continuous snoring, and may lead to some degree of hypoventilation. Episodes of ... positive airway pressure (auto-CPAP) for pressure titration and home .... pressure was approximately known, the technician could more quickly and easily ...
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Sleep Apnoea
Continuous Positive Airway Pressure Titration for Treatment of Obstructive Sleep Apnoea a report by
O r e s t e M a r r o n e and G i u s e p p e I n s a l a c o Sleep Laboratory and Clinical Unit, Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo
Breathing during sleep in patients with obstructive sleep apnoea (OSA) is
The traditional manual-titration procedure consists of repeated manual
characterised by episodes of upper-airway obstruction. These may consist
adjustments of the administered CPAP level during polysomnographic
of sequences of total (obstructive apnoeas) or partial (obstructive
monitoring, so as to identify an ‘optimal’ pressure level that keeps the
hypopnoeas) occlusion, with short intervals with intermittent heavy
upper airway open throughout all sleep time. This level has been variously
snoring and hyperventilation, during which an arousal is usually
identified and consensus has not yet been reached.5 In some older studies
recognised.1 Partial upper-airway obstruction may also be associated with
it was considered as a level reducing the apnoea/hypopnoea index (AHI)
a more stable breathing pattern, usually – but not always – associated with continuous snoring, and may lead to some degree of hypoventilation. Episodes of partial upper-airway obstruction are often followed by an
Breathing during sleep in patients with
arousal (respiratory-effort-related arousal).2 Continuous positive airway
obstructive sleep apnoea (OSA) is
pressure (CPAP) is able to counterbalance forces leading to upper-airway
characterised by episodes of upper-
narrowing or collapse. Its effect is proportional to the level that is administered. A low level of CPAP turns obstructive apnoeas into
airway obstruction.
obstructive hypopnoeas. Higher levels of CPAP eliminate hypopnoeas that are replaced by prolonged inspiratory flow limitation or continuous snoring, variably associated to each other. Further increases lead to
to fewer than 10 episodes per hour (10/h) or below 5/h. Later, it became
unobstructed breathing. As the level of CPAP-normalising breathing
common practice to increase the pressure so as to eliminate not only
pattern changes from subject to subject, it has always been common use
apnoeas and hypopnoeas but also snoring. More strict criteria require
to titrate CPAP before prescribing it.4 Today, not only the procedures to
that inspiratory-flow limitation is also eliminated.
3
titrate but also the need for titration itself are under discussion. This article briefly reviews arguments supporting different theses.
There is little evidence to adopt preferentially one particular definition of optimal pressure. The purposes of CPAP treatment are to eliminate
Oreste Marrone is Head of the Sleep Laboratory of the Institute of Biomedicine and Molecular Immunology of the National Research Council in Palermo, Italy. He is the author of approximately 200 publications, among which are more than 40 research articles that have been published in leading scientific and medical journals. His main subject of interest is obstructive sleep apnoea and his most important studies on this subject have concerned pulmonary haemodynamics during sleep, analysis and control of systemic blood pressure, use of automatic continuous positive airway pressure (auto-CPAP) for pressure titration and home treatment. Dr Marrone first studied sleep respiratory disorders and CPAP treatment at the Sleep Unit of the University of Sydney in 1984. Giuseppe Insalaco is Head of of the Clinical Unit of the Institute of Biomedicine and Molecular Immunology ‘A. Monroy’ (IBIM) of the Italian National Research Council (CNR) in Palermo, Italy. He has authored approximately 200 publications, many of which are peer-reviewed articles in leading scientific and medical journals. His research achievements are in the fields of airway obstruction, upper airway physiology and sleep apnoea. His main studies have concerned obstructive sleep apnoea, sleep and cardiorespiratory control at high altitude, upper airway muscle activity during wakefulness and sleep and nocturnal asthma. Dr Insalaco first studied sleep respiratory disorder diagnosis and treatment at the Department of Physiology and Sleep Unit at the University of Texas Medical Branch in Galveston.
symptoms consequent to upper-airway obstruction and to prevent cardiovascular complications. The degree of residual upper-airway obstruction that can be tolerated and produce the best results from treatment is unknown. Inter-individual correlation between AHI and sleepiness is imprecise, with some patients denying any sleepiness despite AHI >30/h, and others complaining of sleepiness despite very mild upperairway obstruction episodes, such as in the upper-airway-resistance syndrome.6,7 Residual mild upper-airway obstruction during CPAP has been identified as a possible cause of persistence of sleepiness despite treatment.8 However, even an incomplete abolition of apnoeas may be associated with an improvement of symptoms.9 It was tested whether CPAP given at two different levels – one eradicating apnoeas, hypopnoeas and snoring, the other also eliminating flow limitation – could result in different effects: patients treated with the latter CPAP level had a better effect on their sleepiness, but, as they had a higher compliance to treatment, it was not clear if the better improvement was due to the higher level of pressure or to the higher compliance.10 With regard to the relationship between severity of upper-airway obstruction and cardiovascular disease, results are also conflicting, with studies on cohorts of OSA patients showing statistically significant cardiovascular consequences only for AHI exceeding 30/h, and studies – mostly on the general population – showing an association of cardiovascular disease with even very mild ventilatory abnormalities during sleep.11,12
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Continuous Positive Airway Pressure Titration for Treatment of Obstructive Sleep Apnoea
Moreover, any effect on breathing during sleep may be reached with
general, the differences between devices seem to be on the levels and the
different pressures within each night as well as from night to night.
variability of administered pressure rather than their effects on breathing
Recognised causes of pressure requirement variations within a night are
during sleep. Therefore, one more source of variation to discern the
sleep stage and, particularly, body posture.13 For this reason, optimal
constant optimal pressure for treatment is the auto-CPAP device used for
pressure should cover patients’ needs in all sleep stages and body
titration. Also, some experiences on night-to-night variability in pressure
postures, which should be proven during titration.
given by auto-CPAP machines showed even greater differences than those observed with repeated manual titrations. In that regard, more accurate studies are needed to demonstrate that the greater night-to-night variations are not due to artefacts during the auto-CPAP application.
The variety of auto-CPAP devices As the most appropriate pressure for treatment is variable, uncertain and
available is increasing manifold, though
imprecise, the complexity and the costs of traditional and officially
not all have been assessed with a
accepted procedures for titration could be disproportionate. Therefore,
sufficient number of studies. Considerable differences between pressures administered by different devices are not rare.
simplified methods to adopt for CPAP prescription have been proposed and tested. In particular, in addition to the unassisted titration by autoCPAP mentioned above, calculation of optimal pressure by predictive equations has been proposed. The first predictive equation to be elaborated was that by Hoffstein et al.,22 which has been the most frequently adopted for later studies. Several other equations followed, of which the formula by Stradling et al. is one of the most extensively tested.23 All predictive equations are based
Uncertain causes of variations in pressure requirements between nights
on parameters relevant to the severity of respiratory disorders during
are sedative drugs, alcohol consumption or previous sleep deprivation. In
sleep and on anthropometric measurements. Pressures predicted by
the long term, changes may be due to weight variations or, perhaps, to
formulas correlated significantly with titrated pressures. Stradling’s
the effects of long-term treatment itself.14,15 Either way, causes of
formula tends to yield higher pressures than Hoffstein’s, which reflects
apparent variations in pressure requirements remain at least partly
the fact that it was elaborated several years later when the definition of
unpredictable. An experience of repeated manual-pressure titrations over
optimal pressure had already begun to require the abolition of snoring
consecutive nights showed that the identified ‘optimal’ pressures in
and, possibly, flow limitation, and auto-CPAP devices able to put an end
single subjects differed by up to 3cm of hydrogen dioxide (H2O).16
to snoring were already commonly used.
