Study of Peripheral Tissue Oxygenation in End-stage Liver Disease Patients During Liver Transplantation

End Stage Liver Disease Clinical Trial

Official title:

Study of Peripheral Microcirculatory Dysfunction in End-stage Liver Disease Patients During Liver Transplantation Using Near Infrared Spectroscopy

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01794637
• Other study ID #: 103363
• Status: Withdrawn
• Phase: N/A
• First received: January 17, 2013
• Last updated: October 1, 2016
• Start date: February 2013
• Est. completion date: March 2016

Study information

• Verified date: October 2016
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Observational [Patient Registry]

Clinical Trial Summary

End - stage liver disease can cause many problems to the patients including fatigue, weakness,jaundice, confusion, abdominal pain and distension. Another important problem is the cardiovascular system (heart and blood vessels). There will be the impairment of heart function to pump blood to the distal part of the body. Blood vessels are also affected by the imbalance of chemical agents which are not detoxified by diseased liver, resulting in impairment of oxygen carrying capacity and tissue oxygen exchange. Mechanism of this process is still poorly understood.

This is a study about the peripheral vascular dysfunction by means of vascular occlusion test (VOT). Blood pressure cuff is inflated (to occlude the proximal vessels and induce distal part ischemia), then deflated and observing the distal tissue oxygenation (StO2)change by the probe (Near-infrared spectroscopy : NIRS) at the hand. From our knowledge, there is no study in patients undergoing liver transplantation.

The study investigator would like to observe the change in peripheral tissue oxygenation in different time points during the liver transplantation. We hypothesize that there is a change in microcirculatory function and StO2 in end-stage liver disease patients detected by VOT and NIRS.

Description:

End - stage liver disease patients scheduled for liver transplantation will be enrolled. They will receive normal standard of care. The VOT assessment using a non-invasive, integrated research device (InspectraTM StO2 Vascular Occlusion test (VOT) Research Device Hutchinson Corp Minn, MN, USA) and 15 mm Inspectra thenar sensor probe. An integrated blood pressure cuff is placed on the right arm and inflated to a pressure sufficient to produce arterial inflow occlusion (50mmHg above systolic pressure). The cuff remains inflated until a StO2 value of 40% is achieved. During the inflation and deflation, various StO2 parameters are measured and recorded at designed time point.

Specific VOT parameters of interest:

• Baseline StO2 (reflective of perfusion/metabolism ratio)

• Ischemia slope (partly reflective of basal O2 consumption)

• Ischemia area (partly reflective of basal O2 consumption)

• Time till 40% ischemic threshold (partly reflective of basal O2 consumption)

• Recovery slope (biphasic and reflective of shear stress and endothelial vasoreactivity)

• Recovery area (reflective of endothelial vasoreactivity)

• Hyperemia area (reflective of endothelial vasoreactivity and tissue metabolic rate) To determine effect of core versus peripheral temperatures, a conventional skin thermocouple will be placed under adhesive patch used to secure NIRS optodes in position on thenar eminence

Data collection

1. Demographic data: a)age, b)sex, c)diagnosis, d)Model of End-stage Liver Disease (MELD) score, Body Mass Index (BMI)

2. Clinical parameter : the investigator will collect clinical data including VOT parameters (from above), hemodynamics parameter, chemical parameters and medications used in specific time frame :

• time frame

1. pre-operative (for base line data)

2. pre-anhepatic phase (15 min. before the inferior vena cava (IVC) clamps)

3. anhepatic phase (30 min. after the IVC clamps),

4. reperfusion phase (30 min. after the release the IVC clamps),

5. immediately post operation (at the skin closure)

• hemodynamics : SpO2 (Pulse oxygen saturation), MAP (mean arterial pressure), HR (heart rate), CVP (Central venous pressure), PAP (Pulmonary artery pressure), CI (Cardiac output index), PCWP (Pulmonary artery wedge pressure), SVRI (Systemic vascular resistance index), PVRI (Pulmonary vascular resistance index), temperature

• chemical : Hb, Platelets, INR (international normalized ratio) (PT : Prothrombin time), PTT (partial thromboplastin time), Lactate, base excess

• Medications : Volatile agents, Vasopressors (Concentration at recorded time points)

Then we will compare the dynamic changes of StO2 parameters in different time points (as mentioned) and compare to the hemodynamics and chemical parameters.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients suffering from end-stage liver disease scheduled for liver transplantation.

