Opioid Sparing Anesthesia in Patients With Liver Cirrhosis Undergoing Liver Resection
Condition: Liver Cirrhosis
MeSH terms: Liver Cirrhosis; Fibrosis
Study type: Interventional
Phase: Phase 3

Summary: 
      This randomized clinical trial will investigate the opioid sparing effect of dexmedetomidine
      and ketmine infusion in cirrhotic patients undergoing liver resection
    

Detailed description: 
      Patient enrollment will start after approval of the study protocol by the local Ethics and
      Research Committee and the Institutional Review Board (IRB) of the Departments of Anesthesia,
      ICU and Pain Management and the National Liver Institute, Faculty of Medicine, Menoufia
      University. The study will be conducted in the Anesthesia Department, National Liver
      Institute and will be registered with the ClinicalTrials.gov (http://www.clinicaltrials.gov)
      before patients enrollment.

      The study will include adult patients with liver cirrhosis undergoing liver resection.
      Patients will be randomly allocated into one of the two study groups using an online
      randomization program (http://www.randomizer.org). Random allocation numbers will be
      concealed in opaque closed envelops. A written informed consent will be taken from each
      patient.

      Five leads electrocardiography, pulse oximetry and peripheral perfusion index using masimo
      pulse oxymetry finger prope (Masimo, Irvine,CA, USA), end-tidal CO2, invasive arterial blood
      pressure, central venous pressure, The electrical cardiometry (EC) (ICON monitor;
      Cardiotronics Inc., La Jolla, CA, USA) for cardiac output monitoring (CO). oesophageal
      temperature, fraction inspired oxygen concentration, fraction inspired and expired
      desflurane. Bispectral index will be used to monitor the depth of anesthesia (BIS Covidien
      USA.), The neuromuscular function will be monitored using TOF-Watch SX (Schering-Plough,
      Swords, Co. Dublin, Ireland).

      All patients fulfilling the study inclusion criteria will undergo a thorough clinical
      evaluation including laboratory assessment of liver and renal functions. Other diagnostic
      and/or laboratory workup will be requested by the attending anesthetist and the surgeon
      according to the patient clinical condition and the proposed surgical intervention.

      Bilateral transversus abdominis plane (TAP) block:

      All patients in the two study groups will receive a single shot ultrasound-guided bilateral
      TAP block using levopubivacaine. The effectiveness and dermatomal distribution of the block
      will be checked after 30 minutes and before induction of general anesthesia.

      Anesthesia will be induced in all patients using fentanyl 2µg/kg, propofol 2 mg/kg, and
      rocuronium 0.6 mg/kg to facilitate endotracheal intubation. After induction of anesthesia,
      patients will be randomly allocated in two groups opioid sparing group (OS) and opioid-based
      group (OB). Patients in the Opioid Sparing group will receive a loading dose of
      dexmedetomidine (1µg/kg over 10 minutes). This will be followed by a fixed continuous
      maintenance infusion of 0.5µg/kg/hour. Furthermore, a single induction analgesic dose of 0.5
      mg/kg ketamine will be given to all patients in the OS group. This will be followed by 0.25
      mg/kg/h continuous maintenance infusion. Dexmedetomidine and ketamine infusions will be
      stopped 30 minutes prior to the conclusion of surgery. Patients in the opioid-based group
      will receive placebo boluses and infusions of saline. The attending anesthesiologist will be
      blinded to the patient group assignment.

      Anesthesia will be maintained with a mixture of air, oxygen and desflurane to keep a BIS
      between 40 and 60. Muscle relaxation will be maintained by additional top-up doses of
      rocuronium 0.15mg/kg and will be guided by the response to ulnar nerve stimulation.
      Ventilation parameters will be adjusted to maintain normocapnia. Intraoperative normothermia
      will be maintained using a forced air warm blanket (Model 750-Bair Hugger Temperature
      Management Unit, SMA MISR, Arizant Healthcare Inc, USA), a humidifier, and warm intravenous
      fluids. Deep venous thrombosis (DVT) prophylaxis will include elastic stockings, sequential
      compression device (SCD) (Kendall Company, Tyco, USA) on the lower limb until early
      ambulation. Intraoperative fluid, fresh frozen plasma, and blood replacement therapy will be
      guided by the continuous monitoring of the central venous pressure and EC Cardiometry. and
      will be titrated to maintain hemodynamic stability and a hemoglobin level of 10 g/dL.

      The intra-operative hemodynamics target will be to maintain the mean arterial blood pressure
      and heart rate within 20% of baseline value. Significant hemodynamic alterations will be
      managed as follows:

        -  Bradycardia (heart rate < 50 beats/min) will be managed by incremental 0.5 mg doses of
           atropine.

        -  Hypertension and/or tachycardia defined as more than 20% increase of the baseline
           readings will be managed by top-up doses of fentanyl 1µg/kg in the two study groups.

        -  Hypotension defined as more than 20% reduction in the baseline mean arterial blood
           pressure will be managed by incremental doses of ephedrine 5mg in the two study groups.

      At the end of surgery and when two responses to train-of-four ulnar nerve stimulation are
      detected (T2), residual rocuronium-induced neuromuscular block will be antagonized by
      sugammadex 2 mg/kg. Patients will be discharged to the surgical intensive care unit after
      extubation. Postoperative analgesia will be achieved using patient-controlled fentanyl
      infusion (PCA fentanyl).
    

Intervention name(s): Opioid-based group (OB) (placebo/saline); Opioid sparing group (OS) (dexmedetomidine (PRECEDEX™ "dexmedetomidine hydrochloride" - Pfizer) and ketamine)
Intervention type(s): Drug; Drug
Intervention description(s): Patients in the opioid-based group will receive placebo boluses and infusions of saline.; Patients in the Opioid Sparing group will receive a dexmedetomidine (PRECEDEX™ "dexmedetomidine hydrochloride" - Pfizer) and ketamine.
Other intervention name(s): OB; OS
Intervention MeSH terms: Dexmedetomidine; Ketamine; Analgesics, Opioid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Dexmedetomidine; ketamine; Liver cirrhosis