Role of Non-Invasive Mechanical Ventilation for Acute Respiratory Failure in Cancer Patients

Results: Among 68 studied patients, the primary reason for the initiation of noninvasive ventilation sepsis (16.32%), pneumonia (10.88%), and lung cancer (10.2%). Postoperative atelectasis, pulmonary edema, and morphine overdose were associated with good respiratory improvement and Intensive care Unit survival (100%, 75%and 66.67% respectively). Respiratory failure with carcinoma lung, lung fibrosis, acute respiratory distress syndrome, terminally ill patients, and patients with low Glasgow Coma Scale had high failure rates (Survival: 13.33%,14.29%,16.67%,0%, and 20% respectively).

Acute Respiratory Failure is one of the most common causes of (Intensive care unit) ICU admission for cancer patients. 1 However invasive mechanical ventilation for severe respiratory failure is a strong predictor of mortality in cancer patients. 2 Hence, at present, the use of Noninvasive ventilation (NIV) is increasing. NIV has been shown to decrease the need for intubation and mortality in an acute care setting. 3 NIV is used for both hypoxemic respiratory failure as well as hypercapnic respiratory failure. 4 Although it is well accepted that intubation and mechanical ventilation should be avoided in cancer patients with acute respiratory failure and NIV is one of the most promising alternatives. However, cancer patients are a diverse group with many variations and confounding factors. Hence, it is important to determine which patients may benefit from NIV. Identification is crucial for both medical and ethical point of view. Hence, the study is to determine the usefulness and efficacy of NIV in the cancer patient.
The objective of this study is to assess the role ( indications, utility, and outcome ) of NIV in cancer patients admitted to ICU for medical or surgical issues.

MATERIALS AND METHODS
It is a cross-sectional study done at the Nepal Cancer Hospital and Research Center. Data of all patients requiring Non-Invasive ventilation from April 14, 2018, to April 13, 2019, at Intensive Care Unit were collected in a performa, tabulated in a master sheet in Microsoft excel 2013, and analyzed manually as well as in SPSS ver 16.0. Relevant statistical tools (Chi-Squared test, fisher's exact test for categorical data and student T-test for continuous data, odds ratio, and Confidence interval) were used.

RESULTS
During the study period, 71 patients required NIV support. Among them, 68 patients were included in the study, as 3 patients' data were missing. The mean age of the patients was 57.57+/-14.95 years while 30.88% were female. Age and gender were not significant for improvement/tolerance and survival. The primary reason for the initiation of noninvasive ventilation is given in table 1. The most common reasons being a respiratory failure are due to sepsis (neutropenic and non-neutropenic), pneumonia, and lung cancer. Postoperative atelectasis, pulmonary edema, and morphine overdose were associated with good respiratory improvement and ICU survival. Respiratory failure with carcinoma lung, lung fibrosis, ARDS, terminally ill gasping patients, and patients with low GCS had high failure rates. While pneumonia, neutropenic sepsis, and COPD may also have some benefit.
Patients with both hypoxemic and hypercapnic respiratory failure were supported with NIV. However, the differences in outcomes were not statistically significant. All 7 patients who received NIV Support with anticipation of respiratory failure (such as postoperative atelectasis) but not hypoxemic or hypercapnic had a good outcome (p=0.003).
Interestingly in patients not improving with NIV, ABG parameters were significantly worse and had higher oxygen requirements before initiating NIV than those patients improving with NIV. The ABG parameters seem to improve and attain a much better value in patients improving with NIV. The initial ABG value just before the initiation of NIV is given in  Regarding the reason for ICU admission, patients admitted for post-operative, respiratory, or cardiac cause had better outcome while those admitted for renal, metabolic, and neurologic reasons had worse outcomes. 45.59% of patients who got NIV support improved. 90.32% of these patients were survived and discharged from ICU. Among the NIV failure, Intolerance, intubation, and cardiac arrest leading to CPR were the commonest reason for termination of NIV support (Table 4). Whatever the reason, survival rates after NIV failure had significantly poor outcomes.

