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Old hat and old hands in controlling breathing (part 2): translating ventilatory drive into breathing
Current Anaesthesia and Critical Care
(1997) 8, 221-230
© 1997 HarcourtBrace & Co Ltd
Focus on: Basic science/homeostasis m e c h a n i s m s
Old hat and old hands in controlling breathing (part 2): translating ventilatory drive into breathing
A. M. S. B l a c k
The generation of spontaneous respiratory rhythm The first of these essays considered what might be an anaesthetist's practical perspective on the classical descriptions of the drive to breathing. These are in terms of minute ventilation (VM) but ventilation must be partitioned into tidal volume (VT) and breathing rate (f), of which the inverse, the total respiratory period (Ttot), must be partitioned into inspiratory period (TO and expiratory period (TE) The influence of mechanical constraints on the partitioning of ventilation is as familiar to anaesthetists having to ventilate patients as it was to classical physiologists studying spontaneous breathing. For instance, resistive loads to breathing are best met with slow deep breaths, and elastic loads by small frequent breaths. Physiologists have teased a bewildering number of inflation and deflation reflexes from the respiratory tract, intrathoracic vasculature and chest wall. Some are plausibly understandable and some seemingly paradoxical. It is unclear whether they should be considered in isolation or whether they should be viewed as components which in concert help to transform a respiratory drive into a breathing pattern based on an appropriate functional residual capacity. It was once popular for respiratory physiologists to regard ventilation as a 'drive' characterized as mean inspiratory flow (VT/T~) and a 'duty cycle' (Ti/Ttot). 1'2 Von Euler 3 proposed a classical descriptive model to explain some externally observable effects: an 'on switch' begins inspiration, during which there is a progressive increase in inspiratory activity at intensity deter-
Dr A. M. S. Black, Consultant SeniorLecturer, Sir HumphryDavy Department of Anaesthesia, Bristol RoyalInfirmary,Bristol BS2 8HW, UK. 221
mined by the drives to breathing until an 'off switch' is triggered after an interval (T~) that depends to some (species-dependent) extent on reflex feedback from the lungs and chest wall. The period between the operation of the off switch and the next on switch (TE) is separately determined. These physiological concepts have their counterparts in the controls on the ventilators used in anaesthesia and intensive care (see below). Most general anaesthetic agents reduce minute ventilation by a combination of reduction in mean inspiratory flow that overrides a tachypnoea attributable mainly to a shortening of TE.2 If, for example, apnoea is caused by induction of anaesthesia with propofol as a sole agent, 4 it is often preceded by a briefly observable tachypnoea that is seen also in the first discernable breaths as breathing is re-established: this is as though the tachypnoeic tendency underlies the whole apnoea but is submerged by a temporary 'zeroing of the gain' on breath size. The tachypnoea caused by intravenous or volatile anaesthetic agents used alone may be misconstrued as a response to pain but, whatever its cause, titration to a satisfactory rate by increments of a suitable opioid is a simple and effective strategy. The rhythm generation underlying tidal breathing resides anatomically in more or less overlapping groups of ueurones in the brainstem) Progress towards their identification began with ablation and stimulation experiments, and progressed to microelectrode recordings. There are several functionally distinct types of cells in pons and medulla, some anatomically distinct and others intermingled with other types of respiratory neurones. Different types can be distinguished by the phase of the breathing cycle at which they are spontaneously active or at which they can be recruited or suppressed by known nervous and pharmacological inputs: the rhythmgenerating neurones may be hard to distinguish from
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CURRENT ANAESTHESIA AND CRITICAL CARE
neurones with other respiratory and para-respiratory functions, such as the motoneurones to the muscles of the upper airway or cell bodies of the descending tracts to spinal respiratory motoneurones. Determining the interconneetions between the neuronal populations is a matter of educated guesswork. Several neural network computer models have been suggested with inherent oscillatory activity that results from interconnections and is fuelled by input from the general nervous traffic passing up and down the brainstem. The test of any model is its ability to simulate responses to as wide a range of inputs as possible. A caveat on any interpretation must be that some form of anaesthesia or decerebration is needed for any study of this sort, and these must inevitably alter the characteristics of the system being studied. There is further scope for using the effects of different combinations of anaesthetic and analgesic drugs to increase the range of effects that need to be correctly simulated: the underlying hope would be that a model that can successfully simulate the effects of a sufficiently wide range of nervous and pharmacological inputs can be a plausible basis for extrapolation to behaviour in the absence of anaesthesia. Any such hope presupposes that there will be a continuum of dose-related response to anaesthetic and related drugs rather than a neural switch between one category of behaviour and another: a hypothesis that has yet to be adequately tested.
The generation of inspiratory gas movement The descending output of the brainstem generators of inspiratory rhythm is detectable in the spinal cord as the central respiratory drive potential that plays upon the segmental motoneurones of the muscles involved in respiratory movement. Its effects via muscles are measurable as the airway pressure when airflow is occluded during attempted inspiration. In conscious subjects, airway occlusion will excite an augmented inspiratory effort by about 200 ms, which is why the pressure after 100 ms (P0.~) became established as a tool for physiological investigation. In the face of varying mechanical loads to breathing, P0.1 correlates better with the integrated phrenic neurogram than does the mean inspiratory flow of the preceding unoccluded breaths. However, the relationship with the neurogram is still not unique but depends on the shape and volume of the lungs. Measurement of P0.1 is now offered as an option in modern state-of-the-art ventilators, though its value as an aid to weaning remains to be established: we are moving away from measurements to help us guess the best time for an all-or-nothing attempt to discontinue ventilatory support, and more towards a gradual approach to weaning based on observed success or failure in coping with a stepwise withdrawal of support. For the anaesthetist, the linkage of neuromuscular output to gas movement through a pressure identifies the ribcage and diaphragm as a pressure generator - not the familiar constant positive inspiratory pressure generator,
but a generator with feedback by which negative intrapleural and alveolar pressures can be varied within and between breaths so that the resulting ventilation achieves physiologically set targets. Figure 1 is a classical depiction of the pressures across the components of the respiratory system as the lung volume is altered by inspiration during positive-pressure or spontaneous breathing. The pressure across the respiratory system (Pr~) at any time is the sum of the pressures across the chest wall (Pc) and the lungs (Pl). At FRC, the inward recoil of the lungs is balanced by the outward recoil of the passive chest wall (Pc ~esting), creating a negative end-expiratory pleural pressure (ppm). During positive-pressure breathing, the pressurevolume relationship of the passive chest wall remains fixed and the pressure across the respiratory system (P~ ~Pev) follows the thick diagonal arrow: it is less than the pressure required to inflate the lungs until the chest wall has been inflated to its natural unstressed volume, and thereafter exceeds the lung-inflating pressure by the additional amount required of inflate the chest wall above its natural volume. The peak inspiratory airway pressure (Paw1) for a given tidal volume is the sum of the pressures required to inflate the chest wall and abdomen to that tidal volume. During spontaneous breathing, the activity of the inspiratory muscles generates the inspiratory pressure to inflate the lungs. It does so by shifting the pressurevolume relationship of the chest wall upwards and to the left. With an open airway, the surrounding atmosphere provides an infinite reserve of flow to respond to the pressure generation (see later). At the peakinspiratory instant of zero flow, the intersection of the active pressure-volume relationship (Pc with inspiratory effort) with the dotted line (-P1) indicates the peak inspiratory pleural pressure (PplI), which is what inflates the lungs to the corresponding tidal volume. The pressure across the respiratory system (Pr~ spont ventilation) follows the more vertical thick arrow. The time course of these changes during spontaneous and positive-pressure inspiration is indicated in Figure 2.
Artificial production of inspiratory gas movement Anaesthetists' postgraduate training requires that they have some formal familiarity with the simple concepts (enunciated by Mapleson) s of artificial ventilators as constant flow or constant pressure generators. 5 In constant flow generators, flow is the independent variable and the time course of the alveolar and airway pressures depends on the flow and the mechanical properties of the lung and chest wall (Fig. 3). In a constant pressure generator, pressure is the independent variable and the flows and volumes depend on the mechanical properties of the lung and chest wall (Fig. 4). This means that flow generators have flow knobs and pressure generators have pressure knobs, and a ventilator that has both knobs can be used in either mode.
CONTROLLINGBREATHING,PART 2 223 A constant flow generator effectively connects the lung during inspiration to a very large reserve of pressure through a resistance that is controlled by the flow knob (Fig. 3). For a sufficiently high driving pressure, the change from end-expiratory to peak inspiratory pressure in the lungs will have a negligible effect on the pressure difference across the resistance: a more or less constant pressure exerted across a constant resistance will give a more or less constant flow. By contrast, a pressure generator connects the lung to the anticipated pressure needed to inflate it to the required tidal volume (Fig. 4). The resistance and compliance of the lung and chest wall determine how quickly and completely the tidal volume is delivered. Pressure generators must have
a large reserve of flow capacity in order to maintain the set pressure in the face of whatever flows and volumes can be accommodated by the mechanical properties of the ventilated system and whatever flows are lost through leaks (which are effectively an infinite compliance accessed by a resistance that may or may not be finite). Some ventilators appear not to fit the recognizable extremes of the Mapleson classification. For instance, many anaesthetists seem satisfied with classifying the classic Manley ventilator as a 'minute volume divider' as though this description precludes classification in, or logical connection with, any other category. But, properly operated, the classic Manley connects the lungs without an intervening resistance to a pressure that is
Patm
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\ Fig. 1 The pressure across the respiratory system (Chest-wall and Lungs) during active inspiration (spontaneous ventilation) and IPPV. P~rv= alveolar pressure, P,tm = atmostpheric pressure, Prs = pressure across respiratory system, P~ = pressure across lungs, Pc = pressure across chest-wall, Pp. = intrapleural pressure, P,w = a i r w a y pressure (IPPV). Breathing phase phase subscripts: I = peak inspiratory, E = end-expiratory.
l
224
CURRENT
ANAESTHESIA
AND
CRITICAL
CARE
.-llb // /,/
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Fig. 2 Time courses of pressures in the respiratory system during spontaneous inspiration and lung inflation by IPPV. Key: see Fig. 1.
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only modestly (2 or 3 times) greater than the pressure required for the desired tidal volume, but limits the tidal volume that can be delivered and allows enough time for delivery to be followed by an inspiratory hold (with zero flow) at a pressure determined by the delivered volume and the stiffness of the lungs. If they have to be classified, they might be called generators of either a non-constant flow or a non-constant pressure. Constant flow generators have been the traditional preference in anaesthesia and intensive care. Provided there are no great leaks or compliance losses in the breathing system, the delivery of a set flow or volume could be guaranteed in the face of whatever changes there may be in the mechanical properties of the respiratory system. With constant pressure generators, the tidal volumes need to be measured with each change of ventilator setting or mechanical loading to ensure that the desired tidal volumes are being delivered: this was tiresome and inconvenient with the mechanical Wright's respirometers that were the clinical mainstay of tidal volume measurement. 6 Like many other anaesthetic traditions, the preference for flow generators has outlived its appropriateness, undermined as it has been by advances in technology and professional recommendation. The minimum standards of monitoring in anaesthesia require expired volumes to be measured irrespective of the type of ventilator that is in use, and electronic flow/volume meters are conveniently built in to modern breathing systems] Besides, if capnography
C O N T R O L L I N G BREATHING, PART 2
225
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is available 6 (though it is not explicitly required), the anaesthetist has access to end-tidal PCO2: a much more appropriate measure of the adequacy of ventilation as balanced by the CO 2 production. 8 Pressure-generating ventilators were traditionally limited to paediatric anaesthesia, because of their ability to cope with the necessary leaks round uncuffed endotracheal tubes, but their reserve flow capacity gives them an overwhelming advantage that has been recognized by the more enlightened intensive care units. The flow capacity allows ventilators to deliver unrestricted flows and volumes of gas to those patients who are able to breathe (i.e. to produce phasic alterations in the pressurevolume relations of their respiratory system; Figs 1 and 2). The first pressure generators made this flow capacity available only during inspiration, but their modern successors make it available throughout the respiratory cycle. Patients can exercise their respiratory muscles while the airway pressure is cycled between a higher and lower positive pressure, the differences in pressure supporting the ventilation and the area under the pressure time course supporting gas exchange (Fig. 5). The two features can be varied independently to tailor respiratory support to the requirements for each of its components. Synchronization of the higher pressure with inspiratory effort is not absolutely necessary but, if it is wanted,
ventilators with a freely available capacity for flow can detect inspiratory demands directly as flow rather than by their potentially more reflexogenic pressure effects in a closed system. New generations of pressure-generating ventilators are already in prospect that can use servo principles to vary the pressure generated within breath so as to produce a specified tidal volume in the face of changing mechanics of the respiratory system, but the more logical use of PCO 2 as the feedback signal awaits the development of a reliable continuous monitor of arterial PC02 or some suitable surrogate thereof.
Artificial generationof breathingpattern The generation of breathing by an artificial ventilator requires cycling from inspiration to expiration within a total respiratory period that is set in one way or another. Mapleson's classic treatise 5 contains references to endinspiratory cycling by pressure or volume in addition to time, but a glance round the modern range of available ventilators should make it clear that time-cycling is the only sensible option. A moment's reflection should be enough to clarify that pressure-cycling of a constant pressure generator will result in a TI of either 0 or infinity, volume cycling will give a Tr that varies up to
226
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Support for pulmonary ventilation (normocapnia)
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infinity and that the T r for time-cycling should be at least three times the time constant of the respiratory system (so that 95% of the possible tidal volume will be delivered; Fig. 4). A flow generator that is pressure-cycled loses the perceived advantage that a set volume can be delivered; it also loses control of the timing of inspiration. With one that is volume-cycled, one must double inspiratory flow (~ri) as one doubles the s e t V T if one wishes to leave TI unaltered and double minute ventilation (VM). With a time-cycled constant flow generator, a doubling of VI will double X)M with no additional adjustments. However, a flow generator can usefully be volume-limited as well as time-cycled (Fig. 6).
