Dexmedetomidine in Transversus Abdominis Plane Block for Laparoscopic Cholecystectomy
Condition: Elective Laparoscopic Cholecystectomy
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The use of dexmedetomidine as an adjunct to bupivacaine in transversus abdominis plane block
      will reduce the cumulative morphine consumption after laparoscopic cholecystectomy.
    

Detailed description: 
      Laparoscopic cholecystectomy, which is a common surgical procedure, is associated with less
      postoperative pain in comparison to open cholecystectomy. However, this pain needs to be
      treated adequately to allow early mobilization.

      Ultrasound guided transversus abdominis plane (TAP) block is an established technique to
      manage post laparoscopic cholecystectomy pain. 1 In addition, the use of TAP blocks reduced
      the need for intraoperative and postoperative opioids and the side-effects associated with
      their use.

      The aim of a TAP block is to deposit local anaesthetic in the plane between the internal
      oblique and transversus abdominis muscles targeting the spinal nerves in this plane. The
      innervation to abdominal skin, muscles and parietal peritoneum will be interrupted.

      Dexmedetomidine which is an Alpha 2-adrenergic agonist produces analgesia via a non-opioid
      mechanism and is also known to enhance central and peripheral neural blockades.2
      Dexmedetomidine added to bupivacaine or levobupivacaine for brachial plexus block shortens
      sensory and motor block onset time, extends motor and sensory block durations, and also
      extends the postoperative analgesia.3, 4

      We postulate that the use of dexmedetomidine as an adjunct to bupivacaine in transversus
      abdominis plane block will reduce the morphine consumption after laparoscopic
      cholecystectomy.

      Based upon previous published data,4 a priori power analysis indicated that 60 patients in
      each group would be sufficient to detect a 30% reduction in the 24-hours cumulative morphine
      consumption, which is considered to be of clinical validity, with a type-I error of 0.0167
      (0.05/4) and a power of 80%. We added 10% extra patients to compensate for possible dropouts.

      All patients will be familiarized with a 10-cm visual analogue scale (VAS) (0= no pain; 10=
      worst imaginable) to assess the intensity of pain and on the use of the patient-controlled
      analgesia (PCA).

      Monitoring includes non-invasive blood pressure, and electrocardiography, pulse oximetry.

      An intravenous infusion of 10 ml kg-1 of Lactated Ringer's solution will be initiated before
      surgery and will be followed by 5 ml kg-1 hr-1 throughout the procedure.

      Anaesthesia technique will be standardized. Anesthesia will be induced by fentanyl of 2-3 µg
      kg-1, propofol 1.5-2.5 mg kg-1, and rocuronium 0.6 mg kg-1. Tracheal intubation will be
      carried out at the development of maximum block as monitored by the train-of-four (TOF).

      Anesthesia, consisting of a 0.7-1.5 minimum alveolar concentration (MAC) of sevoflurane, will
      be administered to maintain heart rate (HR) and mean arterial blood pressure (MAP) values
      below 20% of baseline values. Fentanyl 0.5μg/kg increments will be administered when the HR
      and MAP values are > 20% of baseline values, despite a target sevoflurane of MAC ≥ 1.5. When
      the HR and MAP values < 20% of baseline values, the sevoflurane MAC is decreased gradually to
      0.7 MAC.

      Patients' lungs will be ventilated to achieve a PaCO2 of 35-45 mm Hg. All patients will
      receive intravenous granisetron 1 mg and lornoxicam 16 mg after the induction of anaesthesia.
      Rocuronium increments will be given to maintain suppression of the second twitch in the TOF.

      The anaesthesiologists who will perform the TAP block and give the anaesthetics will not be
      involved in the patients' assessment. All other staff in the operating room is unaware of the
      randomization code.

      The TAP block will be performed using ultrasound (SonoSite M-Turbo®, Sonosite, USA) guidance
      as described by Ra et al

      All operations will be performed by the same surgeons. CO2 pneumoperitoneum will be
      introduced and intra-abdominal insufflation pressure will be limited to 12 mm Hg. After
      introducing of the four trocars, the patient will be placed in the reverse Trendelenburg
      position, using up to 30° of head-up tilt. No supplementary dose of muscle relaxant was
      administered 30 minutes before the end of the surgery.

      After desufflation of CO2 pneumoperitoneum, the patient will be returned to the horizontal
      position and during skin closure; neuromuscular blockade will be antagonized with 50 µg kg-1
      neostigmine and 10 µg kg-1 glycopyrrolate. At the last skin suture, desflurane will be
      discontinued and tracheal extubation will be performed at the discretion of the involved
      anesthetist in the patient's management.

      A standard postoperative analgesic regimen, consisting of 12-hourly intravenous lornoxicam 8
      mg, 6-hourly intravenous paracetamol 1 g and intravenous morphine PCA (incremental dose, 1
      mg; lockout time, 6-min; a maximum 4-hourly limit, 30 mg), will be used in all patients. If
      the patient has persistent postoperative nausea and/or vomiting, metoclopramide 10 mg will be
      administered intravenously when needed.

      Other independent investigators who will be blinded to the study protocol and the patient's
      randomization code will collect the patient's data.
    

Intervention name(s): placebo; bupivacaine; bupivacaine-dexmedetomidine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): transversus abdominis plane block with saline 0.9%; transversus abdominis plane block bupivacaine 0.25%; transversus abdominis plane block with bupivacaine 0.25% with dexmedetomidine 1 µg Kg-1
Intervention MeSH terms: Dexmedetomidine; Bupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment