Does anemia contribute to end-organ dysfunction in ICU patients Statistical Analysis Xue Han, MPH and Matt Shotwell, PhD Department of Biostatistics Vanderbilt University School of Medicine November 7, 2014 Contents 1 Analysis 1: Transitional Model to model next day s effect 3 1.1 Outcome1: Daily Delirium...................................... 3 1.1.1 Descriptive Statistics..................................... 3 1.1.2 Multinomial logistic regression with Normal as the reference level for outcome variable Delirium........................................ 4 1.2 Outcome2: Daily troponin (greater than 0.1) as an index of cardiac dysfunction........ 9 1.2.1 Descriptive Statistics..................................... 9 1.3 Outcome3: Daily renal SOFA score 2.............................. 10 1.3.1 Descriptive Statistics..................................... 10 1.3.2 Logistic regression, Daily renal SOFA 2(Y/N)..................... 12 1.3.3 Proportional odds logistic regression regression, Ordinal response (0-4)......... 12 1.4 Outcome4: Daily resp SOFA score ( 2).............................. 13 1.4.1 Descriptive Statistics..................................... 13 1.4.2 Logistic regression, Daily RESP SOFA 2(Y/N)..................... 14 1.4.3 Proportional odds logistic regression, Ordinal response (0-4)............... 15 1.4.4 Proportional odds logistic regression, Ordinal response (0-4),without three way interaction............................................. 16 1.4.5 Proportional odds logistic regression, Ordinal response (0-4),Sensitivity Analysis... 16 1.4.6 Proportional odds logistic regression, Ordinal response (0-4),Sensitivity Analysis2, without three way interaction................................ 17 1.4.7 Proportional odds logistic regression, Ordinal response (0-4),Marginal Model..... 18 1.4.8 Proportional odds logistic regression, Ordinal response (0-4),Marginal Model with hgb.icu and resp.sofa interaction.............................. 18 1.4.9 Tomorrow resp.sofa 2................................... 21 1.4.10 Tomorrow resp.sofa 3................................... 23 1.4.11 Tomorrow resp.sofa 4................................... 25 1.5 Outcome5: Daily Ventilator (Y/N) as a measure of success of extubation........... 26 1.5.1 Descriptive Statistics..................................... 26 1.5.2 Proportional odds logistic regression, Ordinal response (0-4),Marginal Model..... 26 1.5.3 Logistic regression (Daily Ventilation (Y/N))....................... 26 2 Analysis2: Hb during ICU stay and predicted outcomes 28 2.1 Outcome1: ICU mortality...................................... 28 2.1.1 Descriptive Statistics..................................... 28 2.1.2 Logistic regression for ICU.mortality (Y/N)........................ 28 2.1.3 Time dependent covariate survival analysis for Time to ICU.mortality......... 29 1
2.2 Outcome2: Cardiac dysfunction(tropnin greater than 0.1).................... 30 2.2.1 Correlated time dependent covariate survival analysis for Time to Tropnin greater than 0.1............................................... 30 2.3 Outcome3: Renal dysfunction.................................... 31 2.3.1 Outcome: Time to renal dysfunction Survival analysis with correlated time dependent covariate........................................... 31 2.4 Outcome4: Time to resolution of delirium............................. 31 2.5 Outcome5: Time to successful extubation............................. 31 2
1 Analysis 1: Transitional Model to model next day s effect 1.1 Outcome1: Daily Delirium 1.1.1 Descriptive Statistics Table 1: Descriptive by Icu.status 3 N Normal Discharged Delirious Comatose Deceased Combined Test Statistic N = 1976 N = 697 N = 1994 N = 1917 N = 127 N = 6711 icu.status.today 6711 χ 2 8 = 4326, P < 0.0011 Normal 73% (1451) 66% ( 462) 11% ( 217) 5% ( 88) 9% ( 11) 33% (2229) Delirious 21% ( 410) 28% ( 193) 61% (1210) 20% ( 380) 22% ( 28) 33% (2221) Comatose 6% ( 115) 6% ( 42) 28% ( 567) 76% (1449) 69% ( 88) 34% (2261) Age at enrollment 6711 50 60 70 51 61 71 54 64 73 52 62 70 54 63 73 52 62 71 F 4,6706 = 18, P < 0.001 2 ICU type 6711 Surgical 28% ( 552) 35% ( 242) 42% ( 844) 38% ( 736) 19% ( 24) 36% (2398) χ 2 4 = 112, P < 0.0011 APACHE APS at enrollment 6711 15 20 26 15 21 26 17 23 28 18 24 29 19 25 28 16 22 27 F 4,6706 = 43, P < 0.001 2 Charlson score 6711 1 2 4 1 2 4 1 2 4 1 2 3 1 2 4 1 2 4 F 4,6706 = 8, P < 0.001 2 Framingham stroke risk score 6711 6 9 14 6 10 15 7 11 15 5 9 13 4 9 13 6 10 14 F 4,6706 = 24, P < 0.001 2 Lowest mean arterial pressure, current 24h 6704 55 63 72 58 66 76 55 62 71 54 60 66 46 54 61 55 62 70 F 4,6699 = 51, P < 0.001 2 Was patient in ICU today? 6711 1 ICU 100% (1976) 100% ( 697) 100% (1994) 100% (1917) 100% ( 127) 100% (6711) Study day 6711 3 7 14 3 5 11 3 7 13 2 5 10 3 6 14 3 6 12 F 4,6706 = 35, P < 0.001 2 Septic in the current 24h? 6703 Septic today 60% (1182) 49% ( 344) 67% (1330) 70% (1337) 73% ( 91) 64% (4284) χ 2 4 = 117, P < 0.0011 sevsepsis.l24 6703 Severely septic today 47% ( 926) 34% ( 240) 65% (1302) 69% (1323) 71% ( 89) 58% (3880) χ 2 4 = 406, P < 0.0011 Lowest hemoglobin, current 24h 5837 8.8 9.8 10.8 8.9 9.8 10.8 8.7 9.6 10.7 8.6 9.6 10.7 8.6 9.9 10.6 8.7 9.7 10.7 F 4,5832 = 4.4, P = 0.002 2 a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. N is the number of non missing values. Numbers after percents are frequencies. Tests used: 1 Pearson test; 2 Kruskal-Wallis test
1.1.2 Multinomial logistic regression with Normal as the reference level for outcome variable Delirium 4 Level Discharged vs. Level Normal betahat se pval RRR RRR.lo RRR.up icu.status.todaynormal -2.075 0.720 0.004 0.126 0.031 0.515 icu.status.todaydelirious -1.979 1.058 0.061 0.138 0.017 1.099 icu.status.todaycomatose 0.046 0.264 0.861 1.047 0.625 1.757 age.enroll -0.012 0.006 0.032 0.988 0.978 0.999 icu.typesurgical 0.564 0.136 0.000 1.758 1.347 2.296 apache.aps 0.015 0.008 0.063 1.015 0.999 1.030 charlson.score -0.015 0.026 0.561 0.985 0.935 1.037 stroke.risk 0.027 0.013 0.038 1.027 1.001 1.054 map.low.icu 0.012 0.004 0.008 1.012 1.003 1.021 study.day 0.015 0.064 0.812 1.015 0.896 1.151 sepsis.l24septic today -0.282 0.127 0.026 0.754 0.589 0.967 hgb.icu 0.089 0.060 0.136 1.093 0.972 1.228 study.day:hgb.icu -0.008 0.007 0.210 0.992 0.979 1.005 icu.status.todaydelirious:age.enroll 0.003 0.010 0.806 1.003 0.982 1.023 icu.status.todaycomatose:age.enroll 0.032 0.018 0.077 1.032 0.997 1.069 icu.status.todaydelirious:icu.typesurgical -0.594 0.237 0.012 0.552 0.347 0.879 icu.status.todaycomatose:icu.typesurgical -0.742 0.438 0.090 0.476 0.202 1.123 icu.status.todaydelirious:apache.aps -0.015 0.015 0.310 0.985 0.957 1.014 icu.status.todaycomatose:apache.aps 0.010 0.025 0.690 1.010 0.962 1.060 icu.status.todaydelirious:charlson.score 0.029 0.052 0.577 1.030 0.929 1.141 icu.status.todaycomatose:charlson.score -0.073 0.103 0.479 0.930 0.760 1.138 icu.status.todaydelirious:stroke.risk 0.013 0.025 0.606 1.013 0.965 1.063 icu.status.todaycomatose:stroke.risk -0.081 0.046 0.076 0.922 0.843 1.009 icu.status.todaydelirious:map.low.icu -0.004 0.008 0.665 0.996 0.980 1.013 icu.status.todaycomatose:map.low.icu 0.025 0.015 0.092 1.026 0.996 1.057 icu.status.todaydelirious:study.day 0.155 0.106 0.144 1.167 0.948 1.436 icu.status.todaycomatose:study.day -0.372 0.180 0.039 0.689 0.484 0.981 icu.status.todaydelirious:sepsis.l24septic today -0.245 0.235 0.296 0.783 0.494 1.239 icu.status.todaycomatose:sepsis.l24septic today -0.068 0.403 0.865 0.934 0.424 2.057 icu.status.todaydelirious:hgb.icu 0.032 0.102 0.754 1.032 0.845 1.261 icu.status.todaycomatose:hgb.icu -0.495 0.140 0.000 0.609 0.463 0.802 icu.status.todaydelirious:study.day:hgb.icu -0.010 0.011 0.356 0.990 0.969 1.012 icu.status.todaycomatose:study.day:hgb.icu 0.043 0.019 0.020 1.044 1.007 1.083
5 Level Delirious vs. Level Normal betahat se pval RRR RRR.lo RRR.up icu.status.todaynormal -3.293 0.993 0.001 0.037 0.005 0.260 icu.status.todaydelirious 0.414 0.711 0.561 1.513 0.375 6.099 icu.status.todaycomatose 1.005 0.782 0.199 2.732 0.590 12.644 age.enroll -0.002 0.008 0.777 0.998 0.983 1.013 icu.typesurgical 0.804 0.177 0.000 2.234 1.579 3.160 apache.aps 0.012 0.011 0.246 1.012 0.992 1.034 charlson.score -0.021 0.036 0.566 0.979 0.912 1.052 stroke.risk 0.050 0.017 0.003 1.051 1.017 1.086 map.low.icu -0.006 0.006 0.302 0.994 0.982 1.006 study.day 0.032 0.078 0.683 1.032 0.887 1.202 sepsis.l24septic today 0.332 0.172 0.054 1.393 0.994 1.953 hgb.icu 0.110 0.082 0.183 1.116 0.949 1.311 study.day:hgb.icu -0.007 0.008 0.394 0.993 0.978 1.009 icu.status.todaydelirious:age.enroll 0.013 0.010 0.163 1.013 0.995 1.033 icu.status.todaycomatose:age.enroll 0.032 0.013 0.011 1.033 1.008 1.058 icu.status.todaydelirious:icu.typesurgical -0.783 0.218 0.000 0.457 0.298 0.701 icu.status.todaycomatose:icu.typesurgical -0.348 0.293 0.235 0.706 0.397 1.254 icu.status.todaydelirious:apache.aps -0.003 0.013 0.821 0.997 0.971 1.023 icu.status.todaycomatose:apache.aps 0.015 0.017 0.391 1.015 0.981 1.050 icu.status.todaydelirious:charlson.score 0.021 0.047 0.660 1.021 0.931 1.120 icu.status.todaycomatose:charlson.score -0.029 0.065 0.655 0.971 0.855 1.104 icu.status.todaydelirious:stroke.risk -0.032 0.022 0.141 0.968 0.927 1.011 icu.status.todaycomatose:stroke.risk -0.080 0.030 0.007 0.923 0.870 0.978 icu.status.todaydelirious:map.low.icu 0.007 0.008 0.356 1.007 0.992 1.022 icu.status.todaycomatose:map.low.icu 0.015 0.011 0.187 1.015 0.993 1.037 icu.status.todaydelirious:study.day -0.062 0.098 0.524 0.940 0.776 1.138 icu.status.todaycomatose:study.day -0.223 0.127 0.079 0.800 0.624 1.026 icu.status.todaydelirious:sepsis.l24septic today -0.209 0.218 0.339 0.811 0.529 1.245 icu.status.todaycomatose:sepsis.l24septic today 0.069 0.282 0.807 1.071 0.616 1.863 icu.status.todaydelirious:hgb.icu -0.193 0.101 0.056 0.824 0.676 1.005 icu.status.todaycomatose:hgb.icu -0.334 0.115 0.004 0.716 0.571 0.898 icu.status.todaydelirious:study.day:hgb.icu 0.013 0.010 0.196 1.013 0.993 1.033 icu.status.todaycomatose:study.day:hgb.icu 0.026 0.013 0.050 1.026 1.000 1.053 Level Comatose vs. Level Normal betahat se pval RRR RRR.lo RRR.up
6 icu.status.todaynormal -1.664 1.404 0.236 0.189 0.012 2.968 icu.status.todaydelirious 0.158 0.877 0.857 1.172 0.210 6.540 icu.status.todaycomatose 2.632 0.689 0.000 13.903 3.606 53.603 age.enroll 0.011 0.011 0.294 1.011 0.990 1.033 icu.typesurgical 0.551 0.254 0.030 1.735 1.055 2.856 apache.aps 0.013 0.015 0.374 1.013 0.984 1.044 charlson.score -0.008 0.050 0.871 0.992 0.900 1.094 stroke.risk -0.022 0.025 0.389 0.978 0.931 1.028 map.low.icu -0.013 0.009 0.117 0.987 0.970 1.003 study.day -0.146 0.117 0.214 0.864 0.687 1.088 sepsis.l24septic today 0.403 0.247 0.102 1.497 0.923 2.428 hgb.icu -0.086 0.122 0.480 0.917 0.722 1.165 study.day:hgb.icu 0.010 0.012 0.394 1.010 0.987 1.034 icu.status.todaydelirious:age.enroll 0.013 0.013 0.314 1.013 0.988 1.040 icu.status.todaycomatose:age.enroll 0.017 0.014 0.227 1.018 0.989 1.047 icu.status.todaydelirious:icu.typesurgical -0.582 0.298 0.051 0.559 0.311 1.001 icu.status.todaycomatose:icu.typesurgical -0.397 0.339 0.241 0.672 0.346 1.306 icu.status.todaydelirious:apache.aps -0.020 0.018 0.258 0.980 0.946 1.015 icu.status.todaycomatose:apache.aps 0.023 0.020 0.244 1.023 0.984 1.064 icu.status.todaydelirious:charlson.score -0.036 0.062 0.563 0.965 0.853 1.090 icu.status.todaycomatose:charlson.score -0.083 0.072 0.247 0.920 0.799 1.059 icu.status.todaydelirious:stroke.risk -0.009 0.031 0.763 0.991 0.933 1.052 icu.status.todaycomatose:stroke.risk -0.056 0.035 0.104 0.945 0.883 1.012 icu.status.todaydelirious:map.low.icu 0.009 0.010 0.408 1.009 0.988 1.029 icu.status.todaycomatose:map.low.icu 0.005 0.012 0.676 1.005 0.981 1.030 icu.status.todaydelirious:study.day 0.120 0.138 0.384 1.128 0.860 1.479 icu.status.todaycomatose:study.day 0.072 0.150 0.633 1.074 0.800 1.442 icu.status.todaydelirious:sepsis.l24septic today -0.191 0.297 0.519 0.826 0.462 1.478 icu.status.todaycomatose:sepsis.l24septic today 0.026 0.325 0.936 1.027 0.543 1.941 icu.status.todaydelirious:hgb.icu -0.001 0.142 0.995 0.999 0.756 1.320 icu.status.todaycomatose:hgb.icu -0.045 0.142 0.754 0.956 0.724 1.264 icu.status.todaydelirious:study.day:hgb.icu -0.008 0.014 0.571 0.992 0.965 1.020 icu.status.todaycomatose:study.day:hgb.icu -0.005 0.015 0.769 0.995 0.966 1.026 Level Deceased vs. Level Normal betahat se pval RRR RRR.lo RRR.up icu.status.todaynormal -1.472 0.076 0.000 0.229 0.198 0.266 icu.status.todaydelirious -0.994 0.138 0.000 0.370 0.282 0.485 icu.status.todaycomatose -0.468 0.553 0.398 0.627 0.212 1.851
7 age.enroll -0.023 0.025 0.355 0.978 0.932 1.026 icu.typesurgical 0.489 0.581 0.400 1.630 0.522 5.092 apache.aps 0.007 0.034 0.841 1.007 0.942 1.077 charlson.score 0.174 0.089 0.051 1.190 1.000 1.417 stroke.risk -0.038 0.061 0.531 0.963 0.854 1.084 map.low.icu -0.012 0.019 0.530 0.988 0.951 1.026 study.day -0.231 0.140 0.098 0.793 0.603 1.044 sepsis.l24septic today 0.479 0.568 0.399 1.614 0.530 4.915 hgb.icu -0.222 0.161 0.168 0.801 0.584 1.098 study.day:hgb.icu 0.028 0.014 0.042 1.029 1.001 1.057 icu.status.todaydelirious:age.enroll 0.036 0.034 0.290 1.037 0.969 1.110 icu.status.todaycomatose:age.enroll 0.062 0.029 0.033 1.064 1.005 1.126 icu.status.todaydelirious:icu.typesurgical -0.377 0.746 0.613 0.686 0.159 2.960 icu.status.todaycomatose:icu.typesurgical -1.181 0.707 0.095 0.307 0.077 1.226 icu.status.todaydelirious:apache.aps 0.021 0.044 0.630 1.022 0.936 1.115 icu.status.todaycomatose:apache.aps 0.012 0.040 0.764 1.012 0.936 1.094 icu.status.todaydelirious:charlson.score 0.011 0.134 0.935 1.011 0.778 1.314 icu.status.todaycomatose:charlson.score -0.162 0.121 0.180 0.850 0.670 1.078 icu.status.todaydelirious:stroke.risk 0.083 0.081 0.305 1.087 0.927 1.274 icu.status.todaycomatose:stroke.risk -0.067 0.073 0.359 0.935 0.811 1.079 icu.status.todaydelirious:map.low.icu -0.031 0.025 0.217 0.970 0.924 1.018 icu.status.todaycomatose:map.low.icu -0.044 0.023 0.058 0.957 0.914 1.002 icu.status.todaydelirious:study.day -0.070 0.206 0.735 0.933 0.622 1.398 icu.status.todaycomatose:study.day 0.458 0.188 0.015 1.581 1.094 2.286 icu.status.todaydelirious:sepsis.l24septic today 0.014 0.778 0.986 1.014 0.220 4.662 icu.status.todaycomatose:sepsis.l24septic today 0.213 0.676 0.753 1.237 0.329 4.656 icu.status.todaydelirious:hgb.icu -0.075 0.222 0.734 0.927 0.600 1.432 icu.status.todaycomatose:hgb.icu 0.339 0.189 0.073 1.403 0.969 2.033 icu.status.todaydelirious:study.day:hgb.icu 0.009 0.021 0.658 1.009 0.969 1.051 icu.status.todaycomatose:study.day:hgb.icu -0.054 0.020 0.006 0.948 0.912 0.985 Level Withdrawn vs. Level Normal betahat se pval RRR RRR.lo RRR.up icu.status.todaynormal 0.116 0.156 0.455 1.123 0.828 1.524 icu.status.todaydelirious -0.038 0.088 0.668 0.963 0.811 1.144 icu.status.todaycomatose -0.044 0.053 0.407 0.957 0.862 1.062 age.enroll 0.004 0.036 0.917 1.004 0.935 1.078 icu.typesurgical 0.735 0.569 0.196 2.085 0.684 6.356 apache.aps -0.009 0.054 0.860 0.991 0.892 1.100
8 charlson.score 0.160 0.123 0.195 1.173 0.921 1.494 stroke.risk -0.055 0.090 0.544 0.947 0.793 1.130 map.low.icu -0.030 0.026 0.251 0.970 0.921 1.022 study.day -0.232 0.439 0.598 0.793 0.335 1.876 sepsis.l24septic today 0.131 0.500 0.793 1.140 0.428 3.035 hgb.icu -0.308 0.224 0.169 0.735 0.473 1.140 study.day:hgb.icu 0.011 0.048 0.824 1.011 0.920 1.110 icu.status.todaydelirious:age.enroll -0.061 0.051 0.230 0.941 0.852 1.039 icu.status.todaycomatose:age.enroll -0.027 0.066 0.687 0.974 0.855 1.109 icu.status.todaydelirious:icu.typesurgical -0.096 0.835 0.909 0.909 0.177 4.669 icu.status.todaycomatose:icu.typesurgical 0.665 0.581 0.253 1.944 0.622 6.072 icu.status.todaydelirious:apache.aps -0.014 0.074 0.852 0.986 0.853 1.140 icu.status.todaycomatose:apache.aps 0.106 0.102 0.301 1.112 0.910 1.359 icu.status.todaydelirious:charlson.score -0.283 0.262 0.280 0.754 0.451 1.259 icu.status.todaycomatose:charlson.score -0.039 0.348 0.912 0.962 0.486 1.903 icu.status.todaydelirious:stroke.risk 0.334 0.121 0.006 1.396 1.102 1.769 icu.status.todaycomatose:stroke.risk -0.157 0.219 0.475 0.855 0.556 1.314 icu.status.todaydelirious:map.low.icu 0.005 0.039 0.893 1.005 0.932 1.085 icu.status.todaycomatose:map.low.icu -0.037 0.064 0.556 0.963 0.850 1.091 icu.status.todaydelirious:study.day -0.213 0.640 0.740 0.808 0.231 2.832 icu.status.todaycomatose:study.day 0.330 0.531 0.534 1.391 0.491 3.940 icu.status.todaydelirious:sepsis.l24septic today -0.354 0.771 0.646 0.702 0.155 3.179 icu.status.todaycomatose:sepsis.l24septic today -1.137 0.608 0.061 0.321 0.098 1.056 icu.status.todaydelirious:hgb.icu 0.166 0.333 0.619 1.180 0.614 2.267 icu.status.todaycomatose:hgb.icu 0.148 0.487 0.761 1.160 0.447 3.012 icu.status.todaydelirious:study.day:hgb.icu 0.026 0.066 0.697 1.026 0.902 1.168 icu.status.todaycomatose:study.day:hgb.icu -0.003 0.058 0.965 0.998 0.891 1.117
1.2 Outcome2: Daily troponin (greater than 0.1) as an index of cardiac dysfunction 1.2.1 Descriptive Statistics Table 2: Descriptive by Troponin (greater than 0.1) 9 N No Yes Combined Test Statistic N = 5710 N = 137 N = 5847 tro.imp.cat 6704 χ 2 1 = 369, P < 0.0011 Yes 5% ( 271) 43% ( 59) 6% ( 330) Highest troponin, current 24h (missing = <0.1) 6704 0.026 0.053 0.080 0.052 0.096 0.920 0.026 0.053 0.080 F 1,5840 = 80, P < 0.001 2 trop.tomo 5847 0.025 0.050 0.076 0.230 0.726 2.110 0.026 0.051 0.078 F 1,5845 = 431, P < 0.001 2 Age at enrollment 6711 52 62 71 54 68 71 52 62 71 F 1,5845 = 3.6, P = 0.057 2 ICU type 6711 Surgical 36% (2067) 36% ( 49) 36% (2116) χ 2 1 = 0.01, P = 0.921 APACHE APS at enrollment 6711 16 22 27 19 23 29 16 22 27 F 1,5845 = 3.5, P = 0.061 2 Charlson score 6711 1 2 4 1 3 4 1 2 4 F 1,5845 = 4.8, P = 0.029 2 Framingham stroke risk score 6711 6 9 14 7 11 15 6 10 14 F 1,5845 = 8.1, P = 0.004 2 Lowest mean arterial pressure, current 24h 6704 55 62 70 49 57 66 55 62 70 F 1,5840 = 18, P < 0.001 2 Was patient in ICU today? 6711 1 ICU 100% (5710) 100% ( 137) 100% (5847) Septic in the current 24h? 6703 Septic today 65% (3732) 65% ( 89) 65% (3821) χ 2 1 = 0.01, P = 0.911 sevsepsis.l24 6703 Severely septic today 60% (3443) 60% ( 82) 60% (3525) χ 2 1 = 0.01, P = 0.911 Lowest hemoglobin, current 24h 5837 8.7 9.6 10.7 8.9 9.8 10.9 8.7 9.7 10.7 F 1,5157 = 2.1, P = 0.14 2 a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. N is the number of non missing values. Numbers after percents are frequencies. Tests used: 1 Pearson test; 2 Wilcoxon test Table 3: Outcome:Tropnin ( 0.1).. P-values less than 0.05 are in red. tro.imp.cat=yes 6.461 2.314 639.977 ( 6.862, 59686.403) 0.005 age.enroll 0.003 0.012 1.003 ( 0.980, 1.027) 0.799 icu.type=surgical -0.003 0.254 0.998 ( 0.607, 1.641) 0.992 apache.aps 0.015 0.015 1.015 ( 0.986, 1.046) 0.322 charlson.score 0.058 0.054 1.059 ( 0.953, 1.177) 0.283 stroke.risk 0.061 0.025 1.063 ( 1.011, 1.117) 0.016 map.low.icu -0.017 0.010 0.983 ( 0.965, 1.002) 0.083 study.day 0.096 0.138 1.100 ( 0.839, 1.443) 0.489 sepsis.l24=septic today -0.045 0.252 0.956 ( 0.584, 1.565) 0.859 hgb.icu 0.067 0.117 1.069 ( 0.850, 1.345) 0.569 study.day * hgb.icu -0.015 0.015 0.985 ( 0.957, 1.014) 0.315 tro.imp.cat=yes * age.enroll -0.018 0.021 0.983 ( 0.944, 1.023) 0.395 tro.imp.cat=yes * icu.type=surgical 0.826 0.422 2.285 ( 0.999, 5.229) 0.050 tro.imp.cat=yes * apache.aps -0.020 0.025 0.981 ( 0.933, 1.030) 0.439
Table 3: (continued) tro.imp.cat=yes * charlson.score -0.082 0.093 0.921 ( 0.768, 1.105) 0.376 tro.imp.cat=yes * stroke.risk -0.092 0.044 0.912 ( 0.836, 0.995) 0.039 tro.imp.cat=yes * map.low.icu -0.011 0.017 0.989 ( 0.957, 1.021) 0.489 tro.imp.cat=yes * study.day -0.746 0.331 0.474 ( 0.248, 0.908) 0.024 tro.imp.cat=yes * sepsis.l24=septic today 0.523 0.422 1.687 ( 0.738, 3.859) 0.215 tro.imp.cat=yes * hgb.icu -0.139 0.176 0.871 ( 0.617, 1.229) 0.430 tro.imp.cat=yes * study.day * hgb.icu 0.084 0.034 1.087 ( 1.017, 1.163) 0.014 1.3 Outcome3: Daily renal SOFA score 2 1.3.1 Descriptive Statistics Table 4: Descriptive by next day s Renal SOFA score 2 10 N No Yes Combined Test Statistic N = 4319 N = 1528 N = 5847 sofa.renal.cat 6704 χ 2 1 = 4270, P < 0.0011 Yes 4% ( 185) 90% (1380) 27% (1565) SOFA renal component score 6704 0 69% (2971) 1% ( 11) 51% (2982) χ 2 4 = 4375, P < 0.0011 1 27% (1161) 9% ( 134) 22% (1295) 2 4% ( 172) 48% ( 726) 15% ( 898) 3 0% ( 6) 21% ( 317) 6% ( 323) 4 0% ( 7) 22% ( 337) 6% ( 344) renal.tomo 5847 0 71% (3061) 0% ( 0) 52% (3061) χ 2 4 = 5847, P < 0.0011 1 29% (1258) 0% ( 0) 22% (1258) 2 0% ( 0) 58% ( 886) 15% ( 886) 3 0% ( 0) 20% ( 303) 5% ( 303) 4 0% ( 0) 22% ( 339) 6% ( 339) Age at enrollment 6711 51 61 71 55 64 71 52 62 71 F 1,5845 = 22, P < 0.001 2 ICU type 6711 Surgical 39% (1668) 29% ( 448) 36% (2116) χ 2 1 = 42, P < 0.0011 APACHE APS at enrollment 6711 16 21 26 19 25 31 16 22 27 F 1,5845 = 158, P < 0.001 2 Charlson score 6711 1 2 3 2 3 4 1 2 4 F 1,5845 = 307, P < 0.001 2 Framingham stroke risk score 6711 6 9 14 6 10 15 6 10 14 F 1,5845 = 20, P < 0.001 2 Lowest mean arterial pressure, current 24h 6704 56 63 71 51 58 65 55 62 70 F 1,5840 = 213, P < 0.001 2 Was patient in ICU today? 6711 1 ICU 100% (4319) 100% (1528) 100% (5847) Septic in the current 24h? 6703 Septic today 65% (2823) 65% ( 998) 65% (3821) χ 2 1 = 0, P = 0.971 sevsepsis.l24 6703 Severely septic today 59% (2533) 65% ( 992) 60% (3525) χ 2 1 = 19, P < 0.0011 Lowest hemoglobin, current 24h 5837 8.8 9.7 10.8 8.6 9.4 10.5 8.7 9.7 10.7 F 1,5157 = 34, P < 0.001 2 a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. N is the number of non missing values. Numbers after percents are frequencies. Tests used: 1 Pearson test; 2 Wilcoxon test
Table 5: Descriptive by next day s Renal SOFA score (0-4) 11 N 0 1 2 3 4 Combined Test Statistic N = 3061 N = 1258 N = 886 N = 303 N = 339 N = 5847 sofa.renal.cat 6704 χ 2 4 = 4379, P < 0.0011 Yes 0% ( 12) 14% ( 173) 85% ( 756) 98% ( 295) 97% ( 329) 27% (1565) SOFA renal component score 6704 0 92% (2820) 12% ( 151) 1% ( 7) 1% ( 2) 1% ( 2) 51% (2982) χ 2 16 = 11626, P < 0.0011 1 7% ( 227) 74% ( 934) 14% ( 122) 2% ( 5) 2% ( 7) 22% (1295) 2 0% ( 7) 13% ( 165) 73% ( 642) 22% ( 66) 5% ( 18) 15% ( 898) 3 0% ( 2) 0% ( 4) 10% ( 88) 59% ( 179) 15% ( 50) 6% ( 323) 4 0% ( 3) 0% ( 4) 3% ( 26) 17% ( 50) 77% ( 261) 6% ( 344) Age at enrollment 6711 51 60 70 52 63 72 56 64 71 60 66 72 47 60 66 52 62 71 F 4,5842 = 22, P < 0.001 2 ICU type 6711 Surgical 40% (1215) 36% ( 453) 35% ( 310) 22% ( 68) 21% ( 70) 36% (2116) χ 2 4 = 77, P < 0.0011 APACHE APS at enrollment 6711 16 21 26 17 22 27 19 24 30 20 27 33 17 23 29 16 22 27 F 4,5842 = 52, P < 0.001 2 Charlson score 6711 1.0 2.0 3.0 1.0 2.0 3.0 2.0 3.0 4.0 2.0 3.0 5.0 2.0 3.0 5.5 1.0 2.0 4.0 F 4,5842 = 93, P < 0.001 2 Framingham stroke risk score 6711 5 9 14 6 10 15 6 10 15 7 12 16 5 8 14 6 10 14 F 4,5842 = 19, P < 0.001 2 Lowest mean arterial pressure, current 24h 6704 57 64 72 53 60 67 51 58 65 52 60 66 50 58 67 55 62 70 F 4,5837 = 84, P < 0.001 2 Was patient in ICU today? 6711 1 ICU 100% (3061) 100% (1258) 100% ( 886) 100% ( 303) 100% ( 339) 100% (5847) Septic in the current 24h? 6703 Septic today 66% (2032) 63% ( 791) 67% ( 589) 61% ( 184) 67% ( 225) 65% (3821) χ 2 4 = 8.4, P = 0.0791 sevsepsis.l24 6703 Severely septic today 58% (1781) 60% ( 752) 66% ( 583) 61% ( 184) 67% ( 225) 60% (3525) χ 2 4 = 23, P < 0.0011 Lowest hemoglobin, current 24h 5837 8.8 9.8 10.8 8.7 9.6 10.7 8.6 9.5 10.5 8.8 9.5 10.5 8.4 9.2 10.4 8.7 9.7 10.7 F 4,5154 = 11, P < 0.001 2 a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. N is the number of non missing values. Numbers after percents are frequencies. Tests used: 1 Pearson test; 2 Kruskal-Wallis test
1.3.2 Logistic regression, Daily renal SOFA 2(Y/N) Table 6: Outcome:Daily renal SOFA =2.. P-values less than 0.05 are in red. 12 sofa.renal.cat=yes 3e+00 1.426 19.367 ( 1.184, 316.697) 0.038 age.enroll 9e-03 0.009 1.009 ( 0.992, 1.026) 0.302 icu.type=surgical -3e-01 0.190 0.739 ( 0.509, 1.073) 0.112 apache.aps 2e-02 0.011 1.024 ( 1.001, 1.047) 0.043 charlson.score 1e-01 0.039 1.100 ( 1.019, 1.189) 0.015 stroke.risk -3e-02 0.021 0.969 ( 0.930, 1.010) 0.142 map.low.icu -4e-02 0.007 0.964 ( 0.950, 0.977) <0.001 study.day 1e-02 0.089 1.010 ( 0.848, 1.202) 0.911 sepsis.l24=septic today 1e-02 0.192 1.011 ( 0.694, 1.471) 0.956 hgb.icu -4e-02 0.091 0.964 ( 0.806, 1.153) 0.689 study.day * hgb.icu -1e-03 0.009 0.999 ( 0.981, 1.017) 0.904 sofa.renal.cat=yes * age.enroll 7e-04 0.012 1.001 ( 0.978, 1.024) 0.952 sofa.renal.cat=yes * icu.type=surgical 5e-02 0.258 1.050 ( 0.634, 1.741) 0.849 sofa.renal.cat=yes * apache.aps -1e-02 0.015 0.985 ( 0.957, 1.015) 0.327 sofa.renal.cat=yes * charlson.score 1e-02 0.057 1.011 ( 0.905, 1.130) 0.845 sofa.renal.cat=yes * stroke.risk 4e-02 0.028 1.039 ( 0.985, 1.097) 0.163 sofa.renal.cat=yes * map.low.icu 4e-02 0.010 1.039 ( 1.020, 1.059) <0.001 sofa.renal.cat=yes * study.day -9e-02 0.123 0.912 ( 0.717, 1.159) 0.451 sofa.renal.cat=yes * sepsis.l24=septic today 3e-01 0.258 1.359 ( 0.820, 2.254) 0.234 sofa.renal.cat=yes * hgb.icu -7e-02 0.121 0.935 ( 0.738, 1.185) 0.578 sofa.renal.cat=yes * study.day * hgb.icu 1e-02 0.013 1.012 ( 0.987, 1.038) 0.346 1.3.3 Proportional odds logistic regression regression, Ordinal response (0-4) Table 7: Outcome:Daily renal SOFA (0-4).. P-values less than 0.05 are in red. sofa.renal 3.202 0.396 24.575 (11.321, 53.346) <0.001 age.enroll 0.009 0.005 1.010 ( 0.999, 1.020) 0.077 icu.type=surgical -0.158 0.119 0.854 ( 0.676, 1.079) 0.185 apache.aps 0.022 0.007 1.023 ( 1.008, 1.037) 0.002 charlson.score 0.061 0.026 1.063 ( 1.009, 1.119) 0.021 stroke.risk -0.012 0.013 0.988 ( 0.964, 1.014) 0.368 map.low.icu -0.027 0.005 0.974 ( 0.965, 0.983) <0.001 study.day -0.027 0.056 0.973 ( 0.872, 1.086) 0.628 sepsis.l24=septic today 0.041 0.120 1.042 ( 0.823, 1.319) 0.736 hgb.icu -0.020 0.056 0.980 ( 0.879, 1.093) 0.721 study.day * hgb.icu 0.002 0.006 1.002 ( 0.991, 1.014) 0.722
Table 7: (continued) sofa.renal * age.enroll -0.003 0.003 0.997 ( 0.991, 1.003) 0.361 sofa.renal * icu.type=surgical -0.006 0.074 0.994 ( 0.860, 1.149) 0.936 sofa.renal * apache.aps -0.011 0.004 0.989 ( 0.981, 0.997) 0.006 sofa.renal * charlson.score -0.011 0.015 0.989 ( 0.960, 1.019) 0.464 sofa.renal * stroke.risk 0.005 0.007 1.005 ( 0.990, 1.019) 0.534 sofa.renal * map.low.icu 0.010 0.003 1.010 ( 1.004, 1.015) <0.001 sofa.renal * study.day -0.016 0.032 0.984 ( 0.924, 1.047) 0.608 sofa.renal * sepsis.l24=septic today -0.004 0.071 0.996 ( 0.866, 1.146) 0.959 sofa.renal * hgb.icu -0.006 0.033 0.994 ( 0.932, 1.059) 0.845 sofa.renal * study.day * hgb.icu 0.003 0.003 1.003 ( 0.996, 1.009) 0.420 1.4 Outcome4: Daily resp SOFA score ( 2) 1.4.1 Descriptive Statistics Table 8: Descriptive by next day s RESP SOFA score ( 2) 13 N No Yes Combined Test Statistic N = 276 N = 5571 N = 5847 sofa.resp.cat 6704 χ 2 1 = 2576, P < 0.0011 Yes 39% ( 107) 99% (5510) 96% (5617) SOFA respiratory component score 6704 0 0% ( 0) 0% ( 9) 0% ( 9) χ 2 4 = 2717, P < 0.0011 1 61% ( 169) 1% ( 47) 4% ( 216) 2 34% ( 95) 51% (2852) 50% (2947) 3 4% ( 12) 45% (2505) 43% (2517) 4 0% ( 0) 3% ( 153) 3% ( 153) resp.tomo 5847 0 3% ( 8) 0% ( 0) 0% ( 8) χ 2 4 = 5847, P < 0.0011 1 97% ( 268) 0% ( 0) 5% ( 268) 2 0% ( 0) 57% (3152) 54% (3152) 3 0% ( 0) 41% (2285) 39% (2285) 4 0% ( 0) 2% ( 134) 2% ( 134) Age at enrollment 6711 53 62 70 52 62 71 52 62 71 F 1,5845 = 0.13, P = 0.72 2 ICU type 6711 Surgical 23% ( 64) 37% (2052) 36% (2116) χ 2 1 = 21, P < 0.0011 APACHE APS at enrollment 6711 11 19 26 17 22 27 16 22 27 F 1,5845 = 33, P < 0.001 2 Charlson score 6711 0 2 4 1 2 4 1 2 4 F 1,5845 = 0.71, P = 0.4 2 Framingham stroke risk score 6711 6 9 13 6 10 14 6 10 14 F 1,5845 = 2.4, P = 0.12 2 Lowest mean arterial pressure, current 24h 6704 55 64 73 55 62 70 55 62 70 F 1,5840 = 9.6, P = 0.002 2 Was patient in ICU today? 6711 1 ICU 100% ( 276) 100% (5571) 100% (5847) Septic in the current 24h? 6703 a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. χ 2 1 = 157, P < 0.0011 N is the number of non missing values. Numbers after percents are frequencies. Tests used: 1 Pearson test; 2 Wilcoxon test
Table 8: (continued) N No Yes Combined Test Statistic N = 276 N = 5571 N = 5847 Septic today 30% ( 84) 67% (3737) 65% (3821) sevsepsis.l24 6703 Severely septic today 22% ( 61) 62% (3464) 60% (3525) χ 2 1 = 177, P < 0.0011 Lowest hemoglobin, current 24h 5837 9.4 10.4 11.3 8.7 9.6 10.7 8.7 9.7 10.7 F 1,5157 = 38, P < 0.001 2 a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. N is the number of non missing values. Numbers after percents are frequencies. Tests used: 1 Pearson test; 2 Wilcoxon test Table 9: Descriptive by next day s RESP SOFA score (0-4) 14 N 0 1 2 3 4 Combined Test Statistic N = 8 N = 268 N = 3152 N = 2285 N = 134 N = 5847 sofa.resp.cat 6704 χ 2 4 = 2633, P < 0.0011 Yes 88% ( 7) 37% ( 100) 99% (3102) 100% (2275) 99% ( 133) 96% (5617) SOFA respiratory component score 6704 0 0% ( 0) 0% ( 0) 0% ( 7) 0% ( 2) 0% ( 0) 0% ( 9) χ 2 16 = 5156, P < 0.0011 1 12% ( 1) 63% ( 168) 1% ( 40) 0% ( 6) 1% ( 1) 4% ( 216) 2 38% ( 3) 34% ( 92) 76% (2404) 19% ( 435) 10% ( 13) 50% (2947) 3 50% ( 4) 3% ( 8) 22% ( 685) 76% (1744) 57% ( 76) 43% (2517) 4 0% ( 0) 0% ( 0) 0% ( 13) 4% ( 96) 33% ( 44) 3% ( 153) renal.tomo 5847 0 75% ( 6) 44% ( 119) 55% (1718) 51% (1158) 45% ( 60) 52% (3061) χ 2 16 = 101, P < 0.0011 1 0% ( 0) 16% ( 44) 20% ( 644) 23% ( 534) 27% ( 36) 22% (1258) 2 25% ( 2) 15% ( 40) 14% ( 441) 17% ( 380) 17% ( 23) 15% ( 886) 3 0% ( 0) 7% ( 19) 6% ( 182) 4% ( 95) 5% ( 7) 5% ( 303) 4 0% ( 0) 17% ( 46) 5% ( 167) 5% ( 118) 6% ( 8) 6% ( 339) Age at enrollment 6711 56 63 77 53 62 70 53 62 71 51 61 70 44 56 66 52 62 71 F 4,5842 = 11, P < 0.001 2 ICU type 6711 Surgical 75% ( 6) 22% ( 58) 37% (1177) 37% ( 841) 25% ( 34) 36% (2116) χ 2 4 = 39, P < 0.0011 APACHE APS at enrollment 6711 20 24 29 11 19 26 17 22 28 16 22 27 13 22 26 16 22 27 F 4,5842 = 11, P < 0.001 2 Charlson score 6711 0.0 0.5 4.5 0.0 2.0 4.0 1.0 2.0 4.0 1.0 2.0 3.0 0.0 2.0 3.0 1.0 2.0 4.0 F 4,5842 = 6.4, P < 0.001 2 Framingham stroke risk score 6711 9.8 11.0 15.5 6.0 9.0 13.0 6.0 10.0 15.0 6.0 9.0 14.0 3.0 7.0 10.0 6.0 10.0 14.0 F 4,5842 = 11, P < 0.001 2 Lowest mean arterial pressure, current 24h 6704 58 64 68 55 64 74 55 62 70 54 61 68 52 60 70 55 62 70 F 4,5837 = 8.9, P < 0.001 2 Was patient in ICU today? 6711 1 ICU 100% ( 8) 100% ( 268) 100% (3152) 100% (2285) 100% ( 134) 100% (5847) Septic in the current 24h? 6703 Septic today 75% ( 6) 29% ( 78) 64% (2024) 71% (1611) 76% ( 102) 65% (3821) χ 2 4 = 192, P < 0.0011 sevsepsis.l24 6703 Severely septic today 62% ( 5) 21% ( 56) 60% (1876) 66% (1505) 62% ( 83) 60% (3525) χ 2 4 = 205, P < 0.0011 Lowest hemoglobin, current 24h 5837 9.0 9.7 11.4 9.4 10.4 11.3 8.8 9.7 10.7 8.6 9.5 10.6 9.0 9.8 10.6 8.7 9.7 10.7 F 4,5154 = 12, P < 0.001 2 a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. N is the number of non missing values. Numbers after percents are frequencies. Tests used: 1 Pearson test; 2 Kruskal-Wallis test 1.4.2 Logistic regression, Daily RESP SOFA 2(Y/N)
Table 10: Outcome:Daily resp SOFA =2.P-values less than 0.05 are in red. 15 sofa.resp.catyes 5.698 1.246 298.327 ( 25.931, 3432.121) <0.001 age.enroll -0.003 0.022 0.997 ( 0.955, 1.041) 0.896 icu.typesurgical 0.974 0.486 2.648 ( 1.022, 6.859) 0.045 apache.aps 0.038 0.024 1.038 ( 0.991, 1.088) 0.111 charlson.score -0.060 0.083 0.942 ( 0.801, 1.107) 0.468 stroke.risk 0.036 0.044 1.037 ( 0.952, 1.130) 0.402 map.low.icu -0.021 0.013 0.980 ( 0.956, 1.004) 0.105 study.day -0.206 0.267 0.814 ( 0.482, 1.373) 0.440 sepsis.l24septic today 0.629 0.418 1.876 ( 0.826, 4.261) 0.133 hgb.icu -0.153 0.223 0.858 ( 0.554, 1.329) 0.492 study.day:hgb.icu 0.014 0.026 1.014 ( 0.963, 1.068) 0.588 sofa.resp.catyes:age.enroll 0.001 0.025 1.001 ( 0.954, 1.050) 0.962 sofa.resp.catyes:icu.typesurgical -0.843 0.537 0.430 ( 0.150, 1.233) 0.116 sofa.resp.catyes:apache. -0.019 0.027 0.981 ( 0.930, 1.035) 0.486 sofa.resp.catyes:charlson.score -0.039 0.093 0.962 ( 0.801, 1.155) 0.675 sofa.resp.catyes:stroke.risk -0.016 0.050 0.984 ( 0.893, 1.085) 0.748 sofa.resp.catyes:map.low.icu 0.004 0.015 1.004 ( 0.975, 1.034) 0.801 sofa.resp.catyes:study.day 0.246 0.286 1.279 ( 0.730, 2.243) 0.390 sofa.resp.catyes:sepsis.l24septic today 0.435 0.473 1.546 ( 0.611, 3.908) 0.357 sofa.resp.catyes:hgb.icu 0.013 0.241 1.014 ( 0.632, 1.624) 0.956 sofa.resp.catyes:study.day:hgb.icu -0.020 0.028 0.981 ( 0.928, 1.036) 0.484 1.4.3 Proportional odds logistic regression, Ordinal response (0-4) Table 11: Outcome:Daily resp SOFA (0-4).. P-values less than 0.05 are in red. sofa.resp 2.246 0.613 9.452 ( 2.842, 31.428) <0.001 age.enroll -0.012 0.013 0.989 ( 0.964, 1.013) 0.361 icu.type=surgical 1.724 0.293 5.610 ( 3.157, 9.969) <0.001 apache.aps 0.031 0.016 1.032 ( 1.000, 1.064) 0.047 charlson.score -0.036 0.063 0.964 ( 0.852, 1.091) 0.565 stroke.risk 0.100 0.030 1.105 ( 1.042, 1.173) <0.001 map.low.icu -0.023 0.010 0.978 ( 0.958, 0.998) 0.030 study.day -0.017 0.136 0.983 ( 0.753, 1.283) 0.899 sepsis.l24=septic today 1.510 0.291 4.529 ( 2.562, 8.005) <0.001 hgb.icu -0.319 0.136 0.727 ( 0.557, 0.949) 0.019 study.day * hgb.icu -0.003 0.014 0.997 ( 0.970, 1.024) 0.829 sofa.resp * age.enroll 0.005 0.005 1.005 ( 0.995, 1.014) 0.317 sofa.resp * icu.type=surgical -0.675 0.113 0.509 ( 0.408, 0.635) <0.001 sofa.resp * apache.aps -0.015 0.006 0.985 ( 0.974, 0.997) 0.016 sofa.resp * charlson.score -0.011 0.025 0.989 ( 0.942, 1.039) 0.662
Table 11: (continued) sofa.resp * stroke.risk -0.040 0.011 0.961 ( 0.940, 0.983) <0.001 sofa.resp * map.low.icu 0.005 0.004 1.005 ( 0.998, 1.013) 0.182 sofa.resp * study.day -0.009 0.053 0.991 ( 0.894, 1.099) 0.869 sofa.resp * sepsis.l24=septic today -0.476 0.112 0.622 ( 0.499, 0.775) <0.001 sofa.resp * hgb.icu 0.098 0.050 1.103 ( 1.000, 1.218) 0.050 sofa.resp * study.day * hgb.icu 0.003 0.005 1.003 ( 0.992, 1.013) 0.622 1.4.4 Proportional odds logistic regression, Ordinal response (0-4),without three way interaction Table 12: Outcome:Daily resp SOFA (0-4).. P-values less than 0.05 are in red. 16 sofa.resp 2.062 0.487 7.865 ( 3.029, 20.423) <0.001 age.enroll -0.012 0.013 0.988 ( 0.964, 1.013) 0.349 icu.type=surgical 1.721 0.293 5.592 ( 3.148, 9.935) <0.001 apache.aps 0.031 0.016 1.032 ( 1.000, 1.064) 0.048 charlson.score -0.037 0.063 0.964 ( 0.852, 1.091) 0.561 stroke.risk 0.101 0.030 1.107 ( 1.043, 1.174) <0.001 map.low.icu -0.022 0.010 0.978 ( 0.958, 0.998) 0.030 study.day -0.082 0.039 0.922 ( 0.854, 0.994) 0.035 sepsis.l24=septic today 1.510 0.291 4.526 ( 2.561, 8.000) <0.001 hgb.icu -0.366 0.098 0.694 ( 0.573, 0.840) <0.001 sofa.resp * age.enroll 0.005 0.005 1.005 ( 0.996, 1.014) 0.308 sofa.resp * icu.type=surgical -0.674 0.113 0.510 ( 0.409, 0.636) <0.001 sofa.resp * apache.aps -0.015 0.006 0.985 ( 0.974, 0.997) 0.017 sofa.resp * charlson.score -0.011 0.025 0.989 ( 0.942, 1.039) 0.669 sofa.resp * stroke.risk -0.040 0.011 0.961 ( 0.939, 0.983) <0.001 sofa.resp * map.low.icu 0.005 0.004 1.005 ( 0.998, 1.013) 0.183 sofa.resp * study.day 0.017 0.008 1.017 ( 1.001, 1.033) 0.036 sofa.resp * sepsis.l24=septic today -0.475 0.112 0.622 ( 0.499, 0.775) <0.001 sofa.resp * hgb.icu 0.117 0.034 1.124 ( 1.051, 1.202) <0.001 study.day * hgb.icu 0.004 0.003 1.004 ( 0.997, 1.010) 0.270 1.4.5 Proportional odds logistic regression, Ordinal response (0-4),Sensitivity Analysis
Table 13: Outcome:Daily resp SOFA (0-4).. P-values less than 0.05 are in red. 17 sofa.resp 2.671 0.723 14.458 ( 3.508, 59.591) <0.001 age.enroll -0.008 0.013 0.992 ( 0.966, 1.019) 0.557 icu.type=surgical 1.783 0.310 5.945 ( 3.240, 10.911) <0.001 apache.aps 0.026 0.017 1.026 ( 0.994, 1.060) 0.117 charlson.score 0.024 0.067 1.024 ( 0.898, 1.169) 0.721 stroke.risk 0.083 0.032 1.086 ( 1.020, 1.156) 0.009 map.low.icu -0.024 0.011 0.976 ( 0.956, 0.997) 0.025 study.day -0.030 0.170 0.970 ( 0.696, 1.353) 0.858 sepsis.l24=septic today 1.562 0.305 4.766 ( 2.624, 8.658) <0.001 hgb.icu -0.221 0.159 0.802 ( 0.587, 1.095) 0.166 study.day * hgb.icu -0.001 0.017 0.999 ( 0.966, 1.032) 0.932 sofa.resp * age.enroll 0.003 0.005 1.003 ( 0.993, 1.013) 0.582 sofa.resp * icu.type=surgical -0.692 0.119 0.501 ( 0.396, 0.632) <0.001 sofa.resp * apache.aps -0.012 0.006 0.988 ( 0.975, 1.000) 0.055 sofa.resp * charlson.score -0.030 0.027 0.970 ( 0.920, 1.022) 0.256 sofa.resp * stroke.risk -0.033 0.012 0.967 ( 0.945, 0.991) 0.006 sofa.resp * map.low.icu 0.006 0.004 1.006 ( 0.998, 1.014) 0.155 sofa.resp * study.day 0.001 0.067 1.001 ( 0.878, 1.141) 0.984 sofa.resp * sepsis.l24=septic today -0.488 0.118 0.614 ( 0.487, 0.773) <0.001 sofa.resp * hgb.icu 0.062 0.059 1.064 ( 0.947, 1.195) 0.295 sofa.resp * study.day * hgb.icu 0.002 0.007 1.002 ( 0.989, 1.015) 0.815 1.4.6 Proportional odds logistic regression, Ordinal response (0-4),Sensitivity Analysis2, without three way interaction Table 14: Outcome:Daily resp SOFA (0-4).. P-values less than 0.05 are in red. sofa.resp 2.565 0.563 13.003 ( 4.315, 39.179) <0.001 age.enroll -0.008 0.013 0.992 ( 0.966, 1.018) 0.547 icu.type=surgical 1.782 0.310 5.941 ( 3.237, 10.902) <0.001 apache.aps 0.026 0.017 1.026 ( 0.993, 1.060) 0.118 charlson.score 0.025 0.067 1.025 ( 0.898, 1.169) 0.714 stroke.risk 0.083 0.032 1.086 ( 1.021, 1.156) 0.009 map.low.icu -0.024 0.011 0.976 ( 0.956, 0.997) 0.025 study.day -0.069 0.047 0.934 ( 0.852, 1.024) 0.143 sepsis.l24=septic today 1.558 0.304 4.751 ( 2.617, 8.625) <0.001 hgb.icu -0.246 0.115 0.782 ( 0.624, 0.980) 0.032 sofa.resp * age.enroll 0.003 0.005 1.003 ( 0.993, 1.013) 0.573 sofa.resp * icu.type=surgical -0.692 0.119 0.501 ( 0.397, 0.633) <0.001 sofa.resp * apache.aps -0.012 0.006 0.988 ( 0.975, 1.000) 0.056
Table 14: (continued) sofa.resp * charlson.score -0.031 0.027 0.970 ( 0.920, 1.022) 0.253 sofa.resp * stroke.risk -0.033 0.012 0.967 ( 0.945, 0.990) 0.006 sofa.resp * map.low.icu 0.006 0.004 1.006 ( 0.998, 1.014) 0.156 sofa.resp * study.day 0.017 0.009 1.017 ( 1.000, 1.034) 0.050 sofa.resp * sepsis.l24=septic today -0.487 0.118 0.614 ( 0.488, 0.774) <0.001 sofa.resp * hgb.icu 0.072 0.041 1.075 ( 0.993, 1.164) 0.075 study.day * hgb.icu 0.002 0.004 1.002 ( 0.994, 1.011) 0.564 1.4.7 Proportional odds logistic regression, Ordinal response (0-4),Marginal Model Table 15: Outcome:Daily resp SOFA (0-4).. P-values less than 0.05 are in red. 18 sofa.resp=2 4.1187 0.200 61.480 ( 41.546, 90.980) <0.001 sofa.resp=3 6.6958 0.209 808.992 ( 537.072, 1218.588) <0.001 sofa.resp=4 8.8292 0.294 6830.679 ( 3837.595, 12158.181) <0.001 age.enroll 0.0000 0.003 1.000 ( 0.994, 1.006) 0.994 icu.type=surgical -0.0005 0.068 1.000 ( 0.875, 1.141) 0.994 apache.aps -0.0049 0.004 0.995 ( 0.987, 1.003) 0.226 charlson.score -0.0602 0.016 0.942 ( 0.913, 0.972) <0.001 stroke.risk -0.0028 0.007 0.997 ( 0.983, 1.012) 0.704 map.low.icu -0.0087 0.003 0.991 ( 0.986, 0.996) <0.001 study.day -0.0249 0.031 0.975 ( 0.917, 1.037) 0.428 sepsis.l24=septic today 0.3255 0.070 1.385 ( 1.207, 1.589) <0.001 hgb.icu -0.0463 0.031 0.955 ( 0.898, 1.015) 0.138 study.day * hgb.icu 0.0021 0.003 1.002 ( 0.996, 1.008) 0.520 1.4.8 Proportional odds logistic regression, Ordinal response (0-4),Marginal Model with hgb.icu and resp.sofa interaction Table 16: Outcome:Daily resp SOFA (0-4).. P-values less than 0.05 are in red. sofa.resp=2 4.6349 1.156 103.016 ( 10.688, 992.969) <0.001 sofa.resp=3 5.8547 1.139 348.876 ( 37.384, 3255.765) <0.001 sofa.resp=4 5.8587 1.592 350.262 ( 15.471, 7929.671) <0.001 hgb.icu -0.1025 0.109 0.903 ( 0.728, 1.118) 0.349 age.enroll 0.0005 0.003 1.000 ( 0.995, 1.007) 0.866
Table 16: (continued) icu.type=surgical -0.0055 0.068 0.995 ( 0.871, 1.135) 0.935 apache.aps -0.0058 0.004 0.994 ( 0.986, 1.002) 0.155 charlson.score -0.0640 0.016 0.938 ( 0.909, 0.968) <0.001 stroke.risk -0.0024 0.007 0.998 ( 0.984, 1.012) 0.743 map.low.icu -0.0085 0.003 0.992 ( 0.987, 0.997) 0.001 study.day -0.0451 0.032 0.956 ( 0.898, 1.017) 0.156 sepsis.l24=septic today 0.3276 0.070 1.388 ( 1.209, 1.593) <0.001 sofa.resp=2 * hgb.icu -0.0526 0.112 0.949 ( 0.762, 1.181) 0.638 sofa.resp=3 * hgb.icu 0.0877 0.110 1.092 ( 0.880, 1.354) 0.426 sofa.resp=4 * hgb.icu 0.3011 0.155 1.351 ( 0.997, 1.831) 0.052 hgb.icu * study.day 0.0042 0.003 1.004 ( 0.998, 1.011) 0.205 19
20
1.4.9 Tomorrow resp.sofa 2 Today level 34 Today level 2 0.8 21 P(y>=2) 0.6 Today level 1 1 Today level 2 2 Today level 3 3 Today level 4 4 0.4 Today level 1 0.2 6 8 10 12 14 16 Lowest hemoglobin, current 24h ted to:age.enroll=61.76 icu.type=medical apache.aps=22 charlson.score=2 stroke.risk=10 map.low.icu=62 study.day=6 sepsis.l24=septic today
22
1.4.10 Tomorrow resp.sofa 3 Today level 4 0.8 Today level 3 0.6 23 P(y>=3) Today level 1 1 Today level 2 2 Today level 3 3 Today level 4 4 0.4 0.2 Today level 2 Today level 1 6 8 10 12 14 16 Lowest hemoglobin, current 24h ted to:age.enroll=61.76 icu.type=medical apache.aps=22 charlson.score=2 stroke.risk=10 map.low.icu=62 study.day=6 sepsis.l24=septic today
24
1.4.11 Tomorrow resp.sofa 4 0.8 0.6 Today level 1 1 Today level 2 2 Today level 3 3 Today level 4 4 25 P(y>=4) 0.4 Today level 4 0.2 Today level 3 Today level 12 6 8 10 12 14 16 Lowest hemoglobin, current 24h ted to:age.enroll=61.76 icu.type=medical apache.aps=22 charlson.score=2 stroke.risk=10 map.low.icu=62 study.day=6 sepsis.l24=septic today
1.5 Outcome5: Daily Ventilator (Y/N) as a measure of success of extubation 1.5.1 Descriptive Statistics 1.5.2 Proportional odds logistic regression, Ordinal response (0-4),Marginal Model Table 17: Descriptive by ventilator (Y/N) 26 N No Yes Combined Test Statistic N = 1580 N = 4269 N = 5849 on.vent.l24 6711 χ 2 1 = 3661, P < 0.0011 Yes 25% ( 399) 98% (4198) 79% (4597) Age at enrollment 6711 51 61 70 52 63 71 52 62 71 F 1,5847 = 8.7, P = 0.003 2 ICU type 6711 Surgical 32% ( 500) 38% (1616) 36% (2116) χ 2 1 = 19, P < 0.0011 APACHE APS at enrollment 6711 14 20 26 18 22 28 16 22 27 F 1,5847 = 110, P < 0.001 2 Charlson score 6711 1 2 4 1 2 4 1 2 4 F 1,5847 = 16, P < 0.001 2 Framingham stroke risk score 6711 6 9 14 6 10 14 6 10 14 F 1,5847 = 0.06, P = 0.81 2 Lowest mean arterial pressure, current 24h 6704 56 65 74 54 61 68 55 62 70 F 1,5842 = 83, P < 0.001 2 Was patient in ICU today? 6711 1 ICU 100% (1580) 100% (4269) 100% (5849) Septic in the current 24h? 6703 Septic today 54% ( 858) 69% (2963) 65% (3821) χ 2 1 = 116, P < 0.0011 sevsepsis.l24 6703 Severely septic today 37% ( 587) 69% (2938) 60% (3525) χ 2 1 = 483, P < 0.0011 Lowest hemoglobin, current 24h 5837 8.9 9.8 10.9 8.7 9.6 10.6 8.7 9.7 10.7 F 1,5157 = 29, P < 0.001 2 a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. N is the number of non missing values. Numbers after percents are frequencies. Tests used: 1 Pearson test; 2 Wilcoxon test 1.5.3 Logistic regression (Daily Ventilation (Y/N)) Table 18: Outcome:Daily ventilation (Y/N).. P-values less than 0.05 are in red. on.vent.l24=yes 9e+00 1.801 1e+04 ( 347.618, 405062.160) <0.001 age.enroll 4e-03 0.014 1e+00 ( 0.977, 1.031) 0.783 icu.type=surgical 7e-01 0.285 2e+00 ( 1.123, 3.430) 0.018 apache.aps 1e-02 0.016 1e+00 ( 0.978, 1.043) 0.551 charlson.score 2e-02 0.062 1e+00 ( 0.906, 1.154) 0.722 stroke.risk -7e-03 0.029 1e+00 ( 0.938, 1.052) 0.813 map.low.icu -3e-03 0.010 1e+00 ( 0.979, 1.016) 0.775 study.day 2e-01 0.133 1e+00 ( 0.939, 1.579) 0.137 sepsis.l24=septic today 6e-01 0.286 2e+00 ( 1.016, 3.119) 0.044 hgb.icu 3e-01 0.139 1e+00 ( 0.989, 1.703) 0.060 study.day * hgb.icu -2e-02 0.013 1e+00 ( 0.952, 1.004) 0.093
Table 18: (continued) on.vent.l24=yes * age.enroll 4e-03 0.015 1e+00 ( 0.975, 1.033) 0.805 on.vent.l24=yes * icu.type=surgical -9e-01 0.308 4e-01 ( 0.224, 0.750) 0.004 on.vent.l24=yes * apache.aps 2e-04 0.018 1e+00 ( 0.966, 1.036) 0.990 on.vent.l24=yes * charlson.score -8e-02 0.067 9e-01 ( 0.812, 1.054) 0.241 on.vent.l24=yes * stroke.risk -1e-02 0.032 1e+00 ( 0.926, 1.049) 0.647 on.vent.l24=yes * map.low.icu -3e-02 0.011 1e+00 ( 0.953, 0.993) 0.009 on.vent.l24=yes * study.day -6e-02 0.147 9e-01 ( 0.709, 1.262) 0.704 on.vent.l24=yes * sepsis.l24=septic today -2e-01 0.309 8e-01 ( 0.452, 1.520) 0.544 on.vent.l24=yes * hgb.icu -2e-01 0.148 8e-01 ( 0.584, 1.045) 0.096 on.vent.l24=yes * study.day * hgb.icu 1e-02 0.015 1e+00 ( 0.982, 1.042) 0.450 27
2 Analysis2: Hb during ICU stay and predicted outcomes 2.1 Outcome1: ICU mortality 2.1.1 Descriptive Statistics Table 19: Descriptive by Mortality (Y/N) unique subject) N No Yes Combined Test Statistic N = 685 N = 128 N = 813 Age at enrollment 813 50 61 70 54 63 74 51 61 71 F 1,811 = 4.3, P = 0.038 1 ICU type 813 Surgical 35% (238) 19% ( 24) 32% (262) χ 2 1 = 13, P < 0.0012 APACHE APS at enrollment 813 15 20 26 20 25 29 15 21 26 F 1,811 = 22, P < 0.001 1 Charlson score 813 1.0 2.0 4.0 1.0 2.5 4.0 1.0 2.0 4.0 F 1,811 = 6.5, P = 0.011 1 Framingham stroke risk score 813 6.0 10.0 15.0 4.8 9.0 13.2 6.0 9.0 14.0 F 1,811 = 1.9, P = 0.17 1 lowest.hgb.icu 803 7.9 8.9 10.3 7.7 8.5 9.7 7.9 8.9 10.2 F 1,801 = 4.8, P = 0.029 1 auc.hgb.icu 813 22 43 95 24 51 103 23 45 97 F 1,811 = 0.57, P = 0.45 1 mean.sofa 813 5.6 7.0 9.0 8.2 10.8 13.4 5.8 7.5 9.9 F 1,811 = 134, P < 0.001 1 duration.sepsis 813 0.0 2.0 6.0 1.0 4.0 8.2 0.0 3.0 7.0 F 1,811 = 12, P < 0.001 1 max.sofa.renal 813 0 42% (285) 15% ( 19) 37% (304) χ 2 4 = 44, P < 0.0012 1 24% (163) 23% ( 30) 24% (193) 2 19% (132) 37% ( 47) 22% (179) 3 6% ( 39) 12% ( 16) 7% ( 55) 4 10% ( 66) 12% ( 16) 10% ( 82) a b c represent the lower quartile a, the median b, and the upper quartile c for continuous variables. N is the number of non missing values. Numbers after percents are frequencies. Tests used: 1 Wilcoxon test; 2 Pearson test 2.1.2 Logistic regression for ICU.mortality (Y/N) Two different functional forms of hemoglobin during ICU was considered in the below analysis (two different models) Table 20: Outcome:Mortality.. P-values less than 0.05 are in red. lowest.hgb.icu -0.004 0.077 0.996 (0.857, 1.157) 0.953 age.enroll 0.041 0.011 1.042 (1.019, 1.065) <0.001 icu.type=surgical -0.993 0.273 0.371 (0.217, 0.633) <0.001 apache.aps -0.007 0.015 0.993 (0.964, 1.024) 0.666 charlson.score -0.014 0.051 0.986 (0.892, 1.090) 0.781 stroke.risk -0.049 0.025 0.952 (0.907, 1.000) 0.051 mean.sofa 0.425 0.045 1.530 (1.401, 1.670) <0.001 duration.sepsis 0.021 0.020 1.022 (0.982, 1.063) 0.287 Table 21: Outcome:Mortality.. P-values less than 0.05 are in red. auc.hgb.icu -0.002 0.003 0.998 (0.991, 1.004) 0.452 age.enroll 0.041 0.011 1.042 (1.020, 1.065) <0.001 icu.type=surgical -0.963 0.275 0.382 (0.223, 0.655) <0.001 apache.aps -0.006 0.015 0.994 (0.964, 1.024) 0.672 charlson.score -0.009 0.051 0.991 (0.897, 1.094) 0.858 stroke.risk -0.051 0.025 0.951 (0.905, 0.998) 0.042 mean.sofa 0.428 0.044 1.534 (1.407, 1.674) <0.001 duration.sepsis 0.043 0.033 1.044 (0.978, 1.114) 0.194 28
2.1.3 Time dependent covariate survival analysis for Time to ICU.mortality Variable hgb.icu, daily.sofa, severe sepsis were time variang covariates. charlson.score,stroke.risk did not change over time. Age.enroll, icu.type, apache.aps, Call: coxph(formula = Surv(time1, time2, mortality.censor) ~ hgb.icu + age.enroll + icu.type + apache.aps + charlson.score + stroke.risk + daily.sofa + sevsepsis.l24 + cluster(id), data = brain.dailyobs) coef exp(coef) se(coef) robust se z p hgb.icu 0.0621 1.064 0.0815 0.0746 0.833 4.0e-01 age.enroll 0.0189 1.019 0.0127 0.0104 1.815 7.0e-02 icu.typesurgical -1.0109 0.364 0.3231 0.3094-3.268 1.1e-03 apache.aps 0.0135 1.014 0.0188 0.0159 0.850 4.0e-01 charlson.score 0.1090 1.115 0.0638 0.0650 1.678 9.3e-02 stroke.risk -0.0634 0.939 0.0304 0.0278-2.276 2.3e-02 daily.sofa 0.2553 1.291 0.0422 0.0392 6.504 7.8e-11 sevsepsis.l24severely septic today 0.0903 1.095 0.3161 0.2928 0.309 7.6e-01 Likelihood ratio test=78.3 on 8 df, p=1.05e-13 n= 5848, number of events= 84 (876 observations deleted due to missingness) For every unit increase of hgb.icu, the hazard of mortality in ICU increased by 6.4%. Given the p value equals to 0.4, no evidence to conclude hgb.icu has statistically significant effect on ICU.mortality after controlling for all other covariates. The robust standard error is used due to repeated measurement of hgb.icu on each subject. 29
2.2 Outcome2: Cardiac dysfunction(tropnin greater than 0.1) 2.2.1 Correlated time dependent covariate survival analysis for Time to Tropnin greater than 0.1 Variable hgb.icu, daily.sofa, severe sepsis were time variang covariates. charlson.score,stroke.risk did not change over time. Call: coxph(formula = Surv(time1, time2, tropnin.censor) ~ hgb.icu + age.enroll + icu.type + apache.aps + charlson.score + stroke.risk + daily.sofa + sevsepsis.l24 + cluster(id), data = brain.dailyobs) Age.enroll, icu.type, apache.aps, coef exp(coef) se(coef) robust se z p hgb.icu 0.04474 1.046 0.0546 0.0508 0.8806 0.38000 age.enroll -0.00258 0.997 0.0105 0.0102-0.2537 0.80000 icu.typesurgical -0.02246 0.978 0.2179 0.2860-0.0785 0.94000 apache.aps 0.02061 1.021 0.0140 0.0172 1.1961 0.23000 charlson.score -0.02259 0.978 0.0435 0.0443-0.5095 0.61000 stroke.risk 0.08141 1.085 0.0236 0.0267 3.0440 0.00230 daily.sofa 0.11588 1.123 0.0316 0.0338 3.4259 0.00061 sevsepsis.l24severely septic today 0.06074 1.063 0.2185 0.2141 0.2837 0.78000 Likelihood ratio test=33.4 on 8 df, p=0.0000532 n= 5848, number of events= 129 (876 observations deleted due to missingness) 30
2.3 Outcome3: Renal dysfunction 2.3.1 Outcome: Time to renal dysfunction Survival analysis with correlated time dependent covariate Variable hgb.icu, daily.sofa, severe sepsis were time variang covariates. charlson.score,stroke.risk did not change over time. Call: coxph(formula = Surv(time1, time2, renal.censor) ~ hgb.icu + age.enroll + icu.type + apache.aps + charlson.score + stroke.risk + daily.sofa + sevsepsis.l24 + cluster(id), data = brain.dailyobs) Age.enroll, icu.type, apache.aps, coef exp(coef) se(coef) robust se z p hgb.icu -0.08317 0.920 0.03608 0.05370-1.549 0.12000 age.enroll 0.00604 1.006 0.00500 0.00942 0.641 0.52000 icu.typesurgical -0.78254 0.457 0.12800 0.31420-2.491 0.01300 apache.aps 0.02102 1.021 0.00728 0.01526 1.377 0.17000 charlson.score 0.15526 1.168 0.02410 0.04094 3.792 0.00015 stroke.risk 0.01747 1.018 0.01148 0.02274 0.768 0.44000 daily.sofa 0.27420 1.315 0.01691 0.03085 8.889 0.00000 sevsepsis.l24severely septic today -0.28192 0.754 0.11774 0.17140-1.645 0.10000 Likelihood ratio test=508 on 8 df, p=0 n= 5848, number of events= 557 (876 observations deleted due to missingness) 2.4 Outcome4: Time to resolution of delirium To be continue 2.5 Outcome5: Time to successful extubation To be continue 31