ArticleLiterature Review

Strategies on management of pulmonary hypertension

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Pulmonary hypertension (PH) is the consequence of either acute or chronic diseases resulting in the loss of the low pressure-high flow characteristics of pulmonary circulation. In 1977, Zapol and Snider demonstrated that PH is a physiological hallmark of ARDS as shown by the occurrence of a mean pulmonary arterial pressure (mPAP) > 25 mmHg in 58% of patients with severe ARF in the early phase [1]. In over 100 patients with ARDS, studied from 1–30 days after onset of symptoms, Zapol et al. observed mPAP to be around 22–28 mmHg in absence of severe hypoxemia, and in the range of 28–35 mmHg or more in presence of severe hypoxemia [2].

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Pulmonary embolism (PE) is a major international health problem, with an annual estimated incidence of over 100,000 cases in France, 65,000 cases among hospitalized patients in England and Wales, and at least 60,000 new cases per year in Italy. The diagnosis is often untreated, difficult to obtain and is frequently missed [1]. Mortality in the untreated is approximately 30%, but with adequate treatment this can be reduced to 2–8%. Numerous cases go unrecognized and hence untreated, with poor outcomes. Indeed the prevalence of PE at autopsy (approximately 12–15% in hospitalized patients) has not changed over three decades [2].
The use of inhaled aerosolized prostaglandin E(1) (aerPGE(1)), a pulmonary vasodilator, has not been widely analyzed. In contrast to prostacyclin, PGE(1) has a shorter lifetime and is metabolized in a greater amount from the lungs, lowering the risk of systemic effects. The aim of this study was to analyse the effects of aerPGE(1) administration on pulmonary hemodynamics and oxygenation during lung transplantation. Eighteen patients undergoing lung transplantation were enrolled in this study. During the first lung implantation, systemic and pulmonary hemodynamic and oxygenation data were evaluated in three phases: -- baseline in 100% O(2); during aerPGE(1) -- after 15 min of aerosolized prostaglandin E(1) administration in 100% O(2); after aerPGE(1) -- 15 min after the end of the prostaglandin E(1) administration in 100% O(2). During aerPGE(1) a reduction in mPAP, PVRI, and Qs/Qt and an increase in PaO(2)/FiO(2) were observed. Soon after prostaglandin inhalation was ceased, the mPAP, the PVRI, and the Qs/Qt increased while PaO(2)/FiO(2) decreased. During the study, no significant difference in systemic pressure among the phases was noted. A high correlation between changes in mPAP, Qs/Qt and PaO(2)/FiO(2) after aerPGE(1) administration and baseline values was observed. ROC curve analysis showed that values of 40 mmHg of mPAP, 21.7% of the pulmonary shunt, and 364 mmHg for PaO(2)/FiO(2) predict a decrease in mean pulmonary arterial pressure and pulmonary shunt or an improvement in oxygenation of 10% with respect to baseline values. A low dose of aerosolized prostaglandin E(1) decreases pulmonary arterial pressure and improves oxygenation without impairment on systemic hemodynamics, also during anesthesia for lung transplantation. The effect seems to depend on baseline values, which can be considered to be a predictor of the prostaglandin response.
To evaluate hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide (iNO) and inhaled aerosolized prostcyclin (IAP) during lung transplantation. Prospective study. University hospital. Ten patients scheduled for lung transplantation. Ten patients, with a mean age of 38 years (range, 24 to 56 years), were scheduled for lung transplantation (2 single-lung transplantations and 8 double-lung transplantations). During first lung implantation with single-lung perfusion and ventilation, hemodynamic and oxygenation data were analyzed in 3 phases: (1) baseline, 5 minutes after pulmonary artery clamping; (2) inhaled NO phase, 15 minutes after inhaled NO administration (20 ppm) in 100% oxygen; and (3) IAP-inhaled NO phase, 15 minutes after combined administration of inhaled NO (20 ppm) and IAP (10 ng/kg/min) in 100% oxygen. During the inhaled NO phase, reductions of mean pulmonary arterial pressure (p < 0.05) and intrapulmonary shunt (p < 0.05) were noted. After the start of prostacyclin inhalation, a further decrease in mean pulmonary arterial pressure (p < 0.05) was observed. PaO2/FIO2 increased during the IAP-inhaled NO phase (p < 0.05), whereas intrapulmonary shunt decreased (p < 0.05). This study confirms the action of inhaled NO as a selective pulmonary vasodilator during lung transplantation. Combined therapy with IAP and inhaled NO increases the effects on pulmonary arterial pressure and oxygenation compared with inhaled NO administered alone without any systemic changes.
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To examine the hemodynamic effects of external positive end-expiratory pressure (PEEP) on right ventricular (RV) function in acute respiratory failure (ARF) patients. Prospective, with retrospective analysis on the basis of RV volume response to PEEP. General intensive care unit in a university teaching hospital. 20 mechanically ventilated ARF patients (mean lung injury score = 2.6 +/- 0.45 SD). Incremental levels of PEEP (0-5-10-15 cmH2O) were applied and RV hemodynamics were studied by means of a Swan-Ganz catheter with a fast-response thermistor for right ventricular ejection fraction (RVEF) measurement. According to their response to PEEP 15, two groups of patients were defined: group A (9 patients) with unchanged or increased RV end-diastolic volume index (RVEDVI) and group B (11 patients) with decreased RVEDVI. At zero PEEP (ZEEP) the hemodynamic parameters of the two groups did not differ. In group A, cardiac index (CI) and stroke volume index (SI) decreased at all PEEP levels (5, 10, and 15 cmH2O), while RVEF started to decrease only at a PEEP of 10 cmH2O (-10.8%), and RVES(systolic)VI increased only at PEEP 15 cmH2O (+21.5%). RVEDVI was not affected by PEEP. In group B, CI and SI decreased at all PEEP levels (5, 10, and 15 cmH2O). Similarly, RVEDVI started to decrease at PEEP 5 cmH2O, while RVESVI decreased only at PEEP 15 cmH2O (-21.4%). RVEF was not affected by PEEP in this group. In each patient the slope of the relationship between RVEDVI and right ventricular stroke work index (RVSWI), expressing RV myocardial performance, was studied. This relationship was significant (no change in RV contractility) in 8 of 11 patients in group B and in only 2 patients in group A. In 4 patients in group A, PEEP shifted the RVSWI/RVEDVI ratio rightward in the plot, indicating a decrease in RV myocardial performance in these patients. PEEP affects RV function in ARF patients. The decrease in cardiac output is more often associated with a preload decrease and no change in RV contractility. On the other hand, the finding of increased RV volumes with PEEP may be associated with a reduction in RV myocardial performance. Thus, these results suggest that assessment of RV function by PEEP and preload recruitable stroke work may disclose otherwise unpredictable alterations in RV function.
Prostaglandin E1 (PGE1) was compared to placebo in a 100-patient (50 PGE1, 50 placebo) randomized, double-blind, clinical trial to determine whether PGE1 therapy enhances survival of patients with adult respiratory distress syndrome (ARDS) when infused through a central line at 30 ng/kg/min continuously for seven days. At 30 days postinfusion, 30 PGE1 and 24 placebo patients had died. Total deaths judged to be related to the syndrome were 32 and 28 in the PGE1 and placebo groups respectively at six months. We conclude that PGE1 did not enhance survival in patients with established ARDS. PGE1 augmented the hyperdynamic circulation of these patients by reducing systemic and pulmonary vascular resistance, which resulted in a reduction of blood pressures and increased stroke volume, cardiac output, and heart rate. An improvement in oxygen availability and oxygen consumption was observed with PGE1 therapy. PGE1 was associated with an increased incidence of diarrhea (six patients in the PGE1 group vs one in the placebo group, p less than 0.05). Other adverse effects included hypotension (ten patients in the PGE1 group vs seven in the placebo group), fever (six patients in the PGE1 group vs three in the placebo group), and non-fatal dysrhythmias (ten in the PGE1 group vs five in the placebo group).
We repeatedly assessed pulmonary and systemic hemodynamics in 30 patients undergoing therapy for severe acute respiratory failure of diverse causes. Pulmonary-artery hypertension and elevated pulmonar vascular resistance were observed in all patients after correction of systemic hypoxemia. Increasing pulmonary blood flow by isoproterenol infusion or decreasing pulmonary blood flow by partial bypass of the right side of the heart minimally altered pulmonary-artery pressure. Although neither elevated pulmonary vascular resistance nor low cardiac index reliably predicted death, survivors had preogressive decreases of pulmonary vascular resistance with time, whereas nonsurvivors tended to maintain or increase pulmonary vascular resistance. Right ventricular stroke-work index was markedly elevated in all patients. The work load imposed upon the right ventricle by elevation of pulmonary vascular resistance may be a factor limiting survival in severe acute respiratory failure.
Eight patients who developed pulmonary artery hypertension during the adult respiratory distress syndrome (ARDS) were treated with an infusion of prostacyclin (PGI2, 12.5-35.0 for 45 min. We examined whether reducing the right ventricular (RV) outflow pressures by PGI2 infusion would increase the right ventricular ejection fraction (RVEF) measured by thermodilution. PGI2 reduced the pulmonary artery pressure (PAP) from 35.6 to 29.1 mmHg (p less than 0.01). The cardiac index (CI) increased from 4.2 to 5.81.min-1.m-2 (p less than 0.01) partly due to an increased stroke volume. The decreased PAP together with the increased CI resulted in a fall of the calculated pulmonary vascular resistance index (PVRI, from 5.1 to 2.5 mmHg.min.m2.1-1, p less than 0.01). In the patients with subnormal baseline RVEF the increased stroke volume was associated with an increased RVEF (from 47.6% to 51.8%, p less than 0.05) suggesting improved RV function. This result was underscored by a significant relationship between the changes in PVRI and RVEF (r = 0.789, delta % RVEF = PVRI-1.45). Despite an increased venous admixture from 27.8% to 36.9% (p less than 0.05) the arterial PO2 remained constant resulting in an increased oxygen delivery from 657 to 894 ml.min-1.m-2 (p less than 0.01). We conclude that short term infusions of PGI2 increased CI concomitant to improved RV function parameters when baseline RVEF was depressed. Since improved oxygen availability should be a major goal in the management of patients with ARDS PGI2 may be useful to lower pulmonary artery pressure in ARDS.
To examine the right ventricular response to acute respiratory failure, serial studies of biventricular performance were analysed in 34 such patients, specifically detailing the role of associated underlying disease. During the initial study, the 34 patients with acute respiratory failure had a higher right ventricular end-diastolic volume than the control group (+21%), associated with a decrease in right ventricular ejection fraction, abnormalities which tended to return to normal values in the 15 survivors. In the 9 patients who died of refractory hypoxemia with severe pulmonary hypertension, the right ventricular dilation allowed to maintain stroke volume. In contrast, in 8 patients who died of septic shock, biventricular function was progressively altered (right and left ventricular ejection fraction = -37% and -35%). In 4 patients who died of cardiogenic shock (viral myocarditis), the cardiac function was the lowest (right and left ventricular ejection fraction = -59% and -60%). Only patients with acute respiratory failure associated with septic shock or viral myocarditis are unable to maintain their stroke volume.
A 7-day infusion of prostaglandin E1 (PGE1), an immunomodulator, was evaluated in a prospective, randomized, placebo-controlled, double-blinded trial in surgical patients with the adult respiratory distress syndrome (ARDS). The drug seemed to improve pulmonary function--only two PGE1 patients died with severe pulmonary failure compared with nine placebo patients (p = 0.01). Survival at 30 days after the end of the infusion--the predetermined end point of the study--was significantly better in the patients given PGE1 (p = 0.03), with 15 of 21 PGE1 patients (71%) alive at this time compared with seven of 20 placebo patients (35%). Improvement in overall survival in the PGE1 patients did not reach statistical significance (p = 0.08). Overall survival in patients initially free of severe organ failure, however, was significantly better in the PGE1 patients (p = 0.03). Of the six PGE1 patients free of severe organ failure at time of entry, all survived to leave the hospital; of the 10 placebo patients initially free of severe organ failure, four survived. The drug had no serious side effects and did not potentiate susceptibility to infection. PGE1 is a promising agent for the treatment of ARDS.
Eight patients with acute respiratory failure secondary to chronic bronchitis were studied for up to 5 consecutive days following admission; cardiac output and intravascular pressures, blood volume, arterial blood gas tensions, and body weight were measured. These observations were also compared with further measurements made some weeks later just before the patient was discharged. The effects of oxygen and acetylcholine on the pulmonary circulation were also studied. Pulmonary arterial pressure was raised in all patients during their acute illness and had fallen substantially after recovery. The pulmonary arterial pressure throughout the study correlated directly with the arterial carbon dioxide and inversely with the arterial oxygen tensions. The inhalation of 24% and 28% oxygen and the infusion of acetylcholine into the pulmonary artery resulted in a fall in pulmonary arterial pressure, often to levels close to those subsequently seen after recovery from the acute illness. No significant change in cardiac output was observed. It is suggested that the acute pulmonary hypertension seen in these patients is due primarily to pulmonary vasoconstriction resulting from hypoxia.
Recently, inhalation of prostacyclin (PGI2) has been shown to cause selective pulmonary vasodilation. However, the effects of inhaled PGI2 on right ventricular (RV) performance are still unknown and therefore were compared with those of inhaled nitric oxide (NO). Reported measurements design. Animal research laboratory. Six anesthetized, ventilated dogs (28 +/- 2 kg). Pulmonary hypertension was induced by decreasing FIO2 to 0.09-0.11 ('hypoxic pulmonary vasoconstriction', HPV). Subsequently, a single dose of either NO (50 ppm) or PGI2-aerosol (0.9 +/- 0.3 ng/kg/min) was randomly added to the inspired gas. Measurements were performed before induction of HPV and 10 minutes after application and withdrawal of each drug. Central hemodynamics, global RV function, and local RV function (n = 5, sonomicrometry) were assessed. HPV resulted in an increase of pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), RV stroke work, right coronary artery flow, maximal rate of RV pressure increase (RV dP/dtmax), and maximal velocity of shortening of contractile elements (Vmax). In contrast, RV ejection fraction, RV end-diastolic volume, RV end-diastolic fiber length, and systolic fiber shortening were unchanged. Both PGI2-aerosol and NO attenuated the HPV-induced increase in PAP and PVR without affecting arterial pressure. NO, but not PGI2, resulted in an increase of RV ejection fraction from 42 to 46% (p < 0.05). Right coronary flow dropped from 29 to 21 mL/min during PGI2 (p < 0.05). RV stroke work, RV dP/dtmax, and Vmax decreased subsequent to both NO and PGI2, whereas local RV function was not affected. In pulmonary hypertension induced by HPV, PGI2-aerosol and inhaled NO reduced RV afterload and, hence, RV oxygen demand, with only minor changes of stroke volume and cardiac output, indicating an improvement of overall efficiency of RV contraction. RV ejection fraction increased on NO, but not with PGI2. This might be explained by the fact that the reduction of pulmonary vascular resistance during PGI2 amounted to only 65% of the effect of NO. In summary, both inhaled NO and PGI2-aerosol showed beneficial effects on RV performance and may prove helpful in the treatment of acute pulmonary hypertension.
To compare the effects of inhaled nitric oxide (NO) and an infusion of prostacyclin (PGI2) on right ventricular function in patients with severe acute respiratory distress syndrome (ARDS). Randomized prospective short-term study. Post-surgical ICU in an university hospital. 10 patients with severe ARDS referred to our hospital for intensive care. In random sequence the patients inhaled NO at a concentration of 18 parts per million (ppm) followed by 36 ppm, and received an intravenous infusion of PGI2 (4 Inhalation of 18 ppm NO reduced the mean (+/- SE) pulmonary artery pressure (PAP) from 33 +/- 2 to 28 +/- 1 mmHg (p = 0.008), increased right ventricular ejection fraction (RVEF), as assessed by thermodilution technique, from 28 +/- 2 to 32 +/- 2% (p = 0.005), decreased right ventricular end-diastolic volume index from 114 +/- 6 to 103 +/- 8 ml.m-2 (p = 0.005) and right ventricular end-systolic volume index from 82 +/- 4 to 70 +/- 5 ml.m-2 (p = 0.009). Mean arterial pressure (MAP) and cardiac index (CI) did not change significantly. The effects of 36 ppm NO were not different from the effects of 18 ppm NO. Infusion of PGI2 reduced PAP from 34 +/- 2 to 30 +/- 2 mmHg (p = 0.02), increased RVEF from 29 +/- 2 to 32 +/- 2% (p = 0.02). Right ventricular end-diastolic and end-systolic volume indices did not change significantly. MAP decreased from 80 +/- 4 to 70 +/- 5 mmHg (p = 0.03), and CI increased from 4.0 +/- 0.5 to 4.5 +/- 0.5 l.min-1.m-2 (p = 0.02). Using a new approach to selective pulmonary vasodilation by inhalation of NO, we demonstrate in this group of ARDS patients that an increase in RVEF is not necessarily associated with a rise in CI. The increase in CI during PGI2 infusion is probably related to the systemic effect of this substance.
Inhalation of NO and aerosolization of PGI2 have been suggested to achieve selective pulmonary vasodilation and improvement of arterial oxygenation in patients with ARDS. We directly compared these two modes of transbronchial vasodilator therapy in 16 ARDS patients mechanically ventilated (mean lung injury score [1] 2.75 +/- 0.05). Patients were randomized to receive either first NO and then PGI2, or vice versa. Each drug was individually titrated to find the maximum improvement of arterial oxygenation. Gas exchange variables, including data from the multiple inert gas elimination technique (MIGET), and hemodynamics under application of NO/PGI2 were compared with pre- and post-challenge values. NO (17.8 +/- 2.7 ppm) increased Pa O2/FI O2 from 115 +/- 12 to 144 +/- 15 mm Hg (p<0.01) and reduced the shunt-flow from 33.1 +/- 3.6 to 26.6 +/- 4.5% (p<0.05). Aerosolized PGI2 (7.5 +/- 2.5 ng/kg min) augmented Pa O2/FI O2 from 114 +/- 12 to 135 +/- 12 mm Hg (p<0.01), and decreased shunt from 33.5 +/- 3.8 to 26.0 +/- 3.9% (p<0.05). In 10 patients, both NO and PGI2 caused an increase in Pa O2/FI O2 by at least 10 mm Hg. Two further patients displayed an improvement of arterial oxygenation in response to either NO or PGI2. NO decreased mean pulmonary artery pressure from 34.8 +/- 2.2 to 33.0 +/- 1.8 mm Hg, and PGI2 from 35.0 +/- 2.2 to 31.9 +/- 1.7 mm Hg (p<0.05). We conclude that individually titrated doses of inhaled NO and aerosolized PGI2 effect selective pulmonary vasodilation and redistribute blood-flow from shunt-areas to well-ventilated regions with nearly identical efficacy profiles.
Inhalation of nitric oxide (NO) and prostacyclin (PGI2) may induce selective pulmonary vasodilation and-by improving ventilation-perfusion ratio in ventilated areas of the lung-increase Pao2 in patients with acute lung injury. To assess the therapeutic efficacy of both compounds, dose-response curves were established in patients with adult respiratory distress syndrome (ARDS). Patients received both PGI2 (doses of 1, 10, and 25 ng/kg/min) and NO (concentrations of 1, 4, and 8 ppm). Cardiorespiratory parameters were assessed at control, at each drug concentration, and after withdrawal of NO and PGI2. PGI2 resulted in a significant, dose-dependent and selective reduction of pulmonary artery pressure (PAP) from 35.1 +/- 6.3 mm Hg at control to 33.1 +/- 4.8 (1 ng/kg/min), 31.3 +/- 4.8 mm Hg (10 ng/kg/min) and 29.6 +/- 4.5 mm Hg (25 ng/kg/min), respectively. Inhaled NO reduced PAP from 34.5 +/- 5.6 to 32.1 +/- 5.9 mm Hg at 4 ppm, and to 31.8 +/- 6.1 mm Hg at 8 ppm, respectively, with no effect at 1 ppm. Pao2/Flo2 ratio increased from 105 +/- 37 to 125 +/- 56 mm Hg (range of increase: 0 to 57 mm Hg) at PGI2 10 ng/kg/min and to 131 +/- 63 mm Hg (range: -5 to 89 mm Hg) at 25 ng/kg/min with no effect at 1 ng/kg/min. NO improved Pao2 (e.g., from 116 +/- 47 to 167 +/- 86 mm Hg at 8 ppm) and reduced intrapulmonary shunt at all doses tested. We conclude that both inhaled PGI2 and NO may induce selective pulmonary vasodilation and increase Pao2 in severe ARDS.
To investigate the response to inhaled prostacyclin in patients with primary and secondary pulmonary hypertension and to compare its effects to those of intravenous prostacyclin and inhaled nitric oxide. Twelve patients with pulmonary hypertension (seven primary and five secondary) were studied. All patients had a pulmonary artery balloon flotation catheter inserted into the proximal pulmonary artery and radial arterial line. Prostacyclin was nebulized with 81.min-1 of oxygen and administered in doses increasing from 15 to 50 via a facemask. Eight of these patients also received intravenous prostacyclin in doses of 1 to 5 and nitric oxide in doses of 10 to 100 ppm via a facemask. Haemodynamic measurements were taken during each treatment. In the 12 patients, nebulized prostacyclin produced a significant reduction in mean pulmonary artery pressure from 56 +/- 5 to 45 +/- 4 mmHg (P = 0.0001). The pulmonary vascular resistance decreased by 38% from 964 +/- 169 to 595 +/- 116 (P = 0.0001). Direct comparison with inhaled nitric oxide and intravenous prostacyclin in eight patients demonstrated that nebulized prostacyclin produced a greater fall in mean pulmonary artery pressure than the other two agents without any significant effect on systemic arterial pressure. Nebulized prostacyclin appears to be more effective at reducing pulmonary artery pressure in patients with pulmonary hypertension when compared to intravenous prostacyclin and inhaled nitric oxide. This could have important clinical implications for the management of patients with pulmonary hypertensions.
