The effect of obstructive jaundice on the sensitivity of intravenous anesthetic of remimazolam: study protocol for a controlled multicenter trial

Abstract Background It is well known that obstructive jaundice could affect the pharmacodynamics of some anesthetics, and the sensitivity of some anesthetics would increase among icteric patients. Remimazolam is a new ultra-short-acting intravenous benzodiazepine sedative/anesthetic, which is a high-selective and affinity ligand for the benzodiazepine site on the GABAA receptor. However, no study has reported the pharmacodynamics of remimazolam in patients with obstructive jaundice. We hypothesize that obstructive jaundice affects the pharmacodynamics of remimazolam, and the sensitivity of remimazolam increases among icteric patients. Methods/design The study will be performed as a prospective, controlled, multicenter trial. The study design is a comparison of remimazolam requirements to reach a bispectral index of 50 in patients with obstructive jaundice versus non-jaundiced patients with chronic cholecystitisor intrahepatic bile duct stones. Remimazolam was infused at 6 mg/kg/h until this endpoint was reached. Discussion Remimazolam could be suitable for anesthesia of patients with obstructive jaundice, because remimazolam is not biotransformed in the liver. Hyperbilirubinemia has been well-described to have toxic effects on the brain, which causes the increasing of sensitivity to some anesthetics, such as desflurane, isoflurane, and etomidate. Furthermore, remimazolam and etomidate have the same mechanism of action when exerting an anesthetic effect. We aim to demonstrate that obstructive jaundice affects the pharmacodynamics of remimazolam, and the dose of remimazolam when administered to patients with obstructive jaundice should be modified. Trial registration Chinese Clinical Trial Registry ChiCTR2100043585. Registered on 23 February 2021

Download Full-text

Does the Sensitivity of Intravenous Anesthetic of Remimazolam Increase in Patients With Obstructive Jaundice?

10.21203/rs.3.rs-486781/v1 ◽

2021 ◽

Author(s):

jinchao song ◽

Wen Liu ◽

Jun-Wei Ji ◽

Kun-Ming Tao ◽

Hai-Bo Qiu ◽

...

Keyword(s):

Obstructive Jaundice ◽

Intrahepatic Bile Duct ◽

Multicenter Trial ◽

Bile Duct Stones ◽

Trial Registry ◽

Clinical Trial Registry ◽

Intravenous Anesthetic ◽

Affinity Ligand ◽

The Brain ◽

Benzodiazepine Site

Abstract BackgroundIt is well known that obstructive jaundice could affect the pharmacodynamics of some anesthetics, and the sensitivity of some anesthetics would increase among icteric patients. Remimazolam is a new ultra-short-acting intravenous benzodiazepine sedative/anesthetic, which is a high-selective and affinity ligand for the benzodiazepine site on the GABAA receptor. However, very few studies have been reported the pharmacodynamics of remimazolam in patients with obstructive jaundice. We hypothesize that obstructive jaundice affects the pharmacodynamics of remimazolam, and the sensitivity of remimazolam increases among icteric patients.Methods/designThe study will be performed as a prospective, controlled, multicenter trial. The study design is a comparison of remimazolam requirements to reach a Bispectral Index of 50 in patients with obstructive jaundice versus non-jaundiced patients with chronic cholecystitisor intrahepatic bile duct stones. Remimazolam was infused at 0.03 mg/kg/min until this end point was reached.DiscussionRemimazolam could be suitable for anesthesia of patients with obstructive jaundice, because remimazolam is not biotransformed in the liver. Hyperbilirubinemia has been well-described toxic effects in the brain, which causes the increasing of sensitivity to some anesthetics, such as desflurane, isoflurane and etomidate. Furthmore, remimazolam and etomidate have the same mechanism of action when exerting an anesthetic effect. We aim to demonstrate that obstructive jaundice affects the pharmacodynamics of remimazolam, and the dose of remimazolam when administered to patients with obstructive jaundice should be modified.Trial registrationChinese Clinical Trial Registry ChiCTR2100043585. Date of registration: February 23, 2021.

Download Full-text

The Influence of Differences in Solvents and Concentration on the Efficacy of Propofol at Induction of Anesthesia

Anesthesiology Research and Practice ◽

10.1155/2016/9178523 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4

Author(s):

Yukako Obata ◽

Yushi U. Adachi ◽

Katsumi Suzuki ◽

Taiga Itagaki ◽

Hiromi Kato ◽

...

Keyword(s):

Venous Blood ◽

Surgical Patients ◽

Trial Registry ◽

Clinical Trial Registry ◽

Verbal Command ◽

Age And Gender ◽

Intravenous Anesthetic ◽

Significant Difference ◽

And Gender ◽

Significant Covariates

Background. Propofol is a popular intravenous anesthetic and varieties of formulations were produced from different laboratories. The present study compared efficacy of propofol of different laboratories and different concentrations (1 and 2%) during induction of anesthesia.Methods. Seventy-five scheduled surgical patients were randomly allocated into three groups. The patients of group D1 received AstraZeneca Diprivan 1% (Osaka, Japan) at a rate of 40 mg kg−1 h−1. Group M1 was given 1% Maruishi (Maruishi Pharmaceutical, Osaka, Japan) and group M2 was given 2% formulation at the same rate of propofol. Achieving hypnosis was defined as failure to open their eyes in response to a verbal command and the venous blood sample was withdrawn.Results. The hypnotic doses of M2 were significantly larger (D1:91.4±30.9, M1:90.7±26.7, and M2:118.4±40.2 mg, resp. (mean ± SD).p<0.005). Age and gender were selected as statistically significant covariates using general linear model-ANOVA. The blood concentration showed no significant difference among the groups (3.73±2.34,4.10±3.04, and4.70±2.12 μg mL−1, resp.).Conclusion. The required dose of propofol was different among the formulations; however, the serum concentration showed no significant difference. This trial is registered with UMIN Clinical Trial Registry:UMIN000019925.

Download Full-text

Therapeutic clinical trials to combat COVID-19 pandemic in India: analysis from trial registry

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0208 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Angelika Batta ◽

Raj Khirasaria ◽

Vinod Kapoor ◽

Deepansh Varshney

Keyword(s):

Clinical Trials ◽

De Novo ◽

Treatment Options ◽

Drug Repurposing ◽

Trial Registry ◽

Therapeutic Treatment ◽

Clinical Trial Registry ◽

Clear Cut ◽

Therapeutic Trials ◽

Microsoft Office

AbstractObjectivesWith the emergence of Novel corona virus, hunt for finding a preventive and therapeutic treatment options has already begun at a rapid pace with faster clinical development programs. The present study was carried out to give an insight of therapeutic interventional trials registered under clinical trial registry of India (CTRI) for COVID-19 pandemic.MethodsAll trials registered under CTRI were evaluated using keyword “COVID” from its inception till 9th June 2020. Out of which, therapeutic interventional studies were chosen for further analysis. Following information was collected for each trial: type of therapeutic intervention (preventive/therapeutic), treatment given, no. of centers (single center/multicentric), type of institution (government/private), study design (randomized/single-blinded/double-blinded) and sponsors (Government/private). Microsoft Office Excel 2007 was used for tabulation and analysis.ResultsThe search yielded total of 205 trials, out of which, 127 (62%) trials were interventional trials. Out of these, 71 (56%) were AYUSH interventions, 36 (28.3%) tested drugs, 9 (7%) tested a nondrug intervention, rest were nutraceuticals and vaccines. About 66 (56%) were therapeutic trials. Majority were single-centered trials, i.e. 87 (73.7%). Trials were government funded in 57 (48.3%) studies. Majority were randomized controlled trials, i.e. 67 (56.8%). AYUSH preparations included AYUSH-64, Arsenic Album, SamshamaniVati etc.ConclusionsThe number of therapeutic interventional clinical trials was fair in India. A clear-cut need exists for an increase in both quantity and quality of clinical trials for COVID-19. Drug repurposing approach in all systems of medicine can facilitate prompt clinical decisions at lower costs than de novo drug development.

Download Full-text

Oxycodone versus morphine for analgesia after laparoscopic endometriosis resection

BMC Anesthesiology ◽

10.1186/s12871-021-01417-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lijun Niu ◽

Lihong Chen ◽

Yanhua Luo ◽

Wenkao Huang ◽

Yunsheng Li

Keyword(s):

