Clinical trial NCT04940273: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Hyperventilation
Aneurysmal Subarachnoid Hemorrhage
Cerebral Blood Flow
Keywords: spontaneous hyperventilation
aneurysmal subarachnoid hemorrhage
cerebral blood flow
remifentanil
partial pressure of carbon dioxide
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2021-06-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Explore the effective and safe dose of remifentanil to correct spontaneous hyperventilation in patients with aSAH
timeFrame: The PaCO2 (mmHg) at baseline and 30 minutes following each infusion rate adjustment (0.02、0.04、0.06、0.08μg/kg/min)
Secondary outcomes:
measure: To explore the effect of remifentanil on the cerebral blood flow in patients with aSAH at the different dose
timeFrame: The MFV at baseline and 30 minutes following each infusion rate adjustment (0.02、0.04、0.06、0.08μg/kg/min)
Other outcomes:
Locations:
city: Beijing
country: China
facility: ICU, Beijing Tiantan Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Capital Medical University
name: Zhou Jian-Xin, MD
role: STUDY_DIRECTOR
References:
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.