The median effective concentration of ropivacaine for ultrasound-guided caudal block in children: a dose-finding study.

PURPOSE: To determine the 50% minimum effective concentration (MEC50) and the 95% effective concentration (MEC95) of ropivacaine for ultrasound-guided caudal block during hypospadias repair surgery of pediatric patients. METHODS: Children were enrolled with the American Society of Anesthesiologists (ASA) physical status I-II undergoing elective hypospadias repair surgery. Children were grouped into two age groups: toddlerhood (1-3 years old) and preschool (3-6 years old). We measured The MEC50 using Dixon's up-and-down method. The first children received the caudal block with 1.0 mL/kg of 0.15% ropivacaine. We determined each subsequent patient's concentration based on the previous patient's response and adjusted the concentration in intervals of 0.015%. Meanwhile, the probit regression analysis obtains 95% effective concentration (MEC95). In addition, we recorded the general condition, adverse events, and postoperative pain of each child. RESULTS: 46 children undergoing elective hypospadias repair surgery were included in this study, 22 in the toddlerhood group and 24 in the preschool group. Of the total number of patients, the caudal block was successful in 25 (54%) and failed in 21 (46%). The MEC50 of 1 ml/kg ropivacaine was 0.102% (95% CI 0.099%, 0.138%) in the toddlerhood group and 0.129% (95% CI 0.124%, 0.138%) in the preschool group. The MEC95 of 1 ml/kg ropivacaine was 0.148% (95% CI 0.131%, 0.149%) in the toddlerhood group and 0.162% (95% CI 0.134%, 0.164%) in the preschool group. Our results showed that ropivacaine concentration was statistically different between preschool children and toddlers (P < 0.001). None of the adverse events occurred. CONCLUSIONS: This study showed that children in the preschool group required higher concentrations of ropivacaine than children in the toddler group during ultrasound-guided sacral block combined with non-intubated general anesthesia. At the same time, this method of anesthesia is safe and effective for children undergoing surgery for hypospadias.

Median effective volume of 0.2% ropivacaine for ultrasound-guided supraclavicular brachial plexus block in children aged 1-6 years: a prospective dose-finding study.

Objective: To determine the median effective volume (EV50) of 0.2% ropivacaine for ultrasound-guided supraclavicular brachial plexus block (SC-BPB) in children aged 1-6 years. Methods: Children aged from 1 to 6 years with an American Society of Anaesthesiologists (ASA) physical status I-II who were scheduled for unilateral upper extremity surgery at the Children's Hospital of Chongqing Medical University were recruited. All patients underwent surgery under general anaesthesia combined with brachial plexus block. SC-BPB was guided by ultrasound after anaesthesia induction, and 0.2% ropivacaine was given after localization. In the study, we used Dixon's up-and-down approach with an initial dose of 0.50 ml/kg. Considering the effect of the previous block, a successful or failed block could produce a 0.05 ml/kg decrement or increment in volume, correspondingly. The experiment was stopped when there were 7 inflection points. Using isotonic regression and bootstrapping algorithms, the EV50, the 95% effective volume (EV95) and the 95% confidence interval (CI) were calculated. The patients' general information, postoperative pain scores, and adverse events were also recorded. Results: Twenty-seven patients were involved in this study. The EV50 of 0.2% ropivacaine was 0.150 ml/kg (95% CI, 0.131-0.169 ml/kg) and the EV95 (secondary metric) was 0.195 ml/kg (95% CI, 0.188-0.197 ml/kg). No adverse events occurred during the research study. Conclusions: For ultrasound-guided SC-BPB in children aged 1-6 years undergoing unilateral upper extremity surgery, the EV50 of 0.2% ropivacaine was 0.150 ml/kg (95% CI, 0.131-0.169 ml/kg).

Median effective dose of 0.2% ropivacaine for ultrasound-guided median nerve block in young children.

OBJECTIVE: To determine the median effective dose (ED50) and the 95% effective dose (ED95) of 0.2% ropivacaine for ultrasound-guided lower forearm median nerve block in paediatric patients. METHODS: Eligible children were American Society of Anesthesiologists (ASA) status I-II scheduled to have elective open surgery for trigger thumb repair. Patients were stratified into two age groups: 1- to 3-year-olds and 3- to 6-year-olds. The ED50 was determined by Dixon's up-and-down method. The first patient received an ultrasound-guided median nerve block by injection of 2 mL of 0.2% ropivacaine. Each subsequent patient's dose was determined by the response of the previous patient, the doses being adjusted in intervals of 0.2 mL. In addition, the 95% effective dose (ED95) was obtained using a probit regression approach. The patients' general condition, postoperative pain scores, and adverse events were recorded. RESULTS: A total of 52 children who were scheduled to undergo open surgery for trigger thumb were included in this study: 28 in the 1- to 3-year-olds group and 24 in the 3- to 6-year-olds group. The ED50 (95% confidence interval) values were 0.9 (0.44-1.36) mL in 1- to 3-year-olds and 1.4 (1.14-1.66) mL in 3- to 6-year-olds. The ED95 (95% confidence interval) values were 1.5 (0.98-1.58) mL in 1- to 3-year-olds and 1.7 (1.54-1.78) mL in 3- to 6-year-olds. No adverse events occurred. CONCLUSIONS: A single dose of ropivacaine was an effective agent for young children requiring ultrasound-guided lower forearm median nerve block in open surgery for trigger thumb. The ED50 (95% confidence interval) values were 0.9 (0.44-1.36) mL in 1- to 3-year-olds and 1.4 (1.14-1.66) mL in 3- to 6-year-olds. The ED95 (95% confidence interval) values were 1.5 (0.98-1.58) mL in 1- to 3-year-olds and 1.7 (1.54-1.78) mL in 3- to 6-year-olds.

The 90% minimum effective volume and concentration of ropivacaine for ultrasound-guided median nerve block in children aged 1-3 years: A biased-coin design up-and-down sequential allocation trial.

BACKGROUND: Median nerve block can provide excellent analgesia during open surgery for trigger thumb in children. However, no data on the 90% minimum effective volume (MEV90) and concentration (MEC90) of ropivacaine for ultrasound-guided median nerve block in pediatric patients have been reported. DESIGN: A prospective two-phase study with an up-and-down sequential allocation trial using a biased coin design. PATIENTS: Children aged 1-3 years are experiencing open surgery for trigger thumb. INTERVENTION: This study has 2 parts, one for MEV90 and subsequently studied MEC90 from the former part of the study. The MEV90 and MEC90 of ropivacaine for each subsequent patient were determined by the response of the previous patient, with the biased coin design up-and-down sequential allocation trial. The interval of -volume or concentration was -0.1 ml or 0.01%, respectively. MEASUREMENTS: The MEV90 and MEC90 of ropivacaine for ultrasound-guided median nerve block in pediatric patients, were then used to estimate the 99% minimum effective volume (MEV99) and concentration (MEC99). The patient's general condition, postoperative pain, and adverse events. MAIN RESULTS: A total of one hundred and eighteen children were enrolled for the study, and 56 and 62 patients were enrolled for the MEV90 and MEC90 studies, respectively. The MEV90 of 0.2% ropivacaine was 1.44 ml (95% CI 1.043 ml, 1.466 ml), and the MEC90 of 1.5 ml ropivacaine was 0.195% (95% CI 0.159%, 0.197%). There were no adverse events that occurred. CONCLUSION: For ultrasound-guided median nerve block in children aged 1-3 years old with trigger finger undergoing open surgery, the MEV90 of 0.2% ropivacaine is 1.44 ml (95% CI 1.043 ml, 1.466 ml), and the MEC90 of 1.5 ml of ropivacaine is 0.195% (95% CI 0.159%, 0.197%).

The 90% effective dose of intranasal dexmedetomidine for procedural sedation in children with congenital heart disease before and after surgery: A biased-coin design up-and-down sequential allocation trial.

BACKGROUND: Intranasal dexmedetomidine can provide adequate sedation during short procedures. However, there are few reports investigating the effective dose of intranasal dexmedetomidine for sedation in children with congenital heart disease (CHD) before and after surgery. METHODS: Children aged 13-36 months with acyanotic CHD requiring trans-thoracic echocardiography before cardiac surgery were recruited for this study. One month after the cardiac surgery, the same children were studied again. The 90% effective dose was established using a biased-coin design up-and-down sequential method. Onset time, examination time, wake-up time and adverse effects were measured. Safety was evaluated in terms of changes in vital signs. RESULTS: A total of fifty-eight subjects were recruited for this study. The 90% effective dose of intranasal dexmedetomidine for sedation was 2.13 µg/kg (95% CI, 1.73-2.34 µg/kg) in children with CHD before cardiac surgery and 3.51 µg/kg (95% CI, 2.99-3.63 µg/kg) after cardiac surgery (P < .01). There were no differences between the groups in terms of demographic variables, onset time, examination time, wake-up time or adverse effects. CONCLUSIONS: The 90% effective dose of intranasal dexmedetomidine for sedation in children with CHD was 2.13 µg/kg before cardiac surgery and 3.51 µg/kg after cardiac surgery.

[Comparison of ED50 of intranasal dexmedetomidine sedation in children with acyanotic congenital heart disease before and after cardiac surgery].

OBJECTIVE: To compare the median effective dose (ED50) of intranasal dexmedetomidine for procedural sedation in uncooperative pediatric patients with acyanotic congenital heart disease before and after cardiac surgery. METHODS: We prospectively recruited 47 children (22 in preoperative group and 25 in postoperative group) who needed sedation for transthoracic echocardiography (TTE). A modified up-and-down sequential study design was employed to determine dexmedetomidine dose for each patient with a starting dose of 2 µg/kg in both groups; dexmedetomidine doses for subsequent subjects were determined according to the responses from the previous subject using the up-and-down method at a 0.25 µg/kg interval. The ED95 was determined using probit regression. The onset time, examination time, wake-up time and adverse effects were measured, and the safety was evaluated in terms of changes in vital signs every 5 min. RESULTS: The ED50 value of intranasal dexmedetomidine for sedation was 1.84 µg/kg (95% CI: 1.68-2.00 µg/kg) in children with congenital heart disease before cardiac surgery, and 3.38 µg/kg (95% CI: 3.21-3.54 µg/kg) after the surgery. No significant difference was found between the two groups in the demographic variables, onset time, examination time, wake-up time, or adverse effects. CONCLUSIONS: In children with acyanotic congenital heart disease, the ED50 of intranasal dexmedetomidine for TTE sedation increases to 3.38 µg/ kg after cardiac surgery from the preoperative value of 1.84 µg/kg.

The effects of repeated propofol anesthesia on spatial memory and long-term potentiation in infant rats under hypoxic conditions.

Propofol is widely used as an intravenous drug for induction and maintenance in general anesthesia. Hypoxemia is a common complication during perianesthesia. We want to know the effect of propofol on spatial memory and LTP (Long-term potentiation) under hypoxic conditions. In this study, 84 seven-day-old Sprague-Dawley rats were randomly assigned into six groups (n = 14)-four control groups: lipid emulsion solvent + 50% oxygen (CO), lipid emulsion solvent + room air (CA), lipid emulsion solvent + 18% oxygen (CH), and propofol + 50% oxygen (propofol-oxygen, PO); and two experiment groups: propofol + room air (propofol-air, PA), and propofol + 18% oxygen (propofol-hypoxia, PH). After receiving propofol (50 mg/kg) or the same volume of intralipid intraperitoneal (5.0 ml/kg), injected once per day for seven consecutive days, the rats were exposed to 18% oxygen, 50% oxygen and air, until recovery of the righting reflex. We found that the apoptotic index and activated caspase-3 increased in the PH group (P < 0.05) compared with the PA group, fEPSP (field excitatory postsynaptic) potential and success induction rate of LTP reduced in all propofol groups (P < 0.05). Compared with the PO group, the fEPSP and success induction rate of LTP reduced significantly in the PA and PH groups (P < 0.05). Moreover, compared with CH group, the average time of escape latency was longer, and the number of platform location crossings was significantly reduced in the PH group (P < 0.05). Thus, we believe that adequate oxygen is very important during propofol anesthesia.

The therapeutic effect of controlled reoxygenation on chronic hypoxia-associated brain injury.

Cardiopulmonary bypass (CPB) is the most general technique applied in congenital heart disease (CHD). However, standard CPB poses a specific pathologic condition for patients during surgery: exposure to reoxygenation. When surgery is performed on cyanotic infants, standard CPB is usually initiated at a high concentration of oxygen without consideration of cytotoxic effects. Controlled reoxygenation is defined as using normoxic CPB with a pump primed to the PO2 (oxygen tension in the blood), which is matched to the patient's preoperative saturation. The aim of this study was to determine whether controlled reoxygenation could avoid standard reoxygenation injury and also to clarify the molecular signaling pathways during hypoxia. We successfully reproduced the abnormal brain observed in mice with chronic hypoxia during early postnatal development - equivalent to the third trimester in human. Mice were treated with standard reoxygenation and controlled reoxygenation after hypoxia for 24 h. We then assessed the brain tissue of these mice. In standard reoxygenation-treated hypoxia mice, the caspase-3-dependent neuronal apoptosis was enhanced by increasing concentration of oxygen. Interestingly, controlled reoxygenation inhibited neuron and glial cell apoptosis through suppressing cleavage of caspase-3 and PARP. We also found that controlled reoxygenation suppressed LCN2 expression and inflammatory cytokine (including TNF-α, IL-6, and CXCL10) production, in which the JAK2/STAT3 signaling pathway might participate. In conclusion, our findings propose the novel therapeutic potential of controlled reoxygenation on CPB during CHD.

Median effective dose of intranasal dexmedetomidine sedation for transthoracic echocardiography examination in postcardiac surgery and normal children: An up-and-down sequential allocation trial.

BACKGROUND: Dexmedetomidine (DEX) has been used for sedation in young infants and children undergoing transthoracic echocardiography (TTE). The median effective dose of intranasal DEX has not been described for postcardiac surgery children. Postcardiac surgery children could require more DEX to achieve satisfactory sedation for TTE examination than children suspected of congenital heart disease. OBJECTIVES: To study whether postcardiac surgery children need a larger dose of DEX for TTE than normal children. DESIGN: A double-blind sequential allocation trial with doses determined by the Dixon and Massey up-and-down method. SETTING: A tertiary care teaching hospital from 25 October to 30 November 2016. PATIENTS: Children under the age of 3 years requiring intranasal DEX for TTE. INTERVENTIONS: Children were allocated to a postcardiac surgery group (n = 20) or a normal group (n = 19). The first patient in both groups received intranasal DEX (2 µg kg): using the up-and-down method of Dixon and Massey, the next dose was dependent on the previous patient's response. MAIN OUTCOME MEASURES: Median effective dose was estimated from the up-and-down method of Dixon and Massey and probit regression. A second objective was to study haemodynamic stability and adverse events with these doses. RESULTS: The median effective dose (95% confidence interval) of intranasal DEX was higher in postcardiac surgery children than in normal children, 3.3 (2.72 to 3.78) µg kg versus 1.8 (1.71 to 2.04) (µg kg), respectively (P < 0.05). There were no significant differences in time to sedation, time to wake-up or TTE examination time between the two groups for successful sedation. Additionally, there were no significant adverse events. CONCLUSION: The median effective dose of intranasal DEX for TTE sedation in postcardiac surgery children was higher than in normal children. TRIAL REGISTRATION: chictr.org.cn identifier: ChiCTR-OOC-16009846.

[Effect of propofol on apoptosis of PC12 cells under hypoxic condition and the mechanism].

