Etomidate Combined with Propofol versus Remimazolam for Sedation in Elderly Patients During Gastrointestinal Endoscopy: A Randomized Prospective Clinical Trial.

Purpose: Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy. Patients and Methods: A total of 120 patients aged 60-75 years were randomly allocated to one of two groups. Remifentanil 0.3µg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients' Mini-cog score and recovery questionnaires were compared. Results: Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P<0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P<0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P<0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient's life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05). Conclusion: The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.

Effects of etomidate combined with dexmedetomidine on adrenocortical function in elderly patients: a double-blind randomized controlled trial.

Etomidate has been advocated to be used in anesthesia for the elderly and the critically ill patients due to its faint effect on cardiovascular system. But the dose-dependent suppression of etomidate on adrenal cortex function leads to the limitation of its clinical application. Clinical research showed that dexmedetomidine could reduce the dose requirements for intravenous or inhalation anesthetics and opioids, and the hemodynamics was more stable during the operation. The objective was to observe the effect of etomidate combined with dexmedetomidine on adrenocortical function in elderly patients. 180 elderly patients scheduled for elective ureteroscopic holmium laser lithotripsy were randomly allocated to PR group anesthetized with propofol-remifentanil, ER group anesthetized with etomidate-remifentanil, and ERD group anesthetized with dexmedetomidine combined with etomidate-remifentanil. Patients in each group whose operation time was less than or equal to 1 h were incorporated into short time surgery group (PR1 group, ER1 group and ERD1 group), and whose surgical procedure time was more than 1 h were incorporated into long time surgery group (PR2 group, ER2 group and ERD2 group). The primary outcome was the serum cortisol and ACTH concentration. The secondary outcomes were the values of SBP, DBP, HR and SpO2, the time of surgical procedure, the dosage of etomidate and remifentanil administered during surgery, the time to spontaneous respiration, recovery and extubation, and the duration of stay in the PACU. The Serum cortisol concentration was higher at t1~2 in ERD1 group compared to ER1 group (P < 0.05). The Serum cortisol concentration at t1~3 was higher in ERD2 group than in ER2 group (P < 0.05). The Serum ACTH concentration was lower at t1~2 in ERD1 group compared to ER1 group (P < 0.05). The Serum ACTH concentration at t1~3 was lower in ERD2 group compared to ER2 group (P < 0.05). The SBP at T1 and T3 were higher in ER2 and ERD2 group than in PR2 group (P < 0.05). The DBP in ER1 and ERD1 group were higher at T1 compared to PR1 group (P < 0.05). The dosage of etomidate was significantly lower in ERD1 group and ERD2 group than in ER1 group and ER2 group (P < 0.05), respectively. The administration of dexmedetomidine combined with etomidate can attenuate the inhibition of etomidate on adrenocortical function in elderly patients and maintain intraoperative hemodynamic stability.

The Efficacy and Safety of Remimazolam Tosilate versus Etomidate-Propofol in Elderly Outpatients Undergoing Colonoscopy: A Prospective, Randomized, Single-Blind, Non-Inferiority Trial.

OBJECTIVE: The optimal sedation regime during endoscopy remains controversial, especially for elderly outpatients. In this study, we compared the efficacy and safety between remimazolam tosilate (RT) and etomidate-propofol (EP) in elderly outpatients undergoing colonoscopy. METHODS: A total of 260 elderly outpatients undergoing sedative colonoscopy were randomized into two groups. Patients in the RT group received a 0.075-mg/kg maintenance dose of remimazolam following an initial dose of 0.15 mg/kg, whereas patients in the EP group (10 mL:20 mg etomidate plus 10 mL:100 mg propofol) received a 0.05-mL/kg maintenance dose following an initial dose of 0.1 mL/kg to maintain a Modified Observer's Assessment of Alertness/Sedation score of ≤3 during the procedure. The primary endpoint was the success of the procedure. Secondary endpoints included time metrics, hemodynamics, consumption of fentanyl, etomidate, propofol, and remimazolam, intraoperative body movement, patient and endoscopist satisfaction scores, supplemental dose of sedative and fentanyl, and incidence and severity of adverse events. RESULTS: The procedure success rate was 96.52% in the RT group and 100% in the EP group. The difference in procedure success rate between the RT and EP groups was -3.48% (95% confidence interval: -6.81%, -0.15%). Four patients in the RT group required rescue midazolam. Compared with patients in the RT group, the onset time of the EP group was significantly lower (p < 0.05), whereas time to fully alert (p = 0.001), ready for discharge (p = 0.001), and hospital discharge (p = 0.002) were all significantly higher in the EP group. However, there were no significant differences in procedure time (p = 0.846) or cecal intubation time (p = 0.320) between the two groups. Although the frequency of intraoperative body movement was higher in the RT group, the difference was not significant (p = 0.508). There were no significant differences in patients' demographic and baseline characteristics, supplemental doses of sedative and fentanyl, or patient and endoscopist satisfaction scores (p > 0.05). Muscular tremor and pain on injection were recorded more frequently in the EP group (p < 0.05). However, there were no significant differences in hypoxia, respiratory depression, or incidence of postoperative nausea and vomiting. The severity of adverse events was all mild (grade 1) across both groups. CONCLUSION: RT may have non-inferior efficacy and a higher safety profile than EP in elderly outpatients undergoing colonoscopy, which suggests that RT may be more suitable for elderly outpatients undergoing colonoscopy.

Para-chloro-2-[18F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging.

Introduction: [11C]Metomidate ([11C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [11C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting. Objectives: The aim of this study was to further evaluate the previously published fluorine-18 (T1/2=109.5 min) etomidate analogue, para-chloro-2-[18F]fluoroethyl etomidate; [18F]CETO, as an adrenal PET tracer. Methods: In vitro experiments included autoradiography on human and cynomolgus monkey (non-human primate, NHP) tissues and binding studies on adrenal tissue from NHPs. In vivo studies with [18F]CETO in mice, rats and NHP, using PET and CT/MRI, assessed biodistribution and binding specificity in comparison to [11C]MTO. Results: The binding of [18F]CETO in the normal adrenal cortex, as well as in human adrenocortical adenomas and adrenocortical carcinomas, was shown to be specific, both in vitro (in humans) and in vivo (in rats and NHP) with an in vitro Kd of 0.66 nM. Non-specific uptake of [18F]CETO in NHP liver was found to be low compared to that of [11C]MTO. Conclusions: High specificity of [18F]CETO to the adrenal cortex was demonstrated, with in vivo binding properties qualitatively surpassing those of [11C]MTO. Non-specific binding to the liver was significantly lower than that of [11C]MTO. [18F]CETO is a promising new PET tracer for imaging of adrenocortical disease and should be evaluated further in humans.

A multicenter investigation of the hemodynamic effects of induction agents for trauma rapid sequence intubation.

BACKGROUND: Several options exist for induction agents during rapid sequence intubation (RSI) in trauma patients, including etomidate, ketamine, and propofol. These drugs have reported variable hemodynamic effects (hypotension with propofol and sympathomimetic effects with ketamine) that could affect trauma resuscitations. The purpose of this study was to compare the hemodynamic effects of these three induction agents during emergency department RSI in adult trauma. We hypothesized that these drugs would display a differing hemodynamic profile during RSI. METHODS: We performed a retrospective (2014-2019), multicenter trial of adult (≥18 years) trauma patients admitted to eight ACS-verified Level I trauma centers who underwent emergency department RSI. Variables collected included systolic blood pressure (SBP) and pulse before and after RSI. The primary outcomes were change in heart rate and SBP before and after RSI. RESULTS: There were 2,092 patients who met criteria, 85% received etomidate (E), 8% ketamine (K), and 7% propofol (P). Before RSI, the ketamine group had a lower SBP (E, 135 vs. K, 125 vs. P, 135 mm Hg, p = 0.04) but there was no difference in pulse (E, 104 vs. K, 107 vs. P, 105 bpm, p = 0.45). After RSI, there were no differences in SBP (E, 135 vs. K, 130 vs. P, 133 mm Hg, p = 0.34) or pulse (E, 106 vs. K, 110 vs. P, 104 bpm, p = 0.08). There was no difference in the average change of SBP (E, 0.2 vs. K, 5.2 vs. P, -1.8 mm Hg, p = 0.4) or pulse (E, 1.7 vs. K, 3.5 bpm vs. P, -0.96, p = 0.24) during RSI. CONCLUSION: Contrary to our hypothesis, there was no difference in the hemodynamic effect for etomidate versus ketamine versus propofol during RSI in trauma patients. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Clinical observation of the combined use of propofol and etomidate in painless gastroscopy.

OBJECTIVE: This study is aims to compare the anesthetic safety of propofol combined with etomidate for painless gastroscopy. METHODS: Three hundred patients undergoing painless gastroscopy were randomly assigned to P, PE1, and PE2 groups. Patients were anesthetized with propofol (P group) or propofol combined with etomidate (volume ratio 1: 1, PE1 group; volume ratio 2: 1, PE2 group). The hemodynamics and adverse reactions were observed. The sleep quality satisfaction and nature of dreams were recorded. RESULTS: Compared with pre-anesthesia, the mean arterial pressure and heart rate of the 3 groups were significantly slower during the examination and at the end of the examination. PE1 group had a higher incidence of muscle spasm, body moving, choking, and deglutition. The incidence of hypoxemia and injection pain was higher in P group. P and PE2 group had higher sleep quality satisfaction and dream incidence after awaking. However, there was no difference in the nature of dreams among 3 groups. CONCLUSION: Our data indicate that the combination of 10 ml 1.0% propofol and 5 ml 0.2% etomidate for painless gastroscopy reduces adverse reactions while not affecting the patients respiratory function. Moreover, it is safe and effective, which is worthy of clinical application and promotion.

Etomidate infusion at low doses is an effective and safe treatment for severe Cushing's syndrome outside intensive care.

INTRODUCTION: Intravenous etomidate infusion is effective to rapidly lower cortisol levels in severe Cushing's syndrome (CS) in the intensive care unit (ICU). Recently, etomidate treatment has also been proposed at lower doses in non-ICU wards, but it is not yet clear how this approach compares to ICU treatment. METHODS: We compared data from patients with severe CS treated with high starting doses of etomidate (median: 0.30 mg/kg BW/day) in ICU or with lower starting doses (median: 0.025 mg/kg BW/day) in non-ICU medical wards. RESULTS: Fourteen patients were included, among which ten were treated with low starting doses (LD) and four with high starting doses etomidate (HD). All patients had severe and complicated CS related to adrenal carcinoma (n = 8) or ectopic ACTH secretion (n = 6). Etomidate was effective in reducing cortisol levels below 500 nmol/L in a median of 1 day in the HD group compared to 3 days in the LD group (P = 0.013). However, all patients of the HD group had etomidate-induced cortisol insufficiency and needed frequent monitoring, while no patient from the LD group required hydrocortisone supplementation. No patient in either group died from complications of CS or etomidate treatment, but final outcome was poor as six patients in the LD group and all four patients in the HD group died from their cancer during follow-up. CONCLUSION: Our study suggests that, for patients with severe CS who do not require intensive organ-supporting therapy, the use of very low doses of etomidate in medical wards should be considered.

Comparison of drugs used for intubation of pediatric trauma patients.

PURPOSE: Rapid sequence intubation (RSI) drugs, such as propofol, affect clinical outcomes, but this has not been examined in the pediatric population. This descriptive study compares the outcomes associated with intubation drugs used in pediatric traumatic brain injury (TBI) patients. METHODS: A retrospective chart review and descriptive analysis of intubated TBI patients, ages 0-17, admitted to Children's Hospital London Health Sciences Centre (LHSC) from January 2006-December 2016 was performed. RESULTS: Out of 259 patients intubated, complete data was available for 107 cases. Average injury severity score was 28; 46 were intubated at LHSC, 55 at primary care site, and 6 on scene. Intubation attempts were recorded in 87 of 107 paper charts. First-pass intubation success rate was 88.5%. Propofol (n = 21), midazolam (n = 31), etomidate (n = 13), and ketamine (n = 7) were the most commonly used intubation drugs. Paralytics were used in 50% of patients. Following use of propofol, Pediatric Adjusted Shock Index was increased as a result of worsening hypotension. Mean total hospital length of stay was 21 days with 7.5 days in ICU. Survival was 87%. CONCLUSION: Great variability exists in the use of induction agents and paralytics for RSI. Propofol was commonly used and is potentially associated with poorer clinical outcomes. TYPE OF STUDY: Retrospective. LEVEL OF EVIDENCE: IV.

Ketamine/propofol admixture vs etomidate for intubation in the critically ill: KEEP PACE Randomized clinical trial.

