Comparison Between Epidural and Patient Controlled Analgesia on Immunological and Inflammatory Systems Following Radical Retropubic Prostatectomy
Thirty patients (ASA status 1-2) in the age group 50 - 75 years, undergoing elective radical
retropubic prostatectomy would be included in this pilot study. The exact type of cancer,
its staging, degree of spread to proximal or distant sites and the pathologic type of cancer
would be recorded. Patients on chronic analgesic medication, endocrinologic and immunologic
diseases, those with known allergy to LA and those where epidural catheter placement was
contraindicated would be excluded. Patients would be allocated to one of three groups:
General anesthesia combined with Epidural anesthesia during and after the operation (Group
GE; n = 12), General anesthesia combined with Epidural during anesthesia and local
anesthesia postoperatively (Group GL; n = 12), General anesthesia alone (Group GO; n = 10)
Anesthesia and Surgery
All patients would be premedicated with midazolam 0.1 mg/kg 15-30 min before planned
surgery, which is a routine in our hospital. Paracetamol 1 g was given orally every 6 h
starting with the first dose at the time of premedication. IV access would be attained in
the preoperative holding area and further anxiolytic would be given as necessary
In patients in Group GE, an 18 G epidural needle would be inserted at the Th10-12
inter-space using the 'hanging-drop' or loss of resistance technique with the patient in the
sitting position in the holding area. The epidural catheter would be inserted and
subsequently tested for subarachnoid or intravascular placement using 3 ml of mepivacaine 2%
with adrenaline, which is standard practice in our hospital. A bolus dose of 3-4 ml
mepivacaine 2% with adrenaline would subsequently be injected and a loss of sensation to
cold determined after 10 min. If a sensory block to an upper level of Thoracic 8 dermatome
and a minimal lower level of L2 is achieved, the patient would be considered to be ready for
induction of anesthesia. If not, a further dose of 2-3 ml mepivacaine 2% with adrenaline
would be injected epidurally. If this fails to achieve the desired block, it would be
assumed that the catheter was incorrectly placed and the patient offered the choice of one
more attempt at epidural catheter placement, or exclusion from the study.
Patients in Group GO would not have an epidural catheter placed. Following transfer to the
operating room and routine monitoring, anesthesia would be induced in all patients with
fentanyl 2 mg/kg i.v. and propofol 1-2mg/kg until loss of eyelash reflex. Tracheal
intubation would be performed after muscle relaxation with rocuronium 0.5 mg/kg and
anesthesia maintained with 1-3% sevoflurane and 33% oxygen in air. Mechanical ventilation
would be used in a low-flow system in order to maintain an end-tidal CO2 of between 4.5-5.5
kPa. In all patients, sevoflurane concentration would be adjusted in order to maintain
adequate anesthetic depth, which would be measured using Auditory evoked potentials (AEP)
and maintained between 15-25 (A-line). Tachycardia, despite adequate anesthetic depth, would
be treated by giving fentanyl intermittently IV as an analgesic when required during the
operation. At the end of surgery, muscle relaxation would be reversed using glycopyrrolate
(0.2 mg) and neostigmine (2.5 mg). Radical retropubic prostatectomy would be performed in a
standardized way using a lower-abdominal midline incision.
During the first 4 h postoperatively, patients in Group GO would receive morphine 1-2 mg IV
intermittently for pain relief in the post-anesthesia care unit (PACU) in order that the
numeric rating scale (NRS) (0 = no pain, 10 = worst imaginable pain) is < 3. Patients in
Group GE would have an infusion of ropivacaine 0.2% 5-10 ml/h epidurally. In the event of
pain, morphine (1-2 mg) would be administered intravenously as needed in both groups in
order to provide good pain relief and NRS < 3.
All patients would be observed in the PACU for 4 h before being transferred to the general
urological ward. The epidural infusion/PCA pump would be continued as long as pain relief is
needed using these techniques but for a minimum of 48 h. Subsequently, pain relief would be
obtained using oral analgesics using a combination of paracetamol and NSAID drugs.
Recording and Measurements
The total amount of anesthetic and analgesic drugs required during the operation would be
recorded. Anesthetic drug requirement would be determined by two methods: end-tidal
concentration of sevoflurane recorded every 5 min and the weight of the vaporizer before and
after each anesthetic. For all measurements, the time when the anesthetic gases were turned
off was considered to be time zero (t = 0). In addition to the routine postoperative
protocols, the following measurements were recorded:
Pain intensity: At the site of the incision, 'deep' (visceral) pain and pain on coughing at
1, 4, 12, 24 and 48 h was measured using the NRS.
Rescue analgesic (morphine) consumption: during 0-4 h, 4-24 h and 24-48 h. Supplementary
analgesic consumption: Additional analgesics administered in order to relieve pain would be
Side effects: Nausea and/or vomiting (0-4 h, 4-24 h and 24-48 h), pruritus and all other
complications were recorded.
Surgical complications: the surgical incision would be inspected daily for evidence of
infection and graded as either no evidence of infection (= 0), evidence of inflammation (=
1), mild wound dehiscence or suspected infection (= 2) or pus formation with definite
infection (= 3). After 48-72 h, the epidural catheter would be removed and the catheter tip
sent for bacterial culture.
Patient serum or EDTA/Heparin plasma will be assessed for cytokine levels by a Luminex
multiplex assay (Human Inflammation 12-Plex kit; GM.CSF, IFN-g, IL-1b, IL-2, IL-4, IL-5,
IL-6, IL-8, IL-10, IL-12, TNF-a and VEGF from R&D system) and PGE2 levels will be measured
by an ELISA kit from Cayman Chemicals Company. In addition, markers of systemic inflammatory
response, including CRP, white blood cell count, differential count and total platelet
count, will also be measured before and after surgery.
Natural Killer (NK) cell activity in the blood would be measured using the FANKIA assay.
Clusters of differentiation (CD) markers would be measured.
Stress response would be measured using serum cortisol and prolactin levels.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
Natural Killer Cell activity
NK cells are of primary importance in the elimination of tumor target cells at the early stage of tumor development, up to and including tumor metastasis. Decreased NK cell function during the perioperative period is associated with an increased risk of mortality in cancer patients. The NK cell activity would be measured using a special assay called FANKIA
24 h postoperative
Anil Gupta, MD PhD
Orebro University, Sweden
Örebro University, Sweden: