Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06531369
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-06-22
Brief Title:
Flumazenil Antagonism of Remimazolam in Kidney Transplant Patients
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Application of Flumazenil to Antagonize Remimazolam and Evaluation of Remimazolam Plasma Concentration in Kidney Transplant Patients A Randomized Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To investigate the effect of different doses of flumazenil antagonism on remimazolam plasma concentration in patients undergoing renal transplantation under general anesthesia
Detailed Description:
During the surgery other anesthetics intraoperative monitoring fluid management and postoperative pain management were implemented according to a unified standard
1 Intraoperative Monitoring All study participants underwent the following routine intraoperative monitoring blood pressure electrocardiogram pulse oximetry end-tidal CO2 pressure body temperature and depth of anesthesia monitoring Additional monitoring such as central venous pressure invasive continuous arterial blood pressure and cardiac output was selected based on clinical needs and the attending anesthesiologists judgment
2 Anesthetic Regimen
All study participants underwent general anesthesia with endotracheal intubation and received total intravenous anesthesia with remimazolam For anesthesia induction it was recommended to administer remimazolam at a rate of 6-12 mgkgh until loss of consciousness for maintenance it was recommended to administer at a rate of 05-20 mgkgh At the end of anesthesia
C Group Immediately after surgery an equal volume of saline equal to the volume of 05 mg flumazenil was administered followed by an equal volume of saline equal to the volume of 03 mg flumazenil 25 minutes later
R1 Group Immediately after surgery 05 mg flumazenil was administered followed by an equal volume of saline equal to the volume of 03 mg flumazenil 25 minutes later
R2 Group Immediately after surgery 05 mg flumazenil was administered followed by 03 mg flumazenil 25 minutes later
None of the three groups used inhalation anesthetics such as sevoflurane or other intravenous sedatives such as midazolam dexmedetomidine or etomidate Intraoperative analgesics were administered with remifentanil via continuous intravenous infusion Muscle relaxants included cisatracurium with a single intravenous injection of cisatracurium 02 mgkg for induction to meet muscle relaxation conditions for tracheal intubation and intermittent single intravenous bolus of cisatracurium 005 mgkg to maintain muscle relaxation as needed for the surgery
3 Depth of Anesthesia Management Narcotrend was measured as a baseline value within 60 minutes before administration and intraoperative depth of anesthesia monitoring was conducted using Narcotrend The dose of remimazolam was adjusted according to hemodynamics to ensure that the patients anesthesia depth Narcotrend Index NCI was maintained between 27 and 60 If the NCI value could not be maintained at 60 or there were signs of potential inadequate anesthesia eg coughing sweating and patient movement and the maximum bolus and infusion doses of remimazolam had been administered rescue medications such as midazolam or propofol were allowed
4 Blood Pressure Management Intraoperative blood pressure control aimed to maintain a mean arterial pressure MAP of no less than 65 mmHg which was the minimum blood pressure tolerated by the anesthesiologist during surgery not the target value Higher or lower intraoperative blood pressure management targets could be adopted based on the participants condition andor the surgeons requirements The use of vasoactive drugs was minimized If vasoactive drugs were needed ephedrine 5 mg maximum dose not exceeding 30 mg and norepinephrine 10 µg intravenous bolus or continuous infusion were used Norepinephrine was prepared and used as follows 2 mg of norepinephrine bitartrate was diluted in 100 mL of saline to a concentration of 20 µgmL with an initial dose of 001 µgkgmin The dose was adjusted in real-time based on intraoperative blood pressure using the minimum amount of drug necessary to maintain the target MAP In case of severe bradycardia 40 beatsmin the norepinephrine infusion rate could be reduced and an appropriate dose of atropine could be administered intravenously based on the anesthesiologists judgment
