Ketamine for Pain Relief in Bariatric Surgery
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      The surgical interventions for treating morbid obesity, i.e. bypass procedure and sleeve
      gastrectomy are collectively covered under the term 'bariatric surgery'. The growth of
      bariatric surgery has seen consonant development of anaesthesia techniques so as to ensure
      patient safety and facilitate post-surgery outcome. Conventionally, balanced general
      anaesthesia techniques routinely use opioids peri-operatively for intra-operative
      haemodynamic homeostasis and postoperative pain relief. However, since the morbidly obese
      patients have high prevalence of obstructive sleep apnea(OSA) and other co-morbidities the
      same technique when employed in the morbidly obese patients hampers early and intermediate
      postoperative recovery due to the occurrence of side effects, such as, sedation, PONV,
      respiratory depression, depressed GI-mobility. The above stated side effects, have lead to
      increased propensity for postoperative cardiac and pulmonary complications. Obese patients
      are more vulnerable and sensitive to the narcotics and sedatives, these drugs need to be
      employed judiciously in these patients. On the other hand, the reduction in opioid use may
      result in acute post-operative pain that may limit post-surgery rehabilitation. Therefore, we
      need to minimise opioid use and employ some other drugs which besides having analgesia, has a
      opioid-sparing effect also.

      Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has analgesic properties in
      sub-anaesthetic doses. When used in low dose (0.2mg/kg), it is an analgesic,
      anti-hyperalgesic, and prevents development of opioid tolerance. On a conceptual basis, a key
      advantage of ketamine is that it can reduces post-operative pain and use of opioid when used
      per-operatively. Therefore, a regimen which avoid or minimise use of opioid is likely to
      decrease opioid-related postoperative morbidity in these patients undergoing bariatric
      surgery.In view of the above, a clinical research is highly desirable to study techniques to
      decrease the use of opioids in obese surgical patients.This prospective randomised two-arm
      study aims to assess the effect of low-dose ketamine on postoperative pain relief and
      opioid-sparing ability in obese patients undergoing bariatric surgery.
    

Detailed description: 
      After obtaining approval from the hospital ethics committee and written informed consent from
      the patients, this prospective randomised study will be conducted on 76 patients belonging to
      ASA physical patients status II and III of either sex, scheduled to undergo laparoscopic
      bariatric surgery (sleeve gastrectomy, Roux-en-Y gastric bypass) under general anaesthesia.
      The patients will be randomly allocated by computer generated numbers to one of the following
      two groups of 38 patients each.

      Group 1[Ketamine + Fentanyl Group, n=38]: Pre-induction fentanyl 1-mcg/kg, ketamine 0.5-mg/kg
      after induction, followed by intra-operative fentanyl infusion of 0.5-mcg/kg/hr + ketamine
      infusion of 0.2-mg/kg/hr

      Group 2[Fentanyl Group, n=38]: Pre-induction fentanyl 1-mcg/kg, saline after induction
      followed by intra-operative fentanyl infusion of 0.5-mcg/kg/hr + saline infusion.

      Both the groups will receive intravenous PCA of fentanyl post-operatively.

      Randomisation, Allocation Concealment:

      The patients will be randomly allocated to one of the two groups based on a
      computer-generated random number table
      (url:stattrek.com/statistics/random-number-generator.aspx). Randomisation sequence
      concealment will include opaque-sealed envelopes with alphabetic codes whose distribution
      will be in control of an independent analyst. The envelopes will be opened; patient's
      data-slip will be pasted on them, and will be sent back to the control analyst.

      Blinding Strategy:

      The attending anaesthesiologist will be blinded to the intra-operative infusions used.
      Postoperative patient recovery profile will also be evaluated by an independent assess or
      blinded to the intra-operative anaesthesia technique.

      Management of Anaesthesia:

      Premedication

      All patients will be receive tablet ranitidine-150 mg night before and on morning of
      surgery.They will be instructed to fast for at least 8- hours before surgery. Clear fluids
      will be allowed till 2 hours before surgery.

      Intra-operative Monitoring

      Two peripheral venous lines (18G/20G catheter) will be secured. Standard monitoring including
      5-lead ECG, non-invasive blood pressure (NIBP), pulse oximeter, end-tidal carbon dioxide
      (EtCO2) and end-tidal gas monitoring will be applied. Additional monitoring will include
      depth of anaesthesia monitoring using Bi-spectral index (BIS) and neuromuscular monitoring
      using train-of-four response.

