Transversus Abdominis Plane Block With Liposomal Bupivacaine for Pain After Cesarean Delivery in a Multicenter, Randomized, Double-Blind, Controlled Trial

Abstract

Background: In women undergoing cesarean delivery under spinal anesthesia with intrathecal morphine, transversus abdominis plane (TAP) block with bupivacaine hydrochloride (HCl) may not improve postsurgical analgesia. This lack of benefit could be related to the short duration of action of bupivacaine HCl. A retrospective study reported that TAP block with long-acting liposomal bupivacaine (LB) reduced opioid consumption and improved analgesia following cesarean delivery. Therefore, we performed a prospective multicenter, randomized, double-blind trial examining efficacy and safety of TAP block with LB plus bupivacaine HCl versus bupivacaine HCl alone.

Methods: Women (n = 186) with term pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomized (1:1) to TAP block with LB 266 mg plus bupivacaine HCl 50 mg or bupivacaine HCl 50 mg alone. Efficacy was evaluated in a protocol-compliant analysis (PCA) set that was defined a priori. The primary end point was total postsurgical opioid consumption (oral morphine equivalent dosing [MED]) through 72 hours. Pain intensity was measured using a visual analog scale. Adverse events (AEs) after treatment were recorded through day 14.

Results: Total opioid consumption through 72 hours was reduced with LB plus bupivacaine HCl versus bupivacaine HCl alone (least squares mean [LSM] [standard error (SE)] MED, 15.5 mg [6.67 mg] vs 32.0 mg [6.25 mg]). This corresponded to an LSM treatment difference of -16.5 mg (95% confidence interval [CI], -30.8 to -2.2 mg; P = .012). The area under the curve of imputed pain intensity scores through 72 hours supported noninferiority of LB plus bupivacaine HCl versus bupivacaine HCl alone (LSM [SE], 147.9 [21.13] vs 178.5 [19.78]; LSM treatment difference, -30.6; 95% CI, -75.9 to 14.7), with a prespecified noninferiority margin of 36 (P = .002). In an analysis of all treated patients, including those not meeting criteria for inclusion in the PCA, there was no difference in postsurgical opioid consumption between groups. In the LB plus bupivacaine HCl group, 63.6% of patients experienced an AE after treatment versus 56.2% in the bupivacaine HCl-alone group. Serious AEs after treatment were rare (≈3% in both groups).

Conclusions: TAP block using LB plus bupivacaine HCl as part of a multimodal analgesia protocol incorporating intrathecal morphine resulted in reduced opioid consumption after cesarean delivery in the PCA set. Results suggest that with correct TAP block placement and adherence to a multimodal postsurgical analgesic regimen, there is an opioid-reducing benefit of adding LB to bupivacaine TAP blocks after cesarean delivery (ClinicalTrials.gov identifier: NCT03176459).

Figure 1.

Patient disposition. Efficacy was evaluated in a prespecified protocol-compliant analysis set that included patients who underwent cesarean delivery and met the study criteria for correct transversus abdominis plane placement, correct local anesthetic dosing, and adherence to a multimodal postsurgical analgesic regimen. Those who did not meet ≥1 criteria for correct TAP block placement (n = 13), correct local anesthetic dosing (n = 12), or adherence to multimodal postsurgical analgesic regimen (n = 39) were excluded from the protocol-compliant analysis. Patients were considered “lost to follow-up” if the study team could not contact them after at least 3 attempts. BUPI indicates bupivacaine; HCl, hydrochloride; LB, liposomal bupivacaine; mITT, modified intent-to-treat.

Figure 2.

Total opioid consumption at 24, 48, and 72 h and at 7 and 14 d after surgery for cesarean delivery. The primary end point of the study was total opioid consumption through 72 h. Total opioid consumption through 24 and 48 h and 7 and 14 d were secondary end points. BUPI indicates bupivacaine; HCl, hydrochloride; LB, liposomal bupivacaine; LSM, least squares mean; MED, morphine equivalent dose.