这项工作得到了比利时安特卫普大学医院 (UZA) 的多学科疼痛中心、麻醉学和危重护理医学部门的部门赠款的支持。此外, 还从安特卫普大学 (UA) 获得了一项教育补助金 (德豪斯 mandaat)。作者想感谢汤姆 Schepens 博士在修改本文时的专家帮助。

此单中心队列研究是根据 GCP 的道德标准和赫尔辛基宣言在比利时安特卫普大学医院的机构审查委员会和道德委员会批准后进行的 (研究标识符:16/33/334)。这项研究在 Clinicaltrials.gov (NCT02916004) 开始前注册。
所有包括的病人都是按照标准的医院镇静协议, 在学习报名前镇静剂。病人被滴定的里士满搅拌镇静秤 (RASS) 设置由 ICU 医生。患者在研究纳入 RASS 之前被镇静治疗4。所有患者例行滴定的行为疼痛量表 (BPS) 的3由 ICU analgosedation 协议。
注意: 不建议仅根据记录的疼痛反射的兴奋性来确定治疗措施。在解释测量时, 必须考虑反射弧的传出分支可能产生的影响。镇静或麻醉的患者比非镇静病人有更高的疼痛反射阈值。对于反射评估, 可能需要更高的电流。建议对生理参数 (心率、血压、呼吸率) 进行监测。
1. 安全防范措施
<ol><li>验证噪声控制的潜在混杂 (其他设备, 交替床垫)。</li>
	<li>验证环境温度是否在正常范围内。</li>
</ol>2. 主题的定位
<ol><li>将病人放置在床上, 保持臀部屈曲和膝部 130 160°的120°角。</li>
	<li>把手腕的手掌侧向上。</li>
	<li>确保非测量的眼睛在反射记录期间关闭。</li>
</ol>3. 制备电极用皮肤
注: 这将减少电极阻抗。
<ol><li>在应用场所修剪或剃毛。</li>
	<li>检查申请地点, 他们必须干净和干燥。如有必要, 用肥皂和水清洁皮肤, 用干洗布或纱布轻轻擦拭皮肤, 以去除任何身体乳液。</li>
	<li>擦伤使用可用磨料材料的应用现场。使用皮肤准备纸在一个大面积, 而不是只有一个单一的刷卡。</li>
	<li>在皮肤准备后立即应用每个电极。</li>
</ol>4. 电极的放置为瞳孔扩张反射 (民主共和国) 评估
注: 请参阅有关电极应用概述的数字。磁场和电场可能出现在测量轨迹中的背景噪声或其他文物。使用以下协议的最大可接受的噪声级别是从高于10µV 的值设置的. 在刺激之前区域的最大振幅 (即-130 ms 在刺激前达到-10 毫秒) 以上, 定义了高噪声水平, 超过了此可调阈值 ("最大可接受的噪音级别")。噪声值不被用来计算阈值, 刺激是重复的电流强度, 直到一个无噪音的肌电信号信号确定。要限制文物的发生, 请验证设备是否已更新到最新版本。可以通过最佳电极放置和皮肤准备来减少手工制品。
<ol><li>使用银 AgCl 电极与高导电性湿凝胶, 以确保最佳信号在反射记录。</li>
	<li>保持30毫米 (中心到中心) 之间的电极间距离。</li>
	<li>放置两个刺激电极为共和国录音, 在手腕上的皮肤区域支配的正中神经, 保持腕掌侧朝上向上。</li>
</ol>5. 电极的放置对伤害性屈曲反射 (NFR) 评估
注: 请参阅有关电极应用概述的数字。
<ol><li>在脚踝上使用两个刺激电极, 将电极置于侧踝远端, 刺激腓肠神经区。</li>
	<li>使用两个注册电极的肌电信号记录在股二头肌肌肉。将电极四指宽度在腘窝上方, 后侧到髂胫束带上。</li>
	<li>使用一个参考电极, 放置在四头肌肌腱。</li>
</ol>6. 安全检查
<ol><li>识别材料: 电池状态 (民主共和国工具), 附近的插头连接 (NFR 评估监视器) 的可访问性, 导线, 以及与标签设备插座的连接。</li>
