An update on the pharmacological management of acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is characterized by acute inflammatory injury to the lungs, alterations in vascular permeability, loss of aerated tissue, bilateral infiltrates, and refractory hypoxemia. ARDS is considered a heterogeneous syndrome, which complicates the search for effective therapies. The goal of this review is to provide an update on the pharmacological management of ARDS. AREAS COVERED: The difficulties in finding effective pharmacological therapies are mainly due to the challenges in designing clinical trials for this unique, varied population of critically ill patients. Recently, some trials have been retrospectively analyzed by dividing patients into hyper-inflammatory and hypo-inflammatory sub-phenotypes. This approach has led to significant outcome improvements with some pharmacological treatments that previously failed to demonstrate efficacy, which suggests that a more precise selection of ARDS patients for clinical trials could be the key to identifying effective pharmacotherapies. This review is provided after searching the main studies on this topics on the PubMed and clinicaltrials.gov databases. EXPERT OPINION: The future of ARDS therapy lies in precision medicine, innovative approaches to drug delivery, immunomodulation, cell-based therapies, and robust clinical trial designs. These should lead to more effective and personalized treatments for patients with ARDS.

Management of Neuromuscular Blocking Agents in Critically Ill Patients with Lung Diseases.

The use of neuromuscular blocking agents (NMBAs) is common in the intensive care unit (ICU). NMBAs have been used in critically ill patients with lung diseases to optimize mechanical ventilation, prevent spontaneous respiratory efforts, reduce the work of breathing and oxygen consumption, and avoid patient-ventilator asynchrony. In patients with acute respiratory distress syndrome (ARDS), NMBAs reduce the risk of barotrauma and improve oxygenation. Nevertheless, current guidelines and evidence are contrasting regarding the routine use of NMBAs. In status asthmaticus and acute exacerbation of chronic obstructive pulmonary disease, NMBAs are used in specific conditions to ameliorate patient-ventilator synchronism and oxygenation, although their routine use is controversial. Indeed, the use of NMBAs has decreased over the last decade due to potential adverse effects, such as immobilization, venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, ICU-acquired weakness, and residual paralysis after cessation of NMBAs use. The aim of this review is to highlight current knowledge and synthesize the evidence for the effects of NMBAs for critically ill patients with lung diseases, focusing on patient-ventilator asynchrony, ARDS, status asthmaticus, and chronic obstructive pulmonary disease.

The Effect of Recruitment Maneuvers on Cerebrovascular Dynamics and Right Ventricular Function in Patients with Acute Brain Injury: A Single-Center Prospective Study.

BACKGROUND: Optimization of ventilatory settings is challenging for patients in the neurointensive care unit, requiring a balance between precise gas exchange control, lung protection, and managing hemodynamic effects of positive pressure ventilation. Although recruitment maneuvers (RMs) may enhance oxygenation, they could also exert profound undesirable systemic impacts. METHODS: The single-center, prospective study investigated the effects of RMs (up-titration of positive end-expiratory pressure) on multimodal neuromonitoring in patients with acute brain injury. Our primary focus was on intracranial pressure and secondarily on cerebral perfusion pressure (CPP) and other neurological parameters: cerebral autoregulation [pressure reactivity index (PRx)] and regional cerebral oxygenation (rSO2). We also assessed blood pressure and right ventricular (RV) function evaluated using tricuspid annular plane systolic excursion. Results are expressed as the difference (Δ) from baseline values obtained after completing the RMs. RESULTS: Thirty-two patients were enrolled in the study. RMs resulted in increased intracranial pressure (Δ = 4.8 mm Hg) and reduced CPP (ΔCPP = -12.8 mm Hg) and mean arterial pressure (difference in mean arterial pressure = -5.2 mm Hg) (all p < 0.001). Cerebral autoregulation worsened (ΔPRx = 0.31 a.u.; p < 0.001). Despite higher systemic oxygenation (difference in partial pressure of O2 = 4 mm Hg; p = 0.001) and unchanged carbon dioxide levels, rSO2 marginally decreased (ΔrSO2 = -0.5%; p = 0.031), with a significant drop in arterial content and increase in the venous content. RV systolic function decreased (difference in tricuspid annular plane systolic excursion = -0.1 cm; p < 0.001) with a tendency toward increased RV basal diameter (p = 0.06). Grouping patients according to ΔCPP or ΔPRx revealed that those with poorer tolerance to RMs had higher CPP (p = 0.040) and a larger RV basal diameter (p = 0.034) at baseline. CONCLUSIONS: In patients with acute brain injury, RMs appear to have adverse effects on cerebral hemodynamics. These findings might be partially explained by RM's impact on RV function. Further advanced echocardiography monitoring is required to prove this hypothesis.

Anti-inflammatory therapies for acute respiratory distress syndrome.

INTRODUCTION: Treatments for the acute respiratory distress syndrome (ARDS) are mainly supportive, and ventilatory management represents a key approach in these patients. Despite progress in pharmacotherapy, anti-inflammatory strategies for the treatment of ARDS have shown controversial results. Positive outcomes with pharmacologic and nonpharmacologic treatments have been found in two different biological subphenotypes of ARDS, suggesting that, with a personalized medicine approach, pharmacotherapy for ARDS can be effective. AREAS COVERED: This article reviews the literature concerning anti-inflammatory therapies for ARDS, focusing on pharmacological and stem-cell therapies, including extracellular vesicles. EXPERT OPINION: Despite advances, ARDS treatments remain primarily supportive. Ventilatory and fluid management are important strategies in these patients that have demonstrated significant impacts on outcome. Anti-inflammatory drugs have shown some benefits, primarily in preclinical research and in specific clinical scenarios, but no recommendations are available from guidelines to support their use in patients with ARDS, except in particular settings such as different subphenotypes, specific etiologies, or clinical trials. Personalized medicine seems promising insofar as it may identify specific subgroups of patients with ARDS who may benefit from anti-inflammatory treatment. However, additional efforts are needed to move subphenotype characterization from bench to bedside.

Mechanical ventilation in patients with acute respiratory distress syndrome: current status and future perspectives.

INTRODUCTION: Although there has been extensive research on mechanical ventilation for acute respiratory distress syndrome (ARDS), treatment remains mainly supportive. Recent studies and new ventilatory modes have been proposed to manage patients with ARDS; however, the clinical impact of these strategies remains uncertain and not clearly supported by guidelines. The aim of this narrative review is to provide an overview and update on ventilatory management for patients with ARDS. AREAS COVERED: This article reviews the literature regarding mechanical ventilation in ARDS. A comprehensive overview of the principal settings for the ventilator parameters involved is provided as well as a report on the differences between controlled and assisted ventilation. Additionally, new modes of assisted ventilation are presented and discussed. The evidence concerning rescue strategies, including recruitment maneuvers and extracorporeal membrane oxygenation support, is analyzed. PubMed, EBSCO, and the Cochrane Library were searched up until June 2023, for relevant literature. EXPERT OPINION: Available evidence for mechanical ventilation in cases of ARDS suggests the use of a personalized mechanical ventilation strategy. Although promising, new modes of assisted mechanical ventilation are still under investigation and guidelines do not recommend rescue strategies as the standard of care. Further research on this topic is required.