SCCM Resource Library-33-Balanced Crystalloids Versus Saline for Initial Fluid Resuscitation in Children With Septic Shock

Video Transcription

Good evening. I'm Juma Shankar, Associate Professor in the Division of Pediatric Pulmonology  and Critical Care at the All India Institute of Medical Sciences, New Delhi, India. Today,  I'll be presenting the findings of our multicenter clinical trial entitled, Balanced Crystalloids  versus Saline for Initial Fluid Resuscitation in Children with Septic Shock, as part of the STAR research presentations. I have nothing to disclose, and the study was funded by the  Department of Science and Technology, Government of India. These are my co-investigators from the four sides. Fluid resuscitation is a key intervention in septic shock management.  The current surviving success campaign guideline recommends the use of balanced crystalloids over 0.9% saline, except in conditions with compelling indications of  normal saline bolus. However, the current recommendations are not based on high quality evidence. Recent trials in critically ill adults have questioned the safety of normal saline.  Normal saline is hypertonic, hypernatremic, and hyperchloremic relative to plasma. There is increased incidence of acute kidney injury and hyperchloremic acidosis reported  in critically ill adults. In a secondary analysis of the subgroup of patients with sepsis from the SMART trial, the authors observed lower incidence of major adverse kidney events  with the use of balanced crystalloids. The composition of balanced crystalloids is similar to plasma, and decreased incidence of acute kidney injury and metabolic disturbances  have been reported in various adult and pediatric patient populations.  In children, the data so far is limited to two small trials published as conference abstracts,  a propensity matched analysis, and a pragmatic trial that tested the feasibility of conducting  a large trial. All these studies point towards lower mortality and lower incidence of hyperchloremia  with the use of balanced crystalloids. Till date, no adequately powered clinical trial has evaluated the effect of balanced crystalloids on clinical outcomes in children.  The incidence of acute kidney injury is reported to be 25% to 40% in children with septic shock.  The incidence of severe AKI, as for the SPROUD study, was around 20%. And these children with  severe AKI were more likely to have functional disability or died. The mortality due to AKI  from Indian ICUs is reported to be 37% to 42%. In resource-limited settings, such as India and  other countries, the accessibility to renal replacement therapy is restricted. Therefore, safety of fluids causing AKI is a concern.  With this background, we hypothesized that use of balanced crystalloid as initial fluid for resuscitation in children with septic shock is associated with a lower incidence  of new-onset acute kidney injury as compared to the use of normal saline. The primary objective was to examine if use of balanced crystalloid results in lower incidence  of new-onset acute kidney injury in the first seven days after initial fluid resuscitation as compared to the use of normal saline. We define new-onset acute kidney injury  as per the KDO clinical practice guideline published in 2013. And it was defined as increase in serum creatinine by more than 0.3 milligrams per deciliter within 48 hours or to  1.5 times baseline or more within the last seven days, or urine output less than 0.5 ml per kg per  hour for six hours. The secondary objectives were to evaluate the difference between both fluids on the incidence of hyperchloremia and metabolic acidosis at 24, 48, and 72 hours,  on organ dysfunction scores, that is, pSO4 score at 24 and 48 hours, on the ventilator-free days, vasopressor-free days, ICU and hospital-free days, and mortality.  This was a double-blind, multicenter, randomized controlled trial conducted in four sites across the country. And this was conducted over a period of three years.  We obtained institutional ethical clearance from all the four sites, and the trial is registered  in clinical trials. We obtained consent from the parent or guardian in a two-step manner,  verbal followed by written. Children aged two months to 17 years of age with features of septic  shock were eligible for inclusion. Septic shock was defined as suspected infection with at least  two clinical signs of decreased perfusion, with or without hypotension. Those receiving fluid  boluses or those with chronic kidney disease, severely malnourished children, those with  cardiogenic shock, and refusal to participate in the study were excluded. The incidence of AKI across our units is 25%, assuming a type I error of 5% power of 90%. Reduction of 15%  with the use of balanced crystalloids, we calculated that the sample size would be 708,  354 in each group. Block randomization using varying block sizes of two to eight was performed, and the random number table was generated from a computerized software.  For allocation concealment, we had serially numbered sealed identical pouch containing  two sets each of five bags of 500 ml of either balanced crystalloid or normal saline, and the study site were kept as per the allocation sequence.  Thereby, the clinical team and investigators were blinded, and the outcome assessor was also blinded. This is how we blinded the fluids. We packed the fluids in opaque pouches,  and then five of these bags were kept in a pouch, and two of these pouches were kept at the bedside of the patient. This is the study protocol.  Children with sepsis in whom bolus was required were enrolled if they did not have any exclusion  criteria into either the balanced crystalloid or the normal saline group, and fluid boluses  in these patients were given at 20 ml per kg over 15 to 20 minutes, and further fluids were given  based on standard management of shock targeting the therapeutic endpoints. Shock management was  as per the American College of Critical Care Medicine 2017 guidelines. The outcomes were  measured at pre-specified time points, such as proportion with new-onset AKI in the first seven  days and metabolic disturbances at pre-specified time points. A total of 708 children were enrolled, 351 in the balanced crystalloid group and 357 in the normal saline group.  The site-wise enrollment was fairly uniform. We had 1080 children whom we assessed for eligibility,  and 708 of these were randomized, 351 to the balanced crystalloid group and 357 to the saline group. This table shows the baseline characteristics. As we can see, the median age  was about five years. Between the two groups, the age, gender, PIM-3, comorbidities, source of infection, and AKI at admission were comparable.  This table shows the fluids or the intervention that both the groups received. The volume of boluses in the first hour, the median volume was about 30 ml per kg in both the groups,  and in the first six hours, it was about 50 ml per kg. There was no difference with regard to  the total fluid intake in the first 24 hours or 48 hours or 72 hours. Similarly, there was no  difference in the percentage in the fluid overload percentage between the groups in the first 24 or  48 hours. And now the primary outcome, we noted that the incidence, the number, the percentage  of children developing new-onset AKI was 20% in the balanced crystalloid group as compared to 33%  in the normal saline group, and the difference was significant. The relative risk was 0.62,  the 95% CI of 0.48 and 0.80. The number needed to treat was eight. This is the Kaplan-Meier survival estimate, and this shows that there was increased risk of AKI at any time point  in the normal saline group as compared to the balanced crystalloid group.  This table shows the secondary outcomes, and the mortality was about 30% in both the groups.  There was no difference in the risk of mortality, and the risk of hyperchloremia as well as metabolic acidosis was lower in the balanced crystalloid group as compared to the normal  saline group at 24, 48, and 72 hours. The number of children receiving renal replacement therapy during the first seven days was also lower in the balanced crystalloid group,  and the difference was significant. There was the organ dysfunction scores, although lower  in the balanced crystalloid group at 24 and 48 hours, the difference was not significant. There  was no difference in the ventilator-free days, inotrope-free days, PICU-free days, or hospital-free  days between the groups. We also did a post-hoc analysis by excluding those who had AKI at  admission, and we found that the incidence was 17% in the balanced crystalloid group and 29%  in the normal saline group, and the difference was still significant. Across all the four sites,  there was lower incidence of AKI in the first seven days in the balanced crystalloid group as compared to the normal saline group. We observed that the use of balanced  crystalloid as compared to normal saline for initial fluid recitation was associated with significant reduction in new-onset AKI. Greater proportion of children  with AKI required RRT in the normal saline group. There was a higher risk of hyperchloremia, metabolic acidosis in the first 72 hours in the normal saline group. Therefore, balanced  crystalloids may be preferred for initial fluid recitation in children with septic shock.  I'd like to sincerely thank and acknowledge the contributions of Department of Science and Technology, Government of India towards implementation and for providing the logistics  for this project, and I would also like to take this opportunity to thank the PALISI group,  especially the PALISI Global Health Subgroup, for their critical and continued inputs into the designing, initiation, and implementation and completion of this study. Thank you.  you

