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

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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Complications; Acute Kidney Injury; Cytoreductive Surgery; Hydration; Diuresis; Hyperthermic Intraperitoneal Chemotherapy
• Intervention / Treatment: Drug: Forced administration of furosemide; Drug: Routine administration of furosemide; Procedure: Urine-guided hydration; Procedure: Routine hydration

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100049
    • Aerospace Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Routine hydration; 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%.	Drug: Routine administration of furosemide; Routine administration of furosemide; Procedure: Routine hydration; 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%.; Other Names: Routine administration of furosemide
Experimental: Urine-guided hydration; 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%.	Drug: Forced administration of furosemide; Forced administration of furosemide; Procedure: Urine-guided hydration; 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%.; Other Names: Forced administration of furosemide

What is the study measuring?

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
All-cause 30-day mortality	All-cause 30-day mortality	Up to 30 days after surgery
Length of hospital stay after surgery	Length of hospital 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
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
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
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
Classification of AKI within 7 days after surgery	AKI is classified according to the KDIGO criteria.	Up to 7 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of deterioration in renal function	Defined as ≥1 grade decrease in glomerular filtration rate compared with preoperative value.	Up to 6 months after surgery
Recurrence/progress-free survival	Defined as time from surgery to pseudomyxoma peritonei recurrence/progress/metastasis or all-cause death, whichever occurs first.	Up to 6 months after surgery
Event-free survival	Defined as time from surgery to pseudomyxoma peritonei recurrence/progress/metastasis, unplanned re-hospitalization for non-pseudomyxoma peritonei diseases, or all-cause death, whichever occurs first.	Up to 6 months after surgery

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Collaborators: Aerospace Center Hospital
• Investigators: Principal Investigator: Dong-Xin Wang, MD, PhD, Peking University First Hospital, Beijing, CHINA

Publications and helpful links

General Publications

• Hakeam HA, Breakiet M, Azzam A, Nadeem A, Amin T. The incidence of cisplatin nephrotoxicity post hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery. Ren Fail. 2014 Nov;36(10):1486-91. doi: 10.3109/0886022X.2014.949758. Epub 2014 Aug 26.
• Liesenfeld LF, Wagner B, Hillebrecht HC, Brune M, Eckert C, Klose J, Schmidt T, Buchler MW, Schneider M. HIPEC-Induced Acute Kidney Injury: A Retrospective Clinical Study and Preclinical Model. Ann Surg Oncol. 2022 Jan;29(1):139-151. doi: 10.1245/s10434-021-10376-5. Epub 2021 Jul 14.
• Angeles MA, Quenet F, Vieille P, Gladieff L, Ruiz J, Picard M, Migliorelli F, Chaltiel L, Martinez-Gomez C, Martinez A, Ferron G. Predictive risk factors of acute kidney injury after cytoreductive surgery and cisplatin-based hyperthermic intra-peritoneal chemotherapy for ovarian peritoneal carcinomatosis. Int J Gynecol Cancer. 2019 Feb;29(2):382-391. doi: 10.1136/ijgc-2018-000099. Epub 2019 Jan 23.
• Markowiak T, Kerner N, Neu R, Potzger T, Grosser C, Zeman F, Hofmann HS, Ried M. Adequate nephroprotection reduces renal complications after hyperthermic intrathoracic chemotherapy. J Surg Oncol. 2019 Dec;120(7):1220-1226. doi: 10.1002/jso.25726. Epub 2019 Oct 10.
• Solanki SL, Mukherjee S, Agarwal V, Thota RS, Balakrishnan K, Shah SB, Desai N, Garg R, Ambulkar RP, Bhorkar NM, Patro V, Sinukumar S, Venketeswaran MV, Joshi MP, Chikkalingegowda RH, Gottumukkala V, Owusu-Agyemang P, Saklani AP, Mehta SS, Seshadri RA, Bell JC, Bhatnagar S, Divatia JV. Society of Onco-Anaesthesia and Perioperative Care consensus guidelines for perioperative management of patients for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Indian J Anaesth. 2019 Dec;63(12):972-987. doi: 10.4103/ija.IJA_765_19. Epub 2019 Dec 11.
• Briguori C, D'Amore C, De Micco F, Signore N, Esposito G, Visconti G, Airoldi F, Signoriello G, Focaccio A. Left Ventricular End-Diastolic Pressure Versus Urine Flow Rate-Guided Hydration in Preventing Contrast-Associated Acute Kidney Injury. JACC Cardiovasc Interv. 2020 Sep 14;13(17):2065-2074. doi: 10.1016/j.jcin.2020.04.051.
• Luckraz H, Giri R, Wrigley B, Nagarajan K, Senanayake E, Sharman E, Beare L, Nevill A. Reduction in acute kidney injury post cardiac surgery using balanced forced diuresis: a randomized, controlled trial. Eur J Cardiothorac Surg. 2021 Apr 13;59(3):562-569. doi: 10.1093/ejcts/ezaa395.
• Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009 Jul 2;361(1):62-72. doi: 10.1056/NEJMra0801327. No abstract available. Erratum In: N Engl J Med. 2011 May 19;364(20):1982.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2023
• Primary Completion (Actual): July 19, 2024
• Study Completion (Actual): February 4, 2025

Study Registration Dates

• First Submitted: July 2, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 15, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Hydration; Acute Kidney Injury; Diuresis; Postoperative Complications; Hyperthermic Intraperitoneal Chemotherapy; Cytoreductive Surgery
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Acute Kidney Injury; Wounds and Injuries; Fever; Postoperative Complications; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Diuretics; Natriuretic Agents; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 2023-080

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No