Luciana Moraes dos Santos

Intrathecal morphine plus general anesthesia in cardiac surgery: effects on pulmonary function, postoperative analgesia, and plasma morphine concentration

OBJECTIVES: To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery. INTRODUCTION: Lung dysfunction increases morbidity and mortality after cardiac surgery. Regional analgesia may improve pulmonary outcomes by reducing pain, but the occurrence of this benefit remains controversial. METHODS: Forty-two patients were randomized for general anesthesia (control group n=22) or 400 μg of intrathecal morphine followed by general anesthesia (morphine group n=20). Postoperative analgesia was accomplished with an intravenous, patient-controlled morphine pump. Blood gas measurements, forced vital capacity (FVC), forced expiratory volume (FEV), and FVC/FEV ratio were obtained preoperatively, as well as on the first and second postoperative days. Pain at rest, profound inspiration, amount of coughing, morphine solicitation, consumption, and plasma morphine concentration were evaluated for 36 hours postoperatively. Statistical analyses were performed using the repeated measures ANOVA or Mann-Whiney tests (*p<0.05). RESULTS: Both groups experienced reduced FVC postoperatively (3.24 L to 1.38 L in control group; 2.72 L to 1.18 L in morphine FEV1 (p=0.085), group), with no significant decreases observed between groups. The two groups also exhibited similar results for FEV1/FVC (p=0.68) and PaO2/FiO2 ratio (p=0.08). The morphine group reported less pain intensity (evaluated using a visual numeric scale), especially when coughing (18 hours postoperatively: control group= 4.73 and morphine group= 1.80, p=0.001). Cumulative morphine consumption was reduced after 18 hours in the morphine group (control group= 20.14 and morphine group= 14.20 mg, p=0.037). The plasma morphine concentration was also reduced in the morphine group 24 hours after surgery (control group= 15.87 ng.mL−1 and morphine group= 4.08 ng.mL−1, p=0.029). CONCLUSIONS: Intrathecal morphine administration did not significantly alter pulmonary function; however, it improved patient analgesia and reduced morphine consumption and morphine plasma concentration.

Determining Plasma Morphine Levels Using Gc-Ms After Solid Phase Extraction to Monitor Drug Levels in the Postoperative Period

OBJECTIVE To implement a selective and sensitive analytical method to quantify morphine in small volumes of plasma by gas-liquid chromatography-mass spectrometry (GC-MS), aimed at post-operatively monitoring the drug. METHOD A gas-liquid chromatographic method with mass detection has been developed to determine morphine concentration in plasma after solid phase extraction. Morphine-d3 was used as an internal standard. Only 0.5 mL of plasma is required for the drug solid-phase extraction in the Bond Elut-Certify®, followed by the quantification of morphine derivative by GC-MS using a linear temperature program, a capillary fused silica column, and helium as the carrier and make-up gas. The method was applied to determine morphine content in plasma samples of four patients during the postoperative period of cardiac surgery. Patient-controlled analgesia with morphine was performed by a venous catheter, and a series of venous blood samples were collected. After the oro-tracheal extubation, morphine plasma levels were monitored for up to 36 hours. RESULTS The run time was 16 minutes because morphine and the internal standard were eluted after 8.8 minutes. The GC-MS method had 0.5–1000 ng/mL linearity range (r2=0.9995), 0.1 ng/mL limit of detection, intraday and interday precision equivalent to 1.9% and 6.8%, and 0.1% and 0.8% systematic error (intraday and interday, respectively). The analytical method showed optimal absolute (98%) and relative (100.7%) recoveries. Morphine dose requirements and plasma levels are discussed. CONCLUSION The analytical gas-liquid chromatography-mass spectrometry method is selective and adequate for morphine measurements in plasma for applications in clinical studies.

Avaliação dos níveis de citocinas e da função pulmonar de pacientes submetidos à cirurgia cardíaca com circulação extracorpórea

JUSTIFICATIVA Y OBJETIVOS: El Sindrome de la Respuesta Inflamatoria Sistemica es algo habitual en las cirugias cardiacas con circulacion extracorporea (CEC). El objetivo de este estudio fue evaluar los niveles sistemicos y pulmonares de citocinas y la correlacion con la funcion pulmonar en los pacientes sometidos a la revascularizacion miocardica (RM) con CEC. METODOS: El estudio fue aprobado por la Comision de Etica Institucional, con la evaluacion de 13 pacientes sometidos a la RM con CEC. Despues de la induccion anestesica al termino de la CEC, se realizaron dosificaciones plasmaticas y tambien en el lavado broncoalveolar de IL-1β, IL-6, IL-8, IL-10 y TNF-α. Se evaluaron el tiempo de CEC y de cirugia, la relacion PaO2/FiO2, el gradiente alveolo-arterial de oxigeno (GA-aO2), el shunt y la complacencia pulmonares. Los resultados fueron sometidos al analisis de variancia para medidas repetidas (*p < 0,05) y al coeficiente de correlacion de Spearman. RESULTADOS: Se observo un aumento en los niveles de citocinas en el plasma y en el lavado broncoalveolar despues de la CEC y una relacion directa entre el aumento de la IL-1β y la disminucion de la complacencia pulmonar (p = 0,0439), como tambien una relacion inversa entre el aumento de la IL-10 y la reduccion de la complacencia (p = 0,0325). El aumento de la IL-6 tuvo una relacion directa con el tiempo de CEC (p = 0,012), mientras que el aumento de la IL-8 tuvo una relacion directa con el tiempo de cirugia (p < 0,0001). Los niveles de IL-1β, IL-8 y TNF-α fueron mayores en el LBA con relacion al plasma. CONCLUSIONES: Ocurre un aumento de los niveles de citocinas en el plasma y en el lavado broncoalveolar despues de la CEC, con una correlacion entre el aumento de los niveles de citocinas y el tiempo de CEC y de cirugia, y las alteraciones en la complacencia pulmonar.

Evaluation of Cytokine Levels and Pulmonary Function in Patients Undergoing Coronary Artery Bypass Graft

BACKGROUND AND OBJECTIVES Systemic inflammatory response syndrome is commonly observed in coronary artery bypass grafts (CABG) with cardiopulmonary bypass (CB). The objective of this study was to evaluate the systemic and pulmonary levels of cytokines and their correlation with lung function in patients undergoing myocardial revascularization (MR) with CB. METHODS This study was approved by the Institutional Ethics Committee, and 13 patients undergoing MR with CB were evaluated. After anesthetic induction and at the end of CB, plasma and bronchoalveolar lavage levels of IL-1β, IL-6, IL-8, IL-10, and TNF-α were determined. The duration of CB and surgery, PaO(2)/FiO(2) ratio, alveolar-arterial oxygen gradient (A-a gradient), shunt, and lung compliance were evaluated. Results were submitted to analysis of variance for repeated measurements (*p < 0.05) and Spearmans correlation coefficient. RESULTS We observed increased levels of cytokines in plasma and bronchoalveolar lavage after CB and a direct relationship between the increase in IL-1β and decrease in lung compliance (p = 0.0439), as well as the inverse relationship between the increase in IL-10 and a decrease in compliance (p = 0.0325). The increase in IL-6 was directly related to the duration of CB (p = 0.012), while the increase in IL-8 was directly related to the duration of surgery (p < 0.0001). Levels of interleukin-1β, IL-8, and TNF-α in bronchoalveolar lavage were higher than in plasma. CONCLUSIONS There is an increase in cytokine levels in plasma and bronchoalveolar lavage after CB, as well as a correlation between increased cytokine levels and CB duration and surgery and changes in lung compliance.

Broncho-alveolar lavage cellularity in patients submitted to myocardial revascularization with cardiopulmonary bypass: three case reports

BACKGROUND AND OBJECTIVES Cardiopulmonary bypass (CPB) is a primary determinant of systemic inflammatory response (SIRS) during cardiac procedures. It has been shown in an experimental model that CPB may increase cytokine production. This study aimed at evaluating post-CPB lung cell activation by investigating broncho-alveolar lavage (BAL) cellularity in patients submitted to myocardial revascularization (MR) with CPB. CASE REPORTS Participated in this prospective study 3 adult patients submitted to MR with CPB. After general anesthesia induction and tracheal intubation, mechanical ventilation was installed with valve circle system; except during CPB, tidal volume was maintained between 8 and 10 mL.kg-1 with 50% O2 and air. Before aortic unclamping, 40 cmH2O pulmonary inflations were performed. Two BAL samples were collected from all patients at beginning and end of procedure, after anticoagulation reversion. BAL was aspired after 60 mL infusion of 0.9% saline through the bronchofibroscope tube. Material was then referred to laboratorial processing. Analysis has evidenced mean increase in total number of cells from 0.6 x 10(6)cel.dL-1 to 6.8 x 10(6) cel.dL-1 with increased neutrophils from 0.8% to 4.7%; 0.6% to 6.2% and 0.5% to 5.3% for each patient, respectively. There has been increased pulmonary fluid cellularity after CPB. CONCLUSIONS Leukocyte inflow is described in different clinical pulmonary inflammatory conditions, such as adult respiratory distress syndrome. It is known that CPB is related to systemic and pulmonary inflammation with increased number of cells after CPB and predominance of macrophages.JUSTIFICATIVA Y OBJETIVOS: La circulacion extracorporea (CEC) es uno de los principales determinantes de la respuesta inflamatoria sistemica (SIRS) en cirugia cardiaca. Quedo demostrado en modelo experimental que la CEC puede llevar a un aumento en la produccion de las citocinas. Con el objetivo de evaluar la activacion celular en el pulmon despues del CEC, se estudio la celularidad en el lavado bronco-alveolar (LBA) en pacientes sometidos a la cirugia de revascularizacion del miocardio (RM) con CEC. RELATO DE LOS CASOS: Se estudiaron, como sondeo, tres pacientes adultos sometidos a la RM con CEC. Despues de la induccion de anestesia general e intubacion traqueal, la ventilacion mecanica se realizo con sistema circular valvular; excepto durante la CEC, el volumen corriente se mantuvo entre 8 y 10 mL.kg-1 con O2 y aire, en una proporcion de 50%. Antes del despinzamiento de la aorta, se realizaron insuflaciones pulmonares con presion de 40 cmH2O y recolectadas dos muestras de LBA de cada paciente, al comienzo de la intervencion quirurgica y al final del procedimiento, despues de la reversion de la anticoagulacion. Despues de la infusion de 60 mL de solucion fisiologica a 0,9% por el canal del broncofibroscopio, se aspiro el LBA, siendo el material enviado al laboratorio. El analisis mostro un aumento del numero total de celulas, como promedio, de 0,6.106 cel.dL-1 para 6,8.106 cel.dL-1 con aumento de neutrofilos de 0,8% para 4,7%; 0,6% para 6,2% y 0,5% para 5,3% en cada paciente, respectivamente. Se observo en la lamina el aumento de celularidad en el fluido pulmonar despues de la CEC. CONCLUSIONES: El influjo de leucocitos se describe en diversas condiciones clinicas pulmonares inflamatorias como en el sindrome de la angustia respiratoria del adulto. Se conoce que la CEC esta relacionada con la inflamacion sistemica y pulmonar, demostrando aumento del numero de celulas despues de la CEC con el predominio de macrofagos.

Pharmacokinetic Assessment of Sufentanil in Cardiac Surgery

Plasma monitoring and pharmacokinetic assessment are important tools used in therapeutic control. Sufentanil is responsible for the hemodynamic stabilization of patients, providing better suppression of the neuroendocrine response compared to its analogue fentanyl. This study aims to use the plasma monitoring of sufentanil in patients undergoing cardiac surgery with extracorporeal circulation (ECC, group 1) or without ECC (group 2) to assess the pharmacokinetics of the compound.The 42 patients in this study received 0.5 μg/kg of sufentanil through bolus injection followed by a maintenance infusion of 0.5 μg/kg.h. Serial blood samples were collected during the post induction intraoperative period and during the postoperative period until 36 h after sufentanil administration. The plasma concentrations were determined by a validated method utilizing liquid chromatography coupled to mass spectrometry. The pharmacokinetic modeling was performed using a 3-compartment model fit.The surgical patients included in the protocol were adults of both genders, with 30 patients in the ECC group and 12 in the group without ECC. The plasma concentrations obtained were significantly different between the 2 groups. During the extracorporeal circulation procedure, intense fluctuations were observed in the sufentanil plasma concentrations. Compared with the results of group 2, the ECC procedure reduced the terminal or gamma half-life from 36.35 ± 6.37 h to 23.25 ± 2.75 h in group 1. In addition, the ECC procedure promoted higher fluctuations in the sufentanil plasma concentrations without causing alterations in the area under the curve, distribution volume, clearance or the distributional (alpha) and rapid elimination (beta) half-lives (t1/2α and t1/2β, respectively).

Proteção renal na unidade de terapia intensiva cirúrgica

JUSTIFICATIVA E OBJETIVOS: A disfuncao renal perioperatoria e importante causa de aumento de morbimortalidade. Com o aumento da expectativa de vida, pacientes mais idosos e com maior numeros de co-morbidades estao sendo submetidos a procedimentos cirurgicos de alto risco, o que torna as praticas da protecao orgânica possiveis modificadoras de prognostico a curto e longo prazo. Nesse contexto, esta revisao sobre a protecao renal na unidade de terapia intensiva cirurgica objetivou destacar os fatores de riscos peri-operatorios e discutir as atuais evidencias cientificas direcionadas para a dimi nuicao da disfuncao renal peri-operatoria. CONTEUDO: Apesar da baixa extracao e adequada reserva renal de oxigenio, o rim e extremamente sensivel

Proteção miocárdica em cirurgia cardíaca

JUSTIFICATIVA Y OBJETIVOS: La proteccion miocardica define el conjunto de estrategias que tienen por objetivo atenuar la intensidad de la lesion de isquemia-reperfusion miocardica durante la cirugia cardiaca y sus consecuencias sobre la funcion miocardica. Un mejor entendimiento de los fenomenos fisiopatologicos relacionados a la isquemia-reperfusion miocardica y de la cardioproteccion promovida por determinados farmacos y tecnicas anestesicas ha dado al anestesiologista papel importante en la proteccion miocardica durante el procedimiento quirurgico. El objetivo de esta revision fue abordar los mecanismos de la lesion miocardica y las modalidades de proteccion miocardica con enfoque para la tecnica anestesica. CONTENIDO: Son abordados los mecanismos de lesion miocardica durante los eventos de isquemia-reperfusion y sus consecuencias clinicas asi como las tecnicas de proteccion realizadas durante la cirugia cardiaca. Enfasis especial fue dada a los farmacos y tecnicas anestesicas, como anestesicos halogenados, opioides y farmacos adyuvantes, pues estos han mostrado efectos cardioprotectores en cirugia cardiaca. CONCLUSIONES: La asociacion de la tecnica anestesica adecuada con agentes anestesicos cardioprotectores a las tecnicas habituales de proteccion miocardica realizadas por el cirujano puede aportar para la prevencion de disfuncion miocardica y promover mejor recuperacion en el periodo pos-operatorio.BACKGROUND AND OBJECTIVES Myocardial protection defines the set of strategies aiming at attenuating the intensity of myocardial ischemia-reperfusion injury during heart surgery and its harmful consequences on myocardial function. A better understanding of pathophysiological phenomena related to ischemia-reperfusion events and of the anesthetic-induced heart protection has given to the anesthesiologist a major role in intraoperative myocardial protection. The objective of this update was to review the mechanisms of ischemia-reperfusion-induced myocardial injury and myocardial protection modalities focusing on anesthetic techniques. CONTENTS Ischemia-reperfusion-induced myocardial injury mechanisms and their clinical consequences on heart as well as myocardial protection techniques used during heart surgery are addressed in this review. Special emphasis is given to the role of anesthetic drugs and techniques such as inhaled halogenate anesthetics, opioids and adjuvant anesthetic drugs, since they have been shown to have heart protecting effects during cardiac surgery. CONCLUSIONS The association of adequate anesthetic technique using heart protecting agents to usual myocardial protection modalities performed by the surgeon may contribute to the prevention of cardiac surgery-induced myocardial dysfunction and improve postoperative outcome.

Influência da circulação extracorpórea sobre as concentrações plasmáticas de atenolol

BACKGROUND Betablockers are used in the treatment of angina pectoris and others ischemic coronary diseases, reducing mortality and cardiovascular events. Atenolol is a hydrophilic betablocker which is characterized by gastrointestinal absorption, small extent of distribution and renal function-dependent elimination. OBJECTIVE The study objective was to determine the inter-individual variability of atenolol in coronary patients. METHODS Plasma atenolol was quantified in six blood samples collected during the preoperative period from seven patients with coronary insufficiency and surgical indication, chronically treated with atenolol PO 25 to 100 mg/day. All patients presented a normal or slightly reduced renal function. RESULTS All enrolled patients presented normal or slightly reduced renal function as a result of age and underlying disease. Atenolol plasma concentrations showed a monoexponential decline, confirming the first-order pharmacokinetics at the doses employed for the control of coronary insufficiency (mean +/- SD): 123 +/- 56, 329 +/- 96, 288 +/- 898, 258 +/- 85, 228 +/- 79 and 182 +/- 73 ng/ml at times zero, 2, 4, 6, 8 and 12h after dose administration. The investigated group showed a small inter-patient variability of atenolol administrated at multiple regimens due to the hydrophilic characteristic of the drug. Furthermore, accumulation of atenolol administered chronically was greater in coronary patients, compared to healthy subjects. CONCLUSION In view of its cardio-selectivity and low-variability, atenolol should be used as the first-choice drug for the treatment of acute coronary syndrome and other cardiovascular diseases.

