2023指南共识:脑出血、蛛网膜下腔出血或急性缺血性卒中患者的目标温度管理:神经保护治疗共识评论(NTCR)组更新的共识指南建议

本文由“麻醉新超人”授权转载

Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuroprotective Therapy Consensus Review (NTCR) group  

脑出血、蛛网膜下腔出血或急性缺血性卒中患者的目标温度管理:神经保护治疗共识评论(NTCR)组更新的共识指南建议

ABSTRACT

Background: There is a lack of consistent, evidence-based guidelines for the management of patients with fever after brain injury. The aim was to update previously published consensus recommendations on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care.

摘要  

背景:目前对于脑损伤后发热患者的管理，临床缺乏一致的、循证的指南。该研究的目的是更新之前发表的关于需要急诊治疗的患者脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性卒中后目标温度管理的共识建议。

Methods:  A modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), included 19 international neuro-intensive care experts with a subspecialty interest in the acute management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. An online, anonymised survey was completed ahead of the meeting before the group came together to consolidate consensus and finalise recommendations on targeted temperature management. A threshold of 80% for consensus was set for all statements.  

方法:一项改进的德尔非共识，即神经保护治疗共识综述(NTCR)，包括19名国际神经重症监护专家，他们对急性脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性卒中的急性治疗有兴趣。在会议召开前，一项匿名在线调查已经完成，之后，该小组就目标温度管理达成了共识，并最终确定了建议，对所有的陈述都设定了80%的共识门槛。     

Results:  Recommendations were formulated based on existing evidence, literature review, and consensus. After intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require critical care admission, core temperature should ideally be monitored continuously and maintained between 36.0℃ and 37.5℃using automated feedback-controlled devices, where possible. Targeted temperature management should be commenced within 1 h of first fever identification with appropriate diagnosis and treatment of infection, maintained for as long as the brain remains at risk of secondary injury, and rewarming should be controlled. Shivering should be monitored and managed to limit risk of secondary injury. Following a single protocol for targeted temperature management across intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke is desirable.

结果:建议是基于现有证据、文献综述和共识制定的。在需要重症治疗的患者出现脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性卒中后，理想情况下应持续监测核心温度，尽可能使用自动反馈控制设备将核心温度维持在36.0℃至37.5℃之间。应在首次发热确诊后1小时内开始有针对性的温度管理，并对感染进行适宜的诊断和治疗，只要大脑仍有继发性损伤的风险，就应保持温度管理，并应控制复温。应监测和控制寒战，以限制继发性损伤的风险。在脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性中风中采用单一的温度管理方案是可取的。

Conclusions:  Based on a modified Delphi expert consensus process, these guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, highlighting the need for further research to improve clinical guidelines in this setting.

结论:基于改进的德尔菲专家共识过程，这些指南旨在提高重症治疗中脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性卒中患者目标温度管理的质量，强调需要进一步研究以改善这种情况下的临床指南。

Keywords: guidelines; intensive care; intracerebral haemorrhage; neurocritical care; normothermia; stroke; subarachnoid haemorhhage; targeted temperature management  

关键词:指南;重症治疗;脑出血;神经危重症护理;正常体温;卒中;蛛网膜下腔出血;目标温度管理

Editor’s key points  

Consensus recommendations were developed on targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in patients who require admission to critical care.

A modified Delphi consensus process involving 19 international neurocritical care experts formulated recommendations based on existing evidence, literature review, and consensus.

Core temperature should be monitored continuously and targeted temperature management commenced within 1h of first fever with temperature maintained between 36.0℃and 37.5℃using automated feedback-controlled devices, where possible, with shivering managed to limit risk of secondary injury.

These guidelines aim to improve the quality of targeted temperature management for patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in critical care, and highlight the need for further research to improve clinical guidelines in this setting.

编者要点  

在需要接受重症治疗的患者中，针对脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性卒中后的目标温度管理提出了共识建议。

一个改进的德尔菲共识过程涉及19个国际神经危重症护理专家，根据现有的证据，文献综述和共识制定了建议。

应持续监测核心温度，并在首次发热1小时内开始有针对性的温度管理，使用自动反馈控制设备将温度保持在36.0℃至37.5℃之间，尽可能控制寒战以限制继发伤害的风险。

这些指南旨在提高重症监护中脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性卒中患者目标温度管理的质量，并强调需要进一步研究以完善这方面的临床指南。

Stroke, a heterogenous syndrome caused by a disruption of cerebral blood flow, can be followed by sustained loss of neurological function and tissue damage. It is a leading cause of disability with a significant economic burden, and one of the top causes of years of life lost, along with ischaemic heart disease, lower respiratory infections, and diabetes mellitus. Stroke is categorised as haemorrhagic or ischaemic stroke, with haemorrhagic stroke being sub-categorised as subarachnoid haemorrhage and intracerebral haemorrhage.5 Targeted temperature management.

中风是一种由脑血流中断引起的异质性综合征，可继之而来的是神经功能的持续丧失和组织损伤。它是造成残疾的主要原因，造成了巨大的经济负担，也是导致寿命减少的主要原因之一，与缺血性心脏病、下呼吸道感染和糖尿病并列。中风分为出血性中风和缺血性中风，出血性中风又分为蛛网膜下腔出血和脑出血。

(TTM) is a complex intervention that aims to minimise further brain injury and improve neurological outcomes after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. It involves controlling core body temperature at a specific level to achieve the desired temperature to prevent fever, maintain normothermia, or induce hypothermia.

目标温度管理(TTM)是一种复杂的干预措施，旨在减少进一步的脑损伤，改善脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性卒中后的神经系统预后它包括将核心体温控制在一个特定的水平，以达到预期的温度，以防止发烧、保持体温正常或诱发体温过低。

Fever is frequently observed in the neuro-intensive care unit (NICU). Neurogenic fever is a non-infectious fever that is common after severe brain insult from intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke, and has been linked to both higher clinical severity and worse outcome, including increased risk of death, longer ICU and hospital length of stay, lower functional status, and dependence in activities of daily living. There are, however, conflicting opinions in the current literature with regards to whether treating fever leads to improved outcome for patients. Sample sizes in published studies are often small, with few randomised controlled trials (RCTs), and different definitions of fever or therapeutic approaches to addressing fever.

神经重症监护室(NICU)经常观察到发热。神经源性发热是一种非传染性发热，常见于由脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性卒中引起的严重脑损伤后，并与更高的临床严重程度和更坏的结果有关，包括死亡风险增加，更长的ICU和住院时间。更低下的机体功能现状和日常生活活动依赖性。然而，在目前的文献中，对于治疗发烧是否能改善患者的预后，存在着相互矛盾的观点。在已发表的研究中，样本量通常较小，很少有随机对照试验(RCTs)，而且对发烧治疗方法的定义也不同。

Therapeutic hypothermia is suggested to provide robust neuroprotection because of its multifaceted physiological mechanism of action. Although laboratory and preclinical studies have contributed useful knowledge to the practice of TTM within the complex clinical scenario of stroke, there are obstacles that hinder its routine application in clinical practice. Despite the need for efficient and effective fever management, there is a lack of consistent, evidence-based guidelines for management of patients with fever after brain insult. The goal of this modified Delphi consensus, the Neuroprotective Therapy Consensus Review (NTCR), was to build on existing data7 and to discuss and identify practice recommendations for the application of TTM in patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke managed within a critical care environment.

治疗性低温由于其多方面的生理作用机制，被建议使用以提供强有力的神经保护。尽管实验室和临床前研究已经为TTM在卒中复杂临床场景中的实践贡献了有用的知识，但在临床实践中，TTM的常规应用仍存在障碍。尽管需要高效和有效的发烧管理，但对于脑损伤后发热患者的管理，缺乏一致的、循证的指南。这项改进的德尔非共识，即神经保护治疗共识综述(NTCR)，旨在建立在现有数据的基础上，讨论并确定TTM在脑出血、动脉瘤性蛛网膜下腔出血患者中的应用实践建议。急性缺血性中风在重症监护环境中进行治疗。

Methods  

A modified Delphi consensus method was used, involving a combination of an online survey (Round 1), a face-to-face meeting (Round 2), and post-meeting reviews of the consensus results (Round 3). The questions asked at Round 1 are in Supplementary data, and the results from validation at the face-to-face meeting are in Table 1. Round 1 was conducted via the SurveyMonkey® online platform, and Round 2 was held at the Park Plaza London Waterloo Hotel on October 11, 2022. AL acted as Chair, with an independent facilitator moderating the meeting. There were 10 panel members present in person, and nine panel members who joined virtually via Microsoft Teams. After the initial meeting, the recommendations and final manuscript (Round 3) were developed, with documents shared by e-mail and feedback collected independently from each participant by the facilitator. The agreed cut-off for the consensus was to have 80% of panel members in agreement, with methodology adopted from the manuscript published by Andrews and colleagues (2018).7 The process for the Delphi panel and subsequent manuscript development is shown in Figure 1.  

方法  

采用改进的德尔菲共识法，包括在线调查(第1轮)、面对面会议(第2轮)和会后对共识结果的回顾(第3轮)。第1轮的问题在补充数据中，面对面会议的验证结果在表1中。第1轮通过在线平台SurveyMonkey®进行，第2轮于2022年10月11日在伦敦滑铁卢酒店的公园广场举行。AL担任主席，由一名独立的主持人主持会议。有10名小组成员亲自出席，还有9名小组成员通过Microsoft Teams视频参加。在最初的会议之后，建议和最终的手稿(第3轮)被开发出来，由主持人通过电子邮件共享文件和从每个参与者独立收集的反馈。达成共识的标准是80%的小组成员同意，采用的方法来自Andrews和同事(2018)发表的手稿Delphi面板和后续手稿，开发的过程如图1所示。

Participants  

A total of 19 experts in the management of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in the critical care setting participated in the consensus process. The participants were selected based on their clinical role, and both their experience of managing stroke severe enough to warrant admission to critical care, managing fever in these patients, and using TTM. All of the participants were selected from leading intensive and neurocritical care groups: 17 from within the Neuro Anaesthesia and Critical Care Society (NACCS) UK network, and two from Italy.

参与者  

共有19名在重症监护环境中处理脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性卒中的专家参与了共识过程。参与者的选择是基于他们的临床角色，以及他们管理严重到需要接受重症监护的中风患者和发烧患者的经验，以及使用TTM。所有参与者都是从主要的重症监护和神经危重症治疗小组中挑选出来的:17人来自神经麻醉和神经危重症护理协会(NACCS)英国网络，2人来自意大利。

Rounds 1 and 2  

Statements and questions for each round were prepared by the independent facilitator in consultation with ALand delivered by SurveyMonkey® to each attendee by e-mail for them to complete an onymously online. Statements and questions were informed by a literature search, which identified publications relevant to the specific topics under discussion. The literature search focused on publications released since 2017. Round 1 comprised 23 statements and questions related to the clinical use of TTM for neurogenic fever in patients with intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke. These had been created in consultation with the meeting chair. All Round 1 questions were in amultiple-choice format. All questions were mandatory and included a comment box where participants could provide additional comments or insights.

Pooled responses to the Round 1 questions were displayed on screen to the whole group during the face-to-face meeting, and the results and comments were discussed during Round 2. All responses were reviewed and discussed regardless of the level of consensus. Where consensus (80% agreement) was achieved, the discussion focused on improvements in the phrasing or scope of the initial question to arrive at a final statement that clearly captured the consensus views of all experts. Where consensus was not reached, detailed facilitated discussion was undertaken to identify the reasons behind the lack of agreement.

第1轮和第2轮  

每一轮的的陈述和问题由独立主持人与ALand协商后准备，通过SurveyMonkey®通过电子邮件发送给每位参与者，让他们在网上匿名完成。陈述和问题是通过文献检索得到的，检索结果确定了与讨论中的特定主题有关的出版物。文献检索以2017年以来出版的出版物为主。第1轮包括23个陈述和问题，涉及TTM在脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性中风患者神经源性发热的临床应用。这些会议是在与会议主席协商后制定的。第1轮的所有问题都是选择题。所有的问题都是强制性的，并包括一个评论框，参与者可以提供额外的评论或见解。

在面对面的会议中，将第1轮问题的汇总回答显示在屏幕上，并在第2轮讨论结果并进行评论。无论协商一致程度如何，都要对所有答复进行了审查和讨论。共识（80%及以上认同者）和讨论的重点是如何改进最初问题的措辞或范围，以达成一份明确包含所有专家一致意见的最终声明。在未能达成协商一致意见的情况下，也要进行详细的讨论，以查明未能达成协议的原因。

Round 3 and final validation  

The responses from the meeting were captured in a summary document that showed how the consensus evolved ahead of, and during the meeting. For Round 3, this summary was distributed to all participants via e-mail, with meeting attendees asked to review and confirm the accuracy of the content in relation to the meeting discussions and provide any comments. Areas requiring additional discussion were identified, and the process for addressing these was guided by AL. A manuscript was prepared, structuring the recommendations, offering additional narrative, and providing context in relation to current clinical practice. The manuscript was distributed to all authors for parallel data analysis and interpretation, review of the article, and final validation and approval.

第3轮和最后验证  

会议的回应被记录在一个总结文档中，该文档显示了在会议之前和会议期间的共识是如何演变的。对于第3轮，该摘要通过电子邮件分发给所有与会者，与会者被要求审查和确认与会议讨论相关的内容的准确性，并提供任何意见。确定了需要额外讨论的领域，解决这些问题的过程由AL指导，他编写了一份手稿，构建了建议，提供了额外的叙述，以及与当前临床实践相关的背景。该手稿被分发给所有作者进行并行数据分析和解释，审查文章，并最终验证和批准。

Results  

The results of the final consensus agreements are presented in Table 1. To provide additional context around each recommendation, and the debate that took place ahead of reaching consensus, further explanation is given in the discussion section. Because of the expertise and specialities of the panel and the wide varieties of patients seen in non-critical care settings, the group agreed that their recommendations would focus solely on patients who had suffered a brain insult as a result of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke serious enough to warrant admission to a critical care environment.

结果  

最终协商一致协议的结果见表1。为了提供每项建议的附加背景，以及在达成协商一致意见之前进行的辩论，讨论部分给出了进一步的解释。考虑到专家小组的专业知识和专长，以及在非危重护理环境中看到的各种各样的患者，小组一致认为，他们的建议将只针对因脑出血、动脉瘤性蛛网膜下腔出血而遭受脑损伤的患者，或者严重到需要进入重症监护环境的急性缺血性中风患者。

Discussion   

To date, a relatively small amount of homogenous data has been published around the use of TTM with an automated feedback-controlled device for managing neurogenic fever in intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke, leading to the development of this consensus discussion. The Delphi method is an iterative process allowing the anonymous inclusion of a number of individuals across diverse locations and areas of expertise and avoiding dominance by any one individual. It uses a systematic progression of repeated rounds of voting and is an effective process for determining expert group consensus where there is little or no definitive evidence and where opinion is important.

讨论：

到目前为止，关于使用TTM和自动反馈控制装置来管理脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性中风中的神经源性发热，已经发表了相对少量的同质数据，这促进了这一共识讨论的发展。德尔菲法是一种迭代过程，允许匿名地将来自不同地点和专业领域的多个个体纳入其中，避免任何一个个体主导。它使用了一个系统的重复轮投票进程，是一个有效的确定专家的过程，相对少量的同质数据已经发布使用TTM与一个自动反馈控制设备用于管理脑出血，动脉瘤性蛛网膜下腔出血的神经源性发热，而急性缺血性卒中，引发了这一共识的发展讨论。德尔菲法是一种迭代过程，允许匿名地将来自不同地点和专业领域的多个个体纳入其中，避免任何一个个体主导。它采用了一种系统的、反复的投票过程，在没有或很少有确凿证据的情况下，在意见很重要的情况下，它是确定专家组共识的有效过程。 

The modified Delphi approach used in this case combined the early flow of structured information and submission of anonymous responses with the face-to-face discussion of responses and further voting to gain consensus and expert insight into usual practice regarding non-pharmacological TTM with an automated feedback-controlled device.

本案例中使用的改进的德尔菲法结合了早期的结构化信息流程和匿名回复的提交，以及面对面的回复讨论和进一步的投票，以获得共识和专家对带有自动反馈控制设备的非药理学TTM常规实践的深刻见解。

How to use targeted temperature management.

(i) An automated feedback-controlled device for targeted temperature management is indicated for high-quality temperature control for the treatment of neurogenic fever in adult patients with intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke in a critical care setting.

(ii)Temperature should be measured in ventilated patients with intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke managed in an ICU or high dependency unit (HDU) setting continuously, or at least hourly.

如何使用目标温度管理

(i)一种用于目标温度管理的自动反馈控制装置，用于在危重护理环境中治疗伴有脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性中风的成年患者的神经源性发热的高质量温度控制。

(ii)在ICU或高度依赖病房(HDU)环境中连续或至少每小时测量伴有脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性卒中的通气患者的体温。

The group debated the strength of indication of a TTM device for precise temperature control for the treatment of neurogenic fever, and concluded, after extensive discussion, that in these vulnerable patients, the reactive use of an automated feedback controlled device is indicated for TTM for fever control and to reestablish normothermia. As a second wave of the discussion, the group agreed that it may, in fact, be essential. Automated feedback-controlled devices for TTM are powerful tools, encouraging the delivery of quality care and aiming to improve neurological outcome. The TTM process can be divided into three phases: induction, maintenance, and rewarming. Although nonautomated methods of temperature control such as the infusion of ice-cold fluids are cheaper and easier to apply, the level of control offered is poor and their use should be limited to the induction phase, in combination with automated devices.

该小组讨论了TTM设备用于神经源性发热治疗的精确温度控制的适应症强度，并在广泛讨论后得出结论，在这些脆弱的患者中，自动反馈控制设备的反应性使用适用于TTM来控制发热和恢复正常体温。作为第2轮讨论，工作组一致认为，这实际上可能是必不可少的。TTM的自动反馈控制设备是强大的工具，鼓励提供高质量的护理，并旨在改善神经结果。TTM过程可分为诱导、维护、复温三个阶段。尽管诸如注入冰冷液体这样的自动化温度控制方法更便宜，也更容易应用，但所提供的控制水平较差，它们的使用应限制在诱导阶段，与自动化设备结合使用。

The group agreed that, fundamentally, temperature is an important vital parameter after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke. Active temperature control should continue for as long as the brain is at risk of secondary injury. The group confirmed that the determination of risk of secondary injury was to be based on local expertise but should include neuroimaging and neuromonitoring where available, including bedside indices of autoregulation such as the pressure reactivity index, brain metabolism such as microdialysis, and brain oximetry. Discussions initially focused on grouping patients into ventilated and non-ventilated cohorts, which led to agreement on a question re-phrase to avoid focusing on a widely heterogenous patient population. Consensus was reached on continuous monitoring of temperature in patients who are mechanically ventilated whenever feasible, and where continuous monitoring is not possible, at least hourly monitoring was recommended. Supporting literature describing the use of TTM after cardiac arrest emphasises the recommendation of continuous monitoring where possible, highlighting the likelihood of intermittent recording missing large fluctuations in temperature, and resulting in the potential for harm. In patients who have had a stroke but are not mechanically ventilated, consensus was reached on the pragmatic measuring of temperature at least every 4 h, acknowledging the importance of allowing the patient to rest. However, such patients found to be clinically unstable or deteriorating should have temperature measured more frequently.

研究小组一致认为，从根本上说，温度是脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性中风后的一个重要参数。只要大脑处于继发性损伤的危险中，就应该持续主动控制体温。该小组确认，继发性损伤风险的确定应基于当地的专业知识，但应包括神经成像和神经监测，如压力反应性指数，脑代谢(如微透析)和脑氧饱和度。讨论最初集中于将患者分为通气和非通气组，这将对问题的重新定义达成了一致，避免了关注广泛异质性的患者群体。在可行的情况下，对机械通气患者的温度进行连续监测已达成共识，如果不可能进行连续监测，则建议至少每小时监测一次。描述心脏骤停后使用TTM的支持性文献强调，在可能的情况下推荐持续监测，强调间歇记录可能遗漏较大的温度波动，并导致潜在的伤害。在没有机械通气的中风患者中，至少每4小时测量一次体温达成了共识，承认了让患者休息的重要性。然而，这类患者被发现临床上不稳定或病情恶化，应更频繁地测量体温。

Temperature measurement  

(i) In the absence of direct measurements, core temperature is the most useful surrogate measure of brain temperature.

The panel debated the various surrogates for the measure of brain temperature in the absence of direct measurements, focusing on core, tympanic, and axillary temperature, with core temperature being accepted as the most useful surrogate measure. Within the core temperature option, discussions centred around oesophageal, bladder, rectal, and intravascular measurements. After acknowledgement of their limitations, bladder and oesophageal were singled out as the favoured core temperature measurements. Rectal temperature monitoring was widely regarded as impractical for reasons such as the lag time, a high rate of dislocation, and potential embarrassment for the patient. Peripheral sites were unanimously deemed to be insufficiently accurate to guide temperature treatment in this context.8 In non-ventilated subjects, and in particular where oesophageal or bladder temperature measurements are not available, tympanic temperature measurement is preferred.

