Opioid Free VS Opioid Anesthesia for Craniotomies
Condition: Supratentorial Neoplasms
MeSH terms: Supratentorial Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      Hemodynamic control during craniotomies can be a bit hectic specially during periods of
      intense noxious stimulation. For long anesthesiologists used high doses of opioids such as
      fentanyl and remifentanyl to provide analgesia with a good hemodynamic control during
      intraoperative period in patients undergoing craniotomies. However, the use of opioids was
      not devoid of side effects. Exploring other anesthetic plans using multiple opioid free
      anesthetic adjuvants that have analgesic effects given together in small doses appear to be
      appealing plan. This idea is the basis of our proposed study in which we compare the
      hemodynamic effects of using opioid free anesthesia versus opioid anesthesia in cranial
      surgeries.
    

Detailed description: 
      Anesthesia for craniotomies can be very challenging because of the presence of periods of
      noxious stimuli that interposes with periods of little stimulation which makes hemodynamic
      control a little bit more complicated. Intraoperative episodes of hypertension during periods
      of intense stimulations and early postoperative hypertension may lead to serious
      complications as post craniotomy intracranial hemorrhage and vasogenic brain edema.
      Anesthetic techniques based on usage of high doses of potent opioid analgesics such as
      fentanyl and remifentanil have been widely popular among anesthesiologists. However, the
      intra operative use of large bolus doses or continuous infusions of potent opioids may be
      associated with postoperative hyperalgesia and increased analgesic consumption.

      More recently, concerns have arisen about impaired healing,immunosuppression,and worsening of
      oncologic outcomes with systemic opioids. Another technique that started gaining its
      popularity is opioid free anesthesia (OFA) technique whose corner stone is depending on
      multiple anesthetic adjuvants that have analgesic effects, , therefore when given together in
      small doses they result in good anesthesia with less side effects and faster recovery
      compared with opioids. This technique has been successfully used in anesthesia for bariatric
      surgeries combining multiple drugs as dexmedetomidine, lidocaine, ketamine, ketorolac and
      magnesium.

      Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, anxiolytic and
      analgesic properties that has minimal effects on respiratory drive. Although preoperative
      intravenous dexmedetomidine administration is associated with a reduction in postoperative
      pain intensity, analgesic consumption and nausea, the analgesic property of dexmedetomidine
      is less effective compared with opioids. Intravenous lidocaine has been described as having
      analgesic, anti-hyperalgesic, and anti-inflammatory properties. Intravenous lidocaine
      infusion in the perioperative period is safe and has clear advantages, such as decreased
      intra operative anesthetic requirements, lower pain scores, reduced postoperative analgesic
      requirements, as well as faster recovery. In addition to ketamine magnesium is also reported
      to enhance analgesia by blocking NMDA receptor, also magnesium has the properties of a
      sympatholytic and has been introduced as a safe component of balanced anesthesia.

      This comparative study between Opioid free anesthesia (OFA) and Opioid anesthesia (OA) aims
      to compare the effect of both techniques on intra operative hemodynamics, intracranial
      tension and recovery in cranial surgeries for supratentorial tumors.

      After obtaining an informed written consent from the patients or their responsible relative,
      patients will be divided into 2 groups randomly using computer software (research
      randomizer.org); Opioid free Anesthesia group (OFA) and Opioid Anesthesia group (OA). To
      assure blindness, numbers will be concealed by closed envelope, analgesic infusions will
      prepared by a clinical pharmacist not included in data collection and the attending
      anesthetist will be blinded to the type of analgesic solution injected.

      Over 10 minutes prior to induction of analgesia patients in the OFA group will receive small
      doses of demedetomidine, ketamine, lidocaine and magnesium along with ketorlac and
      acetaminophen. an infusion afterwards will be administered through the operation containing
      dexmedetomidine, ketamine and lidocaine. In the OA group, over 10 minutes, patients will
      receive a loading dose of fentanyl followed by fentanyl infusion through the operation.
      General anesthesia will be induced using the same drugs and the same parameters in both
      groups after the completion of the initial analgesic infusions The primary outcome parameter
      will be the percentage of patients experiencing hemodynamic instability at Burr Hole (defined
      as recording an increase or decrease of the mean arterial blood pressure by 25 % of the
      baseline reading) Assuming the rate of hemodynamic instability (defined as increase or
      decrease of the mean blood pressure by 25 % of the baseline reading) would be 40 % in the
      control arm, a clinically meaningful reduction of the rate of hemodynamic instability to 10 %
      in the investigational arm with a statistical power of 80 % and an alpha error of less than
      0.05 would require recruiting 29 patients in each group (a total of 58 patients).

      Continuous data will be presented as mean + (SD). Categorical variables will be represented
      as frequencies and percentages. According to the type of data Comparison between the two
      groups will be performed using either Chi square test or Fisher's exact test. Hemodynamic
      variables will be compared to baseline using repeated measures analysis of variance (ANOVA)
      with post hoc scheffe's test for positive data. P values less than 0.05 will be considered
      statistically significant.
    

Intervention name(s): Opioid free anesthetics; Opioid Anesthetics
Intervention type(s): Drug; Drug
Intervention description(s): Patients will receive over the 10 minutes prior to induction:
Acetaminophen 1 gm i.v. infusion in 100ml over 10 minutes.
Ketorolac 30 mg i.v. infusion in100 ml over 10 minutes.
Mg SO4 loading dose 30 mg/kg i.v. infusion in 100 ml over 10 minutes.
Dexmedetomidine loading dose 1 μg/kg i.v. infusion.
Lidocaine loading dose 1.5 mg/kg i.v. infusion.
Ketamine loading dose 0.25 mg/kg i.v. infusion.
The weight based doses of dexmedetomidine, lidocaine, ketamine will be prepared on 20 ml syringe and infused over 10 minutes prior to induction. In a dose of 0.1 ml/kg
Then after induction maintenance analgesic infusion will start in a rate that ranges from 0.025 to 0.05 ml/kg/h which is equivalent to:
Dexmedetomidine 0.25-0.5 μg/kg/h
Lidocaine 0.375-0.75 mg/kg/h
Ketamine 0.0625- 0.125 mg/kg/h; Placebo equivalent to acetaminophen, ketorolac, magnesium sulphate will be infused as 100 ml normal saline each over 10 minutes ,patients will receive fentanyl 2 μg/kg loading dose which will be prepared over 20 ml syringe and infused over 10 minutes prior to induction, Then after induction maintenance of analgesic infusion by fentanyl 0.5-1 μg/kg/h.
Other intervention name(s): OFA; OA
Intervention MeSH terms: Analgesics, Opioid; Anesthetics
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Opioid free Anesthesia; Craniotomies; Dexmedetomidine; Ketamine; Fentanyl; Lidocaine; Magnesium sulphate; supratentorial tumors