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Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery

Not Applicable
Completed
Conditions
Acute Cholecystitis
Endothelial Dysfunction
Interventions
Procedure: Remote Ischemic Preconditioning (RIPC)
Registration Number
NCT04156711
Lead Sponsor
Zealand University Hospital
Brief Summary

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.

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Remote Ischemic PreconditioningRemote Ischemic Preconditioning (RIPC)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
Primary Outcome Measures
NameTimeMethod
Changes in endothelial function measured by reactive hyperemia index (RHI)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)

Secondary Outcome Measures
NameTimeMethod
Changes in ascorbic acid24 hours

Changes in ascorbic acid in ng/μL from baseline til 24h post-surgery

Changes in angiotensin II24 hours

Changes in angiotensin II in pg/mL from baseline til 24h post-surgery

Changes in p-L-arginine24 hours

Changes in p-L-arginine in μmol/L from baseline til 24h post-surgery

Changes in soluble plasma (P-) selectin24 hours

Changes in soluble P-selectin in ng/ml from baseline til 24h post-surgery

Changes in calcitonin-gene related peptide24 hours

Changes in calcitonin-gene related peptide in pg/mL from baseline til 24h post-surgery

Changes in serotonin24 hours

Changes in serotonin in ng/mL from baseline til 24h post-surgery

Changes in endothelin-124 hours

Changes in endothelin-1 in pg/mL from baseline til 24h post-surgery

Differences in Self reported pain on a 0-10 scale between arms in the trial24 hours

Self reported pain on a 0-10 scale at baseline and 24 hours after surgery between study arms (intervention and controls)

Changes in soluble endothelial (E-) selectin24 hours

Changes in soluble E-selectin in ng/ml from baseline til 24h post-surgery

Changes in syndecan-124 hours

Changes in syndecan-1 in pg/ml from baseline til 24h post-surgery

Changes in dehydroascorbic acid24 hours

Changes in dehydroascorbic acid in ng/μL from baseline til 24h post-surgery

Changes in platelets24 hours

Changes in platelets x 109/L from baseline til 24h post-surgery

Changes in adenosin24 hours

Changes in adenosin μmol/L from baseline til 24h post-surgery

Changes in interleukin-6(IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta)24 hours

Changes in IL-6, IL-10, TNF-Alpha, TGF-beta in pg/mL from baseline til 24h post-surgery

Heart rate variability24 hours

Changes in Heart rate variability measured with eMotion Faros from baseline and 24 hours consecutively.

Changes in p-asymmetric dimethylarginine24 hours

Changes in p-asymmetric dimethylarginine in μmol/L from baseline til 24h post-surgery

Changes in Intercellular Adhesion Molecule 1 (ICAM-1)24 hours

Changes in soluble Intercellular Adhesion Molecule 1 (ICAM-1) in ng/ml from baseline til 24h post-surgery

Changes in thrombomodulin24 hours

Changes in thrombomodulin in pg/ml from baseline til 24h post-surgery

Changes in adrenalin24 hours

Changes in adrenalin in ng/ml from baseline til 24h post-surgery

Changes in noradrenalin24 hours

Changes in noradrenalin in pg/ml from baseline til 24h post-surgery

Changes in prostacyclin24 hours

Changes in prostacyclin in pg/mL from baseline til 24h post-surgery

Changes in adrenomedullin24 hours

Changes in adrenomedullin in ng/mL from baseline til 24h post-surgery

Differences in postoperative quality of recovery score 15 (QoR-15) between arms in the trial30 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)

Changes in arginine vasopressin24 hours

Changes in arginine vasopressin in ng/ml from baseline til 24h post-surgery

Changes in gene expression autoimmune human pathway panel from NanoString4 hours

Changes in gene expression profiles in the autoimmune human pathway panel from NanoString from baseline until four hours post-surgery.

Local complications to RIPC24 hours

Pain, changed sensibility or decreased function of the upper extremity where remote ischemic preconditioning were carried out preoperatively.

Changes in p-biopterins24 hours

Changes in p-biopterins in ng/ml from baseline til 24h post-surgery

Changes in bradykinin24 hours

Changes in bradykinin in pg/mL from baseline til 24h post-surgery

Trial Locations

Locations (1)

Center for Surgical Science, Surgical Department, Zealand University Hospital

🇩🇰

Køge, Zealand, Denmark

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