Effect of Pneumoperitoneum and Neuromuscular Block on Renal Function in Diabetes Patients

Study Overview
=================
Brief Summary
-----------------
In this single center, double-blind, randomized controlled clinical trial, we will include 648 diabetes patients aged 18-70 undergoing laparoscopic pelvic tumor resection. They will be randomized to the following four groups: high-pressure pneumoperitoneum (10mmHg)+ deep neuromuscular block group, high-pressure pneumoperitoneum (15mmHg)+moderate neuromuscular block group, low-pressure pneumoperitoneum + deep neuromuscular block group and low-pressure pneumoperitoneum+moderate neuromuscular block group. Deep neuromuscular block is defined as post tetanic count (PTC) 1-2, and low neuromuscular block is defined as train-of-four (TOF) twitch 1-2. The outcomes will be indicators for acute kidney injury and surgical condition.

Detailed Description
-----------------
In this single center, double-blind, randomized controlled clinical trial, we will include 648 diabetes patients aged 18-70 undergoing laparoscopic pelvic tumor resection under general anesthesia. They will be randomized to the following four groups: high-pressure pneumoperitoneum (10mmHg)+ deep neuromuscular block group, high-pressure pneumoperitoneum (15mmHg)+moderate neuromuscular block group, low-pressure pneumoperitoneum + deep neuromuscular block group and low-pressure pneumoperitoneum+moderate neuromuscular block group. Neuromuscular block will be induced by rocuronium bolus and maintained by a continuous infusion of rocuronium. Deep neuromuscular block is defined as PTC 1-2, and low neuromuscular block is defined as train-of-four TOF twitch 1-2. The primary outcome will be serum Cystatin C level, and the secondary outcomes will be serum creatine level, urinary sediment, intraoperative urine output, duration of surgery, surgical space condition and occurrence bucking and body movement.

Official Title
-----------------
Effect of Pneumoperitoneum Pressure and the Extent of Neuromuscular Block on Renal Function in Patients With Diabetes Undergoing Laparoscopic Pelvic Surgery

Conditions
-----------------
Diabetes Mellitus, Acute Kidney Injury, Laparoscopic Surgical Procedure, Neuromuscular Blockade

Intervention / Treatment
-----------------
* Procedure: high pressure
* Drug: deep neuromuscular block
* Procedure: low pressure
* Drug: moderate neuromuscular block


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18-70; American Society of Anesthesiologist physical status (ASA) II-Ⅲ; Diagnosed of diabetes; Undergoing elective laparoscopic pelvic tumor resection under general anesthesia; Estimated duration of operation >2h; Exclusion criteria: Not willing to participate in the study or not able to sign the informed consent； Diagnosed of other kidney diseases except diabetic nephropathy; Severe renal insufficiency defined as serum creatine level > 2 times the upper limit of normal, or urine output < 0.5ml/kg/h, or estimated glomerular filtration rate < 60ml/h; Severe liver, lung or heart dysfunction; Known or suspect neuromuscular disease; Use of drugs that may affect neuromuscular block monitoring; Severe diabetic neuropathy or other peripheral neuropathy； Known or suspect allergy to general anesthetics； Family history of malignant hyperthermia； Previous history of pelvic surgery.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: high pressure + deep block<br>Intra-abdominal pressure will be set to 12-15 mmHg during the surgery. Deep neuromuscular block will be induced by rocuronium bolus 1 mg/kg, maintained by a continuous infusion of rocuronium (0.6mg/kg/h), and titrated towards post-tetanic count (PTC) 1-2. | Procedure: high pressure<br>* High-pressure pneumoperitoneum is defined as intra-abdominal pressure 12-15 mmHg.<br>Drug: deep neuromuscular block<br>* Deep neuromuscular block is defined as PTC 1-2.<br>|
| Experimental: high pressure + moderate block<br>Intra-abdominal pressure will be set to 12-15 mmHg during the surgery. Moderate neuromuscular block will be induced by rocuronium bolus 0.6 mg/kg, maintained by a continuous infusion of rocuronium (0.3mg/kg/h), and titrated towards train-of-four (TOF) twitch 1-2. | Procedure: high pressure<br>* High-pressure pneumoperitoneum is defined as intra-abdominal pressure 12-15 mmHg.<br>Drug: moderate neuromuscular block<br>* Moderate neuromuscular block is defined as TOF twitch 1-2.<br>|
| Experimental: low pressure + deep block<br>Intra-abdominal pressure will be set to 7-10 mmHg during the surgery. Deep neuromuscular block will be induced by rocuronium bolus 1 mg/kg, maintained by a continuous infusion of rocuronium (0.6mg/kg/h), and titrated towards PTC 1-2. | Drug: deep neuromuscular block<br>* Deep neuromuscular block is defined as PTC 1-2.<br>Procedure: low pressure<br>* Low-pressure pneumoperitoneum is defined as intra-abdominal pressure 7-10 mmHg.<br>|
| Experimental: low pressure + moderate block<br>Intra-abdominal pressure will be set to 7-10 mmHg. Moderate neuromuscular block will be induced by rocuronium bolus 0.6 mg/kg, maintained by a continuous infusion of rocuronium (0.3mg/kg/h), and titrated towards TOF twitch 1-2. | Drug: deep neuromuscular block<br>* Deep neuromuscular block is defined as PTC 1-2.<br>Drug: moderate neuromuscular block<br>* Moderate neuromuscular block is defined as TOF twitch 1-2.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum cystatin C (CysC) level | CysC is a sensitive indicator for early kidney injury, and can be used to estimate glomerular filtration rate (GFR). | 30 minutes before pneumoperitoneum insufflation | 
| Serum cystatin C (CysC) level | CysC is a sensitive indicator for early kidney injury, and can be used to estimate glomerular filtration rate (GFR). | 30 minutes after pneumoperitoneum deflatation | 
| Serum cystatin C (CysC) level | CysC is a sensitive indicator for early kidney injury, and can be used to estimate glomerular filtration rate (GFR). | Postoperative 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum creatine level | Creatine is also an indicator for kidney injury | 30 minutes before pneumoperitoneum insufflation | 
| Serum creatine level | Creatine is also an indicator for kidney injury | 30 minutes after pneumoperitoneum deflatation | 
| Serum creatine level | Creatine is also an indicator for kidney injury | Postoperative 24 hours | 
| The volume of intraoperative urine output | A urine tube will be inserted just before the surgery, so the urine can be drained into a bag. The volume of urine in the bag at the end of the surgery will be the volume of intraoperative urine output. | At the end of the surgery | 
| The presence of isomorphic or dysmorphic erythrocyte in urinary sediment | Erythrocyte in urinary sediment is also an indicator of renal injury. | Postoperative day 1 | 
| Duration of surgery | Duration of surgery is an indicator for procedure difficulty | Intraoperative | 
| Leiden-surgical rating scale | We will use Leiden surgical rating scale (Martini et al.) to assess surgical condition. It is a 5-point scale, the minimum and maximum values are 1 and 5, respectively. Higher score indicates better surgical condition. | The moment when trocars are introduced into pelvic cavity, and then every 15 minutes till the end of surgery. | 
| The number of bucking and body movement during the surgery | The occurrence of bucking or body movement is an indicator for the sufficiency of muscle relaxant. | Intraoperative | 
| Renal tissue oxygen saturation | Renal oxygen saturation is an indicator for renal tissue oxygenation. | Intraoperative |