The disposition of bupivacaine following a 72 h interpleural infusion in cholecystectomy patients.

Abstract

The disposition of bupivacaine and degree of analgesia following a 72 h interpleural infusion was investigated in 12 adult patients undergoing elective cholecystectomy. The infusion regimen of an initial interpleural bolus dose of 20 ml of 0.5% bupivacaine HCI with adrenaline (1:200,000) followed by continuous infusion at a rate of 8 ml h-1 of 0.25% plain bupivacaine HCI was designed to achieve continuous post-operative pain relief for 72 h. In practice an additional bolus dose (identical to the first) administered 5 h after infusion commencement was required to achieve adequate pain relief on the first postoperative day. The mean measured steady-state plasma bupivacaine concentration was 2.1 mg 1'1 (s.d. ± 0.54, range 1.3-3.2 mg 1-1). Disposition parameters for bupivacaine measured for the infusion were calculated by non-compartmental methods and compared with previous values obtained after single and multiple interpleural bolus dose administration. No statistically significant differences were noted and, in particular, the systemic clearance of bupivacaine (mean 10.2 1 h-' s.d ± 3.0; range 6.3-16.0 1 h-') remained unchanged following the long-term interpleural infusion. Analgesia was deemed satisfactory throughout the entire post-operative period.

Interpleural analgesia for attenuation of postoperative pain after hepatic resection*

“…Numerous studies demonstrate an acceptable safety profile with bupivacaine administered via the interpleural route [6, 8, 12–14, 16, 19]. In our study we used a conservative dosing regime and found no reported symptoms consistent with local anaesthetic toxicity.…”

“…Whilst there are sufficient patients to detect a clinically important difference in the primary endpoint, we are unable to detect the true incidence of complications from interpleural analgesia due to the relatively small sample size. Plasma levo‐bupivacaine levels were not evaluated as they have been well reported in numerous other studies [1, 6, 8, 12, 13, 16, 19, 26]. Although we found no reported symptoms of local anaesthetic toxicity, it is possible that plasma levels may have demonstrated concentrations above the accepted safe range.…”

“…The catheter was aspirated to exclude intravascular placement and a test dose of 2 ml levo‐bupivacaine 0.5% was administered. The patient was then placed in supine position and a loading dose of 20 ml levo‐bupivacaine 0.5% with adrenaline 1:200 000 was administered, as previously described [1, 2, 6–8, 13, 16, 19]. To ensure even and optimum spread of the local anaesthetic solution, the patient was left in the supine position for 10 min [20].…”

“…Derangements in coagulation after hepatic resection have favoured systemic multimodal analgesia in preference to neuraxial techniques as the preferred method for effective delivery of postoperative analgesia in many institutions. Several studies report the use of interpleural local anaesthetic solutions as an effective technique for analgesia following unilateral upper abdominal surgery [1–19]; however, it is unknown if interpleural analgesia is effective for patients receiving a right subcostal surgical incision with a midline abdominal incision extension (reverse‐L incision), a commonly used surgical incision for patients undergoing this procedure. For patients undergoing hepatic resection we think that interpleural analgesia is a beneficial analgesic adjunct to systemic morphine patient controlled analgesia.…”

Estimated Plasma Bupivacaine Concentration After Single Dose and Eight‐Hour Continuous Intra‐Articular Infusion of Bupivacaine in Normal Dogs

“…[1][2][3] Toxicity is inconsistent as signs of toxicity have been reported in humans administered doses below the toxic dose, 11 but toxicity did not occur in others administered doses causing plasma concentrations to go higher than that considered toxic. 12,13 Absorption of local anesthetics after extravascular infiltration is dependent on the chemical nature of the drug, where the drug is administered, dose, concentration of the drug, vascularity of the infiltrated site, and the presence or absence of vasoactive drugs such as epinephrine in the anesthetic solution. 4 Extravascular administration of bupivacaine will undergo slow systemic absorption with rapid clearance; hence, plasma concentrations are not expected to reach toxic concentrations.…”