BACKGROUND: This prospective, randomized, double blinded, controlled study was designed to compare effects of intravenous co-administration of clonidine, magnesium, or ketamine on anesthetic consumption, intraoperative hemodynamics, postoperative analgesia and recovery indices during Bispectral Index (BIS) guided total intravenous anesthesia (TIVA). METHODS: After ethical committee approval and written informed consent, 120 adult patients ASA I and II scheduled for open cholecystectomy were randomly assigned to one of 4 equal groups. Group CL received clonidine 3 microg/kg and maintained by 2 microg/kg/h. Group MG received magnesium sulphate 50 mg/kg and maintained by 8 mg/kg/h. Group KET received racemic ketamine 0.4 mg/kg and maintained by 0.2 mg/kg/h. Control group (CT) received the same volume of isotonic saline. Anesthesia was induced and maintained by fentanyl, propofol and rocuronium. Propofol infusion was adjusted to keep the BIS value between 45-55. Intraoperative hemodynamics, induction time, anesthetic consumption, recovery indices, and PACU discharge were recorded. RESULTS: Induction time, propofol requirements for induction and maintenance of anesthesia, intraoperative fentanyl and hemodynamic values were significantly lower with Groups CL and MG compared to Groups KET and CT (P < 0.05). Patients in Group MG showed significantly lower muscle relaxant consumption, delayed recovery and PACU discharge than other groups (P < 0.05). First, analgesic requirement was significantly longer and total postoperative analgesic consumption was significantly lower in the adjuvant groups versus Group CT (P < 0.05). CONCLUSIONS: Clonidine, magnesium, and ketamine can be useful adjuvant agents to BIS-guided TIVA. Pharmacokinetic studies of such drug combinations were recommended to investigate their interaction.
Adjuvants, Anesthesia ; Adult ; Analgesia ; Androstanols ; Anesthesia ; Anesthesia, Intravenous ; Cholecystectomy ; Clonidine ; Drug Combinations ; Fentanyl ; Hemodynamics ; Humans ; Informed Consent ; Ketamine ; Magnesium ; Muscles ; Propofol ; Prospective Studies

Objective: To evaluate the combination therapy of pyronaridine tetraphosphate and diminazene aceturate against Babesia in vitro and in vivo. Methods: Bioinformatic analysis was performed using atom pair fingerprints. An in vitro combination test was performed against Babesia bovis and Theileria equi. Moreover, the in vivo chemotherapeutic efficacy of pyronaridine tetraphosphate in combination with diminazene aceturate was investigated against the growth of Babesia microti in mice using a fluorescence inhibitory assay. Results: Pyronaridine tetraphosphate and diminazene aceturate exhibited nearly similar molecular weights. The in vitro combination of pyronaridine tetraphosphate and diminazene aceturate was synergistic on Babesia bovis and additive on Theileria equi. In addition, 5 mg/kg pyronaridine tetraphosphate combined with 10 mg/kg diminazene aceturate inhibited Babesia microti growth significantly compared with those observed after treatment with 25 mg/kg diminazene aceturate alone from day 6 post treatment to day 12 post treatment. The combination therapy also normalized the hematological parameters of infected mice. Conclusions: An oral dose of pyronaridine tetraphosphate combined with a subcutaneous dose of diminazene aceturate inhibits Babesia in vitro and in mice, suggesting it might be a new paradigm for the treatment of babesiosis.