Análise da celularidade do lavado bronco-alveolar em pacientes submetidos à revascularização do miocárdio com circulação extracorpórea: relato de três casos

BACKGROUND AND OBJECTIVES Cardiopulmonary bypass (CPB) is a primary determinant of systemic inflammatory response (SIRS) during cardiac procedures. It has been shown in an experimental model that CPB may increase cytokine production. This study aimed at evaluating post-CPB lung cell activation by investigating broncho-alveolar lavage (BAL) cellularity in patients submitted to myocardial revascularization (MR) with CPB. CASE REPORTS Participated in this prospective study 3 adult patients submitted to MR with CPB. After general anesthesia induction and tracheal intubation, mechanical ventilation was installed with valve circle system; except during CPB, tidal volume was maintained between 8 and 10 mL.kg-1 with 50% O2 and air. Before aortic unclamping, 40 cmH2O pulmonary inflations were performed. Two BAL samples were collected from all patients at beginning and end of procedure, after anticoagulation reversion. BAL was aspired after 60 mL infusion of 0.9% saline through the bronchofibroscope tube. Material was then referred to laboratorial processing. Analysis has evidenced mean increase in total number of cells from 0.6 x 10(6)cel.dL-1 to 6.8 x 10(6) cel.dL-1 with increased neutrophils from 0.8% to 4.7%; 0.6% to 6.2% and 0.5% to 5.3% for each patient, respectively. There has been increased pulmonary fluid cellularity after CPB. CONCLUSIONS Leukocyte inflow is described in different clinical pulmonary inflammatory conditions, such as adult respiratory distress syndrome. It is known that CPB is related to systemic and pulmonary inflammation with increased number of cells after CPB and predominance of macrophages.JUSTIFICATIVA Y OBJETIVOS: La circulacion extracorporea (CEC) es uno de los principales determinantes de la respuesta inflamatoria sistemica (SIRS) en cirugia cardiaca. Quedo demostrado en modelo experimental que la CEC puede llevar a un aumento en la produccion de las citocinas. Con el objetivo de evaluar la activacion celular en el pulmon despues del CEC, se estudio la celularidad en el lavado bronco-alveolar (LBA) en pacientes sometidos a la cirugia de revascularizacion del miocardio (RM) con CEC. RELATO DE LOS CASOS: Se estudiaron, como sondeo, tres pacientes adultos sometidos a la RM con CEC. Despues de la induccion de anestesia general e intubacion traqueal, la ventilacion mecanica se realizo con sistema circular valvular; excepto durante la CEC, el volumen corriente se mantuvo entre 8 y 10 mL.kg-1 con O2 y aire, en una proporcion de 50%. Antes del despinzamiento de la aorta, se realizaron insuflaciones pulmonares con presion de 40 cmH2O y recolectadas dos muestras de LBA de cada paciente, al comienzo de la intervencion quirurgica y al final del procedimiento, despues de la reversion de la anticoagulacion. Despues de la infusion de 60 mL de solucion fisiologica a 0,9% por el canal del broncofibroscopio, se aspiro el LBA, siendo el material enviado al laboratorio. El analisis mostro un aumento del numero total de celulas, como promedio, de 0,6.106 cel.dL-1 para 6,8.106 cel.dL-1 con aumento de neutrofilos de 0,8% para 4,7%; 0,6% para 6,2% y 0,5% para 5,3% en cada paciente, respectivamente. Se observo en la lamina el aumento de celularidad en el fluido pulmonar despues de la CEC. CONCLUSIONES: El influjo de leucocitos se describe en diversas condiciones clinicas pulmonares inflamatorias como en el sindrome de la angustia respiratoria del adulto. Se conoce que la CEC esta relacionada con la inflamacion sistemica y pulmonar, demostrando aumento del numero de celulas despues de la CEC con el predominio de macrofagos.