	<li>识别病人: 病人数量, 病史, 当前药物, 行为疼痛量表, 镇静深度。</li>
</ol>7. 瞳孔扩张反射评估: 入门
<ol><li>将引线连接到手腕上的刺激电极上。验证黑色标记部件是否连接到最远端电极。</li>
	<li>打开红外线摄像机。</li>
	<li>选择测量协议: "瞳孔疼痛指数" (PPI), 通过菜单选择触摸屏显示。执行由有色符号指示的阻抗控制, 如有必要, 重复准备过程。</li>
	<li>用清水清洁照相机和眼睛驾驶室, 并对其进行消毒。</li>
</ol>8. 瞳孔扩张反射评估: 安装
<ol><li>打开眼睑, 将相机置于最佳位置。<ol>
<li>让橡胶眼罩在轨道上休息, 包围整个眼睛。</li>
		<li>验证是否正确设置了瞳孔检测并在必要时调整照相机。操作者可能需要提高眼睑。</li>
		<li>中心的瞳孔在屏幕中间, 并通过追求一个完全有色绿色的瞳孔来验证位置。</li>
	</ol>
</li>
	<li>关闭对侧眼睛, 减少一致的光反应。</li>
	<li>等待至少5秒钟开始测量, 确保学生住宿所需的稳定期 (暗测量环境)。</li>
</ol>9. 瞳孔扩张反射评估: 测量
<ol><li>按下触发器按钮开始测试。按住按钮直到瞳孔评估完成 (几秒钟)。确保整个测量周期由2个可听到的信号执行 (首先在开始时, 第二次测试结束时)<ol>
<li>测量时请勿移动摄像机;当刺激强度从10毫安增加到最大60毫安时, 屏幕上会显示倒计时。</li>
	</ol>
</li>
	<li>识别屏幕上15秒后自动显示的结果 基线瞳孔大小 (毫米) 在有害刺激之前 (黄色水平线)。 最大瞳孔大小 (毫米) 在有害刺激 (白色水平线) 以后。 不同级别的有害刺激的颜色带和价值。 最大瞳孔变异 (% 和毫米)。 PPI 评分</li>
	<li>在瞳孔评估后按下图标保存测量结果。</li>
</ol>10. 伤害屈曲反射评估: 入门
<ol><li>连接导线以进行刺激、记录和参考。验证黑色标记部件是否附着在最远端电极上;白色用于记录膝部的参考值。</li>
	<li>连接到电源时打开设备。如果需要数据存储, 请标识 USB 闪存驱动器。</li>
</ol>11. 伤害屈曲反射评估: 安装
<ol><li>按 "设置" 按钮转到 "配置" 菜单, 以验证在无意识镇静病人中反射测量的刺激设置和阈值确定程序。<ol>
<li>验证测量技术在阈值跟踪中。</li>
		<li>验证刺激类型是否确定为RIII 反射。</li>
		<li>当要求卢比输入时, 请选择 "关闭"。</li>
		<li>选择Z 峰值评分作为评价标准。</li>
		<li>使用 > 100 的刺激次数。</li>
		<li>启动刺激的强度为1毫安, 最小和最大步长为0.5 毫安。</li>
		<li>验证Interstimulus 间隔定义为8秒,反射范围为 90-180 毫秒。</li>
	</ol>
</li>
</ol>12. 伤害屈曲反射评估: 测量
<ol><li>开始测量,即自动反射阈值跟踪。</li>
	<li>通过重复皮肤准备协议, 在 "高噪声水平" 出现时减少阻抗。</li>
	<li>识别反射特征。<ol>
<li>确定应用于患者的电流和刺激的数量。</li>
		<li>通过大腿肌电图电极的刺激, 识别出200毫秒前显示的原始肌电图 300 ms。</li>
		<li>识别反射范围和反射阈值。参数以数字显示 (mA 中的值)。</li>
	</ol>
</li>
</ol>

