Microcirculatory Oxygen Uptake in Sepsis

Sepsis Clinical Trial

Official title:

Microcirculatory Oxygen Uptake in Sepsis, Severe Sepsis and Septic Shock

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02430142
• Other study ID #: 2014-428M-MA
• Status: Completed
• Start date: April 2015
• Est. completion date: August 1, 2017

Study information

• Verified date: May 2018
• Source: Universitätsmedizin Mannheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Forearm vasoocclusive testing (VOT) will be performed with laser-doppler spectrophotometry system in septic patients on ICU. Microcirculatory oxygen uptake will be checked for prognostic value and for associations with tissue hypoxia markers and high central venus saturations.

Description:

Sepsis remains a common entity in critical care patients with remarkable mortality. Microcirculatory dysfunction plays a pivotal role in the pathophysiology of sepsis and organ dysfunction. The main causal mechanisms are vasoactive substances such as nitric oxide and endothelin, destroyed endothelial surfaces and microvascular occlusion by activated coagulation and leucocytes. Furthermore there is some knowledge from vasooclussive testing (VOT) based on near-infrared spectroscopy (NIRS) and assessing the proportion of perfused vessels determined with orthogonal polarization spectral and sidestream darkfield imaging techniques (SDF) that impaired microcirculation is associated with organ dysfunction and increased mortality. Despite these well-recognised evidence previous trails proving therapy guidance with microcirculatory parameters failed in demonstrating optimised outcome . Recent guidelines still recommend fluid therapy based on central venous pressure, mean arterial pressure, urine output and or blood lactate concentration. But especially the parameter central venous oxygen saturation (ScvO2) seems to be not unproblematic. Retrospective data analysis found higher mortality rates if ScvO2 is elevated.

In the present study patients with sepsis, severe sepsis and septic shock will be evaluated on day 1 and day 4 and a follow up will be performed on day 180.

Additional to clinical parameters of organ function, infection markers, global parameters of tissue hypoxia will be captured by measurements of adenosine and whose metabolites.

Macrocirculatory cardiovascular function delivered by transpulmonary thermodilution technique will be assessed and local tissue perfusion and oxygen uptake will be measured with a transcutaneous laser-doppler spectrophotometry system in VOT.

The aim of this study is to check:

1. Is microcirculatory oxygen uptake a prognostic value in sepsis?

2. Is it correlated with biomarkers of hypoxia?

3. Are high levels of ScvO2 caused by microcirculatory impairments or by hyperdynamic macrocirculation?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: August 1, 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Criteria according to the SSC for sepsis, severe sepsis and septic shock

• Admission to the ICU within 24 hours

Exclusion Criteria:

• Pregnancy

• Cardiopulmonary resuscitation within the last 5 days

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock, Septic
• Toxemia

Intervention

Other:
• Vasoocclusive testing
Forearm vasoocclusive testing with a laser-doppler spectrophotometry system, transpulmonary thermodilution and blood sampling;

Locations

Country	Name	City	State
Germany	University Medical Centre, Department of Anaesthesiology and Surgical Intensive Care Medicine	Mannheim

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsmedizin Mannheim

Country where clinical trial is conducted

Germany, 

References & Publications (7)

Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. Review. Erratum in: N Engl J Med. 2013 Nov 21;369(21):2069. — View Citation

De Backer D, Donadello K, Cortes DO. Monitoring the microcirculation. J Clin Monit Comput. 2012 Oct;26(5):361-6. doi: 10.1007/s10877-012-9383-8. Epub 2012 Jul 26. Review. — View Citation

Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af. — View Citation

Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2004 Sep;32(9):1825-31. — View Citation

Shapiro NI, Arnold R, Sherwin R, O'Connor J, Najarro G, Singh S, Lundy D, Nelson T, Trzeciak SW, Jones AE; Emergency Medicine Shock Research Network (EMShockNet). The association of near-infrared spectroscopy-derived tissue oxygenation measurements with sepsis syndromes, organ dysfunction and mortality in emergency department patients with sepsis. Crit Care. 2011;15(5):R223. doi: 10.1186/cc10463. Epub 2011 Sep 22. — View Citation

Textoris J, Fouché L, Wiramus S, Antonini F, Tho S, Martin C, Leone M. High central venous oxygen saturation in the latter stages of septic shock is associated with increased mortality. Crit Care. 2011 Jul 26;15(4):R176. doi: 10.1186/cc10325. — View Citation

van der Voort PH, van Zanten M, Bosman RJ, van Stijn I, Wester JP, van Raalte R, Oudemans-van Straaten HM, Zandstra DF. Testing a conceptual model on early opening of the microcirculation in severe sepsis and septic shock: a randomised controlled pilot study. Eur J Anaesthesiol. 2015 Mar;32(3):189-98. doi: 10.1097/EJA.0000000000000126. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	ICU-Mortality, 60-days-mortlity, 180-days-mortality will be recorded and correlated with baseline and postischemic microcirculatory oxygen delivery and uptake.	180 days
Secondary	Connection between ScvO2 and microcirculatory oxygen uptake	The investigators will prove, if high values of central venous saturation (>75%) are associated with impaired tissue oxygen uptake.	Day 1 and day 4
Secondary	Connection between adenosine-metabolites and microcirculatory oxygen uptake	The investigators will prove, if high values of the adenosine-metabolite hypoxanthine (ng/ml) in plasma are associated with impaired tissue oxygen uptake.	Day 1 and day 4
Secondary	Physical condition	Physical status at 180 days (Rankin-Scale) will be recorded and correlated with baseline and postischemic microcirculatory oxygen delivery and uptake.	180 days