Colonic Polyp, Sedation Complication
Conditions
Keywords
Remimazolam besylate, Propofol, Procedural sedation, Polypectomy, Circulatory stability, Respiratory stability, Respiratory depression
Brief summary
The goal of this prospective, randomized, controlled study is to compare remimazolam besilat/sufentanyl and propofol/sufentanyl in patients during colonoscopic polypectomies procedures. Patients undergoing colonoscopic polypectomies in procedural sedation using remimazolam besylate/sufentanyl are circulatory and respiratory as or more stable when compared with propofol/sufentanyl sedation.
Detailed description
Following the approval for the research by the Ethics Committee (Clinical Hospital Center, Zagreb, Croatia), a total of ninety (90) patients will be included in the research. Forty five (45) patients will be assigned to the study group (SG) and forty five (45) patients to the control group (CG). Research Goals: Primary goals 1. Observe and compare circulatory and respiratory stability in patients undergoing procedural sedation with either remimazolam besylate or propofol during colonoscopic polypectomies 2. Define and compare the incidence of hypotension between the study grou and the control group. 3. Define and compare the incidence of respiratory depression between the study group and the control group. Secondary goals 1. Define and compare the success of remimazolam besylate sedation compared with propofol. 2. Define and compare the time required to achieve adequate sedation between the two observed groups. 3. Define and compare the time to achieve full consciousness between the two observed groups. 4. Define and compare the time to complete recovery between the two groups. Patients from both groups, upon arrival to the gastroenterology ward will have a peripheral venous line installed by puncturing one of the veins on the dorsum of the hand or forearm. The veins of choice include the rete venosum dorsale manus, vena cephalica and vena basilica, and an 18 G or 20 G intravenous cannula will be placed. After confirming the functionality of the venous line, the intravenous administration of Fifty will follow. The infusion rate will depend on the patient's BMI and circulatory status. Study Group (SG): A total of 45 patients are included in this group. After non-invasive monitoring, positioning the patient in the left lateral position and placing a nasal catheter with a continuous oxygen flow of 3 l/min, the patient will receive the intravenous opioid analgesic Sufentanyl 0.2 mcg/kg over a period of 30 seconds. After 1 to 2 minutes the patient will receive remimazolam besylate intravenously in a dose of 5.0 mg over a period of 1 minute. After two minutes, a maintenance dose of 2.5 mg will be administered using the titration method over a period of 15 seconds until the desired sedation effect is achieved.The maximum intravenous dose of administered remimazolam besylate will be 33 mg.BIS monitoring and a modified MOAA/S (Modified Observers Assessment of Alertness and Sedation Scale) scale will be used to assess the depth of sedation. The first measurement of the depth of sedation will be initially following the complete administration of the sedative remimazolam besylate and will serve as the initial/starting point. Afterwards, a measurement of the MOAA/S scale will be performed every 30 seconds for a total of 3 minutes. The most desirable level of sedation for the planned procedure is defined as a MOAA/S measurement of \<3. Control group (CG) A total of 45 patients will be included in this group. Firstly, non-invasive monitoring will be applied to the patient, then they will be placed in the left lateral position and through a nasal catheter a continuous oxygen flow of 3l/min will be administered. The patient will be given intravenous opioid analgesia Sufentanyl 0.2 mg/kg. within 30 seconds. After approximately 1-2 minutes the patient will receive the titrated anesthetic propofol intravenously at a dose of 1.5 to 2.5 mg/kg, (20.0 to 30.0 mg propofol every 10 seconds). In elderly patients and patients with ASA grade III, the total dose of propofol will be at least 1 mg/kg with an administration rate of 10.0 to 20.0 mg every 10 seconds. Sedation will be maintained using propofol in a continuous intravenous infusion. The maintenance dose given will be 0.5 to 1.0 mg propofol/kg/hour. BIS monitoring and a modified MOAA/S (Modified Observers Assessment of Alertness and Sedation Scale) scale will be used to assess the depth of sedation. The first measurement of the MOAA/S score will be conducted after the total intravenous propofol dose was administered and this first measurement will be considered the starting/zero measurement. MOAA/S scale point will be measured every 30 seconds for a total of 3 minutes. A measurement of \<3 points will be considered the most desirable level of sedation for the planned procedure. In both study groups the following parameters will continuously be measured: 1. Pulse oxymetry (SpO2), respiratory rate (RR), EKG, heart rate (HR) and rhythm, systolic, diastolic and mean arterial pressure. 2. Circulatory parameters including systolic, diastolic and mean arterial pressure will be measured: Primary measurement: Upon patients' arrival to the pre-op room (first measurement) and 5 minutes before proceeding to the operating theater. During the procedure: Before administering the sedative remimazolam besylate or propofol and at 3, 5, 10, and 15 minutes. (every 5 minutes during the procedure) until the patient is consciousness, followed by the first of five sets of MOAAS/S measurements upon completion of the procedure or when the last dose of medication is given. Frequency of hypotension in both groups of patients and comparing the results between the SG and CG. Hypotension during the procedure using sedation or propofol is defined as: a decrease in systolic systemic pressure of 20% or more compared with the first measurement before the administration of remimazolam besylata or propofol. A mean arterial pressure of ≤60 mmHg during while the patient is under sedation. 4\. Sinus bradycardia is defined as a decreased cardiac rate. 5. The frequency of respiratory depression compared between the two groups, SG and CG. Respiratory depression during sedation is defined as: Respiratory rate of \<8 breaths per minute and/or a peripheral blood oxygen percentage of (SpO2) \<90. 6\. BIS monitoring. 7. The success of procedural sedation using remimazolam besylate and sedation using propofol: Will be shown as the percentage of successfully sedated patients defined as: The completion of endoscopic polypectomy, without the need for rapid/fast acting emergency sedation or a maximum number of 5 additional doses given withing 15 minutes of the first dose to maintain adequate sedation. 8\. The time to achieve adequate sedation is defined as the time from administering the first dose of medication until achieving \<3 points on the MOAA/S scale and/ora BIS. 9\. The time to achieve full consciousness is defined as the time since the administration of the last dose of medication until the patient is fully aware, or until the patients has 5 points on the MOAA/S scale. 10\. The time needed for the patient to fully recover after the procedure in both groups is defined by the criteria for patient dismissal using the - Modified Aldrete score scale. The total volume of the given crystalloid solution (Plasma-lyte) will be measured in both groups.
Interventions
DRUGRemimazolam besylate
The patient will receive the intravenous opioid analgesic sufentanyl 0.2 mcg/kg over a period of 30 seconds. After 1 to 2 minutes the patient will receive remimazolam besylate intravenously in a dose of 5.0 mg over a period of 1 minute. After two minutes, a maintenance dose of 2.5 mg will be administered using the titration method over a period of 15 seconds until the desired sedation effect is achieved.The maximum intravenous dose of administered remimazolam besylate will be 33 mg.BIS monitoring and a modified MOAA/S scale will be used to assess the depth of sedation. The first measurement of the depth of sedation will be initially following the complete administration of the sedative remimazolam besylate and will serve as the initial/starting point. Afterwards, a measurement of the MOAA/S scale will be performed every 30 seconds for a total of 3 minutes. The most desirable level of sedation for the planned procedure is defined as a MOAA/S measurement of \<3.
DRUGPropofol
The patient will be given intravenous opiod analgesia sufentanyl 0,2 mg/kg.within 30 seconds. After approximately 1-2 minutes the patient will receive the titrated anestetic propofol intravenously at a dose of 1,5 to 2,5 mg/kg (20,0 mg. propofol evry 10 seconds). In elderly patients and patients with ASA grade III, the total dose of propofol will be least 1 mg/kg with an administration rate of 10 every 10 seconds.
Sponsors
Clinical Hospital Centre Zagreb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Considering that this is a single blind study, neither the controlled group nor the study group will be aware of which medication they are given because the method of administration is the same (therapeutic gold standard). The only individual who will know which medication is administered will be the primary researcher/anesthesiologist who will be administering the medication themselves.
Intervention model description
Comparation of two drug grups in controlled medical environment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients both male and female * ages 18 to 60 years, * with one or more colonic polyps confirmed by colonoscopy and scheduled for a colonoscopy and polypectomy * The duration of the colonoscopy ranges from 30 to 50 minutes. * ASA status (American Society of Anaesthesiologists physical status) I-III. * BMI (Body mass index) 18.5-29.9 kg/m2. * Only patients who signed an informed consent waiver and consented to participate in the research study.
