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Applied respiratory physiology
PHYSIOLOGY
Applied respiratory physiology
Learning objectives After reading this article, you should be able to: C describe how anaesthesia affects the mechanics of breathing and the implications on compliance, work of breathing and ventilationeperfusion matching C recall the effects of positioning, obesity, abdominal surgery and smoking on such a patient’s respiratory system C describe the respiratory responses to exercise and applications in clinical practice
Derek Randles Stuart Dabner
Abstract Anaesthesia has many effects on respiratory physiology, the knowledge of which is relevant to clinical practice. Anaesthesia causes decreased muscle tone in the upper airway, which can lead to airway obstruction. Pulmonary hypoventilation occurs in the spontaneously breathing patient. There is a progressive decrease in the ventilatory response to CO2 with increasing concentration of volatile agents, and even low doses of volatile have a profound effect on the ventilatory response to hypoxia. Functional residual capacity (FRC) is significantly reduced in the anaesthetized patient. Airway closure occurs when closing capacity exceeds FRC, with a reduced FRC this is more likely to happen especially in older patients or patients with coexisting lung pathology when closing capacity may be increased. The resulting atelectasis will affect oxygenation. Respiratory system compliance reduces very early during anaesthesia and there is little difference between the paralysed and spontaneously breathing patient. Alveolar dead space is decreased due to impairment of V/Q matching. During anaesthesia, venous admixture accounts for 10% of cardiac output due to increased shunt and changes in V/Q scatter. During anaesthesia and surgery patient position, type of surgery, smoking and obesity all have specific effects on respiratory physiology. Exercise physiology parameters such as anaerobic threshold have a role as a measure of cardiorespiratory fitness such as in cardiopulmonary exercise testing (CPX). CPX is increasingly used in risk stratification in patients undergoing major surgery. Anaerobic threshold is the point at which oxygen delivery mechanisms can no longer match the oxygen demand required in exercise.
Anaesthesia Anaesthesia has diverse effects on respiratory physiology. The knowledge of such effects is important in the safe and effective conduct of anaesthesia. Effects on respiratory muscles On induction of anaesthesia the nasopharynx is occluded by the soft palate falling against the posterior pharyngeal wall.1 Pharyngeal dilator muscle tone is also reduced resulting in posterior movement of the tongue and epiglottis on inspiration. Together this leads to obstruction of the airway unless airway adjuncts or manoeuvres are used. Although diaphragmatic muscular function is relatively unaffected during anaesthesia in a spontaneously breathing patient, both inspiratory intercostal and scalene muscle activity are often markedly reduced. This may result in a paradoxical pattern of ventilation with the drawing in of the ribcage and expansion of the abdomen on inspiration. This occurs especially in children, in whom chest wall compliance is increased, or in adults with respiratory pathology. Control of breathing General anaesthesia often results in pulmonary hypoventilation and hypercapnia in the spontaneously breathing patient owing to its effects on chemoreceptor reflexes. There is a progressive decrease in the ventilatory response to CO2 with increasing end-expiratory volatile concentration of a number of agents (Figure 1).2 However, not all agents are equal in this respect; for example, ether and ketamine have a much lesser respiratory depressant effect. This quality makes these agents particularly useful in field anaesthesia, or in the developing world, where effective monitoring is often unavailable. The situation with low doses of anaesthetic agents is complex. Although there have been a number of conflicting reports in the literature, a recent systematic review3 concluded that low doses of anaesthetic agents (0.2 minimum alveolar concentration, MAC) had much more profound effects on the respiratory response to hypoxia than on that to hypercapnia. Furthermore, the depression of hypoxic ventilatory drive was dependent on the anaesthetic agent chosen so that, on average, halothane depressed acute hypoxic ventilatory response the most, followed by enflurane, then isoflurane, then sevoflurane.4 Many patients will fail to mount an adequate response to hypoxia, especially in relative isolation from hypercapnia. The effect is compounded in the chronic respiratory patient with already impaired hypercapnic drive, and will persist postoperatively.5
Keywords Anaesthesia; applied respiratory physiology; exercise; obesity; smoking; surgery Royal College of Anaesthetists CPD Matrix: 1A01
There are many areas of applied respiratory physiology which raise both fascinating and relevant issues. This article addresses the effects of anaesthesia, noting specific circumstances such as the smoker and types of surgery, and also explores the effects of exercise.
Derek Randles MB BS FRCA is a Consultant in Anaesthesia and Intensive Care, University Hospital of North Durham, Durham, UK. Conflicts of interest: none declared. Stuart Dabner MB BS FRCA is a Consultant Anaesthetist, University Hospital of North Durham, Durham, UK. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE --:-
1
Ó 2017 Published by Elsevier Ltd.
