Use of Remimazolam for procedural sedation in real-life Digestive Endoscopy

Use of Remimazolam for procedural sedation in real-life Digestive Endoscopy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Use of Remimazolam for procedural sedation in real-life Digestive Endoscopy Rita Conigliaro, Flavia Pigò, Anna Caiazzo, Giuseppe Grande, Salvatore Russo, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4564245/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and aim Remimazolam has proved to be a very promising sedative drug in randomized clinical trials for usage in a wide spectrum of patients, including critically ill ones. The purpose of our study was to verify efficacy and safety of remimazolam for procedural sedation during diagnostic and first level operative endoscopy in a real-world setting. Methods This single centre prospective study evaluated sedation regimen with remimazolam for EGDS and fentanyl and remimazolam for colonoscopy in consecutive ASA I-III patients. Results 71 patients underwent 73 procedures (25 EGDS, 48 colonoscopies) with a total amount of 13.2 ± 8.7 mg and 10.2 ± 6.2 mg of remimazolam administered respectively. In 6 EGDS rescue sedation with propofol was needed. Transient hypotension was frequent (41.7%) and no cases of hypoxia occurred. One case of suspected allergy (erythema of the trunk) without anaphylaxis was reported. Conclusions Procedural sedation can be applied with remimazolam without the use of propofol, obtaining effective sedation in colonoscopies while in EGDS remimazolam alone guarantees the result in a percentage of around 70–75% of cases. Background and aims Remimazolam is a novel ultra-short-acting intravenous benzodiazepine that targets γ-aminobutyric acid type A (GABA-A) receptors. Because of its self-metabolizing and organ independent design, it is promptly hydrolysed as an inactive carboxylic acid by tissue esterase enzymes found in the blood ( 1 ). Remimazolam has been successfully used for the induction and maintenance of procedural sedation and general anaesthesia due to its rapid onset, short and predictable duration of sedative action, fast recovery time, rare accumulation after long-term infusion, and fewer serious side effects when compared to other currently used benzodiazepine. These properties make remimazolam a very promising sedative for usage in a wide spectrum of patients, including critically ill ones ( 2 – 3 ). In patients undergoing colonoscopy, clinical trials demonstrated that a combination of fentanyl and remimazolam is a safe and effective sedative for use, also among high-risk ASA III/IV patients. ( 4 – 8 ). Research on EGDS revealed that remimazolam (0.10–0.20 mg/kg) can be administered safely and efficiently as a single dosage for procedure sedation. These findings are supported by the observation that elderly patients having upper gastrointestinal endoscopy demonstrated both acceptable mental functioning and notably steady hemodynamic ( 9 – 10 ). To our knowledge, no study exists about clinical efficacy and safety of remimazolam for gastrointestinal endoscopy in a real-world setting. Clinical trials, however, may not provide a thorough representation of the patient population or reflect the drug's actual clinical efficacy and safety in real-life patients due to restrictive inclusion and exclusion criteria for patient participation. Purpose of the study was to verify remimazolam efficacy and safety profile for procedural sedation during diagnostic and first level operative endoscopic examinations in a real -world setting. Concurrently we evaluated if sedation with remimazolam alone was sufficient or if a rescue therapy with propofol was needed. In our centre, procedural sedation routinely includes midazolam (2 to 4 mg) plus propofol (titrated on target) during EGDS and Fentanyl (0.5–0.7 mcg/Kg) plus propofol during colonoscopies. Secondary aims of the study were to evaluate the level of intraprocedural awareness and to check the discharge times in patients. Methods Consecutive patients presenting for elective outpatient/inpatient colonoscopy or EGDS in a tertiary referral centre were enrolled in the study (target 100 participants). This number would permit detection of deep sedation episodes occurring at a frequency of at least 5%. Inclusion criteria were age > 18 years of age, patients undergoing diagnostic or simple operative endoscopy, ASA score I-II or III with no cardiorespiratory involvement, patients able to sign the informed consent. Exclusion criteria were allergy or hypersensitivity to benzodiazepines and/or flumazenil, pregnancy and clear signs of ongoing alcohol abuse. The study protocol was approved by our institutional review board. Only one peripheral intravenous access was obtained. Prior to sedation, blood pressure, heart rate, respiratory rate and oxygen saturation were assessed. Degree of anxiety was evaluated throughout VAS (Visual Analogic Scale) scale ( 11 ). ECG monitoring was applied only in case of cardiac disease. Blood pressure was taken every two minutes. Heart rate, respiratory rate and saturation were regularly measured. In addition, abdominal wall and chest excursions were employed to assess breathing effort. For procedural sedation, three healthcare professionals were required: one endoscopist, one nurse aiding the endoscopist, and one nurse for patient drug administration and monitoring. The endoscopist directed the nurse to administer drugs. Since 2007, all endoscopists and nurses have been qualified through continual and regular training in advanced life support. drug infusion started with a dose of fentanyl (1 mcg/kg), in case of colonoscopy, and was followed by a single dose of remimazolam. According to the clinical status of the population, the investigator could select the initial dose of remimazolam from a range between 2.5 to 5.0 mg. In case of EGDS, induction dose of remimazolam ranged from 2.5 to 7 mg according to clinical impairment of the patients. Then, top-up doses of remimazolam ranging from 1.5 mg to 2.5 mg were administered to reach deep sedation. Additional oxygen (4–5 L/min) were given in accordance with guidelines. Ramsay scale was used to assess the depth of sedation ( 12 ). The endoscopists selected when to administer additional remimazolam boluses, providing the nurse verbal instructions as needed. Elevated blood pressure, phonation, and spontaneous movement of the patient were considered indicators of the need of higher dosages. The endoscopist made all essential decisions about the patient's airway management or care as they were deteriorating, including whether to terminate sedation, increase oxygen flow, or begin mask ventilation. The most frequent adverse events during procedural sedation were oxygen desaturations, bradycardia, hypotension. In case of oxygen desaturation, remimazolam was stopped and simple airway techniques such head extension, jaw push, and/or chin lift were started. High-flow oxygen was also administered via a bag and mask. The anaesthesiologist was immediately called (estimated response time from 1 to 6 minutes) if these manoeuvres failed. Bradycardia was treated with atropine boluses (0.4 mg to a maximum dose of 2 mg). The patient was placed in the Trendelenburg position, and fluid infusion was given in the case of hypotension. In case of a lack of proper response, ephedrine was administered at doses ranging from 3 mg to a maximum of 9 mg. If the patient does not respond with an increase in pressure, the anaesthetist on duty must be notified. Adverse events were defined as follows, according to the same criteria of similar studies ( 4 , 6 , 9 ): - Hypoxia: oxygen saturation < 90% for ≥ one minute, or any decline requiring medical intervention - Bradycardia: < 40 beats/minute or drop-in heart rate equal to or greater than 20% from baseline that has lasted continuously for at least 30 seconds. - Hypertension: an increase in systolic blood pressure to ≥ 180 mmHg or diastolic blood pressure to ≥ 100 mmHg, or an increase in systolic or diastolic blood pressure of 20% or more from baseline or requiring medical intervention. - Hypotension, defined as a fall in systolic blood pressure to ≤ 80 mmHg or diastolic blood pressure to ≤ 40 mmHg, or a fall in systolic or diastolic blood pressure 20% or more below baseline or requiring medical intervention. - Prolonged sedation (i.e., Ramsay ≥ 5 for more than 60 minutes after the last dose of study drug) including the need to administer flumazenil at the discretion of the investigator. - Altered respiratory rate: 25. In this study the failure of procedural sedation was defined as inability to start or complete the procedure after the first dose and a maximum of 33 mg of remimazolam boluses (17.5 mg in case of low clinical status of the patient) within 15 minutes. In case of treatment failure, propofol boluses of 20 mg were given to complete the procedure. The interval between the end of examination and recovering was defined as recovery time. Before discharging from the recovery room, heart rate, blood pressure, respiratory rate, and saturation level were assessed by a dedicated nurse. The recovery nurse used The Aldrete scale ( 13 ) to reevaluate patients' awareness and their capacity to move or walk as before procedural sedation before releasing them from the hospital. Vital parameters (oxygen saturation, blood pressure, heart rate, respiratory rate), VAS anxiety scale and Ramsay scores were recorded before, during the procedure, at the end of examination and at arrival in the recovery room. Before hospital discharge the Aldrete scale was evaluated and recorded. The Brice Questionnaire (Table 1 ) was applied within 10 min after the patient reached fully alert status and 24 hours after examination through a phone call ( 14 ). Table 1 Brice Questionnaire From a scale of 0 to 10: - how much do you remember about the procedure? - how satisfied are you with the sedation? - how many unpleasant memories do you have? Statistics Continuous variables were expressed as mean ± standard deviation or median (IQR 25–75%) if parametric or not parametric distribution respectively. Categorical variables were expressed as number and percentages. Comparison among continuous and categorical variables were made with T-Test or Fisher Test respectively. Stata 13 ® (Texas, USA) was used as statistical software. Results Patients 73 patients received remimazolam protocol sedation for 75 procedures. 2 patients were excluded because of procedure failure. Finally, 71 patients and 73 procedures were analysed. 2 patients had double examination (EGDS + colonoscopy). Mean age was 62.0 ± 15.2 years old with a mean BMI of 25.2 ± 4.7. 33.8% of patients had no comorbidities and in 91.5% of cases were ASA 1 o 2. Characteristics of patients were shown in the Table 2 . Table 2. Characteristics of patients Characteristics Patients 71 Age 62.0 ± 15.2 Sex Female Male 38 (54) 33 (46) BMI 25.2 ± 4.7 Comorbidities Cardiac Dyslipidaemia Diabetes Neurologic Pulmonary OSAS Renal Hepatic ≥3 None 34 (48) 19 (27) 6 (8) 3 (4) 8 (11) 0 2 (3) 3 (4) 5 (7) 24 (34) ASA score 1 2 3 28 (39) 37 (52) 6 (9) Mallampati 1 2 3 4 7 (10) 56 (79) 8 (11) 0 Indication Scheduled Urgent 71 (100) 0 State of anxiety None-Low Medium High 16 (23) 55 (77) 0 State of consciousness Ramsay 1 Ramsay 2 70 (99) 1 (1) Results expressed as mean ± standard deviation or number and percentages Procedures 25 EGDS and 48 colonoscopies received sedation with remimazolam. In 31% and 87%, EGDS and colonoscopies were performed by a trainee endoscopist with supervision of a senior. Induction of the sedation was performed with 3.7 ± 1.7 mg and 4.5 ± 0.8 mg for EGDS and colonoscopies respectively. Total amount of the drugs administered was 13.2 ± 8.7 mg and 10.2 ± 6.2 mg respectively. In 3 EGDS (2 in the frailer categories) and in 1 colonoscopy in a frail patient, total dose of remimazolam reached the maximum allowed in the protocol. In 6 procedures of EGDS, rescue sedation with propofol was necessary. In 3 cases rescue sedation was performed after maximum reached dose of remimazolam. No rescue sedation was needed for colonoscopies. Recovery time was 21.8 ± 10.0 for EGDS and 16.9 ± 8.0 for colonoscopies. Ramsay scale ranged from 1, before the sedation, to 2 ± 0.8 during the examination and promptly returned to 1 ± 0.6 at the end. Aldrete score, before dismission was 9.8 ± 0.2. Characteristics of procedures are shown in the Table 3 . Table 3 Characteristics of procedures EGDS (25) Colonoscopy (48) Remimazolam induction (mg) 3.7 ± 1.7 4.5 ± 0.8 Remimazolam maintenance (mg) 10.5 ± 7.2 8.7 ± 5.5 Remimazolam total (mg) 13.2 ± 8.7 10.2 ± 6.2 Fentanyl (mcg) NA 50 ± 37 Remimazolam maximum reached dose 3 (12%) 1 ( 2 ) Remimazolam induction ≥ 65ys/ASA3 (mg) 3.0 ± 1.2 4.2 ± 1.0 Remimazolam total ≥ 65ys/ASA3 (mg) 9.0 ± 4.6 9.2 ± 5.0 Remimazolam maximum reached dose ≥ 65ys/ASA3 2 (8%) 1 (2%) Rescue sedation 6 (24%) 0 Remimazolam maximum reached dose in failure sedation 3 (12%) 0 Examination time (min) 20.3 ± 11.0 27.0 ± 8.5 Recovery time (min) 21.8 ± 10.0 16.9 ± 8.0 ASA 1 2 3 8 (32%) 15 (60%) 2 (8%) 20 (42%) 24 (50%) 4 (8%) Trainee involvement 15 (60%) 33 (68%) Biopsy/polypectomy 13 (52%) 19 (39%) Results expressed as mean ± standard deviation or number and percentages Safety Safety of procedural sedation with remimazolam was calculated in procedures with no failure (68 patients). 28 patients (41.7%) experienced a transitory hypotensive episode during examination. We only reported two cases of hypotension related to systolic pressure < 80 mmHg or diastolic pressure 20 mmHg. Only in 2 cases fluid supplementation (maximum 500ml of physiologic solution) was needed. Bradycardia was associated only with colonoscopies and was never registered during EGDS. No cases of hypoxia or hypertension occurred. Adverse events of procedures are described in the Table 4 . One case of allergy was registered: a 61-year-old female, with no co-morbidities, immediately after infusion of the drug during the colonoscopy, presented erythema of the trunk. The patient was quickly treated with infusion of clorfenamine and hydrocortisone with complete remission of symptom Because the patients did not before any sedation, it was not possible to attribute the allergic manifestation to remimazolam or fentanyl. Table 4. Minor adverse events of procedures (67) with remimazolam sedation protocol Characteristics Hypotension Bradycardia Hypoxia N° (%) 28 (42) 10 (15) 0 Age 65.7± 13.8 58± 17.6 Sex (male) 16 8(7) 4 (40) BMI 23.9 ± 3.2 23.5 ± 5.4 Comorbidities (at least one) 18 (64) 6 (60) ASA 1 2 3 8 (29) 16 (57) 4 (14) 9 (90) 2 (10) 0 Mallampati 1 2 3 2 (7) 22 (79) 4 (14) 0 8 (80) 2 (20) Examination EGDS Colonoscopy 10 (36) 18 (64) 0 10 (100) Drugs administered Remimazolam induction (mg) Remimazolam maintenance (mg) Remimazolam total (mg) 4.2 ± 1.2 9.2 ± 6.5 11.5 ± 7.5 4.7 ± 0.7 8.2 ± 6.2 11.5 ± 6.7 Systolic pressure 117 ± 19 132 ± 19 Saturation oxygen 98 ± 1.8 99 ± 1.1 Heart rate/min 77 ± 12 65 ± 8 Respiratory rate (min) 19 ± 5 18 ± 1 Ramsay scale 2.1 ± 0.8 1.9 ± 0.7 Results expressed as mean ± standard deviation or number and percentages No significant differences of vital parameters and Ramsay scale was noted among group of frail and not frail patients (Table 5 ). Only systolic pressure was significantly higher in the frail group (p-value 0.007). Table 5 Vital parameters and adverse events of patients during the examination Characteristics Patients aged < 65 yrs/ASA 1 or 2 Patients aged ≥ 65 yrs/ASA 3 p-value N° 30 41 Systolic pressure 118 ± 19 132 ± 21 0.007 Hypotension 9 (30) 19 (46) 0.214 Saturation oxygen 98.6 ± 1.5 98.2 ± 1.6 0.384 Desaturation 0 0 NA Heart rate/min 75 ± 16 73 ± 14 0.689 Bradycardia 5 ( 17 ) 5 ( 12 ) 0.731 Respiratory rate (min) 18 ± 3 20 ± 6 0.143 Ramsay scale 2.1 ± 0.7 2.3 ± 0.9 0.364 Results expressed as mean ± standard deviation or number and percentages Recall Follow-up Brice Questionnaire for satisfaction showed from a scale from 0 to 10 a recall of 2.8 ± 3.1, a satisfaction of 9.2 ± 1.0 and unpleasant memories of 0.3 ± 1.1 Discussion This study on real world setting showed that remimazolam is effective and safe for first level EGDS and colonoscopy. The efficacy results are comparable to randomized controlled trials that used the same sedation regimen as in our study. As regards EGDS, Borkett et al ( 9 ) demonstrated that a dose of 0.2 mg/kg of remimazolam was effective in 64% of cases. The success rate of sedation in the study of Chen et al. ( 10 ), showed that remimazolam was 97% even if a pre-medication with lidocaine spray was administered before the EGDS. Regarding the efficacy in colonoscopy, our results confirm that the balanced sedation with remimazolam and fentanyl is effective in 100% of cases. Similar controlled trials by Rex in 2018 ( 4 ) and in 2021 showed that remimazolam allowed a complete colonoscopy with no need for rescue medication in 91% and 87% of cases. The cohort of patients studied by Rex in 2021 ( 6 ) was composed only by ASA 3. In our study colonoscopies in ASA 3 patients were only 4 and none was ASA IV but there was no sedation failure among them. In all three studies, patients received fentanyl before receiving remimazolam. Respect to