Farmacologia clínica da metadona peridural e intravenosa em cães / Clinical pharmacology of peridural and intravenous methadone in dogs

A metadona é um opióide que possui potência analgésica semelhante à da morfina. Doses elevadas de metadona intravenosa (0,5-1,0 mg/kg), apesar de reduzirem a concentração alveolar mínima do isoflurano (CAMISO), resultam em maior depressão cardíaca que a observada com a morfina intravenosa (1,0 mg/kg) em cães. Com a hipótese de que a metadona peridural poderia proporcionar vantagens clínicas em relação à metadona intravenosa (maior potencialização da anestesia inalatória e maior eficácia analgésica), os estudos apresentados objetivaram comparar aspectos farmacocinéticos e farmacodinâmicos destas vias de administração da metadona em cães. Nos dois estudos iniciais (Capítulos 1 e 2), os mesmos seis animais foram anestesiados com isoflurano e tratados com metadona (0,5 mg/kg) peridural ou intravenosa em ocasiões distintas. No primeiro estudo (Capítulo 1), para comparação da farmacocinética destas duas vias de administração, a concentração de metadona foi determinada no plasma e no líquor da cisterna magna antes e durante 450 minutos após a administração do opióide. No segundo estudo (Capítulo 2), a CAMISO foi mensurada antes e após 2,5 e 5 horas da administração da metadona, mediante a aplicação da estimulação nociceptiva em membro pélvico e torácico (via peridural) ou em membro pélvico apenas (via intravenosa). No último estudo (Capítulo 3), cadelas apresentando tumores mamários, após serem tratadas de forma preemptiva com metadona (0,5 mg/kg) peridural ou intravenosa (10 animais por grupo), foram submetidas à mastectomia unilateral. Nesta etapa, avaliou-se a concentração expirada de isoflurano (ETISO) necessária à realização da mastectomia e, no período pós-operatório, avaliou-se os escores de dor, limiares nociceptivos mecânicos (LNM) das cadeias mamárias e requerimento de resgates analgésicos...

Methadone is an opioid that has analgesic potency comparable to that of morphine. High doses of intravenous methadone (0.5-1.0 mg/kg), in spite of reducing the minimum alveolar concentration of isoflurane (MACISO), cause greater cardiac depression than intravenous morphine (1 mg/kg) in dogs. The studies presented here aimed to compare some pharmacokinetic and pharmacodynamic aspects of peridural and intravenous methadone in dogs, testing the hypothesis that peridural methadone could result in clinical advantages when compared to intravenous methadone (greater reduction in anesthetic requirements and greater analgesic efficacy). In the first 2 studies (Chapters 1 and 2), the same six animals underwent isoflurane anesthesia and were treated with methadone (0.5 mg/kg) administered via the peridural or intravenous routes during different occasions. During the first study (Chapter 1), in order to compare the pharmacokinetics of these two administration routes, methadone concentrations were determined in plasma and in the cisternal cerebrospinal fluid before and for 450 minutes after opioid injection. During the second study (Chapter 2), MACISO was measured before, 2.5 and 5 hours after methadone injection via nociceptive stimulation of the thoracic and pelvic limb (peridural) or the pelvic limb (intravenous). During the last series of studies (Chapter 3), bitches presented with mammary gland tumors were preemptively treated with peridural or intravenous methadone (0.5 mg/kg) (10 animals per group) and underwent unilateral mastectomy. The end-tidal isoflurane concentration (ETISO) necessary for maintaining surgical anesthesia was evaluated and, during the postoperative period, parameters evaluated included Glasgow pain scores, mechanical nociceptive thresholds (MNT) in the mammary glands, and requirement for supplemental analgesia...

Role of the endothelial factors: Nitric oxide, substance P and endothelin, in mediating circulatory effects of halothane and isoflurane

Endothelial cells [ECs] contribute to the regulation of blood pressure and blood flow by releasing vasodilators such as nitric oxide [NO], substance P [SP], prostacyclin [PGI [2]] and adrenomedullin, as well as vasoconstrictors including endothelin [ET] and platelet-activating factor [PAF]. Several previous studies have discussed the relation between anaesthetics and the vascular endothelium in vitro only and demonstrated that volatile anaesthetics [halothane and isoflurane] can alter endothelium-dependant vasodilatation in vitro. In vivo studies are scarce in that field. This could be attributed to the radical nature of NO and its very short half-life and involvement of labor-intensive assay and handling of radioactive isotopes. Consequently, determination of the more stable end products of NO, nitrite and nitrate, was used as a measure for NO production. It is the aim of the current study to make use of this technique to ascertain whether NO, as well as SP and ET, is actually involved in the circulatory effects of isoflurane/halothane, in the clinical context. The study was conducted on 40 patients of [ASA classes I and II], scheduled for open abdominal and/or pelvic procedures of minimum 1 hour duration. Reduction of MBP more than 20% of the preoperative level was considered hypotension. Induction in both groups was done by IV fentanyl [2 micro g/ kg], sodium thiopentone [4-7mg/kg] followed by vecuronium [0.1mg/kg] for intubation and long acting muscle relaxation. Anaesthesia was maintaied using 100% oxygen and halothane 0.5-1%, or isoflurane 0.6-1-2%, in groups Land II respectively. Mechanical ventilation was adjusted to maintain normocapnia. Nitrous oxide was omitted and increments of fentanyl and vecuronium were titrated to the patients' needs. Monitoring of arterial blood pressure and heart rate was done every 5 minutes. Reversal was done using prostigmine [0.08mg/kg] and atropine sulphate [0.02mg/kg]. Venous blood samples were collected before induction, 15, 30 and 60 minutes after initiation of anaesthesia [T0, T1, T2, T3], at cessation of anesthesia and fifteen minutes later [T4 and T5]. Plasma endothelin concentration was determined by enzyme immunoassay technique. Plasma substance P was measured by radioimmunoassay. Determination of serum nitrite and nitrate was done by a colorimetric assay. We have succeeded in ascertaining the role of nitric oxide in isoflurane-induced hypotension, but not halothane. The hypotensive effect of isoflurane which is known to be basically related to peripheral vasodilator mechanism may be via its stimulatory effect on vasodilator mediator [NO]. The role of ET and SP could be related to the short-term changes, mediated by the endothelium, in vasomotor tone in response to alterations in shear stress, in face of the significant hypertension that follows cessation of isoflurane anaesthesia

Sevoflurane versus isoflurane in normal and pre-eclamptic parturients undergoing cesarean delivery

One hundred and twenty pregnant women were randomly assigned to receive either isoflurane two groups] or sevoflurane [two groups] using on open [non-blinded] study design. Anesthesia was maintained with either isoflurane 0.5% end tidal or sevoflurane 1% end tidal in combination with nitrous [N2O] 50% in oxygen. Liver functions, kidney functions, complete blood count and coagulation profile were measured and recorded. Pharmacokinetic study included serum inorganic fluoride concentration and kinetics of serum inorganic fluoride. Also, blood pressure, heart rate, central venous pressure [CVP] monitoring, ECG, estimation of intra-operative blood loss, uterine tone, recovery profile and urine in 24 hours were also studied. Infant outcome was also evaluated by Apgar score, neurologic adaptive capacity score [NACS], umbilical artery blood gas, acid base status and serum fluoride level. From the results obtained, it was concluded that sevoflurane appears to be similar to isoflurane with a few exceptions. It appears similar to isoflurane in its effect on regional blood flows including the hepatic and renal circulation. The use of sevoflurane resulted in faster emergence than after isoflurane. The high serum fluoride levels associated with administration of sevoflurane anesthesia were not dangerous, because it did not reach the level that cause nephrotoxicity. Neonatal outcomes were similar after anesthesia with either isoflurane or sevoflurane. So, sevoflurane 1.0% is a suitable alternative to isoflurane 0.5% for maintenance of anesthesia in such cases, but in this era of cost containment and rationing of health resources, it remains to be seen whether sevoflurane will supplant isoflurane for obstetrical anesthesia

Effects of Electroacupuncture on Minimum Alveolar Concentration of Isoflurane and Cardiovascular System in Isoflurane Anesthetized Dogs

The effects of electroacupuncture (EA) on the minimum alveolar concentration (MAC) and on the cardiovascular system were evaluated with dogs under isoflurane anesthesia. Eight healthy male beagles were randomly assigned to six study groups (five heads/group) with washout intervals of 7 ~ 31 days between experiments for recovery and anesthetic clearance. MAC of isoflurane and cardiovascular parameters were determined after EA at nonacupoint and and at acupoints LI-4, SP-6, ST-36 and TH-8. Electroacupuncture for 30 minutes at LI-4, SP-6, ST-36 and TH-8 acupoints lowered the MAC of isoflurane by 17.5 +/- 3.1%, 21.3 +/- 8.0%, 20.5 +/- 8.2% and 15.6 +/- 3.1%, respectively (p < 0.05). However, electrical stimulation of nonacupoint did not induce a significant change in MAC of isoflurane. In the cardiovascular system, the ST-36 group did not induce any significant change in cardiovascular parameters. In the TH-8 group, the mean and diastolic arterial pressure and the systemic vascular resistance were decreased. In the LI-4 group, cardiac output and cardiac index decreased after EA. These results indicate that EA at LI-4, SP-6 and ST-36 have advantages in isoflurane anesthesia in terms of reducing the dose of anesthetics and minimizing cardiovascular side effects.