温度测量  

(i)在没有直接测量的情况下，核心温度是最有用的替代测量脑温度的方法。

该小组讨论了在没有直接测量的情况下测量大脑温度的各种替代方法，重点是核心温度、鼓室温度和腋窝温度，核心温度被认为是最有用的替代方法。在核心温度选项中，讨论集中在食道、膀胱、直肠和血管内测量。在认识到他们的局限性后，膀胱和食道被挑出来作为首选的核心温度测量。直肠温度监测被广泛认为是不切实际的，如延迟时间、高脱位率和潜在的尴尬患者。在这种情况下，一致认为外围位点不够精确，不能指导温度处理在不通气的受试者中，特别是当食道或膀胱温度无法测量时，鼓室温度测量是首选。

Temperature maintenance  

(i) The target temperature for patients with intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke should be between 36.0℃ and 37.5℃.

温度保持  

(i) 脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性卒中患者的目标温度应在36.0℃至37.5℃之间。

The main aims of TTM in a critical care setting, while the brain is at risk, should be maintenance of temperature between 36.0℃and 37.5℃and prevention of an increase in temperature above 37.5℃. The panel noted that temperature should ideally be centred at 36.5℃ on the understanding that the maintained temperature will be susceptible to the accuracy of the device and the variability of individual techniques, and that brain temperature can be up to 2℃ higher than core temperature. The group agreed that the maximum temperature variation that these patients should experience during TTM for normothermia is ideally less than plus or minus 0.5℃per hour, and<1℃per 24h period. Practically, this translates as a recommendation to initiate TTM when core temperature exceeds 37.5℃, and to select a target temperature between 36.5℃and 37.0℃.

在危重病护理环境下，当大脑处于危险状态时，TTM的主要目标是:该小组指出，考虑到维持的温度受设备的准确性和个别技术的变化的影响，温度最好集中在36.5℃。大脑温度可能比核心温度高2℃。研究小组一致认为，在正常体温状态下，这些患者在TTM期间应该经历的最高温度变化理想情况是小于±0.5 ℃每小时，并且小于1 ℃每24小时。实际上，这意味着建议在核心温度超过37.5℃时启动TTM，并选择在36.5℃至37.0℃之间的目标温度。

The group noted that there is a level of pragmatism to be adopted in avoiding fever, discussing that while more time spent in fever can negatively impact neurological outcome, fluctuations in temperature can also affect outcome. Fluctuations and increases in body temperature have been associated with poor outcome after stroke, worse modified Rankin Scale scores, and increased morbidity and mortality. Consensus was reached on the importance of maintaining temperature at a consistent level to ensure optimal recovery in patients with intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke.

该小组注意到，在避免发烧方面需要采取一定程度的实用主义，他们讨论了虽然发烧时间更长会对神经系统结果产生负面影响，但温度的波动也会影响结果。体温波动和升高与中风后预后不良、改良Rankin量表评分更差以及发病率和死亡率增加有关。对于将体温维持在一致水平的重要性达成了共识，以确保脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性卒中患者达到最佳康复。

Targeted temperature management for neurogenic fever  

(i)Neurogenic fever in patients with intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke can adversely affect patient outcome.

(ii)When used reactively once fever is detected, targeted temperature management should be initiated with an automated feedback-controlled device in these patients at 37.5 C, and ideally within 1 h from fever onset.  

神经源性发热的目标温度管理  

(i)脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性卒中患者的神经源性发热可对患者预后产生不利影响。

(ii)一旦检测到发热，应采用反应性的方法，在这些患者中使用自动反馈控制设备，温度控制在37.5℃，最好在发热开始后1小时内进行。

Fever is commonly found in patients admitted to neurocritical care. It has been found to increase the risk of complications and is often associated with unfavourable clinical outcome, whether the neurological injury was ischaemic, haemorrhagic, or traumatic in origin and whether the outcome being measured was clinical, functional, or economic. Although panel discussions focused on neurogenic fever, the group emphasised that it is important to correctly diagnose central fever vs fever of infectious origin because of the ramifications of failing to identify a treatable condition, the negative consequences of antibiotic overuse, and the detrimental effect of hyperthermia on brain-injured patients. Equally, TTM can mask development of worsening pyrexia secondary to infection. It was widely agreed by the group that the development of neurogenic fever in patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke negatively affects patient outcome, so within critical care settings, it is of utmost importance to prevent or promptly treat fever when detected.

在接受神经危重症治疗的病人中，发烧很常见。已经发现它会增加并发症的风险，并常常与不良的临床结果相关，无论神经损伤是缺血性的，出血的，还是外伤性的，以及测量的结果是临床的，功能性的，还是经济性的。虽然小组讨论的重点是神经源性发热，但小组强调，由于未能确定可治疗的情况的后果、抗生素过度使用的负面后果、以及热疗对脑损伤患者的不利影响，TTM可以掩盖继发于感染的发热恶化的发展。研究小组普遍认为，脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性卒中后的神经源性发热会对患者的预后产生负面影响，因此在重症监护环境中，发现发热时预防或及时治疗是至关重要的。

When using core temperature as a proxy of brain temperature, the group agreed that TTM should be initiated at 37.5℃, and whereas the definition of what constitutes pyrexia is debatable, it was flagged that waiting for a higher temperature would result in a potential overshoot and could subsequently be more difficult to correct and control. It was agreed that TTM should be initiated as soon as possible, with the group highlighting that this conveys the urgency but accepts the variability in feasibility across different centres and team settings, such as staff numbers and access to training and equipment.