A philosophy of knobs
On the principle that it is better to sit and think rather than just sit, meditation on the number of knobs on intheatre ventilators is good for the soul. Thus, anaes-
thetists control pulmonary ventilation (VM) in order t o control end-tidal or arterial P C O 2. 1 # ~rM = V T X f or "QM= VT × (Ill'tot) Either expression for Vr~ has three variables. If any two are fixed, so is the third: there are two degrees of freedom, and two knobs (besides the on/off knob) would be enough to control all three ventilatory variables. With a minute volume divider, VM would be set, and setting either f o r V T would set the other of the pair; alternatively one could have a VT knob and f knob, and V M would be the dependent variable. With a two-knob ventilator, one would have no control over the I:E ratio. This third degree of freedom in control would need a third knob on the ventilator, but there is some choice in the functions to be assigned to each knob. If Trot is already determined, the addition of a T I knob would indirectly determine T E ( T E = Tto t - TI) or the addition of an I:E knob would indirectly determine both T~ and T E.
CONTROLLINGBREATHING,PART 2 227
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Alternatively, the three knobs could consist simply of an inspiratory flow ('VI) knob, a T~ knob and a T E knob, as in the Penlon 200 ventilator, so that VM = (9~ X TI) x (1/[T: + TE]) A three-knob constant flow-generating ventilator will not allow for any inspiratory hold. This would require a four-knob ventilator, which could function as a volumelimited, time-cycled flow generator (Fig. 6). As with a three-knob flow generator, there is a wide choice about which functions can be assigned to which knobs, but there will still be only four degrees of freedom. For example, a Drager Narkomed 2 ventilator has a V~ knob, anfknob, an I:E knob and a Vr-limiting knob. The inspiratory flow will continue, only until the set VT has been delivered. Provided the V: has been set high enough to deliver it within the indirectly set T~ (see above), there
will be an inspiratory flow period T:(~ow)and an inspiratory hold period T:(hold); if not, the volume limit does not apply and the ventilator will function as a three-knob ventilator (time-cycled flow generator). For the controls on the Drager ventilator, the equation for "~M would be expressed as xOM
~-~ (91X =
T:(~o.~))× (I/[T:(~qw)+ T~(hold) + TEl)
(v(ZI X V T / V I ) x ( 1 / [ V T / V I -[-
{T: -
VT/V:} + TB])
In the Servo ventilators in flow-generating mode, there is a VM knob, an f knob, an I:E knob and an inspiratory hold knob. In the classic Manley ventilators, the rotameters on the anaesthetic machine serve as a composite "VMknob and the V T is limited by the trigger setting on the curved V T slide (which indirectly sets the minimum f and the maximum Ttot): the T I is set within the s e t Ttot by the T I slide, and the speed at which the VT is delivered is set by adjusting the mechanical advantage of the weight on the bellows. If the weight is far enough out for the bellows to empty the set VT, the Manley will operate as a volume-limited time-cycled non-constant flow or pressure generator (see above), but if the weight cannot generate enough pressure to empty the bellows, the set V T limit does not apply, nor the time-cycling that depends on it. The Manley ventilator 'chatters', func-
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tioning as a constant pressure generator that is cycled indirectly by the volume that the pressure can deliver. Though four knobs are needed for a constant flow generator to produce an inspiration with a flow phase and a hold phase, a constant pressure generator can approximate this with three knobs: one to set the pressure, one to set the f o r Ttot and one to set the T I. If the T~ is set at three times the time constant of the respiratory system (resistance times compliance) and if the gas delivery is approximately monoexponential, the ventilator will deliver about 95% of the V T producable by the set pressure and the compliance: 67% of the producable V T will be delivered in the first time constant, and 85% by the second, so that only about 10% of the producable VT will be delivered in the last time constant. This is a fair approximation to an inspiratory hold. The missing degree of freedom over the four-knob flow generator is that the shape of the inspiratory flow profile is fixed by the time constant of the respiratory system so that the ratio of the notional Tmo w to the notional Tmold cannot be varied independently.
Ribcage and abdominal contributions to tidal volume As well as the partitioning of VM between VT and f, there is a partitioning of Vr between the contribution from the ribcage and the abdomen. 9 For research, it is conventional to measure some externally measurable change in a ribcage dimension (A~c)and abdominal dimension (AAB), and to express Vr as a weighted sum of these measurements VT = A. ARc + B.AAB where the weights A and B are 'volume-motion' coefficients that are estimated by calibration against a directly measured VT. The relative contributions of ribcage and abdomen will clearly depend on mechanical loadings. For example, the supine posture favours relatively more ribcage movement, an effect accentuated by advanced pregnancy. Anaesthetists are used to observing and interpreting clinically observed movements of ribcage and abdomen. Normally, both expand synchronously, but 'paradoxical breathing' is an important clinical sign. For instance, patients with a transection or transverse myelitis of the spinal cord at a high thoracic level, or a high spinal anaesthetic, can breathe only with their diaphragm: because their intercostal muscles cannot stabilize their ribcage against the negative pressure generated by the diaphragm, the ribcage is drawn in as the diaphragm pushes the abdomen out. Such paradoxical breathing is seen more often with upper airway obstruction, arising because the diaphragm has a better mechanical advantage than the ribcage muscles. But paradoxical breathing does not reliably indicate that breathing is obsmacted (even in patients with normal spinal cords). Anaesthetized patients tend to use their expiratory muscles to assist in expiration, and the offset of that expiratory effort
allows an abdominal expansion in early inspiration that is often accompanied by some indrawing of the ribcage. The general lesson is that ribcage and abdominal movements cannot be interpreted reliably without additional information from intrathoracic (intra-oesophageal) and intra-abdominal (intragastric) pressures and, even with electromyography of the diaphragm and abdominal wall, interpretation can be equivocal. Thus the interpretation of chest wall movements from the measurements that can be made clinically is often likely to be questionable, in particular inferences of respiratory obstruction from degrees of paradox between ribcage and abdomen. 9'1°
Monitoring spontaneous breathing Basic sciences information is desirable in clinical medicine for predicting avoidable disaster. But prediction is only guesswork, educated more or less. Tendencies may be predictable but the confidence intervals on individual prediction can be wide. When individuals are at particular risk, no amount of education can substitute for continuous vigilance and preparedness to intervene when necessary. The vigilance may depend on the special senses of personal attendants or on instruments intended to complement, supplement or replace personal contact. Monitoring spontaneous breathing during anaesthesia is not particularly problematical, 6 particularly since the advent of the laryngeal mask airway, through which one can capture the tidal gas flows for the purposes of measurement and gas analysis. The presence of a vigilant anaesthetist assisted by instrumental monitoring provides the greatest assurance of safety. True, the measurement of expired volume may be somewhat inaccurate, as may be the estimation of P a C O 2 from end-tidal PCO2, especially in patients with abnormal lungs or rapid shallow breathing. But apnoea is likely to be detected well before, or very soon after, it becomes a threat to oxygenation. There is no need to resort to physiology and pharmacology to inform one's guesswork on the likelihood of apnoea. Applying the minimum standards of anaesthetic monitoring to all patients detects the occasional few who actually do stop breathing, and remedial action can be taken easily. There is always an anxious few seconds after removal of an artificial airway, when instrumental monitoring may be reduced to a pulse oximeter: one's eyes and ears are the most immediate monitors, and poor lighting and background theatre noise heighten anxiety. There is a more prolonged but much lower grade of worry over the large number of postoperative patients who are nursed on general wards and who have to share the attentions of a barely adequate number of nursing staff. The worry is heightened over candidates for unavailable high dependency care: the elderly, infirm and recipients of novel and possibly controversial forms of pain relief. The anxiety of the medical and nursing attendants could be relieved and pain relief could be more confidently supplied if there were some instrumental means of monitoring spontaneous breathing that
CONTROLLING BREATHING, PART 2
did not involve invading the airway. Pulse oximeters are the best available and can probably be improved by development of detector probes that can be more securely attached, but they detect the effects of breathing disturbances somewhat downstream - later than the disturbances themselves. Devices that detect fluctuations in pressure or CO2 concentrations at the mouth or nose suffer from the need to monitor both orifices in most people to avoid false alarms when the unmonitored orifice is being used. 11 Approaches such as respiratory inductance plethysmography that depend on calibrating the change in no more than two externally measured dimensions of the chest wall are plagued by the impossibility of maintaining stable volume-motion calibrations. A very accurate calibration would be needed, for instance, to detect a totally obstructed breath in which abdominal expansion would have to be detected as exactly equal and opposite to the indrawing of the ribcage. It is a justifiable expectation that incorporating an increased number of externally measured dimensions into some already available imaging approach could build up a three-dimensional real-time picture of the chest wall that would not need calibrating. But the venture capital for such an enterprise awaits demonstration that there would be a worthwhile return on investment, which implies that the resulting monitor would return sufficiently meaningful information with such minimal inconvenience that it would excite an overwhelming demand from clinical practice. The best current contender for clinical interest relies on an impedance-based indication of one external dimension, a microphone over the trachea and a pulse oximeter. The respiratory monitor of the future will probably have to contend with the problem of making itself wireless, to avoid tangling or even strangling the patient. The technology exists for some sort of radio frequency transmission between a monitor on the patient and a receiver at the bedside, but it may be difficult to find enough frequencies that do not interfere with each other or with other communication devices. Meanwhile, a persistent few (who include myself) pursue what information there might be in uncalibrated respiratory inductance plethysmography. 12 It is established that the patterning of breathing in individual patients is a fairly stable characteristic, ~3'14possibly more so than their sensitivity to CO~ or the ventilation/PCO2 set point about which they regulate their breathing. The question is whether there are patterns of breathing within an individual's 'signature tune' that indicate some fragility in his or her control of breathing that might predispose to either central or obstructive apnoea. There are several conventional statistical and machine-learning approaches to data analysis that might reasonably be applied to this problem, but collecting the data in clinical conditions is enormously time-consuming, and any set that has been successfully collected 1° is immensely valuable. Whether the important information (if it exists) is confined to respiratory signals is a question worth
229
considering. Respiratory sinus arrhythmia is a longrecognized phenomenon. A more recent intriguing observation is that the start times of individual breaths may be linked to the timing of individual heart beats or vice versa. Is The extent to which such observations result from interplay of peripheral reflexes or the intermeshing of central neuronal mechanisms probably varies from situation to situation but, because its absence in conscious people seems to have adverse prognostic significance, it is unlikely to be a mere accident of the way the respiratory and cardiovascular systems have been put together. The existence and prognostic significance of sinus arrhythmia suggests an interesting general hypothesis that many diverse aspects of bodily wellbeing or ill-health are related to active 'connectivity' between the functioning of the subsystems of the body.
Conclusion: final connections One corollary of 'connectivity' is that stable homeostasis through feedback control, despite its appearance of being a default state except in the critically ill, requires active and continuous intercommunication. (The analogous contrast is between the traditional design of aircraft to be inherently stable and the design of modern fighter aeroplanes in which stability has to be actively and continuously imposed by complex technological interplay as a price for manoeuvrability.) A second corollary is the final reflection for this paper, which is to question the traditionally perceived advantages of basic biological scientists in exploding living systems to study their components separately. Clinicians have as much opportunity and a clear obligation to be basic scientists by pursuing holistic study of their patients and their circumstances.
References 1. Cunningham D J C, Robbins P A, Wolff C B. Integration of respiratory responses to changes in alveolar partial pressures of CO2 and 02 and in arterial pH. In: Cherniac N, Widdicombe J, eds. Handbook of physiology, section 3: the respiratory system. Vol II. Control of breathing, part 2, Bethesda: Americal Physiological Society, 1986: 457-527. 2. Goodman N W. Control of breathing - effects of anaesthesia. In: Brown B R, Prys-Roberts C, eds. International practice of anaesthesia (incorporating general anaesthesia, 6th ed). Oxford: Butterworth Heinemann, 1996: ch 58. 3. Von Euler C. Neural organisation and rhythm generation. In: Crystal R, West J, eds. The lung: scientific foundations. New York: Raven Press, 1991: 1307-1318. 4. Goodman N W, Black A M S, Carter J W. Some ventilatory effects of propofol as a sole anaesthetic agent. Br J Anaesth 1987; 59: 1497-1503. 5. Mapleson W W, Rendell-Baker L, Thompson P W, eds. Automatic ventilation of the lungs. Oxford: Blackwell Scientific, 1959. 6. Clutton-Brock T, Hutton P. In: Brown B R, Prys-Roberts C, eds. International practice of anaesthesia (incorporating general anaesthesia, 6th ed). Oxford: Butterworth Heinemann, 1996: ch 158. 7. Greenbaum R. Safety and standards in anaesthesia. In: Brown B R, Prys-Roberts C, eds. International practice of anaesthesia (incorporating general anaesthesia, 6th ed). Oxford: Butterworth Heinemann 1996: ch 151. 8. Black A M S. Old hat and old hands in controlling breathing (part 1): the drives to breathing. Current Anaesthesia and Critical Care 1997; 8: 214-220.
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9. Drummond G B. Mechanics of breathing - effects of anaesthesia. In: Brown B R, Prys-Roherts C, eds. International practice of anaesthesia (incorporating general anaesthesia, 6th ed). Oxford: Butterworth Heinemann, 1996: ch 59. 10. Nimmo A F, Drumond G B. Respiratory mechanics after abdominal surgery measured with continuous analysis of pressure, flow and volume signals. Br J Anaesth 1996; 77: 317-326. 11. Black A. Tools for increased safety in the management of severe postoperative pain. In: Chrubasik J, Cousins M, Martin E, eds. Advances in pain therapy II. Springer Verlag, 1993: 226-240. 12. Black A, Habib N, Goodman N, Prys-Roberts C O, Dixon J,
Kunst G. Discriminating information in uncalibrated respiratory inductance plethysmography. Br J Anaesth 1997; 78:471P. 13. Tobiu M J, Mador J, Guenther S M, Lodato R F, Sakner M A. Variability of resting respiratory drive and timing in healthy subjects. J Appl Physiol 1988; 65:309-317. 14. Shea S A, Homer R L, Benchetrit G, Guz A. The persistence of a respiratory 'personality' into stage IV sleep in man. Respir Physiol 80: 33-44. 15. Galletly D C, Larsen P D. Coupling of spontaneous ventilation to heart beat during benzodiazepine sedation. Br J Anaesth 1997; 78: 100-101.
(1997) 8, 221-230
© 1997 HarcourtBrace & Co Ltd
Focus on: Basic science/homeostasis m e c h a n i s m s
Old hat and old hands in controlling breathing (part 2): translating ventilatory drive into breathing
A. M. S. B l a c k
The generation of spontaneous respiratory rhythm The first of these essays considered what might be an anaesthetist's practical perspective on the classical descriptions of the drive to breathing. These are in terms of minute ventilation (VM) but ventilation must be partitioned into tidal volume (VT) and breathing rate (f), of which the inverse, the total respiratory period (Ttot), must be partitioned into inspiratory period (TO and expiratory period (TE) The influence of mechanical constraints on the partitioning of ventilation is as familiar to anaesthetists having to ventilate patients as it was to classical physiologists studying spontaneous breathing. For instance, resistive loads to breathing are best met with slow deep breaths, and elastic loads by small frequent breaths. Physiologists have teased a bewildering number of inflation and deflation reflexes from the respiratory tract, intrathoracic vasculature and chest wall. Some are plausibly understandable and some seemingly paradoxical. It is unclear whether they should be considered in isolation or whether they should be viewed as components which in concert help to transform a respiratory drive into a breathing pattern based on an appropriate functional residual capacity. It was once popular for respiratory physiologists to regard ventilation as a 'drive' characterized as mean inspiratory flow (VT/T~) and a 'duty cycle' (Ti/Ttot). 1'2 Von Euler 3 proposed a classical descriptive model to explain some externally observable effects: an 'on switch' begins inspiration, during which there is a progressive increase in inspiratory activity at intensity deter-
Dr A. M. S. Black, Consultant SeniorLecturer, Sir HumphryDavy Department of Anaesthesia, Bristol RoyalInfirmary,Bristol BS2 8HW, UK. 221
mined by the drives to breathing until an 'off switch' is triggered after an interval (T~) that depends to some (species-dependent) extent on reflex feedback from the lungs and chest wall. The period between the operation of the off switch and the next on switch (TE) is separately determined. These physiological concepts have their counterparts in the controls on the ventilators used in anaesthesia and intensive care (see below). Most general anaesthetic agents reduce minute ventilation by a combination of reduction in mean inspiratory flow that overrides a tachypnoea attributable mainly to a shortening of TE.2 If, for example, apnoea is caused by induction of anaesthesia with propofol as a sole agent, 4 it is often preceded by a briefly observable tachypnoea that is seen also in the first discernable breaths as breathing is re-established: this is as though the tachypnoeic tendency underlies the whole apnoea but is submerged by a temporary 'zeroing of the gain' on breath size. The tachypnoea caused by intravenous or volatile anaesthetic agents used alone may be misconstrued as a response to pain but, whatever its cause, titration to a satisfactory rate by increments of a suitable opioid is a simple and effective strategy. The rhythm generation underlying tidal breathing resides anatomically in more or less overlapping groups of ueurones in the brainstem) Progress towards their identification began with ablation and stimulation experiments, and progressed to microelectrode recordings. There are several functionally distinct types of cells in pons and medulla, some anatomically distinct and others intermingled with other types of respiratory neurones. Different types can be distinguished by the phase of the breathing cycle at which they are spontaneously active or at which they can be recruited or suppressed by known nervous and pharmacological inputs: the rhythmgenerating neurones may be hard to distinguish from
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CURRENT ANAESTHESIA AND CRITICAL CARE
neurones with other respiratory and para-respiratory functions, such as the motoneurones to the muscles of the upper airway or cell bodies of the descending tracts to spinal respiratory motoneurones. Determining the interconneetions between the neuronal populations is a matter of educated guesswork. Several neural network computer models have been suggested with inherent oscillatory activity that results from interconnections and is fuelled by input from the general nervous traffic passing up and down the brainstem. The test of any model is its ability to simulate responses to as wide a range of inputs as possible. A caveat on any interpretation must be that some form of anaesthesia or decerebration is needed for any study of this sort, and these must inevitably alter the characteristics of the system being studied. There is further scope for using the effects of different combinations of anaesthetic and analgesic drugs to increase the range of effects that need to be correctly simulated: the underlying hope would be that a model that can successfully simulate the effects of a sufficiently wide range of nervous and pharmacological inputs can be a plausible basis for extrapolation to behaviour in the absence of anaesthesia. Any such hope presupposes that there will be a continuum of dose-related response to anaesthetic and related drugs rather than a neural switch between one category of behaviour and another: a hypothesis that has yet to be adequately tested.
The generation of inspiratory gas movement The descending output of the brainstem generators of inspiratory rhythm is detectable in the spinal cord as the central respiratory drive potential that plays upon the segmental motoneurones of the muscles involved in respiratory movement. Its effects via muscles are measurable as the airway pressure when airflow is occluded during attempted inspiration. In conscious subjects, airway occlusion will excite an augmented inspiratory effort by about 200 ms, which is why the pressure after 100 ms (P0.~) became established as a tool for physiological investigation. In the face of varying mechanical loads to breathing, P0.1 correlates better with the integrated phrenic neurogram than does the mean inspiratory flow of the preceding unoccluded breaths. However, the relationship with the neurogram is still not unique but depends on the shape and volume of the lungs. Measurement of P0.1 is now offered as an option in modern state-of-the-art ventilators, though its value as an aid to weaning remains to be established: we are moving away from measurements to help us guess the best time for an all-or-nothing attempt to discontinue ventilatory support, and more towards a gradual approach to weaning based on observed success or failure in coping with a stepwise withdrawal of support. For the anaesthetist, the linkage of neuromuscular output to gas movement through a pressure identifies the ribcage and diaphragm as a pressure generator - not the familiar constant positive inspiratory pressure generator,
but a generator with feedback by which negative intrapleural and alveolar pressures can be varied within and between breaths so that the resulting ventilation achieves physiologically set targets. Figure 1 is a classical depiction of the pressures across the components of the respiratory system as the lung volume is altered by inspiration during positive-pressure or spontaneous breathing. The pressure across the respiratory system (Pr~) at any time is the sum of the pressures across the chest wall (Pc) and the lungs (Pl). At FRC, the inward recoil of the lungs is balanced by the outward recoil of the passive chest wall (Pc ~esting), creating a negative end-expiratory pleural pressure (ppm). During positive-pressure breathing, the pressurevolume relationship of the passive chest wall remains fixed and the pressure across the respiratory system (P~ ~Pev) follows the thick diagonal arrow: it is less than the pressure required to inflate the lungs until the chest wall has been inflated to its natural unstressed volume, and thereafter exceeds the lung-inflating pressure by the additional amount required of inflate the chest wall above its natural volume. The peak inspiratory airway pressure (Paw1) for a given tidal volume is the sum of the pressures required to inflate the chest wall and abdomen to that tidal volume. During spontaneous breathing, the activity of the inspiratory muscles generates the inspiratory pressure to inflate the lungs. It does so by shifting the pressurevolume relationship of the chest wall upwards and to the left. With an open airway, the surrounding atmosphere provides an infinite reserve of flow to respond to the pressure generation (see later). At the peakinspiratory instant of zero flow, the intersection of the active pressure-volume relationship (Pc with inspiratory effort) with the dotted line (-P1) indicates the peak inspiratory pleural pressure (PplI), which is what inflates the lungs to the corresponding tidal volume. The pressure across the respiratory system (Pr~ spont ventilation) follows the more vertical thick arrow. The time course of these changes during spontaneous and positive-pressure inspiration is indicated in Figure 2.
