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

Acute Kidney Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05939193
• Other study ID #: 2023(080)
• Status: Recruiting
• Phase: N/A
• Start date: July 24, 2023
• Est. completion date: January 2025

Study information

• Verified date: November 2023
• Source: Peking University First Hospital
• Contact: Dong-Xin Wang, MD, PhD
• Phone: 010-83572784
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 168
• Est. completion date: January 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Cytoreductive Surgery
• Diuresis
• Fever
• Hydration
• Hyperthermia
• Hyperthermic Intraperitoneal Chemotherapy
• Postoperative Complications
• Wounds and Injuries

Intervention

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%.
• 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%.

Drug:
• Forced administration of furosemide
Forced administration of furosemide
• Routine administration of furosemide
Routine administration of furosemide

Locations

Country	Name	City	State
China	Aerospace Center Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University First Hospital	Aerospace Center Hospital

Country where clinical trial is conducted

China, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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	Classification of AKI within 7 days after surgery	AKI is classified according to the KDIGO criteria.	Up to 7 days after surgery
Secondary	Intensive care unit (ICU) admission after surgery	ICU admission after surgery	Up to 30 days after surgery
Secondary	Length of ICU stay after surgery	Length of ICU stay after surgery	Up to 30 days after surgery
Secondary	Duration of mechanical ventilation after surgery	Duration of mechanical ventilation after surgery	Up to 30 days after surgery
Secondary	Length of hospital stay after surgery	Length of hospital stay after surgery	Up to 30 days after surgery
Secondary	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
Secondary	All-cause 30-day mortality	All-cause 30-day mortality	Up to 30 days after surgery
Secondary	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