Neuromuscular blocking agents and reversal agents

The neuromuscular junction consists of the motor nerve terminal, the synaptic cleft and post-synaptic nicotinic receptors on the motor end-plate of striated muscle. Neuromuscular blocking drugs are categorized into depolarizing and non-depolarizing agents. They are structurally related to acetylcholine (ACh), containing at least one positively charged quaternary ammonium radical that binds to the nicotinic receptor. Depolarizing agents (e.g. suxamethonium) act as agonists like ACh at the nicotinic receptor, but cause a more prolonged depolarization of the motor end-plate, thus rendering the ion channel insensitive to further action potentials. Non-depolarizing agents, in contrast, compete directly with ACh for nicotinic receptor binding sites and prevent neurotransmitter–receptor binding. These are either benzylisoquinoliniums (e.g. atracurium) or aminosteroids (e.g. rocuronium). Once recovery has commenced, neuromuscular block can be reversed with anticholinesterases (e.g. neostigmine). In contrast, the novel cyclodextrin sugammadex can be used to reverse any degree of neuromuscular block produced by rocuronium or vecuronium.     

Neuromuscular blocking agents and reversal agents

The neuromuscular junction consists of the motor nerve terminal, the synaptic cleft and post-synaptic nicotinic receptors on the motor end-plate of striated muscle. Neuromuscular blocking drugs are categorized into depolarizing and non-depolarizing agents. They are structurally related to acetylcholine (ACh), containing at least one positively charged quaternary ammonium radical that binds to the nicotinic receptor. Depolarizing agents (e.g. suxamethonium) act as agonists like ACh at the nicotinic receptor, but cause a more prolonged depolarization of the motor end-plate, thus rendering the ion channel insensitive to further action potentials. Non-depolarizing agents, in contrast, compete directly with ACh for nicotinic receptor binding sites and prevent neurotransmitter–receptor binding. These are either benzylisoquinoliniums (e.g. atracurium) or aminosteroids (e.g. rocuronium). Once recovery has commenced, neuromuscular block can be reversed with anticholinesterases (e.g. neostigmine). In contrast, the novel cyclodextrin sugammadex can be used to reverse any degree of neuromuscular block produced by rocuronium or vecuronium.     

Neuromuscular blocking agents and reversal agents

The neuromuscular junction consists of the motor nerve terminal, the synaptic cleft and post-synaptic nicotinic receptors on the motor endplate of striated muscle. Neuromuscular blocking drugs are categorized into depolarizing and non-depolarizing agents. They are structurally related to acetylcholine (ACh), containing at least one positively charged quaternary ammonium radical which binds to the nicotinic receptor. Depolarizing agents (e.g. suxamethonium) act as agonists like ACh at the nicotinic receptor, but cause a more prolonged depolarization of the motor end-plate, thus rendering the ion channel insensitive to further action potentials. Non-depolarizing agents, in contrast, compete directly with ACh for nicotinic receptor binding sites and prevent neurotransmitter–receptor binding. These are either benzylisoquinoliniums (e.g. atracurium) or aminosteroids (e.g. rocuronium). Neuromuscular block can be reversed once recovery has commenced with anticholinesterases (e.g. neostigmine). In contrast, the novel cyclodextrin sugammadex can be used to reverse any degree of neuromuscular block produced by rocuronium or vecuronium.     

抗骨吸收和促骨形成药物在骨质疏松症治疗中的联合应用

骨质疏松症是一种以骨量减少、骨组织细微结构受损,导致脆性骨折为特征的一种常见疾病。随着人类寿命延长和老年人口的增加,骨质疏松症患病率持续增高,且所致的疼痛和骨折严重影响患者的生活质量,故骨质疏松症的治疗非常重要。目前抗骨质疏松症药物的疗效和安全性比较明确,是防治骨质疏松症的主要手段,但临床上发现单药治疗作用有限,基于不同的作用机制,有学者提出抗骨质疏松症药物的联合治疗。本文针对抗骨质疏松症药物中的两类即抗骨吸收和促骨形成药物之间的联合应用进展做一综述。     

The principles of anaesthesia

The understanding and safety of anaesthesia has advanced significantly over the last two centuries, facilitating most of the surgical advances seen in this period. This article covers essential elements of both general and local anaesthetic agents, describing the anaesthetic triad, the component parts of a typical general anaesthetic, and adjunctive drugs and techniques.     

