Postoperative Pain, Recovery and Discharge Following Robot-assisted Laparoscopic Prostatectomy
Condition: Radical Prostatectomy; Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 3

Summary: 
      Prostate cancer is the commonest cancer form in men in Northern Europe. Management of the
      cancer often includes surgical removal of the primary tumor. In the last 5-10 years, robot
      assisted laparoscopic prostatectomy (RALP) has become common. Good pain relief is central to
      early mobilization and greater patient satisfaction. Randomized controlled studies on pain
      relief following RALP are few and the role of spinal analgesia in pain management following
      robotic surgery has not been described. Techniques available for pain relief following RALP
      include spinal anesthesia with or without opiates, intravenous analgesia with morphine or a
      multimodal pain management technique using a combination of several analgesics. Spinal
      anesthesia and analgesia reduces the surgical stress and inflammatory response following
      laparoscopic colorectal surgery and may offer similar benefit even during RALP.

      Early perioperative complications may cause postoperative morbidity following robotic
      surgery, and sometimes delay home discharge. Since all robotic operations in the pelvic
      region are performed in a deep Trendelenberg position, this can even have negative
      consequences for the heart, brain and the lungs. Cardiac complications in the form of minimal
      cardiac injury or mild heart failure have not been previously studied following RALP.
      Additionally, patients are sometimes delirious in the early postoperative period following
      RALP. The precise cause for this remains unclear and may be related to pain, cognitive
      dysfunction or an urge to pass urine despite a urinary catheter.

      In addition to good postoperative pain relief, early postoperative mobilization and home
      discharge are important milestones in recovery of full function following major surgery. With
      improvement in surgical technique, the time has come to evaluate if RALP can be performed on
      an ambulatory basis. The main aims of this study are:

        1. Can RALP be performed on an ambulatory basis and patients ready to be discharged home at
           8 pm?

        2. To determine if spinal anesthesia reduces pre-discharge pain intensity, stress response
           and other perioperative side effects.

        3. Is sufentanil or fentanyl the analgesic of choice when administered spinally together
           with bupivacaine as an analgesic.

        4. To determine the frequency and severity of cardiac and respiratory complications in the
           steep Trendelenberg position during RALP.

        5. To assess the quality of recovery, quality of life and activities of daily living
           following ambulatory RALP?
    

Detailed description: 
      Prospective, randomized study blinded to observers (spinal or no-spinal). All formal
      approvals will be obtained from different authorities prior to study start. It will be
      registered in an international database (clinicaltrials.gov).

      Patients > 18 years, ASA I-III, undergoing RALP will be included into the study. Patients on
      chronic opiate medication, those with contraindications to spinal anesthesia or allergy to
      any component drugs used during spinal anesthesia or other analgesics used in the study will
      be excluded. Patients living alone or having no adult at home to look after them during the
      first 24 h after home discharge will also be excluded. Informed written consent will be
      obtained from all patients. On the morning of surgery, all patients will receive paracetamol
      1 g orally 1 h before planned surgery, and will be randomized to one of two groups as shown
      below:

      Robot-assisted laparoscopic prostatectomy (RALP) (morning surgery)

        1. Group MM: This group of patients will not receive spinal anesthesia but have multimodal
           pain management including COX-2 blockers, pregabalin and oxycontin for pain management

        2. Group SF (Spinal/Fentanyl): Spinal anesthesia with bupivacaine 12.5 mg+fentanyl 15 ug
           Robot-assisted laparoscopic prostatectomy (RALP) (afternoon surgery)

      1. Group MM: This group of patients will not receive spinal anesthesia but have multimodal
      pain management including COX-2 blockers, pregabalin and oxycontin for pain management 2.
      Group SS (Spinal/Sufentanil): Spinal anesthesia with bupivacaine 12.5 mg+sufentanil 5 ug

      Anesthesia will be standardized in all other aspects in all groups and basically include
      propofol for induction, rocuronium as muscle relaxant, sevoflurane and remifentanil for pain
      management and betamethasone + ondansetron as prophylaxis against post-operative nausea or
      vomiting (PONV). Surgery will also be standardized in all patients and follow the routines
      already established in the hospital.

      At the end of surgery, patients will be transferred to the post-anesthesia care unit (PACU)
      where they will remain for 4 h observation and subsequently transferred to the general
      surgical wards for observation and discharge home. All measurement times will be taken from
      the end of surgery, which will be considered as t = 0.

      The following parameters will be recorded:

        1. Total morphine consumption during 0-4, 4-home discharge and analgesic supplements after
           home discharge and up to 1 week will be recorded. Time to first morphine administration
           after surgery will be registered.

        2. Blood tests for measurement of cortisol, glucose, insulin, creatinine, NTproBNP and
           hsTnT will be taken at fixed time points before and after surgery.

        3. Pain intensity will be registered using NRS after 1, 2, 3, 4 and every 4 h until home
           discharge, and thereafter every 24 h for 1 week.

        4. All side effects (PONV, pruritus, respiratory depression, oxygen saturation and need for
           supplementary oxygen) and complications (bleeding, reoperation, pneumothorax etc.) will
           be recorded. Postoperative delirium will be assessed 0-2 h postoperatively. Prolonged
           PACU stay or re-admission to PACU will be registered. Clavien-Dindo classification for
           grade of complication will be registered as also Postoperative Morbidity score (POMS).

        5. Respiratory function will be recorded in the following ways: blood gas (after 1 and 4
           h), saturation, spirometry, maximum expiratory pressure preoperatively and after 4 h.
           Need for supplementary oxygen to maintain SpO2 > 93% will be registered.

        6. Time to mobilization, time to discharge to the general ward (from PACU), "home
           readiness" (primary endpoint) and home discharge will be registered in accordance with
           standardized criteria. Criteria for home readiness: normal vital signs, pain intensity <
           4 (NRS 0-10), minimal or no postoperative nausea or vomiting, able to sit, walk and go
           unhindered, no surgical complication (bleeding, fever), fully awake and able to follow
           instructions (normal cognition), normally functioning urinary catheter and an adult at
           home during the first 24 h after discharge home).

        7. Quality of Recovery 15 (QoR 24) will be measured before home-discharge and after 24 h
           using a standardized questionnaire.

        8. Quality of life will be measured preoperatively and after 7 and 30 days using the
           questionnaire EQ5D and WHODAS.
    

Intervention name(s): Bupivacaine; Analgesics
Intervention type(s): Drug; Drug
Intervention description(s): Spinal anesthesia with a combination of bupivacaine and fentanyl or sufentanil; Combination of paracetamol + non-steroidal anti-inflammatory drug + morphine to all patients
Other intervention name(s): Marcain spinal; paracetamol + NSAID + morphine
Intervention MeSH terms: Morphine; Analgesics; Bupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective, randomized, observer-blinded
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Robot assisted surgery; Prostatectomy; Spinal anesthesia; Postoperative pain; Home discharge