5 Respiratory Management A lung-protective ventilation strategy was recommended during surgery setting a tidal volume of 6-8 mLkg an inspiratory-expiratory ratio of 12 and adjusting positive end-expiratory pressure PEEP to 5-10 cmH2O maintaining end-tidal CO2 pressure between 35-45 mmHg and using periodic lung recruitment maneuvers Spontaneous breathing was restored as soon as possible at the end of surgery and the endotracheal tube was removed
6 Fluid Management Crystalloids were the primary fluids recommended during surgery following a moderately liberal fluid management strategy
7 Other Management Points Comprehensive warming measures were recommended during surgery to maintain core temperature at 37C Blood transfusions were recommended based on bleeding and arterial blood gas analysis to maintain hemoglobin levels at 70 gL Postoperative pain management was selected based on the participants preoperative preferences and the anesthesiologists judgment to provide the best pain relief for the participant
8 Postoperative Management C Group Immediately after surgery an equal volume of saline equal to the volume of 05 mg flumazenil was administered followed by an equal volume of saline equal to the volume of 03 mg flumazenil 25 minutes later
R1 Group Immediately after surgery 05 mg flumazenil was administered followed by an equal volume of saline equal to the volume of 03 mg flumazenil 25 minutes later
R2 Group Immediately after surgery 05 mg flumazenil was administered followed by 03 mg flumazenil 25 minutes later
Arterial blood samples of 3 mL were collected in plastic tubes containing EDTA K3 Becton Dickinson Germany at T1 end of surgery T2 25 minutes after the end of surgery and T3 50 minutes after the end of surgery The arterial catheter was flushed with 2 mL of saline after each sample collection Samples were kept on ice water and centrifuged at approximately 2000 rpm at 4C for 10 minutes within 40 minutes of collection Plasma was separated into polypropylene tubes Nunc cryogenic vial cryo tubes Thermo Fisher Scientific USA within 15 minutes and stored at -70C The sample collection time was recorded The samples were sent to a third-party testing company for analysis within two months of collection
Data recorded included the time to eye-opening extubation time the amount of remimazolam used intraoperative analgesic use hemodynamic parameters at T0 admission T1 T2 and T3 MMSE scores 24h and 72h before and after surgery Narcotrend values at T0 T1 T2 and T3 PACU stay time and the incidence of nausea and vomiting during PACU stay postoperative complications such as atelectasis cardiovascular and cerebrovascular events stroke myocardial infarction all-cause mortality within 30 days postoperatively total length of hospital stay days for survivors within 30 days postoperatively and unplanned readmissions within 30 days postoperatively
1 Intraoperative Monitoring All study participants underwent the following routine intraoperative monitoring blood pressure electrocardiogram pulse oximetry end-tidal CO2 pressure body temperature and depth of anesthesia monitoring Additional monitoring such as central venous pressure invasive continuous arterial blood pressure and cardiac output was selected based on clinical needs and the attending anesthesiologists judgment
2 Anesthetic Regimen
All study participants underwent general anesthesia with endotracheal intubation and received total intravenous anesthesia with remimazolam For anesthesia induction it was recommended to administer remimazolam at a rate of 6-12 mgkgh until loss of consciousness for maintenance it was recommended to administer at a rate of 05-20 mgkgh At the end of anesthesia
C Group Immediately after surgery an equal volume of saline equal to the volume of 05 mg flumazenil was administered followed by an equal volume of saline equal to the volume of 03 mg flumazenil 25 minutes later
R1 Group Immediately after surgery 05 mg flumazenil was administered followed by an equal volume of saline equal to the volume of 03 mg flumazenil 25 minutes later
R2 Group Immediately after surgery 05 mg flumazenil was administered followed by 03 mg flumazenil 25 minutes later
None of the three groups used inhalation anesthetics such as sevoflurane or other intravenous sedatives such as midazolam dexmedetomidine or etomidate Intraoperative analgesics were administered with remifentanil via continuous intravenous infusion Muscle relaxants included cisatracurium with a single intravenous injection of cisatracurium 02 mgkg for induction to meet muscle relaxation conditions for tracheal intubation and intermittent single intravenous bolus of cisatracurium 005 mgkg to maintain muscle relaxation as needed for the surgery
