Respiratory Failure in Obstructive Lung Disease

#### **Chapter 2**

## Acute Respiratory Failure in Exacerbations of Bronchial Asthma

*Eva Sánchez*

#### **Abstract**

Asthma is defined as a chronic inflammatory disease of the respiratory tract in which various cells and inflammatory mediators are involved. It is characterized by remodeling of the airway wall. Multiple inflammatory mediators may be involved, including interleukins. Physiologically, acute asthma has an early component, with an acute bronchospastic aspect marked by smooth muscle bronchoconstriction and a later inflammatory component, resulting in airway swelling and edema. In the early stages of asthma, hypoxemic respiratory failure occurs. If the asthmatic crisis is maintained over time, it will produce a status of severe acute asthma (ASA), which is characterized by hypercapnic respiratory failure.

**Keywords:** airway resistance (Raw), functional residual capacity (FRC), ventilation/perfusion (V/Q ), interleukins (IL), acute severe asthma (ASA)

#### **1. Introduction**

From a pragmatic point of view, asthma could be defined as a chronic inflammatory disease of the airways in which various cells and inflammatory mediators are involved, conditioned in part by genetic factors, which occurs with bronchial hyperreactivity (BHR). Acute asthma attacks can cause great variability in gas exchange, as can be seen by measuring both the pressures of oxygen and carbon dioxide (PaO2 and PaCO2) on an arterial blood gas analysis, the same which may remain within normal values or experience a slight variation up to values that reflect severe hypoxemia, accompanied or not by hypercapnia.

#### **2. Concept**

Asthma is a chronic inflammatory disease in the airways. This state of chronic inflammation causes bronchial *hyperresponsiveness*, which leads to the narrowing of the conductive airways with airflow obstruction, which can be reversible spontaneously or with treatment. Asthma is a syndrome that includes various clinical phenotypes that share similar clinical manifestations but of probably different etiologies. From a pragmatic point of view, it could be defined as a chronic inflammatory disease of the respiratory tract, in the pathogenesis of which various

cells and inflammatory mediators are involved, conditioned in part by genetic factors and which occurs with bronchial hyperresponsiveness (BHR). In patients with asthma, during acute attacks, arterial oxygen and carbon dioxide (PaO2 and PaCO2) values can range from nearly normal or slightly abnormal to extremely altered, ultimately resulting in profound hypoxemia with or without hypercapnia [1, 2].

#### **3. Pathogenesis**

One of the main triggers for an acute asthma attack is exposure to an allergen, which in susceptible people causes inflammation of the respiratory airways. The inflammation is generally predominantly eosinophilic, although the involvement of other cells, such as T cells, neutrophils, and mast cells, has also been identified. Many inflammatory mediators are involved in this process, including interleukins (IL)-3, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-13, leukotrienes, and granulocyte-macrophage colony-stimulating factors (GM-CSF). In cases of sudden-onset, as is often with near fatal asthma, the infiltration is usually predominantly neutrophilic.

From the physiological point of view, acute asthma has two components: an early acute aspect marked by bronchoconstriction that occurs at the smooth muscle level; this, bronchoconstriction is usually episodic (asthmatic crisis or exacerbation); and an inflammatory component that develops later and causes edema of the airways [3, 4].

#### **3.1 Early bronchospastic response**

This response develops within minutes after exposure to a certain allergen and is characterized by the degranulation of mast cells or mast cells. This degranulation causes the release of immunoreactive mediators, such as histamine, prostaglandins, leukotrienes, and proinflammatory cytokines. These mediators produce smooth muscle bronchoconstriction and can compromise any level of the tracheobronchial tree, mainly compromising the peripheral airway (less than 2 mm in diameter in an adult). Other alterations that are observed are increased capillary permeability, mucus secretion, and activation of neural reflexes. This early response is characterized by a good response to inhalation therapy with beta 2-agonists [5].

#### **3.2 Later inflammatory response**

It is currently known that the airway epithelium is not only a passive barrier but an essential part of the local immune response in the airways, bridging innate and adaptive immunity against various environmental insults [2]. The release of inflammatory mediators primes adhesion molecules on the airway epithelium and capillary endothelium, allowing inflammatory cells, such as eosinophils, neutrophils, and basophils, to adhere to the epithelium and endothelium, and subsequently migrate to the tissues of the respiratory tract. A key inflammatory cell in asthma is the eosinophil of which there are increased numbers both locally and systemically in individuals with asthma. Eosinophils release eosinophil cationic protein (ECP) and major basic protein (MBP), and both ECP and MBP can cause desquamation of the airway epithelium and expose nerve endings. This interaction promotes increased airway hyperresponsiveness in asthma. This inflammatory component can even manifest in individuals with a mild exacerbation of asthma.

Bronchospasm, mucus secretion, and edema produced in the peripheral airways increase airway resistance and obstruction, by causing, in addition to airway closure, mucous plugging, and impaired mucociliary clearance. It has been determined that airway obstruction does not occur uniformly in the different lung areas. Air trapping will lead to lung hyperinflation, ventilation/perfusion (V/Q ) mismatch, and increased dead space. The lung will then inflate near the end of the inspiration on the lung compliance curve and, consequently, can have a variable degree of increase in the work of breathing.

Lung obstruction and hyperinflation, resulting from increased pulmonary and pleural pressures, together with increased mechanical forces of alveolar distension, lead to decreased alveolar perfusion. The formation of atelectasis, together with decreased perfusion, causes a V/Q imbalance in the lung units with the consequent hypoxemia and an increase in minute ventilation [5].

In this sensitization phase, inhaled allergens are captured by dendritic cells (DCs) and presented to naïve CD4+ T cells in the presence of coactivators, including epithelium-derived cytokines, which promote T helper cell activation and polarization of 2 (Th2) that produce IL-4, IL-5, and IL-13. These T2 cytokines are also produced by type 2 innate lymphoid cells (ILC2) and are prominent orchestrators of the allergic inflammatory cascade that occurs in asthma. IL-4 drives B cell isotype switching and the production of IgE, which binds to the high-affinity IgE receptor on mast cells. Re-exposure to allergens results in allergen-mediated IgE cross-linking, causing rapid activation and degranulation of mast cells. IL-5 promotes airway eosinophilia, IL-4, and IL-13 act directly on the airway epithelium to induce goblet cell metaplasia and mucus hypersecretion, and IL-13 mediates airway eosinophilia. Airway hyperresponsiveness through effects on airway smooth muscle cells [5].

#### **3.3 Airway remodeling phenomenon**

Asthma is characterized by remodeling of the airway wall: epithelial cell loss, goblet cell hyperplasia, airway smooth muscle hyperplasia and hypertrophy, and thickening of the basement membrane, with increased collagen deposition and increased vascular density.

The lesion-repair processes cause structural changes in the bronchial wall (fibrosis, hyperplasia and hypertrophy, denudation of the epithelium) that are an expression of the remodeling experienced by the asthmatic patient's airway and will be responsible for a particular phenotype that shows worse airway control of the clinical parameters and response to treatment [3, 6].

This remodeling begins in the early stages of asthma, and a correlation has been established between the thickness of the airway wall and the severity of the disease. The thickening, along with the effects of increased vasculature, favors airway narrowing, the main long-term complication of asthma [3, 6].

Below is the basement membrane, which can increase up to five times in some asthmatic patients. This thickening has an impact on the efficacy of treatment since it correlates with limited responsiveness to glucocorticoid treatment.