作者没有什么可透露的。

本文介绍了两种伤害性反射装置在成人 ICU 患者客观 (患者独立) 疼痛评估中的应用。此外, 还介绍了 NFR 的评价和特征。
疼痛和谵妄在住院病人中很常见, 通常是结合在一起, 可能会对结果参数产生不利影响。在 ICU, 阿片类药物经常被管理, 有时与其他镇静剂结合, 以保护病人免受压力刺激, 如护理或各种诊断或治疗程序, 并改善机械通气治疗, 或他们可能是必要的, 因为严重的疾病。然而, 广泛的证据表明, (不必要的) 长期管理 analgosedation 对 ICU 患者的发病率和死亡率有负面影响。此外, 实施可靠的基于证据的 analgosedation 协议可进一步改善患者结局36、37、38。
所描述的反射评估技术可以被认为是医疗保健中的质量指标, 与阿片类药物的使用密切相关;进一步实施可能会缩短 ICU 的停留时间, 改善短期和远期结局。此外, 通过伤害性评估测量伤害性反射阈值可能导致靶向和患者特定的阿片类药物管理。因此, 迫切需要对危重患者现有的客观疼痛评估工具进行评估和验证。用于民主评估的红外线 pupillometry 显示出有希望的结果39,40。与以前的研究一致, 这项研究表明, pupillometry 在一个非常技术环境中的无意识患者是可行的, 快速的, 直接41,42。此外, 使用衍生的 PPI 评分, 临床医生提供的水平的镇痛。我们的研究清楚地表明, NFR 可以定期评估在 ICU 患者。然而, 它提出了一些重要的观点。首先, 尽管最大的皮肤准备, NFR 评估可能无法测量由于持续高电极阻抗。其次, 我们确定了 NFR 不存在的患者, 即使是最大的刺激强度。尽管 NFR 测量更具挑战性, NFR 阈值评估在异丙酚-瑞芬太尼镇静43的患者中表现出了可喜的效果。
改进反射评估技能, 作者建议执行者考虑一些关键步骤。为了产生高质量的输出, 必须追求低电极阻抗。因此, 用异丙醇清洁皮肤应限于在电极粘连可能有问题 (乳液覆盖皮肤) 的患者, 因为它可能脱水皮肤, 因此增加阻抗。研磨的皮肤在电极应用网站与预期的材料将优化测量变量。然而, 应该注意不要伤害病人的皮肤。在反射评估之前, 用户可以很容易地执行阻抗控制以相似的方式为两个设备, 看在主屏幕的色的电极标志。绿色符号表示最佳电极阻抗, 黄色符号意味着 "良好" 阻抗。当该符号为红色时, 阻抗过高, 无法测量, 应重复皮肤准备过程。此外, 建议使用 (非常) 小刺激电极 (即, 45 毫米 x 30 毫米), 以避免电极重叠, 这可能导致不正确的反射记录。最后, 在启动反射测量之前, 探索设备设置, 因为默认设置或刺激特性可以在不同的患者群体之间发生变化。明显关注的问题是高不必要的电流应用主要是清醒的, 有意识的病人。
尽管对无意识患者2、16、17、18的生理疼痛评估的兴趣与日俱增, 但这两种设备都需要承认一些局限性。最值得注意的是, pupillometer 使用一种内置的测量模型, 称为 "瞳孔疼痛指数", 包含逐步增加的强直刺激。当瞳孔从基线尺寸 (固定截止标准) 扩张超过13% 时, 测量协议就停止了。采用这种内在的限制, 假设发生的心动过速和高血压的伤害刺激反应。虽然 pupillometry 刺激模型更频繁地被使用, 数据证实这个假说是缺乏的。此外, 这一模式的真正挑战在于这些测试在常规临床实践中的实际实施。虽然更客观和患者独立的伤害性反射测量可能为止痛治疗提供新的观点, 准备和测量需要大约15分钟 (特别为 NFR 评估), 仍然挑战在一个快节奏的工作环境中。此外, 在危重病人中, 目前尚无标准数据可用于 "正常反射范围"。在使用这些高度创新的工具方面, 优化医护人员的技能和专长可能会产生非凡的结果, 可以进一步分类镇痛水平, 改善疼痛检测, 预防慢性疼痛紊乱并使 (重新评估疼痛管理。此外, 可能出现经济测算的机会, 使用客观的疼痛评估工具可以为测试新的药理、镇痛化合物提供独特的平移平台。
测量更客观的伤害性反应, 如共和国和 NFR, 可以帮助临床医生评估病人的具体镇痛需要, 尤其是那些谁不能报告疼痛水平本身。这两种评估工具能否在日常实践中广泛应用还有待确定。这两种创新装置都能预测伤害状态, 并能指导临床医生优化非沟通性危重患者的镇痛治疗, 值得进一步调查。

