Effect of Terlipressin on Cerebral Oxygen Saturation During Liver Transplantation

Effect of Terlipressin on Cerebral Oxygen Saturation and Cerebral Blood Flow During Living Donor Liver Transplantation

in our study the investigators aim to assess the effect of terlipressin on cerebral oxygenation monitored by cerebral oxymetry and cerebral blood flow measured by transcranial doppler.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Terlipressin Adverse Reaction
• Intervention / Treatment: Drug: Terlipressin; Drug: Normal saline

Detailed Description

All patients will receive 6ml /kg/h Ringer acetate solution as a maintenance intraoperative fluid. If pulse pressure variations (PPV) is more than 15%, the patient will be considered as fluid responder and will receive a 250-ml bolus of albumin 5% to maintain PPV ≤15%. Blood transfusion will be given based on a hemoglobin level (< 7 g/dl) in both (control group) and (terlipressin group). Other blood products will be transfused guided by lab result; Fresh frozen plasma will be given when INR > 2 and platelets will be given when platelets <30.000/mm3. The patients will be randomly allocated into 2 groups; Group T (Terlipressin group) and group S (Normal saline 0.9%).

For (terlipressin group) all patients will receive loading dose of terlipressin (1mg diluted with 50 ml of normal saline 0.9% solution over 30 min) and it will be maintained by continuous infusion at rate of 160 μg per hour (8 ml/h).

For (control group) all patient will receive 50 ml of normal saline 0.9% solution over 30 min and will be maintained continuous infusion at rate of 8 ml/h.

Drugs will be prepared by the nurse and the investigator will be blinded to the drug given.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Kasr Alainy Hospital , Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA II-IV undergoing orthotopic liver transplantation.
• Age above 18 years.

Exclusion Criteria:

• Age below 18 years.
• Patients on Terlipressin preoperative.
• Patients known allergic to Terlipressin.
• Portal vein thrombosis.
• Ischemic heart disease.
• Patients with T. bilirubin level above 7 mg/dl

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: terlipressin group; group will receive terlipressin infusion one mg in 50 ml normal saline will be given over 30 minute as loading dose then will be maintained as infusion of 160 μg per hour (8 ml/h).	Drug: Terlipressin; drug will be given after 30 minutes of induction of anesthesia
Placebo Comparator: saline (control) group; group will receive normal saline infusion 50 ml normal saline will be given over 30 minute as loading dose then will be maintained as infusion of (8 ml/h).	Drug: Normal saline; drug will be given after 30 minutes as placebo in control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cerebral oxygen saturation	regional oxygen saturation assessed by cerebral oxymetry with probes applied on forehead	one hour after infusion of drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cerebral oxygen saturation	regional oxygen saturation assessed by cerebral oxymetry with probes applied on forehead	baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion
resistive index of middle cerebral artery	assessed by trans cranial Doppler	baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 1 hour after drug infusion, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion
peak velocity, end diastolic velocity of middle cerebral arteries	assessed by trans cranial Doppler	baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 1 hour after drug infusion, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion
End diastolic velocity of middle cerebral arteries	assessed by trans cranial Doppler	baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 1 hour after drug infusion, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion
Heart rate		baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 1 hour after drug infusion, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion
Systolic blood pressure		baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 1 hour after drug infusion, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion
Diastolic blood pressure		baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 1 hour after drug infusion, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion
PH	assessed by arterial blood gases	baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 1 hour after drug infusion, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion
PCo2	assessed by arterial blood gases	baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 1 hour after drug infusion, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion
Po2	assessed by arterial blood gases	baseline 5 minutes after induction anesthesia,dissection phase 30 minutes after induction of anesthesia, 1 hour after drug infusion, 15 minutes after start of anhepatic phase, 5 minutes after reperfusion

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital

Publications and helpful links

General Publications

• Bechstein WO, Neuhaus P. [Bleeding problems in liver surgery and liver transplantation]. Chirurg. 2000 Apr;71(4):363-8. doi: 10.1007/s001040051066. German.
• Joshi B, Ono M, Brown C, Brady K, Easley RB, Yenokyan G, Gottesman RF, Hogue CW. Predicting the limits of cerebral autoregulation during cardiopulmonary bypass. Anesth Analg. 2012 Mar;114(3):503-10. doi: 10.1213/ANE.0b013e31823d292a. Epub 2011 Nov 21.
• Czosnyka M, Brady K, Reinhard M, Smielewski P, Steiner LA. Monitoring of cerebrovascular autoregulation: facts, myths, and missing links. Neurocrit Care. 2009;10(3):373-86. doi: 10.1007/s12028-008-9175-7. Epub 2009 Jan 6.
• Joshi B, Brady K, Lee J, Easley B, Panigrahi R, Smielewski P, Czosnyka M, Hogue CW Jr. Impaired autoregulation of cerebral blood flow during rewarming from hypothermic cardiopulmonary bypass and its potential association with stroke. Anesth Analg. 2010 Feb 1;110(2):321-8. doi: 10.1213/ANE.0b013e3181c6fd12. Epub 2009 Dec 11.
• Dhiman RK, Kurmi R, Thumburu KK, Venkataramarao SH, Agarwal R, Duseja A, Chawla Y. Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver. Dig Dis Sci. 2010 Aug;55(8):2381-90. doi: 10.1007/s10620-010-1249-7. Epub 2010 May 28.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2018
• Primary Completion (Actual): November 25, 2018
• Study Completion (Actual): November 25, 2018

Study Registration Dates

• First Submitted: December 25, 2017
• First Submitted That Met QC Criteria: January 4, 2018
• First Posted (Actual): January 10, 2018

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: N-113-2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No