Condition category
Surgery
Date applied
17/05/2016
Date assigned
10/06/2016
Last edited
22/06/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Patients undergoing surgery are often told not to eat or drink anything for 12 hours before the procedure, and so patients may be dehydrated when they arrive in operating room. It is standard practice to administer IV fluids (through a drip) when a person is anesthetized (put to sleep) and woken up after surgery, this technique is called volume loading (VL) and acts to control bodily processes under anesthesia. Giving too much of these fluids (hypervolemia) can lead to serious complications, including tissue edema (fluid retention), heart and lung complications and a prolonged hospital stay. Tissue edema formation at least in part is influenced by damage done to lining of blood vessels – glycocalyx, by large volumes of infused fluids. The direct mechanism of damage could be down to a substance called Brain Natriuretic Peptide (BNP), which is released from stretched heart chambers in response to hypervoleamia. The aim of this study is to analyse what happens to the fluids being infused during anesthesia, in order to find out if the standard approach used is capable of causing damage to blood vessels, and consequently tissue edema.

Who can participate?
Adults aged between 20 and 55 who are going to have a laparotomy under a general anesthetic.

What does the study involve?
Participants are randomly allocated to one of two groups. Participants in both groups are anesthetised and then started on a type of fluid called Ringer’s lactate solution (which contains similar salt concentrations as the body), at a rate of 25ml/kg in 30 minutes. For those in the first group, anaesthesia is maintained using sevoflurane (an anaesthetic that is inhaled) and for those in the second group, anaesthesia is maintained using propofol (an anaesthetic administered through a vein). For all participants, blood and urine samples are taken just before anesthesia. Blood samples are repeated every 10 minutes and urine samples every 20 minutes starting from the beginning of fluid infusion and lasting for at least 90 minutes.

What are the possible benefits and risks of participating?
There are no direct benefits or risks involved for participants taking part in this study.

Where is the study run from?
Pauls Stradiņš Clinical University Hospital (Latvia)

When is the study starting and how long is it expected to run for?
December 2015 to December 2016

Who is funding the study?
1. Pauls Stradiņš Clinical University Hospital (Latvia)
2. Mats Mats Kleberg Foundation

Who is the main contact?
Dr Janis Nemme

Trial website

Contact information

Type

Scientific

Primary contact

Dr Janis Nemme

ORCID ID

Contact details

Pauls Stradiņš Clinical University Hospital
13 Pilsonu street
Riga
LV 1002
Latvia

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

R-GS2016

Study information

Scientific title

The relationship between dehydration, fluid volume distribution and damage to the glycocalyx layer during general anaesthesia with sevoflurane and propofol

Acronym

Study hypothesis

Primary hypothesis:
Rapid infusion of 25 ml/kg of buffered Ringer´s solution during surgery causes an increase in plasma brain natriuretic peptide (BNP)

Secondary hypotheses:
1. The fluid load causes shedding of the glycocalyx layer which possibly correlated with changes in plasma BNP
2. Rapid fluid loading, BNP increase and/or shedding own the glycocalyx layer affects the capillary leakage of albumin

Ethics approval

Ethics commitee of Pauls Stradiņš Clinical University Hospital, 27/01/2016, ref: 270116 - 17L

Study design

Interventional open label randomised parallel trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Condition

Perioperative fluid management

Intervention

Participants are randomly allocated to one of two groups using closed envelope randomisation.

Group 1: Anesthesia is gently induced with midazolam, phentanyl, propofol and atracurium without starting iv fluids. Patients are intubated, samples of blood and urine are collected again and immediately fluid load - Ringer Lactate 25 ml/kg in 30 minutes is started. The anesthesia is provided with sevoflurane, phentanyl and atracurium.

Group 2: Anesthesia is gently induced with midazolam, phentanyl, propofol and atracurium without starting iv fluids. Patients are intubated, samples of blood and urine are collected again and immediately fluid load - Ringer Lactate 25 ml/kg in 30 minutes is started. The anesthesia is provided with propofol for 10 minutes at a rate of 10ml/kg/hour, next 10 minutes 8 ml/kg/hour and afterwards - 6-7 ml/kg/hour.

For participants in both groups, further blood samples are taken every 10 minutes till the end of infusion. After the end of infusion 4 blood samples are taken every 5 minutes and afterwards switched back to 10 minutes regimen till the end of anesthesia. Urinary samples are taken every 30 minutes starting from induction of anesthesia. Last samples are taken 2 hours after the end of anesthesia. Every time blood samples has been taken - patients blood pressure and pulse rate is documented.

Intervention type

Drug

Phase

Drug names

1. Sevoflurane
2. Propofol

Primary outcome measures

Brain natriuretic peptide (BNP) levels in plasma and urine after rapid fluid infusion are measured using chemiluminescent microparticle immunoassay (CMIA) at baseline (immediately before anaesthesia), immediately after anaesthesia induction, at 30 minute intervals throughout anaesthesia, and two hours after anaesthesia.

Secondary outcome measures

1. Changes in glycocalyx shedding products after rapid fluid loading are measured using ELISA at baseline (immediately before anaesthesia), immediately after anaesthesia induction, at 30 minute intervals throughout anaesthesia, and two hours after anaesthesia
2. Capillary leakage is assessed by measuring plasma albumin levels using IL Test Albumin at baseline (immediately before anaesthesia), immediately after anaesthesia induction at 10 minute intervals, every five minutes for 20 minutes after the end of fluid infusion phase, at 10 minutes intervals until the end of anesthesia and two hours after anaesthesia
3. Fluid kinetics of the infused volume of fluids are measured using Haemoglobin (Hgb) levels detected by Coulter HMX methodology at the same frequency as albumin at baseline (immediately before anaesthesia), immediately after anaesthesia induction at 10 minute intervals, every five minutes for 20 minutes after the end of fluid infusion phase, at 10 minutes intervals until the end of anesthesia and two hours after anaesthesia

Overall trial start date

01/12/2015

Overall trial end date

31/12/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Pateints scheduled for elective laparotomy under general anesthesia
2. Aged between 20 and 55
3. ASA I-II

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

24

Participant exclusion criteria

1. Urgent surgery patients
2. ASA III-IV
3. Refusal to participate
4. Pregnancy
5. Those undergoing operations under spinal or epidural anaesthesia
6. Blood loss more than 500 ml
7. Acute or chronic kidney disease

Recruitment start date

01/02/2016

Recruitment end date

31/12/2016

Locations

Countries of recruitment

Latvia

Trial participating centre

Pauls Stradiņš Clinical University Hospital
Pilsoņu iela 13
Riga
LV 1002
Latvia

Sponsor information

Organisation

Pauls Stradiņš Clinical University Hospital

Sponsor details

13 Pilsonu street
Riga
LV 1002
Latvia
+371 67 069 601
stradini@stradini.lv

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Pauls Stradiņš Clinical University Hospital

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Mats Kleberg Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a peer reviewed journal

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

22/06/2016: The participant information sheet has been uploaded.