Drug Intervention of Spontaneous Hyperventilation in Patients With Aneurysmal Subarachnoid Hemorrhage
Primary Purpose
Hyperventilation, Aneurysmal Subarachnoid Hemorrhage, Cerebral Blood Flow
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Remifentanil Injection [Ultiva]
Sponsored by
About this trial
This is an interventional treatment trial for Hyperventilation focused on measuring spontaneous hyperventilation, aneurysmal subarachnoid hemorrhage, cerebral blood flow, remifentanil, partial pressure of carbon dioxide
Eligibility Criteria
Inclusion Criteria:
- Aneurysmal subarachnoid hemorrhage, after craniotomy or clipping
- Arterial blood gas satisfy with PaCO2<35mmHg and pH>7.45
- Presence of an endotracheal tube
- Assisted ventilation mode,CPAP/PSV
- ICP monitoring
Exclusion Criteria:
- Age <18 years
- Pregnancy
- Chronic obstructive pulmonary disease
- Allergy to opioids
- Clinically relevant hepatic or renal failure
- Hemodynamic instability
- TCD windows cannot detect cerebral blood flow
- Refuse to participate the study
Sites / Locations
- ICU, Beijing Tiantan Hospital, Capital Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
remifentanil
Arm Description
Continuous infusion of remifentanil at a dose of 0.02、0.04、0.06、0.08 ug/kg/min for 30 minutes in sequence.
Outcomes
Primary Outcome Measures
Explore the effective and safe dose of remifentanil to correct spontaneous hyperventilation in patients with aSAH
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).
Secondary Outcome Measures
To explore the effect of remifentanil on the cerebral blood flow in patients with aSAH at the different dose
The differences of mean cerebral flow velocity (MFV) 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04940273
Brief Title
Drug Intervention of Spontaneous Hyperventilation in Patients With Aneurysmal Subarachnoid Hemorrhage
Official Title
Intervention of Spontaneous Hyperventilation in Patients With Aneurysmal Subarachnoid Hemorrhage: the Feasibility of Drug Therapy and Its Impact on Cerebral Blood Flow
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
December 31, 2021 (Anticipated)
Study Completion Date
March 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Capital Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Although spontaneous hyperventilation patients with aneurysmal subarachnoid hemorrhage closely associated with poor outcomes, the standard therapy remains unavailable. Remifentanil has the pharmacological characterization of respiratory inhibition, mainly prolonging the expiratory time and decreasing the respiratory rate while preserving the respiratory drive. The investigators hypothesis that spontaneous hyperventilation could be corrected by titrating the dose of remifentanil and cerebral blood flow will augment during this process.
Detailed Description
Evidence has shown a high incidence of spontaneous hyperventilation in patients with aneurysmal subarachnoid hemorrhage (aSAH), which is associated with poor outcomes. It's well established that the hypocapnia caused by hyperventilation leads to cerebral vasoconstriction, reduces the cerebral blood flow, and decreases the cerebral blood volume and intracranial pressure consequently. However, persistent cerebral vascular constriction increases the risk of cerebral ischemia; therefore, maintaining a partial pressure of arterial carbon dioxide (PaCO2) in the range of 35-40mmHg is recommended to minimize the hazard hypocapnia.
There's still no standard method to deal with spontaneous hyperventilation. Based on the pharmacology and clinical experience, remifentanil seems to be an ideal choice since it could inhibit the respiratory rate in a dose-dependent fashion. As one of the most used short-acting opioids, remifentanil could prolong the expiratory time, meanwhile not influencing the inspiratory time and respiratory drive, consequently decreasing respiratory rate and maintaining the tidal volume.
In this exploratory physiology study, the investigators will test the hypothesis that spontaneous hyperventilation could be suppressed by titrating the dose of remifentanil and could be realized as the target of PaCO2. The investigators will determine the optimal amount of remifentanil, which fulfills the criteria of efficacy and safety, and evaluate its effect on the cerebral blood flow velocity of both the middle cerebral artery and internal carotid artery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperventilation, Aneurysmal Subarachnoid Hemorrhage, Cerebral Blood Flow
Keywords
spontaneous hyperventilation, aneurysmal subarachnoid hemorrhage, cerebral blood flow, remifentanil, partial pressure of carbon dioxide
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
remifentanil
Arm Type
Experimental
Arm Description
Continuous infusion of remifentanil at a dose of 0.02、0.04、0.06、0.08 ug/kg/min for 30 minutes in sequence.
Intervention Type
Drug
Intervention Name(s)
Remifentanil Injection [Ultiva]
Other Intervention Name(s)
remifentanil hydrochloride for injection
Intervention Description
Continuous infusion of remifentanil at a dose of 0.02、0.04、0.06、0.08 ug/kg/min for 30 minutes in sequence.
Primary Outcome Measure Information:
Title
Explore the effective and safe dose of remifentanil to correct spontaneous hyperventilation in patients with aSAH
Description
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).
Time Frame
The PaCO2 (mmHg) at baseline and 30 minutes following each infusion rate adjustment (0.02、0.04、0.06、0.08μg/kg/min)
Secondary Outcome Measure Information:
Title
To explore the effect of remifentanil on the cerebral blood flow in patients with aSAH at the different dose
Description
The differences of mean cerebral flow velocity (MFV) 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.
Time Frame
The MFV at baseline and 30 minutes following each infusion rate adjustment (0.02、0.04、0.06、0.08μg/kg/min)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aneurysmal subarachnoid hemorrhage, after craniotomy or clipping
Arterial blood gas satisfy with PaCO2<35mmHg and pH>7.45
Presence of an endotracheal tube
Assisted ventilation mode,CPAP/PSV
ICP monitoring
Exclusion Criteria:
Age <18 years
Pregnancy
Chronic obstructive pulmonary disease
Allergy to opioids
Clinically relevant hepatic or renal failure
Hemodynamic instability
TCD windows cannot detect cerebral blood flow
Refuse to participate the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhou Jian-Xin, MD
Phone
010-59976518
Email
zhoujx.cn@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Li Hong-Liang, MD
Phone
15910678616
Email
arnold_lhl@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhou Jian-Xin, MD
Organizational Affiliation
Capital Medical University
Official's Role
Study Director
Facility Information:
Facility Name
ICU, Beijing Tiantan Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian-Xin Zhou, MD
Email
zhoujx.cn@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
36351728
Citation
Su R, Zhou J, Zhu N, Chen X, Zhou JX, Li HL. Efficacy and safety of remifentanil dose titration to correct the spontaneous hyperventilation in aneurysmal subarachnoid haemorrhage: protocol and statistical analysis for a prospective physiological study. BMJ Open. 2022 Nov 9;12(11):e064064. doi: 10.1136/bmjopen-2022-064064.
Results Reference
derived
Learn more about this trial
Drug Intervention of Spontaneous Hyperventilation in Patients With Aneurysmal Subarachnoid Hemorrhage
We'll reach out to this number within 24 hrs