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Respiratory physiology and
anaesthesia
Gary H Mills BMedSci MBChB FRCA
Anaesthesia affects all aspects of respiratory
system function. This can be considered in
terms of effects on the control of breathing,
chemoreceptors, upper airway, respiratory muscles and lung mechanics (including lung volume and airway resistance) and the impact
these factors have on ventilation and perfusion.
Control of breathing
Anaesthetic agents influence rate, rhythm and
intensity of discharge from the respiratory
centres which receive input from the
chemoreceptors, cortex, hypothalamus, pharyngeal mechanoreceptors, vagus nerve and
other afferents. The respiratory centres are
located in the pons and the medulla. These contain many different types of inspiratory and
expiratory neurons that fire during the three
phases of the respiratory cycle:
Inspiratory phase: A sudden onset is followed
by a ramp increase in discharge to the
inspiratory muscles and the dilator muscles
of the pharynx.
Post-inspiratory phase: A gradual decline of
discharge to the inspiratory muscles leads
to a gradual reduction in tone which modulates expiratory flow.
Expiratory phase: Both expiratory and inspiratory muscles are silent unless forced expiration or high minute ventilation (>40
l min–1) is required.
The medulla contains cells that discharge
rhythmically, including the dorsal and ventral
groups of respiratory neurons. The dorsal area
lies close to the tractus solitarius and mainly
discharges on inspiration. The ventral area also
contains some inspiratory neurons, i.e. the
nucleus paraambiguus (controls force of inspiration) and the nucleus ambiguus (dilates the
upper airway). However, most cells are expira-
tory, including the expiratory Botzinger complex and the nucleus retroambigualis. The pons
has a lesser role, adjusting the fine control of the
respiratory rhythm, including setting the volume at which inspiration is terminated.
Upper motor neurons from the respiratory
centres pass via the ventrolateral part of the
cord to the anterior horn cells. Their effect is
combined with voluntary inputs that pass via
the ventrolateral and dorsolateral cord, as well
as involuntary inputs such as coughing and
swallowing. Tension in the respiratory muscles
is adjusted by the muscle spindles which are
present in small numbers in the diaphragm.
The effect of anaesthetic agents
on respiratory drive
Most inhalational anaesthetic agents increase
respiratory frequency by shortening inspiratory and to a larger extent expiratory time.
Tidal volume is depressed, as is ventilatory
response to PaCO2. There is active contraction of the abdominal muscles during expiration and there may be paradoxical inward
movement of the ribcage in early inspiration.
Each anaesthetic agent has a slightly different
effect on inspiratory and expiratory time and
tidal volume. Ether has little effect on PaCO2 at
low concentrations and nitrous oxide is not generally depressant. The response to hypoxaemia
may be diminished by very low concentrations
of volatile agents, but the degree of depression is
a matter of debate. This effect is produced by
action on the respiratory centre rather than a
slight effect on peripheral chemoreceptors. If
obstruction of the airway occurs during anaesthesia, pressures produced by the respiratory
muscles in response to the obstruction are well
preserved and are comparable to the awake state.
Current intravenous induction agents produce a brief stimulation on induction which
British Journal of Anaesthesia | CEPD Reviews | Volume 1 Number 2 2001
© The Board of Management and Trustees of the British Journal of Anaesthesia 2001
Key points
Observation of respiration in the undisturbed
patient has great value
after anaesthesia
After anaesthesia,
decreased upper airway
tone allows obstruction
at less negative airway
pressures
Anaesthesia reduces
chest wall and diaphragm
tone causing functional
residual capacity to fall
rapidly to or below closing volume
Ventilation perfusion mismatch is increased by
anaesthesia during spontaneous breathing and
intermittent positive
pressure ventilation
Respiratory complications and mortality are
reduced by regional
anaesthesia
Gary H Mills
BMedSci MBChB FRCA
Honorary Consultant Anaesthetist
and Senior Lecturer in Anaesthesia
and Intensive Care Medicine, Section
of Anaesthesia, Department of
Surgical and Anaesthetic Sciences,
K Floor, Royal Hallamshire Hospital,
Glossop Road,
Sheffield S10 2JF, UK
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Respiratory physiology and anaesthesia
increases tidal volume, inspiratory flow and frequency. This is
abruptly followed by a fall in ventilatory drive, accompanied by
a fall in tidal volume, inspiratory flow and, possibly, a period of
apnoea followed by more rapid shallow breaths. Propofol
appears to abolish the response to hypoxaemia and is a potent
depressor of chemoreceptor activity and upper airway reflexes.
Ketamine is unusual; it is less depressant and associated with
greater inspiratory flows and marked expiratory braking.
Opioids have a powerful effect on respiratory drive. They
prolong the expiratory pause, thus slowing respiratory rate and
obtunding the response to rising PaCO2. They also suppress
REM sleep and, therefore, increase rebound REM that occurs
when they are discontinued. Benzodiazepines in premedicant
doses usually decrease chemosensitivity. Airway obstruction is
a major risk, especially in elderly patients whose level of
arousal has been reduced by regional anaesthesia. α2Adrenergic agonists can produce sedation and have been shown
to decrease the response to elevations in PaCO2, so reducing the
gradient of the ventilation response CO2 curve, but not the resting response. Intravenous lidocaine (1.5 mg kg–1) slows respiratory rate by increasing expiratory time and reduces tidal volume. Doxapram is a central ventilatory stimulant that leads to
increased respiratory drive, increasing tidal volume and, to a
lesser extent, respiratory rate.
Chemoreceptors
Peripheral and central chemoreceptors provide inputs to the
respiratory centres. The peripheral chemoreceptors lie in the
carotid and aortic bodies. The carotid bodies are more important in stimulating ventilation, while the aortic bodies are also
capable of responding to hypotension. The peripheral
chemoreceptors in both sites respond to hypoxaemia (unlike
the central receptors), hypercapnia and hydrogen ion concentration. The carotid body receives a very high blood flow,
enabling it to respond rapidly to changes in partial pressure.
The bodies consist of structural type II cells and chemoreceptor type I or glomus cells, which contain many neurotransmitters. They appear to be inhibited by exogenous dopamine
and α2-adrenergic agonists, but are stimulated by nicotine,
atropine, doxapram and almitrine.
The central chemoreceptors lie close to the origins of the
glossopharyngeal and vagus nerves on the anterolateral surface of the medulla. They are within the blood brain barrier
and are bathed in CSF. This slows the response of the central
chemoreceptors relative to the peripheral sites. Carbon dioxide diffuses across the blood-brain barrier into the CSF, which
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is less buffered than the plasma. This causes a fall in CSF pH
which stimulates the central chemoreceptors. If PaCO2 is
maintained at abnormal values for several days, CSF pH is
restored to normal by changes in CSF bicarbonate.
Sleep affects the changes which would normally be produced by the action of the chemoreceptors on the medulla,
allowing PaCO2 to rise by 0.15–0.3 kPa in non-REM sleep
and increasing the apnoeic threshold. The response to
mechanical loading on the inspiratory system is reduced in
non-REM sleep. These effects are greater in REM sleep but
more difficult to assess because of irregular breathing patterns
associated with this stage of sleep. REM sleep also results in
increased airway resistance and decreased upper airway tone,
potentially increasing the risk of upper airway obstruction.
Ventilation – PaO2 response curve
The relationship is a rectangular hyperbola, with little
response to high values of PaO2. Ventilation begins to increase
at a PaO2 of 7–8 kPa and rapidly at 4.3 kPa. Sudden acute
hypoxaemia stimulates ventilation within a few seconds.
Ventilation – PaCO2 response curve
The response is slower than that of hypoxaemia but is linear
up to high values of PaCO2. However, ventilation becomes
depressed at values of somewhere between 13 and 26 kPa.
The response curves have the same gradient but are displaced
to the left in acidosis. Opioids and inhalational agents displace
the curve to the right and flatten the gradient. The gradient of
the response curve for a given pH is steeper in hypoxaemia.
The effect of anaesthesia on the upper
airway
Upper airway patency relies on the muscles of the upper airway. These are either dilators, which maintain patency, or
constrictors, which are involved with swallowing. They are
orientated in a radial direction to open the airway, e.g. levator
veli palatini, or longitudinally acting on the hyoid bone to pull
the airway open, e.g. geniohyoid and thyrohyoid (Fig. 1).
When conscious, the airway will remain patent even in the
presence of negative intrathoracic pressures of –60 cm H2O.
However, when asleep, this falls to –13 cm H2O. Anaesthesia
lowers the tone of the upper airway muscles and further promotes airway occlusion. Topical local anaesthesia of the upper
airway increases airway resistance and makes collapse more
likely. Agents such as benzodiazepines, barbiturates, alcohol
and halothane reduce the activity of the nerves supplying the
British Journal of Anaesthesia | CEPD Reviews | Volume 1 Number 2 2001
Respiratory physiology and anaesthesia
Mandible
Myelohyoid
Geniohyoid
Hyoid
Hyoid displaced
anteriorly
Thyrohyoid
Thyroid
Fig. 1 Geniohyoid and thyrohyoid tense longitudinally, producing a force vector that displaces the hyoid anteriorly, assisting the maintenance of a patent
upper airway (based on Drummond, 1996).
upper airway more than they affect the diaphragm. However,
ketamine maintains airway patency by promoting muscle
activity. The sensitivity of different muscle groups to the
effect of neuromuscular blockade varies. Importantly, the ability to cough or swallow and co-ordinate the larynx and upper
airway may lag behind the recovery of the diaphragm.
Narrowing of the airway with an ET tube or mucosal
swelling results in increased resistance during inspiration and
thus down-stream pressure becomes even more negative, further promoting airway collapse.
Reflex responses occur in all parts of the upper airway, particularly in children, where laryngospasm and apnoeic
responses to stimulation are common and a deep plane of
anaesthesia is required if coughing, laryngospasm or bronchospasm are not to occur on stimulation. Propofol is particularly effective in overcoming upper airway reflexes. Coughing
may occur on recovery at a depth of anaesthesia where regular respirations have not yet returned.
The respiratory muscles
Respiratory muscles can be subdivided into inspiratory and
expiratory. Inspiratory muscles include the diaphragm, upper
intercostals and parasternals and the accessory muscles (sternocleidomastoids, strap muscles of the neck, trapezius and the
pectoral muscles when the shoulders are braced). Expiration is
normally passive, but can be active using the lower intercostals
and the abdominal muscles. Coughing additionally requires
co-ordinated closing and opening of the glottis.
The diaphragm is a bi-domed structure attached by the crura
to the lumbar vertebrae. When this area contracts, it moves
downward, producing a fall in intrathoracic pressure. The
descent increases intra-abdominal pressure which is transmitted laterally to the lower rib cage via the zone of apposition
where the diaphragm is flat against the adjacent pleura and the
lower ribs. This forces the rib cage outward and, as the
abdominal pressure rises, the abdominal contents act like a
fulcrum which prevents further diaphragmatic descent as the
diaphragm shortens. Therefore, the lateral margins of the
diaphragm are pulled upward, further elevating and swinging
the ribs into a more horizontal position. This widens and elevates the rib cage. Simultaneously, the intercostals and scalene muscles contract in a complex and rapid descending
sequence, expanding, elevating and stabilising the rib cage.
This lowers further intrapleural pressure and prevents the
increasingly negative intrathoracic pressure from pulling the
rib cage inwards. The intercostals and the abdominal muscles
also aid in the maintenance of posture, while the external
oblique and transverus abdominis are tonically active, keeping
the diaphragm at the optimal stretch and shape.
The effect of anaesthesia on the respiratory
muscles
General anaesthesia may affect the tone or strength of the respiratory muscles. This may explain why functional residual
capacity (FRC) falls during the first 15–40 s after induction of
anaesthesia. There is debate as to the relative contribution of
the rib cage and the diaphragm and whether some of the
changes are due to relaxation of postural muscles altering the
position of the chest. FRC is reduced during anaesthesia
employing a spontaneous breathing technique or positive
pressure ventilation with paralysis. The fall in FRC, when
measured using gas dilution techniques, may be exaggerated
by gas trapping. However, other studies using specially adapted body box plethysmography, impedance plethysmography
and spiral CT, have shown that this is not the only factor.
Posture affects FRC, even in awake subjects. Using the
example of a 70 kg male with an FRC of approximately 3 l,
moving from the upright to supine position decreases FRC by
700 ml. Anaesthesia decreases FRC by another 300–500 ml,
but some of this may be accounted for by further changes in
body position as postural muscles relax. To eliminate this factor, measurements have been made while supporting the spine
with a VacPac mattress to reduce skeletal movements. This
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Respiratory physiology and anaesthesia
Excursion of diaphragm (anaesthetised,
mechanical ventilation and neuromuscular
blockade)
Abdominal wall
Rib cage
Resting position of
diaphragm
Decreased functional
residual capacity
Blood volume
Excursion of diaphragm
(awake)
Excursion of diaphragm
(anaesthetised, spontaneous
breathing)
Fig. 2 The diaphragm (D) excursion when awake is compared with the anaesthetised state with spontaneous breathing and anaesthesia with paralysis and
mechanical ventilation.The diaphragm is displaced rostrally during anaesthesia,
but the excursion is primarily anteriorly during IPPV with paralysis and posteriorly during spontaneous breathing.The rib cage (RC) moves inwards, reducing FRC, as does the abdominal wall (AB).The central blood volume pools in
the abdomen during mechanical ventilation.
has demonstrated a fall in rib cage volume of approximately
300 ml after induction of anaesthesia with propofol, but no
change in the abdominal compartment volume, suggesting
that the position and shape of the diaphragm is less affected
than those of the rib cage. There is evidence that tonic activity in the scalenes, sternocleidomastoids and, to a lesser extent,
the intercostals, is abolished by thiopentone.
The evidence for changes in position of the diaphragm is
less clear. However, in the paralysed ventilated patient and
during anaesthesia with spontaneous breathing, there is a significant cephalad displacement of the dome of the diaphragm.
Therefore, changes in lung volume are likely to be due to a
fall in chest wall tone with or without a fall in diaphragmatic
tone (Fig. 2).
The contribution of changes in disposition of the blood volume during spontaneous breathing to changes in FRC is not
well established. It is possible that increasing intrathoracic
blood volume could displace some of the air filled lung volume in the thorax. However, studies using inductive plethysmography, which measures change in total chest or abdominal
volume regardless of the cause, suggest that, during quiet and
unobstructed spontaneous breathing under anaesthesia, movement of blood into the thorax is not a major factor affecting
FRC. More recent studies, using chest and abdominal CT
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combined with central blood volume measurement by dye
dilution and multiple breath nitrogen washout techniques,
have suggested that blood pools in the abdomen during IPPV
with paralysis and there is a reduction in the transverse area of
the chest with cephalad movement of the diaphragm.
Consequences of a fall in lung volume
during anaesthesia
Atelectasis occurs by three methods: (i) absorption of gases
behind blocked airways; (ii) compression; and (iii) loss of surfactant. Fall in FRC has consequences for ventilation and perfusion. A decrease in lung volume will reduce traction on air
passages and lead to a narrowing of bronchi and bronchioles
leading to increased airway resistance, airway collapse and
atelectasis. This results in reduced compliance and increased
work of breathing. Compression atelectasis would occur particularly at the lung bases if there was a reduction in diaphragmatic tone allowing the pressure in the posterior upper
abdomen to be transmitted to the lower posterior lung units.
Indeed, rapid onset of postero-basal atelectasis has been visualised by CT, shortly after induction of anaesthesia.
Closing volume (CV) is the lung volume at which small airway collapse begins. CV is >FRC in neonates and the over
40-year-olds. Anaesthesia reduces FRC close to, or below,
closing volume in those in the middle age range. The effect is
increased at the extremes of age, obesity and even in those
with an abnormally high FRC, but poor lung elasticity and
high resistance, e.g. emphysema. This causes airway closure
and alveolar collapse. The lack of regular lung expansion will
reduce the formation and spread of surfactant thus worsening
the situation. Once airways close off, atelectasis will be hastened during periods of 100% oxygen administration or by the
replacement of nitrogen with nitrous oxide.
Ventilation-perfusion mismatch in
anaesthesia
Changes in lung volume and airway patency cause a mismatch of lung ventilation and perfusion (V/Q mismatch). The
V/Q ratio may be very low or zero in areas that are perfused
but not ventilated, or extremely high in those areas where
there is ventilation but no perfusion (dead space). A range of
states between these two extremes may exist, usually with
good matching in most of the lung. During anaesthesia, these
two extremes are more prevalent than in awake subjects. This
has been confirmed by the finding of an increased spread of
V/Q ratios during anaesthesia.
British Journal of Anaesthesia | CEPD Reviews | Volume 1 Number 2 2001
Respiratory physiology and anaesthesia
Hypoxic pulmonary vasoconstriction (HPV) normally
reduces blood flow in areas of atelectasis, so promoting the
matching of ventilation and perfusion. However, volatile
agents impair this process, as alveolar anaesthetic concentration rises. For example, in human studies, HPV was reduced
by 50% by 1 MAC halothane and 20% by isoflurane. Studies
attempting to reduce atelectasis during anaesthesia have
required airway pressures to be increased to 40 cm H2O for 15
s to re-open the airways. These pressures are above those normally seen during IPPV in theatre. Studies employing single
photon emission computerised tomography to record the passage of radiolabelled aerosols and lung perfusion by radiolabelled albumin have shown that shunt is solely located in the
atelectatic regions during anaesthesia.
Reduction in FRC and amount of atelectasis is similar during anaesthesia with either spontaneous breathing or artificial
ventilation. However, the lower-most dependent part of the
diaphragm moves more during spontaneous breathing, suggesting that regional ventilation is different. During artificial
ventilation, more gas passes to the upper (anterior) alveoli,
which may become relatively overstretched, while the lower
(posterior) alveoli are compressed by the weight of the heart
and abdominal contents. Despite this, ventilation-perfusion
studies have failed to find any great differences between the
two types of anaesthesia, with shunt fractions of 1% awake,
11% during spontaneous breathing and 14% during artificial
ventilation. Ketamine is once again unusual; during spontaneous breathing, no V/Q mismatch is seen. However, when
artificial ventilation is commenced, areas of atelectasis and
shunt begin to appear.
breathing. This may be exacerbated by poor pain relief and
increased ventilatory demands in the cold, shivering and catabolic postoperative patient. In this situation, the load on the
respiratory system may exceed capacity and failure will occur.
Adequate analgesia, routine use of warming techniques, intraoperative PEEP, ventilation regimes including air, extubation
in a sitting up posture (where possible) and early use of postoperative CPAP may reduce these problems.
Postoperative lung function
Rodgers A, Walker N, Schug S, McKee A, Kehlet H, van Zundert A et al.
Reduction of postoperative mortality and morbidity with epidural or
spinal anaesthesia: results from overview of randomised trials. BMJ
2000; 321: 1493–7
Postoperative lung function is most impaired in patients with
upper abdominal surgery because of basal atelectasis, V/Q
mismatch, upper airway obstruction and increased work of
Effect of regional anaesthesia on physiology,
morbidity and mortality
The effects depend on the extent of the blockade. Blocks
which affect all lumbar and thoracic segments decrease inspiratory capacity by 20% and reduce expiratory reserve to
almost zero. Expiratory muscle strength is greatly reduced
during the action of lumbar spinal anaesthesia, temporarily
reducing cough efficiency. However, most blocks are not so
extensive and, in these situations, V/Q mismatch is close to
the normal situation. Overall mortality is reduced by one-third
in patients undergoing local anaesthesia. This is due, at least
in part, to the significant reduction in respiratory complications including pulmonary emboli, respiratory depression and
pneumonia especially after general, orthopaedic, urological
and vascular surgery.
Key references
Drummond GB. Mechanics of breathing: effects of anaesthesia. In: PrysRoberts C, Brown B. (eds) International Practice of Anaesthesia: Oxford:
Butterworth Heineman 1996; 1/59/1–26
Hedenstierna G, Rothen HU. Pulmonary gas exchange, effect of anaesthesia and of mechanical ventilation. In: Prys-Roberts C, Brown B.
(eds) International Practice of Anaesthesia: Oxford: Butterworth
Heineman 1996; 1/60/1–13
See multiple choice questions 17–21.
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