【作者】 裴先波；

【导师】 李建国；

【作者基本信息】 武汉大学 ， 外科学， 2015， 博士

【摘要】 背景重症医学中,休克极为常见,ICU中的1/3病人存在休克。血管活性药物是休克治疗中的重要循环支持手段。休克时血管活性药物的选择和应用一直以来都是讨论的热点。国外已有的血管活性药临床观察性研究结果显示,不同的ICU医生血管活性药物的应用存在较大的差异,甚至在欧洲和北美发达国家的ICU医生之间,这样的差异也较明显。这种差异存在的原因之一是在休克治疗中,很难确切地认为某一种血管活性药物在维持血流动力学稳定和生存率方面优于另一种血管活性药物,其应用策略也没有统一的方案。休克治疗指南(综合了目前最新的研究证据)可以一定程度上协助ICU医生做出决策,目前的休克指南发展最完善的是感染性休克指南。然而,一个前瞻性的队列研究结果显示,ICU医生对感染性休克指南依从性并不高,包括血管活性药物的应用；另外,不同国家和地区的ICU的依从性存在较大的差异。而这种不同ICU医生血管活性药物应用的差异会对病人造成伤害。我国各地ICU医生血管活性药物应用现状及是否存在较大的差异还未知,目前国内还没有这方面的临床研究报道。目的本研究主要目的是调查我国ICU医生血管活性药物应用的现状,探讨不同ICU医生血管活性药物应用的差异,分析可能的原因以及规范合理使用血管活性药物的对策。方法采用问卷调查的方法,用立意抽样(purposed sampling)选取样本。(1)调查对象： 研究者从中华医学会重症医学分会委员中选取来自全国不同地区的负责人。由各地区负责人确定他们所在地区接受问卷调查的ICU医生。原则是选取的样本尽量具有代表性,需要考虑到医院等级、是否是教学医院、ICU类型、ICU医生职称。本抽样样本代表性在一定程度上依赖各地区负责人可联系到的ICU医生及问卷回复情况。(2)调查工具： 自行编制"ICU血管活性药物的应用情况调查问卷”,该调查问卷是在参考国内外文献、访谈ICU医生及反复修订后确定。在正式调查前进行了一次预调查,并根据预调查的结果对问卷进行了进一步修订。正式调查问卷包括血管活性药物应用概况、休克治疗中血管活性药的选择、血管活性药应用的管理(包括应用缩血管药的MAP目标值、正性肌力药的应用指征和疗效判断依据和低剂量多巴胺的应用)及血管活性药物应用过程中的监测策略4个方面共26问题。(3)调查方法： 正式调查问卷通过电子邮件的方式发送和回收,先由研究者将问卷发送给各地区负责人,各地区负责人再发送给其选取的ICU医生,各地区负责人收集好问卷后再发送给研究者。为了提高回收率,其间有两次向各地区负责人电子邮件提醒。本问卷调查自2012年5月开始发放,2012年9月结束回收。结果(1)一般资料本调查发放问卷900份,回收有效问卷586份,有效回收率65.1%。回复者主要来自三级医院,占77.8%；教学医院的回复者395人,占67.4%,非教学医院的回复者191人,占32.6%；回复问卷的医生中,初中级职称者338名,占57.7%,高级职称者有248人,占42.3%。地区分布为我国31省市中的29个省市,没有收到来自西藏和甘肃省的问卷。(2)血管活性药的选择对于感染性休克,70.8%(415/586)的回复者首选缩血管药是去甲肾上腺素,其次是多巴胺(27.6%,162/586)。然而,对于低血容量性休克和心源性休克,分别有73.4%(430/586)和68.3%(400/586)的回复者首选的缩血管药是多巴胺,其次是去甲肾上腺素(低血容量性休克22.7%,33/586;心源性休克18.9%,111/586)。对不同ICU医生首选缩血管药物进行比较,结果发现三种类型休克中教学医院回复者首选去甲肾上腺素的比例均比非教学医院回复者的比例高,而非教学医院回复者首选多巴胺的比例均比教学医院回复者的比例高,差异有统计学意义。而不同职称回复者首选缩血管药物无统计学差异。由于低血容量性休克使用正性肌力药物的几率较小,586位回复者中只有321位会考虑低血容量性休克中使用正性肌力药。对于感染性休克,84.1%(493/586)的回复者首选正性肌力药是多巴酚丁胺,其次是洋地黄类药物(11.9%,70/586)。对于低血容量性休克和心源性休克,分别有64.5%(207/321)和60.6%(355/586)的回复者首选多巴酚丁胺,其次是洋地黄类药物(低血容量性休克27.7%,89/321；心源性休克29.7%,174/586)。对不同ICU医生首选正性肌力药物进行比较,结果发现三种类型休克中教学医院回复者首选多巴酚丁胺的比例均较非教学医院回复者的比例高,而非教学医院回复者选择洋地黄类约物的比例均较教学医院回复者的比例高,差异具有统计学意义。而不同职称回复者首选缩血管药物无统计学差异。当问及休克病人是否会使用扩血管药,回复使用频率为“不用”的回复者占13.1%(77/586),“偶尔用”占74.6%(437/586),“常用”占12.3%(72/586),没有回复者报告“全部用”。根据休克类型的不同可能用到扩血管药的频率依次为心源性休克67.1%(393/586)、感染性休克32.3%(189/586)、低血容量性休克6.5%p8/586)。最常用到的扩血管药排在前三位依次是硝酸甘油(71.2%,417/586)、硝普钠(45.6%267/586)、酚妥拉明(32.9%,193/586)。非教学医院回复者管理休克时,有更高比例医生倾向应用扩血管药,中初级职称回复者管理休克时,有更高比例医生倾向应用扩血管药,差异具有统计学意义。(3)应用缩血管药的MAP目标值接近半数回复者认为不同类型休克应用缩血管药的MAP目标值均相同,这种观点在非教学医院回复者中的比例更高。对于感染性休克,应用缩血管药的MAP目标值为64.3±7.5mmHg；教学医院回复者应用缩血管药的MAP目标值较非教学医院回复者高,差异具有统计学差异。而不同职称回复者应用缩血管药的MAP目标值比较无统计学差异。(4)正性肌力药的应用指征和疗效判断指标正性肌力药物的应用指征排在前四位的依次是低血压(80.2%,470/586)、低心输出量(66.4%,389/586)、末稍低灌注(37.0%,217/586)和少尿(30.9%,181/586)。正性肌力药物的疗效判断指标排在前4位的依次是血压(86.7%,508/586)、尿量(58.9%,345/586)、心输出量(50.2%,294/586)和血乳酸浓度(40.8%,239/586)。教学医院回复者更倾向选择心输出量作为正性肌力药的应用指征。而非教学医院回复者更倾向选择少尿为正性肌力药的应用指征。对于正性肌力药应用的疗效判断指标,仅尿量的选择在教学医院和非教学医院回复者之间存在统计学差异。高级职称和初中级职称回复者在正性肌力药的应用指征和疗效判断指标的选择,差异均无统计学差异。(5)低剂量多马胺的应用为了改善肾脏灌注保护肾功能,有28.3%的回复者(166/586)选择应用低剂量多巴胺。与教学医院回复者(24.8%)相比较,非教学医院回复者(35.6%)更倾向使用低价量多巴胺改善肾脏灌注,差异具有统计学意义。与高级职称回复者(25.8%)比较,初中级职称回复者(30.2%)更倾向使用低剂量多巴胺改善肾脏灌注,但差异不具有统计学差异。(6)血管活性药使用过程中的监测全部回复者报告常规监测的项目有心率、袖带血压、脉搏血氧饱和度。其它常规监测的项目依次为血气(98.5%,577/586)、血乳酸测定(84.6%,496/586)、中心静脉压(87.9%,515/586),而有创动脉血压常规监测的仅为44.2%(259/586)。教学医院回复者常规监测血乳酸和常规有创动脉压监测的比例较非教学医院回复者高,差异具有统计学意义。对不同职称回复者常规监测方法的选用均不具有统计学意义。血管活性药物使用过程中,特殊监测及其应用频率情况如表28所示。回复特殊监测方法使用频率为“常用”的依次为脉搏指示连续心排血量(21.8%,128/586)、肺动脉导管(3.6%,21/586)、经胸廓超声心动图(1.0%,6/586)和经食道超声心动图(0.3%,2/586)。微循环监测使用情况极少,分别仅有3个回复者常用胃黏膜CO2张力监测和舌下微循环监测。各监测方法“偶尔”用到的比例也并不高。教学医院回复者在选择脉搏指示连续心排血量监测、肺动脉导管监测和经胸廓超声心动图监测方面比例较高,有统计学差异。不同职称回复者特殊监测方法选用方面差异均不具有统计学意义。结论中国ICU医生在血管活性药物的选择、缩血管药物的血压目标值、正性肌力药应用指征和疗效判断指标、低剂量多巴胺应用和监测策略各方面均存在较大的差异。(1)部分ICU医生对血管活性药物的应用没有很好地遵循最新的研究证据和新近指南的推荐意见,仍延续以往的经验。(2)ICU医生在感染性休克血管活性药物的应用中能较好地遵从最新的循证证据,而在低血容量性休克和心源性休克中较差。(3)与非教学医院ICU医生相比,教学医院的ICU医生在血管活性药物的应用方面相对较规范。本研究结果提示,感染性休克管理指南的推广和学术交流对临床具有很大的指导性意义,系统的培训教育能够显著改进临床医生的行为。为了规范ICU血管活性药物的应用,应该加强血管活性药物应用及休克管理的规范化培训,不断进行知识更新,从而提高临床救治休克病人的水平。更多还原

【Abstract】 Background Therapy with vasoactive agents, including vasopressors, inotropes and vasodilators, is prescribed to correct abnormal vascular tone, and/or to improve cardiac output (CO) in order to restore tissue perfusion and normalize oxygen consumption. Currently, this therapy is considered basic management practice in the care of patients with shock in intensive care units (ICU). However, previous surveys have suggested that inconsistencies in the use of vasoactive agents existed among ICU physicians, even in Europe or North America. One reason for this inconsistency is that the optimal selection and titration of vasoactive agents to treat shock, especially vasopressors, still remains debatable. In addition, compliance with the Surviving Sepsis Campaign’s resuscitation and management bundles including use of vasopressors, reported by a prospective cohort study, is poor, and differences existed among different countries or regions. There are no published reports about vasoactive agent titration strategies by Chinese ICU physicians caring for clients with shock.Objectives This study was conducted to include questions on the selection of vasoactive agents, management during the use of vasoactive agent therapy, monitoring protocols when using these agents, and demographic characteristics of Chinese physicians in ICUs nationwide.Methods A nationwide survey of physicians was conducted. The survey protocol was used according to the published recommendations for survey methodology. A questionnaire was developed after reviewing previous surveys about the use of vasoactive agents and a review of the guidelines for vasoactive agent therapy in the treatment of septic, hypovolemic and cardiogenic shock. Focus groups were used to review and refine the questionnaire. It consisted of 26 questions and was divided into 4 parts. A core group of physician coordinators were selected from the Chinese Society for Critical Care Medicine. This group was selected because they represent 31 regions or provinces in China’s mainland. The coordinators were asked to contact physicians they knew and/or who cared for critically ill adults in an ICU located in their region or province about participation in this study. The coordinators sent the questionnaire via email to potential participants. Completed questionnaires were then returned to the coordinators and forwarded to the authors of this study.Results The response rate was 65.1% with physicians returning 586 valid questionnaires.Norepinephrine was the first choice of a vasopressor used to treat septic shock by 70.8% of respondents; 73.4% of respondents favored dopamine for hypovolemic shock; and 68.3% of respondents preferred dopamine for cardiogenic shock. Physicians working in teaching hospitals preferred norepinephrine for management of all types of shock at a statistically significant higher rate than physicians working in non-teaching hospitals. Yet, physicians from non-teaching hospitals preferred dopamine as their first choice of vasopressors. A statistically significant difference was not found between senior and junior physicians related to the first choice of vasopressors.All participants reported their first choice of inotropes for management of septic and cardiogenic shock, but 54.7%(321/586) reported they also used these agents in management of hypovolemic shock. Dobutamine was selected by 84.1%,64.5% and 60.6% of respondents for septic, hypovolemic and cardiogenic shock, respectively. A statistically significant larger percentage of physicians choosing dobutamine were from teaching hospitals as compared to physicians from non-teaching hospitals. A statistically significant higher percentage of physicians choosing dobutamine were from teaching hospitals as compared to physicians from non-teaching hospitals. Following dobutamine, digitalis was the second agent most often selected by physicians. It was selected more often for management of cardiogenic shock (29.7%, 174/586) than for hypovolemic (27.7%,89/321) or septic shock (11.9%,70/586). The percentage of physicians from non-teaching hospitals choosing digitalis to treat all forms of shock was significantly higher than physicians from teaching hospitals. A significant difference in the first choice of inotropes was not found between senior and junior physicians.Vasodilator agents were prescribed by physicians in the management of cardiogenic shock (67.1%) rather than for septic (32.3%) and hypovolemic shock (6.5%). However, a significantly higher percentage of junior physicians, and physicians from non-teaching hospitals reported no use of vasodilators in management of shock. In addition, the most commonly used vasodilators were nitroglycerine (71.2%,417/586), sodium nitroprusside (45.6%,267/586) and phentolamine (32.9%,193/586). There was no significant difference in the choice of vasodilators between physicians from teaching and non-teaching hospitals. But, when compared with senior physicians, a significantly low percentage of junior physicians used each of the vasodilators for management of shock.Nearly half of respondents believed that the mean arterial pressure (MAP) target for maintenance of vasopressor therapy were the same among the different forms of shock. The percentage of physicians from non-teaching hospitals who answered "yes" for MAP target to this item on the questionnaire was statistically significant when compared with physicians from teaching hospitals who answered "yes" to this same item. The target MAP was 64.3 ±7.5mmHg for maintaining vasopressor therapy to treat septic shock. A higher mean (SD) value of MAP target for maintaining vasopressor therapy to treat septic shock was preferred by physicians from teaching hospitals and this was statistically significant when compared with physicians from non-teaching hospitals. But, no statistical differences were found between junior and senior physicians related to the target MAP target for maintaining vasopressor therapy.The primary indications were hypotension (80.2%,470/586), low cardiac output/cardiac index (CO/CI) (66.4%,389/586), cold extremities (37%,217/586) and oliguria (30.9%,181/586). Parameters used for endpoints included MAP (86.7%, 508/586), urine output (58.9%,345/586), CO/CI (50.2%,294/586) and blood lactate concentration (40.8%,239/586). The percentage of physicians from teaching hospitals who selected a low CO/CI as the indication was significantly higher than physicians from non-teaching hospitals. Oliguria was selected by more physicians from non-teaching hospitals. Urine output was the only parameter used for the endpoint of inotropic therapy with a greater difference in percentages of physicians from teaching and non-teaching hospitals. There were no differences between senior and junior physicians in the percentages of selecting both the indications and parameters used for endpoints for inotropic therapy.Some participants (28.3%,166/586) indicated their preference for low-dose dopamine in management of shock to improve renal function. The percentage of participants from non-teaching hospitals was higher (35.6%,68/191) than from teaching hospitals (24.8%,98/395) and statistically significant. When comparing junior physicians (30.2%,102/338) with senior physicians (25.8%,64/248) regarding the use of low-dose dopamine, a higher percentage was reported but this was not statistically significantThe items on the questionnaire related to routine and advanced monitoring devices/parameters were in multiple response format. All respondents reported that they used electrocardiograph, noninvasive blood pressure, pulse oximetry and temperature as routine hemodynamic monitoring practices. Other frequently used monitoring devices/parameters included blood gas analysis (98.5%,577/586), central venous pressure (87.9%,515/586), blood lactate concentration (84.6%,496/586) and invasive blood pressure (IBP) (44.2%,259/586).Advanced monitoring devices/parameters were investigated in this survey. The most often used was pulse index contour continuous cardiac output (PICCO) chosen by 26.8%(106/395) of respondents from teaching hospitals and 14.7%(28/191) in non-teaching hospitals. Other advanced monitoring devices/parameters, including pulmonary artery catheter (PAC), transesophageal echocardiography gastric mucosal microcirculatory monitoring and sublingual microcirculatory monitoring, were chosen by less than 5% of respondents. There was no statistically significant difference between senior and junior physicians. PICCO and PAC were used more often in teaching hospitals than in non-teaching hospitals.Conclusions In conclusion, discrepancies exist in the use of vasoactive agent therapy by Chinese physicians in intensive care settings. It appears that the majority of Chinese physicians in ICUs follow the recommended guidelines related to the first-line choice of vasoactive agents when managing patients with septic shock. But, the rate of compliance with first-line vasoactive agent therapy when managing patients with hypovolemic and cardiogenic show is very low. Both senior and junior physicians in non-teaching hospitals are more apt to select inappropriate choices about the use of vasoactive medications than the same groups of physicians from teaching hospital ICUs. These research findings suggest that physicians lack information on the evidence-based guidelines for management of clients in shock and this contributed to varied practices in the selection and titration of vasoactive agents. As a result, education resources and programs about vasoactive therapy in shock management are suggested for all physicians.更多还原