Artificial production of inspiratory gas movement Anaesthetists' postgraduate training requires that they have some formal familiarity with the simple concepts (enunciated by Mapleson) s of artificial ventilators as constant flow or constant pressure generators. 5 In constant flow generators, flow is the independent variable and the time course of the alveolar and airway pressures depends on the flow and the mechanical properties of the lung and chest wall (Fig. 3). In a constant pressure generator, pressure is the independent variable and the flows and volumes depend on the mechanical properties of the lung and chest wall (Fig. 4). This means that flow generators have flow knobs and pressure generators have pressure knobs, and a ventilator that has both knobs can be used in either mode.
CONTROLLINGBREATHING,PART 2 223 A constant flow generator effectively connects the lung during inspiration to a very large reserve of pressure through a resistance that is controlled by the flow knob (Fig. 3). For a sufficiently high driving pressure, the change from end-expiratory to peak inspiratory pressure in the lungs will have a negligible effect on the pressure difference across the resistance: a more or less constant pressure exerted across a constant resistance will give a more or less constant flow. By contrast, a pressure generator connects the lung to the anticipated pressure needed to inflate it to the required tidal volume (Fig. 4). The resistance and compliance of the lung and chest wall determine how quickly and completely the tidal volume is delivered. Pressure generators must have
a large reserve of flow capacity in order to maintain the set pressure in the face of whatever flows and volumes can be accommodated by the mechanical properties of the ventilated system and whatever flows are lost through leaks (which are effectively an infinite compliance accessed by a resistance that may or may not be finite). Some ventilators appear not to fit the recognizable extremes of the Mapleson classification. For instance, many anaesthetists seem satisfied with classifying the classic Manley ventilator as a 'minute volume divider' as though this description precludes classification in, or logical connection with, any other category. But, properly operated, the classic Manley connects the lungs without an intervening resistance to a pressure that is
Patm
I
I
Palv- Patm = Prs = Pl + Pc = (Palv - Ppl) + ( P p l - Paun)
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inspiratory effort
. ~
%
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A ;,..U 0
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Tidal volume
0@"
\ Fig. 1 The pressure across the respiratory system (Chest-wall and Lungs) during active inspiration (spontaneous ventilation) and IPPV. P~rv= alveolar pressure, P,tm = atmostpheric pressure, Prs = pressure across respiratory system, P~ = pressure across lungs, Pc = pressure across chest-wall, Pp. = intrapleural pressure, P,w = a i r w a y pressure (IPPV). Breathing phase phase subscripts: I = peak inspiratory, E = end-expiratory.
l
224
CURRENT
ANAESTHESIA
AND
CRITICAL
CARE
.-llb // /,/
Spontaneous
/I
-I-
I
IPPV
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i
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r
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Fig. 2 Time courses of pressures in the respiratory system during spontaneous inspiration and lung inflation by IPPV. Key: see Fig. 1.
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INSPIRATION
Flow
Volume
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Volume & I / C Pressure
:
Fig. 3
Time
Generation of inspiratory flow in a constant flow
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only modestly (2 or 3 times) greater than the pressure required for the desired tidal volume, but limits the tidal volume that can be delivered and allows enough time for delivery to be followed by an inspiratory hold (with zero flow) at a pressure determined by the delivered volume and the stiffness of the lungs. If they have to be classified, they might be called generators of either a non-constant flow or a non-constant pressure. Constant flow generators have been the traditional preference in anaesthesia and intensive care. Provided there are no great leaks or compliance losses in the breathing system, the delivery of a set flow or volume could be guaranteed in the face of whatever changes there may be in the mechanical properties of the respiratory system. With constant pressure generators, the tidal volumes need to be measured with each change of ventilator setting or mechanical loading to ensure that the desired tidal volumes are being delivered: this was tiresome and inconvenient with the mechanical Wright's respirometers that were the clinical mainstay of tidal volume measurement. 6 Like many other anaesthetic traditions, the preference for flow generators has outlived its appropriateness, undermined as it has been by advances in technology and professional recommendation. The minimum standards of monitoring in anaesthesia require expired volumes to be measured irrespective of the type of ventilator that is in use, and electronic flow/volume meters are conveniently built in to modern breathing systems] Besides, if capnography
C O N T R O L L I N G BREATHING, PART 2
225
..""""""""..........7
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is available 6 (though it is not explicitly required), the anaesthetist has access to end-tidal PCO2: a much more appropriate measure of the adequacy of ventilation as balanced by the CO 2 production. 8 Pressure-generating ventilators were traditionally limited to paediatric anaesthesia, because of their ability to cope with the necessary leaks round uncuffed endotracheal tubes, but their reserve flow capacity gives them an overwhelming advantage that has been recognized by the more enlightened intensive care units. The flow capacity allows ventilators to deliver unrestricted flows and volumes of gas to those patients who are able to breathe (i.e. to produce phasic alterations in the pressurevolume relations of their respiratory system; Figs 1 and 2). The first pressure generators made this flow capacity available only during inspiration, but their modern successors make it available throughout the respiratory cycle. Patients can exercise their respiratory muscles while the airway pressure is cycled between a higher and lower positive pressure, the differences in pressure supporting the ventilation and the area under the pressure time course supporting gas exchange (Fig. 5). The two features can be varied independently to tailor respiratory support to the requirements for each of its components. Synchronization of the higher pressure with inspiratory effort is not absolutely necessary but, if it is wanted,
ventilators with a freely available capacity for flow can detect inspiratory demands directly as flow rather than by their potentially more reflexogenic pressure effects in a closed system. New generations of pressure-generating ventilators are already in prospect that can use servo principles to vary the pressure generated within breath so as to produce a specified tidal volume in the face of changing mechanics of the respiratory system, but the more logical use of PCO 2 as the feedback signal awaits the development of a reliable continuous monitor of arterial PC02 or some suitable surrogate thereof.
Artificial generationof breathingpattern The generation of breathing by an artificial ventilator requires cycling from inspiration to expiration within a total respiratory period that is set in one way or another. Mapleson's classic treatise 5 contains references to endinspiratory cycling by pressure or volume in addition to time, but a glance round the modern range of available ventilators should make it clear that time-cycling is the only sensible option. A moment's reflection should be enough to clarify that pressure-cycling of a constant pressure generator will result in a TI of either 0 or infinity, volume cycling will give a Tr that varies up to
226
CURRENTANAESTHESIAAND CRITICALCARE
Support for pulmonary ventilation (normocapnia)
I IPPV P r e s s u
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Increases FRC & compliance Improves V/Q distribution
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r e Support for pulmonary ventilation and gas exchange Fig. 5 Supports for different components of respiratory compromise.
infinity and that the T r for time-cycling should be at least three times the time constant of the respiratory system (so that 95% of the possible tidal volume will be delivered; Fig. 4). A flow generator that is pressure-cycled loses the perceived advantage that a set volume can be delivered; it also loses control of the timing of inspiration. With one that is volume-cycled, one must double inspiratory flow (~ri) as one doubles the s e t V T if one wishes to leave TI unaltered and double minute ventilation (VM). With a time-cycled constant flow generator, a doubling of VI will double X)M with no additional adjustments. However, a flow generator can usefully be volume-limited as well as time-cycled (Fig. 6).
A philosophy of knobs
On the principle that it is better to sit and think rather than just sit, meditation on the number of knobs on intheatre ventilators is good for the soul. Thus, anaes-
thetists control pulmonary ventilation (VM) in order t o control end-tidal or arterial P C O 2. 1 # ~rM = V T X f or "QM= VT × (Ill'tot) Either expression for Vr~ has three variables. If any two are fixed, so is the third: there are two degrees of freedom, and two knobs (besides the on/off knob) would be enough to control all three ventilatory variables. With a minute volume divider, VM would be set, and setting either f o r V T would set the other of the pair; alternatively one could have a VT knob and f knob, and V M would be the dependent variable. With a two-knob ventilator, one would have no control over the I:E ratio. This third degree of freedom in control would need a third knob on the ventilator, but there is some choice in the functions to be assigned to each knob. If Trot is already determined, the addition of a T I knob would indirectly determine T E ( T E = Tto t - TI) or the addition of an I:E knob would indirectly determine both T~ and T E.
CONTROLLINGBREATHING,PART 2 227
Volume-limited time-cycled flow generator
~me-cycled flow generator
~,
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o
I
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m
~
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i • ~*~
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Time-cycledflowgeneratorandvolume-limitedtime-cycledflowgenerator.
TI = Trot/[TE:T: + 1] and T E - T,ot/[T::T~ + 1].
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i- * ~ VOlume& I/C |.-
(1/[T~ + {Tto,- T:}])
Alternatively, the three knobs could consist simply of an inspiratory flow ('VI) knob, a T~ knob and a T E knob, as in the Penlon 200 ventilator, so that VM = (9~ X TI) x (1/[T: + TE]) A three-knob constant flow-generating ventilator will not allow for any inspiratory hold. This would require a four-knob ventilator, which could function as a volumelimited, time-cycled flow generator (Fig. 6). As with a three-knob flow generator, there is a wide choice about which functions can be assigned to which knobs, but there will still be only four degrees of freedom. For example, a Drager Narkomed 2 ventilator has a V~ knob, anfknob, an I:E knob and a Vr-limiting knob. The inspiratory flow will continue, only until the set VT has been delivered. Provided the V: has been set high enough to deliver it within the indirectly set T~ (see above), there
will be an inspiratory flow period T:(~ow)and an inspiratory hold period T:(hold); if not, the volume limit does not apply and the ventilator will function as a three-knob ventilator (time-cycled flow generator). For the controls on the Drager ventilator, the equation for "~M would be expressed as xOM
~-~ (91X =
T:(~o.~))× (I/[T:(~qw)+ T~(hold) + TEl)
(v(ZI X V T / V I ) x ( 1 / [ V T / V I -[-
{T: -
VT/V:} + TB])
In the Servo ventilators in flow-generating mode, there is a VM knob, an f knob, an I:E knob and an inspiratory hold knob. In the classic Manley ventilators, the rotameters on the anaesthetic machine serve as a composite "VMknob and the V T is limited by the trigger setting on the curved V T slide (which indirectly sets the minimum f and the maximum Ttot): the T I is set within the s e t Ttot by the T I slide, and the speed at which the VT is delivered is set by adjusting the mechanical advantage of the weight on the bellows. If the weight is far enough out for the bellows to empty the set VT, the Manley will operate as a volume-limited time-cycled non-constant flow or pressure generator (see above), but if the weight cannot generate enough pressure to empty the bellows, the set V T limit does not apply, nor the time-cycling that depends on it. The Manley ventilator 'chatters', func-
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tioning as a constant pressure generator that is cycled indirectly by the volume that the pressure can deliver. Though four knobs are needed for a constant flow generator to produce an inspiration with a flow phase and a hold phase, a constant pressure generator can approximate this with three knobs: one to set the pressure, one to set the f o r Ttot and one to set the T I. If the T~ is set at three times the time constant of the respiratory system (resistance times compliance) and if the gas delivery is approximately monoexponential, the ventilator will deliver about 95% of the V T producable by the set pressure and the compliance: 67% of the producable V T will be delivered in the first time constant, and 85% by the second, so that only about 10% of the producable VT will be delivered in the last time constant. This is a fair approximation to an inspiratory hold. The missing degree of freedom over the four-knob flow generator is that the shape of the inspiratory flow profile is fixed by the time constant of the respiratory system so that the ratio of the notional Tmo w to the notional Tmold cannot be varied independently.
Ribcage and abdominal contributions to tidal volume As well as the partitioning of VM between VT and f, there is a partitioning of Vr between the contribution from the ribcage and the abdomen. 9 For research, it is conventional to measure some externally measurable change in a ribcage dimension (A~c)and abdominal dimension (AAB), and to express Vr as a weighted sum of these measurements VT = A. ARc + B.AAB where the weights A and B are 'volume-motion' coefficients that are estimated by calibration against a directly measured VT. The relative contributions of ribcage and abdomen will clearly depend on mechanical loadings. For example, the supine posture favours relatively more ribcage movement, an effect accentuated by advanced pregnancy. Anaesthetists are used to observing and interpreting clinically observed movements of ribcage and abdomen. Normally, both expand synchronously, but 'paradoxical breathing' is an important clinical sign. For instance, patients with a transection or transverse myelitis of the spinal cord at a high thoracic level, or a high spinal anaesthetic, can breathe only with their diaphragm: because their intercostal muscles cannot stabilize their ribcage against the negative pressure generated by the diaphragm, the ribcage is drawn in as the diaphragm pushes the abdomen out. Such paradoxical breathing is seen more often with upper airway obstruction, arising because the diaphragm has a better mechanical advantage than the ribcage muscles. But paradoxical breathing does not reliably indicate that breathing is obsmacted (even in patients with normal spinal cords). Anaesthetized patients tend to use their expiratory muscles to assist in expiration, and the offset of that expiratory effort
allows an abdominal expansion in early inspiration that is often accompanied by some indrawing of the ribcage. The general lesson is that ribcage and abdominal movements cannot be interpreted reliably without additional information from intrathoracic (intra-oesophageal) and intra-abdominal (intragastric) pressures and, even with electromyography of the diaphragm and abdominal wall, interpretation can be equivocal. Thus the interpretation of chest wall movements from the measurements that can be made clinically is often likely to be questionable, in particular inferences of respiratory obstruction from degrees of paradox between ribcage and abdomen. 9'1°
Monitoring spontaneous breathing Basic sciences information is desirable in clinical medicine for predicting avoidable disaster. But prediction is only guesswork, educated more or less. Tendencies may be predictable but the confidence intervals on individual prediction can be wide. When individuals are at particular risk, no amount of education can substitute for continuous vigilance and preparedness to intervene when necessary. The vigilance may depend on the special senses of personal attendants or on instruments intended to complement, supplement or replace personal contact. Monitoring spontaneous breathing during anaesthesia is not particularly problematical, 6 particularly since the advent of the laryngeal mask airway, through which one can capture the tidal gas flows for the purposes of measurement and gas analysis. The presence of a vigilant anaesthetist assisted by instrumental monitoring provides the greatest assurance of safety. True, the measurement of expired volume may be somewhat inaccurate, as may be the estimation of P a C O 2 from end-tidal PCO2, especially in patients with abnormal lungs or rapid shallow breathing. But apnoea is likely to be detected well before, or very soon after, it becomes a threat to oxygenation. There is no need to resort to physiology and pharmacology to inform one's guesswork on the likelihood of apnoea. Applying the minimum standards of anaesthetic monitoring to all patients detects the occasional few who actually do stop breathing, and remedial action can be taken easily. There is always an anxious few seconds after removal of an artificial airway, when instrumental monitoring may be reduced to a pulse oximeter: one's eyes and ears are the most immediate monitors, and poor lighting and background theatre noise heighten anxiety. There is a more prolonged but much lower grade of worry over the large number of postoperative patients who are nursed on general wards and who have to share the attentions of a barely adequate number of nursing staff. The worry is heightened over candidates for unavailable high dependency care: the elderly, infirm and recipients of novel and possibly controversial forms of pain relief. The anxiety of the medical and nursing attendants could be relieved and pain relief could be more confidently supplied if there were some instrumental means of monitoring spontaneous breathing that