当使用核心温度作为大脑温度的代表时，小组一致认为TTM应该在37.5℃开始，而发热的定义是有争议的，它被标记为等待更高的温度，将导致潜在的超调，并可能更难以纠正和控制。与会者同意应尽快启动TTM，专家组强调这传达了紧迫性，但也接受不同中心和团队设置的可行性存在差异，例如工作人员数量和获得培训和设备的机会。

(i) It is important for neurogenic fever in intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke to be treated with a single local targeted temperature management protocol.

(i) 对于脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性中风引起的神经源性发热，采用单一的局部目标温度管理方案进行治疗非常重要。

The panel felt that the term ‘protocol’ implies a large amount of detail, often being used as a ‘catch-all’ term that may lack clarity. The group discussed in depth whether it would be more beneficial to have a different protocol for intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke. After extensive discussion and acknowledgement of the regional differences in access to resources and for ease of adoption across the multidisciplinary team (MDT), it was agreed that a single protocol for the implementation of TTM for intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke would be the most effective method for managing neurogenic fever.

专家组认为，术语“医疗方案”意味着大量的细节，经常被用作“包罗一切”的术语，可能缺乏清晰度。该小组深入讨论了对脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性中风采用不同的治疗方案是否更有益。经过广泛的讨论，确认了区域在获取资源方面的差异，以及为便于跨多学科团队(MDT)采用，一致同意采用单一方案实施TTM治疗脑出血、动脉瘤性蛛网膜下腔出血、急性缺血性中风是治疗神经源性发热最有效的方法。

Targeted temperature management for shivering  

(i) It is important to manage shivering in patients after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke during temperature control in a critical care setting.

寒战的目标温度管理  

(i) 在危重病护理环境中，温度控制期间处理脑出血、动脉瘤性蛛网膜下腔出血或急性缺血性卒中患者的寒战是很重要的。

Shivering is common during TTM, and control of shivering can be challenging if clinicians are not familiar with the available options and recommended approaches. Shivering can cause a decrease in brain tissue oxygen leading to cerebral metabolic stress, potentially eliminating the benefits of the TTM.

在TTM中，寒战是常见的，如果临床医生不熟悉可用的选项和推荐的方法，控制寒战可能具有挑战性。发抖会导致脑组织氧气的减少，从而导致大脑代谢压力，这可能会消除TTM疗法的益处。根据目前的文献，该研究小组一致认为，寒战必须得到控制。

The group agreed, in line with current literature, that shivering must be managed. It was agreed that for effective temperature control, counter warming, paracetamol, sedatives, magnesium, opioids, and neuromuscular blocking agents should be included in a protocol to manage shivering. Such measures could be utilised in a stepwise approach, from non-sedating interventions to sedatives and neuromuscular blocking agents if first-line interventions have no positive effect. The panel highlighted that whilst non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage fever and shivering in clinical practice, there exists a range of contraindications to NSAIDs after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke, and that their use should be based on individual assessment of risks and benefits

大家一致认为，为了有效控制体温，应对升温、扑热息痛、镇静、镁、阿片类药物和神经肌肉阻断剂应包括在治疗寒战的方案中。如果一线干预措施没有积极效果，可以逐步使用这些措施，从非镇静干预到镇静剂和神经肌肉阻断剂。专家组强调，虽然在临床实践中，非甾体抗炎药(NSAIDs)通常用于控制发烧和寒战，但在脑出血、动脉瘤性蛛网膜下腔出血和急性缺血性中风后，NSAIDs存在一系列禁药，它们的使用应该基于对风险和收益的个人评估。

(ii) Controlled rewarming should take place at a speed of 1℃per day.

(iii) Normothermia should be maintained for as long as the brain is at risk once the patient is rewarmed.

(ii)控制复温应以每天1℃的速度进行。

(iii)只要患者被重新加热，大脑就处于危险状态，所以应保持正常体温。

The group highlighted that controlled rewarming is an essential component of high-quality TTM to avoid shivering. Following a second-round vote, the panel agreed that 1℃   per day was the optimum speed to rewarm patients, noting that rebound hyperthermia is common and should be avoided if the brain remains at risk. Reinstating TTM can be considered in the case of rebound hyperthermia. The group advised that the speed of rewarming to normothermia should be slow and controlled, within time-controlled parameters. If body temperature and shivering are not adequately monitored, induction is delayed, body temperature remains variable using nonautomated methods, and spontaneous and fast rewarming occur, the patient will be exposed to ‘low-quality TTM’ and the likelihood of a beneficial effect will be compromised.

该小组强调，可控复温是高质量TTM的一个重要组成部分，以避免发抖。在第二轮投票后，专家组一致认为，每天1℃是给患者重新加热的最佳速度，并指出反弹式热疗是常见的，如果大脑仍然处于危险中，应该避免。在回弹热疗的情况下可以考虑恢复TTM。该小组建议，恢复体温到正常体温的速度应该是缓慢和可控的，在时间可控的参数范围内。如果体温和寒颤没有得到充分监测，诱导被延迟，体温使用非自动化方法保持可变，并且自发和快速的复温发生，患者将暴露于“低质量的TTM”，有益效果的可能性将被削弱。

Outcome assessment  

The group extensively debated the best utility metrics for measuring the quality of TTM in patients after acute stroke. In addition to compliance with local protocols, the group agreed that in a critical care environment the amount of time spent within the target temperature range of 36.0-37.5℃ and outcome scores, such as the modified Rankin scale, would be valid measures of the quality of TTM delivery. The quality of TTM is multifactorial, with significant variability induced by human factors, such as staff numbers and access to training and equipment. Adopting a holistic approach to TTM and physiological optimisation is of utmost importance and aims to deliver high-quality care with the aim of ensuring patients achieve the best possible quality of life after brain insult from intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, or acute ischaemic stroke.

