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氯胺酮对呼吸刺激和跨肺压的影响

2026年4月27日 更新者:Lorenzo Berra, MD、Massachusetts General Hospital

亚麻醉氯胺酮对机械通气危重患者呼吸刺激和跨肺压的影响

气道通畅受损是拔管失败的常见原因,阿片类药物和安眠药会对气道通畅产生不利影响。 与其他麻醉剂不同,氯胺酮是 N-甲基-D-天冬氨酸 (NMDA) 的非竞争性拮抗剂,可激活呼吸作用并促进支气管扩张。 在亚麻醉血浆浓度下,氯胺酮减少阿片类药物和异丙酚的需求。

该药物-生理学相互作用试验的目的是评估氯胺酮对机械通气患者呼吸和脑电图的影响。

研究概览

详细说明

保持镇静和麻醉患者的上呼吸道通畅具有挑战性,尤其是当患者准备好脱离机械通气时。 自主呼吸试验 (SBT) 用于加快撤机过程,这通常需要减少和/或停用镇静剂和止痛剂。 在一些手术患者中,减少这些药物的使用会导致疼痛相关的躁动和无法进行 SBT,这可能会延长机械通气的需要。 使用具有麻醉保护作用且不会引起呼吸抑制的药物可以减少或停用抑制呼吸驱动并随后促进拔管的药物。

多年来,氯胺酮一直用于危重病人的镇静和镇痛。 这种 N-甲基-D-天冬氨酸 (NMDA) 的非竞争性拮抗剂用作麻醉剂和镇痛剂,已被证明可以减少阿片类药物的消耗并防止阿片类药物耐受性的发展。 与其他麻醉剂不同,氯胺酮可激活呼吸作用并促进支气管扩张。 在亚麻醉血浆浓度下,氯胺酮减少阿片类药物和异丙酚的需求。

该药物-生理学相互作用试验的目的是评估亚麻醉剂量的氯胺酮对呼吸和脑电图的影响。 研究人员假设以亚麻醉输注速率(低剂量氯胺酮 5 - 10 mcg/kg/min)滴注氯胺酮与呼吸刺激作用相关,并且不会显着增加机械通气患者的跨肺压。

主要结果是呼吸功能,通过峰值吸气流量、潮气量、呼吸频率、占空比和每分钟通气量进行评估,这些指标在氯胺酮输注开始前 15 分钟(作为基线)、氯胺酮输注 5mcg/60 分钟时测量kg/min,再以 10mcg/kg/min 输注 60 分钟,此时停止输注 3 小时以进行最后一组测量。

研究类型

介入性

注册 (实际的)

15

阶段

  • 不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • Beth Israel Deaconess Medical Center
      • Boston、Massachusetts、美国、02114
        • Massachusetts General Hospital

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

描述

纳入标准:

  • 年龄 ≥ 18 岁入住 ICU 需要机械通气
  • 适用于自主呼吸试验
  • 初级重症监护团队接受低剂量氯胺酮的候选人

排除标准:

  • 食道损伤
  • 对氯胺酮过敏
  • 已知的神经退行性疾病
  • 主要神经系统疾病(ICP 升高)

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:队列
成人机械通气患者被认为有资格进行自主呼吸试验,并且是接受初级重症监护团队亚麻醉氯胺酮治疗的候选人。
以亚麻醉输注速率滴注氯胺酮(低剂量氯胺酮 5 - 10 mcg/kg/min)

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Inspiratory Airflow
大体时间:During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min
Inspiratory airflow measured during spontaneous breathing trials without ventilator support using a calibrated pneumotachometer connected to the ventilatory circuit. Airflow signals were recorded along with airway and esophageal pressures and analyzed. Inspiratory airflow represents the rate of air entering the lungs during inspiration and is reported in liters per second (L/s). Higher values indicate greater inspiratory airflow during spontaneous breathing. Measurements were obtained during brief spontaneous breathing trials performed at predefined study time points.
During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min

