Introduction
Methods
Study setting
Study population
Data collection
Measurement of fluid biomarkers
Outcome
Statistical analysis
Results
Baseline characteristics
Factor | CPC All | Good neurological outcome, CPC 1–2 | Poor neurological outcome, CPC 3–5 | p value |
---|---|---|---|---|
N, n (%) | 164 (100%) | 66 (40%) | 98 (60%) | |
Sociodemographics | ||||
Age, mean (SD) | 63 (15) | 60 (17) | 65 (14) | 0.027 |
Male, n (%) | 117 (71.3%) | 55 (83%) | 62 (63%) | 0.008 |
Comorbidities | ||||
Coronary heart disease, n (%) | 109 (66.5%) | 50 (76%) | 59 (60%) | 0.044 |
Congestive heart failure, n (%) | 20 (12.2%) | 7 (11%) | 13 (13%) | 0.81 |
COPD, n (%) | 15 (9.1%) | 3 (5%) | 12 (12%) | 0.11 |
Liver disease, n (%) | 3 (1.8%) | 0 (0%) | 3 (3%) | 0.27 |
Hypertension, n (%) | 86 (52.4%) | 37 (56%) | 49 (50%) | 0.52 |
Diabetes, n (%) | 39 (23.8%) | 9 (14%) | 30 (31%) | 0.015 |
Chronic kidney disease, n (%) | 24 (14.6%) | 8 (12%) | 16 (16%) | 0.51 |
Malignant disease, n (%) | 14 (8.5%) | 2 (3%) | 12 (12%) | 0.047 |
Neurological disease, n (%) | 13 (7.9%) | 2 (3%) | 11 (11%) | 0.077 |
Resuscitation measures | ||||
No-flow time, min, mean (SD) | 4.22 (5.93) | 1.70 (2.96) | 6.02 (6.83) | < 0.001 |
Low-flow time, min, mean (SD) | 20.42 (15.13) | 16.53 (14.30) | 23.12 (15.17) | 0.006 |
Cardiac arrest setting | ||||
At home | 63 (38.4%) | 16 (24%) | 47 (48%) | < 0.001 |
In public | 78 (47.6%) | 43 (65%) | 35 (36%) | |
In hospital | 23 (14.0%) | 7 (11%) | 16 (16%) | |
Witnessed | 137 (83.5%) | 63 (95%) | 74 (76%) | < 0.001 |
Bystander CPR | 103 (62.8%) | 51 (77%) | 52 (53%) | 0.002 |
Initial heart rhythm | ||||
Ventricular tachycardia | 6 (3.7%) | 2 (3%) | 4 (4%) | < 0.001 |
Ventricular fibrillation | 88 (53.7%) | 53 (80%) | 35 (36%) | |
Asystole | 35 (21.3%) | 2 (3%) | 33 (34%) | |
Pulseless electrical activity | 29 (17.7%) | 6 (9%) | 23 (23%) | |
Unknown | 6 (3.7%) | 3 (5%) | 3 (3%) | |
Epinephrine during resuscitation (mg), mean (SD) | 2.18 (2.55) | 1.08 (1.76) | 2.96 (2.73) | < 0.001 |
Targeted temperature management (TTM), n (%) | 109 (66.5%) | 40 (61%) | 69 (70%) | 0.19 |
Initial clinical parameter and levels of routine blood markers | ||||
GCS, mean (SD) | 7.3 (4.1) | 7 (5) | 4 (1) | < 0.001 |
pH, mean (SD) | 7.25 (0.12) | 7.29 (0.09) | 7.22 (0.13) | 0.003 |
Lactate, mean (SD) | 7.3 (4.1) | 5.9 (3.3) | 8.3 (4.2) | < 0.001 |
NfL (pg/ml), mean (SD) | 429 (1415) | 49 (111) | 685 (1787) | 0.004 |
NfL (pg/ml), median (IQR) | 51 (21, 173) | 27 (13, 46) | 116 (41, 330) | < 0.001 |
Primary endpoint: Poor neurological outcome measured with the cerebral performance category (CPC) score
Good neurological outcome (CPC 1–2) | Poor neurological outcome (CPC 3–5) | p value | Univariate | Multivariatea adjusted | NFL and OHCA score: multivariatea adjusted | NFL and CAHP score: multivariatea adjusted | ||||
---|---|---|---|---|---|---|---|---|---|---|
n = 66 | n = 98 | OR (95% CI), p | AUC | OR (95% CI), p | OR (95% CI), p | AUC combined with NFL | OR (95% CI), p | AUC combined with NFL | ||
Primary endpoint: neurological outcome (CPC) | ||||||||||
NfL, mean (SD) | 49 (111) | 685 (1787) | 0.004 | 2.93 (2.01, 4.27), p < 0.001 | 0.82 | 3.44 (2.13, 5.55), p < 0.001 | 2.81 (1.69, 4.67), p < 0.001 | 0.89 | 3.45 (1.89, 6.29), p < 0.001 | 0.92 |
NfL, median (IQR) | 27 (13, 46) | 116 (41, 330) | < 0.001 | |||||||
Quartiles of NFL | ||||||||||
1st quartile | 29 (44%) | 12 (12%) | < 0.001 | Reference group | Reference group | Reference group | Reference group | |||
2nd quartile | 25 (38%) | 16 (16%) | 1.55 (0.62, 3.88), p = 0.35 | 1.35 (0.46, 4.03), p = 0.59 | 1.02 (0.28, 3.7), p = 0.97 | 1.01 (0.24, 4.23), p = 0.98 | ||||
3rd quartile | 10 (15%) | 31 (32%) | 7.49 (2.81, 19.96), p < 0.001 | 5.59 (1.65, 18.94), p = 0.006 | 3.33 (0.82, 13.41), p = 0.091 | 3.99 (0.84, 18.96), p = 0.08 | ||||
4th quartile | 2 (3%) | 39 (40%) | 47.12 (9.78, 227.01), p < 0.001 | 127.26 (16.53, 979.47), p < 0.001 | 92.39 (8.47, 1007.63), p < 0.001 | 140.48 (10.5, 1880.26), p < 0.001 | ||||
OHCA, mean (SD) | 11 (16) | 32 (17) | < 0.001 | 1.08 (1.05, 1.1), p < 0.001 | 0.82 | 1.08 (1.05, 1.11), p < 0.001 | 1.07 (1.04, 1.11), p < 0.001 | |||
CAHP, mean (SD) | 118 (41) | 182 (38) | < 0.001 | 1.04 (1.03, 1.05), p < 0.001 | 0.89 | 1.04 (1.03, 1.05), p < 0.001 | 1.04 (1.02, 1.06),p < 0.001 |
Good neurological outcome (mRs 0–2) | Poor neurological outcome (mRs 3–6) | p value | Univariate | Multivariatea adjusted | NFL and OHCA score: multivariatea adjusted | NFL and CAHP score: multivariatea adjusted | ||||
---|---|---|---|---|---|---|---|---|---|---|
n = 53 | n = 111 | OR (95% CI), p | AUC | OR (95% CI), p | OR (95% CI), p | AUC combined with NFL | OR (95% CI), p | AUC combined with NFL | ||
Secondary endpoint: Neurological outcome (mRs) | ||||||||||
NFL, mean (SD) | 51 (123) | 609 (1691) | 0.018 | 2.72 (1.85, 3.98), p < 0.001 | 0.8 | 3.01 (1.88, 4.83), p < 0.001 | 2.47 (1.52, 4.04), p < 0.001 | 0.87 | 2.78 (1.64, 4.72), p < 0.001 | 0.88 |
NfL, median (IQR) | 21 (12, 40) | 92 (37, 284) | < 0.001 | |||||||
Quartiles of NFL | ||||||||||
1st quartile | 26 (49.1%) | 15 (13.5%) | < 0.001 | Reference group | Reference group | Reference group | Reference group | |||
2nd quartile | 18 (34.0%) | 23 (20.7%) | 2.21 (0.91, 5.37), p = 0.078 | 2.11 (0.73, 6.1), p = 0.17 | 1.8 (0.56, 5.83), p = 0.326 | 1.89 (0.55, 6.46), p = 0.309 | ||||
3rd quartile | 7 (13.2%) | 34 (30.6%) | 8.42 (3, 23.64), p < 0.001 | 6.14 (1.73, 21.8), p = 0.005 | 3.6 (0.9, 14.41), p = 0.07 | 3.97 (0.94, 16.7), p = 0.06 | ||||
4th quartile | 2 (3.8%) | 39 (35.1%) | 33.8 (7.13, 160.31), p < 0.001 | 66.08 (9.66, 452.17), p < 0.001 | 42.17 (4.72, 376.98), p = 0.001 | 53.32 (5.52, 514.78), p = 0.001 | ||||
OHCA, mean (SD) | 11 (16) | 30 (18) | < 0.001 | 1.06 (1.04, 1.09), p < 0.001 | 0.79 | 1.07 (1.04, 1.1), p < 0.001 | 1.06 (1.03, 1.08), p < 0.001 | |||