OBJECTIVE: To investigate the mechanism by which propofol exposure causes PC12 cell apoptosis under hypoxic conditions. METHODS: PC12 cells were exposed to room air, 35% oxygen, or 5% oxygen (hypoxia) for 24 h in the presence of either 10 µmol/L lipid emulsion or 10 µmol/L propofol. After the treatments, the cell apoptosis was measured by flow ceytometry, and the level of reactive oxygen species (ROS) and the activity of superoxide dismutase (SOD) were evaluated. RESULTS: In room air, PC12 cells treated with propofol showed increased apoptosis rate and ROS production as compared with the cells treated with the lipid emulsion; propofol treatment of the cells exposed to 35% oxygen showed obvious enhancement of the apoptosis rate, ROS production and SOD activity. Under the hypoxic condition, propofol treatment even further increased the apoptosis rate, ROS production and SOD activity. Lipid emulsion caused no such changes in cells exposed to room air, 35% oxygen or 5% oxygen. CONCLUSION: Under hypoxic conditions, propofol can cause apoptosis in PC12 cells by inducing oxidative stress injury.

IGF-1 reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt and MAPK/ERK1/2 signaling pathways.

Insulin-like growth factor 1 (IGF-1) stimulates α-secretase processing of amyloid precursor protein (APP) and decreases Aß production. Little is known about the relationship between IGF-1 and ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1), the protease essential for the production of ß-amyloid peptides (Aß). Here, we investigated the effect of IGF-1 on BACE-1 in PC12 cells. Quantitative polymerase chain reaction analysis and western blot showed that treatment of cells with IGF-1 significantly decreased the levels of BACE-1 mRNA and protein. Furthermore, IGF-1 increased the phosphorylation of Akt and ERK1/2. The presence of the phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 and the mitogen-activated protein kinase kinases (MEK) inhibitor PD98059 blocked the effect of IGF-1 on BACE-1. Our data indicated that IGF-1-induced reduction of BACE-1 might involve the PI3-K/Akt and MAPK/ERK1/2 signaling pathways.

REG gamma: a potential marker in breast cancer and effect on cell cycle and proliferation of breast cancer cell.

To investigate the expression and significance of proteasomes reactivator REG gamma (γ) in breast cancer. First, we showed the expression of REGγ in breast cancer, metastatic lymph nodes and normal breast tissues. Meanwhile, we also analyzed the relationship between REGγ and estrogen receptor (ER), CerBb-2, lymph nodes metastasis and clinical stage of breast cancer. REGγ expression was determined by immunohistochemical staining and western blot. Secondly, we detected the expression of REGγ and REGγ-mRNA in human breast cancer cell lines (MDA-MB-231, MCF-7) and human breast ductal epithelial cell line (HBL-100) by western blot and real-time PCR. Finally, in order to identify effect of REGγ on breast cancer cell cycle and proliferation, we constructed recombinant plasmid of PcDNA3.1-REGγ and designed siRNA for REGγ in vitro. Cell cycle was assayed by flow cytometer (FCM), proliferation was measured by methyl thiazolyl tetrazolium (MTT). The results demonstrated abnormal high expression of REGγ in breast cancer and its metastatic lymph nodes. REGγ expression was related to breast cancer and its status of ER, CerBb-2 and lymph nodes metastasis. REGγ is one of the potential markers in breast cancer. REGγ could facilitate the growth of breast cancer cells.

Hydrogen sulfide reduces mRNA and protein levels of ß-site amyloid precursor protein cleaving enzyme 1 in PC12 cells.

Hydrogen sulfide (H(2)S) is now identified as a new neuromodulator. Increasing evidence suggest that H(2)S may play an important role in the progression of Alzheimer's disease (AD). The aim of the present study is to investigate the effects of H(2)S on beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) expression and amyloid beta (Aß) secretion in PC12 cells. The levels of BACE-1 mRNA were measured by quantitative polymerase chain reaction analysis. BACE-1 protein levels were assessed by Western blot. Cellular culture medium levels of Aß1-42 were analyzed by ELISA. We found that sodium hydrosulfide (NaHS), a H(2)S donor, decreased BACE-1 mRNA and protein levels and Aß1-42 release. Furthermore, NaHS promoted the phosphorylation of Akt and ERK but not JNK or p38 MAPK. However, the effects of NaHS on BACE-1 expression and Aß1-42 secretion were abolished by inhibitors of phosphatidylinositol 3-kinase (PI3-K), but not of mitogen-activated protein kinase kinases (MEK). Our data indicate that H(2)S reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt signaling pathways. H(2)S releasing drugs may have therapeutic potential in AD patients.