Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Luigi Pisani, Anna Geke Algera, Ary Serpa Neto, Luciano Azevedo, Tài Pham, Frederique Paulus, Marcelo Gama de Abreu, Paolo Pelosi, Arjen M Dondorp, Giacomo Bellani, John G Laffey, Marcus J Schultz, ERICC study investigators, LUNG SAFE study investigators, PRoVENT study investigators, PRoVENT-iMiC study investigators

Abstract

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies.

Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality.

Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001).

Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status.

Funding: No funding.

Conflict of interest statement

Declaration of interests We declare no competing interests.

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Ventilation parameters on the first day of mechanical ventilation in patients stratified by economic group Cumulative frequency distribution of tidal volume (A), positive end-expiratory pressure (B), plateau pressure (C), and driving pressure (D). Vertical dotted lines represent the cutoff for each variable and horizontal dotted lines represent the respective proportion of patients reaching each cutoff.
Figure 2
Figure 2
Marginal effect plot (A) showing the predicted mortality according to the SOFA score at day 1 and variable life-adjusted display (B) to assess cumulative excess survival according to income groups ICU=intensive care unit. SOFA=sequential organ failure assessment.
Figure 3
Figure 3
Scatter plot exploring the association between crude intensive care unit mortality and gross domestic product per capita Each circle represents a country. The size of the circle reflects the number of enrolled patients in the country (appendix pp 8–9). Middle-income countries were further divided into lower-middle-income (red) and upper-middle-income countries (green). Countries that recruited fewer than 50 patients were excluded.

References

    1. Inglis R, Ayebale E, Schultz MJ. Optimizing respiratory management in resource-limited settings. Curr Opin Crit Care. 2019;25:45–53.
    1. Lalani HS, Waweru-Siika W, Mwogi T, et al. Intensive care outcomes and mortality prediction at a national referral hospital in western Kenya. Ann Am Thorac Soc. 2018;15:1336–1343.
    1. Schultz MJ, Dunser MW, Dondorp AM, et al. Current challenges in the management of sepsis in ICUs in resource-poor settings and suggestions for the future. Intensive Care Med. 2017;43:612–624.
    1. 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;193:52–59.
    1. Misango D, Pattnaik R, Baker T, Dünser MW, Dondorp AM, Schultz MJ. In: Sepsis management in resource-limited settings. Dondorp A, Dünser M, Schultz M, editors. Springer; Cham: 2019. Hemodynamic assessment and support in sepsis and septic shock in resource-limited settings; pp. 151–162.
    1. Andrews B, Semler MW, Muchemwa L, et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. JAMA. 2017;318:1233–1240.
    1. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011;364:2483–2495.
    1. Serpa Neto A, Schultz MJ, Festic E. Ventilatory support of patients with sepsis or septic shock in resource-limited settings. Intensive Care Med. 2016;42:100–103.
    1. Laffey JG, Madotto F, Bellani G, et al. Geo-economic variations in epidemiology, patterns of care, and outcomes in patients with acute respiratory distress syndrome: insights from the LUNG SAFE prospective cohort study. Lancet Respir Med. 2017;5:627–638.
    1. Austin S, Murthy S, Wunsch H, et al. Access to urban acute care services in high- vs. middle-income countries: an analysis of seven cities. Intensive Care Med. 2014;40:342–352.
    1. Mackenbach JP, Stirbu I, Roskam A-JR, et al. Socioeconomic inequalities in health in 22 European countries. N Engl J Med. 2008;358:2468–2481.
    1. Dewan P, Rørth R, Jhund PS, et al. Income inequality and outcomes in heart failure: a global between-country analysis. JACC Heart Fail. 2019;7:336–346.
    1. Bellani G, Laffey JG, Pham T, et al. 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.
    1. Pham T, Serpa Neto A, Pelosi P, et al. Outcomes of patients presenting with mild acute respiratory distress syndrome: insights from the LUNG SAFE study. Anesthesiology. 2019;130:263–283.
    1. Gajic O, Dara SI, Mendez JL, et al. Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med. 2004;32:1817–1824.
    1. Neto AS, Barbas CSV, Simonis FD, et al. Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study. Lancet Respir Med. 2016;4:882–893.
    1. Simonis FD, Serpa Neto A, Binnekade JM, et al. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: a randomized clinical trial. JAMA. 2018;320:1872–1880.
    1. Adhikari NKJ, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet. 2010;376:1339–1346.
    1. Wunsch H. Mechanical ventilation in COVID-19: interpreting the current epidemiology. Am J Respir Crit Care Med. 2020;202:1–4.
    1. Azevedo LC, Park M, Salluh JI, et al. Clinical outcomes of patients requiring ventilatory support in Brazilian intensive care units: a multicenter, prospective, cohort study. Crit Care. 2013;17:R63.
    1. Pisani L, Algera AG, Serpa Neto A, et al. Epidemiological characteristics, ventilator management, and clinical outcome in patients receiving invasive ventilation in intensive care units from 10 Asian middle-income countries (PRoVENT-iMiC): an international, multicenter, prospective study. Am J Trop Med Hyg. 2021;104:1022–1033.
    1. Pisani L, Algera AG, Serpa Neto A, et al. Practice of ventilation in middle-income countries (PRoVENT-iMIC): rationale and protocol for a prospective international multicentre observational study in intensive care units in Asia. BMJ Open. 2018;8
    1. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307:2526–2533.
    1. Gajic O, Dabbagh O, Park PK, et al. Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study. Am J Respir Crit Care Med. 2011;183:462–470.
    1. Vincent J-L, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26:1793–1800.
    1. The World Bank World Bank country classification.
    1. Estenssoro E, Alegría L, Murias G, et al. Organizational issues, structure, and processes of care in 257 ICUs in Latin America: a study from the Latin America intensive care network. Crit Care Med. 2017;45:1325–1336.
    1. Baelani I, Jochberger S, Laimer T, et al. Availability of critical care resources to treat patients with severe sepsis or septic shock in Africa: a self-reported, continent-wide survey of anaesthesia providers. Crit Care. 2011;15:R10.
    1. Arabi YM, Phua J, Koh Y, et al. Structure, organization, and delivery of critical care in Asian ICUs. Crit Care Med. 2016;44:e940–e948.
    1. Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308:1651–1659.
    1. Neto AS, Simonis FD, Barbas CSV, et al. Lung-protective ventilation with low tidal volumes and the occurrence of pulmonary complications in patients without acute respiratory distress syndrome: a systematic review and individual patient data analysis. Crit Care Med. 2015;43:2155–2163.
    1. Rackley CR, MacIntyre NR. Low tidal volumes for everyone? Chest. 2019;156:783–791.
    1. McNicholas BA, Madotto F, Pham T, et al. Demographics, management and outcome of females and males with acute respiratory distress syndrome in the LUNG SAFE prospective cohort study. Eur Respir J. 2019;54
    1. Schultz MJ, Karagiannidis C. Is gender inequity in ventilator management a “women's issue”? Eur Respir J. 2019;54
    1. Kor DJ, Carter RE, Park PK, et al. Effect of aspirin on development of ARDS in at-risk patients presenting to the emergency department the LIPS-a randomized clinical trial. JAMA. 2016;315:2406–2414.
    1. Chebib N, Kreitmann L, Guérin C. Acute respiratory distress syndrome-a worldwide economic perspective. J Thorac Dis. 2018;10:570–575.
    1. Bonell A, Azarrafiy R, Huong VTL, et al. A systematic review and meta-analysis of ventilator-associated pneumonia in adults in Asia: an analysis of national income level on incidence and etiology. Clin Infect Dis. 2019;68:511–518.
    1. Karthikeyan B, Kadhiravan T, Deepanjali S, Swaminathan RP. Case-Mix, Care processes, and outcomes in medically-ill patients receiving mechanical ventilation in a low-resource setting from southern India: a prospective clinical case series. PLoS One. 2015;10
    1. Checkley W, Martin GS, Brown SM, et al. Structure, process, and annual ICU mortality across 69 centers: United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. Crit Care Med. 2014;42:344–356.
    1. Dondorp AM, Iyer SS, Schultz MJ. Critical care in resource-restricted settings. JAMA. 2016;315:753–754.
    1. Sjoding MW, Dickson RP. Economic disparities and survival from critical illness. Lancet Respir Med. 2017;5:601–603.
    1. Phua J, Joynt GM, Nishimura M, et al. Withholding and withdrawal of life-sustaining treatments in low-middle-income versus high-income Asian countries and regions. Intensive Care Med. 2016;42:1118–1127.

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