Ventilatory Support and Oxygen Therapy in Elder, Palliative and End-of-Life Care Patients

By Antonio M. Esquinas

This book provides readers with a comprehensive and up-to-date guide to non-invasive mechanical ventilation in palliative medicine, focusing on why and when it may be necessary. Physicians will find a practical guide to this specific context, particularly focused on pulmonary function and physiology in the elderly, and on ventilatory management in surgery and chronic stable conditions. The book provides detailed information on the rationale for invasive and non-invasive ventilation, the different modes of ventilation, indications and contraindications, prognostic factors, and outcomes. It addresses in detail the role of postoperative mechanical ventilation following various forms of surgery, and discusses key aspects of withdrawal from ventilatory support. Attention is also devoted to the use of mechanical ventilation within and beyond the ICU. The concluding part of the book focuses on important topics such as ethics, legal issues, home mechanical ventilation, drug therapy,  rehabilitation and end-of-life.

Its multidisciplinary approach, bringing together contributions from international experts in different specialties, ensures that the book will be of interest to a broad range of health professionals involved in the management of older patients admitted to the ICU, including intensivists, anesthesiologists, and geriatricians.

• Language: English
• Publisher: Springer
• Release date: Oct 26, 2019
• ISBN: 9783030266646

Book preview

Part IPulmonary Function and Physiology in Elderly

© Springer Nature Switzerland AG 2020

A. M. Esquinas, N. Vargas (eds.)Ventilatory Support and Oxygen Therapy in Elder, Palliative and End-of-Life Care Patients https://doi.org/10.1007/978-3-030-26664-6_1

1. Spontaneous Breathing Pattern

Lorena Olivencia Peña¹  , María Sevilla Martínez¹   and Alberto Fernández Carmona¹  

(1)

Intensive Care Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain

Lorena Olivencia Peña (Corresponding author)

María Sevilla Martínez

Alberto Fernández Carmona

Abbreviations

CO2

Carbon dioxide

FEV 1

Forced expiratory volume in 1 s

O2

Oxygen

PaCO2

Partial pressure of carbon dioxide inarterial blood

PaO2

Partial pressure of oxygen in arterial blood

TE

Expiratory time

TI

Inspiratory time

TTOT

Total cycle time

VT

Tidal volume

1.1 Introduction

In adult awake human subjects at rest, there exists a diversity in the breathing pattern not only in terms of tidal volume and inspiratory and expiratory duration and derived variables (TTOT, VT/TI, and TI/TTOT) but also in the airflow profile. Besides this diversity, in every recording of ventilation at rest in steady-state condition breath-to-breath fluctuations are observed in ventilatory variables. This variability is non-random and may be explained either by a central neural mechanism or by instability in the chemical feedback loops. Beyond this variability, each individual appears to select one particular pattern among the infinite number of possible combination of ventilatory variables and airflow profile.

To maintain accurate control, the respiratory system has a central respiratory pacemaker located within the medulla of the brainstem. Neural output travels from this center through the spinal cord to the muscles of respiration. The changes are effected through two groups of muscles, inspiratory and expiratory, which contract and relax to produce a rhythmic respiratory rate and pattern. In most individuals with unchanging metabolic demand, the rate and pattern are surprisingly constant, only interrupted every several minutes by a larger inspiratory effort or sigh. Ventilation at rest in most individuals requires only the inspiratory muscles. Expiration is usually passive and is secondary to the respiratory system returning to its resting state. Therefore, with quiet breathing the inspiratory time is the period of active respiratory pacemaker output. Adjusting the rate, length, and intensity of neural output from the pacemaker will lead to changes in the breaths per minute and the volume of each inspiration or tidal volume. These final outputs of the respiratory pacemaker, the rate and tidal volume, are the two components of ventilation. The expiratory muscles begin to play a role with disease or increased ventilatory demands. When this occurs, the length of time it takes to empty the lungs adequately will also lead to changes in rate and tidal volume.

Minute ventilation is the product of rate and tidal volume. It is important to differentiate between the effect changes in rate and tidal volume have on gas exchange. Any given tidal volume is divided into two components. One part is the dead space. This is the portion of the volume moved into the lungs during ventilation that does not come into contact with functioning pulmonary capillaries. An example is air at the end of inspiration, which reaches only the trachea or bronchi where there are no capillaries. Since there is no air–blood interface, O2 cannot reach the circulation nor can any CO2 be removed. The other component is called the alveolar volume. This is the part of a tidal breath that enters the air spaces of the lung that are perfused by functioning capillaries. In normal individuals, these air spaces are the terminal respiratory unit and include the respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli. Only the alveolar volume component of each tidal breath contributes to gas exchange; the rest is really wasted ventilation. If minute ventilation is increased by making the tidal volume larger, it will have a greater effect on gas exchange than if the same minute ventilation is reached by increasing the rate.

An infinite number of possible combinations of tidal volume and breathing frequency, as well as pattern of airflow, can achieve the alveolar ventilation required for normal gas exchange. Individuals appear to select one particular pattern.

