Drug Intervention of Spontaneous Hyperventilation in Patients With Aneurysmal Subarachnoid Hemorrhage

Sponsor

Capital Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04940273

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperventilation Aneurysmal Subarachnoid Hemorrhage Cerebral Blood Flow	Drug: Remifentanil Injection [Ultiva]	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Intervention of Spontaneous Hyperventilation in Patients With Aneurysmal Subarachnoid Hemorrhage: the Feasibility of Drug Therapy and Its Impact on Cerebral Blood Flow

Actual Study Start Date :

Jun 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: remifentanil Continuous infusion of remifentanil at a dose of 0.02、0.04、0.06、0.08 ug/kg/min for 30 minutes in sequence.	Drug: Remifentanil Injection [Ultiva] Continuous infusion of remifentanil at a dose of 0.02、0.04、0.06、0.08 ug/kg/min for 30 minutes in sequence. Other Names: remifentanil hydrochloride for injection

Arm

Intervention/Treatment

Experimental: remifentanil

Continuous infusion of remifentanil at a dose of 0.02、0.04、0.06、0.08 ug/kg/min for 30 minutes in sequence.

Drug: Remifentanil Injection [Ultiva]

Continuous infusion of remifentanil at a dose of 0.02、0.04、0.06、0.08 ug/kg/min for 30 minutes in sequence.

Other Names:

remifentanil hydrochloride for injection

Outcome Measures

Primary Outcome Measures

Explore the effective and safe dose of remifentanil to correct spontaneous hyperventilation in patients with aSAH [The PaCO2 (mmHg) at baseline and 30 minutes following each infusion rate adjustment (0.02、0.04、0.06、0.08μg/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).

Secondary Outcome Measures

To explore the effect of remifentanil on the cerebral blood flow in patients with aSAH at the different dose [The MFV at baseline and 30 minutes following each infusion rate adjustment (0.02、0.04、0.06、0.08μg/kg/min)]
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.