The Colder Fluids - Intravenous Infusion of 10 Degrees Celsius Fluids and Its Effects on Circulation and Hemostasis

Rapid Intravenous Infusion of 10 and 22 Degrees Celsius Ringer's Lactate in Healthy Volunteers and Its Effects on Circulation and Hemostasis - a Randomized Crossover Trial

The aim of this study is to investigate the effect of respectively 10 and 22 degrees Celsius Ringer's lactate solution on the physiological response in healthy adults. In a single center crossover study the investigators will include and randomize 25 healthy volunteers to receive 1 liter of Ringer's lactate either cold (10°C, 50°F), or at room temperature (22°C, 71,6°F) with 100 ml/min. Fluids will be administered through a peripheral vein. After a minimum "washout period" of 24 hours, subjects are switched to receive infusion at the other aforementioned temperatures.

The main outcomes of this study are:

Primary:

• The increase in Mean Arterial Pressure (MAP) 30 minutes after started infusion

Secondary:

• Time until return of MAP to baseline value after infusion.
• Changes in Visual Analog Scale (VAS) of discomfort during infusion
• Changes in temperature, blood pressure, heart rate, peripheral oxygen saturation cardiac index, cardiac output, total peripheral resistance index and stroke volume
• Changes in the intravascular volume status and the fluid responsiveness
• Changes in biochemical parameters at baseline, 30 and 60 minutes.
• Changes in Rotational thromboelastometry (ROTEM) analysis at baseline, 30 and 60 minutes

Study Overview

• Status: Completed
• Conditions: Hemodynamic Instability
• Intervention / Treatment: Drug: Ringer's Lactate

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age between 18-64

Exclusion Criteria:

• Pre-existing medical problems that are contraindicated for cold crystalloid infusions.
• Pregnancy (validated through a certified urine pregnancy test)
• Body mass index >35 kg/m2
• Medication use, including over-the-counter anti-pyretics within 48 hours, with exception of allergy medication and contraceptives.
• Any family history or predisposition of coagulopathies.
• Any intake of inhibitors of 11β-Hydroxysteroid dehydrogenase the past 48 hours (products containing liquorice)

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
Active Comparator: Cold - Room temperature; Trial day 1: Participants receive Ringer's lactate cold (10°C, 50°F), Trial day 2: Participants receive Ringer's lactate at room temperature (22°C, 71.6°F)	Drug: Ringer's Lactate; On the first trial day healthy volunteers are randomized to receive 1 liter of Ringer's lactate either cold (10°C, 50°F), or at room temperature (22°C, 71.6°F) with 100 ml/min. After a minimum "washout period" of 24 hours, subjects are switched to receive infusion at the other aforementioned temperatures.
Active Comparator: Room temperature - Cold; Trial day 1: Participants receive Ringer's lactate at room temperature (22°C, 71.6°F), Trial day 2: Participants receive Ringer's lactate cold (10°C, 50°F)	Drug: Ringer's Lactate; On the first trial day healthy volunteers are randomized to receive 1 liter of Ringer's lactate either cold (10°C, 50°F), or at room temperature (22°C, 71.6°F) with 100 ml/min. After a minimum "washout period" of 24 hours, subjects are switched to receive infusion at the other aforementioned temperatures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Increase in Mean Arterial Pressure (MAP) 30 minutes after started infusion	Trial day 1 & Trial day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time until return of Mean Arterial Pressure (MAP) to baseline value after infusion		Trial day 1 & Trial day 2
Changes in Visual Analog Scale (VAS) of discomfort during infusion	Visual analoge scale of discomfort to assess participants discomfort during the trial. A scale labelled from 0=no discomfort to 10=maximum discomfort imaginable.	Trial day 1 & Trial day 2
Changes in physiological parameter temperature measured in degrees Celcius		Trial day 1 & Trial day 2
Changes in physiological parameter blood pressure measured in millimeter of mercury (mmHg)		Trial day 1 & Trial day 2
Changes in physiological parameter peripheral oxygen saturation measured in percent (%)		Trial day 1 & Trial day 2
Changes in physiological parameter cardiac index measured in L/min/m2		Trial day 1 & Trial day 2
Changes in physiological parameter cardias output measured in L/min		Trial day 1 & Trial day 2
Changes in physiological parameter total peripheral resistance index measured in dyn·s/cm5		Trial day 1 & Trial day 2
Changes in physiological parameter stroke volume measured in mL		Trial day 1 & Trial day 2
Changes in physiological parameter intravascular volume status and fluid responsiveness measured in vena cava inferior maximum diameter and index via ultrasound		Trial day 1 & Trial day 2
Changes in physiological parameter of INR blood test measured in prothrombin time at baseline, after 30 minutes and after 60 minutes		Trial day 1 & Trial day 2
Changes in physiological parameter APTT blood test measured in seconds at baseline, after 30 minutes and after 60 minutes		Trial day 1 & Trial day 2
Changes in physiological parameter Fibrinogen blood test measured in µmol/L at baseline, after 30 minutes and after 60 minutes		Trial day 1 & Trial day 2
Changes in physiological parameter Platelet count blood test measured in 109/L at baseline, after 30 minutes and after 60 minutes		Trial day 1 & Trial day 2
Changes in physiological parameter Flowcytometry blood tests (CD63, CD62p, PAC-1) measured in % at baseline, after 30 minutes and after 60 minutes		Trial day 1 & Trial day 2
Changes in physiological parameter Rotational thromboelastometry (EXTEM, INTEM, FIBTEM analysis of Clotting time and maximum clot formation) measured in seconds and millimeters, respectively, at baseline, after 30 minutes and after 60 minutes		Trial day 1 & Trial day 2

Collaborators and Investigators

• Sponsor: Esbjerg Hospital - University Hospital of Southern Denmark
• Collaborators: Odense University Hospital
• Investigators: Principal Investigator: Mikkel Brabrand, MD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2023
• Primary Completion (Actual): December 20, 2023
• Study Completion (Actual): December 20, 2023

Study Registration Dates

• First Submitted: June 17, 2024
• First Submitted That Met QC Criteria: September 30, 2024
• First Posted (Actual): October 2, 2024

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: October 4, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 2023-506018-35-00

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