Exclusion Criteria:

• Patients with known peripheral vascular disease

• Patients receiving Oxygen therapy

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• End Stage Liver Disease
• Liver Diseases

Locations

Country	Name	City	State
Canada	University Hospital, London Health Science Center	London	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Lawson Health Research Institute

Country where clinical trial is conducted

Canada, 

References & Publications (12)

Al-Hamoudi WK, Alqahtani S, Tandon P, Ma M, Lee SS. Hemodynamics in the immediate post-transplantation period in alcoholic and viral cirrhosis. World J Gastroenterol. 2010 Feb 7;16(5):608-12. — View Citation

Caraceni P, Dazzani F, Salizzoni E, Domenicali M, Zambruni A, Trevisani F, Bernardi M. Muscle circulation contributes to hyperdynamic circulatory syndrome in advanced cirrhosis. J Hepatol. 2008 Apr;48(4):559-66. doi: 10.1016/j.jhep.2007.12.016. Epub 2008 Jan 31. — View Citation

Groszmann RJ. Hyperdynamic circulation of liver disease 40 years later: pathophysiology and clinical consequences. Hepatology. 1994 Nov;20(5):1359-63. Review. — View Citation

Harel F, Denault A, Ngo Q, Dupuis J, Khairy P. Near-infrared spectroscopy to monitor peripheral blood flow perfusion. J Clin Monit Comput. 2008 Feb;22(1):37-43. Epub 2007 Nov 27. — View Citation

Helmy A, Newby DE, Jalan R, Johnston NR, Hayes PC, Webb DJ. Nitric oxide mediates the reduced vasoconstrictor response to angiotensin II in patients with preascitic cirrhosis. J Hepatol. 2003 Jan;38(1):44-50. — View Citation

Hickman PE, Potter JM, Pesce AJ. Clinical chemistry and post-liver-transplant monitoring. Clin Chem. 1997 Aug;43(8 Pt 2):1546-54. Review. — View Citation

Okumura H, Aramaki T, Katsuta Y, Terada H, Satomura K, Akaike M, Sekiyama T. Regional differences in peripheral circulation between upper and lower extremity in patients with cirrhosis. Scand J Gastroenterol. 1990 Sep;25(9):883-9. — View Citation

Poeze M. Tissue-oxygenation assessment using near-infrared spectroscopy during severe sepsis: confounding effects of tissue edema on StO2 values. Intensive Care Med. 2006 May;32(5):788-9. Epub 2006 Mar 17. — View Citation

Seino Y, Ohki K, Nakamura T, Tsukamoto H, Takano T, Aramaki T, Okumura H, Hayakawa H. Pathophysiological characteristics of cutaneous microcirculation in patients with liver cirrhosis: relationships to cardiovascular hemodynamics and plasma neurohormonal factors. Microvasc Res. 1993 Sep;46(2):206-15. — View Citation

Shelly MP, Dixon JS, Park GR. The pharmacokinetics of midazolam following orthotopic liver transplantation. Br J Clin Pharmacol. 1989 May;27(5):629-33. — View Citation

Steib A, Freys G, Gohard R, Curzola U, Ravanello J, Lutun P, Boudjema K, Otteni JC. Tissue oxygenation during liver transplantation. Crit Care Med. 1992 Jul;20(7):977-83. — View Citation

Thomson SJ, Cowan ML, Forton DM, Clark SJ, Musa S, Grounds M, Rahman TM. A study of muscle tissue oxygenation and peripheral microcirculatory dysfunction in cirrhosis using near infrared spectroscopy. Liver Int. 2010 Mar;30(3):463-71. doi: 10.1111/j.1478-3231.2009.02157.x. Epub 2009 Nov 16. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the significant changes in StO2 between anhepatic and reperfusion phase of the end-stage liver disease patient undergoing liver transplantation	Our data measured will be included only during the operation and at skin closure can reflect early postoperative period.	compare the change of StO2 during different phase of the liver transplantation (base line, pre-anhepatic phase, anhepatic phase, re-perfusion phase and at skin closure)	Yes
Secondary	dynamic changes in StO2 during liver transplantation with possible correlation with hemodynamic or chemical parameters in different time points	from previous study indicates that new liver start its metabolic function well right after the vascular connection complete. So, the investigator want to analyze the correlation between the dynamic StO2 changes during operative period	preoperative for baseline data, intraoperative (during different phase of liver transplantation) and finish data record at skin closure time)	Yes