Skip to main content

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review

Abstract

Introduction

Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care.

Methods

A systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method.

Results

Clinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy.

Conclusions

This systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.

Introduction

Pulmonary vascular dysfunction is a broad term and may be central to several disease processes in the intensive care unit (ICU). Components include pulmonary endothelial dysfunction, altered lung microvascular permeability, vasoactive mediator imbalance, abnormal hypoxic vasoconstriction, pulmonary metabolic failure, microvascular thrombosis, and later, vascular remodelling [1–3]. The resulting elevation in pulmonary vascular resistance (PVR) and pulmonary hypertension (PH) may increase the transpulmonary gradient, and the right ventricular "pressure overload" can in turn result in right ventricular (RV) dysfunction and failure [4]. RV dysfunction may also result from volume overload or a primary RV pathology reducing contractility, including RV infarction and sepsis (Table 1) [4–7].

Table 1 Causes of pulmonary hypertension and right ventricle failure in the ICU

PH is defined at right-heart catheterization in the outpatient setting, with resting mPAP exceeding 25 mm Hg, and a PVR greater than 240 dyn.s.cm-5 (3 Wood units) [8]. At echocardiography, the presence of PH is suggested by the estimated RV systolic pressure (RVSP) exceeding 35 mm Hg (being severe if >50 mm Hg) (see later) [9], and the pulmonary arterial acceleration time (PAT) may be shortened [10]. Pulmonary arterial hypertension (PAH) defines PH not due to left-heart disease, with PAOP <15 mm Hg or without echocardiographic evidence of increased left atrial pressure. The severity of PH may depend on the chronicity: the actual pulmonary artery pressure generated will increase with time as the RV hypertrophies.

RV dysfunction describes reduced RV contractility, which may be detected in several ways. At echocardiography, RV distention causes the intraventricular septum to deviate, with resulting paradoxic septal movement that impinges on LV function [11]. RV function may be difficult to assess on echocardiography, especially in ventilated patients, and measurement of the descent of the RV base toward the apex (tricuspid annular systolic excursion, TAPSE) or RV fractional shortening may useful [12, 13]. Invasive monitoring may show a CVP exceeding the PAOP, or increasing CVP and PVR with a decreasing cardiac output (and mPAP may therefore decrease), and high right ventricular end-diastolic filling pressure is characteristic. By using an RV ejection fraction (RVEF) PAC, an increase in RV end-diastolic index and a reduction in RVEF are seen [14]. We have defined RV failure to be the clinical result of RV dysfunction with the onset of hypotension or any resulting end-organ (for example, renal, liver, or gastrointestinal) dysfunction. Acute cor pulmonale (ACP) refers to acute right heart failure in the setting of acutely elevated PVR due to pulmonary disease [15, 16].

Pulmonary hypertension per se is frequently encountered in the ICU. It is commonly due to elevated pulmonary venous pressure in the setting of left-sided heart disease, or in patients with preexisting pulmonary vascular disease. It is well recognized after cardiothoracic surgery, in part related to the endothelial dysfunction seen with cardiopulmonary bypass (CPB) [17, 18]. PH is also associated with sepsis [19]; acute respiratory distress syndrome (ARDS) [20–22] (with associated acute RV failure in 10% to 25% of cases [23, 24]), and in up to 60% of patients after massive pulmonary embolism (PE) [25]. PH is important to recognize in the ICU because its presence predicts increased mortality in these conditions [19, 23, 25–31] as well as after surgical procedures [32–42]. Mortality from cardiogenic shock due to RV infarction (> 50%) exceeds that due to LV disease [5]. We therefore thought that a systematic review of the current evidence for the management of PH, resulting RV dysfunction, and failure in adult patients in the ICU, would be a useful addition to the critical care literature.

The pulmonary circulation and pathophysiology of right ventricular failure

The normal pulmonary circulation is a high-flow, low-pressure system. Unlike the left ventricle (LV), the thin-walled right ventricle tolerates poorly acute increases in afterload. This may lead to acute distention (Figure 1) [4, 43], with a resulting increase in oxygen consumption and reduction in contractility [44]. The dilated RV, together with paradoxic intraventricular septal movement [45], lead to reduced LV filling [46], cardiac output (CO), and oxygen delivery [47]. The principle of ventricular interdependence is important in most settings: superficial myocardial fibers encircle both ventricles; thus they are contained within the same pericardial cavity (except maybe after cardiac surgery), as well as sharing a septum, effectively existing "in series" [48, 49]. This explains the decrease in LV output seen during positive-pressure ventilation [48, 50, 51] and why RV pressure and volume overload cause diastolic dysfunction of the LV [52]. Furthermore, because of the RV/LV interactions, the LV may markedly depend on atrial contraction for filling and may tolerate atrial fibrillation and vasodilating therapy particularly poorly [49, 53, 54].

Figure 1
figure 1

Short-axis view of a transthoracic echocardiogram in a normal subject (a) and a patient with an acutely dilated right ventricle (RV) in the setting of high pulmonary vascular resistance (b). The intraventricular septum (IVS) is D-shaped in (b), reflecting the acute RV pressure overload in this patient, and marked enlargement of the RV in (b) compared with (a). Courtesy of Dr Susanna Price, Royal Brompton Hospital, London, UK.

In addition, perfusion of the right coronary artery is usually dependent on a pressure gradient between the aorta and the right ventricle, which, in the setting of increased RV afterload and decreased coronary blood flow, may lead to RV ischemia [55], with further severe hemodynamic decompensation [56] (Figure 2). In acute-on-chronic RV-pressure overload, the already-hypertrophied RV tolerates much higher pressures before decompensation [57, 58], although the ability of the RV to augment CO in chronic PH may be restricted by its relatively "fixed" afterload. In any setting, the most common cause of increased RV afterload is an increase in PVR (Table 2).

Figure 2
figure 2

Pathophysiology of right ventricular failure in the setting of high PVR. CO, cardiac output; LV, left ventricle; MAP, mean arterial pressure; PVR, pulmonary vascular resistance; RV, right ventricle.

Table 2 Local factors increasing pulmonary vascular tone

The gold standard for the diagnosis and management of PH and RV dysfunction in the ICU setting is considered by some to be through pulmonary artery catheterization (PAC), even though most of the information can be obtained noninvasively by echocardiography: the requirement for PAC in this population remains controversial. It must, however, be acknowledged that it provides the only direct continuous measurement of right-sided pressures and direct measurement of RV afterload, whereby, through measurement of cardiac output, pulmonary pressures and the pulmonary artery occlusion pressure (PAOP, the "wedge"), the PVR can be calculated (Figure 3). Overall outcomes are not improved when the PAC is used in general in critically ill patients; and complications do occur [59]: the use in general is therefore declining. However, no studies have been done in the "pulmonary vascular" subpopulation. Alternative invasive hemodynamic measurements, such as CVP, may be useful surrogates for volume status in RV failure, by using the diastolic component of the CVP. Importantly, when monitoring CVP in patients with significant tricuspid regurgitation (TR), the variable V wave may be misleading, as it is included in the mean CVP calculation on most automated machines, and if rising, indicates RV overdistention. In the setting of cardiac surgery, one study shows that PAC use has reduced from 100% to 9% from 1997 to 2001, thought to reflect increased use of transesophageal echocardiography (TEE) [60]. In the setting of cardiac surgery, PAC may remain indicated for patients with PH and low CO and those predicted to have a difficult postoperative course [60], when a Swan introducer sheath may be inserted preemptively, or inserted for continuous monitoring after a diagnosis of RV dysfunction made with echocardiography [61]. PAC is also a useful cardiac monitor with intraaortic balloon counterpulsation. Few data exist on PAC in other settings of pulmonary vascular dysfunction in the ICU, but one study suggests that PVR may be a poor indicator of pulmonary-circulation status in ventilated patients with ALI/ARDS [62]. The role of echocardiography, both transthoracic (TTE) and TEE, is increasingly recognized in assessing RV function in many ICU settings [63–65] and provides essential information about RV geometry and function. PA pressures may be assessed by estimating the systolic-pressure gradient across the tricuspid valve by using the modified Bernoulli equation [9, 66, 67], and although the correlation between invasive and sonographic measurement has been shown to be excellent in these studies, no studies have correlated PAC with echocardiographic measurements in the ICU population. In reality, a combination of invasive and noninvasive techniques is used. Biomarkers such as brain natriuretic peptide (BNP) are useful in monitoring chronic PAH [68], in risk-stratifying acute pulmonary embolism (see later) [69–71], and in identifying ARDS-related pulmonary vascular dysfunction [72], although their role is less clear in other ICU settings.

Figure 3
figure 3

Calculation of pulmonary vascular resistance. Normal range, 155-255 dynes/sec/cm5. CO, cardiac output; mPAP, mean pulmonary artery pressure; PAOP, pulmonary arterial occlusion pressure.

The diagnosis and management of acute pulmonary embolism (PE) warrants a specific mention, as it is a relatively common cause of acute RV failure in the ICU [73]. Available therapies include thrombolysis and embolectomy, reducing the clot burden and acute mortality [74, 75], as well as reducing the longer-term risk of chronic thromboembolic PH [76]. Given that more than half of related deaths occur within an hour of the onset of symptoms [77], effective supportive treatment of shock is paramount. Patients presenting with acute PE are risk stratified according to the effects of elevated RV afterload: hypotensive patients and those with elevated cardiac biomarkers or echocardiographic indices of RV strain, or both, are deemed at increased risk, and thrombolysis is indicated [78].

The management of PH and RV dysfunction in the ICU is challenging. No agreed algorithms exist, although treatment should aim to prevent pulmonary hypertensive crises and acute cor pulmonale [79]. These comprise the spectrum of acute pulmonary vascular dysfunction and may result in cardiovascular collapse due to resulting biventricular failure. Management principles include the following: 1) optimization of RV preload, 2) optimization of RV systolic function, 3) reduction of afterload by reduction of increased PVR, and 4) maintenance of aortic root pressure to ensure sufficient right coronary artery filling pressure (Table 3).

Table 3 Management principles in pulmonary vascular dysfunction

Materials and methods

Systematic review of ICU management of pulmonary vascular and RV dysfunction

We performed a systematic review of the literature over the period from 1980 to 2010, by using set search terms, and the electronic database of the US National Library of Medicine and National Institute of Health (PubMed). After initial identification, abstracts were reviewed for relevance, and appropriate studies were included in the review. Reference lists of relevant articles were hand-searched for further studies and reports. The search was limited to publications in English. Studies were deemed suitable for inclusion according to the criteria listed and where the patient population and study design was defined; and the outcomes were limited to those depending on the specific GRADE question (see Additional file 1). The breakdown of articles obtained by the systematic search is shown (Table 4). After identification, relevant studies were included and subjected to a GRADE analysis [80, 81] to see whether we could make specific management recommendations.

Table 4 Breakdown of clinical articles

Results and Discussion

ICU management of pulmonary vascular and RV dysfunction

Management of PH with associated RV dysfunction in the ICU setting can be broken down into several treatment goals (Table 3). The first is to ensure adequate but not excessive RV filling or preload in the context of sufficient systemic blood pressure. The second goal is to maximize RV myocardial function, whether with inotropic support, rate or rhythm management, atrioventricular synchronization [82, 83], or by using mechanical devices. The third is to offload the right ventricle by reducing the PVR with pulmonary vasodilators as well as by ensuring adequate oxygenation, avoiding hypercapnia and acidosis, and by minimizing mechanical compression of pulmonary vessels (for example, due to excessive airway plateau pressure). The fourth is to maintain adequate aortic root pressure to allow sufficient right coronary arterial perfusion.

Management of volume and use of vasopressors

Systemic hypotension may relate to sepsis, overdiuresis, or progression of RV failure itself. Principles of volume management and vasopressor use are summarized.

Volume management

With a normal RV, RV ejection fraction is usually primarily dependent on RV preload [84]. In the setting of excessive myocardial distention (by fluids), wall tension increases according to the Frank-Starling mechanism, and muscle fiber length is increased, beyond a certain point at which ventricular function will fail. This situation may be precipitated sooner in the setting of PH and RV dysfunction, in which both hypo- and hypervolemia may reduce cardiac output [78, 85, 86]. In stable patients with PAH, high plasma volumes are associated with worse outcomes [87], but very few clinical studies have been performed in pulmonary vascular dysfunction, and the use of fluid loading remains controversial. Some animal studies show that fluids increase the cardiac index [88]; others show that they worsen shock by inducing RV ischemia or decreasing LV filling or both as the result of ventricular diastolic interdependence (due to an increase in RV volume) [89–91].

In acute cor pulmonale after massive PE, increased filling may be at least initially required [4, 92]. In observational studies in sepsis, up to 40% of patients have evidence of RV failure [93], predominantly due to primary RV dysfunction [7]. These patients have a higher CVP at baseline [94] and are unable to augment stroke volume or perfusion pressure with fluid challenges alone, and so usually also require catecholamines [93, 94].

RV volume overload is a very important principle to recognize and treat promptly in RV failure. It may be identified by a rising V wave on the CVP trace, or by increased TR due to RV overdistention seen at echocardiography. In this situation of "backwards" heart failure, no further escalation of vasoactive agents is likely to be helpful (and may even be harmful), and management involves fluid removal (by using diuresis [95] or hemofiltration [96]) and avoidance of excessive RV afterload [97]. Unmonitored fluid challenges are inadvisable in any setting of RV failure [98, 99].

GRADE RECOMMENDATION 1

Based on overall very-low-quality evidence (see Additional file 1), the following WEAK recommendation is made: Close monitoring of fluid status according to effects on RV function is recommended. Initial carefully monitored limited volume loading may be useful after acute PE, but may also worsen RV performance in some patients with pulmonary vascular dysfunction, and vasoactive agents may be required.

Vasopressors

An essential goal is to maintain systemic blood pressure above pulmonary arterial pressures, thereby preserving right coronary blood flow: unlike left coronary artery perfusion, which occurs only during diastole (as aortic pressure exceeds LV pressure only during this period), perfusion of the right coronary artery usually occurs throughout the cardiac cycle, dominating in systole. It is understood that, as PVR approaches SVR, coronary perfusion will decrease, and if PVR exceeds SVR, coronary filling will occur only in diastole. By augmenting aortic root pressure by using vasopressors in the setting of increased RV afterload, RV ischemia can therefore be reversed [55]. Vasopressors will, however, inevitably have direct effects on the pulmonary circulation as well as myocardial effects (Table 5).

Table 5 Pulmonary vascular properties of vasoactive agents
Sympathomimetic pressors

These include the catecholaminergic pressor, norepinephrine, and the noncatecholaminergic pressor phenylephrine. Their complex effects on the pulmonary circulation depend on the dose-related relative α- and β-adrenoreceptor stimulation as well as the degree and nature of RV dysfunction [99, 100]. All may potentially lead to tachydysrhythmias, diastolic dysfunction, myocardial ischemia, hyperlactatemia, and hypercoagulability [101].

Norepinephrine

Norepinephrine (NE) exerts its systemic vasopressor effects through α-1 agonism [102]. Activation of these receptors also causes pulmonary vasoconstriction [102, 103], although the potential adverse effects on PVR are likely to occur only at high doses. Most evidence supporting this comes from animal studies in models of pulmonary vascular dysfunction, with NE at doses less than 0.5 μg/kg/min not increasing PVR [44]. In persistent PH of the newborn, low-dose NE (0.5 μg/kg/min) reduces the PVR/SVR ratio [104]. In adults with septic shock, higher doses of NE increase PVR/SVR, although without worsening RV performance [105]. In patients with sepsis, PH, and associated RV dysfunction, NE increases SVR and improves the RV oxygen supply/demand ratio, although it does not increase RVEF and does increase PVR [106]. Importantly, NE is positively inotropic through β-1 receptor agonism, thus improving RV/pulmonary arterial coupling, CO, and RV performance in studies of acute RV dysfunction due to PH [44, 89, 107–109], illustrated in a case report of acute PH after MVR surgery [110]. In patients with chronic PH, NE reduces the PVR/SVR ratio, although it may not improve CI [100], which may relate to the "fixed" elevation in PVR [99].

Phenylephrine

Phenylephrine (PHE) is a direct α-agonist. Its use improves right coronary perfusion in RV failure [55] without causing tachycardia, although this benefit may be offset by worsening RV function due to increased PVR [100, 108, 111].

GRADE RECOMMENDATION 2

Based on mostly low-quality evidence (see Additional file 1), the following WEAK recommendation is made: NE may be an effective systemic pressor in patients with acute RV dysfunction and RV failure, as it improves RV function both by improving SVR and by increasing CO, despite potential increases in PVR at higher doses.

Nonsympathomimetic pressors: Vasopressin

Arginine vasopressin (AVP) causes systemic vasoconstriction via the vasopressinergic (V1) receptor. Experimental studies have revealed vasodilating properties at low doses that include pulmonary vasodilatation [112] through an NO-dependent mechanism via V1 receptors [113, 114]. This property manifests clinically as a reduction in PVR and PVR/SVR ratio [105, 115, 116]. AVP has also been used as a rescue therapy in patients during PH crises [117–119], in which untreated equalization of systemic and pulmonary pressures may be rapidly fatal. At low doses (0.03-0.067 U/min), it has been used safely in sepsis [105, 120–124], as well as in patients with acute PH and RV failure with hypotension after cardiac surgery [115, 116, 125, 126] and hypotension associated with chronic PH in several settings [117, 118, 127, 128].

AVP leads to a diuretic effect in vasodilatory shock [129], reduces the heart rate [105, 121, 130–132], and induces fewer tachyarrhythmias in comparison to NE [105, 131]. However, bradycardia [133] may be encountered at high clinical doses [134, 135]. AVP may cause dose-related adverse myocardial effects at infusion rates exceeding 0.4 U/min [134, 135], or even above 0.08 U/min in cardiogenic shock [136], which probably relate to direct myocardial effects, including coronary vasoconstriction [132, 137–139].

GRADE RECOMMENDATION 3

Based on mostly low-quality evidence (see Additional file 1), the following WEAK recommendation is made: In patients with vasodilatory shock and pulmonary vascular dysfunction, low-dose AVP may be useful in difficult cases that are resistant to usual treatments, including norepinephrine.

Inotropic augmentation of RV myocardial function

The next major goal is to improve RV myocardial function by using inotropes. The use of mechanical support is discussed later. For sympathomimetic agents, desirable cardiac β1 effects at lower doses maybe offset by chronotropic effects precipitating tachyarrhythmias [140], as well as worsening pulmonary vasoconstriction at higher doses [102] through α-agonism. Systemic hypotension may result from these agents and with phosphodiesterase inhibitors, which may necessitate co-administration of vasopressors.

