Acute respiratory distress syndrome: how do patients fare after the intensive care unit?

Roselaine Pinheiro de Oliveira Cassiano Teixeira Régis Goulart Rosa About the authors

RESUMO

Os pacientes com síndrome do desconforto respiratório agudo requerem estratégias ventilatórias que demonstraram ser importantes na redução da mortalidade em curto prazo, como ventilação protetora e ventilação em posição prona. No entanto, os pacientes que sobrevivem têm permanência prolongada, tanto na unidade de terapia intensiva como no hospital, e experimentam redução na satisfação global com a vida (independência, aceitação e perspectiva positiva), na saúde mental (ansiedade, depressão e sintomas de transtorno de estresse pós-traumático), na saúde física (estado físico, atividades da vida diária, fadiga e fraqueza muscular), na saúde social e na capacidade de realização de suas atividades sociais (amigos ou relações familiares, hobbies e atividades sociais).

Descritores:
Síndrome do desconforto respiratório do adulto; Qualidade de vida; Unidades de terapia intensiva

ABSTRACT

Patients with acute respiratory distress syndrome require ventilation strategies that have been shown to be important for reducing short-term mortality, such as protective ventilation and prone position ventilation. However, patients who survive have a prolonged stay in both the intensive care unit and the hospital, and they experience a reduction in overall satisfaction with life (independence, acceptance and positive outlook) as well as decreased mental health (including anxiety, depression and posttraumatic stress disorder symptoms), physical health (impaired physical state and activities of daily living; fatigue and muscle weakness), social health and the ability to participate in social activities (including relationships with friends and family, hobbies and social gatherings).

Keywords:
Respiratory distress syndrome, adult; Quality of life; Intensive care units

INTRODUCTION

Acute respiratory distress syndrome (ARDS) is characterized by bilateral opacities, noncardiogenic pulmonary edema and hypoxemia, with arterial oxygen partial pressure to fractional inspired oxygen ratio (PaO2/FIO2) < 300 and positive end-expiratory pressure (PEEP) ≥ 5cmH2O; it may occur in response to different insults, such as sepsis, trauma, pneumonia or massive transfusion.(11 ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-33.,22 Bell RC, Coalson JJ, Smith JD, Johanson WG Jr. Multiple organ system failure and infection in adult respiratory distress syndrome. Ann Intern Med. 1983;99(3):293-8.) Due to hypoxemia, patients with ARDS require ventilation strategies (protective ventilation and prone ventilation) that have been shown to be important in reducing short-term mortality.(33 Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-8.

4 Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, Di Giulio P, Fumagalli R, Pelosi P, Brazzi L, Latini R; Prone-Supine Study Group. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med. 2001;345(8):568-73.
-55 Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guérin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107-16.) However, surviving patients have prolonged stays in both the intensive care unit (ICU) and the hospital, and they experience reduced overall satisfaction with life (independence, acceptance and positive outlook), mental health (anxiety, depression and symptoms of posttraumatic stress disorder - PTSD), physical health (physical state, activities of daily living, fatigue and muscle weakness), social health and the ability to participate in social activities (relationships with friends and family, hobbies and social gatherings).(66 Hashem MD, Nallagangula A, Nalamalapu S, Nunna K, Nausran U, Robinson KA, et al. Patient outcomes after critical illness: a systematic review of qualitative studies following hospital discharge. Crit Care. 2016;20(1):345.) This combination of sequelae is called "post-intensive care syndrome" and is a complex combination of cognitive, psychological and motor symptoms.(77 Rawal G, Yadav S, Kumar R. Post-intensive care syndrome: an overview. J Transl Int Med. 2017;5(2):90-2.)

The objective of this review was to describe findings of post-intensive care syndrome in patients with ARDS who survived the ICU stay.

LONG-TERM MORTALITY

Unlike other critical diseases, ARDS is associated with a substantial risk of in-hospital mortality but a surprisingly low risk of long-term mortality. Apparently, the first six months after discharge represent the period of greatest lethality for this population, and the estimated mortality of ARDS survivors is 12% at 1 year, 15% at 2 years and 19% at the 5-year follow-up.(88 Baldwin M, Wunsch H. Mortality after critical illness. In: Stevens RD, Hart N, Herridge MS, editors. Textbook of post-ICU medicine: the legacy of critical care. United Kingdom: Oxford University Press; 2014.) These data differ from the findings of general cohorts of ICU survivors, for whom excessive mortality in the first 5 years of follow-up is reported. These cohorts include patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) or with respiratory failure secondary to septic shock, clinical situations with pathophysiological mechanisms of lung injury different from those found in ARDS. In particular, patients with COPD tend to have poor long-term outcomes after severe illness, with a 5-year mortality rate of 76%.(88 Baldwin M, Wunsch H. Mortality after critical illness. In: Stevens RD, Hart N, Herridge MS, editors. Textbook of post-ICU medicine: the legacy of critical care. United Kingdom: Oxford University Press; 2014.)

PHYSICAL STATE AND ACTIVITIES OF DAILY LIVING

Biehl et al.(99 Biehl M, Kashyap R, Ahmed AH, Reriani MK, Ofoma UR, Wilson GA, et al. Six-month quality-of-life and functional status of acute respiratory distress syndrome survivors compared to patients at risk: a population-based study. Critical Care. 2015;19:356.) evaluated the functional status (using the 12-Item Health Survey - SF-12 and Barthel's index) of ARDS survivors six months after discharge from the ICU and found no differences when compared to critically ill patients without ARDS. The inability to perform activities of daily living prior to ICU admission seems to be an important marker of functional decline in this population.(99 Biehl M, Kashyap R, Ahmed AH, Reriani MK, Ofoma UR, Wilson GA, et al. Six-month quality-of-life and functional status of acute respiratory distress syndrome survivors compared to patients at risk: a population-based study. Critical Care. 2015;19:356.) In turn, the severity of respiratory failure does not seem to affect prognosis according to a comparison of patients who underwent extracorporeal membrane oxygenation (ECMO) with those who did not.(1010 Wang ZY, Li T, Wang CT, Xu L, Gao XJ. Assessment of 1-year outcomes in survivors of severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation or mechanical ventilation: a prospective observational study. Chin Med J (Engl). 2017;130(10):1161-8.)

The impact of post-ICU muscle weakness was assessed in 156 survivors of ARDS.(1111 Dinglas VD, Aronson Friedman L, Colantuoni E, Mendez-Tellez PA, Shanholtz CB, Ciesla ND, et al. Muscle weakness and 5-year survival in acute respiratory distress syndrome survivors. Crit Care Med. 2017;45(3):446-53.) At hospital discharge, 38% of the survivors were diagnosed with muscle weakness, and the 5-year mortality rate was three times higher in this group. Each point on the Medical Research Council (MRC) scale was associated with increased survival (hazard ratio (HR): 0.96; 95% confidence interval (95%CI): 0.94 - 0.98), and after 5 years, 50% of the survivors still had muscle weakness. Interestingly, even those who recovered muscle strength after hospital discharge experienced significantly high mortality. Patients with ICU-acquired weakness have significant morphological muscle damage.(1111 Dinglas VD, Aronson Friedman L, Colantuoni E, Mendez-Tellez PA, Shanholtz CB, Ciesla ND, et al. Muscle weakness and 5-year survival in acute respiratory distress syndrome survivors. Crit Care Med. 2017;45(3):446-53.,1212 Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz- Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348(8):683-93.) Studies that included muscle biopsies of ARDS survivors showed chronic myopathic changes up to 2 years after the acute episode, suggesting that the residual muscle injury may be correlated with the functional disability observed in these patients.(1313 Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364(14):1293-304.

14 Herridge MS, Moss M, Hough CL, Hopkins RO, Rice TW, Bienvenu OJ, et al. Recovery and outcomes after the acute respiratory distress syndrome (ARDS) in patients and their family caregivers. Intensive Care Med. 2016;42(5):725-38.
-1515 Angel MJ, Bril V, Shannon P, Herridge MS. Neuromuscular function in survivors of the acute respiratory distress syndrome. Can J Neurol Sci. 2007;34(4):427-32.) In addition, there is a significant loss of lean mass in some of these patients.(1616 Chan KS, Mourtzakis M, Aronson Friedman L, Dinglas VD, Hough CL, Ely EW, Morris PE, Hopkins RO, Needham DM; National Institutes of Health National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Syndrome (ARDS) Network. Evaluating muscle mass in survivors of acute respiratory distress syndrome: a 1-year multicenter longitudinal study. Crit Care Med. 2018;46(8):1238-46.)

Brosky et al.(1717 Brodsky MB, Huang M, Shanholtz C, Mendez-Tellez PA, Palmer JB, Colantuoni E, et al. Recovery from dysphagia symptoms after oral endotracheal intubation in acute respiratory distress syndrome survivors. A 5-year longitudinal study. Ann Am Thorac Soc. 2017;14(3):376-83.) demonstrated that one-third of survivors of ARDS have symptoms of dysphagia at the time of hospital discharge but experience full recovery of symptoms after 5 years of follow-up.

MENTAL STATE

The psychiatric dysfunction of post-ICU syndrome involves anxiety, depression and PTSD. Symptoms of PTSD are found less frequently than symptoms of anxiety and depression, regardless of the length of follow-up;(1818 Angus DC, Musthafa AA, Clermont G, Griffin MF, Linde-Zwirble WT, Dremsizov TT, et al. Quality-adjusted survival in the first year after the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001;163(6):1389-94.,1919 Bienvenu OJ, Friedman LA, Colantuoni E, Dinglas VD, Sepulveda KA, Mendez-Tellez P, et al. Psychiatric symptoms after acute respiratory distress syndrome: a 5-year longitudinal study. Intensive Care Med. 2018;44(1):38-47.) however, the prevalence of PTSD does not differ from that of populations of critically ill patients without ARDS.(2020 Huang M, Parker AM, Bienvenu OJ, Dinglas VD, Colantuoni E, Hopkins RO, Needham DM; National Institutes of Health, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. National Institutes of Health, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Psychiatric symptoms in acute respiratory distress syndrome survivors: a 1-year National Multicenter Study. Crit Care Med. 2016;44(5):954-65.) At hospital discharge, approximately 40% of patients with ARDS present with PTSD.(2121 Chiumello D, Coppola S, Froio S, Gotti M. What's next after ARDS: long-term outcomes. Respir Care. 2016;61(5):689-99.) At one year of follow-up, symptoms of anxiety and depression occur in 66% of cases (416/629 patients).(2020 Huang M, Parker AM, Bienvenu OJ, Dinglas VD, Colantuoni E, Hopkins RO, Needham DM; National Institutes of Health, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. National Institutes of Health, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Psychiatric symptoms in acute respiratory distress syndrome survivors: a 1-year National Multicenter Study. Crit Care Med. 2016;44(5):954-65.) Two years after discharge from the ICU, the prevalence of PTSD is 22% to 24%,(2222 Bienvenu OJ, Colantuoni E, Mendez-Tellez PA, Shanholtz C, Dennison-Himmelfarb CR, Pronovost PJ, et al. Cooccurrence of and remission from general anxiety, depression, and posttraumatic stress disorder symptoms after acute lung injury: a 2-year longitudinal study. Crit Care Med. 2015;43(3):642-53.) that of anxiety is 38% to 44% and that of depression is 26% to 33%.(2323 Rattray J. Life after critical illness: an overview. J Clin Nurs. 2014;23(5-6):623-33.) After 5 years, 28% had a diagnosis of PTSD, and after 8 years, 23.9% did.(2121 Chiumello D, Coppola S, Froio S, Gotti M. What's next after ARDS: long-term outcomes. Respir Care. 2016;61(5):689-99.) Interestingly, many patients exhibit symptoms in all three psychiatric domains simultaneously.

Similar to findings regarding the physical state, greater severity of ARDS does not seem to correlate with the prevalence of psychiatric symptoms after discharge from the ICU.(2121 Chiumello D, Coppola S, Froio S, Gotti M. What's next after ARDS: long-term outcomes. Respir Care. 2016;61(5):689-99.,2424 Adhikari NK, McAndrews MP, Tansey CM, Matté A, Pinto R, Cheung AM, et al. Self-reported symptoms of depression and memory dysfunction in survivors of ARDS. Chest. 2009;135(3):678-87.) However, younger age, unemployment, female gender and alcohol use were related to a higher prevalence of psychological syndromes. In these subgroups, clinically significant persistent or recurrent symptoms of anxiety (38%), depression (32%) and PTSD (23%) were common in the first 5 years after ARDS.(2424 Adhikari NK, McAndrews MP, Tansey CM, Matté A, Pinto R, Cheung AM, et al. Self-reported symptoms of depression and memory dysfunction in survivors of ARDS. Chest. 2009;135(3):678-87.)

The etiology of psychiatric disorders associated with ARDS is unknown.(2121 Chiumello D, Coppola S, Froio S, Gotti M. What's next after ARDS: long-term outcomes. Respir Care. 2016;61(5):689-99.) Most of the literature suggests that pathophysiological changes related to critical illness (hypoxemia, activation of the hypothalamic-pituitary axis, elevated cytokines and organ dysfunction) and to the use of drugs (norepinephrine and sedatives) contribute to the onset of long-term psychological disorders.(2424 Adhikari NK, McAndrews MP, Tansey CM, Matté A, Pinto R, Cheung AM, et al. Self-reported symptoms of depression and memory dysfunction in survivors of ARDS. Chest. 2009;135(3):678-87.) A previous history of depression is strongly associated with psychiatric morbidity after ARDS.(2424 Adhikari NK, McAndrews MP, Tansey CM, Matté A, Pinto R, Cheung AM, et al. Self-reported symptoms of depression and memory dysfunction in survivors of ARDS. Chest. 2009;135(3):678-87.)

The social impact of depression is substantial because patients with moderate to severe psychiatric symptoms have greater difficulty returning to work than those with mild to moderate symptoms.(2525 Pfoh ER, Chan KS, Dinglas VD, Girard TD, Jackson JC, Morris PE, Hough CL, Mendez-Tellez PA, Ely EW, Huang M, Needham DM, Hopkins RO; NIH NHLBI ARDS Network. Cognitive screening among acute respiratory failure survivors: a cross-sectional evaluation of the Mini-Mental State Examination. Crit Care. 2015;19:220.) Individuals with PTSD have a greater tendency toward somatization and anxiety in addition to major impairment in some dimensions of health-related quality of life (HRQoL), such as general health, social function and mental health.(2626 Deja M, Denke C, Weber-Carstens S, Schröder J, Pille CE, Hokema F, et al. Social support during intensive care unit stay might improve mental impairment and consequently health-related quality of life in survivors of severe acute respiratory distress syndrome. Crit Care. 2006;10(5):R147.) A positive correlation was found between the number of traumatic memories and the experience of anxiety and the severity of PTSD.(2626 Deja M, Denke C, Weber-Carstens S, Schröder J, Pille CE, Hokema F, et al. Social support during intensive care unit stay might improve mental impairment and consequently health-related quality of life in survivors of severe acute respiratory distress syndrome. Crit Care. 2006;10(5):R147.) Regarding aspects related to ICU interventions, the duration of sedation and mechanical ventilation are considered long-term predictors of PTSD.(2727 Kapfhammer HP, Rothenhäusler HB, Krauseneck T, Stoll C, Schelling G. Posttraumatic stress disorder and health-related quality of life in long-term survivors of acute respiratory distress syndrome. Am J Psychiatry. 2004;161(1):45-52.)

COGNITIVE STATE

Little is known about the pathophysiology of neurocognitive impairment after ARDS. It is likely that different mechanisms contribute to the development of neurocognitive dysfunction (hypoxemia, delirium, changes in blood glucose, the effects of sedatives and pre-existing cognitive impairment). Approximately 50% of survivors may develop cognitive dysfunction in the long term (1 to 2 years), especially in terms of attention, memory, mental processing speed and executive function.(99 Biehl M, Kashyap R, Ahmed AH, Reriani MK, Ofoma UR, Wilson GA, et al. Six-month quality-of-life and functional status of acute respiratory distress syndrome survivors compared to patients at risk: a population-based study. Critical Care. 2015;19:356.) Biehl et al.(99 Biehl M, Kashyap R, Ahmed AH, Reriani MK, Ofoma UR, Wilson GA, et al. Six-month quality-of-life and functional status of acute respiratory distress syndrome survivors compared to patients at risk: a population-based study. Critical Care. 2015;19:356.) found no difference in the SF-12 mental component between critically ill patients with and without ARDS at a long-term evaluation. The classic study by Pandharipande et al.(2828 Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-16.) found that critically ill patients with shock or acute respiratory failure had a high risk of cognitive impairment in the first year after hospital discharge. In addition, one-fourth of elderly patients (> 65 years) had neurological examination results compatible with dementia after 1 year of follow-up. In a cross-sectional study,(2424 Adhikari NK, McAndrews MP, Tansey CM, Matté A, Pinto R, Cheung AM, et al. Self-reported symptoms of depression and memory dysfunction in survivors of ARDS. Chest. 2009;135(3):678-87.) at the 12th month after ICU discharge, 71% of the patients had abnormal neuropsychological tests. Additionally, in this domain, the severity of the disease does not seem to increase the risk of cognitive deficit, based on the comparison of patients with ARDS who did and did not receive ECMO.(1010 Wang ZY, Li T, Wang CT, Xu L, Gao XJ. Assessment of 1-year outcomes in survivors of severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation or mechanical ventilation: a prospective observational study. Chin Med J (Engl). 2017;130(10):1161-8.)

PULMONARY FUNCTION

In patients with ARDS, the reduction in pulmonary function does not seem to be as significant as initially thought.(1212 Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz- Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348(8):683-93.,1313 Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364(14):1293-304.) Spirometry (which assesses static and dynamic pulmonary volumes) and diffusion capacity (which assesses the capacity for gas exchange through the alveolar barrier) are the techniques used to assess pulmonary function.(2929 Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948-68.) The 6-minute walk test (which assesses overall cardiopulmonary function) is also used to assess pulmonary function alone.(2929 Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948-68.) Of these, diffusion capacity seems to be the parameter that is universally acutely affected, and although there was an improvement from 62 - 63% to 72 - 77% of the predicted value, it remained at the lower limit of normal during the first year after ARDS.(30.31) Studies indicate that lung volumes show a strong tendency to return to normal 3 to 6 months after the acute phase.(1212 Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz- Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348(8):683-93.,1313 Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364(14):1293-304.,3030 Cooper AB, Ferguson ND, Hanly PJ, Meade MO, Kachura JR, Granton JT, et al. Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma. Crit Care Med. 1999;27(12):2616-21.,3131 Orme J Jr, Romney JS, Hopkins RO, Pope D, Chan KJ, Thomsen G, et al. Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2003;167(5):690-4.) However, 6% to 43% of patients develop an obstructive pattern and 15% to 58% develop a restrictive pattern in the first year of follow-up.(1212 Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz- Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS; Canadian Critical Care Trials Group, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med. 2003;348(8):683-93.,1313 Herridge MS, Tansey CM, Matté A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364(14):1293-304.,3030 Cooper AB, Ferguson ND, Hanly PJ, Meade MO, Kachura JR, Granton JT, et al. Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma. Crit Care Med. 1999;27(12):2616-21.,3131 Orme J Jr, Romney JS, Hopkins RO, Pope D, Chan KJ, Thomsen G, et al. Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2003;167(5):690-4.) It is believed that a restrictive pattern may be explained by the progression to pulmonary fibrosis and/or the development of ICU-acquired respiratory muscle weakness. One year after discharge, patients had increase in the distance covered in the 6-minute walk test compared to the findings in the immediate postdischarge period.(3030 Cooper AB, Ferguson ND, Hanly PJ, Meade MO, Kachura JR, Granton JT, et al. Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma. Crit Care Med. 1999;27(12):2616-21.,3131 Orme J Jr, Romney JS, Hopkins RO, Pope D, Chan KJ, Thomsen G, et al. Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2003;167(5):690-4.) There is still controversy regarding whether the inability to exercise is due to dyspnea or muscle weakness. It is likely to be multifactorial, as no correlation was found between parenchymal abnormalities detected with computed tomography, respiratory symptoms, pulmonary function tests and the 6-minute walk test. It is important to note that some patients maintain the changes in diffusion capacity and the 6-minute walk test for up to 5 years after ARDS.(2121 Chiumello D, Coppola S, Froio S, Gotti M. What's next after ARDS: long-term outcomes. Respir Care. 2016;61(5):689-99.)

Although short-term survival is significantly better in patients with ARDS who are ventilated using a protective strategy, there is no evidence of altered pulmonary function up to two years after the resolution of the acute phase compared to conventionally ventilated patients.(3030 Cooper AB, Ferguson ND, Hanly PJ, Meade MO, Kachura JR, Granton JT, et al. Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma. Crit Care Med. 1999;27(12):2616-21.) There also appears to be no difference in spirometric values between patients with pulmonary and extrapulmonary ARDS or between those ventilated in the prone position and those ventilated in the standard position.(3030 Cooper AB, Ferguson ND, Hanly PJ, Meade MO, Kachura JR, Granton JT, et al. Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma. Crit Care Med. 1999;27(12):2616-21.)

RETURN TO WORK AND REHOSPITALIZATION

The possibility of returning to work is an important quality of life indicator for critical illness survivors. Myhren et al.(3232 Myhren H, Ekeberg Ø, Stokland O. Health-related quality of life and return to work after critical illness in general intensive care unit patients: a 1-year follow-up study. Crit Care Med. 2010;38(7):1554-61.) showed that 55% of previously active patients with ARDS returned to work or school within 1 year of follow-up. A recent study(3333 Kamdar BB, Huang M, Dinglas VD, Colantuoni E, von Wachter TM, Hopkins RO, Needham DM; National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Joblessness and lost earnings after acute respiratory distress syndrome in a 1-year national multicenter study. Am J Respir Crit Care Med. 2017;196(8):1012-20.) conducted with 922 ARDS survivors in 43 American hospitals showed that 44% of patients were unemployed 1 year after hospital discharge. A reduction in earnings was reported by 71% of patients, and the variables associated with unemployment were length of hospital stay and age.

Ruhl et al.(3434 Ruhl AP, Huang M, Colantuoni E, Karmarkar T, Dinglas VD, Hopkins RO, Needham DM; With the National Institutes of Health, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Healthcare utilization and costs in ARDS survivors: a 1-year longitudinal national US multicenter study. Intensive Care Med. 2017;43(7):980-91.) found that 40% of ARDS survivors experience at least one hospitalization after discharge during the first 12 months of follow-up. Physical or psychological decline was associated with subsequent hospitalization.

HEALTH-RELATED QUALITY OF LIFE

There are still many uncertainties in the assessment of HRQoL in patients with ARDS after their discharge from the ICU.(3535 Dowdy DW, Eid MP, Dennison CR, Mendez-Tellez PA, Herridge MS, Guallar E, et al. Quality of life after acute respiratory distress syndrome: a meta-analysis. Intensive Care Med. 2006;32(8):1115-24.) Differences in assessment time points and the heterogeneity of the scales used complicate the interpretation of findings.(3636 McHorney CA, Ware JE Jr, Raczek AE. The MOS 36-Item Short- Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care. 1993;31(3):247-63.)

In a meta-analysis,(3535 Dowdy DW, Eid MP, Dennison CR, Mendez-Tellez PA, Herridge MS, Guallar E, et al. Quality of life after acute respiratory distress syndrome: a meta-analysis. Intensive Care Med. 2006;32(8):1115-24.) the HRQoL of ARDS survivors was significantly decreased in the first year after ICU discharge compared to that of the general population, especially due to worsening of the physical domain. In a secondary analysis of the OSCAR study (n = 795),(3737 Marti J, Hall P, Hamilton P, Lamb S, McCabe C, Lall R, et al. One-year resource utilization, costs and quality of life in patients with acute respiratory distress syndrome (ARDS): secondary analysis of a randomized controlled trial. J Intensive Care; 2016;4:56.) ARDS survivors reported a significantly lower HRQoL than the age- and sex-matched reference population. This finding was more marked in patients younger than 65 years. Bienvenu et al.(2222 Bienvenu OJ, Colantuoni E, Mendez-Tellez PA, Shanholtz C, Dennison-Himmelfarb CR, Pronovost PJ, et al. Cooccurrence of and remission from general anxiety, depression, and posttraumatic stress disorder symptoms after acute lung injury: a 2-year longitudinal study. Crit Care Med. 2015;43(3):642-53.) demonstrated that patients had at least one psychological diagnosis associated with a reduction in the physical domain of HRQoL at 2 years after hospital discharge. In a multivariate analysis, improvement in physical performance was associated with a greater likelihood of remission of psychiatric symptoms. In an assessment of the HRQoL of patients five years after ICU discharge, ARDS survivors had a 25% reduction in physical function and a 17.5% reduction in general health compared to the general population.(3838 Schelling G, Stoll C, Vogelmeier C, Hummel T, Behr J, Kapfhammer HP, et al. Pulmonary function and health-related quality of life in a sample of long-term survivors of the acute respiratory distress syndrome. Intensive Care Med. 2000;26(9):1304-11.) Even younger individuals (< 52 years old)(3838 Schelling G, Stoll C, Vogelmeier C, Hummel T, Behr J, Kapfhammer HP, et al. Pulmonary function and health-related quality of life in a sample of long-term survivors of the acute respiratory distress syndrome. Intensive Care Med. 2000;26(9):1304-11.) and individuals with few comorbidities(3939 Heyland DK, Groll D, Caeser M. Survivors of acute respiratory distress syndrome: relationship between pulmonary dysfunction and long-term health-related quality of life. Crit Care Med. 2005;33(7):1549-56.,4040 Garland A, Dawson NV, Altmann I, Thomas CL, Phillips RS, Tsevat J, Desbiens NA, Bellamy PE, Knaus WA, Connors AF Jr; SUPPORT Investigators. Outcomes up to 5 years after severe, acute respiratory failure. Chest. 2004;126(6):1897-904.) showed a reduction in the physical domain.

Additionally, in an assessment of HRQoL, the severity of ARDS did not seem to influence long-term outcomes.(1010 Wang ZY, Li T, Wang CT, Xu L, Gao XJ. Assessment of 1-year outcomes in survivors of severe acute respiratory distress syndrome receiving extracorporeal membrane oxygenation or mechanical ventilation: a prospective observational study. Chin Med J (Engl). 2017;130(10):1161-8.) In that study, ECMO and non-ECMO survivors had similar HRQoL one year after ICU discharge, but when compared with the general population, both groups showed significantly lower HRQoL.

Curiously, ARDS survivors seem to display four distinct long-term progression patterns: (a) mildly impaired physical and mental health, (b) moderately impaired physical and mental health, (c) severely impaired physical health with moderately impaired mental health and (d) severely impaired physical and mental health.(4141 Hopkins RO, Weaver LK, Collingridge D, Parkinson RB, Chan KJ, Orme JF Jr. Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2005;171(4):340-7.,4242 Brown SM, Wilson EL, Presson AP, Dinglas VD, Greene T, Hopkins RO, Needham DM; with the National Institutes of Health NHLBI ARDS Network. Understanding patient outcomes after acute respiratory distress syndrome: identifying subtypes of physical, cognitive and mental health outcomes. Thorax. 2017;72(12):1094-103.) This phenotypic division may, in the near future, guide therapy after hospital discharge.

To clarify the specific contribution of ARDS to long-term outcomes, some studies(1414 Herridge MS, Moss M, Hough CL, Hopkins RO, Rice TW, Bienvenu OJ, et al. Recovery and outcomes after the acute respiratory distress syndrome (ARDS) in patients and their family caregivers. Intensive Care Med. 2016;42(5):725-38.,4343 Granja C, Morujão E, Costa-Pereira A. Quality of life in acute respiratory distress syndrome survivors may be no worse than in other ICU survivors. Intensive Care Med. 2003;29(10):1744-50.) compared the HRQoL of ARDS survivors with that of ICU survivors without ARDS and found no difference at six months after discharge. However, these results should be interpreted with caution considering the heterogenous criteria for acute lung disease included in the definition of ARDS over the years and the different baseline characteristics of studied populations in terms of age, preexisting lung disease and number of comorbidities.

PREVENTION OF SEQUELAE

Little is known about the prevention of post-intensive care syndrome.(77 Rawal G, Yadav S, Kumar R. Post-intensive care syndrome: an overview. J Transl Int Med. 2017;5(2):90-2.,88 Baldwin M, Wunsch H. Mortality after critical illness. In: Stevens RD, Hart N, Herridge MS, editors. Textbook of post-ICU medicine: the legacy of critical care. United Kingdom: Oxford University Press; 2014.) Early mobilization therapy has been reported to prevent or attenuate the impairment of physical function in critically ill patients.(4444 Bein T, Bischoff M, Breuckner U, Gebhardt K, Henzler D, Hermes C, et al. S2e guideline: positioning and early mobilization in prophylaxis or therapy of pulmonary disorders: Revision 2015: S2e guideline of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI). Anaesthesist. 2015;64 Suppl 1:1-26.) An improvement in physical function associated with early goal-oriented mobilization was observed in a cohort of surgical patients;(4545 Schaller SJ, Anstey M, Blobner M, Edrich T, Grabitz SD, Gradwohl-Matis I, Heim M, Houle T, Kurth T, Latronico N, Lee J, Meyer MJ, Peponis T, Talmor D, Velmahos GC, Waak K, Walz JM, Zafonte R, Eikermann M; International Early SOMS-guided Mobilization Research Initiative. Early, goal-directed mobilization in the surgical intensive care unit: a randomized controlled trial. Lancet. 2016;388(10052):1377-88.) however, these positive results have not yet been replicated in patients with acute respiratory failure.(4646 Moss M, Nordon-Craft A, Malone D, Van Pelt D, Frankel SK, Warner ML, et al. A randomized trial of an intensive physical therapy program for patients with acute respiratory failure. Am J Respir Crit Care Med. 2016;193(10):1101-10.,4747 Morris PE, Berry MJ, Files DC, Thompson JC, Hauser J, Flores L, et al. Standardized rehabilitation and hospital length of stay among patients with acute respiratory failure: a randomized clinical trial. JAMA. 2016;315(24):2694-702.) The support of family and caregivers during the ICU stay and motor rehabilitation seem to prevent the onset of PTSD.(2626 Deja M, Denke C, Weber-Carstens S, Schröder J, Pille CE, Hokema F, et al. Social support during intensive care unit stay might improve mental impairment and consequently health-related quality of life in survivors of severe acute respiratory distress syndrome. Crit Care. 2006;10(5):R147.,4848 Iwashyna TJ, Walsh TS. Interplay of physiology, social, familial and behavioral adaptation in the long-term outcome of ARDS. Thorax. 2017;72(10):872-3.)

FINAL COMMENTS

Although mortality from ARDS has decreased in recent years, those who survive develop changes in lung function, reduced quality of life and functional status, and the onset of neuropsychiatric disorders up to 5 years after their critical illness. The cause, pathophysiological manifestation and clinical progress of patients with ARDS may be different from those of patients with other critical diseases. The hypothesis that ARDS has a distinct and unique pattern of long-term sequelae may derive from specific characteristics of ARDS: mechanical ventilation may be more harmful in ARDS than in other critical diseases; hypoxemia is a specific complication of ARDS, and survivors can face particular exposure to its negative effects; additionally, patients with ARDS receive specific therapies (extracorporeal membrane oxygenation, prone-position ventilation, muscle blockade and sedoanalgesia) that may influence the long-term outcome.(4949 Bein T, Weber-Carstens S, Apfelbacher C. Long-term outcome after the acute respiratory distress syndrome: different from general critical illness? Curr Opin Crit Care. 2018;24(1):35-40.)

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Publication Dates

  • Publication in this collection
    20 Jan 2020
  • Date of issue
    Oct-Dec 2019

History

  • Received
    16 Oct 2018
  • Accepted
    04 Mar 2019
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