ASA 1 and ASA 2 patients, remimazolam in ASA 3 patients appears less effective to complete a procedural sedation but with a good balance between efficacy and safety. Incidence and frequency of major adverse events were comparable in all the studies, and independent of ASA status. It is interesting to note that the criteria for defining minor adverse events are not the same between our study and the various studies cited for EGDS. This makes the safety data difficult to compare even if no major adverse event occurred in any patient cohort. Characteristics of studies compared in the discussion are shown in the Table 6 . Table 6 Main Clinical studies of Remimazolam for Sedation of EGDS and colonoscopy study Patients Efficacy Safety EGDS Conigliaro 2024 ASA1/2/3 - no rescue sedation after a maximum dose of 33 mg of (17.5 mg in case of frail patients):76% - Hypotension (SBP ≤ 80 mmHg or DBP ≤ 40 mmHg or drop in SBP/DP > 20%): 40% - Hypoxia (02 saturation < 90% for ≥ one minute): 0% Borkett 2015 ASA1/2 25 patients No rescue sedation after a maximum dose of 0.2 mg/kg: 64% - hypotension: SBP ≤ 80 mm Hg: 0 - hypoxia: O2 saturation 20% in SBP or MAP < 60 mmHg): 13% - hypoxia (RR < 8 breaths/minute and 02 saturation < 90%): 1% Colonoscopy Conigliaro 2024 ASA1/2/3 48 patients - no rescue sedation after a maximum dose of 33 mg of (17.5 mg in case of frail patients):100% Hypotension (SBP ≤ 80 mmHg or DBP ≤ 40 mmHg or drop in SBP/DP > 20%): 37% Hypoxia (02 saturation < 90% for ≥ one minute): 0% Rex 2018 ASA1/2/3 296 patients - no rescue sedation after a maximum dose of 33 mg of (17.5 mg in case of frail patients):91% - hypotension (SBP ≤ 80 mmHg/DBP ≤ 40 mmHg, or drop > 20% in SBP/DBP): 39% - hypoxia (02 saturation 20% in SBP/DBP): 58% - hypoxia (02 saturation < 90% for ≥ one minute): 19% We observed a case, not confirmed by a skin test or a provocative test, of skin allergy without anaphylaxis. To our knowledge, 12 cases of anaphylaxis have been reported. When anaphylaxis occurs during procedural sedation, remimazolam should be kept in mind as the causative drug ( 15 – 21 ). In our study the time to sedation recovery (21.8 for EGDS and 16.9 for colonoscopies) is longer than in the mentioned trials (6–11 minutes). It is probably due to the data collection method which, in our case, happens with delivery of the report ( 4 , 6 , 9 – 10 ). The assessment of exam recall was homogeneous compared to randomized controlled trials. Approximately 80% of patients had no unpleasant memories related to the exam ( 4 , 6 , 9 ). During the central moment of the exam, according to our data, the patient had a level of consciousness of 2.1 ± 0.8 in “young” patients and 1.9 ± 0.7 in frail patients. Even though the patient can be awakened with verbal call, they did not remember the exam and were satisfied with the sedation when the Brice questionnaire was used 24 hours after the examination. These data confirm the good safety and efficacy profile of the drug in the different categories of patients. This drug, as shown by Rex et al., could have a preferrable indication to ASA III/IV. Safety was also studied in elderly patients by Liu et al on EGDS and colonoscopies ( 22 ). 107 elderly patients in the remimazolam group and 109 elderly patients in the propofol group were analysed. The incidence of moderate hypoxemia was 2.8% in the remimazolam group and 17.4% in the propofol group (p < 0.001) without significant difference in the incidence of severe hypoxemia between the two groups (4.7% vs. 5.5%; p = 0.781). Similarly, Guo et al reported that haemodynamic events and respiratory depression in the remimazolam group were less frequent than those in the propofol group (15% vs. 44%, P = 0.005), (5% vs. 23%, P = 0.026). ( 23 ). Conclusions Regarding our goal of being able to complete the procedure without resorting to propofol the important result is that it was necessary to resort to rescue sedation only in EGDS (24%) and in no case in colonoscopies. Therefore, from these preliminary data it is concluded that procedural sedation can be applied with remimazolam without the use of propofol, obtaining effective sedation in colonoscopies while in EGDS remimazolam alone guarantees the result in a percentage of around 70–75% of cases. Other studies will be necessary to confirm these preliminary data which will allow us to find the right indications for the use of remimazolam in routine diagnostic and first level operative endoscopic examinations in real-life. Declarations Funding: the research did not receive funding Author Contribution Conigliaro R. create and reviewed the study, Pigò F. collected and analyzed the data and wrote the manuscript, Caiazzo A.;, Grande G., Russo S., Cocca S., Lupo M., Marocchi M., Marsico M. collected the data, Sculli S.and Bertani H. reviewed the study Acknowledgements: not applicable Data Availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request References Rogers WK, McDowell TS. Remimazolam, a short-acting GABA(A) receptor agonist for intravenous sedation and/or anesthesia in day-case surgical and non-surgical procedures. IDrugs. 2010;13:929–937. Oka S, Satomi H, Sekino R, et al. Sedation outcomes for remimazolam, a new benzodiazepine. J Oral Sci. 2021;63:209–211. Antonik LJ, Goldwater DR, Kilpatrick GJ et al. 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Discharge readiness after remimazolam versus propofol for colonoscopy: a randomised, double-blind trial. Eur J Anaesthesiol. 2022;39:911–917. Pambianco DJ, Borkett KM, Riff DS et al. A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2016;83:984–92. Borkett KM, Riff DS, Schwartz HI et al. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg. 2015;120:771–80. Chen SH, Yuan TM, Zhang J et al. Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial. J Gastroenterol Hepatol. 2021;36:474–481. Cao X, Yumul R, Elvir Lazo OL et al. A novel visual facial anxiety scale for assessing preoperative anxiety. PLoS One. 2017;12:e0171233. Ramsay MA, Savage TM, Simpson B, et al: Controlled sedation with alphaxalone-alphadolone. 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Hu, X., Tang, Y., Fang, X. Laryngeal edema following remimazolam-induced anaphylaxis: A rare clinical manifestation. BMcAnesthesiol. 2023; 23: 99. Lee S, Park J, Kim NH, et al. Remimazolam Anaphylaxis during Induction of General Anesthesia Confirmed by Provocation Test-A Case Report and Literature Review. Medicina (Kaunas). 2023;59:1915. Liu F, Cheng X, Wang Y, et al. Effect of remimazolam tosilate on the incidence of hypoxemia in elderly patients undergoing gastrointestinal endoscopy: A bi-center, prospective, randomized controlled study. Front Pharmacol. 2023;14:1131391. Guo J, Qian Y, Zhang X, et al. Remimazolam tosilate compared with propofol for gastrointestinal endoscopy in elderly patients: a prospective, randomized and controlled study. BMC Anesthesiol. 2022;22:180. Additional Declarations No competing interests reported. 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Pigò","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIie3PIQ7DIBSAYThB7Y5RRdOkaQ8y8whJp+YnKsCsV8BPz06zNNlMM2yTmnKDHmHABXhyyfgNiPflASG53E9G5b6RJlyUwRKlgfTRYgmhnkzxhiNVcVOSX217Hye/ZWiOSVJrF8gqHjP35NWfZYqUy3PcYF4FM55QOaGIkjB/BLMOS6zy5GJatmC31JoGIoAtfgtg/lIVbyf3su2YPbltHxrEww4QTx4nITUeSWHi2WGGc7lc7k/7Ahd3T8q2rgm/AAAAAElFTkSuQmCC","orcid":"","institution":"Azienda Ospedaliero Universitaria Modena","correspondingAuthor":true,"prefix":"","firstName":"Flavia","middleName":"","lastName":"Pigò","suffix":""},{"id":320827724,"identity":"771c7af8-c899-4b8c-8b4a-ad4bd8c9768b","order_by":2,"name":"Anna Caiazzo","email":"","orcid":"","institution":"University Federico II","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Caiazzo","suffix":""},{"id":320827725,"identity":"7d9e6d10-aeb7-4704-8578-a4e197b35e35","order_by":3,"name":"Giuseppe 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Modena","correspondingAuthor":false,"prefix":"","firstName":"Marinella","middleName":"","lastName":"Lupo","suffix":""},{"id":320827729,"identity":"ae2b6580-2829-4058-bf1e-1aed91ddddd5","order_by":7,"name":"Margherita Marocchi","email":"","orcid":"","institution":"Azienda Ospedaliero Universitaria Modena","correspondingAuthor":false,"prefix":"","firstName":"Margherita","middleName":"","lastName":"Marocchi","suffix":""},{"id":320827730,"identity":"ceaf68b2-a7eb-498c-927b-452cf247f98e","order_by":8,"name":"Maria Marsico","email":"","orcid":"","institution":"Azienda Ospedaliero Universitaria Modena","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Marsico","suffix":""},{"id":320827731,"identity":"baf52e9e-e615-4b9a-b48f-cf7191f4c514","order_by":9,"name":"Simone Sculli","email":"","orcid":"","institution":"Azienda Ospedaliero Universitaria Modena","correspondingAuthor":false,"prefix":"","firstName":"Simone","middleName":"","lastName":"Sculli","suffix":""},{"id":320827732,"identity":"ee9338ba-1bdd-4cd8-87f7-4c3608439463","order_by":10,"name":"Helga Bertani","email":"","orcid":"","institution":"Azienda Ospedaliero Universitaria Modena","correspondingAuthor":false,"prefix":"","firstName":"Helga","middleName":"","lastName":"Bertani","suffix":""}],"badges":[],"createdAt":"2024-06-11 12:51:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4564245/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4564245/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60885891,"identity":"539f48a5-edc6-4e64-91cc-59c14c64d465","added_by":"auto","created_at":"2024-07-23 07:56:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":787995,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4564245/v1/7e77199a-f4bc-4616-ac75-c4c281cc4492.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Use of Remimazolam for procedural sedation in real-life Digestive Endoscopy","fulltext":[{"header":"Background and aims","content":"\u003cp\u003eRemimazolam is a novel ultra-short-acting intravenous benzodiazepine that targets γ-aminobutyric acid type A (GABA-A) receptors. Because of its self-metabolizing and organ independent design, it is promptly hydrolysed as an inactive carboxylic acid by tissue esterase enzymes found in the blood (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Remimazolam has been successfully used for the induction and maintenance of procedural sedation and general anaesthesia due to its rapid onset, short and predictable duration of sedative action, fast recovery time, rare accumulation after long-term infusion, and fewer serious side effects when compared to other currently used benzodiazepine. These properties make remimazolam a very promising sedative for usage in a wide spectrum of patients, including critically ill ones (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn patients undergoing colonoscopy, clinical trials demonstrated that a combination of fentanyl and remimazolam is a safe and effective sedative for use, also among high-risk ASA III/IV patients. (\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Research on EGDS revealed that remimazolam (0.10\u0026ndash;0.20 mg/kg) can be administered safely and efficiently as a single dosage for procedure sedation. These findings are supported by the observation that elderly patients having upper gastrointestinal endoscopy demonstrated both acceptable mental functioning and notably steady hemodynamic (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo our knowledge, no study exists about clinical efficacy and safety of remimazolam for gastrointestinal endoscopy in a real-world setting. Clinical trials, however, may not provide a thorough representation of the patient population or reflect the drug's actual clinical efficacy and safety in real-life patients due to restrictive inclusion and exclusion criteria for patient participation.\u003c/p\u003e \u003cp\u003ePurpose of the study was to verify remimazolam efficacy and safety profile for procedural sedation during diagnostic and first level operative endoscopic examinations in a real -world setting. Concurrently we evaluated if sedation with remimazolam alone was sufficient or if a rescue therapy with propofol was needed. In our centre, procedural sedation routinely includes midazolam (2 to 4 mg) plus propofol (titrated on target) during EGDS and Fentanyl (0.5\u0026ndash;0.7 mcg/Kg) plus propofol during colonoscopies. Secondary aims of the study were to evaluate the level of intraprocedural awareness and to check the discharge times in patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eConsecutive patients presenting for elective outpatient/inpatient colonoscopy or EGDS in a tertiary referral centre were enrolled in the study (target 100 participants). This number would permit detection of deep sedation episodes occurring at a frequency of at least 5%. Inclusion criteria were age\u0026thinsp;\u0026gt;\u0026thinsp;18 years of age, patients undergoing diagnostic or simple operative endoscopy, ASA score I-II or III with no cardiorespiratory involvement, patients able to sign the informed consent. Exclusion criteria were allergy or hypersensitivity to benzodiazepines and/or flumazenil, pregnancy and clear signs of ongoing alcohol abuse. The study protocol was approved by our institutional review board.\u003c/p\u003e\u003cp\u003eOnly one peripheral intravenous access was obtained. Prior to sedation, blood pressure, heart rate, respiratory rate and oxygen saturation were assessed. Degree of anxiety was evaluated throughout VAS (Visual Analogic Scale) scale (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). ECG monitoring was applied only in case of cardiac disease. Blood pressure was taken every two minutes. Heart rate, respiratory rate and saturation were regularly measured. In addition, abdominal wall and chest excursions were employed to assess breathing effort. For procedural sedation, three healthcare professionals were required: one endoscopist, one nurse aiding the endoscopist, and one nurse for patient drug administration and monitoring. The endoscopist directed the nurse to administer drugs. Since 2007, all endoscopists and nurses have been qualified through continual and regular training in advanced life support.\u003c/p\u003e \u003cp\u003edrug infusion started with a dose of fentanyl (1 mcg/kg), in case of colonoscopy, and was followed by a single dose of remimazolam. According to the clinical status of the population, the investigator could select the initial dose of remimazolam from a range between 2.5 to 5.0 mg. In case of EGDS, induction dose of remimazolam ranged from 2.5 to 7 mg according to clinical impairment of the patients. Then, top-up doses of remimazolam ranging from 1.5 mg to 2.5 mg were administered to reach deep sedation. Additional oxygen (4\u0026ndash;5 L/min) were given in accordance with guidelines.\u003c/p\u003e \u003cp\u003eRamsay scale was used to assess the depth of sedation (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The endoscopists selected when to administer additional remimazolam boluses, providing the nurse verbal instructions as needed. Elevated blood pressure, phonation, and spontaneous movement of the patient were considered indicators of the need of higher dosages. The endoscopist made all essential decisions about the patient's airway management or care as they were deteriorating, including whether to terminate sedation, increase oxygen flow, or begin mask ventilation.\u003c/p\u003e \u003cp\u003eThe most frequent adverse events during procedural sedation were oxygen desaturations, bradycardia, hypotension. In case of oxygen desaturation, remimazolam was stopped and simple airway techniques such head extension, jaw push, and/or chin lift were started. High-flow oxygen was also administered via a bag and mask. The anaesthesiologist was immediately called (estimated response time from 1 to 6 minutes) if these manoeuvres failed. Bradycardia was treated with atropine boluses (0.4 mg to a maximum dose of 2 mg). The patient was placed in the Trendelenburg position, and fluid infusion was given in the case of hypotension. In case of a lack of proper response, ephedrine was administered at doses ranging from 3 mg to a maximum of 9 mg.\u003c/p\u003e \u003cp\u003eIf the patient does not respond with an increase in pressure, the anaesthetist on duty must be notified.\u003c/p\u003e \u003cp\u003eAdverse events were defined as follows, according to the same criteria of similar studies (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e):\u003c/p\u003e\u003cp\u003e- Hypoxia: oxygen saturation\u0026thinsp;\u0026lt;\u0026thinsp;90% for \u0026ge;\u0026thinsp;one minute, or any decline requiring medical intervention\u003c/p\u003e\u003cp\u003e- Bradycardia: \u0026lt; 40 beats/minute or drop-in heart rate equal to or greater than 20% from baseline that has lasted continuously for at least 30 seconds.\u003c/p\u003e\u003cp\u003e- Hypertension: an increase in systolic blood pressure to \u0026ge;\u0026thinsp;180 mmHg or diastolic blood pressure to \u0026ge;\u0026thinsp;100 mmHg, or an increase in systolic or diastolic blood pressure of 20% or more from baseline or requiring medical intervention.