CAHP, mean (SD) | 117 (42) | 175 (42) | < 0.001 | 1.03 (1.02, 1.04), p < 0.001 | 0.84 | 1.03 (1.02, 1.04), p < 0.001 | 1.03 (1.02, 1.04), p < 0.001 |
Survivors | Non-Survivors | p value | Univariate | Age, gender, comorbidities adjusted | NFL and OHCA score: multivariatea adjusted | NFL and CAHP score: multivariatea adjusted | ||||
---|---|---|---|---|---|---|---|---|---|---|
n = 73 | n = 91 | OR (95% CI), p | AUC | OR (95% CI), p | OR (95% CI), p | AUC combined with NFL | OR (95% CI), p | AUC combined with NFL | ||
Secondary endpoint: 30-day mortality | ||||||||||
NfL, mean (SD) | 136 (701) | 664 (1763) | 0.017 | 2.77 (1.94, 3.95), p < 0.001 | 0.83 | 2.97 (1.91, 4.62), p < 0.001 | 2.42 (1.54, 3.8), p < 0.001 | 0.87 | 2.59 (1.6, 4.2), p < 0.001 | 0.89 |
NfL, median (IQR) | 27 (13, 47) | 128 (45, 330) | < 0.001 | |||||||
Quartiles of NFL | ||||||||||
1st quartile | 33 (45%) | 8 (9%) | < 0.001 | Reference group | Reference group | Reference group | Reference group | |||
2nd quartile | 25 (34%) | 16 (18%) | 2.64 (0.98, 7.14), p = 0.056 | 2.47 (0.75, 8.1), p = 0.135 | 2.29 (0.62, 8.42), p = 0.211 | 2.32 (0.58, 9.3), p = 0.235 | ||||
3rd quartile | 11 (15%) | 30 (33%) | 11.25 (3.99, 31.71), p < 0.001 | 7.85 (2.19, 28.09), p = 0.002 | 5.49 (1.39, 21.76), p = 0.015 | 5.87 (1.35, 25.57), p = 0.019 | ||||
4th quartile | 4 (5%) | 37 (41%) | 38.16 (10.52, 138.44), p < 0.001 | 92.29 (15.16, 561.71), p < 0.001 | 49.33 (7.29, 333.79), p < 0.001 | 65.12 (8.32, 509.95), p < 0.001 | ||||
OHCA, mean (SD) | 14 (18) | 32 (17) | < 0.001 | 1.06 (1.04, 1.09), p < 0.001 | 0.77 | 1.07 (1.04, 1.1), p < 0.001 | 1.05 (1.03, 1.08), p < 0.001 | |||
CAHP, mean (SD) | 123 (43) | 182 (38) | < 0.001 | 1.03 (1.02, 1.04), p < 0.001 | 0.85 | 1.03 (1.02, 1.04), p < 0.001 | 1.03 (1.02, 1.04), p < 0.001 |
CPC score | mRS | Mortality 30 days | |||||||
---|---|---|---|---|---|---|---|---|---|
NfL cut-off 25 pg/ml | NfL cut-off 50 pg/ml | NfL cut-off 75 pg/ml | NfL cut-off 25 pg/ml | NfL cut-off 50 pg/ml | NfL cut-off 75 pg/ml | NfL cut-off 25 pg/ml | NfL cut-off 50 pg/ml | NfL cut-off 75 pg/ml | |
Poor outcome/total per group | 12/43 | 15/38 | 71/83 | 16/43 | 21/38 | 74/83 | 8/43 | 15/38 | 68/83 |
Sensitivity Pr(+ A) | 87.80% | 72.40% | 61.20% | 85.60% | 66.70% | 55.00% | 91.20% | 74.70% | 63.70% |
Specificity Pr(− N) | 47.00% | 81.80% | 90.90% | 50.90% | 83.00% | 90.60% | 47.90% | 79.50% | 89.00% |
ROC area (sens. + spec.)/2 | 0.67 | 0.77 | 0.76 | 0.68 | 0.75 | 0.73 | 0.7 | 0.77 | 0.76 |
Likelihood ratio ( +) Pr(+ A)/Pr(+ N) | 1.65 | 3.98 | 6.73 | 1.74 | 3.93 | 5.83 | 1.75 | 3.64 | 5.82 |
Likelihood ratio (−) Pr(− A)/Pr(− N) | 0.26 | 0.34 | 0.43 | 0.28 | 0.4 | 0.5 | 0.18 | 0.32 | 0.41 |
Odds ratio LR( +)/LR(−) | 6.35 | 11.83 | 15.79 | 6.17 | 9.78 | 11.71 | 9.56 | 11.43 | 14.28 |
Positive predictive value Pr(A +) | 71.10% | 85.50% | 90.90% | 78.50% | 89.20% | 92.40% | 68.60% | 81.90% | 87.90% |
Negative predictive value Pr(N −) | 72.10% | 66.70% | 61.20% | 62.80% | 54.30% | 49.00% | 81.40% | 71.60% | 66.30% |