3 Depth of Anesthesia Management Narcotrend was measured as a baseline value within 60 minutes before administration and intraoperative depth of anesthesia monitoring was conducted using Narcotrend The dose of remimazolam was adjusted according to hemodynamics to ensure that the patients anesthesia depth Narcotrend Index NCI was maintained between 27 and 60 If the NCI value could not be maintained at 60 or there were signs of potential inadequate anesthesia eg coughing sweating and patient movement and the maximum bolus and infusion doses of remimazolam had been administered rescue medications such as midazolam or propofol were allowed
4 Blood Pressure Management Intraoperative blood pressure control aimed to maintain a mean arterial pressure MAP of no less than 65 mmHg which was the minimum blood pressure tolerated by the anesthesiologist during surgery not the target value Higher or lower intraoperative blood pressure management targets could be adopted based on the participants condition andor the surgeons requirements The use of vasoactive drugs was minimized If vasoactive drugs were needed ephedrine 5 mg maximum dose not exceeding 30 mg and norepinephrine 10 µg intravenous bolus or continuous infusion were used Norepinephrine was prepared and used as follows 2 mg of norepinephrine bitartrate was diluted in 100 mL of saline to a concentration of 20 µgmL with an initial dose of 001 µgkgmin The dose was adjusted in real-time based on intraoperative blood pressure using the minimum amount of drug necessary to maintain the target MAP In case of severe bradycardia 40 beatsmin the norepinephrine infusion rate could be reduced and an appropriate dose of atropine could be administered intravenously based on the anesthesiologists judgment
5 Respiratory Management A lung-protective ventilation strategy was recommended during surgery setting a tidal volume of 6-8 mLkg an inspiratory-expiratory ratio of 12 and adjusting positive end-expiratory pressure PEEP to 5-10 cmH2O maintaining end-tidal CO2 pressure between 35-45 mmHg and using periodic lung recruitment maneuvers Spontaneous breathing was restored as soon as possible at the end of surgery and the endotracheal tube was removed
6 Fluid Management Crystalloids were the primary fluids recommended during surgery following a moderately liberal fluid management strategy
7 Other Management Points Comprehensive warming measures were recommended during surgery to maintain core temperature at 37C Blood transfusions were recommended based on bleeding and arterial blood gas analysis to maintain hemoglobin levels at 70 gL Postoperative pain management was selected based on the participants preoperative preferences and the anesthesiologists judgment to provide the best pain relief for the participant
8 Postoperative Management C Group Immediately after surgery an equal volume of saline equal to the volume of 05 mg flumazenil was administered followed by an equal volume of saline equal to the volume of 03 mg flumazenil 25 minutes later
R1 Group Immediately after surgery 05 mg flumazenil was administered followed by an equal volume of saline equal to the volume of 03 mg flumazenil 25 minutes later
R2 Group Immediately after surgery 05 mg flumazenil was administered followed by 03 mg flumazenil 25 minutes later
Arterial blood samples of 3 mL were collected in plastic tubes containing EDTA K3 Becton Dickinson Germany at T1 end of surgery T2 25 minutes after the end of surgery and T3 50 minutes after the end of surgery The arterial catheter was flushed with 2 mL of saline after each sample collection Samples were kept on ice water and centrifuged at approximately 2000 rpm at 4C for 10 minutes within 40 minutes of collection Plasma was separated into polypropylene tubes Nunc cryogenic vial cryo tubes Thermo Fisher Scientific USA within 15 minutes and stored at -70C The sample collection time was recorded The samples were sent to a third-party testing company for analysis within two months of collection
Data recorded included the time to eye-opening extubation time the amount of remimazolam used intraoperative analgesic use hemodynamic parameters at T0 admission T1 T2 and T3 MMSE scores 24h and 72h before and after surgery Narcotrend values at T0 T1 T2 and T3 PACU stay time and the incidence of nausea and vomiting during PACU stay postoperative complications such as atelectasis cardiovascular and cerebrovascular events stroke myocardial infarction all-cause mortality within 30 days postoperatively total length of hospital stay days for survivors within 30 days postoperatively and unplanned readmissions within 30 days postoperatively
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None