\u003c/p\u003e\u003cp\u003e- Hypotension, defined as a fall in systolic blood pressure to \u0026le;\u0026thinsp;80 mmHg or diastolic blood pressure to \u0026le;\u0026thinsp;40 mmHg, or a fall in systolic or diastolic blood pressure 20% or more below baseline or requiring medical intervention.\u003c/p\u003e\u003cp\u003e- Prolonged sedation (i.e., Ramsay\u0026thinsp;\u0026ge;\u0026thinsp;5 for more than 60 minutes after the last dose of study drug) including the need to administer flumazenil at the discretion of the investigator.\u003c/p\u003e\u003cp\u003e- Altered respiratory rate: \u0026lt;8 breaths/minute or increased to \u0026gt;\u0026thinsp;25.\u003c/p\u003e \u003cp\u003eIn this study the failure of procedural sedation was defined as inability to start or complete the procedure after the first dose and a maximum of 33 mg of remimazolam boluses (17.5 mg in case of low clinical status of the patient) within 15 minutes. In case of treatment failure, propofol boluses of 20 mg were given to complete the procedure.\u003c/p\u003e \u003cp\u003eThe interval between the end of examination and recovering was defined as recovery time. Before discharging from the recovery room, heart rate, blood pressure, respiratory rate, and saturation level were assessed by a dedicated nurse. The recovery nurse used The Aldrete scale (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) to reevaluate patients' awareness and their capacity to move or walk as before procedural sedation before releasing them from the hospital.\u003c/p\u003e \u003cp\u003eVital parameters (oxygen saturation, blood pressure, heart rate, respiratory rate), VAS anxiety scale and Ramsay scores were recorded before, during the procedure, at the end of examination and at arrival in the recovery room. Before hospital discharge the Aldrete scale was evaluated and recorded. The Brice Questionnaire (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) was applied within 10 min after the patient reached fully alert status and 24 hours after examination through a phone call (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBrice Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"1\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrom a scale of 0 to 10:\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- how much do you remember about the procedure?\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- how satisfied are you with the sedation?\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e- how many unpleasant memories do you have?\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistics\u003c/h2\u003e \u003cp\u003eContinuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (IQR 25\u0026ndash;75%) if parametric or not parametric distribution respectively. Categorical variables were expressed as number and percentages. Comparison among continuous and categorical variables were made with T-Test or Fisher Test respectively. Stata 13 \u0026reg; (Texas, USA) was used as statistical software.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003e73 patients received remimazolam protocol sedation for 75 procedures. 2 patients were excluded because of procedure failure. Finally, 71 patients and 73 procedures were analysed. 2 patients had double examination (EGDS\u0026thinsp;+\u0026thinsp;colonoscopy). Mean age was 62.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.2 years old with a mean BMI of 25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7. 33.8% of patients had no comorbidities and in 91.5% of cases were ASA 1 o 2. Characteristics of patients were shown in the Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003eTable 2. Characteristics of patients\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e71\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e62.0 \u0026plusmn; 15.2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e38 (54)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e33 (46)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e25.2 \u0026plusmn; 4.7\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCardiac\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDyslipidaemia\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetes\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNeurologic\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOSAS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRenal\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHepatic\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026ge;3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNone\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e34 (48)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e19 (27)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e6 (8)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e3 (4)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e8 (11)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e2 (3)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e3 (4)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e5 (7)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e24 (34)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eASA score\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e28 (39)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e37 (52)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e6 (9)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMallampati\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e7 (10)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e56 (79)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e8 (11)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndication\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eScheduled\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eUrgent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e71 (100)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eState of anxiety\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNone-Low\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e16 (23)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e55 (77)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eState of consciousness\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRamsay 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRamsay 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e70 (99)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e1 (1)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eResults expressed as mean \u0026plusmn; standard deviation or number and percentages\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eProcedures\u003c/h2\u003e \u003cp\u003e25 EGDS and 48 colonoscopies received sedation with remimazolam. In 31% and 87%, EGDS and colonoscopies were performed by a trainee endoscopist with supervision of a senior. Induction of the sedation was performed with 3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 mg and 4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 mg for EGDS and colonoscopies respectively. Total amount of the drugs administered was 13.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7 mg and 10.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 mg respectively. In 3 EGDS (2 in the frailer categories) and in 1 colonoscopy in a frail patient, total dose of remimazolam reached the maximum allowed in the protocol. In 6 procedures of EGDS, rescue sedation with propofol was necessary. In 3 cases rescue sedation was performed after maximum reached dose of remimazolam. No rescue sedation was needed for colonoscopies. Recovery time was 21.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0 for EGDS and 16.