The ventilatory effect of High Velocity Nasal Insufflation versus Non-invasive Positive Pressure Ventilation in the treatment of acute hypercapnic respiratory failure in patients with AECOPD.

Introduction

Acute Exacerbation COPD is an episode marked by increased dyspnea, coughing and expectoration that worsens in less than two weeks. It may also be accompanied by increased heart rate and/or RR and is frequently associated with increased local and systemic inflammation brought by infection, pollution, or another insult to the airway ⁽¹⁾.

Hypercapnic respiratory failure is an  elevation in PaCO₂ greater than 45 mmHg and a pH lower than 7.35 resulting from respiratory pump failure and/or increased carbon dioxide production ⁽²⁾. 

Hypercapnic respiratory failure is a common problem. For respiratory support in this condition, NIV has been the main modality. However, due to poor mask tolerance, it is inappropriate for certain individuals. When patients are unable to tolerate conventional NIV, HFNC is frequently used to successfully manage hypercapnic respiratory failure since it is more easily tolerated. Nishimura et al.,2016 ⁽³⁾ stated that each person's response to HFNC differed: some people had a drop in RR, while others experienced a decrease in PaCO₂.

High Velocity Nasal Insufflation, a type of HFNC that uses a tiny bore nasal cannula to replace larger bore HFNC to create greater gas delivery velocities. With flow rates of thirty-five liters per minute, it can completely clear extrathoracic dead space and in those suffering from acute type II respiratory failure, besides oxygenation support, it may also be able to provide ventilatory assistance ⁽⁴⁾.

High-Velocity Nasal Insufflation is a type of NIV that doesn't require a face mask and is used to help oxygenate patients experiencing respiratory distress due to pulmonary reasons such as dyspnea, hypoxemia, hypercapnia or non-pulmonary causes of respiratory distress. Hi-VNI has an advantage over HFNC in that, even at 40 l/min, the small-bore cannulas produce higher velocity, can rapidly remove expiratory gas with a high CO2 concentration from dead space in the upper airways. So, a new gas reservoir is produced and reduce the breathing effort. Patients with acute respiratory failure who have higher RR and shorter intervals between breaths for gas exchange can benefit from Hi-VNI ⁽⁵⁾.

Methods

This is an analytical hospital based cross sectional study that was performed on 74 AECOPD cases presented to Cardiothoracic Minia University Hospital by acute hypercapnic respiratory failure during the period from November 2022 to January 2024. Patients were divided into two groups based on the first line of ventilatory support applied, including NIPPV group (40 patients) and Hi-VNI group (34 patients).

Inclusion criteria: 

• All AECOPD patients presented to the emergency room at Cardiothoracic Minia University Hospital by Respiratory acidosis (PaCO2 greater than 45 mmHg and a pH lower than 7.35) ⁽⁶⁾.
• patients presented to the emergency room on NIV from another hospital.

Exclusion criteria:

• Asthmatic patients.
• End stage cancer.
• Respiratory and cardiac arrest.
• Hemodynamic instability.
• Decreased mental status (GCS <9).
• Left sided heart failure.
• Other causes of hypoventilation as: obesity hypoventilation syndrome, obstructive sleep apnea, neuromuscular diseases and drug overdose.

Ethical consideration:

• The whole study design was approved by the Research Ethics Committee of Faculty of Medicine, Minia University. The ethical number was 538:2022.
• Confidentiality and personal privacy were respected in all levels of the study.
• Patients feel free to withdraw from the study at any time without any consequences.

The following were applied to patients:

• Detailed medical history.
• Thorough clinical examination, both general and local chest examination.
• Routine laboratory tests including complete blood count, renal function tests, liver function tests, C- reactive protein and serum electrolytes.
• Plain Chest Radiographs and Computed Tomography if indicated.
• Analysis of Arterial Blood Gases (ABGs): done by Sensacor ST-200CC including PH, PaO2, PaCO2, bicarbonate concentration (HCO₃). These values were measured on admission, after 1 hour, 2hrs, 6hrs, 24hrs and on discharge.
•  
• Echocardiography if needed.

Study interventions:

Patients were randomly assigned to either NIPPV or Hi-VNI. NIPPV was provided by a [AVEA ventilator USER INTERFACE MODULE or Maquet caro AB Servo-a BASE UNIT] with the initial parameters of 10:20 cm H₂O for the inspiratory positive airway pressure, 5:10 cm H₂O for the expiratory positive airway pressure, and 1.0 for the fractional inspirated oxygen (fiO₂).

Hi-VNI was supplied using a Vapotherm Precision Flow [Precision Flow Plus, Vapotherm, INC. U.S.A. device]. The starting flow rate was thirty-five L/min and the temperature adjusted at 35:37°C and a FiO₂ of 1.0.

The goals of both approaches were to increase patient comfort as evaluated by the clinician, relieve respiratory distress  by a reduction of RR < 25 breaths / minute and to keep saturation levels over 88% ⁽⁷⁾. ABG at 0, 1h, 2hrs, 6hrs, 24hrs and on discharge were collected and analyzed. Treatment failure was defined as the need for invasive mechanical ventilation or shift to the other device.

Statistical analysis:

Data were analyzed via SPSS version 26 for windows (SPSS Inc., Chicago, IL, USA).

The Shapiro Walk test was used to determine if the data were normally distributed. Frequencies and relative percentages were used to display the qualitative data. Using Fisher exact and the Chi square test, categorical data was compared. Quantitative data was stated as mean ± standard deviation for parametric, median and range for non-parametric data.

For parametric and non-parametric variables, respectively, the difference between the quantitative variables in 2 related groups was determined using the Paired Sample T test and the Wilcoxon Sign Rank Test.

Every statistical difference between groups was examined using the one-way analysis of variance (ANOVA) and Friedman test.

Each significant statistical comparison a P-value of less than or equal 0.05 suggests a significant difference, p <0.001 a highly significant difference, and P> 0.05 a non-significant difference.

Results

The study was performed on 74 AECOPD cases who were admitted to the Respiratory Intensive Care Unit at Cardiothoracic Minia University

Hospital by acute hypercapnic respiratory failure. The involved patients were classified into two groups based on the first line of ventilatory support used, including NIPPV group (40 patients) and Hi-VNI group (34 patients).

As shown in Figure 1 27 cases from the total number of NIV group (40 cases) improved and the remaining 13 cases failed. 3 cases out of the 13 failed cases were shifted to Hi-VNI and the remaining 10 cases were intubated. Out of 3 shifted cases, all of them were improved. On the other hand, 22 cases improved from the Hi-VNI group (34 cases), and the other 12 remaining cases failed; 11 cases from the failure group were shifted to NIV while 1 case was intubated. Out of 11 shifted cases, there were 6 cases improved and 5 cases intubated.

By comparing both NIPPV group and HI-VNI group regarding RR on admission, after 1hr, 2hrs, 6hr, 24hrs and on discharge, the results were non-statistically significant different (p value >0.05) (Table 1).

While for intra group comparison, there were statistically significant decline in RR after 1hour, 2hrs, 6hrs, 24hrs and on discharge compared to baseline RR either in NIPPV group or in HI-VNI group (Figure 2).

Regarding PH on admission, after 1hr, 2hrs, 6hrs, 24hrs and on discharge, there were non-statistically significant differences among NIPPV and HI-VNI groups (p value >0.05) (Table 1).

On the other hand, for intra group comparison, there were statistically significant increase in PH after 1hr compared to PH on admission, also after 2hr, 6hrs, 24hrs and on discharge compared to baseline either in NIV group or in HI-VNI group. (Figure 3).

As regards PaCO₂ on admission, after 1hr, 2hrs, 6hrs, 24hrs and on discharge, there were non-statistically significant differences among the 2 groups (p value >0.05) (Table 1).

While inside the same group, there were statistically significant decrease in PaCO₂ after 1 hour compared to PaCO₂ on admission, also after 2hrs, 6hrs, 24hrs and on discharge compared to baseline either in NIPPV group or in HI-VNI group (P value <0.05) (Figure 4).

By comparing both NIPPV group and HI-VNI group regarding PaO₂ on admission, after 1hr, 2hrs, 6hrs, 24hrs and on discharge, the study deduced non-statistically significant differences among the 2 groups (p value >0.05) (Table 1).

On the other hand, there were statistically significant increase in PaO₂ after 1 hour compared to PaO2 on admission, also after 2hrs, 6hrs, 24hrs and on discharge compared to baseline either in NIV group or in HI-VNI group. (P value <0.05). (Figure 5).

By comparing both NIPPV group and HI-VNI group regarding clinical outcomes, table 2 elucidated that there were statistically significant differences regarding transformation to another device and total length of hospital stay in days (p value <0.05) as total duration of hospital admission was more in NIPPV group (mean was 17.5 days) than in HI-VNI group (mean was 15 days). Regarding shift to another device, 3 cases shifted from NIV to HI-VNI (7.5%) compared to 11 cases shifted from HI-VNI to NIV (32.4%). While there were no significant differences among the 2 groups in success rate, duration of device application, need for intubation, duration of invasive mechanical ventilation, duration of ICU stay, intubation after device shift, in-hospital mortality and 30 days mortality (p value >0.05).

Discussion

Among the several types of obstructive lung illnesses, COPD is distinguished by airflow limitation and persistent breathing troubles. It is very common among the older people. Due to its widespread occurrence, the disease has a high rate of morbidity and mortality. According to WHO, COPD is the 7^th leading cause of disability and the 4^th leading cause of death worldwide ^(8,9).

Patients with COPD have a significantly reduced quality of life as a result of their declining lung function. AECOPD is brought on by environmental variables (air pollution and weather influences) as well as bacterial or viral infections ⁽¹⁰⁾.

The symptoms, which include increasing dys-pnea, coughing, sputum production, and sputum purulence are its defining characteristics ⁽¹¹⁾. AECOPD is treated acutely with broncho-dilators, steroids, antibiotics, oxygen, and NIV, depending on the severity ⁽¹²⁾.

NIPPV is currently a commonly utilized and highly efficient treatment for people with respiratory insufficiency. However, this approach somewhat hinders the comfort and compliance of the patients ⁽¹³⁾.

High Velocity Nasal Insufflation, a type of HFNC that uses a tiny bore nasal cannula to replace larger bore HFNC create greater gas delivery velocities. With flow rates of thirty-five liters per minute, it can completely clear extrathoracic dead space and in those suffering from acute type II respiratory failure, besides oxygenation support, it may also be able to provide ventilatory assistance ⁽¹⁴⁾.

In the present study, by comparing both NIPPV group and HI-VNI group regarding RR, PH, PaCO₂ and PaO₂ on admission, after 1hr, 2hrs, 6hrs, 24hrs and on discharge, there were no statistically significant differences between the two groups. While for intra group comparison, there were statistically significant decline in RR and PaCO₂ after 1hr compared to RR and PaCO₂ on admission, also after 2hrs, 6hrs, 24hrs and on discharge compared to baseline either in NIPPV group or in HI-VNI group and there was statistically significant increase in the values of PH and PaO₂ after 1hr compared to PH and PaO₂ on admission, also after 2hrs, 6hrs, 24hrs and on discharge compared to baseline either in NIV group or in HI-VNI group.

These findings are consistent with those of Doshi et al., 2020 ⁽⁴⁾ who proved that no statistically significant variations were shown between the groups under study regarding RR, PH, PaCO₂, PaO₂ on admission, at 60 min and at 240 min. While for intra group comparison, there were statistically significant decline in RR and PaCO₂ after 30min compared to RR and PaCO₂ on admission, also after 240min either in NIPPV group or in HI-VNI group and there was statistically significant increase in the values of PH and PaO₂ after 60min compared to PH and PaO₂ on admission, also after 240min either in NIV group or in HI-VNI group.

Furthermore, Papachatzakis et al., 2020⁽¹⁵⁾ found no statistically significant changes among the groups under study in PH, PaCO₂ and PaO₂ on admission and after 24h.

Added to that, Cortegiani et al., 2020 ⁽¹⁶⁾ proved that there was no statistically significant difference among the investigated groups as regard baseline PaO₂. Also, Cortegiani et al., 2020⁽¹⁶⁾, Jing et al., 2019⁽¹⁷⁾ and Sun et al., 2019⁽¹⁸⁾  revealed that baseline PH and PaCO₂ did not statistically significantly differ across the study groups.

The current findings are consistent with McKinstry et al., 2019 ⁽¹⁹⁾ who found that there were no statistically significant variations in RR at any particular time point between the groups under study. While for intra group comparison, there were significant decline in RR at different time intervals.

As well, Cong et al, 2019 ⁽²⁰⁾  demonstrated that serum PH and PaO₂ did not statistically significantly differ between the groups under investigation.

By comparing both NIPPV group and HI-VNI group regarding clinical outcomes, the present study found that there were statistically significant differences among the studied groups in transformation to another device because there was worry from the treating staff about switching deteriorating patients from NIV to Hi-VNI as NIV is the gold standard in treating AECOPD. In accordance with these results, Cortegiani A et al., 2020⁽¹⁶⁾ reported that 32.5% of patients treated with HFNT were shifted to NIV, even when a patient's illness was somewhat less severe, but only 7.7% of patients treated with NIV were shifted to HFNT and they explained that from a clinical point of view, a  method that allows for a higher and faster decarboxylation may be preferred by the clinician.

Additionally, there were significant variations (p value <0.05) in the duration of hospital admission among the studied groups.

These results contrast with Ali et al., 2023 ⁽²²⁾, Fang G et al., 2021⁽²³⁾, Cong L et al., 2019⁽²⁰⁾ who proved that there was no significant difference between the studied groups as regard duration of hospital admission. This may be due to variability in the severity of exacerbation between the 2 groups that was not assessed in the current study.

While there were non- statistically significant differences among NIPPV group and HI-VNI

group in success rate, duration of device application, need for intubation, duration of IMV, duration of ICU stay, intubation after device shift, in-hospital mortality and 30 days mortality (p value >0.05).

In accordance with these results, Doshi PB et al., 2020⁽²¹⁾ reported that there was no significant difference among the investigated groups in duration of ICU admission. As well, Papachatzakis Y et al., 2020⁽¹⁵⁾ and Cortegiani A et al., 2020⁽¹⁶⁾ demonstrated that  there was no statistically significant difference among the studied groups in mortality rate. Moreover, Sun J et al., 2019 ⁽¹⁸⁾ reported that there was  no statically significant difference among the studied groups regarding duration of ICU admission and 28-day mortality.

Similarly, Jing G et al., 2019⁽¹⁷⁾ found that there were no significant differences among the studied groups as regard IMV duration, duration of HFNC or NIV, ICU stay and 28 days mortality.