Oxigenação por membrana extracorpórea versus terapia convencional em pacientes com insuficiência respiratória aguda: Revisão sistemática com metanálise de ensaios clínicos randomizados

Abstract

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by the accumulation of fluid in the pulmonary alveoli, depriving organs of receiving oxygen and posing a risk of death to the patient. One of the methods of oxygen therapy for this syndrome involves the use of mechanical ventilation, which can be invasive or non-invasive. However, in some cases, ARDS may be refractory to conventional oxygen therapy by mechanical ventilation, necessitating other supportive patient therapies such as extracorporeal membrane oxygenation (ECMO). The objective of this study was to identify whether the use of extracorporeal membrane oxygenation therapy, compared to conventional invasive and non-invasive mechanical ventilation, can reduce mortality rates, and improve patients' quality of life. The length of hospital stays and adverse events that occurred during the studies were also evaluated. A systematic review of controlled randomized clinical trials (RCTs) was proposed, following the Cochrane methodology and guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The research question was formulated using the PICO-S framework, where the study population comprised, patients aged 12 years or older, admitted to intensive care units (ICUs) with moderate or severe ARDS. The search was conducted in the following databases: Cochrane Library, Bireme, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), Web of Science, Scielo, and Latin American and Caribbean Health Sciences Literature (LILACS). Grey literature studies were also included to minimize publication bias. The selected studies were RCTs without language restrictions, following pre-established inclusion and exclusion criteria. Two researchers conducted the literature search, assessed study eligibility criteria, extracted data, and in cases of disagreement, consensus discussions were held without the involvement of a third reviewer. An assessment of risk of bias was conducted using the Cochrane Risk of Bias Tool for Randomized Trials (RoB-2) version 2019. The quality of evidence was evaluated using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) tool. Heterogeneity was assessed using the I2 statistic and Chi-squared test. Clinical data were extracted as reported in the studies, analyzed for comparability between participants and interventions, and, when possible, tabulated and examined in a forest plot. The primary outcome, mortality, was considered as a dichotomous variable, and a fixed-effect model was chosen using the PETO method (odds ratio) for analysis. The secondary outcome, length of hospital stay, was treated as a continuous variable, employing the inverse variance statistical method, and the standardized mean difference (SMD) was used as the measure of effect. Out of the 2,561 articles identified in the conducted searches, 6 studies were selected. Within these six studies, 1,050 participants with the identified inclusion criteria characteristics were identified. Only one of the studies was conducted at a single healthcare center, while the others were conducted at multiple healthcare centers. Following the randomization criteria, 519 patients were allocated to the ECMO intervention group, and 531 patients were allocated to the conventional treatment group. Participants in the intervention group underwent the following types of extracorporeal ventilation therapy: VA-ECMO, VV-ECMO, VV-ECCO2-R, and AV-ECCO2-R. In the bias risk analysis, 3 of the studies yielded "some concerns" results, while the other 3 studies were classified as "high risk of bias," mainly due to the assessment of the "deviations from intended/planned interventions" domains and the "selection of reported outcomes”. For the evaluation of the primary outcome of 30-day mortality, the odds ratio (OR) found was 0.90 (95% CI: 0.66 - 1.21); for 60-day mortality, the OR was 0.78 (95% CI:0.50 - 1.21); for 90-day mortality, the OR was 0.90 (95% CI: 0.66 - 1.21); and for 180-day mortality, the OR was 0.62 (95% CI: 0.36 - 1.06). Therefore, no significant difference was observed between the groups within the confidence intervals. The assessment of heterogeneity for this outcome was low, with an I2 below 25% and p > 0.10. Regarding the evaluation of the quality of evidence, mortality at 30 and 90 days was classified as "very low"; for 60-day mortality, the classification was "low"; and for 180-day mortality, it was classified as "moderate". The secondary outcome of total hospital stay showed a standardized mean difference of 0.39 (95% CI: 0.13 - 0.65); whereas the ICU stay had a standardized mean difference of 0.33 (95% CI: 0.05 - 0.60), indicating a favorable trend towards a shorter hospital stay for patients undergoing conventional treatment, despite substantial heterogeneity among the studies with an I2 above 69% and p < 0.10. The evaluation of the quality of evidence for both overall hospital stays and ICU stay was classified as "moderate". No statistically significant difference in mortality was observed between the intervention group (ECMO) and the control group (VM) during the various analyzed periods. However, it was statistically proven that participants in the conventional therapy group had a shorter length of hospital stay, both in total hospital stay and in ICU stay, although with high heterogeneity among the studies for this outcome. Regarding quality of life, the studies provided limited contribution for a more conclusive assessment. As for adverse events, similarities were observed in some common events, but bleeding (non-neurological), thrombocytopenia, hemolysis, and issues with the cannulation process were clearly evident in the extracorporeal therapy groups.