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0 for colonoscopies. Ramsay scale ranged from 1, before the sedation, to 2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 during the examination and promptly returned to 1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 at the end. Aldrete score, before dismission was 9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2. Characteristics of procedures are shown in the Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of procedures\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEGDS (25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eColonoscopy (48)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemimazolam induction (mg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemimazolam maintenance (mg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemimazolam total (mg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFentanyl (mcg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u0026thinsp;\u0026plusmn;\u0026thinsp;37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemimazolam maximum reached dose\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemimazolam induction\u0026thinsp;\u0026ge;\u0026thinsp;65ys/ASA3 (mg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemimazolam total\u0026thinsp;\u0026ge;\u0026thinsp;65ys/ASA3 (mg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemimazolam maximum reached dose\u0026thinsp;\u0026ge;\u0026thinsp;65ys/ASA3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRescue sedation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemimazolam maximum reached dose in failure sedation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (12%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExamination time (min)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRecovery time (min)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eASA\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026nbsp;\u003c/p\u003e\u003cp\u003e8 (32%)\u003c/p\u003e \u003cp\u003e15 (60%)\u003c/p\u003e \u003cp\u003e2 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026nbsp;\u003c/p\u003e\u003cp\u003e20 (42%)\u003c/p\u003e \u003cp\u003e24 (50%)\u003c/p\u003e \u003cp\u003e4 (8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTrainee involvement\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (68%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBiopsy/polypectomy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (39%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eResults expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or number and percentages\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSafety\u003c/h2\u003e \u003cp\u003eSafety of procedural sedation with remimazolam was calculated in procedures with no failure (68 patients). 28 patients (41.7%) experienced a transitory hypotensive episode during examination. We only reported two cases of hypotension related to systolic pressure\u0026thinsp;\u0026lt;\u0026thinsp;80 mmHg or diastolic pressure\u0026thinsp;\u0026lt;\u0026thinsp;40 mmHg. In most of cases the majority (26 cases), hypotension was related to a delta\u0026thinsp;\u0026gt;\u0026thinsp;20 mmHg. Only in 2 cases fluid supplementation (maximum 500ml of physiologic solution) was needed. Bradycardia was associated only with colonoscopies and was never registered during EGDS. No cases of hypoxia or hypertension occurred. Adverse events of procedures are described in the Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. One case of allergy was registered: a 61-year-old female, with no co-morbidities, immediately after infusion of the drug during the colonoscopy, presented erythema of the trunk. The patient was quickly treated with infusion of clorfenamine and hydrocortisone with complete remission of symptom Because the patients did not before any sedation, it was not possible to attribute the allergic manifestation to remimazolam or fentanyl.\u003c/p\u003e \u003cp\u003eTable 4. Minor adverse events of procedures (67) with remimazolam sedation protocol\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypotension\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBradycardia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypoxia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u0026deg; (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e28 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e10 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e65.7\u0026plusmn; 13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e58\u0026plusmn; 17.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex (male)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e16 8(7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e4 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e23.9 \u0026plusmn; 3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e23.5 \u0026plusmn; 5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities (at least one)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e18 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e6 (60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eASA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (29)\u003c/p\u003e\n \u003cp\u003e16 (57)\u003c/p\u003e\n \u003cp\u003e4 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (90)\u003c/p\u003e\n \u003cp\u003e2 (10)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMallampati\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (7)\u003c/p\u003e\n \u003cp\u003e22 (79)\u003c/p\u003e\n \u003cp\u003e4 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e8 (80)\u003c/p\u003e\n \u003cp\u003e2 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eExamination\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eEGDS\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eColonoscopy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (36)\u003c/p\u003e\n \u003cp\u003e18 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e10 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrugs administered\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRemimazolam induction (mg)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRemimazolam maintenance (mg)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRemimazolam total (mg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.2 \u0026plusmn; 1.2\u003c/p\u003e\n \u003cp\u003e9.2 \u0026plusmn; 6.5\u003c/p\u003e\n \u003cp\u003e11.5 \u0026plusmn; 7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.7 \u0026plusmn; 0.7\u003c/p\u003e\n \u003cp\u003e8.2 \u0026plusmn; 6.2\u003c/p\u003e\n \u003cp\u003e11.5 \u0026plusmn; 6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSystolic pressure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e117 \u0026plusmn; 19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e132 \u0026plusmn; 19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSaturation oxygen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e98 \u0026plusmn; 1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e99 \u0026plusmn; 1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeart rate/min\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e77 \u0026plusmn; 12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e65 \u0026plusmn; 8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRespiratory rate (min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e19 \u0026plusmn; 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e18 \u0026plusmn; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.52996845425867%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRamsay scale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.665615141955836%\" valign=\"top\"\u003e\n \u003cp\u003e2.1 \u0026plusmn; 0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.820189274447948%\" valign=\"top\"\u003e\n \u003cp\u003e1.9 \u0026plusmn; 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.984227129337539%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eResults expressed as mean \u0026plusmn; standard deviation or number and percentages\u003c/p\u003e \u003cp\u003eNo significant differences of vital parameters and Ramsay scale was noted among group of frail and not frail patients (Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Only systolic pressure was significantly higher in the frail group (p-value 0.007).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVital parameters and adverse events of patients during the examination\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients aged\u0026thinsp;\u0026lt;\u0026thinsp;65 yrs/ASA 1 or 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients aged\u0026thinsp;\u0026ge;\u0026thinsp;65 yrs/ASA 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN\u0026deg;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystolic pressure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132\u0026thinsp;\u0026plusmn;\u0026thinsp;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypotension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.214\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSaturation oxygen\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDesaturation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHeart rate/min\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.689\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBradycardia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.731\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRespiratory rate (min)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRamsay scale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eResults expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or number and percentages\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eRecall\u003c/h2\u003e \u003cp\u003eFollow-up Brice Questionnaire for satisfaction showed from a scale from 0 to 10 a recall of 2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1, a satisfaction of 9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 and unpleasant memories of 0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study on real world setting showed that remimazolam is effective and safe for first level EGDS and colonoscopy. The efficacy results are comparable to randomized controlled trials that used the same sedation regimen as in our study. As regards EGDS, Borkett et al (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) demonstrated that a dose of 0.2 mg/kg of remimazolam was effective in 64% of cases. The success rate of sedation in the study of Chen et al. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), showed that remimazolam was 97% even if a pre-medication with lidocaine spray was administered before the EGDS.\u003c/p\u003e \u003cp\u003eRegarding the efficacy in colonoscopy, our results confirm that the balanced sedation with remimazolam and fentanyl is effective in 100% of cases. Similar controlled trials by Rex in 2018 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) and in 2021 showed that remimazolam allowed a complete colonoscopy with no need for rescue medication in 91% and 87% of cases. The cohort of patients studied by Rex in 2021 (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) was composed only by ASA 3. In our study colonoscopies in ASA 3 patients were only 4 and none was ASA IV but there was no sedation failure among them. In all three studies, patients received fentanyl before receiving remimazolam.\u003c/p\u003e \u003cp\u003eRespect to ASA 1 and ASA 2 patients, remimazolam in ASA 3 patients appears less effective to complete a procedural sedation but with a good balance between efficacy and safety. Incidence and frequency of major adverse events were comparable in all the studies, and independent of ASA status.\u003c/p\u003e \u003cp\u003eIt is interesting to note that the criteria for defining minor adverse events are not the same between our study and the various studies cited for EGDS. This makes the safety data difficult to compare even if no major adverse event occurred in any patient cohort. Characteristics of studies compared in the discussion are shown in the Table \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMain Clinical studies of Remimazolam for Sedation of EGDS and colonoscopy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003estudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEfficacy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSafety\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEGDS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConigliaro 2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASA1/2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e- no rescue sedation after a maximum dose of 33 mg of (17.5 mg in case of frail patients):76%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e- Hypotension (SBP\u0026thinsp;\u0026le;\u0026thinsp;80 mmHg or DBP\u0026thinsp;\u0026le;\u0026thinsp;40 mmHg or drop in SBP/DP\u0026thinsp;\u0026gt;\u0026thinsp;20%): 40%\u003c/p\u003e \u003cp\u003e- Hypoxia (02 saturation\u0026thinsp;\u0026lt;\u0026thinsp;90% for \u0026ge;\u0026thinsp;one minute): 0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBorkett 2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASA1/2\u003c/p\u003e \u003cp\u003e25 patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo rescue sedation after a maximum dose of 0.2 mg/kg: 64%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e- hypotension: SBP\u0026thinsp;\u0026le;\u0026thinsp;80 mm Hg: 0\u003c/p\u003e \u003cp\u003e- hypoxia: O2 saturation\u0026thinsp;\u0026lt;\u0026thinsp;90%: 24%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChen 2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASA1/2\u003c/p\u003e \u003cp\u003e189 patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo rescue sedation after a maximum dose of 17.5 mg: 97%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e- hypotension (drop\u0026thinsp;\u0026gt;\u0026thinsp;20% in SBP or MAP\u0026thinsp;\u0026lt;\u0026thinsp;60 mmHg): 13%\u003c/p\u003e \u003cp\u003e- hypoxia (RR\u0026thinsp;\u0026lt;\u0026thinsp;8 breaths/minute and 02 saturation\u0026thinsp;\u0026lt;\u0026thinsp;90%): 1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eColonoscopy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConigliaro 2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASA1/2/3\u003c/p\u003e \u003cp\u003e48 patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e- no rescue sedation after a maximum dose of 33 mg of (17.5 mg in case of frail patients):100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHypotension (SBP\u0026thinsp;\u0026le;\u0026thinsp;80 mmHg or DBP\u0026thinsp;\u0026le;\u0026thinsp;40 mmHg or drop in SBP/DP\u0026thinsp;\u0026gt;\u0026thinsp;20%): 37%\u003c/p\u003e \u003cp\u003eHypoxia (02 saturation\u0026thinsp;\u0026lt;\u0026thinsp;90% for \u0026ge;\u0026thinsp;one minute): 0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRex 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASA1/2/3\u003c/p\u003e \u003cp\u003e296 patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e- no rescue sedation after a maximum dose of 33 mg of (17.5 mg in case of frail patients):91%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e- hypotension (SBP\u0026thinsp;\u0026le;\u0026thinsp;80 mmHg/DBP\u0026thinsp;\u0026le;\u0026thinsp;40 mmHg, or drop\u0026thinsp;\u0026gt;\u0026thinsp;20% in SBP/DBP): 39%\u003c/p\u003e \u003cp\u003e- hypoxia (02 saturation\u0026thinsp;\u0026lt;\u0026thinsp;90% for \u0026ge;\u0026thinsp;one minute): 1%%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRex 2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eASA 3/4\u003c/p\u003e \u003cp\u003e31 patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo rescue sedation after a maximum dose of 17.5 mg:87%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e- hypotension (SBP\u0026thinsp;\u0026le;\u0026thinsp;80 mmHg/DBP\u0026thinsp;\u0026le;\u0026thinsp;40 mmHg, or drop\u0026thinsp;\u0026gt;\u0026thinsp;20% in SBP/DBP): 58%\u003c/p\u003e \u003cp\u003e- hypoxia (02 saturation\u0026thinsp;\u0026lt;\u0026thinsp;90% for \u0026ge;\u0026thinsp;one minute): 19%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe observed a case, not confirmed by a skin test or a provocative test, of skin allergy without anaphylaxis. To our knowledge, 12 cases of anaphylaxis have been reported. When anaphylaxis occurs during procedural sedation, remimazolam should be kept in mind as the causative drug (\u003cspan additionalcitationids=\"CR16 CR17 CR18 CR19 CR20\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study the time to sedation recovery (21.8 for EGDS and 16.9 for colonoscopies) is longer than in the mentioned trials (6\u0026ndash;11 minutes). It is probably due to the data collection method which, in our case, happens with delivery of the report (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe assessment of exam recall was homogeneous compared to randomized controlled trials. Approximately 80% of patients had no unpleasant memories related to the exam (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDuring the central moment of the exam, according to our data, the patient had a level of consciousness of 2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 in \u0026ldquo;young\u0026rdquo; patients and 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 in frail patients. Even though the patient can be awakened with verbal call, they did not remember the exam and were satisfied with the sedation when the Brice questionnaire was used 24 hours after the examination. These data confirm the good safety and efficacy profile of the drug in the different categories of patients.\u003c/p\u003e \u003cp\u003eThis drug, as shown by Rex et al., could have a preferrable indication to ASA III/IV. Safety was also studied in elderly patients by Liu et al on EGDS and colonoscopies (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). 