Inotropes

Sympathomimetic inotropes

Few clinical studies of these agents have been done in patients with PH and RV dysfunction. Dopamine increases CO, although it may cause a mild tachycardia in patients with PH [141] and increase the PVR/SVR ratio [142]. Dopamine also tends to increase the heart rate and to have less-favorable hemodynamic effects in patients with cardiomyopathy than dobutamine [143], although it does not increase PVR at doses up to 10 μg/kg/min in animals with pulmonary vascular dysfunction [144]. In patients with septic shock, PH, and RV dysfunction, dopamine improves CI without an increase in PVR [145]. In the recent large randomized controlled study comparing dopamine with norepinephrine in patients with septic shock, dopamine increased arrhythmic events and, in patients with cardiogenic shock, increased the risk of death [146]. In patients with primary RV dysfunction (without PH) due to septic shock, epinephrine improves RV contractility despite an 11% increase in mPAP [14]. In animal studies, epinephrine reduces the PVR/SVR more than does dopamine [147]. Isoproterenol has been used in RV failure primarily as a chronotrope after cardiac transplantation [148], although it may induce arrhythmias [149].

Dobutamine

At clinical doses up to 5 μg/kg/min in heart failure, dobutamine increases myocardial contractility, reduces PVR and SVR, and induces less tachycardia than does dopamine [143]. It improves RV performance in patients with PH at liver transplantation [150], after RV infarction[151], and is used in PAH exacerbations [152]. It is synergistic with NO in patients with PH [153]. Experimentally, dobutamine has favorable pulmonary vascular effects at lower doses [44, 154], although it leads to increased PVR, tachycardia, and systemic hypotension at doses exceeding 10 μg/kg/min [155]. Given the adverse effects of systemic hypotension in these patients, it is important to anticipate and treat it with vasopressors when using dobutamine.

Inodilators

An inodilator increases myocardial contractility while simultaneously causing systemic and pulmonary vasodilatation. Inodilators include the phosphodiesterase (PDE) III inhibitors and levosimendan.

PDE3 inhibitors

Several types of PDE are recognized: PDEIII usually deactivates intracellular cyclic adenosine monophosphate (cAMP), and PDE3 inhibitors therefore increase cAMP and augment myocardial contractility while dilating the vasculature [156–158]. The selective PDEIII inhibitors include enoximone, milrinone, and amrinone. They are most suited to short-term use because of tachyphylaxis [159], and mild tachycardia is common. Milrinone is most frequently used and has been shown to reduce pulmonary pressures and augment RV function in many studies in patients with pulmonary vascular dysfunction [160–164]. Enoximone improves RV function in pulmonary vascular dysfunction after cardiac surgery [165, 166] and in patients with decompensated chronic obstructive pulmonary disease (COPD) [167]. Enoximone leads to fewer postoperative myocardial infarctions than does dobutamine [168, 169], which may relate to the resulting improved gas exchange when compared with dobutamine and GTN [170]. Concerns regarding platelet aggregation with amrinone [171] do not appear to arise with enoximone [172] or milrinone after cardiac surgery [173, 174]. As with dobutamine, resulting reversible systemic hypotension means that coadministration with pressors is often necessary. Agents such as norepinephrine, phenylephrine or vasopressin are used, with the latter reducing PVR/SVR more than norepinephrine [115]. PDEIII inhibitors may also improve RV function in chronic PH [175].

Nebulized milrinone is increasingly used to manage PH crises in several settings [176–179]. Through pulmonary selectivity, it results in less systemic hypotension and less V/Q mismatch compared with intravenous use in patients with PH after mitral valve replacement surgery [177, 178]. The combination of milrinone-AVP reduces PVR/SVR and may be preferable to milrinone-NE in RV dysfunction [115].

Levosimendan

Levosimendan sensitizes troponin-C to calcium and selectively inhibits PDE III, improving diastolic function and myocardial contractility without increasing oxygen consumption [180–183]. It also acts as a vasodilator through calcium desensitization, potassium channel opening, and PDEIII inhibition [184]. Levosimendan leads to a rapid improvement in hemodynamics, including reduction in PVR in patients with decompensated heart failure [185], with significant benefit on RV efficiency [182], with effects lasting several days [186]. Levosimendan improves RV-PA coupling in experimental acute RV failure [187–189] more than dobutamine [188]. These effects have been shown clinically with improvements in RV function and reduction in PVR in ischemic RV failure [190–194], ARDS [195], and after mitral valve replacement surgery [196, 197]. In chronic PH, repetitive doses reduce mPAP and PVR from baseline and improve SvO2 [198].

GRADE RECOMMENDATION 4

Based on low-moderate-quality evidence (see Additional file 1), a WEAK recommendation can be made that low-dose dobutamine (up to 10 μg/kg/min) improves RV function and may be useful in patients with pulmonary vascular dysfunction, although it may reduce SVR. Dopamine may increase tachyarrhythmias and is not recommended in the setting of cardiogenic shock (STRONG recommendation based on high-quality evidence level).

GRADE RECOMMENDATION 5

Based on mostly moderate-quality evidence (see Additional file 1), a STRONG recommendation can be made that PDE III inhibitors improve RV performance and reduce PVR in patients with acute pulmonary vascular dysfunction, although systemic hypotension is common, usually requiring coadmininstration of pressors. Based on low-quality evidence (see Additional file 1), a WEAK recommendation can be made that inhaled milrinone may be useful to minimize systemic hypotension and V/Q mismatch in pulmonary vascular dysfunction.

GRADE RECOMMENDATION 6

Based on mostly low-quality evidence (see Additional file 1), a WEAK recommendation can be made that levosimendan may be considered for short-term improvements in RV performance in patients with biventricular heart failure.

Reduction of right ventricular afterload

Physiologic coupling between the RV and the pulmonary circulation is a vital form of autoregulation of pulmonary circulatory flow (Figure 2). The RV is even less tolerant of acute changes in afterload than the LV, presumably because of the lower myocardial muscle mass [199]. In sepsis, a reduction in PVR will increase the RV ejection fraction at no additional cost to cardiac output [47], but at levels beyond moderate PH, LV filling may be reduced, and ultimately cardiac output will decrease [199]. Measures to reduce RV afterload may be nonpharmacologic (Table 3) or pharmacologic (Table 6).

Table 6 Agents used to reduce PVR in the ICU setting

Pulmonary vasodilator therapy

Specific pulmonary vasodilators may be useful both to reduce RV afterload and to manipulate hypoxic vasoconstriction in patients with severe hypoxia. Agents are classically subdivided according to their action on the cyclic GMP, prostacyclin, or endothelin pathways [200]. In the nonacute setting, these agents also target remodeling of"resistance" pulmonary vessels and have revolutionized the care of patients with PAH [201]. Importantly, however, the management with pulmonary vasodilators in chronic PH patients differs in several ways from that with acute pulmonary vascular dysfunction, notably in terms of rapid changes in RV volume status, and potential adverse hemodynamic effects of nonselective pulmonary vasodilators in unstable patients.

Pulmonary vasodilators should be used after optimization of RV perfusion and CO. Systemic administration of pulmonary vasodilators may reduce systemic blood pressure [202], potentially reducing RV preload and worsening RV ischemia [86]. Exclusion of a fixed elevated pulmonary venous pressure is important, as increased transpulmonary flow may precipitate pulmonary edema [203, 204]. Furthermore, nonselective actions of vasodilators may result in worsening ventilation/perfusion (V/Q) matching [205]. This risk is reduced with the use of inhaled pulmonary vasodilators, with which the agent will reach vessels in only ventilated lung units [206].

Adenosine

Adenosine increases intracellular cAMP via A2 receptor agonism [207], and when administered intravenously, acts as a potent selective pulmonary vasodilator because of its rapid endothelial metabolism [208]. It has been used as a therapy for adult PH in some settings, including after cardiac surgery [209], but may elevate LV end-diastolic pressure [210] and cause bradycardia and bronchospasm [211]. It is currently therefore recommended as an alternative to NO and prostacyclin in dynamic vasoreactivity studies rather than as treatment for PH [201].

Inhaled nitric oxide

Inhaled nitric oxide (NO) is a potent pulmonary vasodilator with a short half-life due to rapid inactivation by hemoglobin. This minimizes systemic vasodilatation, although it necessitates continuous delivery into the ventilator circuit [206]. NO selectively reduces PVR and improves CO in PAH [212], secondary PH [205, 213, 214], acute PE [215, 216], ischemic RV dysfunction [217, 218], and postsurgical PH [202, 219–234]. NO also improves oxygenation [235], RVEF, and reduces vasopressor requirements in PH after cardiac surgery [236], especially in patients with higher baseline PVR [237], with no augmented effect seen at doses above 10 ppm in these patients [238]. Use of NO (or inhaled PGI2) after mitral valve replacement surgery results in easier weaning from cardiopulmonary bypass and shorter ICU stays [239, 240].

NO has been shown to reduce PVR and improve CO in several studies in patients with acute RV failure due to ARDS [79, 241–246] and to improve oxygenation at lower doses than the RV effects [247]. Administration of NO does need to be continuous for PVR reduction, and a potential exists for worsening oxygenation at excessive doses [248]. The reduction in RV afterload, however, does not correlate with clinical-outcome benefits [249–251]. Similarly, despite short-term improvements in oxygenation in ARDS [252], no studies show a survival benefit [249, 250, 253–257].

NO provides synergistic pulmonary vasodilatation with intravenous prostacyclin [258], inhaled iloprost [259], and oral sildenafil [260, 261]. Limitations include accumulation of toxic metabolites, although this is not usually a clinically significant problem [206]. Rebound PH with RV dysfunction may occur after weaning from NO [262–264], which may be reduced with PDE5 inhibitors [265–270].

Prostanoids

Prostanoids include prostaglandin-I2 (prostacyclin, PGI2) and its analogues, (iloprost) and prostaglandin-E1 (alprostadil, PGE1). An important difference between their formulations is their resulting half-life (Table 6). Prostacyclin is a potent systemic and pulmonary vasodilator, with antiplatelet [271] and antiproliferative effects [272]. In PAH, these agents reduce PVR, increase CO, and improve clinical outcomes [273–279], and are used in patients with NYHA III-IV symptoms [201].

The use of prostanoids is most commonly described in ICU after cardiac surgery or transplantation. Intravenous prostacyclin [18, 280], PGE1 [281–285], inhaled prostacyclin [223, 286–290], and iloprost [291–297] all reduce PVR and improve RV performance in these settings, with inhaled agents being most selective. Intravenous PGE1 may cause marked desaturation in patients with lung disease [205]. Inhaled prostacyclin has short-term equivalence to NO [226], and inhaled iloprost has been shown to be even more effective than NO at acutely reducing PVR and augmenting CO in PH after CPB [298] and in PAH [277]. Inhaled PGI2 also acutely improves pulmonary hemodynamics after acute massive PE [299]. Although PGI2 impairs platelet aggregation, clinical bleeding was not increased in one study [300]. The potential anticoagulant effect should be remembered, however, especially in patients after surgery and receiving concomitant heparin.

In ARDS, intravenous prostacyclin reduces PVR and improves RV function, although it may increase intrapulmonary shunt [301]. Inhaled prostacyclin [302–305] and inhaled PGE1 [306] improve oxygenation and reduce PVR in ARDS, with minimal effects on SVR. NO and intravenous PGI2 have been combined in ARDS with effective reduction of PVR without adverse effects [307].

PDE5 inhibitors

PDE5 inhibitors, including sildenafil and vardenafil, increase downstream cGMP signaling, potentiating the beneficial effects of NO (Figure 4). PDE5 inhibitors acutely reduce PVR [308, 309], and increase CO and reduce PAOP more than does NO [310]. These agents improve clinical end-points in PAH [311], where endothelial NO is reduced [312] and PDE5 expression is upregulated [313, 314]. PDE5 inhibitor may also exert milrinone-like effects through PDEIII inhibition, augmenting RV function [310, 311, 315]. Despite their relative pulmonary selectivity and rapid onset, however, adverse effects may include reduced SVR with potential effects on RV performance [316]. Oral sildenafil has been used to reduce PVR effectively in well-selected patients with PH after cardiac surgery without reducing the SVR [269, 317–319]. Even a single dose may facilitate weaning from NO [266], also without reducing SVR [266–269]. Sildenafil may also improve myocardial perfusion and reduce platelet activation [320] as well as endothelial dysfunction after CPB [321]. Oral sildenafil has been effective in patients with PH due to left ventricular systolic dysfunction, reducing PVR and increasing CO, although reducing the SVR [260]. Sildenafil has also been used in selected patients with PH due to selected cases of chronic respiratory disease without worsening oxygenation or SVR [322, 323]. A single dose of 50 mg nasogastric sildenafil has been studied in a small cohort of consecutive ARDS patients, lowering MAP, and worsening oxygenation due to increased V/Q mismatch, although RV performance did improve [324]. Intravenous sildenafil has been shown to reduce SVR and PVR in end-stage congestive heart failure patients [325], although it is not available commercially, and its use is not licensed in unstable patients (Table 6).

Figure 4
figure 4

Increased PVR at extremes of lung volumes. This figure represents measurements made in an animal-lobe preparation in which the transmural pressure of the capillaries is held constant. It illustrates that at low lung volumes (as may occur with atelectasis), extraalveolar vessels become narrow, and smooth muscle and elastic fibers in these collapsed vessels increase PVR. At high lung volumes, as alveolar volumes are increased and walls are thinned, capillaries are stretched, reducing their caliber and also increasing PVR. (Adapted from John West's Essential Physiology, 10th edition, Philadelphia: Lippincott & Williams, with permission).

GRADE RECOMMENDATION 7

Based on mostly moderate-quality evidence (see Additional file 1), the following STRONG recommendation is made: pulmonary vasodilators reduce PVR, improve CO and oxygenation, and may be useful when PH and RV dysfunction are present, notably after cardiac surgery.

Based on mostly moderate-quality evidence (see Additional file 1), the ICU side-effect profile of intravenous pulmonary vasodilators may be less favorable than that of inhaled agents. The following STRONG recommendation is therefore made: Consideration should be given to the use of inhaled rather than systemic agents when systemic hypotension is likely, and concomitant vasopressor use should be anticipated.

Based on mostly high-quality evidence (see Additional file 1), the following STRONG recommendation is made: give consideration for the use of NO as a short-term therapy to improve oxygenation indices but not outcome in patients with ARDS. Based on low-quality evidence (see Additional file 1), a WEAK recommendation is made that pulmonary vasodilators may also be useful treat PH associated with RV dysfunction in ARDS.

Based on mostly low-quality evidence (see Additional file 1), the following WEAK recommendation is made: Oral sildenafil may reduce PVR and facilitate weaning from NO after cardiac surgery in selected patients with PH, without adverse effects on systemic blood pressure in well-selected patients.

Nonpharmacologic Management

This encompasses RV "protective" strategies to avoid factors (Table 3) that may further increase PVR. Mechanical devices are also increasingly used to give a failing RV a bridge to recovery or transplantation.

Ventilatory strategies

Important variables that may reduce pulmonary blood flow during ventilation include hypoxia, hypercapnia, and compression of the pulmonary vasculature at the extremes of lung volumes (Figure 4). Acute hypoxia leading to hypoxic pulmonary vasoconstriction is well described [326] and may be augmented by many factors, including acidosis [327]. Acute hypercapnia also leads to pulmonary vasoconstriction [328, 329], although this may be attenuated with NO [330], and, when associated with high PEEP, leads to RV dilatation and reduced cardiac output in severe ARDS [328, 329]. A reduction in pulmonary blood flow occurs both at low volumes, such as in areas of atelectasis, and at high lung volumes, such as with increased airway plateau pressure (Pplat): Increased RV afterload, reduced venous return, and acute RV dysfunction may result [331]. Both atelectasis and ventilation at high lung volumes should therefore be avoided in patients with RV dysfunction.

Before the era of protective ventilatory strategies in ARDS, the incidence of acute RV failure was 60% [332] and has since decreased to 10% to 25% [24]. This is thought to reflect the change in ventilatory practice: lower Pplat reduces the incidence of RV failure [333]. Prone ventilation may also reduce Pplat and pCO2 sufficiently to improve acute RV failure [334]. In ARDS, transition to high-frequency oscillation leads to an increase in CVP and a minor decrease in cardiac output due to preload reduction [335], and RV function may decrease during recruitment maneuvers [336]. In children after Fontan procedures, the hemodynamic effects of negative-pressure ventilation (NPV) are nicely illustrated by measuring pulmonary blood flow: after a switch from conventional intermittent positive pressure ventilation (IPPV) to NPV by using cuirass ventilation, pulmonary blood flow, stroke volume, and cardiac output increased up to 50%, and decreased to baseline when IPPV was reinstituted [337, 338].

Mechanical support

Mechanical support for the RV may be appropriate in reversible settings or as a bridge to definitive treatment. RV-assist devices (RVADs) may be used in primary RV dysfunction [339] and have been used with coexisting PH [340, 341]. There is, however, concern that pulsatile devices may cause pulmonary microcirculatory damage in PH [342, 343]. A pumpless "lung assist" device has been used in patients bridging to transplant [344]. Extracorporeal membrane oxygenation (ECMO) has been used in severe PH [345–348], as a bridge to transplant [349, 350], and after endarterectomy [351] or massive PE [352–355]. Intraaortic balloon counterpulsation (IABP) has been used for RV failure after CPB [356] and transplantation [357], thought to improve CO by augmenting left coronary flow rather than by direct RV effects [358]. Atrial septostomy creates a right-to-left shunt that improves left atrial filling and LV function while reducing RV end-diastolic pressure and improving RV contractility. It is sometimes used as a bridge to transplantation in severe PAH [359], although not in patients with very severe RV failure [360].

GRADE RECOMMENDATION 8

Based on mostly very-low-quality evidence, the following WEAK recommendation is made: Mechanical therapies including ECMO and IABP may have a role as rescue therapies in reversible pulmonary vascular dysfunction or while awaiting definitive treatment.

Conclusions

Pulmonary vascular and right ventricular dysfunction may complicate many ICU illnesses: the diagnosis may be difficult, and the acute management, challenging. Their presence is associated with a worse outcome. This review highlights that some recommendations can be made, despite limitations of the GRADE analysis. However, we do consider that "weak GRADE recommendations" could be interpreted as "management suggestions" and treated with appropriate caution. A further limitation is that several pathologies have been grouped together as one syndrome, although this relates to both the rarity of the syndrome and the lack of high-quality evidence: further research is desperately needed. In particular, only then will we learn whether PAH-targeted therapy such as use of PDE5 inhibitors or endothelin-receptor antagonists, so effective in idiopathic PAH, have a role in the ICU setting.

Key messages

  • Pulmonary hypertension (PH) and associated right ventricular (RV) failure are associated with worse outcomes in critical care, and because of nonspecific presenting symptoms and signs, may be difficult to recognize: echocardiography is a very useful initial test, and invasive monitoring may be helpful in some cases for more continuous monitoring and accurate measurement of pulmonary vascular resistance.

  • Volume loading of the right ventricle may worsen its performance: all fluid challenges should be closely monitored.

