Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04974060 |
| Other study ID # |
KY2021-002 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2021 |
| Est. completion date |
March 31, 2022 |
Study information
| Verified date |
July 2021 |
| Source |
Capital Medical University |
| Contact |
Jian-Xin Zhou, MD |
| Phone |
010-59978019 |
| Email |
zhoujx.cn[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
