INTRODUCTION

The emergency department (ED) is a unique environment where a variety of procedures with emergent and urgent indications are managed. Many of these procedures result in significant pain and are associated with varying degrees of anxiety and agitation.Accordingly, the management of sedation and analgesia is an important component of comprehensive emergency medical care for patients of all ages. Controlling anxiety may improve quality of care and patient satisfaction by facilitating interventional procedures and minimizing patient suffering.

Among different procedures done in emergency room, replacing joint dislocations occur frequently.Anterior shoulder dislocation is the most commonly dislocated joint that necessitates emergency referral and reduction. Most (90%-97%) shoulder dislocations are anterior.[1] It consists of up to 50% of all joint dislocations. In 70% of cases it is seen in people under 30 years old.[2] Patients must have their shoulder muscles relaxed before any reduction can be easily effected so analgesic and muscle-relaxing medications are required. Procedural sedation and analgesia(PSA) refers to the use of analgesic, dissociative, and sedative agents to relieve pain and anxiety associated with diagnostic and therapeutic procedures performed in various settings. PSA is an integral element of emergency medicine. Various drugs have been tried to alleviate pain and anxiety in patients suffering shoulder dislocation for example midazolam+ fentanyl or midazolam+ ketamine are among most popular combinations in PSA.[3] In recent years etomidate has favorably been chosen as an induction agent in contrast to other drugs because of the low risk of apnea and hypotension.[4-6] While doing PSA, patients should be monitored closely with capnography.[3,7]

实际上，直到8月13日，当各路小道消息显示西王集团即将接手山东男篮时，高速男篮俱乐部相关负责人还通过媒体进行了辟谣：假消息，从没听说过此事，也从未跟西王集团有任何接触。

人像蚕一样拼命织关系的网，但织成之后，却又千方百计逃之夭夭。范坚强给了一杭一个逃离的机会，可以放下一切，每日枕着书香入眠。一杭成为这间石屋实质上的主人以后，范坚强给他送来了书，让他在漫长的白天与黑夜，不至于孤独。但单纯的生活结束了，石屋的门终于打开来。

Midazolam is a benzodiazepine and its clinical effects are sedation, motion control and anxiolytic. Its initial IV sedative dose is 0.05-0.1 mg/kg or 1 mg and then titrated to max dose of 5 mg. As IV form, it has an onset of action near 2-3 minutes and duration of sedation is 45-60 minutes.[8]

Thiopental has been used in different short surgeries.Its clinical action is sedation, motion control and anxiolytic. It has a very short onset of action near 10-15 seconds and half-life is almost 5-10 minutes. Initial IV sedative dose is 3-4 mg/kg or 50-100 mg first then repeated every 10 minutes[8,9]

Burton et al[5] in 2002 conducted a randomized controlled trial to compare etomidate and midazolam for reduction of anterior shoulder dislocation. They concluded that etomidate provided effective PSA and when compared with midazolam it conferred a significantly shorter period of PSA.

杨力生母亲却叹着气说：“唉，漂亮什么呀！她那两个门牙有点大，腿长得也太长了。勤快姑娘多了去了，俺力生不缺这样的。”

Falk et al[6] in 2004 did a systematic review to compare the efficacy and safety of etomidate for PSA in ED. They found that etomidate’s onset of action and time to recovery was rapid and comparable to that of thiopental but significantly faster than that of midazolam.

The only study compared midazolam and thiopental’s sedation, was by Barry A. R. Bland in 1987 that evaluated the two drugs for rapid sequence anesthetic induction for elective cesarean section. They showed that maintenance of anesthesia and hemodynamic responses were identical in both groups but they concluded that midazolam was less suitable than thiopental for anesthetic induction.[10]

Since there are not enough studies about sedative effect of thiopental in procedures, we conducted an RCT to compare thiopental with midazolam in reduction of shoulder dislocation. Our primary outcomes were number of times other methods except tractioncounteraction were used and the degree of muscle relaxation was induced by thiopental.

METHODS

Participants

We conducted a randomized double blind parallel group study (with block randomization) in patients with shoulder dislocation recruited from the EDs of Shariati and Imam Khomeini Hospitals, two tertiary referral center, from August to December 2014. We got the approval from the ethics committee of Tehran University of Medical Sciences. Eligible patients were aged ＞18 years old who were diagnosed with anterior shoulder dislocation based on their clinical findings and X rays. We excluded patients with other types of shoulder dislocation, severe neurovascular injury,dislocation longer than 24 hours, fracture dislocation,multiple trauma mechanism, no consent to participate in the study, decreased level of consciousness, systolic hypotension＜90 mmHg, drugs hypersensitivity, illicit drug use, age＜18 years, pregnancy or hepatorenal disorders (Figure 1). The treating emergency physician confirmed the diagnosis and contacts the chief investigator. The subjects were randomly divided into two groups of 35 each: a midazolam group (A) and a thiopental group (B). One of our triage nurses used a random number table to block randomize subjects, she was the only person aware of this randomization. Each patient had a code in block randomization, and only the chief investigator and the triage nurse were aware of the assignment and patient’s group. The specified drug and dose were provided by the triage nurse based on the code (all syringes covered) and injected to the patient by the emergency physician who was blinded to the study.All dislocations were anterior and initially reduced by traction-countertraction and if it was unsuccessful, other methods would be tried and recorded. All study outcomes were evaluated and recorded by the emergency physician doing the procedure, who was blinded to the patient group.

Drug administration

All patients were interviewed and the method of drug administration, visual analogue pain score (VAS; where 10 represented the worst imaginable pain and 0 was pain-free) and possible complications were explained to them and informed written consent was obtained.Demographic data including age, sex, number of times other methods except traction-countertraction were used, patients and physician’s satisfaction, difficulty of procedure, degree of muscle relaxation, time of sedation and complete recovery, number of patients had apnea episode, O2 saturation, patient’s pain score before drug infusion and after procedure completion and adverse events were all recorded by the emergency physician responsible for the patients. In group A 0.1 mg/kg IV midazolam+ 2 µg/kg IV fentanyl and in group B 2 mg/kg IV thiopental+ 2 µg/kg IV fentanyl were administered.Both drug syringes were covered in order to not recognize them based on their color.

Statistical analysis and sample size calculation

For sample size calculation we used the variable“number of times the procedure was repeated by other methods except traction-counteraction” as the main primary outcome. Based on the reference number 12,in order to produce statistically significant difference between the two groups, with Power of 90%, CI of 95%,a sample size of 15 per treatment group was calculated by means of the following formula:

Muscle tone in group B decreased more (P-value=0.014).Performing the procedure in group B was easier than in group A (P-value=0.043). There were no significant difference in time of sedation and complete recovery,patient and doctor satisfaction, or O2 saturation between the study groups. Within each group O2 saturation was reduced significantly during dislocation replacement(P-value=0.000). There was no need to conduct other maneuvers for reduction, except traction-countertraction,in either group.

在日常生活中，签名是很常见的行为，如合同的签署，订单的确认，支票的签发，回复文件，通常来说传统的签名都是手写签名。随着网络技术的飞速发展，人们希望突破传统签名带来的种种弊端，信息的发送者希望通过签名来使信息的接受者确定信息的真实性，于此与此同时，当出现纠纷的时候，信息的接受者可以通过数字签名来追踪到信息的发送者来进行承担相应的责任。可以说，在现代社会，数字签名技术正在潜移默化影响我们的生活。

RESULTS

One study that compared midazolam and thiopental sedation, by Wakamoto et al[10] in 1987, evaluated the two drugs for rapid sequence anesthetic induction for elective cesarean section. They showed that maintenance of anesthesia and hemodynamic responses were identical in both groups but midazolam was less suitable than thiopental for anesthetic induction.

The mean ages of group A and B were similar(25.77±3.69 and 27.94±5.56 years, respectively)(P-value=0.60). Incidentally all patients were men (Table 1). Side effects including apnea episode are shown in Table 2. Apnea episodes had no significant difference between the two groups (P-value=0.39).

Table 1. Demographic feature of study groups (% of all patients in each group)

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Table 2. Side effects of study groups (% of all patients in each group)

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Figure 1. CONSORT fl ow diagram.

Table 3 describes study end points. Before drug infusion the mean±SD VAS scores were 8.37±2.21 in the midazolam group (A) and 8.94±1.78 in the thiopental group (B); mean difference 0.57, 95% CI= -0.38 to 1.52(P-value=0.238). After completion of the procedure, the mean ±SD VAS scores in groups A and B were 3.20±1.30 vs. 3.65±1.30; mean difference -0.45, 95% CI= -1.07 to 0.16 (P-value=0.147).

Because one of our drugs, thiopental was not studied with this purpose in PSA, we supposed the error 100%and estimated a sample size 30 patients in each group.All data were analyzed using SPSS V.22 software. In order to evaluate the normal distribution of quantitative data such as VAS score, we conducted a Kolmogorov-Smirnov (KS) test. We analyzed normally distributed continuous data by independent t test and median of ordinal, non-continuous and non-normal data by analysis of Mann-Whitney U test. We analyzed normally distributed qualitative data by Chi square test.

DISCUSSION

优质的内容是线上竞争的核心竞争力，年轻人乐于分享、热衷模仿，选取极具特色景点，多元融合创造趣味性，移动互联网时代的短视频肯定不同于以往的电视广告，短视频创造了新的平等对话语境，一定要有原创性，使用平台内容的调性。如西瓜视频具有精致化、精品化的特征，而抖音则带有节奏的嘻哈快感，迎合年轻人的口味。原创内容即是用户心理的表现，也是用户内心情感的宣泄，同时还能表达用户的生活态度，所以容易产生共鸣，创造出魔性内容，更具传播性。

Midazolam has been used as sedative in different procedures with a relatively short-acting time, few hemodynamic effects and significant anterograde amnesic properties. As IV form, it has an onset of action near 2-3 minutes and duration of sedation is 45-60 minutes.[8]

Thiopental clinical action is sedation, motion control and anxiolysis. It has a very short onset of action near 10-15 seconds and half-life is almost 5-10 minutes.Initial IV sedative dose is 3-4 mg/kg or 50-100 mg first then repeated every 10 minutes[8,9]

In conclusion, from the sedative viewpoint, thiopental proved an effective intravenous anxiolytic agent for shoulder dislocation reduction, comparable in most respects to midazolam. Thiopental had some theoretical advantages like more relaxation and reduction in muscle tone and shorter sedative and complete recovery time.