重症监护病房 (ICU) 中的许多危重病人在日常护理或诊断或治疗过程中往往会遇到疼痛。不符合标准的伤害评估和随后的次优疼痛管理可能会增加压力和焦虑1。持续性疼痛不仅增加循环儿茶酚胺, 损害组织灌注和减少氧传递2 , 但也激活代谢高代谢, 从而导致高血糖, 脂肪和肌肉损失。所有这些因素都损害了愈合过程, 并增加了感染的风险3,4,5,6。
正如国际疼痛研究协会 (IASP) 所指出的, 临床医生必须使用对所有患者都有效的疼痛评估工具, 自我报告仍然是疼痛评估的黄金标准。然而, 有许多情况下, 病人无法沟通, 特别是由于严重的疾病或当他们是机械通气 (MV)。随着对 ICU 患者相关结局措施的兴趣增加, 在病人无法报告疼痛和不适时, 需要有结构可靠的伤害性评估技术。由于缺乏具体、可重复和可行的监测工具, 解决这一需要的努力受到阻碍。近年来, 为医生提供更客观的伤害参数, 已有相当大的努力。然而, 在 ICU 中执行的许多研究都集中在使用生命体征作为疼痛评估的可能替代因素, 而不使用血压或心率作为疼痛7、8的具体参数。
正如先前的研究报告所报道的, 未经治疗的疼痛会严重损害患者的预后, 因此, 应始终独立评估生命体征, 评估不应受患者无法沟通7的影响, 8,9,10,11,12。由于疼痛已知的负面后果, 这种客观伤害评估方法得到了相当大的支持。特别是在 ICU 患者中, 生理和心理的影响可以是可观的和长期的, 可能会显著降低健康相关的生活质量13,14。
目前, 尚无客观的疼痛监测协议, 可以很容易地应用于一大群危重病患者。在 ICU 患者中实施客观评估工具, 可以优化疼痛管理, 防止中枢性敏化综合征的发展。此外, 阿片诱导的痛觉 (OIH), chronification 疼痛和长期疼痛相关的发病率可能会下降。最后, 应用伤害性反射评估工具可以提供一个独特的翻译平台, 新的药理镇痛化合物可以测试。
拟议方法的目的是提供技术要求的概览, 并详细说明用于评估非交际性 ICU 患者的伤害性反应的议定书。总的来说, 我们的目的是为在 ICU 和在其他情况下, 需要评估镇静剂或无意识的病人, 提供一个全面的指南, 以使用客观的疼痛测量工具。
从2016年10月到 2017年12月, 被纳入 ICU 的危重昏迷成人被筛选为研究对象。所有机械通气, 并接受了严格的 analgosedation 协议, 含有异丙酚/瑞芬太尼或异丙酚/舒芬太尼, 这是两个最常用的方案在我院。眼科手术病史, 已知瞳孔反射障碍, 霍纳或阿迪综合征, 前眼外伤, 颅神经损伤或急性颅内高压引起的颅脑损伤, 肿瘤压迫或出血, 暴发性中风,已知 (聚) 神经病变与糖尿病或其他神经疾病相关, 已知影响反射活动, 内或体外治疗 (起搏器, 主动脉内球囊泵, 体外生命支持), 慢性阿片类药物使用 (> 3 月), 年龄< 18 年来, 使用局部干扰眼药水 (阿托品, 肾上腺素), α2肾上腺素激动剂15, 使用其他 analgosedation 协议比描述的纳入标准或神经肌肉阻滞药被定义为排除标准。
从数字病人数据管理系统 (例如, Metavision) 提取了注册科目的人口统计学变量和医学数据, 包括简化的急性生理学评分 ii (sap ii),16 。
疼痛评估
ICU 患者被筛选为研究纳入, 这需要一个病史和入院诊断, 以评估纳入和排除标准上述。在现实生活条件下, 在 ICU 环境中评估生理反应: 没有对温度或噪声控制进行具体的修改。反射评估在日间工作时间在大约20°c 的单独患者房间执行了。当在触摸屏显示器上启用此功能时, 所有生成的数据 (反射特性) 都可以存储在两个设备中。
瞳孔扩张反射的测量
采用红外视频记录法对瞳孔扩张反射 (pupillometry) 进行定量瞳孔大小评价。对于标准伤害刺激的应用, 两个低阻抗的银 AgCl 电极被放置在皮肤区域支配由正中神经在左侧手臂后, 皮肤准备 (图 1)。电流固定在 60 milliampères (mA), 最大可接受电阻为5欧姆, 定义电压限制为300伏特 (V)。
通过内置的瞳孔疼痛指数 (PPI) 测量协议, 为动态瞳孔反射评估生成自动电刺激模式, 进行了民主评估。标准化的有害刺激被应用了以增加的强度 (从 10 ma 到 60 ma 以增量步 10 ma, 期间 1 s 和脉宽200µs) 直到瞳孔膨胀大于 13% ([最大直径最小直径]/最大直径 * 100) 或最大刺激 60 mA 达到。当达到定义的标准时, 刺激被自动中断, 并显示 PPI 评分 (表 1)。基线瞳孔大小 (标准的有害刺激之前), 瞳孔反射幅度 (PRA), 刺激强度和 PPI 评分记录。根据所需刺激的数量, 民主共和国的测量时间为2至16秒。
一些研究表明, pupillometry 在非交际性 ICU 成人中的应用。保卢斯等人表明, 民主评估可能预测的镇痛要求在气管吸入17。此外, 这种方法可能能够揭示不同程度的镇痛, 并可能有歧视性的性质, 对不同类型的有害程序18,19。最近, 由于其低刺激电流, 科学上的兴趣已经转向使用特定的《民主共和国评估议定书》。我们的方法中建议的 PPI 协议以前曾在麻醉成人中进行过调查, 揭示了民主共和国与阿片管理20之间的显著相关性。此外, Sabourdin等。21表明, 可用于指导个别术中瑞芬太尼的管理, 从而减少术中阿片的消耗和术后抢救镇痛的要求。
痛觉屈曲反射的测量
为了评估初级传入纤维在痛觉受器外周向交感神经链中的伤害信号传输中的作用, 评估了伤害性屈曲反射 (NFR)。反射诱导是介导的一个三角洲纤维被激活后, 神经元之间的复杂相互作用位于脊髓背角的22。Rhudy 和同事们描述了 RIII 反射, NFR 在 nociceptor 激活后, 以高阈值伤害性特征测量 electromyographically (肌电图) 的晚期反应。23
增加电刺激是通过皮肤银 AgCl 电极在侧踝, 触发单一感觉腓肠神经。通过肌电信号记录的时间和振幅来评估反射响应 (图 2;经博士批准转载. 1月 Baars, 董事总经理, Dolosys 有限公司。
跟随冷漠等, 使用描述的反射注册设置, 需要刺激强度引出 NFR (阈值跟踪) 可以作为一个客观伤害评估相关的主观疼痛评分24,25,26,27,28. 随后, 已进行了大量研究, 以确定反射性特征 (主要是反射阈值和振幅) 及其与有意识成人疼痛强度感觉的相关性。这些研究表明, 反射阈值和反应振幅与疼痛强度27、29、30密切相关。此外, 标准的 NFR 评分标准, 如反射峰和平均反射肌电图活动, 可作为可靠的标准, 以确定这 NFR23,31,32。根据最近的研究, 所定义的反射特性贡献的 NFR, 尽管他们的经验来源, 显示良好的测试重测信度33,34。NFR 记录的持续时间, 考虑到 (可变) 步长范围 (0.5 毫安-2 ma), interstimulus 间隔8秒, 间隔随机化 20%, 以避免在刺激90后 180-35 毫秒之间可能的适应和反射范围, 是在5和15分钟之间取决于必要的刺激强度, 以引出 NFR, 因此, 所需刺激性的数量 (最多 100 mA)。