CONTROLLING BREATHING, PART 2
did not involve invading the airway. Pulse oximeters are the best available and can probably be improved by development of detector probes that can be more securely attached, but they detect the effects of breathing disturbances somewhat downstream - later than the disturbances themselves. Devices that detect fluctuations in pressure or CO2 concentrations at the mouth or nose suffer from the need to monitor both orifices in most people to avoid false alarms when the unmonitored orifice is being used. 11 Approaches such as respiratory inductance plethysmography that depend on calibrating the change in no more than two externally measured dimensions of the chest wall are plagued by the impossibility of maintaining stable volume-motion calibrations. A very accurate calibration would be needed, for instance, to detect a totally obstructed breath in which abdominal expansion would have to be detected as exactly equal and opposite to the indrawing of the ribcage. It is a justifiable expectation that incorporating an increased number of externally measured dimensions into some already available imaging approach could build up a three-dimensional real-time picture of the chest wall that would not need calibrating. But the venture capital for such an enterprise awaits demonstration that there would be a worthwhile return on investment, which implies that the resulting monitor would return sufficiently meaningful information with such minimal inconvenience that it would excite an overwhelming demand from clinical practice. The best current contender for clinical interest relies on an impedance-based indication of one external dimension, a microphone over the trachea and a pulse oximeter. The respiratory monitor of the future will probably have to contend with the problem of making itself wireless, to avoid tangling or even strangling the patient. The technology exists for some sort of radio frequency transmission between a monitor on the patient and a receiver at the bedside, but it may be difficult to find enough frequencies that do not interfere with each other or with other communication devices. Meanwhile, a persistent few (who include myself) pursue what information there might be in uncalibrated respiratory inductance plethysmography. 12 It is established that the patterning of breathing in individual patients is a fairly stable characteristic, ~3'14possibly more so than their sensitivity to CO~ or the ventilation/PCO2 set point about which they regulate their breathing. The question is whether there are patterns of breathing within an individual's 'signature tune' that indicate some fragility in his or her control of breathing that might predispose to either central or obstructive apnoea. There are several conventional statistical and machine-learning approaches to data analysis that might reasonably be applied to this problem, but collecting the data in clinical conditions is enormously time-consuming, and any set that has been successfully collected 1° is immensely valuable. Whether the important information (if it exists) is confined to respiratory signals is a question worth
229
considering. Respiratory sinus arrhythmia is a longrecognized phenomenon. A more recent intriguing observation is that the start times of individual breaths may be linked to the timing of individual heart beats or vice versa. Is The extent to which such observations result from interplay of peripheral reflexes or the intermeshing of central neuronal mechanisms probably varies from situation to situation but, because its absence in conscious people seems to have adverse prognostic significance, it is unlikely to be a mere accident of the way the respiratory and cardiovascular systems have been put together. The existence and prognostic significance of sinus arrhythmia suggests an interesting general hypothesis that many diverse aspects of bodily wellbeing or ill-health are related to active 'connectivity' between the functioning of the subsystems of the body.
Conclusion: final connections One corollary of 'connectivity' is that stable homeostasis through feedback control, despite its appearance of being a default state except in the critically ill, requires active and continuous intercommunication. (The analogous contrast is between the traditional design of aircraft to be inherently stable and the design of modern fighter aeroplanes in which stability has to be actively and continuously imposed by complex technological interplay as a price for manoeuvrability.) A second corollary is the final reflection for this paper, which is to question the traditionally perceived advantages of basic biological scientists in exploding living systems to study their components separately. Clinicians have as much opportunity and a clear obligation to be basic scientists by pursuing holistic study of their patients and their circumstances.
References 1. Cunningham D J C, Robbins P A, Wolff C B. Integration of respiratory responses to changes in alveolar partial pressures of CO2 and 02 and in arterial pH. In: Cherniac N, Widdicombe J, eds. Handbook of physiology, section 3: the respiratory system. Vol II. Control of breathing, part 2, Bethesda: Americal Physiological Society, 1986: 457-527. 2. Goodman N W. Control of breathing - effects of anaesthesia. In: Brown B R, Prys-Roberts C, eds. International practice of anaesthesia (incorporating general anaesthesia, 6th ed). Oxford: Butterworth Heinemann, 1996: ch 58. 3. Von Euler C. Neural organisation and rhythm generation. In: Crystal R, West J, eds. The lung: scientific foundations. New York: Raven Press, 1991: 1307-1318. 4. Goodman N W, Black A M S, Carter J W. Some ventilatory effects of propofol as a sole anaesthetic agent. Br J Anaesth 1987; 59: 1497-1503. 5. Mapleson W W, Rendell-Baker L, Thompson P W, eds. Automatic ventilation of the lungs. Oxford: Blackwell Scientific, 1959. 6. Clutton-Brock T, Hutton P. In: Brown B R, Prys-Roberts C, eds. International practice of anaesthesia (incorporating general anaesthesia, 6th ed). Oxford: Butterworth Heinemann, 1996: ch 158. 7. Greenbaum R. Safety and standards in anaesthesia. In: Brown B R, Prys-Roberts C, eds. International practice of anaesthesia (incorporating general anaesthesia, 6th ed). Oxford: Butterworth Heinemann 1996: ch 151. 8. Black A M S. Old hat and old hands in controlling breathing (part 1): the drives to breathing. Current Anaesthesia and Critical Care 1997; 8: 214-220.
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9. Drummond G B. Mechanics of breathing - effects of anaesthesia. In: Brown B R, Prys-Roherts C, eds. International practice of anaesthesia (incorporating general anaesthesia, 6th ed). Oxford: Butterworth Heinemann, 1996: ch 59. 10. Nimmo A F, Drumond G B. Respiratory mechanics after abdominal surgery measured with continuous analysis of pressure, flow and volume signals. Br J Anaesth 1996; 77: 317-326. 11. Black A. Tools for increased safety in the management of severe postoperative pain. In: Chrubasik J, Cousins M, Martin E, eds. Advances in pain therapy II. Springer Verlag, 1993: 226-240. 12. Black A, Habib N, Goodman N, Prys-Roberts C O, Dixon J,
Kunst G. Discriminating information in uncalibrated respiratory inductance plethysmography. Br J Anaesth 1997; 78:471P. 13. Tobiu M J, Mador J, Guenther S M, Lodato R F, Sakner M A. Variability of resting respiratory drive and timing in healthy subjects. J Appl Physiol 1988; 65:309-317. 14. Shea S A, Homer R L, Benchetrit G, Guz A. The persistence of a respiratory 'personality' into stage IV sleep in man. Respir Physiol 80: 33-44. 15. Galletly D C, Larsen P D. Coupling of spontaneous ventilation to heart beat during benzodiazepine sedation. Br J Anaesth 1997; 78: 100-101.