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Pharmacokinetics of Bupivacaine Following Administration by an Ultrasound-Guided Transversus Abdominis Plane Block in Cats Undergoing Ovariohysterectomy.

ABSTRACT: Bupivacaine is commonly used for peripheral nerve block in veterinary medicine. This study described the pharmacokinetics of two doses of bupivacaine following administration by an ultrasound-guided transversus abdominis plane (TAP) block in cats undergoing ovariohysterectomy. Twelve healthy female adult cats were included in a randomized, prospective, blinded clinical trial. Anaesthetic protocol included acepromazine-buprenorphine-propofol-isoflurane-meloxicam. Each cat received 1 mL/kg of bupivacaine 0.2% or 0.25% (BUPI-2 and BUPI-2.5, respectively) via bilateral two-point TAP block before surgery (n = 6/group). Plasma concentrations of bupivacaine were detected using liquid chromatography-mass spectrometry. A one-compartment model and non-compartmental analysis described the pharmacokinetic parameters. Bupivacaine was detected up to 480 min (335 ± 76 in BUPI-2 and 485 ± 198 ng/mL in BUPI-2.5). For BUPI-2 and BUPI-2.5, maximum plasma concentrations were 1166 ± 511 and 1810 ± 536 ng/mL at 33 ± 14 and 47 ± 22 min, clearance was 5.3 ± 1.8 and 4.9 ± 1.5 mL/min/kg, and elimination half-life were 253 ± 55 and 217 ± 52 min, respectively. The two doses of bupivacaine via TAP block produced concentrations below toxic levels in cats. A dose of 2.5 mg/kg bupivacaine was safe to be administered using this block in healthy cats.

SUBMITTER: Garbin M

PROVIDER: S-EPMC9331386 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDespite the growing interest in dexmedetomidine as an adjunct to truncal blocks, little is known about the systemic absorption of dexmedetomidine after these blocks and its role in analgesia and in hemodynamics.ObjectiveWe investigated the pharmacokinetics and pharmacodynamics of dexmedetomidine as an adjunct to transversus abdominis plane (TAP) block in patients undergoing lower abdominal cancer surgery.MethodsTwenty-four adult patients were randomized to receive a bilateral single-injection TAP block before surgery with 20 mL of bupivacaine 0.5% (TAP group, n = 12) or combined with 1 µg/kg dexmedetomidine (TAP-DEX group, n = 12) and diluted with saline to a volume of 40 mL (20 mL on each side). Plasma concentrations of dexmedetomidine and its pharmacokinetics were investigated using non-compartmental methods, postoperative analgesia, hemodynamics, and adverse events (nausea, vomiting, itching, hypotension, bradycardia, and respiratory depression).ResultsDexmedetomidine was detected in the plasma of 11 patients in the TAP-DEX group. The mean dexmedetomidine peak plasma concentration (Cmax) was 0.158 ± 0.085 (range, 0.045-0.31) ng/mL. The median time to reach peak plasma concentration of dexmedetomidine (Tmax) was 15 (15-45) min. From 2 to 8 h postoperatively, visual analog pain scale (VAS) scores at rest and during movement were significantly lower in the TAP-DEX group. Analgesia time was (11.3 ± 3.12 vs 9.0 ± 4.69 h; P = 0.213) and postoperative morphine consumption was (7.4 ± 3.24 vs 11.5 ± 4.46 mg; P = 0.033) in TAP-DEX and TAP groups, respectively. Lower mean heart rate and mean blood pressure were recorded in the TAP-DEX group intraoperatively and 2 h postoperatively (P < 0.05). Except for mild nausea and vomiting, no adverse events were recorded in either group.ConclusionSystemic absorption of dexmedetomidine administered in a TAP block is common. Direct central effects on the locus coeruleus caused by this systemic absorption may play a role in the analgesia and hemodynamic effects produced by TAP-dexmedetomidine in addition to local mechanisms.Trial registrationClinicalTrial.gov (identifier: NCT03328299).

Project description:BackgroundIn 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.MethodsWomen (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.ResultsTotal 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).ConclusionsTAP 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).

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Pharmacokinetics of Bupivacaine Following Administration by an Ultrasound-Guided Transversus Abdominis Plane Block in Cats Undergoing Ovariohysterectomy.

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