Efficacy of Continuous S(+)-Ketamine Infusion for Postoperative Pain Control: A Randomized Placebo-Controlled Trial.

Aim. A double-blind, randomized, placebo-controlled trial was designed to evaluate the efficacy of continuous intraoperative infusion of S(+)-ketamine under intravenous anesthesia with target-controlled infusion of remifentanil and propofol for postoperative pain control. Methods. Forty-eight patients undergoing laparoscopic cholecystectomy were assigned to receive continuous S(+)-ketamine infusion at a rate of 0.3 mg·kg(-1)·h(-1) (n = 24, intervention group) or an equivalent volume of saline at the same rate (n = 24, placebo group). The same target-controlled intravenous anesthesia was induced in both groups. Pain was assessed using a 0 to 10 verbal numeric rating scale during the first 12 postoperative hours. Pain scores and morphine consumption were recorded in the postanesthesia care unit (PACU) and at 4 and 12 hours after surgery. Results. Pain scores were lower in the intervention group at all time points. Morphine consumption did not differ significantly between groups during PACU stay, but it was significantly lower in the intervention group at each time point after PACU discharge (P = 0.0061). At 12 hours after surgery, cumulative morphine consumption was also lower in the intervention group (5.200 ± 2.707) than in the placebo group (7.525 ± 1.872). Conclusions. Continuous S(+)-ketamine infusion during laparoscopic cholecystectomy under target-controlled intravenous anesthesia provided better postoperative pain control than placebo, reducing morphine requirement. Trial Registration. This trial is registered with ClinicalTrials.gov NCT02421913.

Comparative study between fast and slow induction of propofol given by target-controlled infusion: expected propofol concentration at the effect site. Randomized controlled trial / Estudo comparativo entre indução rápida e lenta de propofol em infusão alvo-controlada: concentração de propofol prevista no local de ação. Ensaio clínico aleatório / Estudio comparativo entre inducción rápida y lenta de propofol en infusión objetivo-controlada: concentración de propofol prevista en la región de acción. Ensayo clínico aleatorizado

BACKGROUND AND OBJECTIVE: Studies have shown that the rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26 min-1) in loss of consciousness during fast or slow induction. METHOD: The study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26 min-1) with target concentration (Tc) at 2.0-µg mL-1 were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1 µg mL-1, successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0 µg mL-1) at effect site, and waited until loss of consciousness. RESULTS: In rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67 ± 0.76 and 2.50 ± 0.56 µg mL-1, respectively, p = 0.004). CONCLUSION: The predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site. .

JUSTIFICATIVA E OBJETIVO: estudos mostraram que a taxa de infusão de propofol pode influenciar na concentração prevista de propofol no local de ação (Ce). O objetivo deste estudo foi avaliar a Ce prevista pelo modelo farmacocinético de Marsh (ke0 0,26 min-1) na perda da consciência durante indução rápida ou lenta. MÉTODO: participaram deste estudo 28 pacientes, divididos aleatoriamente em dois grupos iguais. No grupo indução lenta (L), foram induzidos com propofol em infusão alvo-controlada (IAC) plasmática, modelo farmacocinético de Marsh (ke0 0,26 min-1), com concentração alvo (Ca) em 2,0 µg.ml-1. Quando a concentração de propofol prevista no local de ação (Ce) atingia metade do valor da Ca, aumentava-se a Ca para Ca anterior + 1 µg.ml-1. Assim sucessivamente até o momento da perda da consciência do paciente. No grupo indução rápida (R), os pacientes foram induzidos com propofol em IAC plasmática com Ca em 6,0 µg.ml-1 e aguardava-se a perda da consciência do paciente. RESULTADOS: no grupo indução rápida, a Ce na perda da consciência foi significativamente mais baixa em relação ao grupo de indução lenta (1,67 ± 0,76 e 2,50 ± 0,56 µg.ml-1, respectivamente, p = 0,004). CONCLUSÃO: a concentração prevista de propofol no local de ação durante a perda da consciência é diferente numa indução rápida e numa indução lenta, até com o mesmo modelo farmacocinético de propofol e a mesma constante de equilíbrio entre o plasma e o local de ação. .

JUSTIFICACIÓN Y OBJETIVO: Varios estudios han demostrado que la tasa de infusión del propofol puede influir en la concentración prevista de propofol en la región de acción (Ce). El objetivo de este estudio fue evaluar la Ce prevista por el modelo farmacocinético de Marsh (ke0 0,26 min-1) en la pérdida de la consciencia durante inducción rápida o lenta. MÉTODO: Participaron en este estudio 28 pacientes, divididos aleatoriamente en 2 grupos iguales. En el grupo de inducción lenta, se administró una inducción de propofol en infusión objetivo-controlada plasmática, modelo farmacocinético de Marsh (ke0 0,26 min-1), con concentración objetivo (Ca) en 2µg/ml-1. Cuando la concentración de propofol prevista en la Ce alcanzaba la mitad del valor de la Ca, esta aumentaba a la Ca anterior +1 µg/ml-1. Así fue sucesivamente hasta el momento de la pérdida de la consciencia del paciente. En el grupo de inducción rápida, los pacientes recibieron inducción con propofol en infusión objetivo-controlada plasmática con Ca en 6 µg/ml-1 y se esperó hasta la pérdida de consciencia del paciente. RESULTADOS: En el grupo inducción rápida, la Ce en la pérdida de la consciencia fue significativamente más baja con relación al grupo de inducción lenta (1,67 ± 0,76 y 2,50 ± 0,56 µg/ml-1, respectivamente; p = 0,004). CONCLUSIÓN: La concentración prevista de propofol en la Ce durante la pérdida de la consciencia es diferente en una inducción rápida y en una inducción lenta, hasta con el mismo modelo farmacocinético de propofol y la misma constante de equilibrio entre el plasma y la región de acción. .

[Comparative study between fast and slow induction of propofol given by target-controlled infusion: expected propofol concentration at the effect site. Randomized controlled trial]. / Estudo comparativo entre indução rápida e lenta de propofol em infusão alvo-controlada: concentração de propofol prevista no local de ação. Ensaio clínico aleatório.

BACKGROUND AND OBJECTIVE: studies have shown that rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26min(-1)) in loss of consciousness during fast or slow induction. METHOD: the study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26min(-1)) with target concentration (Tc) at 2.0-µg.mL(-1) were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1µg.mL(-1), successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0µg.ml(-1)) at Es, and waited until loss of consciousness. RESULTS: in rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67±0.76 and 2.50±0.56µg.mL(-1), respectively, p=0.004). CONCLUSION: the predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site.

Pharmacodynamic evaluation and physical/chemical analysis of two formulations of propofol used in target-controlled infusion.

BACKGROUND AND OBJECTIVES: There are several formulations of propofol available to the anesthesiologist for clinical use. The aim of this study was to analyze the physicochemical properties, pharmacodynamic effect, and pharmaceutical and clinical equivalence of the reference drug propofol as well as a similar formulation. METHOD: Sixteen volunteers were enrolled in this randomized, double-blind, and paired study of Diprivan and Propovan formulations. Formulations were given as target-controlled infusion with target concentration of 3.0 µg.mL(-1) for 15 minutes. Variables studied were the area under the curve (AUC) of the bispectral index (BIS) graph regarding time, minimum BIS reached and time to reach it, and recovery time. The two formulations were sent to analysis of particle size of lipid emulsion, surface potential, and active principle quantification. RESULTS: There was no difference between the formulations when comparing AUC, minimum BIS reached and time to reach it. The similar formulation recovery time was lower compared to the reference formulation (eight and 10 min, respectively, p=0.014). Mean particle size of lipid emulsion, surface potential, and active ingredient quantification were similar for both formulations. CONCLUSION: There was no clinically significant difference between the use of propofol, reference Diprivan, and the similar Propovan during infusion. However, the recovery time was longer with the reference drug. Although analysis of both formulations studied show similar results regarding its physicochemical characterization, further studies should be conducted to justify this difference.

Avaliação farmacodinâmica e análise físico-química de duas formulações de propofol usadas em infusão alvo-controlada / Pharmacodynamic evaluation and physical/chemical analysis of two formulations of propofol used in target-controlled infusion / Evaluación farmacodinámica y análisis físico-químico de dos formulaciones de propofol usadas en infusión objeto-controlada

JUSTIFICATIVA E OBJETIVOS: Existem várias formulações de propofol para uso clínico à disposição do anestesiologista. O objetivo desse estudo foi analisar as propriedades físico-químicas, o efeito farmacodinâmico e a equivalência farmacêutica e clínica do fármaco referência de propofol e uma formulação similar. MÉTODOS: Dezesseis voluntários participaram desse estudo aleatório, duplamente encoberto e pareado entre as formulações Diprivan® e Propovan®. As formulações foram administradas em regime de infusão alvo-controlada com concentração-alvo de 3,0 µg.mL-1 por 15 minutos. As variáveis estudadas foram a área sob a curva (ASC) do gráfico do índice bispectral (BIS) em relação ao tempo, o BIS mínimo atingido e o tempo para tal e o tempo de recuperação. As duas formulações foram submetidas às análises de tamanho de partículas da emulsão lipídica, potencial de superfície e quantificação de princípio ativo. RESULTADOS: Não houve diferença entre as formulações quando se comparou a ASC, BIS mínimo atingido e o tempo decorrido para tal. O tempo de recuperação com a formulação similar foi menor em relação à referência (oito e 10 min, respectivamente, p = 0,014). O tamanho médio de partículas da emulsão lipídica, potencial de superfície e a quantificação de princípio ativo foram semelhantes nas duas formulações. CONCLUSÃO: Não houve diferença clínica significativa entre o uso de propofol referência Diprivan® e seu similar Propovan® durante a infusão. Entretanto, o tempo de recuperação foi mais prolongado com o fármaco referência. Embora as análises com as duas formulações estudadas mostrarem resultados semelhantes quanto a sua caracterização físico-química, outros estudos devem ser realizados para justificar tal diferença.

BACKGROUND AND OBJECTIVES: There are several formulations of propofol available to the anesthesiologist for clinical use. The aim of this study was to analyze the physicochemical properties, pharmacodynamic effect, and pharmaceutical and clinical equivalence of the reference drug propofol as well as a similar formulation. METHOD: Sixteen volunteers were enrolled in this randomized, double-blind, and paired study of Diprivan® and Propovan® formulations. Formulations were given as target-controlled infusion with target concentration of 3.0 μg.mL-1 for 15 minutes. Variables studied were the area under the curve (AUC) of the bispectral index (BIS) graph regarding time, minimum BIS reached and time to reach it, and recovery time. The two formulations were sent to analysis of particle size of lipid emulsion, surface potential, and active principle quantification. RESULTS: There was no difference between the formulations when comparing AUC, minimum BIS reached and time to reach it. The similar formulation recovery time was lower compared to the reference formulation (eight and 10 min, respectively, p = 0.014). Mean particle size of lipid emulsion, surface potential, and active ingredient quantification were similar for both formulations. CONCLUSION: There was no clinically significant difference between the use of propofol, reference Diprivan®, and the similar Propovan® during infusion. However, the recovery time was longer with the reference drug. Although analysis of both formulations studied show similar results regarding its physicochemical characterization, further studies should be conducted to justify this difference.

JUSTIFICATIVA Y OBJETIVOS: Existen varias formulaciones de propofol para el uso clínico que están disponibles para el anestesiólogo. El objetivo de este estudio, fue analizar las propiedades físico-químicas, el efecto farmacodinámico y la equivalencia farmacéutica y clínica del fármaco referencia de propofol y una formulación similar. MÉTODO: Dieciséis voluntarios participaron en este estudio aleatorio, doble ciego y pareado entre las formulaciones Diprivan® y Propovan®. Las formulaciones fueron administradas en un régimen de infusión objeto-controlada con una concentración objetivo de 3,0 µg.mL-1 durante 15 minutos. Las variables estudiadas fueron el área bajo la curva (ASC) del gráfico del índice bispectral (BIS) con relación al tiempo, el BIS mínimo alcanzado y el tiempo para tal, y el tiempo de recuperación. Las dos formulaciones se sometieron a los análisis de tamaño de partículas de la emulsión lipídica, potencial de superficie y cuantificación del principio activo. RESULTADOS: No hubo diferencia entre las formulaciones cuando se comparó la ASC, el BIS mínimo alcanzado y el tiempo transcurrido para tal. El tiempo de recuperación con la formulación similar fue menor con relación a la referencia (8 y 10 min, respectivamente, p = 0,014). El tamaño promedio de partículas de la emulsión lipídica, potencial de superficie y la cuantificación del principio activo, fueron similares en las dos formulaciones. CONCLUSIONES: No hubo diferencia clínica significativa entre el uso de propofol referencia Diprivan® y su similar Propovan® durante la infusión. Sin embargo, el tiempo de recuperación se extendió más con el fármaco de referencia. Aunque los análisis de las formulaciones estudiadas muestren resultados similares en cuanto a su caracterización físico-química, otros estudios deben ser realizados para justificar tal diferencia.

Pharmacodynamic evaluation and physical/chemical analysis of two formulations of propofol used in target-controlled infusion.

BACKGROUND AND OBJECTIVES: There are several formulations of propofol available to the anesthesiologist for clinical use. The aim of this study was to analyze the physicochemical properties, pharmacodynamic effect, and pharmaceutical and clinical equivalence of the reference drug propofol as well as a similar formulation. METHOD: Sixteen volunteers were enrolled in this randomized, double-blind, and paired study of Diprivan® and Propovan® formulations. Formulations were given as target-controlled infusion with target concentration of 3.0 µg.mL(-1) for 15 minutes. Variables studied were the area under the curve (AUC) of the bispectral index (BIS) graph regarding time, minimum BIS reached and time to reach it, and recovery time. The two formulations were sent to analysis of particle size of lipid emulsion, surface potential, and active principle quantification. RESULTS: There was no difference between the formulations when comparing AUC, minimum BIS reached and time to reach it. The similar formulation recovery time was lower compared to the reference formulation (eight and 10 min, respectively, p = 0.014). Mean particle size of lipid emulsion, surface potential, and active ingredient quantification were similar for both formulations. CONCLUSION: There was no clinically significant difference between the use of propofol, reference Diprivan®, and the similar Propovan® during infusion. However, the recovery time was longer with the reference drug. Although analysis of both formulations studied show similar results regarding its physicochemical characterization, further studies should be conducted to justify this difference.

Avaliação clínica de duas ke0 no mesmo modelo farmacocinético de propofol: estudo da perda e recuperação da consciência / Clinical evaluation of two ke0 in the same pharmacokinetic propofol model: study on loss and recovery of consciousness / Evaluación clínica de dos ke0 en el mismo modelo farmacocinético de propofol: estudio de la pérdida y de la recuperación de la conciencia

JUSTIFICATIVA E OBJETIVOS: A constante de equilíbrio entre o plasma e o sítio efetor (ke0) é utilizada pelos modelos farmacocinéticos para prever a concentração do fármaco em seu local de ação (Ce). Seria interessante que a Ce de propofol fosse semelhante na perda e na recuperação da consciência. O objetivo deste estudo foi avaliar o desempenho clínico de duas diferentes ke0 (rápida = 1,21 min-1 e lenta = 0,26 min-1) com relação à Ce durante a perda e a recuperação da consciência, usando o modelo farmacocinético de Marsh. MÉTODO: Participaram deste estudo 20 voluntários adultos sadios do sexo masculino. Em todos os voluntários, administrou-se propofol em regime de infusão alvo-controlada, modelo farmacocinético de Marsh ke0 rápida e, em outra oportunidade, usou-se o mesmo modelo farmacocinético com a ke0 lenta. Inicialmente, o propofol foi infundido em concentração-alvo plasmática de 3,0µg.mL-1. A perda de consciência e a recuperação de consciência basearam-se na resposta ao estímulo verbal. A Ce foi anotada no momento da perda e da recuperação da consciência. RESULTADOS: Na perda e na recuperação da consciência a Ce pela ke0 rápida foi diferente (3,64 ± 0,78 e 1,47 ± 0,29µg.mL-1, respectivamente, p < 0,0001), enquanto com a ke0 lenta a Ce foi semelhante (2,20 ± 0,70 e 2,13 ± 0,43µg.mL-1, respectivamente, p = 0,5425). CONCLUSÕES: Do ponto de vista clínico, a ke0 lenta (0,26 min-1) incorporada ao modelo farmacocinético de Marsh apresentou melhor desempenho que a ke0 rápida (1,21 min-1), uma vez que a concentração de propofol prevista em seu local de ação na perda e recuperação da consciência foi semelhante.