Please cite this article in press as: Randles D, Dabner S, Applied respiratory physiology, Anaesthesia and intensive care medicine (2017), https:// doi.org/10.1016/j.mpaic.2017.11.007
PHYSIOLOGY
dependent areas occurs in up to 90% of patients during general anaesthesia and may persist postoperatively. This is particularly the case in patients with poor lung function and sputum retention, and when chest movement is reduced, for example as a result of pain after upper abdominal surgery.7
Minute ventilatory volume (litres/minute)
PCO2/ventilatory response relationship with different end-expiratory concentrations of halothane 35
Halothane (end-expiratory)
Prevention of atelectasis8 High inspired oxygen concentrations promote atelectasis, most notably during induction and emergence when inhalation of 100% oxygen is routine. If 60% oxygen is used, collapse of alveoli is reduced significantly.9 The absorption of oxygen is rapid owing to alveolarearterial (Aea) O2 pressure gradients of 80 kPa (600 mmHg) resulting in alveolar collapse in a matter of minutes. Nitrogen is less soluble, with a tension slightly below that of mixed venous blood, resulting in slow absorption and collapse over a course of hours. As such preoxygenation and emergence could in theory be considered with an Fio2 of 0.8 or even 0.6 rather than 1.0, to markedly reduce atelectasis, and not significantly increase the risk of hypoxia during periods of apnoea. However, it must be stressed that this is not currently a widely accepted practice, although it could potentially improve oxygenation well into the recovery period. Positive airway pressures during induction and maintenance of anaesthesia reduce the occurrence of atelectasis and the rapidity of desaturation during apnoeic episodes.10 High levels of positive end-expiratory pressure (PEEP) are required to expand pre-existing atelectasis, and may cause further ventilation/ perfusion (V/Q) mismatch and cardiovascular disturbance at high inflation pressures. These manoeuvres are generally more effective in obese patients.
30
Awake 25
20
15
0.81% 10
5
1.5%
0 4
6
8
10
End-expiratory P CO (kPa) The points on each line represent equilibration for a given depth of anaesthesia. Movement along this line represents ventilatory response with the addition or removal of carbon dioxide.
Figure 1
Functional residual capacity Functional residual capacity (FRC) is the lung volume at the end of normal expiration. It is significantly reduced in the anaesthetized patient, and, depending on factors such as position (e.g. head down), obesity, late pregnancy, and restrictive lung pathology, can be reduced by up to 50%. This happens on induction and very early in anaesthesia,6 and continues well into the postoperative period, whether or not the patient has been paralysed. This reduction in FRC is due to both a change in chest wall shape secondary to impairment of respiratory muscle activity and reduction of normal end-expiratory diaphragmatic muscle tone with loss of forces which oppose the elastic recoil of lung tissue and cephalad movement of abdominal viscera into dependent regions when supine.7 This results in a decreased alveolar volume, decreased ventilationeperfusion ratios and makes airway closure and alveolar collapse more likely.
Respiratory mechanics Airways resistance increases exponentially with a reduction in lung volume. Although there is an increase as the patient lies supine, much of the further increase expected with general anaesthesia is offset by bronchodilatational effects of inhalational anaesthetic agents. They cause suppression of airway vagal reflexes, directly relax airway smooth muscle and inhibit release of bronchoconstrictor mediators. Total respiratory system compliance is reduced very early during anaesthesia11 (Figure 2). This is illustrative of the change in position on the compliance curve reflecting a reduction in FRC. Smaller alveoli require greater forces of expansion despite a relatively thicker layer of surfactant. A major contribution is also due to the pulmonary atelectasis described above. Relative hypoventilation during anaesthesia without periodic large breaths corresponding to sighs may exacerbate poor compliance. Many patients take high-volume breaths on emergence, possibly reducing the insult in the recovery period. There is very little difference between anaesthesia with or without paralysis because the major changes are in lung rather than chest wall compliance.11
Airway closure and atelectasis Airway closure affects oxygenation when closing capacity exceeds FRC and small airways close during normal tidal ventilation, trapping gas in distal airways. This is particularly apparent in older patients or in those with diffuse lung pathology who have an increased closing capacity through loss of supporting elastic tissue. Airway closure occurs in these patients when they are awake and supine. It is exaggerated by general anaesthesia. Even without complete obstruction, airway narrowing creates areas with low ventilationeperfusion ratios and impaired gas exchange. The bronchodilating effects of anaesthesia attenuate this to some degree. Gas trapped distal to obstruction in an airway is rapidly absorbed. The resulting atelectasis in these
ANAESTHESIA AND INTENSIVE CARE MEDICINE --:-
Gas exchange Alveolar dead space is increased during anaesthesia owing to impairment of V/Q matching. Apparatus dead space is important. When including connections, dead space can be 50% of tidal volume e more in face mask anaesthesia, forcing hypercarbia or increased work of breathing. Some compensation occurs in reduced anatomical dead space at lower tidal volumes as
2
Ó 2017 Published by Elsevier Ltd.
Please cite this article in press as: Randles D, Dabner S, Applied respiratory physiology, Anaesthesia and intensive care medicine (2017), https:// doi.org/10.1016/j.mpaic.2017.11.007
PHYSIOLOGY
in both spontaneously breathing and paralysed patients is distributed to the upper lung, and perfusion to the lower lung. Atelectasis and shunt magnitude are similar. The prone patient is different. FRC is increased. There may also be more uniform distribution of blood flow and less atelectasis formation in the dependent areas, which are reduced in volume by the mediastinum. The lithotomy position has little further effect on respiratory physiology.
Compliance curves and the effects of anaesthesia Lung volume (% of conscious total lung capacity)
100
80
60
Laparoscopic surgery Inflation of the abdomen reduces compliance and increases airway resistance, particularly in obese patients. This means that very high lung inflation pressures are required, often despite permissive hypercapnia. The head-down position will exacerbate such changes. Furthermore, an increase in ventilation of 20 e25% is required to eliminate the CO2 absorbed from the inflated abdomen. Normocapnia may be more difficult to achieve in patients with lung pathology, and sustained hypercapnia will result in an increase in the body’s CO2 stores. Consequently, hypercapnia may be present for some hours into the recovery period, which has implications for patients’ ventilatory requirements.
