Sepsis, Septic Shock
Conditions
Brief summary
Sepsis is one of the leading causes of death in intensive care. About 50% of patients with septic shock die after 1 year; and 50% of survivors suffer from cognitive decline. The pathophysiological mechanisms of serious complications of sepsis are now well known. In fact, the systemic inflammation related to sepsis amplifies the release of pro-inflammatory cytokines and neurotoxic mediators, hence an increase in deleterious phenomena such as oxidative stress, mitochondrial dysfunction, endothelial activation, disruption of the blood-brain barrier, neuroinflammation (astrocytic and microglial activation) leading to multi-organ failure which compromises the patient's vital and functional prognosis. Although there has been progress in the understanding of its pathophysiology, the management of sepsis and septic shock in intensive care relies mainly on anti-infective treatments and the restoration of cardiovascular and respiratory functions. There is virtually no adjuvant therapy for the management of sepsis, apart from a few hormonal therapies such as insulin to maintain blood glucose levels below 180 mg / dL and low doses of corticosteroids and vasopressin. There is therefore a pressing need to develop innovative treatments targeting inflammatory and immunological processes in order to reduce the complications of sepsis and improve patient prognosis. Some recent work has shown that electrical vagus nerve stimulation (SNV), a technique used for the treatment of drug-resistant epilepsy, can modulate inflammatory and immune responses and control inflammation syndrome in animal models of sepsis, arthritis and rheumatism in humans. In this pilot study the investigators plan to evaluate the efficacy of transcutaneous (non-invasive) SNV as an adjuvant treatment in patients with sepsis in intensive care.
Interventions
OTHERSNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve )
A transcutaneous stimulator of the atrial branch of the vagus nerve of the TENS eco Plus type (Schwa-medico) will be used. SNV stimulation will be applied in the concha of the left ear to the subcutaneous area of the atrial branch of the vagus nerve in the left ear (cymba conchae) for each patient, at an intensity of 2 mA, 30 minutes per day for 5 consecutive days, from the day of inclusion / randomization.
OTHERPlacebo group
For the control group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age\> 18 years old * Adult man or woman, hospitalized in intensive care, presenting with sepsis for at least 24 hours according to the diagnostic criteria (Singer et al., 2016). * Informed consent signed by patient or family member/trusted support person * In an emergency situation, in the absence of family members/trusted family/trusted support person
Exclusion criteria
* Patient under guardianship or curatorship * Patient in a severe state of agitation. * Patient in a state of brain death or active limitation of treatment. * Multiple trauma patient, with multiple fractures of the skull. * Refusal to participate in the study or to sign the informed consent by the patient or his loved one, * Pregnant or breastfeeding woman, * No affiliation to a social security scheme. * Patient with cochlear implant * Patient with heart disease * Patient with asthma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | at day 90 | Overall death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of delirium and its duration | up to day 90 | — |
| Proportion of patients having been the subject of a decision to limit or withdraw care | at day 90 | — |
| Duration of use of vasopressors | at day 90 | — |
| Number of days alive with a Sequential Organ Failure Assessment Score (SOFA) score <6 | at day 90 | Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function |
| Length of stay in intensive care and hospitalization in all patients and in survivors | at day 90 | — |
| Measurements of changes in C-reactive protein (CRP) | at inclusion | — |
| Measurements of changes in fibrinogen level | at inclusion | — |
| Cumulative incidence of mechanical ventilation and its duration | up to day 90 | — |
| Measurements of changes in interleukin-1β (IL-1β) | at inclusion | — |
| Measurements of changes in tumor necrosis factor α (TNF-α) | at inclusion | — |
| Measurements of changes in the calcium binding protein B S100B (S100B) | at inclusion | — |
| Measurements of changes in the arterial lactate level | at inclusion | — |
| Characteristics of the EEG | at inclusion | — |
| Mortality rate | at day 28 | Overall death |
| Neurological fate of patients | at day 90 | Neurological fate of patients will evaluated using Glasgow Outcome Scale (GOS) |
| Measurements of changes in interleukin-6 (IL-6) | at inclusion | — |
Countries
France
Contacts
Primary ContactEric AZABOU
Backup ContactMatthieu Resche-Rigon
Outcome results
None listed