BACKGROUND: Periintubation hypotension is associated with poor outcomes in the critically ill. We aimed to determine if an admixture of ketamine and propofol for emergent endotracheal intubation in critically ill patients was superior to etomidate. Primary endpoint was the change in mean arterial pressure from baseline to 5 minutes postdrug administration. METHODS: Emergent-use, stratified (shock status and unit type), multiunit, randomized, parallel-group superiority clinical trial was conducted at a tertiary academic medical center. Adult medical/surgical and transplant/oncologic intensive care unit patients undergoing emergent intubation were assigned randomly to receive either ketamine/propofol admixture (0.5 mg/kg of ketamine and propofol each) or reduced dose etomidate (0.15 mg/kg) for emergent intubation. RESULTS: One hundred sixty participants were randomized, and 152 (79 ketamine/propofol admixture, 73 etomidate) were included in the intention-to-treat analysis. There was no statistically significant difference in mean arterial pressure change from baseline to 5 minutes postdrug administration (treatment difference [ketamine/propofol admixture-etomidate]: -2.1 mm Hg; 95% confidence interval, -6.9 mm Hg to +2.7 mm Hg; p = 0.385). In addition, no statistically significant difference was demonstrated in the change of mean arterial pressure from baseline at 10 minutes and 15 minutes postdrug administration, no statistical difference in the use of new-onset vasoactive agents or difficulty of intubation between groups. More patients in the etomidate group required non-red blood cell transfusions (16 [22%] vs. 8 [10%], p = 0.046). For patients who had adrenal testing performed, more patients in the etomidate group developed immediate adrenal insufficiency (13 [81%] of 16 vs. 5 [38%] of 13, p = 0.027). Serious adverse events were rare, 2 (3%) (cardiac arrest, hypotension) in ketamine/propofol admixture and 4 (5%) (hypertension, hypotension) in etomidate (p = 0.430). CONCLUSION: In a heterogeneous critically ill population, ketamine/propofol admixture was not superior to a reduced dose of etomidate at preserving per-intubation hemodynamics and appears to be a safe alternative induction agent in the critically ill. LEVEL OF EVIDENCE: Therapeutic/Care Management, level II. TRIAL REGISTRY: ClinicalTrials.gov, NCT02105415, Ketamine/Propofol Admixture "Ketofol" at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial, IRB 13-000506, Trial Registration: March 31, 2014.

Safety and efficacy of combined use of propofol and etomidate for sedation during gastroscopy: Systematic review and meta-analysis.

BACKGROUND: Sedation with etomidate or propofol alone during gastroscopy has many side effects. A systematic review and meta-analysis were conducted to evaluate the safety and efficacy of the combined use of propofol and etomidate for sedation during gastroscopy. METHODS: PubMed, Embase, Medline (via Ovid SP), Cochrane library databases, CINAHL (via EBSCO), China Biology Medicine disc (CBMdisc), Wanfang, VIP, and China National Knowledge Infrastructure (CNKI) databases were systematically searched. We included randomized controlled trials (RCTs) comparing the combined use of propofol and etomidate vs etomidate or propofol alone for sedation during gastroscopy. Data were pooled using the random-effects models or fixed-effect model based on heterogeneity. RESULTS: Fifteen studies with 2973 participants were included in the analysis. Compared to propofol alone, the combined use of propofol and etomidate possibly increased recovery time (SMD = 0.14, 95% CI = 0.04-0.24; P = .005), and the risk for myoclonus (OR = 3.07, 95% CI = 1.73-5.44; P < .001), injection pain, and nausea and vomiting. Furthermore, compared to propofol alone, the combination of propofol and etomidate produced an apparent beneficial effect for mean arterial pressure (MAP) after anesthesia (SMD = 1.32, 95% CI = 0.38-2.26; P = .006), SPO2 after anesthesia (SMD = 0.99, 95% CI = 0.43-1.55; P < .001), apnea or hypoxemia (OR = 0.16, 95% CI = 0.08-0.33; P < .001), injection pain, and body movement. Further, compared to etomidate alone, the combination of propofol and etomidate reduced the risk for myoclonus (OR = 0.15, 95% CI = 0.11-0.22; P < .001), body movement, and nausea and vomiting. CONCLUSION: The combination of propofol and etomidate might increase recovery time vs that associated with propofol, but it had fewer side effects on circulation and respiration in patients undergoing gastroscopy. The combined use of propofol and etomidate can improve and produce an apparent beneficial effect on the adverse effects of propofol or etomidate alone, and it was safer and more effective than propofol or etomidate alone.

Etomidate Sedation for Advanced Endoscopic Procedures.

BACKGROUND AND STUDY AIM: Although propofol is widely used for sedation for endoscopic procedures, concerns remain regarding cardiopulmonary adverse events. Etomidate has little effect on the cardiovascular and respiratory systems, but patient satisfaction analysis is lacking. We compared the efficacy and safety of balanced propofol and etomidate sedation during advanced endoscopic procedures. METHODS: As a randomized noninferiority trial, balanced endoscopic sedation was achieved using midazolam and fentanyl, and patients were randomly assigned to receive propofol (BPS) or etomidate (BES) as add-on drug. The main outcomes were sedation efficacy measured on a 10-point visual analog scale (VAS) and safety. RESULTS: In total, 186 patients (94 in the BPS group and 92 in the BES group) were evaluated. BES did not show noninferiority in terms of overall patient satisfaction, with a difference in VAS score of -0.35 (97.5 % confidence interval -1.03 to ∞, p = 0.03). Among endoscopists and nurses, BES showed noninferiority to BPS, with differences in VAS scores of 0.06 and 0.08, respectively. Incidence of cardiopulmonary adverse events was lower in the BES group (27.7 versus 14.1 %, p = 0.023). Hypoxia occurred in 5.3 and 1.1 % of patients in the BPS and BES group (p = 0.211). Myoclonus occurred in 12.1 % (11/92) in the BES group. BES had lower risk of overall cardiopulmonary adverse events (odds ratio 0.401, p = 0.018). CONCLUSIONS: BES was not noninferior to BPS in terms of patient satisfaction. However, BES showed better safety outcomes in terms of cardiopulmonary adverse events.

Effects of dexmedetomidine, propofol and etomidate on the intraoperative wake-up in the cerebral functional area under the guidance of entropy index.

Objective: The study observed the efficacy and safety of dexmedetomidine, propofol and etomidate on brain functional areas in patients undergoing wake-up brain surgery under the guidance of entropy index. Methods: Sixty patients undergoing wake-up brain surgery on brain functional areas were enrolled, and randomly divided into three groups: dexmedetomidine group (group D), propofol group (group P) and etomidate group (group E), 20 in each. The vital signs, entropy indices of each time point, wake-up time, wake-up quality and adverse reaction in the wake-up period were observed and compared. Results: There were no differences in the duration of wake-up, duration of anesthesia, duration of surgery and postoperative wake-up time between the three groups (P> 0.05). The wake-up quality in group D was significantly better than group P and group E (P <0.05), group P was better than group E (P <0.05). The incidence of adverse events in group D was lower than that in groups P and E (P <0.05). The incidence of adverse events in group P was lower than that in group E (P <0.05). Conclusion: Under the guidance of entropy index, anesthesia induced by dexmedetomidine, propofol and etomidate combined with remifentanil can safely and effectively be used to the wake-up brain functional areas surgery, but the wake-up quality with use of dexmedetomidine is highest, and the incidence of adverse events is the lowest during wake-up period.

Steroid administration after anaesthetic induction with etomidate does not reduce in-hospital mortality or cardiovascular morbidity after non-cardiac surgery.

BACKGROUND: We tested the primary hypothesis that corticosteroid administration after etomidate exposure reduces a composite of in-hospital mortality and cardiovascular morbidity after non-cardiac surgery. METHODS: We evaluated ASA physical status III and IV patients who had non-cardiac surgery with general anaesthesia at the Cleveland Clinic. Amongst 4275 patients in whom anaesthesia was induced with etomidate, 804 were also given steroid intraoperatively, mostly dexamethasone at a median dose of 6 mg. We successfully matched 582 steroid patients with 1023 non-steroid patients. The matched groups were compared on composite of in-hospital mortality and cardiovascular morbidity using a generalized-estimating-equation model. Secondly, the matched groups were compared on length of hospital stay using a Cox proportional hazard model, and were descriptively compared on intraoperative blood pressures using a standardized difference. RESULTS: There was no significant association between intraoperative steroid administration after anaesthetic induction with etomidate and the composite of in-hospital mortality or cardiovascular morbidity; the estimated common odds ratio across the two components of the composite was 0.86 [95% confidence interval (CI): 0.64, 1.16] for steroid vs non-steroid, P=0.33. The duration of postoperative hospitalisation was significantly shorter amongst steroid patients [median (Q1, Q3): 6 (3, 10) days] than non-steroid patients [7 (4, 11) days], with an estimated hazard ratio of 0.89 (0.80, 0.98) for steroid vs non-steroid, P=0.01. Intraoperative blood pressures were similar in steroid and non-steroid patients. CONCLUSIONS: Steroid administration after induction of anaesthesia with etomidate did not reduce mortality or cardiovascular morbidity.

