Pediatric anesthesia in China.

In China, healthcare has lagged relative to its economic boom during the past 40 years. While the top tier hospitals offer pediatric perioperative care like high-income countries, lower-tier hospitals deliver lesser services of variable quality and safety related to equipment, supplies, clinician education, and availability. The national residency training program and the pediatric anesthesia fellowship program was established in 2013 and 2018 respectively. Increasing clinician workload from patient demand and a lack of consistency in quality and capability between rural and urban areas remain challenging.

Ketamine modulates neural stem cell differentiation by regulating TRPC3 expression through the GSK3ß/ß-catenin pathway.

Ketamine, a popular anesthetic, is often abused by people for its hallucinogenic effect. Thus, the safety of ketamine in pediatric populations has been called into question for potential neurotoxic effects. However, ketamine also has neuroprotective effects in many brain injury models. The differentiation of neural stem cells (NSCs) was influenced significantly by ketamine, but the molecular mechanism is still unclear. NSCs were extracted from the hippocampi of postnatal day 1 rats and treated with ketamine to induce NSCs differentiation. Our results found that ketamine promoted neuronal differentiation of NSCs dose-dependently in a small dose range (P < 0.001). The main types of neurons from NSCs were cholinergic (51 ± 4 %; 95 % CI: 41-61 %) and glutamatergic neurons (34 ± 3 %; 95 % CI: 27-42 %). Furthermore, we performed RNA sequencing to promise a more comprehensive understanding of the molecules regulated by ketamine. Finally, we combined bioimaging and multiple molecular biology techniques to clarify that ketamine influences NSC differentiation by regulating transient receptor potential canonical 3 (TRPC3) expressions. Ketamine dramatically repressed TRPC3 expression (MD [95 % CI]=0.67 [0.40-0.95], P < 0.001) with a significant increase of phosphorylated glycogen synthase kinase 3ß (p-GSK3ß; MD [95 % CI]=1.00 [0.74-1.27], P < 0.001) and a decrease of ß-catenin protein expression (MD [95 % CI]=0.60 [0.32-0.89], P = 0.001), thereby promoting the differentiation of NSCs into neurons and inhibiting their differentiation into astrocytes. These results suggest that TRPC3 is necessary for ketamine to modulate NSC differentiation, which occurs partly via regulation of the GSK3ß/ß-catenin pathway.

Efficacy of different doses of intranasal dexmedetomidine in preventing emergence agitation in children with inhalational anaesthesia: A prospective randomised trial.

BACKGROUND: Emergence agitation is a common paediatric complication after inhalational anaesthesia. Intranasal dexmedetomidine can prevent emergence agitation effectively, but the optimal dose is uncertain. OBJECTIVE: The aim of our study was to investigate the 95% effective dose (ED 95 ) of intranasal dexmedetomidine for the prevention of emergence agitation after inhalational anaesthesia for paediatric ambulatory surgery. DESIGN: A prospective, randomised, placebo-controlled, double-blind, clinical trial. SETTING: The study was conducted in Guangzhou Women and Children's Medical Center in China from August 2017 to December 2018. PATIENTS: Three hundred and eighteen children scheduled for ambulatory surgery were enrolled into two age groups of less than 3 years and at least 3 years. INTERVENTIONS: The children in each age group were randomised into five equal subgroups to receive either intranasal dexmedetomidine 0.5, 1.0, 1.5 or 2.0 µg kg -1 (Groups D 0.5 , D 1.0 , D 1.5 and D 2.0 ), or intranasal isotonic saline (group C) after induction. MAIN OUTCOME MEASURES: The primary outcome was the ED 95 dose of intranasal dexmedetomidine for preventing emergence agitation after inhalational anaesthesia for paediatric ambulatory surgery. RESULTS: The incidences of emergence agitation for Groups C, D 0.5 , D 1.0 , D 1.5 and D 2.0 were 63, 40, 23, 13 and 3% in children less than 3 years, and 43, 27, 17, 7 and 3% in children at least 3 years. The ED 95 of intranasal dexmedetomidine for preventing emergence agitation was 1.99 µg kg -1 [95% confidence interval (CI), 1.83 to 3.80 µg kg -1 ] in children less than 3 years, and 1.78  µg kg -1 (95% CI, 0.93 to 4.29 µg kg -1 ) in children at least 3 years. LMA removal time for groups D 1.5 and D 2.0 was 9.6 ±â€Š2.2 and 9.7 ±â€Š2.5 min, respectively, for children less than 3 years, and 9.4 ±â€Š2.0 and 9.9 ±â€Š2.7 min in children at least 3 years, respectively. Length of stay in the postanaesthesia care unit for Groups D 1.5 and D 2.0 was 34.3 ±â€Š9.6 and 37.1 ±â€Š11.2 min, respectively, in children less than 3 years, and 34.7 ±â€Š10.2 and 37.3 ±â€Š8.3 min in children at least 3 years, respectively. These times were longer in the D 1.5 and D 2.0 subgroups than in the control subgroup in the two age groups of less than 3 years and at least 3 years, respectively: 7.2 ±â€Š1.9 min in children less than 3 years and 7.3 ±â€Š2.5 min in children at least 3 years for LMA removal time, 22.2 ±â€Š7.9 min in children less than 3 years and 22.0 ±â€Š7.7 min in children at least 3 years for PACU stay time in control subgroup, respectively ( P  < 0.05). CONCLUSION: Intranasal dexmedetomidine prevented emergence agitation after paediatric surgery in a dose-dependent manner. The optimal dose of intranasal dexmedetomidine for preventing emergence agitation was higher in younger children. TRIAL REGISTRY: chictr.org.cn: ChiCTR-IOR-17012415.

The impact of height on the spread of spinal anesthesia and stress response in parturients undergoing caesarean section: a prospective observational study.

BACKGROUND: The spread of spinal anesthesia was influenced by many factors, and the effect of body height on spinal anesthesia is still arguable. This study aimed to explore the impact of height on the spread of spinal anesthesia and the stress response in parturients. METHODS: A total of ninety-seven parturients were allocated into two groups according to their height: the shorter group (body height was shorter than 158 cm) and taller group (body height was taller than 165 cm). Spinal anesthesia was performed with the same amount of 12 mg plain ropivacaine in mothers of different heights. The primary outcome of the study was the success or failure of the spinal anesthesia. The secondary outcomes of the study were stress response, time to T6 sensory level, the incidence of hypotension, the satisfaction of abdominal muscle relaxation and patient VAS scores. RESULTS: The rate of successful spinal anesthesia in the shorter group was significantly higher than that in the taller group (p = 0.02). The increase of maternal cortisol level in the shorter group was lower than that in the taller group at skin closure (p = 0.001). The incidence of hypotension (p = 0.013), time to T6 sensory block (p = 0.005), the quality of abdominal muscle relaxation (p <  0.001), and VAS values in stretching abdominal muscles and uterine exteriorization (p <  0.001) in the shorter group were significantly different from those in the taller group. Multivariate analysis showed that vertebral column length (p <  0.001), abdominal girth (p = 0.022), amniotic fluid index (p = 0.022) were significantly associated with successful spinal anesthesia. CONCLUSIONS: It's difficult to use a single factor to predict the spread of spinal anesthesia. Patient's vertebral column length, amniotic fluid index and abdominal girth were the high determinant factors for predicting the spread of spinal anesthesia. TRIALS REGISTRATION: ChiCTR-ROC-17012030 ( Chictr.org.cn ), registered on 18/07/2017.

An improved automated zebrafish larva high-throughput imaging system.

As a typical multicellular model organism, the zebrafish has been increasingly used in biological research. Despite the efforts to develop automated zebrafish larva imaging systems, existing ones are still defective in terms of reliability and automation. This paper presents an improved zebrafish larva high-throughput imaging system, which makes improvements to the existing designs in the following aspects. Firstly, a single larva extraction strategy is developed to make larva loading more reliable. The aggregated larvae are identified, classified by their numbers and patterns, and separated by the aspiration pipette or water stream. Secondly, the dynamic model of larva motion in the capillary is established and an adaptive robust controller is designed for decelerating the fast-moving larva to ensure the survival rate. Thirdly, rotating the larva to the desired orientation is automated by developing an algorithm to estimate the larva's initial rotation angle. For validating the improved larva imaging system, a real-time heart rate monitoring experiment is conducted as an application example. Experimental results demonstrate that the goals of the improvements have been achieved. With these improvements, the improved zebrafish larva imaging system remarkably reduces human intervention and increases the efficiency and success/survival rates of larva imaging.

Activation of α2 adrenoceptor attenuates lipopolysaccharide-induced hepatic injury.

Sepsis induces hepatic injury but whether alpha-2 adrenoceptor (α2-AR) modulates the severity of sepsis-induced liver damage remains unclear. The present study used lipopolysaccharide (LPS) to induce hepatic injury and applied α2-AR agonist dexmedetomidine (DEX) and/or antagonist yohimbine to investigate the contribution of α2-AR in LPS-induced liver injury. Our results showed that LPS resulted in histological and functional abnormality of liver tissue (ALT and AST transaminases, lactate), higher mortality, an increase in proinflammatory cytokines (IL-1ß, IL-6 & TNF-α), as well as a change in oxidative stress (MDA, SOD). Activation of α2-AR by dexmedetomidine (DEX) attenuated LPS-induced deleterious effects on the liver and block of α2-AR by yohimbine aggravated LPS-induced liver damage. Our data suggest that α2-AR plays an important role in sepsis-induced liver damage and activation of α2-AR with DEX could be a novel therapeutic avenue to protect the liver against sepsis-induced injury.

Estimation of the minimum effective dose of tramadol for postoperative analgesia in infants using the continual reassessment method.

Tramadol is a potent analgesic. However, the analgesia efficacy of tramadol, particularly its minimum effective dose (MED), is not clear. The aim of this study is to find MED of tramadol for postoperative analgesia in infants. The continual reassessment method (CRM) was performed to find MED. Infants undergoing surgeries were included in the 3 phases of this series. In each phase, 24 participants were allocated a different tramadol dose. Pain intensity was measured by face, legs, activity, cry, consolability (FLACC) measurement at 3-hour intervals. Tramadol was considered ineffective if the FLACC score was higher than 4 in 10 at anytime. In phase 1, seven dose levels were used within the range 0.1-0.4 mg·kg(-1)·h(-1). Phase 1 was insufficient to identify the MED, and we increased the dose to 0.4-0.8 mg·kg(-1)·h(-1) in phase 2. Phase 2 was insufficient to identify the MED. In phase 3, local anesthetic wound infiltration was introduced, and the tramadol dose levels tested were the same as in phase 1. The successful analgesia probability of tramadol 0.4 mg·kg(-1)·h(-1) was 82.1% (95% CI, 0.742-0.925) in phase 1. In phase 2, it was 84.7% (95% CI, 0.789-0.991) with the dose 0.8 mg·kg(-1)·h(-1). Phase 1 and phase 2 were insufficient to identify the MED. In phase 3, the successful analgesia probability for dose 0.35 mg·kg(-1)·h(-1) was 96.7% (95% CI, 0.853-0.997).We have demonstrated that tramadol provides insufficient analgesia for surgeries considered to cause moderate-to-severe postoperative pain in infants if used as the sole analgesic, and that local anesthetic wound infiltration enhances the efficacy of tramadol.