Respiratory Depression ◽

Visceral Pain ◽

Deep Infiltrating Endometriosis ◽

Trial Registry ◽

Clinical Trial Registry ◽

Morphine Group ◽

Registration Number ◽

To Receive ◽

Registry Record ◽

Infiltrating Endometriosis

Abstract Background The objective of this study was to compare the analgesic potency of oxycodone versus morphine after laparoscopic deep infiltrating endometriosis resection. Methods Fifty patients undergoing laparoscopic deep infiltrating endometriosis resection were randomized to receive oxycodone or morphine intravenous-PCA after surgery. The primary outcome was opioid consumption during the 24 h after surgery. Secondary outcomes included time to first request for analgesia, the number of bolus, pain, sedation, nausea, vomiting, respiratory depression, and bradycardia. The prominent pain that caused patients to press the analgesic device was also recorded. Results Oxycodone consumption (14.42 ± 2.83) was less than morphine consumption (20.14 ± 3.83). Compared with the morphine group, the total number of bolus (78 vs 123) was less and the average time to first request for analgesia (97.27 ± 59.79 vs 142.17 ± 51) was longer in the oxycodone group. The incidence of nausea was higher in the morphine group than in the oxycodone group at 0–2 h (45.45% vs 17.19%), 2–4 h (50% vs 17.19%),12–24 h (40.91% vs 13.04%) and 0–24 h (39.17% vs 19.13%). The overall incidence of vomiting was higher in the morphine group (27.27% vs 13.92%). There was no difference in visual analogue scale score, the incidence of respiratory depression, and bradycardia between groups. Of the three types of pain that prompted patients to request analgesia, the incidence of visceral pain was highest (59.9%, P < 0.01). Conclusion Oxycodone was more potent than morphine for analgesia after laparoscopic endometriosis resection, and oxycodone has fewer side effects than morphine. Name of the registry: Chinese Clinical Trial Registry Trial registration number: ChiCTR1900021870 URL of trial registry record:http://www.chictr.org.cn/edit.aspx?pid=35799&htm=4 Date of registration: 2019/3/13 0:00:00

Download Full-text

Contribution of specific binding to the central benzodiazepine site to the brain concentrations of two novel benzodiazepine site ligands

Biopharmaceutics & Drug Disposition ◽

10.1002/bdd.553 ◽

2007 ◽

Vol 28 (6) ◽

pp. 275-282 ◽

Cited By ~ 2

Author(s):

Andrew Pike ◽

Susan M. Cook ◽

Alan P. Watt ◽

Paul Scott-Stevens ◽

Thomas W. Rosahl ◽

...

Keyword(s):

Specific Binding ◽

The Brain ◽

Benzodiazepine Site

Download Full-text

Primary success of electrical cardioversion for new-onset atrial fibrillation and its association with clinical course in non-cardiac critically ill patients: sub-analysis of a multicenter observational study

Journal of Intensive Care ◽

10.1186/s40560-021-00562-8 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Nozomu Shima ◽

Kyohei Miyamoto ◽

Seiya Kato ◽

Takuo Yoshida ◽

Shigehiko Uchino ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Trial ◽

Sinus Rhythm ◽

Trial Registry ◽

Clinical Trial Registry ◽

Icu Discharge ◽

Primary Success ◽

Success Group ◽

Onset Atrial Fibrillation ◽

New Onset

Abstract Background Electrical cardioversion (ECV) is widely used to restore sinus rhythm in critically ill adult patients with atrial fibrillation, although its prognostic value is uncertain. This study aims to elucidate the clinical meaning of successful ECV. Methods This is a sub-analysis of the AFTER-ICU study, a multicenter prospective study with a cohort of 423 adult non-cardiac patients with new-onset atrial fibrillation (AF). Patients that underwent ECV within 7 days after initial onset of AF were included in the sub-analysis. We compared intensive care unit (ICU) and overall hospital mortality, survival time within 30 days, cardiac rhythm at ICU discharge, and the length of ICU and overall hospital stay between patients whose sinus rhythm was restored immediately after the first ECV session (primary success group) and those in whom it was not restored (unsuccessful group). To find the factors related to the primary success of ECV, we also compared patient characteristics, the delivered energy, and pretreatment. Results Sixty-five patients received ECV and were included in this study. Although 35 patients (54%) had primary success, recurrence of AF occurred in 24 of these patients (69%). At ICU discharge, three patients still had AF in the unsuccessful group, but no patients in the primary success group still had AF. ICU mortality was 34% in the primary success group and 17% in the unsuccessful group (P = 0.10). Survival time within 30 days did not differ between the groups. Delivered energy and pretreatment were not associated with primary success of ECV. Conclusions The primary success rate of ECV for new-onset AF in adult non-cardiac ICU population was low, and even if it succeeded, the subsequent recurrence rate was high. Primary success of ECV did not affect the rate of mortality. Pretreatment and delivered energy were not associated with the primary success of ECV. Trial registration UMIN clinical trial registry, the Japanese clinical trial registry (registration number: UMIN000026401, March 31, 2017).

Download Full-text

Effect of pressure-controlled ventilation-volume guaranteed mode combined with individualized positive end-expiratory pressure on respiratory mechanics, oxygenation and lung injury in patients undergoing laparoscopic surgery in Trendelenburg position

Journal of Clinical Monitoring and Computing ◽

10.1007/s10877-021-00750-9 ◽

2021 ◽

Author(s):

Jianli Li ◽

Saixian Ma ◽

Xiujie Chang ◽

Songxu Ju ◽

Meng Zhang ◽

...

Keyword(s):

Laparoscopic Surgery ◽

Lung Injury ◽

Respiratory Mechanics ◽

Lung Mechanics ◽

Trial Registry ◽

Positive End Expiratory Pressure ◽

Clinical Trial Registry ◽

Trendelenburg Position ◽

Pressure Controlled Ventilation ◽

Pressure Controlled

AbstractThe study aimed to investigate the efficacy of PCV-VG combined with individual PEEP during laparoscopic surgery in the Trendelenburg position. 120 patients were randomly divided into four groups: VF group (VCV plus 5cmH2O PEEP), PF group (PCV-VG plus 5cmH2O PEEP), VI group (VCV plus individual PEEP), and PI group (PCV-VG plus individual PEEP). Pmean, Ppeak, Cdyn, PaO2/FiO2, VD/VT, A-aDO2 and Qs/Qt were recorded at T1 (15 min after the induction of anesthesia), T2 (60 min after pneumoperitoneum), and T3 (5 min at the end of anesthesia). The CC16 and IL-6 were measured at T1 and T3. Our results showed that the Pmean was increased in VI and PI group, and the Ppeak was lower in PI group at T2. At T2 and T3, the Cdyn of PI group was higher than that in other groups, and PaO2/FiO2 was increased in PI group compared with VF and VI group. At T2 and T3, A-aDO2 of PI and PF group was reduced than that in other groups. The Qs/Qt was decreased in PI group compared with VF and VI group at T2 and T3. At T2, VD/VT in PI group was decreased than other groups. At T3, the concentration of CC16 in PI group was lower compared with other groups, and IL-6 level of PI group was decreased than that in VF and VI group. In conclusion, the patients who underwent laparoscopic surgery, PCV-VG combined with individual PEEP produced favorable lung mechanics and oxygenation, and thus reducing inflammatory response and lung injury.Clinical Trial registry: chictr.org. identifier: ChiCTR-2100044928

Download Full-text

Expression of inflammatory mediators in biofilm samples and clinical association in inflammatory bowel disease patients—a preliminary study

Clinical Oral Investigations ◽

10.1007/s00784-021-04093-2 ◽

2021 ◽

Author(s):

Mayte Buchbender ◽

Jakob Fehlhofer ◽

Peter Proff ◽

Tobias Möst ◽

Jutta Ries ◽

...

Keyword(s):

Clinical Trial ◽

Inflammatory Bowel Disease ◽

Oral Cavity ◽

Bowel Disease ◽

Trial Registry ◽

Clinical Trial Registry ◽

Clinical Trial Registration ◽

Expression Levels ◽

Inflammatory Bowel ◽

Group 2

Abstract Objectives Inflammatory bowel disease (IBD) has multiple impacts on soft and hard tissues in the oral cavity. The aim of this study was to analyze the expression of cytokines in biofilm samples from patients suffering from IBD and compare them to healthy patients. It was hypothesized that different cytokine expression levels and clinical associations might be drawn. Material and methods A total of 56 biofilm samples from three different patient cohorts (group 0 = healthy, HC n = 30; group 1 = Crohn’s disease, CD, n = 19; group 2 = ulcerative colitis, UC, n = 7) were examined for the expression levels of the cytokine interleukins IL-2, -6, and -10; matrix metalloproteinases 7 and 9; and surface antigens CD90/CD11a by quantitative real-time PCR and according to clinical parameters (plaque index, BOP, PD, DMFT, CAL). Relative gene expression was determined using the ∆∆CT method. Results The mean BOP values (p = 0.001) and PD (p = 0.000) were significantly higher in the CD group compared to controls. Expression of IL-10 was significantly higher in the CD (p = 0.004) and UC groups (p = 0.022). Expression of MMP-7 was significantly higher in the CD group (p = 0.032). IBD patients treated with TNF inhibitors (p = 0.007) or other immunosuppressants (p = 0.014) showed significant overexpression of IL-10 compared to controls. Conclusion Different expression levels of IL-10 and MMP-7 were detected in plaque samples from IBD patients. As only BOP was significantly increased, we conclude that no clinical impairment of periodontal tissue occurred in IBD patients. Clinical relevance With the worldwide increasing incidence of IBD, it is important to obtain insights into the effects of the disease on the oral cavity. The study was registered (01.09.2020) at the German clinical trial registry (DRKS00022956). Clinical trial registration The study is registered at the German clinical trial registry (DRKS00022956).

Download Full-text