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

Sepsis Clinical Trial

— MADAME  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05874895
• Other study ID #: MADAME trial
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: University Hospital Ostrava
• Contact: Jirí Hyncica
• Phone: 0042059737
• Email: jiri.hyncica[@]fno.cz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Inflammatory Response
• Multiorgan Failure
• Multiple Organ Failure
• Sepsis
• Septic Shock
• Shock
• Shock, Septic

Intervention

Procedure:
• 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.
• Usual Care
Usual care provided for patients in septic shock.

Locations

Country	Name	City	State
Czechia	University Hospital Ostrava	Ostrava	Moravian-Silesian Region

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Ostrava

Country where clinical trial is conducted

Czechia, 

References & Publications (13)

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

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility Outcome - number of patients undergoing manual lymphatic drainage procedure.	The anticipated number of patients is 2 per month.	12 months
Primary	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
Primary	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
Primary	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
Primary	Safety Outcome - incidence of thromboembolic events	The presumed incidence is assumed in 0 per cent of cases	12 months
Primary	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
Primary	Efficacy Outcome - incidence of delirium	Incidence of delirium for the period from randomisation until discharge from ICU	12 months
Primary	Efficacy Outcome - 28-day mortality	28-day mortality will be observed	12 months