Further down, we enter the submucosa, which in asthmatic patients is characterized by a marked increase in the vasculature and an increased presence of eosinophils and mast cells. These vessels are more permeable, which leads to edema and inflammation of tissues. The vasculature may contribute to the pathology of asthma in several ways: First, this increased angiogenesis with more permeable vessels may cause tissue edema and thus narrow airways; second, the exudation of plasma

can aggravate local inflammation and remodeling; and third, an increased blood supply provides the hyperplastic and hypertrophied smooth muscle cells with the nutrients and oxygen necessary for their maintenance [6].

Even further down, we find the smooth muscle cells, which are the effectors that determine the diameter of the airways, causing them to relax or constrict according to different stimuli. Bronchoconstriction is the most serious symptom of an asthma attack, and these cells are the main effectors. In asthma, these cells are characterized by hypersensitivity to low doses of stimuli and hyperreactivity that produce a bronchoconstrictor response. This increased smooth muscle mass is already present in asthmatic children and youth without any signs of eosinophilic inflammation, suggesting that it could be the cause, rather than the consequence, of disease progression [6].

#### **3.4 Other factors: Microbiome, microbiota, and asthma**

It is estimated that the intestinal microbiome (a community of microorganisms that occupies a particular environment and performs a function within a specific environment) contains 150 more genes than the human being and there is a constant interaction between the two that, under normal circumstances, can thrive *via* symbiosis. Circumstances such as the country of origin, the route of delivery (vaginal or by cesarean section), and the use of antibiotics or lactation (maternal or artificial) influence the establishment of the microbiota.

Although we have less knowledge about how infections by viruses or bacteria, which cause many of the exacerbations of chronic respiratory diseases, modify the respiratory microbiota, recent studies have revealed the relationship between infections by certain respiratory viruses in childhood and predisposition to asthma.

When compared to that of healthy subjects, the microbiota of patients with asthma has a higher bacterial load, especially of the genus Proteobacteria, and less diversity in their lower airways. Instead, the Firmicutes and Actinobacteria genera are more common in healthy subjects. There is a relationship between the microbiota and certain characteristics of asthma, such as disease severity or resistance to treatment, as well as bronchial hyperreactivity. In fact, some of the bacteria could potentiate the allergic response of the airway. Other cohort studies, with various platforms, have shown that resistance to corticosteroids could be related to changes in the microbiome of patients. Thus, it has been shown that corticosteroid-resistant patients have a higher load of proteobacteria, including Neisseria and Hemophilus, while members of the Bradyrhizobium and Fusobacterium families predominate in corticosensitive patients [7, 8].

#### **4. Pathophysiology of acute asthma**

Various phenomena can be observed in acute asthma, the most characteristic functional alteration of asthma being increased airway resistance (Raw), particularly those located in the periphery (<2 mm in diameter). The main factors that cause a decrease in its lumen are smooth muscle contraction, mucus hypersecretion, and wall thickening due to inflammation and/or remodeling. There are also two important factors that also favor the closure of the airway in asthma: the alteration of the surfactant produced by the protein exudate of the inflammatory process, which can also undergo degradation by eosinophilic enzymes; and decreased *transpulmonary pressure* (TP),

#### *Acute Respiratory Failure in Exacerbations of Bronchial Asthma DOI: http://dx.doi.org/10.5772/intechopen.110278*

also called elastic recoil pressure. Under normal conditions, at the end of a passive expiration, there is a balance between the tendency of the lung to collapse and that of the ribcage to expand. The decrease in elastic recoil is important because when traction is lost in areas of the peripheral airway, they tend to close prematurely at the end of expiration, causing classic air entrapment. The classic airway changes in asthma (bronchospasm, mucus hypersecretion, inflammation, and remodeling) are added to this tendency to premature collapse. Air entrapment is manifested by an increase in residual volume at the expense of a decrease in vital capacity.

When an asthma exacerbation occurs, the lung loses elasticity, that is, the decrease in TP is accentuated, causing the equilibrium point between the lung and the rib cage to be reached at higher volumes (increased functional residual capacity [FRC]), which implies that the patient may breathe the same tidal volume, but with more inflated lungs. During forced expiration, the premature closure of the airways causes air entrapment, that is, an increase in the residual volume. If the asthmatic exacerbation is severe, regional abnormalities in ventilation may become unbalanced with respect to blood perfusion, causing hypoxemia, likewise, increased work of breathing can lead to muscle fatigue, hypoventilation, and hypercapnia [4, 9].

#### **4.1 Bronchial obstruction**

The basic functional impairment in asthma is airflow obstruction caused by a decrease in the caliber of the airway, especially during expiration. Bronchial obstruction is a diffuse and heterogeneous phenomenon, resulting from a mixture of spasm-inflammation and mucous plugs, which causes a significant reduction in airflow (peak expiratory flow, PEF, maximum expired volume in the first second of forced expiration, and FEV1). Sometimes it is found that there are no such mucous plugs, which suggests that bronchospasm alone can cause mortality asphyxia.

Although during an exacerbation, obstruction can occur at any level of the tracheobronchial tree, the peripheral airway (less than 2 mm in diameter in an adult) seems to be the main site of obstruction. Other functional abnormalities may arise from this alteration, such as increased work of breathing, alteration of lung mechanics and lung volumes, imbalance of the ventilation/perfusion (V/Q ) ratio, and compromised gas exchange.

Although bronchospasm is the most important phenomenon, it would be simplistic to reduce the problem to obstruction since it underestimates the consequences that this causes on the distribution of ventilation [4, 9, 10].

#### **4.2 Dynamic hyperinflation due to pulmonary overdistension**

In acute severe asthma (ASA), the increase in airway resistance prevents the respiratory system from reaching its end-expiratory resting volume or functional residual capacity (FRC), because exhalation is incomplete, and alveolar pressure remains positive at the end of expiration. Lung hyperinflation places the diaphragm at a mechanical disadvantage, which causes the appearance of progressive pulmonary overdistension, which in turn causes an increase in end-expiratory intra-alveolar pressure (intrinsic PEEP or auto-PEEP), which is known as dynamic lung hyperinflation.

The respiratory pattern that the patient adopts in response to this is what contributes to the appearance of this phenomenon. Tachypnea and active expiration further limit expiratory flow by shortening expiratory time and dynamic airway

collapse, respectively. Consequently, the balance point of the respiratory system moves to a greater volume than that of the FRC, which implies a greater workload for the inspiratory muscles, placing them in a position of mechanical disadvantage due to an unfavorable muscle length-tension relationship.

In all acute states of bronchial asthma, the ventilation/perfusion ratio (V/Q ) imbalance is the main mechanism of alteration of arterial gases, being the determining factor of the degree of hypoxemia. On the other hand, hypercapnia is attributable to V/Q imbalance, although alveolar hypoventilation due to fatigability and/or weakness of the respiratory muscles also play an important role [11, 12].

#### *4.2.1 Dynamic hyperinflation: Predisposing factors*

Factors that predispose to dynamic hyperinflation are reduced expiratory time and increased respiratory rate, tidal volume, or inspiratory time. The initial tachypnea achieves an increase in minute ventilation and hypocapnia. However, the increased minute ventilation in the setting of airflow obstruction leads to dynamic hyperinflation, that is, incomplete exhalation and air-trapping. If the exhalation is incomplete, the alveolar pressure remains positive at the end of expiration; this is termed auto-positive end-expiratory pressure (PEEP). Lung hyperinflation places the diaphragm at a mechanical disadvantage [12].

A randomized placebo-controlled trial, which included 32 asthma patients on inhaled glucocorticoid therapy, showing dynamic hyperinflation, defined by a ⩾10% reduction in inspiratory capacity measured by standardized metronomepaced tachypnea test, showed that treatment with systemic glucocorticoids partly reversed dynamic hyperinflation, suggesting that it is caused by inflammatory processes that affect the airway in asthmatic patients. It was also observed that this improvement was more marked within the group of patients who presented greater eosinophilia [11].

#### *4.2.2 Hemodynamic impact*

Dynamic hyperinflation leads to hemodynamic consequences that represent the deleterious effect that air trapping causes on intrathoracic blood volume and can lead to cardiac dynamics. Pulmonary hypertension, due to compression of the pulmonary vasculature, alters the compliance of the right ventricle and causes displacement of the septum toward the left ventricle (LV). This phenomenon, known as ventricular interdependence, adds to reduced venous return's effect on LV end-diastolic volume and leads to a drop in cardiac output. The paradoxical pulse then appears as an expression of cardiorespiratory interactions in the severe exacerbation of asthma.

#### **5. Acute respiratory failure**

In the early stages of asthma, hypoxemic respiratory failure (type I) occurs, which can be observed on arterial blood gas examination as a blood pressure of oxygen (PaO2) less than 60 mm Hg together with a blood pressure of carbon dioxide (PaCO2) abnormal or low. This is the most common form of respiratory failure that accompanies most acute lung diseases and is generally due to fluid filling or collapse of the alveolar units. The disease process that causes progressive airway obstruction results in decreased oxygen available in the distal airways for uptake through the

pulmonary capillaries. Through hypoxic pulmonary vasoconstriction, the blood flow of these lung units decreases, but this decrease is of less magnitude than that observed in the availability of oxygen.

If the asthmatic crisis is maintained over time, it will produce a status of acute severe asthma or *Asthmatic Status* (ASA), which is characterized by hypercapnic respiratory failure (type II) caused by excessive CO2 production or decreased effective alveolar ventilation and characterized by a PaCO2 higher than 50 mm Hg. The pH depends on the bicarbonate level, which, in turn, depends on the duration of hypercapnia.

All asthmatic patients are susceptible and at risk of developing status asthmaticus, which is a life-threatening episode of asthma that is refractory to usual therapy. Recent studies report an increase in the severity and mortality associated with asthma. In the airways, inflammatory cell infiltration and activation and cytokine generation produce airway injury and edema, bronchoconstriction, and mucus plugging. The key pathophysiological consequence of severe airflow obstruction is dynamic hyperinflation. The resulting hypoxemia, tachypnea, together with increased metabolic demands on the muscles of respiration, may lead to respiratory muscle failure [12]. If this state is maintained over time, it can inevitably lead to death.

#### **6. Conclusions**


*Respiratory Insufficiency*

### **Author details**

Eva Sánchez JUAN PABLO II" Private Hospital, Chiclayo, Perú

\*Address all correspondence to: evasan2015@gmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

[1] Moral VP et al. GEMA 4.0. Guidelines for Asthma Management. Archivos de Bronconeumología. 2015;**51**(Supl. 1):2-54

[2] Rodríguez E. Essential Guide to Non-invasive Mechanical Ventilation Methodology. Editorial Panamericana; 2010. pp. 199-202

[3] Calvén J, Ax E, Rådinger M. The airway epithelium, a central player in asthma pathogenesis, review. International Journal of Molecular Sciences. 2020;**21**:8907. DOI: 10.3390/ ijms21238907

[4] Rossi A, Roussos C, editors. Acute severe asthma: Pathophysiology and pathobiology of gas exchange abnormalities. In: Series "Clinical Physiology in Respiratory Intensive Care". Eur Respir J. Number 16 in this Series. Vol. 10. 1997. pp. 1359-1371

[5] Saadeh CK. In: Oppenheimer JJ, editor. Status Asthmaticus Updated. Jun 17, 2020

[6] Keglowich LF, Borger P. The three A's in asthma – airway smooth muscle, airway remodeling and angiogénesis. The Open Respiratory Medicine Journal. 2015;**9**:70-80

[7] García-Rivero JL. The microbiome and asthma. Archivos de Bronconeumologia. 2020;**56**(1):1-2

[8] Frati F, Salvatori C, et al. Review: The role of the microbiome in asthma: The gut–lung axis. International Journal of Molecular Sciences. 2019;**20**:123

[9] Michael J. In: Mosenifar Z, editor. Morris Asthma. Updated. May 11 2022

[10] Focused Updates to the Asthma Management Guidelines. A report

from the National Asthma Education and prevention program coordinating committee expert panel working group. The Journal of Allergy and Clinical Immunology. 2020;**146**(6):1217-1270. DOI: 10.1016/j.jaci.2020.10.003

[11] van der Meer A-N, de Jong K, Hoekstra-Kuik A, Bel EH, ten Brinke A. Targeting dynamic hyperinflation in moderate-to-severe asthma: A randomised controlled trial. ERJ Open Research. 2021;**7**:00738-02020

[12] Shapiro JM. Management of respiratory failure in status asthmaticus. American Journal of Respiratory Medicine. 2002;**1**(6):409-416

#### **Chapter 3**

## Respiratory Support for Obstructive Syndromes

*Alexey Gritsan*

#### **Abstract**

This chapter will present data on the biomechanics of respiration and gas exchange in acute respiratory failure of obstructive etiology. This chapter delineates main general principles of respiratory support, including non-invasive ventilation, and "traditional" mechanical ventilation. The principles of choosing positive end-expiratory pressure (PEEP) depending on the auto-PEEP are substantiated. The most commonly used respiratory support parameters for obstructive acute respiratory failure are presented. It is argued that the volume control (VC) ventilation modality is preferable in patients with asthma, since in this regimen positive inspiratory pressure (PIP) and inspiratory plateau pressure (Pplat) can be directly controlled, in contrast to the pressure control (PC) ventilation modality. The main options for selecting the ventilation mode will be presented.

**Keywords:** COPD, bronchial asthma, respiratory support, ventilation graphics, obstructive pulmonary disease

#### **1. Introduction**

Chronic obstructive pulmonary disease and bronchial asthma exacerbation are manifested by severe respiratory failure, which requires various methods of respiratory therapy. To date, enough information has already been accumulated to develop clinical recommendations for respiratory support in these diseases. We believe that special attention should be paid to the biomechanics of respiration in obstructive pulmonary diseases, the algorithm (step by step) of respiratory support, and indications and contraindications for non-invasive ventilation of the lungs. The choice of parameters for conventional lung ventilation is presented within the framework of the concept of protective ventilation; all the main complexities of mechanical ventilation management are identified; as well as the principles of weaning the patient from the ventilator.

#### **2. Biomechanics of respiration and gas exchange in acute respiratory failure of obstructive genesis**

It is well known that, like other skeletal muscles, the respiratory muscles can work with a load of about 60% of their maximum power indefinitely and without fatigue.

**Figure 1.**

*Mechanism of formation of PEEPi, due to early expiratory closure of the airways (adapted from: Tuxen and Lane [1]).*

Conceptually, if the load on the respiratory muscle's increases, or their maximum contractility decreases, then the respiratory muscles become fatigued, and eventually respiratory failure occurs. In bronchial asthma and chronic obstructive pulmonary disease (COPD), respiratory failure can occur against the background of the above factors (breathing demand and power (contractility) of the respiratory muscles).

Respiratory failure in bronchial asthma (BA) or obstructive pulmonary disease is associated with a sufficiently large increase in airway resistance (Raw) and increased work of breathing. As a rule, this is due to the presence of bronchospasm, the presence of a large amount of mucus in the tracheobronchial tree, inflammatory or fibrotic changes in the airways, or decreased lung compliance in emphysema.

The phenomenon of early expiratory airway closure that develops against this background leads to air entrapment (tidal volume (Vt) > exhaled tidal volume (Vte)), an increase in functional residual lung capacity (FRC), and, consequently, to overdistension of the alveoli with the formation of internal positive end-expiratory pressure (PEEPi) (**Figure 1**). The captured volume increases FRC and results in PEEPi (auto-PEEP). After each respiratory cycle, the "residual" volume increases. The consequence of these disorders is increased work of breathing, hypoxemia, and hypercapnia.

It is important to note that in bronchial asthma, these changes are usually acute (occuring during an exacerbation), while in COPD, the patient may be on the verge of respiratory muscle fatigue almost constantly, because of which even small changes in his somatic status can lead to respiratory failure.

Acute respiratory failure (ARF) of obstructive genesis is usually accompanied by overdistension of the lungs, which in most cases moves spontaneous breathing to a higher (less elastic) part of the volume/pressure curve (Vt/Paw), which inevitably leads to an increase in the elastic and resistive components of the work of breathing [2].

An increase in the work of breathing inevitably causes an increase in oxygen consumption and carbon dioxide production. Attempts to maintain the patient's PaCO2 and pH at normal levels due to the more active work of the respiratory muscles lead to even greater production of CO2.

Patients with COPD also have higher levels of dead space ventilation (up to 60–70% of Vt), which inevitably requires even higher minute ventilation and more work of the respiratory muscles to maintain pH at a safe level.

In patients with COPD, the activity of the respiratory center is also increased, but they are not capable of it in response to an additional load on the respiratory muscles.

#### *Respiratory Support for Obstructive Syndromes DOI: http://dx.doi.org/10.5772/intechopen.109931*

The high stimulus manifests itself in high inspiratory flow rates with a corresponding increase in the work of breathing during the inspiratory phase. This failure of the respiratory center may add a central component to the development of respiratory failure.

As the demand for work of breathing increases, the ability of the respiratory muscles to do work is hampered by the obstructive process. Hyperdistention of the lungs is the single most significant mechanism in COPD, acting in such a way that the diaphragm enters a biomechanically unfavorable position in which it becomes unable to perform adequate work of breathing. Therefore, prevention and correction of lung hyperdistention are the two main goals of respiratory support in the management of patients with obstructive acute respiratory failure.

It is generally known that the tension developed by a contracting muscle is directly proportional to the length of the muscle at rest. In an emphysematous (inflated) chest, the diaphragm flattens and therefore geometrically shortens. The resulting shortening of the muscle fiber in the relaxation (rest) phase reduces the maximum level of contraction that can develop with diaphragmatic contraction.

The tension (T) that occurs in this case is inversely proportional to the speed of muscle contraction. When a patient with COPD or asthma and respiratory failure breathes rapidly and shallowly, the rate of diaphragmatic contraction increases, and maximum tension decreases. The amount of pressure that can be generated by a contracting diaphragm is determined by La Place's law:

$$\mathbf{P} = \mathbf{Z}\mathbf{T}/\mathbf{R},\tag{1}$$

which means that the transdiaphragmatic pressure (P) for a given contraction is inversely proportional to the radius (R) of the curvature of the diaphragm. The increased radius of the flattened diaphragm significantly hinders its force of contraction.

As the overstretched diaphragm descends, its position in relation to the ribs becomes more horizontal, which prevents the ribs in the lower chest from participating in the inspiratory phase (Hoover's syndrome).

It is important to remember that diaphragmatic contractility is also affected by hypoxemia, hypercapnia, and acidosis.

The level of gas exchange disorders in obstructive ARF is characterized by hypercapnia with mild to moderate hypoxemia. Hypoxemia is caused by the following combination of factors:

1.violation of the ventilation–perfusion ratio (VA/Q)

2.intrapulmonary shunting of blood (Qs/Qt)

3.decrease in alveolar oxygen tension (PAO2) due to hypoventilation of the alveoli.

As a rule, hypoxemia is easily corrected by a moderate increase in the oxygen fraction in the inhaled gas mixture.

The increase in PaCO2 is due to decreased ventilation, increased carbon dioxide production, and increased dead space (Vd). Hypercapnia may further increase with the correction of hypoxemia through (Haldane), the essence of which is to raise the level of PaCO2 with an increase in PaO2 [3].

Thus, changes in the biomechanics of respiration and gas exchange during exacerbation of chronic obstructive pulmonary diseases and bronchial asthma, on which the tactics and strategy of respiratory support depend, are characterized by the following key criteria [4]:


#### **3. Basic principles of intensive care**

The principles of intensive care in patients with obstructive acute respiratory failure depend on the severity of the ARF itself and are aimed at the following main goals:


In this chapter, we will focus more on methods of correcting and maintaining adequate gas exchange using various respiratory support options.

#### **4. Respiratory support**

In the 80s, on an average, about 15–16% of patients with acute severe bronchial asthma required intubation and mechanical ventilation [5–7], while currently it is 2– 4% on average [8, 9]. Bronchial asthma is a rather labile pathological process which may rapidly develop manifestations of acute respiratory failure requiring an

*Respiratory Support for Obstructive Syndromes DOI: http://dx.doi.org/10.5772/intechopen.109931*

immediate initiation of mechanical ventilation. However, in some cases, "aggressive" therapy aimed at eliminating bronchospasm, removing sputum from the tracheobronchial tree and/or mask (non-invasive) positive pressure ventilation can avoid intubation and mechanical ventilation.

Emergency intubation of a patient with bronchial asthma may become necessary in the following cases [9]:


4. the appearance of life-threatening cardiac arrhythmias or cardiac arrest.

#### **4.1 Evidence of progressive exhaustion**

At the same time, it should be remembered that the lack of response to drug therapy, severe metabolic acidosis, persistent hypoxemia, and patient anxiety can also be indications for patient intubation and respiratory support.

In patients with chronic obstructive pulmonary diseases, indications of mechanical ventilation include alveolar hypoventilation, a decrease in pulmonary-thoracic compliance, inadequate work of breathing, and unstable neuro-respiratory drive [10]. It should be remembered that patients with COPD, depending on the neuro-respiratory drive, are divided into two types: "Pink Puffer"—an almost normal respiratory drive and "normal" PaCO2 and "Blue Bloaters"—a reduced respiratory drive and increased PaCO2.

Tracheal intubation should be performed using a low-pressure cuffed endotracheal tube, and the largest possible endotracheal tube diameter should be used to reduce airway pressure levels. Orotracheal intubation is less comfortable for the patient, and there is a greater risk (compared to nasotracheal intubation) of unintentional extubation.

The main tasks of respiratory support in obstructive ARF are as follows:


However, it should be remembered that mechanical ventilation is a form of "physiological" support and should be carried out in combination with "aggressive" drug therapy for the underlying disease. Respiratory support should not exacerbate existing pathophysiological processes; it should be carried out in such a way as to minimize the occurrence of various complications. Withdrawal of respiratory support should not be attempted until the patient's underlying condition and comorbidities (if any) have improved.

#### **4.2 Respiratory support algorithm**

Correction and maintenance of gas exchange at various stages of intensive care in obstructive ARF is carried out using various types of mechanical ventilation modes: continuous mechanical ventilation (CMV), assist control mechanical ventilation (A/C MV), continuous positive pressure ventilation (CPPV), pressure support ventilation (PSV), intermittent mandatory ventilation/synchronized intermittent mandatory ventilation (IMV/SIMV), or continuous positive airway pressure (CPAP) or their analogues.

