Dexmedetomidine Versus Clonidine in TAP Block
Condition: Transversus Abdominis Plane Block
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      A laparoscopic approach offers several advantages over an open procedures; potentially
      reduces the surgical stress and fluid shifts that may accompany it; in addition there is less
      need for postoperative analgesia, reduction of postoperative respiratory and wound
      complications.

      Despite the minimally invasive nature, pain can be moderate to severe in the immediate
      postoperative period that requires multimodal analgesia. Inadequate control of post-operative
      pain leads to several unwanted adverse events ranging from patients' discomfort and prolonged
      immobilization to thromboembolic phenomenon and pulmonary complications.

      Transversus abdominis plane (TAP) block is a type of peripheral nerve block that involves
      innervation of the anterolateral abdominal wall. With the aid of ultrasound, local anesthetic
      (LA) is injected into the transversus abdominis fascial plane, where the nerves from T6 to L1
      are located.

      Ultrasound TAP block is accompanied by a good pain relief and reduced intraoperative and
      postoperative opioids requirements after laparoscopic surgery. In this case a bilateral TAP
      block is necessary because the abdominal skin incisions for the ports of laparoscopic
      procedure are performed on both sides.

      Unfortunately, TAP block duration is limited to the effect of administered LA. Recently,
      adjuvant medications were added to LA to prolong the effect of TAP block. Dexmedetomidine is
      a selective alpha 2 (α2) adrenergic agonist with both analgesic and sedative properties. Its
      use with bupivacaine either epidurally or intrathecally is associated with prolongation of
      the LA effect. A major advantage of dexmedetomidine is its higher selectivity compared with
      clonidine for α2A receptors, responsible for the hypnotic and analgesic effects of such
      drugs.10 Clonidine action, similar to local anesthetic action, and its interaction with local
      anesthetics have been explained by three possible mechanisms. First, clonidine blocks Ad and
      C fibers. Secondly, clonidine may cause local vasoconstriction, thus decreasing local
      anesthetic spread and removal around neural structures. Thirdly, clonidine used in peripheral
      blocks intensifies and prolongs analgesia.
    

Detailed description: 
      Preoperative assessment:

      The day prior to surgery, all children will undergo pre-anesthetic checkup including detailed
      history, thorough general, physical, systemic examination and weight of the patient. All
      children will be kept nil per mouth 8 hours for solids and 2 hours for clear liquids.

      Preparation of the patient:

        -  Written consent, coagulation profile, emergency resuscitation equipments including
           airway devices, pediatric advanced life support drugs for LA toxicity will be available.

        -  All patients will be pre-medicated with oral midazolam of 0.5 mg/kg about 20 minutes
           before induction of anesthesia.

      Intraoperative management:

      Intraoperative monitoring will include ECG, pulse oximetry, non-invasive blood pressure,
      capnography and temperature probes.

      All patients in this study will be anesthetized by the same team of anesthesiologists and
      operated upon by the same team of surgeons who will be unaware of the study medications.

      General anesthesia will be standardized for all patients in both groups using 6-8 MAC
      sevoflurane in 100% O2 with appropriate size face mask. After intravenous access securing,
      atropine 0.02 mg/kg and fluid bolus of 10 ml/kg will be given to offset hemodynamic effects
      when pneumoperitoneum is created. Endotracheal intubation with appropriate size to the
      patient's age will be inserted and secured after administration of 2 mg/kg propofol and 0.5
      mg/kg of atracurium. After tracheal intubation, the stomach is deflated with an orogastric
      tube and bladder catheterization is inserted in order to decrease the risk of visceral injury
      during trocar insertion. Controlled mechanical ventilation will be used to maintain end-tidal
      CO2 at 35±5 mmHg. General anesthesia will be maintained with 2-3 MAC sevoflurane delivered in
      100% O2.

      Technique of TAP block:

      Patient will be placed in the supine position and TAP block will be performed under
      ultrasound guidance. After skin preparation, the linear ultrasound probe (high frequency
      probe 7-12 MHz) connected to a portable ultrasound unit ( MANDRAY ) will be placed in the
      axial plane across the mid-axillary line midway between the costal margin and the highest
      point of iliac crest. A 22 G × 50 mm PAJUNK needle attached with tubing system to a syringe
      filled with the LA solution will be inserted in plane with the ultrasound probe and advanced
      until it reaches the plane between the internal oblique and transversus abdominis muscles.
      After careful aspiration to exclude vascular puncture, injection of the study medication will
      be performed leading to separation between the internal oblique and the transversus abdominis
      muscles which will appear as a hypoechoic space on ultrasound. This procedure will be
      repeated on the opposite side of the midline.

      HR, MAP, SpO2 and ETCO2 will be recorded before induction of anesthesia, before block, after
      the block and every 10 minutes till end of surgery. Skin incision will be made 15-20 minutes
      after TAP block. 4 An increase in HR and MAP above 20% of baseline values with skin incision
      will be considered signs of inadequate analgesia. In these cases, fentanyl 1 μg/kg will be
      given intravenously, and the case will be excluded from the study.

      The operative table position itself may need to be changed repeatedly during the operation;
      both the Trendelenburg and the reverse Trendelenburg positions are often used. Children may
      be placed near the foot end of the table. Accordingly, care must be taken to secure the
      patient to the table (e.g. using rolls of gauze and tape). Well padding of extremities should
      be ensured.

      Restriction of the intra-abdominal pressure to 6-12 mmHg in children will be recommended.
      These pressures have minimal effects on cardiac index. Intraoperative hypotension defined as
      fall in MAP by 20% from the baseline requiring a fluid bolus and bradycardia defined as a
      decrease in HR by 20% from the baseline value requiring atropine will be recorded.
      Perioperative blood loss will be replaced using crystalloids and blood as indicated.

      After completion of the surgical procedure, reversal of neuromuscular blockade effect
      (Neostigmine 0.04 mg/kg and Atropine 0.02 mg/kg) and extubation will be done after ensuring
      adequate orogastric suction and empting of pneumoperitonem. Bilateral air entry should be
      checked at the end of anesthesia. Patients will be transferred to the postanesthesia care
      unit (PACU).

      In PACU: HR, MAP, SpO2 modified CHEOPS and nausea & vomiting score will be recorded on
      admission to PACU, 1, 2, 4, 8, 12, 18, 24 h postoperatively by an observer who will be
      unaware of the study protocol.

      CHEOPS = SUM (points for all 6 parameters)

      Interpretation:

        -  Minimum score: 4

        -  Maximum score: 13 Patients with modified CHEOPS ≥ 4 will be given rescue analgesia with
           15 mg/kg paracetamol intravenously (Perfalgan_, Paracetamol 1000 mg. UPSA laboratories,
           France). Pain scores will be recorded every 10 minutes after administration of rescue
           analgesia to evaluate pain relief or need for further rescue analgesia. The number of
           children who will need postoperative rescue analgesics and the durations of analgesia
           will be recorded.

      Patients will be discharged from the hospital when they are pain free and there is no other
      medical reason to admit them to a surgical ward. The parents who will be involved in the
      clinical trial will be invited to complete a postoperative chart with a simple pain scale (0
      = no pain/child calm; 1 = minimum pain/child irritable; 2 = mild pain/child consolable; and 3
      = severe pain/child inconsolable). Parents will be instructed to give their children oral
      Ibuprofen 10 mg/kg when pain scores 2 or 3, and not more frequently than every 8 hours.

      Postoperative vomiting episodes will be recorded and treated with intravenous Metoclopramide
      0.5 mg/kg. Postoperative sedation will be assessed using sedation score described by Culebras
      et al, 2001 (1. Awake and alert. 2. Sleeping but easily arouses to voice or light touch. 3.
      Arouses to loud voice or shaking. 4. Arouses with painful stimuli only. 5. Unrousable).

      Other postoperative complications as infection or hematoma formation will be recorded.

      Parents will be asked to evaluate their satisfaction regarding pain control at the end of 24
      hours postoperatively through 5-point Likert scale (1 = very satisfied, 2 = satisfied, 3 =
      neither satisfied nor dissatisfied, 4 = dissatisfied, 5 = very dissatisfied).
    

Intervention name(s): Dexmedetomidine; Clonidine; Levobupivacaine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): patients will receive ultrasound-guided TAP block using 0.3 ml/kg levobupivacaine (0.125%) with a maximum volume of 20 ml each side + 0.5 ug/kg dexmedetomidine Hydrochloride dissolved in 2 ml normal saline (NaCl 0.9%); patients will receive ultrasound-guided TAP block using 0.3 ml/kg levobupivacaine (0.125%) with a maximum volume of 20 ml + 0.5 ug/kg clonidine dissolved in 2 ml normal saline (NaCl 0.9%); patients will receive ultrasound-guided TAP block using 0.3 ml/kg levobupivacaine (0.125%) with a maximum volume of 20 ml + 2 ml normal saline (NaCl 0.9%).
Other intervention name(s): Control
Intervention MeSH terms: Clonidine; Dexmedetomidine; Levobupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: TAP block; Dexmedetomidine; Clonidine