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Positive airway pressure therapy for post-stroke sleep disordered breathing: a systematic review, meta-analysis and meta-regression

Zheng An Toh, Ling Jie Cheng, Xi Vivien Wu, Deidre Anne De Silva, Hui Xian Oh, Si Xian Ng, Hong-Gu He, Minna Pikkarainen
European Respiratory Review 2023 32: 220169; DOI: 10.1183/16000617.0169-2022
Zheng An Toh
1Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2Division of Nursing, National University Hospital, Singapore
3National University Health System, Singapore
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Ling Jie Cheng
3National University Health System, Singapore
4Saw Swee Hock School of Public Health, National University of Singapore, Singapore
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Xi Vivien Wu
1Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
3National University Health System, Singapore
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Deidre Anne De Silva
5Department of Neurology, Singapore General Hospital Campus, National Neuroscience Institute, Singapore
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Hui Xian Oh
1Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2Division of Nursing, National University Hospital, Singapore
3National University Health System, Singapore
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Si Xian Ng
1Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2Division of Nursing, National University Hospital, Singapore
3National University Health System, Singapore
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Hong-Gu He
1Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
3National University Health System, Singapore
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  • For correspondence: nurhhg@nus.edu.sg
Minna Pikkarainen
6Department of Occupational Therapy, Prosthetics and Orthoptics, Faculty of Health Sciences and Department of Product Design, Faculty of Technology, Art and Design, Oslo Metropolitan University, Oslo, Norway
7Martti Ahtisaari Institute, University of Oulu, Oulu, Finland
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  • FIGURE 1
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    FIGURE 1

    PRISMA-P flowchart for selection of studies included in the meta-analysis. PAP: positive airway pressure therapy; SDB: sleep disordered breathing.

  • FIGURE 2
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    FIGURE 2

    Forest plot of risk ratio or Hedges’ g (95% CI) showing the effectiveness of positive airway pressure therapy (PAP) on a) recurrent vascular events, b) neurological deficit, c) cognition, d) functional independence, e) daytime sleepiness and f) depression. SMD: standardised mean difference.

Tables

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  • TABLE 1

    Characteristics of the included studies (n=24)

    First author [ref.]YearCountryTotal and group sample size (n); age (years)#Stroke phaseStroke type; SDB typeAttrition rate (n/N (%))Missing data managementFunding; protocol registration
    Aaronson [25]2016The NetherlandsT: 36
    I: 20; 61.1±8.2
    C: 16; 56.7±8.8
    16.8 days after strokeIschaemic and haemorrhagic;
    OSA
    I: 3/20 (15)
    C: 2/16 (12.5)
    T: 5/36 (13.9)
    ITT analysisNo;
    yes
    Bernasconi [88]2020Switzerland, Germany, ItalyT: 41
    I: 19; 64.1±6.7
    C: 22; 64.7±6.6
    3 months after strokeIschaemic;
    CSA and OSA
    I: 3/19 (15.8)
    C: 4/22 (18.2)
    T: 7/41 (17.1)
    ITT analysisYes;
    yes
    Bravata [23]2011USAT: 55
    I: 31; 70.6±9.4
    C: 24; 71.6±13.3
    ≤72 h of strokeIschaemic;
    CSA and OSA
    I: 9/31 (29)
    C: 3/24 (12.5)
    T: 12/55 (21.8)
    ITT analysisYes;
    yes
    Bravata [54]2010USAT: 70
    I: 31; 66.3±11.9
    C: 24; 67.4±12.8
    Majority ≤48 h of strokeTIA;
    CSA and OSA
    I: 9/45 (20)
    C: 5/25 (20)
    T: 14/70 (20)
    ITT analysisYes;
    yes
    Brown [55]2013USAT: 32
    I: 15; 61±22.22
    C: 17; 70±19.3
    ≤7 days of strokeIschaemic;
    CSA and OSA
    I: 7/15 (46.7)
    C: 6/17 (35.3)
    T: 13/32 (40.6)
    UnreportedYes;
    yes
    Cui [52]2017ChinaT: 145
    I: 73; 66.2±5.6
    C: 72; 68.4±13.9
    UnspecifiedIschaemic;
    OSA
    UnreportedUnreportedUnreported;
    no
    Dong [61]2017ChinaT: 80; 38–74Unspecified; acute phaseIschaemic;
    OSA
    UnreportedPer-protocol analysisYes;
    no
    Gao [62]2013ChinaT: 78
    I: 44; 67.93±7.28
    C: 34; 67.68±6.54
    Unspecified; acute phaseIschaemic;
    OSA
    UnreportedUnreportedUnreported;
    no
    Gupta [89]2018IndiaT: 70
    I: 30; 24±80
    C: 40; 33±82.5
    ≥6 weeks after strokeIschaemic and haemorrhagic;
    OSA
    I: 4/34 (11.8)
    C: 0
    Crossed over from I to CYes;
    yes
    Hsu [26]2006UKT: 30
    I: 15; 76±5.93
    C: 15; 71.67±8.89
    Days 21–25 after strokeNo restriction;
    unclear
    I: 5/15 33.3
    C: 0
    T: 5/30 (16.7)
    ITT analysisYes;
    no
    Kim [73]2019South KoreaT: 43
    I: 20; 63.3±13.1
    C: 20; 66.9±12.3
    4.6±2.8 days after stroke onsetIschaemic and haemorrhagic;
    CSA, OSA and mixed apnoea
    I: 3/23 (13)
    C: 0
    T: 3/43 (7)
    Withdrawn patients excludedYes;
    yes
    Li [63]2020ChinaT: 82
    I: 39; 59.95±4.17
    C: 43; 60.21±5.97
    UnspecifiedIschaemic;
    OSA
    UnreportedPer-protocol analysisUnreported;
    no
    Liu [58]2014ChinaT: 71
    I: 34; 62.05±8.30
    C: 37; 61.89±8.09
    UnspecifiedIschaemic;
    OSA
    UnreportedUnreportedUnreported;
    no
    Ning [66]2019ChinaT: 80
    I: 37; 69.37±5.67
    C: 43; 68.37±5.15
    Unspecified; non-acute strokeIschaemic;
    OSA
    UnreportedUnreportedUnreported;
    no
    Parra [22]2015SpainT: 140
    I: 57; 63.7±9.1
    C: 69; 65.5±9.1
    4.6±2.8 days after stroke onsetIschaemic;
    CSA and OSA
    I: 14/71 (19.7)
    C: 0
    T: 14/140 (10)
    Per-protocol analysisYes;
    yes
    Parra [60]2011SpainT: 140
    I: 57; 63.7±9.1
    C: 69; 65.5±9.1
    4.6±2.8 days after stroke onsetIschaemic;
    CSA and OSA
    I: 14/71 (19.7)
    C: 0
    T: 14/140 (10)
    Per-protocol analysisYes;
    yes
    Ryan [24]2011CanadaT: 48
    I: 22; 62.8±12.8
    C: 22; 60.7±10.3
    Within 3 weeks of stroke onsetIschaemic and haemorrhagic;
    OSA
    I: 3/25 (12)
    C: 1/23 (4.3)
    T: 4/48 (8.3)
    Withdrawn patients excludedYes;
    yes
    Sandberg [90]2001SwedenT: 63
    I: 31; 78.1±6.4
    C: 28; 76.8±7.9
    2–4 weeks after strokeIschaemic and haemorrhagic;
    CSA and OSA
    I: 2/33 (6.1)
    C: 2/30 (6.7)
    T: 4/63 (6.3)
    Missing data were replaced with meanYes;
    no
    Su [68]2011ChinaT: 60
    I: 30; 56–76
    C: 30; 58–73
    Unspecified; acute phaseIschaemic;
    OSA
    UnreportedUnreportedUnreported;
    no
    Tu [64]2015ChinaT: 140
    I: 70; 48.15±9.85
    C: 70; 47.68±8.96
    Within 1 week of strokeIschaemic;
    OSA
    UnreportedUnreportedUnreported;
    no
    Wan [67]2018ChinaT: 49
    I: 20; 63.32±11.79
    C: 29; 57.48±10.40
    Unspecified; during hospitalisationUnspecified;
    OSA
    I: 5/25 (20)
    C: 0/29
    T: 5/54 (9.3)
    Withdrawn patients excludedYes;
    no
    Wang [91]2015ChinaT: 86
    I: 43; 64.5±9.7
    C: 43; 64.2±8.6
    Unspecified; acute phaseIschaemic;
    OSA
    UnreportedUnreportedUnreported;
    no
    Xu [65]2020ChinaT: 81
    I: 41; 68.2±11.8
    C: 40; 69.1±12.3
    Unspecified; non-acute strokeIschaemic;
    OSA
    UnreportedUnreportedUnreported;
    no
    Yuan [59]2016ChinaT: 107
    I: 51; 65.2±14.6
    C: 56; 64.4±13.9
    UnspecifiedUnspecified;
    OSA
    UnreportedUnreportedUnreported;
    no