1.2 Breathing Pattern

1.2.1 Regulation of Pacemaker Output

The medullary respiratory control center, or pacemaker, receives three kinds of feedback. These impulses are integrated within the control center. The output from the respiratory center is then altered in timing or intensity, leading to changes in the rate and tidal volume. The three kinds of feedback are chemical, mechanical, and input from higher cortical centers.

The normal individual is able to keep PaO2, PaCO2, and pH within narrow limits. In order to accomplish this level of control, the respiratory center receives input from both peripheral and central chemoreceptors. The major peripheral receptors are located within the carotid bodies found in the bifurcation of each common carotid artery. There are also similar structures in the aorta, but less is known about these aortic bodies. The afferent limb of these receptors responds to PaO2 and pH changes. The efferent limb produces changes in minute ventilation through the respiratory control center. The response to changing PaO2 levels can be detected as high as 550 mmHg, but at that PaO2 level the resulting change in rate and volume is small. As the PaO2 drops to 55–60 mmHg, there is a much greater and more important respiratory response with large increases in minute ventilation for each mmHg change in PaO2. The carotid body also responds to small changes in pH, but approximately two-thirds of the response to pH is a result of the central chemoreceptors. The response of the carotid bodies to PaCO2 is secondary to changes in pH resulting from the PaCO2 change.

The medullary chemoreceptor is located on the ventral surface of the medulla. This receptor responds to changes in pH and is the most important receptor regarding respiratory changes to acid-base alterations. It responds to changes in cerebrospinal fluid rather than blood and is very sensitive to very small changes in the hydrogen ion concentration in the cerebrospinal fluid. Since CO2 rapidly crosses the blood–brain barrier, it rapidly alters the pH of the spinal fluid. An increase of 1 mmHg of paCO2 in the cerebrospinal fluid leads to an increased ventilation of 2–3 L per minute. The medullary chemoreceptor also adjusts the respiratory response to altered pH secondary to metabolic acidosis or alkalosis. With the slower equilibration of hydrogen or bicarbonate across the blood–brain barrier, however, these changes are not as quick as the rapid respiratory changes produced by a change in PCO2.

Another neural input to the respiratory pacemaker comes from receptors in the lung and is related to the mechanical properties of the lung. An individual who elected to breathe at a rate of 5 breaths per minute with a large tidal volume would have efficient gas exchange because the ratio of dead space to tidal volume would be low. The larger the inspiratory lung volume, however, the greater becomes the elastic recoil of the lung. At greater lung volumes, chest wall elasticity is also added and must be overcome. Therefore, the larger the inspiratory lung volume, the greater the inspiratory pressure needed to overcome the elastic recoil and expand the lung. The greater the inspiratory pressure, the greater is the work of breathing by the respiratory muscles. The respiratory system appears to choose a rate that requires the least amount of mechanical work while maintaining adequate gas exchange. There is a wide range of tidal volumes before the mechanical limitation comes into effect, but there appear to be lower limits of rates that are not tolerated because of the required increase in inspiratory work.

Receptors in the lung itself appear to contribute to this inspiratory limitation. One group is the stretch receptors. Efferents from these increase their neural output the larger a given lung volume becomes. In some animals, these reflexes are very important, but in normal humans they appear to be less important and can be easily overcome by other neural inputs. The output of these receptors can, however, limit the degree of inspiration by means of the Hering-Breur reflex. Probably in disease states this reflex plays a more important role in limiting inspiration. The other lung parenchymal receptors that may play a role in limiting the size of each tidal volume are the juxtapulmonary capillary receptors, or J-receptors. These receptors fire when pulmonary capillaries are distended.

A final modulator of the central respiratory drive is input from higher centers. For example, the state of being awake is associated with important neural inputs to the respiratory center that will play a large role in determining an individual’s respiratory rate and pattern. When an individual falls asleep, the cortical input decreases, as does the respiratory center output. During nondreaming or non-rapid-eye-movement sleep, the input from the chemical receptors becomes increasingly important. If absent, apnea may result. During sleep associated with rapid eye movements or dreaming, the breathing patterns may be related to the contents of the dreams and again reflect input from higher cortical centers. Higher center input also accounts for hyperventilation associated with anxiety and other behavioral factors.

1.2.2 Diversity in the Pattern of Breathing

All three types of input are integrated in the medullary respiratory center and lead to changes in the minute ventilation. These changes are seen as changes in rate, volume, or both. Table 1.1 demonstrates how these factors may interrelate in normal individuals. If the ventilation during a minute (minute ventilation) was 6 L and was done at a rate of 60 breaths with a tidal volume of 100 cc each, there would be no alveolar ventilation at all. This is because the normal dead space consisting of the trachea and some bronchi is about 150 cc. Even if the rate was slowed to 30 breaths per minute, the result would be an alveolar ventilation of only 1.50 L. This would be inadequate to meet CO2 production and would lead to an elevation of the PaCO2 and a lowering of the pH. Both the central and peripheral chemoreceptors would be stimulated. There might also be a concomitant fall in PaO2, which would lead to increased neural output from the carotid bodies. The result of the increase of input to the central center would be an alteration in the rate and pattern of breathing.

Table 1.1

The effect of changes of respiratory rate and tidal volume on alveolar ventilation

aA dead space of 150 mL/breath is assumed

A third breathing alternative would be choosing a respiratory rate of 2 per minute. This would give an extremely efficient breath with very little wasted as dead space. The problem with the large volume is that it would require increased work of breathing and stimulate stretch receptors. Therefore, unless a constant conscious effort was maintained, the respiratory central center would inhibit inspiratory effect before reaching tidal volumes of 3 L. Furthermore, the very efficient gas exchange could lead to a lowered PaCO2. The resulting increased pH would produce less drive to breathe and lower minute ventilation. The best alternative in a normal individual would be to choose an intermediate rate of 10–20 breaths per minute. The example of 15 breaths per minute would meet metabolic needs effectively.

In normal individuals, multiple factors affect the respiratory rate and pattern at rest. Normal people also must adjust to changing metabolic demands, as seen with exercise. Using the input from various receptors, the respiratory center finely adjusts both rate and pattern to keep PaO2 and pH within a relatively small range in spite of increased metabolic demands of 15 or more times the needs at rest.

The earliest data available on spontaneous breathing frequency values are those of Quetelet [1] on 300 subjects and of Hutchinson [2] on 1714 adult subjects. These data appear to be the most extensive so far published and show the very wide frequency range (between 6 and 31 breaths per minute) observed in adults.

The inspiratory and expiratory durations introduce an additional factor of diversity into the breathing pattern. For a given duration of respiratory cycle (TTOT), there may be several combinations of inspiratory (TI) and expiratory (TE) times within, however, the constraint that TI is less than TE (TI < TE).

The diversity in tidal volume was first described by Dejours et al. [3], the range of VT observed in human subjects at rest being from 442 to 1549 mL. These values were neither related to the height of the subjects, the vital capacity, FEV1, nor to the inspiratory and expiratory resistances. The devices used for measuring VT have been blamed for introducing errors not only in the values of VT but also in the values of timing components of the breathing pattern. However, these errors appear to affect only the base line values and not the range of the diversity. Indeed, in one of the most recent studies (Perez and Tobin [4]) conducted on 16 subjects the mean ± S.D. values of the respiratory variables remained approximately the same whatever the instrumentation used for recording breathing.

The VT/TI and TI/TTOT are widely used because of their physiological significance and relevance. However, being ratios, the diversity in their values may be reduced if both terms of the ratio vary in the same direction or, alternatively, may derive from the diversity of one or both of the ratio terms. Thus, they are not the most adequate descriptors of the diversity of the breathing pattern.

The Flow profile. Bretschger [5] analyzed and classified patterns of pneumotachograms and concluded that the optimal airflow pattern minimizing mechanical work is rectangular with constant airflow rates during inspiration and expiration. The flow profile was also analyzed to determine, as in Proctor and Hardy [6] subtitle to their article, the significance of the normal pneumotachogram. The quantitative analysis performed by these authors include measurements of acceleration, velocity, and time relationships at various points during the cycle. Patterns that seem quite similar in shape, when submitted to such methods of quantitative analysis, yield widely differing figures. One of the possible explanations they proposed was that the methods of quantitative analysis may not include the fundamental characteristics of the pattern. Perhaps an analysis of the total shape of the curve is required.

Gray and Grodins [7] have further proposed that transformation of the tracings to a completely non-dimensional form should be the first step in analyzing the significance of their shape as far as no two respiratory cycles yield identical curves with respect to both shape and dimensions. Such methods of global flow profile analysis have been proposed by several authors. These methods provide the possibility of obtaining mean flow profiles under different conditions and of comparing resting and stimulated patterns.

The existence of the individuality of the breathing pattern has been observed by all the investigators who have had to perform several recordings on one subject. Dejours et al. [3] introduced the concept of la personnalite ventilatoire, claiming that different people breathe in different ways in terms of tidal volume, respiratory frequency, and airflow shape, and that this is a relatively stable characteristic of an adult individual. In addition, Golla and Antonovich [8] found that some normal subjects had habitually a regular breathing pattern while others a habitually irregular one. We have also observed (unpublished observation) this phenomenon and found that the regular or irregular breathing pattern was reproducible for the same subjects under the same conditions, and that the regular or irregular nature of the breathing pattern is thus part of the personnalite respiratoire.

1.2.3 Abnormal Central Respiratory Control

Altered respiratory rate and pattern often accompany a variety of disease states. These diseases frequently lead to alterations in one of the three kinds of feedback to the central respiratory control center or in the control center itself [9]. For example, pathological conditions altering PaO2, PaCO2, or pH can obviously alter the input from both the carotid body and the medullary chemoreceptors. The usual response to any altered chemoreceptor input is, first, a change in tidal volume, followed by change in respiratory rate. Therefore, lung diseases that cause acute hypoxemia to a level lower than 55–60 mmHg will usually produce increased ventilation. The response to increasing PaCO2, and lowered pH can produce rapid changes in minute ventilation also by stimulating the chemoreceptors. The elevation of PaCO2 is not always associated with the expected increase in minute ventilation, however. Elevation of PaCO2 can lead to CO2 narcosis and depression of the respiratory center. Metabolic acidosis, in contrast, will most likely increase the ventilation predominantly by increasing the tidal volume. Kussmaul respiration (Fig. 1.1), the classic pattern seen in diabetic ketoacidosis, consists of slow, deep breaths that reflect the increased tidal volume and actual slowing of rate. The occurrence of respiratory compensation for a metabolic change may be slowed because cerebrospinal fluid changes lag behind blood changes. An acute pH drop in the blood will stimulate the peripheral chemoreceptors, leading to hyperventilation and acutely lowering the PaCO2.

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Fig. 1.1

Abnormal respiratory patterns

This will lead to a lowered PCO2 in the cerebrospinal fluid. Since the hydrogen ion associated with the metabolic acidosis does not cross the blood–brain barrier immediately, the medullary chemoreceptors may initially reduce respiration because the reduced PCO2 will make the cerebrospinal fluid alkalotic. In a matter of hours, the spinal fluid pH is decreased, and the appropriate response will occur. Ventilation will also be slowed with metabolic alkalosis. This change may not be detectable on routine physical examination. Nevertheless, it can also lead to enough slowing that the PaCO2 becomes markedly elevated.

Mechanical properties also are altered by diseases. Interstitial disease probably enhances the stretch receptor response, leading to rapid shallow ventilation. This is efficient because the lung with interstitial disease is less compliant, requiring more distending pressure per unit of volume than normal. By breathing at lower tidal volumes, the work of breathing is diminished. Congestive heart failure can produce a similar effect. This is partly related to the reduced compliance, but also may be a result of stimulation of the J-receptors, which lie right next to the capillaries.

The respiratory center feedback from the higher cortical centers can also be modulated with diseases. Anxiety can increase the respiratory rate and pattern. The acute hyperventilation syndrome is an example where drive from higher centers can maintain a high minute ventilation in face of an elevated pH. Increased intracranial pressure leads to a rapid and deep breathing pattern. This pattern is frequently seen with head trauma. Pain contributes to a rapid respiratory rate. A fractured rib produces pain on inspiration and therefore leads to a low-volume, rapid-rate pattern. Tachypnea is commonly part of any chest pain and is partly modulated through higher cortical input.

The central controlling center can be affected directly. Any central nervous system depressing drug will reduce the respiratory rate and pattern. It will also blunt the response to other neural inputs. The patient with obstructive lung disease who receives a narcotic frequently will elevate the PaCO2 even further. The same is true for many drug overdoses. If the central nervous system is depressed by drugs, the depression of the respiratory center leads to CO2 retention.

1.2.4 Central Nervous System Abnormalities

The changing rate and pattern of respiration can often suggest localization of CNS changes. Understanding of the areas of the brain involved with specific patterns has come from animal studies. Lesions or cuts made in various parts of the brain lead to specific breathing patterns. Transection of the pons will not affect normal breathing if the vagi are intact. If vagi are cut, however, larger tidal volumes with a slower rate are observed. A midpons transection will lead to maintenance of spontaneous breathing but with a slow and regular pattern. If the vagi are cut, apneustic breathing occurs. This is sustained inspiratory spasm. Pontomedullary junction transection will lead to an irregular, ataxic breathing pattern.

1.2.5 Abnormal Respiratory Patterns

Cheyne–Stokes breathing is a classic breathing pattern seen in both normal individuals at altitude and individuals with severe neurological or cardiac disease [10]. The pattern (Fig. 1.1) demonstrates periods of hyperventilation alternating with periods of apnea. The apneic spells can last as long as 45 s. The abnormality appears to be related to a slow feedback loop and an enhanced response to PaCO2. During periods of hyperventilation, the PaCO2 is at its highest, while the PaO2 is at its lowest. As ventilation slows, the PaCO2 drops and reaches its lowest level during apnea. It is important to observe that PaCO2 levels do not exceed the normal range during any part of the cycle.

There are several probable causes of this abnormal breathing pattern. Many cases have diffuse cerebral damage, whereas some individuals are in congestive heart failure. It is seen in normal individuals during sleep at altitude. It has been shown in dogs that a markedly prolonged circulation time from the left ventricle back to the brain can also induce Cheyne–Stokes respiration. In individuals with either neurological or cardiac disease, it frequently is a poor prognostic sign. Treatment is usually improvement of the underlying disease, but aminophylline has been effective in some cases.

A Cheyne–Stokes respiratory pattern can also be seen in individuals with much more severe neurological depression. These individuals have a low pontine or upper medullary lesion. Unlike the more classic Cheyne–Stokes respiration, these individuals are cyanotic and have CO2 retention. They have reduced sensitivity to CO2. Oxygen will enhance this pattern, while it may reduce the more classic picture.

Biot respiration, or cluster breathing (Fig. 1.1), is also periodic in nature but does not have the crescendo–decrescendo pattern seen with Cheyne–Stokes respiration. It is clusters of irregular breaths that alternate with periods of apnea. This breathing pattern is seen in individuals with pontine lesions. Ataxic breathing is one of varying tidal volumes and rates. These individuals can frequently keep their rate more rhythmic if they try consciously. The abnormality is in the medullary chemoreceptor or the medullary respiratory control center.

One other aspect of respiratory pattern must be considered. This is the coordination between the chest wall and abdomen. Normal individuals contract both the diaphragm and external intercostal muscles during inspiration. On physical examination, the action of both inspiratory muscle actions can be determined. The diaphragm, when contracting normally, moves the abdominal contents downward and outward. On physical examination, it is felt as an anterior movement of the abdomen. The other major groups of inspiratory muscles, the external intercostals, move the chest wall outward. This can also be determined by feeling an anterior movement of the chest wall during inspiration and is reflected in the figure as an upward deflection. In normal persons, therefore, there is a coordinated movement of the chest wall and abdomen moving outward on inspiration and inward on expiration. Alterations in this pattern will allow diagnosis of changing respiratory muscle contribution to the tidal breath.

Paralysis of the intercostals results from cervical spinal cord injury. In this group of patients on physical exam, there is a paradoxical movement of the chest wall inward and the abdomen outward during inspiration. This reflects the passive movement of the chest wall. The pattern results from the tidal breath being produced by diaphragmatic contraction. Diaphragmatic paralysis can be diagnosed or suggested by an inward movement of the diaphragm during inspiration. This movement is accentuated in the supine position. In that position, diaphragmatic contraction produces approximately two-thirds of the inspiratory volume as compared to one-third in the upright position.

Diaphragmatic dysfunction can also be diagnosed with the finding of the same paradoxical inward abdominal movement during inspiration. This pattern of respiration is seen in some individuals with severe emphysema and air trapping. The air trapping leads to a low, flat diaphragm. The diaphragm no longer can contract effectively. This inability to contract is demonstrated by the inward inspiratory movement of the abdomen. The movement results from the ineffective diaphragm being pulled into the thorax during inspiration. This breathing pattern has been reported to have a predictive value for impending respiratory failure.

Another value of determining changes in chest wall abdominal breathing patterns has been seen in individuals being weaned from mechanical ventilation. They develop a respiratory alternans pattern. A series of tidal breaths alternates between a short period of abdominal inward movement during inspiration followed by a period of chest.

1.2.6 Spontaneous Respiratory Patterns and Interation with Mechanical Ventilation

Understanding respiratory rate and pattern is a very important addition in dealing with many respiratory, cardiac, and neurological diseases. Nevertheless, understanding the role of rate and tidal volume is also essential in managing individuals requiring mechanical ventilation. This is one clinical situation where the physician can directly manipulate the respiratory rate and pattern to produce the appropriate arterial blood gases. The sum of each alveolar volume over 1 min is the alveolar ventilation and is inversely related to the PaCO2.

Hyperventilation reduces PaCO2, leading to decreased respiratory drive and a patient who does not trigger the ventilator. Hypoventilation produces CO2 retention and increased respiratory drive by the patient. This leads to either rapid ventilation rates triggered by the patient or a patient demonstrating marked discomfort. Consideration of dead space is important. Diseases can increase the dead space by reducing the capillary bed. Therefore, larger tidal volumes may be necessary to get adequate gas exchange. Finally, volumes that are too large lead to asychrony by the patient who tries to start the next breath before the ventilator is ready. This may relate to stretch receptor responses, but is a fatiguing and inefficient mode of gas exchange.

1.3 Conclusion

The existence of the diversity and individuality in breathing pattern suggests that there are degrees of freedom in the resting pattern, and an infinite number of possible combinations of the ventilatory components and airflow shape exists capable of achieving the same minute ventilation.

The presentation of varying breathing patterns under the umbrella term of dysfunctional breathing appears to be relatively widely appreciated (anecdotally), but there is little recognition of this in the literature, and hence the topic presents a significant challenge for clinicians. Hyperventilation syndrome remains the most extensively studied dysfunctional breathing pattern although other forms may coexist or appear in isolation.

References

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Quetelet MA. A treatise on man and the development of his faculties. Cited by Mead J., 1963. Control of respiratory frequency. J Appl Physiol. 1842;15:325–36.

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Hutchinson J. Todd’s cyclopaedia of anatomy and physiology. Cited by Mead J., 1963. Control of respiratory frequency. J Appl Physiol. 1850;15:325–36.

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Dejours P, Bechtel-Labrousse Y, Monzein P, Raynaud J. Etude de la diversité des régimes ventilatoires chez l’homme. J Physiol Paris. 1961;53:320–1.PubMed

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Perez W, Tobin MJ. Separation of factors responsible for change in breathing pattern induced by instrumentation. J Appl Physiol. 1985;59:1515–20.Crossref

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Bretschger HJ. Die Geschwindigkeitskurve der menschlichen Atemluft (Pneumotachogramm). Pflugers Arch Ges Physiol. 1925;210:134–48.Crossref

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Proctor DF, Hardy JB. Studies of respiratory airflow. 1. Significance of the normal pneumotachogram. Bull Johns Hopkins Hosp. 1949;85:253–80.PubMed

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Gray JS, Grodins FS. Respiration. Annu Rev Physiol. 1951;13:217–32.Crossref

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Golla FL, Antonovich S. The respiratory rhythm in its relation to the mechanism of thought. Brain. 1929;52:491–509.Crossref

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Kryger MH. Abnormal control of breathing. In: Kryger MH, editor. Pathophysiology of respiration. New York: Wiley; 1981. p. 103–22.

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Tobin MJ, Snyder JV. Cheyne-Stokes respiration revisited: controversies and implications. Crit Care Med. 1984;12:882–7.Crossref

© Springer Nature Switzerland AG 2020

A. M. Esquinas, N. Vargas (eds.)Ventilatory Support and Oxygen Therapy in Elder, Palliative and End-of-Life Care Patients https://doi.org/10.1007/978-3-030-26664-6_2

2. Gas Exchange and Control of Breathing in Elderly and End-of-Life Diseases

Annamaria Romano¹   and Rosalba Romano²  

(1)

Division of Respiratory Medicine, San Giuseppe Moscati Hospital, Avellino, Italy

(2)

Department of Surgery and Cancer, Imperial College London, London, UK

Annamaria Romano (Corresponding author)

Rosalba Romano

2.1 Introduction

Lungs are known to deteriorate with aging due to changes in both structure and function occurring in the absence of lung disease in healthy elderly people, including:

a decline in muscle strength, with substitution of the muscle with fat tissue

an increased alveolar size leading to reduced elastic recoil

a reduction in chest wall compliance

an increase in pulmonary compliance

a decrease in oxygen diffusion capacity

the premature airway closure with ventilation-perfusion mismatch

the small airway closure with air trapping

decreased expiratory flow rates

The reduction in pulmonary function must be distinguished from the reduction due to normal aging, a progressive decrease in lung performance which usually does not affect the capacity to maintain an adequate gas exchange in the absence of pathological conditions, although it becomes crucial when the physiologic demand increases above the reduced capacity [1].

In addition, aging is characterized by a progressive decline in arterial oxygen tension (PaO2) and transfer capacity of the lungs for carbon monoxide (DLCO). On the other hand, the arterial carbon dioxide tension (PaCO2) remains constant and the ventilation is still able to meet the CO2 elimination demand at rest. A good understanding of these changes is an essential tool to recognize and diagnose the manifestations of lung disease in geriatric patients [2].

The most frequent risk factors leading to respiratory impairment in elders are environmental exposures, including tobacco smoke, respiratory infections, air pollution, and occupational dusts. The respiratory system is particularly vulnerable because of its large surface area (85 m² compared to 1.8 m² of the skin and the 300 m² of the gut) [3]. A history of non-smoking does not exclude prior smoking exposure because of the environmental tobacco smoke [4]. Respiratory infections are also highly prevalent in older population.

2.2 Structural and Functional Changes with Age

The entire respiratory system, including thoracic cage, lungs, and respiratory muscles, undergoes structural and functional changes with aging. As a result, the total respiratory system compliance is significantly affected. Chest wall compliance is reduced by osteoporosis changes with shortening of the thoracic vertebrae, age-related kyphosis, and calcification of the rib cage. The increased stiffness of the chest wall reduces the elastic load during inspiration and the ability to expand properly during inspiration [5]. On the other hand, with aging the lungs, that are primarily responsible for the rate and the force of the expiration, become more distensible, but the elastic recoil is significantly reduced contributing to air trapping. The reduced elastic recoil of the lungs is balanced by an increased elastic load from the chest wall, with additional burden on the diaphragm and the respiratory muscles because of the stiffness of the chest wall. In elders, the total lung capacity (TLC) does not change significantly with aging, but the residual volume (RV) is increased and the vital capacity (VC) is significantly reduced. Nevertheless, elders appear to breathe at higher lung volumes than younger subjects showing an increased functional residual capacity (FRC). This increase is estimated at 20% at rest. Furthermore, elders show an increase of the closing volume (CV), the volume at which the small airways start closing during expiration [6].

