Impact of Remimazolam on Prognosis After Bladder Cancer Surgery
- Conditions
- Bladder CancerDeliriumBenzodiazepinesCancer RecurrenceSurgery
- Interventions
- Registration Number
- NCT04532606
- Lead Sponsor
- Peking University First Hospital
- Brief Summary
Bladder cancer is one of the most common genitourinary cancers. Transurethral resection of bladder tumor (TURBT) is the standard therapy for nonmuscle invasive bladder cancer. However, patients after TURBT are at risk for recurrence and progression. Benzodiazepines are proved to inhibit proliferation of multiple types of cancer cells in vitro. Delirium is an acute onset and transient cerebral dysfunction and is associated with worse outcomes. Previous studies indicated that benzodiazepines increase incidence of postoperative delirium. Remimazolam is a new benzodiazepine with rapid onset and ultra-short activity. The aims of this study are to explore the impact of remimazolam for general anesthesia on emergency delirium and recurrence-free survival in patients undergoing bladder cancer surgery.
- Detailed Description
Bladder cancer is one of the most common genitourinary cancers. Approximately 70-80% of bladder cancers are nonmuscle invasive, including those of Ta-T1 stage and carcinoma in situ. Transurethral resection of bladder tumor (TURBT) is the standard therapy for nonmuscle invasive bladder cancer. However, patients after TURBT are at a high risk of recurrence and progression.
Recently, impacts of anesthetic agents on tumor cells have attracted more attention. Benzodiazepines are found to inhibit proliferation of lymphoma, neural tumor, lung cancer, rectal cancer and breast cancer cells in vitro. Midazolam may have anti-tumor effects through induction of apoptosis and inhibition of inflammatory reaction. However, clinical evidence regarding effects of benzodiazepines on outcomes after cancer surgery remains lacking.
Remimazolam is a new benzodiazepine with rapid onset and ultra-short activity. It is rapidly metabolized by tissue esterases to inactive metabolite and can be reversed by flumazenil. Therefore, patients wake up rapidly even after prolonged infusions. It is also found to produce less respiratory and circulatory depression when compared with propofol.
Delirium is an acute onset and transient cerebral dysfunction, and is associated with worse outcomes including prolonged hospitalization, worse functional recovery, cognitive decline, and increased mortality rate. Previous studies indicated that benzodiazepines increase incidence of postoperative delirium, possibly due to prolonged action. With the property of ultra-short activity, remimazolam may not increase the incidence of delirium. But evidence is lacking in this aspect.
The aims of this study are to explore the impact of remimazolam on emergency delirium and recurrence-free survival in patients undergoing bladder cancer surgery.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1128
- Age ≥50 years and <90 years;
- Preoperative diagnosis is non-muscle-invasive bladder cancer(Ta-T1);
- Scheduled to undergo transurethral resection of bladder tumor;
- Agree to participate, and provide written informed consent.
- Refuse to participate;
- Emergent surgery;
- Combined with other malignant tumors;
- Use of benzodiazepines for 1 week within the last month before surgery;
- Preoperative history of schizophrenia, epilepsy, parkinsonism or myasthenia gravis;
- Inability to communicate in the preoperative period due to coma, profound dementia, language barrier, or end-stage disease;
- Critical illness (preoperative American Society of Anesthesiologists physical status classification ≥IV), severe hepatic dysfunction (Child-Pugh class C), or severe renal dysfunction (undergoing dialysis before surgery);
- The purpose of surgery is to make a diagnosis or preoperative judgement is that tumor cannot be completely removed.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Remimazolam group Remimazolam Remimazolam is administered intravenously for anesthesia induction and maintenance. The dose and infusion rate is adjusted to maintain Bispectral Index (BIS) value between 40 and 60. Analgesia is maintained with remifentanil and/or sufentanil. Muscle relaxation is maintained with rocuronium and/or cisatracurium. Sevoflurane inhalation is provided when considered necessary. Propofol group Propofol Propofol is administered intravenously for anesthesia induction and maintenance. The dose and infusion rate is adjusted to maintain BIS value between 40 and 60. Analgesia is maintained with remifentanil and/or sufentanil. Muscle relaxation is maintained with rocuronium and/or cisatracurium. Sevoflurane inhalation is provided when considered necessary.
- Primary Outcome Measures
Name Time Method Incidence of emergence delirium (early). Up to 2 hours during the stay in post-anesthesia care unit after surgery. Emergence delirium is assessed with the Confusion Assessment Method for the Intensive Care Unit at 10 and 30 minutes after admission to the post-anesthesia care unit after surgery.
Recurrence-free survival (long-term). Up to 3 years after surgery. Time from surgery to recurrence/metastasis or all-cause death, whichever come first.
- Secondary Outcome Measures
Name Time Method All-cause 30-day mortality (early). Up to 30 days after surgery. All-cause 30-day mortality.
Overall survival (long-term). Up to 3 years after surgery. Time from surgery to all-cause death.
Incidence of postoperative delirium (early). During the first 3 days after surgery. Delirium is assessed twice daily with the Chinese version of the 3-minute diagnostic interview for Confusion Assessment Method-defined delirium.
Incidence of postoperative nausea and vomiting (early). Up to 24 hours after surgery. Incidence of postoperative nausea and vomiting.
Health related quality of life of 1-year survivors (long-term). At the end of the 1st year after surgery. Health related quality of life is assessed with the World Health Organization Quality of Life-brief version (WHOQOL-BREF) which is a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.
Length of stay in hospital after surgery (early). Up to 30 days after surgery. Length of stay in hospital after surgery.
Incidence of non-delirium complications (early). Up to 30 days after surgery. Non-delirium complications are defined as newly occurred medical conditions other than delirium that are harmful for patients' recovery and required therapeutic intervention, i.e., grade 2 or higher on Clavien-Dindo classification.
Incidence of intraoperative awareness (early). Up to 1 day after surgery. Intraoperative awareness is assessed with modified Brice interview before discharge from the post-anesthesia care unit and on the 1st day after surgery. The interview included five questions: (1) What was the last thing you remembered happening before you went to sleep? (2) What is the first thing you remember after your operation? (3) Can you remember anything in between? (4) Can you remember if you had any dreams during your operation? (5) What was the worst thing about your operation?
Event-free survival (long-term). Up to 3 years after surgery. Time from surgery to serious events, cancer recurrence/metastasis, or all-cause death, whichever come first. Serious events are defined as any new onset disease that required hospitalization and/or surgical intervention.
Trial Locations
- Locations (6)
The Sixth Medical Center of PLA General Hospital
🇨🇳Beijing, Beijing, China
Beijing Tsinghua Chang Gung Hospital
🇨🇳Beijing, Beijing, China
Guizhou Provincial People's Hospital
🇨🇳Guiyang, Guizhou, China
Jiangsu Provincial People's Hospital
🇨🇳Nanjing, Jiangsu, China
Shanghai 10th People's Hospital
🇨🇳Shanghai, Shanghai, China
Peking University First Hospital
🇨🇳Beijin, Bejing, China