40
Conscious (supine) Anaesthetized Anaesthetized and paralysed
20
0 +10 FRC
+20
+30
Pressure gradient (cmH2O)
Total compliance curves (lungs and chest wall) before and following the induction of anaesthesia, with and without paralysis. Note the major difference in functional residual capacity (FRC) and slope following induction, and also the insignificant differences made by paralysis
Open abdominal surgery has major consequences in the postoperative period as pain, muscle spasm and diaphragmatic splinting cause a reduction in FRC with resultant shunting possibly taking weeks to resolve.
Figure 2
Smoking Smokers have impaired ciliary activity and increased sputum production and retention. Airways are narrower, and airway closure is more likely with impaired V/Q matching. Smokers have more sensitive airway reflexes, especially to irritant inhalational anaesthetic agents. Coughing, bronchospasm and laryngospasm are more likely.
a result of axial streaming and the mixing effect of the heart beat. The anaesthetized patient also has a reduced metabolic rate. Expected VO2 will be reduced by 15e20% to approximately 175 e200 ml/minute in the normothermic patient.12 Shunt Venous admixture accounts for only 1e2% of cardiac output in the conscious, healthy individual. During anaesthesia, this increases to around 10%. To compensate for this an FiO2 of 0.3e0.4 is usually required. The extent of atelectasis (see above) correlates to shunt magnitude7 and is responsible for around 50% of venous admixture. The other 50% is due to V/Q scatter. Ventilation is preferentially distributed to the ventral areas, and there is a more marked distribution of perfusion towards dependent areas. This distribution is exacerbated by the attenuation of hypoxic pulmonary vasoconstriction by inhalational anaesthetic agents, and by high inspired oxygen concentrations, which may also increase V/Q dispersion. Paralysis makes little difference in parameters of gas exchange. The increase in venous admixture is more marked in the elderly, who also have a widened distribution when awake. Higher closing capacity in the elderly, which often exceeds FRC, causes more airway collapse and increased shunt, explaning these exaggerated changes in venous admixture. PEEP may worsen oxygenation by reducing cardiac output and mixed venous oxygenation. Furthermore, preferential ventilation of those alveoli with already high V/Q ratios may exacerbate this issue. This contrasts with the situation of stiff, often oedematous lungs encountered in the critical care environment.
Obesity Given the increased oxygen demand and carbon dioxide production, obese patients require an increased minute ventilation. Their FRC is reduced, as is thoracic compliance, increasing the work of breathing further and increasing atelectasis and V/Q mismatch. This results in an increased likelihood of hypoxaemia and increasing fractional oxygen requirement. Spontaneous ventilation is often inadequate, and intermittent positive pressure ventilation (IPPV) requires high inflation pressures. Pre-existing alveolar hypoventilation syndrome may lead to pulmonary hypertension and right ventricular dysfunction, which have specific anaesthetic considerations. Postoperatively, atelectasis and hypoventilation are common, with resultant hypoxaemia, respiratory failure and risk of infection.
Exercise Oxygen consumption Oxygen consumption is closely related to external power produced during exercise. At rest, oxygen consumption is approximately 200e250 ml/minute, or 3.5 ml/kg/minute. This is defined as 1 metabolic equivalent (MET). This increases with graded exercise, such that during a brisk walk consumption will increase to 1000 ml/minute, or 4 METs.
Patient position Relative to the physiology in the supine position, described above, the lateral position increases V/Q scattering. Ventilation
ANAESTHESIA AND INTENSIVE CARE MEDICINE --:-
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PHYSIOLOGY
With increasing exercise intensity, oxygen delivery mechanisms can eventually no longer account for the entire increase in oxygen demand. Beyond this, energy requirements are met by anaerobic metabolism. This point is referred to as the anaerobic threshold (Figure 3). Many factors dictate this threshold, including the degree of training, changing environment, such as altitude, and the muscle fibre types utilized. With severe exercise lactate continues to rise, and is the limiting factor in a further increase in intensity. An oxygen debt ensues, and continues into the recovery phase when oxygen consumption remains high as lactate is oxidized and the oxygen debt is ‘paid off’. Metabolic rate (and oxygen consumption) remains elevated long after the oxygen debt has been resolved and is probably related to increased metabolic processes, notably fatty acid metabolism, and increased circulating catabolic hormones.
Oxygen delivery In response to exercise, cardiac output increases, mainly by stroke volume in mild-to-moderate exertion; with increased exertion, cardiac output increases by a chronotropic response. Oxygen extraction also increases at the capillary level. At rest oxygen saturations are approximately 70%, dropping to around 25% with severe exertion. This is achieved without tissue hypoxia owing to the fall occurring on the steep part of the oxyhaemoglobin dissociation curve. An increase in lactate augments this by a right shift in the curve. This additional oxygen consumption and desaturated blood makes demands on the respiratory system, which exhibits an instant response by increasing minute volume. This may actually occur before demand increases. A further graduated increase occurs with moderate exercise. It then plateaus. In severe exertion this may continue to rise in response to rising lactate levels. Respiratory reserves are significantly greater than cardiovascular reserves in the healthy population. Maximum breathing capacity (MBC) is approximately 200 litres/minute. In severe exercise, cardiac output reaches 25 litres/minute, while VMV is 120 litres/ minute or 60% of MBC. This represents a 20-fold compared with a fivefold rise in output. Minute volume and oxygen consumption, the ventilatory equivalent for oxygen (VE/Vo2), are well matched, with a ratio of approximately 30:1 (see Figure 3). However, during heavy exercise the slope increases. This is driven by lactate, and this break is higher in trained athletes, corresponding to a higher anaerobic threshold. The control of ventilation in response to exercise is not entirely clear. Chemoreceptors become more responsive to hypoxia; however, blood gases exhibit little change, certainly up to an exercise intensity of around 12 METs, and so it is likely that they make little contribution. There is undoubtedly an anticipatory behavioural response, given that minute volume increases in many cases prior to exertion. Afferents from muscles and joint proprioception may also have an important role, and, finally, during severe exertion, lactate and possibly hyperthermia make a significant contribution.
Vo2max Vo2max is the maximal oxygen consumption when exercising at the highest possible intensity. In a fit 70-kg adult this corresponds to around 3 litres/minute; however, a sedentary existence may halve this. Training will often increase Vo2max to 5 litres/ minute. Elite athletes such as rowers record a Vo2max of up to 6.5 litres/minute, which may require a ventilatory minute volume (VMV) of up to 200 litres/minute; 80% of such consumption is used by locomotor muscles and approximately 10% by respiratory muscles (in contrast to the 1e2% of basal oxygen consumption by the respiratory muscles at rest). Anaerobic threshold and Vo2max are used in exercise physiology as a measure of cardiorespiratory fitness, so-called cardiopulmonary exercise testing (CPX). Important areas include risk stratification of patients undergoing major surgery13,14 and prognostication in patients with heart failure.15
Cardiopulmonary exercise in a 40-year-old athlete 6000
Diffusion capacity across the lung does not usually limit increasing oxygen consumption. In the healthy lung, gas exchange is completed long before red cell corpuscles exit the pulmonary capillaries. During exercise, unperfused capillaries open (recruitment) and perfused capillaries expand (distension). As a result blood flow through the lung becomes more uniform and diffusion capacity increases markedly. V/Q mismatch decreases, and as a result alveolar oxygen tension (Pao2) is unaffected by severe exertion. During activity at high altitude the situation changes when the concentration gradient across the alveolar capillary membrane decreases, as does transit time. As a result, equilibration may not occur during capillary transit. A
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REFERENCES 1 Nandi PR, Charlesworth CH, Taylor SJ, et al. Effect of general anaesthesia on the pharynx. Br J Anaesth 1991; 66: 157e62. 2 Munson ES, Larson CP, Babad AA, et al. The effects of halothane, fluroxene and cyclopropane on ventilation: a comparative study in man. Anesthesiol 1966; 27: 716e28.
The vertical line represents the anaerobic threshold, at which point we see both the VCO / VO and / VO slopes sharply increase secondary to an increase in anaerobic metabolism and lactate concentration respectively. is implied from the top of the curve VO
Figure 3
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PHYSIOLOGY
3 Pandit JJ. Effect of low dose inhaled anaesthetic agents on the ventilatory response to carbon dioxide in humans, a quantitative review. Anaesthesia 2005; 60: 461e9. 4 Pandit JJ. The variable effect of low-dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans, a quantitative review. Anaesthesia 2002; 57: 632e43. 5 Kirkman E. Respiration: control of ventilation. Anaesthesia & Intensive Care Medicine 2008; 10: 437e40. 6 Rutherford JS, Logan MR, Drummond GB. Changes in endexpiratory lung volume on induction of anaesthesia with thiopentone or propofol. Br J Anaesth 1994; 73: 579e82. 7 Warner DO, Warner MA, Ritman EL. Atelectasis and chest wall shape during halothane anaesthesia. Anesthesiol 1970; 36: 533e9. 8 Magnussen L, Spahn DR. New concepts of atelectasis during general anaesthesia. Br J Anaesth 2003; 91: 61e72. 9 Edmark L, Kostova-Aherdan K, Enlund M, Hedenstierna G. Optimal oxygen concentration during induction of general anaesthesia. Anesthesiol 2003; 98: 28e33.
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10 Rusca M, Proietti S, Schnyder P, et al. Prevention of atelectasis formation during induction of anaesthesia. Anaesth Analg 2003; 97: 1835e9. 11 Westbrook PR, Stubbs SE, Sessler AD, et al. Effects of anaesthesia and muscle paralysis on respiratory mechanics in normal man. J Appl Phys 1973; 34: 81e6. 12 Nunn JF, Matthews RL. Gaseous exchange during halothane anaesthesia: the steady respiratory state. Br J Anaesth 1959; 31: 330e40. 13 Older P, Hall A. Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly. Chest 1999; 116: 355e62. 14 Snowden CP, Prentis J, Anderson H, et al. Submaximal cardiopulmonary exercise testing predicts complications and hospital length of stay in patients undergoing major elective surgery. Ann Surg 2010; 251: 541e7. 15 Ingle L. Prognostic value and diagnostic potential of cardiopulmonary exercise testing in patients with chronic heart failure. Eur J Heart Fail 2008; 10: 112e8.
5
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Please cite this article in press as: Randles D, Dabner S, Applied respiratory physiology, Anaesthesia and intensive care medicine (2017), https:// doi.org/10.1016/j.mpaic.2017.11.007
Applied respiratory physiology
Learning objectives After reading this article, you should be able to: C describe how anaesthesia affects the mechanics of breathing and the implications on compliance, work of breathing and ventilationeperfusion matching C recall the effects of positioning, obesity, abdominal surgery and smoking on such a patient’s respiratory system C describe the respiratory responses to exercise and applications in clinical practice
Derek Randles Stuart Dabner
Abstract Anaesthesia has many effects on respiratory physiology, the knowledge of which is relevant to clinical practice. Anaesthesia causes decreased muscle tone in the upper airway, which can lead to airway obstruction. Pulmonary hypoventilation occurs in the spontaneously breathing patient. There is a progressive decrease in the ventilatory response to CO2 with increasing concentration of volatile agents, and even low doses of volatile have a profound effect on the ventilatory response to hypoxia. Functional residual capacity (FRC) is significantly reduced in the anaesthetized patient. Airway closure occurs when closing capacity exceeds FRC, with a reduced FRC this is more likely to happen especially in older patients or patients with coexisting lung pathology when closing capacity may be increased. The resulting atelectasis will affect oxygenation. Respiratory system compliance reduces very early during anaesthesia and there is little difference between the paralysed and spontaneously breathing patient. Alveolar dead space is decreased due to impairment of V/Q matching. During anaesthesia, venous admixture accounts for 10% of cardiac output due to increased shunt and changes in V/Q scatter. During anaesthesia and surgery patient position, type of surgery, smoking and obesity all have specific effects on respiratory physiology. Exercise physiology parameters such as anaerobic threshold have a role as a measure of cardiorespiratory fitness such as in cardiopulmonary exercise testing (CPX). CPX is increasingly used in risk stratification in patients undergoing major surgery. Anaerobic threshold is the point at which oxygen delivery mechanisms can no longer match the oxygen demand required in exercise.
Anaesthesia Anaesthesia has diverse effects on respiratory physiology. The knowledge of such effects is important in the safe and effective conduct of anaesthesia. Effects on respiratory muscles On induction of anaesthesia the nasopharynx is occluded by the soft palate falling against the posterior pharyngeal wall.1 Pharyngeal dilator muscle tone is also reduced resulting in posterior movement of the tongue and epiglottis on inspiration. Together this leads to obstruction of the airway unless airway adjuncts or manoeuvres are used. Although diaphragmatic muscular function is relatively unaffected during anaesthesia in a spontaneously breathing patient, both inspiratory intercostal and scalene muscle activity are often markedly reduced. This may result in a paradoxical pattern of ventilation with the drawing in of the ribcage and expansion of the abdomen on inspiration. This occurs especially in children, in whom chest wall compliance is increased, or in adults with respiratory pathology. Control of breathing General anaesthesia often results in pulmonary hypoventilation and hypercapnia in the spontaneously breathing patient owing to its effects on chemoreceptor reflexes. There is a progressive decrease in the ventilatory response to CO2 with increasing end-expiratory volatile concentration of a number of agents (Figure 1).2 However, not all agents are equal in this respect; for example, ether and ketamine have a much lesser respiratory depressant effect. This quality makes these agents particularly useful in field anaesthesia, or in the developing world, where effective monitoring is often unavailable. The situation with low doses of anaesthetic agents is complex. Although there have been a number of conflicting reports in the literature, a recent systematic review3 concluded that low doses of anaesthetic agents (0.2 minimum alveolar concentration, MAC) had much more profound effects on the respiratory response to hypoxia than on that to hypercapnia. Furthermore, the depression of hypoxic ventilatory drive was dependent on the anaesthetic agent chosen so that, on average, halothane depressed acute hypoxic ventilatory response the most, followed by enflurane, then isoflurane, then sevoflurane.4 Many patients will fail to mount an adequate response to hypoxia, especially in relative isolation from hypercapnia. The effect is compounded in the chronic respiratory patient with already impaired hypercapnic drive, and will persist postoperatively.5
Keywords Anaesthesia; applied respiratory physiology; exercise; obesity; smoking; surgery Royal College of Anaesthetists CPD Matrix: 1A01
There are many areas of applied respiratory physiology which raise both fascinating and relevant issues. This article addresses the effects of anaesthesia, noting specific circumstances such as the smoker and types of surgery, and also explores the effects of exercise.
Derek Randles MB BS FRCA is a Consultant in Anaesthesia and Intensive Care, University Hospital of North Durham, Durham, UK. Conflicts of interest: none declared. Stuart Dabner MB BS FRCA is a Consultant Anaesthetist, University Hospital of North Durham, Durham, UK. Conflicts of interest: none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE --:-
1
Ó 2017 Published by Elsevier Ltd.
