The Effects of Method of Anaesthesia on the Safety and Effectiveness of Radical Retropubic Prostatectomy

Study Overview
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Brief Summary
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Prostate cancer is one of the most commonly diagnosed neoplasm in men worldwide. The gold standard of therapy is radical prostatectomy, a wide surgical excision of the neoplasm and can be performed either open, laparoscopic or robotic. The open retropubic approach, still performed today, can be completed under either general anaesthesia or combined (spinal/epidural) anaesthesia without any clear guideline on which one should be preferred. In this study the investigators aim to evaluate general anaesthesia and combined (spinal/ epidural) anaesthesia in patients undergoing open retropubic radical prostatectomy and define whether these may have an impact on the oncological outcome and safety of the procedure.

Official Title
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Comparative Study of the Effects of Combined Spinal Anaesthesia and General Anaesthesia on the Safety and Effectiveness of Radical Retropubic Prostatectomy in Patients With Localised Prostate Cancer

Conditions
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Prostatic Neoplasm

Intervention / Treatment
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* Procedure: General Anaesthesia
* Procedure: Combined (Epidural and Spinal) Anaesthesia
* Procedure: Open Retropubic Radical Prostatectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with localised prostate cancer Eligible for open retropubic radical prostatectomy Exclusion Criteria: Metastatic prostate cancer History of severe heart disease History of haemostasis disorders History of previous pelvic surgery History of lung disease
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: General Anaesthesia<br>Patients undergoing open retropubic radical prostatectomy under general anaesthesia | Procedure: General Anaesthesia<br>* All patients in the general anaesthesia group will be premedicated with intravenously administered (iv) midazolam (2mg) and fentanyl (100 mcg). Induction will be performed using intravenous propofol (2.5-3mg/kg) and lidocaine (40mg); dexamethasone 8mg, metoclopramide 10mg and omeprazole 40mg will also be administered. After successful tracheal intubation, total intravenous anaesthesia will be maintained by administering propofol (0.05 mg/kg/sec iv) and remifentanil (0.2 mcg/kg/sec iv). Pain management will be achieved by paracetamol (1g iv) and tramadol (100mg iv) whereas muscle relaxation by vecuronium (0.6 mg/kg iv).<br>Procedure: Open Retropubic Radical Prostatectomy<br>* All patients will undergo a nerve-sparing open retropubic radical prostatectomy<br>|
| Active Comparator: Combined (Epidural and Spinal) Anaesthesia<br>Patients undergoing open retropubic radical prostatectomy under combined (epidural and spinal) anaesthesia | Procedure: Combined (Epidural and Spinal) Anaesthesia<br>* Combined (epidural and spinal) anaesthesia will be performed using an epidural 18G needle and a spinal 27G needle, in the L2-L3 or L3-L4 interspace. Induction will be carried out by spinal intrathecal administration of levobupivacaine (2.6-3ml of 0.5%) and mild sedation by midazolam (5mg iv in bolus). All patients will be administered dexamethasone 8mg, metoclopramide 10mg and omeprazole 40mg iv. Maintenance will be performed 75 minutes after induction and obtained using an epidural administration of levobupivacaine (4-5ml of 0.5%).<br>Procedure: Open Retropubic Radical Prostatectomy<br>* All patients will undergo a nerve-sparing open retropubic radical prostatectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure Change | Measurement of patients systolic and diastolic blood pressure during the operation and post-operatively for 72 hours. | Peri-operatively | 
| Heart Rate Change | Measurement of patients Heart Rate during the operation and post-operatively for 72 hours. | Peri-operatively | 
| Surgical APGAR Score | Calculation of the Surgical APGAR score for each patient during surgery. The lower the score, on a scale of 1-10, the worst the prognosis of the patient. SAS is calculated using three variables: Estimated blood loss (on a 0-3 scale, 0 points >1000 ml, 1 point 601-1000ml, 2 points 101-600 ml, 3 points <100ml) Lowest mean arterial pressure (on a 0-3 scale, 0 points <40 mmHg, 1 point 40-54 mmHg, 2 points 55-69 mmHg, 3 points >70 mmHg) Lowest heart rate (on a 0-4 scale, 0 points >85 bpm, 1 points 76-85 bpm, 2 points 66-75 bmp, 3 points 56-65 bmp, 4 points <55 bmp) during surgery. | Peri-operatively | 
| Blood Loss During Surgery | Measured from suction contents intra-operatively in ml | Peri-operatively | 
| Haemoglobin Change | Haemoglobin measurement before the operation and at 12-, 24- and 48-hours post-operatively, in g/dL | Peri-operatively | 
| Operation Time | Time required for: Induction of anaesthesia Completion of the operation Post-operative time until the patient is successfully transferred to the recovery room | Peri-operatively | 
| Pain Assessed by the VAS Scale | Measured using a pain Visual Analogue Scale (VAS) at 6-, 24- and 48-hours after the operation. VAS is a self-reporting pain scale based on a 0 to 10-point system, with each point measuring 10mm on a linear line. Every patient was asked to indicate his pain levels from No Pain (equals 0) to Worst Pain Imaginable (equals 10). | Peri-operatively | 
| Complication Rate | Complications related to the procedure: Intraoperative bleeding Post-operative bleeding Bowel perforation Cardiovascular Respiratory Complications related to the anaesthesia technique performed: Post-operative headache Nausea and vomiting Any signs of potential nerve damage (manifested as inability to gain leg motility) | Peri-operatively and up to 1 year after the operation | 
| Change From Baseline PSA Levels at 6-months | Measurement of Prostatic Specific Antigen (PSA) levels at 6 to establish a PSA nadir value | 6 months post-operative | 
| Change from 6-month PSA Levels at 12-months | Measurement of Prostatic Specific Antigen (PSA) levels at 12 post-operation to detect any biochemical recurrence | 12 months post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Erectile Function after Radical Prostatectomy | Measured using the International Index of Erectile Function (IIEF-5) questionnaires pre-operatively and at 3-, 6- and 12-months post-surgery. The test is composed of 5 questions with 5 points for each question. Patients are evaluated accordingly: Score 22 or more = No Erectile Disfunction Score 17-21 = Mild Erectile Disfunction Score 12-16 = Mild to moderate Erectile Disfunction Score 8-11 = Moderate Erectile Disfunction Score 7 or less = Severe Erectile Disfunction Results will be: Analysed and compared to evaluate any potential difference of the two methods of anaesthesia, on post-operational erectile function Analysed comparing pre-operation with post-operation questioners overall, to evaluate erectile disfunction after radical prostatectomy regardless of method of anaesthesia. | Up to 1 year after the operation | 
| Post-operative Urinary Incontinence | Measured using the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form at 12 months post-surgery. The Questionnaire is consisted of 4 questions: Frequency How often do you leak urine? on a scale of 0 (never) to 5 (all the time) Amount of leakage How much urine do you leak? on a scale to 0 (none) to 3 (a large amount) Overall impact on quality of life How much does it interfere with your life? on a scale of 0 (not at all) to 10 (a great deal) Timing of leakage When does urine leak? | 1 year after the operation | 
| Total Hospital Stay | Days until patient discharge from the hospital. | Peri-operative | 
| Patient Satisfaction Assessed by the Short Assessment of Patient Satisfaction (SAPS) Questionnaire | Satisfaction, using the Short Assessment of Patient Satisfaction (SAPS) Questionnaire, is measured in a scale of 0 to 28, with 0 to 10 equals to Very Dissatisfied, 11-18 equals to Dissatisfied, 19-26 equals to Satisfied and 27-28 equals to Very Satisfied | Peri-operative |