Application of Perioperative Remote Ischemic Conditioning in Patients Undergoing Hepatectomy

Study Overview
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Brief Summary
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Our primary aim is to investigate whether perioperative remote ischemic conditioning (PRIC) as an adjunctive treatment can improve postoperative recovery in patients undergoing hepatectomy as an adjunct to standard treatment.

Detailed Description
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Remote Ischemic Conditioning (RIC) can be applied as repeated short-lasting ischemia in a distant tissue that results in protection against subsequent long-lasting ischemic injury in the target organ. This protection can be applied prior to or during a prolonged ischemic event as remote ischemic pre-conditioning (RIPreC) and per-conditioning (RIPerC), respectively, or immediate after reperfusion as remote ischemic post-conditioning (RIPostC). RIC is a non-pharmacologic and non-invasive treatment without noticeable discomfort, commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of limb ischemia alternating with 5 minutes of reperfusion. However, whether perioperative remote ischemic conditioning (PRIC) can improve postoperative recovery in patients undergoing hepatectomy has never been investigated in a randomized controlled trial.

Official Title
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Application of Perioperative Remote Ischemic Conditioning in Patients Undergoing Hepatectomy

Conditions
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Hepatic Hemangioma, Liver Cancer, Hepatolithiasis, Hepatectomy

Intervention / Treatment
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* Device: Sham-Remote Ischemic Conditioning
* Device: Remote Ischemic Conditioning Once Daily
* Device: Remote Ischemic Conditioning Twice Daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing hepatectomy under general anesthesia American Society of Anesthesiology (ASA) grade of II   III Male and female patients, age 25 to 75 years New York Heart Association (NYHA) grade of I   III Exclusion Criteria: Patients with limb deformity or peripheral vascular disease affecting upper limb function Patients with a medical history of nervous system, immune system and mental illness Patients who have received hepatectomy in the past, have important organ diseases or have undergone surgical treatment recently Patients who have recently used anti-inflammatory analgesics, anticoagulants, hormone drugs, immunosuppressants, and ATP-sensitive K-channel blockers (KATP) Preoperative severe renal insufficiency (serum creatinine > 442 umol/L, with or without serum potassium > 6.5 mmol/L, or the clinician-recognized need for renal replacement therapy), liver insufficiency (Child-Pugh grade C) Patients and/or their family members refuse to participate in the program

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, randomized, patient-assessor blinded, sham-controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham-Remote Ischemic Conditioning<br>Sham remote ischemic conditioning (Sham-RIC) is applied in the perioperative using an automated Sham-RIC device. | Device: Sham-Remote Ischemic Conditioning<br>* Sham-Remote Ischemic Conditioning (at the time points of 30 min before anesthesia, 30 min after surgery, the morning of the postoperative day 1, the afternoon of the postoperative day 1, the morning of the postoperative day 2, the afternoon of the postoperative day 2): Three cycles (30 minutes), each consisting of five minutes of cuff inflation followed by five minutes with a deflated cuff, but the cuff pressure will be 0 mmHg.<br>|
| Active Comparator: Remote Ischemic Conditioning Once Daily<br>Remote ischemic conditioning (RIC) is applied in the perioperative using an automated RIC device once daily. | Device: Remote Ischemic Conditioning Once Daily<br>* Remote Ischemic Conditioning (at the time points of 30 min before anesthesia, the morning of the postoperative day 1, the morning of the postoperative day 2): Three cycles (30 minutes), each consisting of five minutes of cuff inflation followed by five minutes with a deflated cuff. The cuff pressure will be 200 mmHg. Sham-Remote Ischemic Conditioning (at the time points of 30 min after surgery, the afternoon of the postoperative day 1, the afternoon of the postoperative day 2): Three cycles (30 minutes), each consisting of five minutes of cuff inflation followed by five minutes with a deflated cuff, but the cuff pressure will be 0 mmHg.<br>|
| Active Comparator: Remote Ischemic Conditioning Twice Daily<br>Remote ischemic conditioning (RIC) is applied in the perioperative using an automated RIC device twice daily. | Device: Remote Ischemic Conditioning Twice Daily<br>* Remote Ischemic Conditioning (at the time points of 30 min before anesthesia, 30 min after surgery, the morning of the postoperative day 1, the afternoon of the postoperative day 1, the morning of the postoperative day 2, the afternoon of the postoperative day 2): Three cycles (30 minutes), each consisting of five minutes of cuff inflation followed by five minutes with a deflated cuff. The cuff pressure will be 200 mmHg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alanine aminotransferase (ALT) | The levels of ALT in perioperative period | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aspartate aminotransferase (AST) | The levels of AST in perioperative period | 7 days | 
| Total bilirubin (TBIL) | The levels of TBIL in perioperative period | 7 days | 
| International normalized ratio (INR) | The levels of INR in perioperative period | 7 days | 
| Albumin (ALB) | The levels of ALB in perioperative period | 7 days | 
| Tumor necrosis factor-α (TNF-α) | The levels of TNF-α in perioperative period | 7 days | 
| Malondialdehyde (MDA) | The levels of MDA in perioperative period | 7 days | 
| Heme oxygenase-1 (HO-1) | The levels of HO-1 in perioperative period | 7 days | 
| Nuclear Factor-κB (NF-κB) | The levels of NF-κB in perioperative period | 7 days | 
| High mobility group box1 (HMGB1) | The levels of HMGB1 in perioperative period | 7 days | 
| Platelet | The levels of platelet in perioperative period | 7 days | 
| White blood cell (WBC) | The levels of WBC in perioperative period | 7 days | 
| Neutrophil granulocyte percentage | The levels of neutrophil granulocyte percentage in perioperative period | 7 days | 
| Time to gastrointestinal tolerance | Gastrointestinal tolerance was defined as transanal or stoma defecation and oral dietary tolerance. | 7 days | 
| Prolonged postoperative ileus | Prolonged postoperative ileus was diagnosed if patients met two or more of the following conditions on or after postoperative day 4: inability to tolerate the oral diet over the past 24 h, nausea or vomiting, without flatus over the past 24 h, abdominal distension or radiological evidence of intestinal distension without mechanical intestinal obstruction. | 7 days | 
| Rate of postoperative complications | The postoperative complications were recorded using the Clavien-Dindo classification system and included: nausea or vomiting, abdominal distension, anastomotic leakage, new pulmonary infection, poor wound healing, cognitive dysfunction, unplanned reoperation, and 30-day readmission rate. | 30 days |