The increase in the air trapping and the hyperinflation contribute to the senile emphysema. The periphery of the lungs changes with age showing and increase in the diameters of the small airways (<2 mm), respiratory bronchioles and alveolar ducts, due to the degeneration of the elastic fibers of the wall. These changes are homogenous within the lungs and not accompanied by any sign of inflammation as opposed to the heterogeneity and the evidence of inflammation in the emphysema. The loss of supporting tissue causes the premature closure of the small airways and the increase of the closing volume and the air trapping. The total content of elastin and collagen in the lungs does not show any change. Nevertheless, the lungs appear stiffer and the elastic recoil is reduced due to the increase of the intermolecular crosslinks. The alveolar wall remains intact, but the alveoli become smaller determining an effective decline in the total alveolar surface, which starts in the adult life and reaches a reduction of 15% at the age of 70 years, and 25% at the age of 90 years [6, 7].

2.3 Gas Exchange in Elders

The alveolar capillary membrane is essential for the gas exchange. The diffusion through the membrane is directly proportional to the alveolar surface and inversely proportional to the thickness of the membrane itself. The effectiveness of the gas exchange depends also on the matching of ventilation and perfusion in the lungs. Consequently, the presence of low V/Q lung zones in elders is probably one of the most important mechanisms of the decline in PaO2 and the increase in PA-a O2 in the elders. Furthermore, the heterogeneity in the distribution of the V/Q zones with inequality between different areas can play a crucial role in the worsening of the gas exchange. The V/Q inequality is associated with the increasing stiffness of the pulmonary vasculature and the development of pulmonary hypertension. Due to the presence of high V/Q zones that determines an increase in the dead space ventilation, elders need to increase their total minute ventilation in order to maintain the CO2 levels within normal range. Other factors affecting the gas exchange are the reduction of the alveolar surface area, the density of lung capillaries and the capillary blood volume. All these factors contribute to the decrease in the capacity of O2 and CO2 to diffuse through the membrane (Fig. 2.1). In particular, the changes in this capacity can be evaluated by the measurement of the diffusion capacity of the lung for carbon monoxide (DLCO), which is a measure of the transfer ability of oxygen across the alveolar capillary membrane [8].

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Fig. 2.1

Mechanisms of deterioration of the gas exchange in elders

The progressive decline in the total surface of the alveolar area, the pulmonary capillary volume, the density of pulmonary capillary, and the progressive increase of the closing volume (CV) during expiration determine heterogeneity of the ventilation/perfusion ratio (V/Q) within the lungs and reduction of the diffusion capacity of the lung for carbon monoxide (DLCO), with subsequent decline in the PaO2 and increase of the arterial-alveolar oxygen gradient (A-a DO2). The PaCO2 remains stable due to the increase of the ventilation for the higher dead space and the altered neural sensitivity to elevated PaCO2.

In elder subjects, there is a progressive reduction in PaO2 from 95 to 75 mmHg, due to the ventilation/perfusion ratio (V/Q) mismatch and the parenchymal structure changes, whereas the PaO2 is stable after the age of 70 [9]. In particular, the reduction in PaO2 is related to the increasing numbers of dependent parts of the lungs with poor ventilation as reflected by the evidence of an increased closing volume with age. Subsequently, this reduction causes an increase in the difference between the alveolar and the arterial oxygen pressures (A-a DO2). The reference values for PaO2 in elders are usually extrapolated by studies performed in adult populations including few, sometimes very few, elders [3, 9]. Sorbini et al. described the trend for decreasing PaO2 values in 152 adult subjects, but also showed that in a subgroup of 24 elders (>60 years) the mean PaO2 was lower than in the younger groups with a difference of 20 mmHg in the 2 extreme groups (74.3 ± 4.4 mmHg in elders and 94.2 + 3.31 in younger subjects (<30 years)) [3]. Sorbini et al. also proved a linear negative correlation between age and PaO2 (PaO2 = 109 − 0.43 ∗ age), which has not been demonstrated by other groups more recently [6, 7]. As a result, it is well known that the PaO2 declines with age, but this reduction is not linear, especially in elders. In clinical practice, there are several formulas to calculate the PaO2 for age, with discordant results [4]. On the other hand, the CO2 values remain quite stable over the years due to the increase of the ventilation for the higher dead space and the altered neural sensitivity to elevated PaCO2 [3].

2.4 Gas Exchange and Control of Breathing

Elders are extremely vulnerable to hypoxemia or hypercapnia, due to the loss of protective mechanisms and the decline in the neurologic control of the respiratory muscles. The ventilatory response to hypoxemia or hypercapnia appears profoundly impaired in elders. Kronenberg et al. showed a 50% reduction in response to hypoxemia and 40% reduction in response to hypercapnia compared to young adults. Similar results were reported later by Peterson et al. [5, 10, 11]. However, elders show higher response to CO2 during exercise compared to younger subjects. Furthermore, during exercise there is a decline of the oxygen consumption (VO2) in the adults, estimated as 9% per decade, more relevant in sedentary subjects, due to the decline in the cardiac output and the reduced peripheral muscle mass [6].

2.5 Gas Exchange in Palliative and End-of-Life Care Patients

The extension of life expectancy is nowadays a reality, but it comes with an increase in frailty and multi-morbidities. Frail patients are significantly vulnerable when exposed to stress because of a profound depletion of the physiological reserve and the co-existence of several clinically manifest comorbidities [12].

Various studies showed an increase in chronic respiratory diseases in elderly, including asthma and COPD. Gas exchange is profoundly altered in patients with chronic respiratory disease characterized by parenchymal and vascular changes and in patients with severe comorbidities. Physiological mechanisms determining increase of the arterial-alveolar CO2 difference will increase the dead space and the extent of the V/Q heterogeneity. In these conditions, any stimulus leading to increased V/Q, such as hyperventilation due to exercise, will increase the dead space as well [13]. The presence of additional comorbidities, a more pronounced lung function and immunological decline result in a higher predisposition to respiratory infections. Patients with chronic heart failure show altered lung diffusion capacity and impaired lung mechanics determining abnormal spirometry with increase of the alveolar Vd/Vt (dead-space-to-tidal-volume ratio) [14].

It is still controversial if the use of supplemental oxygen to relieve dyspnea in palliative care is useful or if it is better to use palliative sedation, which on the other hand can affect the respiratory drive. Conscious patient with severe hypoxemia clearly benefit for oxygen treatment. High-flow cannula can provide a high oxygen concentration, heated and humidified, and, when compared to cold, dry gas, may have a mild bronchodilator effect. In addition, the high flow provides a certain amount of continuous positive airway pressure increasing the alveolar ventilation and decreasing the physiological dead space and the work of breathing [15, 16].

2.6 Conclusions

Aging is associated with several changes of the respiratory system, including increased stiffness of the chest wall and lung parenchyma, alterations of the lung volumes with senile emphysema, and tendency towards an impaired gas exchange. The decline of the alveolar surface area, the density of the pulmonary capillaries, and the pulmonary capillary volume, with the increase of the closing volume during normal expiration, leads to V/Q heterogeneity and impaired DLCO with lower PaO2 and increased PA-a O2.

These alterations of the gas exchange are not clinically relevant at rest, but it becomes significant during exercise or in the presence of pathological conditions when the supply is not enough identifying elders as more fragile compared to younger subjects.

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Part IIVentilatory Management Epidemiology and Trends Management

© Springer Nature Switzerland AG 2020

A. M. Esquinas, N. Vargas (eds.)Ventilatory Support and Oxygen Therapy in Elder, Palliative and End-of-Life Care Patients https://doi.org/10.1007/978-3-030-26664-6_3

3. Acute and Acute-on-Chronic Respiratory Failure: Impact of Chronic Lung Comorbidities

Filippo Luca Fimognari¹  

(1)

Division of Acute Geriatrics, Annunziata-Mariano Santo-S. Barbara Hospital, Cosenza, Italy

Filippo Luca Fimognari

Abbreviations

ACRF

Acute-on-chronic acute respiratory failure

ARDS

Acute respiratory distress syndrome

ARF

Acute respiratory failure

CO2

Carbon dioxide

COPD

Chronic obstructive pulmonary disease

COT

Conventional oxygen therapy

CT

Computed tomography

FEV1

Forced expiratory volume in the first second

FiO2

Fraction of inspired oxygen

FVC

Forced vital capacity

HFNC

High-flow nasal cannula

IPF

Idiopathic pulmonary fibrosis

NIV

Non-invasive ventilation

RLD

Restrictive lung disease

V/Q

Ventilation/perfusion

3.1 Introduction

The prevalence and incidence of acute respiratory failure (ARF) and acute-on-chronic respiratory failure (ACRF) is rapidly increasing worldwide, due to the progressive aging of populations [1, 2]. Acute respiratory compromise, intended as an abrupt deterioration in respiratory function with a high risk of progression to respiratory failure requiring mechanical ventilation, occurs more commonly in patients with baseline chronic cardio-respiratory disorders [3]. Older age independently predicts the onset of acute respiratory compromise in hospitalized patients [4]. The development of ARF (or ACRF) poses a risk of in-hospital mortality of about 40%, much higher than for cancer, renal failure, stroke, or congestive heart failure without ARF or ACRF [5]. When respiratory failure occurs in a complex scenario of chronic comorbidities, which is the rule in older patients, the hospital management may be highly challenging. In this chapter, we focus on the diagnostic and therapeutic issues that need to be addressed by clinicians when managing ARF older patients with pre-existing chronic lung comorbidities.

3.2 Acute or Acute-on-Chronic Respiratory Failure: Diagnostic Challenges in Patients with Chronic Lung Comorbidities

In the diagnostic approach to older patients with ARF or ACRF, the clinicians should attempt identifying the possible acute mechanism(s) of de novo or worsening hypoxemia (with or without hypercapnia), often represented by exacerbations of underlying chronic illnesses (mainly cardio-respiratory). The incidence of respiratory failure increases with age [5, 6], but only