Balanced Crystalloid vs. Saline in Children With Septic Shock

NCT02835157 | Completed DMC

• 1 other identifier: IEC/NP-424/09.10.2015
• Study Type: interventional
• Target: 708
• Locations: 1 country
• Sites: 4

Brief Summary

Fluid resuscitation is the cornerstone of pediatric shock management; current practices of fluid resuscitation in children are not evidence based. Normal saline is the preferred crystalloid recommended during initial resuscitation in shock, as the incidence of hyponatremia is lower with normal saline compared to all other fluids available and commonly used. However, normal saline has its own set of undesired physicochemical actions. Emerging data strongly indicate the increased incidence of hyperchloremia, metabolic acidosis and consequently, acute kidney injury associated with infusion of large volumes of normal saline. Balanced salt solutions or crystalloids, which have composition resembling plasma but lower chloride concentrations than normal saline, clearly decrease the risk of hyperchloremia and metabolic acidosis in adult as well as pediatric studies when used during the peri-operative period. The results favored balanced solutions in comparison to normal saline. Recent systematic reviews comparing balanced or buffered versus non-buffered fluids for surgery in adults favored the former solution as the metabolic derangements were less with the use of this type of fluid. In adult patients, the two solutions have been compared in various other settings as well such as in traumatic brain injury and in shock. The results favored balanced solutions in comparison to normal saline. However, in the non-surgical setting there is a paucity of evidence on the use of these solutions in children with shock and more evidence needs to be generated to support or refute the use of this fluid as compared to normal saline. Given this background, the investigators decided to compare the effect of two solutions on the incidence of acute kidney injury in children resuscitated with either of the two fluids. Children receiving at least one fluid bolus at 20 ml/kg in the first hour would be enrolled and followed up for the proposed outcome variables. The investigators plan to enroll 708 patients over a period of 3 years. The investigators believe that the proposed study will provide answer to the research question of which of the fluids could be preferred for resuscitation.

Conditions

Septic Shock; Shock

Keywords

Normal saline; Multiple electrolyte solution; Septic shock; Children; Hyperchloremia; Acute kidney injury; 0.9% saline; Balanced crystalloid

Outcome Measures

Primary Outcomes (1)

• New or progressive acute kidney injury defined as increase in serum creatinine by > 0.3mg/dL within 48 hours or to 1.5 times baseline or more within the last 7 days or urine output less than 0.5 mL/kg/h for 6 hours

  Incidence of new or progressive AKI in first 7 days after randomization/ intervention

  From the time of randomization/intervention to 7 days of admission

Secondary Outcomes (8)

• Proportion of patients with serum chloride levels > 108 meq/L at admission, 6, 24, 48 and 72 hours

  At 6, 24, 48 and 72 hours after randomization

• Number of fluid boluses received in the first 6 hours after randomization

  From the time of randomization to 6 hours

• Total fluids received in the first 24 hours, 24-48 hours and 48-72hrs in ml/kg after randomization

  From the time of randomization to 72 hours

• Mortality (serious adverse event)

  From the time of randomization till death or discharge from ICU, whichever came first assessed upto 100 days

• Time to resolution of AKI

  From the time of onset of AKI after randomization till death or discharge from hospital, whichever came first assessed upto 100 days

Other Outcomes (3)

• Safety outcome 1

  From the time of randomization/intervention to 7 days of admission

• Safety outcome 2

  From the time of randomization/intervention to mortality

• Safety outcome 3

  From the time of initiating the bolus to its completion

Study Arms (2)

Balanced crystalloid or multiple electrolyte solution group

EXPERIMENTAL

After enrollment, a fluid bolus comprising of 'multiple electrolyte solution (Plasma-Lyte P)' solution at a dose of 20 ml/kg over 15-20 minutes (recommended) with careful monitoring for features of fluid overload would be administered to each child. Fluid resuscitation will be targeted at achieving the therapeutic end points as given in study definitions. After this the management protocol will be as per recommendations of the American College of Critical Care Medicine 2017 for septic shock in children.

Drug: Balanced crystalloid solution

0.9% saline or saline group

ACTIVE COMPARATOR

After enrollment, a fluid bolus comprising of 'saline' solution at a dose of 20 ml/kg over 15-20 minutes (recommended) with careful monitoring for features of fluid overload would be administered to each child. Fluid resuscitation will be targeted at achieving the therapeutic end points as given in study definitions. After this the management protocol will be as per recommendations of the American College of Critical Care Medicine 2017 for septic shock in children.

Drug: 0.9%sodium chloride

Interventions

Balanced crystalloid solution DRUG

Multiple electrolyte solution as boluses would be administered.

Also known as: Plasma-Lyte A 148, Multiple electrolyte solution

Balanced crystalloid or multiple electrolyte solution group

0.9%sodium chloride DRUG

saline as boluses would be administered

Also known as: Saline

0.9% saline or saline group

Eligibility Criteria

• Age: 2 Months - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children 2 month to ≤ 15 years with features of septic shock - defined as children who have a suspected infection manifested by hypothermia or hyperthermia and have at least two clinical signs of decreased perfusion with or without hypotension

You may not qualify if:

• Children receiving fluid boluses before enrollment
• Children with cardiogenic shock
• Known patient with chronic kidney disease with baseline deranged renal function (eGFR \< 90 ml/1.73 m2/min)
• Severe malnutrition
• Children whose parents refuse to give an informed consent

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead
• Post Graduate Institute of Medical Education and Research, Chandigarh: collaborator
• Jawaharlal Institute of Postgraduate Medical Education & Research: collaborator
• St Johns Medical College Hospital, Bangalore, India: collaborator

Study Sites (4)

St Johns Medical College and Hospital

Bengaluru, Karnataka, 560034, India

Location

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

PGIMER

Chandigarh, India

Location

JIPMER

Puducherry, 605006, India

Location

Related Publications (1)

• Sankar J, Muralidharan J, Lalitha AV, Rameshkumar R, Pathak M, Das RR, Nadkarni VM, Ismail J, Subramanian M, Nallasamy K, Dev N, Kumar UV, Kumar K, Sharma T, Jaravta K, Thakur N, Aggarwal P, Jat KR, Kabra SK, Lodha R. Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial. Crit Care Med. 2023 Nov 1;51(11):1449-1460. doi: 10.1097/CCM.0000000000005952. Epub 2023 Jun 9.

  PMID: 37294145 DERIVED

MeSH Terms

Conditions

Shock, Septic; Shock; Acute Kidney Injury

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Jhuma Sankar, MD Ped

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Sushil K Kabra, MD Ped

  All India Institute of Medical Sciences

  STUDY CHAIR

• Rakesh Lodha, MD Ped

  All India Institute of Medical Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Serially numbered, sealed, opaque pouches containing 10 bags of 500 ml of either MES or saline each will be kept at the study site. Each of the 500 ml bags will be packed in sealed opaque covers inside the pouches as well.The research staff will pick the bag of fluids kept as per allocation sequence and start the bolus in the patient.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Additional Professor Pediatrics

Model Details: The enrolled children will be randomized to either balanced crystalloid (Plasma-Lyte A or multiple electrolyte solutions or MES group) or 0.9% saline (saline group).

Study Record Dates

• First Submitted: March 1, 2016
• First Posted: July 15, 2016
• Study Start: April 1, 2017
• Primary Completion: January 15, 2020
• Study Completion: January 15, 2020
• Last Updated: December 21, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

IN (4)