Although the acute respiratory distress syndrome (ARDS) was identified as long as 30 years ago, potential therapeutic objectives have been defined from small series rather than large trials. Moreover, relationships between ARDS and hemodynamics are unclear. The European Collaborative ARDS Study was designed to identify factors influencing the pathogenesis, severity, and prognosis of ARDS. Analysis of the hemodynamic profiles collected during this study and of their contribution to the above-mentioned facets of ARDS is the focus of the present report. Prospective clinical study. 38 European intensive care units (ICUs). We collected 2758 sets of data from 586 patients, including baseline data, data on proven or suspected causes of ARDS differentiating direct and nondirect lung injury, and data on baseline status including multiple organ dysfunction (MOD) with differentiation of primary ARDS from ARDS secondary to severe systemic disorders. Events during follow-up were also recorded, including whether the acute respiratory failure did or did not improve after 24 h (groups A and B, respectively). When available, hemodynamic data were recorded at enrollment (day 0), on days 1-3, 7, 14, and 21, and at discharge or at the time of death in the ICU. Although the rate of pre-existing disease and the nature and rate of complications varied widely among etiologic categories, differences in the hemodynamic profile occurred only between primary and secondary ARDS. Both at inclusion and during the course of the illness, variables that were used to investigate Va/Q mismatch [arterial oxygen tension (PaO2, arterial oxygen saturation, right-to-left shunt, and the PaO2/fractional inspired oxygen (FIO2) ratio] predicted survival. High pulmonary artery pressure (PAP) and low systemic artery pressure (SAP) were also related to the prognosis. In the logistic regression model including hemodynamic and oxygen-related variables, however, the only independent predictors of survival were the ratio of right over left ventricular stroke work (RVSW/LVSW) and the PaO2/FIO2 ratio at admission. On day 2, the best prognostic model included: age [odds ratio (OR) = 1.04, p = 0.0004], opportunistic pneumonia as the cause of ARDS (OR = 3.2, p = 0.03), existence of MOD (OR = 1.9, p = 0.03), PaO2/FIO2 (OR = 0.96, p = 0.005), and RVSW/LVSW (OR = 25, p = 0.02). A high RVSW/LVSW ratio, high systolic PAP, low diastolic SAP, and low PaO2/FIO2, and increased right atrial pressure were negative prognostic indicators during follow-up. In addition to the cause of ARDS and the early time-course of lung function, a high systolic PAP and a low diastolic SAP were strong independent indicators of survival.
We critically reviewed English-language articles indexed on MEDLINE from 1966-1998 and those cited in indexed articles describing or investigating administration of nitric oxide (NO) in adult respiratory distress syndrome (ARDS). Studies evaluating NO exclusively in the pediatric population and in conditions other than ARDS (chronic obstructive pulmonary disease, asthma, cardiac surgery, pulmonary hypertension) were excluded, as were those published exclusively as abstracts. Of the 22 papers selected, 5 studies were dose-response trials, eight were comparative, and the rest were noncomparative. Dose-dependent decreases in pulmonary artery pressures and increases in arterial oxygenation were observed; however, the minimal effective dose varied. Several short-term noncomparative and small noncomparative prospective trials concluded that NO improves oxygenation and decreases pulmonary vasoconstriction without effects on systemic hemodynamics. However, evidence that NO improves outcomes in patients with ARDS is insufficient because mortality remained high, and the number of subjects in each study was low. Since improvements in oxygenation are not seen in all patients and outcomes or mortality might not be altered, NO should be reserved for selected patients in whom conventional therapy is not sufficient to maintain acceptable oxygenation levels.
Pulmonary circulation during adult pulmonary distress syndrome Acute respiratory failure
  • Wm Zapol
  • Mt Snider
  • Ma Rie
Effects of continuous administration of aerosolized prostacyclin on hemodynamics and gas exchange in ARDS
  • N Brienza
  • S Grasso
  • F Bruno
Incidence of pulmonary arterial hypertension and right ventricular impairment in moderate and severe acute respiratory failure
  • A Brienza
  • G Cinnella
  • M Dambrosio
Prostaglandin E1 in the ARDS. Benefit for pulmonary hypertension and cost for pulmonary gas exchange
  • C P Melot
  • M Lejeune
  • J J Leeman
  • CP Melot
Prostaglandin E1 and survival in patients with the adult distress syndrome
  • J W Holcroft
  • M J Vossar
  • C J Weber
  • JW Holcroft
Pulmonary circulation during adult pulmonary distress syndrome
  • W M Zapol
  • M T Snider
  • M A Rie
  • WM Zapol