ABSTRACT Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

OBJECTIVES: Inhalant anesthesia induces dose-dependent cardiovascular depression, but whether fluid responsiveness is differentially influenced by the inhalant agent and plasma volemia remains unknown. The aim of this study was to compare the effects of isoflurane, sevoflurane and desflurane on pulse pressure variation and stroke volume variation in pigs undergoing hemorrhage. METHODS: Twenty-five pigs were randomly anesthetized with isoflurane, sevoflurane or desflurane. Hemodynamic and echocardiographic data were registered sequentially at minimum alveolar concentrations of 1.00 (M1), 1.25 (M2), and 1.00 (M3). Then, following withdrawal of 30% of the estimated blood volume, these data were registered at a minimum alveolar concentrations of 1.00 (M4) and 1.25 (M5). RESULTS: The minimum alveolar concentration increase from 1.00 to 1.25 (M2) decreased the cardiac index and increased the central venous pressure, but only modest changes in mean arterial pressure, pulse pressure variation and stroke volume variation were observed in all groups from M1 to M2. A significant decrease in mean arterial pressure was only observed with desflurane. Following blood loss (M4), pulse pressure variation, stroke volume variation and central venous pressure increased (p<0.001) and mean arterial pressure decreased in all groups. Under hypovolemia, the cardiac index decreased with the increase of anesthesia depth in a similar manner in all groups. CONCLUSION: The effects of desflurane, sevoflurane and isoflurane on pulse pressure variation and stroke volume variation were not different during normovolemia or hypovolemia.

JUSTIFICATIVA E OBJETIVOS: Hipoxemia grave é uma complicação freqüente no pós-operatório imediato de revascularização do miocárdio (RM), promovendo aumento da duração da ventilação mecânica, da incidência de infecções pulmonares, dos custos e da mortalidade. O objetivo desse estudo foi identificar fatores preditivos de hipoxemia grave em pacientes submetidos à RM. MÉTODO: Foram estudados 481 pacientes adultos submetidos à RM eletiva entre outubro de 2003 e março de 2004. Considerou-se hipoxemia grave uma relação PaO2/FiO2 < 150 na admissão à UTI. A análise estatística foi realizada por meio de teste de Qui-quadrado, t de Student ou Wilcoxon, seguida de análise multivariada por meio de regressão logística (RL) para variáveis com valor p < 0,25 na análise univariada. Considerou-se valor de p > 0,2 para exclusão da variável do modelo de RL e p < 0,1 como sendo significativo. RESULTADOS: O tempo para extubação dos pacientes com hipoxemia grave foi maior que nos outros pacientes (p < 0,001). Na análise multivariada, as variáveis idade (p = 0,081), peso (p = 0,001), necessidade de CEC prolongada (p = 0,033) e disfunção ventricular esquerda (p = 0,082) foram identificadas como preditores independentes para hipoxemia grave. CONCLUSÕES: Pacientes com idade e peso elevados, disfunção ventricular esquerda e necessidade de CEC apresentaram risco aumentado para hipoxemia grave após RM. Nesses pacientes, o uso de estratégias ventilatórias perioperatória com pressões positivas expiratórias mais elevadas e manobra de recrutamento alveolar devem ser consideradas tendo como objetivo a prevenção da disfunção pulmonar pós-operatória.

BACKGROUND AND OBJECTIVES: Severe hypoxemia is complication frequently seen in the immediate postoperative period of myocardial revascularization (MR), increasing the duration of mechanical ventilation, the incidence of pulmonary infections, hospital costs, and mortality. The objective of this study was to identify predictive factors of severe hypoxemia in patients undergoing MR. METHODS: Four-hundred and eighty-one adult patients undergoing elective MR between October 2003 and March 2004 were enrolled in this study. Severe hypoxemia was defined as PaO2/FiO2 < 150 upon admission to the ICU. The Chi-square test, Student's t or Wilcoxon test, followed by multivariate analysis and logistic regression (LR) for parameters with p < 0.25 in the univariate analysis, were used for the statistical analysis. A p > 0.2 was required to exclude the parameter from the LR model, and a p < 0.1 was considered significant. RESULTS: Time for extubation was greater in patients with severe hypoxemia (p < 0.001). Multivariate analysis identified age (p = 0.081), weight (p = 0.001), need of prolonged CBP (p = 0.033), and left ventricular dysfunction (p = 0.082) as independent predictors of severe hypoxemia. CONCLUSIONS: Older and overweighted patients, those with left ventricular dysfunction, and those who needed CPB presented an increased risk of severe hypoxemia after MR. In those patients, the use of perioperative ventilatory strategies, with elevated positive expiratory pressures and alveolar recruitment maneuver should be considered to prevent postoperative pulmonary dysfunction.

JUSTIFICATIVA Y OBJETIVOS: La hipoxemia grave es una complicación frecuente en el postoperatorio inmediato de revascularización del miocardio (RM), promoviendo un aumento de la duración de la ventilación mecánica, de la incidencia de infecciones pulmonares, de los costos y de la mortalidad. El objetivo de este estudio fue identificar factores de predicción de hipoxemia grave en pacientes sometidos a la RM. MÉTODO: Se estudiaron 481 pacientes adultos sometidos a la RM electiva entre octubre de 2003 y marzo de 2004. Se tomó en consideración hipoxemia grave en una relación PaO2/FiO2 < 150 en la admisión a la UCI. El análisis estadístico fue realizada a través de test de cui cuadrado, t de Student o Wilcoxon, seguido de análisis multivariado a través de regresión logística (RL) para variables con valor p < 0,25 en el análisis univariado. Se tuvo en cuenta el valor de p > 0,2 para la exclusión de la variable del modelo de RL y p < 0,1 como siendo significativo. RESULTADOS: El tiempo para la extubación de los pacientes con hipoxemia grave fue mayor que en los otros pacientes (p < 0,001). En el análisis multivariado, las variables edad (p = 0,081), peso (p = 0,001), necesidad de CEC prolongada (p = 0,033) y disfunción ventricular izquierda (p = 0,082) fueron identificadas como de predicción independientes para hipoxemia grave. CONCLUSIONES: Pacientes con edad y peso elevados, disfunción ventricular izquierda y necesidad de CEC presentaron un riesgo aumentado para hipoxemia grave después de la RM. NE estos pacientes, el uso de estrategias ventilatorias perioperatoria con presiones positivas de expiración más elevadas y la maniobra de reclutamiento alveolar deben ser consideradas teniendo en cuenta la prevención de la disfunción pulmonar postoperatoria.

FUNDAMENTO: Os betabloqueadores são usados no tratamento da angina pectoris e outras doenças coronarianas isquêmicas, reduzindo mortalidade e eventos cardiovasculares. O atenolol é um betabloqueador hidrofílico, de absorção gastrointestinal, extensão de distribuição pequena e eliminação função renal-dependente. OBJETIVO: O objetivo deste estudo é o de determinar a variabilidade inter-individual do atenolol em pacientes coronarianos. MÉTODOS: Quantificou-se o atenolol plasmático em 6 amostras sangüíneas coletadas no pré-operatório de sete indivíduos portadores de insuficiência coronariana e indicação cirúrgica de revascularização do miocárdio, tratados cronicamente com atenolol, com doses diárias variando entre 25 a 100 mg PO. Todos os pacientes apresentavam função renal dentro da normalidade ou levemente reduzida. RESULTADOS: As concentrações plasmáticas obtidas evidenciaram decaimento monoexponencial, confirmando que o atenolol apresenta farmacocinética de primeira ordem nas doses empregadas para o controle da insuficiência coronariana grave (médias ± DP): 123 ± 56, 329 ± 96, 288 ± 898, 258 ± 85, 228 ± 79 e 182 ± 73 ng/mL, nos tempos zero, 2, 4, 6, 8 e 12 horas após a administração da dose. Registrou-se pequena variabilidade inter-pacientes nas concentrações plasmáticas de atenolol no grupo investigado tratado em regime de doses múltiplas, devido à característica hidrofílica do fármaco. Registrou-se ainda, maior persistência do atenolol nos pacientes coronarianos investigados, comparado a indivíduos saudáveis. CONCLUSÃO: Em virtude da sua cardioseletividade e baixa variabilidade, sugere-se que o atenolol deve ser empregado como fármaco de primeira escolha para o tratamento da síndrome coronariana aguda e outras doenças cardiovasculares.

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.