An Observational Study of the Pharmacokinetics of Surgeon-Performed Intercostal Nerve Blockade With Liposomal Bupivacaine for Posterior-Lateral Thoracotomy Analgesia

Abstract

BACKGROUND: Intercostal nerve blocks with liposomal bupivacaine are commonly used for thoracic surgery pain management. However, dose scheduling is difficult because the pharmacokinetics of a single-dose intercostal injection of liposomal bupivacaine has never been investigated. The primary aim of this study was to assess the median time to peak plasma concentration (T max) following a surgeon-administered, single-dose infiltration of 266 mg of liposomal bupivacaine as a posterior multilevel intercostal nerve block in patients undergoing posterolateral thoracotomy. METHODS: We chose a sample size of 15 adults for this prospective observational study. Intercostal injection of liposomal bupivacaine was considered time 0. Serum samples were taken at the following times: 5, 15, and 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours. The presence of sensory blockade, rescue pain medication, and pain level were recorded after the patient was able to answer questions. RESULTS: Forty patients were screened, and 15 patients were enrolled in the study. Median (interquartile range [IQR]) T max was 24 (12) hours (confidence interval [CI], 19.5–28.5 hours) with a range of 15 minutes to 48 hours. The median (IQR) peak plasma concentration (C max) was 0.6 (0.3) μg/mL (CI, 00.45–0.74 μg/mL) in a range of 0.3–1.2. The serum bupivacaine concentration was undetectable (<0.2 μg/mL) at 96 hours in all patients. There was significant variability in reported pain scores and rescue opioid medication across the 15 patients. More than 50% of patients had return of normal chest wall sensation at 48 hours. All patients had resolution of nerve blockade at 96 hours. No patients developed local anesthetic toxicity. CONCLUSIONS: This study of the pharmacokinetics of liposomal bupivacaine following multilevel intercostal nerve blockade demonstrates significant variability and delay in systemic absorption of the drug. Peak serum concentration occurred at 48 hours or sooner in all patients. The serum bupivacaine concentration always remained well below the described toxicity threshold (2 μg/mL) during the 96-hour study period.

Multimodal opioid‐sparing pain management after lung transplantation and the impact of liposomal bupivacaine intercostal nerve block

“…33 LB-INB may also be of more value in lung transplantation as the C max of 24 h would coincide with the median extubation time in our cohort, whereas most general thoracic surgery patients are extubated in the operating room. 33 Although median pain scores were slightly higher in the LB-INB cohort, more of these patients were off opioids by POD4. The impact of LB-INB on acute opioid consumption should lead to further investigation into its routine incorporation into post-lung transplant pain management protocols in lieu of the more invasive and restrictive TEA.…”

“…While it seems counterintuitive that the prolonged release would not offer benefit in certain studies over the immediate release, variability in response may be explained by differences in infiltration technique and interpatient pharmacokinetics 33 . LB‐INB may also be of more value in lung transplantation as the C max of 24 h would coincide with the median extubation time in our cohort, whereas most general thoracic surgery patients are extubated in the operating room 33 . Although median pain scores were slightly higher in the LB‐INB cohort, more of these patients were off opioids by POD4.…”

“…Liposomal bupivacaine has the added benefit of drug diffusion in the injected tissues for up to 72–96 h after a single administration, without losing the initial benefit of an immediate‐release formulation 32 . While it seems counterintuitive that the prolonged release would not offer benefit in certain studies over the immediate release, variability in response may be explained by differences in infiltration technique and interpatient pharmacokinetics 33 . LB‐INB may also be of more value in lung transplantation as the C max of 24 h would coincide with the median extubation time in our cohort, whereas most general thoracic surgery patients are extubated in the operating room 33 .…”

A multimodal protocol utilizing liposomal bupivacaine rib blocks leads to opioid reduction in patients undergoing the Nuss procedure

“…The protocol we have implemented incorporates existing evidence-based strategies for postoperative pain control and early recovery, augmented by the addition of the use of LB for longer-lasting local analgesia in the perioperative period, which has a duration of 1-4 days (25). In addition to early mobilization and elimination of urinary catheter placement, a major tenet of our protocol is to address pain in the preoperative, intraoperative, and postoperative phases.…”

Plasma bupivacaine levels (total and free/unbound) during epidural infusion in liver resection patients: a prospective, observational study

“…Sample size calculations were not done, but rather (like other LA blood studies),3 4 7 10 12 15 16 a convenience sample of 27 consecutive patients who met eligibility were recruited. Inclusion criteria were adults (≥18 years) competent to consent, scheduled for major (≥3 segments) hepatectomy (at our tertiary care and academic center) with bupivacaine CEA for postoperative analgesia.…”