次要结果测量

结果测量
措施说明
大体时间
EEG Beta-gamma Power
大体时间:Baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Electroencephalogram (EEG) power spectrum density was measured using four frontal electrodes with the SedLine monitor and analyzed using multitaper spectral methods. Changes in beta-gamma power (19-44 Hz) were expressed in decibels (dB) relative to baseline using artifact-free ~3-minute segments at predefined time points. The reported value represents the maximum increase in spectral power across the frequency range, capturing the strongest frequency-specific effect, which may be diluted by averaging across the band if central tendency is used. This approach is standard in spectral analyses to detect peak effects and potential frequency shifts. Power spectra are continuous functions and peak values are the dominant signal components because they represent the strongest oscillatory activity the brain could achieve in a predefined frequency range.
Baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Minute Ventilation
大体时间:During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Minute ventilation measured during spontaneous breathing trials without ventilator support using a calibrated pneumotachometer connected to the ventilatory circuit. Minute ventilation represents the total volume of air inhaled or exhaled per minute and is calculated as tidal volume multiplied by respiratory rate. Values are reported in liters per minute (L/min). Higher values indicate greater overall ventilation during spontaneous breathing. Measurements were derived from airflow recordings.
During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Tidal Volume
大体时间:During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Tidal volume measured during spontaneous breathing trials without ventilator support using a calibrated pneumotachometer connected to the ventilatory circuit. Tidal volume represents the volume that enters the lungs during a single breath and is reported in liters (L). Values were derived from airflow recordings analyzed using spirometry software. Higher values indicate larger breath volumes during spontaneous breathing at the predefined study time points.
During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Work of Breathing
大体时间:During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Inspiratory work of breathing measured during spontaneous breathing trials using esophageal pressure (Pes) and tidal volume recordings. Work of breathing was calculated from the area under the inspiratory limb of the esophageal pressure-volume loop for each breathing cycle. Values were averaged across breaths during the recording period and normalized to tidal volume. Work of breathing was expressed in joules per liter (J/L). Higher values indicate greater mechanical effort required to inhale.
During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Inspiratory Airway Resistance
大体时间:During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Inspiratory airway resistance measured during spontaneous breathing trials using airway flow and esophageal pressure recordings. Resistance was estimated using the Mead and Whittenberger method, calculated as (Pes - PesLR)/V̇, where Pes is esophageal pressure, PesLR is the pressure on the lung elastic recoil curve at the same tidal volume, and V̇ is airflow. Measurements were made at an absolute tidal volume of 100 ml and averaged across breathing cycles during the recording period. Values are reported in cmH2O/L/s. Higher values indicate greater resistance to airflow during inspiration.
During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Lung Compliance
大体时间:During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.
Lung compliance measured during spontaneous breathing trials using tidal volume and esophageal pressure recordings. Compliance was calculated as the change in tidal volume divided by the change in esophageal pressure (ΔVT/ΔPes) measured between zero-flow states at the beginning and end of inspiration. Values represent respiratory system compliance and are reported in milliliters per centimeter of water pressure (mL/cmH2O). Higher values indicate greater lung compliance, reflecting a larger volume change for a given pressure change.
During spontaneous breathing trials at baseline (prior to ketamine infusion), after 60 minutes of ketamine infusion at 5 mcg/kg/min, and after 60 minutes of ketamine infusion at 10 mcg/kg/min.

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 研究主任:Matthias Eikermann, MD, PhD、Beth Israel Deaconess Medical Center
  • 首席研究员:Lorenzo Berra, MD、Massachusetts General Hospital

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2014年1月1日

初级完成 (实际的)

2022年12月1日

研究完成 (实际的)

2022年12月1日

研究注册日期

首次提交

2013年10月8日

首先提交符合 QC 标准的

2013年10月21日

首次发布 (估计的)

2013年10月25日

研究记录更新

最后更新发布 (实际的)

2026年5月19日

上次提交的符合 QC 标准的更新

2026年4月27日

最后验证

2026年4月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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