Pharmacological interventions in acute respiratory distress syndrome

Abstract

Pharmacological interventions are commonly considered in acute respiratory distress syndrome (ARDS) patients. Inhaled nitric oxide (iNO) and neuromuscular blockers (NMBs) are used in patients with severe hypoxemia. No outcome benefit has been observed with the systematic use of iNO. However, a sometimes important improvement in oxygenation can occur shortly after starting administration. Therefore, its ease of use and its good tolerance justify iNO optionally combined with almitirne as a rescue therapy on a trial basis. Recent data from the literature support the use of a 48-h infusion of NMBs in patients with a PaO2 to FiO2 ratio <120 mmHg. No strong evidence exists on the increase of ICU-acquired paresis after a short course of NMBs. Fluid management with the goal to obtain zero fluid balance in ARDS patients without shock or renal failure significantly increases the number of days without mechanical ventilation. On the other hand, patients with hemodynamic failure must receive early and adapted fluid resuscitation. Liberal and conservative fluid strategies therefore are complementary and should ideally follow each other in time in the same patient whose hemodynamic state progressively stabilizes. At present, albumin treatment does not appear to be justified for limitation of pulmonary edema and respiratory morbidity. Aerosolized β2-agonists do not improve outcome in patients with ARDS and one study strongly suggests that intravenous salbutamol may worsen outcome in those patients. The early use of high doses of corticosteroids for the prevention of ARDS in septic shock patients or in patients with confirmed ARDS significantly reduced the duration of mechanical ventilation but had no effect or even increased mortality. In patients with persistent ARDS after 7 to 28 days, a randomized trial showed no reduction in mortality with moderate doses of corticosteroids but an increased PaO2 to FiO2 ratio and thoracopulmonary compliance were found, as well as shorter durations of mechanical ventilation and of ICU stay. Conflicting data exist on the interest of low doses of corticosteroids (200 mg/day of hydrocortisone) in ARDS patients. In the context of a persistent ARDS with histological proof of fibroproliferation, a corticosteroid treatment with a progressive decrease of doses can be proposed.

Impact of mechanical ventilation on the pathophysiology of progressive acute lung injury

“…Deconstruction of the entire mechanical breath will be necessary to identify the optimal combination of MB P parameters, in addition to PEEP, necessary to optimally prevent edema formation. In conjunction with using mechanical ventilation to reduce edema formation, conservative fluid management should also be part of the total treatment package (110).…”

Prescribing Patterns of Drugs in Acute Respiratory Distress Syndrome (ARDS): An Observational Study

“…Neuromuscular blockers agents (NMBA) in ARDS facilitate mechanical ventilation and control patient/ventilator asynchrony [25]. In comparison with placebo or no intervention, systematic review and meta-analysis of RCTs examining the effect of using NMBA (cisatracurium) resulted in a significant reduction in risk of death at 28 days and at ICU and hospital discharge [26].…”

The hypoxic pulmonary vasoconstriction

“…[ 71 ] In patients with acute respiratory failure, iv administration of almitrine has produced short-term improvement in blood oxygenation, particularly when it was combined with selective vasorelaxant drugs (e.g., inhaled NO and PGI 2 ) however, it has been abandoned given the occurrence of lactic acidosis, worsening pulmonary hypertension and liver dysfunction. [ 72 ] In thoracic surgery, almitritine has been shown effective to attenuate the fall in PaO 2 during OLV under iv anesthesia but not under sevoflurane anesthesia. [ 73 74 75 ]…”