Septic Shock
Conditions
Keywords
Sepsis
Brief summary
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. It is the most expensive healthcare condition to treat in United States and has a mortality rate of nearly 30%. It is widely known that exaggerated inflammation and imbalance between sympathetic and parasympathetic arms of the autonomic nervous system (ANS) contribute to progression and adverse outcomes in sepsis. The role of unchecked inflammation and unregulated ANS as a potential treatment target is an important gap in our knowledge that should be explored. Cholinergic anti-inflammatory pathway (CAP) is an intricate network where the ANS senses inflammation by vagus nerve afferents and tries to regulate it by vagus nerve efferents to the reticuloendothelial system. The central hypothesis of this pilot clinical trial is that transcutaneous vagus nerve stimulation (TVNS) at tragus of the external ear can activate the CAP to suppress inflammation and improve autonomic imbalance as measured by inflammatory cytokine levels and heart rate variability (HRV) analysis. The investigators plan to randomize patients with septic shock into active and sham stimulation groups and study the effects of vagal stimulation on inflammatory cytokines, HRV and a clinical severity score of sepsis. Both groups will continue to receive the standard of care treatment for sepsis irrespective of group assignments. The investigators hypothesize that 4 hours of TVNS will suppress inflammatory markers and improve the balance between sympathetic and parasympathetic arms of ANS as measured by HRV, resulting in improved Sequential Organ Failure Assessment Score (SOFA). The preliminary data generated from this pilot study will lay the foundation for a larger clinical trial.
Interventions
Stimulation of the auricular branch of the vagus nerve at tragus of the external ear delivered by Parasym device.
Sponsors
Oklahoma City VA Medical Center
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Double blind
Intervention model description
Randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Septic shock (meeting severe sepsis and having persistent systolic blood pressure \<90mmHg despite adequate fluid resuscitation).
Exclusion criteria
* Unilateral or bilateral vagotomy * History of myocardial infarction or stroke in the last 1 year * Recurrent vasovagal syncope * Sick sinus syndrome without pacemaker * Bifascicular heart block * 2nd or 3rd-degree heart block * Hypotension due to autonomic dysfunction * Pregnant women * Prisoners and patients with suicidal ideation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inflammatory Cytokine Tumor Necrosis Factor Alpha | Baseline to 4 hours and baseline to 24 hours post stimulation | Serum inflammatory cytokine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Heart Rate Variability | Baseline to 4 hours post stimulation | Time domain and frequency domain measures of heart rate variability |
| Change in Sequential Organ Failure Assessment Score | Baseline to 24 hours post stimulation | Sequential Organ Failure Assessment Score calculation |
Countries
United States
Contacts
CONTACTHoussein Youness, MD
CONTACTZain Ul Abideen Asad, MD
PRINCIPAL_INVESTIGATORHoussein Youness, MD
University of Oklahoma
PRINCIPAL_INVESTIGATORZain Ul Abideen Asad, MD
University of Oklahoma
Outcome results
None listed