Does Neurocritical Care Improve Mortality

The effect of secular trends and specialist neurocritical care on mortality for patients with

Intracerebral Haemorrhage, Myasthenia Gravis, and Guillain-Barré syndrome admitted to

critical care

An analysis of the Intensive Care National Audit & Research Centre (ICNARC) national United

Kingdom database

– Supplement Document

Maxwell Damian 1, Yoav Ben-Shlomo 2, Robin Howard 3, Tony Bellotti 4, David Harrison 4, Kathryn

Griggs 4, Kathryn Rowan 4.

1 Neurosciences Critical Care Unit and Department of Neurology, Addenbrooke’s Hospital, Cambridge

CB2 0QQ and Ipswich Hospital, Ipswich IP5 4PD

2 School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS

3 The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG and St.

Thomas’ Hospital, London SE1 7EH

4 ICNARC, Tavistock House, Tavistock Square, London WC1H 9HR

Table S1. Descriptive statistics for admissions with Myasthenia Gravis by unit group.

NCCU GICU-FNS GICU-LNS All Number of admissions 254 308 502 1,064 Number women (%) 141 (55.5) 159 (51.6) 286 (57.0) 586 (55.1) Age, mean (sd) 62.7 (18.1) 63.5 (17.3) 63.0 (20.1) 63.1 (18.8) IMD quintile, n (%): 1 (least deprived) 52 (20.5) 46 (14.9) 91 (18.1) 189 (17.8) 2 29 (11.4) 46 (14.9) 110 (21.9) 185 (17.4) 3 58 (22.8) 67 (21.8) 108 (21.5) 233 (21.9) 4 58 (22.8) 70 (22.7) 104 (20.7) 232 (21.8) 5 (most deprived) 44 (17.3) 61 (19.8) 64 (12.8) 169 (15.9) ICNARC score, mean (sd) 16.1 (7.5) 15.7 (8.9) 15.6 (8.1) 15.8 (8.2) Lowest Glasgow coma score in first 24 12.4 (3.9) 13.5 (3.3) 13.6 (3.2) 13.3 (3.4) hours *, mean (sd) Number of admissions with 1 or more 53 (20.9) 91 (29.6) 111 (22.1) 255 (24.0) severe comorbidities, n (%) Ventilated in the first 24 hours, n (%) 167 (65.8) 177 (57.5) 314 (62.6) 658 (61.8) Source of admission, n (%): Same hospital: 221 (87.0) 265 (86.0) 430 (85.7) 916 (86.1) Other hospital 33 (13.0) 43 (14.0) 72 (14.3) 148 (13.9) Admission type, n (%) Non-surgical (medical) 245 (96.5) 281 (91.2) 466 (92.8) 992 (93.2) Emergency surgical 9 (3.5) 27 (8.8) 36 (7.2) 72 (6.8) Transferred to other ICU **, n (%) 14 (6.1) 37 (13.0) 56 (12.3) 107 (11.0) CCU length of stay 6.7 [2.6, 13.5] 3.4 [1.3, 9.0] 4.4 [1.5, 10.2] 4.6 [1.7, 10.8] median [IQR]; geometric mean 6.2 3.3 3.7 4.0 Acute hospital length of stay *** 38 [21, 75] 29 [16, 53] 26 [11, 49] 22.5 29 [14, 55] median [IQR]; geometric mean 36.3 28.5 27.0 CCU mortality ***, 22 (9.8) 19 (7.0) 41 (9.2) 82 (8.7) n (%) [95%CI] [6.6, 14.4] [4.5, 10.6] [6.9, 12.3] [7.1 – 10.7] Acute hospital mortality ***, 41 (19.3) 60 (22.8) 97 (22.8) 198 (22.0) n (%) [95%CI] [14.6, 25.2] [18.2, 28.3] [19.0, 27.0] [19.4 – 24.8]

For readmissions within the same acute hospital stay CCU mortality is calculated as 1 episode. * Excluding admissions that were sedated or paralysed during the first 24 hours ** Percentage of unit survivors *** Excluding readmissions to the critical care unit during the hospital stay

GICU-FNS: General ICU with full-time neurological support. GICU-LNS: General ICU with limited neurological support. Table S2. Descriptive statistics for admissions with Guillain-Barré syndrome by unit group.

NCCU GICU-FNS GICU-LNS All Number of admissions 372 487 1,047 1,906 Number women (%) 155 (41.7) 218 (44.8) 476 (45.5) 849 (44.5) Age, mean (sd) 57.0 (18.1) 56.1 (18.4) 56.8 (18.4) 56.7 (18.3) IMD quintile, n (%): 1 (least deprived) 71 (19.1) 69 (14.2) 199 (19.0) 339 (17.8) 2 50 (13.4) 89 (18.3) 203 (19.4) 342 (17.9) 3 84 (22.6) 95 (19.5) 206 (19.7) 385 (20.2) 4 68 (18.3) 118 (24.2) 224 (21.4) 410 (21.5) 5 (most deprived) 85 (22.9) 91 (18.7) 162 (15.5) 338 (17.7) ICNARC score, mean (sd) 15.5 (7.9) 14.6 (7.6) 13.7 (7.5) 14.3 (7.6) Lowest Glasgow coma score in first 24 12.1 (4.2) 13.5 (3.2) 13.9 (2.6) 13.4 (3.2) hours *, mean (sd) Number of admissions with 1 or more 21 (5.7) 47 (9.7) 53 (5.1) 121 (6.4) severe comorbidities, n (%) Ventilated in the first 24 hours, n (%) 245 (65.9) 295 (60.6) 574 (54.8) 1,114 (58.5) Source of admission, n (%): Same hospital: 296 (79.6) 388 (79.7) 820 (78.3) 1,504 (78.9) Other hospital 75 (20.2) 98 (20.1) 226 (21.6) 399 (20.9) Admission type, n (%) Non-surgical (medical) 366 (98.4) 480 (98.6) 1,035 (98.9) 1,881 (98.7) Elective surgical 2 (0.5) 4 (0.8) 6 (0.6) 12 (0.6) Emergency surgical 4 (1.1) 2 (0.4) 6 (0.6) 12 (0.6) Transferred to other ICU **, n (%) 72 (20.6) 108 (24.1) 146 (15.2) 326 (18.5) CCU length of stay (days) 10.2 [3.8, 24.4] 7.9 [2.8, 23.1] 7.0 [2.4, 21.7] 8.0 [2.7, 22.8] median [IQR]; geometric mean 8.7 7.3 6.6 7.2 Acute hospital length of stay (days) 63 [34, 101] 55 [26, 109] 45 [21, 94] 52 [24 – 99] ***, 56.4 50.9 42.4 46.9 median [IQR]; geometric mean CCU mortality ***, 19 (5.7) 34 (7.7) 82 (8.4) 135 (7.7) n (%) [95%CI] [3.6, 8.7] [5.5, 10.5] [6.8, 10.4] [6.5, 9.0] Acute hospital mortality ***, 44 (14.6) 75 (18.5) 151 (16.7) 270 (16.8) n (%) [95%CI] [11.0, 19.0] [15.0, 22.5] [14.4, 19.3] [15.0, 18.7]

GICU-FNS: General ICU with full-time neurological support. GICU-LNS: General ICU with limited neurological support. Table S3. Descriptive statistics for admissions with Intracerebral Haemorrhage by unit group.

NCCU GICU-FNS GICU-LNS All Number of admissions 3,753 1,808 4,752 10,313 Number women (%) 1,555 (41.4) 733 (40.5) 1,913 (40.3) 4,201 (40.7) Age, mean (sd) 53.7 (15.3) 55.7 (16.7) 56.2 (16.4) 55.2 (16.1) IMD quintile, n (%): 1 (least deprived) 507 (13.5) 269 (14.9) 723 (15.2) 1,499 (14.5) 2 645 (17.2) 292 (16.2) 785 (16.5) 1,722 (16.7) 3 686 (18.3) 355 (19.6) 874 (18.4) 1,915 (18.6) 4 745 (19.9) 355 (19.6) 897 (18.9) 1,997 (19.4) 5 (most deprived) 940 (25.1) 411 (22.7) 1,142 (24.0) 2,493 (24.2) ICNARC score, mean (sd) 17.8 (7.6) 20.7 (9.3) 20.4 (9.0) 19.5 (8.6) Lowest Glasgow coma score in first 24 6.6 (4.0) 6.0 (4.1) 5.7 (4.1) 6.1 (4.1) hours *, mean (sd) Number of admissions with 1 or more 251 (6.7) 154 (8.5) 282 (5.9) 687 (6.7) severe comorbidities, n (%) Ventilated in the first 24 hours, n (%) 3,328 (88.7) 1,611 (89.1) 4,206 (88.5) 9,145 (88.7) Source of admission, n (%): Same hospital: 2,435 (64.9) 1,545 (85.5) 4,120 (86.7) 8,100 (78.5) Other hospital 1,310 (34.9) 261 (14.4) 617 (13.0) 2,188 (21.2) Admission type, n(%) Non-surgical (medical) 2,297 (61.2) 1,685 (93.2) 4,605 (96.9) 8,587 (83.3) Elective surgical 120 (3.2) 19 (1.1) 25 (0.5) 164 (1.6) Emergency surgical 1,335 (35.6) 104 (5.8) 118 (2.5) 1,557 (15.1) Transferred to other ICU **, n (%) 121 (4.8) 302 (31.0) 733 (29.9) 1,156 (19.4) CCU length of stay (days) 3.8 [1.5, 9.0] 1.3 [0.5, 3.5] 1.2 [0.5, 3.2] 1.8 [0.7, 5.2] median [IQR]; geometric mean 3.5 1.2 1.1 1.7 Acute hospital length of stay (days) 18 [5, 45] 6 [1, 28] 4 [1, 22] 9 [2, 33] ***, 15.9 8.3 7.0 9.8 median [IQR]; geometric mean CCU mortality ***, 1,192 (32.6) 830 (46.3) 2,288 (48.4) 4,310 (42.4) n (%) [95%CI] [31.1, 34.1] [44.0, 48.7] [47.0, 49.8] [41.4 – 43.3] Acute hospital mortality ***, 1,694 (49.5) 1,182 (67.9) 3,155 (69.5) 6,031 (62.1) n (%) [95%CI] [47.8, 51.1] [65.6, 70.0] [68.2, 70.8] [61.2, 63.1]

GICU-FNS: General ICU with full-time neurological support. GICU-LNS: General ICU with limited neurological support. Table S4. Multi-level models of acute hospital mortality for patients with MG Model 1 Model 2 OR (p-value) OR (p-value) [95% CI] [95% CI] Sample size 852 – 901 852 Covariates: Unit type (p-value) (0.59); (0.34)2 (0.49); (0.77)2 NCCU ¹ 1 1 GICU-FNS 1.25 [0.73, 2.13] 1.26 [0.76, 2.09] GICU-LNS 1.29 [0.79, 2.12] 0.98 [0.61, 1.57] Age (per 10 years) 1.71 (<0.001) [1.50, 1.76 (<0.001) [1.51, 2.06] 1.96] Sex (p-value) (0.45) (0.02) Male 0.88 [0.63, 1.22] 0.64 [0.44, 0.93] Female¹ 1 1 IMD score (p-value) (0.41) (0.60) Quintile 1 ¹ 1 1 Quintile 2 1.37 [0.81, 2.32] 1.40 [0.79, 2.48] Quintile 3 0.98 [0.58, 1.65] 0.94 [0.53, 1.66] Quintile 4 0.81 [0.47, 1.41] 1.14 [0.63, 2.06] Quintile 5 1.03 [0.59, 1.79] 1.31 [0.71, 2.43] ICNARC score (per point) 1.10 (<0.001) [1.07, 1.09 (<0.001) [1.07, 1.12] 1.12] No. comorbidities (p-value) (0.68) (0.031) 0¹ 1 1 1 0.98 [0.65, 1.47] 1.28 [0.82, 2.00] 2 1.64 [0.74, 3.64] 4.25 [1.59, 11.38] 3+ 0.00 [-] 0.00 [-] Source of admission (p-value) (0.04) (0.07) Same hospital 0.63 [0.41, 0.97] 0.63 [0.38, 1.03] Other hospital ¹ 1 1 Surgical status (p-value) (0.26) (0.50) Non-surgical (medical)¹ 1 1 Emergency surgical 0.68 [0.34, 1.34] 0.76 [0.35, 1.67] Calendar period (per year) 0.96 (0.15) [0.92, 0.96 (0.19) [0.91, 1.02] 1.01] Unit length of stay (p-value) (0.23) - Quintile 1 (<1 day) 0.81 [0.49, 1.33] - Quintile 2 (1 day) 0.93 [0.52, 1.65] - Quintile 3 ¹ (2 days) 1 - Quintile 4 (3-6 days) 1.16 [0.67, 1.99] - Quintile 5 (≥7 days) 1.38 [0.81, 2.32] - Within-unit rho 2 - 0.00 (0.50) Model 1= each variable alone with no adjustment; Model 2= mutually adjusted for all variables ¹ Reference categories 2 p-values for test of heterogeneity and test for trend, respectively

GICU-FNS: General ICU with full-time neurological support; GICU-LNS: General ICU with limited neurological support Table S5. Multi-level models of acute hospital mortality for patients with GBS Model 1 Model 2 OR (p-value) OR (p-value) [95% CI] [95% CI] Sample size 1,535 – 1,611 1,532 Covariates: Unit type (p-value) (0.39); (0.59)2 (0.32); (0.53)2 NCCU ¹ 1 1 GICU-FNS 1.33 [0.88, 1.99] 1.44 [0.90, 2.30] GICU-LNS 1.18 [0.82, 1.69] 1.23 [0.81, 1.87] Age (per 10 years) 1.90 (<0.001) [1.70, 1.88 (<0.001) [1.66, 2.14] 2.13] Sex (p-value) (0.67) (0.75) Male 1.06 [0.81, 1.38] 0.95 [0.70, 1.30] Female¹ 1 1 IMD score (p-value) (0.72) (0.93) Quintile 1 ¹ 1 1 Quintile 2 1.11 [0.72, 1.71] 1.06 [0.65, 1.75] Quintile 3 0.94 [0.61, 1.45] 1.05 [0.64, 1.72] Quintile 4 1.14 [0.76, 1.73] 1.23 [0.76, 1.99] Quintile 5 0.88 [0.56, 1.39] 1.11 [0.66, 1.89] ICNARC score (per point) 1.12 (<0.001) [1.10, 1.09 (<0.001) [1.07, 1.12] 1.14] No. comorbidities (p-value) (<0.001) (<0.001) 0¹ 1 1 1 2.52 [1.51, 4.21] 1.88 [1.02, 3.44] 2 9.08 [3.72, 22.16] 27.41 [8.28, 90.75] 3+ 13.97 [2.69, 72.46] 48.89 [6.83, 349.84] Source of admission (p-value) (0.76) (0.77) Same hospital 0.95 [0.69, 1.30] 0.95 [0.65, 1.38] Other hospital ¹ 1 1 Surgical status (p-value) (0.34) (0.53) Non-surgical (medical)¹ 1 1 Elective surgical3 - - Emergency surgical 2.48 [0.74, 8.31] 2.09 [0.57, 7.62] Calendar period (per year) 0.98 (0.22) [0.94, 1.00 (0.83) [0.95, 1.04] 1.01] Unit length of stay (p-value) (0.43) - Quintile 1 (<1 day) 0.86 [0.57, 1.31] - Quintile 2 (1 day) 0.80 [0.53, 1.21] - Quintile 3 ¹ (2 days) 1 - Quintile 4 (3-6 days) 0.78 [0.50, 1.21] - Quintile 5 (≥7 days) 1.09 [0.72, 1.64] - Within-unit rho 2 - 0.00 (0.50) Model 1= each variable alone with no adjustment; Model 2= mutually adjusted for all variables ¹ Reference categories 2 p-values for test of heterogeneity and test for trend, respectively 3 Excluded from model due to small numbers GICU-FNS: General ICU with full-time neurological support; GICU-LNS: General ICU with limited neurological support Adjusting for length of stay had little effect on associations with unit type (NCCU 1, GICU-FNS 1.46 [0.91, 2.35], GICU-LNS 1.22 [0.80, 1.86], p value for trend 0.58)