Video Summary

In this video, Dr. Juma Shankar presents the findings of a multicenter clinical trial comparing balanced crystalloids and normal saline for fluid resuscitation in children with septic shock. The study aimed to determine if the use of balanced crystalloids resulted in a lower incidence of acute kidney injury (AKI) compared to normal saline. The trial included 708 children and found that the balanced crystalloid group had a significantly lower incidence of AKI compared to the normal saline group. The study also found a lower risk of hyperchloremia and metabolic acidosis in the balanced crystalloid group. Based on these findings, balanced crystalloids may be preferred for fluid resuscitation in children with septic shock.

Asset Subtitle

Pediatrics, Sepsis, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Jhuma Sankar

Introduction/Hypothesis: Use of 'Balanced Crystalloids' as compared to 'Normal Saline' as initial fluid for resuscitation in children with septic shock may be associated with decreased risk of acute kidney injury (AKI) in the first 7 days.

Methods: Children <17 years' age with septic shock were randomized to receive boluses of either Balanced Crystalloids (Plasma-Lyte A; 'BC group') or Normal Saline ('NS group') for initial resuscitation at 4 study sites from 2017 to 2019. All children were managed as per the Surviving Sepsis Campaign Guidelines 2017 and were monitored till discharge/death. AKI was defined as per 2012 KDIGO clinical practice guidelines. Risk of AKI in the first 7 days after initial fluid resuscitation was the primary outcome. Other important outcomes were requirement of renal replacement therapy (RRT), risk of hyperchloremia and mortality.

Results: We enrolled 708 children: 351 and 357 in the 'BC' and 'NS' groups, respectively. Baseline characteristics were comparable. The fluid volumes received in the first 24 hours were similar in both groups (107 ml/kg in the 'BC' vs. 110 ml/kg in the 'NS' group; p= 0.93). There was a significant reduction in the risk of AKI (20% vs. 33%; RR: 0.62; 95% CI 0.48 to 0.80; p=0.0001) and requirement of RRT (10% vs. 20%; RR 0.50; 0.34 to 0.73; p=0.0002) in the 'BC group'. The risk of hyperchloremia at 72 hours was also lower in the 'BC group'. The mortality in both groups was however, similar (33% vs. 34%; RR 0.96; 0.78 to 1.19).

Conclusions: Use of Balanced Crystalloids for initial fluid resuscitation in children with septic shock was associated with significant reduction in the risk of new onset acute kidney injury. Balanced crystalloids should be preferred over Normal Saline for initial fluid resuscitation.

Meta Tag

Content Type Presentation

Knowledge Area Pediatrics

Knowledge Area Sepsis

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Shock

Tag Fluids Resuscitation Management

Year 2021

Keywords

Dr. Juma Shankar

multicenter clinical trial

balanced crystalloids

normal saline

acute kidney injury (AKI)

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