Non-invasive Ventilation (NIV) has revolutionized the management of patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) with hypercapnic respiratory failure or Type 2 Respiratory failure. NIV has been very much useful in reducing the need for hospital and ICU stay length, need for Invasive Mechanical Ventilation and morbidity and mortality. Minimizing the duration of non-invasive ventilation (NIV) is often desirable, similar to that of invasive mechanical ventilation, to reduce potential complications. Prolonged use of NIV can lead to issues such as pressure sores, facial discomfort, gastric distension, and, in some cases, aspiration or lung injury. Furthermore, extended NIV use can increase the risk of hospital-acquired infections, muscle weakness, and psychological stress^1,2. The goal is to use NIV as a supportive measure to stabilize the patient, while addressing the underlying condition, and gradually transitioning to spontaneous breathing when possible². Early weaning and appropriate monitoring of the patient’s response to NIV are critical to minimize these risks and prevent complications associated with extended hospital stays^3,4.

Multiple studies have been conducted and guidelines laid down regarding when to start and when to withdraw NIV^5-10. However there is not much data regarding proper weaning of NIV.  Hence we have conducted this study to compare among three possible weaning strategies. There may be three possible weaning strategies that can be potentially used: stepwise reduction of duration of NIV use, stepwise reduction pressure support of NIV and immediate withdrawal of NIV.

Despite several multinational studies, there is no consensus as to the optimal weaning method⁴. Brochard's work highlighted that reducing PS stepwise could be more effective than other methods of weaning patients from mechanical ventilation. Following this, other trials have compared this PS method with daily (or multiple) T-piece trials (SBTs), and findings have suggested that SBTs can be just as effective as progressively reducing PS when it comes to weaning patients off ventilation

Patient-specific factors are likely more influential than the specific weaning protocol used in determining how long the weaning process will take. This suggests that factors like the patient’s underlying conditions, respiratory mechanics, and overall clinical status may be more critical than whether a particular protocol (like PS or T-piece) is followed.

It is also interesting to note the consensus around the Synchronised Intermittent Mandatory Ventilation (SIMV) method, which is considered inferior to Pressure Support (PS) and T-piece weaning. While SIMV has been historically used in weaning, the growing evidence suggests it may not be as effective in promoting extubation or improving patient outcomes compared to other methods. Standardized and systematic weaning protocols are often associated with better outcomes because they ensure a structured approach to weaning, and staff who are familiar with these protocols can make quicker and more informed decisions, reducing the risk of errors or delays⁵. The objectives of the study are as below:

1. The primary objective of the study was to compare the rate of successful withdrawal of non-invasive ventilation (NIV) across three different groups. Successful withdrawal was defined as the absence of any need to reinstitute NIV within 48 hours after it was initially withdrawn.
2. Secondary objectives of the study included comparing the total number of days of non-invasive ventilation (NIV) use and the length of hospital stay across the three groups.

This study was a randomised controlled trial performed in a tertiary care teaching hospital named Institute of Medical Sciences, BHU in Varanasi, Uttar Pradesh. A randomized control trial was done on total 120 AECOPD patients admitted in Chest Ward of SSH, IMS BHU, Varanasi in the period of January 2023 to January 2024. Patients have been randomly allocated either of the three weaning strategy groups. Thereafter they were assessed for weaning outcome (successful/failure) based on ABG pH, saturation, respiratory rate and heart rate. Inclusion Criteria: 1. Patient diagnosed with Acute exacerbation of COPD with Type 2 respiratory failure 2. Haemodynamically stable patient. Exclusion Criteria: 1. Patient not giving consent 2. Patients with other lung diseases such as ILD, Asthma, pulmonary TB. 3. Haemodynamic instability. 4. Patients with contraindications to NIV (Inability to protect airways – such as unconscious patients, cerebrovascular accidents, confused and agitated patients). Methods (figure 2): A total of 134 patients diagnosed with COPD with type 2 respiratory failure were screened. Of which 14 of them were excluded and the remaining 120 patients were further randomised and allotted either of the 3 groups: Group A: Immediate withdrawal was followed Group B: Stepwise reduction of pressure support Group C: Stepwise reduction of duration of NIV Of the 14 patients those who were excluded from the study, 7 of them were discharged against medical advice, 3 of them were intubated after shifting to ICU and 4 of them were discharged with home NIV. Weaning from NIV was started as per ISCCM Guidelines 2020 and the weaning strategy was followed as per the group allotted. • Immediate withdrawal of NIV (Group A): patients were immediately withdrawn from NIV and monitored on spontaneous breathing • Stepwise reduction of pressure support (Group B): pressure support was reduced by around 2cm H2O every 4–6 h with vitals and blood gas monitoring till IPAP of <10 cm of H2O and EPAP of <6cm of H2O was attained after which NIV was completely withdrawn. • Stepwise reduction of duration (Group C): the duration of NIV was reduced stepwise once the patient improved and met the ISCCM criteria for weaning. On day 1 of weaning, the patient was put on NIV for 2 hrs and removed for 1 hour and the cycle was continued. On the following day NIV was put on for 1 hour and removed for 2 hours. On day 3 the patient was kept on NIV only during the night. Thereafter the NIV was completely removed. Figure 1: A patient on NIV in Chest ward, IMS BHU Data was collected and subjected to statistical analysis. The statistical analysis was performed using IBM SPSS Statistics software (Version 26). All statistical tests were two-tailed, and a p-value of ≤ 0.05 was considered statistically significant. A one-way analysis of variance (ANOVA) was performed to compare the three groups. Figure 2: Methodology

The age, gender, smoking status, comorbidities, Ph at admission, PaCO2 at admission, EPAP initially and EPAP maximum are not statistically significant within groups A, B and C with p values (0.96, 0.78,0.96,0.290,0.569,0.918,0.341 and 0.433) respectively. The IPAP initially and IPAP maximum is statistically significant within groups A, B and C with p values (0.017, 0.075) respectively as shown in table 1. 

Table 1: Baseline characteristics among the study groups

Table 2 shows the outcome in the form of successful withdrawal, total duration of NIV (h) and length of stay in hospital within groups A, B and C. The successful withdrawal is maximum in group B (85%), minimum in group A (77.5%) and 82.5% in group C. The mean duration of NIV (h) is 5.67±1.96 in group A, 6.9±2.27 in group B and 6.02±1.52 in group C. The length of stay in hospital(days) is 7.87 in group A, 9.3 in group B and 8.2 in group C. Successful withdrawal and length of stay in hospital is not statistically significant within group A, B and C (p value: 0.677 and 0.438) respectively. Total duration of NIV is statistically significant within group A, B and C (p value: 0.017).  

Table 2: Clinical outcomes among the study groups

Graph 1: Length of stay in hospital (days), mean

The NIV duration in successful withdrawal group was approximately 5.8 days whereas in failure withdrawal group was 6.33 days. The IPAP maximum value went up to approximately 14.87 in the successful withdrawal group while in the failure group it went up to around 15.38. The EPAP maximum value went up to approximately 6.19 in the successful withdrawal group while in the failure group it went up to around 6.35. The GCS at admission was about 14.82 in the successful withdrawal group while in the failure group it was around 14.62. The Ph at admission was about 7.27 in the successful withdrawal group while in the failure group it was 7.2. Similarly, the PaCO2 at admission was about 70.82 in the successful withdrawal group while in the failure group it was 71.23. None of the above parameters were statistically significant within the successful withdrawal and failure withdrawal groups (table 3).

Table 3: Comparison between successful withdrawal and failure withdrawal on the basis of various parameters

This randomised trial was performed in a tertiary centre of Varanasi (IMS BHU) comparing the three weaning strategies of NIV in patients of acute exacerbation of COPD with type 2 respiratory failure. The 3 groups were- Group A were the patients had immediate withdrawal of NIV, Group B in which the patients had stepwise reduction of pressure support (pressure weaning) and Group C in which the patients had stepwise reduction of duration of NIV. Each of the three groups had different success rates.

The primary objective of this study was to find the success rates in each group. NIV was successfully withdrawn in 31 out of 40 patients in Group A with a success rate of 77.5%. NIV was successfully withdrawn in 34 out of 40 patients in Group B with a success rate of 85% and 33 out of 40 patients in Group C with a success rate of 82.5%. Among the patients who failed NIV (n=22), they were again started on NIV and subsequently weaned off once the respiratory failure resolved.

The secondary objective was to compare the total duration of NIV used in each group and the length of hospital stay. The total duration of NIV use was longer in both stepwise withdrawal groups (Groups B and C) compared to immediate withdrawal (Group A).  The mean duration of NIV usage was 5.67, 6.9 and 6.02 in Group A, Group B and Group C respectively. The mean length of hospital stay was 7.87 in Group A, 9.3 in Group B and 8.2 in Group C. So it is evident that though the success rate in Group B is the highest (85%), but it has greater duration of NIV usage and length of hospital stay.

The NIV duration in successful withdrawal group was approximately 5.8 days whereas in failure withdrawal group was 6.33 days. The IPAP maximum value went up to approximately 14.87 in the successful withdrawal group while in the failure group it went up to around 15.38. The EPAP maximum value went up to approximately 6.19 in the successful withdrawal group while in the failure group it went up to around 6.35. The GCS at admission was about 14.82 in the successful withdrawal group while in the failure group it was around 14.62. The Ph at admission was about 7.27 in the successful withdrawal group while in the failure group it was 7.2. Similarly, the PaCO2 at admission was about 70.82 in the successful withdrawal group while in the failure group it was 71.23. None of the above parameters were statistically significant within the successful withdrawal and failure withdrawal groups.

Among all the comorbidities found in this study, Hypertension ranks the most. 25.7% of the male patients and 18% of female patients had hypertension. Diabetes was seen in 7.1% of males and 16% of females. Hypertension and diabetes co-existed in 4.3% of males and in 10% of females. CAD was seen in 2% of females.

In a study by Hadda V et al8, patients with AECOPD and hypercapnic respiratory failure (HcRF) who showed improvement on NIV were randomized into three groups: immediate withdrawal (Group A), stepwise reduction of pressure support (Group B), and stepwise reduction of duration (Group C) of NIV. The probability of successful withdrawal was then compared among the three group. The mean pH and PaCO2 at admission were 7.23 ± 0.04 and 84.4 ± 12.0 mm Hg, respectively. The average duration of NIV received before randomization was 31.6 ± 9.2 hours, with maximum inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) of 17.6 ± 2.7 cm H2O and 7.4 ± 1.4 cm H2O, respectively. NIV was successfully withdrawn in 23 out of 30 (76.6%) patients in Group A, 27 out of 30 (90%) in Group B, and 26 out of 30 (86.6%) in Group C (P = 0.31). The total duration of NIV use and length of hospital stay were significantly lower in Groups A and B compared to Group C (P = 0.001). Immediate withdrawal of NIV after recovery from hypercapnic respiratory failure (HcRF) in patients with acute exacerbation of COPD (AECOPD) is feasible and did not increase the risk of weaning failure.

Another study conducted in Department of Pulmonary Critical Care and Sleep Medicine, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi by Swetabh Purohit et al9 compared immediate against stepwise reduction in NIV. There was a study conducted by Rebecca Payne et al10 at the Kettering general hospital. Between August 2018 and August 2019, the Palliative Care Team at Northamptonshire Healthcare Foundation Trust and the Respiratory Team at Kettering General Hospital (KGH) collaborated to review the medical notes of patients who had been admitted to KGH. These patients were coded for Type 2 Respiratory Failure (T2RF) and Non-Invasive Ventilation (NIV) and had died during that admission. Clear plans regarding the ceiling of treatment at the initiation of NIV were documented in 73% of cases. Discussions about NIV withdrawal took place with patients and/or their relatives in all cases, but only 15% of patients were directly involved due to confusion or reduced consciousness. The plan for NIV withdrawal was documented in 58% of cases. Forty-six percent of patients were referred to the Palliative Care team, though 58% of these referrals occurred after NIV was withdrawn. There was notable variation in prescribing practices, with only six patients receiving medication before NIV withdrawal. Additionally, 69% of patients had anticipatory end-of-life medications prescribed, though there was variability in the choice of opioid, antiemetic, and antisecretory medications used.

