Remote liver ischemic preconditioning protects against renal ischemia/reperfusion injury via phosphorylation of extracellular signal-regulated kinases 1 and 2 in mice.

Perioperative acute kidney injury (AKI), which is mainly mediated by renal ischemia‒reperfusion (I/R) injury, is commonly observed in clinical practice. However, effective measures for preventing and treating this perioperative complication are still lacking in the clinic. Thus, we designed this study to examine whether remote liver ischemic preconditioning (RLIPC) has a protective effect on damage caused by renal I/R injury. In a rodent model, 30 mice were divided into five groups to assess the effects of RLIPC and ERK1/2 inhibition on AKI. The groups included the sham-operated (sham), kidney ischemia and reperfusion (CON), remote liver ischemic preconditioning (RLIPC), CON with the ERK1/2 inhibitor U0126 (CON+U0126), and RLIPC with U0126 (RLIPC+U0126). RLIPC consisted of 4 liver ischemia cycles before renal ischemia. Renal function and injury were assessed through biochemical assays, histology, cell apoptosis and protein phosphorylation analysis. RLIPC significantly mitigated renal dysfunction, tissue damage, inflammation, and apoptosis caused by I/R, which was associated with ERK1/2 phosphorylation. Furthermore, ERK1/2 inhibition with U0126 negated the protective effects of RLIPC and exacerbated renal injury. To summarize, we demonstrated that RLIPC has a strong renoprotective effect on kidneys post I/R injury and that this effect may be mediated by phosphorylation of ERK1/2.

Prehabilitation of surgical patients: a bibliometric analysis from 2005 to 2023.

BACKGROUND: Good preoperative conditions help patients to counteract surgical injury. Prehabilitation is a multimodal preoperative management strategy, including physical, nutritional, psychological, and other interventions, which can improve the functional reserve of patients and enhance postoperative recovery. The purpose of this study is to show the evolution trend and future directions of research related to the prehabilitation of surgical patients. METHODS: The global literature regarding prehabilitation was identified from The Web of Science Core Collection database. Bibliometric methods of the Bibliometrix package of R (version 4.2.1) and VOSviewer were used to analyze publication trends, cooperative networks, study themes, and co-citation relationships in the field. RESULTS: A total of 638 publications were included and the number of publications increased rapidly since 2016, with an average annual growth rate of 41.0%. "Annals of Surgery", "British Journal of Surgery" and "British Journal of Anesthesia" were the most cited journals. Experts from the USA, Canada, the UK, and the Netherlands contributed the most in this field, and an initial cooperative network among different countries and clinical teams was formed. Malnutrition, older patients, frailty, and high-risk patients were the hotspots of recent studies. However, among the top 10 cited articles, the clinical effects of prehabilitation were conflicting. CONCLUSION: This bibliometric review summarized the most influential publications as well as the publication trends and clarified the progress and future directions of prehabilitation, which could serve as a guide for developing evidence-based practices.

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.

Anesthesia management for a child with the Koolen-de Vries syndrome: a case report.

BACKGROUND: The Koolen-de Vries syndrome (KdVS) is a relatively new rare disease caused by micro-deletion of 17q21.31 which was first reported by Koolen in 2006. Typical phenotypes for KdVS include hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Up to now, there was only one case report about anesthesia management of patient diagnosed KdVS. It was a 2-year-old girl who experienced an MRI exam under anesthesia. CASE PRESENTATION: We described a 21-month-old boy who planned to undergo an orchidopexy under general anesthesia diagnosed with KdVS. He had an intellectual disability, characteristic facial dysmorphism, tracheo/laryngomalacia, patent foramen ovale, and cryptorchidism related to KdVS. Due to the complex condition especially the presence of tracheo/laryngomalacia, we took some special measures, including reducing the amount of long-acting opioid, keeping the spontaneous breath, performing a caudal block, and applying the laryngeal mask. But the laryngeal mask was changed to an endotracheal tube because it failed to provide adequate ventilation. The boy experienced mild laryngeal spasm and hypoxia after extubation, but lateral position and etomidate eased his breathing problem and re-intubation was avoided. It is indicated that anesthesia management for patients with orphan disease is a real challenge for all anesthesia providers. CONCLUSIONS: The Koolen-de Vries syndrome is a relatively new orphan disease involving multiple systems. Keeping spontaneous breath, evaluating airway potency to anesthetics, applying endotracheal tube, and post-extubation lateral or prone position may be helpful for airway management for patient with hypotonia and tracheo/laryngomalacia. KdVS patient needs prolonged post-anesthesia monitoring and/or medication for airway complications.

Current perioperative nociception monitoring and potential directions.

Perioperative nociception-antinociception balance is essential for the prevention of adverse postoperative events. Estimating the nociception level helps optimize intraoperative management. In the past two decades, various nociception monitoring devices have been developed for the identification of intraoperative nociception. However, each type of nociception monitoring device has advantages and disadvantages, limiting their clinical application in particular patients and settings. Therefore, this review aimed to summarize the information on nociceptor monitoring in current clinical settings, explore each technique's particularities, and possible future directions to provide a reference for clinicians and researchers.

A case of tricuspid valve stenosis after pacemaker implantation with infective endocarditis.

A 68-year-old male patient was admitted for extremities edema and diagnosed with infective endocarditis (IEIE). The patient underwent mitral and aortic valve mechanical valve replacement due to rheumatic heart valve disease 26 years ago. He underwent mechanical aortic valve and bioprosthetic tricuspid valve replacement due to mechanical aortic valve dysfunction and severe tricuspid valve regurgitation 1 year ago. Two months ago, the patient underwent emergency permanent pacemaker implantation due to syncope caused by a third-degree atrioventricular block. The patient was admitted to the emergency with fever and worsening dyspnea 1 h ago. Transthoracic echocardiography revealed prosthetic aortic valve severe paravalvular leak and tricuspid valve stenosis with vegetation. The patient was scheduled to undergo mechanical aortic valve and bioprosthetic tricuspid valve replacement under median thoracotomy. The intraoperative transesophageal echocardiography (TEE) view showed severe paravalvular aortic valve leakage and tricuspid valve vegetation. The coronary sinus was significantly enlarged with thrombus formation, vegetation can be seen in the bioprosthetic tricuspid valve leaflets. This is a rare case of infective endocarditis with tricuspid stenosis and coronary sinus thrombosis after the placement of implanted pacemakers.

Comparison of S-ketamine and midazolam for intravenous preoperative sedative and anxiolytic effects in preschool children: study protocol for a randomized controlled clinical trial.

BACKGROUND: Preoperative anxiety management is gaining particular attention in paediatric anaesthesia. Pharmacological and non-pharmacological resorts can be implemented to address this special issue. Despite the various approaches currently used for preoperative sedation in children, the different sedative and anti-anxiety effects between the newly marketed anaesthetic, S-ketamine, and the traditional sedative, midazolam, are still unclear. METHODS: This is a patient- and assessor-blinded randomized controlled clinical trial. Participants (n = 110) will receive S-ketamine (0.5 mg/kg) or midazolam (0.08 mg/kg) intravenously administrated at a ratio of 1:1 in the anaesthesia holding area. The primary outcome of this study is the sedative effect evaluated via the change in the modified Yale preoperative anxiety scale. It will be performed at two timepoints: in the pre-anaesthetic holding area before premedication (baseline, marked as T0) and about 5 min after premedication in the operating room without the existence of their guardians (marked as T1). Our secondary objectives include the parent separation anxiety score, postoperative agitation, caregivers' and anaesthesia care providers' satisfaction, and mask compliance. DISCUSSION: This randomized controlled trial is the first study to compare the anti-anxiety effect of intravenous S-ketamine and midazolam. We will provide a new approach for the clinical management of preoperative anxiety in preschool children posted for elective surgery. TRIAL REGISTRATION: ChiCTR2300069998. Registered on 30 March 2023.

Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C.

Malignant hyperthermia (MH) is an inherited skeletal muscle disorder caused primarily by a genetic mutation, usually in the calcium channel gene of the muscle. This mutation can lead to muscle hypersensitivity to volatile anesthetics (such as sevoflurane) and the depolarizing muscle relaxant succinylcholine, resulting in hyperthermia, muscle stiffness, metabolic disturbances, and other severe physiological reactions. This condition may prove fatal unless it is recognized in its early stages and treatment is administered promptly and aggressively. We report a 13-year-old adolescent who underwent laparoscopic appendectomy and developed MH after the use of inhalational anesthetics, manifested by unremitting hyperthermia with a maximum temperature of 44.2°C, muscle rigidity, tachycardia, hypercapnia; and malignant arrhythmias, cardiogenic shock, hyperkalemia, metabolic, and respiratory acidosis. After early and timely recognition, multidisciplinary management and administration of dantrolene, the case was successfully treated. Exome sequencing revealed a point mutation (amino acid change) on the RYR1 gene: c.12700G>C(p.Val4234Leu). Due to the lack of ready-made dantrolene in our hospital, the patient in this case received dantrolene treatment only 6 h after the first observation of high body temperature. We review the development of the disease and summarize the success of treatment and what can be done to improve the chances of saving the patient's life if dantrolene is not available in time.

Abnormal phosphorylation of protein tyrosine in neurodegenerative diseases.

Neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis, are chronic disorders of the CNS that are characterized by progressive neuronal dysfunction. These diseases have diverse clinical and pathological features and their pathogenetic mechanisms are not yet fully understood. Currently, widely accepted hypotheses include the accumulation of misfolded proteins, oxidative stress from reactive oxygen species, mitochondrial dysfunction, DNA damage, neurotrophin dysfunction, and neuroinflammatory processes. In the CNS of patients with neurodegenerative diseases, a variety of abnormally phosphorylated proteins play important roles in pathological processes such as neuroinflammation and intracellular accumulation of ß-amyloid plaques and tau. In recent years, the roles of abnormal tyrosine phosphorylation of intracellular signaling molecules regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) in neurodegenerative diseases have attracted increasing attention. Here, we summarize the roles of signaling pathways related to protein tyrosine phosphorylation in the pathogenesis of neurodegenerative diseases and the progress of therapeutic studies targeting PTKs and PTPs that provide theoretical support for future studies on therapeutic strategies for these devastating and important neurodegenerative diseases.

Attention to pulmonary arteriovenous fistula in a case of transient hypoxemia and cerebral infarction during pregnancy: a case report and literature review.

BACKGROUND: Pulmonary arteriovenous fistula is rare during pregnancy. Pulmonary arteriovenous fistula presents no pulmonary symptoms in most patients but can be exacerbated by pregnancy. If not diagnosed and treated promptly, pulmonary arteriovenous fistula can lead to respiratory failure, stroke, spontaneous hemothorax, or other fatal complications. CASE PRESENTATION: A 29-year-old healthy pregnant woman presented with a transient drop in blood oxygen level of unknown cause during a routine examination at 34 weeks of gestation and during a cesarean section at 38 weeks of pregnancy. The patient's oxygen saturation quickly returned to normal and was not further investigated. On day 3 postpartum, the patient suddenly displayed slurred speech and right limb myasthenia. A head magnetic resonance imaging revealed cerebral infarction in the left basal ganglia. Subsequent computed tomography pulmonary arteriography revealed bilateral pulmonary arteriovenous fistula, which was likely the cause of cerebral infarction. The patient was transferred to the Department of Thoracic Surgery after one month of treatment and successfully underwent percutaneous embolization of pulmonary arteriovenous fistula. CONCLUSION: Pulmonary arteriovenous fistula should not be neglected if a pregnant woman presents with transient hypoxemia and cerebral infarction. A transient decrease in pulse oxygen saturation that cannot be explained by common clinical causes can be an early warning sign of the disease. Early diagnosis and multidisciplinary management could improve the prognosis.

