufficient evidence to strongly recommend a specific crystalloid fluid type for resuscitation of children with septic shock …”

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Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: The PRoMPT BOLUS Randomized Controlled Trial Pilot Feasibility Study

Balamuth

Kittick

McBride

et al. 2019

Academic Emergency Medicine

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Background: Resuscitation with crystalloid fluid is a cornerstone of pediatric septic shock treatment. However, the optimal type of crystalloid fluid is unknown. We aimed to determine the feasibility of conducting a pragmatic randomized trial to compare balanced (lactated Ringer's [LR]) with 0.9% normal saline (NS) fluid resuscitation in children with suspected septic shock.Methods: Open-label pragmatic randomized controlled trial at a single academic children's hospital from January to August 2018. Eligible patients were >6 months to <18 years old who were treated in the emergency department for suspected septic shock, operationalized as blood culture, parenteral antibiotics, and fluid resuscitation for abnormal perfusion. Screening, enrollment, and randomization were carried out by the clinical team as part of routine care. Patients were randomized to receive either LR or NS for up to 48 hours following randomization. Other than fluid type, all treatment decisions were at the clinical team's discretion. Feasibility outcomes included proportion of eligible patients enrolled, acceptability of enrollment via the U.S. federal exception from informed consent (EFIC) regulations, and adherence to randomized study fluid administration.Results: Of 59 eligible patients, 50 (85%) were enrolled and randomized. Twenty-four were randomized to LR and 26 to NS. Only one (2%) of 44 patients enrolled using EFIC withdrew before study completion. Total median (interquartile range [IQR]) crystalloid fluid volume received during the intervention window was 107 (60 to 155) mL/ kg and 98 (63 to 128) mL/kg in the LR and NS arms, respectively (p = 0.50). Patients randomized to LR received a median (IQR) of only 20% (13 to 32) of all study fluid as NS compared to 99% (64% to 100%) of study fluid as NS in the NS arm (absolute difference = 79%, 95% CI = 48% to 85%).C onclusions: A pragmatic study design proved feasible to study comparative effectiveness of LR versus NS fluid resuscitation for pediatric septic shock.From the

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Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study

Cited by 56 publications

References 39 publications

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

Fluid Overload in Critically Ill Children

Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: The PRoMPT BOLUS Randomized Controlled Trial Pilot Feasibility Study

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