Acute Cholecystitis, Endothelial Dysfunction
Conditions
Keywords
Remote ISchemic Preconditioning (RIPC), Acute surgery, Acute cholecystitis, Endothelial dysfunction, Heart Rate Variability (HRV)
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).
Interventions
PROCEDURERemote Ischemic Preconditioning (RIPC)
Cycles of forearm ischemia and reperfusion by the inflation of a blood-pressure cuff over the systemic blood pressure for brief periods
Sponsors
Zealand University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Masking description
Outcomes assessor are partly blinded and data analysis will be blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in p-L-arginine | 24 hours | Changes in p-L-arginine in μmol/L from baseline til 24h post-surgery |
| Changes in p-asymmetric dimethylarginine | 24 hours | Changes in p-asymmetric dimethylarginine in μmol/L from baseline til 24h post-surgery |
| Changes in p-biopterins | 24 hours | Changes in p-biopterins in ng/ml from baseline til 24h post-surgery |
| Changes in soluble endothelial (E-) selectin | 24 hours | Changes in soluble E-selectin in ng/ml from baseline til 24h post-surgery |
| Changes in soluble plasma (P-) selectin | 24 hours | Changes in soluble P-selectin in ng/ml 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 syndecan-1 | 24 hours | Changes in syndecan-1 in pg/ml from baseline til 24h post-surgery |
| Changes in thrombomodulin | 24 hours | Changes in thrombomodulin in pg/ml from baseline til 24h post-surgery |
| Changes in arginine vasopressin | 24 hours | Changes in arginine vasopressin in ng/ml from baseline til 24h post-surgery |
| Changes in adrenalin | 24 hours | Changes in adrenalin in ng/ml from baseline til 24h post-surgery |
| Changes in noradrenalin | 24 hours | Changes in noradrenalin in pg/ml from baseline til 24h post-surgery |
| Changes in ascorbic acid | 24 hours | Changes in ascorbic acid in ng/μL from baseline til 24h post-surgery |
| Changes in dehydroascorbic acid | 24 hours | Changes in dehydroascorbic acid in ng/μL from baseline til 24h post-surgery |
| Heart rate variability | 24 hours | Changes in Heart rate variability measured with eMotion Faros from baseline and 24 hours consecutively. |
| Changes in bradykinin | 24 hours | Changes in bradykinin in pg/mL from baseline til 24h post-surgery |
| Changes in calcitonin-gene related peptide | 24 hours | Changes in calcitonin-gene related peptide in pg/mL from baseline til 24h post-surgery |
| Changes in prostacyclin | 24 hours | Changes in prostacyclin in pg/mL from baseline til 24h post-surgery |
| Changes in serotonin | 24 hours | Changes in serotonin in ng/mL from baseline til 24h post-surgery |
| Changes in endothelin-1 | 24 hours | Changes in endothelin-1 in pg/mL from baseline til 24h post-surgery |
| Changes in adrenomedullin | 24 hours | Changes in adrenomedullin in ng/mL from baseline til 24h post-surgery |
| Changes in platelets | 24 hours | Changes in platelets x 109/L from baseline til 24h post-surgery |
| Changes in adenosin | 24 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 |
| Changes in gene expression autoimmune human pathway panel from NanoString | 4 hours | Changes in gene expression profiles in the autoimmune human pathway panel from NanoString from baseline until four hours post-surgery. |
| Local complications to RIPC | 24 hours | Pain, changed sensibility or decreased function of the upper extremity where remote ischemic preconditioning were carried out preoperatively. |
| Differences in postoperative quality of recovery score 15 (QoR-15) between arms in the trial | 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) |
| Differences in Self reported pain on a 0-10 scale between arms in the trial | 24 hours | Self reported pain on a 0-10 scale at baseline and 24 hours after surgery between study arms (intervention and controls) |
| Changes in angiotensin II | 24 hours | Changes in angiotensin II in pg/mL from baseline til 24h post-surgery |
Countries
Denmark
Outcome results
None listed