The evaluation of the potential damage to vascular wall in the perioperative settings during periods of dehydration and following infusion of cristalloid solutions during general anaesthesia
| ISRCTN | ISRCTN81005631 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN81005631 |
| Secondary identifying numbers | R-GS2016 |
- Submission date
- 17/05/2016
- Registration date
- 10/06/2016
- Last edited
- 30/11/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Plain English summary of protocol
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
Contact information
Scientific
Pauls Stradiņš Clinical University Hospital
13 Pilsonu street
Riga
LV 1002
Latvia
Study information
| Study design | Interventional open label randomised parallel trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | ISRCTN81005631_PIS_01Jun16.doc |
| Scientific title | The relationship between dehydration, fluid volume distribution and damage to the glycocalyx layer during general anaesthesia with sevoflurane and propofol |
| Study objectives | 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(s) | Ethics commitee of Pauls Stradiņš Clinical University Hospital, 27/01/2016, ref: 270116 - 17L |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | |
| Drug / device / biological / vaccine name(s) | 1. Sevoflurane 2. Propofol |
| Primary outcome measure | 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 study start date | 01/12/2015 |
| Completion date | 30/06/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 24 |
| Total final enrolment | 25 |
| Key inclusion criteria | 1. Patients scheduled for elective laparotomy under general anesthesia 2. Aged between 20 and 55 3. ASA I-II |
| Key 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 |
| Date of first enrolment | 01/02/2016 |
| Date of final enrolment | 31/12/2017 |
Locations
Countries of recruitment
- Latvia
Study participating centre
Riga
LV 1002
Latvia
Sponsor information
Hospital/treatment centre
13 Pilsonu street
Riga
LV 1002
Latvia
| Phone | +371 67 069 601 |
|---|---|
| stradini@stradini.lv | |
"ROR" |
https://ror.org/00h1aq868 |
Funders
Funder type
Hospital/treatment centre
No information available
No information available
Results and Publications
| Intention to publish date | 30/06/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a peer reviewed journal |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 01/06/2016 | 22/06/2016 | No | Yes | |
| Results article | results | 22/08/2017 | 30/11/2020 | Yes | No |
| Results article | results | 25/04/2020 | 30/11/2020 | Yes | No |
Additional files
- ISRCTN81005631_PIS_01Jun16.doc
- Uploaded 22/06/2016
Editorial Notes
30/11/2020: Publication references and total final enrolment added.
26/10/2017: Internal review.
28/02/2017: The overall trial end date has been updated from 31/12/2016 to 30/06/2018 and the recruitment end date has been updated from 31/12/2016 ti 31/12/2017.
22/06/2016: The participant information sheet has been uploaded.
