The Impact of Prone Position Ventilation on Survival in Patients with Severe Acute Respiratory Distress Syndrome (ARDS)

INTRODUCTION: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition characterized by hypoxemic respiratory failure, leading to significant morbidity and mortality among critically ill patients. Mechanical ventilation is a cornerstone in the management of ARDS, aiming to improve oxygenation and support respiratory function. Despite advancements in ventilation strategies, mortality rates remain high in severe ARDS cases. Prone position ventilation, involving placing patients in a face-down position during mechanical ventilation, has shown promising results in improving oxygenation and lung mechanics by optimizing ventilation-perfusion relationships. Previous studies have suggested that prone positioning may reduce mortality rates and improve outcomes in patients with severe ARDS. However, the evidence supporting its impact on survival remains inconclusive, necessitating further investigation. BACKGROUND: In the last few years prone positioning has been used increasingly in the treatment of patients with acute respiratory distress syndrome (ARDS) and this manoeuvre is now considered a simple and safe method to improve oxygenation. However, the physiological mechanisms causing respiratory function improvement as well as the real clinical benefit are not yet fully understood. The aim of this review is to discuss the physiological and clinical effects of prone positioning in patients with ARDS. The main physiological aims of prone positioning are: 1) to improve oxygenation; 2) to improve respiratory mechanics; 3) to homogenise the pleural pressure gradient, the alveolar inflation and the ventilation distribution; 4) to increase lung volume and reduce the amount of atelectatic regions; 5) to facilitate the drainage of secretions; and 6) to reduce ventilator-associated lung injury. OBJECTIVES: To evaluate the impact of prone position ventilation on mortality rates in patients with severe ARDS. To assess the effects of prone positioning on oxygenation indices, ventilation parameters, and potential adverse events. To provide evidence-based recommendations for clinical practice and future research. MATERIALS & METHODS: This randomized clinical trial involved 77 non-intubated patients aged over 65 years in a general ICU. We conducted a retrospective observational cohort study of critically ill intubated patients with COVID-19 who were placed in the prone position between May, 2023 and November, 2023. Exclusion criteria were pregnancy, reintubation, and previous prone positioning at a referring hospital. Patients were followed up until hospital discharge. The primary outcome was oxygenation assessed by partial pressure of oxygen/fraction of inspired oxygen ratio (PaO2/FiO2) ratio. A positive response to proning was defined as an increase in PaO2/FiO2 ratio ≥20%. Treatment failure of prone positioning was defined as death or requirement for extracorporeal membrane oxygenation (ECMO). RESULTS: Forty-two subjects (29 males; age: 59 [52e69] yr) were eligible for analysis. Nine subjects were placed in the prone position only once, with 25 requiring prone positioning on three or more occasions. A total of 31/42 (74%) subjects survived to discharge, with five requiring ECMO; 11/42 (26%) subjects died. After the first prone positioning session, PaO2/FiO2 (mean (standard deviation)) ratio increased from 17.9 kPa (7.2) to 28.2 kPa (12.2) (P<0.01). After the initial prone positioning session, subjects who were discharged from hospital were more likely to have an improvement in PaO2/FiO2 ratio ≥20%, compared with those requiring ECMO or who died. DISCUSSION: Managing delirium is a vital objective when caring for ICU patients, particularly the elderly population. Prolonged delirium is associated with elevated mortality rates and an increased likelihood of hospital readmissions (18). Previous studies have shown that brain volume and weight decreased with age (20-22), and structural and functional changes in brain regions, such as the hippocampus, have been reported in older populations (24-26). As a result, elderly patients experience a higher occurrence of delirium than other populations. Moreover, patients with delirium lasting less than 24 hours tend to have similar outcomes to those without delirium. (Therefore, the presen tstudy evaluated delirium in patients over 65 years. This open-label randomized clinical trial compared the safety and efficacy of low-dose ketamine to dexmedetomidine in the incidence and control of delirium among elderly ICU patients. The study showed no significant difference between the two treatment sinterms of delirium (basedon RASS scores) at different times (5, 10, and 15 minutes) after the intervention in older patients. This finding suggests that both ketamine and dexmedetomidine had a similar effect on delirium in this specific population. These findings indicate that when it comes to the primary outcome of reducing delirium, there was no advantage of using one medication over the other. Additionally, the present study did not show any significant side effects associated with either ketamine or dexmedetomidine treatment. The absence of significant side effects observed in the dexmedetomidine group is an important finding, indicating that low-dose dexmedetomidine was well tolerated by the elderly ICU patients in the trial. This is a positive outcome as it suggests that this medication canbe safely used in this context without causing significant adverse effects. Therefore, dexmedetomidine can be considered a safe option for managing delirium in this specific patient group. On the other hand, the study demonstrated a significant reduction in RASS scores within each treatment group at 5, 10, and 15 minutes, compared to the baseline of 0 minutes. This reduction in RASS scores indicated that low-dose ketamine was effective in reducing delirium among these patients. Therefore, the study concludes that dexmedetomidine was successful in achieving the desired outcome of reducing delirium severity in elderly ICU patients. Overall, based on the aforementioned findings, the study suggests that low-dose ketamine and dexmedetomidine have similar efficacy and safety profiles in the prevention and management of delirium among elderly ICU patients, and these results suggest that low-dose dexmedetomidine can be considered a viable option for the control of delirium in elderly ICU patients. The present study's findings contrast with those of Heydari et al.'s randomized clinical trial conducted in 2018. The aforementioned study demonstrated that the time required to achieve adequate sedation was significantly longer in the Dexmedetomidine group (0.2 μg/kg/h, titrated by 0.1 μg/kg/h) than in the ketamine group (4 mg/kg). However, there was no difference in sedation scores between the two groups 15 minutes after the intervention. CONCLUSIONS: The present study suggests that the administration of low-dose Dexmedetomidine to elderly ICU patients might reduce delirium incidence, supporting its beneficial effect for delirium control. KEYWORDS: Delirium, Ketamine, Dexmedetomidine, Elderly patients, ICU