Clinical Study
Peritoneal Nebulization of Ropivacaine during Laparoscopic
Cholecystectomy: Dose Finding and Pharmacokinetic Study
Massimo Allegri,
1,2,3
Martina Ornaghi,
4
Catherine E. Ferland,
3,5,6
Dario Bugada,
1,2,3,7
Yash Meghani,
5
Serena Calcinati,
4
Manuela De Gregori,
3,7,8
Federica Lovisari,
4
Krishnaprabha Radhakrishnan,
5
Maria Cusato,
9
Stefano Scalia Catenacci,
4
Marta Somaini,
10
Guido Fanelli,
1,2
and Pablo Ingelmo
3,5,6
1
Department of Anaesthesia, ICU and Pain Terapy, University Hospital of Parma, Parma, Italy
2
Department of Surgical Sciences, University of Parma, Parma, Italy
3
SIMPAR Group (Study in Multidisciplinary Pain Research), Parma, Italy
4
Department of Anaesthesia and Intensive Care, San Gerardo Hospital of Monza, Milan Bicocca University, Milan, Italy
5
Department of Anaesthesia, Montreal Children’s Hospital, McGill University, Montr´ eal, QC, Canada
6
Alan Edwards Centre for Research on Pain, Montreal, QC, Canada
7
YAP Group (Young Against Pain), Firenze, Italy
8
Pain Terapy Service, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy
9
Laboratory of Clinical Pharmacokinetics, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy
10
Department of Anaesthesia and Intensive Care I, ASST Grande Ospedale Metropolitano Niguarda, University of Milano-Bicocca,
Milan, Italy
Correspondence should be addressed to Catherine E. Ferland; catherine.ferland@mcgill.ca
Received 30 November 2016; Accepted 30 January 2017; Published 20 February 2017
Academic Editor: Volkan Hancı
Copyright © 2017 Massimo Allegri et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Background. Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption afer laparoscopic
surgery. Te aim of this multicenter double-blind randomized controlled trial was to assess the efcacy of diferent doses and
dose-related absorption of ropivacaine when nebulized in the peritoneal cavity during laparoscopic cholecystectomy. Methods.
Patients were randomized to receive 50, 100, or 150 mg of ropivacaine 1% by peritoneal nebulization through a nebulizer. Morphine
consumption, pain intensity in the abdomen, wound and shoulder, time to unassisted ambulation, discharge time, and adverse
efects were collected during the frst 48 hours afer surgery. Te pharmacokinetics of ropivacaine was evaluated using high
performance liquid chromatography. Results. Nebulization of 50 mg of ropivacaine had the same efect of 100 or 150 mg in terms
of postoperative morphine consumption, shoulder pain, postoperative nausea and vomiting, activity resumption, and hospital
discharge timing (>0.05). Plasma concentrations did not reach toxic levels in any patient, and no signifcant diferences were
observed between groups ( > 0.05). Conclusions. Tere is no enhancement in analgesic efcacy with higher doses of nebulized
ropivacaine during laparoscopic cholecystectomy. When administered with a microvibration-based aerosol humidifcation system,
the pharmacokinetics of ropivacaine is constant and maintains an adequate safety profle for each dosage tested.
1. Introduction
Postoperative pain remains a major problem afer laparo-
scopy, having direct consequences on the patient’s quality of
life as well as increasing health care costs [1, 2]. Pain afer
laparoscopic surgery is usually attributed to surgical manipu-
lations, including intraperitoneal insufation of carbon diox-
ide, resulting in peritoneal stretching, diaphragmatic irrita-
tion, changes in intra-abdominal pH, and retention of the
insufated gas within the abdominal cavity afer surgery [3].
Hindawi Publishing Corporation
Pain Research and Management
Volume 2017, Article ID 4260702, 9 pages
http://dx.doi.org/10.1155/2017/4260702