Clinical trial NCT03277677: The Effect of Fluid Resuscitation With 0.9% Sodium Chloride Versus Balanced Crystalloid Solution on Renal Function of Sepsis Patients
Official title: The Effect of Fluid Resuscitation With 0.9% Sodium Chloride Versus Balanced Crystalloid Solution on Renal Function of Sepsis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sepsis
Septic Shock
Acute Kidney Injury
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
First posted: 2017-09-11
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The incidence of acute kidney injury for any stage and severity
timeFrame: at day 7
Secondary outcomes:
measure: The neutrophil function (chemotaxis, CD11b ) between two randomized groups at
timeFrame: 0, 24, and 72 hours after resuscitation.
measure: The monocyte function (HLA-DR) between two randomized groupsafter resuscitation.
timeFrame: at 0, 24, and 72 hours after resuscitation.
measure: The inflammatory marker (IL-6, IL-10) between two randomized groups at
timeFrame: 0, 24, and 72 hours after resuscitation.
measure: Urinary neutrophil gelatinase-associated lipocalin (NGAL) after randomization and after resuscitation with trial fluid
timeFrame: at 0,24 and 72 hours after resuscitation.
measure: Urinary liver-type fatty acid binding protein (L-FABP)
timeFrame: at 0,24 and 72 hours after resuscitation.
measure: Sequential [Sepsis-related] Organ Failure Assessment (SOFA) Score. (excluding Glasgow Coma Score) at 72 hours after randomization.
timeFrame: at 72 hours after randomization.
measure: Need of renal replacement therapy within 72 hours after randomization
timeFrame: within 72 hours after randomization
measure: Days alive without renal replacement therapy
timeFrame: in 28 days after randomization
measure: Hospital length of stay for survivors sanctioned
timeFrame: at 28 days after randomization
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Chulalongkorn university
Study officials:
References: