Electronic Supplementary Material

Effects of propofol on sleep quality

in mechanically ventilated critically ill patients – A Physiological study

Eumorfia Kondili, Christina Alexopoulou, Nectaria Xirouchaki and Dimitris Georgopoulos

Intensive Care Medicine Department, University Hospital of Heraklion, School of Medicine, University of Crete, Heraklion, Crete, Greece

Correspondence:

D. Georgopoulos,

Professor of Medicine,

Director of Intensive Care Medicine Department

University Hospital of Heraklion,

Heraklion, Crete, Greece

Fax: +30 2810 392409

e-mail:


Additional Methods details

Measurements

Flow (V’) at the airway opening was measured with a heated pneumotachograph (Hans-Rudolf 3700, Kansas, USA) and a differential pressure transducer (Micro-Switch 140PC, Honeywell, Ontario, Canada), placed between the endotracheal tube and the Y-piece of the ventilator. Flow was electronically integrated to provide volume (V). Airway pressure (Paw; Micro-Switch 140PC, Honeywell, Ontario, Canada) was measured from a side port between the pneumotachograph and the endotracheal tube. Partial pressure of end-tidal CO2 was measured at the distal end of the endotracheal or tracheostomy tube using a mainstream capnometer (Alice, Respironics, Pittsburgh, U.S.A.). Pulse oxymetry was recorded continuously with a finger probe. The motion of the rib cage and abdomen was measured using respiratory inductive plethysmography (Alice, Respironics, Pittsburgh, U.S.A.). Electroencephalogram (EEG) (C4/A1, C3/A2, O1/A2, O2/A1), right and left electrooculogram, submental electromyogram, and electrocardiogram signals were amplified, filtered recorded, and stored with other signals in a data acquisition system (Alice, Respironics, Pittsburgh, U.S.A.).

Data analysis

Sleep architecture was scored manually in 30-s period epochs according to standard criteria [1]. Total sleep time (TST) was defined as the sum of total time spent in all sleep stages during the total time monitored [1]. The percentage of time spent in each stage of sleep during TST was calculated. EEG arousals were defined as an abrupt shift in EEG frequency consisting of theta, α, and/or frequencies greater than 12 Hz lasting 3 seconds or longer [1]. Awakenings were defined as EEG features compatible with wakefulness and lasting > 15 sec of an epoch preceded and followed by an epoch of sleep [1]. Total sleep fragmentation index was calculated as the sum of arousals and awakenings per hour of sleep [1]. Central apneas were defined as the absence of airflow, based on pneumotachography, for 10 seconds or longer, occurring in the absence of detectable respiratory effort on respiratory inductive plethysmography [1].

Total respiratory cycle time (TTOT), end-tidal CO2, tidal volume (TV) and peak inspiratory airway pressure (Pawpeak) were measured on a breath-by-breath basis [2]. TTOT were calculated from the flow signal. Breath components (TTOT, TV), end-tidal CO2, and Pawpeak were measured during NREM sleep, and in a similar fashion during wakefulness. Major patient-ventilator asynchrony, such as ineffective efforts, autotriggering and double triggering, was evaluated breath by breath by inspection of flow-time and Paw-time waveforms as described previously [2]. Analysis of breathing pattern and end-tidal CO2 during sleep was confined to nonrapid eye movement sleep (NREM) because of the greater variability of breathing pattern expected during rapid eye movement sleep [3]. Periodic breathing was identified visually by the presence of gross fluctuations in TV and/or ventilator rate with a periodicity consistent with Cheyne-Stokes breathing (0.7to 3.0cycles/min) [4, 5]. We did not set a specific threshold (for the amplitude of TV oscillation or ventilator rate change) with which to define Chyene-Stokes breathing.


Additional results

Table S1: Patients’ characteristics.

Patient
No. / Sex / Age
(years) / APACHE II
On admission / Admission Diagnosis / Days
on MV / Mode
of MV / PEEP
(cmH2O) / FIO2
(%)
1 / F / 75 / 16 / MODS / 25 / PS / 7 / 0.5
2 / M / 75 / 32 / COPD/Pneumonia / 16 / CPAP / 5 / 0.3
3 / M / 63 / 15 / Sepsis / 20 / PS / 6 / 0.45
4 / F / 73 / 16 / Pneumonia / 11 / PS / 5 / 0.35
5 / M / 49 / 12 / SCI/Sepsis / 39 / PS / 5 / 0.40
6 / F / 73 / 18 / COPD/Pneumonia / 34 / PAV+ / 6 / 0.35
7 / F / 70 / 22 / MODS/Sepsis / 24 / PS / 6 / 0.30
8 / F / 75 / 25 / MODS / 22 / PS / 6 / 0.40
9 / M / 72 / 22 / AECOPD / 23 / PS / 7 / 0.30
10 / M / 46 / 18 / Pneumonia / 21 / PS / 5 / 0.50
11 / F / 72 / 30 / COPD/Pneumonia / 43 / PS / 6 / 0.50
12 / M / 78 / 17 / ARDS/Sepsis / 6 / PS / 6 / 0.26
Median IQR / 72.5
63-75 / 22.5
16-34 / 18.0
16-25 / 6.0
5-6 / 0.38
0.30-0.50

F; female. M; male. MODS; multiple organ dysfunction syndrome. ARDS; acute respiratory distress syndrome. COPD; chronic obstructive pulmonary disease. AECOPD; acute exacerbation of COPD. SCI; spinal cord injury. PEEP; positive end-expiratory airway pressure. MV; mechanical ventilation. PS; pressure support. CPAP; continuous positive airway pressure. PAV+; proportional assist ventilation with load adjustable gain factors. FIO2; fractional concentration of inspired O2. IQR; interquartile range.


Table S2: Individual arousals awakening and total sleep fragmentation indices with and without propofol

Without Propofol / With Propofol
Patient no. / AI / AwI / TSFI / AI / AwI / TSFI
1 / 8.26 / 1.81 / 10.07 / 27.80 / 21.95 / 49.76
2 / 0.00 / 1.69 / 1.69 / 8.23 / 1.23 / 9.46
3 / 3.67 / 1.22 / 4.90 / 2.87 / 0.72 / 3.58
4 / 4.25 / 1.86 / 6.11 / 4.33 / 13.61 / 17.94
5 / 10.43 / 41.74 / 52.17 / 8.40 / 7.29 / 15.69
6 / 11.73 / 3.65 / 15.38 / 4.49 / 1.50 / 5.98
7 / 2.00 / 0.25 / 2.25 / 0.13 / 0.00 / 0.13
8 / 2.36 / 2.96 / 5.32 / 1.45 / 0.97 / 2.42
9 / 6.13 / 9.73 / 15.86 / 2.84 / 0.71 / 3.55
10 / 16.28 / 2.93 / 19.21 / 9.10 / 2.04 / 11.13
11 / 0.00 / 0.00 / 0.00 / 0.00 / 0.00 / 0.00
12 / 7.64 / 8.73 / 16.36 / 0.62 / 0.31 / 0.93
Median IQR / 5.19
2.09-9.89 / 2.40
1.34-7.46 / 8.09
2.91-16.24 / 3.60
0.83-8.36 / 1.10
0.41-5.98 / 4.78
1.30-14.55

AI, AwI, TSFI; arousals index, awakening index, total sleep fragmentation index, respectively (events/hr). IQR; interquartile range.

On both study nights patient no. 11 did not achieve sleep.


Table S3: Arterial blood gasses in the beginning and at the end of each study night.

Without Propofol / With Propofol
Beginning / End / p values / Beginning / End / p values
PaO2 / 92.3 (77.0-96.1) / 87.4 (78.2-103.0) / 0.79 / 103.0 (88.6-124.0) / 98.0 (80.0-118.2) / 0.75
PaCO2 / 45.0 (40.1-47.3) / 43.5 (41.0-51.1) / 0.48 / 44.5 (41.4-50.0) / 47.6 (41.0-52.8) / 0.09
pH / 7.40 (7.38-7.45) / 7.40 (7.36-7.43) / 0.36 / 7.40 (7.36-7.44) / 7.39 (7.35-7.42) / 0.21

Values are median (interquartile range). PaO2 and PaCO2; partial pressure of arterial O2 and CO2, respectively.


References

1. (2007) The AASM manual for the scoring of sleep and associated events: rules, terminology, and technical specification,. Westchester, IL: American Academy of Sleep Medicine

2. Georgopoulos D, Prinianakis G, Kondili E, (2006) Bedside waveforms interpretation as a tool to identify patient-ventilator asynchronies. Intensive Care Med 32: 34-47

3. Alexopoulou C, Kondili E, Vakouti E, Klimathianaki M, Prinianakis G, Georgopoulos D, (2007) Sleep during proportional-assist ventilation with load-adjustable gain factors in critically ill patients. Intensive Care Med 33: 1139-1147

4. Irwin M, Rinetti G, Redwine L, Motivala S, Dang J, Ehlers C, (2004) Nocturnal proinflammatory cytokine-associated sleep disturbances in abstinent African American alcoholics. Brain Behav Immun 18: 349-360

5. Klimathianaki M, Kondili E, Alexopoulou C, Prinianakis G, Georgopoulos D, (2010) Effect of propofol on breathing stability in adult ICU patients with brain damage. Respir Physiol Neurobiol 171: 232-238

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