<table border="0" cellpadding="0" cellspacing="0" width="1021">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Neurolight Algiscan</td>
			<td style="width:215px;">ID Med, Marseille, France&#160;</td>
			<td style="width:221px;">Pupillometre 13235</td>
			<td style="width:369px;">Infra red camera for pupil dilation reflex measurement</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Paintracker</td>
			<td style="width:215px;">Dolosys GmbH, Belin, Germany</td>
			<td style="width:221px;">Paintracker V1 2497</td>
			<td>Nociception flexion reflex assessment tool</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Red DotTrace Prep</td>
			<td style="width:215px;">3M, Ontario, Canada</td>
			<td style="width:221px;">CV-0001-7353-0</td>
			<td>Skin surface preparation tape</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Electrodes - BlueSensor N</td>
			<td style="width:215px;">Ambu, Ballerup, Denmark</td>
			<td style="width:221px;">BlueSensor N N-00-S/25&#160;</td>
			<td>Low-impedance Ag-AgCl skin electrodes</td>
		</tr>
	</tbody>
</table>

objective nociceptive assessment in ventilated icu patients: a feasibility study using pupillometry and the nociceptive flexion reflex

客观伤害评估和最佳疼痛管理的概念得到了越来越多的关注。尽管已知的疼痛或过度 analgosedation 的负面短期和长期后果, 但在非交际性的、危重的成年人中, 充分的伤害性监测仍然具有挑战性。重症监护病房 (ICU) 采用机械通气患者的行为疼痛量表 (BPS) 对护理人员进行常规伤害评估。这种评估受药物使用的限制 (例如,神经肌肉阻断剂) 和第三方伤害评估固有的主观特征。
在这里, 我们描述了使用两个伤害性反射测试设备作为工具, 客观的疼痛评估: 瞳孔扩张反射 (民主) 和伤害屈曲反射 (NFR)。这些测量工具是非侵入性和良好耐受性, 为临床医生和研究人员提供了关于两种不同伤害处理途径的客观信息: (1) 与疼痛相关的自主反应性和 (2) 体感系统的提升分量。目前, 使用共和国和 NFR 测量仅限于专门的疼痛诊所和研究机构, 因为这些印象表明, 这些技术要求很高或耗时, 甚至是因为缺乏对其存在。
本文通过对上述两种伤害性反射评估的研究, 评价其作为一种生理疼痛测量方法在日常实践中的可行性。采用新的技术来评估无意识患者的镇痛水平, 可以进一步改善个体的药理治疗和患者相关的结局指标。因此, 未来的研究必须包括在现实生活环境中进行的大型精心设计的临床试验。

