Pharmacokinetics and Pharmacodynamics of Dexmedetomidine Administered as an Adjunct to Bupivacaine for Transversus Abdominis Plane Block in Patients Undergoing Lower Abdominal Cancer Surgery

Abstract

Fatma A El Sherif,1 Hala Abdel-Ghaffar,2 Ahmed Othman,1 Sahar Mohamed,1 Mervat Omran,3 Samia Shouman,4 Nivin Hassan,5 Ayat Allam,6– 8 Sahar Hassan9 1Anesthesia, Intensive Care and Pain Management Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt; 2Anesthesia and Intensive Care Department, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Cancer Biology Department (Pharmacology and Experimental Oncology), National Cancer Institute, Cairo University, Cairo, Egypt; 4Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 5Cancer Biology Department (Pharmacology and Experimental Oncology), South Egypt Cancer Institute, Assiut University, Assiut, Egypt; 6Pharmaceutics Department, Faculty of Pharmacy, Assiut University, Assiut, 71515, Egypt; 7Pharmaceutics Department, Faculty of Pharmacy, Sphinx University, New Assiut City, Egypt; 8Assiut International Center of Nanomedicine, AL-Rajhy Liver Hospital, Assiut University, Assiut, 71515, Egypt; 9Clinical Pharmacy Department, Faculty of Pharmacy, Assiut University, Assiut, EgyptCorrespondence: Ahmed Othman Tel [phone]Fax [phone]Email [email protected]: Despite 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.Objective: We investigated the pharmacokinetics and pharmacodynamics of dexmedetomidine as an adjunct to transversus abdominis plane (TAP) block in patients undergoing lower abdominal cancer surgery.Methods: Twenty-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).Results: Dexmedetomidine 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.Conclusion: Systemic 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 Registration: ClinicalTrial.gov (identifier: NCT03328299).Keywords: analgesia, transversus abdominis plane block, dexmedetomidine, pharmacokinetics, pharmacodynamics

Keywords

• analgesia
• transversus abdominis plane block
• dexmedetomidine
• pharmacokinetics
• pharmacodynamics.