Treatment of Spontaneous Hyperventilation With Remifentanil in Traumatic Brain Injury Patients

NCT ID: NCT04974060

Last Updated: 2021-07-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2022-03-31

Brief 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. 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.

Conditions

Hyperventilation; Traumatic Brain Injury

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Remifentanil intervention

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.

Group Type: EXPERIMENTAL

Remifentanil Injection

Intervention Type: DRUG

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.

Interventions

Remifentanil 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.

Intervention Type: DRUG

Other Intervention Names

remifentanil hydrochloride for injection

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Capital Medical University

OTHER

Sponsor Role: lead

Responsible Party

Jian-Xin Zhou

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jian-Xin Zhou, MD

Role: STUDY_CHAIR

Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University

Locations

Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jian-Xin Zhou, MD

Role: CONTACT

zhoujx.cn@gmail.com

010-59978019

Hong-Liang Li, MD

Role: CONTACT

arnold_lhl@126.com

15910678616

Facility Contacts

Jian-Xin Zhou, MD

Role: primary

zhoujx.cn@gmail.com

010-59978019

Other Identifiers

KY2021-002

Identifier Type: -

Identifier Source: org_study_id