我们使用先前描述的议定书, 在 ICU 部门总共用了40个严重不适通气对象 (38% 名女性) 进行反射评估。analgo 镇静的患者包括: 58% 为原发性呼吸功能不全, 23% 由于多器官衰竭, 10% 的患者有感染性休克, 9% 被定义为其他原因的镇静剂 (例如,心源性原因)。所有测量都由同一调查员执行。镇静剂剂量在评估期间从未被调整过。瞳孔特征和肌电图反应见表 2。
在测量过程中, 生命体征保持不变, 即使有高 (> 60 mA) 伤害刺激。因此, 由于血压、心率或通气参数的变化, 没有任何伤害反射评估必须提前终止。在所有受试者中, 使用所述议定书可以确定该共和国的身份。然而, NFR 仅在72% 的患者中被发现。此外, NFR 阈值跟踪是不可能的, 在13% 的病人, 尽管最佳的测量条件, 暗示了深刻的 analgosedation 水平。然而, 过度的伤害刺激 (即, 刺激电流超过 100 mA) 没有使用。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/57972/57972fig1.jpg"> 图 1: 用于诱导民主共和国的标准化伤害刺激电极应用示意图.两种刺激电极在支配的皮肤区域的应用。
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/57972/57972fig2.jpg"> 图 2: 用于 NFR 评估的电极应用示意图.应用两个刺激电极在皮肤区域支配由腓肠神经, 两个记录电极放置在同侧二头肌和1参考电极。请注意, 黑色引线连接到最远端放置电极, 红色引线连接到近端电极 (Dolosys GmbH, PD 博士. 1月 Baars, 总经理)。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/57972/57972fig2large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody>
<tr>
<td>最大刺激强度 (mA)</td>
			<td>学生反应性</td>
			<td>生成的 PPI 评分</td>
		</tr>
<tr>
<td>10</td>
			<td>10-mA 刺激时瞳孔扩张大于13%</td>
			<td>9</td>
		</tr>
<tr>
<td>20</td>
			<td>20-mA 刺激时瞳孔扩张大于13%</td>
			<td>8</td>
		</tr>
<tr>
<td>30</td>
			<td>30-mA 刺激时瞳孔扩张大于13%</td>
			<td>7</td>
		</tr>
<tr>
<td>40</td>
			<td>40-mA 刺激时瞳孔扩张大于13%</td>
			<td>6</td>
		</tr>
<tr>
<td>50</td>
			<td>50-mA 刺激时瞳孔扩张大于13%</td>
			<td>5</td>
		</tr>
<tr>
<td>60</td>
			<td>60-mA 刺激时瞳孔扩张大于13%</td>
			<td>4</td>
		</tr>
<tr>
<td>60</td>
			<td>瞳孔扩张大于13% 在第二次 60 mA 刺激</td>
			<td>3</td>
		</tr>
<tr>
<td>60 (5% < 膨胀 < 13%)</td>
			<td>在第三次 60-mA 刺激期间瞳孔扩张大于13%</td>
			<td>2</td>
		</tr>
<tr>
<td>60 (膨胀≤ 5%)</td>
			<td>在过去的 60-mA 刺激中瞳孔扩张大于13%</td>
			<td>1</td>
		</tr>
<tr>
<td colspan="2">注: 如果在刺激过程中瞳孔扩张超过 20%, PPI 评分增加一点</td>
			<td></td>
		</tr>
</tbody></table>表 1: PPI 评分算法。
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody>
<tr>
<td>镇痛协议</td>
			<td>整体</td>
			<td>瑞芬太尼</td>
			<td>舒芬太尼</td>
			<td>无阿片类</td>
		</tr>
<tr>
<td>科目数目</td>
			<td>40</td>
			<td>32</td>
			<td>5</td>
			<td>3</td>
		</tr>
<tr>
<td>elicitable 共和国</td>
			<td>100%</td>
			<td>100%</td>
			<td>100%</td>
			<td>100%</td>
		</tr>
<tr>
<td>民主共和国刺激强度 (平均数, mA)</td>
			<td>49.75 @ 12.91</td>
			<td>49.69 @ 2.31</td>
			<td>54.00 @ 6.00</td>
			<td>43.33 @ 6.67</td>
		</tr>
<tr>
<td>PPI 评分 (平均)</td>
			<td>4.55 @ 0.39</td>
			<td>5.09 @ 0.50</td>
			<td>4.00 @ 1.73</td>
			<td>6.33 @ 0.88</td>
		</tr>
<tr>
<td>NFR elicitable</td>
			<td>72%</td>
			<td>69%</td>
			<td>80k</td>
			<td>0%</td>
		</tr>
<tr>
<td>NFR 测量误差 (无反射评估)</td>
			<td>15%</td>
			<td>19%</td>
			<td>20%</td>
			<td>-</td>
		</tr>
<tr>
<td>NFR 阈值 (平均值 * SD)</td>
			<td>44.93 @ 4.93</td>
			<td>39.93 @ 4.65</td>
			<td>48.22 @ 16.84</td>
			<td>53.33 @ 8.37</td>
		</tr>
</tbody></table>表 2: 伤害性反射评估后瞳孔特征和肌电图反应.在测量过程中, 误差测量被定义为高阻抗或噪声问题。这可以解释为皮肤保湿问题或皮肤病理导致次最佳测量或壁出口障碍。

Watch this Scientific Journal Video about Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex at JoVE.com

Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex

尽管开发了创新的客观疼痛评估工具, 但在麻醉病人中无法以任何方式与外界交流的疼痛评估仍然具有挑战性。本项目对危重、机械通气的成人患者进行瞳孔扩张反射和伤害屈曲反射的评估。

应用 Pupillometry 和伤害性屈曲反射的可行性研究--通气 ICU 患者的客观伤害评估

The concept of objective nociceptive assessment and optimal pain management have gained increasing attention. Despite the known negative short- and ...

objective-nociceptive-assessment-ventilated-icu-patients-feasibility

Nanyang Technological University

Research

Education

JoVE Journal

JoVE Core

Nursing

Medicine

Unit 1

Ethical and Legal Aspects in Nursing

Communication

SCIENTISTS IN ACTION

8.7K 次观看.  Antwerp University Hospital (UZA), University of Antwerp (UA). 尽管开发了创新的客观疼痛评估工具, 但在麻醉病人中无法以任何方式与外界交流的疼痛评估仍然具有挑战性。本项目对危重、机械通气的成人患者进行瞳孔扩张反射和伤害屈曲反射的评估。

视频: Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can.
Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD 17, 7, 4, 10. We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects 17, 7, 10, 9. Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E 13), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation.
The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools 18. This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.

We describe a rat model of post traumatic stress disorder (PTSD) that reveals the persistent alterations in neuroendocrine function and the delayed long-term, exaggerated fear response, characteristic of PTSD patients. The animal model and methods described here are useful for correlating biomarkers in brain nuclei, which are mechanistic but cannot be measured in patients, with biomarkers in peripheral white blood cells, which can.

