Efficacy and safety of remimazolam besylate in bronchoscopy for adults: A multicenter, randomized, double-blind, positive-controlled clinical study.

Background: With the development of fiberoptic bronchoscopy in the diagnosis and treatment of various pulmonary diseases, the anesthesia/sedation requirements are becoming more demanding, posing great challenges for patient safety while ensuring a smooth examination/surgery process. Remimazolam, a brand-new ultra-short-acting anesthetic, may compensate for the shortcomings of current anesthetic/sedation strategies in bronchoscopy. Methods: This study was a prospective, multicenter, randomized, double-blind, parallel positive controlled phase 3 clinical trial. Subjects were randomized to receive 0.2 mg/kg remimazolam besylate or 2 mg/kg propofol during bronchoscopy to evaluate the efficacy and safety of remimazolam. Results: A total of 154 subjects were successfully sedated in both the remimazolam group and the propofol group, with a success rate of 99.4% (95%CI of the adjusted difference -6.7 × 10%-6% to -5.1 × 10%-6%). The sedative effect of remimazolam was noninferior to that of propofol based on the prespecified noninferiority margin of -5%. Compared with the propofol group, the time of loss of consciousness in the remimazolam group (median 61 vs. 48s, p < 0.001), the time from the end of study drug administration to complete awakening (median 17.60 vs. 12.80 min, p < 0.001), the time from the end of bronchoscopy to complete awakening (median 11.00 vs. 7.00 min, p < 0.001), the time from the end of study drug administration to removal of monitoring (median 19.50 vs. 14.50 min, p < 0.001), and the time from the end of bronchoscopy to removal of monitoring (median 12.70 vs. 8.60 min, p < 0.001) were slightly longer. The incidence of Adverse Events in the remimazolam group and the propofol group (74.8% vs. 77.4%, p = 0.59) was not statistically significant, and none of them had Serious Adverse Events. The incidence of hypotension (13.5% vs. 29.7%, p < 0.001), hypotension requiring treatment (1.9% vs. 7.7%, p = 0.017), and injection pain (0.6% vs. 16.8%, p < 0.001) were significantly lower in the remimazolam group than in the propofol group. Conclusion: Moderate sedation with 0.2 mg/kg remimazolam besylate is effective and safe during bronchoscopy. The incidence of hypotension and injection pain was less than with propofol, but the time to loss of consciousness and recovery were slightly longer. Clinical Trial Registration: clinicaltrials.gov, ChiCTR2000039753.

Bezold-Jarisch reflex occurred in a pediatric patient with giant intra-abdominal teratoma during induction of anesthesia: A case report.

RATIONALE: Bezold-Jarisch reflex (BJR) occurs when the cardioinhibitory receptors in the walls of ventricles are activated by various stimuli, with typical features of bradycardia, vasorelaxation, and hypotension. This reflex usually happens in parturient intrathecal anesthesia, as a result of decreased venous return by compression of inferior vena cava, but it is only rarely reported during general anesthesia. PATIENT CONCERNS: Severe bradycardia and hypotension, indicating BJR, occurred during the induction of general anesthesia in a 3-month-old female child with giant intra-abdominal teratoma. DIAGNOSES: A giant intra-abdominal teratoma was detected by computed tomography scanning. The decreased left ventricular ejection faction along with increased troponin I and N-terminal pro-B-type natriuretic peptide indicated a preoperative mild cardiac dysfunction. BJR was diagnosed on the basis of the severe bradycardia and hypotension observed during the induction of general anesthesia, INTERVENTIONS:: Atropine failed to increase heart rate. Cardiopulmonary resuscitation was initiated immediately and epinephrine was injected intravenously because of sudden circulatory collapse. Soon after the return of spontaneous circulation, a central venous line was placed and invasive blood pressure was monitored. Vital signs and homeostasis were kept stable during teratoma resection. OUTCOMES: The child was extubated after emergence from anesthesia in the operating room. Eleven days later, she had recovered without complications and was discharged. LESSONS: General anesthesia should be induced with great care in patients with giant intra-abdominal masses, and the patient should be kept in the left-lateral table tilt position before induction.

Anatomic variations of neck vessels and the course of pediatric internal jugular veins.

BACKGROUND: Landmark-guided internal jugular vein cannulation is difficult for pediatric patients but useful, especially when ultrasound equipment is unavailable. Therefore, it is important to define the adjacent anatomic characteristics of the pediatric internal jugular vein. METHODS: In 210 children the course of the internal jugular vein, and common carotid and vertebral arteries was measured from the level of the cricoid cartilage to the supraclavicular area using ultrasound. RESULTS: From the level of the cricoid cartilage to the supraclavicular area, vessel diameter increased with internal jugular vein increasing by 12%, and common carotid and vertebral arteries increasing by 5% each. From the level of the cricoid cartilage to the supraclavicular area, the number of patients with a medial common carotid artery position relative to the internal jugular vein increased, whereas those with a lateral position decreased; the number of patients with nonoverlapped common carotid artery-internal jugular vein increased, and those with totally overlapped decreased. In contrast, the overlapping status of vertebral artery-internal jugular vein changes oppositely. More than 97.14% of the vertebral artery lies lateral to the internal jugular vein at these levels. The minimal vertebral artery-internal jugular vein depth decreased from 0.46±0.20 to 0.37±0.19 cm. The angle from the internal jugular vein line to the horizontal line of the body was 83.35±9.04 degrees. CONCLUSION: The common carotid artery and internal jugular vein are farther apart as one moves down the neck, whereas the vertebral artery and internal jugular vein are getting together. Additionally, the diameter of the internal jugular vein increased.

[Comparison of efficacy for laryngeal mask airway-Supreme(TM) versus common laryngeal mask airway in children].

OBJECTIVE: To compare the efficacy of laryngeal mask airway-Supreme(TM) versus common laryngeal mask airway in children with general anesthesia. METHODS: With local research ethics committee's approval and written informed parental consent, 100 children were randomly divided into groups L (size 2.0 common laryngeal mask airway) and S (size 2.0 laryngeal mask airway-Supreme(TM)) according to random number (n = 50 each). After anesthesia induction, a common laryngeal mask airway or laryngeal mask airway-Supreme(TM) was inserted and mechanically ventilated. Time and ease for insertion, insertion success rate, airway leak pressure, success rate and ease of disposal sputum collecting tube insertion in group S, quality of airway during anesthetic maintenance, abdominal circumference changes and complications within 24 h post-operation were measured. RESULTS: Compared with group L, abdominal circumference increased less in group S (0.90 ± 0.35 vs 0.43 ± 0.18 cm, n = 46, P < 0.01). No significant inter-group differences existed for other measurements. Disposal sputum collecting tube was successfully placed in group S(100%). CONCLUSION: In children with mechanical ventilation, laryngeal mask airway-Supreme(TM) can be effectively applied to maintain a good airway. And the incidence of gastric insufflation is lower. It is particularly useful for those requiring evacuation of gastric contents during general anesthesia.

Effects of breviscapine on pulmonary inflammatory response and lung injury in children undergoing open heart surgery.

This study examined the effects of breviscapine (1) on pulmonary inflammatory response and lung function in pediatric patients undergoing open heart surgery. Forty-five children (ASA II or III, aged 2-72 months) were randomly assigned to control group (saline, Group C), low dose 1 group (0.5 mg/kg, Group Bre0.5), and high dose 1 group (1.0 mg/kg, Group Bre1.0), 15 cases each group. Plasma concentrations of procalcitonin (PCT) and neutrophil elastase (NE) were measured and compared at different time points. Plasma concentrations of PCT and NE were increased after cardiopulmonary bypass (CPB) induction, and the concentrations were lower in 1-treated groups. The present results indicated that continuous infusion of 1 before the CPB suppressed the production of PCT and NE attenuated systemic inflammatory response, which could result in lung protective effect in children undergoing open heart surgery.

[Effect of pediatric TCI system for propofol plus remifentanil in pediatric short-duration surgery with laryngeal mask airway anesthesia].

OBJECTIVE: To study the effect of a pediatric TCI patent system for propofol plus remifentanil in pediatric short-duration surgery with laryngeal mask airway (LMA) anesthesia. METHODS: A total of 120 pediatric patients underwent short-duration elective surgery, aged 3 - 9 years old, weighted 13 - 26 kg, ASAI grade, were randomly divided into 3 groups (n = 40 each). The propofol concentrations of effect compartment were set at 2 µg/ml in Group A, 3 µg/ml in Group B and 4 µg/ml in Group C. The remifentanil initial concentration of plasma compartment was 2 ng/ml and increased stepwise by 0.5 ng/ml until a successful insertion of LMA. The remifentanil concentration was recorded when LMA was successfully inserted and the cases were numerated at the each remifentanil concentration. Heart rate (HR), mean arterial pressure (MAP), BIS (bispectral index) values and postoperative adverse events were also recorded at the time points of pre-induction (T0), 2 min post-remifentanil TCI (T1), LMA insertion (T2), skin incision (T3), 5 min post-skin incision (T4), 10 min post-skin incision, (T5) and beginning surgery (T6). RESULTS: The satisfactory ratios of a successful insertion of LMA were highest in remifentanil 3.0 ng/ml (AR subgroup), 2.5 ng/ml (BR subgroup) and 2.0 ng/ml (CR subgroup) respectively. The laryngeal mask satisfactory ratio was high in BR subgroup (P < 0.05). There were significantly differences of T1-T5 values of HR, MAP and BIS in AR and CR subgroups (P < 0.05), but not in BR subgroup. The above-mentioned monitoring indices at T2 in AR subgroup and T3 in CR subgroup were significantly higher than those in BR subgroup. There were more adverse reactions in CR and AR subgroups versus BR subgroup (P < 0.05). CONCLUSION: The patented system for propofol 3 µg/ml effect compartment concentration plus remifentanil 2.5 ng/ml plasma concentration TCI displays stable hemodynamics, less stress, fewer complications and better clinical outcomes in pediatric short-duration surgery with LMA anesthesia.

[Effect of the new propofol target controlled infusion system in children undergoing high ligation of hernial sac].

