Therapy with Acute Respiratory Distress Syndrome (ARDS) (Research Paper Sample)

INHALED NITRIC OXIDE VERSUS CONVENTIONAL THERAPY WITH ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
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Institutional Affiliations
Inhaled Nitric Oxide versus Conventional Therapy with Acute Respiratory Distress Syndrome (ARDS)
Acute respiratory distress syndrome is characterized by an inflammatory process that causes disruption of the alveolar-capillary barrier leading to the alveolar and interstitial edema. Ronchi et al. (2013, p. 119) argue that there is also an increase in pulmonary vascular resistance, which has a rapid onset and persists even after hypoxia correction. Acute respiratory distress syndrome is a life-threatening syndrome that often requires mechanical ventilation.
According to Ronchi et al. (2013, p. 121), although mechanical ventilation is important for patients with acute respiratory distress syndrome, the large inspired tidal volume/ high ventilator pressures can cause additional injury to the lungs. Therefore, alternative ventilatory mechanisms such as high-frequency oscillatory ventilation have been touted as safer because the method uses lower tidal volume but high-than normal psychological breathing frequency. This protects lungs against the large alveolar pressure characteristic of the conventional mechanical ventilation. The whole point of using high frequency oscillatory ventilation is to improve oxygenation, reduce lung injury, and reduce inflammatory and histopathological damage.
Inhaled nitric oxide is a potent vasodilator with potential to help patients with ARDS without causing adverse effects such as hypotension. Studies show that the effects of inhaled nitric acid on inflammatory mediators is still controversial with some claiming that it increases the release of inflammatory mediators while others reduce decrease their release. However, nitric oxide can cause damaging effects to patients if applied in higher doses. Nitric oxide can react with molecules to form toxic compounds such as peroxynitrite through the process of peroxidation. Reactive nitrogen species can cause damage to macromolecules through either nitration or redox reactions. However, my opinion is that inhaled nitric oxide with mechanical ventilator has more effect on ARDS patients more than using only mechanical ventilator.
Counter-arguments
Various studies have been carried out in order to determine various negative effects of using nitric oxide in treatment of ARDS patients. Alfshari et al. (2010, p. 43) reviewed the effects of inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults. Acute lung injury and acute respiratory distress syndrome both are critical conditions associated with high mobility and morbidity in all ages. The study found no benefits of inhaled nitric oxide on survival. They found that inhaled nitric oxide increased the risk of renal failure among the adult population. The authors postulate that there are several possible explanations for why inhaled nitric oxide may not be beneficial in patients with ARDS. Inhaled nitric oxide initially improves oxygenation by reducing the ventilation-perfusion mismatch that exists in patients with ARDS. However, they suggested that inhaled nitric oxide actually worsened the clinical condition of ARDS patients by reversing hypoxic pulmonary vasoconstriction, “thereby causing vasodilation of poorly ventilated areas, increasing the ventilation-perfusionmismatch and resulting in worsening oxygenation” (Alfshari et al. 2010, p. 48).
Based on the work of Gerlach (2003, p. 5), Alfshari et al. (2010, p. 53) argued that prolonged exposure to inhaled nitric oxide and its toxic metabolites could have unprecedented effects and nullify the possible benefits of inhaled nitric oxide. Since improved oxygenation does not necessarily imply improved lung function, healed lungs or treatment of the underlying cause of acute respiratory distress syndrome, inhaled nitric acid is not associated with increased survival. It is feared that changes in nitric oxide production could have adverse effects on renal function. The peroxidation effects of nitric oxide are likely to affect the glomerular function, mitochondrial function, various enzymes, DNA, and membranes (Alfshari et al 2010, p. 54).
A more recent study supports the findings of Alfshari et al. (2010, p. 55) that inhaled nitric oxide increases the risk of renal failure in ARDS patients (Sheng-Yuan et al. 2016, p. 1518). Sheng-Yuan et al. conducted a cohort study using data from a tertiary teaching hospital to evaluate the risk of incident renal replacement therapy in users of inhaled nitric oxide. They found that inhaled nitric oxide substantially increased the risk of renal dysfunction in patients with ARDS with older patients more susceptible to this adverse event. According to this study, several risk factors enhance the vulnerability of the kidney to the nephrotoxic effects of drugs. Age, sex, and chronic kidney disease are important patient-specific factors associated with increased vulnerability to drug-related kidney injury. Their study reveals that older patients and female patients are more susceptible to inhaled nitric oxide-associated renal dysfunction. The study also attempts to reveal the phenomenon and mechanism of lung-kidney correlation. They suggest that positive-pressure ventilation alters venous return, neurohormonal system, pulmonary vascular resistance, and right ventricular function.
The mechanisms accounting for inhaled nitric oxide-associated renal dysfunction are still not clear. However, nitric oxide metabolites and their by-products might play a direct or indirect role. The nitric oxide metabolites can increase protein nitrosation and increase the oxidative load functions in tissues. The inhaled nitric oxide by products and metabolites such as methaemoglobin can have renal effects. In addition, circulating nitrogen dioxide may lead to cytotoxic effects on parenchymal cells of the kidney (Sheng-Yuan et al. 2016, p. 1538).
Supporting Arguments
Despite the criticisms of various authors about the application of inhaled nitric oxide in acute respiratory distress syndrome patients, various studies support the use of inhaled nitric oxide in ARDS patients. There is a compelling argument among most of the studies that inhaled nitric oxide is beneficial in improving oxygenation of ARDS patients for the initial 48 hours (Manktelow, 1997; Troncy et al., 1998; Rossaint, Lewandowski and Zapol, 2014; Hager, 2015). However, while some studies do not support the use of inhaled nitric oxide in ARDS patients citing the adverse effects on renal function of ARDS patients, others support its application because of its improved oxygenation of patients during the first crucial hours of treatment.
Troncy et al. (1998, p. 1483) conducted a randomized controlled clinical trial of patients with ARDS to study the impact of inhaled nitric oxide on lung function, morbidity, and mortality. Their study confirmed those of previous studies “in so far as showing that inhaled nitric oxide initially exerts a moderate pulmonary vasodilatory effect that is accompanied by an improvement in alveolocapillary gas exchange and an absence of clinical systemic hemodynamic effects” (Troncy et al. 1998, p. 1485). They did not observe any negative response to the introduction of inhaled nitric oxide in ARDS patients. They suggested that the improved oxygenation resulting from the introduction of inhaled nitric oxide is related to the redistribution of blood flow from unventilated shunted areas to ventilated but under perfused areas.
In support of the use of inhaled nitric oxide, Rossaint et al. (1993, p.1650) investigated inhaled nitric oxide for the adult respiratory distress syndrome. They reported that inhaling nitric oxide in very low doses of up to 80 ppm reversed hypoxic pulmonary vasoconstriction without affecting the systemic flow of blood. Inhaled nitric oxide prevents pulmonary hypertension and reverses bronchoconstriction. They also reported that nitric acid inhalation improved oxygenation and pulmonary artery pressure. Their research findings reflect those of Troncy et al. (1998, p. 1651) that the improved oxygenation resulting from the introduction of inhaled nitric oxide is related to the redistribution of blood flow from unventilated shunted areas to ventilated but under perfused areas. The benefits of nitric oxide inhalation are also reflected in the reduction of pulmonary artery pressure. This reduction of pressure is beneficial to patients with severe ARDS because patients in this state tend to suffer from pulmonary vasoconstriction and vascular obstruction.
Hager (2015, p. 488) reviewed recent advances in the management of acute ARDS. While acknowledging the numerous studies that have been conducted on the potential benefits of inhaled nitric oxide, he suggested that the application of inhaled nitric oxide does not seem to have a mortality benefit. However, his review points to the fact that inhalation of nitric oxide does seem to improve oxygenation during the first 48 -72 hours. The study also revealed inhalation of nitric oxide puts the ARDS patients at the risk of renal insufficiency. Nevertheless, the use of inhaled nitric oxide continues to be used because it helps the patients with breathing difficulties to buy time as the underlying lung problem is treated with other interventions such as antibiotics (Hager 2015, p. 489).
Ronchi et al. (1993, p.120) investigated the synergistic effects of using inhaled nitric oxide together with the conventional mechanical ventilation. They found that inhaled nitric oxide improves arterial oxygenation...