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Brain InjuryMICRONORNCT05285514

Macro- and Microcirculation Crosstalk in Brain-damaged Patients Under Anesthesia or in Intensive Care

An observational study of Brain Injury, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

In patients with severe brain injury, maintenance and control of blood pressure is at the very first point in the management strategy, whether in anesthesia or in intensive care. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Injury
What is being tested?
Comparison of macro- and microcirculatory parameters
How many people
85 participants
Where
1 siteFrance
Study dates
Jun 2023to Jul 2025
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Adult patients (≥ 18 years old) with brain damage, undergoing general anesthesia or intensive care justifying, due to their severity, monitoring of blood pressure and cardiac output.

Who may be able to join

  • Adult patients (≥ 18 years old)
  • With brain damage
  • Benefiting from general anesthesia or resuscitation justifying the placement of an arterial catheter and monitoring of cardiac output
  • With hypotension or arterial hypertension requiring intravenous administration of a vasoactive agent to meet the target cerebral perfusion pressure (CPP) of 60-70 mmHg
  • Not subject to a measure of legal protection (tutorship/curatorship)
  • Patients informed and having expressed their non-objection to participation in this research, or, where applicable, a person of trust / family member / relative of the patient who is unable to express her or his agreement

Who cannot join

  • Patients under the age of 18
  • Pregnant woman
  • Patient without affiliation to a social security scheme
  • Patient, or, where applicable, person of trust / family member / relative of the patient unable to express her or his agreement, opposed to participation in the study
  • Patient subject to a legal protection measure
  • Patient benefiting from the State medical assistance (AME) program

Trial locations and contacts

1 site in 1 country.

Fabrice VALLEE, MD, PhD contact

+33 (0)1 49 95 80 71

vallee@gmail.com

France1 site, 1 recruiting
  • AP-HP, Lariboisière Hospital, Department of Anesthesiology and Intensive Care

    Paris, 75010

    Joaquim MATEO, MD, +33 (0)1 49 95 83 74, joaquim.mateo@aphp.fr

    Fabrice VALLEE, MD, PhD, +33 (0)1 49 95 80 71, vallee@gmail.com

    Recruiting

Other trials in France

About this study

Official title: Analysis of the Macro-microcirculatory Coupling in the Course of Using the Vasoactive Substances During Anesthesia-resuscitation of Brain-damaged Patients

In patients with severe brain injury, maintenance and control of blood pressure is at the very first point in the management strategy, whether in anesthesia or in intensive care. In order to restore cerebral perfusion pressure (CPP) to appropriate levels (60-70 mmHg) while ensuring optimal perfusion of other vital organs, intravenous administration of vasodilator, inodilator or vasoconstrictor vasoactive agents is commonly used.

These vasoactive agents, widely used to correct hypotension or hypertension, have their own effects on the load conditions of the left ventricle and the tone of the arterial tree, but also have effects on the microcirculation.

Read more

The microcirculatory status of a tissue cannot be reliably predicted by considering only the macrocirculatory parameters usually measured.

Therefore, in situations where organ perfusion is inadequate or compromised, patient management that includes the integration of the impact of vasoactive agents on the microcirculation seems essential for comprehensive hemodynamic treatment.

The non-invasive study of microcirculatory perfusion and its interactions with the macrocirculatory network, using a minimally invasive method such as videomicroscopy, should allow a better use of the treatments used.

For cerebral patients, routine management already includes very complete monitoring of all cardiopulmonary and cerebral systemic parameters.

It is therefore imperative to study and propose new minimally invasive modalities for monitoring the microcirculation in order to define new therapeutic targets that take into account the microcirculatory compartment.

Read the detailed description

In patients with severe brain injury, maintenance and control of blood pressure is at the primary focus of the management strategy in both anesthesia and intensive care. In order to restore cerebral perfusion pressure (CPP) to appropriate levels (60-70 mmHg) while ensuring optimal perfusion of other vital organs, intravenous administration of vasodilator, ino-dilator or vasoconstrictor agents is widely used.

These vasoactive agents widely used to correct hypotension or hypertension have their own effects on left ventricular loading conditions, arterial tree tone, but also effects on microcirculation.

Currently, the vast majority of anaesthesias and organ resuscitations are carried out from a macrocirculatory view of the system. Hemodynamic optimization is then based on the monitoring of macrocirculatory parameters such as arterial pressure, and sometimes cardiac output coupled with parameters of adequacy of tissue oxygenation (arterial and venous O2 saturation).

The microcirculatory status of a tissue cannot be reliably predicted by considering only the usually measured macrocirculatory parameters. Peripheral capillary perfusion pressure is the result of the coupling between peripheral microcirculatory tone and resistance and macrocirculatory impedance.

The response of microvessels to the various vasoactive agents widely used in the clinic has been little studied.

However, it should be noted that excessive use of vasoconstrictor amines, particularly in the presence of hypovolemia, may, paradoxically to the macrocirculatory impression, induce closure of the capillary network and aggravate tissue ischemia. This capillary de-recruitment is due in particular to the dissipation of pressure in the systemic arterial system, due to the excessively high peripheral resistances and fatally leads to a rarefaction of the open capillaries.

In addition, the increased macrocirculatory impedance imposes a myocardial workload that may cause a decrease in cardiac output, amplifying the tissue damage. This leads to a new situation of uncoupling, characterized by decreased macrocirculatory flow and elevated microcirculatory resistance.

This is why, in situations where organ perfusion is inadequate or weakened, patient management that includes the integration of the impact of vasoactive agents on the microcirculation seems essential for global hemodynamic treatment.

Impaired microcirculation is a key pathophysiological factor in organ failure and death in patients. The impact of organ failure (renal, respiratory, cardiac, etc.) on the quality of cerebral oxygenation is major and conditions the brain's recovery potential. Organ failure by its repercussions on the conditions of brain recovery severely worsens the prognosis of brain damaged patients (secondary brain insults of systemic origin (SBISOs)

In order to recognize and avoid the pitfalls associated with these aortocapillary uncoupling mechanisms, specific monitoring of microcirculatory flow and tissue perfusion during the administration of vasoactive agents is largely relevant. The major obstacle is the difficulty of studying microcirculatory behavior at the bedside in a non or minimally invasive manner.

Direct visualization of the capillary circulation in vivo is now possible using a minimally invasive technique of orthogonal spectral polarization (OSP) videomicroscopy and, more recently, Sidestream Dark Field imaging (SDF).

This last technique, validated in humans mainly in septic shock situations, uses a polarized light source whose absorbance by hemoglobin and reflection by other tissues allows the construction of a contrasted image. This technique allows the visualization of capillary networks on the surface of solid organs covered with a thin epithelial layer to a depth of about 300 µm. An analysis of the recorded image assisted by calculation software allows the semi-quantitative calculation of capillary density (proportion of perfused vessels; PPVSL), capillary flow (Microcirculatory Flow Index; MFISL) and heterogeneity (heterogeneity index; HETSL) of these.

To date, several non-invasive techniques are available, each measuring different parameters specific to this microcirculation:

Capillary density, capillary or tissue flow estimation, hemoglobin saturation, oxygenation and tissue CO2 pressure measurements.

The non-invasive study of microcirculatory perfusion and its interactions with the macrocirculatory network, thanks to a minimally invasive method such as videomicroscopy, should allow a better use of the treatments used.

Overall, the trend in anaesthesia and intensive care is increasingly towards individualized management, and the use of monitoring (macro- and microcirculatory) associated with a thorough knowledge of the treatments used (vasoconstrictors, vasodilators and vascular filling in particular) seems to be an essential basis for these considerations.

The empirical use of vasoactive agents, without specific monitoring of these effects, and the unpredictable impact of changes in one of the two compartments on the final state of the system during adequate macrocirculatory resuscitation could even be deleterious at the microcirculatory level.

These pathophysiological concepts specific to macro/microcirculation cross-talk demonstrate the imperative of developing monitoring specific to the microvascular network in critical patients.

The techniques have evolved and the tools are now available and can be used safely in patients.

For brain-damaged patients, routine management already includes a very complete monitoring including all systemic cardio-pulmonary and cerebral parameters. Participants receive interventions as part of routine medical care to restore Cerebral Perfusion pressure (CPP) to appropriate levels (60-70 mmHg)

The availability of minimally invasive monitoring tools of the microcirculation such as videomicroscopy allows the study of the functional capillary situation according to the vasoactive agent used.

The study of microcirculatory perfusion and its interactions with the macrocirculatory network, using a minimally invasive method such as videomicroscopy, should allow a better use of the treatments used.

Conditions
Brain Injury
Being tested
Comparison of macro- and microcirculatory parameters
Keywords
Hemodynamic monitoring, Microcirculation, Macro-microcirculation crosstalk, Vasoactive agents
Medical subject headings
Brain Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Comparison of macro- and microcirculatory parametersDiagnostic test

    Microcirculation examination using sublingual videomicroscopy, tissue O2 saturation (StO2) by NIRS and transcutaneous CO2 pressure (tcpCO2) monitoring, in conjunction with macrocirculatory parameters measures including cardiac output, arterial pressure and pulsed O2 saturation, in order to establish the relationship between the macrocirculatory changes in blood pressure and cardiac output and the microcirculatory flow and capillary density during vasoactive agent use." . Participants receive interventions as part of routine medical care to restore Cerebral Perfusion pressure (CPP) to appropriate levels (60-70 mmHg)

Study groups in NCT05285514
Study groupRoleWhat they receive
Brain-damaged patients under anesthesia and requiring the administration of a vasoactive agentPatients with severe brain injuries over 18 years of age are eligible to participate in this protocol: head trauma, subarachnoid hemorrhage, ischemic or hemorrhagic stroke and requiring the administration of a vasoactive agent as part of routine medical care to restore Cerebral Perfusion pressure (CPP).
Receives: Diagnostic Test: Comparison of macro- and microcirculatory parameters

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Capillary density

    For all patients, Capillary density by sublingual video microscopy (proportion of perfused vessels; PPVSL / percentage and the heterogeneity index; HETSL / H-unit) will be collected in separate time periods:

    1. Baseline before administration of the vasoactive agent
    2. After 5 minutes
    3. After stabilization 15 minutes

    Measured: Duration of the surgical intervention (1 day)

  2. Microcirculatory flow

    For all patients, Capillary flow estimation using sublingual videomicroscopy (Microcirculatory Flow Index MFISL/ unit FI) will be collected in separate time periods:

    1. Baseline before administration of the vasoactive agent
    2. After 5 minutes
    3. After stabilization 15 minutes

    Measured: Duration of the surgical intervention (1 day)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2022
  2. Study startJun 2023 (estimated)
  3. Primary completionJun 2025 (estimated)
  4. Study completionJul 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
85 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05285514
Sponsor's protocol ID
APHP211317
Other IDs
2021-A02375-36
Acronym
MICRONOR
Status last verified
Apr 2023
First submitted
9 Mar 2022
Last updated
27 Apr 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

An observational study of Brain Injury, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Joaquim MATEO, MD (+33 (0)1 49 95 83 74, joaquim.mateo@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Capillary density (time frame: Duration of the surgical intervention (1 day)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2023.

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