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Critical care outcomes in patients with pre-existing pulmonary hypertension: insights from the ASPIRE registry

Kris Bauchmuller, Robin Condliffe, Jennifer Southern, Catherine Billings, Athanasios Charalampopoulos, Charlie A. Elliot, Abdul Hameed, David G. Kiely, Ian Sabroe, A.A. Roger Thompson, Ajay Raithatha, Gary H. Mills
ERJ Open Research 2021 7: 00046-2021; DOI: 10.1183/23120541.00046-2021
Kris Bauchmuller
1Dept of Critical Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
4These authors contributed equally
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Robin Condliffe
2Sheffield Pulmonary Vascular Disease Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
3Dept of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
4These authors contributed equally
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Jennifer Southern
1Dept of Critical Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
4These authors contributed equally
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Catherine Billings
2Sheffield Pulmonary Vascular Disease Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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Athanasios Charalampopoulos
2Sheffield Pulmonary Vascular Disease Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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Charlie A. Elliot
2Sheffield Pulmonary Vascular Disease Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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Abdul Hameed
2Sheffield Pulmonary Vascular Disease Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
3Dept of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
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David G. Kiely
2Sheffield Pulmonary Vascular Disease Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
3Dept of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
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Ian Sabroe
2Sheffield Pulmonary Vascular Disease Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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A.A. Roger Thompson
2Sheffield Pulmonary Vascular Disease Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
3Dept of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
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Ajay Raithatha
1Dept of Critical Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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Gary H. Mills
1Dept of Critical Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
3Dept of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
4These authors contributed equally
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  • FIGURE 1
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    FIGURE 1

    Histograms demonstrating in-hospital mortality in medical patients according to quintiles of a) APACHE II (Acute Physiology and Chronic Health Evaluation II) score, b) platelet count, c) serum sodium level, d) age, e) oxygen saturation measure by pulse oximetry (SpO2)/inspiratory oxygen fraction (FiO2) ratio and f) lactate. Each bar represents 20% of the population for that parameter.

  • FIGURE 2
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    FIGURE 2

    OPALS score. Risk of hospital mortality in medical patients based on number of adverse single risk factors. OPALS: oxygen (oxygen saturation measured by pulse oximetry/inspiratory oxygen fraction ratio) ≤185; platelets ≤196×109·L−1; age ≥37.5 years; lactate ≥2.45 mmol·L−1; sodium ≤130.5 mmol·L−1).

  • FIGURE 3
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    FIGURE 3

    Long-term survival of patients discharged from hospital following their first presentation to critical care. p=0.008 medical versus surgical, p=0.001 medical versus obstetric, p=0.073 surgical versus obstetric.

Tables

  • Figures
  • TABLE 1

    Baseline characteristics

    Subjects n242
    Age years52.5 (17–87)
    Female68.2
    PH diagnostic group
     1 Pulmonary arterial hypertension162 (66.9)
      Idiopathic/heritable/drugs and toxins96 (59.3)
      Connective tissue disease associated40 (24.7)
      Congenital heart disease associated18 (11.1)
      Others8 (4.9)
     2 PH due to left heart disease13 (5.3)
     3 PH due to lung disease/chronic hypoxia14 (5.8)
     4 Chronic thromboembolic PH39 (16.1)
     5 Unclear/multifactorial14 (5.8)
    WHO functional class#
     I1.4
     II14.9
     III70.2
     IV13.5
    ISWD m#190 (0–1020)
    Pulmonary haemodynamics¶
     mRAP mmHg10.0 (1–34)
     mPAP mmHg47 (14–74)
     PAWP mmHg10 (0–33)
     CO L·min−14.7 (1.87–14.2)
     CI L·min−1·m−22.6 (1.2–6.0)
     PVR dyn·s−1·cm−5561 (84–2400)
     SvO2 %65 (35–86)

    Data are presented as median (min–max), % or n (%), unless otherwise stated. PH: pulmonary hypertension; WHO: World Health Organization; ISWD: incremental shuttle walk distance; mRAP: mean right atrial pressure; mPAP: mean pulmonary artery pressure; PAWP: pulmonary arterial wedge pressure; CO: cardiac output; CI: cardiac index; PVR pulmonary vascular resistance; SvO2: mixed venous oxygen saturations. #: 2 weeks to 18 months prior to admission; ¶: nearest prior to admission.