Because airway resistance (Raw) can change very quickly in this type of acute respiratory failure, pressure-controlled (PC) ventilation cannot guarantee adequate minute ventilation. Therefore, volume-controlled ventilation (VC, CMV) is preferred for most patients. A high level of Raw can lead to quite high values of peak inspiratory pressure (PIP), and therefore, a modern respirator is needed that can provide a given Vt at a PIP of at least 80 mbar. However, in some cases, when ventilation in VC (CMV) mode is unable to overcome high airway resistance, it may be necessary to switch to PC mode. In such a situation, dynamic control of the gas composition of the blood, SaO2 and PetCO2, is mandatory.

Typically, the starting mode of ventilation for patients with obstructive ARF is A/C MV. CMV is preferred for restless patients who have difficulty in comfortable synchronization with the ventilator and for patients with extremely high PIPs. Complete control of the patient's ventilation can be achieved through continuous sedation as well as the administration of muscle relaxants. Typically, CMV is continued until airway resistance and wheezing decrease. In patients with BA, improvement in the condition can be observed within a few hours, while in COPD this process may extend for several days.

Modes A/CMV or SIMV (or their equivalents) are more suitable for patients with comorbidities who are not prone to hyperventilation. However, when using these modes of respiratory support, the respiratory muscles perform part of the work of breathing, most of which can be spent to initiate mechanical (hardware) inspiration. At the same time, the fatigue of the respiratory muscles will persist, and the dependence on the respirator will be prolonged. Patients with extremely high respiratory drive may ventilate with A/CMV or SIMV at a high respiratory rate, which will inevitably lead to an increase in PEEPi and hemodynamic disturbances.

The respiratory support algorithm for obstructive ARF is presented as follows (**Figure 2**).

Based on this algorithm, the tactics and strategy of respiratory support are carried out in the following order.

Firstly, attention is given to oxygen inhalation or the so-called oxygen therapy. This technique is not a separate option for respiratory support; however, oxygen inhalations quite often accompany medical treatment of patients with COPD and BA in a hospital setting. One of the main goals of oxygen therapy is to achieve a satisfactory level of oxygenation (PaO2 ≥ 60 mmHg or SaO2 ≥ 90%), which is quickly achieved in non-severe forms of obstructive ARF.

Since asthma has a low level of carbon dioxide retention, oxygen therapy is prescribed with medications (if there are no obvious contraindications). The starting level of oxygen concentration varies within 40–50% through a face mask or at a rate of 5 l/min through nasal cannulas. Subsequently, based on the data of the gas analysis of blood, the oxygen fraction in the inhaled gas mixture is corrected.

#### **Figure 2.** *Respiratory support algorithm for obstructive ARF.*

At the same time, in most patients with COPD, the level of PaCO2 in response to oxygen therapy will first increase by an average of 10–15, and then, it will stabilize. Therefore, a starting FiO2 is set between 24 and 30% using a face mask or 3–4 L/min via nasal cannulas. At the same time, the PaCO2 level should be carefully monitored (risk of carbon dioxide retention).

If, after 20–30 minutes of oxygen inhalation in a patient with obstructive ARF, the effectiveness of oxygen therapy is minimal or absent, and a decision should be made on the use of assisted ventilation.

When signs of ARF appear (increase in F, Raw, Vd/Vt, PaCO2 (PetCO2), decrease in Clt, VA/Q, PaO2, PaO2/FiO2), respiratory support begins with oxygen therapy or non-invasive ventilation (CPAP) followed by transition to CPAP + PSV. If NIV is ineffective, they switch to traditional mechanical ventilation in the following modes: CMV (VC), A/CMV, PC, SIMV, PSV + PEEP + kinetic therapy. Individual selection of Vt and/or PIP is carried out by the Paw/Vt loop, and the value of the hardware PEEP is selected in accordance with the level of PEEPi. Correction of Ti, I/E ratio is done on the Flow/Vt loop and flow/time curve by increasing the inspiratory flow rate and/or applying a decelerating flow waveform. With regression of signs of ARF (decrease in F, Raw, Vd/Vt, PaCO2 (PetCO2), increase in Clt, VA/Q, PaO2, PaO2/FiO2), respiratory support is withdrawn, followed by extubation. Detailed description is shown in the text below. Abbreviations: F—number of breaths, Raw —airway resistance, Vd/Vt—ratio of dead space ventilation to tidal volume, снижение Clt—pulmonary-thoracic compliance, VA/Q—ventilation/perfusion ratio, CPAP—continuous positive airway pressure, PSV—pressure support ventilation,

CMV—continuous mechanical ventilation, VC—volume control, A/CMV—assisted CMV, PC—pressure control, SIMV—synchronized intermittent mandatory ventilation, PSV—pressure support ventilation, Vt—tidal volume, PIP—peak inspiratory pressure, Paw/Vt loop—tidal volume/airway pressure loop, PEEPi—internal positive end-expiratory pressure, Ti—inspiratory time, and I/E ratio—ratio of the phases of inhalation and exhalations.

#### **4.3 Non-invasive respiratory support**

Non-invasive respiratory support includes the actual non-invasive artificial ventilation of the lungs (through masks or helmets), as well as high-flow oxygenation through special nasal cannulas.

Non-invasive ventilation of the lungs (compared to "invasive" ventilation through an endotracheal tube and standard oxygen therapy) has several advantages and disadvantages.

The advantages of NIV over invasive ventilation are as follows:


The advantages of NIV over standard oxygen therapy through a face mask or nasal prongs are as follows:


The disadvantages of NIV are as follows:

1. the need for active cooperation of the patient with medical personnel

2.inability to apply high inspiratory and expiratory pressures


5.high risk of aspiration of the contents of the mouth and stomach

6.maceration and necrosis of the skin in places where the mask fits

7.hypoxemia when the mask is displaced

8.conjunctivitis

9.drying of the oropharynx and nasopharynx

10.nosebleed.

The use of non-invasive mechanical ventilation leads to an improvement in gas exchange, a decrease in the work of breathing, and an improvement in the prognosis compared with oxygen therapy alone (through a face mask or cannulas) in exacerbation of COPD (with the development of moderate respiratory acidosis (7.35 > pH > 7.25) and compensated ARF) [11–14].

The criterion for choosing non-invasive ventilation during exacerbation of COPD is the presence of respiratory acidosis, and not the level of hypercapnia: in the absence of respiratory acidosis, NIV has no advantages over standard oxygen therapy, at pH = 7.25–7.35 NIV should be used to prevent tracheal intubation, and when pH less than 7.20—as an alternative to mechanical ventilation [15–17].

In general, the main indications for the initiation of non-invasive respiratory support are the following clinical and laboratory criteria:


5.increase in airway resistance (Raw) from the norm by 1.5–2 times.

Non-invasive respiratory support should not be used in the following cases:

1.lack of spontaneous breathing (apnea)


Tt is recommended to initiate non-invasive ventilation with a standard technique. For non-invasive respiratory support, the PEEP (CPAP) mode with a

pressure level of 5 to 10–12 mbar, or its combination with PSV (IPAP). Currently, NIV modes are practically no different from "invasive" ventilation modes (CPAP, CPAP + PS, pressure-controlled ventilation volume guaranteed (PCV-VG)), proportional auxiliary ventilation (proportional assist ventilation (PAV) and proportional pressure ventilation (PPV)), adaptive support ventilation (adaptive support ventilation (ASV)), in the settings of the device there is a setting for the backup mode of ventilation, and it is also possible to set both inspiratory and expiratory triggers. Randomized trials have not shown the benefits of any regimen for NIV [18–20].

The standard technique for conducting NIV is as follows:


• Increase PEEP to 8–10 mbar in patients with SpO2 less than 88% against the background of FiO2 0.3 with an increase in PEEP tolerance.

High levels of PEEP/CPAP (>12 mbar) and/or PS (>20 mbar), despite a temporary improvement in oxygenation, lead to patient discomfort and reduced efficacy of NIV.

Reduction of dyspnea is usually achieved soon after an adequate ventilation regimen is established, while correction of hypercapnia and/or hypoxemia may take several hours.

In the first hours, assisted non-invasive ventilation of the lungs should be carried out continuously. Further, after a gradual decrease in respiratory support, it is possible to switch to NIV sessions for 3–6 hours a day until it is completely liberated.

It should be noted that NIV can also be carried out in volume, also equal to 6–8 ml/ kg of proper body weight [21].

In the process of conducting NIV, it is necessary to monitor and evaluate the effectiveness of non-invasive ventilation of the lungs. If mask ventilation is ineffective, the patient should be intubated immediately, and "invasive" mechanical ventilation should be started.

Criteria for the ineffectiveness of NIV:

1. Inability of the patient to wear the mask due to discomfort or pain

2.Failure of mask ventilation to improve gas exchange or reduce dyspnea


#### **4.4 Invasive (traditional) mechanical ventilation**

In those cases when the patient's non-invasive ventilation is ineffective (or unavailable), invasive (traditional) ventilation is performed. This type of respiratory support is selected initially if there are indications for its implementation upon admission of the patient.

The main indications for the start of invasive mechanical ventilation are the following clinical and laboratory criteria:

1.ineffectiveness of non-invasive respiratory support


Initial modes (depending on the clinical situation) can be CMV (VC), PC, A/CMV, PSV, or SIMV (and their analogues). When using CMV, A/CMV, PC, and SIMV, it is most appropriate to use the following starting ventilation parameters: Vt = 6–8 ml/kg (with PC PIP level = 25–30 mbar), FiO2 = 0.6, F = 80% of the age norm), I/E = 1:2, PEEP = 5 mbar, and flow = 35–40 l/min. If the PSV mode is selected, the selection of parameters is carried out similarly to the technique used for non-invasive PSV (see above).

A/CMV and PSV modes (or their analogues) require the installation of a trigger pressure on the respirator ((1.5)–(2.0) mbar) or flow (3–4 l/min).

Upon reaching, against the background of the above parameters of respiratory support, sufficient chest excursion, improvement in the conduction of respiratory sounds, PaO2 ≥ 65 mm Hg, SaO2 = 93–95%, the oxygen concentration in the inhaled gas mixture is reduced to 0.45–0.3 under the control of SaO2.

If the movements of the chest are limited, then it is necessary to increase Vt in steps by 30–50 ml (or PIP by 2–3 mbar) until a "normal" level of chest excursion is reached and evaluate the result.

While maintaining PaO2 at a level of less than 60 mmHg at FiO2 = 0.6, it is necessary to increase the level of PEEP in steps of 1–2 mbar until PaO2 ≥ 65 mm Hg, SaO2 ≥ 92%.

Hypoxemia in obstructive ARF is usually a consequence of alteration of the ventilation–perfusion ratio and easily responds to a moderate increase in FiO2. Setting FiO2 = 30–45% is usually sufficient for SaO2 > 90% or PaO2 = 60–70 mmHg [2, 22]. High levels of oxygen concentration in the inhaled gas mixture may be necessary for patients with concomitant shunt-diffusive respiratory failure associated with acute respiratory distress syndrome, pulmonary edema, etc.

Further, after the improvement of oxygenation, hypercapnia, acidosis, the phenomenon of early expiratory closure of the airways and hyper distension of the lungs are corrected by optimizing the main parameters of respiratory support (Vt, MV, PEEP, Ti, I/E, and flow) in accordance with the concept of "safe" mechanical ventilation.

During selection of tidal volume, it is advisable to carry out based on the analysis of the Vt/Paw loop as follows: a stepwise increase or decrease in Vt by 20–30 ml until the "beak" appears or disappears on the volume/pressure loop (when ventilation is in PC mode, change the PIP value step by step by 1–2 mbar). That is, with the "optimal" Vt, there should not be a "beak" on the Vt/Paw loop.

*Respiratory Support for Obstructive Syndromes DOI: http://dx.doi.org/10.5772/intechopen.109931*

Minute ventilation (MV) should be managed to correct the patient's respiratory acidosis over several hours by changing the number of machine breaths and/or Vt. It is important to note that pH is a much more important parameter than the PaCO2 at which this pH is reached. Rapid correction of hypercapnia and acidosis can lead to post-hypercapnic metabolic alkalosis, hypokalemia, and hypophosphatemia.

In patients with COPD, one should not achieve a PaCO2 value of 40 mm Hg and a pH of 7.40, since it is more physiological for them to maintain these indicators at the level that they have in remission. Slight hypercapnia and a moderate decrease in pH to 7.35–7.38 will help to avoid the occurrence of alkalosis and will not cause a decrease in neuro-respiratory drive or an increase in the severity of ARF during the transition to spontaneous breathing [2, 22].

#### *4.4.1 Internal positive end-expiratory pressure and selection of hardware positive end-expiratory pressure*

In everyday clinical practice, the most difficult is the selection of positive airway pressure, considering the level of internal positive end-expiratory pressure (PEEPi) [23].

PEEPi is the result of overstretching and high residual volume. PEEPi is detected in most patients with obstructive respiratory failure at levels often exceeding 10 mbar [24, 25]. If the expiratory time is insufficient, the high alveolar pressure will encourage exhalation to continue at the start of the next ventilatory breath. PEEPi has the same hemodynamic consequences as externally applied PEEP and can cause significant hypotension with tachycardia after just a few machine breaths in hyperventilated patients. Quickly disconnecting the patient from the ventilator helps identify the cause of hypotension, as blood pressure returns to normal immediately.

PEEPi also places additional stress on the respiratory muscles and contributes to the difficulty in withdrawing respiratory support. The value of auto-PEEP can be minimized by limiting the value of Vt and the frequency of machine breathing, as well as by lengthening the exhalation time and machine PEEP.

Clinical experience has shown that two techniques can be used to select the "optimal" level of PEEP and eliminate the phenomenon of early expiratory airway closure.

The essence of the first (the simplest) is to titrate the hardware PEEP (from the starting level) in steps of 1–2 mbar until the moment when, during auscultation of the lungs, the patient's exhalation becomes audible until the start of the next hardware breath.

The second technique is carried out under the control of PaCO2 and PetCO2 as follows:


increase in PetCO2 by an average of 15–25% of the initial level. An increase in PetCO2 is observed within 20–40 min, followed by a decrease to 37–40 mm Hg.

In both cases, after selection, the value of the hardware PEEP varies within 9–14 mbar. The criteria for obtaining an effect when using the methods are as follows: (1) a decrease in PaCO2 by 25–35% of the initial level (according to the control gas analysis of blood taken 2–3 hours after the selection of PEEP); (2) spontaneous synchronization of the patient with the respirator, including after the abolition of sedation and/or muscle relaxation (if they were used).

#### *4.4.2 Further steps of the respiratory support algorithm*

The next step in "optimizing" the respiratory support parameters is the selection of the inspiratory time and the I/E ratio.

As previously stated, since lung hyper distension is always present in obstructive ARF, normalization of lung volume becomes the main goal. Functional residual capacity (FRC) depends on the ratio between the time needed to empty the lungs and the time to exhale. If the duration of the expiratory phase is insufficient, then the functional residual capacity of the lungs will exceed the normal FRC value. Each successive breath progressively increases lung volume until a new steady state is reached, typically 2–4 L above normal FRC [26, 27].

