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J Pain Res. 2017 Oct 31;10:2515-2524. doi: 10.2147/JPR.S139856. eCollection 2017.

Continuous wound infusion with chloroprocaine in a pig model of surgical lesion: drug absorption and effects on inflammatory response.

Author information

1
Department of Medicine and Surgery, University of Parma, Parma.
2
SIMPAR Group (Study in Multidisciplinary PAin Research).
3
Department of Anaesthesia and ICU, ASST Papa Giovanni XXIII, Bergamo.
4
Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo.
5
Laboratory of Transplant Immunology/Cell Factory, IRCCS Foundation Policlinico San Matteo.
6
Clinical epidemiology and Biometrics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia.
7
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan.
8
I.B.I.M., C.N.R., Palermo.
9
PhD School, University of Pavia.
10
Department of Pediatric Surgery, Fondazione IRCCS Policlinico San Matteo, Pavia.
11
Department of Pediatric Surgery, "V. Buzzi" Children's Hospital, Milan.
12
Department of Public Health, Experimental and Forensic Medicine, University of Pavia.
13
Department of Surgical, Clinical, Paediatric and Diagnostic Science, University of Pavia.
14
General Surgery 1, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.

Abstract

Continuous wound infusion (CWI) may protect from inflammation, hyperalgesia and persistent pain. Current local anesthetics display suboptimal pharmacokinetic profile during CWI; chloroprocaine (CP) has ideal characteristics, but has never been tested for CWI. We performed an animal study to investigate the pharmacokinetic profile and anti-inflammatory effect of CP during CWI. A total of 14 piglets received an infusion catheter after pararectal laparotomy and were randomly allocated to one of three groups: 5 mL/h infusion of saline (group A), CP 1.5% (group B) and CP 0.5% (group C). Blood sampling was performed to assess absorption and systemic inflammation at 0, 3, 6, 12, 24, 48, 72, 96, 102 and 108 hours. The wound and contralateral healthy abdominal wall were sampled for histological analyses. Absorption of CP from the site of infusion, evaluated as the plasmatic concentrations of CP and its metabolite, 4-amino-2-chlorobenzoic acid (CABA), showed a peak during the first 6 hours, but both CP and its metabolite rapidly disappeared after stopping CP infusion. Local inflammation was reduced in groups B and C (CP-treated p < 0.001), in a CP dose-dependent fashion. While CP inhibited in a dose-dependent manner pig mononuclear cells (MNCs) in vitro proliferation to a polyclonal activator, no effect on systemic cytokines' concentrations or on ex vivo monocytes' responsiveness was observed, suggesting the lack of systemic effects, in line with the very short half-life of CP in plasma. CP showed a very good profile for use in CWI, with dose-dependent local anti-inflammatory effects, limited absorption and rapid clearance from the bloodstream upon discontinuation. No cytotoxicity or side effects were observed. CP, therefore, may represent an optimal choice for clinical CWI, adaptable to each patient's need, and protective on wound inflammatory response (and hyperalgesia) after surgery.

KEYWORDS:

chloroprocaine; continuous wound infusion; inflammation; pharmacokinetics; pig model; postoperative pain

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