BACKGROUND AND OBJECTIVE: The constant equilibrium between the plasma and effect site (ke0) is used by pharmacokinetic models to calculate a drug concentration in its site of action (Ce). It would be interesting if Ce of propofol was similar at loss and recovery of consciousness. The objective of this study was to evaluate the clinical performance of two different ke0 (fast = 1.21 min-1, and slow = 0.26 min-1) in relation to Ce during loss and recovery of consciousness using Marsh pharmacokinetic model. METHODS: Twenty healthy adult male volunteers participated in this study. In all volunteers propofol was administered as target-controlled infusion, Marsh pharmacokinetic model for fast ke0 and, at a different time, the same pharmacokinetic model with slow ke0 was used. Initially, propofol was infused with a serum target-controlled infusion of 3.0 µg.mL-1. Loss of consciousness and recovery of consciousness were based on response to verbal stimulus. Ce was recorded at the moment of loss and recovery of consciousness. RESULTS: On loss and recovery of consciousness, the Ce for fast ke0 was different (3.64 ± 0.78 and 1.47 ± 0.29 µg.mL-1, respectively, p < 0.0001), while with slow ke0 the Ce was similar (2.20 ± 0.70 and 2.14 ± 0.43 µg.mL-1, respectively, p = 0.5425). CONCLUSIONS: Clinically, the slow ke0 (0.26 min-1) incorporated in the Marsh pharmacokinetic model showed better performance than the fast ke0 (1.21 min-1), since the calculated concentration of propofol at the effect site on loss and recovery of consciousness was similar.

JUSTIFICATIVA Y OBJETIVOS: La constante de equilibrio entre el plasma y el sitio efector (ke0), se usa por los modelos farmacocinéticos para prever la concentración del fármaco en su región de acción (Ce). Sería interesante que el Ce de propofol fuese similar en la pérdida y en la recuperación de la conciencia. El objetivo de este estudio, fue evaluar el desempeño clínico de dos diferentes ke0 (rápida = 1,21 min-1 y lenta = 0,26 min-1), con relación a la Ce durante la pérdida y la recuperación de la conciencia, usando el modelo farmacocinético de Marsh. MéTODO: Participaron en este estudio, 20 voluntarios adultos sanos del sexo masculino. A todos los voluntarios se les administró propofol en régimen de infusión objeto controlada, modelo farmacocinético de Marsh ke0 rápida y en otro momento, se usó el mismo modelo farmacocinético con a ke0 lenta. Inicialmente, el propofol se infundió en concentración-objeto plasmática de 3,0 µg.mL-1. La pérdida de la conciencia y la recuperación de la conciencia estuvieron basadas en la respuesta al estímulo verbal. La Ce fue anotada en el momento de la pérdida y de la recuperación de la conciencia. RESULTADOS: En la pérdida y en la recuperación de la conciencia, la Ce por la ke0 rápida, fue diferente (3,64 ± 0,78 y 1,47 ± 0,29 µg.mL-1, respectivamente, p < 0,0001), mientras que con la ke0 lenta la Ce fue parecida (2,20 ± 0,70 y 2,13 ± 0,43 µg.mL-1, respectivamente, p = 0,5425). CONCLUSIONES: Desde el punto de vista clínico, la ke0 lenta (0,26 min-1) incorporada al modelo farmacocinético de Marsh, presentó un mejor desempeño que la ke0 rápida (1,21 min-1), pues la concentración de propofol prevista en su región de acción en la pérdida y en la recuperación de la conciencia fue similar.

Clinical evaluation of two Ke0 in the same pharmacokinetic propofol model: study on loss and recovery of consciousness.

BACKGROUND AND OBJECTIVE: The constant equilibrium between the plasma and effect site (ke0) is used by pharmacokinetic models to calculate a drug concentration in its site of action (Ce). It would be interesting if Ce of propofol was similar at loss and recovery of consciousness. The objective of this study was to evaluate the clinical performance of two different ke0 (fast = 1.21 min(-1), and slow = 0.26 min(-1)) in relation to Ce during loss and recovery of consciousness using Marsh pharmacokinetic model. METHODS: Twenty healthy adult male volunteers participated in this study. In all volunteers propofol was administered as target-controlled infusion, Marsh pharmacokinetic model for fast ke0 and, at a different time, the same pharmacokinetic model with slow ke0 was used. Initially, propofol was infused with a serum target-controlled infusion of 3.0 µg.mL(-1). Loss of consciousness and recovery of consciousness were based on response to verbal stimulus. Ce was recorded at the moment of loss and recovery of consciousness. RESULTS: On loss and recovery of consciousness, the Ce for fast ke0 was different (3.64 ± 0.78 and 1.47 ± 0.29 µg.mL(-1), respectively, p < 0.0001), while with slow ke0 the Ce was similar (2.20 ± 0.70 and 2.14 ± 0.43 µg.mL(-1), respectively, p = 0.5425). CONCLUSIONS: Clinically, the slow ke0 (0.26 min(-1)) incorporated in the Marsh pharmacokinetic model showed better performance than the fast ke0 (1.21 min(-1)), since the calculated concentration of propofol at the effect site on loss and recovery of consciousness was similar.

[Efficacy of intraoperative methadone and clonidine in pain control in the immediate postoperative period after the use of remifentanil]. / Eficácia do emprego da metadona ou da clonidina no intraoperatório para controle da dor pós-operatória imediata após uso de remifentanil.