DISCUSSION
Noninvasive ventilation has been perceived as the most promising alternative to endotracheal intubation. However, cancer patients are a diverse group and the need for respiratory support is also varied. This study aims to describe the indication, uses, and limitations of NIV.
In this study of 68 cancer patients, being treated medically or surgically and requiring NIV were observed, 45.59% patient improved while 44.18% patient had survived and discharged from ICU. Our results are in accordance with the results published by A.P meert 5 who showed a success rate of 57.5% in a retrospective study of 40 cancer patients. Another study done by Azoulay et al. 6 also showed a crude ICU discharge rate of 56.3% in a cohort study of 48 cancer patients exposed to NIV. Interestingly, our study shows that noninvasive ventilatory assistance is also an effective and safe alternative to standard mechanical ventilation in cancer patients. Among 31 improved patients, 28 i.e. 90.3% of patients were discharged from ICU as survived patients.
According to the study carried out by Carlson Robert H 7 , noninvasive ventilation is more effective than standard oxygen therapy in reducing the respiratory rate, dyspnea and also reduces patients' reliance on morphine and preserves normal swallowing, speech and cough mechanism in cancer patients. This effect can be explained by the fact that BiPAP is effective in correcting gas exchange abnormalities. Cancer patients are often frail and anemic because of their underlying disease and subsequent treatment (chemotherapy/radiotherapy/surgery). When increased work of breathing is needed to maintain oxygenation, the demand of the respiratory muscles can become excessive, causing fatigue and carbon dioxide retention. BiPAP is effective in improving oxygenation, recruiting under-ventilated alveoli, preventing alveolar collapse, and reducing the work of breathing. In a study done by Cuomo et al 8 , among 23 cancer patients, 53% have survival rates with the support of NIV.
In our study, the main cause for the use of NIV is pneumonia with a survival rate of 50% followed by ca lung and sepsis with a survival rate of 13% and 33% respectively. Our Study also reflects the significance of ABG in support of proper outcomes while using NIV. The outcome of patients with better ABG values at the initiation of NIV are significantly better thus suggesting earlier use of NIV could result in improved outcome. ABG value at 1 hour is also shown to be a good predictor of NIV success. This finding supplements the recommendation given by Pastores et al 9 who suggested timely diagnosis and treatment of reversible causes of respiratory failure, including earlier use of noninvasive ventilation and judicious ventilator and fluid management in patients, are essential for achieving an optimal outcome.
NIV could be of particular importance in a cancer patient who are immuno-compromised and whom the risk of developing infections such as ventilator-associated pneumonia, sinusitis, and sepsis during mechanical ventilation is especially high.
The endotracheal tube is one of the most significant factors predisposing patients to nosocomial pneumonia which it does by causing local damage and by by-passing the mechanical defenses of the upper airways.
NIV has been shown to involve a lower incidence of pneumonia than conventional mechanical ventilation. In the studies of Hilbert 10 and Antonelli 11 , 100% of immunosuppressed patients with ventilator-associated pneumonia died in ICU.
In our study, 41% of cancer patients were discharged from ICU as the survived patient. This is in accordance with the literature. Finally, BiPAP ventilation offers an important advantage for patients for whom it has been decided not to perform such lifesupportive critical care techniques as mechanical ventilation or for patients refusing intubation. This can be crucial in getting patients through an acute and reversible medical problem. Besides, even if respiratory failure is not resolved, NIV can attenuate dyspnea. Moreover, communication and physical interaction with relatives or medical and nursing staff can be maintained, since sedation remains minimal allowing more psychological comfort in endof-life patients.

CONCLUSIONS
Noninvasive ventilation appears to be an effective ventilation approach for cancer patients. Judicial selection of patients and timely initiation of NIV is of utmost importance for a better outcome. Further prospective studies in larger patient populations are required to determine prognostic factors that can predict whether this supportive treatment will be successful in general cancer patient populations and take account of variables relating to both the respiratory failure and the underlying neoplastic disease. Other areas of interest will be studying noninvasive ventilation eases end of life for a cancer patient.