Perioperative Evaluation of Terlipressin Infusion During Living Donor Liver Transplantation on Incidence of Acute Kidney
Condition: Acute Kidney Injury; Liver Transplantation; Terlipressin; NGAL
MeSH terms: Acute Kidney Injury
Study type: Interventional
Phase: Phase 4

Summary: 
      To study the impact of intra and post-operative Terlipressin infusion on the occurrence of
      acute kidney injury after LDLT To investigate perioperative Neutrophil Gelatinase Associated
      Lipocalin (NGAL) changes and study the effect of Terlipressin on NGAL blood levels
    

Detailed description: 
      The study will be conducted after approval of the local ethics and research committee of
      anesthesia, ICU and pain management of both Faculty of Medicine and Liver Institute, Menoufia
      University, Egypt. This study will be conducted in Anesthesia Department, National Liver
      Institute hospital on patients undergoing liver transplantation. They will be simply
      randomized with closed envelopes into two groups. Terlipressin group and Control group. A
      written informed consent will be taken from every patient.

      Inclusion criteria: Adult living donor liver transplant recipients with no preoperative renal
      dysfunction Exclusion criteria: patients with renal insufficiency defined as serum creatinine
      > 2 mg/dl and GFR <60 ml/min by isotope scanning of the kidney.

      Anesthetic Technique:

      All patients will be monitored by electrocardiography, noninvasive and invasive arterial
      blood pressure, pulse oximetry, capnography, fraction inspired oxygen concentration (FiO2).
      After preoxygenation, general anesthesia will be induced with Propofol 2 mg/kg IV, Fentanyl 2
      µg/kg IV and Rocronium 0.9 mg/kg IV followed by endotracheal intubation and maintenance with
      a mixture of air, oxygen 50% with Desﬂurane. Mechanical ventilation will be adjusted to
      maintain end-tidal CO2 between 35-40 mmHg. Central venous line will be inserted for
      monitoring of central venous pressure (CVP) with ultrasonography guidance.

      The esophageal Doppler probe will then be inserted orally and positioned approximately 35-40
      cm from the teeth (CardioQTM®, Deltex Medical, Chichester, UK). Normothermia (core
      temperature > 36°C) will be maintained intraoperatively using forced warming air blanket
      (Bair Hugger®; Arizant, UK).

      After induction of anesthesia patients will be randomly divided into two groups Terlipressin
      group, Terlipressin (Glypressin®, Rentschler biotechnology Gmbh, Erwin, Germany) will be
      started by continuous infusion at a dose of 1-4 µg/kg/h till day 4 postoperatively. In the
      control group, continuous placebo infusion will be started. The Anesthesia team will be kept
      blind to the contents of the infusion.

      Rotetional thromboelastometry [ROTEM] will guide intraoperative blood transfusion protocol as
      prescribed by the study of Gorlinger K will be followed in both groups. (13) Platelets will
      be substituted when maximum clot firmness of (MCF EXTEM) <45mm and maximum clot firmness of
      FIBTEM (MCF FIBTEM) >8mm.

      Fresh frozen plasma will be administerd when clot formation time representing extrinsic
      coagulation pathway (CFT EXTEM) was >240sec. Hematocrite will be kept more than or equal to
      25 with packed red blood cells units.

      All patients will receive intraoperative methylprednisolone (10 mg/kg). Hemodynamics will be
      maintained, keeping mean blood pressure above 60 mmHg by fluids and vasoactive drugs.

      After surgery, all patients will be transferred to the intensive care unit for controlled
      mechanical ventilation. The patients will be extubated when hemodynamics are stable, liver
      graft functions satisfactory, sufficient spontaneous breathing, and core temperature >36°C.

      Measured Parameters:

      -Evaluation of renal function and injury:

        -  Serum Cr levels and BUN will be determined preoperatively and then daily up to 5 days
           after surgery.

        -  The glomerular ﬁltration rate (GFR) or the nearest approximation of GFR will be
           calculated from the equation of modiﬁcation of Diet in Renal Disease Study on the basis
           of obtained serum Cr levels and patient demographics.

        -  Urine output

        -  Determination of NGAL Blood samples for the determination of NGAL will be drawn at 3
           different time points: immediately after the induction of anesthesia, 2 hours after
           reperfusion, and 24 hours after reperfusion.

      Blood samples will be drawn at the predetermined time points and processed within 2 hours
      after collection. Serum will be collected and subsequently frozen at -80°Celsius until
      further analysis -Hemodynamic parameters:

      • Heart rate, mean arterial blood pressure [MABP], and CVP, cardiac output (COP), stroke
      volume (SV), corrected flow time (FTc), systemic vascular resistance (SVR) will be recorded
      after induction of anesthesia, then every hour during the operation.

      Other parameters:

        -  Anhepatic phase time, warm and cold ischemia time.

        -  Graft weight , recipient graft body weight ratio.

        -  Fluid, blood product transfusion.

        -  Blood glucose level, postoperative complication.

        -  ICU stay, length of hospital stay.

        -  30 days mortality The need for postoperative renal replacement therapy.
    

Intervention name(s): Terlipressin; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Terlipressin (Glypressin®) will be started by continuous infusion at a dose of 1-4 µg/kg/h till day 4 postoperatively
Other intervention name(s): Glypressin
Intervention MeSH terms: Terlipressin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Terlipressin; Acute kidney injury; Liver transplantation; NGAL