J Auler

Inhaled nitric oxide leading to pulmonary edema in stable severe heart failure.

Abstract The mechanism of increased pulmonary wedge pressure and cardiac output after nitric oxide inhalation is not clear. Nitric oxide is rapidly inactivated by hemoglobin before it can produce systemic effects. 3 Thus, selective nitric oxide pulmonary vasodilator effects led to these preliminary results. The hypothesis is that acute reduction in right ventricular afterload caused an acute increment of right ventricular cardiac output. The acute increment of blood return to the impaired left ventricle not associated with reduction in afterload caused the increase in wedge pressure and consequently pulmonary edema. In addition, acute reduction in right ventricular afterload could lead to redistribution of blood volume to pulmonary circulation. The absence of pulmonary edema in these patients in the nitroprusside study reinforces the importance of selective nitric oxide effects in pulmonary circulation.

Pulse pressure variation: beyond the fluid management of patients with shock

In anesthetized patients without cardiac arrhythmia the arterial pulse pressure variation (PPV) induced by mechanical ventilation has been shown the most accurate predictor of fluid responsiveness. In this respect, PPV has so far been used mainly in the decision-making process regarding volume expansion in patients with shock. As an indicator of the position on the Frank–Starling curve, PPV may actually be useful in many other clinical situations. In patients with acute lung injury or with acute respiratory distress syndrome, PPV can predict hemodynamic instability induced by positive end-expiratory pressure and recruitment maneuvers. PPV may also be useful to prevent excessive fluid restriction/depletion in patients with pulmonary edema, and to prevent excessive ultrafiltration in critically ill patients undergoing hemodialysis or hemofiltration. In the operating room, a goal-directed fluid therapy based on PPV monitoring has the potential to improve the outcome of patients undergoing high-risk surgery.

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 +/- 0.79 cmH2O l-1 s-1 at ZEEP, 11.94 +/- 0.55 cmH2O l-1 s-1 (P<0.0197) at 5 cmH2O of PEEP, 11.42 +/- 0.71 cmH2O l-1 s-1 (P<0.0255) at 10 cmH2O of PEEP, and 10.32 +/- 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 +/- 1.21) to 5 cmH2O (21.89 +/- 0.70). However, a significant decrease (P<0.0003) at 10 cmH2O PEEP (18.86 +/- 1.13), as well as (P<0.0001) at 15 cmH2O (18.41 +/- 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 +/- 0.22 at ZEEP, 3.43 +/- 0.17 (P<0. 0260) at 5 cmH2O of PEEP, 3.31 +/- 0.22 (P<0.0260) at 10 cmH2O of PEEP, and 3.10 +/- 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 +/- 2.28 at ZEEP to 11.66 +/- 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.

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 m(2)), 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% CI = 3.9-6.9) to 10.6 h (95% CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3) to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6) vs 10.7 ml min(-1) kg(-1) (95% 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 inhaled nitric oxide on respiratory system mechanics, hemodynamics, and gas exchange after cardiac surgery

OBJECTIVE To evaluate the hemodynamic and respiratory effects of inhaled nitric oxide (NO) in postoperative cardiac patients. DESIGN A prospective evaluation. SETTING A university hospital intensive care unit. PARTICIPANTS Fourteen adults with pulmonary hypertension, studied postoperatively. INTERVENTIONS 60 minutes of NO inhalation (20 ppm). MEASUREMENTS AND MAIN RESULTS Respiratory mechanics were analyzed by inflating the relaxed respiratory system with constant flow, followed by rapid airway occlusion at end-inflation, which was maintained until a plateau in tracheal pressure was obtained. Gas exchange and hemodynamics were evaluated by conventional means. The data were studied using the analysis of variance for repeated measures. Minimum airway resistance (Rmin) increased significantly from 8.87+/-3.24 cm H2O/L x s to 9.69 +/-3.22 cm H2O/L x s at the end of NO inhalation and remained elevated after NO was discontinued. A selective vasodilator effect on pulmonary vasculature was observed in the pulmonary-systemic vascular resistance ratio, which decreased from 0.18+/-0.11 to 0.13+/-0.08 at the end of inhalation and returned to baseline values after gas suspension. No significant alterations in oxygenation were observed. CONCLUSION The effects of NO as a powerful and useful vasodilator agent were confirmed. However, it is important to be aware that the effects observed on respiratory mechanics may interfere with the final response of the respiratory system to NO.

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/m(2)). LHM was performed applying continuous positive airway pressure (CPAP) with a face mask, increased by 3-cmH(2)O steps up to 20 cmH(2)O every 5 breaths. At CPAP 20 cmH(2)O, an inspiratory pressure of 20 cmH(2)O above CPAP was applied, reaching an airway pressure of 40 cmH(2)O for 10 breaths. CPAP was then decreased stepwise. Blood samples were collected before and 2 and 12 h after LHM. TNF-alpha, IL-1beta, 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-alpha: 1.2 +/- 3.8 vs 6.4 +/- 8.6 pg/mL; IL-1beta: 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.

Hemodynamic effects of PEEP in a porcine model of HCl-induced mild acute lung injury.

Background: Positive end‐expiratory pressure (PEEP) and sustained inspiratory insufflations (SI) during acute lung injury (ALI) are suggested to improve oxygenation and respiratory mechanics. We aimed to investigate the hemodynamic effects of PEEP with and without alveolar recruiting maneuver in a mild ALI model induced by inhalation of hydrochloric acid.

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol

The pharmacokinetics of some beta-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32 degrees C). On the day before and on the first day after surgery, blood samples were collected before beta-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 +/- 0.75 to 11.46 +/- 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 +/- 2.83 to 19.33 +/- 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 +/- 1.60 to 11.44 +/- 2.89 h) or atenolol volume of distribution (from 2.90 +/- 0.36 to 3.83 +/- 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.

Perioperative Cardiac Risk Stratification

Cardiovascular events are considered the main cause of death in the perioperative period. The most important events are acute myocardial infarction (MI), unstable angina, cardiac failure, severe arrhythmias, nonfatal cardiac arrest, and death. Patients experiencing an MI after noncardiac surgery have a hospital mortality rate of 15–25% [1, 2], and nonfatal perioperative MI is an independent risk factor for cardiovascular death and nonfatal MI during the 6 months following surgery. Patients who have a cardiac arrest after noncardiac surgery have a hospital mortality rate of 65%, and nonfatal perioperative cardiac arrest is a risk factor for cardiac death during the 5 years following surgery [3, 4]. The objectives of preoperative evaluation are: (a) performing an evaluation of the patient’s current medical status; (b) making recommendations concerning the evaluation, management, and risk of cardiac problems over the entire perioperative period; and (c) providing a clinical risk profile that the patient, primary physician, anesthesiologist, and surgeon can use in making treatment decisions that may influence short- and long-term outcomes. No test should be performed unless it is likely to influence patient treatment [5]. The cost of risk stratification cannot be ignored. Accurate estimation of a patient’s risk for postoperative cardiac events (MI, unstable angina, ventricular tachycardia, pulmonary edema, and death) after surgery can guide allocation of clinical resources, use of preventive therapies, and priorities for future research.

Pulmonary Effects of Acute Normovolaemic Haemodilution

Transfusion therapy risks have been clarified in a consistent literature for decades [1]. Transmission of infectious diseases, transfusion reactions, immunosuppression, transfusion-related acute lung injury and high costs have led to investigations regarding alternatives to allogenic red blood cell transfusion, and physiological effects of lower haemoglobin levels have been developed. Preoperative and intraoperative restrictive red cell transfusion strategies may be used individually or in combination. They include: preoperative autologous blood donation; preoperative use of erythropoietin; acute normovolaemic haemodilution; intraoperative cell salvage and pre-transfusion; pharmacological treatment (aprotinin, e-aminocaproic acid, tranexamic acid); anaesthesia technique (normothermia, fluid replacement, hyperoxic ventilation, hypotensive anaesthesia); minimal haemoglobin levels; and transfusion algorithms based on coagulation monitoring and artificial O2 carriers [2]. Acute normovolaemic haemodilution (ANH) has been used in an attempt to decrease the need for allogenic blood transfusion in the course of a variety of surgical procedures [3]. Many controversies exist concerning ANH, such as the target haematocrit, the most appropriate fluid to be used [4], the risks incurred [5], the real benefits [6]–[8], and how the anaesthetic technique may influence the compensatory mechanisms [9]–[11].