Exclusion criteria
* Patients aged \>60 years * ASA status IV-V, * BMI \>29.9 kg/m2, * a high risk of vomiting, regurgitation and/or aspiration of gastric contents. * Patients with: * uncontrolled hypertension (systolic pressure \>160 mmHg), * heart disease (cardiomyopathy, cardiac-rhythm disorder, left ventricular ejection fraction \<45%, stenosis or heart valve insufficiency and coronary heart disease) * lung disease (pneumonia, chronic obstructive pulmonary disease, asthma and pulmonary tumors), * kidney diseases (kidney failure, GF 30/59 ml/min/1.73m2), * liver diseases, * coagulation disorders * lymphatic tissue diseases * extended malignant disease. * History of allergy on nutritional allergens including soy bean, benzodiazepines, propofol or opioids. * Patients who currently use analgesic medications or other psycho-pharmaceuticals. * History of illicit drug use. * Children, pregnant and nursing women. * Alcohol dependency. * Patients involved in other clinical research studies, * patients who refused to take part in the research or have not signed the written informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemodynamic Stability - Mean Arterial Pressure (MAP) | from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant. | Mean arterial pressure (mmHg) measured at multiple timepoints to assess overall circulatory stability. Comparison of MAP values between remimazolam and propofol groups. |
| Hemodynamic Stability - Systolic and Diastolic Blood Pressure | from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant. | Systolic and diastolic blood pressure (mmHg) measured at multiple timepoints to assess circulatory stability. Comparison between remimazolam and propofol groups. |
| Hemodynamic Stability - Heart Rate | from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant. | Heart rate (beats per minute) measured continuously via ECG monitoring. Comparison of heart rate values between study groups. |
| Incidence of Hypotension | from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant. | Percentage of participants experiencing hypotension defined as either: Decrease in systolic blood pressure ≥20% from baseline value (measured before remimazolam or propofol administration), OR Mean arterial pressure (MAP) ≤60 mmHg during procedural sedation |
| Incidence of Bradycardia | from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant. | Bradycardia is defined as a heart rate (HR) below 50 beats per minute (bpm), or a clinically significant decrease in HR of ≥20% from the pre-induction baseline, sustained for ≥1 minute and/or requiring pharmacological or non-pharmacological intervention (e.g., atropine administration, reduction or discontinuation of the study drug). HR will be continuously monitored via standard intraoperative ECG monitoring and recorded at predefined time points: baseline (pre-induction), immediately post-induction (T1), at 5-minute intervals intraoperatively, at emergence from anesthesia, and at 15 and 30 minutes postoperatively in the post-anesthesia care unit (PACU). The incidence of bradycardia will be expressed as the proportion of patients experiencing at least one episode meeting the above criteria within the defined observation window. |
| Respiratory Stability - Oxygen Saturation (SpO₂) | from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant. | Peripheral oxygen saturation (%) measured continuously via pulse oximetry. Comparison of SpO₂ values between study groups. |
| Incidence of Respiratory Depression | from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant. | Percentage of participants experiencing respiratory depression defined as: Respiratory rate \<8 breaths per minute, AND/OR Peripheral oxygen saturation (SpO₂) \<90% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Procedural Sedation Success Rate | During the endoscopic procedure (estimated 30-50 minutes | Percentage of participants achieving successful sedation defined as: Completion of entire endoscopic polypectomy procedure, AND No need for rescue sedation (defined as propofol 1.5-2.5 mg/kg IV by titration for inadequate sedation level in either group), AND Maximum of 5 additional drug doses within 15 minutes of initial dose |
| Time to Adequate Sedation Level | From first drug administration until adequate sedation achieved (estimated 1-5 minutes) | Time in minutes from first drug dose to achievement of adequate sedation level, defined as MOAA/S (Modified Observer's Assessment of Alertness/Sedation) score \<3 AND/OR BIS (Bispectral Index) value 50-70 |
| Time to Full Alertness | From last drug administration until full alertness (estimated 10-20 minutes post-procedure) | Time in minutes from last drug dose to full patient alertness, defined as achieving MOAA/S score of 5 |
| Time to Recovery Room Discharge Readiness | From last drug administration until meeting discharge criteria (estimated 15-30 minutes post-procedure) | Time in minutes from last drug dose to patient meeting discharge criteria from recovery room using Modified Aldrete Scoring System |
| Depth of Sedation - BIS Values | From baseline through procedure completion until full alertness (estimated 30-60 minutes) | Bispectral Index (BIS) values (0-100 scale) measured continuously to assess depth of sedation. Target range 50-70. Comparison of BIS values between study groups throughout procedure. |
| Depth of Sedation - MOAA/S Scores | Baseline, immediately after drug administration, then every 30 seconds for 3 minutes, then as clinically indicated during procedure | Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores (0-5 scale) measured at baseline, after total drug dose (time zero), then every 30 seconds for 3 minutes. Target score \<3 for adequate sedation. |
| Total Drug Dosage | During procedure (estimated 30-50 minutes) | Total dose of remimazolam besilate (mg) administered during procedure in the intervention group and total dose of propofol (mg) administered during procedure in the control group. Total dose of sufentanil (micrograms) administered in both groups (0.2 mcg/kg initial dose) |
| Procedure and sedation duration | From first drug administration to full alertness (estimated 30-60 minutes) From procedure start to procedure completion (estimated 30-50 minutes) | Duration of sedation and colonoscopic polypectomy procedure in minutes |
| Total Crystalloid Infusion Volume | During procedure and recovery (estimated 30-90 minutes) | Total volume (mL) of Plasma-Lyte crystalloid solution administered during procedure |
| Incidence of Post-Procedure Pain, nausea and vomiting | ost-procedure assessment before recovery room discharge (estimated 30-60 minutes after last drug dose) | Percentage of participants experiencing pain, nausea or vomiting in the post-procedure period |
| Satisfaction Score | Post-procedure before recovery room discharge | Patient-reported satisfaction with sedation procedure (VAS from 0-10) Endoscopist-reported satisfaction with sedation quality for procedure performance (VAS from 0-10) |
Countries
Croatia
Contacts
CONTACTŽeljko Drvar, MD, PhD
Outcome results
None listed