However, adequately powered, multicenter studies are needed to assess the impact of the immediate withdrawal strategy on various outcomes, such as the time spent on NIV, duration of ICU and hospital stay, and the overall cost of care.

The variations observed in practice concerning communication, medical management, and the process of withdrawal highlight a lack of a standardized approach. While individualized patient care is crucial, there may be a need for structured guidelines to ensure that necessary conversations take place, the need for symptomatic relief before withdrawal is considered, and medications are prescribed in anticipation of potential distress.

Of the total number of smokers allotted in the study, a significant proportion among them were males. Among comorbidities in the study population, hypertension was more prevalent in the male population while all the other comorbidities were comparatively higher among females. We found out that Pressure weaning in NIV had the best success rate, followed by Time weaning and Immediate withdrawal. Both the duration of NIV usage and length of hospital stay was shortest in the immediate withdrawal group.

1. Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive sum mary. Am J Respir Crit Care Med. 2017;195:557–582.
2. Davidson AC, Banham S, Elliott M, Kennedy D, Gelder C, Glossop A, et al; BTS Standards of Care Committee Member, British Thoracic Society/Intensive Care Society Acute Hypercapnic Respiratory Failure Guideline Development Group, On behalf of the British Thoracic Society Standards of Care Committee. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax. 2016 Apr;71(2):ii1-35.
3. Khilnani GC, Jain N. Do we need a protocol for weaning patients from noninvasive ventilation? Indian J Crit Care Med 2014;18:775 7.

‌4. Hadda V, Kumari R. Protocols for weaning from NIV: Appraisal of evidence. Insights Chest Dis 2016;1:14.

5. Briones Claudett KH, Briones Claudett M, Chung Sang, Wong M, Martinez AN, Espinoza RS, Montalvo M, et al. Noninvasive mechanical ventilation with average volume assured pressure support (AVAPS) in patients with chronic obstructive pulmonary disease and hypercapnic encephalopathy. BMC Pulm Med. 2013.
6. Cao Z, Luo Z, Hou A, Nie Q, Xie B, An X, et al. Volume-targeted versus pressure-limited noninvasive ventilation in subjects with acute hypercapnic respiratory failure: a multicenter randomized controlled trial. Respir Care. 2016;61(11):1440–1450.
7. Gay PC, Hess DR, Hill NS. Noninvasive proportional assist ventilation for acute respiratory insufficiency. Am J Respir Crit Care Med. 2001;164(9):1606–1611.
8. Hadda V, Venkatnarayan K, Khilnani G, Madan K, Mohan A, Pandey R, et al. A comparison of three strategies for withdrawal of noninvasive ventilation in chronic obstructive pulmonary disease with acute respiratory failure: Randomized trial. Lung India. 2020;37(1):3.
9. Purohit S, Madan M, Kumar R, Kaushik R, Ish P, Aj M, et al. Comparison of immediate withdrawal and stepwise reduction in duration of non-invasive ventilation in chronic obstructive pulmonary disease patients presenting with acute hypercapnic respiratory failure. Monaldi Arch Chest Dis. 2023;94(3).
10. Payne R, Wiseman F, Wenzel D, Kiran S, Hussain F. 60 Withdrawal of non-invasive ventilation in patients with type 2 respiratory failure at kettering general hospital. Poster presentations. 2021;A30.2-A30.