To the Editor:
Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure accounting for at least 10% of global intensive care unit (ICU) admissions (1–5). The Berlin definition for diagnosing ARDS is expensive for most resource-constrained settings to apply (6–8). There are therefore very limited data reporting on the burden of ARDS in low-income countries. We sought to determine the prevalence of ARDS among mechanically ventilated Ugandan ICU patients using the Kigali modification.
Methods
Study design, study setting, and procedure
We conducted a prospective prevalence study. Patients admitted to one of six participating Ugandan ICUs, aged ⩾18 years, who had a chest X-ray and were receiving mechanical ventilation for ⩾48 hours, were considered eligible. The setting was recently described (9). Informed consent was obtained and approval to conduct the study was obtained from the School of Medicine Research and Ethics Committee of Makerere University. Those who met these criteria were then assessed for ARDS diagnosis based on onset ⩽7 days, bilateral lung opacities on chest radiograph, and ratio of oxygen saturation as measured by pulse oximetry (SpO2) to fraction of inspired oxygen (FiO2) of <315. The study team extracted demographic and clinical data from medical records. The lowest SpO2 and other patient vitals on the day of enrollment were recorded, as was any clinician diagnosis of ARDS documented on the medical charts at any time during the follow-up period. Cardiac causes as an exclusion criteria were ascertained from medical charts or echocardiograms. Only chest X-ray interpretations as reported by radiologists were considered. Lung ultrasound was not routinely done.
Analyses
Data were analyzed using STATA (StataCorp. 2014. Stata Statistical Software: Release 14.1). The proportion of participants meeting the study definition was calculated. Data are summarized using proportions and/or percentages for categorical variables and means with standard deviations (SDs) for continuous data. In addition, continuous, nonnormally distributed variables are summarized as medians and interquartile ranges. To compare characteristics between categorical variables, the chi-square and Fisher’s exact tests were used. Logistic regression analyses were used to identify predictors of mortality among patients with and without ARDS. Bivariate analysis was performed for each of the independent predictors of interest, and all those with P values of 0.2 and less were included in a multivariable logistic model. We also included variables that are known risk factors for mortality in an ARDS population. Significance was established at a P value of ⩽0.05. A sample size of 229 was calculated.
Results
Of 312 patients assessed for eligibility, 231 were enrolled (Figure 1). The majority were male, and the mean age was 44.5 (SD, 17.7). The average length of stay was 8.1 days (SD, 7.5). The mean SpO2 was 93% (SD, 8.6), and mean arterial pressure (MAP) was 77.3 mm Hg (SD, 21.9). Traumatic brain injury (24.2%), acute respiratory failure (17.3%), and postoperative care (for respiratory support) were the most common indications for admission. Sepsis was the most common comorbidity, and 29 (12.4%) patients had septic shock requiring vasopressors. (Table 1)
Figure 1.
Study flow diagram. ARDS = acute respiratory distress syndrome.
Table 1.
Baseline patient demographics and admission clinical characteristics
| Characteristics | ARDS by Modified Criteria |
Overall [N = 231 (100)] | |
|---|---|---|---|
| Yes [n = 163 (70.6)] | No [n = 68 (29.4)] | ||
| Sex | |||
| Male | 103 (71.0) | 42 (29.0) | 145 (62.8) |
| Female | 60 (69.8) | 26 (30.2) | 86 (37.2) |
| Age, yr, mean (SD) | 45.1 (18.3) | 43.1 (16.4) | 44.5 (17.7) |
| Primary admission diagnosis* | |||
| Traumatic brain injury | 33 (61.1) | 21 (38.9) | 54 (24.2) |
| ARDS | 34 (85) | 6 (15) | 40 (17.3) |
| Septic shock | 7 (87.5) | 1 (12.5) | 8 (3.4) |
| Post-cardiac arrest | 8 (72.7) | 3 (27.2) | 11 (4.8) |
| Neurological (medical)† | 12 (57.1) | 9 (42.9) | 21 (9) |
| Postoperative‡ | 28 (77.8) | 8 (22.2) | 36 (15.6) |
| Obstetric§ | 13 (76.5) | 4 (23.5) | 17 (7.3) |
| Cardiac | 7 (70) | 3 (30) | 10 (4.3) |
| Otherǁ | 16 (76.2) | 5 (23.8) | 21 (9) |
| Common admission comorbidities | |||
| Sepsis | 36 (75) | 12 (25) | 48 (20.8) |
| HIV positive | 19 (70.4) | 8 (29.6) | 27 (11.7) |
| Acute kidney injury | 13 (86.7) | 2 (13.3) | 15 (6.5) |
| Pneumonia | 6 (75) | 2 (25) | 8 (3.5) |
| Peritonitis | 6 (67) | 3 (33) | 9 (3.8) |
| Cancer | 8 (88.9) | 1 (11.1) | 9 (3.8) |
| Diabetes mellitus | 5 (83.3) | 1 (16.7) | 6 (2.5) |
| Malaria | 4 (80) | 1 (20) | 5 (2.1) |
| Additional organ support | |||
| Vasopressors for septic shock | 25 (86.2) | 4 (13.8) | 29 (12.4) |
| Renal replacement therapy for AKI | 5 (71.4) | 2 (28.6) | 7 (3.0) |
| Outcome | |||
| Discharged | 93 (62.4) | 56 (37.6) | 149 (64.5) |
| Died | 70 (85.4) | 12 (14.6) | 82 (35.5) |
Definition of abbreviations: AKI = acute kidney injury; ARDS = acute respiratory distress syndrome; HIV = human immunodeficiency virus; SD = standard deviation.
Data are shown as n (%) unless otherwise noted.
As indicated in patient charts.
Includes diagnoses such as stroke, meningitis, Guillain-Barré syndrome, and encephalopathies.
Did not include obstetric surgical patients.
Includes preeclampsia, postpartum hemorrhage, and high spinal injections.
Includes acute poisoning and liver failure.
Although 70% (163/231) of the patients met the criteria for ARDS by the modified method, only 17% (40/231) had ARDS as a clinician diagnosis. When stratified by the severity of hypoxemia, 21% had severe ARDS and 28% had moderate ARDS (Table 2).
Table 2.
Bivariable and multivariable analysis of factors associated with mortality
| Characteristic | Outcome [n (%)] |
Crude Prevalence Ratio (95% CI) | P Value | Adjusted Prevalence Ratio (95% CI) | P Value | |
|---|---|---|---|---|---|---|
| Died | Discharged | |||||
| Overall | 82 (35.5) | 149 (64.5) | ||||
| Sex | ||||||
| Male | 52 (35.9) | 93 (64.1) | 1.00 | |||
| Female | 30 (34.9) | 56 (65.1) | 1.02 (0.83–1.24) | 0.880 | ||
| Age, yr* | ||||||
| ⩽42 | 74 (61.7) | 46 (38.3) | 1.00 | |||
| ⩾43 | 75 (67.6) | 36 (32.4) | 1.10 (0.90–1.33) | 0.350 | ||
| HIV status* | ||||||
| Negative | 133 (65.2) | 71 (34.8) | 1.00 | |||
| Positive | 16 (59.3) | 11 (40.7) | 0.91 (0.65–1.26) | 0.570 | ||
| Diagnosis of sepsis*† | ||||||
| No | 52 | 110 | 1 | 0.123 | 0.85 (0.68–1.06) | 0.163 |
| Yes | 30 | 39 | 0.83 (0.65–1.05) | |||
| Severity of hypoxemia*‡ | ||||||
| Normal (⩾316) | 12 (38.8) | 56 (61.2) | 1.00 | 1.00 | ||
| Mild (201–315) | 18 (62.5) | 30 (37.5) | 1.61 (1.06–2.44) | 0.024 | 1.97 (1.26–3.09) | 0.003 |
| Moderate (101–200) | 22 (66.7) | 44 (33.3) | 1.72 (1.16–2.54) | 0.001 | 1.81 (1.10–3.98) | 0.019 |
| Severe (⩽100) | 30 (82.4) | 19 | 2.12 (1.47–3.07) | <0.001 | 2.40 (1.52–3.79) | <0.001 |
| ARDS by modified criteria | ||||||
| Normal (⩾316) | 12 (17.6) | 56 (82.4) | 1.00 | 1.00 | ||
| ⩽315 | 70 (42.9) | 93 (57.1) | 1.44 (1.21–1.72) | <0.001 | 1.38 (1.15–1.65) | <0.01 |
| Respiratory rate | ||||||
| Normal | 91 (66.6) | 48 (34.5) | 1.00 | |||
| 25–30 | 36 (66.7) | 18 (33.3) | 1.02 (0.81–1.27) | 0.874 | ||
| ⩾31 | 22 (57.9) | 16 (42.1) | 0.88 (0.66–1.19) | 0.418 | ||
| Hypotension | ||||||
| Normal (⩾65) | 116 (68.2) | 54 (31.8) | 1.00 | 1.00 | ||
| Abnormal (<65) | 32 (53.3) | 28 (46.7) | 0.78 (0.60–1.01) | 0.062 | 0.82 (0.63–1.07) | 0.142 |
Definition of abbreviations: ARDS = acute respiratory distress syndrome; CI = confidence interval; FiO2 = fraction of inspired oxygen; HIV = human immunodeficiency virus; SpO2 = oxygen saturation as measured by pulse oximetry.
Known risk factors for mortality in ARDS.
As diagnosed and documented by attending physician team.
Severity of hypoxemia was graded using the SpO2:FiO2 ratio.
The all-cause ICU mortality was 35.5% (Table 1). There was statistically significant higher mortality among patients with ARDS according to modified criteria. Mortality was also associated with a worsening severity of hypoxemia (adjusted prevalence ratio 2.40, 95% confidence interval, 1.52–3.79; P < 0.01) (Table 2).
Discussion
The prevalence of ARDS among mechanically ventilated patients in our population was higher than that reported in high-income countries (3) We used the Kigali modification (7) to guide the diagnosis of ARDS. A Ghanaian study reported (10) a much lower prevalence of ARDS in a mechanically ventilated population. However, it was in a single center with a smaller sample size. This high prevalence in our setting, also reported in previous studies (11, 12), may have been related to our limitations in ICU bed capacity (9, 13), and therefore, only the sickest patients make it to the ICU.
Patients who met criteria for ARDS were more likely to die than those who did not, and overall ICU mortality in our study was higher than that found in high-income countries. This may be due to higher severity of illness among our ICU population despite the younger age of our patients, as has been previously documented (12). We also cannot rule out the fact that skill, human, and other resource limitations contributed to the high mortality.
There were significantly fewer clinician diagnoses than those made by modification of the criteria, and there was nothing in the charts to suggest any methods or severity of hypoxemia-based stratification. Underdiagnosis of ARDS has been reported in several studies, even in high-income countries (3–5).
Strategies such as proning and lung protective ventilation are the mainstay of treatment for patients with ARDS (14). We did not assess for either strategy in this study population, and we consider this a limitation.
We found that the severity of hypoxemia was significantly associated with mortality. In a large, French multicenter, 1-day point prevalence study, it was found that the presence of hypoxemia was associated with higher mortality and ICU length of stay and that the association with mortality was even stronger in the severe hypoxemia group (15).
Our study had several limitations. Because patients were excluded if no chest radiographs had been performed and because patients were not followed for the development of ARDS throughout their ICU stay, we may have underestimated the prevalence of ARDS.
We were unable to standardize SpO2 measurements in the different ICUs and might have missed potential artifactual SpO2 values.
The accuracy of pulse oximetry among dark-skinned individuals has recently been questioned in a recent analysis that showed a threefold likelihood of occult hypoxemia among Black patients (16). We are not sure that this significantly affected our results.
As shown elsewhere, SpO2/FiO2 ratio could serve as a viable alternative for the ratio of arterial oxygen tension/pressure to FiO2 in the risk stratification of such patients (17). In addition, an external validation of the Kigali modification was also performed in the Netherlands with a satisfactory degree of correlation (18).
In conclusion, our study has shown a high prevalence of ARDS and ARDS-related mortality in a low-income setting with little evidence of ARDS management practices.
Footnotes
Supported by the Developing Excellence in Leadership, Training and Science (DELTAS) Africa Initiative grant #DEL-15-011 to Training Health Researchers into Vocational Excellence (THRiVE) THRiVE-2. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences’ Alliance for Accelerating Excellence in Science in Africa and is supported by the New Partnership for Africa’s Development Planning and Coordinating Agency, with funding from Wellcome (Wellcome Trust grant # 107742/Z/15/Z) and the UK government. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Author Contributions: A.K. conceptualized and designed the study and analyzed the data. D.P.K., L.N., J.N., C.N., A.M., and E.O. participated in the study design and data collection. R.S., N.K., and J.T. participated in the data analysis. D.K., R.C.B., J.T., and C.S. participated in manuscript preparation. All authors read and approved the final manuscript. A.K. confirms that this manuscript (including the data and data analysis) is a publication of the authors’ original research.
Data sharing statement: Data will be available upon reasonable request.
Author disclosures are available with the text of this letter at www.atsjournals.org.
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