Področna anestezija zgornje in spodnje čeljusti pri psu: farmakodinamika in farmakokinetika deksmedetomidina in levobupivakaina

Pavlica, Matic (author), Seliškar, Alenka (mentor)

Namen raziskave je bil pridobiti vpogled v farmakokinetiko in odgovor obtočil na perinevralno aplikacijo deksmedetomidina (DEX) in levobupivakaina (LB) in ugotoviti, ali DEX omeji odgovor organizma na stres. Štiridesetim psom, pri katerih smo v splošni anesteziji z izofluranom opravili stomatološki poseg, smo aplicirali 0,5 % LB za omrtvičenje obeh infraorbitalnih (IO) živcev (0,11 mL/kg2/3) in obeh inferiornih alveolarnih (IA) živcev (0,18 mL/kg2/3). Desetim psom smo poleg LB aplicirali DEX (0,5 µg/kg) perinevralno ob IO živec (LB+DEX IO), desetim ob IA živec (LB+DEX IA), desetim pa intravensko (LB+DEX IV). Desetim psom smo intravensko aplicirali placebo (LB+PLC IV). Za določanje koncentracije LB in DEX s pomočjo analize LC-MS/MS smo odvzeli kri pred in po aplikaciji obeh učinkovin ter 1, 2, 5, 10, 15, 30, 45, 60, 90 in 120 minut po aplikaciji. Srčno-žilne parametre smo prvih 12 minut po aplikaciji zdravil odčitali vsako minuto, nato pa na pet minut do konca posega. Za določanje koncentracije kortizola in glukoze smo odvzeli kri po uvodu v anestezijo in na koncu posega. V nadaljevanju smo v raziskavo vključili še 20 psov in jim samo na eno mesto aplicirali LB (IO ali IA blok). Kri za določanje koncentracije LB smo jim odvzeli ob enakih časovnih točkah kot v prvem delu raziskave. Absorpcija DEX je bila neznačilno hitrejša pri LB+DEX IO, medtem ko je bila pri LB+DEX IA boljša biološka razpoložljivost (56 % proti 48 %) in hitrejša eliminacija. Frekvenca srca je bila v primerjavi s placebo skupino značilno nižja pri vseh skupinah psov, ki so prejele DEX. Srednji arterijski tlak je bil v primerjavi z LB+PLC IV skupino značilno višji pri LB+DEX IV in LB+DEX IA. Koncentracija kortizola je bila neznačilno nižja na koncu posega pri vseh skupinah, koncentracija glukoze pa je bila značilno nižja na koncu posega le pri LB+DEX IA skupini. Stopnjo bolečine je 14 dni po posegu značilno nižje ocenil le stomatolog, ne pa tudi anestezist in lastnik psa. Levobupivakain se je najhitreje absorbiral po aplikaciji ob IA živec (LB IA), vendar razlika v primerjavi z aplikacijo ob IO živec ni bila značilna. Lokacija perinevralne aplikacije DEX in LB ni vplivala na hitrost in količino sistemske absorpcije, DEX pa ni omejil perioperacijskega stresnega odgovora, najverjetneje zaradi izredno nizkega odmerka.

• Language: Slovenian
• Keywords: področna anestezija, ustna votlina, pes, živčni bloki, deksmedetomidin, levobupivakain, farmakokinetika, srčno-žilni parametri
• Work type: Doctoral dissertation
• Organization: VF - Veterinary Faculty
• Year: 2023
• PID: 20.500.12556/RUL-164802
• Publication date in RUL: 13.11.2024

Secondary language

• Language: English
• Title: Regional anaesthesia of upper and lower jaw in dog: pharmacodynamics and pharmacokinetics of dexmedetomidine and levobupivacaine

Abstract

The aim of this study was to gain insight into the pharmacokinetics and cardiovascular response to perineural administration of dexmedetomidine (DEX) and levobupivacaine (LB) and to determine whether DEX limits the perioperative stress response. Forty dogs undergoing dental procedure under general anaesthesia with isoflurane were administered 0.5% LB to both infraorbital (IO) blocks (0.11 mL/kg2/3) and both inferior alveolar (IA) blocks (0.18 mL/kg2/3). In addition to LB, 10 dogs were administered DEX (0.5 µg/kg) perineurally at IO nerve (LB + DEX IO), ten dogs at IA nerve (LB + DEX IA), and 10 dogs were administered DEX intravenously (LB + DEX IV). Ten dogs were administered a placebo intravenously (LB + PLC IV). Blood was collected to determine the concentration of LB and DEX using the LC-MS /MS analysis before and after administration of the two drugs and also at 1, 2, 5, 10, 15, 30, 45, 60, 90, and 120 minutes thereafter. Cardiovascular parameters were measured every minute for the first 12 minutes and then every five minutes until the end of the procedure. Blood was drawn to determine cortisol and glucose concentrations after the induction of general anaesthesia and at the end of the procedure. Twenty additional dogs were included in the study and applied LB to only one site (IO or IA block). For the determination of LB, blood was collected at the same time points as in the first part of the study. The absorption of DEX was non-significantly faster in the LB + DEX IO group, whereas in the LB + DEX IA group, better bioavailability (56% vs. 48%) and faster elimination were observed. Heart rate was significantly lower in all groups of dogs receiving DEX compared to the placebo group. Mean arterial pressure was significantly higher in the LB + DEX IV and LB + DEX IA groups compared to the LB + PLC IV group. Cortisol concentration was non-significantly lower at the end of the procedure in all groups, and glucose concentration was significantly lower at the end of the procedure only in the LB + DEX IA group. Only the stomatologist, but not the anaesthesiologist and the dog owner, determined a significantly lower level of pain 14 days after the procedure. The fastest absorption of LB occurred after administration near the IA nerve (LB IA). The site of perineural application of DEX and LB did not affect the rate and amount of systemic absorption, and DEX did not limit the perioperative stress response, probably because of the low dose we used.

• Keywords: regional anaesthesia, oral cavity, dog, nerve blocks, dexmedetomidine, levobupivacaine, pharmacokinetics, cardiovascular parameters