Salvage therapies for refractory hypoxemia in ARDS

Abstract

Acute Respiratory Distress Syndrome (ARDS) is a condition of varied etiology characterized by the acute onset (within 1 week of the inciting event) of hypoxemia, reduced lung compliance, diffuse lung inflammation and bilateral opacities on chest imaging attributable to noncardiogenic (increased permeability) pulmonary edema. Although multi-organ failure is the most common cause of death in ARDS, an estimated 10-15% of the deaths in ARDS are caused due to refractory hypoxemia, i.e.- hypoxemia despite lung protective conventional ventilator modes. In these cases, clinicians may resort to other measures with less robust evidence -referred to as "salvage therapies". These include proning, 48 h of paralysis early in the course of ARDS, various recruitment maneuvers, unconventional ventilator modes, inhaled pulmonary vasodilators, and Extracorporeal membrane oxygenation (ECMO). All the salvage therapies described have been associated with improved oxygenation, but with the exception of proning and 48 h of paralysis early in the course of ARDS, none of them have a proven mortality benefit. Based on the current evidence, no salvage therapy has been shown to be superior to the others and each of them is associated with its own risks and benefits. Hence, the order of application of these therapies varies in different institutions and should be applied following a risk-benefit analysis specific to the patient and local experience. This review explores the rationale, evidence, advantages and risks behind each of these strategies.

An Update on Current Therapeutic Drugs Treating COVID-19

“…The Surviving Sepsis Campaign suggested a trial of inhaled pulmonary vasodilator method as rescue therapy in mechanically ventilated adults with COVID-19, severe ARDS, and hypoxemia despite optimized ventilation and other rescue strategies. Inhaled nitric oxide (iNO) and inhaled epoprostenol (iEPO, a naturally occurring prostaglandin) are two common pulmonary vasodilators that have been widely studied [93][94][95]. Experience in patients with ARDS indicates that iNO can substantially reduce mean pulmonary artery pressure and improve oxygenation in such patients.…”

“…Furthermore, in vitro evidence of direct antiviral activity against SARS-CoV was studied and the genetic similarity between SARS-CoV and SARS-CoV-2 suggests their potential effectiveness against SARS-CoV-2 [96]. For iEPO, dosages up to 50 ng/kg per minute have been used [93,94,97,98]. Previous studies reported that to provide a clinically important increase in PaO2 and reduction in pulmonary artery pressure, the most effective and safe dosage appears to be 20-30 ng/kg per minute in adults and 30 ng/kg per minute in pediatric patients [98].…”

Management of Respiratory Distress Syndrome due to COVID-19 infection

“…Nitric Oxide and Prostaglandins (e.g. PGI 2 [epoprostenol]), despite its pulmonary vasodilatory properties have failed to demonstrate a mortality benefit in ARDS [ 44 ]. Nitric Oxide use during the COVID-19 patients is controversial [ 45 ].…”

Using In Situ Simulation to Develop a Prone Positioning Protocol for Patients With ARDS

“…6,7 Severe cases may require additional evidence-lacking therapies such as therapeutic paralysis, inhaled vasodilators, and extracorporeal membrane oxygenation. 8,9 Prone positioning, in use since the 1970s, has been shown to decrease mortality in patients with severe ARDS. 1 Prone positioning remains underused in ARDS patients owing to variety of barriers, including lack of confidence, lack of staff competency, and concerns about possible complications.…”

“…11 However, prone positioning remains underused in ARDS patients owing to a variety of identified barriers, including lack of confi-� dence in performing the maneuver, lack of staff competency due to absence of formal policies or training, and concerns about possible complications resulting from providing nursing care to patients in the prone position. 4,9,[12][13][14][15] Prone positioning is regarded as a high-risk procedure, with possible adverse outcomes including loss of airway, loss of central catheters and peripheral intravenous access, and pressure injury of the anterior surface of the body, including the face. [16][17][18] If cardiac arrest occurs in a critically ill patient in the prone position, the outcome may be disastrous in the absence of properly trained staff.…”