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.

Effects of acute hypovolaemia by furosemide on tracheal transepithelial potential difference and mucus in dogs.

Furosemide is a potent diuretic that affects water transfer across the respiratory epithelium, which is closely related to the transepithelial potential difference (PD). Water is a critical factor that determines mucus transport; an important lung defence mechanism that removes particles and microorganisms from the respiratory system. The aim of the present study was to investigate the acute effects of furosemide and hypovolaemia on tracheal PD and mucus properties. A total of 36 male mixed-breed dogs were submitted to anaesthesia, mechanical ventilation and haemodynamic monitoring. They were randomly assigned to three groups consisting of: a control group, a furosemide (40 mg i.v.) + hypovolaemia group, and a furosemide (40 mg i.v.) + volume replacement group. Tracheal PD and mucus samples were collected at time 0, 1 and 2 h after intervention. Mucus properties were analysed by means of a magnetic microrheometer and in vitro mucociliary transportability on the frog palate. Compared to controls, furosemide decreased PD to intermediate values, and only significantly when associated with hypovolaemia (-13+/-5 and -8+/-2 mV, time 0 and 2 h, respectively). In addition to the direct effect of furosemide, these results indicate that hypovolaemia also affects ion transport in the tracheal membrane. Furosemide and hypovolemia have no acute effects on respiratory mucus properties.

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

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 ...

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