Introduction
This literature review analyses the complexity of acute respiratory distress syndrome (ARDS), which has been studied extensively for half a century. However, despite improved comprehension, ARDS remains associated with 10% of all intensive care unit (ICU) admissions and high 35-46% mortality (Bellani et al., 2016). NHS UK (2020) states that 1 in 3 ARDS patients die. ARDS represents inflammatory processes that lead to lung injury, reducing lung compliance that leads to severe hypoxemia (Nanchal and Truwit 2018). Ranieri et al. (2012) dwelled on the updated and revised Berlin Definition for ARDS and proposed three categories of ARDS based on the level of hypoxemia: mild (PaO2/FIO2 ≤ 300 mmHg), moderate (PaO2/FIO2 ≤ 200 mmHg), and severe (PaO2/FIO2 ≤ 100 mmHg), in conjunction with the accompanying factors for severe ARDS (Figure 1).
Once patients develop ARDS, the primary interventions aim to reduce Ventilator-Induced Lung injury (VILI) (Thompson, Chambers, and Liu, 2017). Several improved interventions are used for ARDS patients (ECMO) (He et al., 2022). Furthermore, neuromuscular blocking agents (NMBAs) are a known prescription for ARDS; as believed, they minimize inflammation, rate of oxygen use, and blood pumped per minute, and most importantly, assist with ventilator synchrony (Torbic and Duggal, 2019). The assessment of available literature on the treatment of ARDS is essential in understanding the progress and challenges in the treatment of the problem.
In 2010, the ACURASYS trial was conducted by 20 ICUs reporting improved adjusted survival using early neuromuscular blockade (NMB) for moderate to severe ARDS (Papazian et al., 2010). However, there was a notable reluctance to NMB usage due to the side effects. Furthermore, many argued that the mortality difference was insignificant and that the study was underpowered, involving only 340 participants. Subsequently, in 2019, the Faculty of Intensive Care Medicine (FICM) and Intensive Care Society (ICS), supported by the British Thoracic Society (BTS), formed guidelines for the management of adult patients with ARDS recommending using NMB. On the other hand, due to a lack of studies comparing NMB with deep sedation with light sedation only, the ROSE trial was conducted and published in 2019, reporting that neuromuscular blockade was not beneficial in patients with ARDS (Huang et al., 2017). However, it had a higher positive end-expiratory pressure (PEEP), which proved helpful for ARDS patients and could have affected the results.
Aim
This literature review deals with the effectiveness of NMB with heavy sedation compared to usual care with light sedation in patients with moderate to severe ARDS. The primary outcome will be to investigate the effect of NMB on 28-day mortality. The secondary products are to examine its impact on the 90-day mortality rate, VILI prevention/reduction, and increased ventilator-free days. The author recognizes the importance of improving the management of ARDS patients because of reducing mortality and will examine and evaluate existing literature to support or challenge current practice.
Search Strategy
The acquisition of studies on ARDS was made through an online search in reputable medical journals. The selected journals include CINAHL, Medline, and Cochrane Library. Several studies were reviewed, and five have been selected for this paper. The research studies have been chosen by the criteria of a study’s sample size, sample size estimates, generalisability to clinical practice, and comparison to other research. Trial sequential analysis was used in the investigation, and the results showed that the present information size did not exceed the sequential monitoring barrier created by the ideal information size, indicating an inadequate sample size for examining the shortened mortality. The perfect patient sample size was calculated to achieve the attainable endpoint.
Literature Review
The first article is by Wongtangman et al. (2021). The study was published in July 2021. The researchers aimed to examine the impacts of optimal sedation in patients who received neuromuscular blocking agent infusions to treat ARDS. The quantitative study used a cohort study approach to collect data. The methodology entailed the assessment of the outcomes for prolonged deeper sedation of patients who received neuromuscular blocking agent infusions compared to those who did not receive neuromuscular blocking agent infusions. The inclusion criteria encompassed being an ARDS patient intubated and mechanically ventilated in the ICU within the selected hospital network (a sample population of 3,419, of which 577 were treated with neuromuscular blocking agent infusions). From the point of EBP, the outcomes revealed that prolonged high proportion deeper sedation is associated with higher mortality for patients with respiratory distress syndrome as the sample population with increased mortality had an outcome p < 0.001. The replicability of and reliance on existing clinical data could contribute to treating patients with respiratory distress syndrome.
The methodology was effective in acquiring the required data to meet the research aims. The approach supports evidence-based practice by addressing a clinical problem affecting patient outcomes. The study’s outcomes will be essential in informing practice approaches for physicians treating patients with the same issue. The research does not show bias since the selected sample population is patients whose data was already recorded. The validity of the outcomes is assured through the methodology that relies on a proven method (Wongtangman et al., 2021). The reliability of the results may be challenged due to the limitations present in the demographic of the patients.
The drawback in the methodology relates to the demographic of the sample population. The study used samples from seven ICUs from one hospital network. While the patients treated during the study are many, it may be difficult to replicate similar outcomes in areas that do not share similar characteristics with the ICUs used in this study. The study outcomes can be generalized in clinical practice since sedation is already discouraged in treating ARDS. The study’s outcomes align with previous studies that do not promote the use of sedation in ARDS treatment.
The second study was written by Chang et al. and published in February 2020. This investigation aimed to synthesize up-to-date trials to validate the effects of neuromuscular blocking agents (NMBA)’ effects in patients receiving ARDS. The researchers used a qualitative study approach adopting the meta-analysis method to assess studies done on ARDS. The methodology used in this study aimed to evaluate all identified randomized trials that assessed the use of NMBA. The researchers did not provide information on the calculation of the sample size for the articles that were included in the meta-analysis. The inclusion criteria used in the study was a randomized trial investigating the use of NMBAs in patients with moderate-to-severe ARDS. Included articles were also required to report mortality data. The search strategy was not as effective as expected since only seven trials that had enrolled 1598 patients were included in the meta-analysis, indicating that research on the topic requires more research.
The study results were retested using both fixed-effects and random-effects models, and neither model’s favoring directions changed. The retesting was vital in ensuring the reliability of the study outcomes. From the point of EBP, the findings are important because they indicated that using NMBAs could dramatically lower mortality in patients with moderate-to-severe ARDS and lower the risk of barotrauma during mechanical breathing (Chang et al., 2020). The impact of NMBA use in ARDS needs to be further validated by more large-scale randomized trials. The study’s methodology has strengths in terms of its replicability. It allows other researchers to test the validity of the outcomes. The reliability of the outcomes is ensured in the retesting done on the results, ensuring that the outcomes will be replicated in similar studies. The researchers were thorough in the methodology, which is essential in ensuring that the study outcomes can be generalized. The existence of bias in the selection of studies that will be synthesized may interfere with the use of the study outcomes and their generalisability. The study outcomes are generalizable in clinical practice and conform to other researchers who have attained similar outcomes.
The article by Tarazan et al. (2020) was the third study in the review. The researchers aimed to validate using neuromuscular blocking agents to treat ARDS in acute respiratory distress syndrome. They used a qualitative study approach in which systematic review and meta-analysis were used for data collection and assessment. The inclusion criterion for the study entailed being a randomized continuous trial published in the selected journal databases and clinical trial registries. The randomized trials should compare the effects of NMBA as a continuous infusion with a placebo or no NMBA infusion. The EBP-based benefit of the study conducted by Tarazan et al. (2020) was that the researchers investigated NMBA infusion’s effect on mortality depending on the control arm’s approach, exhibiting decreased mortality compared to profound sedation but no benefit compared to milder sedation of P = 0.008 from a low certainty of P = 0.003. Although NMBAs lessen barotrauma, how they affect other outcomes is still unknown. The replicability of their methodology will be essential in proving the study outcomes when the same method is used to measure the same issue.
Some of the experimental findings in this updated systematic review may be further clarified by future research, such as a meta-analysis of individual patient data. The methodology effectively addressed the research aim (Tarazan et al., 2020). The step-by-step approach can allow replication of the study to determine the accuracy of the outcomes. The methodology showed rigor in selecting studies to be included in the review and meta-analysis. Validity and reliability are achieved through the researchers’ use of the meta-analytical method to identify the most relevant studies. The drawbacks of the methods include possible bias in the selection of studies since a clear inclusion criterion for the studies is not specified.
The fourth study was done by Shao, Kang, and Tong, whose research was published in 2020. The qualitative research adopted the systematic review and meta-analysis approaches to examine the use of early neuromuscular blocking agents to treat adults with acute respiratory distress syndrome. The inclusion criterion was the use of randomized control trials that compared the treatment of the impact of NMBA with traditional treatment. The strength of the sample is not determined. The study has its share of advantages and disadvantages. This paper offers an exhaustive systematic assessment of the effectiveness of neuromuscular blocking drugs for patients with acute respiratory distress syndrome, including meta-analysis and meta-regression. Of all reviews on the subject, it contains the most randomized controlled trials. This was beneficial to the EBP potential of the research because short-term and long-term mortality rates were analyzed using sequential trial analysis to improve the accuracy and stability of findings. The outcomes of the study are generalizable to clinical practice and similar to previous studies.
It was challenging to reach definitive conclusions because the systematic evaluation comprised research generally of low quality. The potential cause of heterogeneity in the 90-day mortality data was not identified in the meta-regression (Shao, Kang, and Tong 2020). The meta-regression analysis for the 21–28-day mortality revealed that heterogeneity was related to the difference in sample size. Drawbacks are common in systematic reviews because the inclusion of research manuscripts relies on the researchers’ preferences. The step-by-step approach could result in replicating the process to determine outcome accuracy. The methodology was thorough in selecting studies for the review and meta-analysis. The researchers’ use of the meta-analytical method, based on validity and reliability, facilitated the identification of the most relevant studies. The replicability of their methodology will be essential in proving the study outcomes when the same method is used to measure the same issue.
The fifth article is by Tao et al. (2018), where the study used the qualitative method in which the meta-analysis approach was used to examine the use of neuromuscular blocking agents to treat adult patients with acute respiratory distress syndrome. The aim was to determine whether neuromuscular blocking agents (NMBAs) affect adult patients with acute respiratory distress syndrome. Being in line with EBPs, the current article contains knowledge bases in addition to randomized controlled trials that assessed NMBAs compared to placebo or standard care in adult patients with ARDS. The inclusion criteria were the use of randomized control trials that compared the treatment of the impact of NMBA with traditional treatment. The outcomes of the latest experiment support the value of NMBAs. With ARDS, the present meta-analysis has several restrictions. First, the trials used in the recent study’s limitations, small sample size, absence of long-term data, and other issues with meta-analysis follow-up for paresis and severe sedation were utilized as a preventative measure of possible bias and heterogeneity caused by the cohort. The outcomes of the study are generalizable to clinical practice and similar to previous studies.
Discussion
Acute respiratory distress syndrome is a significant health issue causing a high number of ICU admissions to infected people and increasing the risk of mortality. The considerable threats associated with ARDS have led to more studies to determine the most effective approaches to addressing the issue (Hasan et al., 2020). Current literature shows that several interventions have been developed to try and treat ARDS. Neuromuscular blockades are the most common interventions among physicians. The intervention has been under research by scholars who have shown promising outcomes with continued research. Several trends were evident in the review that assessed the treatment of ARDS and associated factors.
The review had five articles addressing various factors. Four manuscripts identified and included in the study were systematic reviews and meta-analyses. One cohort study measured the correlation between sedation and ARDS outcomes (Wongtangman et al., 2021). Based on the outcomes, physicians are recommended to limit the use of sedation in interventions due to the positive correlation that was established between mortality and ARDS patients who were sedated. The outcomes of the reviews and meta-analyses showed that NMBs are the most popular intervention for various patient populations. Common trends in the outcomes included NMBs being identified to be effective in reducing mortality rates among patients with moderate to severe ARDS (Chang et al., 2020). The clinical intervention was determined to be effective in achieving positive outcomes. However, the scholars recommended that studies be conducted to determine the impacts of the intervention on other health-related areas.
Other factors affecting the results include initial admission for acute respiratory failure, chronic kidney disease, the day and severity of ARDS, clinically severe obesity, fluid-management strategy, and nutritional support. Still, they were not evaluated in the five RCTs that made up the current meta-analysis. Re-evaluation of the Systemic Early Neuromuscular Blockade (ROSE) experiment, another multicentre clinic trial, will offer conclusive early neuromuscular blockade data with a sizable sample size, background care in line with current best practice, and extensive long-term results. Due to the restricted data, subgroup analyses stratified by patient populations, such as those with sepsis, injuries, and other reasons, were planned but not carried out. According to observational research comparing cisatracurium and vecuronium in patients at risk for and already suffering from ARDS, there was no discernible difference in death or hospital days between the two groups.
In contrast to the vecuronium group, the cisatracurium group had fewer ventilator days and ICU days. The ROSE trial will exclusively study cisatracurium; the impact of other frequently used NMBAs on ARDS has not yet been determined. In conclusion, NMBA-based protective breathing techniques for treating patients with moderate to severe ARDS reduce mortality. Further studies should be done to measure the effectiveness of the various interventions that are used for ARDS. Future studies should address the prevalence of multiple forms of bias to enhance the validity of their studies.
Conclusion
Infusions of neuromuscular blocking agents have conflicting results in two previously published trials on individuals with acute respiratory distress syndrome. The amount of more profound sedation is thought to be a mediator of the impact on mortality. It was discovered that persistent, high levels of profound sedation were linked to higher mortality. The information supports the idea that doctors should shorten deeper sedative periods once patients recover from neuromuscular infusions. This meta-analysis ultimately comprised seven trials, including 1598 patients. Using neuromuscular blocking agents (NMBA) may reduce mortality in patients with moderate-to-severe ARDS. In terms of ICU and ventilation-free days, there was no discernible difference between the NMBA and control groups. The authors note that additional large-scale randomized trials are required to confirm the impact of NMBA usage in ARDS. NMBAs could dramatically lower the incidence of barotrauma during mechanical breathing, according to a previous version of this article.
Neuromuscular blocking medications are supported by current clinical practice recommendations for acute respiratory distress syndrome. A recent randomized clinical investigation has raised concerns about this procedure. An earlier systematic study was revised to assess the effectiveness and safety of NMBAs in ARDS. Carefully chosen randomized controlled trials (RCTs) compared the therapeutic effect of NMBAs with conventional therapy in patients with ARDS. 90-day mortality was the main result. Secondary outcomes were death in the 21–28-day range, problems linked to NMBA, days without ventilation, and days spent outside the ICU by day 28. The findings suggested that using NMCAs might lower mortality for 21–28 days. They did not lower acute respiratory distress syndrome patients’ mortality rates. Agents that suppress neuromuscular activity significantly lead to lower critical care unit mortality. Patients with moderate to severe ARDS have a lower mortality rate while receiving protective breathing techniques based on NMBA therapy.
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