Lung hyperinflation stimulates the release of inflammatory mediators in spontaneously breathing subjects

Lung hyperinflation up to vital capacity is used to re-expand collapsed lung areas and to improve gas exchange during general anesthesia. However, it may induce inflammation in normal lungs. The objective of this study was to evaluate the effects of a lung hyperinflation maneuver (LHM) on plasma cytokine release in 10 healthy subjects (age: 26.1 ± 1.2 years, BMI: 23.8 ± 3.6 kg/m²). LHM was performed applying continuous positive airway pressure (CPAP) with a face mask, increased by 3-cmH2O steps up to 20 cmH2O every 5 breaths. At CPAP 20 cmH2O, an inspiratory pressure of 20 cmH2O above CPAP was applied, reaching an airway pressure of 40 cmH2O for 10 breaths. CPAP was then decreased stepwise. Blood samples were collected before and 2 and 12 h after LHM. TNF-á, IL-1â, IL-6, IL-8, IL-10, and IL-12 were measured by flow cytometry. Lung hyperinflation significantly increased (P < 0.05) all measured cytokines (TNF-á: 1.2 ± 3.8 vs 6.4 ± 8.6 pg/mL; IL-1â: 4.9 ± 15.6 vs 22.4 ± 28.4 pg/mL; IL-6: 1.4 ± 3.3 vs 6.5 ± 5.6 pg/mL; IL-8: 13.2 ± 8.8 vs 33.4 ± 26.4 pg/mL; IL-10: 3.3 ± 3.3 vs 7.7 ± 6.5 pg/mL, and IL-12: 3.1 ± 7.9 vs 9 ± 11.4 pg/mL), which returned to basal levels 12 h later. A significant correlation was found between changes in pro- (IL-6) and anti-inflammatory (IL-10) cytokines (r = 0.89, P = 0.004). LHM-induced lung stretching was associated with an early inflammatory response in healthy spontaneously breathing subjects.

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m²), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95 percent CI = 3.9-6.9) to 10.6 h (95 percent CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95 percent CI = 3.2-14.3) to 8.3 l/kg (95 percent CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95 percent CI = 7.7-24.6) vs 10.7 ml min-1 kg-1 (95 percent CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

A micromethod for quantitation of debrisoquine and 4-hydroxydebrisoquine in urine by liquid chromatography

We describe a new simple, selective and sensitive micromethod based on HPLC and fluorescence detection to measure debrisoquine (D) and 4-hydroxydebrisoquine (4-OHD) in urine for the investigation of xenobiotic metabolism by debrisoquine hydroxylase (CYP2D6). Four hundred µl of urine was required for the analysis of D and 4-OHD. Peaks were eluted at 8.3 min (4-OHD), 14.0 min (D) and 16.6 min for the internal standard, metoprolol (20 µg/ml). The 5-µm CN-reverse-phase column (Shimpack, 250 x 4.6 mm) was eluted with a mobile phase consisting of 0.25 M acetate buffer, pH 5.0, and acetonitrile (9:1, v/v) at 0.7 ml/min with detection at lexcitation = 210 nm and lemission = 290 nm. The method, validated on the basis of measurements of spiked urine, presented 3 ng/ml (D) and 6 ng/ml (4-OHD) sensitivity, 390-6240 ng/ml (D) and 750-12000 ng/ml (4-OHD) linearity, and 5.7/8.2 percent (D) and 5.3/8.2 percent (4-OHD) intra/interassay precision. The method was validated using urine of a healthy Caucasian volunteer who received one 10-mg tablet of Declinax®, po, in the morning after an overnight fast. Urine samples (diuresis of 4 or 6 h) were collected from zero to 24 h. The urinary excretion of D and 4-OHD, Fel (0-24 h), i.e., fraction of dose administered and excreted into urine, was 6.4 percent and 31.9 percent, respectively. The hydroxylation capacity index reported as metabolic ratio was 0.18 (D/4-OHD) for the person investigated and can be compared to reference limits of < 12.5 for poor metabolizers (PM) and < 12.5 for extensive metabolizers (EM). In parallel, the recovery ratio (RR), another hydroxylation capacity index, was 0.85 (4-OHD: SD + 4-OHD) versus reference limits of RR < 0.12 for PM and RR > 0.12 for EM. The healthy volunteer was considered to be an extensive metabolizer on the basis of the debrisoquine test.