结果评估  

该小组广泛讨论了衡量急性脑卒中患者TTM质量的最佳效用指标。除了遵守当地的规程外，该小组同意，在重症监护环境中，在36.0-37.5℃的目标温度范围内花费的时间和结果分数，如修改后的饮酒量表，将是有效的测量TTM分娩质量的方法。TTM的质量是受到多因素影响的，由于人员数量、培训和设备等人为因素的影响，其可变性显著。采用整体的TTM方法和生理优化至关重要，目的是提供高质量的护理，以确保患者在颅内出血、动脉瘤性蛛网膜下腔出血或急性缺血性中风造成的脑损伤后实现最好的生活质量。

It was agreed that the question of what functional outcome measure was most useful was beyond the scope of the panel. It was agreed, however, that it is important to measure efficacy of TTM, with relevant metrics including compliance to local protocols, time within target temperature range, time to achieve normothermia, and avoidance of fever. Tracking these measures over time and ensuring correction through implementation of measures to improve performance, such as staff training, was also highlighted as a key aspect of quality care.

大家一致认为，什么功能结果测量方法最有用的问题超出了小组的范围。然而，人们一致认为，重要的是测量TTM的有效性，相关指标包括是否遵守当地协议、目标温度范围内的时间、达到正常体温的时间和避免发烧。会议还强调，要长期跟踪这些措施，并通过实施改善工作表现的措施(例如培训工作人员)来确保纠正，这是优质护理的一个关键方面。

Limitations  

This consensus review was carried out to evaluate current evidence in the literature on the use of TTM in the management of fever after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in a critical care setting, and to develop a set of practical recommendations addressing the current gaps in published evidence. Conflicting reports of its safety and feasibility and differing recommendations around its use in clinical settings have led to a range of guidelines and recommendations being developed, with no clear conclusion. Although early clinical trials such as COOL AID and ICTuS offered support for its safety and feasibility, more evidence is needed to help prove its utility in clinical practice.3 Several surveys have reported that a lack of treatment protocols, knowledge deficiencies, limited access to dedicated equipment, cost, and increased workloads are major barriers to TTM implementation.

局限性  

这项共识性综述是为了评估目前文献中使用TTM在重症监护环境中治疗脑出血后发热、动脉瘤性蛛网膜下腔出血和急性缺血性卒中的证据。并提出一套切实可行的建议，以解决已发表证据中目前存在的差距。关于其安全性和可行性的相互矛盾的报告，以及在临床环境中对其使用的不同建议，导致了一系列指南和建议的制定，没有明确的结论。虽然COOL AID、ICTuS等早期临床试验为其安全性和可行性提供了支持，但在临床应用中还需要更多的证据来证明其实用性几项调查表明，缺乏治疗方案、知识不足、专用设备有限、成本高和工作量增加是实施TTM的主要障碍。

A key limitation of this report is that the recommendations from the group are based on experience in two relatively highresource countries, the UK and Italy, so have potentially limited applicability to lower-resource settings and populations noted to be disproportionately at risk of stroke. This highlights the need for future recommendations and reports that address these, and other, underrepresented groups.

本报告的一个关键局限性是，该小组的建议是基于两个资源相对丰富的国家——英国和意大利的经验，因此对资源较少的环境和中风风险较高的人群的适用性可能有限。这突出表明今后有必要提出解决这些和其他代表人数不足的群体的建议和报告。

This report was written by an expert panel comprised of specialists in neurocritical care, and the recommendations are therefore limited to patients managed in a critical care or high dependency care environment. Although the recommendations are relevant to patients managed in other settings such as acute stroke units or thrombectomy patients managed in postanaesthesia care units, local practice, staff training, and the availability of equipment will differ in such settings. In addition, the heterogenous nature of stroke patients within critical care must be highlighted. The recommendations offered must be contextualised to individual patient and system needs, with treatment and management implemented according to the severity of brain injury and clinical course.6 Future research and additional studies should allow for recommendations of greater certainty and more definitive standards of TTM care across different hospital care settings.

本报告由神经危重症护理专家组成的专家小组撰写，因此建议仅限于危重症护理或高度依赖护理环境下的患者。虽然这些建议适用于在其他环境下管理的患者，如急性卒中单位或血栓切除患者在麻醉后护理单位管理，但当地的实践、工作人员培训和设备的可用性在这些环境中会有所不同。此外，必须强调危重护理中中风患者的异质性。所提供的建议必须根据患者个人和系统的需要，根据脑损伤的严重程度和临床过程实施治疗和管理未来的研究和额外的研究应该允许在不同的医院护理环境中对TTM护理提出更大的确定性和更明确的标准。

As the ECHO group noted, the Delphi process has some drawbacks. The group discussion after the anonymous online survey completion can be impacted by social bias, with live voting and displays shown on screen potentially affecting attendees’ ability to vote and comment freely. The opinions of the nine panel members who joined virtually might have been unequally weighted in comparison to those joining in person, highlighting the potential need to carry out future panel meetings with all members joining in the same format.