研究区位于山东省威海市最东端，北、东、南三面濒临黄海，海岸线长近500km。全市辖12个镇、10个街道，其中，崖头街道、寻山街道、崂山街道、城西街道4个街道由荣成经济开发区管理。土地总面积为1528km2，占威海市面积26.3%。呈典型的温带大陆性季风性湿润气候，四季变化和季风进退都较明显[13]，年平均气温11.3℃，年均降水量800mm。区内生态环境较宜居，旅游资源丰富，森林覆盖率达43.1%，居于全省前列。

This study demonstrated that muscle tone was decreased and relaxed more with thiopental sedation than midazolam and PSA with thiopental was easier than midazolam in reduction of shoulder dislocation. Patient and doctor’s satisfaction, O2 saturation, risk of apnea,number of other reduction methods used except tractioncountertraction and patients’ pain score had no significant difference between the study groups. Three patients in group B and none in group A had nausea and vomiting.

During the study period 80 patients were diagnosed with shoulder dislocation and 10 patients were excluded:2 patients had posterior shoulder dislocation, 2 didn’t consent to participate in the study, three had fracture dislocation, 1 patient were ＜18 y/o and 2 patients had neurovascular impairment. The remaining 70 patients were randomly divided into two groups of 35 each(Figure 1).

Bland et al[11-13] evaluated sedative effect of propofolfentanyl vs. thiopental-sevoflurane in diagnostic bronchoscopy and they added that the first group performed better anesthesia than the second because of its superior maintenance of cardiovascular stability.

Etomidate has been recently evaluated with midazolam and thiopental in different setups. In 2005 Hunt GB et al compared etomidate with midazolam and concluded that etomidate could provide a significant reduction in recovery time while providing equal sedation quality.[4] In 2002 Burton et al[5] tried etomidate and midazolam for reduction of anterior shoulder dislocation and they found that etomidate provided a significantly shorter period of PSA. Falk et al[6] in 2004 showed that etomidate onset of action and time to recovery were rapid and comparable to that of propofol and thiopental but significantly faster than that of midazolam.

2016年12月和2017年6月分到连队的新职工党亚龙、马彦霞、张兆杰，对植棉技术和栽培模式不懂，张兰花就担当起了每年新来职工的业余技术员，进行现场讲解、实地示范。2018年党亚龙、马彦霞、张兆杰承包的55亩、53亩、48亩棉花，单产达438公斤、520公斤、470公斤，分获收入13.84万元、15.74万元、12.97万元，使这些新来职工在团场综合配套改革首年就真正尝到了科技致富、勤劳致富带来的殷实生活。

Limitations of the study

One limitation of our study was that we were notable to determine the onset of action of both drugs. Our sample size was not sufficient to detect the exact drugs’effects and adverse events. Further clinical trials with larger sample sizes and longer follow-up should therefore be performed to identify adverse events.

Table 3. Comparison of primary outcomes of study groups

¹ Ordinal scale (1: totally flaccid; 2: tone just noticeable; 3: slight resistance; 4: obvious resistance; 5: impeding relocation); ² Ordinal scale (1:very easy; 2: easy; 3: average; 4: difficult; 5: very difficult); ³ Ordinal scale (1: very good; 2: good; 3: average; 4: bad; 5: very bad).

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CONCLUSION

This study shows that thiopental sedation might be as effective as midazolam in replacement of shoulder dislocation with more reduction in muscle tone.

Funding: This study was not funded.

Ethical approval: The study was approved by ethics committee of Tehran University of Medical Sciences.

过去我们比较多地从国家和社会的需要出发，设计和安排思想政治教育活动，对教育对象的“前理解”以及由此形成的接受能力研究不足，不能有针对性地设计教育内容和教育方法。思想政治教育对象的“前理解”研究包括：结合实证调查，从传统文化、市场经济生活、信息时代、日常生活等方面，综合把握教育对象“前理解”的状况；辩证分析教育对象的“前理解”在思想政治教育接受中的作用。

Conflicts of interest: The authors state they have no competing interests.

Contributors: MS: study design and supervision; RH: data gathering and analysis; EV: data analysis and drafting; MM: data gathering and drafting; MS: critical revision.

REFERENCES

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12 Yamaguchi S, Koguchi T, Midorikawa Y, Okuda Y, Kitajima T. Comparative evaluation of TIVA with propofol-fentanyl and thiopental-sevoflurane anesthesia using laryngeal mask airway for diagnostic bronchoscopy. J Anesth. 1998;12(2):53-6.

13 Taylor DM, O’Brien D, Ritchie P, Pasco J, Cameron PA.Propofol versus midazolam/ fentanyl for reduction of anterior shoulder dislocation. Acad Emerg Med. 2005; 12(1): 13-9.