Avaliação da analgesia pós-operatória da metadona, da cetamina ou da sua associação em gatas submetidas a ovariossalpingo-histerectomia / Evaluation of postoperative analgesia of methadone, ketamine or their associations in cats undergoing ovariohysterectomy

A prevenção e o controle da dor são componentes básicos para um procedimento anestésico adequado. Objetivou-se com este estudo avaliar a analgesia pós-operatória da cetamina, em dose subanestésica, da metadona e da associação de ambas pela via intramuscular em felinos. Foram utilizadas 24 gatas, hígidas, submetidas à ovariossalpingo-histerectomia eletiva. No dia anterior ao início do estudo, os animais foram anestesiados para colocação de cateter na veia jugular, para posterior coleta de sangue para mensuração da concentração sérica do cortisol. No dia do experimento, os animais foram alocados aleatoriamente em três grupos (n=oito), os quais receberam cetamina (GC), na dose de 0,5mg/kg; ou metadona (GM), na dose de 0,3mg/kg; ou cetamina e metadona (GCM), nas doses de 0,5mg/kg e 0,3mg/kg, respectivamente, todos pela via intramuscular. Todos os grupos receberam os fármacos 20 minutos antes da indução anestésica, a qual foi realizada com propofol, e a manutenção com isoflurano. Os parâmetros avaliados foram a mensuração do cortisol nos momentos M0 (basal - antes da cirurgia), M1(transoperatório), M2, M3, M4, M8, M12 e M24 (duas, três, quatro, oito, 12 e 24 horas após o término da cirurgia),e a do escore de dor por meio da escala multidimensional de dor aguda em felinos nos momentos M0, M2, M3, M4, M8, M12 e M24. Os valores de cortisol foram maiores no GC em comparação ao GM e ao GCM em M2 e M3. Os escores de dor foram maiores no GC nos momentos M2 e M3 em comparação ao GM e ao GCM, respectivamente. No somatório de pontos, no M2, o GC apresentou valores maiores que o GM e o GCM, e, no M4, o GC obteve valores maiores que o GCM. Em relação ao número de resgates no pós-operatório no GC, 8/8 dos animais necessitaram de resgate, no GM 5/8 e no GCM 3/8. Conclui-se que a associação de metadona e cetamina em gatas submetidas à OSH eletiva promove analgesia pós-operatória adequada e, assim, reduz o requerimento de analgésicos no período pós-operatório.(AU)

The prevention and control of pain are basic components to have an adequate anesthesia. The aim of this study was to investigate the postoperative analgesia of ketamine in subanestesica dose, of methadone and the association of both intramuscularly in cats. A total of 24 cats proven healthy were referred for elective ovariossalpingohisterectomia. The day before the beginning of the experiment animals were anesthetized for placing a catheter in the jugular vein for subsequent blood sampling for measurement of serum concentration of cortisol. The next day, animals were randomly allocated to three groups (n = 8), which received ketamine (GC) at a dose of 0.5mg/kg; methadone (GM) at a dose of 0.3mg/kg; methadone and ketamine (GCM) at doses of 0.5mg/kg and 0.3mg/kg, respectively, all in the intramuscular route. All groups received the drug 20 minutes before induction of anesthesia, which was performed with propofol and maintained with isoflurane. The parameters evaluated were the measurement of cortisol in moments M0 (baseline-before surgery), M1(intraoperative), M2, M3, M4, M8, M12 and M24 (2,3,4,8,12 and 24 hours after the end of surgery) and evaluation of pain score by multidimensional scale of acute pain in cats in the moments M0, M2, M3, M4, M8, M12 and M24. The cortisol levels were higher in GC compared to GM and GCM in M2 and M3. Pain scores were higher in GC in moments M2 and M3 compared to GM and GCM, respectively. In summation of points in M2, GC showed higher values than GM and GCM, and M4, GC obtained values greater than GCM. Comparing the number of rescues postoperatively in GC 8/8 of animals required rescue, in GM /8 and in GCM 3/8. It was concluded that the combination of methadone and ketamine in cats undergoing elective OSH provides adequate postoperative analgesia, reducing the requirement for analgesics in the postoperative period.(AU)

Solid-phase microextraction in the determination of methadone in human saliva by gas chromatography-mass spectrometry.

Solid-phase microextraction (SPME) with a 100-microm polydimethylsiloxane film fiber was applied to the determination of methadone and 2-ethylidine-3,3-diphenylpyrrolidine (EDDP) by GC-MS in human saliva and compared with liquid-liquid extraction. A shorter extraction time of 30 min with the fiber was obtained, speeding up the total analysis time. Linearity was found for SPME from 0.05 to 2.0 microg/mL (r = 0.9976 for methadone; r = 0.9988 for EDDP) with precision between 0.7 and 4.3% for saliva spiked with 0.2 and 1.5 microg/mL of methadone and EDDP. The limit of detection using SPME was 0.04 microg/mL for methadone and 0.008 microg/mL for EDDP. Analytical recoveries of SPME and liquid-liquid extraction ranged from 98.8 to 103.6%. The use of deuterated internal standard by both methods have yielded comparable results. Thus, the SPME method is highly accurate, precise, and useful for determination of methadone and EDDP in saliva.

Use of solid-phase microextraction (SPME) for the determination of methadone and EDDP in human hair by GC-MS.

Solid-phase microextraction (SPME) is a new extraction technique with many advantages: small sample volume, simplicity, quickness and solvent-free. It is mainly applied to environmental analysis, but is also useful for the extraction of drugs from biological samples. In this paper the use of SPME is proposed for the determination of methadone and its main metabolite EDDP in hair by GC-MS. The hair samples were washed, cut into 1-mm segments, and incubated with Pronase E for 12 h. A 100-micron polydimethylsiloxane (PDMS) film fibre was submerged for 30 min in a diluted solution of the hydrolysis liquid (1:4 with borax buffer) containing methadone-d3 and EDDP-d3 as internal standards. Once the microextraction was concluded the fibre was directly inserted into the CG injection port. Linearity was found for methadone and EDDP in the range studied, 1.0-50 ng/mg hair, with correlation coefficients higher than 0.99. Interassay relative standard deviation (R.S.D) was determined to be less than 13.30% for methadone and less than 8.94% for EDDP, at 3.0 and 30.0 ng/mg. Analytical recoveries were close to 100% for both compounds on spiked samples. The method was applied to the analysis of real hair samples from eight patients of a methadone maintenance programme. The concentration of methadone in hair ranged from 2.45 to 78.10 ng/mg, and for EDDP from 0.98 to 7.76 ng/mg of hair.