在动物模型揭示神经，血液，创伤后应激障碍和行为相关因素的生物标志物

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

科研

医学

Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies

A punch biopsy of the skin is commonly used to quantify intraepidermal nerve fiber densities (IENFD) for the diagnosis of peripheral polyneuropathy 1,2. At present, it is common practice to collect 3 mm skin biopsies from the distal leg (DL) and the proximal thigh (PT) for the evaluation of length-dependent polyneuropathies 3. However, due to the multidirectional nature of IENFs, it is challenging to examine overlapping nerve structures through the analysis of two-dimensional (2D) imaging. Alternatively, three-dimensional (3D) imaging could provide a better solution for this dilemma.
In the current report, we present methods for applying 3D imaging to study painful neuropathy (PN). In order to identify IENFs, skin samples are processed for immunofluorescent analysis of protein gene product 9.5 (PGP), a pan neuronal marker. At present, it is standard practice to diagnose small fiber neuropathies using IENFD determined by PGP immunohistochemistry using brightfield microscopy 4. In the current study, we applied double immunofluorescent analysis to identify total IENFD, using PGP, and nociceptive IENF, through the use of antibodies that recognize tropomyosin-receptor-kinase A (Trk A), the high affinity receptor for nerve growth factor 5. The advantages of co-staining IENF with PGP and Trk A antibodies benefits the study of PN by clearly staining PGP-positive, nociceptive fibers. These fluorescent signals can be quantified to determine nociceptive IENFD and morphological changes of IENF associated with PN. The fluorescent images are acquired by confocal microscopy and processed for 3D analysis. 3D-imaging provides rotational abilities to further analyze morphological changes associated with PN. Taken together, fluorescent co-staining, confocal imaging, and 3D analysis clearly benefit the study of PN.

In order to study the changes of nociceptive intraepidermal nerve fibers (IENFs) in painful neuropathies (PN), we developed protocols that could directly examine three-dimensional morphological changes observed in nociceptive IENFs. Three-dimensional analysis of IENFs has the potential to evaluate the morphological changes of IENF in PN.

三维成像伤害表皮内神经纤维在人体皮肤活检

A punch biopsy of the skin is commonly used to quantify intraepidermal nerve fiber densities (IENFD) for the diagnosis of peripheral polyneuropathy 1,2. ...

Computerized Dynamic Posturography for Postural Control Assessment in Patients with Intermittent Claudication

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic conditions. As part of a diagnostic assessment, the early detection of postural deficits is important so that appropriate and targeted interventions can be prescribed. The Sensory Organization Test (SOT) on the EquiTest determines an individual&#39;s use of the sensory systems (somatosensory, visual, and vestibular) that are responsible for postural control. Somatosensory and visual input are altered by the calibrated sway-referenced support surface and visual surround, which move in the anterior-posterior direction in response to the individual&#39;s postural sway. This creates a conflicting sensory experience. The Motor Control Test (MCT) challenges postural control by creating unexpected postural disturbances in the form of backwards and forwards translations. The translations are graded in magnitude and the time to recover from the perturbation is computed.
Intermittent claudication, the most common symptom of peripheral arterial disease, is characterized by a cramping pain in the lower limbs and caused by muscle ischemia secondary to reduced blood flow to working muscles during physical exertion. Claudicants often display poor balance, making them susceptible to falls and activity avoidance. The Ankle Brachial Pressure Index (ABPI) is a noninvasive method for indicating the presence of peripheral arterial disease and intermittent claudication, a common symptom in the lower extremities. ABPI is measured as the highest systolic pressure from either the dorsalis pedis or posterior tibial artery divided by the highest brachial artery systolic pressure from either arm. This paper will focus on the use of computerized dynamic posturography in the assessment of balance in claudicants.

Individuals with intermittent claudication exhibit poor balance compared to healthy controls. Computerized dynamic posturography is an objective method for measuring an individual's postural responses to balance disturbances. This provides an objective reflection of the person&#x2019;s ability to respond to situations under which sensory stimuli are altered and unexpected perturbations occur.

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic ...

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

心肌梗死和功能预后评估的猪

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this is only partially explained by traditional CVD risk factors. Vascular dysfunction is an important non-traditional risk factor, characterized by vascular endothelial dysfunction (most commonly assessed as impaired endothelium-dependent dilation [EDD]) and stiffening of the large elastic arteries. While various techniques exist to assess EDD and large elastic artery stiffness, the most commonly used are brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV), respectively. Both of these noninvasive measures of vascular dysfunction are independent predictors of future cardiovascular events in patients with and without kidney disease. Patients with CKD demonstrate both impaired FMDBA, and increased aPWV. While the exact mechanisms by which vascular dysfunction develops in CKD are incompletely understood, increased oxidative stress and a subsequent reduction in nitric oxide (NO) bioavailability are important contributors. Cellular changes in oxidative stress can be assessed by collecting vascular endothelial cells from the antecubital vein and measuring protein expression of markers of oxidative stress using immunofluorescence. We provide here a discussion of these methods to measure FMDBA, aPWV, and vascular endothelial cell protein expression.

The degree of vascular dysfunction and contributing physiological mechanisms can be assessed in patients with chronic kidney disease by measuring brachial artery flow-mediated dilation, aortic pulse-wave velocity, and vascular endothelial cell protein expression.

血管功能在慢性肾脏疾病的评估

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this ...

