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

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.

Intravenous lidocaine to prevent endothelial dysfunction after major abdominal surgery: a randomized controlled pilot trial

“…Amide-linked local anesthetics (LAs) such as lidocaine and ropivacaine have an anti-inflammatory effect [1][2][3][4][5]. Their use in the peri-operative setting for this purpose was proposed more than one decade ago [1][2][3][4][5]. Continuous intravenous infusion of lidocaine reduced pain scores after major abdominal surgery, improves gastrointestinal recovery and potentially reduces the in-hospital length of stay [6].…”

Intravenous lidocaine to prevent endothelial dysfunction after major abdominal surgery: A randomized controlled pilot trial

“…Based on previous studies demonstrating the anti-in ammatory properties of amide-linked LAs 3 and its effects on bowel motility, 2 we hypothesised that lidocaine could reduce uid extravasation and tissue edema by protecting the EG. Even if this was a pilot study, with a reduced population number, endothelial dysfunction in major abdominal surgery is probably overestimated when studied in a controlled setting.…”

“…[1][2][3][4][5] Their use in the peri-operative setting for this purpose was proposed more than one decade ago. [1][2][3][4][5] Continuous intravenous infusion of lidocaine reduced pain scores after major abdominal surgery, improves gastrointestinal recovery and potentially reduces the in-hospital length of stay. 6 Whether these effects are related to sodium-channel blockade is debated.…”

Intravenous lidocaine to prevent endothelial dysfunction after major abdominal surgery: A randomised controlled pilot trial

“…Amide-linked local anesthetics (LAs) such as lidocaine and ropivacaine have an anti-inflammatory effect. [1][2][3][4][5] Their use in the peri-operative setting for this purpose was proposed more than one decade ago. [1][2][3][4][5] Continuous intravenous infusion of lidocaine reduced pain scores after major abdominal surgery, improves gastrointestinal recovery and potentially reduces the in-hospital length of stay.…”