Diaphragm hIbernation and itS Driving factorS in mEChanically venTilated ICU Patients: the DISSECT Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Blood C reactive protein level
研究概览
简要总结
Rationale:
Patients with invasive mechanical ventilation (IMV) frequently develop diaphragm dysfunction and experience difficult weaning. Recent ex vivo work suggests that a subset of mechanically ventilated ICU patients may exhibit diaphragm hibernation, an energy conserving myosin state that reduces force generation and may lead to a reversible increase in diaphragm strength over time. However, it is unknown whether diaphragm hibernation can be demonstrated in vivo during IMV and which clinical and biological factors are associated with this phenotype.
Objective:
Primary objective is to determine the driving factors (biomarkers) of diaphragm hibernation during IMV. Secondary objectives are to determine the proportion of ventilated critically ill patients who exhibit diaphragm hibernation during IMV, to investigate inflammatory and metabolic factors and other clinical exposures associated with diaphragm hibernation, and to explore associations between diaphragm hibernation and weaning related and survival outcomes.
Study design:
Prospective, observational, longitudinal cohort study.
Study population:
Adult ICU patients receiving IMV, expected to remain mechanically ventilated for at least 72 hours.
Intervention (if applicable):
Not applicable. This is an observational study. Study specific procedures consist of repeated phrenic nerve magnetic stimulation and additional blood sampling.
Main study parameters/endpoints:
The primary study parameter is the proportion of participants exhibiting diaphragm hibernation during IMV. Diaphragm hibernation is defined as an increase in stimulated twitch tracheal pressure (Ptr,stim), a measure of diaphragm strength, of at least 10% relative to baseline (Day 0-1) at any follow up assessment (Day 2, 3, 5, or 7) obtained before extubation or death. Ptr,stim will be assessed repeatedly on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Participant burden is limited and mainly consists of repeated phrenic nerve magnetic stimulation during a ventilator delivered end expiratory occlusion and additional blood sampling of 9.5 mL per time point, up to a total of 47.5 mL across the study period. Magnetic stimulation is non-invasive and expected discomfort is transient. Rare transient physiological changes may occur and measurements are performed under continuous ICU monitoring and will be postponed or omitted if considered unsafe or interfering with clinical care. Direct benefit for participants is limited, but the study may provide clinically relevant knowledge on diaphragm hibernation and its driving factors. The research questions are specific to diaphragm physiology during IMV in critically ill patients, therefore the study is group related and cannot be performed in a different population.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Receiving invasive mechanical ventilation at screening.
- •Expected to remain mechanically ventilated for ≥ 72 hours from enrolment.
- •The first study assessment can be performed within 36 hours after initiation of invasive mechanical ventilation.
排除标准
- •Pre-existing neuromuscular disease affecting the diaphragm (e.g. motor neuron disease, myasthenia gravis, advanced muscular dystrophy, high cervical spinal cord injury) or use of neuromuscular blocker.
- •Known phrenic nerve palsy or prior diaphragmatic paralysis.
- •Long-term home mechanical ventilation (invasive or non-invasive) prior to ICU admission.
- •Post-operative patients after planned diaphragm or phrenic nerve surgery.
- •Contraindications to phrenic nerve magnetic stimulation (e.g., unstable cervical spine injury, uncontrolled intracranial hypertension, metallic implants in stimulation area as per manufacturer guidance).
- •Pregnancy.
- •Participation in another interventional trial that explicitly prohibits co-enrolment or is expected to substantially influence diaphragm function (e.g. experimental neuromuscular blocking strategies), as decided by the principal investigator.
研究组 & 干预措施
Patients with expected > 3 days of invasive mechanical ventilation
Patients expected > 3 days of invasive mechanical ventilation will be included in this study. Blood sample and diaphragm strength will be assessed repeatedly, until 7 days after initiation of invasive mechanical ventilation, extubation or death.
结局指标
主要结局
Blood C reactive protein level
时间窗: C reactive protein will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
C reactive protein will be assessed by blood sample.
Blood procalcitonin level
时间窗: Procalcitonin will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Procalcitonin will be assessed by blood sample.
Blood metabolic biomarkers level
时间窗: Metabolic biomarkers will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Metabolic biomarkers will be assessed by blood sample using OLINK Target 96 panel.
Blood TNF-α level
时间窗: TNF-α will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
TNF-α will be assessed by blood sample.
Blood IL-10 level
时间窗: IL-10 will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
IL-10 will be assessed by blood sample.
Blood IL-8 level
时间窗: IL-8 will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
IL-8 will be assessed by blood sample.
Blood IL-6 level
时间窗: IL-6 will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
IL-6 will be assessed by blood sample.
Blood ferritin level
时间窗: Ferritin will be assessed on Day 0-1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.
Ferritin will be assessed by blood sample.
次要结局
- Proportion of participants exhibiting diaphragm hibernation during invasive mechanical ventilation(Ptr,stim will be assessed repeatedly on Day 0 to 1, Day 2, Day 3, Day 5, and Day 7, or until extubation or death, whichever occurs first.)
- Number of days from intubation to successful extubation(Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first)
- Number of days from first SBT to successful extubation(Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first)
- Incidence of weaning failure(Collected from study inclusion until Day 28, or ICU/hospital discharge or death, whichever occurs first)
- ICU length of stay(Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first)
- Hospital length of stay(Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first)
- ICU mortality(Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first)
- Hospital mortality(Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first)
- Day 28 all-cause mortality(Collected from study inclusion until Day 28 or death, whichever occurs first)
- ICU-free days through day 28(Collected from ICU discharge until Day 28 or death, whichever occurs first)
- Hospital-free days through day 28(Collected from hospital discharge until Day 28 or death, whichever occurs first)
- Time to ICU discharge alive through day 28(Collected from study inclusion until Day 28, or ICU discharge or death, whichever occurs first)
- Time to hospital discharge alive through day 28(Collected from study inclusion until Day 28, or hospital discharge or death, whichever occurs first)