Effect of Urine-guided Hydration on Acute Kidney Injury After CRS-HIPEC

Study Overview
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Brief Summary
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Acute renal injury (AKI) is a common complication after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), and is associated with worse outcomes. Available evidences show that maintaining intraoperative urine output ≥ 200 ml/h by fluid and furosemide administration may reduce the incidence of AKI in patients undergoing cardiopulmonary bypass. The investigators hypothesize that, for patients undergoing CRS-HIPEC, intraoperative urine-volume guided hydration may also reduce the incidence of postoperative AKI.

Detailed Description
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Acute renal injury (AKI) is a common complication after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), and is associated with worse outcomes. Studies showed that less intraoperative urine volume was associated with AKI. In studies of contrast-associated AKI, intraoperative and 4-h postoperative hydration and forced diuresis to achieve urine output ≥ 300 ml/h reduces the incidence of AKI by 44%. In patients undergoing cardiac surgery under cardiopulmonary bypass, maintaining intraoperative and 6-h postoperative urine output ≥200 ml/h by fluid and furosemide administration reduces the incidence of AKI by 52%. For patients with rhabdomyolysis, it is recommended to maintain urine output at approximately 3 ml/kg/h (200 ml/h) with volume supplementation. We suppose that forced diuresis with simultaneous hydration (balancing urine output with intravenous fluid infusion) may reduce AKI after CRS-HIPEC. The purpose of this randomised controlled trial is to investigate whether maintaining urine output at 200 ml/h (3 ml/kg/h) or higher by forced diuresis with simultaneous hydration can reduce the incidence of AKI after CRS-HIPEC.

Official Title
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Effect of Urine-guided Intraoperative Hydration on the Incidence of Postoperative Acute Kidney Injury and Long-term Outcomes in Patients With Pseudomyxoma Peritonei Receiving CRS-HIPEC: a Prospective, Randomized, Controlled Trial

Conditions
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Cytoreductive Surgery, Hyperthermic Intraperitoneal Chemotherapy, Hydration, Diuresis, Acute Kidney Injury, Postoperative Complications

Intervention / Treatment
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* Procedure: Urine-guided hydration
* Procedure: Routine hydration
* Drug: Forced administration of furosemide
* Drug: Routine administration of furosemide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years; Diagnosed as pseudomyxoma peritonei, scheduled for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy under general anesthesia; At least 14 days since the last treatment of chemotherapy, radiotherapy, or immunotherapy; Consent to participate in this study. Exclusion Criteria: Persistent preoperative atrial fibrillation, or new-onset cardiovascular event (acute coronary syndrome, stroke, or congestive heart failure) in the past 3 months; Requirement of vasopressors to maintain blood pressure before surgery; Known furosemide hypersensitivity; Chronic kidney disease stage 5 or requirement of renal replacement therapy; Other conditions that are considered unsuitable for the study participation.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Urine-guided hydration<br>The target is to maintain urine output at 200 ml/h (3 ml/kg/h) or higher by intravenous injection/infusion of furosemide throughout surgery. That is, a loading dose of 20 mg is injected at the beginning of surgery; if the urine output does not reach the target value, furosemide will be continuously infused at 10 mg/h until the end of the surgery as needed, with a maximum cumulative dose not exceeding 250 mg. Intravenous hydration is performed to balance urine output and to maintain the SVV≤10%. | Procedure: Urine-guided hydration<br>* The target is to maintain urine output at 200 ml/h (3 ml/kg/h) or higher by intravenous injection/infusion of furosemide throughout surgery. That is, a loading dose of 20 mg is injected at the beginning of surgery; if urine output does not reach the target value, furosemide will be continuously infused at 10 mg/h until the end of surgery, with a cumulative dose not exceeding 250 mg. Intravenous rehydration is performed to balance urine output and to maintain the SVV ≤10%.<br>* Other names: Forced administration of furosemide;Drug: Forced administration of furosemide<br>* Forced administration of furosemide<br>|
| Active Comparator: Routine hydration<br>The target is to maintain urine output at 0.5 ml/kg/h or higher as per current medical practice. That is, furosemide is only administered when clinically necessary or at the discretion of attending anesthesiologists. Intravenous hydration is performed to maintain the SVV≤10%. | Procedure: Routine hydration<br>* The target is to maintain urine output at 0.5 ml/kg/h or higher according to routine practice. That is, furosemide is only administered when clinically necessary or at discretion of responsible anesthesiologists; intravenous rehydration is performed to maintain the SVV ≤10%.<br>* Other names: Routine administration of furosemide;Drug: Routine administration of furosemide<br>* Routine administration of furosemide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute kidney injury (AKI) within 7 days after surgery | Acute kidney injury (AKI) is diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. | Up to 7 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Classification of AKI within 7 days after surgery | AKI is classified according to the KDIGO criteria. | Up to 7 days after surgery | 
| Intensive care unit (ICU) admission after surgery | ICU admission after surgery | Up to 30 days after surgery | 
| Length of ICU stay after surgery | Length of ICU stay after surgery | Up to 30 days after surgery | 
| Duration of mechanical ventilation after surgery | Duration of mechanical ventilation after surgery | Up to 30 days after surgery | 
| Length of hospital stay after surgery | Length of hospital stay after surgery | Up to 30 days after surgery | 
| Incidence of other organ injuries within 7 days after surgery | Including delirium (assessed with the Confusion Assessment Method [3D-CAM] for patients without mechanical ventilation and CAM-ICU for patients with mechanical ventilation]) within 5 days after surgery, myocardial injury and other organ injuries other than AKI. | Up to 7 days after surgery | 
| All-cause 30-day mortality | All-cause 30-day mortality | Up to 30 days after surgery | 
| Incidence of postoperative major complications | Postoperative major complications were defined as new-onset conditions that were harmful for patients' recovery and required therapeutic intervention, i.e., grade 2 or higher on Clavien-Dindo classification. | Up to 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytoreductive Surgery, Hyperthermic Intraperitoneal Chemotherapy, Hydration, Diuresis, Acute Kidney Injury, Postoperative Complications