The effects of positive end-expiratory pressure on respiratory system mechanics and hemodynamics in postoperative cardiac surgery patients

We prospectively evaluated the effects of positive end-expiratory pressure (PEEP) on the respiratory mechanical properties and hemodynamics of 10 postoperative adult cardiac patients undergoing mechanical ventilation while still anesthetized and paralyzed. The respiratory mechanics was evaluated by the inflation inspiratory occlusion method and hemodynamics by conventional methods. Each patient was randomized to a different level of PEEP (5, 10 and 15 cmH2O), while zero end-expiratory pressure (ZEEP) was established as control. PEEP of 15-min duration was applied at 20-min intervals. The frequency dependence of resistance and the viscoelastic properties and elastance of the respiratory system were evaluated together with hemodynamic and respiratory indexes. We observed a significant decrease in total airway resistance (13.12 + or - 0.79 cmH2O l-1 s-1 at ZEEP, 11.94 + or - 0.55 cmH2O l-1 s-1 (P<0.0197) at 5 cmH2O of PEEP, 11.42 + or - 0.71 cmH2O l-1 s-1 (P<0.0255) at 10 cmH2O of PEEP, and 10.32 + or - 0.57 cmH2O l-1 s-1 (P<0.0002) at 15 cmH2O of PEEP). The elastance (Ers; cmH2O/l) was not significantly modified by PEEP from zero (23.49 + or - 1.21) to 5 cmH2O (21.89 + or - 0.70). However, a significant decrease (P<0.0003) at 10 cmH2O PEEP (18.86 + or - 1.13), as well as (P<0.0001) at 15 cmH2O (18.41 + or - 0.82) was observed after PEEP application. Volume dependence of viscoelastic properties showed a slight but not significant tendency to increase with PEEP. The significant decreases in cardiac index (l min-1 m-2) due to PEEP increments (3.90 + or - 0.22 at ZEEP, 3.43 + or - 0.17 (P<0.0260) at 5 cmH2O of PEEP, 3.31 + or - 0.22 (P<0.0260) at 10 cmH2O of PEEP, and 3.10 + or - 0.22 (P<0.0113) at 15 cmH2O of PEEP) were compensated for by an increase in arterial oxygen content owing to shunt fraction reduction from 22.26 + or - 2.28 at ZEEP to 11.66 + or - 1.24 at PEEP of 15 cmH2O (P<0.0007). We conclude that increments in PEEP resulted in a reduction of both airway resistance and respiratory elastance. These results could reflect improvement in respiratory mechanics. However, due to possible hemodynamic instability, PEEP should be carefully applied to postoperative cardiac patients

Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB), 3 females and 7 males aged 65 ñ 11 years, 74 ñ 16 kg body weight, 166 ñ 9 cm height and 1.80 ñ 0.2l m2 body surface area (BSA), and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 ñ 14 years, 66 ñ 14 kg body weight, 159 ñ 9 cm height and 1.65 ñ 0.16 m2 BSA (mean ñ SD). Sodium diclofenac (1 mg/kg, im Voltaren 75( twice a day) was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale(VAS) during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (EMA were: 25 per cent VAS (CPB) vs 1O per cent VAS (control), P<0.05, median measured by the visual analogue scale where lOO per cent is equivalent to the highest level of pain. To correlate the effect versus plasma diclofen levels, the EMAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTEMAX) was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinicall relevant kinetic-dynamic consequences.

Anestesia para cardiopatas subemtidos a cirurgia näo-cardíaca / Anesthesia in non-cardiac surgery of cardiac patients

Atualmente o crescimento demográfico da populaçäo e, em determinadas classes sociais, o aumento da expectativa de vida, tornam cada vez maior a probabilidade de pacientes cardiopatas necessitarem de cirurgias näo-cardíacas. Existe sempre grande receio por parte da equipe médica da descompensaçäo destes pacientes frente à anestesia. O objetivo deste capítulo é abordar alguns pontos fundamentais relacionados à anestesia de pacientes cardiopata, pois frequentemente existem dúvidas quanto a conduta, principalmente entre anestesiologistas e cardiologistas que convivem pouco com este problema. Um dos pontos que nos parece bastante aflitivo está relacionado com a avaliaçäo do risco pré-operatório. O que realmente o anestesiologista precisa saber de avaliaçäo cardiológica pré-operatória que possa influenciar na escolha da técnica e das drogas anestésicas nem sempre é fieto com clareza ou profundidade. Por outro lado, as mudanças fisiológicas provocadas pela anestesia e pela açäo farmacodinâmica das drogas anestésicas nem sempre säo levadas em conta pela equipe que faz a avaliaçäo. Nesta mesma linha de pensamento presume-se que o anestesiologista, que propöe-se a anestesiar cardiopatas, conheça em profundidade a fisipatologia de cada cardiopatia e a repercussäo das dorgas e da técnica de anestesia a ser empregada. Na discussäo multidisciplinar que antecede o ato cirúrgico destes pacientes, a pergunta que se faz inicialmente está relacionada ao risco representado pela cardiopatia e sua influência na evoluçäo clínica frente ao impacto da anestesia e cirurgia. neste aspecto, a técnica de anestesia com as respectivas drogas, bem como a monitorizaçäo intra-operatória necessária para o ato cirúrgico, tem recebido atençäo crescente. Estes fatos estäo fundamentados em trabalhos que demonstram a eficácia da monitorizaçäo em diminuir a incidência de complicaçöes ...

Avaliação neurológica de 118 pacientes no primeiro período pós operatório de cirurgia cardiovascular / Neurologic evaluation of 118 patients in the first postoperative period of cardiovascular surgery

118 patients (79 mean and 39 women, mean age of 50.7 years) who underwent cardiovascular surgery and extracorporeal oxygenation were prospectively evaluated for neurologic complication and its correlation with risk factors. 71 were submitted to coronary artery graft by-pass (RM), 18 to valve replacement (TV), 6 to prosthetic valve replacement (RV), 11 to commissurotomy(Co), 5 to thoracic aortic aneurysm correction (An Ao T) and 7 to other surgeries (OT). All of them received extracorporeal oxygenation. No deaths were registered; 14 (11.9%) patients had neurologic abnormalities: delirium in 7 cases, ischemic stroke in 6, epileptic seizure in 3. Patients with systemic arterial hypertension and older patients exhibited a statistically significant (p < 0.05) higher risk of complication. Compared to data of the literature, we had a lower index of morbidity and mortality.

PAF-acether, superoxide anion and beta-glucurinidase as parameters of polymorphonuclear cell activation associated with cardiac surgery and cardiopulmonary bypass

Seven patients submitted to myocardial revascularization surgery with cardiopulmonary bypass were studied. Blood samples were obtained immediately before and 24 h after surgery. The parameters studied were the production of platelet activating factor (PAF-acether) and superoxide anion, cellular beta-glucuronidase activity as well as polymorphonuclear cell(PMN) and platelet count. Twenty-four h after surgery, there was a 54% decrease in platelet number (P<0.005), a 121% increase in PMN number (P<0.005), a 353% increase in PAF-acether (P<0.01), a 211% increase in superoxide anion (O2-) and a 104% increase in beta-glucuronidase (P<0.05) levels when compared with the pre-surgery levels. The present results indicate that PMN are more reactive after surgery with cardiopulmonary bypass

Nutrição entérica em cirurgia cardiovascular. Resultados em 14 pacientes com complicações pré e pós-operatórias / Enteral feeding in cardiovascular surgery. Results in 14 patients with pre and postoperative complications

Foi utilizada a hiperalimentacao enterica atraves de uma sonda de Dobbhoff para nutrir 14 pacientes com graves complicacoes pre e pos-operatorias, submetidos a cirurgia cardiovascular. Analisam os resultados comparando os valores da albumina serica, linfocitos totais e peso corporal no inicio e no fim do tratamento (media de 25 dias), obtendo elevacao progressiva dos valores da albumina serica, linfocitos perante manutencao e peso corporal. Como a intervencao cirurgica por si so, ja exerce influencia negativa sobre o metabolismo proteico, os autores preconizam criteriosa avaliacao do estado nutritivo e o estabelecimento precoce de suporte calorico proteico nos pacientes com graves complicacoes no pre e/ou no pos-operatorio

Monitorização hemodinâmica no pós-operatório de crianças submetidas a correção de cardiopatia congênita / Hemodynamic monitoring in postoperative period of children subjected to correction of congenital heart diseases

Propõe-se um método de monitorização hemodinâmica que compreende a avaliação do debito cardíaco, pressões atriais, pressão arterial, frequência cardíaca, temperatura corporal e volume urinário. Esta monitorização mais ampla foi utilizada em 12 crianças com media de idade 24 meses (desvio padrão 17 meses). As principais indicações foram: idade e peso reduzidos, necessidade de drogas inotrópicas ao sair de circulação extracorpórea, complexidade da cardiopatia e da correção cirúrgica, e insuficiência cardíaca ou respiratória antes da operação. São analisados os resultados terapêuticos, através de curva de função ventricular e particularidades na evolução hemodinâmica no pós-operatório em gráficos separados. O debito cardíaco foi obtido por termodiluição e são discutidos aspectos relacionados com o método utilizado em sua determinação. O procedimento revelou-se seguro e reprodutível, fornecendo subsídios importantes para decisões terapêuticas

Ventriculos em posicao supero-inferior associados a transposicao das grandes arterias. Correcao cirurgica em um caso. / Ventricles in the superior-inferior position associated with transposition of great vessel. Surgical correction in a case

Apresenta-se o caso de um paciente com 10 meses de idade com transposicao das grandes arterias (TGA) associada aos ventriculos em posicao supero-inferior, sem defeito do septo interventricular. As atrioseptostomias com o balao de Rashkind, realizadas aos 11 dias e aos 3 meses, permitiram bom desenvolvimento fisico ate os 10 meses, quando foi submetido a operacao de Senning para correcao da TGA. A operacao pode ser realizada sem maiores dificuldades tecnicas a despeito da superposicao ventricular e outras alteracoes anatomicas do coracao. O cateterismo pos-operatorio identificou a presenca de estenose subpulmonar que nao aparecia nos anteriores, possivelmente surgida entre os 3 e os 12 meses de idade. O paciente teve alta hospitalar no 41o. dia apos a operacao, em bom estado geral, acianotico, ganhando peso. Vinte e dois meses apos a operacao, estava assintomatico, sem medicacao, com desenvolvimento fisico normal

Variante tecnica para reoperacao de coarctacao do arco aortico. / Technical variant for reoperation of aortic arch coarctation

Os autores relatam a tecnica operatoria e o resultado da reoperacao de coarctacao calcificada no arco aortico. O acesso por esternotomia mediana anterior longitudinal e o auxilio da circulacao extracorporea, possibilitaram interpor uma protese de dacron-woven precoagulada entre a aorta ascendente e a aorta descendente e acima do diafragma. A abertura do pericardio posterior permitiu a disseccao da aorta descendente para a anastomose distal Esta tecnica mostrou-se segura, de facil execucao e eficiente no alivio dos sintomas da paciente, sendo tambem util em casos com lesoes cirurgicas associadas a coarctacao da aorta