First described more than five decades ago by Ashbaugh and colleagues,1today acute respiratory distress syndrome (ARDS) continues to be one of the most challenging clinical conditions with a high morbidity and mortality.2 Till 1994, several definitions of ARDS were being used both for clinical care as well as for research purposes. The American-European Consensus Conference definition3 provided a uniform standardised definition of ARDS and this facilitated meaningful comparison of research carried out on ARDS across the globe. As the American-European Consensus Conference definition of ARDS3 was being used, several limitations with the use of this definition became evident. These limitations were addressed and the Berlin definition of ARDS4 was published. While the earlier definitions relied on clinical features and chest imaging as surrogates, the Berlin definition4 considered timing, i.e. onset within 1 week of clinical recognition of a trigger insult, bilateral opacities on chest radiograph or CT (not fully explained by lung collapse or effusion), respiratory failure (not fully explained by fluid overload or cardiac failure) and arterial hypoxaemia [based on ratio of partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FIO2) at a positive end expiratory pressure (PEEP) ≥5 cm of water].4 Further, the Berlin definition4 classified the severity into three categories (mild, moderate and severe) based on the PaO2/FIO2 ratio and the PEEP to facilitate estimation of the prognosis of ARDS. Presently the Berlin definition4 is being used world over in research on ARDS.
Recent clinical trial data suggest that pneumonia, aspiration of gastric contents and sepsis, were the most common aetiological causes of ARDS accounting for almost 85% of cases.2 In tropical countries, in addition to these causes, other causes, such as tuberculosis,5-6 malaria,7 leptospirosis,8 enteric fever9 and scrub typhus,10 have been documented to be the aetiological causes of ARDS. The aetiological spectrum of ARDS appears to be different in various parts of the world,10-11 and this has necessitated periodically documenting the current aetiological spectrum of ARDS.
The prospective study by Balakrishnan et al.12 featured in this issue of the Journal of the Royal College of Physicians of Edinburgh, attempted to describe the aetiology and short-term outcome of ARDS (n = 42; mean age 42.6 ± 15.3 years; 21 males) in the medical intensive care unit (MICU) at their tertiary care teaching hospital located in Puducherry, in south India. Of these, 22 patients has ARDS at admission and the rest developed ARDS during their in-hospital stay. Pulmonary ARDS was present in 13 out of 42 (31%) patients, with community-acquired pneumonia being the most common aetiological cause (n = 6), followed by hospital-acquired pneumonia. Majority of the cases were extrapulmonary ARDS [29 out of 42 (69%)], with sepsis (n = 16) being the most common cause followed by scrub typhus (n = 8). As per the Berlin criteria,4 13 (31%), 14 (33%) and 15 (36%) patients had mild, moderate and severe ARDS, respectively. Thirty three (79%) patients died; all the survivors (n = 9) had extrapulmonary ARDS. On univariate analysis, nonsurvivors had a significantly lower mean systolic blood pressure (BP), diastolic BP, mean arterial pressure and mean PaO2/FIO2 ratio; higher occurrence of complications such as acute kidney injury, thrombocytopenia, requirement for vasopressors and severe ARDS. Further, both acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were significantly higher in nonsurvivors.
Certain issues related to the study by Balakrishnan et al.12 need consideration. It is a single-centre study with a small sample size. The patients were evaluated till discharge from hospital or till death; the median (interquartile range) duration of hospital stay was 6 (3.75–10) days. There were a large number of patients with viral pneumonia compared with other Indian studies,10,13,14 which was explained by authors12 to be due to seasonal increase in the place of study. In extrapulmonary ARDS, following sepsis, scrub typhus accounted for the majority of cases, which was attributed to endemicity of the disease.
In a recently published study11 3,022 out of 29,144 patients (10%) screened for inclusion in 459 ICUs in 50 countries fulfilled ARDS criteria during their ICU stay. In this study,11 hospital mortality was 35%, 40% and 46% in patients with mild, moderate and severe ARDS, respectively. The mortality in the present study12 (33 out of 42; 79%) was much higher than that reported in other recent studies where the in-hospital hospital mortality was 63 out of 170 (37%)13 and 34 out of 75 (45%),10 and 28-day mortality was 36 out of 64 (56%).14 Balakrishnan et al.12 attributed this high mortality to seasonal rise in H1N1 cases, and the fact that some patients were ventilated outside the ICU because of limited number of beds in ICU and transferred later on to ICU, and severe underlying organ dysfunction at admission. Furthermore, seven out of nine survivors had scrub typhus as the aetiological cause.
