Multiple Electrolytes Injection (II) and Normal Saline on Hyperchloremia in Severe Hemorrhagic Stroke (MERIT)

The Impact of Multiple Electrolytes Injection (II) and Normal Saline on Hyperchloremia in Severe Hemorrhagic Stroke Patients: A Prospective, Multicenter, Open-label, Randomized Controlled Study

Normal saline (0.9% sodium chloride), a classical crystalloid solution, is widely used to maintain fluid balance, volume resuscitation and dilute drugs during clinical practice. However, the chloride concentration of normal saline (154mmol/L) is much higher than human plasma, and a large amount of infusion may lead to iatrogenic hyperchloremia in ICU patients. In contrast, the concentrations of Multiple electrolytes II is more similar to those of plasma and is considered to be a better fluid choice than normal saline.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemorrhagic Stroke; Critical Care; Hyperchloremia
• Intervention / Treatment: Drug: Multiple Electrolyte; Drug: Normal Saline

Detailed Description

Fluid therapy remains an important part of the treatment and management of critically ill patients. An everyday fluid intake can be simplely divided into: resuscitation fluid, maintenance fluid, nutrition, blood products, drugs and drug carriers. Daily resuscitation and maintenance fluids can account for 31.2% of the total fluid intake and increase during the first 3 days of admission, up to 58.1%, resulting in heavy sodium and chloride loads.

Among them, normal saline (0.9% sodium chloride), a classical crystalloid solution, is widely used to maintain fluid balance, volume resuscitation and dilute drugs. However, the chloride concentration of normal saline (154mmol/L) is much higher than that of human plasma, and a large amount of infusion may lead to iatrogenic hyperchloremia in ICU patients. Hyperchloremia is thought to cause acidosis, decrease in the glomerular filtration rate, impaired renal function, and even mortality. In contrast, the concentrations of balanced crystalloid solutions are more similar to those of plasma and is considered to be a better fluid choice than normal saline.

Hemorrhagic Stroke, which includes spontaneous cerebral hemorrhage and subarachnoid hemorrhage (SAH), is characterized by high mortality and disability. According to the latest studies, there are approximately 1.7 million new hemorrhagic strokes in China each year, and hemorrhagic strokes account for only 30% of all new stroke cases, but 60% of stroke deaths. There is a lack of relevant research on fluid recommendation for this population. One study of subarachnoid hemorrhage suggested that saline caused hyperchloremia, hypertonia, and positive fluid balance over 1500 mL in a large number of patients early after SAH.

Multiple electrolytes II, as a new isotonic balanced salt solution, contains a variety of cations (sodium, potassium, calcium, magnesium) and a lower chloride concentration than normal saline. A study of 30 patients demonstrated that it improved acid-base balance when used in neurosurgery. It may be a new alternative to sodium chloride solution.

• Study Type: Interventional
• Enrollment (Estimated): 342
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jian-Xin Zhou, MD; Phone Number: +86 13801183875; Email: zhoujx.cn@icloud.com
• Study Contact Backup: Name: Yuqing Duan; Phone Number: +86 13811505591

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100038
      • Beijing Shijitan Hospital
      • Contact: Jian-Xin Zhou, MD; Phone Number: +8613801183875; Email: zhoujx.cn@icloud.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a diagnosis of hemorrhagic stroke (cerebral hemorrhage, intraventricular hemorrhage, or subarachnoid hemorrhage confirmed by CT or MRI, except for subdural or extradural hemorrhage caused by tramma)
• Patients requiring fluid therapy
• Patients over 18 years old

Exclusion Criteria:

• Hemorrhage onset more than 72hours
• Preexisting hyperchloremia(blood chloride > 110mmol/L)
• Presence of hypothalamic disease or cerebral salt wasting syndrome
• Patients who can eat by themselves
• Patients receiving routine RRT
• Patients with known allergic or adverse reactions to the liquid used
• Patients with organ failure (such as heart failure, renal failure, liver failure) or end-stage disease
• Patients with autoimmune diseases, inflammatory diseases, metabolic diseases and blood diseases
• Patients with serious heart disease or arrhythmia
• Patients who are expected to have difficulty complying with the study plan or collecting data completely
• Pregnant or lactating women
• No informed consent was signed
• Patients participating in other clinical trials
• Other conditions deemed by the investigator to be ineligible for participation in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multiple Electrolyte; Multiple Electrolytes Injection(II): contains sodium chloride 6.799g, potassium chloride 0.2984g, calcium chloride 0.3675g, magnesium chloride 0.2033g, sodium acetate 3.266g, L-malic acid 0.671, sodium hydroxide 0.200g per 1000mL.	Drug: Multiple Electrolyte; Patients who are randomized to multiple electrolyte group will be receiving Multiple Electrolytes injection II for 72 hours continously after inrollment as maintence and rescutation fluids. Infusion speed and volume will be determained by physicians.; Other Names: Multiple Electrolytes injection II
Active Comparator: Normal Saline; Sodium chloride injection: contains sodium chloride 9.0g per 1000mL.	Drug: Normal Saline; Patients who are randomized to normal saline group will be receiving Sodium Chloride injection for 72 hours continously after inrollment as maintence and rescutation fluids. Infusion speed and volume will be determained by physicians.; Other Names: Sodium Chloride injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hyperchloremia	The incidence of hyperchloremia	At 24 hours, 48 hours, 72 hours after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hospital length of stay	hospital length of stay	recorded at discharge or 28 days after enrollment
Hyperchloremia acidosis	Incidence of hyperchloremia acidosis	At 24 hours, 48 hours, 72 hours after enrollment
Plasma osmolality	Plasma osmolality calculate by algorithm	At 24 hours, 48 hours, 72 hours after enrollment
AKI	Incidence of acute kidney injury	recorded till day 7 after enrollment
RRT	Incidence of new renal replacement therapy	recorded till day 7 after enrollment
ICU length of stay	ICU length of stay	recorded at ICU discharge or 28 days after enrollment
hospitalization expense	hospitalization expense	recorded at discharge or 28 days after enrollment

Collaborators and Investigators

• Sponsor: Capital Medical University
• Investigators: Principal Investigator: Jian-Xin Zhou, MD, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Saline; Crystalloid Solution
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Hemorrhagic Stroke
• Other Study ID Numbers: IIT2023-020-002

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