Safety and efficacy of target-controlled infusion versus intermittent bolus administration of propofol for sedation in colonoscopy: a randomized controlled trial

Abstract Background: Our objective was to compare the safety and efficacy of Target-Controlled Infusion (TCI) versus intermittent bolus of propofol for colonoscopy sedation. Methods: We conducted a randomized (1:1), single-blind, parallel-group superiority trial with fifty ASA I or II patients, both sexes, aged 18 to 65 years, Body Mass Index ≤ 30 kg.mr-2, undergoing colonoscopy, allocated to receive propofol by TCI (effect-site, 2 μg.mL-1 plus 0.5 μg.mL-1 until unconsciousness and as necessary for agitation) or intermittent bolus (1 mg.kg-1 plus 0.5 mg.kg-1 every 5 minutes or as above). The primary safety outcome was the need for airway maneuvers and the primary efficacy outcome was the need for interventions to adjust the level of sedation. Secondary outcomes included incidence of agitation, propofol dose, and time to recovery. Results: The median (IQR) number of airway maneuvers and interventions needed to adjust sedation was 0 (0-0) vs. 0 (0-0) (p = 0.239) and 1 (0-1) vs. 3 (1-4) (p < 0.001) in the TCI and control groups, respectively. Agitation was more common in the intermittent bolus group - 2 (0-2) vs. 1 (0-1), p < 0.001. The mean ± SD time to recovery was 4.9 ± 1.4 minutes in the TCI group vs. 2.3 ± 1.6 minutes in the control group (p < 0.001). The total propofol dose was higher in the TCI group (234 ± 46 μg.kg-1.min-1 vs. 195 ± 44 μg.kg-1.min-1 (p = 0.040)). Conclusions: During colonoscopy, TCI is as safe as intermittent bolus of propofol while reducing the incidence of agitation and the need for dose adjustments. However, intermittent bolus administration was associated with lower total propofol dose and earlier recovery.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Presentación de un caso y revisión de literatura: anestesia total intravenosa en cirugía de estesioneuroblastoma / Presentation of a case and literature review: total intravenous anesthesia in estesioneuroblastoma surgery

Resumen: El estesioneuroblastoma es una neoplasia de las células del neuroepitelio olfatorio. Tiene una baja incidencia de 0.4 por cada millón de habitantes. Se caracteriza por síntomas como sinusitis, epistaxis, cefalea, discapacidad visual, obstrucción nasal, hiposmia y rinorrea. En este reporte se presenta el caso de un paciente masculino de 29 años con estesioneuroblastoma estadio Kadish C, quien fue programado para resección quirúrgica bajo anestesia total intravenosa con resultados satisfactorios durante el procedimiento quirúrgico.

Abstract: Esthesioneuroblastoma is a neoplasm of the olfactory neuroepithelium cells, it has a low incidence of 0.4 per million inhabitants. It is characterized by symptoms such as sinusitis, epistaxis, headache, visual impairment, nasal obstruction, hyposmia, and rhinorrhea. We present the case of a 29-year-old male patient with Kadish C stage esthesioneuroblastoma, who was scheduled for surgical resection under total intravenous anesthesia with satisfactory results during the surgical procedure.

A comparison between propofol and sevoflurane for easy insertion of laryngeal mask airway among adults in minor elective surgeries: An observational study

Background: The laryngeal mask airway (LMA) has reached ample popularity for the management of airway during surgery. Propofol, used as induction agent, causes change in blood pressure and heart rate (HR) while insertion of LMA. Sevoflurane, whereas, has the potential to be a good induction agent as propofol. We have compared propofol and sevoflurane for easy insertion of LMA among adults in minor surgeries. Aim and Objectives: The primary objective of the study was to compare the ease of insertion of LMA and its characteristics related to insertion among adults in minor elective surgeries using intravenous propofol or inhalational sevoflurane. While time taken to set induction and actual event of LMA insertion along with number of attempts, jaw relaxation time, LMA insertion time, apnea time, monitoring hemodynamic changes, and occurrence of complications were taken as secondary objectives. Materials and Methods: It was a prospective and observational study done in Department of Anesthesiology and Operation Theaters of Fortis Hospital, Kolkata, after getting ethical approval. Total 100 patients were recruited by consecutive sampling and divided into two groups - P (propofol) and S (sevoflurane) group. Anesthesia induction time, jaw relaxation time, LMA insertion time, etc. were noted. LMA insertion conditions were assessed by a 3-point scale using six variables, total score was calculated for each group. Hemodynamic parameters and induction complications were also recorded. Results: There was no significant difference in demographic parameters, American Society of Anesthesiologists class, Modified Mallampati Grading, and LMA size, between the groups. LMA insertion time was comparable between the two groups. Regarding complications, there was no incidence of coughing while minor gagging (4%) and laryngospasm (6%) were noted only with sevoflurane. Final summation of scores showed excellent insertion characteristics with propofol (94%) and sevoflurane (84%), respectively, with no significant difference. Conclusion: Inhalational sevoflurane may be regarded as a viable alternative to inj. propofol for insertion of laryngeal mask among adults in minor elective surgeries.

Síndrome de infusión de propofol y COVID-19. Reporte de caso / Propofol and COVID-19 infusion syndrome. Case report

Resumen: La forma grave de neumonía por SARS-CoV-2 (COVID-19) cursa en la mayoría de los casos con un síndrome de dificultad respiratoria aguda (SDRA). Es necesario emplear sedación durante su ventilación mecánica, el propofol es el que más de utiliza por su farmacocinética y farmacodinamia. El propofol es un anestésico que se usa ampliamente en las unidades de cuidados intensivos. Su empleo puede provocar un efecto adverso poco frecuente, pero en extremo grave, conocido como síndrome por infusión de propofol (SIP), el cual se encuentra estrechamente asociado a la velocidad de infusión aunado a factores de riesgos propios del paciente. Se caracteriza principalmente por inestabilidad hemodinámica, acidosis láctica y por progresión a disfunción multiorgánica. Se presenta un caso de SIP en paciente con síndrome de dificultad respiratoria aguda (SDRA) secundario a SARS-CoV-2 que desarrolla esta complicación asociada a la sedación. Se discute fisiopatológica clínica y consideraciones que deberán tomarse en cuenta al momento de su utilización en infusión continua.

Abstract: The severe form of SARS-CoV-2 pneumonia (COVID-19) occurs in most cases with acute respiratory distress syndrome (ARDS), requiring the use of sedation during mechanical ventilation, with propofol being the most widely used for its pharmacokinetics and pharmacodynamics. Propofol is a widely used anesthetic in intensive care units (ICU). Its use can cause an infrequent but extremely serious adverse effect, known as propofol infusion syndrome (PRIS), which is closely associated with the speed of infusion coupled with risk factors specific to the patient, the clinical features of PRIS are hemodynamic instability, lactic acidosis and with progression to multi-organ dysfunction. We present a case of SIP in a patient with acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 who develops this complication associated with sedation, discusses clinical pathophysiology and considerations that should be taken into account when using it in continuous infusion.

Comparative-study-of-etomidate-and-propofol-for-induction-of-general-anesthesia-in-elderly-patients

Introduction: An ideal induction agent for general anesthesia should have hemodynamic stability, minimal respiratory side effect and rapid recovery. Presently etomidate and propofol are popular rapid acting inducing agents. Material and methods: After obtaining informed written consent from patients this prospective, randomized, double blind study was conducted in 100 patients of ASA grade 3 and 4 posted for elective surgeries under general anaesthesia. They were divided into two groups of 50 in each group based on random number as group A and group B. The patients in Group A given Inj. Propofol and the patients in Group B received Inj. Etomidate. Parameters such as heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and spo2 were monitored continuously and recorded. Incidence and degree of pain of myoclonic movements were recorded. Demographic variables such as age,Result: gender, weight and ASA grade were comparable no significant difference existed between both the groups.Baseline mean heart rate, mean systolic blood pressure and mean diastolic blood pressure were comparable in both the Groups. (P>0.05)Significant (P<0.05) fall in mean systolic blood pressure, mean diastolic pressure and mean arterial pressure was observed immediately after induction, at 2, 5, 10 minutes up to 30 minutes in group A (propofol) compare to group B (etomidate). After then no significant difference seen in mean systolic pressure, mean diastolic pressure and mean arterial pressure. Etomidate was found ideal for its hemodynamic stability when compared to PropofolConclusion: along with less incidence of pain on injection, the only drawback being high incidence of myoclonus elderly patient.

Effects of dexmedetomidine combined with propofol on cognitive function, hemodynamics and diaphragm movement in elderly patients undergoing painless gastroenteroscopy / 中国医师进修杂志

Objective:To investigate the effects of dexmedetomidine combined with propofol on cognitive function, hemodynamics and diaphragm movement in elderly patients undergoing painless gastroenteroscopy.Methods:The clinical data of 82 patients who underwent painless gastroenteroscopy in Fuyang Minsheng Hospital from April 2021 to November 2022 were retrospectively collected, and they were divided into the control group and the observation group by anesthesia induction method, each group with 41 cases. The control group was anesthetized with propofol, and the observation group was anesthetized with dexmedetomidine and propofol. The recovery time, orientation recovery time and satisfaction of the two groups were compared; the cognitive function before anesthesia, 1, 12 h after anesthesia and 1, 7 d after anesthesia were compared; the changes of hemodynamics and diaphragm movement before anesthesia induction (T 0), 5 min after anesthesia induction (T 1) and at awakening (T 2) and adverse reactions were compared. Results:The recovery time, orientation recovery time in the observation group were shorter than those in the control group: (9.87 ± 1.52) min vs. (11.92 ± 1.74) min, (15.87 ± 2.31) min vs.(18.79 ± 2.54) min; the dosage of propofol was less than that in the control group: (200.21 ± 50.46) mg vs. (300.23 ± 60.29) mg; the satisfaction scores was higher than that in the control group: (9.54 ± 0.32) scores vs. (8.81 ± 0.47) scores, there were statistical differences ( P<0.05). The scores of Mini-Mental State Examination (MMSE) at 1 h after anesthesia and 12 h after anesthesia in the observation group were higher than those in the control group: (23.12 ± 1.86) scores vs. (20.31 ± 1.65) scores, (26.21 ± 1.43) scores vs. (24.12 ± 1.57) scores, there were statistical differences ( P<0.05). The scores of MMSE at 1, 7 d after anesthesia had no statistical differences between the two groups ( P>0.05). The levels of mean arterial pressure (MAP) and heart rate (HR) at T 1 and T 2 were decreased and the levels of MAP and HR at T 1 and T 2 in the observation group were higher than those in the control group: (76.48 ± 4.01) mmHg (1 mmHg = 0.133 kPa) vs. (72.31 ± 3.26) mmHg, (82.31 ± 3.27) mmHg vs. (77.97 ± 3.64) mmHg; (78.72 ± 2.17) bpm vs. (76.23 ± 2.35) bpm, (82.19 ± 3.08) bpm vs. (79.63 ± 2.56) bpm, there were statistical differences( P<0.05). The diaphragm thickness fraction (DTF) and diaphragmatic motion amplitude (DM) at T 1 and T 2 were decreased and the levels of DTF and DM at T 1 and T 2 in the observation group were higher than those in the control group: 0.21 ± 0.02 vs. 0.17 ± 0.03, 0.26 ± 0.03 vs. (0.22 ± 0.04); (15.67 ± 0.81) mm vs. (14.21 ± 0.77) mm, (16.72 ± 0.68) mm vs. (15.46 ± 0.82) mm, there were statistical differences ( P<0.05). The adverse reactions in the two groups had no significant difference ( P>0.05). Conclusions:The combination of dexmedetomidine and propofol has little effect on cognitive function, hemodynamics and diaphragm movement in elderly patients undergoing painless gastroenteroscopy, which can accelerate the recovery of patients and improve patient satisfaction.

Effects of different carbon dioxide pneumoperitoneum pressures combined general anesthesia with sevoflurane-propofol on cerebral oxygenmetabolism balance and stress response in elderly patients undergoing colorectal cancer surgery / 中国医师进修杂志

Objective:To study the effects of different carbon dioxide (CO 2) pneumoperitoneum pressures combined general anesthesia with sevoflurane-propofol on cerebral oxygenmetabolism balance and stress response in elderly patients undergoing colorectal cancer surgery. Methods:A retrospective collection of 100 colon cancer cases from February 2020 to February 2021 in the Jiading Branch of Shanghai First People′s Hospital (Jiangqiao Hospital, Jiading District) and the Shanghai First People′s Hospital were divided into low pressure group and high pressure group according to different CO 2 pneumoperitoneum pressure values, each with 50 cases and 12 mmHg(1 mmHg = 0.133 kPa) and 18 mmHg CO 2 pneumoperitoneum pressure values were used to inflate, and the perioperative status, cerebral oxygen metabolism status, and stress response of the two groups were observed. Results:The take food time, first time out of bed in the low pressure group were lower than those in the high pressure group: (45.67 ± 7.34) h vs. (49.67 ± 8.16) h, (34.69 ± 8.26) h vs. (39.87 ± 7.16) h, there were statistical differences( P<0.05). The time of first anal exhaust and hospital stay in the two groups had no significant differences ( P>0.05). Repeated measures analysis of variance results showed that the levels of partial pressure of carbon dioxide in artery, oxyhemoglobin saturation, arterial blood lactate acid, benous blood lactic acid were different followed the time and treatment methods ( P<0.05). The levels of heart rate, mean arterial pressure, cortisol and thyroid stimulating hormone in the low pressure group were higher than those in the high pressure group: (73.68 ± 6.35) beats/min vs. (84.84 ± 6.86) beats/min, (81.67 ± 13.68) mmHg vs. (93.68 ± 14.37) mmHg, (100.24 ± 12.34) μg/L vs. (135.68 ± 13.69) μg/L, (3.12 ± 0.43) mU/L vs. (3.54 ± 0.34) mU/L, there were statistical differences ( P<0.05). Conclusions:Different CO 2 pneumoperitoneal pressures affect the brain oxygen metabolism of patients, and clinical attention should be paid to them.

Activation of GABAergic neurons in the zona incerta accelerates anesthesia induction with sevoflurane and propofol without affecting anesthesia maintenance or awakening in mice / 南方医科大学学报

OBJECTIVE@#To explore the regulatory effects of GABAergic neurons in the zona incerta (ZI) on sevoflurane and propofol anesthesia.@*METHODS@#Forty-eight male C57BL/6J mice divided into 8 groups (n=6) were used in this study. In the study of sevoflurane anesthesia, chemogenetic experiment was performed in 2 groups of mice with injection of either adeno-associated virus carrying hM3Dq (hM3Dq group) or a virus carrying only mCherry (mCherry group). The optogenetic experiment was performed in another two groups of mice injected with an adeno-associated virus carrying ChR2 (ChR2 group) or GFP only (GFP group). The same experiments were also performed in mice for studying propofol anesthesia. Chemogenetics or optogenetics were used to induce the activation of GABAergic neurons in the ZI, and their regulatory effects on anesthesia induction and arousal with sevoflurane and propofol were observed; EEG monitoring was used to observe the changes in sevoflurane anesthesia maintenance after activation of the GABAergic neurons.@*RESULTS@#In sevoflurane anesthesia, the induction time of anesthesia was significantly shorter in hM3Dq group than in mCherry group (P < 0.05), and also shorter in ChR2 group than in GFP group (P < 0.01), but no significant difference was found in the awakening time between the two groups in either chemogenetic or optogenetic tests. Similar results were observed in chemogenetic and optogenetic experiments with propofol (P < 0.05 or 0.01). Photogenetic activation of the GABAergic neurons in the ZI did not cause significant changes in EEG spectrum during sevoflurane anesthesia maintenance.@*CONCLUSION@#Activation of the GABAergic neurons in the ZI promotes anesthesia induction of sevoflurane and propofol but does not affect anesthesia maintenance or awakening.

Quality of psychomotility recovery after propofol sedation for painless gastroscopy and colonoscopy / 北京大学学报(医学版)

OBJECTIVE@#To study the effect of propofol used for painless gastroscopy and colonoscopy on psychomotility recovery.@*METHODS@#One hundred adult patients undergoing painless gastroscopy and colonoscopy were recruited, aged 18-72 years, with American Society of Anesthesiologist (ASA) physical status Ⅰ-Ⅱ. According to age, the patients were divided into youth group (20-39 years old, 27 cases), middle age group (40-54 years old, 37 cases), and elder group (55-64 years old, 36 cases). Propofol was continuously infused according to the patients' condition to mantain the bispectal index (BIS) score 55-64. All the patients received psychomotility assesment 30 min before the operations when the discharge criteria were met including number cancellation test, number connection test and board test. The heart rate, blood pressure, saturation of pulse oximetry, electrocardiograph and BIS were monitored during the operation. The operating time, recovery time, total volume of propofol and discharge time were recorded. If the results obtained were inferior to those before operation, a third assessment was taken 30 minutes later until the results recovered or being superior to the baseline levels.@*RESULTS@#All the patients completed the first and second assessments, and 25 patients had taken the third assessment. There was no statistically significant difference in the results of psychomotility assessment when the patients met the discharge standard. Furthermore, the results were analyzed by grouping with age, and there was no statistical difference in the test results of the youth and middle age groups compared with the preoperative group, among which, the efficiency of the number cancellation test was significantly better than that before operation in the youth group (P < 0.05). However, in the elderly patients the number cancellation efficiency, number connection test and board test were significantly inferior to that before operation (P < 0.05). There was no significant difference in the accuracy of number cancellation compared with that before operation. The patients who needed the third test in the elder group were significantly more than in the other groups (P < 0.05). Compared with the preoperative results, there was no statistical difference in the test results of those who completed the third test.@*CONCLUSION@#The psychomotility function of the patients who underwent painless gastroscopy and colonoscopy was recovered when they met discharge criteria. The elderly patients had a prolonged recovery period.

Effects of Sevoflurane and Propofol on Neurological Recovery of Traumatic Brain Injury Patients in the Early Postoperative Stage: A Retrospective Cohort Study / 中国医学科学杂志(英文版)

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury (TBI) patients in the early postoperative stage.Methods We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy. Generalized additive mixed model (GAMM) was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale (GCS) on postoperative days 1, 3, and 7. Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale (GOS) at discharge.Results A total of 340 TBI patients were enrolled in this study. There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group, and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group. It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients (β = 0.75, 95%CI: -0.55 to 2.05, P = 0.260). However, elevation in GCS from baseline was 1.73 points (95%CI: -2.81 to -0.66, P = 0.002) less in the sevoflurane group than that in the propofol group on postoperative day 1, 2.03 points (95%CI: -3.14 to -0.91, P < 0.001) less on day 3, and 1.31 points (95%CI: -2.43 to -0.19, P = 0.022) less on day 7. The risk of unfavorable GOS (GOS 1, 2, and 3) at discharge was higher in the sevoflurane group (OR = 4.93, 95%CI: 1.05 to 23.03, P = 0.043). No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS.Conclusions Compared to propofol, sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy. This difference was not detected in TBI patients undergoing decompressive craniectomy.

Anestesia intravenosa total para cirugía videolaparoscópica electiva en pacientes geriátricos / Total intravenous anesthesia for elective videolaparoscopic surgery in geriatric patients

Introducción: El surgimiento de fármacos anestésicos de corta duración estimularon a los anestesiólogos a plantearse un nuevo enfoque para la cirugía videolaparoscópica en el adulto mayor. Analgesia intensa, menor consumo de opioides, rápida recuperación de la conciencia y ventilación espontánea; extubación precoz, disminución de complicaciones y reducción de la estancia hospitalaria. Objetivo: Evaluar en los pacientes geriátricos programados para colecistectomía videolaparoscópica electiva, el efecto de la anestesia intravenosa total con la asociación ketamina/propofol en comparación con fentanil/propofol. Métodos: Se realizó un estudio cuasiexperimental en 40 pacientes con 60 años y más, estado físico II-III según la clasificación de ASA, en el Hospital Universitario "Faustino Pérez Hernández" de Matanzas, programados para cirugía videolaparoscópica electiva. Resultados: La edad promedio osciló entre 63 y 78 años, con una superioridad del sexo femenino y la raza blanca, la clasificación ASA II fue la más representativa en ambos grupos. Imperaron los antecedentes cardiovasculares, hubo ligera disminución de valores espirados de CO2 respecto a los basales, sin diferencias significativas. Hubo variación de la TAM indistintamente en ambos grupos. En el grupo 1 la frecuencia cardiaca posterior a la inducción disminuyó (70 ± 5 lat/min) y se mantuvieron valores inferiores a los basales durante los primeros 20 min, el tiempo medio de recuperación fue significativamente menor en el grupo 2. Conclusiones: La asociación ketamina/propofol proporciona resultados positivos finales.

Introduction: The emergence of short-acting anesthetic drugs stimulated the anesthesiologist to consider a new approach for videolaparoscopic surgery in the elderly. Intense analgesia, decreased opioid consumption, rapid recovery of consciousness, and spontaneous ventilation; early extubation, reduction of complications and reduction of hospital stay. Objective: To evaluate in geriatric patients scheduled for elective videolaparoscopic cholecystectomy the effects of total intravenous anesthesia with the combination of ketamine / propofol, comparing it with fentanyl / propofol. Materials and methods: a descriptive, prospective, longitudinal study was carried out in 40 patients aged 60 years and over, ASA II-III at the "Faustino Pérez Hernández" University Hospital in Matanzas in 2018, scheduled for elective videolaparoscopic surgery. Results: The average age ranged between 63 and 78 years, with a superiority of the female sex and the white race. The ASA II classification was the most representative in both groups. Cardiovascular antecedents prevailed, there was a slight decrease in expired CO2 values compared to baseline, without significant differences. There was variation of the TAM indistately in both groups. In group 1, the heart rate after induction decreased (70 ± 5 beats/min) and values lower than baseline were maintained during the first 20 min. The mean recovery time was significantly shorter in group 2. Conclusions: The association ketamine / propofol provides final positive results.

Effect of combined sedation using multiple drugs on inflammatory cytokines in patients with acute respiratory distress syndrome

Abstract he innate immune response plays an important role in the pathophysiology of acute respiratory distress syndrome (ARDS); however, no drug has been proven to be beneficial in the management of ARDS. Therefore, the aim of this study was to investigate the effects of using combined sedatives on systemic inflammatory responses in patients with ARDS. A total of 90 patients with ARDS and an intubation time of > 120 h were randomly divided into the propofol group (group P), midazolam group (group M), and combined sedation group (group U). Patients in groups P and M were sedated with propofol and midazolam, respectively, whereas patients in group U were sedated with a combination of propofol, midazolam, and dexmedetomidine. The dosage of sedatives and vasoactive drugs, duration of mechanical ventilation, and incidence of sedative adverse reactions were documented. The dosage of sedatives and vasoactive drugs, as well as the incidence of sedative adverse reactions in group U, was significantly lower than those in groups P and M. Similarly, the duration of mechanical ventilation in group U was significantly shorter than that in groups P and M. Hence, inducing sedation through a combination of multiple drugs can significantly reduce their adverse effects, improve their sedative effect, inhibit systemic inflammatory responses, and improve oxygenation in patients with ARDS

Propofol inhibits myocardial injury induced by microvesicles derived from hypoxiareoxygenated endothelial cells via lncCCT4-2/CCT4 signaling

Background Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. Methods Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. Results In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes. Conclusions Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis. Highlights Microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs) exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes. Microvesicles from propofol post-treated HUVECs ((HR + P)-EMVs) induced diminished oxidative stress and apoptosis in IR-injured cardiomyocytes compared with microvesicles from hypoxic/reoxygenated HUVECs (HR-EMVs). lncCCT4-2 was significantly highly expressed in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs, and reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. lncCCT4-2 inhibited HR-EMVs induced oxidative stress and apoptosis in HR-injured AC16 cells by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in AC16 cells.

Role of melatonin in attenuation of hemodynamic response to intubation and anesthetic requirements: a randomized, controlled, double-blind study

Abstract Background Melatonin has been studied to have anxiolytic, sedative, and analgesic effects. However, there is limited data on the effect of melatonin in the attenuation of hemodynamic response to intubation. We aimed to study whether preanesthetic oral melatonin attenuates hemodynamic responses to intubation and anesthetic requirements. Methods Sixty-four patients scheduled for laparoscopic cholecystectomy were randomized into melatonin or placebo group (n = 32 each). Melatonin group received two tablets (3 mg each) of melatonin, and the placebo group received two tablets of vitamin D3 120 min before induction. Hemodynamic parameters were recorded during induction and postintubation for 15 minutes. Total induction dose of propofol, total intraoperative fentanyl consumption, and adverse effects of melatonin were also noted. Results Postintubation rise in heart rate (HR) was less in the melatonin group compared to the placebo group (10.59% vs. 37.08% at 1 min, respectively) (p< 0.0001). Maximum percentage increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was lesser in melatonin group than placebo group (SBP 9.25% vs. 37.73%, DBP 10.58% vs. 35.51%, MBP 9.99% vs. 36.45% at 1 min postintubation. respectively) (p< 0.0001). Induction dose of propofol (1.42 mg.kg-1 vs. 2.01 mg.kg-1) and the number of patients requiring additional fentanyl intraoperatively (3 vs. 11) were also significantly reduced in the melatonin group. Conclusion Premedication with 6 mg of oral melatonin resulted in significant attenuation of postintubation rise in HR, SBP, DBP, and MBP. It also reduced the induction dose of propofol, total intraoperative fentanyl consumption without any adverse effects.

Effects of propofol on glutamatergic neuronal activity in paraventricular thalamus / 药学学报

This study explored the effects of propofol on the activity of glutamatergic neurons in the paraventricular thalamus (PVT) and the underlying mechanisms at the molecular level using whole-cell patch-clamp techniques. Acute brain slices containing the PVT were obtained from 8 weeks old C57BL/6J mice. The electrophysiological characteristics of PVT neurons were recorded in current-clamp mode, then single-cell sequencing was used to identify neuronal types. The firing frequencies before, during, and after propofol or intralipid application were recorded as FB, FD and FW; and the membrane potentials were recorded as MPB and MPD. Picrotoxin (PTX) was used to block inhibitory gamma-aminobutyric acid type A (GABAA) receptors during the application of propofol at 10 μmol·L-1. Then, GABAA receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) were recorded, and the effects of 10 μmol·L-1 propofol were investigated. The animal experiments were approved by the Medical Animal Administrative Committee of Shanghai Medical College Fudan University. The results showed that there were no significant differences in FB, FD and FW during intralipid and 2 μmol·L-1 propofol application. With propofol at 5, 10 and 20 μmol·L-1, FD decreased significantly when compared with FB, and FW increased significantly as compared with FD (P < 0.01). The inhibition degree of the three concentration groups was significantly different (P < 0.01). In addition, with propofol at 20 μmol·L-1, MPD hyperpolarized significantly (P < 0.01). In the presence of PTX, 10 μmol·L-1 propofol could not suppress the firing frequency of PVT glutamatergic neurons. Propofol at 10 μmol·L-1 prolonged the decay time of sIPSCs (P < 0.01) and mIPSCs (P < 0.05), and increased the amplitude (P < 0.01) of mIPSCs of PVT glutamatergic neurons. Together, these results indicate that propofol can inhibit the activity of PVT glutamatergic neurons in a concentration-dependent and reversible manner, and the effect is likely to be mediated by postsynaptic GABAA receptors.

Effects of midazolam combined with propofol on recovery of patients with laparoscopic cholecystectomy / 药学实践杂志

Objective To explore the effect midazolam combination with propofol on postoperative recovery in patients undergoing laparoscopic cholecystectomy. Methods A total of 162 patients who were admitted to the hospital for laparoscopic cholecystectomy from April 2019 to January 2021 were selected. According to different anesthesia methods, they were divided into control group (midazolam anesthesia) and observation group (midazolam combined with propofol anesthesia), with 81 cases in each group. The stress index levels before and after operation, MoCA scores before operation (T0), 24 h after operation (T1) and 48 h after operation (T2), sleep quality at T0, the first day after operation (T3) and the second day after operation (T4), the perioperative recovery were compared between the two groups. Results The levels of Cor and NE, the recovery time of eyes opening, extubation, orientation, and the incidence of adverse reactions in the observation group were lower than those in the control group (P<0.05). Observation group MMSE score when T1, T2, T3, T4 sleep quality score were higher than control group (P<0.05). Conclusion Midazolam combined with propofol was safe and had good postoperative recovery in patients undergoing laparoscopic cholecystectomy.

Role of Nrf2/HO-1 signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in neonatal rats / 中华麻醉学杂志

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in the neonatal rats.Methods:Eighty SPF healthy newborn Sprague-Dawley rats of both sexes, aged 7 days, weighing 15-20 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), edaravone+ propofol group (group EP) and Nrf2 inhibitor ML385+ edaravone+ propofol group (group MEP). Propofol 75 mg/kg was intraperitoneally injected once a day for 7 consecutive days in P group, EP group and MEP group, respectively, while the equal volume of medium/long chain fat emulsion injection was intraperitoneally injected in C group. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before each propofol injection in EP and MEP groups, and ML385 15 mg/kg was intraperitoneally injected simultaneously in group MEP. The spontaneous activity was evaluated by the open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. The rats were sacrificed after the end of water maze test, and brains were removed and hippocampal tissues were obtained for determination of reactive oxygen species (ROS) levels (by flow cytometry), superoxide dismutase (SOD) and malondialdehyde (MDA) levels (by enzyme-linked immunosorbent assay) and expression of Nrf2 and HO-1 (by Western blot) and for microscopic examination of the pathological changes in the hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and time of stay at the center of the open field among the four groups ( P>0.05). Compared with C group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was observed in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the levels of MDA and ROS in the hippocampus were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological injury in the hippocampal CA1 region was significantly alleviated in EP group. Compared with EP group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was aggravated in the hippocampal CA1 region in MEP group. Conclusions:The mechanism by which edaravone attenuates long-term cognitive impairment caused by long-time sedation with propofol is related to activation of Nrf2/HO-1 signaling pathway and inhibition of oxidative stress in the neonatal rats.

Effects of propofol and remifentanil in different TCI sequences on hypotension during induction of general anesthesia in hypertensive patients / 中华麻醉学杂志

Objective:To evaluate the effect of propofol and remifentanil in different target-controlled infusion(TCI) sequences on hypotension during induction of general anesthesia in hypertensive patients.Methods:A total of 132 patients with hypertension of both sexes, aged 50-75 yr, of American Society of Anesthesiologists Physical Status classificationⅡ or Ⅲ, with body mass index of 18-30 kg/m 2, scheduled for elective tracheal intubation under general anesthesia, were divided into 3 groups( n=44 each) using a random number table method: group C, PR group and RP group. In group C, propofol(target effect-site concentration 5 μg/ml) and remifentanil(target effect-site concentration 5 ng/ml) were simultaneously given by TCI. Propofol was given by TCI followed by TCI of remifentanil in PR group. Remifentanil was given by TCI followed by TCI of propofol in RP group. The development of hypotension was observed within 10 min after induction of general anesthesia, and the consumption of propofol, remifentanil and ephedrine, time of loss of consciousness, time of tracheal intubation and adverse reactions during the perioperative period were recorded. Results:Compared with group C, the incidence of hypotension during induction was significantly decreased, the consumption of propofol and ephedrine was decreased, and the BIS value was increased when consciousness disappeared, the time of loss of consciousness and time of tracheal intubation were prolonged, the BIS value was increased at loss of consciousness in PR group, and the consumption of ephedrine was significantly decreased, and the time of loss of consciousness and time of tracheal intubation were prolonged in RP group( P<0.05). Compared with PR group, the consumption of ephedrine was significantly decreased, and the time of loss of consciousness was prolonged in RP group( P<0.05). There was no significant difference in the incidence of responses to tracheal intubation, injection pain, bucking, inhibition ratio, postoperative delirium, postoperative nausea and vomiting, and intraoperative awareness during induction among the three groups( P>0.05). Conclusions:TCI of remifentanil followed by TCI of propofol can decrease the development of hypotension during induction of general anesthesia in hypertensive patients.

Median effective dose of alfentanil combined with propofol inhibiting responses to laryngeal mask airway insertion in children / 中华麻醉学杂志

Objective:To determine the median effective dose(ED 50) of alfentanil combined with propofol inhibiting responses to the laryngeal mask airway(LMA) insertion in children. Methods:American Society of Anesthesiologists Physical Status classification Ⅰ children, aged 6-10 yr, with body mass index of 18-24 kg/m 2, undergoing facial skin pigmented nevus resection, were selected. Propofol(target plasma concentration 3 μg/ml) was given by the target-controlled infusion, alfentanil was intravenously injected, 2 min later LMA was inserted, and anesthesia was maintained with 2%-3% sevoflurane until the end of surgery. The dose of alfentanil was determined by the up-and-down sequential method, the initial dose of alfentanil was 15 μg/kg, when the response to LMA insertion was positive/negative, the dose of alfentanil increased/decreased by 1 μg/kg in the next case. The LMA insertion response was defined as swallowing, bucking, body movement occurred during insertion of the LMA, and this process was repeated until 7th turning points appeared. The ED 50 and 95% confidence interval of alfentanil combined with propofol inhibiting responses to LMA insertion in children were calculated using probit method. Results:The ED 50 of alfentanil combined with propofol inhibiting responses to LMA insertion was 13.18(95% confidence interval 12.43-13.79) μg/kg in children. Conclusions:The ED 50 of alfentanil combined with propofol inhibiting responses to LMA insertion is 13.18 μg/kg in children.