Ricardo Francisco Simoni

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.

Efficacy Of Intraoperative Methadone And Clonidine In Pain Control In The Immediate Postoperative Period After The Use Of 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.

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.

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.

Avaliação farmacodinâmica e análise físico-química de duas formulações de propofol usadas em infusão alvo-controlada

JUSTIFICATIVA E OBJETIVOS: Existem varias formulacoes de propofol para uso clinico a disposicao do anestesiologista. O objetivo desse estudo foi analisar as propriedades fisico-quimicas, o efeito farmacodinâmico e a equivalencia farmaceutica e clinica do farmaco referencia de propofol e uma formulacao similar. METODOS: Dezesseis voluntarios participaram desse estudo aleatorio, duplamente encoberto e pareado entre as formulacoes Diprivan® e Propovan®. As formulacoes foram administradas em regime de infusao alvo-controlada com concentracao-alvo de 3,0 µg.mL-1 por 15 minutos. As variaveis estudadas foram a area sob a curva (ASC) do grafico do indice bispectral (BIS) em relacao ao tempo, o BIS minimo atingido e o tempo para tal e o tempo de recuperacao. As duas formulacoes foram submetidas as analises de tamanho de particulas da emulsao lipidica, potencial de superficie e quantificacao de principio ativo. RESULTADOS: Nao houve diferenca entre as formulacoes quando se comparou a ASC, BIS minimo atingido e o tempo decorrido para tal. O tempo de recuperacao com a formulacao similar foi menor em relacao a referencia (oito e 10 min, respectivamente, p = 0,014). O tamanho medio de particulas da emulsao lipidica, potencial de superficie e a quantificacao de principio ativo foram semelhantes nas duas formulacoes. CONCLUSAO: Nao houve diferenca clinica significativa entre o uso de propofol referencia Diprivan® e seu similar Propovan® durante a infusao. Entretanto, o tempo de recuperacao foi mais prolongado com o farmaco referencia. Embora as analises com as duas formulacoes estudadas mostrarem resultados semelhantes quanto a sua caracterizacao fisico-quimica, outros estudos devem ser realizados para justificar tal diferenca.

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.

Avaliação clínica de duas ke0 no mesmo modelo farmacocinético de propofol: estudo da perda e recuperação da consciência

JUSTIFICATIVA Y OBJETIVOS: La constante de equilibrio entre el plasma y el sitio efector (ke0), se usa por los modelos farmacocineticos para prever la concentracion del farmaco en su region de accion (Ce). Seria interesante que el Ce de propofol fuese similar en la perdida y en la recuperacion de la conciencia. El objetivo de este estudio, fue evaluar el desempeno clinico de dos diferentes ke0 (rapida = 1,21 min-1 y lenta = 0,26 min-1), con relacion a la Ce durante la perdida y la recuperacion de la conciencia, usando el modelo farmacocinetico de Marsh. MeTODO: Participaron en este estudio, 20 voluntarios adultos sanos del sexo masculino. A todos los voluntarios se les administro propofol en regimen de infusion objeto controlada, modelo farmacocinetico de Marsh ke0 rapida y en otro momento, se uso el mismo modelo farmacocinetico con a ke0 lenta. Inicialmente, el propofol se infundio en concentracion-objeto plasmatica de 3,0 µg.mL-1. La perdida de la conciencia y la recuperacion de la conciencia estuvieron basadas en la respuesta al estimulo verbal. La Ce fue anotada en el momento de la perdida y de la recuperacion de la conciencia. RESULTADOS: En la perdida y en la recuperacion de la conciencia, la Ce por la ke0 rapida, 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 clinico, la ke0 lenta (0,26 min-1) incorporada al modelo farmacocinetico de Marsh, presento un mejor desempeno que la ke0 rapida (1,21 min-1), pues la concentracion de propofol prevista en su region de accion en la perdida y en la recuperacion de la conciencia fue similar.

Continuous infusion of remifentanil vs. 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 × 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.

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.JUSTIFICATIVA Y OBJETIVOS: En las complicaciones de la embarazada con una lesion medular se incluyen infecciones urinarias, calculosis renal, anemia, ulceras de decubito, espasmos musculares, sepsis, hiperactividad uterina y la hiperreflexia autonomica. Durante la anestesia la hiperreflexia autonomica es la complicacion mas importante, que debe ser, antes de todo, prevenida. Ella es frecuentemente desarrollada en pacientes con transeccion medular al nivel de la quinta a la septima vertebra toracica, o encima. Nuestro relato tiene como objetivo presentar un caso de embarazada tetraplejica, con lesion al nivel de la sexta vertebra cervical, que se sometio a operacion cesariana bajo anestesia peridural continua con bupivacaina a 0,25% sin vasoconstrictor, asociada al fentamil. RELATO DE CASO: Paciente tetraplejica, primigesta a termino, edad gestacional de 39 semanas, blanca, 22 anos, 63 kg, 168 cm de altura, estado fisico ASA II, internada para ser sometida a cesariana electiva. Relataba trauma raquimedular al nivel de C6 hace 3 anos. Despues de hidratacion previa con 1500 ml de solucion fisiologica, siguio anestesia peridural con puncion mediana en el espacio L3-L4 con la paciente en decubito lateral, aguja Tuohy desechable calibre 17G y sin boton anestesico previo. Inmediatamente despues de la introduccion de la aguja, se observo contraccion de la musculatura paravertebral adyacente, aumento de la presion arterial (PA = 158 x 72 mmHg) y aumento de la frecuencia cardiaca (FC = 90 bpm). No obstante, la paciente no relataba dolor. Se retiro la aguja y se hizo boton anestesico, dandose secuencia al bloqueo peridural, con inyeccion de 20 ml de bupivacaina a 0,25% sin vasoconstrictor asociados a 100 µg de fentamil espinal y pasaje de cateter peridural en sentido cefalico (3 a 4 cm). La cirugia transcurrio sin interocurrencias, no habiendo necesidad de complementacion de bloqueo en ningun momento. Hubo dos episodios de hipotension arterial en las primeras 24 horas del pos-operatorio, tratados con infusion de solucion de Ringer con lactato. El cateter peridural fue mantenido por 48 horas. El alta hospitalar ocurrio despues de tres dias de internacion. CONCLUSIONES: Para embarazadas paraplejicas o tetraplejicas, la anestesia peridural continua con baja concentracion de anestesico local sin vasoconstrictor asociado al fentamil, es una buena indicacion para la conduccion del parto normal instrumentado o no, como el parto cesariano, con la finalidad de evitar la hiperreflexia autonomica. Tambien se debe dar importancia a la permanencia del cateter peridural en el pos-operatorio por lo menos 24 horas despues del parto, con la intencion de bloquear la aferencia simpatica, en el caso de que pueda suceder alguna crisis.

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.