Safety and feasibility of ultrasound-guided serratus anterior plane block and intercostal nerve block for management of post-sternotomy pain in pediatric cardiac patients: A prospective, randomized trial.

BACKGROUND: Postoperative analgesia in the cardiothoracic ICU has traditionally relied on intravenous opioids. Thoracic nerve blocks are attractive alternatives for analgesia that reduce the requirement for opioids, but their safety and feasibility remain unclear. METHODS: Sixty children were allocated randomly to three groups: group C received intravenous opioids alone, while group SAPB (deep serratus anterior plane block) and group ICNB (intercostal nerve block) received opioids combined with ultrasound-guided regional nerve blocks (0.2% ropivacaine 2.5 mg.kg-1) after patients were transferred to the ICU. The primary outcome was opioid requirement in the first 24 h after surgery. Other outcomes included the postoperative FLACC scale value, tracheal extubation time, and plasma ropivacaine concentrations after the block. RESULTS: The mean [sd] cumulative dose of opioids administered postoperatively within 24 h in the SAPB (168.6 [76.9] µg.kg-1) and ICNB groups (170.0 [86.8] µg.kg-1) were significantly lower by nearly 53% than those in group C (359.3 [125.3] µg.kg-1, p = 0.000). The tracheal extubation time was shorter in the regional block groups than that in the control group, but the difference was not statistically significant (p = 0.177). The FLACC scale values at 0, 1, 3, 6, 12, and 24 h post-extubation were similar in the three groups. The mean peak plasma ropivacaine concentrations in the SAP and ICNB groups were 2.1 [0.8] and 1.8 [0.7] mg.L-1, respectively, 10 min post-block and then slowly decreased. No noticeable complications associated with regional anesthesia were observed. CONCLUSIONS: Ultrasound-guided SAPB and ICNB provided safe and satisfactory early postoperative analgesia while reducing opioid consumption following sternotomy in pediatric patients. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiChiCTR2100046754.

Complications and related risk factors of transradial access cannulation for hemodynamic monitoring in general surgery: a prospective observational study.

PURPOSE: To examine the short-term complications of arterial cannulation for intraoperative monitoring and their related risk factors. METHODS: We included adult inpatients (≥ 18 years old) who underwent an initial transradial access (TRA) cannulation and were scheduled for general surgery between April 8 and November 30, 2020. We used 20G arterial puncture needles for puncturing and manual compression for hemostasis. Demographic, clinical, surgical, anesthetic, and laboratory data were extracted from electronic medical records. Vascular, neurologic, and infectious complications of TRA cannulation were recorded and analyzed. Logistic regression analyses were used to identify risk factors related to TRA cannulation for intraoperative monitoring. RESULTS: Among 509 included patients, 174 developed TRA cannulation-related complications. Puncture site bleeding/hematoma and median nerve injury were observed in 158 (31.0%) and 16 (3.1%) patients, respectively. No patient developed cannula-related infections. Logistic regression analysis revealed increased odds of puncture site bleeding/hematoma in women (odds ratio 4.49, 95% CI 2.73-7.36; P < 0.001) and patients who received intraoperative red blood cell (RBC) suspension transfusion ≥ 4U (odds ratio 5.26, 95% CI 1.41-19.57; P = 0.01). No risk factors for nerve injury were identified. CONCLUSION: Bleeding/hematoma were a common complication of TRA cannulation for intraoperative hemodynamic monitoring during general surgery. Median nerve injury may be an under recognized complication. Female sex and extensive intraoperative RBC transfusion are associated with an increased risk of bleeding/hematoma; however, the risk factors for nerve injury remain unclear. TRIAL REGISTRATION: The study protocol was registered at https://www.chictr.org.cn (ChiCTR1900025140).