BACKGROUND AND OBJECTIVES: Due to its pharmacokinetic characteristics, remifentanil does not promote residual analgesia in the immediate postoperative period. The objective of this study was to compare the efficacy of methadone and clonidine in the control of postoperative pain of videolaparoscopic surgeries under total intravenous anesthesia with target-controlled remifentanil infusion. METHODS: One hundred and twenty-six patients, ages 18 to 65 years, ASA I and II, of both genders, scheduled for laparoscopic surgeries, participated in this randomized, double- blind, placebo-controlled study. After venipuncture, intravenous ketoprofen and dypirone were administered. Target-controlled infusion of remifentanil and propofol was used for induction and maintenance of anesthesia. Before beginning the procedure, an intravenous solution containing 0.1 mg.kg-1 of methadone (methadone group), 2.0 (1/4)g.kg-1 of clonidine (clonidine group), or NS (placebo group) was administered. In the post-anesthetic care unit, postoperative pain was evaluated by the Verbal Numeric Scale (VNS). Absence of pain was defined as a score < 2, and pain as a score of > 3. RESULTS: The incidence of pain in the methadone group was significantly lower than in the clonidine and placebo groups (11, 21, and 23, respectively; p < 0.02). Significant differences in the incidence of pain in the placebo and clonidine groups were not observed. CONCLUSIONS: Methadone was more effective than clonidine in the control of postoperative pain in videolaparoscopic surgeries under total intravenous anesthesia with remifentanil; and using clonidine was not better than not using it.

Eficácia do emprego da metadona ou da clonidina no intraoperatório para controle da dor pós-operatória imediata após uso de remifentanil / Eficacia del empleo de la metadona o de la clonidina en el intraoperatorio para control del dolor postoperatorio inmediato después del uso de remifentanil / Efficacy of intraoperative methadone and clonidine in pain control in the immediate postoperative period after the use of remifentanil

JUSTIFICATIVA E OBJETIVOS: Por suas características farmacocinéticas, o remifentanil não promove efeito analgésico residual no pós-operatório imediato. O objetivo deste estudo foi comparar a eficácia da metadona e da clonidina no controle da dor pós-operatória de intervenções cirúrgicas videolaparoscópicas sob anestesia venosa total com infusão alvo-controlada de remifentanil. MÉTODO: Participaram deste estudo aleatório, duplamente encoberto e placebo-controlado, 126 pacientes com idade entre 18 e 65 anos, ASA PS 1 e 2 de ambos os sexos, que estavam previamente programados para a realização de intervenções cirúrgicas laparoscópicas. Após venopunção, os pacientes receberam por via venosa cetoprofeno e dipirona. A indução e manutenção da anestesia foram realizadas com infusão alvo-controlada de remifentanil e propofol. Antes do início da operação, os pacientes recebiam por via venosa a solução contendo metadona 0,1 mg.kg-1 (grupo metadona), clonidina 2,0 »g.kg-1 (grupo clonidina) ou solução fisiológica a 0,9 por cento (grupo placebo). Na sala de recuperação pós-anestésica, a dor pós-operatória foi avaliada através da escala numérica verbal (ENV). Foi considerado paciente sem dor quando a ENV < 2 e paciente com dor quando > 3. RESULTADOS: A incidência de dor no grupo metadona foi significativamente menor em relação ao grupo clonidina e grupo placebo (11, 21 e 23, respectivamente; p < 0,02). Não houve diferença significativa na incidência de dor entre pacientes do grupo clonidina e placebo. CONCLUSÕES: Em relação ao controle da dor pós-operatória de intervenções cirúrgicas videolaparoscópicas sob anestesia venosa total com uso de remifentanil, o emprego da metadona foi mais eficaz que a clonidina; e usar clonidina não foi melhor que não usar.

BACKGROUND AND OBJECTIVES: Due to its pharmacokinetic characteristics, remifentanil does not promote residual analgesia in the immediate postoperative period. The objective of this study was to compare the efficacy of methadone and clonidine in the control of postoperative pain of videolaparoscopic surgeries under total intravenous anesthesia with target-controlled remifentanil infusion. METHODS: One hundred and twenty-six patients, ages 18 to 65 years, ASA I and II, of both genders, scheduled for laparoscopic surgeries, participated in this randomized, double- blind, placebo-controlled study. After venipuncture, intravenous ketoprofen and dypirone were administered. Target-controlled infusion of remifentanil and propofol was used for induction and maintenance of anesthesia. Before beginning the procedure, an intravenous solution containing 0.1 mg.kg-1 of methadone (methadone group), 2.0 »g.kg-1 of clonidine (clonidine group), or NS (placebo group) was administered. In the post-anesthetic care unit, postoperative pain was evaluated by the Verbal Numeric Scale (VNS). Absence of pain was defined as a score < 2, and pain as a score of > 3. RESULTS: The incidence of pain in the methadone group was significantly lower than in the clonidine and placebo groups (11, 21, and 23, respectively; p < 0.02). Significant differences in the incidence of pain in the placebo and clonidine groups were not observed. CONCLUSIONS: Methadone was more effective than clonidine in the control of postoperative pain in videolaparoscopic surgeries under total intravenous anesthesia with remifentanil; and using clonidine was not better than not using it.

JUSTIFICATIVA Y OBJETIVOS: El remifentanil, por sus características farmacocinéticas, no genera un efecto analgésico residual en el postoperatorio inmediato. El objetivo de este estudio fue comparar la eficacia de la metadona y de la clonidina en el control del dolor postoperatorio de intervenciones quirúrgicas videolaparoscópicas bajo anestesia venosa total con infusión objeto controlada de remifentanil. MÉTODO: Participaron en este estudio aleatorio, doble ciego y placebo-controlado, 126 pacientes con una edad entre los 18 y los 65 años, ASA PS 1 y 2 de ambos sexos, que estaban previamente programados para la realización de las intervenciones quirúrgicas laparoscópicas. Después de la venopunción, los pacientes recibieron por vía venosa cetoprofeno y dipirona. La inducción y el mantenimiento de la anestesia fue realizada con infusión objeto controlada de remifentanil y propofol. Antes del inicio de la operación, los pacientes recibieron por vía venosa la solución conteniendo metadona 0,1 mg.kg-1 (grupo metadona), clonidina 2,0 »g.kg-1 (grupo clonidina) o solución fisiológica a 0,9 por ciento (grupo placebo). En la sala de recuperación postanestésica, el dolor postoperatorio se evaluó a través de la escala numérica verbal (ENV). Se tuvo en cuenta el paciente sin dolor cuando la ENV era < 2 y el paciente con dolor cuando había > 3. RESULTADOS: La incidencia de dolor en el grupo metadona fue significativamente menor con relación al grupo clonidina y al grupo placebo (11, 21 y 23, respectivamente; p < 0,02). No hubo diferencia significativa en la incidencia de dolor entre los pacientes del grupo clonidina y placebo. CONCLUSIONES: Con relación al control del dolor postoperatorio de intervenciones quirúrgicas videolaparoscópicas bajo anestesia venosa total con el uso de remifentanil, el empleo de la metadona fue más eficaz que la clonidina. Y usar clonidina no fue mejor que no usarla.

Remifentanil versus Sufentanil em infusão contínua em intervenções cirúrgicas videolaparoscópicas: estudo comparativo / Continuous infusion of remifentanil versus sufentanil in videolaparoscopic surgeries: a comparative study

JUSTIFICATIVA E OBJETIVOS: A infusão contínua (IC) de remifentanil na técnica de anestesia venosa total é prática comum. Já o sufentanil em IC para cirurgias de curta/média duração tem sido pouco utilizado. O objetivo desse estudo foi comparar duas técnicas de anestesia venosa total, utilizando remifentanil ou sufentanil em IC, quanto ao comportamento anestésico no intra-operatório e às características da recuperação anestésica em pacientes submetidos à videolaparoscopia. MÉTODO: Participaram desse estudo 60 pacientes divididos em 2 grupos iguais (GR e GS). O GR foi induzido com remifentanil IC e o GS com sufentanil em bolus associado à IC. A IC de remifentanil era desligada ao fim da cirurgia, enquanto a IC de sufentanil, 20 minutos antes. Os pacientes receberam no intra-operatório cetoprofeno e dipirona. Como analgésico de resgate na sala de recuperação pós-anestésica (SRPA) foi utilizado tramadol. Foram analisados as variações da pressão arterial média (PAM) e freqüência cardíaca (FC), o tempo de despertar, o consumo de propofol, as intercorrências na SRPA e o tempo de permanência na SRPA. RESULTADOS: A média da PAM foi maior no GS em relação ao GR (91,9 × 77,6, p < 0,0001). A incidência de dor foi significativamente maior no GR em relação ao GS (22 × 1 paciente, p < 0,0001). A incidência de NVPO foi maior no GR em relação ao GS (10 × 2 pacientes, p = 0,0098). A média do tempo de permanência na SRPA foi maior no GR em relação ao GS (76 × 49 min, p < 0,0001). CONCLUSÕES: O controle hemodinâmico foi satisfatório nos grupos. A IC de sufentanil promoveu melhor controle da dor no pós-operatório com menor consumo de analgésico de resgate; conseqüentemente, houve menor incidência de NVPO e menor tempo de permanência na SRPA.

BACKGROUND AND OBJECTIVES: Continuous infusion (CI) of remifentanil is common in total intravenous anesthesia. On the other hand, CI of sufentanil for short/medium-term surgeries has not been widely used. The objective of this study was to compare two techniques of total intravenous anesthesia, using CI of remifentanil or sufentanil, regarding their intraoperative behavior and characteristics of recovery of patients undergoing videolaparoscopic surgeries. METHODS: Sixty patients, equally divided in 2 groups (RG and SG), participated in this study. Continuous infusion of remifentanil was used for anesthetic induction in RG, while a bolus of sufentanil associated with CI of this drug was used in SG. The CI of remifentanil was discontinued at the end of the surgery, while the CI of sufentanil was discontinued 20 minutes before the end of the surgery. Patients received ketoprofen and dypirone intraoperatively. Tramadol was used for rescue analgesia in the recovery room. Variations of mean arterial pressure (MAP) and hard reate (HR), time for awakening, propofol consumption, intercurrences in the recovery room, and time of stay in the recovery room were analyzed. RESULTS: Mean MAP was greater in SG than in RG (91.9 × 77.6, p < 0.0001). The incidence of pain was significantly greater in RG than on SG (22 × 1 patient, p < 0.0001). The incidence of postoperative nausea and vomiting (PONV) was greater in RG than in SG (10 × 2 patients, p < 0.0098). The mean time of stay in the recovery room was greater in RG than in SG (76 × 49 min, p < 0.0001). CONCLUSIONS: Hemodynamic control was satisfactory in both groups. Continuous infusion of sufentanil promoted better postoperative pain control with decreased consumption of rescue analgesic and, consequently, reduced incidence of PONV and reduced time of stay in the recovery room.

JUSTIFICATIVA Y OBJETIVOS: La infusión continua (IC) de remifentanil en la técnica de anestesia venosa total es una práctica común. Ya el sufentanil en IC para cirugías de corta/media duración ha sido poco utilizado. El objetivo de este estudio fue el de comparar dos técnicas de anestesia venosa total, utilizando remifentanil o sufentanil en IC, en cuanto al comportamiento anestésico en el intraoperatorio y en cuanto a las características de la recuperación anestésica en pacientes sometidos a la videolaparoscopía. MÉTODO: Participaron en el estudio 60 pacientes divididos en 2 grupos iguales (GR y GS). El GR fue inducido con remifentanil IC y el GS con sufentanil en bolus asociado a IC. La IC de remifentanil se desconectaba al final de la cirugía, mientras que la IC de sufentanil 20 minutos antes. Los pacientes recibieron en el intraoperatorio cetoprofeno y dipirona. Como analgésico de rescate en la sala de recuperación pos anestésica (SRPA) se usó el tramadol. Fueron analizadas las variaciones de la PAM y FC, tiempo de despertar, consumo de propofol, intercurrencias en la SRPA y tiempo de permanencia en la SRPA. RESULTADOS: El promedio de la PAM fue mayor en el GS con relación al GR (91,9 × 77,6, p < 0,0001). La incidencia de dolor fue significativamente mayor en el GR con relación al GS (22 × 1 paciente, p < 0,0001). La incidencia de NVPO fue mayor en el GR con relación al GS (10 × 2 pacientes, p = 0,0098). El promedio del tiempo de permanencia en la SRPA fue mayor en el GR en con relación al GS (76 × 49 min, p < 0,0001). CONCLUSIONES: El control hemodinámico fue satisfactorio en los grupos. La IC de sufentanil generó un mejor control del dolor en el pos operatorio con menor consumo de analgésico de rescate, por lo tanto, se registró una menos incidencia de NVPO y un menor tiempo de permanencia en la SRPA.

Continuous infusion of remifentanil versus sufentanil in videolaparoscopic surgeries. A comparative study.

BACKGROUND AND OBJECTIVES: Continuous infusion (CI) of remifentanil is common in total intravenous anesthesia. On the other hand, CI of sufentanil for short/medium-term surgeries has not been widely used. The objective of this study was to compare two techniques of total intravenous anesthesia, using CI of remifentanil or sufentanil, regarding their intraoperative behavior and characteristics of recovery of patients undergoing videolaparoscopic surgeries. METHODS: Sixty patients, equally divided in 2 groups (RG, and SG), participated in this study. Continuous infusion of remifentanil was used for anesthetic induction in RG, while a bolus of sufentanil associated with CI of this drug was used in SG. The CI of remifentanil was discontinued at the end of the surgery, while the CI of sufentanil was discontinued 20 minutes before the end of the surgery. Patients received ketoprofen and dypirone intraoperatively. Tramadol was used for rescue analgesia in the recovery room. Variations of mean arterial pressure (MAP) and hard reate (HR), time for awakening, propofol consumption, intercurrences in the recovery room, and time of stay in the recovery room were analyzed. RESULTS: Mean MAP was greater in SG than in RG (91.9 x 77.6, p < 0.0001). The incidence of pain was significantly greater in RG than on SG (22 x 1 patient, p < 0.0001). The incidence of postoperative nausea and vomiting (PONV) was greater in RG than in SG (10 x 2 patients, p < 0.0098). The mean time of stay in the recovery room was greater in RG than in SG (76 x 49 min, p < 0.0001). CONCLUSIONS: Hemodynamic control was satisfactory in both groups. Continuous infusion of sufentanil promoted better postoperative pain control with decreased consumption of rescue analgesic and, consequently, reduced incidence of PONV and reduced time of stay in the recovery room.

Hiperreflexia autonômica em gestante tetraplégica: relato de caso / Autonomic hyperreflexia in tetraplegic pregnant patient: case report

JUSTIFICATIVA E OBJETIVOS: As complicações da gestante com lesäo medular incluem infecções urinárias, calculose renal, anemia, úlceras de decúbito, espasmos musculares, sepsis, hiperatividade uterina e a hiperreflexia autonômica. Durante a anestesia a hiperreflexia autonômica é a complicaçäo mais importante, que deve ser, antes de tudo, prevenida. Ela é freqüentemente desenvolvida em pacientes com transecçäo medular ao nível da quinta à sétima vértebra torácica, ou acima. Nosso relato tem com objetivo apresentar um caso de gestante tetraplégica, com lesäo ao nível da sexta vértebra cervical, que se submeteu à operaçäo cesariana sob anestesia peridural contínua com bupivacaína a 0,25 por cento sem vasoconstritor, associada ao fentanil. RELATO DO CASO: Paciente tetraplégica, primigesta à termo, idade gestacional de 39 semanas, branca, 22 anos, 63 kg, 168 cm de altura, estado físico ASA II, internada para ser submetida a cesariana eletiva. Relatava trauma raquimedular ao nível de C6 há 3 anos. Após hidrataçäo prévia com 1500 ml de soluçäo fisiológica, procedeu-se à anestesia peridural com punçäo mediana no espaço L3-L4 com a paciente em decúbito lateral, agulha Tuohy descartável calibre 17G e sem botäo anestésico prévio. Imediatamente após a introduçäo da agulha, observou-se contraçäo da musculatura paravertebral adjacente, aumento da pressäo arterial (PA = 158 x 72 mmHg) e aumento da freqüência cardíaca (FC = 90 bpm). No entanto, a paciente näo relatava dor. Retirou-se agulha e fez-se o botäo anestésico, dando-se seqüência ao bloqueio peridural, com injeçäo de 20 ml de bupivacaína a 0,25 por cento sem vasoconstritor associados a 100 æg de fentanil espinhal e passagem de cateter peridural em sentido cefálico (3 a 4 cm). A cirurgia transcorreu sem intercorrências, näo havendo necessidade de complementaçäo do bloqueio em nenhum momento. Houve dois episódios de hipotensäo arterial nas primeiras 24 horas do pós-operatório, tratados com infusäo de soluçäo de Ringer com lactato. O cateter peridural foi mantido por 48 horas. A alta hospitalar ocorreu após três dias de internaçäo. CONCLUSÕES: Para gestantes paraplégicas ou tetraplégicas a anestesia peridural contínua com baixa concentraçäo de anestésico local sem vasoconstritor associado ao fentanil é uma boa indicaçäo para conduçäo do parto normal instrumentado ou não,...

[Autonomic hyperreflexia in tetraplegic pregnant patient: case report]. / Hiperreflexia autonômica em gestante tetraplégica: relato de caso.

BACKGROUND AND OBJECTIVES: Complications of pregnant patients with medullary injury include urinary infection, renal stones, anemia, decubitus ulcers, muscle spasms, sepsis, uterine hyperactivity and autonomic hyperreflexia. Autonomic hyperreflexia is the most severe anesthetic complication and should, before all, be prevented. It is often developed in patients with medullary transection at the level of the 5th to 7th thoracic vertebra or above. This report aims at presenting a case of tetraplegic pregnant patient with injury at the level of the 6th cervical vertebra, submitted to Cesarean section under continuous epidural anesthesia with 0.25% bupivacaine without vasoconstrictor associated to fentanyl. CASE REPORT: Caucasian, tetraplegic primiparous term patient, 39 weeks of gestational age, 22 years old, 63 kg, 168 cm, physical status ASA II, admitted for elective Cesarean section. Patient reported spinomedullary trauma at C6, three years ago. After previous hydration with 1500 ml saline, epidural anesthesia was induced with medial puncture at L3-L4 interspace with the patient in the lateral position, disposable 17G Tuohy needle and without previous local infiltration anesthesia. Immediately after needle insertion, there was adjacent paravertebral muscles contraction, blood pressure increase (BP = 158 x 72 mmHg) and heart rate increase (HR = 90 bpm). Patient, however, did not refer pain. Needle was removed and local anesthesia was induced. Epidural block proceeded with 20 ml of 0.25% bupivacaine without vasoconstrictor associated to 100 microg spinal fentanyl and epidural catheter insertion in the cephalad direction (3 to 4 cm). Surgery went on without intercurrences with no need for blockade complementation. There were two arterial hypotension episodes in the first 24 postoperative hours, which were treated with lactated Ringers solution. Epidural catheter was maintained for 48 hours. Patient was discharged three days after. CONCLUSIONS: For paraplegic or tetraplegic pregnant patients, continuous epidural anesthesia with low local anesthetic concentration without vasoconstrictor and associated to fentanyl is a good indication for instrumented or not vaginal delivery, and Cesarean sections to prevent autonomic hyperreflexia. It is also important that the epidural catheter remains for at least 24 hours after delivery to block sympathetic afference in case a crisis is triggered.

Analgesia controlada pelo paciente com morfina ou fentanil no pós-operatório de reconstruçäo de ligamentos do joelho: estudo comparativo / Patient controlled analgesia with morphine or fentanyl in knee ligament reconstruction postoperative period: a comparative study

Justificativa e objetivos - a morfina ou o fentanil têm sido utilizados para analgesia pós-operatória, por via peridural, de forma contínua com bomba de infusäo, permitindo também que a analgesia seja controlada pelo paciente (ACP). O objetivo deste estudo foi avaliar a qualidade da analgesia, o consumo de opióides e os efeitos colaterais do emprego de infusäo contínua e de ACP com morfina ou fentanil, no pós-operatório de pacientes submetidos a reconstruçäo de ligamento do joelho, sob anestesia peridural com bupivacaína associada ao fentanil. Método - participaram do estudo 42 pacientes com idade entre 16 e 50 anos, estado físico ASA I e II, divididos aleatoriamente em dois grupos de 21: Grupo M (Morfina) e Grupo F (Fentanil). Todos os pacientes foram submetidos a anestesia peridural com bupivacaína a 0,5 por cento (100 mg) associada a fentanil (100 µg). Ao final da cirurgia os pacientes receberam morfina (Grupo M) ou fentanil (Grupo F) em regime de ACP, por via peridural, através de bomba de infusäo. No Grupo M foi utilizada soluçäo fisiológica (93 ml) contendo morfina 2 mg (2ml) e bupivacaína 0,5 por cento (5 ml). No Grupo F foi utilizada soluçäo fisiológica (85 ml) contendo fentanil 500 µg (10 ml), bupivacaína (5 ml a 5 por cento) sem adrenalina. Para os dois grupos foi programado inicialmente infusäo contínua de 4 ml.h elevado a menos um, com doses de 2 ml em bolus liberado pelo paciente num intervalo de 30 minutos. Foram comparados os seguintes parâmetros: dor; número de bolus acionados; consumo de opióides; bloqueio motor; sedaçäo e efeitos colaterais (prurido, náuseas, vômitos e retençäo urinária). Resultados - Näo houve necessidade de suplementaçäo anestésica no per-operatório. A maioria dos pacientes (85,7 por cento) obteve excelente grau de analgesia pós-operatória (EAV 0a 2), sem diferença significativa entre os grupos. A média de bolus acionados näo diferiu nos dois grupos. O consumo médio de morfina foi de 1,663 ñ 0,384 mg sendo o de fentanil de 0,435 ñ 0,083 mg. Näo houve bloqueio motor após a instituiçäo da ACP. A incidência de sedaçäo e de outros efeitos colaterais foi também significativamente maior no grupo da morfina