    • TABLE 2

      Patient characteristics on critical care admission

      Subjects
      Patient group
       Medical167 (69.0)
       Surgical50 (20.7)
       Obstetric25 (10.3)
      Main reason for admission
       Medical patients
        Isolated heart failure63 (37.7)
        Respiratory failure/chest sepsis44 (26.4)
        Sepsis (other)13 (7.8)
        Renal failure12 (7.2)
        Arrhythmia14 (8.4)
        PE6 (3.6)
        Other15 (9)
       Surgical patients
        Peri-operative (planned):42 (84)
         Orthopaedic18 (36)
         Hernia repair4 (8)
         Other general surgery7 (14)
         Urological3 (6)
         Miscellaneous#10 (20)
        Peri-operative (emergency):8 (16)
         Urological3 (6)
         Neurosurgical2 (4)
         General1 (2)
         Gynaecological1(2)
         Orthopaedic1 (2)
       Obstetric patients
        Peri-partum19 (76)
        Other pregnancy related causes6 (24)
      Physiological parametersMedical¶Surgical/obstetric+p-value
      APACHE II15.0 (2–31)10 (2–21)<0.001
      Heart rate99 (48–163)80 (49–126)<0.001
      mSAP mmHg79 (41–140)85 (56–117)0.001
      Respiratory rate24 (12–52)17 (9–39)<0.001
      SpO2/FiO2 ratio168 (68–467)278 (108–467)<0.001
      PaO2 kPa10.4 (4.3–28.9)13.7 (6.9–25.3)<0.001
      PaO2/FiO2 ratio22 (5–72)49 (9–89)<0.001
      CVP mmHg18 (2–35)8 (3–22)<0.001
      Glasgow Coma Scale15 (3–15)15 (13–15)0.010
      pH7.43 (6.98–7.54)7.41 (7.31–7.51)0.253
      Base excess mmol·L−1−2.6 (−20.4–26.9)−1.75 (−8.5–7.2)0.219
      Lactate mmol·L−11.2 (0.4–14.1)1.0 (0.5–2.4)0.006
      Sodium mmol·L−1135 (113–147)138 (127–146)<0.001
      Urea mmol·L−110.2 (2.5–59.4)3.9 (1.2–16.1)<0.001
      Creatinine μmol·L−1117 (3–891)61.5 (26–181)<0.001
      Bilirubin μmol·L−117 (1–131)11 (2–55)<0.001
      AST IU·L−127 (6–4733)18 (11–150)<0.001
      CRP mg·L−138 (1–471)11.6 (0.3–340)<0.001
      Haemoglobin g·L−1119 (53–204)113 (86–166)0.027
      Platelets ×109·L−1194 (32–859)202 (73–448)0.297

      Data are presented as n (%) or median (min–max), unless otherwise stated. Comparisons made using Mann–Whitney U-test, medical versus surgical/obstetric groups. PE: pulmonary embolism; APACHE II: Acute Physiology and Chronic Health Evaluation II; mSAP: mean systemic arterial pressure; SpO2: oxygen saturation measured by pulse oximetry; FiO2: inspiratory oxygen fraction; PaO2: arterial oxygen tension; CVP: central venous pressure; AST: aspartate aminotransferase; CRP: C-reactive protein. #: neurosurgery, spinal surgery, vascular, breast and gynaecological; ¶: n=167; +: n=75.

      • TABLE 3

        Critical care and hospital survival according to patient group and intensive care unit (ICU) therapy

        NICU survivalHospital survival90-day survival1-year survivalN#5-year survival#
        Overall242190 (78.5)169 (69.8)158 (65.3)132 (54.5)14645 (30.8)
        Patient group
         Medical167120 (71.9)99 (59.3)91 (54.5)68 (40.7)11426 (22.8)
         Surgical5047 (94.0)47 (94.0)45 (90)42 (84)1910 (52.6)
         Obstetric2523 (92.0)23 (92.0)22 (88)22 (88)139 (69.2)
        PH group
         1 PAH162127 (78.4)115 (71.0)107 (66.0)90 (55.6)9532 (33.7)
         2 PH due to left heart disease1311 (84.6)10 (76.9)10 (76.9)8 (61.5)72 (28.6)
         3 PH due to lung disease/hypoxia149 (64.3)8 (57.1)7 (50)6 (42.9)100 (0)
         4 Chronic thromboembolic PH3934 (87.2)29 (74.4)27 (69.2)24 (61.5)2610 (38.5)
         5 Unclear/multifactorial149 (64.3)7 (50)7 (50)4 (28.6)81 (12.5)
        ICU therapy (medical patients only)
         CPAP as highest level of ventilatory support5334 (64.1)27 (50.9)25 (47.1)20 (37.7)332 (6.1)
         NPPV as highest level of ventilatory support159 (60)6 (40)5 (33.3)3 (20)100 (0)
         IPPV as highest level of ventilatory support93 (33.3)1 (11.1)1 (11.1)1 (11.1)90 (0)
         CRRT2217 (77.3)11 (50.0)9 (40.9)7 (31.8)205 (25)
         Vasopressors received4923 (46.9)16 (32.7)15 (30.6)11 (22.4)283 (10.7)
         Inotropes received3717 (45.9)13 (35.1)12 (32.4)7 (18.9)293 (10.3)
         Prostaglandins (intravenous) received11378 (69.0)68 (60.2)61 (54)45 (39.8)7318 (24.7)

        Data are presented as n (%), unless otherwise stated. PH: pulmonary hypertension; PAH: pulmonary arterial hypertension; CPAP: continuous positive airway pressure; NPPV: non-invasive positive pressure ventilation: IPPV: invasive positive pressure ventilation; CRRT: continuous renal replacement therapy. #: patients admitted prior to 31 December 2013 for whom 5 years of survival data is available.

        • TABLE 4

          Medical patients: univariate predictors of hospital mortality

          VariableNOR (95% CI)p-value
          Age years1671.02 (1.01–1.04)0.005
          Female (ref.)1670.914 (0.481–7.738)0.784
          PH group1670.704
           1 Pulmonary arterial hypertensionRef.
           2 PH due to left heart disease1.568 (0.303–8.120)0.592
           3 PH due to lung disease/hypoxia1.307 (0.376–4.541)0.674
           4 Chronic thromboembolic PH0.882 (0.359–2.169)0.785
           5 Unclear/multifactorial2.195 (0.656–7.350)0.202
          Admission reason#1670.03
           Heart failureRef.Ref.
           Respiratory failure/chest sepsis0.554 (0.254–1.208)0.138
           Sepsis (other)0.356 (0.099–1.277)0.113
           Pulmonary embolism0.800 (0.150–4.274)0.794
           Arrhythmia0.133 (0.028–0.646)0.012
           Renal failure0.267 (0.066–1.079)0.064
           Other0.200 (0.051–0.779)0.020
          ISWD1020.998 (0.995–1.001)0.242
          APACHE II1371.180 (1.095–1.270)<0.001
          Heart rate1661.011 (0.995–1.028)0.190
          mSAP mmHg1630.983 (0.964–1.003)0.100
          Respiratory rate1671.046 (1.005–1.087)0.026
          SpO2 %1670.984 (0.939–1.030)0.482
          FiO21655.896 (1.445–24.061)0.013
          PaO2 kPa1420.959 (0.888–1.036)0.292
          SpO2/FiO2 ratio1340.997 (0.993–1.001)0.114
          PaO2/FiO2 ratio1340.983 (0.959–1.008)0.187
          Central venous pressure mmHg541.096 (1.021–1.177)0.011
          Glasgow Coma Scale1380.727 (0.539–0.980)0.036
          pH1480.007 (0.000–0.393)0.016
          Base excess mEq·L−11470.933 (0.886–0.984)0.01
          Lactate mmol·L−11411.425 (1.117–1.817)0.004
          Serum sodium mmol·L−11570.937 (0.884–0.993)0.027
          Serum urea mmol·L−115612.7 (4.37–80.2)0.001
          Serum creatinine µmol·L−11551.005 (1.001–1.009)0.013
          Total bilirubin µmol·L−11436.08 (2.97–19.8)0.022
          AST IU·L−11230.999 (0.995–1.002)0.456
          CRP mg·L−11411.005 (1.000–1.009)0.054
          Haemoglobin g·L−11570.990 (0.978–1.003)0.123
          Platelets ×109·L−11560.997 (0.994–1.000)0.033
          Right atrial pressure mmHg1091.044 (0.990–1.101)0.108
          Mean PAP mmHg1141.005 (0.973–1.037)0.775
          PAWP mmHg1021.000 (0.919–1.088)1.000
          Cardiac output L·min−11100.909 (0.743–1.112)0.352
          Cardiac index L·min−1·m−21040.838 (0.584–1.201)0.335
          PVR dyn·s−1·cm−5991.000 (0.999–1.001)0.482
          SvO2 %1020.966 (0.929–1.005)0.087

          Variables either at most recent review prior to admission (Right heart catheter data, ISWD at 2 weeks to 18 months prior to admission) or at critical care admission (e.g. laboratory tests and physiological observations). Bold indicates statistical significance. PH: pulmonary hypertension; ISWD: incremental shuttle walking distance; APACHE II: Acute Physiology and Chronic Health Evaluation II; mSAP: mean systemic arterial pressure; SpO2: oxygen saturation measured by pulse oximetry; FiO2: inspiratory oxygen fraction; PaO2: arterial oxygen tension; AST: aspartate aminotransferase; CRP: C-reactive protein; PAP: pulmonary artery pressure; PAWP: pulmonary arterial wedge pressure; PVR: pulmonary vascular resistance; SvO2: mixed venous oxygen saturation. #: main indication for critical care admission.

          • TABLE 5

            Medical patients: multivariate predictors of hospital mortality

            VariableOR (95% CI)p-value
            Model 1#
             APACHE II per point1.148 (1.052–1.253)0.002
             Sodium mmol·L−10.927 (0.864–0.996)0.038
             Platelets ×109·L−10.997 (0.993–1.000)0.052
             SpO2/FiO2 ratio0.997 (0.992–1.001)0.104
             Bilirubin IU·L−10.997 (0.970–1.024)0.806
             Creatinine µmol·L−10.999 (0.995–1.004)0.790
             Lactate mmol·L−11.292 (0.983–1.700)0.067
            Model 2¶
             Age years1.045 (1.018–1.073)0.001
             Sodium mmol·L−10.901 (0.836–0.971)0.007
             Platelets ×109·L−10.996 (0.993–1.000)0.038
             SpO2/FiO2 ratio0.995 (0.991–0.999)0.020
             Total bilirubin µmol·L−10.993 (0.966–1.021)0.620
             Creatinine µmol·L−11.002 (0.998–1.006)0.333
             Lactate mmol·L−11.562 (1.181–2.066)0.002

            APACHE II: Acute Physiology and Chronic Health Evaluation II; SpO2: oxygen saturation measured by pulse oximetry; FiO2: inspiratory oxygen fraction. #: incorporating APACHE II; ¶: excluding APACHE II.

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            Critical care outcomes in patients with pre-existing pulmonary hypertension: insights from the ASPIRE registry
            Kris Bauchmuller, Robin Condliffe, Jennifer Southern, Catherine Billings, Athanasios Charalampopoulos, Charlie A. Elliot, Abdul Hameed, David G. Kiely, Ian Sabroe, A.A. Roger Thompson, Ajay Raithatha, Gary H. Mills
            ERJ Open Research Apr 2021, 7 (2) 00046-2021; DOI: 10.1183/23120541.00046-2021

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            Critical care outcomes in patients with pre-existing pulmonary hypertension: insights from the ASPIRE registry
            Kris Bauchmuller, Robin Condliffe, Jennifer Southern, Catherine Billings, Athanasios Charalampopoulos, Charlie A. Elliot, Abdul Hameed, David G. Kiely, Ian Sabroe, A.A. Roger Thompson, Ajay Raithatha, Gary H. Mills
            ERJ Open Research Apr 2021, 7 (2) 00046-2021; DOI: 10.1183/23120541.00046-2021
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