Peritoneal Nebulization of Ropivacaine during Laparoscopic Cholecystectomy: Dose Finding and Pharmacokinetic Study.
Background. Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption after laparoscopic surgery. The aim of this multicenter double-blind randomized controlled trial was to assess the efficacy of different 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 effects were collected during the first 48 hours after surgery. The pharmacokinetics of ropivacaine was evaluated using high performance liquid chromatography.Results. Nebulization of 50 mg of ropivacaine had the same effect 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 significant differences were observed between groups (P> 0.05).Conclusions. There is no enhancement in analgesic efficacy with higher doses of nebulized ropivacaine during laparoscopic cholecystectomy. When administered with a microvibration-based aerosol humidification system, the pharmacokinetics of ropivacaine is constant and maintains an adequate safety profile for each dosage tested.
Department of Anaesthesia, ICU and Pain Therapy, University Hospital of Parma, Parma, Italy; Department of Surgical Sciences, University of Parma, Parma, Italy; SIMPAR Group (Study in Multidisciplinary Pain Research), Parma, Italy.
Massimo
M
Allegri
Department of Anaesthesia and Intensive Care, San Gerardo Hospital of Monza, Milan Bicocca University, Milan, Italy.
Martina
M
Ornaghi
SIMPAR Group (Study in Multidisciplinary Pain Research), Parma, Italy; Department of Anaesthesia, Montreal Children's Hospital, McGill University, Montréal, QC, Canada; Alan Edwards Centre for Research on Pain, Montreal, QC, Canada.
Catherine E
0000-0002-5236-4215
CE
Ferland
Department of Anaesthesia, ICU and Pain Therapy, University Hospital of Parma, Parma, Italy; Department of Surgical Sciences, University of Parma, Parma, Italy; SIMPAR Group (Study in Multidisciplinary Pain Research), Parma, Italy; YAP Group (Young Against Pain), Firenze, Italy.
Dario
0000-0002-8363-6674
D
Bugada
Department of Anaesthesia, Montreal Children's Hospital, McGill University, Montréal, QC, Canada.
Yash
Y
Meghani
Department of Anaesthesia and Intensive Care, San Gerardo Hospital of Monza, Milan Bicocca University, Milan, Italy.
Serena
S
Calcinati
SIMPAR Group (Study in Multidisciplinary Pain Research), Parma, Italy; YAP Group (Young Against Pain), Firenze, Italy; Pain Therapy Service, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
Manuela
0000-0002-3507-497X
M
De Gregori
Department of Anaesthesia and Intensive Care, San Gerardo Hospital of Monza, Milan Bicocca University, Milan, Italy.
Federica
F
Lovisari
Department of Anaesthesia, Montreal Children's Hospital, McGill University, Montréal, QC, Canada.
Krishnaprabha
K
Radhakrishnan
Laboratory of Clinical Pharmacokinetics, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
Maria
M
Cusato
Department of Anaesthesia and Intensive Care, San Gerardo Hospital of Monza, Milan Bicocca University, Milan, Italy.
Stefano
S
Scalia Catenacci
Department of Anaesthesia and Intensive Care I, ASST Grande Ospedale Metropolitano Niguarda, University of Milano-Bicocca, Milan, Italy.
Marta
M
Somaini
Department of Anaesthesia, ICU and Pain Therapy, University Hospital of Parma, Parma, Italy; Department of Surgical Sciences, University of Parma, Parma, Italy.
Guido
G
Fanelli
SIMPAR Group (Study in Multidisciplinary Pain Research), Parma, Italy; Department of Anaesthesia, Montreal Children's Hospital, McGill University, Montréal, QC, Canada; Alan Edwards Centre for Research on Pain, Montreal, QC, Canada.
Pablo
P
Ingelmo
D000293:Adolescent; D000328:Adult; D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D017081:Cholecystectomy, Laparoscopic / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D017063:Outcome Assessment, Health Care; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy* / Q000209:etiology*; D000077212:Ropivacaine; D055815:Young Adult
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine