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

NCT ID: NCT05874895

Last Updated: 2025-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-01

Study Completion Date

2025-11-28

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.

Conditions

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Sepsis Multiorgan Failure Inflammatory Response Septic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study subjects will be randomized in two study arms.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

No masking will be used in this study.

Study Groups

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Manual Lymphatic Drainage

In addition to usual care, daily manual lymphatic drainage will be performed for five consecutive days. After this period.

Group Type EXPERIMENTAL

Manual Lymphatic Drainage

Intervention Type PROCEDURE

Manual lymphatic drainage massage involves gently manipulating specific areas of the body to help lymph move to an area with working lymph vessels.

Usual Care

Usual care for patients with septic shock will be provided.

Group Type ACTIVE_COMPARATOR

Usual Care

Intervention Type PROCEDURE

Usual care provided for patients in septic shock.

Interventions

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Manual Lymphatic Drainage

Manual lymphatic drainage massage involves gently manipulating specific areas of the body to help lymph move to an area with working lymph vessels.

Intervention Type PROCEDURE

Usual Care

Usual care provided for patients in septic shock.

Intervention Type PROCEDURE

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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Ostrava

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Roman Kula, MD,CSc

Role: PRINCIPAL_INVESTIGATOR

University Hospital Ostrava

Locations

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University Hospital Ostrava

Ostrava, Moravian-Silesian Region, Czechia

Site Status

Countries

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Czechia

References

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Pruitt LG. Lymphatic flow modulation as adjunct therapy for septic shock. Med Hypotheses. 2020 Sep;142:109748. doi: 10.1016/j.mehy.2020.109748. Epub 2020 Apr 20.

Reference Type BACKGROUND
PMID: 32339860 (View on PubMed)

Alitalo K. The lymphatic vasculature in disease. Nat Med. 2011 Nov 7;17(11):1371-80. doi: 10.1038/nm.2545.

Reference Type BACKGROUND
PMID: 22064427 (View on PubMed)

Venero Galanternik M, Stratman AN, Jung HM, Butler MG, Weinstein BM. Building the drains: the lymphatic vasculature in health and disease. Wiley Interdiscip Rev Dev Biol. 2016 Nov;5(6):689-710. doi: 10.1002/wdev.246. Epub 2016 Aug 30.

Reference Type BACKGROUND
PMID: 27576003 (View on PubMed)

Oliver G, Kipnis J, Randolph GJ, Harvey NL. The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease. Cell. 2020 Jul 23;182(2):270-296. doi: 10.1016/j.cell.2020.06.039.

Reference Type BACKGROUND
PMID: 32707093 (View on PubMed)

Vairo GL, Miller SJ, McBrier NM, Buckley WE. Systematic review of efficacy for manual lymphatic drainage techniques in sports medicine and rehabilitation: an evidence-based practice approach. J Man Manip Ther. 2009;17(3):e80-9. doi: 10.1179/jmt.2009.17.3.80E.

Reference Type BACKGROUND
PMID: 20046617 (View on PubMed)

Scallan JP, Zawieja SD, Castorena-Gonzalez JA, Davis MJ. Lymphatic pumping: mechanics, mechanisms and malfunction. J Physiol. 2016 Oct 15;594(20):5749-5768. doi: 10.1113/JP272088. Epub 2016 Aug 2.

Reference Type BACKGROUND
PMID: 27219461 (View on PubMed)

Klaourakis K, Vieira JM, Riley PR. The evolving cardiac lymphatic vasculature in development, repair and regeneration. Nat Rev Cardiol. 2021 May;18(5):368-379. doi: 10.1038/s41569-020-00489-x. Epub 2021 Jan 18.

Reference Type BACKGROUND
PMID: 33462421 (View on PubMed)

Vieira JM, Norman S, Villa Del Campo C, Cahill TJ, Barnette DN, Gunadasa-Rohling M, Johnson LA, Greaves DR, Carr CA, Jackson DG, Riley PR. The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction. J Clin Invest. 2018 Aug 1;128(8):3402-3412. doi: 10.1172/JCI97192. Epub 2018 Jul 9.

Reference Type BACKGROUND
PMID: 29985167 (View on PubMed)

Frohlich E. Acute Respiratory Distress Syndrome: Focus on Viral Origin and Role of Pulmonary Lymphatics. Biomedicines. 2021 Nov 20;9(11):1732. doi: 10.3390/biomedicines9111732.

Reference Type BACKGROUND
PMID: 34829961 (View on PubMed)

Schwager S, Detmar M. Inflammation and Lymphatic Function. Front Immunol. 2019 Feb 26;10:308. doi: 10.3389/fimmu.2019.00308. eCollection 2019.

Reference Type BACKGROUND
PMID: 30863410 (View on PubMed)

Kraft JD, Blomgran R, Lundgaard I, Quiding-Jarbrink M, Bromberg JS, Borgeson E. Specialized Pro-Resolving Mediators and the Lymphatic System. Int J Mol Sci. 2021 Mar 9;22(5):2750. doi: 10.3390/ijms22052750.

Reference Type BACKGROUND
PMID: 33803130 (View on PubMed)

Fanous MY, Phillips AJ, Windsor JA. Mesenteric lymph: the bridge to future management of critical illness. JOP. 2007 Jul 9;8(4):374-99.

Reference Type BACKGROUND
PMID: 17625290 (View on PubMed)

Wu C, Li H, Zhang P, Tian C, Luo J, Zhang W, Bhandari S, Jin S, Hao Y. Lymphatic Flow: A Potential Target in Sepsis-Associated Acute Lung Injury. J Inflamm Res. 2020 Nov 23;13:961-968. doi: 10.2147/JIR.S284090. eCollection 2020.

Reference Type BACKGROUND
PMID: 33262632 (View on PubMed)

Other Identifiers

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MADAME trial

Identifier Type: -

Identifier Source: org_study_id

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