    #: Age data are presented as mean±sd or range. SDB: sleep disordered breathing; T: total; I: intervention; C: control; OSA: obstructive sleep apnoea; ITT: intention-to-treat; CSA: central sleep apnoea; TIA: transient ischaemic attack.

    • TABLE 2

      Subgroup analyses of primary and secondary outcomes (n=24 studies)

      Outcome and subgroupsStudies (n)Total (n)Risk ratio# or Hedges’ g¶95% CI95% PIHeterogeneity I2 (%), τ2, p-valuez-test, p-value+Subgroup difference (χ2), p-value+
      Recurrent vascular events (n=8)
       Follow-up period
        ≤12 months65180.450.23–0.870.08–2.577, 0.28, 0.37−2.37, 0.020.01, 0.92
        >12 months21600.420.18–0.970, <0.01, 0.94−2.03, 0.04
       Adherence
        <4 hNA
        ≥4 h86780.470.28–0.780.14–1.580, 0.18, 0.55−2.91, <0.01
       Stroke phase
        <2 weeks32510.360.16–0.800.00–97.190, 0.03, 0.75−2.51, 0.010.42, 0.81
        ≥2 weeks21040.260.05–1.460, 0.005, 0.79−1.53, 0.13
       PAP device
        Auto-CPAP75520.460.25–0.850.11–1.960, 0.22, 0.49−2.51, 0.010.02, 0.88
        CPAP
        Nasal CPAP11260.430.18–1.01
       Baseline SDB severity
        AHI ≤30 events·h−154480.460.22–0.980.05–4.3711, 0.35, 0.35−2.02, 0.040.10, 0.75
        AHI >30 events·h−132300.390.17–0.850.00–77.200, 0.01, 0.85−2.37, 0.02
      Neurological deficit (n=12)
       Follow-up period
        ≤3 months11756−0.73−1.05– −0.41−1.85–0.3978, 0.22, <0.01−4.43, <0.011.19, 0.55
        3–6 months2162−1.32−3.28–0.6497, 1.92, <0.01−1.32, 0.19
        >6 months2233−0.30−1.20–0.6192, 0.39, <0.01−0.64, 0.52
       Adherence
        <4 h385−0.29−0.73–0.15−3.36–2.780, 0.01, 0.76−1.28, 0.208.45, 0.01
        ≥4 h8638−0.92−1.45– −0.38−2.81–0.9890, 0.53, <0.01−3.37, <0.01
       Stroke phase
        <2 weeks4325−0.34−0.93–0.25−2.96–2.2889, 0.28, <0.01−1.13, 0.264.72, 0.09
        ≥2 weeks4191−0.68−1.05– −0.31−1.93–0.5617, 0.05, 0.31−3.63, <0.01
       PAP device
        Auto-CPAP5425−0.97−1.45– −0.49−2.66–0.7365, 0.22, 0.02−3.98, <0.0110.83, 0.01
        CPAP4242−1.08−1.92– −0.25−4.97–2.8088, 0.63, <0.01−2.55, 0.01
        Nasal CPAP21560.02−0.45–0.4931, 0.05, 0.230.09, 0.93
       Baseline SDB severity
        AHI ≤30 events·h−16470−1.13−1.75– −0.50−3.32–1.0784, 0.52, <0.01−3.54, <0.018.22, 0.02
        AHI >30 events·h−15312−0.31−0.67–0.05−1.42–0.8066, 0.09, 0.02−1.69, 0.09
      Cognition (n=8)
       Follow-up period
        ≤1 month42250.28−0.16–0.73−1.55–2.1260, 0.13, 0.061.24, 0.222.79, 0.25
        1–3 months31610.25−0.12–0.62−2.92–3.420, 0.03, 0.421.33, 0.18
        3–6 months32321.770.02–3.53−20.7–24.296, 2.32, <0.011.98, 0.05
       Adherence
        <4 h130−0.10−0.81–0.623.43, 0.06
        ≥4 h74240.980.10–1.86−2.20–4.1692, 1.33, <0.012.17, 0.03
       Stroke phase
        <2 weeks1400.640.00–1.280.32, 0.85
        ≥2 weeks52831.01−0.30–2.32−4.12–6.1495, 2.15, <0.011.51, 0.13
       PAP device
        Auto-CPAP21190.54−0.07–1.1665, 0.13, 0.091.73, 0.087.18, 0.07
        CPAP32061.75−0.03–3.54−21.0–24.595, 2.39, <0.011.93, 0.05
        Nasal CPAP289−0.06−0.48–0.350, <0.01, 0.92−0.30, 0.76
       Baseline SDB severity
        AHI ≤30 events·h−121260.870.50–1.230, <0.01, 0.704.60, <0.0162.0, <0.01
        AHI >30 events·h−152480.33−0.06–0.72−0.91–1.5655, 0.11, 0.071.64, 0.10
      Functional independence (n=17)
       Follow-up period
        ≤3 months137650.29−0.10–0.68−1.21–1.7985, 0.42, <0.011.46, 0.140.93, 0.63
        3–6 months53420.93−0.32–2.19−3.96–5.8395, 1.95, <0.011.46, 0.14
        >6 months43360.34−0.13–0.81−1.70–2.3880, 0.17, <0.011.42, 0.16
       Adherence
        <4 h385−0.14−0.64–0.36−4.39–4.110, 0.05, 0.44−0.56, 0.584.38, 0.11
        ≥4 h128800.630.11–1.16−1.45–2.7289, 0.81, <0.012.35, 0.02
       Stroke phase
        <2 weeks3185−0.03−0.44–0.38−3.91–3.850, 0.05, <0.011.35, 0.183.68, 0.16
        ≥2 weeks84330.56−0.25–1.37−2.39–3.5192, 1.28, 0.001.52, 0.13
       PAP device
        Auto-CPAP63880.42−0.05–0.89−1.14–1.9875, 0.26, <0.011.77, 0.083.85, 0.28
        CPAP63820.71−0.42–1.84−3.44–4.8795, 1.91, <0.011.24, 0.22
        Nasal CPAP32150.02−0.26–0.30−1.90–1.940, <0.01, 0.780.15, 0.88
       Baseline SDB severity
        AHI ≤30 events·h−153300.48−0.12–1.08−1.72–2.6879, 0.38, <0.011.57, 0.122.83, 0.24
        AHI >30 events·h−184740.11−0.09–0.31−0.26–0.470, 0.01, 0.831.05, 0.30
      Daytime sleepiness (n=11)
       Follow-up period9440−0.59−1.06– −0.13−2.20–1.0180, 0.40, <0.01−2.50, 0.011.96, 0.38
        ≤3 months3221−1.57−3.26–0.12−23.2–20.196, 2.15, <0.01−1.82, 0.07
        3–6 months3248−0.91−1.24– −0.58−3.98–2.1518, 0.03, 0.29−5.42, <0.01
       Adherence
        <4 h3850.14−0.30–0.58−2.91–3.190, 0.01, 0.720.61, 0.5421.4, <0.01
        ≥4 h7471−1.37−2.05– −0.70−3.76–1.0188, 0.74, <0.014.45, 0.00
       Stroke phase
        <2 weeks259−0.46−1.56–0.6476, 0.46, 0.04−0.82, 0.410.86, 0.65
        ≥2 weeks6341−1.17−2.21– −0.14−4.95–2.6093, 1.57, <0.01−2.22, 0.03
       PAP device
        Auto-CPAP6397−0.88−1.32– −0.43−2.34–0.5966, 0.23, 0.01−3.86, <0.0110.45, 0.02
        CPAP3160−1.64−3.48–0.19−25.0–21.896, 2.51, <0.01−1.75, 0.08
        Nasal CPAP1300.35−0.38–1.07
       Baseline SDB severity
        AHI ≤30 events·h−14241−0.87−1.56– −0.17−4.00–2.2673, 0.40, 0.01−2.44, 0.014.79, 0.09
        AHI >30 events·h−15225−0.49−1.00–0.02−2.25–1.2767, 0.24, 0.02−1.88, 0.06
      Depression (n=7)
       Follow-up period
        ≤1 month3139−0.33−0.79–0.14−5.00–4.3440, 0.08, 0.19−1.38, 0.170.08, 0.78
        >1 month4178−0.75−3.70–2.2−15.1–13.697, 8.86, <0.01−0.50, 0.62
       Adherence
        <4 h3850.94−0.30–2.18−14.1–15.980, 0.99, <0.011.49, 0.144.95, 0.03
        ≥4 h4232−1.71−3.69–0.27−11.3–7.8996, 3.96, <0.01−1.69, 0.09
       Stroke phase
        <2 weeks1192.301.08–3.5325.2, <0.01
        ≥2 weeks5249−0.98−2.85–0.90−8.35–6.3996, 4.45, <0.01−1.02, 0.31
       PAP device
        Auto-CPAP2680.51−2.86–3.8896, 5.67, <0.010.30, 0.771.11, 0.57
        CPAP3160−1.64−4.65–1.38−40.5–37.298, 6.98, <0.01−1.06, 0.29
        Nasal CPAP289−0.03−1.33–1.2789, 0.78, <0.01−0.04, 0.97
       Baseline SDB severity
        AHI ≤30 events·h−12630.95−1.53–3.4293, 2.95, <0.010.75, 0.4560.5, <0.01
        AHI >30 events·h−14174−0.30−1.10–0.51−3.98–3.3983, 0.57, <0.01−0.72, 0.47

      95% CI: 95% confidence interval; 95% PI: 95% prediction interval; (C)PAP: (continuous) positive airway pressure; SDB: sleep disordered breathing; AHI: apnoea–hypopnoea index; NA: not applicable. #: risk ratio was used to report recurrent vascular events only; ¶: Hedges' g was used to report neurological deficit, cognition, functional independence and daytime sleepiness; +: bold indicates statistically significant.

      • TABLE 3

        Results of random effects univariate meta-regression on neurological deficit, functional independence and daytime sleepiness

        Neurological deficitFunctional independenceDaytime sleepiness
        βse95% CIp-valueβse95% CIp-valueβse95% CIp-value
        Mean age0.030.03−0.04–0.090.44−0.010.02−0.03–0.060.61−0.0030.03−0.06–0.050.92
        Proportion of males0.030.02−0.12–0.070.230.0010.01−0.03–0.030.93−0.060.02−0.10– −0.010.01*
        Sample size−0.0040.01−0.02–0.010.480.010.01−0.004–0.030.16−0.020.01−0.04–0.0020.08
        Year of publication−0.080.04−0.17–0.020.110.080.040.004–0.160.04*−0.120.07−0.26–0.020.08

        *: p<0.05.

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        Positive airway pressure therapy for post-stroke sleep disordered breathing: a systematic review, meta-analysis and meta-regression
        Zheng An Toh, Ling Jie Cheng, Xi Vivien Wu, Deidre Anne De Silva, Hui Xian Oh, Si Xian Ng, Hong-Gu He, Minna Pikkarainen
        European Respiratory Review Mar 2023, 32 (167) 220169; DOI: 10.1183/16000617.0169-2022

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        Positive airway pressure therapy for post-stroke sleep disordered breathing: a systematic review, meta-analysis and meta-regression
        Zheng An Toh, Ling Jie Cheng, Xi Vivien Wu, Deidre Anne De Silva, Hui Xian Oh, Si Xian Ng, Hong-Gu He, Minna Pikkarainen
        European Respiratory Review Mar 2023, 32 (167) 220169; DOI: 10.1183/16000617.0169-2022
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