  • It is essential to maintain adequate aortic root pressure to prevent the onset of RV ischemia. Vasopressors are useful in this setting, including low-dose norepinephrine as a first-line agent. Low-dose vasopressin may also be useful in some resistant cases but has adverse myocardial effects at higher doses. Potentially useful inotropes in RV failure include dobutamine and those with additional pulmonary vasodilating effects, including PDE III inhibitors, although co-administration with pressors is often necessary. The effects of any vasoactive drug may be unpredictable in an individual and require close clinical observation of circulatory performance, potentially assisted by echocardiography.

  • Pulmonary vasodilators are useful to reduce RV afterload in several ICU settings, including PH and RV failure after cardiac surgery. Systemic administration may worsen systemic hemodynamics and oxygenation because of ventilation-perfusion mismatching.

  • The use of mechanical therapies to manage acute PH and enhance RV performance is expanding, although with evidence currently limited to case series, and may be useful in experienced centers to ameliorate RV failure while awaiting definitive therapy.

Abbreviations

ACP:

acute cor pulmonale

ARDS:

acute respiratory distress syndrome

AVP:

arginine vasopressin

cAMP:

cyclic adenosine 3',5'-cyclic monophosphate

cGMP:

cyclic guanosine 3',5'-cyclic monophosphate

CI:

cardiac index

CO:

cardiac output

COPD:

chronic obstructive pulmonary disease

CPB:

cardiopulmonary bypass

CVP:

central venous pressure

ECMO:

extracorporeal membrane oxygenation

ICU:

intensive care unit

IABP:

intraaortic balloon pump

LV:

left ventricle

MVR:

mitral valve replacement

NE:

norepinephrine

NO:

nitric oxide

PAC:

pulmonary artery catheter

PAH:

pulmonary arterial hypertension

PAOP:

pulmonary arterial occlusion pressure

PDE:

phosphodiesterase

PE:

pulmonary embolism

PGE1:

prostaglandin E1

PH:

pulmonary hypertension

PHE:

phenylephrine

PVR:

pulmonary vascular resistance

RV:

right ventricle

RVEF:

right ventricular ejection fraction

RVF:

right ventricular failure

SvO2:

mixed venous oxygen saturation

SVR:

systemic vascular resistance

TEE:

transesophageal echocardiography

TR:

tricuspid regurgitation

V/Q mismatch:

ventilation/perfusion mismatch.

References

  1. Snow RL, Davies P, Pontoppidan H, Zapol WM, Reid L: Pulmonary vascular remodeling in adult respiratory distress syndrome. Am Rev Respir Dis. 1982, 126: 887-892.

    CAS  PubMed  Google Scholar 

  2. Gillis CN, Pitt BR, Wiedemann HP, Hammond GL: Depressed prostaglandin E1 and 5-hydroxytryptamine removal in patients with adult respiratory distress syndrome. Am Rev Respir Dis. 1986, 134: 739-744.

    CAS  PubMed  Google Scholar 

  3. Greene R, Zapol WM, Snider MT, Reid L, Snow R, O'Connell RS, Novelline RA: Early bedside detection of pulmonary vascular occlusion during acute respiratory failure. Am Rev Respir Dis. 1981, 124: 593-601.

    CAS  PubMed  Google Scholar 

  4. Piazza G, Goldhaber SZ: The acutely decompensated right ventricle: pathways for diagnosis and management. Chest. 2005, 128: 1836-1852. 10.1378/chest.128.3.1836.

    PubMed  Google Scholar 

  5. Jacobs AK, Leopold JA, Bates E, Mendes LA, Sleeper LA, White H, Davidoff R, Boland J, Modur S, Forman R, Hochman JS: Cardiogenic shock caused by right ventricular infarction: a report from the SHOCK registry. J Am Coll Cardiol. 2003, 41: 1273-1279. 10.1016/S0735-1097(03)00120-7.

    PubMed  Google Scholar 

  6. Kimchi A, Ellrodt AG, Berman DS, Riedinger MS, Swan HJ, Murata GH: Right ventricular performance in septic shock: a combined radionuclide and hemodynamic study. J Am Coll Cardiol. 1984, 4: 945-951. 10.1016/S0735-1097(84)80055-8.

    CAS  PubMed  Google Scholar 

  7. Parker MM, McCarthy KE, Ognibene FP, Parrillo JE: Right ventricular dysfunction and dilatation, similar to left ventricular changes, characterize the cardiac depression of septic shock in humans. Chest. 1990, 97: 126-131. 10.1378/chest.97.1.126.

    CAS  PubMed  Google Scholar 

  8. Rubin LJ: Primary pulmonary hypertension. N Engl J Med. 1997, 336: 111-117. 10.1056/NEJM199701093360207.

    CAS  PubMed  Google Scholar 

  9. Berger M, Haimowitz A, Van Tosh A, Berdoff RL, Goldberg E: Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J Am Coll Cardiol. 1985, 6: 359-365. 10.1016/S0735-1097(85)80172-8.

    CAS  PubMed  Google Scholar 

  10. Dabestani A, Mahan G, Gardin JM, Takenaka K, Burn C, Allfie A, Henry WL: Evaluation of pulmonary artery pressure and resistance by pulsed Doppler echocardiography. Am J Cardiol. 1987, 59: 662-668. 10.1016/0002-9149(87)91189-1.

    CAS  PubMed  Google Scholar 

  11. Bossone E, Bodini BD, Mazza A, Allegra L: Pulmonary arterial hypertension: the key role of echocardiography. Chest. 2005, 127: 1836-1843. 10.1378/chest.127.5.1836.

    PubMed  Google Scholar 

  12. Forfia PR, Fisher MR, Mathai SC, Housten-Harris T, Hemnes AR, Borlaug BA, Chamera E, Corretti MC, Champion HC, Abraham TP, Girgis RE, Hassoun PM: Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med. 2006, 174: 1034-1041. 10.1164/rccm.200604-547OC.

    PubMed  Google Scholar 

  13. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ: Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005, 18: 1440-1463. 10.1016/j.echo.2005.10.005.

    PubMed  Google Scholar 

  14. Le Tulzo Y, Seguin P, Gacouin A, Camus C, Suprin E, Jouannic I, Thomas R: Effects of epinephrine on right ventricular function in patients with severe septic shock and right ventricular failure: a preliminary descriptive study. Intensive Care Med. 1997, 23: 664-670. 10.1007/s001340050391.

    CAS  PubMed  Google Scholar 

  15. Vieillard-Baron A, Prin S, Chergui K, Dubourg O, Jardin F: Echo-Doppler demonstration of acute cor pulmonale at the bedside in the medical intensive care unit. Am J Respir Crit Care Med. 2002, 166: 1310-1319. 10.1164/rccm.200202-146CC.

    PubMed  Google Scholar 

  16. Jardin F, Dubourg O, Bourdarias JP: Echocardiographic pattern of acute cor pulmonale. Chest. 1997, 111: 209-217. 10.1378/chest.111.1.209.

    CAS  PubMed  Google Scholar 

  17. Fischer LG, Van Aken H, Burkle H: Management of pulmonary hypertension: physiological and pharmacological considerations for anesthesiologists. Anesth Analg. 2003, 96: 1603-1616. 10.1213/01.ANE.0000062523.67426.0B.

    PubMed  Google Scholar 

  18. Ocal A, Kiris I, Erdinc M, Peker O, Yavuz T, Ibrisim E: Efficiency of prostacyclin in the treatment of protamine-mediated right ventricular failure and acute pulmonary hypertension. Tohoku J Exp Med. 2005, 207: 51-58. 10.1620/tjem.207.51.

    CAS  PubMed  Google Scholar 

  19. Sibbald WJ, Paterson NA, Holliday RL, Anderson RA, Lobb TR, Duff JH: Pulmonary hypertension in sepsis: measurement by the pulmonary arterial diastolic-pulmonary wedge pressure gradient and the influence of passive and active factors. Chest. 1978, 73: 583-591. 10.1378/chest.73.5.583.

    CAS  PubMed  Google Scholar 

  20. Wort SJ, Evans TW: The role of the endothelium in modulating vascular control in sepsis and related conditions. Br Med Bull. 1999, 55: 30-48. 10.1258/0007142991902286.

    CAS  PubMed  Google Scholar 

  21. Albertini M, Clement MG, Hussain SN: Role of endothelin ETA receptors in sepsis-induced mortality, vascular leakage, and tissue injury in rats. Eur J Pharmacol. 2003, 474: 129-135. 10.1016/S0014-2999(03)02037-5.

    CAS  PubMed  Google Scholar 

  22. Rossi P, Persson B, Boels PJ, Arner A, Weitzberg E, Oldner A: Endotoxemic pulmonary hypertension is largely mediated by endothelin-induced venous constriction. Intensive Care Med. 2008, 34: 873-880. 10.1007/s00134-007-0980-9.

    CAS  PubMed  Google Scholar 

  23. Osman D, Monnet X, Castelain V, Anguel N, Warszawski J, Teboul JL, Richard C: Incidence and prognostic value of right ventricular failure in acute respiratory distress syndrome. Intensive Care Med. 2009, 35: 69-76. 10.1007/s00134-008-1307-1.

    PubMed  Google Scholar 

  24. Vieillard-Baron A, Schmitt JM, Augarde R, Fellahi JL, Prin S, Page B, Beauchet A, Jardin F: Acute cor pulmonale in acute respiratory distress syndrome submitted to protective ventilation: incidence, clinical implications, and prognosis. Crit Care Med. 2001, 29: 1551-1555. 10.1097/00003246-200108000-00009.

    CAS  PubMed  Google Scholar 

  25. Vieillard-Baron A, Page B, Augarde R, Prin S, Qanadli S, Beauchet A, Dubourg O, Jardin F: Acute cor pulmonale in massive pulmonary embolism: incidence, echocardiographic pattern, clinical implications and recovery rate. Intensive Care Med. 2001, 27: 1481-1486. 10.1007/s001340101032.

    CAS  PubMed  Google Scholar 

  26. Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, Johnsson H, Jorfeldt L: Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate. Am Heart J. 1997, 134: 479-487. 10.1016/S0002-8703(97)70085-1.

    CAS  PubMed  Google Scholar 

  27. Kasper W, Konstantinides S, Geibel A, Tiede N, Krause T, Just H: Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism. Heart. 1997, 77: 346-349.

    PubMed Central  CAS  PubMed  Google Scholar 

  28. Clowes GH, Farrington GH, Zuschneid W, Cossette GR, Saravis C: Circulating factors in the etiology of pulmonary insufficiency and right heart failure accompanying severe sepsis (peritonitis). Ann Surg. 1970, 171: 663-678. 10.1097/00000658-197005000-00005.

    PubMed Central  PubMed  Google Scholar 

  29. Monchi M, Bellenfant F, Cariou A, Joly LM, Thebert D, Laurent I, Dhainaut JF, Brunet F: Early predictive factors of survival in the acute respiratory distress syndrome: a multivariate analysis. Am J Respir Crit Care Med. 1998, 158: 1076-1081.

    CAS  PubMed  Google Scholar 

  30. Squara P, Dhainaut JF, Artigas A, Carlet J: Hemodynamic profile in severe ARDS: results of the European Collaborative ARDS Study. Intensive Care Med. 1998, 24: 1018-1028. 10.1007/s001340050710.

    CAS  PubMed  Google Scholar 

  31. Leeman M: Pulmonary hypertension in acute respiratory distress syndrome. Monaldi Arch Chest Dis. 1999, 54: 146-149.

    CAS  PubMed  Google Scholar 

  32. Ramakrishna G, Sprung J, Ravi BS, Chandrasekaran K, McGoon MD: Impact of pulmonary hypertension on the outcomes of noncardiac surgery: predictors of perioperative morbidity and mortality. J Am Coll Cardiol. 2005, 45: 1691-1699. 10.1016/j.jacc.2005.02.055.

    PubMed  Google Scholar 

  33. Minai OA, Venkateshiah SB, Arroliga AC: Surgical intervention in patients with moderate to severe pulmonary arterial hypertension. Conn Med. 2006, 70: 239-243.

    PubMed  Google Scholar 

  34. Lai HC, Lai HC, Wang KY, Lee WL, Ting CT, Liu TJ: Severe pulmonary hypertension complicates postoperative outcome of non-cardiac surgery. Br J Anaesth. 2007, 99: 184-190. 10.1093/bja/aem126.

    PubMed  Google Scholar 

  35. Krowka MJ, Plevak DJ, Findlay JY, Rosen CB, Wiesner RH, Krom RA: Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver Transpl. 2000, 6: 443-450. 10.1053/jlts.2000.6356.

    CAS  PubMed  Google Scholar 

  36. Price LC, Montani D, Jais X, Dick JR, Simonneau G, Sitbon O, Mercier FJ, Humbert M: Non-cardiothoracic non-obstetric surgery in mild-moderate pulmonary hypertension: perioperative management of 28 consecutive individual cases. Eur Respir J. 2010, 35: 1294-1302. 10.1183/09031936.00113009.

    CAS  PubMed  Google Scholar 

  37. Bonnin M, Mercier FJ, Sitbon O, Roger-Christoph S, Jais X, Humbert M, Audibert F, Frydman R, Simonneau G, Benhamou D: Severe pulmonary hypertension during pregnancy: mode of delivery and anesthetic management of 15 consecutive cases. Anesthesiology. 2005, 102: 1133-1137. 10.1097/00000542-200506000-00012. discussion 1135A-1136A

    PubMed  Google Scholar 

  38. Bedard E, Dimopoulos K, Gatzoulis MA: Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension?. Eur Heart J. 2009, 30: 256-265. 10.1093/eurheartj/ehn597.

    PubMed  Google Scholar 

  39. Bernstein AD, Parsonnet V: Bedside estimation of risk as an aid for decision-making in cardiac surgery. Ann Thorac Surg. 2000, 69: 823-828. 10.1016/S0003-4975(99)01424-1.

    CAS  PubMed  Google Scholar 

  40. Subramaniam K, Yared JP: Management of pulmonary hypertension in the operating room. Semin Cardiothorac Vasc Anesth. 2007, 11: 119-136. 10.1177/1089253207301733.

    PubMed  Google Scholar 

  41. Morgan JA, John R, Lee BJ, Oz MC, Naka Y: Is severe right ventricular failure in left ventricular assist device recipients a risk factor for unsuccessful bridging to transplant and post-transplant mortality. Ann Thorac Surg. 2004, 77: 859-863. 10.1016/j.athoracsur.2003.09.048.

    PubMed  Google Scholar 

  42. Price LC, Montani D, Jais X, Dick JR, Simonneau G, Sitbon O, Mercier FJ, Humbert M: Noncardiothoracic nonobstetric surgery in mild-to-moderate pulmonary hypertension. Eur Respir J. 35: 1294-1302. 10.1183/09031936.00113009.

  43. McIntyre KM, Sasahara AA: Determinants of right ventricular function and hemodynamics after pulmonary embolism. Chest. 1974, 65: 534-543. 10.1378/chest.65.5.534.

    CAS  PubMed  Google Scholar 

  44. Kerbaul F, Rondelet B, Motte S, Fesler P, Hubloue I, Ewalenko P, Naeije R, Brimioulle S: Effects of norepinephrine and dobutamine on pressure load-induced right ventricular failure. Crit Care Med. 2004, 32: 1035-1040. 10.1097/01.CCM.0000120052.77953.07.

    CAS  PubMed  Google Scholar 

  45. Nath J, Foster E, Heidenreich PA: Impact of tricuspid regurgitation on long-term survival. J Am Coll Cardiol. 2004, 43: 405-409. 10.1016/j.jacc.2003.09.036.

    PubMed  Google Scholar 

  46. Pinsky MR: Heart-lung interactions. Curr Opin Crit Care. 2007, 13: 528-531. 10.1097/MCC.0b013e3282efad97.

    PubMed  Google Scholar 

  47. Sibbald WJ, Driedger AA: Right ventricular function in acute disease states: pathophysiologic considerations. Crit Care Med. 1983, 11: 339-345. 10.1097/00003246-198305000-00004.

    CAS  PubMed  Google Scholar 

  48. Pinsky MR: Recent advances in the clinical application of heart-lung interactions. Curr Opin Crit Care. 2002, 8: 26-31. 10.1097/00075198-200202000-00005.

    PubMed  Google Scholar 

  49. Stojnic BB, Brecker SJ, Xiao HB, Helmy SM, Mbaissouroum M, Gibson DG: Left ventricular filling characteristics in pulmonary hypertension: a new mode of ventricular interaction. Br Heart J. 1992, 68: 16-20. 10.1136/hrt.68.7.16.

    PubMed Central  CAS  PubMed  Google Scholar 

  50. Taylor RR, Covell JW, Sonnenblick EH, Ross J: Dependence of ventricular distensibility on filling of the opposite ventricle. Am J Physiol. 1967, 213: 711-718.

    CAS  PubMed  Google Scholar 

  51. Fellahi JL, Valtier B, Beauchet A, Bourdarias JP, Jardin F: Does positive end-expiratory pressure ventilation improve left ventricular function? A comparative study by transesophageal echocardiography in cardiac and noncardiac patients. Chest. 1998, 114: 556-562. 10.1378/chest.114.2.556.

    CAS  PubMed  Google Scholar 

  52. Louie EK, Lin SS, Reynertson SI, Brundage BH, Levitsky S, Rich S: Pressure and volume loading of the right ventricle have opposite effects on left ventricular ejection fraction. Circulation. 1995, 92: 819-824.

    CAS  PubMed  Google Scholar 

  53. Louie EK, Rich S, Brundage BH: Doppler echocardiographic assessment of impaired left ventricular filling in patients with right ventricular pressure overload due to primary pulmonary hypertension. J Am Coll Cardiol. 1986, 8: 1298-1306. 10.1016/S0735-1097(86)80300-X.

    CAS  PubMed  Google Scholar 

  54. Ricciardi MJ, Bossone E, Bach DS, Armstrong WF, Rubenfire M: Echocardiographic predictors of an adverse response to a nifedipine trial in primary pulmonary hypertension: diminished left ventricular size and leftward ventricular septal bowing. Chest. 1999, 116: 1218-1223. 10.1378/chest.116.5.1218.

    CAS  PubMed  Google Scholar 

  55. Vlahakes GJ, Turley K, Hoffman JI: The pathophysiology of failure in acute right ventricular hypertension: hemodynamic and biochemical correlations. Circulation. 1981, 63: 87-95.

    CAS  PubMed  Google Scholar 

  56. Weitzenblum E: Chronic cor pulmonale. Heart. 2003, 89: 225-230. 10.1136/heart.89.2.225.

    PubMed Central  PubMed  Google Scholar 

  57. Blaise G, Langleben D, Hubert B: Pulmonary arterial hypertension: pathophysiology and anesthetic approach. Anesthesiology. 2003, 99: 1415-1432. 10.1097/00000542-200312000-00027.

    PubMed  Google Scholar 

  58. Chin KM, Kim NH, Rubin LJ: The right ventricle in pulmonary hypertension. Coron Artery Dis. 2005, 16: 13-18. 10.1097/00019501-200502000-00003.

    PubMed  Google Scholar 

  59. Hadian M, Pinsky MR: Evidence-based review of the use of the pulmonary artery catheter impact data and complications. Crit Care. 2006, 10 Suppl 3: S8-10.1186/cc4834.

    PubMed  Google Scholar 

  60. Handa F, Kyo SE, Miyao H: Reduction in the use of pulmonary artery catheter for cardiovascular surgery. Masui. 2003, 52: 420-423.

    PubMed  Google Scholar 

  61. Mebazaa A, Pitsis AA, Rudiger A, Toller W, Longrois D, Ricksten SE, Bobek I, De Hert S, Wieselthaler G, Schirmer U, von Segesser LK, Sander M, Poldermans D, Ranucci M, Karpati PC, Wouters P, Seeberger M, Schmid ER, Weder W, Follath F: Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery. Crit Care. 2010, 14: 201-10.1186/cc8153.

    PubMed Central  PubMed  Google Scholar 

  62. Zapol WM, Kobayashi K, Snider MT, Greene R, Laver MB: Vascular obstruction causes pulmonary hypertension in severe acute respiratory failure. Chest. 1977, 71: 306-307.

    CAS  PubMed  Google Scholar 

  63. Vieillard-Baron A: Assessment of right ventricular function. Curr Opin Crit Care. 2009, 15: 254-260. 10.1097/MCC.0b013e32832b70c9.

    PubMed  Google Scholar 

  64. Gadhinglajkar S, Sreedhar R, Jayakumar K, Misra M, Ganesh S, Panicker V: Intra-operative assessment of biventricular function using trans-esophageal echocardiography pre/post-pulmonary thromboembolectomy in patient with chronic thromboembolic pulmonary hypertension. Ann Card Anaesth. 2009, 12: 140-145. 10.4103/0971-9784.53449.

    PubMed  Google Scholar 

  65. Serra E, Feltracco P, Barbieri S, Forti A, Ori C: Transesophageal echocardiography during lung transplantation. Transplant Proc. 2007, 39: 1981-1982. 10.1016/j.transproceed.2007.05.004.

    CAS  PubMed  Google Scholar 

  66. Currie PJ, Seward JB, Chan KL, Fyfe DA, Hagler DJ, Mair DD, Reeder GS, Nishimura RA, Tajik AJ: Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients. J Am Coll Cardiol. 1985, 6: 750-756. 10.1016/S0735-1097(85)80477-0.

    CAS  PubMed  Google Scholar 

  67. Yock PG, Popp RL: Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation. 1984, 70: 657-662.

    CAS  PubMed  Google Scholar 

  68. Nagaya N, Nishikimi T, Uematsu M, Satoh T, Kyotani S, Sakamaki F, Kakishita M, Fukushima K, Okano Y, Nakanishi N, Miyatake K, Kangawa K: Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation. 2000, 102: 865-870.

    CAS  PubMed  Google Scholar 

  69. Logeart D, Lecuyer L, Thabut G, Tabet JY, Tartiere JM, Chavelas C, Bonnin F, Stievenart JL, Solal AC: Biomarker-based strategy for screening right ventricular dysfunction in patients with non-massive pulmonary embolism. Intensive Care Med. 2007, 33: 286-292. 10.1007/s00134-006-0482-1.

    CAS  PubMed  Google Scholar 

  70. Lega JC, Lacasse Y, Lakhal L, Provencher S: Natriuretic peptides and troponins in pulmonary embolism: a meta-analysis. Thorax. 2009, 64: 869-875. 10.1136/thx.2008.110965.

    PubMed  Google Scholar 

  71. Mehta NJ, Jani K, Khan IA: Clinical usefulness and prognostic value of elevated cardiac troponin I levels in acute pulmonary embolism. Am Heart J. 2003, 145: 821-825. 10.1016/S0002-8703(02)94704-6.

    CAS  PubMed  Google Scholar 

  72. Clark BJ, Brown NJ, Moss M, Bull TM: Increased serum BNP concentrations are associated with pulmonary vascular dysfunction in patients with acute lung injury. Am J Respir Crit Care Med. 2010, 181: A2582-

    Google Scholar 

  73. Alpert JS, Smith R, Carlson J, Ockene IS, Dexter L, Dalen JE: Mortality in patients treated for pulmonary embolism. JAMA. 1976, 236: 1477-1480. 10.1001/jama.236.13.1477.

    CAS  PubMed  Google Scholar 

  74. Goldhaber SZ, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL, Taveira da Silva AM, Come PC, Lee RT, Parker JA: Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet. 1993, 341: 507-511. 10.1016/0140-6736(93)90274-K.

    CAS  PubMed  Google Scholar 

  75. Goldhaber SZ, Morpurgo M: Diagnosis, treatment, and prevention of pulmonary embolism: report of the WHO/International Society and Federation of Cardiology Task Force. JAMA. 1992, 268: 1727-1733. 10.1001/jama.268.13.1727.

    CAS  PubMed  Google Scholar 

  76. Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, Albanese P, Biasiolo A, Pegoraro C, Iliceto S, Prandoni P: Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004, 350: 2257-2264. 10.1056/NEJMoa032274.

    CAS  PubMed  Google Scholar 

  77. Dalen JE, Alpert JS: Natural history of pulmonary embolism. Prog Cardiovasc Dis. 1975, 17: 259-270. 10.1016/S0033-0620(75)80017-X.

    CAS  PubMed  Google Scholar 

  78. Lualdi JC, Goldhaber SZ: Right ventricular dysfunction after acute pulmonary embolism: pathophysiologic factors detection, and therapeutic implications. Am Heart J. 1995, 130: 1276-1282. 10.1016/0002-8703(95)90155-8.

    CAS  PubMed  Google Scholar 

  79. Bhorade S, Christenson J, O'Connor M, Lavoie A, Pohlman A, Hall JB: Response to inhaled nitric oxide in patients with acute right heart syndrome. Am J Respir Crit Care Med. 1999, 159: 571-579.

    CAS  PubMed  Google Scholar 

  80. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schunemann HJ: What is "quality of evidence" and why is it important to clinicians?. BMJ. 2008, 336: 995-998. 10.1136/bmj.39490.551019.BE.

    PubMed Central  PubMed  Google Scholar 

  81. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schunemann HJ: GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008, 336: 924-926. 10.1136/bmj.39489.470347.AD.

    PubMed Central  PubMed  Google Scholar 

  82. Gan CT, Lankhaar JW, Marcus JT, Westerhof N, Marques KM, Bronzwaer JG, Boonstra A, Postmus PE, Vonk-Noordegraaf A: Impaired left ventricular filling due to right-to-left ventricular interaction in patients with pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol. 2006, 290: H1528-H1533.

    CAS  PubMed  Google Scholar 

  83. Zamanian RT, Haddad F, Doyle RL, Weinacker AB: Management strategies for patients with pulmonary hypertension in the intensive care unit. Crit Care Med. 2007, 35: 2037-2050. 10.1097/01.CCM.0000280433.74246.9E.

    PubMed  Google Scholar 

  84. Reuse C, Vincent JL, Pinsky MR: Measurements of right ventricular volumes during fluid challenge. Chest. 1990, 98: 1450-1454. 10.1378/chest.98.6.1450.

    CAS  PubMed  Google Scholar 

  85. Naeije R, Vachiery JL: Medical therapy of pulmonary hypertension conventional therapies. Clin Chest Med. 2001, 22: 517-527. 10.1016/S0272-5231(05)70288-4.

    CAS  PubMed  Google Scholar 

  86. Layish DT, Tapson VF: Pharmacologic hemodynamic support in massive pulmonary embolism. Chest. 1997, 111: 218-224. 10.1378/chest.111.1.218.

    CAS  PubMed  Google Scholar 

  87. James KB, Stelmach K, Armstrong R, Young JB, Fouad-Tarazi F: Plasma volume and outcome in pulmonary hypertension. Tex Heart Inst J. 2003, 30: 305-307.

    PubMed Central  PubMed  Google Scholar 

  88. Mathru M, Venus B, Smith RA, Shirakawa Y, Sugiura A: Treatment of low cardiac output complicating acute pulmonary hypertension in normovolemic goats. Crit Care Med. 1986, 14: 120-124. 10.1097/00003246-198602000-00008.

    CAS  PubMed  Google Scholar 

  89. Molloy WD, Lee KY, Girling L, Schick U, Prewitt RM: Treatment of shock in a canine model of pulmonary embolism. Am Rev Respir Dis. 1984, 130: 870-874.

    CAS  PubMed  Google Scholar 

  90. Ghignone M, Girling L, Prewitt RM: Volume expansion versus norepinephrine in treatment of a low cardiac output complicating an acute increase in right ventricular afterload in dogs. Anesthesiology. 1984, 60: 132-135. 10.1097/00000542-198402000-00009.

    CAS  PubMed  Google Scholar 

  91. Belenkie I, Dani R, Smith ER, Tyberg JV: Effects of volume loading during experimental acute pulmonary embolism. Circulation. 1989, 80: 178-188.

    CAS  PubMed  Google Scholar 

  92. Mercat A, Diehl JL, Meyer G, Teboul JL, Sors H: Hemodynamic effects of fluid loading in acute massive pulmonary embolism. Crit Care Med. 1999, 27: 540-544. 10.1097/00003246-199903000-00032.

    CAS  PubMed  Google Scholar 

  93. Redl G, Germann P, Plattner H, Hammerle A: Right ventricular function in early septic shock states. Intensive Care Med. 1993, 19: 3-7. 10.1007/BF01709270.

    CAS  PubMed  Google Scholar 

  94. Schneider AJ, Teule GJ, Groeneveld AB, Nauta J, Heidendal GA, Thijs LG: Biventricular performance during volume loading in patients with early septic shock, with emphasis on the right ventricle: a combined hemodynamic and radionuclide study. Am Heart J. 1988, 116: 103-112. 10.1016/0002-8703(88)90256-6.

    CAS  PubMed  Google Scholar 

  95. Siva A, Shah AM: Moderate mitral stenosis in pregnancy: the haemodynamic impact of diuresis. Heart. 2005, 91: e3-10.1136/hrt.2004.053017.

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Ducas J, Prewitt RM: Pathophysiology and therapy of right ventricular dysfunction due to pulmonary embolism. Cardiovasc Clin. 1987, 17: 191-202.

    CAS  PubMed  Google Scholar 

  97. Mebazaa A, Karpati P, Renaud E, Algotsson L: Acute right ventricular failure: from pathophysiology to new treatments. Intensive Care Med. 2004, 30: 185-196. 10.1007/s00134-003-2025-3.

    PubMed  Google Scholar 

  98. Goldhaber SZ: The approach to massive pulmonary embolism. Semin Respir Crit Care Med. 2000, 21: 555-561. 10.1055/s-2000-13184.

    CAS  PubMed  Google Scholar 

  99. Forrest P: Anaesthesia and right ventricular failure. Anaesth Intensive Care. 2009, 37: 370-385.

    CAS  PubMed  Google Scholar 

  100. Kwak YL, Lee CS, Park YH, Hong YW: The effect of phenylephrine and norepinephrine in patients with chronic pulmonary hypertension. Anaesthesia. 2002, 57: 9-14. 10.1046/j.1365-2044.2002.02324.x.

    CAS  PubMed  Google Scholar 

  101. Dunser MW, Hasibeder WR: Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress. J Intensive Care Med. 2009, 24: 293-316. 10.1177/0885066609340519.

    PubMed  Google Scholar 

  102. Bergofsky EH: Humoral control of the pulmonary circulation. Annu Rev Physiol. 1980, 42: 221-233. 10.1146/annurev.ph.42.030180.001253.

    CAS  PubMed  Google Scholar 

  103. Hanson EL, O'Connor NE, Drinker PA: Hemodynamic response to controlled ventilation during hypoxia in man and animals. Surg Forum. 1972, 23: 207-209.

    CAS  PubMed  Google Scholar 

  104. Tourneux P, Rakza T, Bouissou A, Krim G, Storme L: Pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension. J Pediatr. 2008, 153: 345-349. 10.1016/j.jpeds.2008.03.007.

    CAS  PubMed  Google Scholar 

  105. Morelli A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Cecchini V, Bachetoni A, D'Alessandro M, Van Aken H, Pietropaoli P, Westphal M: Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study. Crit Care. 2009, 13: R130-10.1186/cc7990.

    PubMed Central  PubMed  Google Scholar 

  106. Schreuder WO, Schneider AJ, Groeneveld AB, Thijs LG: Effect of dopamine vs norepinephrine on hemodynamics in septic shock: emphasis on right ventricular performance. Chest. 1989, 95: 1282-1288. 10.1378/chest.95.6.1282.

    CAS  PubMed  Google Scholar 

  107. Ducas J, Duval D, Dasilva H, Boiteau P, Prewitt RM: Treatment of canine pulmonary hypertension: effects of norepinephrine and isoproterenol on pulmonary vascular pressure-flow characteristics. Circulation. 1987, 75: 235-242.

    CAS  PubMed  Google Scholar 

  108. Hirsch LJ, Rooney MW, Wat SS, Kleinmann B, Mathru M: Norepinephrine and phenylephrine effects on right ventricular function in experimental canine pulmonary embolism. Chest. 1991, 100: 796-801. 10.1378/chest.100.3.796.

    CAS  PubMed  Google Scholar 

  109. Martin C, Perrin G, Saux P, Papazian L, Gouin F: function Effects of norepinephrine on right ventricular in septic shock patients. Intensive Care Med. 1994, 20: 444-447. 10.1007/BF01710657.

    CAS  PubMed  Google Scholar 

  110. Bertolissi M, Bassi F, Da Broi U: Norepinephrine can be useful for the treatment of right ventricular failure combined with acute pulmonary hypertension and systemic hypotension: a case report. Minerva Anestesiol. 2001, 67: 79-84.

    CAS  PubMed  Google Scholar 

  111. Rich S, Gubin S, Hart K: The effects of phenylephrine on right ventricular performance in patients with pulmonary hypertension. Chest. 1990, 98: 1102-1106. 10.1378/chest.98.5.1102.

    CAS  PubMed  Google Scholar 

  112. Eichinger MR, Walker BR: Enhanced pulmonary arterial dilation to arginine vasopressin in chronically hypoxic rats. Am J Physiol. 1994, 267: H2413-H2419.

    CAS  PubMed  Google Scholar 

  113. Walker BR, Haynes J, Wang HL, Voelkel NF: Vasopressin-induced pulmonary vasodilation in rats. Am J Physiol. 1989, 257: H415-H422.

    CAS  PubMed  Google Scholar 

  114. Evora PR, Pearson PJ, Schaff HV: Arginine vasopressin induces endothelium-dependent vasodilatation of the pulmonary artery: V1-receptor-mediated production of nitric oxide. Chest. 1993, 103: 1241-1245. 10.1378/chest.103.4.1241.

    CAS  PubMed  Google Scholar 

  115. Jeon Y, Ryu JH, Lim YJ, Kim CS, Bahk JH, Yoon SZ, Choi JY: Comparative hemodynamic effects of vasopressin and norepinephrine after milrinone-induced hypotension in off-pump coronary artery bypass surgical patients. Eur J Cardiothorac Surg. 2006, 29: 952-956. 10.1016/j.ejcts.2006.02.032.

    PubMed  Google Scholar 

  116. Tayama E, Ueda T, Shojima T, Akasu K, Oda T, Fukunaga S, Akashi H, Aoyagi S: Arginine vasopressin is an ideal drug after cardiac surgery for the management of low systemic vascular resistant hypotension concomitant with pulmonary hypertension. Interact Cardiovasc Thorac Surg. 2007, 6: 715-719. 10.1510/icvts.2007.159624.

    PubMed  Google Scholar 

  117. Braun EB, Palin CA, Hogue CW: Vasopressin during spinal anesthesia in a patient with primary pulmonary hypertension treated with intravenous epoprostenol. Anesth Analg. 2004, 99: 36-37. 10.1213/01.ANE.0000121349.15880.DC.

    CAS  PubMed  Google Scholar 

  118. Price LC, Forrest P, Sodhi V, Adamson DL, Nelson-Piercy C, Lucey M, Howard LS: Use of vasopressin after caesarean section in idiopathic pulmonary arterial hypertension. Br J Anaesth. 2007, 99: 552-555. 10.1093/bja/aem180.

    CAS  PubMed  Google Scholar 

  119. Smith AM, Elliot CM, Kiely DG, Channer KS: The role of vasopressin in cardiorespiratory arrest and pulmonary hypertension. QJM. 2006, 99: 127-133. 10.1093/qjmed/hcl009.

    CAS  PubMed  Google Scholar 

  120. Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D: Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008, 358: 877-887. 10.1056/NEJMoa067373.

    CAS  PubMed  Google Scholar 

  121. Torgersen C, Dunser MW, Wenzel V, Jochberger S, Mayr V, Schmittinger CA, Lorenz I, Schmid S, Westphal M, Grander W, Luckner G: Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial. Intensive Care Med. 2010, 36: 57-65. 10.1007/s00134-009-1630-1.

    CAS  PubMed  Google Scholar 

  122. Luckner G, Mayr VD, Jochberger S, Wenzel V, Ulmer H, Hasibeder WR, Dunser MW: Comparison of two dose regimens of arginine vasopressin in advanced vasodilatory shock. Crit Care Med. 2007, 35: 2280-2285. 10.1097/01.CCM.0000281853.50661.23.

    CAS  PubMed  Google Scholar 

  123. Gold J, Cullinane S, Chen J, Seo S, Oz MC, Oliver JA, Landry DW: Vasopressin in the treatment of milrinone-induced hypotension in severe heart failure. Am J Cardiol. 2000, 85: 506-508. 10.1016/S0002-9149(99)00783-3. A511

    CAS  PubMed  Google Scholar 

  124. Argenziano M, Choudhri AF, Oz MC, Rose EA, Smith CR, Landry DW: A prospective randomized trial of arginine vasopressin in the treatment of vasodilatory shock after left ventricular assist device placement. Circulation. 1997, 96: II-286-II-290.

    Google Scholar 

  125. Vida VL, Mack R, Castaneda AR: The role of vasopressin in treating systemic inflammatory syndrome complicated by right ventricular failure. Cardiol Young. 2005, 15: 88-90. 10.1017/S1047951105000193.

    PubMed  Google Scholar 

  126. Scheurer MA, Bradley SM, Atz AM: Vasopressin to attenuate pulmonary hypertension and improve systemic blood pressure after correction of obstructed total anomalous pulmonary venous return. J Thorac Cardiovasc Surg. 2005, 129: 464-466. 10.1016/j.jtcvs.2004.06.043.

    PubMed  Google Scholar 

  127. Wang HJ, Wong CS, Chiang CY, Yeh CC, Cherng CH, Ho ST, Wu CT: Low-dose vasopressin infusion can be an alternative in treating patients with refractory septic shock combined with chronic pulmonary hypertension: a case report. Acta Anaesthesiol Sin. 2003, 41: 77-80.

    PubMed  Google Scholar 

  128. Jain RL, Horn EM: Peripheral vasodilation complicated by pulmonary hypertension: a role for vasopressin. Am J Respir Crit Care Med. 2008, 177: A919-

    Google Scholar 

  129. Holmes CL, Walley KR, Chittock DR, Lehman T, Russell JA: The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series. Intensive Care Med. 2001, 27: 1416-1421. 10.1007/s001340101014.

    CAS  PubMed  Google Scholar 

  130. Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann G, Pajk W, Friesenecker B, Hasibeder WR: Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation. 2003, 107: 2313-2319. 10.1161/01.CIR.0000066692.71008.BB.

    PubMed  Google Scholar 

  131. Dunser MW, Mayr AJ, Stallinger A, Ulmer H, Ritsch N, Knotzer H, Pajk W, Mutz NJ, Hasibeder WR: Cardiac performance during vasopressin infusion in postcardiotomy shock. Intensive Care Med. 2002, 28: 746-751. 10.1007/s00134-002-1265-y.

    CAS  PubMed  Google Scholar 

  132. Lauzier F, Levy B, Lamarre P, Lesur O: Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial. Intensive Care Med. 2006, 32: 1782-1789. 10.1007/s00134-006-0378-0.

    CAS  PubMed  Google Scholar 

  133. Varma S, Jaju BP, Bhargava KP: Mechanism of vasopressin-induced bradycardia in dogs. Circ Res. 1969, 24: 787-792.

    CAS  PubMed  Google Scholar 

  134. Naeije R, Hallemans R, Mols P, Melot C, Reding P: Effect of vasopressin and somatostatin on hemodynamics and blood gases in patients with liver cirrhosis. Crit Care Med. 1982, 10: 578-582. 10.1097/00003246-198209000-00004.

    CAS  PubMed  Google Scholar 

  135. Mols P, Hallemans R, Van Kuyk M, Melot C, Lejeune P, Ham H, Vertongen F, Naeije R: Hemodynamic effects of vasopressin, alone and in combination with nitroprusside, in patients with liver cirrhosis and portal hypertension. Ann Surg. 1984, 199: 176-181. 10.1097/00000658-198402000-00008.

    PubMed Central  CAS  PubMed  Google Scholar 

  136. Migotto WH, Dahi H: Effects of vasopressin on hemodynamics in cardiogenic shock. Chest. 2005, 128: 168S-

    Google Scholar 

  137. Walker BR, Childs ME, Adams EM: Direct cardiac effects of vasopressin: role of V1- and V2-vasopressinergic receptors. Am J Physiol. 1988, 255: H261-H265.

    CAS  PubMed  Google Scholar 

  138. Leather HA, Segers P, Berends N, Vandermeersch E, Wouters PF: Effects of vasopressin on right ventricular function in an experimental model of acute pulmonary hypertension. Crit Care Med. 2002, 30: 2548-2552. 10.1097/00003246-200211000-00024.

    CAS  PubMed  Google Scholar 

  139. Indrambarya T, Boyd JH, Wang Y, McConechy M, Walley KR: Low-dose vasopressin infusion results in increased mortality and cardiac dysfunction following ischemia-reperfusion injury in mice. Crit Care. 2009, 13: R98-10.1186/cc7930.

    PubMed Central  PubMed  Google Scholar 

  140. Tisdale JE, Patel R, Webb CR, Borzak S, Zarowitz BJ: Electrophysiologic and proarrhythmic effects of intravenous inotropic agents. Prog Cardiovasc Dis. 1995, 38: 167-180. 10.1016/S0033-0620(05)80005-2.

    CAS  PubMed  Google Scholar 

  141. Holloway EL, Polumbo RA, Harrison DC: Acute circulatory effects of dopamine in patients with pulmonary hypertension. Br Heart J. 1975, 37: 482-485. 10.1136/hrt.37.5.482.

    PubMed Central  CAS  PubMed  Google Scholar 

  142. Liet JM, Boscher C, Gras-Leguen C, Gournay V, Debillon T, Roze JC: Dopamine effects on pulmonary artery pressure in hypotensive preterm infants with patent ductus arteriosus. J Pediatr. 2002, 140: 373-375. 10.1067/mpd.2002.123100.

    CAS  PubMed  Google Scholar 

  143. Leier CV, Heban PT, Huss P, Bush CA, Lewis RP: Comparative systemic and regional hemodynamic effects of dopamine and dobutamine in patients with cardiomyopathic heart failure. Circulation. 1978, 58: 466-475.

    CAS  PubMed  Google Scholar 

  144. Lejeune P, Naeije R, Leeman M, Melot C, Deloof T, Delcroix M: Effects of dopamine and dobutamine on hyperoxic and hypoxic pulmonary vascular tone in dogs. Am Rev Respir Dis. 1987, 136: 29-35.

    CAS  PubMed  Google Scholar 

  145. Schreuder WO, Schneider AJ, Groeneveld AB, Thijs LG: The influence of catecholamines on right ventricular function in septic shock. Intensive Care Med. 1988, 14 Suppl 2: 492-495.

    CAS  PubMed  Google Scholar 

  146. De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL: Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010, 362: 779-789. 10.1056/NEJMoa0907118.

    CAS  PubMed  Google Scholar 

  147. Barrington KJ, Finer NN, Chan WK: A blind, randomized comparison of the circulatory effects of dopamine and epinephrine infusions in the newborn piglet during normoxia and hypoxia. Crit Care Med. 1995, 23: 740-748. 10.1097/00003246-199504000-00024.

    CAS  PubMed  Google Scholar 

  148. Stobierska-Dzierzek B, Awad H, Michler RE: The evolving management of acute right-sided heart failure in cardiac transplant recipients. J Am Coll Cardiol. 2001, 38: 923-931. 10.1016/S0735-1097(01)01486-3.

    CAS  PubMed  Google Scholar 

  149. Prielipp RC, McLean R, Rosenthal MH, Pearl RG: Hemodynamic profiles of prostaglandin E1, isoproterenol, prostacyclin, and nifedipine in experimental porcine pulmonary hypertension. Crit Care Med. 1991, 19: 60-67. 10.1097/00003246-199101000-00016.

    CAS  PubMed  Google Scholar 

  150. Acosta F, Sansano T, Palenciano CG, Falcon L, Domenech P, Robles R, Bueno FS, Ramirez P, Parrilla P: Effects of dobutamine on right ventricular function and pulmonary circulation in pulmonary hypertension during liver transplantation. Transplant Proc. 2005, 37: 3869-3870. 10.1016/j.transproceed.2005.10.045.

    CAS  PubMed  Google Scholar 

  151. Ferrario M, Poli A, Previtali M, Lanzarini L, Fetiveau R, Diotallevi P, Mussini A, Montemartini C: Hemodynamics of volume loading compared with dobutamine in severe right ventricular infarction. Am J Cardiol. 1994, 74: 329-333. 10.1016/0002-9149(94)90398-0.

    CAS  PubMed  Google Scholar 

  152. Sztrymf B, Souza R, Bertoletti L, Jais X, Sitbon O, Price LC, Simonneau G, Humbert M: Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension. Eur Respir J. 2010, 35: 1286-1293. 10.1183/09031936.00070209.

    CAS  PubMed  Google Scholar 

  153. Vizza CD, Rocca GD, Roma AD, Iacoboni C, Pierconti F, Venuta F, Rendina E, Schmid G, Pietropaoli P, Fedele F: Acute hemodynamic effects of inhaled nitric oxide, dobutamine and a combination of the two in patients with mild to moderate secondary pulmonary hypertension. Crit Care. 2001, 5: 355-361. 10.1186/cc1069.

    PubMed Central  CAS  PubMed  Google Scholar 

  154. Pagnamenta A, Fesler P, Vandinivit A, Brimioulle S, Naeije R: Pulmonary vascular effects of dobutamine in experimental pulmonary hypertension. Crit Care Med. 2003, 31: 1140-1146. 10.1097/01.CCM.0000060126.75746.32.

    CAS  PubMed  Google Scholar 

  155. Bradford KK, Deb B, Pearl RG: Combination therapy with inhaled nitric oxide and intravenous dobutamine during pulmonary hypertension in the rabbit. J Cardiovasc Pharmacol. 2000, 36: 146-151. 10.1097/00005344-200008000-00002.

    CAS  PubMed  Google Scholar 

  156. Honerjager P: Pharmacology of bipyridine phosphodiesterase III inhibitors. Am Heart J. 1991, 121: 1939-1944. 10.1016/0002-8703(91)90828-6.

    CAS  PubMed  Google Scholar 

  157. Young RA, Ward A: Milrinone. A preliminary review of its pharmacological properties and therapeutic use. Drugs. 1988, 36: 158-192. 10.2165/00003495-198836020-00003.

    CAS  PubMed  Google Scholar 

  158. Alousi AA, Johnson DC: Pharmacology of the bipyridines: amrinone and milrinone. Circulation. 1986, 73: III10-III24.

    CAS  PubMed  Google Scholar 

  159. Farah AE, Frangakis CJ: Studies on the mechanism of action of the bipyridine milrinone on the heart. Basic Res Cardiol. 1989, 84 Suppl 1: 85-103. 10.1007/BF02650349.

    CAS  PubMed  Google Scholar 

  160. Oztekin I, Yazici S, Oztekin DS, Goksel O, Issever H, Canik S: Effects of low-dose milrinone on weaning from cardiopulmonary bypass and after in patients with mitral stenosis and pulmonary hypertension. Yakugaku Zasshi. 2007, 127: 375-383. 10.1248/yakushi.127.375.

    CAS  PubMed  Google Scholar 

  161. Kihara S, Kawai A, Fukuda T, Yamamoto N, Aomi S, Nishida H, Endo M, Koyanagi H: Effects of milrinone for right ventricular failure after left ventricular assist device implantation. Heart Vessels. 2002, 16: 69-71. 10.1007/s380-002-8320-z.

    PubMed  Google Scholar 

  162. Fukazawa K, Poliac LC, Pretto EA: Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantation. Clin Transplant. 2010, 24: 515-519. 10.1111/j.1399-0012.2009.01119.x.

    PubMed  Google Scholar 

  163. Harris MN, Daborn AK, O'Dwyer JP: Milrinone and the pulmonary vascular system. Eur J Anaesthesiol Suppl. 1992, 5: 27-30.

    PubMed  Google Scholar 

  164. Eichhorn EJ, Konstam MA, Weiland DS, Roberts DJ, Martin TT, Stransky NB, Salem DN: Differential effects of milrinone and dobutamine on right ventricular preload, afterload and systolic performance in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1987, 60: 1329-1333. 10.1016/0002-9149(87)90616-3.

    CAS  PubMed  Google Scholar 

  165. Boldt J, Knothe C, Zickmann B, Ballesteros M, Russ W, Dapper F, Hempelmann G: The role of enoximone in cardiac surgery. Br J Anaesth. 1992, 69: 45-50. 10.1093/bja/69.1.45.

    CAS  PubMed  Google Scholar 

  166. Tarr TJ, Jeffrey RR, Kent AP, Cowen ME: Use of enoximone in weaning from cardiopulmonary bypass following mitral valve surgery. Cardiology. 1990, 77 Suppl 3: 51-57. 10.1159/000174672. discussion 62-67

    CAS  PubMed  Google Scholar 

  167. Leeman M, Lejeune P, Melot C, Naeije R: Reduction in pulmonary hypertension and in airway resistances by enoximone (MDL 17,043) in decompensated COPD. Chest. 1987, 91: 662-666. 10.1378/chest.91.5.662.

    CAS  PubMed  Google Scholar 

  168. Jenkins IR, Dolman J, O'Connor JP, Ansley DM: Amrinone versus dobutamine in cardiac surgical patients with severe pulmonary hypertension after cardiopulmonary bypass: a prospective, randomized double-blinded trial. Anaesth Intensive Care. 1997, 25: 245-249.

    CAS  PubMed  Google Scholar 

  169. Dupuis JY, Bondy R, Cattran C, Nathan HJ, Wynands JE: Amrinone and dobutamine as primary treatment of low cardiac output syndrome following coronary artery surgery: a comparison of their effects on hemodynamics and outcome. J Cardiothorac Vasc Anesth. 1992, 6: 542-553. 10.1016/1053-0770(92)90096-P.

    CAS  PubMed  Google Scholar 

  170. Hachenberg T, Mollhoff T, Holst D, Hammel D, Brussel T: Cardiopulmonary effects of enoximone or dobutamine and nitroglycerin on mitral valve regurgitation and pulmonary venous hypertension. J Cardiothorac Vasc Anesth. 1997, 11: 453-457. 10.1016/S1053-0770(97)90054-9.

    CAS  PubMed  Google Scholar 

  171. Ansell J, Tiarks C, McCue J, Parrilla N, Benotti JR: Amrinone-induced thrombocytopenia. Arch Intern Med. 1984, 144: 949-952. 10.1001/archinte.144.5.949.

    CAS  PubMed  Google Scholar 

  172. Boldt J, Knothe C, Zickmann B, Herold C, Dapper E, Hempelmann G: Phosphodiesterase-inhibitors enoximone and piroximone in cardiac surgery: influence on platelet count and function. Intensive Care Med. 1992, 18: 449-454. 10.1007/BF01708579.

    CAS  PubMed  Google Scholar 

  173. Kikura M, Lee MK, Safon RA, Bailey JM, Levy JH: The effects of milrinone on platelets in patients undergoing cardiac surgery. Anesth Analg. 1995, 81: 44-48. 10.1097/00000539-199507000-00009.

    CAS  PubMed  Google Scholar 

  174. Levy JH, Bailey JM, Deeb GM: Intravenous milrinone in cardiac surgery. Ann Thorac Surg. 2002, 73: 325-330. 10.1016/S0003-4975(01)02719-9.

    PubMed  Google Scholar 

  175. Chen EP, Bittner HB, Davis RD, Van Trigt P: Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension. Ann Thorac Surg. 1997, 63: 814-821. 10.1016/S0003-4975(97)00011-8.

    CAS  PubMed  Google Scholar 

  176. Buckley MS, Feldman JP: Nebulized milrinone use in a pulmonary hypertensive crisis. Pharmacotherapy. 2007, 27: 1763-1766. 10.1592/phco.27.12.1763.

    CAS  PubMed  Google Scholar 

  177. Wang H, Gong M, Zhou B, Dai A: Comparison of inhaled and intravenous milrinone in patients with pulmonary hypertension undergoing mitral valve surgery. Adv Ther. 2009, 26: 462-468. 10.1007/s12325-009-0019-4.

    CAS  PubMed  Google Scholar 

  178. Haraldssons A, Kieler-Jensen N, Ricksten SE: The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension. Anesth Analg. 2001, 93: 1439-1445. 10.1097/00000539-200112000-00018. table of contents

    Google Scholar 

  179. Sablotzki A, Starzmann W, Scheubel R, Grond S, Czeslick EG: Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates. Can J Anaesth. 2005, 52: 1076-1082. 10.1007/BF03021608.

    PubMed  Google Scholar 

  180. Follath F, Cleland JG, Just H, Papp JG, Scholz H, Peuhkurinen K, Harjola VP, Mitrovic V, Abdalla M, Sandell EP, Lehtonen L: Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet. 2002, 360: 196-202. 10.1016/S0140-6736(02)09455-2.

    CAS  PubMed  Google Scholar 

  181. Barraud D, Faivre V, Damy T, Welschbillig S, Gayat E, Heymes C, Payen D, Shah AM, Mebazaa A: Levosimendan restores both systolic and diastolic cardiac performance in lipopolysaccharide-treated rabbits: comparison with dobutamine and milrinone. Crit Care Med. 2007, 35: 1376-1382. 10.1097/01.CCM.0000261889.18102.84.

    PubMed  Google Scholar 

  182. Ukkonen H, Saraste M, Akkila J, Knuuti J, Karanko M, Iida H, Lehikoinen P, Nagren K, Lehtonen L, Voipio-Pulkki LM: Myocardial efficiency during levosimendan infusion in congestive heart failure. Clin Pharmacol Ther. 2000, 68: 522-531. 10.1067/mcp.2000.110972.

    CAS  PubMed  Google Scholar 

  183. Ukkonen H, Saraste M, Akkila J, Knuuti MJ, Lehikoinen P, Nagren K, Lehtonen L, Voipio-Pulkki LM: Myocardial efficiency during calcium sensitization with levosimendan: a noninvasive study with positron emission tomography and echocardiography in healthy volunteers. Clin Pharmacol Ther. 1997, 61: 596-607. 10.1016/S0009-9236(97)90139-9.

    CAS  PubMed  Google Scholar 

  184. Yildiz O: Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007, 104: 1-5. 10.1254/jphs.CP0060010.

    CAS  PubMed  Google Scholar 

  185. Slawsky MT, Colucci WS, Gottlieb SS, Greenberg BH, Haeusslein E, Hare J, Hutchins S, Leier CV, LeJemtel TH, Loh E, Nicklas J, Ogilby D, Singh BN, Smith W: Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure: study investigators. Circulation. 2000, 102: 2222-2227.

    CAS  PubMed  Google Scholar 

  186. Kivikko M, Antila S, Eha J, Lehtonen L, Pentikainen PJ: Pharmacokinetics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure. Int J Clin Pharmacol Ther. 2002, 40: 465-471.

    CAS  PubMed  Google Scholar 

  187. Leather HA, Ver Eycken K, Segers P, Herijgers P, Vandermeersch E, Wouters PF: Effects of levosimendan on right ventricular function and ventriculovascular coupling in open chest pigs. Crit Care Med. 2003, 31: 2339-2343. 10.1097/01.CCM.0000084844.95073.C0.

    CAS  PubMed  Google Scholar 

  188. Kerbaul F, Rondelet B, Demester JP, Fesler P, Huez S, Naeije R, Brimioulle S: Effects of levosimendan versus dobutamine on pressure load-induced right ventricular failure. Crit Care Med. 2006, 34: 2814-2819. 10.1097/01.CCM.0000242157.19347.50.

    CAS  PubMed  Google Scholar 

  189. Missant C, Rex S, Segers P, Wouters PF: Levosimendan improves right ventriculovascular coupling in a porcine model of right ventricular dysfunction. Crit Care Med. 2007, 35: 707-715. 10.1097/01.CCM.0000257326.96342.57.

    CAS  PubMed  Google Scholar 

  190. Duygu H, Ozerkan F, Zoghi M, Nalbantgil S, Yildiz A, Akilli A, Akin M, Nazli C, Ergene O: Effect of levosimendan on right ventricular systolic and diastolic functions in patients with ischaemic heart failure. Int J Clin Pract. 2008, 62: 228-233. 10.1111/j.1742-1241.2007.01510.x.

    CAS  PubMed  Google Scholar 

  191. Russ MA, Prondzinsky R, Carter JM, Schlitt A, Ebelt H, Schmidt H, Lemm H, Heinroth K, Soeffker G, Winkler M, Werdan K, Buerke M: Right ventricular function in myocardial infarction complicated by cardiogenic shock: improvement with levosimendan. Crit Care Med. 2009, 37: 3017-3023. 10.1097/CCM.0b013e3181b0314a.

    CAS  PubMed  Google Scholar 

  192. Yilmaz MB, Yontar C, Erdem A, Karadas F, Yalta K, Turgut OO, Yilmaz A, Tandogan I: Comparative effects of levosimendan and dobutamine on right ventricular function in patients with biventricular heart failure. Heart Vessels. 2009, 24: 16-21. 10.1007/s00380-008-1077-2.

    PubMed  Google Scholar 

  193. Poelzl G, Zwick RH, Grander W, Metzler B, Jonetzko P, Frick M, Ulmer H, Pachinger O, Roithinger FX: Safety and effectiveness of levosimendan in patients with predominant right heart failure. Herz. 2008, 33: 368-373. 10.1007/s00059-008-3051-2.

    PubMed  Google Scholar 

  194. Parissis JT, Paraskevaidis I, Bistola V, Farmakis D, Panou F, Kourea K, Nikolaou M, Filippatos G, Kremastinos D: Effects of levosimendan on right ventricular function in patients with advanced heart failure. Am J Cardiol. 2006, 98: 1489-1492. 10.1016/j.amjcard.2006.06.052.

    CAS  PubMed  Google Scholar 

  195. Morelli A, Teboul JL, Maggiore SM, Vieillard-Baron A, Rocco M, Conti G, De Gaetano A, Picchini U, Orecchioni A, Carbone I, Tritapepe L, Pietropaoli P, Westphal M: Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress syndrome: a pilot study. Crit Care Med. 2006, 34: 2287-2293. 10.1097/01.CCM.0000230244.17174.4F.

    CAS  PubMed  Google Scholar 

  196. Morais RJ: Levosimendan in severe right ventricular failure following mitral valve replacement. J Cardiothorac Vasc Anesth. 2006, 20: 82-84. 10.1053/j.jvca.2005.01.039.

    PubMed  Google Scholar 

  197. Cicekcioglu F, Parlar AI, Ersoy O, Yay K, Hijazi A, Katircioglu SF: Levosimendan and severe pulmonary hypertension during open heart surgery. Gen Thorac Cardiovasc Surg. 2008, 56: 563-565. 10.1007/s11748-008-0301-4.

    PubMed  Google Scholar 

  198. Kleber FX, Bollmann T, Borst MM, Costard-Jackle A, Ewert R, Kivikko M, Petterson T, Pohjanjousi P, Sonntag S, Wikstrom G: Repetitive dosing of intravenous levosimendan improves pulmonary hemodynamics in patients with pulmonary hypertension: results of a pilot study. J Clin Pharmacol. 2009, 49: 109-115.

    CAS  PubMed  Google Scholar 

  199. Raper R: FMM: The heart and circulation in sepsis. Balliere's Clin Anaesthesiol. 1990, 4: 333-355. 10.1016/S0950-3501(05)80290-9.

    Google Scholar 

  200. Humbert M, Sitbon O, Simonneau G: Treatment of pulmonary arterial hypertension. N Engl J Med. 2004, 351: 1425-1436. 10.1056/NEJMra040291.

    CAS  PubMed  Google Scholar 

  201. Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G: Guidelines for the diagnosis and treatment of pulmonary hypertension: the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Respir J. 2009, 34: 1219-1263. 10.1183/09031936.00139009.

    CAS  PubMed  Google Scholar 

  202. Kieler-Jensen N, Lundin S, Ricksten SE: Vasodilator therapy after heart transplantation: effects of inhaled nitric oxide and intravenous prostacyclin, prostaglandin E1, and sodium nitroprusside. J Heart Lung Transplant. 1995, 14: 436-443.

    CAS  PubMed  Google Scholar 

  203. Creagh-Brown BC, Griffiths MJ, Evans TW: Bench-to-bedside review: inhaled nitric oxide therapy in adults. Crit Care. 2009, 13: 221-10.1186/cc7734.

    PubMed Central  PubMed  Google Scholar 

  204. McNeil K, Dunning J, Morrell NW: The pulmonary physician in critical care, 13: the pulmonary circulation and right ventricular failure in the ITU. Thorax. 2003, 58: 157-162. 10.1136/thorax.58.2.157.

    PubMed Central  CAS  PubMed  Google Scholar 

  205. Channick RN, Hoch RC, Newhart JW, Johnson FW, Smith CM: Improvement in pulmonary hypertension and hypoxemia during nitric oxide inhalation in a patient with end-stage pulmonary fibrosis. Am J Respir Crit Care Med. 1994, 149: 811-814.

    CAS  PubMed  Google Scholar 

  206. Griffiths MJ, Evans TW: Inhaled nitric oxide therapy in adults. N Engl J Med. 2005, 353: 2683-2695. 10.1056/NEJMra051884.

    CAS  PubMed  Google Scholar 

  207. Aranda M, Bradford KK, Pearl RG: Combined therapy with inhaled nitric oxide and intravenous vasodilators during acute and chronic experimental pulmonary hypertension. Anesth Analg. 1999, 89: 152-158. 10.1097/00000539-199907000-00027.

    CAS  PubMed  Google Scholar 

  208. Morgan JM, McCormack DG, Griffiths MJ, Morgan CJ, Barnes PJ, Evans TW: Adenosine as a vasodilator in primary pulmonary hypertension. Circulation. 1991, 84: 1145-1149.

    CAS  PubMed  Google Scholar 

  209. Fullerton DA, Jones SD, Grover FL, McIntyre RC: Adenosine effectively controls pulmonary hypertension after cardiac operations. Ann Thorac Surg. 1996, 61: 1118-1123. 10.1016/0003-4975(95)01149-8. discussion 1123-1114

    CAS  PubMed  Google Scholar 

  210. Haywood GA, Sneddon JF, Bashir Y, Jennison SH, Gray HH, McKenna WJ: Adenosine infusion for the reversal of pulmonary vasoconstriction in biventricular failure: a good test but a poor therapy. Circulation. 1992, 86: 896-902.

    CAS  PubMed  Google Scholar 

  211. Oliveira EC, Ribeiro AL, Amaral CF: Adenosine for vasoreactivity testing in pulmonary hypertension: a head-to-head comparison with inhaled nitric oxide. Respir Med. 104: 606-611. 10.1016/j.rmed.2009.11.010.

  212. Pepke-Zaba J, Higenbottam TW, Dinh-Xuan AT, Stone D, Wallwork J: Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet. 1991, 338: 1173-1174. 10.1016/0140-6736(91)92033-X.

    CAS  PubMed  Google Scholar 

  213. King R, Esmail M, Mahon S, Dingley J, Dwyer S: Use of nitric oxide for decompensated right ventricular failure and circulatory shock after cardiac arrest. Br J Anaesth. 2000, 85: 628-631. 10.1093/bja/85.4.628.

    CAS  PubMed  Google Scholar 

  214. Frostell CG, Blomqvist H, Hedenstierna G, Lundberg J, Zapol WM: Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology. 1993, 78: 427-435. 10.1097/00000542-199303000-00005.

    CAS  PubMed  Google Scholar 

  215. Schenk P, Mittermayer C, Ratheiser K: Inhaled nitric oxide in a patient with severe pulmonary embolism. Ann Emerg Med. 1999, 33: 710-714.

    CAS  PubMed  Google Scholar 

  216. Capellier G, Jacques T, Balvay P, Blasco G, Belle E, Barale F: Inhaled nitric oxide in patients with pulmonary embolism. Intensive Care Med. 1997, 23: 1089-1092. 10.1007/s001340050461.

    CAS  PubMed  Google Scholar 

  217. Inglessis I, Shin JT, Lepore JJ, Palacios IF, Zapol WM, Bloch KD, Semigran MJ: Hemodynamic effects of inhaled nitric oxide in right ventricular myocardial infarction and cardiogenic shock. J Am Coll Cardiol. 2004, 44: 793-798. 10.1016/j.jacc.2004.05.047.

    CAS  PubMed  Google Scholar 

  218. Fujita Y, Nishida O, Sobue K, Ito H, Kusama N, Inagaki M, Katsuya H: Nitric oxide inhalation is useful in the management of right ventricular failure caused by myocardial infarction. Crit Care Med. 2002, 30: 1379-1381. 10.1097/00003246-200206000-00042.

    CAS  PubMed  Google Scholar 

  219. Rich GF, Murphy GD, Roos CM, Johns RA: Inhaled nitric oxide: selective pulmonary vasodilation in cardiac surgical patients. Anesthesiology. 1993, 78: 1028-1035. 10.1097/00000542-199306000-00004.

    CAS  PubMed  Google Scholar 

  220. Macdonald PS, Keogh A, Mundy J, Rogers P, Nicholson A, Harrison G, Jansz P, Kaan AM, Spratt P: Adjunctive use of inhaled nitric oxide during implantation of a left ventricular assist device. J Heart Lung Transplant. 1998, 17: 312-316.

    CAS  PubMed  Google Scholar 

  221. Beck JR, Mongero LB, Kroslowitz RM, Choudhri AF, Chen JM, DeRose JJ, Argenziano M, Smerling AJ, Oz MC: Inhaled nitric oxide improves hemodynamics in patients with acute pulmonary hypertension after high-risk cardiac surgery. Perfusion. 1999, 14: 37-42.

    CAS  PubMed  Google Scholar 

  222. Fernandez-Perez ER, Keegan MT, Harrison BA: Inhaled nitric oxide for acute right-ventricular dysfunction after extrapleural pneumonectomy. Respir Care. 2006, 51: 1172-1176.

    PubMed  Google Scholar 

  223. Fattouch K, Sbraga F, Bianco G, Speziale G, Gucciardo M, Sampognaro R, Ruvolo G: Inhaled prostacyclin, nitric oxide, and nitroprusside in pulmonary hypertension after mitral valve replacement. J Card Surg. 2005, 20: 171-176. 10.1111/j.0886-0440.2005.200383w.x.

    PubMed  Google Scholar 

  224. Takaba K, Aota M, Nonaka M, Sugimoto A, Konishi Y: Successful treatment of chronic thromboembolic pulmonary hypertension with inhaled nitric oxide after right ventricular thrombectomy. Jpn J Thorac Cardiovasc Surg. 2004, 52: 257-260. 10.1007/s11748-004-0120-1.

    PubMed  Google Scholar 

  225. Maxey TS, Smith CD, Kern JA, Tribble CG, Jones DR, Kron IL, Crosby IK: Beneficial effects of inhaled nitric oxide in adult cardiac surgical patients. Ann Thorac Surg. 2002, 73: 529-532. 10.1016/S0003-4975(01)03398-7. discussion 532-523

    PubMed  Google Scholar 

  226. Khan TA, Schnickel G, Ross D, Bastani S, Laks H, Esmailian F, Marelli D, Beygui R, Shemin R, Watson L, Vartapetian I, Ardehali A: A prospective, randomized, crossover pilot study of inhaled nitric oxide versus inhaled prostacyclin in heart transplant and lung transplant recipients. J Thorac Cardiovasc Surg. 2009, 138: 1417-1424. 10.1016/j.jtcvs.2009.04.063.

    CAS  PubMed  Google Scholar 

  227. Carrier M, Blaise G, Belisle S, Perrault LP, Pellerin M, Petitclerc R, Pelletier LC: Nitric oxide inhalation in the treatment of primary graft failure following heart transplantation. J Heart Lung Transplant. 1999, 18: 664-667. 10.1016/S1053-2498(99)00025-X.

    CAS  PubMed  Google Scholar 

  228. Trummer G, Berchtold-Herz M, Martin J, Beyersdorf F: Successful treatment of pulmonary hypertension with inhaled nitric oxide after pulmonary embolectomy. Ann Thorac Surg. 2002, 73: 1299-1301. 10.1016/S0003-4975(01)03265-9.

    PubMed  Google Scholar 

  229. Yoshikawa T, Date H, Yamashita M, Nagahiro I, Aoe M, Shimizu N: Inhaled nitric oxide ameliorates postoperative acute graft dysfunction after living-donor lobar lung transplantation. Jpn J Thorac Cardiovasc Surg. 2000, 48: 742-745.

    CAS  PubMed  Google Scholar 

  230. Girardis M, Pasqualotto A, Colo F, Dal Pos L, Sabbadini D, Pasqualucci A, Pasetto A: Severe hypoxemia and pulmonary hypertension during orthotopic liver transplantation: a successful use of inhaled nitric oxide. Intensive Care Med. 1999, 25: 638-10.1007/s001340050919.

    CAS  PubMed  Google Scholar 

  231. Ralley FE: The use of nitric oxide for managing catastrophic pulmonary vasoconstriction arising from protamine administration. Anesth Analg. 1999, 88: 505-507. 10.1097/00000539-199903000-00007.

    CAS  PubMed  Google Scholar 

  232. Williams TJ, Salamonsen RF, Snell G, Kaye D, Esmore DS: Preliminary experience with inhaled nitric oxide for acute pulmonary hypertension after heart transplantation. J Heart Lung Transplant. 1995, 14: 419-423.

    CAS  PubMed  Google Scholar 

  233. Molmenti EP, Ramsay M, Ramsay K, Lynch K, Tillmann Hein HA, Molmenti H, Levy M, Goldstein R, Ausloos K, East C, Fasola C, Jung G, Escobar J, Klintmalm G: Epoprostenol and nitric oxide therapy for severe pulmonary hypertension in liver transplantation. Transplant Proc. 2001, 33: 1332-10.1016/S0041-1345(00)02807-4.

    CAS  PubMed  Google Scholar 

  234. Snow DJ, Gray SJ, Ghosh S, Foubert L, Oduro A, Higenbottam TW, Wells FC, Latimer RD: Inhaled nitric oxide in patients with normal and increased pulmonary vascular resistance after cardiac surgery. Br J Anaesth. 1994, 72: 185-189. 10.1093/bja/72.2.185.

    CAS  PubMed  Google Scholar 

  235. Bender KA, Alexander JA, Enos JM, Skimming JW: Effects of inhaled nitric oxide in patients with hypoxemia and pulmonary hypertension after cardiac surgery. Am J Crit Care. 1997, 6: 127-131.

    CAS  PubMed  Google Scholar 

  236. Solina A, Papp D, Ginsberg S, Krause T, Grubb W, Scholz P, Pena LL, Cody R: A comparison of inhaled nitric oxide and milrinone for the treatment of pulmonary hypertension in adult cardiac surgery patients. J Cardiothorac Vasc Anesth. 2000, 14: 12-17. 10.1016/S1053-0770(00)90048-X.

    CAS  PubMed  Google Scholar 

  237. Solina AR, Ginsberg SH, Papp D, Pantin EJ, Denny J, Ghandivel I, Krause TJ: Response to nitric oxide during adult cardiac surgery. J Invest Surg. 2002, 15: 5-14. 10.1080/08941930252807732.

    PubMed  Google Scholar 

  238. Solina AR, Ginsberg SH, Papp D, Grubb WR, Scholz PM, Pantin EJ, Cody RP, Krause TJ: Dose response to nitric oxide in adult cardiac surgery patients. J Clin Anesth. 2001, 13: 281-286. 10.1016/S0952-8180(01)00270-7.

    CAS  PubMed  Google Scholar 

  239. Fattouch K, Sbraga F, Sampognaro R, Bianco G, Gucciardo M, Lavalle C, Vizza CD, Fedele F, Ruvolo G: Treatment of pulmonary hypertension in patients undergoing cardiac surgery with cardiopulmonary bypass: a randomized, prospective, double-blind study. J Cardiovasc Med (Hagerstown). 2006, 7: 119-123. 10.2459/01.JCM.0000203850.97890.fe.

    Google Scholar 

  240. Healy DG, Veerasingam D, McHale J, Luke D: Successful perioperative utilisation of inhaled nitric oxide in mitral valve surgery. J Cardiovasc Surg (Torino). 2006, 47: 217-220.

    CAS  Google Scholar 

  241. Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM: Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med. 1993, 328: 399-405. 10.1056/NEJM199302113280605.

    CAS  PubMed  Google Scholar 

  242. Fierobe L, Brunet F, Dhainaut JF, Monchi M, Belghith M, Mira JP, Dall'ava-Santucci J, Dinh-Xuan AT: Effect of inhaled nitric oxide on right ventricular function in adult respiratory distress syndrome. Am J Respir Crit Care Med. 1995, 151: 1414-1419.

    CAS  PubMed  Google Scholar 

  243. Romberg-Camps MJ, Korsten HH, Botman CJ, Bindels AJ, Roos AN: Right ventricular failure in acute respiratory distress syndrome. Neth J Med. 2000, 57: 94-97. 10.1016/S0300-2977(00)00052-8.

    CAS  PubMed  Google Scholar 

  244. Chiche JD, Canivet JL, Damas P, Joris J, Lamy M: Inhaled nitric oxide for hemodynamic support after postpneumonectomy ARDS. Intensive Care Med. 1995, 21: 675-678. 10.1007/BF01711547.

    CAS  PubMed  Google Scholar 

  245. Benzing A, Mols G, Beyer U, Geiger K: Large increase in cardiac output in a patient with ARDS and acute right heart failure during inhalation of nitric oxide. Acta Anaesthesiol Scand. 1997, 41: 643-646. 10.1111/j.1399-6576.1997.tb04758.x.

    CAS  PubMed  Google Scholar 

  246. Bigatello LM, Hurford WE, Kacmarek RM, Roberts JD, Zapol WM: Prolonged inhalation of low concentrations of nitric oxide in patients with severe adult respiratory distress syndrome: effects on pulmonary hemodynamics and oxygenation. Anesthesiology. 1994, 80: 761-770. 10.1097/00000542-199404000-00007.

    CAS  PubMed  Google Scholar 

  247. Hsu CW, Lee DL, Lin SL, Sun SF, Chang HW: The initial response to inhaled nitric oxide treatment for intensive care unit patients with acute respiratory distress syndrome. Respiration. 2008, 75: 288-295. 10.1159/000101478.

    CAS  PubMed  Google Scholar 

  248. Gerlach H, Keh D, Semmerow A, Busch T, Lewandowski K, Pappert DM, Rossaint R, Falke KJ: Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study. Am J Respir Crit Care Med. 2003, 167: 1008-1015. 10.1164/rccm.2108121.

    PubMed  Google Scholar 

  249. Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K, Hyers TM, Papadakos P: Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial: inhaled nitric oxide in ARDS study group. Crit Care Med. 1998, 26: 15-23. 10.1097/00003246-199801000-00011.

    CAS  PubMed  Google Scholar 

  250. Taylor RW, Zimmerman JL, Dellinger RP, Straube RC, Criner GJ, Davis K, Kelly KM, Smith TC, Small RJ: Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. JAMA. 2004, 291: 1603-1609. 10.1001/jama.291.13.1603.

    CAS  PubMed  Google Scholar 

  251. Brett SJ, Hansell DM, Evans TW: Clinical correlates in acute lung injury: response to inhaled nitric oxide. Chest. 1998, 114: 1397-1404. 10.1378/chest.114.5.1397.

    CAS  PubMed  Google Scholar 

  252. Manktelow C, Bigatello LM, Hess D, Hurford WE: Physiologic determinants of the response to inhaled nitric oxide in patients with acute respiratory distress syndrome. Anesthesiology. 1997, 87: 297-307. 10.1097/00000542-199708000-00017.

    CAS  PubMed  Google Scholar 

  253. Adhikari NK, Burns KE, Friedrich JO, Granton JT, Cook DJ, Meade MO: Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis. BMJ. 2007, 334: 779-10.1136/bmj.39139.716794.55.

    PubMed Central  PubMed  Google Scholar 

  254. Sokol J, Jacobs SE, Bohn D: Inhaled nitric oxide for acute hypoxic respiratory failure in children and adults: a meta-analysis. Anesth Analg. 2003, 97: 989-998. 10.1213/01.ANE.0000078819.48523.26.

    PubMed  Google Scholar 

  255. Troncy E, Collet JP, Shapiro S, Guimond JG, Blair L, Ducruet T, Francoeur M, Charbonneau M, Blaise G: Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study. Am J Respir Crit Care Med. 1998, 157: 1483-1488.

    CAS  PubMed  Google Scholar 

  256. Michael JR, Barton RG, Saffle JR, Mone M, Markewitz BA, Hillier K, Elstad MR, Campbell EJ, Troyer BE, Whatley RE, Liou TG, Samuelson WM, Carveth HJ, Hinson DM, Morris SE, Davis BL, Day RW: Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS. Am J Respir Crit Care Med. 1998, 157: 1372-1380.

    CAS  PubMed  Google Scholar 

  257. Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C: Inhalation of nitric oxide in acute lung injury: results of a European multicentre study: the European Study Group of Inhaled Nitric Oxide. Intensive Care Med. 1999, 25: 911-919. 10.1007/s001340050982.

    CAS  PubMed  Google Scholar 

  258. Vater Y, Martay K, Dembo G, Bowdle TA, Weinbroum AA: Intraoperative epoprostenol and nitric oxide for severe pulmonary hypertension during orthotopic liver transplantation: a case report and review of the literature. Med Sci Monit. 2006, 12: CS115-CS118.

    PubMed  Google Scholar 

  259. Flondor M, Merkel M, Hofstetter C, Irlbeck M, Frey L, Zwissler B: The effect of inhaled nitric oxide and inhaled iloprost on hypoxaemia in a patient with pulmonary hypertension after pulmonary thrombarterectomy. Anaesthesia. 2006, 61: 1200-1203. 10.1111/j.1365-2044.2006.04861.x.

    CAS  PubMed  Google Scholar 

  260. Lepore JJ, Maroo A, Bigatello LM, Dec GW, Zapol WM, Bloch KD, Semigran MJ: Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary hypertension: combined administration with inhaled nitric oxide. Chest. 2005, 127: 1647-1653. 10.1378/chest.127.5.1647.

    CAS  PubMed  Google Scholar 

  261. Lepore JJ, Maroo A, Pereira NL, Ginns LC, Dec GW, Zapol WM, Bloch KD, Semigran MJ: Effect of sildenafil on the acute pulmonary vasodilator response to inhaled nitric oxide in adults with primary pulmonary hypertension. Am J Cardiol. 2002, 90: 677-680. 10.1016/S0002-9149(02)02586-9.

    CAS  PubMed  Google Scholar 

  262. Lavoie A, Hall JB, Olson DM, Wylam ME: Life-threatening effects of discontinuing inhaled nitric oxide in severe respiratory failure. Am J Respir Crit Care Med. 1996, 153: 1985-1987.

    CAS  PubMed  Google Scholar 

  263. Atz AM, Adatia I, Wessel DL: Rebound pulmonary hypertension after inhalation of nitric oxide. Ann Thorac Surg. 1996, 62: 1759-1764. 10.1016/S0003-4975(96)00542-5.

    CAS  PubMed  Google Scholar 

  264. Christenson J, Lavoie A, O'Connor M, Bhorade S, Pohlman A, Hall JB: The incidence and pathogenesis of cardiopulmonary deterioration after abrupt withdrawal of inhaled nitric oxide. Am J Respir Crit Care Med. 2000, 161: 1443-1449.

    CAS  PubMed  Google Scholar 

  265. Giacomini M, Borotto E, Bosotti L, Denkewitz T, Reali-Forster C, Carlucci P, Centanni S, Mantero A, Iapichino G: Vardenafil and weaning from inhaled nitric oxide: effect on pulmonary hypertension in ARDS. Anaesth Intensive Care. 2007, 35: 91-93.

    CAS  PubMed  Google Scholar 

  266. Trachte AL, Lobato EB, Urdaneta F, Hess PJ, Klodell CT, Martin TD, Staples ED, Beaver TM: Oral sildenafil reduces pulmonary hypertension after cardiac surgery. Ann Thorac Surg. 2005, 79: 194-197. 10.1016/j.athoracsur.2004.06.086. discussion 194-197

    PubMed  Google Scholar 

  267. Atz AM, Wessel DL: Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology. 1999, 91: 307-310. 10.1097/00000542-199907000-00041.

    CAS  PubMed  Google Scholar 

  268. Namachivayam P, Theilen U, Butt WW, Cooper SM, Penny DJ, Shekerdemian LS: Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med. 2006, 174: 1042-1047. 10.1164/rccm.200605-694OC.

    CAS  PubMed  Google Scholar 

  269. Klodell CT, Morey TE, Lobato EB, Aranda JM, Staples ED, Schofield RS, Hess PJ, Martin TD, Beaver TM: Effect of sildenafil on pulmonary artery pressure, systemic pressure, and nitric oxide utilization in patients with left ventricular assist devices. Ann Thorac Surg. 2007, 83: 68-71. 10.1016/j.athoracsur.2006.08.051. discussion 71

    PubMed  Google Scholar 

  270. Mychaskiw G, Sachdev V, Heath BJ: Sildenafil (Viagra) facilitates weaning of inhaled nitric oxide following placement of a biventricular-assist device. J Clin Anesth. 2001, 13: 218-220. 10.1016/S0952-8180(01)00252-5.

    CAS  PubMed  Google Scholar 

  271. Moncada S, Gryglewski RJ, Bunting S, Vane JR: A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins. 1976, 12: 715-737. 10.1016/0090-6980(76)90048-4.

    CAS  PubMed  Google Scholar 

  272. Clapp LH, Finney P, Turcato S, Tran S, Rubin LJ, Tinker A: Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery. Am J Respir Cell Mol Biol. 2002, 26: 194-201.

    CAS  PubMed  Google Scholar 

  273. Rubin LJ, Mendoza J, Hood M, McGoon M, Barst R, Williams WB, Diehl JH, Crow J, Long W: Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol): results of a randomized trial. Ann Intern Med. 1990, 112: 485-491.

    CAS  PubMed  Google Scholar 

  274. Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH, Koerner SK, Langleben D, Keller CA, Murali S, Uretsky BF, Clayton LM, Jobsis MM, Blackburn DS, Shortino D, Crow JW: A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension: the Primary Pulmonary Hypertension Study Group. N Engl J Med. 1996, 334: 296-302. 10.1056/NEJM199602013340504.

    CAS  PubMed  Google Scholar 

  275. Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, Nikkho S, Speich R, Hoeper MM, Behr J, Winkler J, Sitbon O, Popov W, Ghofrani HA, Manes A, Kiely DG, Ewert R, Meyer A, Corris PA, Delcroix M, Gomez-Sanchez M, Siedentop H, Seeger W: Inhaled iloprost for severe pulmonary hypertension. N Engl J Med. 2002, 347: 322-329. 10.1056/NEJMoa020204.

    CAS  PubMed  Google Scholar 

  276. Hoeper MM, Schwarze M, Ehlerding S, Adler-Schuermeyer A, Spiekerkoetter E, Niedermeyer J, Hamm M, Fabel H: Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med. 2000, 342: 1866-1870. 10.1056/NEJM200006223422503.

    CAS  PubMed  Google Scholar 

  277. Hoeper MM, Olschewski H, Ghofrani HA, Wilkens H, Winkler J, Borst MM, Niedermeyer J, Fabel H, Seeger W: A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension: German PPH study group. J Am Coll Cardiol. 2000, 35: 176-182. 10.1016/S0735-1097(99)00494-5.

    CAS  PubMed  Google Scholar 

  278. Olschewski H, Ghofrani HA, Walmrath D, Temmesfeld-Wollbruck B, Grimminger F, Seeger W: Recovery from circulatory shock in severe primary pulmonary hypertension (PPH) with aerosolization of iloprost. Intensive Care Med. 1998, 24: 631-634. 10.1007/s001340050628.

    CAS  PubMed  Google Scholar 

  279. Sitbon O, Humbert M, Nunes H, Parent F, Garcia G, Herve P, Rainisio M, Simonneau G: Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol. 2002, 40: 780-788. 10.1016/S0735-1097(02)02012-0.

    CAS  PubMed  Google Scholar 

  280. Kieler-Jensen N, Milocco I, Ricksten SE: Pulmonary vasodilation after heart transplantation: a comparison among prostacyclin, sodium nitroprusside, and nitroglycerin on right ventricular function and pulmonary selectivity. J Heart Lung Transplant. 1993, 12: 179-184.

    CAS  PubMed  Google Scholar 

  281. D'Ambra MN, LaRaia PJ, Philbin DM, Watkins WD, Hilgenberg AD, Buckley MJ: Prostaglandin E1: a new therapy for refractory right heart failure and pulmonary hypertension after mitral valve replacement. J Thorac Cardiovasc Surg. 1985, 89: 567-572.

    PubMed  Google Scholar 

  282. Vincent JL, Carlier E, Pinsky MR, Goldstein J, Naeije R, Lejeune P, Brimioulle S, Leclerc JL, Kahn RJ, Primo G: Prostaglandin E1 infusion for right ventricular failure after cardiac transplantation. J Thorac Cardiovasc Surg. 1992, 103: 33-39.

    CAS  PubMed  Google Scholar 

  283. Radovancevic B, Vrtovec B, Thomas CD, Croitoru M, Myers TJ, Radovancevic R, Khan T, Massin EK, Frazier OH: Nitric oxide versus prostaglandin E1 for reduction of pulmonary hypertension in heart transplant candidates. J Heart Lung Transplant. 2005, 24: 690-695. 10.1016/j.healun.2004.04.016.

    PubMed  Google Scholar 

  284. Schmid ER, Burki C, Engel MH, Schmidlin D, Tornic M, Seifert B: Inhaled nitric oxide versus intravenous vasodilators in severe pulmonary hypertension after cardiac surgery. Anesth Analg. 1999, 89: 1108-1115. 10.1097/00000539-199911000-00007.

    CAS  PubMed  Google Scholar 

  285. Elliott CG, Palevsky HI: Treatment with epoprostenol of pulmonary arterial hypertension following mitral valve replacement for mitral stenosis. Thorax. 2004, 59: 536-537. 10.1136/thx.2003.008193.

    PubMed Central  CAS  PubMed  Google Scholar 

  286. Haraldsson A, Kieler-Jensen N, Ricksten SE: Inhaled prostacyclin for treatment of pulmonary hypertension after cardiac surgery or heart transplantation: a pharmacodynamic study. J Cardiothorac Vasc Anesth. 1996, 10: 864-868. 10.1016/S1053-0770(96)80047-4.

    CAS  PubMed  Google Scholar 

  287. Hache M, Denault AY, Belisle S, Couture P, Babin D, Tetrault F, Guimond JG: Inhaled prostacyclin (PGI2) is an effective addition to the treatment of pulmonary hypertension and hypoxia in the operating room and intensive care unit. Can J Anaesth. 2001, 48: 924-929. 10.1007/BF03017361.

    CAS  PubMed  Google Scholar 

  288. De Wet CJ, Affleck DG, Jacobsohn E, Avidan MS, Tymkew H, Hill LL, Zanaboni PB, Moazami N, Smith JR: Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg. 2004, 127: 1058-1067. 10.1016/j.jtcvs.2003.11.035.

    CAS  PubMed  Google Scholar 

  289. Schroeder RA, Wood GL, Plotkin JS, Kuo PC: Intraoperative use of inhaled PGI(2) for acute pulmonary hypertension and right ventricular failure. Anesth Analg. 2000, 91: 291-295. 10.1097/00000539-200008000-00008.

    CAS  PubMed  Google Scholar 

  290. Lowson SM, Doctor A, Walsh BK, Doorley PA: Inhaled prostacyclin for the treatment of pulmonary hypertension after cardiac surgery. Crit Care Med. 2002, 30: 2762-2764. 10.1097/00003246-200212000-00023.

    CAS  PubMed  Google Scholar 

  291. Kramm T, Eberle B, Guth S, Mayer E: Inhaled iloprost to control residual pulmonary hypertension following pulmonary endarterectomy. Eur J Cardiothorac Surg. 2005, 28: 882-888. 10.1016/j.ejcts.2005.09.007.

    PubMed  Google Scholar 

  292. Rex S, Schaelte G, Metzelder S, Flier S, de Waal EE, Autschbach R, Rossaint R, Buhre W: Inhaled iloprost to control pulmonary artery hypertension in patients undergoing mitral valve surgery: a prospective, randomized-controlled trial. Acta Anaesthesiol Scand. 2008, 52: 65-72. 10.1111/j.1399-6576.2007.01476.x.

    CAS  PubMed  Google Scholar 

  293. Yurtseven N, Karaca P, Uysal G, Ozkul V, Cimen S, Tuygun AK, Yuksek A, Canik S: A comparison of the acute hemodynamic effects of inhaled nitroglycerin and iloprost in patients with pulmonary hypertension undergoing mitral valve surgery. Ann Thorac Cardiovasc Surg. 2006, 12: 319-323.

    PubMed  Google Scholar 

  294. Baysal A, Bilsel S, Bulbul OG, Kayacioglu I, Idiz M, Yekeler I: Comparison of the usage of intravenous iloprost and nitroglycerin for pulmonary hypertension during valvular heart surgery. Heart Surg Forum. 2006, 9: E536-E542. 10.1532/HSF98.20051161.

    PubMed  Google Scholar 

  295. Tissieres P, Nicod L, Barazzone-Argiroffo C, Rimensberger PC, Beghetti M: Aerosolized iloprost as a bridge to lung transplantation in a patient with cystic fibrosis and pulmonary hypertension. Ann Thorac Surg. 2004, 78: e48-50. 10.1016/j.athoracsur.2003.12.096.

    PubMed  Google Scholar 

  296. Sablotzki A, Hentschel T, Gruenig E, Schubert S, Friedrich I, Muhling J, Dehne MG, Czeslick E: Hemodynamic effects of inhaled aerosolized iloprost and inhaled nitric oxide in heart transplant candidates with elevated pulmonary vascular resistance. Eur J Cardiothorac Surg. 2002, 22: 746-752. 10.1016/S1010-7940(02)00488-8.

    PubMed  Google Scholar 

  297. Theodoraki K, Rellia P, Thanopoulos A, Tsourelis L, Zarkalis D, Sfyrakis P, Antoniou T: Inhaled iloprost controls pulmonary hypertension after cardiopulmonary bypass. Can J Anaesth. 2002, 49: 963-967. 10.1007/BF03016884.

    PubMed  Google Scholar 

  298. Winterhalter M, Simon A, Fischer S, Rahe-Meyer N, Chamtzidou N, Hecker H, Zuk J, Piepenbrock S, Struber M: Comparison of inhaled iloprost and nitric oxide in patients with pulmonary hypertension during weaning from cardiopulmonary bypass in cardiac surgery: a prospective randomized trial. J Cardiothorac Vasc Anesth. 2008, 22: 406-413. 10.1053/j.jvca.2007.10.015.

    CAS  PubMed  Google Scholar 

  299. Webb SA, Stott S, van Heerden PV: The use of inhaled aerosolized prostacyclin (IAP) in the treatment of pulmonary hypertension secondary to pulmonary embolism. Intensive Care Med. 1996, 22: 353-355. 10.1007/BF01700458.

    CAS  PubMed  Google Scholar 

  300. Haraldsson A, Kieler-Jensen N, Wadenvik H, Ricksten SE: Inhaled prostacyclin and platelet function after cardiac surgery and cardiopulmonary bypass. Intensive Care Med. 2000, 26: 188-194. 10.1007/s001340050044.

    CAS  PubMed  Google Scholar 

  301. Radermacher P, Santak B, Wust HJ, Tarnow J, Falke KJ: Prostacyclin and right ventricular function in patients with pulmonary hypertension associated with ARDS. Intensive Care Med. 1990, 16: 227-232. 10.1007/BF01705156.

    CAS  PubMed  Google Scholar 

  302. Zwissler B, Kemming G, Habler O, Kleen M, Merkel M, Haller M, Briegel J, Welte M, Peter K: Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome. Am J Respir Crit Care Med. 1996, 154: 1671-1677.

    CAS  PubMed  Google Scholar 

  303. van Heerden PV, Barden A, Michalopoulos N, Bulsara MK, Roberts BL: Dose-response to inhaled aerosolized prostacyclin for hypoxemia due to ARDS. Chest. 2000, 117: 819-827. 10.1378/chest.117.3.819.

    CAS  PubMed  Google Scholar 

  304. Walmrath D, Schneider T, Pilch J, Grimminger F, Seeger W: Aerosolised prostacyclin in adult respiratory distress syndrome. Lancet. 1993, 342: 961-962. 10.1016/0140-6736(93)92004-D.

    CAS  PubMed  Google Scholar 

  305. Van Heerden PV, Webb SA, Hee G, Corkeron M, Thompson WR: Inhaled aerosolized prostacyclin as a selective pulmonary vasodilator for the treatment of severe hypoxaemia. Anaesth Intensive Care. 1996, 24: 87-90.

    CAS  PubMed  Google Scholar 

  306. Meyer J, Theilmeier G, Van Aken H, Bone HG, Busse H, Waurick R, Hinder F, Booke M: Inhaled prostaglandin E1 for treatment of acute lung injury in severe multiple organ failure. Anesth Analg. 1998, 86: 753-758. 10.1097/00000539-199804000-00015.

    CAS  PubMed  Google Scholar 

  307. Kuhlen R, Walbert E, Frankel P, Thaden S, Behrendt W, Rossaint R: Combination of inhaled nitric oxide and intravenous prostacyclin for successful treatment of severe pulmonary hypertension in a patient with acute respiratory distress syndrome. Intensive Care Med. 1999, 25: 752-754. 10.1007/s001340050941.

    CAS  PubMed  Google Scholar 

  308. Prasad S, Wilkinson J, Gatzoulis MA: Sildenafil in primary pulmonary hypertension. N Engl J Med. 2000, 343: 1342-10.1056/NEJM200011023431814.

    CAS  PubMed  Google Scholar 

  309. Preston IR, Klinger JR, Houtches J, Nelson D, Farber HW, Hill NS: Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension. Respir Med. 2005, 99: 1501-1510. 10.1016/j.rmed.2005.03.026.