OBJECTIVE: To discuss the effect of the new target controlled infusion (TCI) system in Chinese children undergoing minor operation and compared with TCI system with Marsh parameters. METHODS: Ninety ASA I, aged 3 - 5 yrs children undergoing elective unilateral high ligation of hernial sac under general anesthesia were randomly divided into group L (n = 45) and group M (n = 45) 2 groups. All subjects were unpremedicated. Systolic blood pressure (SBP), diastolic blood pressure (DBP), ECG, SpO2 and BIS were monitored. Patients of Group L and group M were anesthetized with propofol by Lian propofol TCI system and Marsh system respectively, combined with regional block. The target plasma concentration of TCI system was set at 6 microg/ml initially and up-regulated 1 microg/ml gradually if obvious body movement occurred while skin incision. If the target plasma concentration up to 8 microg/ml but there still had body movement, the TCI venous anesthesia was replaced by inhaled anesthesia. HR, RR, SBP, DBP and BIS were recorded in time points of baseline (T(0)), after the induction (T(1)), skin incision (T(2)), 3, 5 min after skin incision (T(3), T(4)), the end of operation (T(5)). Complications, the awakening time and the number of cases which anesthetized with different propofol plasma concentrations or inhaled anesthesia were recorded respectively as well. RESULTS: The number of cases which completed the operation under TCI plasma concentration 6 microg/ml in group L were significantly more than those in group M (P < 0.01). There were significantly different of T(1)-T(4) values of HR, RR, SBP, DBP and BIS in group M (P < 0.05), but not in group L. Compared with group L, T(2)-T(4) values of HR, RR, SBP, DBP and BIS were higher in group M (P < 0.05 or 0.01). Complications were lower in group L than those in group M. CONCLUSION: Compared with Marsh system, propofol 6 microg/ml plasma concentration with the new target controlled infusion system applied in Chinese children undergoing unilateral high ligation of hernial sac could maintain stable hemodynamics, less stress reaction and complications.

[The effect of pulmonary static inflation with sevoflurane during cardiopulmonary bypass on lung function in patients undergoing cardiac valve replacement surgery].

OBJECTIVE: To assess the phenomenon of lung injury after cardiopulmonary bypass (CPB) and the effects of pulmonary static inflation with sevoflurane during CPB on lung function in patients undergoing cardiac valve replacement surgery. METHODS: Sixty adult patients (ASA II or III, aged 20-59 years) were randomly assigned to two groups, control group (n=30): pulmonary static inflation during CPB, no sevoflurane inhaled, sevoflurane group (n=30): pulmonary static inflation with 1.0 MAC sevoflurane during CPB. The pressure of pulmonary static inflation was maintained at 5 cm H2O in both groups. Arterial blood gas analysis was performed at time of operation starting (To)0 1, 3, 6 h after CPB (T1, TZ,2T3). The values of alveolar-arterial oxygen pressure difference ED[A-a)O2)2]respiratory index [RI, D(A-a)O2/2aO2)2and oxygenation index (OI, PaOz/2iOz)2were calculated respectively. RESULTS: Compared with control group, D(A-a)Oz,2RI and OI were not different in sevoflurane group at any stage; Compared with the baseline (To) in both groups, D (A-a)O2 2nd RI increased after CPB, and OI decreased (P < 0.05 or 0.01), the peak of them occurred at 3 h after CPB. CONCLUSIONS: The impact of pulmonary function usually occur after cardiopulmonary bypass (CPB)in patients undergoing cardiac valve replacement surgery, of which peak injury within 6 h presents at 3 h after CPB. Static pulmonary inflation with 1.0 MAC sevoflurane during CPB shows no beneficial effects on lung function in patients undergoing cardiac valve replacement surgery.

Pharmacokinetics of a single bolus of propofol in chinese children of different ages.

BACKGROUND: There is no information about the pharmacokinetic profile of propofol in Chinese children younger than 3 yr. This study was designed to determine a complete pharmacokinetic profile of a single dose of propofol in Chinese children of different ages. METHODS: Arterial blood samples were obtained from 35 children with an American Society of Anesthesiologist physical status of I or II at 2, 4, 6, 8, 10, 20, 30, 45, 60, 90, 120, and 180 min after a single bolus intravenous injection of propofol (3 mg/kg). The plasma concentrations of propofol were measured using high-performance liquid chromatography with an ultraviolet detector. A population model was used to estimate the pharmacokinetics of propofol. RESULTS: A three-compartment pharmacokinetic model best described the pharmacokinetics of propofol. Clearance was 0.185 l/min, the volume of distribution of the central compartment was 7.41 l, the peripheral volumes of distribution were 54.6 and 7.2 l, and the intercompartmental clearances were 0.614 and 0.692 l/min for a child of the average weight of 13.7 kg. The half-lives were 2.67, 14.89, and 310.60 min. Covariate models were applied, and weight was found to be significant covariate for the clearance and volume of distribution parameters. No significant age effect could be demonstrated on clearance or volume of distribution parameters after weight was taken into account. CONCLUSIONS: This study supports the case that the pharmacokinetic properties of propofol do not differ substantially across Chinese children of different ages after weight has been accounted for.