Remote Ischemic Preconditioning in Patients Undergoing Acute Minor Abdominal Surgery: The PUMAS Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Zealand University Hospital
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Changes in endothelial function measured by reactive hyperemia index (RHI)
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Care Provider, Outcomes Assessor)
Masking Description
Outcomes assessor are partly blinded and data analysis will be blinded
Eligibility Criteria
- Ages
- 18 Years to 120 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
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
Intervention: Remote Ischemic Preconditioning (RIPC) (Procedure)
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)
Outcomes
Primary Outcomes
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)
Secondary Outcomes
- Changes in p-L-arginine(24 hours)
- Changes in soluble plasma (P-) selectin(24 hours)
- Changes in calcitonin-gene related peptide(24 hours)
- Changes in serotonin(24 hours)
- Changes in endothelin-1(24 hours)
- Differences in Self reported pain on a 0-10 scale between arms in the trial(24 hours)
- Changes in soluble endothelial (E-) selectin(24 hours)
- Changes in syndecan-1(24 hours)
- Changes in dehydroascorbic acid(24 hours)
- Changes in platelets(24 hours)
- Changes in adenosin(24 hours)
- Changes in interleukin-6(IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta)(24 hours)
- Heart rate variability(24 hours)
- Changes in p-asymmetric dimethylarginine(24 hours)
- Changes in Intercellular Adhesion Molecule 1 (ICAM-1)(24 hours)
- Changes in thrombomodulin(24 hours)
- Changes in adrenalin(24 hours)
- Changes in noradrenalin(24 hours)
- Changes in prostacyclin(24 hours)
- Changes in adrenomedullin(24 hours)
- Differences in postoperative quality of recovery score 15 (QoR-15) between arms in the trial(30 days)
- Changes in arginine vasopressin(24 hours)
- Changes in ascorbic acid(24 hours)
- Changes in angiotensin II(24 hours)
- Changes in gene expression autoimmune human pathway panel from NanoString(4 hours)
- Local complications to RIPC(24 hours)
- Changes in p-biopterins(24 hours)
- Changes in bradykinin(24 hours)