Antoine Vieillard-Baron

Acute cor pulmonale in ARDS.

In 1977, Zapol and colleagues [1] reported that the pulmonary circulation was injured in patients with ARDS, leading to elevated pulmonary vascular resistance and pulmonary hypertension. The investigators suggested that the pathogenesis was related to competition between alveolar distending pressure and blood flow in these patients who were ventilated with high airway pressure [2], as proposed by West et al. [3]. Pulmonary vascular remodeling also occurs with muscularization of normally non-muscularized arteries. Subsequently, using transesophageal echocardiography (TEE), 24 years later Vieillard-Baron et al. [4] reported an incidence of acute cor pulmonale (ACP) of 25 % during the first 3 days in 75 ARDS patients treated with lung protective ventilation. A few years later, the same group reported a much higher incidence of 50 % in more severe patients, all exhibiting a PaO2/FiO2 <100 mmHg [5]. The same group studied 352 patients and found that the incidence of ACP was related to elevated plateau airway pressure (Pplat) with a safe limit for the right ventricle of 27 cmH2O [6]. Since then, several questions are still unresolved, including: What is the actual incidence of ACP in a larger population? Which are the main variables associated with ACP? What is the impact of ACP on prognosis, if any? Should RV function be monitored, and, if so, how? Should clinicians adjust the ventilatory strategy to RV function? Recently published clinical studies provide answers to some of these questions. Boissier et al. [7] reported an incidence of ACP of 22 % (95 % CI 16–27 %) in a prospective single-center study of 226 patients using TEE within the first 3 days following diagnosis of ARDS. Patients met the Berlin definition criteria for moderate to severe ARDS [8]. They were ventilated in a volume control mode with a tidal volume of 6 ml/kg, a Pplat of <30 cmH2O and a PEEP of 8–9 cmH2O [7]. In a multivariate logistic regression, independent factors associated with ACP were an infection as a cause of lung injury and the driving pressure (17 cmH2O in patients with ACP versus 14 cmH2O) [7]. The driving pressure is the distending pressure related to tidal volume, and it then depends on tidal volume (i.e., the ventilatory strategy) and also on compliance of the respiratory system (i.e., the severity of injury). Infection as a factor associated with ACP is interesting. As discussed by Boissier et al. [7], circulating cytokines may contribute to myocardial dysfunction. In addition, inflammation, including infection, is an important component of vascular remodeling in chronic pulmonary hypertension. In the acute setting, vasoconstrictors may be more important, but inflammation may also enhance pulmonary vasoconstriction [9]. In the study by Boissier et al. [7], the consequences of ACP for hemodynamics included a significant increase in heart rate, a decrease in systemic blood pressure and the need for hemodynamic support. ACP was independently associated with 28-day mortality and in-hospital mortality, as well as the McCabe and Jackson class, another cause of lung injury than aspiration, driving pressure (per cmH2O) and an elevated plasma lactate (per mmol/l) [7]. In another large prospective multicenter study of 200 patients with moderate to severe ARDS, Lheritier et al. found a similar incidence of ACP (23, 95 % CI 17–29 %) [10]. The only factor independently associated with ACP was a PaCO2 ≥ 60 mmHg. Data on the driving pressure were not available [10]. This result is interesting because a few years ago Mekontso-Dessap et al. [11] suggested that increased PaCO2 had a major deleterious effect on RV function in very severe ARDS patients, also previously suggested by Vieillard-Baron et al. [4] in 2001. Hypercapnia is a vasoconstrictor of the pulmonary circulation [12]. Elevated PaCO2 can be a consequence of the ventilatory strategy and severity of lung injury, as suggested by the impact of an elevated pulmonary dead space fraction on prognosis [13]. Also, based on the results of the study by Lheriter et al. [10], monitoring RV function by transesophageal echocardiography was much more effective than transthoracic echocardiography. Finally, this study indicated that ACP was not associated with mortality [10]. Why was this result different from the result of the study by Boissier et al.? In the study by Lheritier et al. [10], almost half of the patients with ACP were ventilated in the prone position compared to only 32 % of patients without ACP. It has been clearly reported that lung protective ventilation in the prone position decreases Pplat [14]. In their cohort of 352 patients, Jardin et al. [6] suggested that the effect of ACP on prognosis depends in part on Pplat with a safe limit at 27 cmH2O. These results prompt us to recommend that clinicians consider monitoring RV function using TEE in moderate to severe ARDS patients and to adapt the therapeutic lung protective ventilation strategy according to the function of the right ventricle. This can be considered an “RV protective approach,” as illustrated in the Fig. 1. Recently, in a randomized clinical trial comparing supine to prone positioning (PROSEVA), Guerin et al. [15] reported a large beneficial effect of the prone position on reducing mortality in severe and persistent ARDS with a PaO2/FiO2 <150 mmHg. The prone positioning may have been effective in part because of the beneficial effects on the pulmonary circulation and the right ventricle. The prone position may be an ideal protective approach for improving the function of the RV because it corrects hypoxemia without increasing PEEP, and it decreases the PaCO2 and Pplat by recruiting collapsed lung zones. This result can be contrasted with the “open-lung” approach, as represented by high-frequency oscillation ventilation (HFO), which worsened mortality, with more circulatory failure and a higher vasopressor requirement [16], perhaps reflecting increased RV failure, as shown by Guervilly et al. [17]. In HFO ventilation, airway pressure remains significantly elevated during all the respiratory cycle. Fig. 1 Proposed approach to preventing acute cor pulmonale and limiting its consequences: a right ventricular protective approach. RR respiratory rate, RV right ventricular, HME heat and moisture exchanger, PP prone positioning, PEEP positive end-expiratory ... However, some issues remain unclear. Do we need to turn patients with ACP to the prone position, even though PaO2/FiO2 is still >150 mmHg? Could inflammation-driven pulmonary vasoconstriction be a therapeutic target to reduce injury to the pulmonary microcirculation, for example, with novel therapeutics such as mesenchymal stromal cells or other anti-inflammatory therapies such as statins [18]? What is the effect of isolated RV dilatation without paradoxical septal motion, and is it predictive of imminent ACP/RV failure? How should the level of PEEP be adjusted in individual ARDS patients, providing that the Pplat is maintained below 27 cmH2O? Some preliminary data suggest that the effect of PEEP on the pulmonary circulation and RV function depends on the balance between recruitment and overdistension induced by application of PEEP [11]. Finally, would the RV protective approach, as presented in the Fig. 1, have a beneficial survival effect compared to a more conventional approach? Further clinical and experimental studies will be needed to address these questions.

Rationale and Description of Right Ventricle-Protective Ventilation in ARDS.

Pulmonary vascular dysfunction is associated with ARDS and leads to increased right-ventricular afterload and eventually right-ventricular failure, also called acute cor pulmonale. Interest in acute cor pulmonale and its negative impact on outcome in patients with ARDS has grown in recent years. Right-ventricular function in these patients should be closely monitored, and this is helped by the widespread use of echocardiography in intensive care units. Because mechanical ventilation may worsen right-ventricular failure, the interaction between the lungs and the right ventricle appears to be a key factor in the ventilation strategy. In this review, a rationale for a right ventricle-protective ventilation approach is provided, and such a strategy is described, including the reduction of lung stress (ie, the limitation of plateau pressure and driving pressure), the reduction of PaCO2, and the improvement of oxygenation. Prone positioning seems to be a crucial part of this strategy by protecting both the lungs and the right ventricle, resulting in increased survival of patients with ARDS. Further studies are required to validate the positive impact on prognosis of right ventricle-protective mechanical ventilation.

Value and determinants of the mean systemic filling pressure in critically ill patients

Mean systemic filling pressure (Pmsf) is a major determinant of venous return. Its value is unknown in critically ill patients (ICU). Our objectives were to report Pmsf in critically ill patients and to look for its clinical determinants, if any. We performed a prospective study in 202 patients who died in the ICU with a central venous and/or arterial catheter. One minute after the heart stopped beating, intravascular pressures were recorded in the supine position after ventilator disconnection. Parameters at admission, during the ICU stay, and at the time of death were prospectively collected. One-minute Pmsf was 12.8 ± 5.6 mmHg. It did not differ according to gender, severity score, diagnosis at admission, fluid balance, need for and duration of mechanical ventilation, or length of stay. Nor was there any difference according to suspected cause of death, classified as shock (cardiogenic, septic, and hemorrhagic) and nonshock, although a large variability of values was observed. The presence of norepinephrine at the time of death (102 patients) was associated with a higher 1-min Pmsf (14 ± 6 vs. 11.4 ± 4.5 mmHg), whereas the decision to forgo life-sustaining therapy (34 patients) was associated with a lower 1-min Pmsf (10.9 ± 3.8 vs. 13.1 ± 5.3 mmHg). In a multiple-regression analysis, norepinephrine (β = 2.67, P = 0.0004) and age (β = -0.061, P = 0.022) were associated with 1-min Pmsf. One-minute Pmsf appeared highly variable without any difference according to the kind of shock and fluid balance, but was higher with norepinephrine.

Reply to "Letter to the editor: Comments on 'Value and determinants of the mean systemic filling pressure in critically ill patients'".

reply: We thank Dr. Brengelmann for his letter ([1][1]) regarding our study ([6][2]). Let us focus on three important papers published by Guyton et al. In 1954, he measured mean systemic filling pressure (Pmsf) at zero flow in anesthetized dogs and found a mean value of 6.3 mmHg ([4][3]). In 1955,

Cardiac dysfunction in sepsis.

Introduction The incidence of cardiac dysfunction in septic shock, septic cardiomyopathy, is between 40 and 60 % as diagnosed within the first 3 days [1]. Its recognition, treatment and focus for clinical research are hampered by the lack of a consensus definition. An acute or acute-on-chronic but reversible ventricular dysfunction, typically visualized at echocardiography, is generally agreed upon. The systemic nature of sepsis and the interdependence of the left (LV) and right (RV) ventricles mean that heart function is affected globally. Septic cardiomyopathy results from the infectious process (inflammation, toxins, mitochondrial dysfunction), reduced myocardial perfusion (microthrombi, flow maldistribution) and pulmonary injury (hypoxia, hypercarbia, atelectases). This summary highlights issues related to venous return, heart function and vascular tone. Although loadindependent variables have been called for to disentangle the complexities of cardiac dysfunction in sepsis, the physiological state of ventriculo-arterial coupling challenges this approach. Many issues are still unresolved and future research should focus on optimizing the methodology to assess septic cardiomyopathy and direct therapy (Table 1). The treatment of septic cardiomyopathy requires cardiovascular monitoring [2], including mean arterial pressure (MAP), central venous pressure (CVP) and cardiac output (CO) ideally supported by echocardiography that provides invaluable additional information on myocardial function. The endpoint to which therapy for septic cardiomyopathy must be titrated is the resolution of shock, which may be sequentially assessed from organ function (e.g. biochemistry and SOFA score) and matching of oxygen delivery/consumption (lactate, arteriovenous O2 and venoarterial CO2 gradients, acid–base status) [3].

Echocardiographic Applications of M-Mode Ultrasonography in Anesthesiology and Critical Care

Proficiency in echocardiography and lung ultrasound has become essential for anesthesiologists and critical care physicians. Nonetheless, comprehensive echocardiography measurements often are time-consuming and technically challenging, and conventional 2-dimensional images do not permit evaluation of specific conditions (eg, systolic anterior motion of the mitral valve, pneumothorax), which have important clinical implications in the perioperative setting. M-mode (motion-based) ultrasonographic imaging, however, provides the most reliable temporal resolution in ultrasonography. Hence, M-mode can provide clinically relevant information in echocardiography and lung ultrasound-driven approaches for diagnosis, monitoring, and interventional procedures performed by anesthesiologists and intensivists. Although M-mode is feasible, this imaging modality progressively has been abandoned in echocardiography and is often underutilized in lung ultrasound. This article aims to comprehensively illustrate contemporary applications of M-mode ultrasonography in the anesthesia and critical care medicine practice. Information presented for each clinical application will include image acquisition and interpretation, evidence-based clinical implications in the critically ill and surgical patient, and limitations. The present article focuses on echocardiography and reviews left ventricular function (mitral annular plane systolic excursion, E-point septal separation, fractional shortening, and transmitral propagation velocity); right ventricular function (tricuspid annular plane systolic excursion, subcostal echocardiographic assessment of tricuspid annulus kick, outflow tract fractional shortening, ventricular septal motion, wall thickness, and outflow tract obstruction); volume status and responsiveness (inferior vena cava and superior vena cava diameter and respiratory variability [collapsibility and distensibility indexes]); cardiac tamponade; systolic anterior motion of the mitral valve; and aortic dissection.

Impact of positive pressure ventilation on mean systemic filling pressure in critically ill patients after death

Mean systemic filling pressure (Pms) defines the pressure measured in the venous-arterial system when the cardiac output is nil. Its estimation has been proposed in patients with beating hearts by building the venous return curve, using different pairs of right atrial pressure/cardiac output during mechanical ventilation. We raised the hypothesis according to which the Pms is altered by tidal ventilation and positive end-expiratory pressure (PEEP), which would challenge this extrapolation method based on cardiopulmonary interactions. We conducted a two-center, noninterventional, observational, and prospective study, using an arterial and a venous catheter to measure the pressure in the circulatory system at the time of death in critically ill, mechanically ventilated patients with a PEEP. Arterial (Part) and venous pressures (Pra) were recorded in five conditions: at end expiration and end inspiration with and without PEEP and finally once the ventilator was disconnected. Part and Pra did not differ in any experimental conditions. Tidal ventilation increased Pra and Part by 2.4 and 1.9 mmHg, respectively, whereas PEEP increased both values by 1.2 and 1 mmHg, respectively. After disconnection of the ventilator, Pra and Part were 10.0 ± 4.2 and 9.9 ± 4.2 mmHg, respectively. Pms increases during mechanical ventilation, with an effect of tidal ventilation and PEEP. This calls into question the validity of its evaluation in heart-beating patients using cardiopulmonary interactions during mechanical ventilation.NEW & NOTEWORTHY The physiology of the mean systemic filling pressure (Pms) is not well understood in human beings. This study is the first report of a tidal ventilation- and positive end-expiratory pressure-related increase in Pms in critically ill patients. The results challenge the utility and the value estimating Pms in heart-beating patients by reconstruction of the venous return curve using varying inflation pressures.

What does acute onset means in the context of Staphylococcus aureus infective endocarditis? Description of a hyperacute infective endocarditis.

La Presse Medicale - In Press.Proof corrected by the author Available online since vendredi 1 juillet 2016