Influence of Dexmedetomidine and Lidocaine on Opioid Consumption in Laparoscopic Intestine Resection
Condition: Opioid-Related Disorders; Neuralgia
MeSH terms: Neuralgia; Opioid-Related Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      Using combination of opioid analgesics and analgesics with different mechanism of action the
      investigators can decrease the consumption of opioid analgesics and their side effects. The
      investigators will use opioid analgesic fentanyl alone or in combination with dexmedetomidine
      or lidocaine.The participants scheduled for laparoscopic intestine resection will be divided
      in three groups: in the first group, the participants will receive single boluses of
      fentanyl, in the second group, the participants will receive continuous infusion of lidocaine
      and single boluses of fentanyl, and in the third group, the participants will receive
      continuous infusion of dexmedetomidine and single boluses of fentanyl. Participants with
      intraoperative infusion od dexmedetomidine or lidocaine will need less boluses of fentanyl
      during the operation and less opioid analgesics after the operation in comparison to those
      who will receive only fentanyl boluses. Better cognitive function after the operation is
      expected in participants receiving dexmedetomidine infusion. There will be minimal incidence
      of neuropathic pain because of minimal surgical injury of peripheral nerves in all groups of
      patients.
    

Detailed description: 
      Introduction: The consumption of opioid analgetics and their side effects can be minimized by
      using the combination of opioid analgesics and analgesics with different mechanism of action.
      The investigators will use opioid analgesic fentanyl alone or in combination with
      dexmedetomidine or lidocaine. Dexmedetomidine is alpha 2 adrenergic receptor agonist and is
      used more and more during anesthesia because of its anesthetic and analgesic effects as it
      preserves mental status and decreases the consumption of analgesics. Lidocaine is a local
      anesthetic and antiarrhythmic drug which decreases opioid consumption as well.

      The participants scheduled for laparoscopic intestine resection will be divided in three
      groups: in the first group, the participants will receive single boluses of fentanyl, in the
      second group, the participants will receive continuous infusion of lidocaine and single
      boluses of fentanyl, and in the third group, the participants will receive continuous
      infusion of dexmedetomidine and single boluses of fentanyl.

      Hypothesis: Participants with intraoperative infusion od dexmedetomidine or lidocaine will
      need less boluses of fentanyl during the operation and less opioid analgesics after the
      operation in comparison to those who will receive only fentanyl boluses. Better cognitive
      function after the operation in participants receiving dexmedetomidine infusion is expected.
      There will be minimal incidence of neuropathic pain because of minimal surgical injury of
      peripheral nerves in all groups.

      Justification: Lidocaine and dexmedetomidine are analgesics with different mechanism of
      action in comparison to opioid analgesics. Their use during the operation decreases the
      consumption of opioids intra- and postoperatively. Dexmedetomidine has beneficial effect on
      cognitive function and that is why the investigators expect preserved cognitive function in
      participants after the operation. Because of minimal surgical injury and, therefore, minimal
      probability of peripheral nerve injury, the investigators expect low incidence of neuropathic
      pain in all groups.

      Methods: The investigators will include 60 participants in the study, between 35 to 85 years
      old, ASA 2 - 3 (American Society of Anesthesiologists, ASA) undergoing a planned laparoscopic
      intestine resection. The participants will be randomized into three groups. In the first
      group, fentanyl boluses will be adimistred during the operation, in the second, infusion of
      lidocaine will be added to fentanyl, and in the third, the infusion of dexmedetomidine will
      be added to fentanyl. The investigators will record opioid consumption during the operation
      and two days after the operation. The investigators will use mini mental test for evaluation
      of cognitive function before the operation and at the transfer of the participant
      postoperatively to the surgical ward, in order to explore the influence of analgesics used on
      cognitive function. Two months after the operation the degree of neuropathic pain will be
      evaluated with pain questionnaire. The data will be statistically evaluated.

      Expected results: Participants with intraoperative infusion of lidocaine and dexmedetomidine
      will need less opioid analgesics during and after the operation in comparison to the group
      with fentanyl boluses only. The investigators expect better cognitive function after the
      operation in participants with dexmedetomidine infusion. Because of the minimal surgery
      injury to the peripheral nerves low incidence of neuropathic pain is expected in all groups.

      Study design and methods Inclusion criteria: In our study the investigators will include
      patients aged 35 to 85, ASA 2-3 (according to the classification of American Society of
      Anesthesiologists), undergoing a planned laparoscopic intestine resection at the Department
      of Abdominal Surgery at the University Medical Centre Ljubljana. Included participants will
      sign the consensus for participating in the study after exact explanation and conversation,
      as well as consensus for anesthesia and surgery.

      Exclusion criteria: Participants with allergies to alpha 2 receptor agonists, uncontrolled
      arterial hypertension, 2nd and 3rd degree atrioventricular block, alcohol and illegal drugs
      abusers, patients with clinically important neurological, cardiovascular, respiratory (COPD,
      emphysema), renal, liver, and gastrointestinal disease, will be excluded from our study. The
      investigators will also exclude pregnant women and patients younger than 18 years due to
      their physiological particularities.

      Data collection: The participants will be prepared for the operation as usual according to
      the operative protocol. Cognitive function is going to be assessed with a mini mental test
      before the operation.

      After inserting the peripheral venous line, the induction will be performed with analgesic
      fentanyl (2 mcg/kg) and sedative propofol (1,5-2,5 mg/kg). Muscle relaxant rocuronium will be
      used for easier intubation (0,6 mg/kg; standard dose). The participants will be controlled
      mechanically ventilated with tidal volumes 6-8 ml/kg. Anesthesia will be maintained with
      intravenous anesthetic propofol in doses between 4 - 6 mg/kg/h according to bispectral index
      value (bispectral index, BIS, Vista), which will be kept between 40 and 55, the interval
      suitable for surgical depth of anesthesia. Normothermia and normocapnia will be maintained.
      The fluids will be warmed to 39°C via Hotline, the body temperature and expired CO2 will be
      measured. Mean arterial blood pressure will be maintained within ± 25 % baseline value. When
      mean arterial blood pressure will decrease more than 25% from the baseline value, a bolus of
      a vasoactive drug will be used.

      Beside the standard monitoring (electrocardiogram, pulse oximetry, indirect blood pressure
      management, capnometry), the investigators will use ANI (analgesia nociception index)
      monitoring for the pain measurement. ANI values will be maintained between 50 and 70 and
      between those valuse good analgesia is provided. Muscle relaxation will be measured with TOF
      (train of four) and will be maintained on the level of deep muscle relaxation, that is TOF 0
      and PTC 1 - 2 (posttetanic count).

      Before the operation the investigators will randomize the participants into the three groups,
      which will distinguish according to analgesia used. All participants will get intravenous
      bolus of fentanyl (2 mcg/kg, standard dose) before the incision. All of them will receive
      bolus of fentanyl when ANI will drop below 50 during the operation (2 mcg/kg, recommended
      standard dose, first group). Participants in the second group will receive infusion of
      lidocaine (1,5 mg/kg/h), and participants in the third group infusion of dexmedetomidine (0,5
      µg/kg/h). The consumption of fentanyl and propofol will be measured during the operation. The
      infusion of lidocaine and dexmedetomidine will be stopped 10 minutes before the end of the
      operation. Propofol infusion will be stopped at the end of the final suture. After the
      operation all participants will receive postoperative infusion of piritramide delivered with
      PCA (patient control analgesia). If the pain according to the visual analog scale (VAS) will
      be more than 3, the participants will be given a bolus of the peripheral acting analgesic or
      opioid (paracetamol, metamizol, piritramide). VAS will be reevaluated two days after the
      operation, as well as the consumption of other opioids and other analgesics. Cognitive
      function will be evaluated again on the second day with mini mental test, or at the transfer
      of the participant to the surgical ward with the discontinuation of the opioids and when they
      will be afebrile. Neuropathic pain will be evaluated with the pain questionnaire two months
      after the operation.

      Statistical analysis: Collected data will be presented using descriptive statistics such as
      mean, median and standard deviation. The use of the opioids and other analgesics will be
      compared using paired Student t-test or other suitable nonparametric tests (eg. ANOVA),
      depending on the type of data used.

      Correlation of different factors will be determined using Pearson/Spearman correlation
      coefficient. Deviation from normal distribution of data will be tested with a chi-squared
      test. Predictive value will be determined using logistic regression.

      Expected results: The investigators assume that there will be less opioid consumption in
      participants receiving lidocaine or dexmedetomidine infusion during the operation and the
      following two days compared to participants who received fentanyl boluses only. In
      participants with intraoperative infusion of dexmedetomidine the investigators expect
      preserved cognitive function. Low incidence of neuropathic pain is expected two months after
      the operation in all groups because of minimal peripheral nerve injury during operation.
    

Intervention name(s): Dexmedetomidine; Lidocaine; placebo; Fentanyl
Intervention type(s): Drug; Drug; Other; Drug
Intervention description(s): The participants will be given infusion of dexmedetomidine 0,5 mcg/kg/h intravenously.; The participants will be given infusion of lidocaine 1,5 mg/kg/h intravenously.; The participants will be given infusion of normal saline intravenously.; Fentanyl 2 mcg/kg will be given to all participants for the intubation and during the operation when ANI value drops below 50.
Other intervention name(s): Dexdor; Xylocaine
Intervention MeSH terms: Lidocaine; Fentanyl; Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: dexmedetomidine; lidocaine; neuropathic pain; laparoscopic intestine resection; cognitive function