107 elderly patients in the remimazolam group and 109 elderly patients in the propofol group were analysed. The incidence of moderate hypoxemia was 2.8% in the remimazolam group and 17.4% in the propofol group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) without significant difference in the incidence of severe hypoxemia between the two groups (4.7% vs. 5.5%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.781). Similarly, Guo et al reported that haemodynamic events and respiratory depression in the remimazolam group were less frequent than those in the propofol group (15% vs. 44%, P\u0026thinsp;=\u0026thinsp;0.005), (5% vs. 23%, P\u0026thinsp;=\u0026thinsp;0.026). (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eRegarding our goal of being able to complete the procedure without resorting to propofol the important result is that it was necessary to resort to rescue sedation only in EGDS (24%) and in no case in colonoscopies. Therefore, from these preliminary data it is concluded that procedural sedation can be applied with remimazolam without the use of propofol, obtaining effective sedation in colonoscopies while in EGDS remimazolam alone guarantees the result in a percentage of around 70\u0026ndash;75% of cases.\u003c/p\u003e \u003cp\u003eOther studies will be necessary to confirm these preliminary data which will allow us to find the right indications for the use of remimazolam in routine diagnostic and first level operative endoscopic examinations in real-life.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003ethe research did not receive funding\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConigliaro R. create and reviewed the study, Pig\u0026ograve; F. collected and analyzed the data and wrote the manuscript, Caiazzo A.;, Grande G., Russo S., Cocca S., Lupo M., Marocchi M., Marsico M. collected the data, Sculli S.and Bertani H. reviewed the study\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003enot applicable\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRogers WK, McDowell TS. Remimazolam, a short-acting GABA(A) receptor agonist for intravenous sedation and/or anesthesia in day-case surgical and non-surgical procedures. IDrugs. 2010;13:929\u0026ndash;937.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOka S, Satomi H, Sekino R, et al. Sedation outcomes for remimazolam, a new benzodiazepine. J Oral Sci. 2021;63:209\u0026ndash;211.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAntonik LJ, Goldwater DR, Kilpatrick GJ et al. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): part I. safety, efficacy, and basic pharmacokinetics. Anesth Analg. 2012;115:274\u0026ndash;283.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRex DK, Bhandari R, Desta T, et al. A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2018;88:427\u0026ndash;437.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu X, Ding B, Shi F, et al. The efficacy and safety of remimazolam tosilate versus etomidate-propofol in elderly outpatients undergoing colonoscopy: a prospective, randomized, single-blind, non-inferiority trial. Drug Des Devel Ther. 2021;15:4675\u0026ndash;4685.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRex DK, Bhandari R, Lorch DG et al. Safety and efficacy of remimazolam in high risk colonoscopy: a randomized trial. Dig Liver Dis. 2021;53:94\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYao Y, Guan J, Liu L et al. Discharge readiness after remimazolam versus propofol for colonoscopy: a randomised, double-blind trial. Eur J Anaesthesiol. 2022;39:911\u0026ndash;917.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePambianco DJ, Borkett KM, Riff DS et al. A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2016;83:984\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBorkett KM, Riff DS, Schwartz HI et al. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg. 2015;120:771\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen SH, Yuan TM, Zhang J et al. Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial. J Gastroenterol Hepatol. 2021;36:474\u0026ndash;481.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCao X, Yumul R, Elvir Lazo OL et al. A novel visual facial anxiety scale for assessing preoperative anxiety. PLoS One. 2017;12:e0171233.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamsay MA, Savage TM, Simpson B, et al: Controlled sedation with alphaxalone-alphadolone. British Medical Journal 1974;2:656\u0026ndash;659.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAldrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg. 1970;49:924\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrice DD, Hetherington RR, Utting JE. A simple study of awareness and dreaming during anaesthesia. Br J Anaesth. 1970;42:535\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsurumi K. Takahashi S. Hiramoto Y et al. Remimazolam anaphylaxis during anesthesia induction. J. Anesth. 2021;35:571\u0026ndash;575.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUchida S. Takekawa D. Kitayama M. et al. Two cases of circulatory collapse due to suspected remimazolam anaphylaxis. JA Clin. Rep. 2022; 8: 18.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamaoka M. Kuroda K. Matsumoto N. et al. Remimazolam anaphylaxis confirmed by serum tryptase elevation and skin test. Anaesth. Rep. 2022;10: e12167.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim K.M. Lee, Bang J.Y, Choi B.M. et al. Anaphylaxis following remimazolam administration during induction of anaesthesia. Br. J. Anaesth. 2022; 129; e122\u0026ndash;e124.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHasushita Y., Nagao M., Miyazawa Y. et al. Cardiac Arrest Following Remimazolam-Induced Anaphylaxis: A Case Report. AA Pract. 2022;16: e01616.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu, X., Tang, Y., Fang, X. Laryngeal edema following remimazolam-induced anaphylaxis: A rare clinical manifestation. BMcAnesthesiol. 2023; 23: 99.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee S, Park J, Kim NH, et al. Remimazolam Anaphylaxis during Induction of General Anesthesia Confirmed by Provocation Test-A Case Report and Literature Review. Medicina (Kaunas). 2023;59:1915.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu F, Cheng X, Wang Y, et al. Effect of remimazolam tosilate on the incidence of hypoxemia in elderly patients undergoing gastrointestinal endoscopy: A bi-center, prospective, randomized controlled study. Front Pharmacol. 2023;14:1131391.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo J, Qian Y, Zhang X, et al. Remimazolam tosilate compared with propofol for gastrointestinal endoscopy in elderly patients: a prospective, randomized and controlled study. BMC Anesthesiol. 2022;22:180.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4564245/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4564245/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground and aim\u003c/p\u003e\n\u003cp\u003eRemimazolam has proved to be a very promising sedative drug in randomized clinical trials for usage in a wide spectrum of patients, including critically ill ones. The purpose of our study was to verify efficacy and safety of remimazolam for procedural sedation during diagnostic and first level operative endoscopy in a real-world setting.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003eThis single centre prospective study evaluated sedation regimen with remimazolam for EGDS and fentanyl and remimazolam for colonoscopy in consecutive ASA I-III patients.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003e71 patients underwent 73 procedures (25 EGDS, 48 colonoscopies) with a total amount of 13.2 ± 8.7 mg and 10.2 ± 6.2 mg of remimazolam administered respectively. In 6 EGDS rescue sedation with propofol was needed. Transient hypotension was frequent (41.7%) and no cases of hypoxia occurred. One case of suspected allergy (erythema of the trunk) without anaphylaxis was reported.\u003c/p\u003e\n\u003cp\u003eConclusions\u003c/p\u003e\n\u003cp\u003eProcedural sedation can be applied with remimazolam without the use of propofol, obtaining effective sedation in colonoscopies while in EGDS remimazolam alone guarantees the result in a percentage of around 70–75% of cases.\u003c/p\u003e","manuscriptTitle":"Use of Remimazolam for procedural sedation in real-life Digestive Endoscopy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-12 04:53:24","doi":"10.21203/rs.3.rs-4564245/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"52caf846-4a56-4221-8ba0-917548c114f8","owner":[],"postedDate":"July 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-02T05:22:24+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-12 04:53:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4564245","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4564245","identity":"rs-4564245","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}