Clinical Assessment of Spatiotemporal Gait Parameters in Patients and Older Adults

Spatial and temporal characteristics of human walking are frequently evaluated to identify possible gait impairments, mainly in orthopedic and neurological patients1-4, but also in healthy older adults5,6. The quantitative gait analysis described in this protocol is performed with a recently-introduced photoelectric system (see&#160;Materials table) which has the potential to be used in the clinic because it is portable, easy to set up (no subject preparation is required before a test), and does not require maintenance and sensor calibration. The photoelectric system consists of series of high-density floor-based photoelectric cells with light-emitting and light-receiving diodes that are placed parallel to each other to create a corridor, and are oriented perpendicular to the line of progression7. The system simply detects interruptions in light signal, for instance due to the presence of feet within the recording area. Temporal gait parameters and 1D spatial coordinates of consecutive steps are subsequently calculated to provide common gait parameters such as step length, single limb support and walking velocity8, whose validity against a criterion instrument has recently been demonstrated7,9. The measurement procedures are very straightforward; a single patient can be tested in less than 5 min&#160;and a comprehensive report can be generated in less than 1&#160;min.

This protocol is used to evaluate spatial and temporal gait variables of neurological/orthopedic patients and older persons by means of a recently-introduced floor-based photocell system.

时空步态参数的患者和老年人的临床评估

Spatial and temporal characteristics of human walking are frequently evaluated to identify possible gait impairments, mainly in orthopedic and ...

Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology.

This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

使用Saccadometry与深部脑刺激来研究正常和病理脑功能

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...

Assessment of Child Anthropometry in a Large Epidemiologic Study

A high proportion of children have overweight and obesity in the United States and other countries. Accurate assessment of anthropometry is essential to understand health effects of child growth and adiposity. Gold standard methods of measuring adiposity, such as dual X-ray absorptiometry (DXA), may not be feasible in large field studies. Research staff can, however, complete anthropometric measurements, such as body circumferences and skinfold measurements, using inexpensive portable equipment. In this protocol we detail how to obtain manual anthropometric measurements from children, including standing and sitting height, weight, waist circumference, hip circumference, mid-upper arm circumference, triceps skinfold thickness, and subscapular skinfold thickness, and procedures to assess the quality of these measurements. To demonstrate accuracy of these measurements, among 1,110 school-aged children in the pre-birth cohort Project Viva we calculated Spearman correlation coefficients comparing manual anthropometric measurements with a gold standard measure of body fat, DXA fat mass1. To address reliability, we evaluate intra-rater technical error of measurement at a quality control session conducted on adult female volunteers.

In epidemiologic studies of children, well-trained research staff can accurately and precisely assess weight, height, sitting height, skinfold thicknesses, and body circumferences.

大型流行病学研究儿童人体测量评估

A high proportion of children have overweight and obesity in the United States and other countries. Accurate assessment of anthropometry is essential to ...

Using a Knee Arthrometer to Evaluate Tissue-specific Contributions to Knee Flexion Contracture in the Rat

Normal knee range of motion (ROM) is critical to well-being and allows one to perform basic activities such as walking, climbing stairs and sitting. Lost ROM is called a joint contracture and results in increased morbidity. Due to the difficulty of reversing established knee contractures, early detection is important, and hence, knowing risk factors for their development is essential. The rat represents a good model with which the effect of an intervention can be studied due to the similarity of rat knee anatomy to that of humans, the rat's ability to tolerate long durations of knee immobilization in flexion, and because mechanical data can be correlated with histologic and biochemical analysis of knee tissue.
Using an automated arthrometer, we demonstrate a validated, precise, reproducible, user-independent method of measuring the extension ROM of the rat knee joint at specific torques. This arthrometer can be used to determine the effects of interventions on knee joint ROM in the rat.

The goal of the protocol is to measure the extension range of motion of the rat knee. The effects of various diseases that increase the stiffness of the knee joint and the effectiveness of treatments can be quantified.

用膝关节关节仪评价大鼠膝关节屈曲收缩的特定组织贡献

Normal knee range of motion (ROM) is critical to well-being and allows one to perform basic activities such as walking, climbing stairs and sitting. Lost ...

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of disorders of consciousness, disrupted higher brain function, and verbal disturbances. As a consequence of an insufficient ability to communicate, objective evaluations are needed from family members, medical staff, and caregivers. One such evaluation is the assessment of functioning brain areas. Recently, multimodal brain imaging has been used to explore the function of damaged brain areas. [18F]-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG-PET/CT) is a successful tool for examining brain function. However, the assessment of brain glucose metabolism based on [18F]FDG-PET/CT is not standardized and depends on several varying parameters, as well as the patient&#39;s condition. Here, we describe a series of semiquantitative assessment protocols for a region-of-interest (ROI) image analysis using self-produced [18F]FDG tracers in patients with sTBI. The protocol focuses on screening the participants, preparing the [18F]FDG tracer in the hot lab, scheduling the acquisition of [18F]FDG-PET/CT brain images, and measuring glucose metabolism using the ROI analysis from a targeted brain area.

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography is useful for studying glucose metabolism related to brain function. Here, we present a protocol for an [18F]FDG tracer set-up and semiquantitative assessment of the region-of-interest analysis for targeted brain areas associated with clinical manifestations in patients with severe traumatic brain injury.

[18f] fdg 示踪剂在重型颅脑损伤患者中的半定量评价

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of ...