The study by Balakrishnan et al.12 reiterates the importance of recognising treatable tropical infections as the aetiological causes of ARDS, as early initiation of appropriate antibiotic treatment has potential to significantly decrease the morbidity and mortality in patients with ARDS owing to these causes. Balakrishnan et al.12 also reported the potential usefulness of critical illness scoring systems, such as APACHE II and SOFA score in predicting prognosis. These critical illness scoring systems have been validated in intensive care units (ICUs) outside India. Only univariate analysis has been carried out for predictors of survival. In an adequately powered study with an appropriate sample size, receiver–operator characteristic curve analysis, multivariable analysis could have better established the utility of critical illness scoring systems in predicting outcome in patients with ARDS requiring admission to MICU in the Indian scenario.
ARDS, with its varied aetiological causes, complex pathophysiological mechanisms and potential for lethal complications, still poses a major challenge even in developed countries and ARDS mortality still remains at approximately 40% globally.11 In developing countries, with limited resources and sparsely available, accessible, affordable ICU care facilities, ARDS still remains to be a disease with high mortality for clinicians to contend with. In developing countries, especially in rural settings, variables required for satisfying Berlin definition,4 such as arterial blood gas measurements and chest radiographs, may not be available and several cases of ARDS may, therefore, remain undiagnosed. To overcome this, other options such as the ‘Kigali modification of Berlin’ definition15 have been proposed. Further, the utility of potential therapies for ARDS due tropical aetiological causes, such as use of extracorporeal membrane oxygenation, extracorporeal carbon dioxide removal and prone positioning, among others,16 merits study. Further research is warranted on these issues in ARDS in the tropics.
References
1 Ashbaugh DG, Bigelow DB, Petty TL et al. Acute respiratory distress in adults. Lancet 1967; 2; 319–23.
2 Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med 2017; 377: 562–72.
3 Bernard GR, Artigas A, Brigham KL et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149: 818–24.
4 ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012; 307: 2526–33.
5 Sharma SK, Mohan A, Banga A et al. Predictors of development and outcome in patients with acute respiratory distress syndrome due to tuberculosis. Int J Tuberc Lung Dis 2006; 10: 429–35.
6 Penner C, Roberts D, Kunimoto D et al. Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation. Am J Respir Crit Care Med 1995; 151: 867–72.
7 Mohan A, Sharma SK, Bollineni S. Acute lung injury and acute respiratory distress syndrome in malaria. J Vector Borne Dis 2008; 45: 175–93.
8 Bollineni S, Mohan A, Sharma KK et al. Pulmonary manifestations in acute leptospirosis. Am J Respir Crit Care Med 2007; 175: A218.
9 Agarwal PN, Ramanathan RM, Gupta D et al. Acute respiratory distress syndrome complicating typhoid fever. Ind J Chest Dis Allied Sci 1999; 41: 225–9.
10 Kumar SS, Selvarajan Chettiar KP, Nambiar R. Etiology and outcomes of ARDS in a resource limited urban tropical setting. J Natl Med Assoc 2018; 110: 352–7.
11 Bellani G, Laffey JG, Pham T et al.; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 2016; 315: 788–800.
12 Balakrishnan N, Thabah MM, Dineshbabu S et al. Aetiology and short-term outcome of acute respiratory distress syndrome: a real-world experience from a medical intensive care unit in southern India. J R Coll Physicians Edinb 2020; 12–8.
13 Chawla R, Mansuriya J, Modi N et al. Acute respiratory distress syndrome: predictors of noninvasive ventilation failure and intensive care unit mortality in clinical practice. J Crit Care 2016; 31: 26–30.
14 Sharma SK, Gupta A, Biswas A et al. Aetiology, outcomes & predictors of mortality in acute respiratory distress syndrome from a tertiary care centre in north India. Indian J Med Res 2016; 143: 782–92.
15 Riviello ED, Kiviri W, Twagirumugabe T et al. Hospital incidence and outcomes of the acute respiratory distress syndrome using the Kigali modification of the Berlin definition. Am J Respir Crit Care Med 2016; 193: 52–9.
16 Fan E, Brodie D, Slutsky AS. Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA 2018; 319: 698–710.
