Bicarbonated Ringer's Solution Versus Lactated Ringer's Solution in Patients With Septic Shock

Fluid Resuscitation Management for Patients With Septic Shock: the Efficacy and Safety Comparison Between Bicarbonated Ringer's Solution and Lactated Ringer's Solution

In this prospective randomized controlled trial, investigators aim to study the effects and safety of bicarbonated Ringer's solution in patients with septic shock compared with lactated ringer's solution, and provide evidence for current fluid resuscitation strategies for septic shock.

Study Overview

• Status: Unknown
• Conditions: Septic Shock; Intensive Care Unit; Fluid Resuscitation; Crystalloid Solution
• Intervention / Treatment: Drug: Bicarbonated Ringer's solution; Drug: Lactated Ringer's solution

Detailed Description

Although the latest guidelines recommend crystalloids as the first choice for the patients' fluid resuscitation, it still remains controversial that which crystalloid solution is the best choice. It is reported that balanced crystalloid can result in better outcomes than saline for critically ill patients. However, there are few studies conducted between different crystalloid solutions.

Lactated ringer's solution is the longest-used crystalloid solution. Compared with lactated ringer's solution whose anion is lactate, the anion of bicarbonate ringer's solution is bicarbonate. And lactate needs to be metabolized into bicarbonate through the mitochondria of the liver before it can play an alkalization role. Therefore, in theory, bicarbonate ringer's solution does not need to rely on liver metabolism, the onset time to maintain acid-base balance is shorter, and it may be more suitable for patients with severe acidosis. In patients with septic shock, the incidence of moderate to severe metabolic is increased. Bicarbonate ringer's solution can directly supplement the concentration of bicarbonate, while lactated ringer's solution needs to take time and be metabolized in the liver. Thus, we hypothesize that bicarbonate ringer's solution is more effective for patients with shock and metabolic acidosis than lactated ringer's solution.

• Study Type: Interventional
• Enrollment (Anticipated): 260
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Zhongnan Hospital of Wuhan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. At the age of 18 to 75;
• 2. Being treated in the ICU;
• 3. Diagnosed as septic shock according tho the definition of Sepsis 3.0 with fluid resuscitation requirement.

Exclusion Criteria:

• 1. Severe hepatic failure;
• 2. Possible brain injury;
• 3. With absolute contraindications for central vena catheterization;
• 4. Ever participated in another clinical trial within 30 days prior enrollment;
• 5. Have corrected metabolic acidosis through alkaline drug application within 24 hours prior to enrollment;
• 6. Hypermagnesemia or hypothyroidism;
• 7. Pregnant of breast-feeding women;
• 8. Considered inevitable death;
• 9. Other situations where investigators think enrollment is not appropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bicarbonated ringer's solution; We apply bicarbonated ringer's solution as resuscitation fluid to patients with septic shock.	Drug: Bicarbonated Ringer's solution; Method of administration: intravenous infusion; 500-1000ml each time; Speed of infusion: it is decided by the clinicians.; Other Names: Ringers Bicarbonate
Experimental: lactated ringer's solution; We apply lactated ringer's solution as resuscitation fluid to patients with septic shock.	Drug: Lactated Ringer's solution; Method of administration: intravenous infusion; 500-1000ml each time; Speed of infusion: it is decided by the clinicians.; Other Names: Ringers Lactate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the average doses of vasopressors	total doses of norepinephrine÷weight÷duration of usage	From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the PH value	the potencial of hydrogen of arterial blood	0, 3 hours, 6 hours, 12 hours, 24 hours
the BE value	the base excess of arterial blood	0, 3 hours, 6 hours, 12 hours, 24 hours
shock reversal time	From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs	From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.
total volume of fluids before hemodynamic stabilization	total volume of bicarbonated ringers/lactated ringers before hemodynamic stabilization	From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.
the change of serum lactate value at the 6th hour	serum lactate (6h) - serum lactate (0h)	6 hours
the proportion of patients whose serum lactate decreases 30%	the proportion of patients whose serum lactate decreases 30%	From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.
mortality from any cause	the rate of death from any cause within 28 days after enrollment	on the day28 after enrollment
the rate of metabolic alkalosis	the percentage of metabolic alkalosis (PH>7.45 and HCO3>26mmol/L)	From the onset of shock to the first blood pressure stabilization (MAP≥65mmHg), or serum lactate <2.2mmol/l, or discontinuation of vasoactive drugs. About 24 hours.

Collaborators and Investigators

• Sponsor: Zhongnan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): May 30, 2021
• Study Completion (Anticipated): May 30, 2021

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 29, 2020

Study Record Updates

• Last Update Posted (Actual): June 29, 2020
• Last Update Submitted That Met QC Criteria: June 23, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: intensive care unit; septic shock; fluid resuscitation; crystalloid solution
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Pharmaceutical Solutions
• Other Study ID Numbers: 2020044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No