Single-injection serratus anterior plane block for cardiothoracic surgery via thoracotomy in children: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Serratus anterior plane block (SAPB) has gained popularity in cardiothoracic surgery due to its feasibility and simplicity. However, the efficacy of ultrasound-guided single-injection SAPB in the paediatric population has not been well evaluated, as only a few studies with small sample sizes are available. METHODS: We searched PubMed, Embase (Ovid), Cochrane Central Register of Controlled Trials, Wanfang databases and China National Knowledge Infrastructure from their inception to 31 September 2022 for randomised comparative clinical trials that compared single-injection SAPB with systemic analgesia or different forms of regional analgesia in children. The primary outcomes included postoperative opioid consumption and pain scores within 24 hours. The secondary outcomes included postoperative adverse events, the need for rescue analgesia and the time from the end of surgery to endotracheal tube removal. RESULTS: Five randomised controlled trials with 418 children meeting the inclusion criteria were included. SAPB markedly reduced postoperative opioid consumption up to 24 hours compared with controls (mean difference (MD): -0.29 mg/kg, 95% CI -0.38 to -0.20, I 2 =67%]. The postoperative pain scores were reduced compared with controls: 1 hour (MD -0.6, 95% CI -1.17 to -0.04, I 2 =92%), 4-6 hours (MD -1.16, 95% CI -1.87 to -0.45, I 2 =90%) and 12 hours (MD -0.71, 95% CI -1.35 to -0.08, I 2 =86%). The incidence of postoperative nausea and vomiting was comparable between SAPB and controls. One trial suggested that the analgesic effect of SAPB was comparable to that of ICNB (intercostal nerve block). CONCLUSION: Single-injection SAPB is associated with a reduction in opioid consumption and pain intensity after cardiothoracic surgery via thoracotomy in children. Due to the high heterogeneity, the Grading of Recommendations Assessment, Development and Evaluation scores were low. Clinical trials with rigorous methodological approaches as well as safety endpoints are needed to confirm these preliminary findings. PROSPERO REGISTRATION NUMBER: CRD42021241691.

Role of the Voltage-Gated Proton Channel Hv1 in Nervous Systems.

Hv1 is the only voltage-gated proton-selective channel in mammalian cells. It contains a conserved voltage-sensor domain, shared by a large class of voltage-gated ion channels, but lacks a pore domain. Its primary role is to extrude protons from the cytoplasm upon pH reduction and membrane depolarization. The best-known function of Hv1 is the regulation of cytosolic pH and the nicotinamide adenine dinucleotide phosphate oxidase-dependent production of reactive oxygen species. Accumulating evidence indicates that Hv1 is expressed in nervous systems, in addition to immune cells and others. Here, we summarize the molecular properties, distribution, and physiological functions of Hv1 in the peripheral and central nervous systems. We describe the recently discovered functions of Hv1 in various neurological diseases, including brain or spinal cord injury, ischemic stroke, demyelinating diseases, and pain. We also summarize the current advances in the discovery and application of Hv1-targeted small molecules in neurological diseases. Finally, we discuss the current limitations of our understanding of Hv1 and suggest future research directions.

Disrupting cortical astrocyte Ca2+ signaling in developing brain induces social deficits and depressive-like behaviors.

Astrocytes are present throughout the central nervous system and display complex intracellular Ca2+ signals. However, it is largely unknown regarding how astrocytic Ca2+ signals regulate neural microcircuits in developing brain and mammalian behavior in vivo. In this study, we specifically overexpressed the plasma membrane calcium-transporting ATPase2 (PMCA2) of cortical astrocytes and used immunohistochemistry, Ca2+ imaging, electrophysiology, and behavioral tests to investigate the effects of genetically reducing cortical astrocyte Ca2+ signaling during a critical developmental period in vivo. We found that reducing cortical astrocyte Ca2+ signaling during development led to social interaction deficits, depressive-like behaviors, and abnormal synaptic structure and transmission. In addition, restoring cortical astrocyte Ca2+ signaling using chemogenetic activation of Gq-coupled designer receptors exclusively activated by designer drugs rescued these synaptic and behavioral deficits. Together, our data demonstrate that the integrity of cortical astrocyte Ca2+ signaling in developing mice is critical for neural circuit development and may be involved in the pathogenesis of developmental neuropsychiatric diseases, such as autism spectrum disorders and depression.

Pharmacotherapy for improving postoperative sleep quality: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Improving the quality of sleep may promote enhanced recovery in surgical patients. In addition to controversial or conflicting study conclusions, the current clinical studies on pharmacotherapy for improving postoperative sleep quality are mostly limited to evaluating the effect of a specific drug or supplement compared with placebo, and they lack comparisons between drugs or supplements. Therefore, we plan to conduct a systematic review and network meta-analysis to compare the efficacy of different drugs or supplements for improving postoperative sleep quality. METHODS AND ANALYSIS: We will search the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CNKI and Wanfang databases from the dates of their inception to December 2022. We will only include randomised controlled trials, irrespective of language and publication status. The primary outcome is postoperative sleep quality assessed by any validated tools or polysomnography. We will assess the quality of all included trials according to version 2 of the Cochrane risk-of-bias tool for randomised trials. We will use the GeMTC package of R software to perform direct and indirect comparisons via a Bayesian framework using a random-effects model. We will use the Confidence in Network Meta-Analysis approach to evaluate the quality of evidence. ETHICS AND DISSEMINATION: Ethical approval is not required for this protocol because we will only be pooling published data. We plan to submit our review to academic conferences and peer-reviewed academic journals. PROSPERO REGISTRATION NUMBER: CRD42022356508.

Effectiveness of Sufentanil-Based Patient-Controlled Analgesia Regimen in Children and Incidence of Adverse Events Following Major Congenital Structure Repairs.

The aim of this study was to evaluate postoperative analgesia effectiveness and patient-controlled analgesia (PCA)-related adverse events. The children who received sufentanil-based PCA following major surgery to repair congenital hip dislocation and hypospadias were divided into 3 groups: sufentanil 4 µg/kg + tramadol 10 mg/kg (ST; n = 301), sufentanil 4 µg/kg (S4; n = 211), and sufentanil 5 µg/kg (S5; n = 451). Analgesics with granisetron 0.2 mg/kg were diluted in 0.9% saline to 100 mL and infused continuously at a basal infusion rate of 1 mL/h. A total of 963 children whose average age was 4 years were investigated. The incidence of moderate to severe postoperative pain during rest was significantly lower in the S5 group (0.2%) and ST group (0.3%) compared with the S4 group (3.3%) within 72 hours after surgery (P < .05), and the incidence of moderate to severe pain during activity within 72 hours was also significantly lower in the S5 group (3.5%) compared with the other 2 groups (ST, 21.9%; S4, 33.2%; P < .001). A significant difference was identified among the 3 groups in the total number of PCA administrations, but there was no statistical difference of total usage of opioids among the 3 groups. In terms of PCA-related adverse events, the incidence of postoperative nausea and vomiting in the S5 group was lower compared with the ST group within 72 hours after surgery (P < .001), and there was no significant difference compared with the S4 group (P = .254). There was also no significant difference in the incidence of pruritus and dizziness among the 3 groups. Sufentanil-based PCA can be effectively and safely used in children after major congenital structural malformation repair surgeries. The sufentanil 5 µg/kg dosage in the PCA regimen is superior to sufentanil 4 µg/kg alone or combined with tramadol in lowering moderate to severe pain.

Design, Synthesis, and Biological Evaluation of a Potent Dual EZH2-BRD4 Inhibitor for the Treatment of Some Solid Tumors.

