Outcome of Non-Invasive Ventilation in Severe Corona Virus Disease of 2019 Patients; A Prospective Cohort Study

Objective: To determine the Outcome of non-invasive ventilation in patients with severe COVID-19 pneumonia. Methodology: A prospective cohort study was conducted at Pak Emirates Military Hospital, Rawalpindi, from 4th June to 30th Dec 2021. This study included 87 patients between the ages of 45 and 75 who were admitted due to severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection.Infection was confirmed by SARS-COV-2 PCR (polymerase Chain reaction). These patients were symptomatic with radiological evidence consistent with COVID-19 pneumonia requiring non-invasive ventilation (NIV) trial. The primary outcome was to analyze the success and failure of using NIV, the need for invasive ventilation, as well as the mortality rate. SPSS 21 was used to enter and analyze the data. Results: The mean age was 62.89 ±7.55 years. There were 65(74.7%) males and 22(25.3%) females. NIV was successful in 33 (37.9%) patients, while 54 (62.1%) patients required endotracheal intubation (invasive ventilation). Out of these 54 patients, 44 (81.4%) died after intubation. The mean duration of NIV support was observed as 6.2 ± 3.9 days. Conclusion: NIV can prevent intubation in less than half of the patients, according to our findings.


In trodu ction
Millions of people have been affected by SARS-CoV-2 pandemic, which has caused COVID-19 pneumonia.Roughly 73 million people worldwide have been infected with this disease, with 1.5 million deaths and 41 million recovered cases. 1 Recently, in Pakistan, there were 445,000 confirmed cases of COVID-19 with 9,000 deaths. 2 Severe cases of COVID-19 pneumonia leads to respiratory failure, hypercoagulability, septic shock and multi-organ failure leading to death.
To improve oxygenation in patients with increased severity of symptoms and lung involvement, treatment options like high-flow nasal cannulas, face masks, nebulizing masks & positive-airway pressure are usually suggested. 3Patients who require intubation & ventilator support have a bad prognosis secondary to ventilator induced lung injury. 4Some researchers believe that NIV could be an alternative but are unsure about the success rate of NIV.In COVID-19 acute respiratory failure (ARF), data which favors early intubation is still missing as multiple studies have failed to find a meaningful difference in death rate based on the timing of intubation. 5,6 ][9][10] Few trials showed success rate of 11-50%.Although, outcome of these patients and of those who were put on invasive ventilation due to severity of disease was still unexplained and further trials were required. 11,12herefore, we conducted this trial to find the outcome of

Original Article
NIV in severe COVID-19 pneumonia patients, to prevent intubation and achieve higher success rate in intensive care units.

Meth odo log y
This prospective study was conducted from 4 th June to 30 th December 2022 at Pak Emirates Military hospital, Rawalpindi.Sample size of 87 cases was calculated with 95% confidence interval, 10.5% margin of error and percentage of success of noninvasive ventilation i.e. 48.1% patients. 13In accordance with hospital rules and regulations, written consent was taken before the enrollment of patients in the study.Ethical approval was obtained from the ethical committee of hospital via letter no A/28.Demographic data (age, gender), history of chronic diseases like diabetes, hypertension, ischemic heart disease (IHD) and duration of NIV were recorded.This study included patients irrespective of gender between age group of 45 to 75 years who were admitted with pO2/FiO2 (ratio of partial pressure of oxygen in blood to that in inspired air) 100 & 200 mmHg despite oxygen given through facemask and were SARS CoV-2 PCR positive .The reason for selection of this particular age group was that patients in this age groupad better immunity with less comorbidities and more chances of survival compared to patients who were elder than 75 years.Patients with more than two comorbidities (diabetes, hypertension, IHD) were excluded from the study.The primary outcomes were success of NIV.The length of NIV was a secondary outcome.NIV was gradually weaned off and NRM (non rebreathable mask) oxygen mask was applied, depending on arterial blood gases level when the respiratory rate (RR) was 30 breaths per minute when FiO2 was 50%, the expiratory tidal volume was more than 5 mL/kg and PEEP(positive end expiratory pressure) was less than 8 cmH2O.NIV failure was classified as early (less than 48 hours) or late (more than 48 hours).The persistence of low oxygen saturation, a fast respiratory rate with pO2/FiO2 < 100mmHg was described as NIV failure.With the intention to avoid intubation, and to achieve an oxygen saturation greater than 90%, NIV was titrated with IPAP 20-22 cmH2O, PEEP 10-12 cmH2O, and FiO2 at 40%.The following criteria was used to decide whether or not to intubate a patient: Despite NIV, persistent acute respiratory failure (ARF), worsening (oxygen saturation 36/min), hemodynamic or electrocardiographic instability.Such situations required endotracheal intubation to protect airways or to control profuse tracheal and/or bronchial exudations.
Data was entered and analyzed in SPSS 2021.Age was calculated as mean +SD.Quantitative variables like gender, diabetes, hypertension & outcome were presented as frequency and percentage.Student's t test was used for comparison of two continuous variables.P value < 0.05 was considered as significant.
Arterial blood gases increased with gradual increase in time after admission and NIV application and this increase was statistically significant (p<0.05).(Table I) Out of 87 patients, NIV was successful in 33 (37.9%) while failure was observed in 54 (62.1%) patients.Out of these 54 patients who underwent intubation, 44 (81.4%) died.The mean duration of NIV application was 6.2 ± 3.9 days.The mean duration of NIV support was 7.9 ± 2.8 days in cases who had successful treatment, 3.5 ± 1.7 days in whom NIV failed and 6.8 ± 3.4 days in patients who died.(Table II)

Discussion
NIV is a type of respiratory support in which the main interface is a mask that may be quickly applied and removed from the patient's respiratory system.The negative consequences of invasive ventilation in the treatment of respiratory distress syndrome have prompted a more thorough investigation of NIV.The right patient selection is very important to achieve success of NIV.It's vital to note that NIV requires a very tight patient selection process; the key criteria includes maintaining awareness, patient's consent as well as stable hemodynamics. 14 conducted this trial during the second wave of COVID-19 pandemic, which showed 50.5% in-hospital mortalities in patients who obtained endotracheal intubation after NIV failure.Moreover, length of NIV application outside the ICU exceeded 48 h i.e. 6.2 ± 3.9 days.
In this study, during the initial wave of the pandemic 87 patients were included in the study who underwent NIV support.CPAP was used as NIV support in other units.In limited resources, all patients were admitted to different departments of emergency and divided into three groups based on the degree their respiratory failure.The 1 st group was given only conventional oxygen, the 2 nd was given CPAP & NIV and the 3rd was represented by the ICU, which provided ventilator support.It is significant to note that the majority of patients (about 80.5% of hospitalized cases) had a serious illness, with 38% requiring NIV in the emergency room to treat respiratory failure. 15NIV was previously used in patients with increasing respiratory failure, defined as a PaO2/FiO2 ratio of < 200 & a respiratory rate of more than 25 breaths per minute.As earlier mentioned, due to a lack of medical beds in 1 st wave of pandemic, we were unable to treat patients with NIV early in the process of respiratory failure.
Several prior researchers proposed that the COVID-19 patients who received NIV, outside the intensive care unit, with NIV being used as a "ceiling" treatment in several cases. 11,16 aschetto et al, observed 49.6% 30days death rate with NIV support, which is not similar with our findings, as they found the mortality in 30 days, while we only studied the mortality rate within hospital stay, which was just 5-7 days stay. 17There are no recommendations for NIV in acute respiratory failure due to pandemic viral infection in clinical practice guidelines from the European Respiratory Society. 22Recent studies focused on NIV use in SARS-CoV-2 infection had comparable sample sizes, did not adjust for baseline characteristics, and did not compare effectiveness to traditional MV usage. 23

Conclu sion
We concluded in this trial that NIV was successful in less than half of the patients suffering from severe COVID-19 disease.This information could be helpful for doctors who are considering using NIV in COVID-19 ARDS treatment.So further trials should be done with a larger sample size to confirm the evidence.