The time required to empty the lungs is a function of Raw and Clt and can be represented as a time constant (TC) that is the product of Raw and Clt. Since the time constant is the time required for exhalation from the lungs of 63% of the tidal volume that originally entered the lungs, the normal time constant for humans is about 0.42 s, while in COPD or bronchial asthma, these values are twice as high. Therefore, to avoid air entrapment, the expiratory time (Te) should be 3.5–4.0 TC, or 2.5–3 s [27, 28]. Large tidal volumes can also increase gas retention in the lungs.

Thus, to ensure sufficient expiratory time, Ti should be set as short as possible, and the I/E ratio should be set equal to 1: 2–1:4. At frequencies of 8–12 breaths/min, 4–6 s in each respiratory cycle will be available for exhalation, which in most cases is sufficient to ensure a full exhalation.

In addition to the empirical selection of inspiratory time and I/E ratio, it is advisable to use a graphical analysis of the flow/Vt loop and the flow/time curve (**Figure 3**). Increasing the length of expiration time by decreasing Ti and/or the number of machine respiratory cycles is carried out until a completely closed flow/Vt loop is obtained and the expiratory flow reaches the isoline on the flow/Vt curve at the end of inspiration.

Reducing the inspiratory time, of course, requires a change in the inspiratory flow rate (flow) to deliver a given tidal volume to the airways. That is, "large" Vt and short Ti require high flow rates.

However, one should not forget that the inspiratory flow delivered at a high level of airway resistance (which is present in patients with obstructive ARF) during ventilation in the CMV (VC) mode leads to an increase in peak inspiratory pressure (PIP). Because high PIP has long been suspected of causing pneumothorax and pneumomediastinum, it has been recommended that initial inspiratory flow rates are limited to 35–40 L/min. However, in practice, most of the peak inspiratory pressure is dissipated in the airways and is a less important factor in barotrauma than lung overdistension. Therefore, peak inspiratory flow rates reaching (if necessary for a particular patient) 80–100 l/min can be used [1, 5, 8, 27].

*Respiratory Support for Obstructive Syndromes DOI: http://dx.doi.org/10.5772/intechopen.109931*

#### **Figure 3.**

*Selection of inspiratory time (Ti) and exhalation time (Te)—According to the flow/Vt loop and the flow/t curve. The left side of the figure (a) shows an open flow/Vt loop (a) (shown by a solid arrow) and a flow/Vt curve (b) in which the expiratory flow to the beginning of the next breath (shown by a solid arrow), indicating insufficient time to ensure adequate exhalation (lung emptying). The right side of the figure shows the same graphs after adjusting Ti and expiratory time Te: The flow/Vt loop is closed (s), and the expiratory part of the flow/time curve reaches the isoline by the time the next breath begins (d).*

If the technical capabilities of the respirator allow you to change the waveform of the inspiratory flow, then it is better to use a decelerating waveform, which leads to better gas exchange in the lungs compared to a constant or sinusoidal waveform of the inspiratory flow.

In general, based on this algorithm for the individual choice of mechanical ventilation options, it offers for everyday clinical practice the most used parameters of respiratory support for obstructive ARF, presented in **Table 1**.


#### **Table 1.**

*Most commonly used respiratory support parameters for obstructive acute respiratory failure (based on data from Laher and Buchanan [9]).*

#### **5. Difficulties in managing mechanical ventilation**

Key issues related to the provision of mechanical ventilation in patients with acute and severe asthma and exacerbation of COPD include (1) methods for assessing pulmonary hyperinflation (described at the beginning of this chapter), (2) the effect of mechanical ventilation parameters on the severity of hyperinflation, and (3) the consequences and correction of hypercapnia [8].

It is known that the most common method for assessing hyperinflation is to measure the inspiratory plateau pressure (Pplat) and PEEPi during mechanical ventilation (**Figure 4**).

It should be remembered that PEEPi in severe asthma is often in the range of 10 to 15 mbar (cm H2O) but may be higher.

Hypercapnia is common with mechanical ventilation in patients with severe asthma. At the same time, the PaCO2 level can reach 68 mm Hg, at a pH less than 7.2, and a minute ventilation of 9 l/min [8]. However, the term "permissive" hypercapnia may not be entirely accurate when applied to severe asthma. Since hypercapnia is a consequence of increased dead space ventilation, attempts to lower PaCO2 by increasing minute ventilation will lead to increased hyperinflation and a further increase in physiological dead space.

Serious adverse effects of hypercapnia are rare. Of greatest concern is the effect on the central nervous and cardiovascular systems. Cerebral edema and subarachnoid

#### **Figure 4.**

*Schematic representation of airway pressure (A) and flow (B) during mechanical ventilation. Note that the flow is maintained at the end of exhalation, indicating that the final exhalation of alveolar pressure exceeds circuit pressure (i.e., PEEPi is present). The dotted line represents Palv. Palv—Alveolar pressure; PEEP—Positive endexpiratory pressure; Ppk—Peak inspiratory pressure; Pplat—Inspiratory plateau pressure; Pres—Inspiratory airway resistance.*

#### *Respiratory Support for Obstructive Syndromes DOI: http://dx.doi.org/10.5772/intechopen.109931*

hemorrhage have been associated with hypercapnia but are rare. Acute hypercapnia increases cerebral blood flow and intracranial pressure, an effect of greatest concern in the setting of cerebral anoxia due to circulatory arrest prior to intubation. The cardiac effects of acute hypercapnia include a decrease in intracellular pH, which decreases contractility, but sympathetic activation more than compensates for this direct effect on cardiac contraction and cardiac output, which tend to increase. Arrhythmias associated with hypercapnia are not uncommon in the absence of underlying heart disease.

Alkaline agents may be considered when arterial pH is consistently less than 7.1. Unfortunately, sodium bicarbonate has a limitation in correcting respiratory acidosis. The CO2 produced readily permeates cell membranes and can potentially lead to a significant decrease in intracellular pH during rapid infusions. In addition, even partial correction of severe respiratory acidosis may require several hundred milliequivalents of sodium bicarbonate. Therefore, in the absence of an urgent reason to correct the acidosis (e.g., severe arrhythmias, hyperkalemia, and unexplained hemodynamic instability), it may be prudent to withhold "alkaline therapy" and wait for the hypercapnia to decrease. Many patients experience a decrease in hypercapnia during the first 12 hours of intubation.

Another important point, especially for patients with asthma exacerbation, is the choice of ventilation mode.

The choice of ventilation mode must consider the degree of lower airway resistance and the presence of alveolar hyperinflation and "permissive" hypercapnia (as above). A high PIP, together with an increase in the pressure gradient of PIP to Pplat in the analysis of the graphical ventilation curves, indicates the presence of high resistance. PIP > 80–100 mbar is not an uncommon finding during mechanical ventilation in patients with severe asthma. Because the pathophysiology of asthma is not directly related to the alveoli, Pplat (which reflects lung compliance or alveolar pressure) is expected to be within normal limits (<20 mbar). Therefore, an increase in Pplat suggests the presence or increase in bronchospasm with an increase in hyperinflation or pneumothorax (**Figure 5**).

The VC mode is preferred in patients with asthma because PIP and Pplat can be directly controlled in this mode, in contrast to the PC mode. This should be kept in mind as long as Pplat is maintained below 30 mbar, even a very high PIP level (which is a sign of asthma) will not damage the alveoli (barotrauma).

