HyperventilationNCT04974060
Treatment of Spontaneous Hyperventilation With Remifentanil in Traumatic Brain Injury Patients
A study testing Remifentanil Injection in people with Hyperventilation and Traumatic Brain Injury, run by Capital Medical University at 1 site in China.
Trial summary
Spontaneous hyperventilation is common in severe traumatic brain injury patients and correlates closely with poor outcomes. How to treat this pathological condition remain unsolved. Remifentanil is a frequently used short-acting opioid, has the potent side-effect of dose-dependent respiratory inhibition. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperventilation, Traumatic Brain Injury
- What is being tested?
- Remifentanil Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2021to 31 Mar 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100070
Jian-Xin Zhou, MD, 010-59978019, zhoujx.cn@gmail.com
Jian-Xin Zhou, MD
About this study
Official title: Treatment of Spontaneous Hyperventilation in Severe Traumatic Brain Injury Patients: The Efficiency and Safety of Remifentanil Infusion and Its Impact on Cerebral Blood Flow
Spontaneous hyperventilation is common in severe traumatic brain injury patients and correlates closely with poor outcomes. How to treat this pathological condition remain unsolved. Remifentanil is a frequently used short-acting opioid, has the potent side-effect of dose-dependent respiratory inhibition. Specifically, it prolongs the expiratory time only and does not influence the respiratory drive. Among the safety range, the investigators will determine an ideal dose of remifentanil to maintain PaCO2 between 35 to 45 mmHg. The investigators will monitor the cerebral blood flow of the middle cerebral artery and the internal carotid artery to validate cerebral perfusion improvement.
Read the 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.
- Conditions
- Hyperventilation, Traumatic Brain Injury
- Being tested
- Remifentanil Injection
- Keywords
- Spontaneous Hyperventilation, Severe Traumatic Brain Injury, Cerebral Blood Flow, Remifentanil, Partial pressure of carbon dioxide
- Medical subject headings
- Hyperventilation, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remifentanil InjectionDrug
Also called remifentanil hydrochloride for injection
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.
| Study group | Role | What they receive |
|---|---|---|
| Remifentanil intervention | Experimental | 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. Receives: Drug: Remifentanil Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Explore the effective and safe dose of remifentanil to correct spontaneous hyperventilation in patients with severe traumatic brain injury
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).
Measured: Baseline and 30 minutes following each infusion rate adjustment (0.02, 0.04, 0.06, and 0.08 μg/kg/min)
Secondary outcomes (1)
To explore the effect of remifentanil on the cerebral blood flow in patients with severe traumatic brain injury at the different dose of remifentanil
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.
Measured: Baseline and 30 minutes following each infusion rate adjustment (0.02, 0.04, 0.06, and 0.08 μg/kg/min)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2021
- Study start1 Jun 2021
- Primary completion1 Dec 2021 (estimated)
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperventilationStudies of the same condition, open and under way.
- More trials run by Capital Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Capital Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jian-Xin Zhou, Capital Medical University
- Investigators
- Jian-Xin Zhou, MD, Study chair, Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04974060
- Sponsor's protocol ID
- KY2021-002
- Status last verified
- Jul 2021
- First submitted
- 8 Apr 2021
- Last updated
- 29 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Spontaneous Hyperventilation in Severe Traumatic Brain Injury Patients: The Efficiency and Safety of Remifentanil Infusion and Its Impact on Cerebral Blood Flow
- ClinicalTrials.gov ID
- NCT04974060
- Acronym / sponsor ID
- KY2021-002
- Conditions
- Hyperventilation, Traumatic Brain Injury
- Keywords
- Spontaneous Hyperventilation, Severe Traumatic Brain Injury, Cerebral Blood Flow, Remifentanil, Partial pressure of carbon dioxide
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Capital Medical UniversityUniversity, hospital or other
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 1 Dec 2021 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 23 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Spontaneous hyperventilation is common in severe traumatic brain injury patients and correlates closely with poor outcomes. How to treat this pathological condition remain unsolved. Remifentanil is a frequently used short-acting opioid, has the potent side-effect of dose-dependent respiratory inhibition. Specifically, it prolongs the expiratory time only and does not influence the respiratory drive. Among the safety range, the investigators will determine an ideal dose of remifentanil to maintain PaCO2 between 35 to 45 mmHg. The investigators will monitor the cerebral blood flow of the middle cerebral artery and the internal carotid artery to validate cerebral perfusion improvement.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Remifentanil intervention | Experimental | Drug: Remifentanil InjectionAfter 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remifentanil InjectionAlso: remifentanil hydrochloride for injectionDilute 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. | Drug | Remifentanil intervention |
Primary outcome
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).
1 secondary outcome
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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jian-Xin Zhou, MD study chair
Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remifentanil Injection in people with Hyperventilation and Traumatic Brain Injury, run by Capital Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jian-Xin Zhou, MD (010-59978019, zhoujx.cn@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2021.