[Liposomal bupivacaine-No breakthrough in postoperative pain management]. / Liposomales Bupivacain ­ kein Durchbruch in der postoperativen Schmerztherapie.

One of the main limitations concerning the use of local anesthetics is due to their restricted duration of action. In recent years, liposomal formulations with prolonged release kinetics have been developed to extend the pharmacological duration of action of the 1­stage peripheral regional anesthesia (single-shot procedure) and thus bring about a longer duration of action. The focus here is particularly on achieving postoperative freedom from pain for at least 24 h (or even better 48 h) and thus early mobilization of patients using on-demand medication causing (at most) minor local sensory blockade without causing motor impairments (at least that is the ideal). Therefore, methods of utilizing slow-release drugs as seen in liposomal carrier systems have experienced increasing scientific attention in the last few years. A common modern pharmacological example with a theoretically significantly longer duration of action is liposomal bupivacaine, an amide local anesthetic. Due to a multivesicular liposome structure, the retarded release of the active component bupivacaine HCl leads to a theoretical pharmacological effectiveness of up to 72 h. Previous studies consistently showed a safety profile comparable to conventional bupivacaine HCl. Liposomal bupivacaine has been approved by the U.S. Food and Drug Administration (FDA) under the trade name Exparel© (Pacira Pharmaceuticals, Parsippany, NJ, USA) since 2011; however, its use is currently limited to local wound infiltration, transverse abdominis plane (TAP) blocks, and interscalene nerve blocks of the brachial plexus. In 2020, the European Medicines Agency (EMA) also approved the use of liposomal bupivacaine for blockade of the brachial plexus or the femoral nerve and as a field block or for wound infiltration to treat postoperative pain. So far, studies on the clinical effectiveness of liposomal bupivacaine have been very heterogeneous and there have been no conclusive meta-analyses with sufficient rigor or significance. Recent systematic reviews and meta-analyses, combining the results of clinical studies regarding the analgesic efficiency of liposomal bupivacaine in different fields of application, consistently refuted any benefit of clinical relevance provided by the liposomal formulation. There is currently sufficient evidence to now end the ongoing debate around liposomal bupivacaine. The aim of this work is to give the reader a current, evidence-based overview of this substance.

The analgesic efficacy of liposomal bupivacaine compared with bupivacaine hydrochloride for the prevention of postoperative pain: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND/IMPORTANCE: Liposomal bupivacaine (LB) is a prolonged release formulation of conventional bupivacaine designed for prolonging local or peripheral regional single injection anesthesia. To this day, the benefit of the new substance on relevant end points is discussed controversial. OBJECTIVE: The objective was to determine whether there is a difference in postoperative pain scores and morphine consumption between patients treated with LB and bupivacaine hydrochloride in a systematic review and meta-analysis. EVIDENCE REVIEW: Randomized controlled trials (RCT) were identified in Embase, CENTRAL, MEDLINE and Web of Science up to May 2020. Risk of bias was assessed using Cochrane methodology. Primary end points were the mean pain score difference and the relative morphine equivalent (MEQ) consumption expressed as the ratio of means (ROM) 24 and 72 hours postoperatively. FINDINGS: 23 RCTs including 1867 patients were eligible for meta-analysis. The mean pain score difference at 24 hours postoperatively was significantly lower in the LB group, at -0.37 (95% CI -0.56 to -0.19). The relative MEQ consumption after 24 hours was also significantly lower in the LB group, at 0.85 (0.82 to 0.89). At 72 hours, the pain score difference was not significant at -0.25 (-0.71 to 0.20) and the MEQ ratio was 0.85 (0.77 to 0.95). CONCLUSION: The beneficial effect on pain scores and opioid consumption was small but not clinically relevant, despite statistical significance. The effect was stable among all studies, indicating that it is independent of the application modality.