    PubMed  Google Scholar 

  310. Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S: Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation. 2002, 105: 2398-2403. 10.1161/01.CIR.0000016641.12984.DC.

    CAS  PubMed  Google Scholar 

  311. Archer SL, Michelakis ED: Phosphodiesterase type 5 inhibitors for pulmonary arterial hypertension. N Engl J Med. 2009, 361: 1864-1871. 10.1056/NEJMct0904473.

    CAS  PubMed  Google Scholar 

  312. Giaid A, Saleh D: Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med. 1995, 333: 214-221. 10.1056/NEJM199507273330403.

    CAS  PubMed  Google Scholar 

  313. Black SM, Sanchez LS, Mata-Greenwood E, Bekker JM, Steinhorn RH, Fineman JR: sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2001, 281: L1051-L1057.

    CAS  PubMed  Google Scholar 

  314. Wharton J, Strange JW, Moller GM, Growcott EJ, Ren X, Franklyn AP, Phillips SC, Wilkins MR: Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells. Am J Respir Crit Care Med. 2005, 172: 105-113. 10.1164/rccm.200411-1587OC.

    PubMed  Google Scholar 

  315. Nagendran J, Archer SL, Soliman D, Gurtu V, Moudgil R, Haromy A, St Aubin C, Webster L, Rebeyka IM, Ross DB, Light PE, Dyck JR, Michelakis ED: Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007, 116: 238-248. 10.1161/CIRCULATIONAHA.106.655266.

    CAS  PubMed  Google Scholar 

  316. Packer M: Vasodilator therapy for primary pulmonary hypertension: limitations and hazards. Ann Intern Med. 1985, 103: 258-270.

    CAS  PubMed  Google Scholar 

  317. De Santo LS, Mastroianni C, Romano G, Amarelli C, Marra C, Maiello C, Galdieri N, Della Corte A, Cotrufo M, Caianiello G: Role of sildenafil in acute posttransplant right ventricular dysfunction: successful experience in 13 consecutive patients. Transplant Proc. 2008, 40: 2015-2018. 10.1016/j.transproceed.2008.05.055.

    CAS  PubMed  Google Scholar 

  318. Shim JK, Choi YS, Oh YJ, Kim DH, Hong YW, Kwak YL: Effect of oral sildenafil citrate on intraoperative hemodynamics in patients with pulmonary hypertension undergoing valvular heart surgery. J Thorac Cardiovasc Surg. 2006, 132: 1420-1425. 10.1016/j.jtcvs.2006.08.035.

    CAS  PubMed  Google Scholar 

  319. Madden BP, Sheth A, Ho TB, Park JE, Kanagasabay RR: Potential role for sildenafil in the management of perioperative pulmonary hypertension and right ventricular dysfunction after cardiac surgery. Br J Anaesth. 2004, 93: 155-156. 10.1093/bja/aeh571.

    CAS  PubMed  Google Scholar 

  320. Fung E, Fiscus RR, Yim AP, Angelini GD, Arifi AA: The potential use of type-5 phosphodiesterase inhibitors in coronary artery bypass graft surgery. Chest. 2005, 128: 3065-3073. 10.1378/chest.128.4.3065.

    CAS  PubMed  Google Scholar 

  321. Aubin MC, Laurendeau S, Mommerot A, Lamarche Y, Denault A, Carrier M, Perrault LP: Differential effects of inhaled and intravenous sildenafil in the prevention of the pulmonary endothelial dysfunction due to cardiopulmonary bypass. J Cardiovasc Pharmacol. 2008, 51: 11-17. 10.1097/FJC.0b013e3181598279.

    CAS  PubMed  Google Scholar 

  322. Ghofrani HA, Wiedemann R, Rose F, Schermuly RT, Olschewski H, Weissmann N, Gunther A, Walmrath D, Seeger W, Grimminger F: Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet. 2002, 360: 895-900. 10.1016/S0140-6736(02)11024-5.

    CAS  PubMed  Google Scholar 

  323. Ng J, Finney SJ, Shulman R, Bellingan GJ, Singer M, Glynne PA: Treatment of pulmonary hypertension in the general adult intensive care unit: a role for oral sildenafil?. Br J Anaesth. 2005, 94: 774-777. 10.1093/bja/aei114.

    CAS  PubMed  Google Scholar 

  324. Cornet AD, Hofstra JJ, Swart EL, Girbes AR, Juffermans NP: Sildenafil attenuates pulmonary arterial pressure but does not improve oxygenation during ARDS. Intensive Care Med. 2010, 36: 758-764. 10.1007/s00134-010-1754-3.

    PubMed Central  CAS  PubMed  Google Scholar 

  325. Botha P, Parry G, Dark JH, Macgowan GA: Acute hemodynamic effects of intravenous sildenafil citrate in congestive heart failure: comparison of phosphodiesterase type-3 and -5 inhibition. J Heart Lung Transplant. 2009, 28: 676-682. 10.1016/j.healun.2009.04.013.

    PubMed  Google Scholar 

  326. Moudgil R, Michelakis ED, Archer SL: Hypoxic pulmonary vasoconstriction. J Appl Physiol. 2005, 98: 390-403. 10.1152/japplphysiol.00733.2004.

    CAS  PubMed  Google Scholar 

  327. Lejeune P, Brimioulle S, Leeman M, Hallemans R, Melot C, Naeije R: Enhancement of hypoxic pulmonary vasoconstriction by metabolic acidosis in dogs. Anesthesiology. 1990, 73: 256-264. 10.1097/00000542-199008000-00012.

    CAS  PubMed  Google Scholar 

  328. Balanos GM, Talbot NP, Dorrington KL, Robbins PA: Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography. J Appl Physiol. 2003, 94: 1543-1551.

    PubMed  Google Scholar 

  329. Mekontso Dessap A, Charron C, Devaquet J, Aboab J, Jardin F, Brochard L, Vieillard-Baron A: Impact of acute hypercapnia and augmented positive end-expiratory pressure on right ventricle function in severe acute respiratory distress syndrome. Intensive Care Med. 2009, 35: 1850-1858. 10.1007/s00134-009-1569-2.

    PubMed Central  PubMed  Google Scholar 

  330. Puybasset L, Stewart T, Rouby JJ, Cluzel P, Mourgeon E, Belin MF, Arthaud M, Landault C, Viars P: Inhaled nitric oxide reverses the increase in pulmonary vascular resistance induced by permissive hypercapnia in patients with acute respiratory distress syndrome. Anesthesiology. 1994, 80: 1254-1267. 10.1097/00000542-199406000-00013.

    CAS  PubMed  Google Scholar 

  331. Biondi JW, Schulman DS, Matthay RA: Effects of mechanical ventilation on right and left ventricular function. Clin Chest Med. 1988, 9: 55-71.

    CAS  PubMed  Google Scholar 

  332. Jardin F, Gueret P, Dubourg O, Farcot JC, Margairaz A, Bourdarias JP: Two-dimensional echocardiographic evaluation of right ventricular size and contractility in acute respiratory failure. Crit Care Med. 1985, 13: 952-956. 10.1097/00003246-198511000-00035.

    CAS  PubMed  Google Scholar 

  333. Jardin F, Vieillard-Baron A: Is there a safe plateau pressure in ARDS? The right heart only knows. Intensive Care Med. 2007, 33: 444-447. 10.1007/s00134-007-0552-z.

    PubMed  Google Scholar 

  334. Vieillard-Baron A, Rabiller A, Chergui K, Peyrouset O, Page B, Beauchet A, Jardin F: Prone position improves mechanics and alveolar ventilation in acute respiratory distress syndrome. Intensive Care Med. 2005, 31: 220-226. 10.1007/s00134-004-2478-z.

    PubMed  Google Scholar 

  335. David M, von Bardeleben RS, Weiler N, Markstaller K, Scholz A, Karmrodt J, Eberle B: Cardiac function and haemodynamics during transition to high-frequency oscillatory ventilation. Eur J Anaesthesiol. 2004, 21: 944-952.

    CAS  PubMed  Google Scholar 

  336. Gernoth C, Wagner G, Pelosi P, Luecke T: Respiratory and haemodynamic changes during decremental open lung positive end-expiratory pressure titration in patients with acute respiratory distress syndrome. Crit Care. 2009, 13: R59-10.1186/cc7786.

    PubMed Central  PubMed  Google Scholar 

  337. Shekerdemian LS, Shore DF, Lincoln C, Bush A, Redington AN: Negative-pressure ventilation improves cardiac output after right heart surgery. Circulation. 1996, 94: II49-II55.

    CAS  PubMed  Google Scholar 

  338. Shekerdemian LS, Bush A, Shore DF, Lincoln C, Redington AN: Cardiopulmonary interactions after Fontan operations: augmentation of cardiac output using negative pressure ventilation. Circulation. 1997, 96: 3934-3942.

    CAS  PubMed  Google Scholar 

  339. Giesler GM, Gomez JS, Letsou G, Vooletich M, Smalling RW: Initial report of percutaneous right ventricular assist for right ventricular shock secondary to right ventricular infarction. Catheter Cardiovasc Interv. 2006, 68: 263-266. 10.1002/ccd.20846.

    PubMed  Google Scholar 

  340. Fonger JD, Borkon AM, Baumgartner WA, Achuff SC, Augustine S, Reitz BA: Acute right ventricular failure following heart transplantation: improvement with prostaglandin E1 and right ventricular assist. J Heart Transplant. 1986, 5: 317-321.

    CAS  PubMed  Google Scholar 

  341. Nagarsheth NP, Pinney S, Bassily-Marcus A, Anyanwu A, Friedman L, Beilin Y: Successful placement of a right ventricular assist device for treatment of a presumed amniotic fluid embolism. Anesth Analg. 2008, 107: 962-964. 10.1213/ane.0b013e31817f10e8.

    PubMed  Google Scholar 

  342. Berman M, Tsui S, Vuylsteke A, Klein A, Jenkins DP: Life-threatening right ventricular failure in pulmonary hypertension: RVAD or ECMO?. J Heart Lung Transplant. 2008, 27: 1188-1189. 10.1016/j.healun.2008.07.017.

    PubMed  Google Scholar 

  343. Keogh AM, Mayer E, Benza RL, Corris P, Dartevelle PG, Frost AE, Kim NH, Lang IM, Pepke-Zaba J, Sandoval J: Interventional and surgical modalities of treatment in pulmonary hypertension. J Am Coll Cardiol. 2009, 54: S67-S77. 10.1016/j.jacc.2009.04.016.

    PubMed  Google Scholar 

  344. Strueber M, Hoeper MM, Fischer S, Cypel M, Warnecke G, Gottlieb J, Pierre A, Welte T, Haverich A, Simon AR, Keshavjee S: Bridge to thoracic organ transplantation in patients with pulmonary arterial hypertension using a pumpless lung assist device. Am J Transplant. 2009, 9: 853-857. 10.1111/j.1600-6143.2009.02549.x.

    CAS  PubMed  Google Scholar 

  345. Felton TW, McCormick BA, Finfer SR, Fisher MM: Life-threatening pulmonary hypertension and right ventricular failure complicating calcium and phosphate replacement in the intensive care unit. Anaesthesia. 2006, 61: 49-53. 10.1111/j.1365-2044.2005.04381.x.

    CAS  PubMed  Google Scholar 

  346. Satoh H, Masuda Y, Izuta S, Yaku H, Obara H: Pregnant patient with primary pulmonary hypertension: general anesthesia and extracorporeal membrane oxygenation support for termination of pregnancy. Anesthesiology. 2002, 97: 1638-1640. 10.1097/00000542-200212000-00045.

    PubMed  Google Scholar 

  347. Chan CY, Chen YS, Ko WJ, Wang SS, Chiu IS, Lee YC, Chu SH: Extracorporeal membrane oxygenation support for single lung transplantation in a patient with primary pulmonary hypertension. J Heart Lung Transplant. 1998, 17: 325-327.

    CAS  PubMed  Google Scholar 

  348. Jones RL, St Cyr JA, Tornabene SP, Lauber B, Harken AH: Reversible pulmonary hypertension secondary to mitral valvular disease as an indication for extracorporeal membrane oxygenation. J Cardiothorac Vasc Anesth. 1991, 5: 494-497. 10.1016/1053-0770(91)90126-E.

    CAS  PubMed  Google Scholar 

  349. Gregoric ID, Chandra D, Myers TJ, Scheinin SA, Loyalka P, Kar B: Extracorporeal membrane oxygenation as a bridge to emergency heart-lung transplantation in a patient with idiopathic pulmonary arterial hypertension. J Heart Lung Transplant. 2008, 27: 466-468. 10.1016/j.healun.2008.01.016.

    PubMed  Google Scholar 

  350. Hsu HH, Ko WJ, Chen JS, Lin CH, Kuo SW, Huang SC, Lee YC: Extracorporeal membrane oxygenation in pulmonary crisis and primary graft dysfunction. J Heart Lung Transplant. 2008, 27: 233-237. 10.1016/j.healun.2007.11.570.

    PubMed  Google Scholar 

  351. Berman M, Tsui S, Vuylsteke A, Snell A, Colah S, Latimer R, Hall R, Arrowsmith JE, Kneeshaw J, Klein AA, Jenkins DP: Successful extracorporeal membrane oxygenation support after pulmonary thromboendarterectomy. Ann Thorac Surg. 2008, 86: 1261-1267. 10.1016/j.athoracsur.2008.06.037.

    PubMed  Google Scholar 

  352. Deehring R, Kiss AB, Garrett A, Hillier AG: Extracorporeal membrane oxygenation as a bridge to surgical embolectomy in acute fulminant pulmonary embolism. Am J Emerg Med. 2006, 24: 879-880. 10.1016/j.ajem.2006.03.009.

    PubMed  Google Scholar 

  353. Haller I, Kofler A, Lederer W, Chemelli A, Wiedermann FJ: Acute pulmonary artery embolism during transcatheter embolization: successful resuscitation with veno-arterial extracorporeal membrane oxygenation. Anesth Analg. 2008, 107: 945-947. 10.1213/ane.0b013e31817f91d8.

    PubMed  Google Scholar 

  354. Szocik J, Rudich S, Csete M: ECMO resuscitation after massive pulmonary embolism during liver transplantation. Anesthesiology. 2002, 97: 763-764. 10.1097/00000542-200209000-00059.

    PubMed  Google Scholar 

  355. Arlt M, Philipp A, Iesalnieks I, Kobuch R, Graf BM: Successful use of a new hand-held ECMO system in cardiopulmonary failure and bleeding shock after thrombolysis in massive post-partal pulmonary embolism. Perfusion. 2009, 24: 49-50. 10.1177/0267659109106295.

    CAS  PubMed  Google Scholar 

  356. Gold JP, Shemin RJ, DiSesa VJ, Cohn L, Collins JJ: Balloon pump support of the failing right heart. Clin Cardiol. 1985, 8: 599-602. 10.1002/clc.4960081110.

    CAS  PubMed  Google Scholar 

  357. Arafa OE, Geiran OR, Andersen K, Fosse E, Simonsen S, Svennevig JL: Intraaortic balloon pumping for predominantly right ventricular failure after heart transplantation. Ann Thorac Surg. 2000, 70: 1587-1593. 10.1016/S0003-4975(00)01864-6.

    CAS  PubMed  Google Scholar 

  358. Darrah WC, Sharpe MD, Guiraudon GM, Neal A: Intraaortic balloon counterpulsation improves right ventricular failure resulting from pressure overload. Ann Thorac Surg. 1997, 64: 1718-1723. 10.1016/S0003-4975(97)01102-8. discussion 1723-1714

    CAS  PubMed  Google Scholar 

  359. Rothman A, Sklansky MS, Lucas VW, Kashani IA, Shaughnessy RD, Channick RN, Auger WR, Fedullo PF, Smith CM, Kriett JM, Jamieson SW: Atrial septostomy as a bridge to lung transplantation in patients with severe pulmonary hypertension. Am J Cardiol. 1999, 84: 682-686. 10.1016/S0002-9149(99)00416-6.

    CAS  PubMed  Google Scholar 

  360. Rich S, Dodin E, McLaughlin VV: Usefulness of atrial septostomy as a treatment for primary pulmonary hypertension and guidelines for its application. Am J Cardiol. 1997, 80: 369-371. 10.1016/S0002-9149(97)00370-6.

    CAS  PubMed  Google Scholar 

  361. Druml W, Steltzer H, Waldhausl W, Lenz K, Hammerle A, Vierhapper H, Gasic S, Wagner OF: Endothelin-1 in adult respiratory distress syndrome. Am Rev Respir Dis. 1993, 148: 1169-1173.

    CAS  PubMed  Google Scholar 

  362. Lambermont B, Ghuysen A, Kolh P, Tchana-Sato V, Segers P, Gerard P, Morimont P, Magis D, Dogne JM, Masereel B, D'Orio V: Effects of endotoxic shock on right ventricular systolic function and mechanical efficiency. Cardiovasc Res. 2003, 59: 412-418. 10.1016/S0008-6363(03)00368-7.

    CAS  PubMed  Google Scholar 

  363. Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet JF, Eisner MD, Matthay MA: Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med. 2002, 346: 1281-1286. 10.1056/NEJMoa012835.

    PubMed  Google Scholar 

  364. Marshall BE, Marshall C, Frasch F, Hanson CW: Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 1. Physiologic concepts. Intensive Care Med. 1994, 20: 291-297. 10.1007/BF01708968.

    CAS  PubMed  Google Scholar 

  365. Tomashefski JF, Davies P, Boggis C, Greene R, Zapol WM, Reid LM: The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol. 1983, 112: 112-126.

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

SJB is grateful for the support of the UK NIHR Biomedical Research Centre Scheme.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Laura C Price.

Additional information

Competing interests

LCP has received honoraria from Encysive Pharmaceuticals. SJW has received honoraria from Actelion Pharmaceuticals. SJB has received support for clinical trials from Pfizer, Astra Zeneca, and Baxter Healthcare.

Authors' contributions

LCP and SJB conceived of the review and participated in its design. LCP and SJW carried out the literature search and drafted the initial manuscript. All authors read and approved the final manuscript.

Laura C Price, Stephen J Wort contributed equally to this work.

Electronic supplementary material

13054_2010_8659_MOESM1_ESM.DOC

Additional file 1: Population, Intervention, Comparison and Outcome (PICO) evidence tables. This file contains structured detail for all studies included in the systematic review. According to GRADE method guidelines, a series of eight study questions was devised to approach the questions posed by the systematic literature review. The PICO table then describes each study according to the study type, the population studied, the intervention applied, the nature of the comparison or control group, and the studied outcome of interest appropriate to the study question. The final column grades the evidence according to the GRADE evidence level as very low-, low-, moderate-, or high-level evidence [80, 81]. (DOC 785 KB)

Authors’ original submitted files for images

Rights and permissions

Reprints and permissions

About this article

Cite this article

Price, L.C., Wort, S.J., Finney, S.J. et al. Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review. Crit Care 14, R169 (2010). https://doi.org/10.1186/cc9264

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/cc9264

Keywords