When ventilating asthma patients, it is important to lower the upper pressure limit to a value that is higher than the patient's internal PIP. Failure to do so may result in fatal alveolar hypoventilation secondary to premature cessation of delivery of a given volume. This is better understood with the following example. If the upper pressure limit is set to 40 mbar in an asthmatic patient with severe bronchospasm, then tidal volume delivery will be terminated as soon as 40 mbar is reached. Because the anatomical dead space volume is one third (approximately 150 ml in an adult) of the normal volume (6 ml/kg), alveolar hypoventilation will occur. Therefore, the upper pressure limit should be set above the PIP (> 80 mbar in this hypothetical scenario) to prevent fatal alveolar hypoventilation. With a sudden improvement in bronchospasm (and a decrease in PIP), the patient will continue to receive the target tidal volume without an increase in alveolar pressure (**Figure 6**).

In contrast, PIP and Pplat cannot be controlled in a given pressure ventilation mode. Therefore, the patient will only receive adequate tidal volumes in this mode if the pressure limit as well as the set pressure is maintained above the internal airway pressure. With fluctuations in the degree of bronchospasm and associated changes in airway pressure, which can be sudden, there is a risk of either creating extremely high

#### **Figure 5***.*

*Interpretation of the paw/time VC pressure–time curve in patients with asthma. A, Normal shape curve. B. Paw/ time shape changes secondary to bronchospasm without hyperinflation. Note the increase in both PIP and PIP-Pplat gradient. Since Pplat remains the same as in A, this means an increase in airway resistance only in the absence of gas retention, since there is no change consistent with that in A. C. Changes in paw-time shape, indicating either (1) bronchospasm with gas retention or (2) pneumothorax. Note the same degree of increase in both PIP and Pplat. Since the PIP-Pplat gradient remains the same as in B, no further increase in the degree of bronchospasm occurs (shaded area, normal paw/time form). (Modified from Laher and Buchanan [9]).*

#### **Figure 6***.*

*Ventilate asthma patients using VC (recommended). Left: Patient with severe bronchospasm and PIP = 80 mbar. The upper pressure limit was set too low at 40 mbar; consequently, inhalation stops prematurely. Note the low tidal volume of 270 ml resulting in alveolar hypoventilation. Middle: Same patient with severe bronchospasm and PIP—80 cm mbar. The upper pressure limit is now correctly set to over 80 cm H2O, with the patient now receiving an adequate tidal volume > 450 ml. Note that despite the high PIP (80 mbar), the plateau pressure is 20 mbar, which is within the recommended safe pressure limits. Right: Same patient with sudden improvement in bronchospasm (PIP—50 mbar). Although the upper pressure limit remains unchanged at >80 mbar, delivered tidal volume and plateau pressure remain unchanged at >450 ml and 20 mbar, respectively. (Modified from Laher and Buchanan [9]).*

*Respiratory Support for Obstructive Syndromes DOI: http://dx.doi.org/10.5772/intechopen.109931*

#### **Figure 7***.*

*Ventilate asthma patients using PC mode (not recommended). Left: Patient with severe bronchospasm and PIP— 80 mbar. The upper pressure limit was set too low at 40 mbar, allowing only a tidal volume of 270 ml, resulting in alveolar hypoventilation. Middle: Same patient with severe bronchospasm and PIP—80 mbar. To achieve an adequate tidal volume > 450 ml, pressure control was set to 80 mbar, and the upper pressure limit was set to >80 mbar. Note that in this mode the plateau pressure cannot be determined; therefore, potential causes of high plateau pressure in an asthmatic patient (pneumothorax or gas retention) cannot be easily suspected in this mode. Right: Same patient with sudden improvement in bronchospasm (PIP—50 mbar) and established pressure control >80 mbar. Due to the sudden drop in airway pressure, the tidal volume (controlled by the 80 mbar pressure regulator) is now dangerously high (1000 ml), increasing the risk of barotrauma and pneumothorax. (Modified from Laher and Buchanan [9]).*

and harmful or unacceptably low tidal volumes that may go unnoticed if alarm limits are not meticulously set and the patient is not under close supervision.

For example, if the above patient has severe bronchospasm and an underlying PIP (airway pressure) of 80 mbar, the patient will only receive adequate tidal volumes if an upper pressure limit as well as a pressure control/pressure maintenance level has been set >80 mbar. In case of worsening of bronchospasm, when PIP is increased (e.g., 90 mbar), the patient receives suboptimal tidal volumes, while if bronchospasm is suddenly eliminated (and PIP decreases), the patient is at risk of receiving extremely high and dangerous tidal volumes (**Figure 7**).

#### **6. Weaning of respiratory support**

If the underlying obstructive process is amenable to drug therapy, withdrawal of respiratory support and restoration of spontaneous breathing may be considered.

The patient's respiratory mechanics should be significantly improved by reducing expiratory time, dyspnea, reducing airway resistance and PEEPi, and increasing pulmonary-thoracic compliance. Sufficient oxygenation must be maintained at FiO2 less than 40%.

Patients with asthma may be ready to withdraw within hours, while patients with COPD may not be ready for several weeks. Once the decision to initiate withdrawal has been made, all sedation and muscle relaxation should be discontinued.

With obstructive ARF, it is advisable to use the following additional criteria to make a decision on weaning a patient: (1) a decrease in peak inspiratory pressure to 17–20 mbar up to 8–11 mbar, PEEP up to 4–7 mbar; (2) improvement in the biomechanics of respiration (reduction of Raw to 6–9 mbar/l/s) and gas exchange (SaO2 > 93–94%, PaO2 ≥ 80 mm Hg, PaCO2 ≤ 40–44 mm Hg at FiO2 < 0.35) [4].

One should draw attention to the fact that when canceling respiratory support, it is necessary to strive to optimize the response of the respirator to the patient's inspiratory effort, following the following rules:


To stop respiratory support in patients with regression of ARF, SIMV and BIPAP modes have been used since the advent of microprocessor ventilators, gradually reducing the number of machine breaths, PSV mode, and breathing through a Tshaped tube.

Several subsequent multicenter randomized controlled trials demonstrated the benefit of the spontaneous breathing test using the PSV regimen with pressure support of 7–8 mbar. Over the spontaneous T-tube test and the superiority of both methods over SIMV weaning in duration of ventilator weaning and failure rate [29–31].

The largest and methodologically well-designed study demonstrated a higher rate of successful weaning from mechanical ventilation using a 30-minute spontaneous breathing test with a support pressure of 8 mbar compared with a simple 2-hour Ttube spontaneous breathing test (without pressure support) [29].

Currently, to assess weaning from respiratory support, a spontaneous breathing test (SBT) is recommended for 30 minutes with a small level of pressure support to compensate for the work of breathing to overcome the resistance of the tube [29]:

1.Set CPAP/PEEP mode ≤ mbar. With PS ≤ 8 mbar.

2.Within 30 minutes, assess for intolerance to SBT:


In cases where it is difficult to wean from respiratory support in this category of patients, it is possible to use a semi-sitting position at an angle of 45° to reduce the level of PEEPi and reduce the load on the respiratory muscles [32].

#### **7. Conclusion**

In general, provision of respiratory support in patients with obstructive ARF against the background of COPD and BA requires the physician to both understand the main pathophysiological processes of the occurrence of ARF and a certain patience in the selection of respirator settings due to dynamic changes in the mechanical properties of lungs during therapy.

#### **Conflict of interest**

The authors declare no conflict of interest.

*Respiratory Insufficiency*

### **Author details**

Alexey Gritsan Department of Anesthesiology and Intensive Care, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia

Address all correspondence to: gritsan67@mail.ru

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Respiratory Support for Obstructive Syndromes DOI: http://dx.doi.org/10.5772/intechopen.109931*

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## Section 3
