In this review we evaluate specific therapeutic strategies for the acute respiratory distress syndrome (ARDS)1,2 and make recommendations on their use. We begin with a brief overview of the laboratory tests used to evaluate suspected cases of the syndrome, because these often dictate the subsequent therapeutic approaches. The clinical features, pathogenesis, and pathologic features of ARDS have been reviewed extensively elsewhere.3–18 We recognize that the understanding of ARDS and its optimal clinical management will continue to advance and that our recommendations will therefore be modified. Definition of ARDS The recent European–American Consensus Conference on ARDS developed the following . . .

The Acute Respiratory Distress Syndrome

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, has been shown to decrease pulmonary artery pressures but not increase cardiac output in hemodynamically stable patients with a variety of causes of pulmonary hypertension. The response to iNO in hemodynamically unstable patients with acute right heart syndrome has not been previously described. We determined the response to iNO in 26 critically ill adult patients with acute right heart failure defined by echocardiographic criteria. Patients received iNO through the inspiratory limb of the ventilator in increments of 10 ppm with hemodynamic and gas-exchange measurements made before and after each level. When maximal effect was seen, iNO was discontinued to compare parameters with baseline. iNO significantly increased cardiac output (5.5 +/- 3 to 6.4 +/- 4 L/min), stroke volume (54 +/- 27 to 65 +/- 38 ml), and mixed-venous oxygen saturation (69 +/- 8 to 73 +/- 10%), all p 20%) and in approximately 25% of all patients, the improvement in hemodynamic measures permitted a decrease in other vasoactive drug administration. The mean concentration of iNO required to achieve these effects was 35 ppm, and 85% of patients exhibiting a substantial improvement in hemodynamics did so at a concentration of iNO of less than or equal to 40 ppm. Underlying causes of right heart failure and baseline hemodynamics did not predict response to iNO, but the use of alpha-agonist catecholamines did. We conclude iNO improves hemodynamics in patients with respiratory failure, shock, and right ventricular dysfunction. Although mortality was not a key end point in this pilot study, it was high for both responders and nonresponders to this therapy. Further evaluation of the role of iNO in this patient population is supported by these data.

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.159.2.9804127

Response to Inhaled Nitric Oxide in Patients with Acute Right Heart Syndrome

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 ng·kg−1·min−1) 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<0.01). The cardiac index (CI) increased from 4.2 to 5.81·min−1·m−2 (p<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<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<0.05) suggesting improved RV function. This result was underscored by a significant relationship between the changes in PVRI and RVEF (r=0.789, Δ% RVEF=−2.11·ΔPVRI-1.45). Despite an increased venous admixture from 27.8% to 36.9% (p<0.05) the arterial PO2 remained constant resulting in an increased oxygen delivery from 657 to 894 ml·min−1·m−2 (p<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.

https://link.springer.com/content/pdf/10.1007/BF01705156.pdf

Prostacyclin and right ventricular function in patients with pulmonary hypertension associated with ARDS

Objective: To assess the efficacy of inhaled nitric oxide (NO) in reducing pulmonary hypertension in a porcine model of adult respiratory distress syndrome. Design: Nonrandomized, controlled experiment without blinding. Setting: Surgical research laboratory. Participants: Twelve pigs, matched equally for body weight. Intervention: Acute lung injury was induced by intravenous injection of oleic acid. Animals were then divided into either a control group, for monitoring without any further intervention, or a NO-treatment group, in which NO was administered at concentrations of 10 to 80 ppm, with each step separated by a NO-free interval to assess duration of effect. Main Outcome Measures: Pulmonary artery pressure, systemic blood pressure, PaO2, intrapulmonary shunt fraction, and extravascular lung water. Nitrosylated hemoglobin, arterial methemoglobin, and plasma nitrite and nitrate concentrations. Results: All animals responded to oleic acid injection with rapid development of pulmonary hypertension and deterioration of PaO2and intrapulmonary shunt fraction. Inhaled NO reversed these changes in a concentration-dependent manner. Cessation of NO administration led to a prompt return of pulmonary hypertension. A small but significant drop in systemic blood pressure was observed only at the highest concentration of NO administered (80 ppm). Extravascular lung water almost doubled following oleic acid injury. This increase was sustained in all animals for the remainder of the experiment. Significant increases in circulating methemoglobin and plasma nitrite and nitrate concentrations were measured during NO inhalation. Conclusion: Inhaled NO appears to be a selective pulmonary vasodilator and may prove to be useful in improving gas exchange in adult respiratory distress syndrome. (Arch Surg. 1994;129:158-164)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=SURG&articleId=595865&pdfFileName=archsurg_129_2_007.pdf

Efficacy of Inhaled Nitric Oxide in a Porcine Model of Adult Respiratory Distress Syndrome

1.

According to the Starling resistor model of the pulmonary circulation, the pulmonary hypertension of oleic acid lung injury, an experimental model close to the early stage of clinical ARDS, primarly results from an increased vascular closing pressure which exceeds Pla and becomes the effective outflow pressure of the pulmonary circulation. Therefore, calculated pulmonary vascular resistance should be interpreted cautiously during haemodynamic investigations in patients with ARDS.




2.

Part of this increased vascular closing pressure is functional. During acute lung injury pulmonary vasomotor tone can be reduced by vasodilators or increased by cycloxygenase inhibitors and almitrine.




3.

Pulmonary vasodilation due to infused vasodilators usually impairs gas exchange in ARDS.




4.

There is evidence that HPV is altered during ARDS. Drugs capable of enhancing the efficacy of HPV could improve gas exchange. If proven safe in the future, cyclooxygenase inhibitors and almitrine are interesting compounds to be, tested in ARDS.

David G. Cunningham

Papers

Nitroprusside infusion does not improve biventricular performance in patients with acute hypoxemic respiratory failure