Non-opioid Analgesia for Fast-track Surgery
Condition: Pain
Study type: Interventional

Summary: 
      In this randomized observer-blinded trial the analgesic efficacy of intravenous esmolol, as
      alternative to intraoperative opioids, is tested in patients undergoing laparoscopic
      prostatectomy and upper gastrointestinal surgery (such as Nissen fundoplication). The purpose
      of this study is to determine whether intravenous esmolol improves postoperative analgesia
      and accelerate the surgical recovery. We hypothesize that patients receiving intravenous
      esmolol will consume less analgesic in the postoperative period, will have less
      opioid-related side effects and will recover their functional status faster then patients
      receiving intravenous esmolol.

      Patients will be stratified according to the type of surgical procedure in 2 arms: 40
      patients with prostate cancer and undergoing elective laparoscopic prostatectomy, and 40
      patients with gastro-esophageal reflux undergoing upper gastrointestinal surgery (Nissen
      funduplication) will be enrolled.

      Patients will receive total intravenous anesthesia with propofol and esmolol (Esmolol group,
      n=20 in each arm) or propofol and remifentanil (Remifentanil Group, n=20 in each arm).
    

Detailed description: 
      Outcomes:

        1. Primary: The amount of fentanyl needed in PACU and the amount of PCA morphine used
           during the first 24 postoperative hours.

        2. Secondary: intensity of postoperative pain (visual analogue scale,VAS), opioids side
           effects, length of stay in PACU and in the hospital, short-term SF-36 questionnaire,
           CHAMPS questionnaire, and the 2 and 6 minutes walking tests.

      Methodology:

      In each arm patients will be assigned by computer generated random letters to two groups:

      The Esmolol group: patients will receive no opioids but will receive esmolol at induction and
      as a continuous infusion during the surgery.

      The Remifentanil group: patients will receive remifentanil as sole opioid during induction of
      anesthesia as a continuous infusion during the surgery.

      During the preoperative assessment patients will be asked to fill out the CHAMPS and the
      Short-term SF-36 questionnaires. The 2 and 6 minutes walking tests will be also administered

      On arrival in the operating room, routine monitors will be applied for recording heart rate,
      systolic blood pressure, and oxygen saturation. In addition, the electroencephalographic
      bispectral index (BIS) value was obtained using a single channel sensor in a frontal temporal
      area. The BIS is a standard monitor of depth of anesthesia and measures cortical activation.
      It has been found to be well correlated to electroencephalogram. After obtaining baseline
      values, midazolam 1-2mg IV will be administered for pre-medication. Anesthesia will be
      subsequently induced with Propofol 2-2.5 mg/kg, Rocuronium 0.45-0.9 mg/kg.

      The Esmolol group will receive 1.0 mg/kg of esmolol and the Remifentanil group 1.0 mcg/kg of
      remifentanil for induction of anesthesia. After direct laryngoscopy and tracheal intubation
      will have been performed, anesthesia will be maintained with a continuous infusion of
      propofol 80-250 mcg/kg/min to maintain a "targeted" BIS value of 50 or less (BIS below 60
      signifies the patient is asleep and unaware, 90 and over signifies intraoperative
      wakefulness). Patients will receive either esmolol infusion of 5-15 mcg/kg/min or
      remifentanil infusion of 0.025-0.25mcg/kg/min (in Esmolol group or in the Remifentanil group
      respectively) titrated to maintain HR within 25% of the pre-induction baseline value with
      targeted HR in between 55-90. Furthermore, the patients will also receive IV fluid at 6
      ml/kg. All patients will be mechanically ventilated to maintain the end-tidal carbon dioxide
      (CO2) concentration in the range of 36-44 mm Hg and will receive toward the end of surgery
      Ketorolac 30mg IV, Droperidol 0.625mg IV and neuromuscular reversal if needed. Propofol will
      be discontinued after the last skin suture and the remifentanil or esmolol infusions will be
      stopped. After closure 10cc of bupivacaine 0.25% with epinephrine 1:200.000 will be
      infiltrated in the surgical ports. Nurses in the PACU will be informed that patients are
      taking part of the study but will not be aware of the hypothesis and will provide patients
      with standard care. Patients will have access in PACU to Fentanyl 25mcg IV q5min and to
      Ondansetron 2-8mg IV prn (standard medications used in this institution). Patients will
      receive PCA morphine for 24-48 h with tylenol 650mg PO q4h and naproxen 500mg or celebrex 200
      mg PO bid.

      Heart rate, blood pressure, BIS and oxygen saturation will be recorded at baseline, induction
      of anesthesia, tracheal intubation, skin incision, and subsequently at 5 min intervals until
      the end of surgery. Patients will be extubated in the operating room. They will then be
      transported to the post anesthesia care unit (PACU).

      Assessment:

      Recovery time will be assessed by a blinded observer (research fellow) unaware of the study
      hypothesis from the time the study drugs are discontinued. Times to awakening (opening eyes
      on verbal command), and orientation to person, date and place will be recorded, whereas the
      time to home readiness will be evaluated using standardized discharge criteria as described
      by White-Song17 at 30 min intervals. The score maximum of 12 out of 14 allows the patients to
      be discharged to the surgical ward from the PACU. Pain will be assessed every 15 minutes
      using (visual analog scale) (VAS)18 (0-10 cm) at rest, on movements and on coughing by the
      recovery nurse. Postoperative side effects (nausea, vomiting, pain), requirement for
      analgesics and antiemetics therapy (morphine and zofran respectively), as well as patient
      satisfaction will be assessed on discharge from PACU and 24-48 hrs after the procedure.
    

Intervention name(s): Esmolol; Remifentanil
Intervention type(s): Drug; Drug
Intervention description(s): Induction of anesthesia: 1mg/Kg; Maintenance during surgery: 5-15 mcg/kg/min; At the induction of anesthesia: 1mcg/Kg; Maintenance during surgery: 0.025-0.25mcg/kg/min
Intervention MeSH terms: Remifentanil; Esmolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment