Continuous Local Anesthetic and Steroid Infusion in Abdominal Surgery

NCT02002663 | Completed Phase 3 DMC

• 1 other identifier: PT-SM-13- YR FIRST STEP CWI-PP
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

Abdominal Pain

Outcome Measures

Primary Outcomes (1)

• total morphine consumption

  7 days after surgery

Secondary Outcomes (4)

• pain values

  7 days

• number of patients presenting methylprednisolone side effects

  up to 7 days

• number of patients presenting morphine or ropivacaine side effects

  up to 7 days

• persistent pain at 1 and 3 months

  3 months

Study Arms (2)

ropivacaine + methylprednisolone

EXPERIMENTAL

Continuous infusion of Ropivacaine 0.2% and methylprednisolone 1mg/kg 10ml/h through intralesional catheter for 24 hours

Drug: ropivacaine 0.2%; Drug: Methylprednisolone 1mg/kg

saline

PLACEBO COMPARATOR

Continuous infusion of saline through intralesional catheter for 24 hs

Drug: saline 0.9%

Interventions

ropivacaine 0.2% DRUG

PCA morphine 0.5 mg/ml bolus 1 mg LO 5 min max 20 mg in 4 hs

Also known as: morphine PCA

ropivacaine + methylprednisolone

Methylprednisolone 1mg/kg DRUG

ropivacaine + methylprednisolone

saline 0.9% DRUG

saline

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (2)

•2nd Service of Anesthesia, Intensive Care and Pain Therapy, University Hospital of Parma

Parma, 43126, Italy

Location

Department of Anesthesia and ICU, General Surgery and Urology, S Matteo Hospital

Pavia, 27100, Italy

Location

Related Publications (1)

• Bugada D, De Gregori M, Compagnone C, Muscoli C, Raimondi F, Bettinelli S, Avanzini MA, Cobianchi L, Peloso A, Baciarello M, Dagostino C, Giancotti LA, Ilari S, Lauro F, Grimaldi S, Tasciotti E, Fini M, Saccani Jotti GM, Meschi T, Fanelli G, Allegri M. Continuous wound infusion of local anesthetic and steroid after major abdominal surgery: study protocol for a randomized controlled trial. Trials. 2015 Aug 14;16:357. doi: 10.1186/s13063-015-0874-z.

  PMID: 26272452 DERIVED

MeSH Terms

Conditions

Abdominal Pain

Interventions

Methylprednisolone; Sodium Chloride

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 24, 2013
• First Posted: December 6, 2013
• Study Start: August 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: September 1, 2016
• Last Updated: March 3, 2017

Record last verified: 2017-03

Locations

IT (2)