Influência do sevoflurano e do isoflurano na duraçäo do bloqueio neuromuscular produzido pelo rocurônio / Influence of sevoflurane and isoflurane in rocuronium-induced neuromuscular block duration

Justificativa e objetivos: Os efeitos dos agentes bloqueadores neuromusculares sobre a junçäo neuromuscular säo potencializados por anestésicos voláteis, de forma dose dependente. O objetivo deste estudo foi avaliar a influência do sevoflurano e do isoflurano na recuperaçäo do bloqueio neuromuscular produzido pelo rocurônio. Método: foram estudados 60 pacientes, estado físico ASA I e II, submetidos a cirurgias eletivas sob anestesia geral, distribuídos em dois grupos de acordo com o agente volátil empregado: Grupo I (sevoflurano e Grupo II (isoflurano). Todos os pacientes receberam midazolam (0,1 mg.kg elevado a menos 1) por via muscular como medicaçäo pré-anestésica, 30 minutos antes da cirurgia. A induçäo anestésica foi obtida com propofol (2,5 mg.kg elevado a menos 1). Os pacientes foram ventilados com oxigênio a 100 por cento sob máscara até o desaparecimento das quatro respostas à seqüência de quatro estímulos (SQE), quando foram realizadas as manobras de laringoscopia e intubaçäo traqueal. Os agentes voláteis para a manutençäo da anestesia foram introduzidos após a intubaçäo traqueal e empregados nas concentraçöes de 2 por cento e 1 por cento, respectivamente para o sevoflurano e isoflurano, em mistura de O2eN2O a 50 por cento. Doses adicionais de fentanil foram administradas na vigência de sinais clínicos de anestesia superficial. Os pacientes foram ventilados mecanicamente para manter PetCO2 entre 32 e 36 mmHg. Foram medidas as temperaturas corpórea e da pele sobre a regiäo hipotenar do lado monitorizado, que se mantiveram acima de 35 e 32ºC, respectivamente. A funçäo neuromuscular foi monitorizada com aceleromiografia, empregando-se a SQE a cada 15 segundos. Foram avaliados: a duraçäo clínica do bloqueio neuromuscular (T1 25 por cento) e o índice de recuperaçäo (IR=T1 25 - 75 por cento

Comparación hemodinámica entre isoflurane y sevoflurane en el paciente quemado / Hemodynamic comparison of isoflurane and sevoflurane in the burn patient

Se estudiaron prospectivamente 27 operaciones en 13 pacientes, con una superficie corporal total quemada media de 21 por ciento (10-57). La edad promedio fue de 37 años (16-78). Se excluyeron pacientes con distress respiratorio y/o con repercusión hemodinámica que requirieran drogas vasoactivas. En todos se obtuvo un perfil hemodinámico continuo, en tiempo real y no invasivo del gasto aórtico (GAM), presión arterial media (PAM), resistencia vasculares sistémicas (RVST) e intervalo tiempo sistólicos (ITS), PePi, LVET y relación PePi/LVET. Se inició la anestesia general con sevoflurane o isoflurane en forma randomizada y, en situación estable, se cambió de agente midiendo a los 30 minutos las eventuales repercusiones hemodinámicas. Ninguna de las diferencias fueron estadísticamente significativas. Todos los valores hemodinámicos medios de ambos agentes estuvieron dentro de los rangos de normalidad para esta etapa de los quemados. Como conclusión, parece no haber diferencias hemodinámicas significativas entre ambos agentes en este tipo particular de pacientes estudiado

Uso de la mascarilla laríngea en un paciente con quemadura eléctrica / Laryngeal mask in the anesthetic management in a patient with electrical burn

Se valoran las condiciones de oxigenación, ventilación y estado ácido-base en un paciente masculino de 29 años de edad que sufrió quemadura eléctrica, y que fue sometido a un programa de 11 intervenciones de cirugía reconstructiva bajo anestesia general balanceada con isofluorano-fentanyl y ventilación controlada mediante mascarilla laríngea (MLA). La MLA permitió alcanzar y mantener valores adecuados de PaO2 y SpO2, y PaCO2, durante los tiempos de la anestesia general balanceada que se analizaron; asimismo, las variables del estado ácido-base y función cardiovascular permanecieron en límites aceptables. Se concluye que la MLA es un aditamento útil y seguro para alcanzar y mantener satisfactorias condiciones de oxigenación y ventilación durante la anestesia general balanceada

Modificaciones de la concentración alveolar mínima de isofluorano con la administración de fentanil en infusión continua / Modifications of minimal alveolar concentration of isofluorane with administrations of fentanyl in continuos infusion

Se realizó el presente estudio prospectivo, observacional, transversal y comparativo en el Departamento de Anestesiología del Hospital ABC, en 20 pacientes sometidos a cirugía abdominal con estado físico ASA I-II, sin medicación preanestésica, divididos en dos grupos en forma aleatoria. Grupo control: 10 pacientes con manejo anestésico con técnica inhalatoria con isofluorano; y grupo problema: 10 pacientes con técnica anestésica balanceada con isofluorano y dosis de cebamiento de citrato de fentanil (5 ug/kg) e infusión continua de 0.05 ug/kg/min, comparando constantes hemodinámicas y requerimientos anestésicos en ambos grupos durante la intubación e incisión quirúrgica, contra la toma de parámetros preinducción. Se contrastaron las variables obtenidas por el método de t de Student considerando como valores significativos P< 0.05. Se observó una disminución significativa de la tensión arterial media y frecuencia cardiaca en el grupo manejado con fentanil e infusión continua. Tanbién se observó una reducción en 50 por ciento del requerimiento anestésico en el mismo grupo, siendo significativo estadísticamente