Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study

Abstract Background Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. Methods Twenty pigs were randomly assigned to Control group (n = 10), which received saline solution; or to Sildenafil group (n = 10), which received sildenafil orally (100 mg). After 30 minutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4 µg.kg-1.h-1) for 180 minutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNFα, IL-1β, IL6, and IL10) and troponin I response. Results Significant hemodynamic alterations were observed after 30 minutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19 ± 2 mmHg to LPS30 52 ± 4 mmHg, p< 0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411 ± 29 to LPS180 334 ± 49, p< 0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35 ± 4 mmHg at LPS30, p< 0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. Conclusion Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.

Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis.

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.

Sevoflurane preconditioning during myocardial ischemia-reperfusion reduces infarct size and preserves autonomic control of circulation in rats

ABSTRACT PURPOSE: To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia-reperfusion. METHODS: Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. RESULTS: The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. CONCLUSION: Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period.

Pulse pressure variation and stroke volume variation under different inhaled concentrations of isoflurane, sevoflurane and desflurane in pigs undergoing hemorrhage

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.

Estudo comparativo entre bupivacaína (S75-R25) e ropivacaína para avaliar a segurança cardiovascular em bloqueio do plexo braquial / Comparative study related to cardiovascular safety between bupivacaine (S75-R25) and ropivacaine in brachial plexus block / Estudio comparativo entre la bupivacaína (S75-R25) y la ropivacaína para evaluar la seguridad cardiovascular en el bloqueo del plexo braquial

JUSTIFICATIVA E OBJETIVOS: Bupivacaína é o fármaco de escolha para anestesia regional por causa da eficácia, longa duração e do bloqueio motor menos intenso. Bupivacaína (S75-R25) é uma mistura de isômeros ópticos que contém 75% de levobupivacaína (S-) e 25% de dextrobupivacaína (R+) e foi criada por uma companhia farmacêutica brasileira. Este estudo comparou a eficácia e segurança de bupivacaína S75-R25 com vasoconstritor e ropivacaína para o sistema cardiovascular em bloqueio do plexo braquial. MÉTODOS: Pacientes foram randomizados para receber bloqueio do plexo braquial com bupivacaína S75-R25 (Grupo B) com epinefrina 1:200.000 ou ropivacaína (Grupo R), ambos os fármacos a 0,50%, em 30 mL ECG contínuo (Holter) foi registrado durante todo o procedimento, bem como a escala de força de Lovett, além de monitoramento (frequência cardíaca, oximetria de pulso e pressão arterial não invasiva). A incidência de eventos adversos foi comparada com os testes do qui-quadrado ou exato de Fisher. RESULTADOS: Quarenta e quatro pacientes foram estudados. Não houve diferença significativa em relação à idade, peso, altura, gênero e tempo cirúrgico. Não houve diferença entre arritmias supraventriculares antes ou depois do bloqueio do plexo braquial, independentemente do anestésico local escolhido. A perda de sensibilidade foi mais rápida no Grupo B (23,1 ± 11,7 min) em comparação com o Grupo R (26,8 ± 11,5 min), embora não significativa (p = 0,205, teste t de Student). Houve uma redução da frequência cardíaca, observada durante a monitoração contínua de 24 horas (Holter). CONCLUSÃO: Este estudo demonstrou eficácia semelhante entre bupivacaína S75-R25 e ropivacaína para bloqueio do plexo braquial, com incidências semelhantes de arritmias supraventriculares.

BACKGROUND AND OBJECTIVES: Bupivacaine is a first choice for regional anesthesia considering its effectiveness, long duration and less motor blockade. Bupivacaine (S75-R25) is a mixture of optical isomers containing 75% levobupivacaine (S-) and 25% dextrobupivacaine (R+) created by a Brazilian pharmaceutical company. This investigation compared cardiac safety and efficacy of bupivacaine S75-R25 with vasoconstrictor and ropivacaine for brachial plexus blockade. METHODS: Patients were randomized to receive brachial plexus anesthesia with either bupivacaine S75-R25 with epinephrine 1:200,000 (bupi) or ropivacaine (ropi), both at 0.50%, in 30 mL solution. We registered a continuous Holter ECG throughout the procedure, as well as the Lovett scale of force in addition to monitoring (heart rate, pulse oximetry and non-invasive blood pressure). The incidence of adverse events was compared with the chi-square or Fisher test. RESULTS: We allocated forty-four patients into two groups. They did not show any difference related to age, weight or height, gender, as well as for surgical duration. Supraventricular arrhythmias were not different before or after the plexus blockade, independent of the local anesthetic chosen. Loss of sensitivity was faster for the bupivacaine group (23.1 ± 11.7 min) compared to the ropivacaine one (26.8 ± 11.5 min), though not significant (p = 0.205, Student t). There was a reduction in the cardiac rate, observed during the twenty-four-hour Holter monitoring. CONCLUSIONS: This study showed similar efficacy between bupivacaine S75-R25 for brachial plexus blockade and ropivacaine, with similar incidences of supraventricular arrhythmias.

JUSTIFICATIVA Y OBJETIVOS: La Bupivacaína es el fármaco por elección para la anestesia regional por poseer una eficacia, una larga duración y un bloqueo motor menos intenso. La Bupivacaína (S75-R25) consiste en una mezcla de isómeros ópticos que contienen un 75% de levobupivacaína (S-) y un 25% de dextrobupivacaína (R+), y fue creada por una compañía farmacéutica brasileña. Este estudio comparó la eficacia y la seguridad de la bupivacaína S75-R25 con el vasoconstrictor y la ropivacaína para el sistema cardiovascular en el bloqueo del plexo braquial. MÉTODOS: El equipo de investigación colocó de forma aleatoria a los pacientes que recibirían el bloqueo del plexo braquial con la bupivacaína S75-R25 (Grupo B) o la ropivacaína (Grupo R), ambos fármacos al 0,50%, y 30 mL de epinefrina 1:200.000. El ECG continuo (Holter) se registró durante todo el procedimiento, como también la escala de fuerza de Lovett, además de la monitorización (frecuencia cardíaca, oximetría de pulso y presión arterial no invasiva). La incidencia de eventos adversos fue comparada con los test del Xi-Cuadrado (Xi²) o exacto de Fisher. RESULTADOS: Fueron divididos en dos grupos 44 pacientes. No hubo diferencia significativa con relación a la edad, peso, altura, sexo y tiempo de operación. No hubo diferencia entre las arritmias supraventriculares antes o después del bloqueo del plexo braquial, independientemente del anestésico local elegido. La pérdida de sensibilidad fue más rápida en el Grupo B (23,1 ± 11,7 min) en comparación con el Grupo R (26,8 ± 11,5 min), aunque no fuere significativa (p = 0,205, test t de Student). Hubo una reducción de la frecuencia cardíaca, observada durante la monitorización continua de 24 horas (Holter). CONCLUSIONES: Este estudio demostró una eficacia parecida entre la bupivacaína S75-R25 y la ropivacaína para el bloqueo del plexo braquial, con incidencias parecidas de arritmias supraventriculares.

High levels of B-type natriuretic peptide predict weaning failure from mechanical ventilation in adult patients after cardiac surgery

OBJECTIVE: The failure to wean from mechanical ventilation is related to worse outcomes after cardiac surgery. The aim of this study was to evaluate whether the serum level of B-type natriuretic peptide is a predictor of weaning failure from mechanical ventilation after cardiac surgery. METHODS: We conducted a prospective, observational cohort study of 101 patients who underwent on-pump coronary artery bypass grafting. B-type natriuretic peptide was measured postoperatively after intensive care unit admission and at the end of a 60-min spontaneous breathing test. The demographic data, hemodynamic and respiratory parameters, fluid balance, need for vasopressor or inotropic support, and length of the intensive care unit and hospital stays were recorded. Weaning failure was considered as either the inability to sustain spontaneous breathing after 60 min or the need for reintubation within 48 h. RESULTS: Of the 101 patients studied, 12 patients failed the weaning trial. There were no differences between the groups in the baseline or intraoperative characteristics, including left ventricular function, EuroSCORE and lengths of the cardiac procedure and cardiopulmonary bypass. The B-type natriuretic peptide levels were significantly higher at intensive care unit admission and at the end of the breathing test in the patients with weaning failure compared with the patients who were successfully weaned. In a multivariate model, a high B-type natriuretic peptide level at the end of a spontaneous breathing trial was the only independent predictor of weaning failure from mechanical ventilation. CONCLUSIONS: A high B-type natriuretic peptide level is a predictive factor for the failure to wean from mechanical ventilation after cardiac surgery. These findings suggest that optimizing ventricular function should be a goal during the perioperative period.

Evaluation of hemodynamic effects of xenon in dogs undergoing hemorrhagic shock

OBJECTIVES: The anesthetic gas xenon is reported to preserve hemodynamic stability during general anesthesia. However, the effects of the gas during shock are unclear. The objective of this study was to evaluate the effect of Xe on hemodynamic stability and tissue perfusion in a canine model of hemorrhagic shock. METHOD: Twenty-six dogs, mechanically ventilated with a fraction of inspired oxygen of 21% and anesthetized with etomidate and vecuronium, were randomized into Xenon (Xe; n = 13) or Control (C; n = 13) groups. Following hemodynamic monitoring, a pressure-driven shock was induced to reach an arterial pressure of 40 mmHg. Hemodynamic data and blood samples were collected prior to bleeding, immediately after bleeding and 5, 20 and 40 minutes following shock. The Xe group was treated with 79% Xe diluted in ambient air, inhaled for 20 minutes after shock. RESULT: The mean bleeding volume was 44 mL.kg-1 in the C group and 40 mL.kg-1 in the Xe group. Hemorrhage promoted a decrease in both the cardiac index (p<0.001) and mean arterial pressure (p<0.001). These changes were associated with an increase in lactate levels and worsening of oxygen transport variables in both groups (p<0.05). Inhalation of xenon did not cause further worsening of hemodynamics or tissue perfusion markers. CONCLUSIONS: Xenon did not alter hemodynamic stability or tissue perfusion in an experimentally controlled hemorrhagic shock model. However, further studies are necessary to validate this drug in other contexts.

Diaphragmatic pacing stimulation in spinal cord injury: anesthetic and perioperative management

OBJECTIVE: The standard therapy for patients with high-level spinal cord injury is long-term mechanical ventilation through a tracheostomy. However, in some cases, this approach results in death or disability. The aim of this study is to highlight the anesthetics and perioperative aspects of patients undergoing insertion of a diaphragmatic pacemaker. METHODS: Five patients with quadriplegia following high cervical traumatic spinal cord injury and ventilator-dependent chronic respiratory failure were implanted with a laparoscopic diaphragmatic pacemaker after preoperative assessments of their phrenic nerve function and diaphragm contractility through transcutaneous nerve stimulation. ClinicalTrials.gov: NCT01385384. RESULTS: The diaphragmatic pacemaker placement was successful in all of the patients. Two patients presented with capnothorax during the perioperative period, which resolved without consequences. After six months, three patients achieved continuous use of the diaphragm pacing system, and one patient could be removed from mechanical ventilation for more than 4 hours per day. CONCLUSIONS: The implantation of a diaphragmatic phrenic system is a new and safe technique with potential to improve the quality of life of patients who are dependent on mechanical ventilation because of spinal cord injuries. Appropriate indication and adequate perioperative care are fundamental to achieving better results.

Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial

BACKGROUND: The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days). A p-value of <0.05 was considered significant. RESULTS: The anthropometric and clinical characteristics of the patients from each group were similar, except for weight and body mass index. The mean glucose level during the protocol period was 126.69 mg/dl in the treated group and 168.21 mg/dl in the control group (p<0.0016). There were no differences between groups regarding clinical outcomes, including the duration of mechanical ventilation, length of stay in the intensive care unit, blood transfusion, postoperative infection, hypoglycemic event, neurological dysfunction or 30-day mortality (p>0.05). CONCLUSIONS: In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily...