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Exogenous Surfactants |   |
Drugs for ARDS
At the present time, medications do not play a major role in treating ARDS. However, there are two basic strategies for the using drugs to treat ARDS: improve/correct lung function and prevent/correct lung and systemic inflammation. Drugs for the former consist of almitrine, nitric oxide, surfactant replacement, and prostaglandin E1. For the latter, drugs consist of antioxidants, anticytokines, antiendotoxins, corticosteroids, and monoclonal antibodies.
Almitrine improves PaO2 and decreases PaCO2 in COPD patients through decreasing V/Q mismatch. In ARDS, almitrine has been effective in redistributing blood flow from areas of shunt to normal areas. It gives a similar increase in PaO2 to 10 cm H2O PEEP without the side effects of positive Pressure.
Nitric Oxide (NO) is a potent pulmonary vasodilator when inhaled. It has relatively no effect on the systemic circulation because it is inactivated by hemoglobin. Inhaled NO selectively improves perfusion of ventilated areas, and improves oxygenation in ARDS. Nitric oxide significantly decreases pulmonary artery pressure, decreases shunting and improves PaO2.
However, NO is a toxic component of air pollution, and exposure to it can result in pulmonary edema and unacceptable levels of methemoglobin. Not all patients respond to NO and it is impossible to predict which patients will respond. Effective doses of inhaled NO are less than 20 parts per million (ppm), and at doses less than 20 ppm, NO is considered relatively free of toxicity.
Prostaglandin E1 decreases systemic and pulmonary vascular resistance, decreases blood pressure, increases stroke volume, increases cardiac output, and increases heart rate. It may be useful to decrease pulmonary hypertension and improve cardiac function, but doesn't appear to enhance survival in ARDS.
Antioxidants also may be of use in ARDS. N-acetylcysteine has improved lung function, 02 delivery, and cardiac output in one study. A larger study showed no improvement in oxygenation, but an improvement in compliance. There was no difference in survival with the use of N-acetylcysteine.
Cytokines, such as interleukins, play a major role in causing the systemic effects associated with the sepsis syndrome. Clinical trials of anticytokines have been conducted. Studies of interleukin-1 receptor antagonist showed a minor but statistically insignificant improvement in mortality.
Antiendotoxins may prove useful, particularly in gram negative sepsis. Endotoxins produced by gram negative bacteria cause severe disturbances. Several antibodies against endotoxins have been studied. HA-lA showed an improvement in mortality in patients with gram-negative bacteremia.
Corticosteroids were tried in ARDS treatments in the past, but were relatively unsuccessful. Current emphasis is on the damaging potential of WBCs, however, if WBCs are interfered with by steroids, patients run the risk of increased infection. Steroids may be useful in minimizing fibrosis formation in the latter stages of ARDS. They are recommended if the patient is hypotensive from adrenal insufficiency. They also may be useful in aspiration, fat embolism, and chemical injuries to the airway.
Monoclonal antibodies are being studied to inhibit WBC-adhesion molecules, particularly those of the neutrophil. Neutrophil adhesion to tissue is a critical step in ARDS lung injury.
Use of ibuprofen has showed a decrease in the incidence and development of ARDS, increased rate of reversal, and improved survival. Some soluble protective agents against lung damage are tocopherol, ascorbate, and beta-carotene. These help protect membranes and other cellular elements from oxidant injury, however their value in ARDS remains unconfirmed.