Sleep-Disordered Breathing

Online Supplement (No1)

Sleep-disordered breathing

in unilateral diaphragm paralysis or severe weakness

Joerg Steier, Caroline J Jolley, John Seymour, Sunny Kaul, Yuan M Luo,

Gerrard Rafferty, Nicholas Hart, Michael I Polkey, John Moxham

METHODS

I) Respiratory Muscle Tests [E1]

Two balloon catheters for the measurement of pressure (Cooper Surgical, CT/USA) lubricated with lignocaine (2%) gel, were introduced via one nostril into the oesophagus and stomach in the standard manner [E1, E2]. The distal balloon (filled with 2ml of air) measured the gastric pressure (Pgas); the proximal balloon (filled with 0.5ml of air) measured the oesophageal pressure (Poes). Transdiaphragmatic pressure (Pdi) was the difference between Poes and Pgas. Differential pressure transducers were connected to amplifiers (Validyne®, Northridge, CA, USA) that transmitted the signal via a 16-Channel Powerlab® (ADInstruments®, Colorado Springs, USA) to a computer (Apple iMac® Computers, Cupertino, CA, USA) with Chart® Version 5.4 software (ADInstruments®, Colorado Springs, USA).

Maximum inspiratory mouth pressure (PImax)

Maximum inspiratory pressures were measured from functional residual capacity in the standard way [E1, E3], with the patient seated, wearing a nose-clip and using a flanged mouthpiece (P.K. Morgan Ltd®, Rainham, UK). Repeated efforts were made, until consistent results were achieved, and the numerically largest pressure noted. The average of the pressure over one second was measured [E1].

Maximum expiratory mouth pressure (PEmax)

Maximum expiratory pressures were measured from total lung capacity in the standard way [E1, E3], with the patient seated, wearing a nose-clip and using a flanged mouthpiece. Repeated efforts were made, until consistent results were achieved; the numerically largest pressure averaged over one second was measured [E1].

Sniff oesophageal pressure (Sniff Poes)

Sniff manoeuvres [E1] were performed with the patient seated, without a nose-clip and the balloon catheters in place as described above. At least 5-10 maximal sniffs were measured; the largest numerical pressure was recorded.

Sniff nasal pressure (Sniff Pnasal)

A nasal plug which incorporated the distal 2-3cm of a 30 cm polyethylene catheter with a 2 mm internal diameter (Intersurgical Scientific Instruments®, Oxford, UK) was used to obstruct one nostril. The proximal end of the catheter was attached to a pressure transducer (Validyne®, Northridge, CA, USA). At least 5-10 maximal sniffs were performed until a consistent value of sniff pressure was reached; the numerically largest pressure was recorded.

Sniff transdiaphragmatic pressure (Sniff Pdi)

Pressure catheters were placed and maximal sniff manoeuvres performed as described above. The numerically largest pressure of 5-10 consistent sniffs was recorded.

Cough gastric pressure (Cough Pgas)

Pressure balloons were positioned as described in section 2. The cough manoeuvre was performed as previously reported [E1], the subjects breathing in deeply first, while seated, wearing a nose-clip. Coughs were repeated at least 5-10 times, until consistent results were achieved. The numerically highest value was taken, measuring from relaxed end-expiratory baseline gastric pressure to peak pressure during the cough.

Twitch transdiaphragmatic pressure (Twitch Pdi)

Twitch transdiaphragmatic pressures with left, right and bilateral anterolateral magnetic phrenic nerve stimulation were measured [E4-E9]. The patient was seated, wore a nose-clip, and the mouth was closed. For stimulation a Magstim 200 (Magstim Company Ltd., Whitland, UK) with a 43-mm double coil (P/N9784-00; Magstim Company Ltd., Whitland, UK) was used. Twitch Pdi was derived whilst recording as the difference between Poes and Pgas. After achieving a supramaximal stimulus, at least five consistent twitches were recorded and the average Twitch Pdi calculated.

Twitch gastric pressure (Twitch T10)

Magnetic stimulation of the thoracic nerve roots was performed with a 90mm circular coil (P/N9784-00; Magstim Company Ltd., Whitland, UK) placed with its centre over the 10th thoracic vertebra in the mid-line [E10]. Stimulation was undertaken at functional residual capacity, with the patient seated, wearing a nose-clip, and the mouth closed. Twitches were repeated at least 5-10 times, until consistent measurements were obtained, and mean Twitch T10 was calculated.

II) Activity of the Respiratory Muscles

Electromyogram of the Diaphragm (EMGdi)

A multipair electrode catheter was inserted via one nostril to record the transoesophageal EMGdi (Yinghui Medical Tech Ltd®, Guangzhou, China) [E5, E6]. Confirmation of the correct position of the EMG catheter at the electrically active region of the diaphragm (EARdi) was achieved by magnetic stimulation of the phrenic nerves and inspection of CMAP responses.[E5, E6] Spontaneous EMGdi and compound muscle action potential (CMAP) amplitude and latency after magnetic stimulation of the phrenic nerves were measured [E7]. The catheter was connected to a PClab-3808® biomedical amplifier (Yinghui Medical Tech Ltd®, Guangzhou, China) that further transmitted the signal to an analog-to-digital converter (Powerlab® 16/30, ADInstruments®, Colorado Springs, USA) running with Chart® software (Version 5.4, ADInstruments®, Colorado Springs, USA).

Electromyogram of extra-diaphragmatic respiratory muscles

The surface electrodes were positioned on the sternocleidomastoid (neck) muscle bilaterally 2cm above the clavicle and 3cm beneath the mastoid process (EMGneck). A reference electrode was placed on the skin 6cm lateral to the midline below the clavicles [E12]. For recording the EMG of the parasternal intercostals (EMGpara) electrodes were placed bilaterally 3cm from the midline in the second intercostal space [E12, E13]. The EMG of the abdominal muscles (EMGabdomen) was recorded from electrodes 2-3cm lateral to the umbilicus bilaterally [E14, E15].

III) Recordings

EMG and pressures were recorded:

i.)during resting breathing

ii.)during the following manoeuvres that have been described to achieve maximum activation of the diaphragm [E16, E17]; at least 5 attempts were performed for each, until consistent results were achieved.

− whilst breathing in as much as possible (total lung capacity manoeuvre)

− whilst breathing in as hard as possible against a closed airway (PImax manoeuvre)

− maximal sniffs

− maximum voluntary ventilation over 15s (“sprint MVV”)

iii.)Additionally, during maximal coughs (Cough Pgas manoeuvre) and expiration against an occluded valve (PEmax manoeuvre)

iv.) during all stages of sleep.

The recordings of the spontaneous EMG, and the respiratory pressures, were sampled at 2kHz, and EMG data were filtered with a high-pass 30 Hz and an additional low pass 1kHz filter.The rectified signals of the EMG (root-mean-square of the raw data) were quantified and transformed into percent of maximum activity (maximum as derived from the maximum inspiratory and expiratory manoeuvres described above).

IV) Overnight Surveillance

Full polysomnography was performed using Alice 3® or Alice 4® equipment (Respironics®, Murrysville/PA, USA). Electrical activity of the brain (EEG) was measured with surface electrodes (Gold) according to the ten-twenty system (C3/A2, C4/A1, O1/A2). Sleep and respiratory events were scored with standard terminology [E18-E20]. Electrooculography (EOG) was measured by golden-surface electrodes to detect rapid eye movements (REM). A position electrode measured on which side the patient was lying. Pulse oximetry (Biox 3790 pulse oximeter, Ohmeda, Louisville / USA) sensed the oxygen saturation and pulse frequency. Airflow was measured via a nasal cannula (Respironics, Pennsylvania, USA). Abdominal and chest wall movements were detected via uncalibrated inductance plethysmography bands (RespiTraces, Respironics, Pennsylvania, USA) around the chest and abdomen.

V) Breath-by-breath analysis of EMG during sleep

The overnight EMG data was normalised to the maximum of EMG activity during a maximal effort (see section: Recordings 3ii above) and expressed as percent of maximum EMG activity. To compare REM-related events with the rest of the night, we distinguished between REM-sleep and NREM-sleep. We only included sleep stage 2 and 3 in the analysis, because of the unstable nature of sleep stage 1. We analysed 10min of a deep sleep cycle and compared this to 10 min of a REM sleep cycle. There was a significant impact of posture and arousal on the EMGdi signal. Therefore, we only compared REM to NREM data that was obtained in the supine position and excluded arousal events. The highest RMS of the EMG of every breath was measured and included in the analysis.

VI) Offline Analysis

Sleep data were analysed with Alice 4® software (Respironics®, Murrysville/PA, USA) on a Windows® (Microsoft®, Seattle, USA) based PC. EMG and pressure data were saved and analysed with Chart® Version 5.4 (ADInstruments®, Colorado Springs, USA) on an iMac® Computer (Apple® computers, Cupertino/CA, USA).

RESULTS

This online supplement contains the individual test results of each patient and each control subject in the Tables E1-E5.

All but one patient (Patient 8) performed the volitional respiratory muscle tests satisfactorily. Twitch Pdi and Sniff Pdi were reduced in the patients. PImax, Sniff Poes and Sniff Pnasal were also reduced, whereas PEmax, cough Pgas and Twitch T10 were normal (Table E1).

Phrenic nerve latency was prolonged in nine out of eleven patients on the weak side, and prolonged in five out of eleven patients on the strong side. The compound muscle action potentials (CMAP) were markedly reduced on the weaker side, with ten out of eleven patients having a CMAP less than the lower limit of normal [E7]. On the strong side the CMAP was markedly reduced in four patients (Table E2).

The FEV1 was low in the patient group and compared to the normal group the FEV1/VC ratio indicated a mild obstructive defect. Vital capacity was reduced in the patient group and showed a further fall when supine; patient no 8 was excluded from the analysis of these data because of inability to perform the VC manoeuvre lying supine. Although none of the patients was hypercapnic, PaO2 was mildly reduced (Table E3).

During polysomnography we observed frequent hypopnoeas and apnoeas in REM-sleep (Figure 1 in the manuscript). Only two patients (no 7 and 8) had no SDB, and they had the highest Twitch Pdi on their weak side (5-6cmH2O). Baseline oxygenation in the group was normal during NREM-sleep, but dropped during hypopnoeas in REM-sleep. The RDI in NREM-sleep was more variable in the UDP patients, but not significantly higher than in the normal subjects (Table E4). The RDI was, in NREM-sleep, elevated in a subgroup of patients who had a thoracoabdominal paradox (p=0.002).

Quality of life was significantly reduced in patients compared to the control group (Table E1). Mostly the dimensions “symptoms” and “activity”, measured by the SGRQ, as well as “mean dyspnoea” and “mean fatigue”, measured by the CRDQ, were altered; but also the dimension “impact”, the total score (SGRQ), “emotion” and “mastery” (CRDQ) reached clinical significance. The MRC dyspnoea scale (2.4 (1.0) vs 1.2 (0.4) points, p=0.002) and the Epworth sleepiness scale (11.9 (5.7) vs 3.7 (2.8) points, p<0.001) were significantly increased (Table E5).

REFERENCES

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(E4) Luo YM, Hart N, Mustfa N, Man WD, Rafferty GF, Polkey MI, Moxham J. Reproducibility of twitch and sniff transdiaphragmatic pressures. Respir Physiol Neurobiol 2002;132(3):301-306.

(E5) Polkey MI, Duguet A, Luo YM, Hughes PD, Hart N, Hamnegard CH, Green M, Similowski T, Moxham J. Anterior magnetic phrenic nerve stimulation: laboratory and clinical evaluation. Intensive Care Med 2000;26(8):1065-1075.

(E6) Luo YM, Harris ML, Lyall RA, Watson A, Polkey MI, Moxham J. Assessment of diaphragm paralysis with oesophageal electromyography and unilateral magnetic phrenic nerve stimulation. Eur Respir J 2000;15(3):596-599.

(E7)Luo YM, Lyall RA, Harris ML, Rafferty GF, Polkey MI, Moxham J. Quantification of the esophageal diaphragm electromyogram with magnetic phrenic nerve stimulation. Am J Respir Crit Care Med 1999;160(5Pt1):1629-1634.

(E8) Mills GH, Kyroussis D, Hamnegard CH, Wragg S, Moxham J, Green M. Unilateral magnetic stimulation of the phrenic nerve. Thorax 1995;50(11):1162-1172.

(E9) Mills GH, Kyroussis D, Hamnegard CH, Polkey MI, Green M, Moxham J. Bilateral magnetic stimulation of the phrenic nerves from an anterolateral approach. Am J Respir Crit Care Med 1996;154:1099-1105.

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TABLE LEGENDS

Table E1: Results of respiratory muscle function tests for control group and patients. All pressures recorded in cm H2O. Tw Pdi = twitch transdiaphragmatic pressure, Sniff Pdi = sniff transdiaphragmatic pressure, Sniff Poes = sniff oesophageal pressure, Sniff Pnasal = sniff nasal pressure, PImax = maximal inspiratory mouth pressure, PEmax = maximal expiratory mouth pressure, cough Pgas = cough gastric pressure, Tw T10 = gastric pressure following magnetic stimulation at level of T10. P-values for differences are given in the row of the patients results summary. Tw T10 was not obtained in four patients (N/A). All twitches were elicited with magnetic stimulation.

a unilateral Twitch Pdi in normal subjects with normal hemidiaphragm strength measured on the less strong side.

b unilateral Twitch Pdi in normal subjects with normal hemidiaphragm strength measured on the stronger side.

Table E2: Phrenic nerve conduction studies. Latencies in ms, CMAP=compound muscle action potential in mV. The significance of the differences between patient and control group are given with the p-values. Weaker sides of the hemidiaphragm are indicated, with a ratio (R:L).

a Phrenic nerve latencies and CMAPs in normal subjects with normal hemidiaphragm strength measured on the less strong side.

b Phrenic nerve latencies and CMAPs in normal subjects with normal hemidiaphragm strength measured on the stronger side.

Table E3: Pulmonary function test results. FEV1 as percent predicted, vital capacity (VC) as percent predicted, FEV1/VC ratio as a percentage, VCdrop=fall in VC when changing from the sitting to the supine position as a percentage (patient no 8 was excluded due inability to perform the manoeuvre), PaO2 and PaCO2=partial pressures of oxygen and carbon dioxide in kPa. Differences between patients and control group are indicated by the p-values.

Table E4: Results of polysomnography. TST=total sleep time in minutes, REM=rapid-eye-movement sleep in minutes, RDI=respiratory disturbance index in events/h, SaO2=oxygen saturation (%). Differences between patients and control group are indicated by the p-value.

Table E5: Quality of life as measured with the St George´s Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRDQ). P-values are given in the result summary of the patient group to indicate differences. Mimimal clinical important difference for the SGRQ is four points and for the CRDQ 0.5 points.

TABLES

Table E1

Table E2

Table E3

Table E4