Drug Intervention of Spontaneous Hyperventilation in Patients With Aneurysmal Subarachnoid Hemorrhage

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hyperventilation, Aneurysmal Subarachnoid Hemorrhage, Cerebral Blood Flow

Intervention / Treatment
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* Drug: Remifentanil Injection [Ultiva]


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: remifentanil<br>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]<br>* Continuous infusion of remifentanil at a dose of 0.02、0.04、0.06、0.08 ug/kg/min for 30 minutes in sequence.<br>* Other names: remifentanil hydrochloride for injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | The MFV at baseline and 30 minutes following each infusion rate adjustment (0.02、0.04、0.06、0.08μg/kg/min) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spontaneous hyperventilation, aneurysmal subarachnoid hemorrhage, cerebral blood flow, remifentanil, partial pressure of carbon dioxide