Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery (PUMAS)

September 23, 2021 updated by: Zealand University Hospital

Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery: The PUMAS Study

This study examines if remote ischemic preconditioning in patients undergoing minor acute abdominal surgery (laparoscopic cholecystitis due to acute cholecystitis) is associated with a modulation of endothelial dysfunction. half of the patients will receive remote ischemic preconditioning prior to surgery, the other half will serve as controls.

Study Overview

Detailed Description

Remote ischemic preconditioning (RIPC) consists of cycles of forearm or leg ischemia and reperfusion by the inflation of a blood-pressure cuff over the systemic blood pressure for brief periods. The procedure is simple, safe and with no clear side effects. In clinical studies covering acute cardiology RIPC has effectively reduced myocardial injury, postoperative cardiovascular complications and cardiac mortality. Recently, the effect of RIPC on attenuating ischemia-reperfusion injury has been investigated in non-cardiac surgery as well. The organ specific ischemia-reperfusion injury, systemic oxidative stress and inflammatory response were attenuated due to the intervention but a complete understanding of the underlying protective mechanisms of RIPC is however still lacking.

Experimental and clinical studies have implicated that the stimulus of RIPC is transmitted from the preconditioned tissue to other tissues and organs by humoral, neural and systemic anti-inflammatory mediators. The humoral and neural pathway are thought to be dependent on endogen substances such as adenosine, bradykinin, nitrogen oxide (NO) and calcitonin-gene-related-peptide (CGRP).

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Zealand
      • Køge, Zealand, Denmark, 4600
        • Center for Surgical Science, Surgical Department, Zealand University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients undergoing acute or subacute cholecystectomy due to acute cholecystitis with a maximum of 7 days of symptoms prior to surgery

Exclusion Criteria:

  • Not capable of giving informed consent after oral and written information
  • Surgery within 30 days of study inclusion
  • Conditions that prevent the performance of remote ischemic preconditioning on the upper extremity, e.g. fractures, paresis, lymphedema
  • performance of concomitant endoscopic retrograde cholangiopancreatography (ERCP) during surgery
  • synchronous pancreatitis
  • synchronous cholangitis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Remote Ischemic Preconditioning
Remote ischemic preconditioning is carried out before the induction of general anesthesia. All four cycles will be completed before general anesthesia. The blood pressure cuff is placed on the upper limb. The cuff is inflated to 200 mmHg (if systolic blood pressures exceeds 185 mmHg, the cuff will be inflated to at least 15 mmHg above the systolic blood pressure) resulting in a total occlusion of the blood flow to the limb. After 5 minutes of ischemia, the cuff is deflated, and the limb is reperfused for 5 minutes. This cycle is repeated 4 times. Pulse oximetry is performed on the RIPC limb to make sure that the blood flow is completely interrupted during ischemia
Cycles of forearm ischemia and reperfusion by the inflation of a blood-pressure cuff over the systemic blood pressure for brief periods
No Intervention: Control
Will receive no intervention, but will go through same tests at the same time-points (endothelial function measured by reactive hyperemia index, blood samples, Heart rate variability and questionaires)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in endothelial function measured by reactive hyperemia index (RHI)
Time Frame: 24 hours
Changes in endothelial function measured by reactive hyperemia index (RHI) at baseline, four hours and 24 hours after surgery (cholecystectomy due to acute cholecystitis)
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heart rate variability
Time Frame: 24 hours
Changes in Heart rate variability measured with eMotion Faros from baseline and 24 hours consecutively.
24 hours
Changes in p-L-arginine
Time Frame: 24 hours
Changes in p-L-arginine in μmol/L from baseline til 24h post-surgery
24 hours
Changes in p-asymmetric dimethylarginine
Time Frame: 24 hours
Changes in p-asymmetric dimethylarginine in μmol/L from baseline til 24h post-surgery
24 hours
Changes in p-biopterins
Time Frame: 24 hours
Changes in p-biopterins in ng/ml from baseline til 24h post-surgery
24 hours
Changes in soluble endothelial (E-) selectin
Time Frame: 24 hours
Changes in soluble E-selectin in ng/ml from baseline til 24h post-surgery
24 hours
Changes in soluble plasma (P-) selectin
Time Frame: 24 hours
Changes in soluble P-selectin in ng/ml from baseline til 24h post-surgery
24 hours
Changes in Intercellular Adhesion Molecule 1 (ICAM-1)
Time Frame: 24 hours
Changes in soluble Intercellular Adhesion Molecule 1 (ICAM-1) in ng/ml from baseline til 24h post-surgery
24 hours
Changes in syndecan-1
Time Frame: 24 hours
Changes in syndecan-1 in pg/ml from baseline til 24h post-surgery
24 hours
Changes in thrombomodulin
Time Frame: 24 hours
Changes in thrombomodulin in pg/ml from baseline til 24h post-surgery
24 hours
Changes in arginine vasopressin
Time Frame: 24 hours
Changes in arginine vasopressin in ng/ml from baseline til 24h post-surgery
24 hours
Changes in adrenalin
Time Frame: 24 hours
Changes in adrenalin in ng/ml from baseline til 24h post-surgery
24 hours
Changes in noradrenalin
Time Frame: 24 hours
Changes in noradrenalin in pg/ml from baseline til 24h post-surgery
24 hours
Changes in ascorbic acid
Time Frame: 24 hours
Changes in ascorbic acid in ng/μL from baseline til 24h post-surgery
24 hours
Changes in dehydroascorbic acid
Time Frame: 24 hours
Changes in dehydroascorbic acid in ng/μL from baseline til 24h post-surgery
24 hours
Changes in angiotensin II
Time Frame: 24 hours
Changes in angiotensin II in pg/mL from baseline til 24h post-surgery
24 hours
Changes in bradykinin
Time Frame: 24 hours
Changes in bradykinin in pg/mL from baseline til 24h post-surgery
24 hours
Changes in calcitonin-gene related peptide
Time Frame: 24 hours
Changes in calcitonin-gene related peptide in pg/mL from baseline til 24h post-surgery
24 hours
Changes in prostacyclin
Time Frame: 24 hours
Changes in prostacyclin in pg/mL from baseline til 24h post-surgery
24 hours
Changes in serotonin
Time Frame: 24 hours
Changes in serotonin in ng/mL from baseline til 24h post-surgery
24 hours
Changes in endothelin-1
Time Frame: 24 hours
Changes in endothelin-1 in pg/mL from baseline til 24h post-surgery
24 hours
Changes in adrenomedullin
Time Frame: 24 hours
Changes in adrenomedullin in ng/mL from baseline til 24h post-surgery
24 hours
Changes in platelets
Time Frame: 24 hours
Changes in platelets x 109/L from baseline til 24h post-surgery
24 hours
Changes in adenosin
Time Frame: 24 hours
Changes in adenosin μmol/L from baseline til 24h post-surgery
24 hours
Changes in interleukin-6(IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta)
Time Frame: 24 hours
Changes in IL-6, IL-10, TNF-Alpha, TGF-beta in pg/mL from baseline til 24h post-surgery
24 hours
Changes in gene expression autoimmune human pathway panel from NanoString
Time Frame: 4 hours
Changes in gene expression profiles in the autoimmune human pathway panel from NanoString from baseline until four hours post-surgery.
4 hours
Local complications to RIPC
Time Frame: 24 hours
Pain, changed sensibility or decreased function of the upper extremity where remote ischemic preconditioning were carried out preoperatively.
24 hours
Differences in postoperative quality of recovery score 15 (QoR-15) between arms in the trial
Time Frame: 30 days
Questionnaire on Postoperative quality of recovery with 15 questions comparing scores from baseline, 24 hours and 30 days after surgery between study arms (intervention and controls)
30 days
Differences in Self reported pain on a 0-10 scale between arms in the trial
Time Frame: 24 hours
Self reported pain on a 0-10 scale at baseline and 24 hours after surgery between study arms (intervention and controls)
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Kirsten L Wahlstroem, MD, Center for Surgical Science, Zealand University Hospital,

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 4, 2019

Primary Completion (Actual)

September 14, 2021

Study Completion (Actual)

September 14, 2021

Study Registration Dates

First Submitted

September 23, 2019

First Submitted That Met QC Criteria

November 6, 2019

First Posted (Actual)

November 7, 2019

Study Record Updates

Last Update Posted (Actual)

September 29, 2021

Last Update Submitted That Met QC Criteria

September 23, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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