Collective Review of the Status of Rapid Sequence Intubation Drugs of Choice in Trauma in Low- and Middle-Income Settings (Prehospital, Emergency Department and Operating Room Setting).

INTRODUCTION: Establishing a definitive airway in order to ensure adequate ventilation and oxygenation is an important aspect of resuscitation of the polytrauma patient . AIM: To review the relevant literature that compares the different drugs used for rapid sequence intubation (RSI) of trauma patients, specifically reviewing: premedication, induction agents and neuromuscular blocking agents across the prehospital, emergency department and operating room setting, and to present the best practices based on the reviewed evidence. METHOD: A literature review of rapid sequence intubation in the trauma population was carried out, specifically comparison of the drugs used (induction agent, neuromuscular blocking drugs and adjuncts). DISCUSSION: Studies involving the comparison of drugs used in RSI in, specifically, the trauma patient are sparse. The majority of studies have compared induction agents, etomidate, ketamine and propofol, as well as the neuromuscular blocking agents, succinylcholine and rocuronium. CONCLUSION: There currently exists great variation in the practice of RSI; however, in trauma the RSI armamentarium is limited to agents that maintain hemodynamic stability, provide adequate intubating conditions in the shortest time period and do not have detrimental effects on cerebral perfusion pressure. Further, multicenter randomized controlled studies to confirm the benefits of the currently used agents in trauma are required.

Differential role of intravenous anesthetics in colorectal cancer progression: implications for clinical application.

Anesthetics are unavoidable to colorectal cancer (CRC) patients who underwent surgical treatment. Thus, the molecular mechanisms underlying the role of the intravenous anesthetics in CRC metastasis are still unclear. In this study, the effects of intravenous anesthetics, such as propofol, etomidate and dexmedetomidine, on cell migration were determined. The migration of CRC cells was inhibited by propofol in vitro, but not in vivo. Etomidate, however, promoted the migration of CRC cells both in vitro and in vivo. Epithelial-mesenchymal transition (EMT) mediated the promotive effect of propofol and etomidate on the migration of CRC cells through PI3K/AKT signaling pathway. Dexmedetomidine alone or in combination with propofol or etomidate had minor effect on the migration of CRC cells. These findings indicate that propofol inhibites CRC cell migration in vitro. Etomidate playes a role for prompting CRC metastasis progression by activating (PI3K)/AKT signaling and inducing EMT. It provides an important hint for the clinical application of these anesthetics.

Unrepaired Tetralogy of Fallot-related Pathophysiologic Changes Reduce Systemic Clearance of Etomidate in Children.

BACKGROUND: Pathophysiologic changes in children with congenital heart disease may alter the effect of drugs by influencing the pharmacokinetics (PK). Considering the limited literature that describes the PK of etomidate in pediatric patients, especially in those with tetralogy of Fallot (TOF), our aim was to characterize the PK of etomidate and explore the effects of TOF. METHODS: Twenty-nine pediatric patients (15 with TOF and 14 with normal cardiac anatomy) scheduled to undergo elective surgery under general anesthesia were recruited in the study. All children received etomidate 60 µg/kg/min intravenously until a bispectral index of ≤50 was reached for 5 seconds during anesthesia induction. Arterial blood samples were drawn and analyzed. Population analysis was performed by using NONMEM to define PK characteristics. The estimates were standardized to a 70-kg adult using a per-kilogram model. RESULTS: Data consisting of 244 samples from 29 children with a mean age of 236 days (range, 86-360 days) were used, including a TOF group with a mean age of 250 days (range, 165-360 days) and a normal cardiac anatomy group with a mean age of 221 days (range, 86-360 days). A 3-compartment disposition model was best fitted to describe the PK of etomidate. The introduction of TOF as a covariate for systemic clearance (Cl1) improved the model and resulted in a significant reduction of objective function (Δobjective function = -7.33; P = .0068), which means that TOF was a significant covariate of Cl1, and the etomidate Cl1 in children with TOF (1.67 × (weight [WT]/70 kg) L/min) was lower than those with normal cardiac anatomy (2.28 × (WT/70 kg) L/min). Other PK parameter values were as follows: V1 = 8.05 × (WT/70 kg) L; V2 = 13.7 × (WT/70 kg) L; V3 = 41.3 × (WT/70 kg) L; Cl2 = 3.35 × (WT/70 kg) L/min; Cl3 = 0.563 × (WT/70 kg) L/min. CONCLUSIONS: A decreased systemic clearance for etomidate in children with TOF resulted in a lower required infusion rate and variation with time to achieve the same plasma concentration and maintain an equivalent target concentration or have longer sedation and recovery times after bolus or continuous infusion than normal children.

The Effects of Single-Dose Etomidate Versus Propofol on Cortisol Levels in Pediatric Patients Undergoing Urologic Surgery: A Randomized Controlled Trial.

BACKGROUND: The effects of general anesthetics on the hypothalamus-pituitary-adrenal axis and cortisol release in children are poorly characterized. Normal, daily fluctuation of cortisol levels complicates assessment of these effects. This study aimed to characterize the effects of etomidate compared with propofol on the normal cortisol secretory pattern in children undergoing urologic surgery by using a salivary cortisol assay. METHODS: In this prospective, randomized, double-blind, controlled study, we recruited 80 children aged 3 to 12 years assigned ASA physical status I who were scheduled for urologic surgery and 11 healthy child volunteers. Before surgery, cortisol levels of the 11 volunteers and 15 study patients were tested from 7:00 AM to 9:00 PM every hour for 1 day. The study patients were then randomly allocated into an etomidate group and a propofol group, receiving etomidate 0.3 mg/kg (n = 38) or propofol 2 mg/kg (n = 39) and midazolam 0.1 mg/kg, fentanyl 2 µg/kg, and rocuronium 0.6 mg/kg for induction, respectively. The cortisol levels of the patients were assessed continuously for 2 days postoperatively. RESULTS: The cortisol levels of the etomidate group were continuously and significantly lower than those of the propofol group from the time of discharge from the postanesthesia care unit (approximately 2:00 PM) until 8:00 AM the next morning (all P < 0.0001) and were significantly lower than before surgery at the same time points (all P < 0.0001). Except at 11:00 AM just before the operation, no significant differences in cortisol levels were detected before and after the operation in the propofol group (P max = 0.476, P min = 0.002). Also, no significant differences in clinical outcomes were detected between the 2 groups undergoing surgery (all P > 0.070). CONCLUSIONS: Compared with propofol, a single induction dose of etomidate suppressed postoperative cortisol levels in healthy children undergoing urologic surgery. This suppression lasted approximately 24 hours and was not associated with any changes in clinical outcomes.

The effect of single dose etomidate during emergency intubation on hemodynamics and adrenal cortex.

BACKGROUND: The study aimed to evaluate and compare the effects of a single dose of etomidate and the use of a steroid injection prior to etomidate during rapid sequence intubation on hemodynamics and cortisol levels. METHODS: Sixty patients were divided into three groups (n=20). Before intubation, and at 4 and 24 hours, blood samples were taken for cortisol measurements and hemodynamic parameters (systolic-diastolic-mean arterial pressure, heart rate), and SOFA scores were recorded. Intubation was achieved with 0.3 mg/kg etomidate IV in Group I, 0.3 mg/kg etomidate following 2 mg/kg methylprednisolone IV in Group II, and 0.15 mg/kg IV midazolam in Group III. RESULTS: Mean arterial pressure values were lower in Group I at the 24th hour when compared to Groups II and III. In Group I, heart rate values were higher compared to the other Groups. Cortisol levels were lower in Group I at the 4th and at the 24th hour in Groups II and III. CONCLUSION: Administration of methylprednisolone 2-4 minutes prior to etomidate use in emergency situations can prevent adrenal insufficiency in patients undergoing rapid sequence intubation. Moreover, midazolam can be used in low induction doses as an alternative to etomidate.