正如ECHO小组所指出的，Delphi程序有一些缺点。匿名在线调查完成后的小组讨论可能会受到社会偏见的影响，现场投票和屏幕上的显示结果可能会影响参与者自由投票和评论的想法。和亲自参加的小组成员相比，虚拟参加的9名小组成员的意见可能受到了不平等的重视，这突出了未来所有成员以相同形式参加小组会议的潜在必要性。

Two important questions ‘Which first-line therapeutic option should be included in a protocol to manage shivering?’ and ‘What is a valid metric for measuring the quality of TTM delivery in patients following acute stroke severe enough to be admitted to critical care?’ resulted in no consensus. Whereas it was agreed that a variety of measures could be utilised to control shivering in a stepwise approach from non-sedating interventions to sedatives and neuromuscular block, the panel felt that the choice of first-line interventions are context-sensitive. Whilst NSAIDs represent a valid first-line option in many circumstances, there exists a range of contraindications to their use in this clinical context and their use as first-line options should be based on individual assessment of risks and benefits. Although the panel agreed that outcome scores such as the modified Rankin scale would be valid measures of the quality of TTM delivery, they concluded that the question of what functional outcome score was most useful was beyond the scope of the panel, and that the importance of other metrics such as compliance to local protocols, time within target temperature range, time to achieve normothermia, and avoidance of fever should be highlighted.

两个重要的问题:“治疗寒战的方案中应该包括哪种一线治疗方案?”和“什么是衡量急性中风患者的TTM交付质量的有效指标，严重到需要接受重症监护?”没有达成共识。尽管人们一致认为，可以采用从非镇静干预到镇静和神经肌肉阻滞等多种措施逐步控制寒战，但专家组认为，一线干预措施的选择应视具体情况而定。虽然在许多情况下，非甾体抗炎药是一种有效的一线选择，但在这种临床背景下，它们的使用存在一系列禁忌症，作为一线选择的使用应基于个人的风险和收益评估。尽管专家组一致认为，结果评分(如修改的Rankin量表)将是衡量TTM交付质量的有效方法，但他们得出的结论是，什么功能结果评分最有用的问题超出了专家组的范围，其他指标的重要性，如本地协议的符合性，在目标温度范围内的时间，达到正常体温的时间，以及避免发烧的时间也得到了强调。

Conclusions  

Targeted temperature management is a complex therapy that could have a role in reducing secondary injury and improving long-term neurological outcome for patients.6 However, the use of targeted temperature management in specific settings, and the appropriate methods for its implementation, remain relatively understudied, and high-quality and consistent evidence is lacking. Following agreement from the Delphi panel that there is a clear need for clinical guidance, this review aims to serve as a springboard for further evidence and consensus to be developed for the management of fever with targeted temperature management after intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and acute ischaemic stroke in the critical care setting, and for how the clinical practice of targeted temperature management can be improved.

结论

靶向温度管理是一种复杂的治疗方法，可以减少继发性损伤，改善患者的长期神经系统预后然而，在特定环境下使用有针对性的温度管理及其实施的适当方法仍然缺乏相对的研究，而且缺乏高质量和一致的证据。根据德尔菲小组的共识，明确需要临床指导。本综述旨在作为进一步证据和共识的跳板，为脑出血、动脉瘤性蛛网膜下腔出血后的针对性温度管理发烧提供证据和共识，以及急性缺血性卒中重症监护的设置，以及如何在临床实践中改善针对性的温度管理。

Declarations of interest  

AL received consultancy and speaker fees from Becton, Dickinson and Company (Berkshire UK) for Chairing the Delphi panel and for contributing to the writing of the article. JPC was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.  

利益声明  

AL从贝克顿，迪金森和公司(伯克郡英国)获得了咨询和演讲费，作为Delphi小组的主席和文章的写作。JPC得到了英国国立卫生研究院剑桥生物医学研究中心的支持(BRC-1215-20014)。所表达的观点是作者的观点，不一定是国家卫生和社会福利部或卫生和社会福利部的观点。

Funding  

This article contains the personal and professional opinions of the individual authors and does not necessarily reflect the views and opinions of Becton, Dickinson and Company or any Business Unit or affiliate. The document has been supported by an unrestricted educational grant from Becton, Dickinson and Company (Berkshire UK).

资金支持  

本文包含作者个人和专业的观点，并不一定反映Becton, Dickinson和公司或任何业务单位或附属机构的观点和意见。该文件得到了贝克顿，迪金森和公司(伯克郡英国)不受限制的教育拨款的支持。

Acknowledgements  

The group acknowledge the support of Page & Page and Partners in facilitating the Delphi meeting, and Emily Sidlow in preparing the manuscript. If drugs or medical devices are cited in the article, please consult package insert and instructions for their use to know indications, contraindications, and any other more detailed safety information.

鸣谢  

该组织感谢Page & Page及其合作伙伴在促成Delphi会议方面的支持，以及Emily Sidlow在准备手稿方面的支持。如果文章中引用了药物或医疗器械，请参考说明书和使用说明，了解适应症、禁忌症和其他更详细的安全信息。

Appendix A. Supplementary data  

Supplementary data to this article can be found online at https://doi.org/10.1016/j.bja.2023.04.030.

附录A.补充数据  

本文的补充数据可以在https://doi.org/10.1016/j.bja.2023.04.030网站上找到。

图1。德尔菲程序概述。英国麻醉杂志BJA;神经麻醉和危重症护理学会;NTCR，神经保护治疗共识综述。

免责声明：

文中所涉及药物使用、疾病诊疗等内容仅供医学专业人士参考。

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编辑：MiLu.米鹭

校对：Michel.米萱