      Anaesthesia Technique

      All patients will be pre-oxygenated with 100% oxygen for at least 3-minutes prior to
      induction of anaesthesia. All the drugs (study + control) will be administered based on lean
      body weight (LBW). Patients in the KF group will receive pre-induction fentanyl-citrate
      l-µg/kg IV and ketamine 0.5-mg/kg after induction whereas patients in the Fentanyl group will
      receive pre-induction fentanyl-citrate l-µg/kg IV and saline as in above group. Anaesthesia
      will be induced with propofol 2-2.5mg/kg titrated to a BIS-value of 50.. After induction of
      anaesthesia, atracurium besylate 0.5-mg/kg will be administered for skeletal muscle
      relaxation to facilitate tracheal intubation. Ventilator settings for CMV, tracheal tube size
      [7.5-mm I.D (male), 6.5-mm I.D (female)], and breathing circuit (circle-CO2 absorber system)
      will be the standardised in all the patients. The patients in the Ketamine + Fentanyl group
      will receive fentanyl infusion at 0.5-mcg/kg/hr and ketamine infusion of 0.2-mg/kg/hr. The
      patients in the Fentanyl group will receive fentanyl infusion at 0.5-mcg/kg/hr and saline
      infusion. The LBW in obesity patients scheduled to undergo bariatric surgery will be
      calculated based on the following formulae:

      9270 x TBW (kg)/6680 + (216 x BMI) [men]

      9270 x TBW (kg)/8780 + (244 x BMI) [women]

      Desflurane in oxygen-nitruos oxide mixture (FiO2 0.50) will be used for maintenance in both
      the groups to maintain a BIS of 40-60. Intra-operative muscle relaxation will be maintained
      using atracurium boluses controlled by train-of-four response on peripheral neuromuscular
      monitor. Thirty minutes before the end of surgery, non-opioid analgesics, such as paracetamol
      1-gm will be administered to the patient. Desflurane delivery will be stopped at the point of
      completion of skin closure. Residual neuromuscular blockade (assessed with train-of-four
      response) will be reversed with neostigmine (50-µg/kg) and glycopyrrolate (20-µg/kg).

      After discontinuation of anaesthesia delivery (0-time point) the time to eye opening and time
      to extubation will be determined. After tracheal extubation the patients will be shifted to
      postoperative recovery room adjoining OT suites and will be closely observed for oxygenation
      and ventilation status, pain (visual analogue score [VAS]), sedation (Modified OASS), and
      PONV.

      Intravenous Patient Controlled Analgesia (IV-PCA) pump containing fentanyl citrate-2.5 mcg/ml
      will be attached to all the patients upon shifting to the recovery room. The IV-PCA pump
      settings will be as follows: 0-ml basal dose; 4-ml PCA dose; 15-minutes lock out interval. A
      baseline visual analogue scoring will be done after shifting the patient to the recovery room
      (0-time point) followed by 2-hours, 4-hours, 8-hours, 12-hours, and 24-hours time points from
      the baseline. Any adverse effects such as hypotension/ hypertension, bradycardia/tachycardia,
      hypoxemia, giddiness will be recorded and treated. Post-surgery, time to alimentation post
      surgery will be noted.

      'Rescue' pain relief drug will include: diclofenac sodium 75 mg slow IV bolus for NRS>3 and
      'rescue' antiemesis agent would be ondansetron 4-mg for a PONV score > 1.
    

Intervention name(s): Fentanyl; ketamine
Intervention type(s): Drug; Drug
Intervention description(s): Fentanyl 1mcg/kg will be given at induction of anaesthesia followed by intraoperative infusion of 0.5 mcg/kg/hr in both the arms . Postoperatively IV-PCA pump containing fentanyl will be attached to patients in both the arms; Ketamine 0.5 mg/kg will be given post-induction of anaesthesia followed by infusion of 0.5 mcg/kg /hr in the Ketamine + Fentanyl group arm
Intervention MeSH terms: Fentanyl; Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 76 patients belonging to ASA physical patients status II and III of either sex, scheduled to undergo laparoscopic bariatric surgery (sleeve gastrectomy, Roux-en-Y gastric bypass) under general anaesthesia. The patients will be randomly allocated by computer generated numbers to one of the following two groups of 38 patients each.
Group 1[Ketamine + Fentanyl Group, n=38]: Pre-induction fentanyl 1-mcg/kg, ketamine 0.5-mg/kg after induction, followed by intraoperative fentanyl infusion of 0.5-mcg/kg/hr + ketamine infusion of 0.2-mg/kg/hr.
Group 2[Fentanyl Group, n=38]:Pre-induction fentanyl 1-mcg/kg, saline after induction followed by intraoperative fentanyl infusion of 0.5-mcg/kg/hr + saline infusion.
Both the groups will receive intravenous PCA of fentanyl post-operatively
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: ketamine; fentanyl; postoperative pain