Effectiveness of Non-invasive Vagus Nerve Stimulation as an Adjuvant Treatment in Patients With Sepsis in Intensive Care.

Assistance Publique - Hôpitaux de Paris30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

DOUBLE

Enrollment

Conditions

Sepsis Septic Shock

Interventions

SNV activ group (Non-invasive transcutaneous stimulation of the vagus nerve )OTHER

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.

Placebo groupOTHER

For the control group, the stimulation electrode will be inverted so as to deliver the stimulation to the ear lobule.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Raymond Poincaré Hospital

Garches, France

RECRUITING

Outcomes

Primary Outcomes

Mortality

Overall death

Time frame: at day 90

Secondary Outcomes

Cumulative incidence of delirium and its duration

Time frame: up to day 90

Cumulative incidence of mechanical ventilation and its duration

Time frame: up to day 90

Proportion of patients having been the subject of a decision to limit or withdraw care

Time frame: at day 90

Duration of use of vasopressors

Time frame: at day 90

Number of days alive with a Sequential Organ Failure Assessment Score (SOFA) score <6

Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function

Time frame: at day 90

Length of stay in intensive care and hospitalization in all patients and in survivors

Time frame: at day 90

Measurements of changes in C-reactive protein (CRP)

Time frame: at inclusion

Measurements of changes in C-reactive protein (CRP)

Time frame: at day 7

Measurements of changes in C-reactive protein (CRP)

Time frame: at day 14

Measurements of changes in C-reactive protein (CRP)

Time frame: at day 21

Measurements of changes in C-reactive protein (CRP)

Time frame: at day 28

Measurements of changes in C-reactive protein (CRP)

Time frame: at day 90

Measurements of changes in fibrinogen level

Time frame: at inclusion

Measurements of changes in fibrinogen level

Time frame: at day 7

Measurements of changes in fibrinogen level

Time frame: at day 14

Measurements of changes in fibrinogen level

Time frame: at day 21

Measurements of changes in fibrinogen level

Time frame: at day 28

Measurements of changes in fibrinogen level

Time frame: at day 90

Measurements of changes in interleukin-6 (IL-6)

Time frame: at inclusion

Measurements of changes in interleukin-6 (IL-6)

Time frame: at day 7

Measurements of changes in interleukin-6 (IL-6)

Time frame: at day 14

Measurements of changes in interleukin-6 (IL-6)

Time frame: at day 21

Measurements of changes in interleukin-6 (IL-6)

Time frame: at day 28

Measurements of changes in interleukin-6 (IL-6)

Time frame: at day 90

Measurements of changes in interleukin-1β (IL-1β)

Time frame: at inclusion

Measurements of changes in interleukin-1β (IL-1β)

Time frame: at day 7

Measurements of changes in interleukin-1β (IL-1β)

Time frame: at day 14

Measurements of changes in interleukin-1β (IL-1β)

Time frame: at day 21

Measurements of changes in interleukin-1β (IL-1β)

Time frame: at day 28

Measurements of changes in interleukin-1β (IL-1β)

Time frame: at day 90