Please cite this article in press as: Randles D, Dabner S, Applied respiratory physiology, Anaesthesia and intensive care medicine (2017), https:// doi.org/10.1016/j.mpaic.2017.11.007
PHYSIOLOGY
dependent areas occurs in up to 90% of patients during general anaesthesia and may persist postoperatively. This is particularly the case in patients with poor lung function and sputum retention, and when chest movement is reduced, for example as a result of pain after upper abdominal surgery.7
Minute ventilatory volume (litres/minute)
PCO2/ventilatory response relationship with different end-expiratory concentrations of halothane 35
Halothane (end-expiratory)
Prevention of atelectasis8 High inspired oxygen concentrations promote atelectasis, most notably during induction and emergence when inhalation of 100% oxygen is routine. If 60% oxygen is used, collapse of alveoli is reduced significantly.9 The absorption of oxygen is rapid owing to alveolarearterial (Aea) O2 pressure gradients of 80 kPa (600 mmHg) resulting in alveolar collapse in a matter of minutes. Nitrogen is less soluble, with a tension slightly below that of mixed venous blood, resulting in slow absorption and collapse over a course of hours. As such preoxygenation and emergence could in theory be considered with an Fio2 of 0.8 or even 0.6 rather than 1.0, to markedly reduce atelectasis, and not significantly increase the risk of hypoxia during periods of apnoea. However, it must be stressed that this is not currently a widely accepted practice, although it could potentially improve oxygenation well into the recovery period. Positive airway pressures during induction and maintenance of anaesthesia reduce the occurrence of atelectasis and the rapidity of desaturation during apnoeic episodes.10 High levels of positive end-expiratory pressure (PEEP) are required to expand pre-existing atelectasis, and may cause further ventilation/ perfusion (V/Q) mismatch and cardiovascular disturbance at high inflation pressures. These manoeuvres are generally more effective in obese patients.
30
Awake 25
20
15
0.81% 10
5
1.5%
0 4
6
8
10
End-expiratory P CO (kPa) The points on each line represent equilibration for a given depth of anaesthesia. Movement along this line represents ventilatory response with the addition or removal of carbon dioxide.
Figure 1
Functional residual capacity Functional residual capacity (FRC) is the lung volume at the end of normal expiration. It is significantly reduced in the anaesthetized patient, and, depending on factors such as position (e.g. head down), obesity, late pregnancy, and restrictive lung pathology, can be reduced by up to 50%. This happens on induction and very early in anaesthesia,6 and continues well into the postoperative period, whether or not the patient has been paralysed. This reduction in FRC is due to both a change in chest wall shape secondary to impairment of respiratory muscle activity and reduction of normal end-expiratory diaphragmatic muscle tone with loss of forces which oppose the elastic recoil of lung tissue and cephalad movement of abdominal viscera into dependent regions when supine.7 This results in a decreased alveolar volume, decreased ventilationeperfusion ratios and makes airway closure and alveolar collapse more likely.
Respiratory mechanics Airways resistance increases exponentially with a reduction in lung volume. Although there is an increase as the patient lies supine, much of the further increase expected with general anaesthesia is offset by bronchodilatational effects of inhalational anaesthetic agents. They cause suppression of airway vagal reflexes, directly relax airway smooth muscle and inhibit release of bronchoconstrictor mediators. Total respiratory system compliance is reduced very early during anaesthesia11 (Figure 2). This is illustrative of the change in position on the compliance curve reflecting a reduction in FRC. Smaller alveoli require greater forces of expansion despite a relatively thicker layer of surfactant. A major contribution is also due to the pulmonary atelectasis described above. Relative hypoventilation during anaesthesia without periodic large breaths corresponding to sighs may exacerbate poor compliance. Many patients take high-volume breaths on emergence, possibly reducing the insult in the recovery period. There is very little difference between anaesthesia with or without paralysis because the major changes are in lung rather than chest wall compliance.11
Airway closure and atelectasis Airway closure affects oxygenation when closing capacity exceeds FRC and small airways close during normal tidal ventilation, trapping gas in distal airways. This is particularly apparent in older patients or in those with diffuse lung pathology who have an increased closing capacity through loss of supporting elastic tissue. Airway closure occurs in these patients when they are awake and supine. It is exaggerated by general anaesthesia. Even without complete obstruction, airway narrowing creates areas with low ventilationeperfusion ratios and impaired gas exchange. The bronchodilating effects of anaesthesia attenuate this to some degree. Gas trapped distal to obstruction in an airway is rapidly absorbed. The resulting atelectasis in these
ANAESTHESIA AND INTENSIVE CARE MEDICINE --:-
Gas exchange Alveolar dead space is increased during anaesthesia owing to impairment of V/Q matching. Apparatus dead space is important. When including connections, dead space can be 50% of tidal volume e more in face mask anaesthesia, forcing hypercarbia or increased work of breathing. Some compensation occurs in reduced anatomical dead space at lower tidal volumes as
2
Ó 2017 Published by Elsevier Ltd.
Please cite this article in press as: Randles D, Dabner S, Applied respiratory physiology, Anaesthesia and intensive care medicine (2017), https:// doi.org/10.1016/j.mpaic.2017.11.007
PHYSIOLOGY
in both spontaneously breathing and paralysed patients is distributed to the upper lung, and perfusion to the lower lung. Atelectasis and shunt magnitude are similar. The prone patient is different. FRC is increased. There may also be more uniform distribution of blood flow and less atelectasis formation in the dependent areas, which are reduced in volume by the mediastinum. The lithotomy position has little further effect on respiratory physiology.
Compliance curves and the effects of anaesthesia Lung volume (% of conscious total lung capacity)
100
80
60
Laparoscopic surgery Inflation of the abdomen reduces compliance and increases airway resistance, particularly in obese patients. This means that very high lung inflation pressures are required, often despite permissive hypercapnia. The head-down position will exacerbate such changes. Furthermore, an increase in ventilation of 20 e25% is required to eliminate the CO2 absorbed from the inflated abdomen. Normocapnia may be more difficult to achieve in patients with lung pathology, and sustained hypercapnia will result in an increase in the body’s CO2 stores. Consequently, hypercapnia may be present for some hours into the recovery period, which has implications for patients’ ventilatory requirements.
40
Conscious (supine) Anaesthetized Anaesthetized and paralysed
20
0 +10 FRC
+20
+30
Pressure gradient (cmH2O)
Total compliance curves (lungs and chest wall) before and following the induction of anaesthesia, with and without paralysis. Note the major difference in functional residual capacity (FRC) and slope following induction, and also the insignificant differences made by paralysis
Open abdominal surgery has major consequences in the postoperative period as pain, muscle spasm and diaphragmatic splinting cause a reduction in FRC with resultant shunting possibly taking weeks to resolve.
Figure 2
Smoking Smokers have impaired ciliary activity and increased sputum production and retention. Airways are narrower, and airway closure is more likely with impaired V/Q matching. Smokers have more sensitive airway reflexes, especially to irritant inhalational anaesthetic agents. Coughing, bronchospasm and laryngospasm are more likely.
a result of axial streaming and the mixing effect of the heart beat. The anaesthetized patient also has a reduced metabolic rate. Expected VO2 will be reduced by 15e20% to approximately 175 e200 ml/minute in the normothermic patient.12 Shunt Venous admixture accounts for only 1e2% of cardiac output in the conscious, healthy individual. During anaesthesia, this increases to around 10%. To compensate for this an FiO2 of 0.3e0.4 is usually required. The extent of atelectasis (see above) correlates to shunt magnitude7 and is responsible for around 50% of venous admixture. The other 50% is due to V/Q scatter. Ventilation is preferentially distributed to the ventral areas, and there is a more marked distribution of perfusion towards dependent areas. This distribution is exacerbated by the attenuation of hypoxic pulmonary vasoconstriction by inhalational anaesthetic agents, and by high inspired oxygen concentrations, which may also increase V/Q dispersion. Paralysis makes little difference in parameters of gas exchange. The increase in venous admixture is more marked in the elderly, who also have a widened distribution when awake. Higher closing capacity in the elderly, which often exceeds FRC, causes more airway collapse and increased shunt, explaning these exaggerated changes in venous admixture. PEEP may worsen oxygenation by reducing cardiac output and mixed venous oxygenation. Furthermore, preferential ventilation of those alveoli with already high V/Q ratios may exacerbate this issue. This contrasts with the situation of stiff, often oedematous lungs encountered in the critical care environment.
Obesity Given the increased oxygen demand and carbon dioxide production, obese patients require an increased minute ventilation. Their FRC is reduced, as is thoracic compliance, increasing the work of breathing further and increasing atelectasis and V/Q mismatch. This results in an increased likelihood of hypoxaemia and increasing fractional oxygen requirement. Spontaneous ventilation is often inadequate, and intermittent positive pressure ventilation (IPPV) requires high inflation pressures. Pre-existing alveolar hypoventilation syndrome may lead to pulmonary hypertension and right ventricular dysfunction, which have specific anaesthetic considerations. Postoperatively, atelectasis and hypoventilation are common, with resultant hypoxaemia, respiratory failure and risk of infection.
Exercise Oxygen consumption Oxygen consumption is closely related to external power produced during exercise. At rest, oxygen consumption is approximately 200e250 ml/minute, or 3.5 ml/kg/minute. This is defined as 1 metabolic equivalent (MET). This increases with graded exercise, such that during a brisk walk consumption will increase to 1000 ml/minute, or 4 METs.
Patient position Relative to the physiology in the supine position, described above, the lateral position increases V/Q scattering. Ventilation
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PHYSIOLOGY
With increasing exercise intensity, oxygen delivery mechanisms can eventually no longer account for the entire increase in oxygen demand. Beyond this, energy requirements are met by anaerobic metabolism. This point is referred to as the anaerobic threshold (Figure 3). Many factors dictate this threshold, including the degree of training, changing environment, such as altitude, and the muscle fibre types utilized. With severe exercise lactate continues to rise, and is the limiting factor in a further increase in intensity. An oxygen debt ensues, and continues into the recovery phase when oxygen consumption remains high as lactate is oxidized and the oxygen debt is ‘paid off’. Metabolic rate (and oxygen consumption) remains elevated long after the oxygen debt has been resolved and is probably related to increased metabolic processes, notably fatty acid metabolism, and increased circulating catabolic hormones.
Oxygen delivery In response to exercise, cardiac output increases, mainly by stroke volume in mild-to-moderate exertion; with increased exertion, cardiac output increases by a chronotropic response. Oxygen extraction also increases at the capillary level. At rest oxygen saturations are approximately 70%, dropping to around 25% with severe exertion. This is achieved without tissue hypoxia owing to the fall occurring on the steep part of the oxyhaemoglobin dissociation curve. An increase in lactate augments this by a right shift in the curve. This additional oxygen consumption and desaturated blood makes demands on the respiratory system, which exhibits an instant response by increasing minute volume. This may actually occur before demand increases. A further graduated increase occurs with moderate exercise. It then plateaus. In severe exertion this may continue to rise in response to rising lactate levels. Respiratory reserves are significantly greater than cardiovascular reserves in the healthy population. Maximum breathing capacity (MBC) is approximately 200 litres/minute. In severe exercise, cardiac output reaches 25 litres/minute, while VMV is 120 litres/ minute or 60% of MBC. This represents a 20-fold compared with a fivefold rise in output. Minute volume and oxygen consumption, the ventilatory equivalent for oxygen (VE/Vo2), are well matched, with a ratio of approximately 30:1 (see Figure 3). However, during heavy exercise the slope increases. This is driven by lactate, and this break is higher in trained athletes, corresponding to a higher anaerobic threshold. The control of ventilation in response to exercise is not entirely clear. Chemoreceptors become more responsive to hypoxia; however, blood gases exhibit little change, certainly up to an exercise intensity of around 12 METs, and so it is likely that they make little contribution. There is undoubtedly an anticipatory behavioural response, given that minute volume increases in many cases prior to exertion. Afferents from muscles and joint proprioception may also have an important role, and, finally, during severe exertion, lactate and possibly hyperthermia make a significant contribution.
Vo2max Vo2max is the maximal oxygen consumption when exercising at the highest possible intensity. In a fit 70-kg adult this corresponds to around 3 litres/minute; however, a sedentary existence may halve this. Training will often increase Vo2max to 5 litres/ minute. Elite athletes such as rowers record a Vo2max of up to 6.5 litres/minute, which may require a ventilatory minute volume (VMV) of up to 200 litres/minute; 80% of such consumption is used by locomotor muscles and approximately 10% by respiratory muscles (in contrast to the 1e2% of basal oxygen consumption by the respiratory muscles at rest). Anaerobic threshold and Vo2max are used in exercise physiology as a measure of cardiorespiratory fitness, so-called cardiopulmonary exercise testing (CPX). Important areas include risk stratification of patients undergoing major surgery13,14 and prognostication in patients with heart failure.15
Cardiopulmonary exercise in a 40-year-old athlete 6000
Diffusion capacity across the lung does not usually limit increasing oxygen consumption. In the healthy lung, gas exchange is completed long before red cell corpuscles exit the pulmonary capillaries. During exercise, unperfused capillaries open (recruitment) and perfused capillaries expand (distension). As a result blood flow through the lung becomes more uniform and diffusion capacity increases markedly. V/Q mismatch decreases, and as a result alveolar oxygen tension (Pao2) is unaffected by severe exertion. During activity at high altitude the situation changes when the concentration gradient across the alveolar capillary membrane decreases, as does transit time. As a result, equilibration may not occur during capillary transit. A
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REFERENCES 1 Nandi PR, Charlesworth CH, Taylor SJ, et al. Effect of general anaesthesia on the pharynx. Br J Anaesth 1991; 66: 157e62. 2 Munson ES, Larson CP, Babad AA, et al. The effects of halothane, fluroxene and cyclopropane on ventilation: a comparative study in man. Anesthesiol 1966; 27: 716e28.
The vertical line represents the anaerobic threshold, at which point we see both the VCO / VO and / VO slopes sharply increase secondary to an increase in anaerobic metabolism and lactate concentration respectively. is implied from the top of the curve VO
Figure 3
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PHYSIOLOGY
3 Pandit JJ. Effect of low dose inhaled anaesthetic agents on the ventilatory response to carbon dioxide in humans, a quantitative review. Anaesthesia 2005; 60: 461e9. 4 Pandit JJ. The variable effect of low-dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans, a quantitative review. Anaesthesia 2002; 57: 632e43. 5 Kirkman E. Respiration: control of ventilation. Anaesthesia & Intensive Care Medicine 2008; 10: 437e40. 6 Rutherford JS, Logan MR, Drummond GB. Changes in endexpiratory lung volume on induction of anaesthesia with thiopentone or propofol. Br J Anaesth 1994; 73: 579e82. 7 Warner DO, Warner MA, Ritman EL. Atelectasis and chest wall shape during halothane anaesthesia. Anesthesiol 1970; 36: 533e9. 8 Magnussen L, Spahn DR. New concepts of atelectasis during general anaesthesia. Br J Anaesth 2003; 91: 61e72. 9 Edmark L, Kostova-Aherdan K, Enlund M, Hedenstierna G. Optimal oxygen concentration during induction of general anaesthesia. Anesthesiol 2003; 98: 28e33.
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10 Rusca M, Proietti S, Schnyder P, et al. Prevention of atelectasis formation during induction of anaesthesia. Anaesth Analg 2003; 97: 1835e9. 11 Westbrook PR, Stubbs SE, Sessler AD, et al. Effects of anaesthesia and muscle paralysis on respiratory mechanics in normal man. J Appl Phys 1973; 34: 81e6. 12 Nunn JF, Matthews RL. Gaseous exchange during halothane anaesthesia: the steady respiratory state. Br J Anaesth 1959; 31: 330e40. 13 Older P, Hall A. Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly. Chest 1999; 116: 355e62. 14 Snowden CP, Prentis J, Anderson H, et al. Submaximal cardiopulmonary exercise testing predicts complications and hospital length of stay in patients undergoing major elective surgery. Ann Surg 2010; 251: 541e7. 15 Ingle L. Prognostic value and diagnostic potential of cardiopulmonary exercise testing in patients with chronic heart failure. Eur J Heart Fail 2008; 10: 112e8.
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