The problem of recognising optimal pressure has become even more
The equations were initially proposed as a way of facilitating the task of
complicated since the introduction of auto-CPAP machines for titration.
technicians performing manual titration: once the hypothetical target
Auto-CPAP devices administer variable levels of CPAP according to
pressure was approximately known, the technician could more quickly
instantaneous patient needs. For titration purposes, auto-CPAP devices
and easily determine the real optimal pressure. Later, it was proposed to
may be used during the night in different settings, ranging from a sleep laboratory – where an assisted polysomnography is performed, as recommended by the American Academy of Sleep Medicine17 – to an unassisted environment without any associated monitoring other than that
Some experiences on night-to-night
provided by the machine itself; then, as optimal CPAP to be administered at a constant level during nocturnal home treatment is usually considered
variability in pressure given by auto-
the 90th or 95th percentile pressure – i.e. the pressure level administered
CPAP machines showed even greater
by the auto-CPAP device that has not been exceeded for 90% or 95%, respectively, of the time of its application. The first procedure allows better control of the efficiency of the auto-CPAP and the reliability of its
differences than those observed with repeated manual titrations.
indications on optimal fixed pressure,18 but gives little advantage in terms of simplification of the titration procedure and of cost savings. The second method is more empirical, but could be associated with considerable cost savings and has produced some favourable results.19
use predictive formulas to prescribe CPAP treatment and to modify the administered pressure level in the first days following CPAP initiation on
The software governing CPAP changes is unique to each auto-CPAP
the basis of symptoms possibly reported by the patient and his/her bed
device. The variety of auto-CPAP devices available is increasing manifold,
partner.24 It was reported that, in the medium term, patients treated with
though not all have been assessed with a sufficient number of studies.
a titrated and those treated with a calculated (Hoffstein’s formula) and
According to the available literature, considerable differences between
later modified CPAP level did not show differences in compliance to
pressures administered by different devices are not rare.20,21 The few
treatment, relief of symptoms and change in blood pressure. However, it
available studies suggest that there is no correlation between mean
must be remarked that, in one of these studies, calculated pressures
pressures administered by auto-CPAP machines and their ability to correct
above 9cm H2O were not applied, while 9cm H2O was the highest
respiratory disorders, which could have different explanations.21 In
pressure initially administered for treatment.19 More recently,
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Sleep Apnoea straightforward prescription of the calculated pressure has been
To summarise, the main issues still unresolved with regard to CPAP
proposed (by Stradling’s formula) as medium-term results of treatment
prescription are:
by that pressure were found to be satisfactory.25 • the minimum degree of correction of respiratory disorders during More experience with predictive formulas is desirable before their widespread application. Significant correlations between titrated and calculated pressure values may not exclude cases of extreme discord. In fact, one study demonstrated that agreement between titrated and
sleep that results in the best outcome; • the degree of precision that the pressure identified as the therapeutic level should have; • the most convenient procedure to choose the pressure level for treatment; and • the criteria to best assess effectiveness of CPAP treatment.
The adequacy of a CPAP level for
While, in the past, CPAP titration seemed aimed at finding a very
treatment should be assessed by taking
precise pressure level (about +/-0.5cm H2O) and the correction of any
into account both laboratory and
obstructive respiratory disorders during sleep every night, we are now aware that this is not realistic. It is known that some positive effects
clinical findings.
may be obtained even with suboptimal correction of upper-airway obstruction; however, that does not authorise the oversimplification of procedures. Although the titrated CPAP may alter between one
calculated pressures is acceptable only for intermediate values. For the
night and the next, it is likely that differences do not exceed 2cm or
other values it was found that the lower the titrated pressures, the higher
3cm H2O.
their overestimate by equations, and vice versa.
Therefore, with the
26
application of predictive equations the minority of patients needing high
Both isolated laboratory and clinical assessment of the therapeutic
or low pressures could receive inappropriate treatment. It could be
CPAP level may be misleading: the former due, for example, to an
objected that such patients could be recognised by clinicians following
imperfect performance of an auto-CPAP device; the latter, for example,
their complaints or some unfavourable outcome. This is often true, but an
to subjective improvement in symptoms not warranted by the nocturnal
assessment of effectiveness of treatment in single patients may be
breathing pattern. Therefore, the adequacy of a CPAP level for
difficult; some subjects may report an improvement of symptoms due to
treatment should be assessed by taking into account both laboratory
a placebo effect,27 or have a good compliance to CPAP despite an
and clinical findings. In conclusion – in the authors’ opinion – it is not
insufficient correction of respiratory disorders.
Also, beneficial
yet time to forget the titration procedure. Future studies will hopefully
cardiovascular effects of CPAP in the OSA population are clear, but may
allow us to establish the best criteria to evaluate adequacy of a
be lacking in some individuals.29
CPAP treatment. ■
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