Enhancer of zeste homolog 2 (EZH2) mediates the trimethylation of histone 3 lysine 27 (H3K27) to promote gene silencing. Inhibition of EZH2 is a viable strategy for cancer treatment; however, only a small subset of hematological malignancies are sensitive to small-molecule EZH2 inhibitors. EZH2 inhibitors cause H3K27 acetylation in most solid tumors, leading to drug resistance. Bromodomain-containing protein 4 (BRD4) inhibitors were reported to enhance the sensitivity of solid tumors to EZH2 inhibitors. Thus, we designed and evaluated a series of dual EZH2-BRD4 inhibitors. ZLD-2, the most promising compound, exhibited potent inhibitory activity against EZH2 and BRD4. Compared to the EZH2 inhibitor GSK126, ZLD-2 displayed potent antiproliferation activity against breast, lung, bladder, and pancreatic cancer cells. In vivo, ZLD-2 exhibited antitumor activity in a BxPC-3 mouse xenograft model, whereas GSK126 promoted tumor growth. Thus, ZLD-2 may be a lead compound for treating solid tumors.

Routine administration of neostigmine after recovery of spontaneous breathing versus neuromuscular monitor-guided administration of neostigmine in pediatric patients: a parallel, randomized, controlled study.

BACKGROUND: Neostigmine used to reverse the muscle relaxants should be guided by neuromuscular monitoring, as the degree of spontaneous pre-reversal recovery is the key to success to reverse the neuromuscular block. But neuromuscular monitoring is not always available for some patients during anesthesia and, in consequence, we need to use other clinical judgment to guide the use of neostigmine to reverse the neuromuscular block. In this trial, we aimed to evaluate the incidence of residual neuromuscular blockade (rNMB) in pediatric patients with routine use of neostigmine after recovery of spontaneous breathing compared with the patients with the use of neostigmine guided by neuromuscular monitoring. METHODS: A parallel, randomized, controlled noninferiority study was conducted. We enrolled aged 3 months to 12 years old patients who underwent inguinal hernia repair under general anesthesia. The enrolled patients were randomly divided into experimental and control groups. After surgery, children in the experimental group were given 0.02 mg/kg neostigmine after recovery of spontaneous breathing. Children in the control group were given 0.02 mg/kg neostigmine when the train-of-four (TOF) ratio was between 0.4 and 0.9. However, no neostigmine was administered if the TOF ratio was higher than 0.9. The primary outcome was the incidence of rNMB after extubation (TOF ratio < 0.9). Secondary outcomes included the incidence of neostigmine-induced muscle paralysis, end of surgery - extubation interval, end of surgery - exit OR interval, the length of stay in the PACU, the incidence of hypoxia in the PACU, the number of children who required assisted ventilation during the PACU stay, and neostigmine-related adverse events. RESULTS: A total of 120 children were included in this study, with 60 in the experimental group and 60 in the control group. There was no significant difference in the incidence of rNMB after extubation between the groups (45/60 vs 44/60, RR 1.02 [95% CI, 0.83 to 1.26], p = 0.84). There was no neostigmine-induced muscle paralysis in either group. Adverse events were similar occurred in both groups. However, time from end of the surgery to leaving the operating room was earlier in the experimental group than in the control group (13.6 ± 5.2 vs 15.7 ± 5.6 min, MD -2.10 min [95% CI, -3.70 to -0.50], p = 0.04). The risk ratio of the incidence of TOF ratio < 0.3 for the experimental group was 31.12 (95%CI, 1.89 to 512.61) compared with the control group (12/60 vs 0/60, p = 0.00) in exploratory analysis. CONCLUSIONS: Recovery of spontaneous breathing could be used as a substitute of neuromuscular monitoring to guide neostigmine use in pediatric patients following minor surgeries. However, care should be taken for the residual neuromuscular block. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-17012890. Registered on 5 October 2017.