Continuous Local Anesthetic and Steroid Infusion in Abdominal Surgery
Condition: Abdominal Pain
MeSH terms: Abdominal Pain
Study type: Interventional
Phase: Phase 3

Summary: 
      The aim of the study is the identification, comparing continuous infusion of local
      anesthetics and steroids intralesionally with the current gold standard therapy (PCA), of the
      effective dose of local anesthetics and steroids within 7 days following abdominal surgery in
      order to halve the consumption of opioids and give the best pain control with a lower
      incidence of side effects and persistent chronic pain (at 1 and 3 months) We also plan to
      measure the peripheral inflammation and oxidative stress by analyzing the pro-inflammatory
      cytokines and anti-inflammatory properties.

      Another objective is to investigate the combined effect of polymorphisms of genes related to
      pain sensitivity, and the correlation with the development of the inflammatory response and
      the incidence of chronic post-surgical pain (CPSP), which will be considered to validate the
      genotype-phenotype correlations.

      The intralesional catheter will be placed within the operating field by the surgeon at the
      end of the procedure.

        -  first postoperative 24 hours: ropivacaine 0.2%-methylprednisolone 1 mg/kg/die infusion
           (10ml/h) in the wound. Rescue dose with morphine via intravenous PCA (0.5 mg/ml, bolus 1
           mg, lock-out 5 min, max 20 mg in 4 hours)

        -  from 24 hs to 48 hs: ropivacaine 0.2%-methylprednisolone 1 mg/kg/die infusion (10ml/h)
           or saline 0.9% 10 ml/h in the wound. Rescue dose with morphine via intravenous PCA (0.5
           mg/ml, bolus 1 mg, lock-out 5 min, max 20 mg in 4 hours) . from 48 hs to 7th day:
           ropivacaine 0.2% or saline 0.9% via patient controlled intralesional analgesia (PCIA) (2
           mg/ml, bolus 20 mg, lock-out 60 min, max 80 mg in 4 hours). Rescue dose Tramadol 100 mg.

      The first assessment will be by the anesthetist pre-operatively, to verify the patient
      eligibility.

      All patients will be evaluated at the end of surgery (T0) and after 3-6-12-24-36-48 hours
      after surgery. Further evaluations are scheduled every 24 hours until the seventh
      postoperative day. At each assessment will be recorded: Numeric Rating Scale (NRS) at rest,
      NRS at movement (NRSm) - defined as pain at deep inspiration and cough - ; blood pressure,
      heart rate, respiratory rate, nausea (PONV scale), need of rescue analgesics and presence of
      any complications.

      On the 7th postoperative day, the patient will be reassessed by both pain clinicians and
      surgeon; the surgeon will remove the catheter.

      At 1 month and 3 months after surgery, the patient will be evaluated through phone interview
      to investigate pain persistence.

      Inflammatory response analysis will be performed on the first 15 patients in each group (for
      a total of 30 patients). Before awakening of the patient the surgeon will insert a
      microdialysis catheter in the fat adjacent to the surgical wound with sterile technique. The
      microdialysed liquid will be collected in dedicated tubes directly in the infusion pump. The
      sample of the first hour will be discarded to avoid that microtrauma of catheter positioning
      influences the study. Sampling will be performed every 6 hours the first day, and every 12
      hours in the second and third day. Serum samples will be collected to compare systemic with
      regional samples. All samples will be stored at -80 ° C until sampling. Concentrations
      quantification of different cytokines will be analyzed by ELISA Parma Unit will analyze VNTR
      (variable number of tandem repeats) polymorphism of the ADRB2 gene, directly related to the
      risk of chronic persistent postoperative pain development; Pavia Unit will take care of
      genotyping of polymorphic sites in the following genes: OPRM1 (mu-opioid receptor 1), COMT
      (catecholamine O-methyl transferase), UGT2B7 (UDP-glucuronyl transferase), IL1Ra (interleukin
      1receptor alpha). From the blood samples will be extracted DNA and RNA using standard
      procedures. RNA will be retained for possible future studies on the expression of genes of
      interest. The DNA will be used instead for the study of genetic polymorphisms.

      In this study the formation of free radicals, particularly superoxide will be assessed
      together with lipid peroxidation in both serum and urine, The 8- deoxyguanosine and
      Poly-ADP-ribose polymerase (PARP), the presence of nitrotyrosine.

      Blood samples and urine tests will be carried out before the start of surgery , before the
      bolus of morphine and local anesthetic , at 24 h after the end of the intervention and 48 h
      after end of the intervention
    


Intervention name(s): ropivacaine 0.2%; Methylprednisolone 1mg/kg; saline 0.9%
Intervention type(s): Drug; Drug; Drug
Intervention description(s): PCA morphine 0.5 mg/ml bolus 1 mg LO 5 min max 20 mg in 4 hs
Other intervention name(s): morphine PCA
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Morphine; Ropivacaine; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment