ORIGINAL ARTICLE |
https://doi.org/10.5005/jp-journals-11010-1139 |
Analyzing Factors Influencing Mortality in Acute Respiratory Failure: A Comprehensive Study of 275 Patients
1Department of General Medicine, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
2Department of Hemato-oncology, Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
3Department of Pulmonary Medicine, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
Corresponding Author: Ramya Durgam, Department of Hemato-oncology, Rajiv Gandhi Cancer Institute and Research Center, Delhi, India, Phone: +91 7702260683, e-mail: durgamramya1995@gmail.com
Received: 21 August 2024; Accepted: 04 December 2024; Published on: 17 February 2025
ABSTRACT
Aim and background: To analyze the demographic, clinical, and outcome characteristics of patients with acute respiratory failure (ARF) and to assess the impact of various factors on patient outcomes.
Materials and methods: A total of 275 patients with ARF were included in this study. The mean age of patients was 48.18 ± 16.34 years, with a male predominance (64.0%). The distribution of respiratory failure types was as follows: 78.5% had type 1, 18.5% had both type 1 and type 2, and 2.9% had type 2 respiratory failure. Patients received different types of respiratory support: 50.5% with oxygen therapy (face mask, nasal cannula, etc.), 24.4% with noninvasive ventilation (NIV), and 25.1% required mechanical ventilation.
Results: The most common etiology was pneumonia (18.5%), followed by heart failure (18.2%), poisoning (17.1%), sepsis (16.4%), and acute exacerbation of chronic obstructive pulmonary disease (COPD) (7.3%). Additional etiologies included acute pancreatitis, fluid overload, diabetic ketoacidosis, malignancies, and other less common conditions. The predominant symptom at presentation was breathlessness (58.2%), with fever (33.1%), cough (23.6%), and vomiting (23.3%) also frequently observed. The mortality rate was 77.1%, with 22.9% of patients being discharged. Significant associations were found between mortality and poisoning (χ2 = 13.862, p < 0.001), altered sensorium (χ2 = 4.054, p = 0.044), and vomiting (χ2 = 5.117, p = 0.024). Fever was associated with a higher likelihood of discharge (χ2 = 4.758, p = 0.029). There was no significant difference in outcomes based on the type of respiratory failure (χ2 = 1.144, p = 0.564). However, the type of respiratory support significantly impacted outcomes, with mechanical ventilation being associated with higher mortality (χ2 = 15.873, p < 0.001).
Conclusion: Pneumonia was the most common cause of ARF, and breathlessness was the most common symptom. Mortality was high, with significant associations between certain presenting symptoms and outcomes. Respiratory support type significantly influenced patient outcomes, highlighting the critical role of tailored respiratory management in improving survival.
Clinical significance: Early identification and tailored management of ARF, including careful selection of respiratory support and attention to high-risk symptoms, are crucial for improving outcomes.
Keywords: Mortality, Pneumonia, Poisoning
How to cite this article: Deme S, Durgam R, Kakarla B. Analyzing Factors Influencing Mortality in Acute Respiratory Failure: A Comprehensive Study of 275 Patients. Indian J Respir Care 2024;13(4):233–237.
INTRODUCTION
Acute respiratory failure (ARF) is a medical emergency due to the failure of the pulmonary system to maintain oxygenation and/or ventilation.1 It can be life-threatening and can occur in acute or chronic forms. This condition is categorized by two types: hypoxic (type 1) and hypercapnic (type 2) respiratory failure. Low oxygen levels in the blood (hypoxemia) characterize type 1 failure. It typically occurs when there is a problem with oxygen diffusion in the lungs, a mismatched ventilation and perfusion, a shunt, or hypoventilation. Type 2 is due to inadequate removal of carbon dioxide from the blood (hypercapnia) due to impaired ventilation, increased CO2 production, and decreased tidal volume.2,3 Chronic obstructive pulmonary disease (COPD), chest wall defects, and neuromuscular diseases can lead to type 2 respiratory failure.4 Symptoms of ARF include shortness of breath, confusion, changes in mental alertness, and cyanosis. Studies addressing the etiology, clinical features, and outcomes of ARF are sparse. Most studies on ARF were limited to patients receiving critical care or mechanical ventilation. While clinical features and respiratory support of patients in a critical care setting have been extensively discussed in many studies, the differences in patient characteristics at presentation in relation to progression to the need for critical care and outcomes are yet to be studied. Therefore, we set out to investigate these in our institute.
MATERIALS AND METHODS
This is a prospective observational study conducted in a tertiary center from December 2021 to November 2022. Approval was obtained from the Institutional Ethics Committee under reference number PBAC No. 2179/2021. Informed consent was obtained. A total of 275 patients were recruited who met the inclusion criteria. All patients aged 18 years or above, presenting to the emergency or outpatient departments with clinical features of ARF, with PaO2 <60 mm Hg, PaCO2 >50 mm Hg, or SpO2 <90%, fulfilled the inclusion criteria. PaO2 and PaCO2 were measured with arterial blood gas (ABG) analysis (PaO2 <60 mm Hg and/or PaCO2 >50 mm Hg). SpO2 was measured with the pulse oximeter (at a cutoff for hypoxia <95% in our study) approved by the Food and Drug Administration (FDA)—YIMI LIFE YM201. Detailed medical history, complete physical examination, and all necessary investigations such as complete blood count, chest X-ray, electrocardiogram (ECG), liver function tests, renal function tests, and 2D-ECHO were performed. Patients who did not give informed consent, younger patients (<18 years), patients with type 3 and 4 respiratory insufficiency, patients with traumatic causes of respiratory insufficiency, and patients for whom pulse oximetry was unreliable, such as those in shock, with skin pigmentation, current tobacco use, or the presence of nail polish, were excluded.
Statistical Analysis
The sample size calculation for this study was based on the methodology proposed by Magazine et al. (2017),5 which found that approximately 23.3% of acute respiratory distress syndrome (ARDS) cases were attributed to pneumonia. To ensure that our study had adequate power to detect meaningful differences, we used the following formula for sample size estimation:
N = [Z2 × p × (1 − p)] Δ2
Where,
p = 0.233 (the proportion of ARDS cases attributed to pneumonia, as reported in the literature).
Δ = 0.05 (the desired margin of error, set at 5% to achieve a high level of precision).
Z = 1.96 (the Z-score corresponding to a 95% confidence level, which is standard for clinical studies).
Substituting these values into the formula, we determined that the required sample size was approximately 275 participants. This sample size ensures that our study has sufficient power to detect differences in outcomes based on the distribution of pneumonia and other causes of ARDS.
Data analysis was performed using Statistical Package for the Social Sciences (SPSS) v23 software (IBM Corp.). Descriptive statistics, including means, standard deviations, medians, interquartile ranges (IQRs), and frequencies/percentages, were used to summarize continuous and categorical variables, respectively.
Group comparisons for continuous variables were conducted using:
-
Independent samples t-tests for comparisons between two groups.
-
One-way analysis of variance (ANOVA) for comparisons among more than two groups, followed by Tukey’s honestly significant difference (HSD) post hoc test to control for type I error inflation.
For nonnormally distributed data, nonparametric tests, such as the Wilcoxon test or Kruskal–Wallis test, were employed. Chi-squared tests were used for categorical data comparisons, and Fisher’s exact test was applied when expected frequencies were low (i.e., <5 in >25% of cells).
Linear relationships between continuous variables were assessed using:
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Pearson’s correlation for normally distributed data.
-
Spearman’s correlation for nonnormally distributed data.
Statistical significance was determined at a p-value of <0.05.
RESULTS
The mean age of the participants in our study was 48.18 ± 16.34 years, with 64.0% males and 36.0% females. Two hundred sixteen (78.5%) participants had type 1 respiratory failure, 51 (18.5%) had mixed type 1 + 2 respiratory failure, and 8 (2.9%) had type 2 respiratory failure. Of the total participants, 139 (50.5%) received oxygen therapy via face mask, nasal cannula, Venturi mask, or high-flow oxygen; 67 (24.4%) were managed with noninvasive ventilation (NIV), and 69 (25.1%) required mechanical ventilation (MV).
Overall, 212 (77.1%) participants died, while 63 (22.9%) were discharged (Table 1). This highlights the poor prognosis and high mortality rates associated with ARF. Pneumonia was the most common etiology, affecting 51 (18.5%) patients, followed by heart failure in 50 (18.2%), poisoning in 47 (17.1%), sepsis in 45 (16.4%), and acute exacerbation of COPD in 20 (7.3%) patients.
| Basic details | Mean ± SD || Median (IQR) || min–max || frequency (%) |
|---|---|
| Age (years) | 48.18 ± 16.34 || 52.00 (34.50–62.00) || 18.00–70.00 |
| Age | Number of cases (percentage) |
| ≤20 years | 19 (6.9%) |
| 21–30 years | 34 (12.4%) |
| 31–40 years | 37 (13.5%) |
| 41–50 years | 43 (15.6%) |
| 51–60 years | 54 (19.6%) |
| 61–70 years | 88 (32.0%) |
| Gender | |
| Male | 176 (64.0%) |
| Female | 99 (36.0%) |
| Type of failure | |
| Type 1 | 216 (78.5%) |
| Type 1 + 2 | 51 (18.5%) |
| Type 2 | 8 (2.9%) |
| Respiratory support | |
| O2 (face mask, nasal cannula, venturi, high flow) | 139 (50.5%) |
| NIV | 67 (24.4%) |
| MV | 69 (25.1%) |
| Outcome | |
| Death | 212 (77.1%) |
| Discharge | 63 (22.9%) |
The remaining 62 (22.5%) patients had a variety of other etiologies, including 2.9% with acute pancreatitis, 2.9% with fluid overload (due to acute or chronic liver failure), 2.5% with diabetic ketoacidosis, and 2.1% each with volume overload due to acute or chronic renal failure, malignancies, and other rare causes such as disseminated tuberculosis, upper gastrointestinal bleeding, and metabolic encephalopathy (Table 2).
| S. no. | Diagnosis | Number of subjects (percentage) |
|---|---|---|
| 1. | Pneumonia | 51 (18.5%) |
| 2. | Heart failure (cardiogenic pulmonary edema) | 50 (18.2%) |
| 3. | Poisoning | 47 (17.1%) |
| 4. | Sepsis-related ARDS | 45 (16.4%) |
| 5. | Acute exacerbation of COPD | 20 (7.3%) |
Symptoms at presentation were predominantly shortness of breath in 160 (58.2%) patients, followed by fever in 91 (33.1%), cough in 65 (23.6%), vomiting in 64 (23.3%), abdominal pain in 55 (20.0%), and swelling of limbs in 34 (12.4%). Altered sensorium (including restlessness, agitation, confusion, and loss of consciousness in hypoxemic patients, and somnolence, dizziness, and coma in hypercapnic patients) was present in 33 (12.0%) patients. Other symptoms included chest pain in 26 (9.5%), decreased urine output in 17 (6.2%), and generalized weakness in 6 (2.2%). A subset of patients [62 (22.5%)] had additional symptoms like burning on urination, loose stools, flatulence, nausea, and others (Table 3).
| S. no. | Clinical features | Number of subjects (percentage) |
|---|---|---|
| 1. | Shortness of breath (SOB) | 160 (58.2%) |
| 2. | Fever | 91 (33.1%) |
| 3. | Cough | 65 (23.6%) |
| 4. | Vomiting | 64 (23.3%) |
| 5. | Others | 62 (22.5%) |
| 6. | Pain abdomen | 55 (20.0%) |
| 7. | Swelling of limbs | 34 (12.4%) |
| 8. | Altered sensorium | 33 (12.0%) |
| 9. | Chest pain | 26 (9.5%) |
| 10. | Decreased urine output | 17 (6.2%) |
| 11. | Generalized weakness | 6 (2.2%) |
Shortness of breath was the most common symptom, followed by signs of infection and altered sensorium, which are key features indicative of ARF. Fever was significantly associated with better outcomes, as a greater proportion of patients presenting with fever were discharged (χ2 = 4.758, p = 0.029). However, the impact of this finding on disease progression remains uncertain.
On the other hand, altered sensorium at presentation was associated with a higher likelihood of death (χ2 = 4.054, p = 0.044), suggesting it as a poor prognostic factor. Similarly, vomiting was strongly correlated with poor outcomes, as a greater proportion of patients with vomiting died (χ2 = 5.117, p = 0.024). Vomiting, likely indicative of infection or poor sensorium, may also lead to aspiration, which could explain its association with mortality (Table 4).
| Parameters | Outcome | p-value | |
|---|---|---|---|
| Death (n = 212) | Discharge (n = 63) | ||
| Age | 0.1311 | ||
| ≤20 years | 15 (7.1%) | 4 (6.3%) | |
| 21–30 years | 31 (14.6%) | 3 (4.8%) | |
| 31–40 years | 31 (14.6%) | 6 (9.5%) | |
| 41–50 years | 30 (14.2%) | 13 (20.6%) | |
| 51–60 years | 43 (20.3%) | 11 (17.5%) | |
| 61–70 years | 62 (29.2%) | 26 (41.3%) | |
| Gender | 0.3211 | ||
| Male | 139 (65.6%) | 37 (58.7%) | |
| Female | 73 (34.4%) | 26 (41.3%) | |
| Type of failure | 0.5641 | ||
| Type 1 | 168 (79.2%) | 48 (76.2%) | |
| Type 1 + 2 | 37 (17.5%) | 14 (22.2%) | |
| Type 2 | 7 (3.3%) | 1 (1.6%) | |
| Respiratory support*** | <0.0011 | ||
| O2 | 97 (45.8%) | 42 (66.7%) | |
| NIV | 50 (23.6%) | 17 (27.0%) | |
| MV | 65 (30.7%) | 4 (6.3%) | |
| Comorbidities | |||
| DM | 47 (22.2%) | 17 (27.0%) | 0.4271 |
| HTN | 70 (33.0%) | 22 (34.9%) | 0.7791 |
| CKD | 10 (4.7%) | 3 (4.8%) | 1.0003 |
| COPD | 11 (5.2%) | 5 (7.9%) | 0.3752 |
| CAD | 14 (6.6%) | 6 (9.5%) | 0.4162 |
***P value is significant 1Chi-squared test 2Fisher’s exact test
The mortality rate was highest in the age-group 61–70 years, where 29.2% of patients died (Table 5), indicating a poorer prognosis in older patients. Intoxication was another factor significantly associated with mortality (χ2 = 13.862, p < 0.001). A notable portion of intoxication cases were related to paraquat poisoning (33 cases; 12%), which led to pulmonary fibrosis, necessitating mechanical ventilation, and in some cases, death, due to the lack of effective treatments. Despite early interventions such as hemoperfusion and hemodialysis, and treatment with antioxidants, steroids, and antifibrotic agents, no improvements in outcomes were observed. This could explain the higher prevalence of intoxication as an etiology in our study compared to prior studies.
| Diagnosis | Nonsurvivors | Survivors | |
|---|---|---|---|
| Poisoning*** | 46 (21.7%) | 1 (1.6%) | <0.0011 |
| Heart failure | 38 (17.9%) | 12 (19.0%) | 0.8391 |
| Sepsis-related ARDS | 30 (14.2%) | 15 (23.8%) | 0.0691 |
| Pneumonia | 37 (17.5%) | 14 (22.2%) | 0.3921 |
| Acute exacerbation of COPD | 13 (6.1%) | 7 (11.1%) | 0.1783 |
***P value is significant 1Chi-squared test 3Fisher’s exact test
There was no significant difference in outcomes related to the type of respiratory failure (χ2 = 1.144, p = 0.564). However, there was a significant difference in outcomes based on the type of ventilatory support used (χ2 = 15.873, p < 0.001). Patients who were discharged had a higher proportion receiving oxygen or noninvasive ventilation (NIV), whereas those who died had a higher proportion receiving mechanical ventilation (Table 6). The association between mechanical ventilation and poorer outcomes suggests that these patients were more critically ill, and the use of mechanical ventilation may be a marker of the severity of their condition, rather than an independent cause of poor prognosis.
| Presentation | Nonsurvivors | Survivors | |
|---|---|---|---|
| Fever*** | 63 (29.7%) | 28 (44.4%) | 0.0291 |
| Cough | 46 (21.7%) | 19 (30.2%) | 0.1651 |
| SOB | 118 (55.7%) | 42 (66.7%) | 0.1201 |
| Chest pain | 20 (9.4%) | 6 (9.5%) | 0.9831 |
| Altered sensorium*** | 30 (14.2%) | 3 (4.8%) | 0.0441 |
| Pain abdomen | 43 (20.3%) | 12 (19.0%) | 0.8301 |
| Vomiting*** | 56 (26.4%) | 8 (12.7%) | 0.0241 |
| Generalized weakness | 5 (2.4%) | 1 (1.6%) | 1.0003 |
| Swelling of limbs | 23 (10.8%) | 11 (17.5%) | 0.1621 |
| Decreased urine output | 13 (6.1%) | 4 (6.3%) | 1.0003 |
| Others | 48 (22.6%) | 14 (22.2%) | 0.9441 |
***P value is significant 1Chi-squared test 3Fisher’s exact test
DISCUSSION
This study analyzed 275 cases of ARF, with the majority of patients presenting with type 1 respiratory failure. Pneumonia was the most common etiology (18.5%), followed by congestive heart failure (18.2%), poisoning (17.1%), and sepsis-related ARDS (16.4%). Respiratory distress was the most common presenting symptom. Importantly, poisoning as an etiology, vomiting, altered sensorium, and the need for mechanical ventilation were all statistically significantly associated with mortality (p < 0.05).
Additionally, hypothyroidism and presentation with fever were associated with a higher likelihood of discharge, but the underlying disease progression leading to these outcomes remains unclear. These findings provide valuable insights into patient outcomes based on initial symptoms and etiologies, which can guide clinical decision-making.
Comparison with Previous Studies
The age distribution in this study differed from that seen in earlier research. The mean age of patients in this study was 48.18 ± 16.34 years, which is lower than that in studies by Luhr et al. (62.3 ± 16.1 years) and Stefan et al. (65.8 years).6,7 The exclusion of patients aged over 70 in our study may account for this difference. Furthermore, we observed a linear increase in the number of cases with increasing age, with 6.9% of cases in patients aged ≤20 years compared to 32% in the 61–70 age-group. This finding is consistent with trends observed in previous studies, such as that by Behrendt et al. (2016),8 which also described an increase in ARF cases with advancing age.
In contrast to the lower mean age, our study’s patient demographics (male to female ratio of 1.77:1) were comparable to those in Luhr’s study (1.42:1), which reported a slightly lower male predominance (58.8% male and 41.2% female).6
Etiologies and Disease Progression
Pneumonia was the most common cause of ARF in our cohort, consistent with previous studies (Luhr et al. and Parcha et al.).6,9 In the latter study, influenza pneumonia (41.3%), septicemia (37.8%), and food-borne pneumonitis (16.3%) were the leading causes of ARF, while in our study, pneumonia, heart failure, poisoning, and sepsis-related ARDS were most common. Over time, as seen in Stefan’s national survey (2001–2009), the proportion of ARF cases attributable to pneumonia and sepsis has increased, a trend mirrored in our findings.7
The distribution of etiologies by age-group in our study aligns with data from Behrendt’s study,8 where the prevalence of congestive cardiac failure and COPD was highest in individuals aged 50 years or older. Similarly, the study by Ray et al.10 (in older adults, mean age 80 ± 9 years) reported that cardiac-related pulmonary edema (43%) and community-acquired pneumonia (35%) were the most common causes of ARF in this age-group. Our findings, though slightly different in the types of comorbidities observed, suggest similar trends in the role of age and comorbidity in the progression of ARF.
Clinical Features and Outcomes
The most common clinical features at presentation were shortness of breath (58.2%), fever (33.1%), cough (23.6%), vomiting (23.3%), abdominal pain (20%), and altered sensorium (12%). Vomiting and altered sensorium, in particular, were strongly associated with mortality, highlighting their importance as early clinical indicators of severe disease (χ2 = 5.117, p =0.024). These results suggest that early identification of these symptoms may help identify patients at higher risk for poor outcomes, potentially informing treatment strategies.
Interestingly, fever was associated with discharge (χ2 = 4.758, p =0.029), which may suggest a less severe disease course in these patients. While vomiting and altered sensorium correlated with mortality, fever could indicate a more favorable prognosis. These associations are consistent with previous studies, where clinical features such as vomiting and altered mental status were linked to worse outcomes, while fever was a more favorable prognostic sign.
Age, Comorbidities, and Mortality
The study found that older age and severe chronic comorbidities, such as multiorgan failure, were independent risk factors for mortality, aligning with the findings of Carolyn Behrendt and Chen WL.8,11 The relationship between ventilatory support type and outcomes also merits attention. Mechanical ventilation was associated with a higher probability of death, while noninvasive support (e.g., oxygen therapy and noninvasive ventilation) was linked to a higher probability of discharge. These findings echo data from previous studies, including that of Behrendt, which reported mortality rates of 28–58% in patients requiring mechanical ventilation for ARF.8
Clinical Implications and Impact on Practice
The associations between presenting symptoms (vomiting, altered sensorium) and mortality have important implications for early management. These symptoms should prompt clinicians to consider the possibility of severe intoxication or neurological involvement, and early interventions, including aggressive monitoring and supportive care, may be required to improve outcomes.
The findings also emphasize the importance of age and comorbidities in predicting outcomes. Given the higher mortality in older patients and those with chronic comorbid conditions, early identification of these risk factors could guide more tailored and aggressive treatment strategies, such as early mechanical ventilation or advanced life support.
CONCLUSION
Our study provides valuable insights into the demographics, etiologies, symptoms, and outcomes of patients with ARF. Key findings include a lower mean age compared to previous studies, which may be attributed to differences in inclusion criteria. Pneumonia and congestive heart failure were identified as the most common causes of ARF, consistent with findings from other studies.
Respiratory distress was the predominant presenting symptom, with vomiting and altered sensorium strongly associated with higher mortality. Mechanical ventilation was linked to poorer outcomes, while noninvasive support (e.g., oxygen therapy and noninvasive ventilation) was associated with better survival rates.
Clinical Implications
These findings highlight the importance of early identification of high-risk patients, particularly those presenting with vomiting and altered sensorium, as these symptoms are predictive of poorer outcomes. The association between mechanical ventilation and higher mortality underscores the need for early consideration of noninvasive support whenever possible, especially in younger and less critically ill patients. This study suggests that tailored management strategies, emphasizing early intervention and appropriate ventilatory support, could improve patient outcomes in ARF.
Overall, these results offer actionable recommendations for clinicians, aligning with trends observed in similar studies, and may guide more effective treatment protocols for patients with ARF.
ORCID
Swaroopa Deme https://orcid.org/0000-0002-2760-3923
Ramya Durgam https://orcid.org/0009-0002-9285-3176
Bhaskar Kakarla https://orcid.org/0000-0002-3900-707X
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