Bidirectional relationship between depression and erectile dysfunction

PURPOSE: We specified the interrelationship between depressive mood and erectile dysfunction. MATERIALS AND METHODS: The target population consisted of men who were 50, 60 or 70 years old and residing in the study area in Finland in 1994. Questionnaires were mailed to 3,143 men in 1994 and to 2,837 men 5 years later. The followup sample consisted of 1,683 men who responded to the baseline and followup questionnaires. RESULTS: Erectile dysfunction was strongly associated with untreated and treated depressive symptoms. The prevalence OR adjusted for potential confounders was 2.6 (95% CI 1.8-3.8) for untreated and 3.3 (95% CI 1.6-7.1) for treated depressive symptoms at the beginning of followup. The incidence of erectile dysfunction was 59/1,000 person-years (95% CI 39-90) in men with depressive mood and 37/1,000 person-years (95% CI 32-43) in those free of the disorder. Compared with men free of depressive symptoms who did not use medication for psychological disorders at study entry the adjusted incidence density ratio of erectile dysfunction was 4.5 (95% CI 2.2-9.2) in men with treated depressive symptoms and 1.2 (0.7-2.1) in those with untreated depressive symptoms. The incidence of depressive mood was 20/1,000 person-years in men with erectile dysfunction and 11/1,000 person-years in those free of erectile dysfunction. The adjusted incidence density ratio of depressive mood was 1.9 (95% CI 1.1-3.3) in men with erectile dysfunction compared with those free of it at entry. CONCLUSIONS: Moderate or severe depressive mood or antidepressant medication use may cause erectile dysfunction and erectile dysfunction independently may cause or exacerbate depressive mood.     

The principles of anaesthesia

The understanding and safety of anaesthesia has advanced significantly over the last two centuries, facilitating most of the surgical advances seen in this period. This article covers essential elements of both general and local anaesthetic agents, describing the anaesthetic triad, the component parts of a typical general anaesthetic, and adjunctive drugs and techniques.     

Anabolic and anticatabolic agents used in burn care: What is known and what is yet to be learned

Major thermal injury induces profound metabolic derangements secondary to an inflammatory “stress-induced” hormonal environment. Several pharmacological interventions have been tested in an effort to halt the hypermetabolic response to severe burns. Insulin, insulin growth factor 1, insulin growth factor binding protein 3, metformin, human growth hormone, thyroid hormones, testosterone, oxandrolone, and propranolol, among others, have been proposed to have anabolic or anticatabolic effects. The aim of this broad analysis of pharmacological interventions was to raise awareness of treatment options and to help establishing directions for future clinical research efforts. A PubMed search was conducted on the anabolic and anticatabolic agents used in burn care. One hundred and thirty-five human studies published between 1999 and 2017 were included in this review. The pharmacological properties, rationale for the treatments, efficacy considerations and side effect profiles are summarized in the article. Many of the drugs tested for investigational purposes in the severely thermally injured are not yet gold-standard therapies in spite of their potential benefit. Propranolol and oxandrolone have shown great promise but further evidence is still needed to clarify their potential use for anabolic and anticatabolic purposes.     

环孢霉素A对大鼠神经病理性痛的效应

目的 评价环孢霉素A对大鼠神经病理性痛的效应.方法 清洁级雄性SD大鼠40只,8周龄,体重250～300 g.随机分为4组(n=10):C1组、C2组、CsA1组和CsA2组.采用坐骨神经慢性压迫性损伤(CCI)的方法制备大鼠神经病理性痛模型.C1组和CsA1组测定基础热痛阈和机械痛阈后,分别腹腔注射生理盐水2 ml和环孢霉素A 6mg/kg,1次/d,连续给药18 d,于给药第6天时制备神经病理性痛模型,于CCI前1 d、CCI后第1、3、4、6、8、10和13天(T1～8)时测定热痛阈和机械痛阈;C2组和CsA2组于测定基础热痛阈和机械痛阈后制备神经病理性痛模型,于CCI后第4～24天分别腹腔注射生理盐水2 ml和环孢霉素A6 mg/kg,1次/d,于CCI后第3、4、6、8、10、13、17和24天(T9～16)测定热痛阈和机械痛阈.结果 与C1组比较,CsA1组T2-8时热痛阈升高(P<0.05),机械痛阈差异无统计学意义(P>0.05);与C2组比较,CsA2组T13～16时热痛阈升高,T16时机械痛阈升高(P<0.05).结论 环孢霉素A对大鼠神经病理性痛有一定程度的防治作用.     

CsA、MPA和RPM对CD_(28)通路共刺激后淋巴细IL-4 mRNA表达的影响

目的　观察环孢素Ａ（ＣｓＡ） 、霉酚酸（ ＭＰＡ） 和雷帕霉素（ＲＰＭ） 对ＣＤ２８ 通路共刺激后淋巴细胞ＩＬ４ ｍ ＲＮＡ 表达的影响。　方法　以ＰＣＲ 扩增方法获得ＩＬ４ 特异的ｃＤＮＡ 片段,并将其克隆至ＰＧＥＭ３Ｚ 载体中。以此作为探针对ＲＴＰＣＲ 产物进行杂交定量,比较三种免疫抑制剂对ＣＤ２８通路共刺激后淋巴细胞ＩＬ４ ｍ ＲＮＡ 表达的影响。　结果　以抗ＣＤ３ ｍ Ａｂ ＋ 抗ＣＤ２８ ｍ Ａｂ 共刺激后,发现淋巴细胞稳定地表达ＩＬ４ ｍ ＲＮＡ;ＣｓＡ 和ＭＰＡ 未能抑制淋巴细胞ＩＬ４ ｍ ＲＮＡ 的表达,而ＲＰＭ则能产生显著抑制。　结论　ＲＰＭ 能抑制ＣＤ２８ 通路共刺激后ＩＬ４ ｍ ＲＮＡ 的表达,而ＣｓＡ 和ＭＰＡ对这一过程无抑制作用。     

Treatment with convalescent plasma in solid organ transplant recipients with COVID-19: Experience at large transplant center in New York City

Solid organ transplant (SOT) recipients may be at higher risk for poor outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Convalescent plasma is an investigational therapy that may benefit immunosuppressed patients by providing passive immunity. Convalescent plasma was administered to hospitalized patients with coronavirus disease-2019 (COVID-19) at an academic transplant center in New York City. Eligible patients were hospitalized and required to have positive nasopharyngeal polymerase chain reaction (PCR) diagnosis of SARS-CoV-2 infection, be at least 18 years old, and have either dyspnea, blood oxygen saturation ≤ 93% on ambient air, respiratory frequency ≥ 30 breaths/min, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, or lung infiltrates > 50%. Thirteen SOT recipients received convalescent plasma from April 9, 2020, to May 17, 2020. The median time from symptom onset to plasma infusion was 8 days. Eight of 13 patients (62%) had de-escalating oxygenation support by day 7 post-convalescent plasma. Nine (69%) patients were discharged, 1 (7%) patients remain hospitalized, and 3 (23%) patients died. This series supports the need for additional studies on convalescent plasma use in SOT recipients with COVID-19 to better determine efficacy and identify patients who are likely to benefit.     

The effect of fresh gas flow during induction of anaesthesia on sevoflurane usage: a quality improvement study

Reducing fresh gas flow during inhalational anaesthesia results in cost savings and decreases environmental impact. We are interested in the influence of fresh gas flow on the early (induction) phase of overall fresh gas flow and vapour consumption. This stage is often excluded in studies of fresh gas flow. Data were collected from 3199 sevoflurane anaesthetics over an 11-month period in four operating theatres. We determined fresh gas flow at different stages of anaesthesia, and developed an explanatory model for the influence of the ‘induction’ period. Following a three-month collection of baseline data we emphasised the importance of the early phase to our department repeatedly over a two-week period. We explored the relationship between fresh gas flow and total vapour usage, and used a simple mathematical model to explore the effect of changes in the fresh gas flow and duration of the ‘induction’ phase. Mean fresh gas flow was 1.15 l.min⁻¹ in the baseline period and 0.91 l.min⁻¹ in the two months following our educational effort (p = 0.0005). In the following six months, mean fresh gas flow was 1.17 l.min⁻¹ (p = 0.7726 compared with baseline). These results were driven by changes in both fresh gas flow and duration of the initial high-flow period. We found some correlation (R² = 0.85) between overall fresh gas flow and vapour consumption; a 1 l.min⁻¹ increase in fresh gas flow consumes an additional 18 ml.hr⁻¹ of liquid sevoflurane. This preliminary study demonstrates that an episode of high fresh gas flow at the start of anaesthesia has a large and modifiable effect on overall fresh gas flow and vapour consumption. We also confirmed the linear relationship between fresh gas flow and vapour usage.     

Chemical casualties – recognition and management

Poisoning with chemical agents was once thought to be confined to the battlefield. However, over the past decade there has been an increase in the use of chemical weapon agents and toxic industrial chemicals as weapons of terror. As well as use during conflict, these poisons have been used in other attacks with deadly effects. These agents require particular treatments that fall out with standard medical practice to reduce harm and prevent contamination of medical treatment facilities. The risk of a mass casualty incident with a deliberate or accidental release is a possibility.     

Medical management of motility disorders in patients with intestinal failure: a focus on necrotizing enterocolitis, gastroschisis, and intestinal atresia

Background

Intestinal failure (IF) is the dependence upon parenteral nutrition to maintain minimal energy requirements for growth and development. It may occur secondary to a loss of bowel length, disorders of motility, or both. Short bowel syndrome (SBS) is a malabsorptive state resulting from surgical resection, congenital defect, or diseases associated with loss of absorptive surface area. A particularly vexing problem is associated with whole bowel and/or segmental intestinal dysmotility. Motility disorders within the context of SBS and IF may relate to rapid intestinal transit secondary to loss of intestinal length, dysmotility associated with loss or poor antegrade peristalsis, or gastroparesis. Therapy may be classified into medical (prokinetic and antidiarrheal agents) and surgical to deal with the overdistended poorly motile bowel.

Methods

We performed a systematic review of the literature pertaining to IF, SBS, and dysmotility in the pediatric population with gastroschisis, necrotizing enterocolitis, and intestinal atresia. In addition to the available treatment options, we have provided a review of the literature and a summary of the available evidence.

Conclusion

Despite relatively poor level of evidence regarding the application of promotility and antidiarrheal medications in patients with SBS and IF, these agents continue to be used. Herein, we provide a review of the physiology and pathophysiology of intestinal motility/dysmotility and available strategies for the use of promotility and antidiarrheal agents in patients with IF/SBS.     

SmartTots: a public–private partnership between the United States Food and Drug Administration (FDA) and the International Anesthesia Research Society (IARS)

A history of the public–private partnership ‘SmartTots’ between the IARS and FDA is presented. In order to raise money for research to better understand the relationship between sedative and anesthetic agents and neurotoxicity in the developing brain, the FDA approached the IARS in 2008. A partnership was developed over the following 2 years, then a Scientific Advisory Board was created to develop a research agenda. The IARS contributed $200 000 in 2011 to provide initial funding; 33 proposals were submitted in response to a request for proposals in late 2011 and resulted in the awarding of two, $100 000 grants in 2012. An Executive Board was appointed under the leadership of Michael Roizen to spearhead additional fund‐raising efforts, and a director of development is working with Dr. Roizen and the Board to raise funds from individuals and organizations. Dr. Roizen has personally committed to a matching grant for anesthesiologists, up to $50 000 per year for 20 years ($1 million). Readers of the journal are encouraged to go to the website www.smarttots.org in order to better understand the issue, to contribute to the research fund themselves, and to encourage their own professional organizations to partner with SmartTots in fund‐raising.     

Hormonal contraception for human males： prospects

Development of an ideal hormonal contraceptive for man has been the goal of several research workers during the past few decades. Suppression of pituitary gonadotropic hormones, which in turn would inhibit spermatogenesis while maintaining normal libido and potentia has been the approach for a contraceptive agent. Intramuscularly administered and orally active testosterone or testosterone in combination with progesterone have been shown to cause inhibition of spermatogenesis resulting in azoospermia in normal men. Similarly testosterone has been used in combination with gonadotropin releasing hormone antagonists and agonists to inhibit pituitary gonadotropic hormone release. Immunological approach to neutralize the circulating levels of follicle stimulating hormone has also been shown to cause inhibition of spermatogenesis. The available literature shows that testosterone causes reversible azoospermia without any significant side effects in Asian population effectively and appears to be a promising chemical for control of fertility in man.( Asian J Androl 2000 ; 2 : 46 - 50 )     

Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma

BACKGROUND: Addition of the long acting beta2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma. METHODS: After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 microg with or without salmeterol 50 microg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 microg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period. RESULTS: Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p < 0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p > 0.05). However, adding salmeterol significantly reduced sputum ratios of alpha2-macroglobulin and albumin during the treatment period (p = 0.001). CONCLUSIONS: The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting beta2 agonist is combined with inhaled corticosteroids.     

肌肉松弛药过敏反应研究新动向

背景 肌肉松弛药(肌松药,neuromuscular blocking agents,NMBAs)存在诱发过敏反应的可能.严重的过敏反应发展迅速并危及患者生命. 目的 综述NMBAs诱发过敏反应研究的最新进展,为其安全使用提供参考. 内容 阐述NMBAs过敏反应的临床表现及特点、交叉过敏反应、诊断及治疗进展. 趋向 NMBAs过敏反应的研究能够为临床安全使用NMBAs提供指导.     

Effects of immunosuppressive therapy on wound healing

Immunosuppressive therapy is increasingly being used in clinical practice and has been shown to affect wound healing to varying degrees. This article looks at the effects of the newer immunosuppressive agents on wound healing. It is shown that wound healing is impaired via different mechanisms. Some of the animal and human studies are reviewed in more detail. It is shown that some of the newer agents affect wound healing to such an extent that reduction or avoidance of these drugs until complete wound healing is achieved is advocated. More research is required for these newer agents to determine the most appropriate time to introduce them.