MAnual Lymphatic DrAinage to iMprove the outcomE of Patients After Septic Shock

Study Overview
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Brief Summary
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Antimicrobial and supportive therapeutic interventions in patients with septic shock are usually effective - procalcitonin and interleukin-6 levels fall rapidly in most cases, and noradrenaline support can be discontinued within a few days. Unfortunately, only in a small portion of patients, do the organ functions improve at the same time, and in most of them, multi-organ failure persists. Therefore, it is likely that, in addition to infection and the response to infection, other mechanisms are also involved in the persistence of organ failure in patients after septic shock.

Detailed Description
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One of the possible explanations for prolonged multi-organ dysfunction after an excessive inflammatory phase is a disorder of post-inflammatory cleaning, the so-called resolution of inflammation. The resolution of inflammation is a regulated process in which the controlling action of specialized pro-resolution mediators (lipoxins, resolvins, etc.), conversion of pro-inflammatory macrophages (M1) to pro-resolution (M2., induce the process of structural tissue restoration), autophagy plays a significant role and, of course, the flushing of accumulated interstitial fluid with waste products by lymphatic drainage. Any disturbance in pro-resolution mechanisms can lead to prolonged organ dysfunction. The lymphatic system plays a key role in maintaining fluid homeostasis. Its ability to drain interstitial fluid can increase up to 20 times. However, even such an increase may not be sufficient in the situation of extreme interstitial fluid sequestration that accompanies septic shock. In addition, some inflammatory mediators (for example, nitric oxide, TNF-α, Interleukin-1β) cause relaxation of the vascular structures of the lymphatic system, slowing the flow of lymph. The result is the persistence of tissue swelling with tissue hypoxia due to the extension of the diffusion path for oxygen and the accumulation of waste products of inflammation. Manual lymphatic drainage (MLD) is one of the treatments that stimulate the lymphatic system. In general, it is expected to accelerate the outflow of lymph and waste products from tissues previously affected by inflammation, accelerate the recovery of tissue function, sympatholytic effect and increase the tension of the vagus nerve. It can therefore be assumed that MLD will have a beneficial effect on the course of persistent multi-organ dysfunction in patients after therapeutically managed septic shock.

Official Title
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MAnual Lymphatic DrAinage to iMprove the outcomE of Patients After Septic Shock: A Safety and Feasibility Pilot Randomized Controlled Trial

Conditions
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Sepsis, Multiorgan Failure, Inflammatory Response, Septic Shock

Intervention / Treatment
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* Procedure: Manual Lymphatic Drainage
* Procedure: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of septic shock at admission to ICU sepsis or suspicion of sepsis noradrenaline support required in order to maintain mean arterial pressure ≥ 65 mmHg serum lactate ≥ 2 mmol/L Exclusion Criteria: patients <18 years of age pregnant women with septic shock, in whom the pregnancy has been preserved patients with a history of heart failure with NYHA (New York Heart Association) classification ≥ III patients with a history of thromboembolic events patients with septic shock transferred from another department/hospital, if the length of stay at the previous workplace exceeded 72 hours patients with septic shock and an inauspicious prognosis, or in the phase of withdrawal of treatment patients with uncontrolled infection patients with septic shock who lack informed consent patients with septic shock, in whom the SOFA score decreased by more than 50% during the day following the withdrawal of noradrenaline (i.e. a subgroup of patients with a rapid improvement of the clinical course after the resolution of septic shock).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study subjects will be randomized in two study arms.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Manual Lymphatic Drainage<br>In addition to usual care, daily manual lymphatic drainage will be performed for five consecutive days. After this period. | Procedure: Manual Lymphatic Drainage<br>* Manual lymphatic drainage massage involves gently manipulating specific areas of the body to help lymph move to an area with working lymph vessels.<br>|
| Active Comparator: Usual Care<br>Usual care for patients with septic shock will be provided. | Procedure: Usual Care<br>* Usual care provided for patients in septic shock.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility Outcome - number of patients undergoing manual lymphatic drainage procedure. | The anticipated number of patients is 2 per month. | 12 months | 
| Feasibility Outcome - The percentage of patients suitable for manual lymphatic drainage procedure in whom this procedure has been performed. | It is expected that manual lymphatic drainage procedure will be performed in at least 80 per cent of patients. | 12 months | 
| Safety Outcome - the percentage of cases when the manual lymphatic drainage procedure interferes with standard nursing care | interference is assumed in 0 per cent of cases | 12 months | 
| Safety Outcome - incidence of the need to restart circulatory support with norepinephrine | The presumed incidence is assumed in 0 per cent of cases | 12 months | 
| Safety Outcome - incidence of thromboembolic events | The presumed incidence is assumed in 0 per cent of cases | 12 months | 
| Efficacy Outcome - change in SOFA (sequential organ failure assessment) score | Comparison of the SOFA score on Days 3 and 5 versus Day 0 (randomisation day) | 12 months | 
| Efficacy Outcome - incidence of delirium | Incidence of delirium for the period from randomisation until discharge from ICU | 12 months | 
| Efficacy Outcome - 28-day mortality | 28-day mortality will be observed | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Multiorgan Failure, Excessive Inflammatory Response, Manual Lymphatic Drainage, Lymphatic System, Septic Shock