Department of Surgery and Anaesthesia, Wellington School of Medicine, PO Box 7343, Wellington, New Zealand
Corresponding author. E-mail: peter.larsen@wnmeds.ac.nz LMA® is the property of Intavent Limited.
Accepted for publication: February 24, 2003
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Abstract |
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Methods. We investigated the variables of inspiratory duration (TI), expiratory duration (TE), and tidal volume (VT) where respiratory period variation was bimodal. In 25 anaesthetized spontaneously breathing subjects we took 11 samples of recording where the variation of respiratory period was quantal.
Results. In eight of these epochs the variation in respiratory period was associated with fluctuations in the number of heart beats per breath (entrainment ratio) with a constant time interval between inspiration and the immediately preceding heart beat (coupling interval), which we define as pattern II coupling. During pattern II coupling, the quantal variations in respiratory period were entirely caused by variation in TE, with no associated changes in either TI or VT. The other three epochs with quantal variations in respiratory period were observed in pattern III coupling, where an alternating fluctuation in both entrainment ratio and coupling interval occurs. During pattern III coupling, quantal fluctuations were observed in TE, TI, and VT.
Implications. Cross correlation analysis suggested that when pattern III was present, TI was dependent upon the preceding TE, which differs markedly from traditional views on the interaction between inspiratory and expiratory duration. VT was linearly related to TI, and so could also be determined by the preceding TE during this type of coupling.
Br J Anaesth 2003; 91: 1849
Keywords: cardiorespiratory system, synchronization; ventilation, control
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Introduction |
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During spontaneous breathing under general anaesthesia, each of the primary respiratory variables (TI, TE, and VT) most commonly fluctuates about a mean value with a normal, unimodal distribution.48 However, in 1995 Goodman describes a bimodal breath-to-breath respiratory frequency in patients breathing spontaneously under general anaesthesia.9 The bimodality was caused by breath-to-breath changes in TE, and was not associated with significant changes in either TI or VT, both of which had normal, unimodal distributions.
We have described a phenomenon that we have called cardioventilatory coupling, where the onset of inspiration occurs a fixed time interval after an ECG R wave.1014 We have argued that this coupling is caused by the immediately preceding heart beat triggering the onset of inspiration. A mathematical model based upon this hypothesis can generate the patterns that are seen clinically.15 We have suggested that coupling is responsible for much of the breath-to-breath seen during spontaneous breathing under general anaesthesia, including the bimodality described by Goodman.10 11 16
Breath-to-breath variation associated with cardioventilatory coupling can be described in terms of two factors, the consistency of the coupling interval (the interval between inspiration and the immediately preceding heart beat, termed the RI1 interval), and the consistency of the number of heart beats within each breath (entrainment ratio).10 11 Where both coupling interval and entrainment ratio are constant (pattern I coupling) we have shown that breath-to-breath ventilatory variability is small.11 There are two circumstances in which bimodal (quantal) breath-to-breath respiratory frequency variability is seen. One of these, which we have termed pattern II coupling, is where the coupling interval is constant, but the entrainment ratio varies between breaths. Changes in the entrainment ratio with a constant coupling interval results in a change in ventilatory period corresponding to one or more heart periods. The second circumstance in which quantal breath-to-breath variation is observed we have termed pattern III coupling. During pattern III coupling we observe an alternating fluctuation in both entrainment ratio and coupling interval.10 11 In the case of pattern III coupling, the breath-to-breath fluctuation in ventilatory period is a little less than one heart period, as coupling interval is reduced when the entrainment ratio increases.
We have not investigated previously the relationship between cardioventilatory coupling and any respiratory variable other than inspiratory timing. This study examined the breath-to-breath changes in TI, TE, and VT that occur during cardioventilatory coupling. We chose to look at these changes during the quantal respiratory variation seen in pattern II and pattern III coupling, on the basis that when respiratory period changes significantly and repeatedly, changes in TI, TE, and VT would be easiest to detect. Understanding the influence of cardiac activity on both inspiratory and expiratory duration and tidal volume could improve understanding cardioventilatory coupling in respiratory control, and into the regulation of respiratory timing and respiratory drive.
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Methods |
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All subjects lay supine and were anaesthetized with propofol (3 mg kg1 i.v.) over 30 s. Patients then breathed isoflurane 1% in nitrous oxide 66% and oxygen 33% via a facemask and circle absorption system. A laryngeal mask airway (LMA) was inserted after approximately 2 min.
We measured arterial oxygen saturation (SpO2), end tidal carbon dioxide (Datex Oscar, Datex-Ohmeda, Helsinki, Finland), non-invasive arterial pressure (Dinamap), and ECG (lead CM5, Corometrics Neo-trak 502, Corometrics, CT, USA) in all the patients.
Ventilatory airflow was measured by incorporating a pneumotachograph (Hans Rudolph 4813) connected to a differential pressure transducer (Vacumed 4500, Vacumetrics, CA, USA) between the tracheal tube and the circle absorption system. The ECG and flow signals were digitized at 500 Hz using an A-D conversion board (DAQCard 516, National Instruments, Austin, TX, USA) and recorded a Macintosh G3 laptop computer. Data recording began after a stabilization period of 5 min after laryngeal mask insertion and was for a minimum of 10 min duration before surgery.
Data analysis
The method for determination of cardioventilatory coupling has been described previously.11 From the stored ECG and ventilatory signals we determined the time of each R wave and of the start of each inspiration. From these times we determined the interval between each R wave and the following start of inspiration (RI interval time series). R waves preceding inspiratory onset are given a negative suffix. Thus, the RI1 interval is the interval between inspiration and the R wave that immediately precedes it. The RI interval time series was plotted against the time of R wave occurrence (RI interval plot). In these RI interval plots, horizontal banding indicates cardioventilatory coupling as R waves have a constant time relation to inspiratory onset.
RI interval plots were examined by eye for epochs of at least 30 ventilatory periods that showed patterns I, II, or III defined as:
1. Pattern I. An epoch with at least 95% of breaths containing the same number of heart beats (i.e. identical entrainment ratio) and constant RI1 interval.
2. Pattern II. An epoch length in which entrainment ratio is fluctuating and RI1 interval is constant.
3. Pattern III. An epoch length in which the RI1 interval and the entrainment ratio alternated between two values from breath to breath, the RI1 interval for one breath was similar to that two breaths later.
For each breath, in addition to determining the time of inspiratory onset, we also determined the ventilatory period (inspiratory onset to next inspiratory onset), TI, TE, VT (by digital integration of inspiratory airflow), and VT/TI.
All data acquisition and calculation of variables was done using custom written software in Labview 5.1 (National Instruments). Data are presented as mean (SD).
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Results |
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Pattern II coupling
As described previously,11 pattern II epochs occurred at low respiratory frequencies (10.6 (3.3) bpm). During pattern II coupling, quantal variation in respiratory period was observed (Fig. 1), associated with variations in the entrainment ratio (number of heart beats per breath). The fluctuations in respiratory period were primarily from changes in TE, with little corresponding change in TI (Fig. 2). There was no statistical correlation between TE and either the preceding or following TI in any of the pattern II coupling epochs.
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Pattern III coupling
Pattern III coupling epochs were observed at greater respiratory frequencies than pattern II epochs (23.4 bpm, range 22.225.6). During epochs of pattern III coupling, quantal variation in respiratory period was associated with both alternating entrainment ratios and coupling intervals (Fig. 1). Unlike pattern II coupling, during pattern III coupling quantal variation was observed in both TE and TI, although these two variables changed in a reciprocal manner. Thus, for the example shown in Figure 1, the mean consecutive difference of the ventilatory period (0.46 s) was equal to the mean consecutive difference of TE (0.55 s) minus the mean consecutive difference of TI (0.09 s).
TI and TE were significantly related in all pattern III epochs. Cross correlation analysis showed that in all three cases the strongest statistical relationship was a positive correlation between TE and the following TI. That is, a short TE was followed by a short TI, whereas a long TE was followed by a long TI.
During pattern III coupling, VT was also bimodal. The relationship between VT and TI was linear (Fig. 3); shorter inspirations were associated with reduced tidal volumes, although the time series of VT/TI in Figure 1 does show a slight bimodal distribution. In the other two recorded pattern III epochs, the relationship between VT and TI was also linear, but the time series of VT/TI did not show the bimodal distribution seen in Figure 1.
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Discussion |
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The reciprocal changes in TI and TE observed during pattern III coupling suggest that successive breaths are differentially influenced by cardiac input. We have proposed that during pattern III coupling there is an alternating pattern of cardiac triggered and non-cardiac triggered breaths.15 According to such a model, the triggered breath would be preceded by a shortened TE, and following the early initiation of inspiration, TI would be shortened, while the non-triggered breath would follow a longer TE and be associated with a longer TI. The fluctuations observed in VT may be largely explained on the basis of changes in TI.
If the early initiation of a breath caused by coupling were associated with a reduced TI (and therefore also a reduced VT), then it is possible that in pattern I coupling, where every breath is initiated by a heart beat, every inspiratory period is reduced in length. Examining the pattern I epochs collected in the current study we found four instances where a single breath in the middle of a pattern I epoch appeared to be uncoupled. A representative example of this is shown in Figure 4. In this case the non-coupled breath (defined as the breath preceded by the shorter RI1 interval) was associated with a longer TI, slightly increased VT, and was preceded by a lengthened TE. Thus, the early triggering of breaths that occurs during pattern I cardioventilatory coupling appeared to be associated with a decrease in the preceding expiratory duration, and the subsequent inspiratory duration was as seen during alternate breaths in pattern III coupling epochs. The reduction in TI in turn tends to reduce VT of the triggered breath.
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Because cardioventilatory coupling is the early initiation of inspiration, one consequence of coupling is to increase the respiratory frequency. We have suggested previously that this increase in respiratory frequency may lead to an increase in minute ventilation if tidal volume was unchanged.15 However, any effect of the increase in respiratory frequency observed during coupling on minute ventilation is at least partially offset by the observed decrease in TI and the associated decrease in VT.
Several studies have shown that electrical stimulation of non-respiratory afferents or of specific brain stem regions during expiration can result in the early initiation of inspiration5 17 18 and, in one of these studies, the authors noted that the following inspiratory period was also reduced in length.18 It is therefore possible that there is a considerable range of afferents, both cardiac and non-cardiac, that are capable of the early initiation of inspiration, and that a general consequence of early inspiratory onset may be to shorten the subsequent inspiratory duration. Thus, under circumstances in which inspiration is triggered to occur early, by cardiac, locomotor, auditory, or other inputs, inspiratory duration and tidal volume will depend upon the preceding expiratory duration as in pattern III coupling. This differs markedly from the more commonly described relationship between respiratory variables in which TI determines the following TE.2 4
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