- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04974060
Treatment of Spontaneous Hyperventilation With Remifentanil in Traumatic Brain Injury Patients
Treatment of Spontaneous Hyperventilation in Severe Traumatic Brain Injury Patients: The Efficiency and Safety of Remifentanil Infusion and Its Impact on Cerebral Blood Flow
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Severe Traumatic Brain Injury (sTBI) is a devastating disease with high hospital mortality and disability worldwide. For neurocritical care physicians, avoiding secondary brain injury remains the cornerstone of treatment in treating sTBI patients.
Carbon dioxide is a potent cerebral vascular modulator. By decreasing the arterial partial pressure of carbon dioxide (PaCO2), hyperventilation could induce cerebral vasoconstriction and decrease cerebral blood flow (CBF), which further reduces cerebral blood volume and lowering intracranial pressure. Traditionally, intentional hyperventilation was used to control intracranial hypertension in sTBI patients for decades. However, evidences have shown that the decreased cerebral blood flow may aggravate brain ischemia and worse neural function. The most recent guidelines do not recommend prophylactic use of induced hyperventilation in sTBI patients anymore.
However, the latest research revealed a high prevalence of spontaneous hyperventilation (SHV) in sTBI patients, accompanied by prolonged sedation and analgesia, increased hospital mortality, and long-term adverse clinical outcomes. Although many modalities are available, there is still no consensus on the practical and feasible treatment for SHV in clinical practice.
As one of the most commonly used short-acting analgesic drugs, remifentanil has the characteristic of dose-depended respiratory rate inhibition by prolonging expiratory time, meanwhile preserve the respiratory drive. Among the effective dose range, the continuous infusion of remifentanil does not interfere the cerebral hemodynamics. The investigators hypothesize that SHV could be corrected with remifentanil infusion and anticipate increasing cerebral blood flow and improving the sTBI patients' outcomes.
This exploratory physiological study will titrate the respiratory rate with continuous remifentanil infusion in the sTBI patient with SHV, aiming to maintain the ideal PaCO2 range of 35-45 mmHg. Specifically, after the satisfactory analgesia and sedation achieved with butorphanol and midazolam/propofol, escalating remifentanil doses (0.02, 0.04, 0.06, and 0.08 ug/kg/min) will be tested in sequence from the baseline.
The parameters of vital signs, blood gas analysis, ventilator monitored variables such as tidal volume, minute ventilation, end-tidal carbon dioxide will be collected at the stable period after 30 minutes of drug infusion. Transcranial doppler also will be performed at the same time to evaluate the change of velocity of the middle cerebral artery and internal carotid artery. An efficient and safe dose range will be determined, meanwhile preserve the stability of neural function and hemodynamic.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Jian-Xin Zhou, MD
- Phone Number: 010-59978019
- Email: zhoujx.cn@gmail.com
Study Contact Backup
- Name: Hong-Liang Li, MD
- Phone Number: 15910678616
- Email: arnold_lhl@126.com
Study Locations
-
-
Beijing
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Beijing, Beijing, China, 100070
- Recruiting
- Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University
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Contact:
- Jian-Xin Zhou, MD
- Phone Number: 010-59978019
- Email: zhoujx.cn@gmail.com
-
Principal Investigator:
- Jian-Xin Zhou, MD
-
Sub-Investigator:
- Hong-Liang Li, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 18 years
- Severe TBI (3 < glasgow coma scale (GCS) ≤ 8)
- Hyperventilation (PaCO2 < 35 mmHg and pondus hydrogenii (pH) > 7.45)
- Presence of an endotracheal tube
- Assisted ventilation mode (CPAP/PSV)
Exclusion Criteria:
- Induced/iatrogenic hyperventilation
- No informed consent was signed
- Transcranial doppler sonography (TCD) data collection cannot be completed due to anatomical structure
- Severe multiple organ failure, persistent high fever, massive thoraco-peritoneal effusion
- Medical history of major craniocerebral injury and chronic obstructive pulmonary disease (COPD)
- Conformed or Suspected history of opioid-related adverse reactions
- Withdraw from the study due to the change of patient's condition and other methods of treatment and intervention are needed
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Remifentanil intervention
After the satisfactory analgesia and sedation, remifentanil will continuously infuse an escalating dose in the sequence of 0.02, 0.04, 0.06, and 0.08 μg/kg/min, each dose infusion lasting at least 30 minutes.
|
Dilute 2mg Remifentanil with normal saline to 50 ml (40ug/ml) and continuously intravenous infused at the doses of 0.02, 0.04, 0.06, and 0.08 μg/kg/min for each lasting 30 minutes.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Explore the effective and safe dose of remifentanil to correct spontaneous hyperventilation in patients with severe traumatic brain injury
Time Frame: Baseline and 30 minutes following each infusion rate adjustment (0.02, 0.04, 0.06, and 0.08 μg/kg/min)
|
The differences of partial pressure of carbon dioxide (PaCO2; mmHg) between the respective points (baseline and 30 minutes following each infusion rate adjustment of remifentanil) were recorded to determine the change of PaCO2 (mmHg).
|
Baseline and 30 minutes following each infusion rate adjustment (0.02, 0.04, 0.06, and 0.08 μg/kg/min)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To explore the effect of remifentanil on the cerebral blood flow in patients with severe traumatic brain injury at the different dose of remifentanil
Time Frame: Baseline and 30 minutes following each infusion rate adjustment (0.02, 0.04, 0.06, and 0.08 μg/kg/min)
|
Bilateral mean cerebral blood velocity changes of middle cerebral artery and internal carotid artery between baseline and 30 minutes following each infusion rate adjustment of remifentanil were recorded to determine the change of cerebral blood flow.
|
Baseline and 30 minutes following each infusion rate adjustment (0.02, 0.04, 0.06, and 0.08 μg/kg/min)
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Respiratory Tract Diseases
- Respiration Disorders
- Craniocerebral Trauma
- Trauma, Nervous System
- Signs and Symptoms, Respiratory
- Brain Injuries
- Wounds and Injuries
- Brain Injuries, Traumatic
- Hyperventilation
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Opioid
- Narcotics
- Remifentanil
Other Study ID Numbers
- KY2021-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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