The Effect of Fluid Resuscitation With 0.9% Sodium Chloride Versus Balanced Crystalloid Solution on Renal Function of Sepsis Patients

The high chloride content of 0.9%sodium chloride (0.9%NaCl) leads to adverse pathophysiological effects in both animals and healthy human volunteers. Small randomized trials confirm that the hyperchloremic acidosis induced by 0.9%NaCl also occurs in patients. A strong signal is emerging from recent large propensity-matched and cohort studies for the adverse effects that 0.9% NaCl has on the clinical outcome in surgical and critically ill patients when compared with balanced crystalloids. Major complications are the increased incidences of acute kidney injury and the need for renal replacement therapy, and that pathological hyperchloremia may increase postoperative mortality.

Fluid resuscitation with 0.9% NaCl in animals with sepsis resulted in hyperchloremic metabolic acidosis, worsened AKI, and increased mortality when compared with resuscitation with a balanced crystalloid solution.

Furthermore, hyperchloremic acidosis also resulted in increased concentrations of circulating inflammatory mediators in an experimental model of severe sepsis in rats, with a dose-dependent increase in circulating interleukin-6, tumor necrosis factor-a, and interleukin-10 concentrations with increasing acidosis.

Thus, in this study, investigators compared the effects of a balanced crystalloid solution with 0.9% NaCl on the renal function in severe sepsis/septic shock patients. Investigators hypothesized that balanced crystalloid solution resuscitation would decrease AKI incidence and severity and would improve immunomodulatory effect when compared with 0.9% NaCl resuscitation.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock; Acute Kidney Injury
• Intervention / Treatment: Drug: Normal saline; Drug: Ringer's Acetate

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years old
• Who need fluid resuscitation in the Emergency Room (ER).

• Who have fulfilled the criteria for sepsis/septic shock within the previous 24 hours according to sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.

  o Patients with infection and resulted from a host's systemic inflammatory response syndrome (SIRS) to infection are defined as sepsis if meet the criteria 2 or more of

  • Temperature >38°C or <36°C
  • Heart rate >90/min
  • Respiratory rate >20/min or PaCo2 <32 mm Hg (4.3 kPa)
  • White blood cell count >12000/mm3 or <4000/mm3 or >10% immature bands.

• Patient who have Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.

  o Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation.

• AND where informed consent is obtainable either from the patient or by proxy (first degree relative, spouse) if patients aren't in fully conscious status (eg.comatose, drowsiness, irritable).

Exclusion criteria

Exclusion Criteria:

• Patients with chronic kidney disease (CKD) defined by baseline serum creatinine > 2.0 in male and 1.5 in female.
• Patients with End stage renal disease (ESRD) with or without renal replacement therapy.
• Patients with active cardiac disease : severe valvular heart, cardiomyopathy, decompensated heart failure NYHA II-IV, severe pulmonary hypertension.
• HIV/AIDs Patients.
• Allergy towards 0.9% NaCl or Ringer's Acetate.
• Any form of renal replacement therapy.
• Intracranial bleeding within current hospitalization.
• Therapy with corticosteroid or non steroidal anti-inflammatory substance.
• Patients who predicted not to survive more than 24 hours.
• Pregnant and lactating patients.
• Withdrawal of active therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: normal saline	Drug: Normal saline; for resuscitation in sepsis patients
ACTIVE_COMPARATOR: balanced solution	Drug: Ringer's Acetate; for resuscitation in sepsis patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of acute kidney injury for any stage and severity	at day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
The neutrophil function (chemotaxis, CD11b ) between two randomized groups at	0, 24, and 72 hours after resuscitation.
The monocyte function (HLA-DR) between two randomized groupsafter resuscitation.	at 0, 24, and 72 hours after resuscitation.
The inflammatory marker (IL-6, IL-10) between two randomized groups at	0, 24, and 72 hours after resuscitation.
Urinary neutrophil gelatinase-associated lipocalin (NGAL) after randomization and after resuscitation with trial fluid	at 0,24 and 72 hours after resuscitation.
Urinary liver-type fatty acid binding protein (L-FABP)	at 0,24 and 72 hours after resuscitation.
Sequential [Sepsis-related] Organ Failure Assessment (SOFA) Score. (excluding Glasgow Coma Score) at 72 hours after randomization.	at 72 hours after randomization.
Need of renal replacement therapy within 72 hours after randomization	within 72 hours after randomization
Days alive without renal replacement therapy	in 28 days after randomization
Hospital length of stay for survivors sanctioned	at 28 days after randomization

Collaborators and Investigators

• Sponsor: Chulalongkorn University

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2017
• Primary Completion (ACTUAL): July 1, 2018
• Study Completion (ACTUAL): March 1, 2021

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: September 7, 2017
• First Posted (ACTUAL): September 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 9, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Kidney Diseases; Urologic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Renal Insufficiency; Sepsis; Toxemia; Acute Kidney Injury
• Other Study ID Numbers: IRB.113/60

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No