Continuous Local Anesthetic and Steroid Infusion in Abdominal Surgery
Continuous Local Anesthetic and Steroid Infusion in Abdominal Surgery
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
Inclusion Criteria:

 -  Male and females 18-85 years old scheduled to use PCA with morphine for postoperative
 pain control

 -  HIV-negative

 -  Classification American Society of Anesthesiologists (ASA) I: without systemic disease

 -  Classification ASA II or III (moderate systemic disease or severe systemic disease
 that limits activity without disability)

 -  Scheduled for major abdominal and urologic surgery (no emergency surgery)

 Exclusion Criteria:

 -  regular use of opioid analgesics;

 -  History of abuse of drugs and / or alcohol;

 -  Postoperative hospitalization in intensive care with sedation and / or mechanical
 ventilation;

 -  severe renal impairment (creatinine> 2 g / dl, creatinine clearance <30 ml / h) and /
 or hepatic impairment (cholinesterase <2000 IU);

 -  Cardiac disorders (arrhythmias, heart failure);

 -  Neurological disorders (epilepsy);

 -  Cognitive disorders, mental retardation, psychiatric disorders;

 -  Changes in the normal coagulation or coagulopathy (INR> 2, PTT> 44 sec);

 -  Platelet count less than 100.000/mm3;

 -  BMI> 30;

 -  Allergy to study drugs.

 -  diabetes type I/II