INTRODUCTION
Although invasive ventilation is an essential part of critical care and can be a life-saving intervention, it also has strong potential to cause or worsen lung injury. 1 The risk of the so-called ventilator-induced lung injury can be substantially reduced by applying lung-protective ventilation including a low tidal volume (V T ) and a sufficient positive end-expiratory pressure (PEEP). Two recent worldwide observational studies suggest improvements in ventilator management over recent decades, such as lower V T and higher PEEP, confirming trends observed in earlier service reviews. 2–6 The recent “PRactice of VENTilation (PRoVENT) in critically ill patients without acute respiratory distress syndrome (ARDS)” study 7 and the “Large observational study to UNderstand the Global impact of Severe Acute respiratory Failure” (LUNG SAFE) 8 showed more than half of patients receiving protective ventilation.
Evidence for benefit and implementation of protective ventilation is mostly from high-income countries. 2–4,7–9 It is uncertain to what extent protective ventilation is being practiced in middle-income countries, where intensive care units (ICUs) and thus invasive ventilation are increasingly becoming available. Participation of Asian middle-income country ICUs in recent multinational ventilation studies has been scant. 4,7 Few subnational studies explored the practice of ventilation showing variable adoption of protective ventilation. 5,10 This limitation may lead to a deficient insight on actual use of protective ventilation in resource-limited ICUs. Significant differences with regard to practice of care affect resource-limited settings that go beyond the context-specific patient case mix. 10 Challenges to deliver high-quality ventilation involve equipment itself, as inaccurate flowmeters or malfunctioning sensors hinder ventilator’s reliability. Further challenges derive from monitoring, including continuous pulse oximetry, capnography, repeated blood gas analysis, and blood pressure measurements, as well as human resources and a proper infrastructure. 11,12 These challenges may make invasive ventilation less safe and may hamper implementation of protective ventilation.
The current study aimed to describe current practices of invasive ventilation in ICUs in Asian middle-income countries as well as the epidemiological characteristics and disease outcome of patients receiving invasive ventilation. We performed an international multicenter prospective 4-week cohort study and describe associations between ventilator settings and patient-centered outcomes. We hypothesized that ventilation practices do not routinely include lung-protective settings like a low V T and sufficient PEEP; however, a high number of patients are at risk for or have ARDS.
METHODS
Study design and participants.
PRactice of VENTilation in Middle-income Countries is an investigator-initiated international multicenter prospective cohort study in consecutive ICU patients receiving invasive ventilation during a predefined 4-week period. Patients were recruited in 54 ICUs from 10 Asian countries (a complete list can be found in Supplemental Appendix, p. 3). The study protocol has been published previously, 13 and the current report follows the Strengthening the Reporting of Observational Studies in Epidemiology statement. 14
Participating centers were recruited through national coordinators with help from the members of PRoVENT-iMiC steering committee. Ethics review by the Oxford Tropical Research Ethical Committee on June 9, 2017 designated this study as minimal risk. National and local ethics committees of participating centers, where applicable, approved a waiver of patient-level consent.
Patients who started invasive ventilation in the ICU during the inclusion period were eligible for participation. However, patients who started invasive ventilation in the emergency room, the clinical ward, within the community or in the operating room directly preceding the present ICU admission were also eligible for participation, independently from the number of hours spent under invasive ventilation in these settings. There was no minimum time of invasive ventilation in the participating ICU required to be included in the study. We excluded patients younger than 18 years, patients who received noninvasive ventilation (NIV) not followed by invasive ventilation, patients whose invasive ventilation started before the inclusion period of PRoVENT-iMiC, and patients transferred from another hospital while receiving invasive ventilation.
Procedures.
At the discretion of the national coordinators, each country or region selected a recruitment period of 28 consecutive days. If possible, the period was the same for all centers in one country or region. Site investigators were responsible for patient recruitment and follow-up until ICU discharge. The study endpoint was censored at 60 days post-admission for patients still in the ICU at this time point. National coordinators assisted site investigators and monitored the study according to GCP-guidelines, ensuring integrity and timely completion of data collection. Before the initiation of the study, the national coordinators reviewed the case report forms (CRFs) to evaluate clarity and consistency (see Supplemental Appendix, pp. 24–38). A concise one-off web-based survey on ICU structure and organizational aspects was performed in the participating sites, as suggested by previous literature 12 (see Supplemental Appendix, pp. 39–44).
An extended dataset was collected daily until day 7 and at discharge from the ICU. We defined the first calendar day the patient received invasive ventilation in the ICU as day 0, irrespective of ICU admission date and location of initial intubation. Baseline and demographic variables were collected on the day of admission, including data for calculation of the Sequential Organ Failure Assessment Score (SOFA) and the Lung Injury Prediction Score (LIPS). 15 The presence of ARDS was scored by the site investigators according to the Berlin Definition for ARDS, 16 with the option of stratifying the oxygenation defect according to oxygen saturation (SpO2)/inspired fraction of oxygen (FiO2) instead of Oxygen partial pressure (PaO2)/FiO2 cutoffs. 17–19 Thereafter, each day for the first 3 days of ventilation, around 08:00 hours, ventilation variables and parameters, neurological status, and basic hemodynamic parameters were recorded. Every day until day 7, ICU discharge, or death, the occurrence of predefined pulmonary complications was scored. Pulmonary complications reported in the first 24 hours of invasive ventilation were excluded from main analysis and reported separately (Supplemental Appendix, p. 14), as may have represented the potential reason for intubation. Site investigators also recorded rescue therapies for refractory hypoxemia, including use of neuromuscular blockers, recruitment maneuvers, and prone positioning.
Patient data were entered into a password-secured, Internet-based, electronic CRF (Research Electronic Data Capture, www.projectredcap.org). Before analysis, investigators screened all data for potentially erroneous or incomplete recordings and verified and corrected information as appropriate.
Outcomes.
The study outcomes were represented by main ventilator settings, including V T and PEEP; additional ventilation variables and parameters, including oxygen fraction of inspired air (FiO2), respiratory rate (RR), peak inspiratory airway pressure, plateau, and driving pressure (Ppeak, plateau airway pressure [Pplat], and driving pressure); the proportion of patients at risk for or with ARDS; incidence of pulmonary complications, including pneumonia, ARDS after start of invasive ventilation, pneumothorax, pleural effusion, atelectasis, and cardiogenic pulmonary edema (for definitions, see Supplemental Appendix, p. 5); length of stay in the ICU; and all-cause ICU mortality.
Statistical analysis.
The statistical analysis plan was published before locking of the database, 13 and the final version was uploaded at clinicaltrials.gov before the end of enrolment. Modifications from the original analysis plan are detailed in Supplemental Appendix, p. 6. No formal sample size calculation was performed, but the predicted sample size (> 1,200 patients) based on the allocated time period and a minimum expected enrolment rate of 20 patients/center was deemed sufficient to provide meaningful conclusions.
Data on ventilation variables and parameters are presented in full detail for the day of start of invasive ventilation, and for the successive 3 days. Predicted body weight (PBW) of male patients was calculated as 50 + 0·91 × (height [cm] − 152.4) and for female patients as 45.5 + 0.91 × (height [cm] − 152.4). Driving pressure was calculated by subtracting PEEP from the Pplat (in volume-controlled ventilation) or maximum airway pressure (Pmax) (in pressure-controlled ventilation). Scatterplots were used to present distributions of V T versus PEEP, V T versus RR, V T versus Pplat, and V T versus driving pressure. Cutoffs for ventilator parameters were based on widely accepted published values, 7,8,20 including 8 mL/kg PBW for V T , 5 cmH2O for PEEP, 14 breaths/minute for RR, 30 cmH2O for Pplat, and 15 cmH2O for driving pressure. 7
Patients were stratified in three groups for comparison of the study endpoints: patients with LIPS on day 0 lower than 4 (i.e., not at risk of ARDS according to the LIPS), patients with a LIPS of 4 or more (at risk of ARDS according to the LIPS, but not fulfilling the criteria for ARDS), and patients with ARDS diagnosed by the attending physician at the start of ventilation. The proportion of patients with LIPS ≥ 4, or with ARDS, was calculated by dividing the number of patients with LIPS ≥ 4, or with ARDS, by the total number of patients. The number of patients of patients with LIPS ≥ 4, or with ARDS, was derived per ICU bed over the study period by dividing the number of patients of patients with LIPS ≥ 4, or with ARDS, by the number of ICU beds available.
The number of patients developing one or more pulmonary complications during the first 7 days following start of invasive ventilation and patient outcomes at ICU discharge were reported in absolute numbers and percentages. Each new pulmonary complication was accounted for only once, considering the day of insurgence as the first day it was reported. A competing risk analysis based on cumulative incidence functions and “Fine and Gray” proportional sub-distribution hazards analysis was used to model the probability of discontinuing mechanical ventilation in the presence of the competing risk of death.
Univariable and multivariable analyses were performed to identify risk factors associated with ICU mortality and development of pulmonary complications. Covariates for the univariable models were included based on clinical relevance or the presence of imbalance at baseline. These included, but were not limited to, ventilator settings (in particular V T and PEEP at day 0). Covariates included in the final mixed-effect multivariable models were identified as those with P < 0.2 in the univariable model (including participating center as a random effect), and not statistically associated with other included variables. Linearity assumption was assessed plotting the logit x the predictor values (Supplemental Appendix, p. 23). Thus, nonlinear variables were entered as categorical variables (according to original categories or newly categorized). Pearson correlation coefficients were used to assess collinearity between predictors. Since a high level of collinearity among Ppeak, Pplat, and driving pressure was expected, the main model included the variable with the higher amount of measurements between Ppeak and Pplat. Driving pressure was considered separately in a sensitivity analysis, excluding PEEP, Ppeak, and Pplat. Finally, the intraclass correlation coefficient was assessed, representing the ratio of between-site variance to total variance, ranging from 0 to 1. Multiple imputations of missing values were not performed because of the low number of missing values for the variables considered (see Supplemental Appendix, p. 7). For the models exploring ICU mortality, age and PEEP did not meet the linearity assumption and were entered as categorical variables. For the models exploring pulmonary complications, pulmonary SOFA, PEEP, Ppeak, and LIPS did not meet the linearity assumption (Supplemental Appendix, p. 23). Thus, pulmonary SOFA was entered as a categorical variable (according to original categories), whereas Ppeak, PEEP, and LIPS were categorized according to clinically meaningful categories. Sequential organ failure assessment score, FiO2, PaO2/FiO2, and SpO2/FiO2 were excluded from the multivariable analysis because of relationship and multicollinearity with pulmonary SOFA. HCO3 was excluded because of multicollinearity with pH.
In test groups of continuous normally distributed variables, Student’s t-test and analysis of variance analysis were used. Likewise, the Mann–Whitney U test was used in case of not normally distributed data. Categorical variables were compared with the chi-square test or Fisher’s exact test. Statistical uncertainty was expressed by 95% CI. To account for the potential clustering of observations in participating centers, an additional analysis comparing ventilatory variables and outcomes in the three study groups was performed using linear (for numerical variables) and logistic (for categorical variables) mixed-effects models, with center as the random effect. A P-value of less than 0.05 was considered statistically significant. We did not correct for multiplicity across analyses; hence, the findings should be seen as exploratory. Statistical analysis was conducted using R (www.r-project.org, R version 3.3.1). The study was registered at clinicaltrials.gov, NCT 03188770.
Role of the funding source.
External funding source for this study was sought only in Vietnam (Wellcome Trust grants 107367/Z/15/Z and 089276/B/09/7). The first two authors and Steering Committee members had full access to all study-related data and had final responsibility to submit this report for publication.
RESULTS
Study sites and patients characteristics.
Of 65 ICUs in 11 countries that expressed interest in the study, 54 ICUs from 10 countries took part in the study, including 1,315 patients between November 2017 and December 2018 (Figure 1). Patient characteristics are shown in Table 1; ICU organizational characteristics and available resources are detailed in Supplemental Appendix, pp. 4–5. Three of four centers were public government hospitals, mostly serving a mixed population of surgical and medical patients from both urban and rural settings.
Screening and enrolment. ARDS = acute respiratory distress syndrome; IRB = institutional review board; LIPS = lung injury prediction score; MV = mechanical ventilation.
Citation: The American Journal of Tropical Medicine and Hygiene 104, 3; 10.4269/ajtmh.20-1177
Baseline patient characteristics
| All patients (n = 1,315) | LIPS < 4 (n = 389) | LIPS ≥ 4 (n = 837) | Acute respiratory distress syndrome (n = 89) | P-value LIPS < 4 vs. LIPS ≥ 4 | P-value* | |
|---|---|---|---|---|---|---|
| Age (years) | 57 [40, 67] | 54 [37, 66] | 58 [42, 68] | 49 [35, 62] | 0.018 | 0.0013 |
| Gender, female | 507/1,314 (38.6) | 159 (40.9) | 317/836 (37.9) | 31 (34.8) | 0.355 | 0.462 |
| Sequential Organ Failure Assessment score† | 7 [5, 10] | 6 [4, 8] | 8 [6, 11] | 9 [6, 12] | < 0.001 | < 0.0001 |
| LIPS‡ | 5 [3.5, 7] | 2.5 [2, 3.5] | 6 [5, 8] | 7.5 [6, 8.5] | < 0.001 | < 0.0001 |
| Height (cm) | 163 [156, 170] | 165 [158, 170] | 162 [155, 170] | 165 [160, 170] | 0.07 | 0.087 |
| Weight (kg) | 64 [55, 72] | 62 [55, 72] | 65 [55, 73] | 63 [55, 72] | 0.109 | 0.259 |
| Predicted body weight (kg) | 58 [50.6, 66] | 59 [51,66] | 57 [49,66] | 60 [52,66] | 0.167 | 0.185 |
| Body mass index (kg/m2) | 23.7 [21.5, 26.9] | 23.4 [21.3, 26.4] | 23.9 [21.7, 27.3] | 23.3 [20.8, 25.7] | 0.016 | 0.0134 |
| Ventilation status | ||||||
| Ventilation in ward before admission | 144/1,314 (11.0) | 43/388 (11.1) | 97 (11.6) | 4 (4.5) | 0.871 | 0.125 |
| NIV before invasive ventilation | 191/1,312 (14.6) | 26/388 (6.7) | 124/835 (14.9) | 41 (46.1) | < 0.001 | < 0.0001 |
| NIV duration (minutes) | 180 [36, 660] | 180 [70, 960] | 172 [30, 600] | 220 [62, 765] | 0.172 | 0.262 |
| Reason for ICU admission, n (%) | < 0.001 | < 0.001 | ||||
| Planned surgery | 246 (18.7) | 112 (28.8) | 132/836 (15.8) | 2 (2.2) | ||
| Emergency surgery (excl. trauma) | 145 (11.0) | 31 (8.0) | 107/836 (12.8) | 7 (7.9) | ||
| Trauma | 76 (5.8) | 9 (2.3) | 62/836 (7.4) | 5 (5.6) | ||
| Medical condition | 847 (64.5) | 237 (60.9) | 535/836 (64.0) | 75 (84.3) | ||
| Admission source | 0.036 | < 0.0001 | ||||
| Emergency department | 405/1,305 (31.0) | 122/386 (31.6) | 250/830 (30.1) | 33 (37.1) | ||
| Operating room | 340/1,305 (26.1) | 118/386 (30.6) | 216/830 (26.0) | 6 (6.7) | ||
| Medical or surgical ward | 462/1,305 (35.4) | 114/386 (29.5) | 303/830 (36.5) | 45 (50.6) | ||
| Obstetric ward | 26/1,305 (2.0) | 4/386 (1.0) | 20/830 (2.4) | 2 (2.2) | ||
| Directly from community | 7/1,305 (0.5) | 4/386 (1.0) | 3/830 (0.4) | 0 (0.0) | ||
| Other hospital or ICU | 65/1,305 (5.0) | 24/386 (6.2) | 38/830 (4.6) | 3 (3.4) | ||
| Smoking status | 0.015 | 0.0325 | ||||
| Never | 665/1,314 (50.6) | 211 (54.2) | 401/836 (48.0) | 53 (59.6) | ||
| Former | 216/1,314 (16.4) | 46 (11.8) | 157/836 (18.8) | 13 (14.6) | ||
| Current | 156/1,314 (11.9) | 44 (11.3) | 104/836 (12.4) | 8 (9.0) | ||
| Unknown | 277/1,314 (21.1) | 88 (22.6) | 174/836 (20.8) | 15 (16.9) | ||
| Reason for intubation, n (%)§ | ||||||
| Cardiac arrest | 72 (5.5) | 14 (3.6) | 57 (6.8) | 1 (1.1) | 0.035 | 0.0124 |
| Anaesthesia for surgery | 328 (24.9) | 122 (31.4) | 200 (23.9) | 6 (6.7) | 0.007 | < 0.0001 |
| Hemodynamic instability | 186 (14.1) | 33 (8.5) | 132 (15.8) | 21 (23.6) | 0.001 | < 0.0001 |
| Other | 96 (7.3) | 42 (10.8) | 51 (6.1) | 3 (3.4) | 0.005 | 0.0044 |
| Depressed level of consciousness | 351 (26.7) | 124 (31.9) | 215 (25.7) | 12 (13.5) | 0.029 | 0.0011 |
| Acute respiratory failure | 522 (39.7) | 78 (20.1) | 367 (43.8) | 77 (86.5) | < 0.001 | < 0.0001 |
| Cause of acute respiratory failure | < 0.0001 | |||||
| Community acquired pneumonia | 113/522 (21.6) | 14/78 (17.9) | 85/367 (23.2) | 14/77 (18.2) | ||
| Nosocomial pneumonia | 45/522 (8.6) | 3/78 (3.8) | 38/367 (10.4) | 4/77 (5.2) | ||
| Unplanned postoperative ventilation | 9/522 (1.7) | 2/78 (2.6) | 6/367 (1.6) | 1/77 (1.3) | ||
| Cardiogenic pulmonary oedema | 65/522 (12.5) | 12/78 (15.4) | 51/367 (13.9) | 2/77 (2.6) | ||
| Sepsis (other than pneumonia) | 98/522 (18.8) | 10/78 (12.8) | 79/367 (21.5) | 9/77 (11.7) | ||
| COPD exacerbation | 42/522 (8.0) | 10/78 (12.8) | 32/367 (8.7) | 0/77 (0.0) | ||
| Other | 112/522 (21.5) | 27/78 (34.6) | 76/367 (20.7) | 9/77 (11.7) | ||
| Chronic comorbidities, n (%)‖ | ||||||
| None | 359 (27.3) | 124 (31.9) | 204 (24.4) | 31 (34.8) | 0.007 | 0.0059 |
| Arterial hypertension | 533 (40.5) | 150 (38.6) | 357 (42.7) | 26 (29.2) | 0.196 | 0.0314 |
| Heart failure | 104 (7.9) | 22 (5.7) | 77 (9.2) | 5 (5.6) | 0.045 | 0.0718 |
| Diabetes mellitus | 392 (29.8) | 96 (24.7) | 278 (33.2) | 18 (20.2) | 0.003 | 0.0012 |
| Chronic kidney disease | 175 (13.3) | 46 (11.8) | 117 (14.0) | 12 (13.5) | 0.346 | 0.586 |
| Liver cirrhosis | 58 (4.4) | 13 (3.3) | 41 (4.9) | 4 (4.5) | 0.277 | 0.466 |
| COPD | 84 (6.4) | 18 (4.6) | 61 (7.3) | 5 (5.6) | 0.101 | 0.198 |
| Cancer | 118 (9.0) | 31 (8.0) | 79 (9.4) | 8 (9.0) | 0.465 | 0.704 |
| Neuromuscular disease | 17 (1.3) | 7 (1.8) | 9 (1.1) | 1 (1.1) | 0.442 | 0.573 |
| Other | 212 (16.1) | 62 (15.9) | 133 (15.9) | 17 (19.1) | 1 | 0.731 |
COPD = chronic obstructive pulmonary disease; ICU = intensive care unit; IQR = interquartile range; LIPS = Lung Injury Prediction Score. Data are number of patients/total number of patients (%) or median [IQR]. All parameters are measured in the first day of ventilation.
P-value represents the comparison across the three study groups for each variable.
Scores range from 0 to 24, with 0 the least severe.
Scores range from 0 to 35, with 0 the least severe.
Nonexclusive categories.
Patients can have more than one diagnosis.
Risk and prevalence of ARDS.
Of the included patients, 389 patients (29.6%, 95% CI: 27.1–32.1) had a LIPS < 4, 837 patients (63.7%, 95% CI: 61.1–66.3) had a LIPS ≥ 4, and 89 patients (6.8%, 95% CI: 5.8–8.2) had ARDS at the start of invasive ventilation (Table 1), and their distribution showed substantial geographical variation (Supplemental Appendix, p. 9). Patients with LIPS ≥ 4 and patients with ARDS represented 0.88 and 0.09 cases per ICU bed over a 4-week period, respectively. Of the patients with ARDS at study onset, 26% had mild ARDS, 27% had moderate ARDS, and the remaining patients had severe ARDS. Of note, one of 10 patients were ventilated for more than 12 hours in a clinical ward before being admitted to the ICU, highlighting the issue of accessibility and shortage of ICU beds in these settings.
Ventilation management.
The median and modus absolute V
T
of 450 (400–500) mL and 500 mL resulted in a V
T
of 7.8 (6.8–9.1) mL/kg PBW (Table 2). Tidal volume was similar in patients with LIPS < 4 and patients with LIPS ≥ 4, but was lower in patients with ARDS. Tidal volume was greater than 8.0 mL/kg PBW in 45% of patients with LIPS < 4, in 50% of patients with LIPS ≥ 4, and in 33% of patients with ARDS (Figure 2A). A V
T
≤ 7 mL/kg/PBW was found in one-third of patients without ARDS, but in more than half of patients with ARDS. The variance of V
T
when expressed in mL/kg PBW was large in all centers across countries (Supplemental Appendix, p. 19). Median and mode PEEP was five (5–8) cmH2O and 5 cmH2O, respectively. Positive end-expiratory pressure was similar in patients with LIPS < 4 and LIPS ≥ 4, but was higher in patients with ARDS (Figure 2B). Although approximately two-thirds of patients without ARDS were ventilated with a PEEP of 5 cmH2O or less, this happened only in one-third of patients with ARDS. Distributions of V
T
against various ventilator parameters are shown in
Ventilation characteristics in the first day of mechanical ventilation
| All patients (n = 1,315) | LIPS < 4 (n = 389) | LIPS ≥ 4 (n = 837) | Acute respiratory distress syndrome (n = 89) | P-value LIPS < 4 vs. LIPS ≥ 4 | P-value* | |
|---|---|---|---|---|---|---|
| Absolute V T (mL) | 450 [400, 500] | 450 [400, 500] | 450 [400, 500] | 400 [360, 470] | 0.642 | 0.0001 |
| Absolute V T (mL) mode | 500 | 500 | 500 | 400 | – | – |
| V T PBW (mL/kg PBW) | 7.9 [6.8, 9.1] | 7.9 [6.8, 8.9] | 8.0 [6.8, 9.2] | 7.0 [5.8, 8.4] | 0.621 | 0.0001 |
| Controlled mode | 7.9 [6.8, 9.1] | 7.9 [6.8, 8.9] | 8.0 [6.8, 9.2] | 7.0 [5.8, 8.5] | 0.765 | 0.0002 |
| Spontaneous mode | 8.1 [7.0, 9.2] | 7.8 [6.5, 9.5] | 8.3 [7.4, 9.3] | 7.7 [7.1, 8.0] | 0.372 | 0.4113 |
| ≤ 7.0 | 396 (30.5) | 111 (28.8) | 240 (29.2) | 45 (50.6) | 0.0715 | 0.0002 |
| 7.1–8.9 | 561 (43.2) | 181 (46.9) | 350 (42.5) | 30 (33.7) | – | – |
| 9.0–10.0 | 143 (11.0) | 31 (8.0) | 107 (13.0) | 5 (5.6) | – | – |
| > 10.0 | 198 (15.3) | 63 (16.3) | 126 (15.3) | 9 (10.1) | – | – |
| V T actual body weight (mL/kg) | 7.0 [6.0, 8.2] | 7.1 [6.2, 8.3] | 7.0 [6.0, 8.1] | 6.4 [5.6, 7.3] | 0.016 | 0.0001 |
| Positive end-expiratory pressure (cmH2O) | 5.0 [5.0, 8.0] | 5.0 [5.0, 7.0] | 5.0 [5.0, 7.5] | 10.0 [5.0, 12.0] | 0.123 | < 0.0001 |
| ≤ 5 | 804 (61.1) | 261 (67.1) | 520 (62.1) | 23 (25.8) | 0.232 | < 0.0001 |
| 6–8 | 335 (25.5) | 94 (24.2) | 220 (26.3) | 21 (23.6) | – | – |
| 8–10 | 112 (8.5) | 27 (6.9) | 69 (8.2) | 16 (18.0) | – | – |
| > 10 | 64 (4.9) | 7 (1.8) | 28 (3.3) | 29 (32.6) | – | – |
| Ventilation mode, n (%) | 0.0077 | 0.0001 | ||||
| Volume controlled | 483 (36.7) | 171 (44.0) | 288 (34.4) | 24 (27.0) | – | – |
| Pressure controlled | 327 (24.9) | 80 (20.6) | 218 (26.0) | 29 (32.6) | – | – |
| Pressure support ventilation | 40 (3.0) | 16 (4.1) | 22 (2.6) | 2 (2.2) | – | – |
| Synchronized intermittent mandatory ventilation | 389 (29.6) | 108 (27.8) | 255 (30.5) | 26 (29.2) | – | – |
| Airway pressure release ventilation | 3 (0.2) | 0 (0.0) | 1 (0.1) | 2 (2.2) | – | – |
| Pressure regulated volume-controlled ventilation | 68 (5.2) | 14 (3.6) | 48 (5.7) | 6 (6.7) | – | – |
| Other | 5 (0.4) | 0 (0.0) | 5 (0.6) | 0 (0.0) | – | – |
| Ppeak (cmH2O) | 22 [18, 28] | 21.0 [18, 25] | 22 [18, 28] | 28 [23, 36] | 0.0009 | < 0.0001 |
| Pplat (cmH2O)† | 18 [15, 21] | 16 [14, 18] | 18 [16, 21] | 28 [22, 30] | < 0.0001 | < 0.0001 |
| Driving pressure (cmH2O) | 14 [11, 18] | 13 [10, 17] | 15 [11, 18] | 16 [14, 20] | 0.0705 | 0.0037 |
| Set RR (bpm) | 14 [12, 16] | 14 [12, 16] | 14 [14, 16] | 17 [14, 22] | 0.0011 | < 0.0001 |
| Measured RR (bpm) | 18 [15, 22] | 16 [14, 20] | 18 [15, 22] | 20 [16, 25] | < 0.0001 | < 0.0001 |
| FiO2 (%) | 50 [40, 60] | 40 [40, 50] | 50 [40, 60] | 80 [60, 100] | < 0.0001 | < 0.0001 |
| Oxygen partial pressure/FiO2 (mmHg) | 258 [157, 378] | 311 [229, 419] | 253 [151, 375] | 112 [76, 211] | < 0.0001 | < 0.0001 |
| Pulse oxymetric saturation of haemoglobin/FiO2 | 200 [155, 250] | 245 [194, 250] | 200 [150, 245] | 119 [95, 167] | < 0.0001 | < 0.0001 |
| Arterial pH level | 7.3 [7.3, 7.4] | 7.4 [7.3, 7.4] | 7.3 [7.2, 7.4] | 7.3 [7.2, 7.4] | < 0.0001 | < 0.0001 |
| Carbon dioxide partial pressure (mmHg) | 36 [31, 43] | 35 [29, 40] | 37 [31, 44] | 41 [34, 52] | 0.0020 | < 0.0001 |
| Use of neuromuscular blockers (%) | 225/1,306 (17.2) | 74/385 (19.2) | 117/382 (14.1) | 34 (38.2) | 0.0267 | < 0.0001 |
| Use of prone positioning (%) | 6 (0.5) | 0 (0.0) | 0 (0.0) | 6 (6.7) | – | < 0.0001 |
| Use of recruitment maneuvers (%) | 24 (1.8) | 0 (0.0) | 8 (1.0) | 16 (18.0) | 0.120 | < 0.0001 |
| Tracheostomy | 95 (7.2) | 34 (8.7) | 49 (5.9) | 12 (13.5) | 0.080 | 0.0118 |
Data are number of patients/total number of patients (%) or median [IQR]. FiO2 = fraction of inspired oxygen; PBW = predicted body weight; Ppeak = peak inspiratory airway pressure; Pplat = plateau airway pressure; RR = respiratory rate; V T = tidal volume.
P-value represents comparisons across the three study groups for each variable.
Plateau pressure values are restricted to patients in whom this value was reported and in whom either an assist control mode was used or in whom a mode permitting spontaneous ventilation was used.
Ventilation parameters at admission in patients with LIPS < 4 vs. patients with LIPS ≥ 4 and those with ARDS cumulative frequency distribution of (A) V T , (B) PEEP, (C) plateau pressure, and (D) driving pressure. Vertical dotted lines represent the cutoff for each variable, and horizontal dotted lines represent the respective proportion of patients reaching each cutoff. Cutoffs for ventilator parameters were like those used in previous published reports on invasive ventilation practices, that is, 8 mL/kg PBW for V T , 5 cmH2O for PEEP, 30 cmH2O for Pplat, and 15 cmH2O for driving pressure. 7 ARDS = acute respiratory distress syndrome; PBW = predicted body weight; PEEP = positive end-expiratory pressure; V T = tidal volume. This figure appears in color at www.ajtmh.org.
Citation: The American Journal of Tropical Medicine and Hygiene 104, 3; 10.4269/ajtmh.20-1177
Volume-controlled ventilation and synchronized intermittent mandatory ventilation were the two most commonly used ventilation modes (Table 2 and Supplemental Appendix, pp. 9–11, and 21). Pressure-controlled ventilation was used in about one-fourth of patients, and was the most prevalent mode in patients with ARDS. Median FiO2, RR, Ppeak, and Pplat (Figure 2C) increased from patients with LIPS < 4 to patients with LIPS ≥ 4 and patients with ARDS. Differences in ventilator parameters sustained during the first 3 days of invasive ventilation (Figure 3). In longitudinal analysis, an interaction between time and study group was found only for FiO2 and Pplat; that is, there was a greater decrease of oxygen supplementation in ARDS, whereas Pplat decreased only slightly in ARDS and remained constant for the other two groups. Median driving pressure was similar in patients with LIPS < 4 and patients with LIPS ≥ 4, but was higher in patients with ARDS (Figure 2D).
Ventilatory parameters in the first 4 days of mechanical ventilation. Lines are means and 95% CIs. FiO2 = fraction of inspired oxygen; PBW = predicted body weight; PEEP = positive end-expiratory pressure; Ppeak = peak pressure; Pplat = plateau pressure; V T = tidal volume. P-value is for group and time–group interaction. This figure appears in color at www.ajtmh.org.
Citation: The American Journal of Tropical Medicine and Hygiene 104, 3; 10.4269/ajtmh.20-1177
Pulmonary complications.
Overall, one-fifth of patients developed one or more pulmonary complications during the first 7 days of ICU stay (Table 3 and Supplemental Appendix, pp. 12–13). Pulmonary complication rates were similar in patients with LIPS < 4 and LIPS ≥ 4, but was higher in patients with ARDS. Of all patients without ARDS at the start of ventilation, 51 (4%) developed ARDS during the first 7 days of ICU stay, mostly on day 1 or 2, with no significant difference between patients with LIPS < 4 and LIPS ≥ 4 (P = 0.151). The capacity of the LIPS to predict development of ARDS was poor (ROC AUC of 0.62, 95% CI: 0.54–0.70; Supplemental Appendix, p. 27). Overall, 7% of patients underwent tracheostomy (14% in patients with ARDS), whereas 4% needed re-intubation after an unsuccessful extubation attempt. The frequency of tracheostomy was different among the three groups.
Pulmonary complications observed in first 7 days of mechanical ventilation and clinical outcomes
| All patients (n = 1,315) | LIPS < 4 (n = 389) | LIPS ≥ 4 (n = 837) | ARDS (n = 89) | P-value LIPS < 4 vs. LIPS ≥ 4 | P-value* | |
|---|---|---|---|---|---|---|
| Pulmonary complications, n (%) | ||||||
| Patients with at least one new pulmonary complication† | 283 (21.5) | 72 (18.5) | 177 (21.1) | 34 (38.2) | 0.321 | 0.0002 |
| Pulmonary complication type, n (%) | ||||||
| Pulmonary infection | 110 (8.4) | 34 (8.7) | 65 (7.8) | 11 (12.4) | 0.638 | 0.314 |
| ARDS | 51 (3.9) | 11 (2.8) | 40 (4.8) | – | 0.151 | – |
| Pneumothorax | 10 (0.8) | 1 (0.3) | 8 (1.0) | 1 (1.1) | 0.330 | 0.340 |
| Pleural effusion | 44 (3.3) | 6 (1.5) | 35 (4.2) | 3 (3.4) | 0.0263 | 0.057 |
| Atelectasis | 62 (4.7) | 14 (3.6) | 41 (4.9) | 7 (7.9) | 0.382 | 0.212 |
| Cardiogenic pulmonary edema | 28 (2.1) | 6 (1.5) | 20 (2.4) | 2 (2.2) | 0.456 | 0.631 |
| New pulmonary infiltrates | 72 (5.5) | 21 (5.4) | 40 (4.8) | 11 (12.4) | 0.747 | 0.012 |
| Outcomes | ||||||
| Death in ICU | 388/1,300 (29.8) | 66/383 (17.2) | 282/828 (34.1) | 40 (44.9) | < 0.0001 | < 0.0001 |
| Death during ICU stay | 362/1,300 (27.8) | 60/383 (15.7) | 265/828 (32.0) | 37 (41.6) | < 0.0001 | < 0.0001 |
| Palliative care | 26 (2.0) | 6 (1.6) | 17 (2.1) | 3 (3.4) | 0.726 | 0.540 |
| Duration of MV (days) | 2.0 [1.0, 5.0] | 2.0 [1.0, 5.0] | 2.0 [1.0, 5.0] | 4.0 [2.0, 8.0] | 0.925 | 0.0024 |
| Re-intubation | 52 (4.0) | 16 (4.1) | 34 (4.1) | 2 (2.2) | 1.00 | 0.693 |
| Length of stay in ICU (days) | 4.0 [2.0, 7.0] | 3.0 [2.0, 7.0] | 4.0 [2.0, 7.0] | 5.0 [2.0, 9.0] | 0.187 | 0.0641 |
| Length of stay in survivors | 4.0 [2.0, 7.0] | 3.0 [2.0, 7.0] | 4.0 [2.0, 7.0] | 6.0 [3.0, 9.0] | 0.001 | 0.0001 |
| Length of stay in non-survivors | 3.0 [1.0, 7.0] | 3.0 [2.0, 8.0] | 3.0 [1.0, 6.0] | 3.0 [2.0, 8.0] | 0.122 | 0.239 |
| Ventilator-free days at day 28‡ | 24.0 [0.0, 27.0] | 26.0 [16.5, 27.0] | 23.0 [0.0, 27.0] | 8.0 [0.0, 24.5] | < 0.0001 | < 0.0001 |
| Type of discharge for survivors | ||||||
| Transferred to ward | 689/1,300 (53.0) | 257/383 (67.1) | 399/828 (48.2) | 33 (37.1) | < 0.0001 | < 0.0001 |
| Discharged home | 46/1,300 (3.5) | 11/383 (2.9) | 32/828 (3.9) | 3 (3.4) | 0.483 | 0.683 |
| Transferred to other ICU | 40/1,300 (3.1) | 14/383 (3.7) | 25/828 (3.0) | 1 (1.1) | 0.683 | 0.454 |
| Transferred to intermediate care | 137/1,300 (10.5) | 35/383 (9.1) | 90/828 (10.9) | 12 (13.5) | 0.413 | 0.425 |
ARDS = acute respiratory distress syndrome; ICU = intensive care unit. Data are number of patients/total number of patients (%) or median [IQR].
P-value represents comparison across the three study groups for each variable.
Pulmonary complications diagnosed on the first 24 of invasive ventilation were excluded from analysis and reported separately.
In patients who died while receiving invasive mechanical ventilation, invasive ventilation-free days are counted as 0. Patients discharged alive from ICU were assumed to be alive at day 28.
Patient outcomes.
When mortality in the three groups is taken as a competing risk, at any particular time, patients with LIPS ≥ 4 were 27% less likely, and patients with ARDS were 45% less likely to be extubated than patients with LIPS < 4 (Figure 4). Almost half of patients with ARDS died in ICU, compared with a third of patients with LIPS ≥ 4 and less than a sixth of patients with LIPS < 4. The duration of invasive ventilation was longer in ARDS patients, whereas the length of stay in ICU did not differ between the three patient groups (Table 3). Length of stay in non-surviving patients was shorter of roughly 1 day than that of surviving patients.
Probability of discontinuing mechanical ventilation when accounting for the competing risk of death before extubation in patients with LIPS < 4 vs. patients with LIPS ≥ 4 and those with ARDS estimates is shown as hazard ratio (95% CIs). The cumulative incidence function curves estimate the instantaneous probability over time of extubation (shown in continuous lines) when accounting for the risk set attrition due to the occurrence of the competing risk (death before extubation, shown in survival curves as dotted lines). The “Fine and Gray” proportional sub-distribution hazards analysis was used to model the sub-distribution hazard and derive P-values. ARDS = acute respiratory distress syndrome. This figure appears in color at www.ajtmh.org.
Citation: The American Journal of Tropical Medicine and Hygiene 104, 3; 10.4269/ajtmh.20-1177
Adjunctive treatments were infrequently used, except for muscle paralysis that was used in approximately one in every five patients, and was about twice more frequent in patients with ARDS. Recruitment maneuvers and prone positioning were used infrequently and mostly in patients with ARDS. None of the patients in this study received extracorporeal membrane oxygenation or other extracorporeal techniques.
Univariable and multivariable analyses of factors associated with ICU mortality and pulmonary complications are listed in Table 4 and Supplemental Appendix, pp. 15–16. According to all models and based on clinical relevance, age, non-pulmonary SOFA, LIPS, Ppeak, heart rate, pH, and previous use of NIV before intubation were selected as potential predictors of death in ICU. Pulmonary SOFA, arterial pH levels, and chronic liver failure were consistently selected as potential predictors of pulmonary complications.
Analysis of factors associated with intensive care unit mortality in patients receiving mechanical ventilation
| Unadjusted analyses | Multivariable analyses | |||
|---|---|---|---|---|
| Clinical characteristics and comorbidities | Odds ratio (95% CI) | P value | Odds ratio (95% CI) | P value |
| Age (years) | ||||
| ≤ 65 | 1 (reference) | 1 (reference) | ||
| > 65 | 1.37 (1.02–1.85) | 0.038 | 1.72 (1.18–2.51) | 0.005 |
| Gender, female | 1.07 (0.82–1.39) | 0.628 | – | – |
| Body mass index (kg/m2) | 0.99 (0.86–1.13) | 0.844 | – | – |
| Hypertension | 1.15 (0.88–1.50) | 0.300 | – | – |
| Diabetes mellitus | 1.31 (0.98–1.73) | 0.064 | 1.04 (0.73–1.48) | 0.827 |
| Heart failure | 0.74 (0.43–1.25) | 0.259 | – | – |
| Chronic kidney disease | 1.02 (0.49–1.46) | 0.938 | – | – |
| Chronic liver failure | 2.64 (1.43–4.88) | 0.002 | 1.78 (0.84–3.79) | 0.133 |
| Chronic obstructive pulmonary disease | 0.63 (0.35–1.11) | 0.109 | 0.60 (0.30–1.20) | 0.149 |
| Cancer | 1.22 (0.76–1.96) | 0.406 | – | – |
| Severity of illness | ||||
| SOFA total | 2.14 (1.85–2.49) | < 0.001 | – | – |
| Non-pulmonary SOFA | 2.05 (1.78–2.38) | < 0.001 | 1.65 (1.37–2.00) | < 0.001 |
| Pulmonary SOFA | 1.31 (1.15–1.50) | < 0.001 | 1.09 (0.89–1.33) | 0.401 |
| Lung injury prediction score | 1.86 (1.61–2.15) | < 0.001 | 1.41 (1.16–1.72) | 0.001 |
| Management | ||||
| Tidal volume (mL/kg Predicted body weight) | 0.89 (0.77–1.03) | 0.124 | 0.89 (0.74–1.08) | 0.237 |
| Positive end-expiratory pressure (cmH2O) | 1.10 (1.04–1.16) | 0.001 | ||
| < 8 cmH2O | 1 (reference) | 1 (reference) | ||
| 8–12 cmH2O | 1.52 (1.02–2.26) | 0.037 | 0.82 (0.51–1.34) | 0.434 |
| ≥ 12 cmH2O | 2.47 (1.37–4.45) | 0.002 | 0.72 (0.33–1.57) | 0.408 |
| Use of noninvasive ventilation before intubation | 1.53 (1.03–2.25) | 0.031 | 1.82 (1.12–2.96) | 0.015 |
| Ventilated in ward before admission | 1.47 (0.93–2.30) | 0.095 | 1.07 (0.62–1.86) | 0.803 |
| Maximum airway pressure (cmH2O) | 1.53 (1.30–1.79) | < 0.001 | 1.26 (1.03–1.55) | 0.027 |
| Driving pressure (cmH2O) | 1.43 (1.10–1.88) | 0.008 | – | – |
| Respiratory rate (movements per minute)* | 1.42 (1.22–1.66) | < 0.001 | 1.13 (0.94–1.38) | 0.210 |
| FiO2 (%) | 1.74 (1.51–2.01) | < 0.001 | – | – |
| Laboratory parameters | ||||
| PaO2/FiO2 (mmHg)* | 0.67 (0.57–0.78) | < 0.001 | – | – |
| PaCO2 (mmHg) | 1.10 (0.96–1.26) | 0.157 | 0.91 (0.75–1.11) | 0.342 |
| HCO3 (mEq/L) | 0.68 (0.59–0.79) | < 0.001 | – | – |
| pH* | 0.63 (0.53–0.73) | < 0.001 | 0.77 (0.63–0.94) | 0.001 |
| Vital signs | ||||
| SpO2 (%) | 0.71 (0.61–0.83) | < 0.001 | – | – |
| SpO2/FiO2 (mmHg)* | 0.55 (0.47–0.64) | < 0.001 | – | – |
| Heart rate (bpm)* | 1.49 (1.29–1.70) | < 0.001 | 1.27 (1.06–1.52) | 0.008 |
| Mean arterial pressure (mmHg)* | 0.65 (0.56–0.75) | < 0.001 | 0.85 (0.71–1.02) | 0.080 |
| Pulmonary complications | ||||
| Occurrence of at least one complication | 1.18 (0.86–1.61) | 0.311 | – | – |
BPM = beats per minute; FiO2 = inspired fraction of oxygen; PaO2 = Oxygen partial pressure; SOFA = Sequential Organ Failure Assessment; SpO2 = oxygen saturation. All parameters were measured in the first day of ventilation. Adjusted intraclass correlation coefficient 0.124; HCO3 was excluded from the multivariable analysis because of multicollinearity with pH. Total SOFA score and single-organ SOFA scores were excluded from the multivariable analysis because of multicollinearity with non-pulmonary SOFA. Driving pressure was excluded because of multicollinearity with Pmax and considered in a separate prespecified sensitivity analysis. PaO2/FiO2 and SpO2/FiO2 and FiO2 were excluded because of collinearity with pulmonary SOFA. Age and PEEP did not meet the linearity assumption and were thus entered as categorical variables.
* Numerical variables were standardized in the multivariate analysis to improve convergence of the model.
DISCUSSION
In this international, multicenter, observational study in ICUs in Asian countries, two-thirds of patients undergoing invasive ventilation were at risk for ARDS, according to the LIPS, whereas only a minority of patients actually had ARDS at the start of ventilation. Individualization of V T was applied poorly, but applied V T levels in these limited-resource settings were globally compatible with lung-protective ventilation. A V T < 8 mL/kg PBW was applied in a majority of patients with ARDS, and most patients without ARDS received a V T under 10 mL/kg PBW. Progression to ARDS was observed in one in every 25 patients. Patients with ARDS received higher PEEP than those not having ARDS. Pulmonary complications were frequent and occur more often in patients with ARDS. Crude ICU mortality was markedly different between patients with LIPS < 4 versus patients with LIPS ≥ 4 or with ARDS.
Considerable geographic variation was present in the proportion of patients with LIPS ≥ 4 for ARDS and patients with ARDS. The disparity may be explained by differences in case mixes attributable to factors such as admission policies, season of enrolment, and availability of ICU beds. A cutoff of four for the LIPS was used to define the population at risk for developing ARDS. 13 This cutoff has been used before in several other cohorts, albeit with limited success. 7,15 Using other, higher cutoffs, unfortunately, did not improve its accuracy. 7,15 The proportion of patients with ARDS on admission reported here is similar to the preceding PRoVENT study that was performed in high-income countries, 7 but much lower than the 22% ARDS prevalence on day 1 or 2 observed in LUNG SAFE. 8 Several factors could explain this disparity. There could be a difference in the risk for ARDS. Another factor could be the difference in access to mechanical ventilation. Whereas under-recognition of ARDS may occur in settings studied in the current study, there may have been over-recognition of ARDS by the computer algorithm used in LUNG SAFE. 21
The proportion of patients receiving protective ventilation is comparable to findings reported in two recent investigations, 7,8 challenging the hypothesis that delivering lung protective ventilation is less feasible in more resource-limited settings. These encouraging results in terms of ventilator management, and the fact that ventilator settings were not associated with mortality or pulmonary complications, suggest other variables should also be explored to improve outcome of ventilated patients in resource-limited ICUs. Patients with ARDS were more frequently receiving ventilation with protective settings. In fact, V T in patients with ARDS in these ICUs from Asian middle-income countries was lower than that in those in LUNG SAFE. 8 This could suggest a better implementation of protective ventilation in these settings, 5,10 but may also point to a better titration of V T in clinically recognized ARDS. The improved ventilation settings in physician-recognized ARDS were also observed in LUNG SAFE, 8 emphasizing the possibility that clinical recognition can drive behavioral change.
PRactice of VENTilation in Middle-income Countries shows there is scant individualization in ventilation, similar to previous investigations. 3,4,7 Indeed, although median and mode V T were 450 and 500 mL, there was a large variance in V T expressed as mL/kg PBW. The median V T in terms of mL/kg PBW was very similar to that in another multinational cohort, 7 possibly denoting consideration for the lower average height and thus the PBW in this population of Asian individuals. Tidal volume based on actual body weight (ABW) was consistently lower than the one calculated using PBW, and it is possible several physicians still used ABW to decide on the V T to apply. The fact that V T differences among groups were not significant after accounting for clustering indicates that titration of V T in ARDS did receive more attention in some participating centers. Despite well-contained V T , the calculated driving pressure often reached suboptimal ranges associated with increased lung injury. This parameter, however, could only be calculated in one-third of patients, and Pmax may overestimate Pplat in patients under pressure-controlled ventilation. These findings are important as protective ventilation impacts survival of ICU patients. 4,22–26
Most of the patients received a PEEP ≥ 5 cmH2O, in agreement with a well-documented global upward trend in the application of PEEP. 4 Positive end-expiratory pressure did not differ between patients with LIPS < 4 versus patients with LIPS ≥ 4, but was higher in ARDS. Higher PEEP is mostly used in patients with ARDS, and especially in clinician-recognized ARDS, 8 as was the case of this study. The low rate of use of recruitment maneuvers and prone positioning, mostly observed in ARDS patients in this cohort, is in line with the data reported by LUNG SAFE. 8
Based on LIPS, two-thirds of patients were “at risk for ARDS,” which is twice as high as in high-income countries. 7 The proportion of patients with LIPS ≥ 4 who developed ARDS during follow-up, however, was less than that reported in previous studies in high-income settings (7–9%) 7,27 and also compared with a recent investigation focusing on the development of ARDS in patients in Peruvian ICUs (11%). 28 The current study confirms the poor predictive value of the LIPS for developing ARDS 7 and for pulmonary complications, however, did identify patients at increased risk of death. The higher mortality in the group with LIPS ≥ 4 may be explained, at least in part by differences in age, Body mass index and comorbidities, the SOFA score on admission, and use of noninvasive ventilation before the start of invasive ventilation. Use of noninvasive ventilation was even independently associated with mortality, in line with findings of previous studies in patients receiving invasive ventilation. 4,29
Intensive care unit mortality was considerably lower than that in other cohort studies from low- and middle-income countries (LMICs), 10,11,30 an improvement that mirrors global trends. 4 The benefit in terms of mortality reduction attributable to a wider implementation of protective ventilation is unknown, but possibly significant. This role is important as protective ventilation represents an intervention relatively independent of geo-economic variations between regions that are known to affect survival at least in ARDS. 31 Intensive care unit mortality for the ARDS group was higher than that reported by the LUNG SAFE study, 8 reflecting geo-economic effects on patients’ outcomes. 31
This study has several limitations. First, the willingness to participate may have facilitated a selection bias toward centers with awareness concerning protective ventilation and with more affluent resources. Second, as in any prospective observational study, reporting and observer bias or interference with daily practice cannot be excluded. Third, to limit the investigators’ burden, granular data were limited to the first 4 days of ventilation. This limited information regarding end of ventilation in a quarter of the study cohort. Similarly, extrapulmonary complications which could have included unknown confounders were not captured. Follow-up was also limited to ICU discharge, limiting the available information on post-ICU patient outcomes. Also, no data were collected on the weaning process, which will be investigated in a separate multicenter study. 32 Because of missing data, in the competing risk regression, we could not account for extubations due to life-sustaining therapy withdrawal caused by medical decisions, or by economic restraints of the patient entourage. Access to patients’ data was restricted to local investigators and not externally monitored; thus, inclusion of all consecutive ventilated patients was not confirmed independently. Fourth, overrepresentation of some countries and seasonal differences could not be averted, as the number of centers per country or the 4-week study window was not limited by protocol. Finally, although definitions for pulmonary complications were prepublished and provided to national and local coordinators in local meetings, no formal site training was performed to homogenize complications scoring.
Strengths of this study include the wide variety of settings and participating ICUs, increasing the generalizability of results. The prospective design assured completeness of data collection, whereas the short time frame within which data were collected limited the effect of practice changes during study period. The focus on Asian LMICs allowed us to study a large region that has thus far been underrepresented in ventilation studies, 4,7,8 whereas this region harbors half of the world population.
In conclusion, PRoVENT-iMiC extends the context-specific knowledge of ventilation practices in Asian middle-income countries, showing alignment with other world regions with regard to ventilation management and outcomes. However, the study also suggests areas for quality improvement initiatives and subjects for clinical trials, instrumental to enhance safety, and effectiveness of invasive ventilation in middle-income countries.
PRoVENT-iMiC, “PRactice of VENTilation in Middle-income Countries”
MORU, “Mahidol-Oxford Tropical Medicine Research Unit”, Bangkok, Thailand (www.tropmedres.ac)
PROVE Network, “PROtective VEntilation Network” (www.provenet.eu)
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