Placebo-controlled Evaluation of Ropivacaine Efficacy by Local Infiltrations (DPO)

• Efficacy of ropivacaine versus physiological serum administered by local infiltration and impact on daily morphine consumption [ Time Frame: In the 4 days following the hepatectomy ] [ Designated as safety issue: No ]
• Evaluation of patients' perception of post-surgery pain [ Time Frame: In the 4 days following the hepatectomy ] [ Designated as safety issue: No ]
• Immediate and late complications related to the perfusion, the medical device and other predictable side effects [ Time Frame: In the 4 days following the hepatectomy and one month later ] [ Designated as safety issue: No ]
• Patients' post-surgery rehabilitation [ Time Frame: Between surgery and follow-up visit, one month later ] [ Designated as safety issue: No ]
• Patients' satisfaction with the pain care [ Time Frame: Four days after the hepatectomy ] [ Designated as safety issue: No ]

The purpose of the study is to evaluate the efficacy and impact on morphine consumption of ropivacaine administered by local per and post hepatic surgery infiltration.

Patients will be randomized to either ropivacaine or physiological serum, with equivalent administration modalities in both arms.

Patients will be followed during 4 days after the surgery. They will also come back for a follow-up visit one month later.

It is necessary to enrol 100 patients. The estimated period of inclusion is 24 months.

This is a prospective, comparative, monocentric, double-blind randomized study.

• Hepatectomy
• Pain
• Metastasis

• Drug: Ropivacaine
  40 ml infiltration at the end of the hepatectomy and then continuous local infiltration of 8 ml per hour over the 4 days after the hepatectomy
• Drug: Physiological serum
  40 ml infiltration at the end of the hepatectomy and then continuous local infiltration of 8 ml per hour over the 4 days after the hepatectomy

• Experimental: Ropivacaine
  Ropivacaine administration by local per and post surgery infiltration
  Intervention: Drug: Ropivacaine
• Active Comparator: Physiological serum
  Administration of physiological serum by local per and post surgery infiltration
  Intervention: Drug: Physiological serum

• Beaussier M, El'Ayoubi H, Schiffer E, Rollin M, Parc Y, Mazoit JX, Azizi L, Gervaz P, Rohr S, Biermann C, Lienhart A, Eledjam JJ. Continuous preperitoneal infusion of ropivacaine provides effective analgesia and accelerates recovery after colorectal surgery: a randomized, double-blind, placebo-controlled study. Anesthesiology. 2007 Sep;107(3):461-8.
• Bianconi M, Ferraro L, Ricci R, Zanoli G, Antonelli T, Giulia B, Guberti A, Massari L. The pharmacokinetics and efficacy of ropivacaine continuous wound instillation after spine fusion surgery. Anesth Analg. 2004 Jan;98(1):166-72, table of contents.
• Borromeo CJ, Stix MS, Lally A, Pomfret EA. Epidural catheter and increased prothrombin time after right lobe hepatectomy for living donor transplantation. Anesth Analg. 2000 Nov;91(5):1139-41.
• Godier A, Babinet A, el Metaoua S, Fulgencio JP, Bonnet F. [A new cause of postoperative confusion syndrome: nefopam] Ann Fr Anesth Reanim. 2002 Jun;21(6):538-9. French.
• Ho AM, Lee A, Karmakar MK, Samy W, Lai PB, Ho OA, Cho A. Hemostatic parameters after hepatectomy for cancer. Hepatogastroenterology. 2007 Jul-Aug;54(77):1494-8.
• Jalan R, Williams R, Bernuau J. Paracetamol: are therapeutic doses entirely safe? Lancet. 2006 Dec 23;368(9554):2195-6. No abstract available.
• Kwan AL. Epidural analgesia for patient undergoing hepatectomy. Anaesth Intensive Care. 2003 Apr;31(2):236-7. No abstract available.
• Larson AM. Acetaminophen hepatotoxicity. Clin Liver Dis. 2007 Aug;11(3):525-48, vi. Review.
• Liu SS, Richman JM, Thirlby RC, Wu CL. Efficacy of continuous wound catheters delivering local anesthetic for postoperative analgesia: a quantitative and qualitative systematic review of randomized controlled trials. J Am Coll Surg. 2006 Dec;203(6):914-32. Epub 2006 Oct 25. Review. No abstract available.
• Mazoit JX, Butscher K, Samii K. Morphine in postoperative patients: pharmacokinetics and pharmacodynamics of metabolites. Anesth Analg. 2007 Jul;105(1):70-8.
• Murphy EJ. Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesth Intensive Care. 2005 Jun;33(3):311-22. Review.
• Schumann R, Zabala L, Angelis M, Bonney I, Tighiouart H, Carr DB. Altered hematologic profiles following donor right hepatectomy and implications for perioperative analgesic management. Liver Transpl. 2004 Mar;10(3):363-8.
• Tsui SL, Yong BH, Ng KF, Yuen TS, Li CC, Chui KY. Delayed epidural catheter removal: the impact of postoperative coagulopathy. Anaesth Intensive Care. 2004 Oct;32(5):630-6.
• Urwin SC, Smith HS. Fatal nefopam overdose. Br J Anaesth. 1999 Sep;83(3):501-2.
• Villier C, Mallaret MP. Nefopam abuse. Ann Pharmacother. 2002 Oct;36(10):1564-6.
• Ychou M, Viret F, Kramar A, Desseigne F, Mitry E, Guimbaud R, Delpero JR, Rivoire M, Quénet F, Portier G, Nordlinger B. Tritherapy with fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases. Cancer Chemother Pharmacol. 2008 Jul;62(2):195-201. Epub 2007 Sep 28.

Inclusion Criteria:

• Male or female patients aged ≥ 18 years
• Patients with histologically confirmed cancer
• Patients treated at the Centre Léon Bérard
• Patients requiring a surgery for hepatic metastases
• ASA <= 3
• At least 3 weeks between surgery and chemotherapy
• Total bilirubin < 1.5 x upper limit of normal range
• ASAT and ALAT < 5 times x upper limit of normal range
• Creatinine clearance > 60 ml per hour
• Serum creatinine < 115 µmol/l
• Mandatory affiliation with a health insurance system
• Patients able to understand French
• Signed, written informed consent

Exclusion Criteria:

• Patients with a hepatocellular carcinoma or an initial liver cancer
• Patients treated chronically by morphine
• Patients that already have abdominal pain
• Patients who are allergic either to morphinics, local anesthesics, paracetamol, NSAID or cortisone
• Patients suffering from heart, kidney or liver insufficiency
• Documented history of cognitive or psychiatric disorders
• Pregnant or lactating women
• Difficult follow-up

• AstraZeneca
• Apicil