Clinical Problem and Research Study: Acute Respiratory Distress Syndrome

Abstract

Acute respiratory distress syndrome is a disease that often requires critical care and mechanical ventilation. Effective ventilator management is a significant factor in the progression of this disease and affects mortality rates. Nursing literature supports research regarding this clinical problem and supports the need for further development in guidelines and recommendations for practice. However, when an extensive literature review was conducted, it quickly became clear that the results were far from clear. Ventilator pressure was implicated as a possible factor in lung damage at both high and low values, and the same was true for tidal volume values. This left little room for clear clinical guidelines, though there was a degree of mild consensus among the researchers that lower pressure and higher tidal volume seem to be less destructive to patients’ lung tissue. Fortunately, this plan is easy to implement using only existing tools and methods of documentation, which makes using the clinical guidelines during practice relatively simple.

Clinical Problem

Ventilator-induced lung injury refers to damage caused to the lungs by mechanical ventilation. Mechanical ventilation can cause structural damage to even normal lung tissue. In lungs previously injured by acute respiratory distress syndrome (ARDS), ventilation can make matters even worse. As for the incidence of ARDS, Thomsen and Morris (1995) found “an estimated upper limit for ARDS incidence in Utah of 8.3 ARDS patients per 100,000 . . . [W]e calculated the absolute lower limit for ARDS incidence in Utah to be 4.8 ARDS patients per 100,000” (p. 965). Given that the authors state these numbers agree with other recent estimates in the literature, these seem like safe numbers to rely upon. Since many ARDS patients will be put on ventilators, investigating the damage caused by this is vital. Additionally, there are prevention measures for ventilator-associated pneumonia.

For this clinical problem, the nature of the damage caused by ventilators is part of the definition of the area of interest. From the pathological point of view, the ventilator damage is characterized by the presence of inflammatory-cell infiltrates, hyaline membranes, increased vascular permeability, and pulmonary edema (Kumar, Abbas, Fausto, & Aster, 2012). This collection of symptoms can ultimately be summed up as a range of cellular and histological changes that simply make breathing more difficult for the patient. During the progression of ARDS, there is buildup of fluid in the alveoli, preventing the lungs from filling with air and from moving oxygen into the bloodstream, and because the mortality in patients with ARDS is high, these patients require mechanical ventilation (Kumar et al., 2012). Of course, there is naturally a conflict here in that mechanical ventilation can make ARDS worse, but in the short run, it is often the only way to save the patient’s life. The question then becomes how to mitigate the inevitable damages.

Although necessary, mechanically ventilating already damaged lungs puts ARDS patients at risk for further lung injury. Using ventilator strategies that decrease ventilator-induced injury will decrease mortality rates among patients with ARDS, which is a worthy goal (Kumar et al., 2012). The PICO question related to this clinical problem is: In patients with ARDS who are on mechanical ventilation, how does the use of higher-level positive end-expiratory pressure (PEEP) settings compare to the use of lower-level PEEP settings with respect to mortality rates? This PICO question is the result of revision, as the first clinical problem focused on influenza and mechanical ventilation. This clinical problem proved to have a focus that was too narrow, as the review of the evidence and guidelines available showed that only minimal research and data existed.

For the new clinical problem, the preponderance and the relevance of the research and knowledge available are moderate in both depth and breadth. PubMed was used as was the Cochrane library. Some of the search terms that were used that resulted in the most relevant hits were: ventilator induced lung injury, acute respiratory distress syndrome, mechanical ventilation, PEEP, lung recruitment, and recruitment maneuvers. Combining the results of both search sites, there were over 1200 hits, with approximately 100 of these hits being relevant. Key authors tended to be medical doctors and their key references tended to be those from respiratory and medical journals. The types of research that were most commonly referenced were randomized control trials, prospective randomized studies, and meta-analysis. The evidence was within a recent enough timeframe that much of the research can be considered relevant and appropriate to current practice. Most of the current and relevant literature is from the last five years.

The preponderance and the relevance of the clinical guidelines for this new clinical problem are limited, particularly in terms of the quantity of results, and this constitutes an area where no clear recommendations yet exist. A search for relevant practice guidelines yielded a mere three appropriate practice guidelines. Possible sources that were used for the guidelines search were national guideline clearinghouse and guidelines international network. MEDLINE was used to search for guidelines with the following search terms: pulmonary practice guideline, respiratory practice guideline, thoracic practice guideline, acute respiratory distress syndrome guideline, and recruitment practice guideline. That search resulted in three relevant hits, two of which dated from 2008, and the other of which dated from 2013. The three sources of the guidelines were Tufts Medical Center, University of Washington School of Medicine, and Medscape. Given the relative absence of guidelines, this must be considered the most major of the gaps in the research.

Clinical Question

Justification for a research utilization project is warranted. The amount of relevant research and evidence regarding the PICO question is strong enough to support being used and applied in clinical practice. Clinical guidelines regarding the PICO question are minimal. Further clinical guidelines and recommendations would be beneficial to address this clinical problem, and there is adequate research and evidence to support this.

Literature Review

One of the recurring themes in the literature on ventilator damage in ARDS patients is the conflict over whether higher or lower PEEP values tend to cause greater damage. For example, Stocker et al. (1997) investigated both lower pressure and the use of a prone position with good results, stating, “We assume that our low mortality in patients with severe ARDS might be due mainly to low-volume pressure-limited ventilation and prone positioning. This simple strategy seems to allow successful treatment for patients with severe ARDS” (p. 1008), and the portion of this view related to pressure was supported by the earlier work of Lachmann (1992). This would seem to indicate that lower pressure should be used, although a couple criticisms of the former article might be the small sample size and the inability to separate positioning from PEEP as variables. Regardless, however, later studies show a shift away from this thinking. Though Muscedere, Mullen, Gan, and Slutsky (1994) agreed that high pressure can be damaging at large tidal volumes, they also found that there are cases where low pressure, too, is damaging, explaining, “[V]entilation at very low lung volumes can also worsen lung injury by repeated opening and closing of airway and alveolar duct units . . . In conclusion, ventilation at [low] volumes . . . caused . . . lung injury” (p. 1327). This shows that the PEEP values, whether high or low, have interesting interactions with the tidal volumes, so that it is not enough to point to these levels on the ventilator alone as implicated in lung damage. As so often happens, as the literature progresses, the understanding becomes more complex.

Moving into the modern literature on the topic, it is plain to see that things are not as straightforward as they once seemed and that the issue of how best to treat ARDS patients on ventilators is still very much up for debate. One instance of this arises in Brower et al. (2004), who found that, “These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation . . . clinical outcomes are similar whether lower or higher PEEP levels are used” (p. 327), a result which directly contradicts that of Talmor et al. (2008). Since both studies were generally well-conducted and expressed only minimal limitations, it is an unfortunate finding that the support for various theories seems so mixed. For yet another viewpoint, one might read Meade et al. (2008), who found, “similar mortality in patients with a . . . ventilation strategy designed to open the lung compared with [a low-tidal-volume] ventilation strategy. We found no evidence of . . . increased risk of barotrauma despite the use of higher PEEP” (p. 637). In other words, according to this team, no changes to the ventilator settings seem to be strong predictors of lung trauma and given that the researchers’ final p-values were quite impressive for this study, these results should be given greater weight than some of the others. Yet Tremblay and Slutsky (2012) found results that seem to hearken back to those of the studies done in 1990s, suggesting again that high PEEP values are to blame for damage. As if this did not already confuse the matter enough, there are even stranger results. Added to the earlier finding of low tidal volume being problematic, Ranieri (2013) found that high tidal volume was an issue as well. Taken altogether, the literature seems to be at a bit of a loss over this topic.

Interestingly, though, there have also been recent animal studies on this topic, which of course are usually good sources for information because ethical parameters allow for a more truly experimental approach with animals than with humans. Roy et al. (2013) investigated ways to not only treat but prevent ARDS with the use of a ventilator, explaining that, “[Systemic inflammatory response syndrome]-induced ARDS can be prevented with high airway [pressure time profile] when [airway pressure release ventilation] is used early in the course of mechanical ventilation in a clinically relevant translational porcine model of lung injury” (p. 38). If this can be translated from porcine subjects to human ones, it would be an inspiring outcome for the messy debate over ventilator PEEP levels. Roy et al. explained that airway pressure release ventilation seemed to cancel out pretty much every symptom of ARDS, “ preserving alveolar epithelial integrity, reducing lung edema, preserving surfactant, and maintaining alveolar stability” (p. 38). If this can be translated to humans, perhaps the entire need to debate PEEP values and tidal volume for ARDS patients will disappear as preemptive ways to prevent ARDS are developed. Until then, however, the current contradictory mix of findings in the literature must suffice.

Synthesis of Research

Overall, the research is very unsatisfactory with very few cases where two different studies completely agree. It is unclear why this is the case, but it may simply be that the two primary variables being investigated—namely, PEEP and tidal volume—are not the relevant components for the outcomes of ARDS patients who are placed on ventilators. One of the major gaps in the literature is an attempt to unify all the existing findings in a grand literature review comparing the number of studies in various different categories depending on their findings. This might help to clarify just what is going on with the study of ARDS and ventilator-induced lung damage. It would also be nice to see a study using database information rather than actual patients, as the number of ARDS patients in even the largest hospitals at any given time seems to provide for only rather small sample sizes. If permission could be gained to gather information from multiple hospitals on PEEP values, tidal volumes, and patient outcomes, this could make for a much vaster field of data to work with. Another approach to filling this gap might be to survey doctors and discover which levels are most commonly used for both PEEP and tidal volume, so that at least the general standard of care is better known. Based on the information available at present, however, it may be challenging to devise reasonable clinical practice guidelines.

Clinical Practice Guidelines

For clinical practice, the closest to practice guidelines that can be made would indicate moderately low PEEP levels and moderately high tidal pressure for ARDS patients. There is not quite a consensus on this in the literature, as the results vary, but given that a slight preponderance of the evidence seems to point in this direction, this is the best choice available. Because of the low overall degree of agreement between researchers, in terms of the strength of research taxonomy model, the highest grade the recommendations can be given is a B—also known as level two—if one is to be charitable. On the positive side, at least the studies are usually quite patient-based and are not mere case studies, and the guidelines can be applied quite broadly with no distinctions made between the various demographic or other categories of ARDS patients. Still, the mixed results impact the reliability and the applicability of the guidelines alike.

Applicability of Guidelines

The resources needed to implement and evaluate the guidelines are none, as the only relevant equipment items—the ventilators—are already in locations where ARDS patients will be treated by definition. In terms of knowledge, as well, the resources needed are nil, because doctors, nurses, and technicians in these environments will already know how to operate the equipment and will have an idea of the range of the possible PEEP levels and the possible tidal volume values. Outcomes will be difficult to evaluate on a basis of lung damage alone, which is why mortality rates should be used as a proxy, as they are in many studies. This will fit into the plan for implementation.

Plan for Implementation in a Clinical Setting

Overall, to implement this plan in a clinical setting, one must involve the key stakeholders. In this case, that includes hospital administrators and possibly board members, doctors, nurses, and technicians. Patients, too, can be considered stakeholders, of course, but their role is less relevant. The formal processes that must be put in place overlap with normal documentation and thus, in the end, there is very little extra required to fulfill this plan.

References

Brower, R. G., Lanken, P. N., MacIntyre, N., Matthay, M. A., Morris, A., Ancukiewicz, M., ... & Thompson, B. T. (2004). Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. The New England Journal of Medicine, 351(4), 327-336.

Kumar, V., Abbas, A. K., Fausto, N., & Aster, J. C. (2012). Robbins and Cotran: Pathologic basis of disease (8th ed.). Philadelphia, PA: Elsevier.

Lachmann, B. (1992). Open up the lung and keep the lung open. Intensive Care Medicine, 18(6), 319-321.

Meade, M. O., Cook, D. J., Guyatt, G. H., Slutsky, A. S., Arabi, Y. M., Cooper, D. J., ... & Lung Open Ventilation Study Investigators. (2008). Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: A randomized controlled trial. JAMA, 299(6), 637-645.

Muscedere, J. G., Mullen, J. B., Gan, K., & Slutsky, A. S. (1994). Tidal ventilation at low airway pressures can augment lung injury. American Journal of Respiratory and Critical Care Medicine, 149(5), 1327-1334.

Ranieri, V. M. (2013). Does high tidal volume generate ALI/ARDS in healthy lungs? Applied Physiology in Intensive Care Medicine 2: Physiological Reviews and Editorials, 2, 375.

Roy, S., Habashi, N., Sadowitz, B., Andrews, P., Ge, L., Wang, G., ... & Nieman, G. (2013). Early airway pressure release ventilation prevents ARDS: A novel preventive approach to lung injury. Shock (Augusta, Ga.), 39(1), 28-38.

Stocker, R., Neff, T., Stein, S., Ecknauer, E., Trentz, O., & Russi, E. (1997). Prone positioning and low-volume pressure-limited ventilation improve survival in patients with severe ARDS. CHEST Journal, 111(4), 1008-1017.

Talmor, D., Sarge, T., Malhotra, A., O'Donnell, C. R., Ritz, R., Lisbon, A., ... & Loring, S. H. (2008). Mechanical ventilation guided by esophageal pressure in acute lung injury. New England Journal of Medicine, 359(20), 2095.

Thomsen, G. E., & Morris, A. H. (1995). Incidence of the adult respiratory distress syndrome in the state of Utah. American Journal of Respiratory and Critical Care Medicine, 152(3), 965-971.

Tremblay, L. N., & Slutsky, A. S. (2012). Ventilator-induced lung injury: From the bench to the bedside. In Applied Physiology in Intensive Care Medicine 1 (pp. 343-352). Berlin: Springer Berlin-Heidelberg.