Diagnosis / ICD-9-CM Codes
Septic shock / Primary diagnosis 038, 995.91, 995.92, or 785.52 and
Secondary diagnosis 458.0, 458.8, 458.9, 785.5, 785.51, 785.52, 785.59, or 796.3
Infection source
Pulmonary / 481, 482, 483, 484, 485, 486, 487
Abdominal / 540, 541, 557, 562.1, 567, 569.83, 574, 575,
Skin or soft tissue / 035, 680, 681, 682, 683, 684, 686,
Genitourinary / 590, 599
Acute organ failures
Respiratory / 518.5, 518.81, 518.82, 518.84, 786.09, 799.1,
Neurological / 3483, 293, 348.1, 780.01, 780.09, 348.3
Metabolic (acidosis) / 276.2
Kidney failure / 584
Hematological / 286.2, 286.6, 286.9, 287.3, 287.4, 287.5
Liver / 570, 572.2, 573.3
Pathogen type
Gram negative infection / 038.4, 041.4, 482.0, 482.1, 482.2, 482.83
Gram positive infection / 038.1, 038.2, 041.0, 041.1, 481, 482.3, 482.4
Fungal infection / 112.5
Critical care procedures
Dialysis / Procedure 39.95
Mechanical ventilation / Procedure 96.7
Pulmonary artery catheter / Procedure 89.63, 89.64, 89.66, 89.67, 89.68
Peripheral arterial catheter / 38.91
Central venous catheter / 38.93
Electrolyte disturbance / 276, 275.2
Comorbidity
Heart failure / 398.91, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 425, 428
Diabetes mellitus / 250
Chronic obstructive pulmonary disease / 491, 492, 496
Chronic kidney disease / 403, 404, 582, 583, 585, 586, 588
Dementia / 290, 294, 331
Metastatic or hematologic malignancy / CCS codes 37-42
Chronic liver disease / 571.2, 571.4, 571.5, 571.6, 572.2, 572.3, 572.4, 572.8
Obesity / 278
Myocardial infarction / 412
Paralysis/plegia / 342, 343, 344
Human immunodeficiency virus / 042, 043, 044
Three digit codes contain all sub-codes.
Supplemental Table 2: Characteristics of patients with septic shock by year.N (%) unless otherwise specified / 1998
Weighted N=25,856
Unweighted N=5154 / 2009
Weighted N=182,220
Unweighted N=36175
Age, years, mean (95% CI) / 70.2 (69.8-70.7) / 68.4 (68.2-68.5)
Sex, female / 14104 (54.6) / 91944 (50.5)
Race/ethnicity
White / 14723 (56.9) / 111996 (61.5)
Black / 2965 (11.5) / 21137 (11.6)
Hispanic / 1496 (5.8) / 17093 (9.4)
Other / 8872 (25.8) / 31995 (17.6)
Comorbidities
Total number of comorbidities, mean, (95% CI) / 1.05 (1.03-1.08) / 1.26 (1.25-1.27)
Heart failure / 6102 (23.6) / 46664 (25.6)
Diabetes mellitus / 5524 (21.4) / 44200 (24.3)
Chronic kidney disease / 4163 (16.1) / 40556 (22.3)
Chronic obstructive pulmonary disease / 3890 (15.0) / 32078 (17.6)
Dementia / 2370 (9.2) / 19585 (10.7)
Metastatic or hematologic malignancy / 2592 (10.0) / 17334 (9.5)
Chronic liver disease / 916 (3.5) / 8574 (4.7)
Obesity / 322 (1.2) / 7329 (4.0)
Myocardial infarction / 542 (2.1) / 4372 (2.4)
Paralysis/plegia / 576 (2.2) / 7193 (3.9)
Human immunodeficiency virus / 186 (0.7) / 1132 (0.6)
Acute organ failures
Total # of acute organ failures, mean (95% CI) / 1.86 (1.83-1.89) / 2.69 (2.68-2.71)
Renal failure / 5695 (22.0) / 102176 (56.1)
Respiratory failure / 7963 (30.8) / 94422 (51.8)
Hematologic failure / 3432 (13.3) / 26349 (14.5)
Metabolic failure / 3184 (12.3) / 46149 (25.3)
Neurologic failure / 1365 (5.3) / 27384 (15.0)
Hepatic failure / 589 (2.3) / 12876 (7.1)
Electrolyte abnormality / 14831 (57.4) / 114535 (62.9)
Critical care interventions
Mechanical ventilation / 6195 (24.0) / 70812 (38.9)
Dialysis / 1900 (7.4) / 19162 (10.5)
Pulmonary artery catheterization / 2212 (8.6) / 1274 (0.70)
Peripheral arterial catheter / 1376 (5.3) / 15782 (8.7)
Central venous catheter (any timing) / 5204 (20.1) / 87995 (48.3)
Source of infection
Respiratory / 5266 (20.4) / 71591 (39.3)
Urinary tract / 10378(40.1) / 70813 (38.9)
Abdominal / 2240 (8.7) / 21375 (11.7)
Skin or soft tissue / 1215 (4.7) / 13714 (7.5)
Pathogen type
Gram positive / 5237 (20.3) / 28498 (15.6)
Gram negative / 7563 (29.3) / 35649 (19.6)
None specified / 13050 (50.5) / 117779 (64.6)
US Geographic Region
Northeast / 4689 (18.1) / 33555 (18.4)
Midwest / 4243 (16.4) / 33130 (18.2)
South / 11742 (45.4) / 66238 (36.4)
West / 5182 (20.0) / 42297 (27.1)
Hospital Bed size
Supplemental Table 2: Characteristics of patients with septic shock by year (continued)
1998 / 2009
Small / 3003 (11.6) / 16268 (9.1)
Medium / 7825 (30.3) / 46152 (25.7)
Large / 14977 (58.0) / 117287 (65.3)
Hospital Location - Urban / 21872 (84.8) / 163209 (90.8)
Teaching Hospital / 10107 (39.2) / 75238 (41.9)
Payer
Medicare / 18034 (70) / 120596 (66.3)
Medicaid / 2058 (7.9) / 19109 (10.5)
Private Insurance / 4778 (18.5) / 31094 (17.1)
Self-pay / 671 (2.6) / 6786 (3.7)
Other/No charge / 223 (0.86) / 4411 (2.4)
CI: confidence interval
Weighted N (%)
Unweighted N (%) / No CVC
600,877
122,223 / Early CVC
133,413
27,245 / Late CVC
174,818
35,669 / CVC Timing unspecified
90,438
18,344
Age, years, mean (95% CI) / 70.6 (70.5-70.7) / 67.1 (66.9-67.3) / 68.3 (68.1-68.4) / 66.2 (66.0-66.5)
Sex, female / 311387 (51.8) / 70528 (52.9) / 90999 (52.1) / 46901 (51.9)
Race/ethnicity
White / 335421 (55.8) / 81860 (61.4) / 107334 (61.4) / 33113 (36.6)
Black / 58985 (9.8) / 17775 (13.3) / 23249 (13.3) / 7110 (7.9)
Hispanic / 47648 (7.9) / 11912 (8.9) / 17368 (9.9) / 2472 (2.7)
Other / 158824 (26.4) / 21865 (16.4) / 26867 (15.4) / 47742 (52.8)
Comorbidities
Total # of comorbidities, mean, (95% CI) / 1.22 (1.22-1.23) / 1.21 (1.20-1.22) / 1.25 (1.24-1.26) / 1.09 (1.08-1.11)
Heart failure / 157393 (26.2) / 36609 (27.4) / 53360 (30.5) / 24484 (27.1)
Diabetes mellitus / 137170 (22.8) / 30837 (23.1) / 38833 (22.2) / 16573 (18.3)
Chronic kidney disease / 124653 (20.7) / 26705 (20.0) / 39666 (22.7) / 18069 (20.0)
Chronic obstructive lung disease / 111826 (18.6) / 24966 (18.7) / 32085 (18.4) / 16949 (18.7)
Dementia / 74850 (12.5) / 11116 (8.3) / 14039 (8.0) / 4056 (4.5)
Malignancy / 58469 (9.7) / 10556 (7.9) / 14141 (8.1) / 7333 (8.1)
Chronic liver disease / 22572 (3.8) / 7265 (5.4) / 9556 (5.5) / 4362 (4.8)
Obesity / 14099 (2.3) / 4342 (3.3) / 5121 (2.9) / 2069 (2.3)
Myocardial infarction / 15481 (2.6) / 2996 (2.2) / 2896 (1.7) / 1199 (1.3)
Paralysis/plegia / 15843 (2.6) / 5270 (4.0) / 7209 (4.1) / 3086 (3.4)
Human immunodeficiency virus / 3199 (0.5) / 973 (0.7) / 1123 (0.6) / 754 (0.8)
Acute organ failures
Total # of acute organ failures, mean (95% CI) / 2.13 (2.12-2.14) / 2.84 (2.83-2.86) / 2.70 (2.68-2.71) / 2.78 (2.77-2.80)
Renal failure / 229541 (38.2) / 72419 (54.3) / 92735 (53.0) / 47365 (52.4)
Respiratory failure / 211911 (35.3) / 82677 (62.0) / 99048 (56.7) / 58259 (64.4)
Hematologic failure / 74233 (12.4) / 24802 (18.6) / 31539 (18.0) / 16023 (17.7)
Metabolic failure / 95768 (15.9) / 38658 (29.0) / 40474 (23.2) / 24194 (26.8)
Neurologic failure / 43856 (7.3) / 16162 (12.1) / 20915 (12.0) / 8838 (9.8)
Hepatic failure / 24899 (4.1) / 11048 (8.3) / 11958 (6.8) / 6610 (7.3)
Electrolyte abnormality / 353684 (58.9) / 88044 (66.0) / 113979(65.2) / 58841 (65.1)
Critical care interventions
Mechanical ventilation / 145589 (24.2) / 68460 (51.3) / 79731 (45.6) / 49295 (54.5)
Dialysis / 49927 (8.3) / 12547(9.4) / 22403 (12.8) / 10657 (11.8)
Pulmonary artery catheterization / 12618 (2.1) / 2887 (2.2) / 4741 (2.7) / 3729 (4.1)
Peripheral arterial catheter / 19718 (3.3) / 20532 (15.4) / 16626 (9.5) / 16192 (17.9)
Source of infection
Respiratory / 184715 (30.7) / 50039 (37.5) / 67008 (38.3) / 32991 (36.5)
Urinary tract / 245173 (40.8) / 47932 (35.9) / 71193 (40.7) / 32959 (36.4)
Abdominal / 53824 (9.0) / 14184 (10.6) / 21387 (12.2) / 10325 (11.4)
Skin or soft tissue / 33842 (5.6) / 9049 (6.8) / 16226 (9.3) / 7077 (7.8)
Pathogen type
Gram positive / 87068 (14.5) / 23112 (17.3) / 39538 (22.6) / 19200 (21.2)
Gram negative / 128497(21.4) / 24618 (18.5) / 37262 (21.3) / 17987 (20.0)
None specified / 384844(64.0) / 85441 (64.0) / 97417 (55.7) / 53076 (58.7)
US Geographic Region
Northeast / 120536 (20.1) / 28707 (21.5) / 44519 (25.5) / 2178 (2.4)
Midwest / 121027 (20.1) / 13367 (10.0) / 17284 (9.9) / 47355 (52.4)
Supplemental Table 3: Characteristics of patients with septic shock stratified by timing of central venous catheter (CVC) insertion 1998-2009 (continued)
No CVC / Early CVC / Late CVC / CVC Timing unspecified
South / 218663 (36.4) / 52345 (39.2) / 68964 (39.4) / 23757 (26.3)
West / 140651 (23.4) / 38994 (29.2) / 44051 (25.2) / 17149 (19.0)
Hospital Bed size
Small / 65155 (10.9) / 11854 (8.9) / 15803 (9.1) / 8462 (9.4)
Medium / 154348 (25.8) / 33892 (25.5) / 46304 (26.6) / 20596 (22.8)
Large / 379646 (63.4) / 87007 (65.5) / 111966(64.3) / 61270 (67.8)
Hospital Location - Urban / 520521 (86.9) / 123623 (93.1) / 162941 (93.6) / 83857 (92.8)
Teaching Hospital / 236948 (39.5) / 58593 (44.1) / 72318 (41.5) / 47371 (52.4)
Payer
Medicare / 426064 (71.0) / 87191 (65.4) / 118563 (67.9) / 56994 (63.1)
Medicaid / 51151 (8.5) / 14924 (11.2) / 18638 (10.7) / 10347 (11.5)
Private Insurance / 95536 (15.9) / 22409 (16.8) / 28035 (16.1) / 17690 (19.6)
Self-pay / 16015 (2.7) / 5172 (3.9) / 5139 (2.9) / 2942 (3.3)
Other/No charge / 11356 (1.9) / 3526 (2.6) / 4232 (2.4) / 2370 (2.6)
‘Early’ CVC was placed on day of admission, whereas ‘late’ CVC was placed after day of admission.
CI: confidence interval
Supplemental Table 4: Clinical and demographic characteristics of patients who received an early central venous catheter (CVC) in 1998 and 2009.Characteristics / % of patients receiving early CVC
with each characteristic
N (%) unless otherwise specified / 1998
N=295
Weighted N=1474 / 2009
N=6980
Weighted N=35047
Age, years, mean (95% CI) / 69.0 (67.2-70.7) / 66.8 (66.4-67.2)
Sex, female / 59.5 / 50.5
Race/ethnicity
White / 61.2 / 63.6
Black / 16.6 / 13.2
Hispanic / 5.1 / 9.8
Other / 17.1 / 13.2
Comorbidities
Total # of comorbidities, mean (95% CI) / 1.09 (0.98-1.20) / 1.21 (1.19-1.23)
Heart failure / 21.8 / 26.6
Diabetes mellitus / 26.1 / 23.7
Chronic kidney disease / 14.5 / 19.8
Chronic obstructive pulmonary disease / 14.7 / 18.4
Dementia / 6.8 / 8.4
Metastatic or hematologic malignancy / 11.8 / 7.6
Chronic liver disease / 5.9 / 5.2
Obesity / 0.35 / 4.2
Myocardial infarction / 3.2 / 2.1
Paralysis/plegia / 3.2 / 4.3
Human immunodeficiency virus / 0.71 / 0.61
Acute organ failures
Total # of acute organ failures, mean (95% CI) / 2.20 (2.07-2.33) / 3.03 (3.00-3.06)
Renal failure / 29.4 / 61.5
Respiratory failure / 47.8 / 65.3
Hematologic failure / 15.6 / 16.8
Metabolic failure / 17.7 / 32.1
Neurologic failure / 7.1 / 18.1
Hepatic failure / 2.1 / 9.5
Electrolyte abnormality / 58.8 / 66.3
Critical care interventions
Mechanical ventilation / 39.6 / 53.6
Dialysis / 5.7 / 10.3
Pulmonary artery catheterization / 10.7 / 0.76
Peripheral arterial catheter / 13.8 / 14.7
Supplemental Table 5: Sensitivity analyses
Analysis / % patients with septic shock receiving early CVC
(95% CI) / Early CVC-associated mortality
Adjusted odds ratio
(95% CI)
1998 / 2009 / 1998 / 2009
Primary multivariable-adjusted analysisa
Unweighted N=203,481 / 5.7
(5.1-6.3%) / 19.2
(18.7-19.5) / 1.27
(0.96-1.68) / 0.88
(0.83-0.95)
Secondary adjusted analysisb
Unweighted N=203,481 / 5.7
(5.1-6.3%) / 19.2
(18.7-19.5) / 1.69
(1.32-2.16) / 1.41
(1.33-1.50)
No Mechanical Ventilationc
Unweighted N=133,782 / 4.5
(3.9-5.2) / 14.6
(14.1-15.1) / 1.42
(1.00-2.00) / 0.92
(0.82-1.02)
Mechanical ventilationc
Unweighted N=69,699 / 9.4
(7.8-11.1) / 26.5
(25.8-27.3) / 1.11
(0.69-1.78) / 0.83
(0.76-0.91)
States included in all years NISa
Unweighted N =137,500 / 5.6
(5.0-6.3) / 22.0
(21.5-22.6) / 1.24
(0.93-1.67) / 0.87
(0.80-0.95)
Exclude patients transferred outa
Unweighted N=134,347 / 5.9
(5.2-6.7) / 19.8
(19.3-20.3) / 1.40
(0.97-2.02) / 0.91
(0.83-1.00)
CVC: central venous catheter, CI: confidence interval, NIS: Nationwide Inpatient Sample
aAdjusted for patient demographics (age, sex, race/ethnicity), comorbid conditions (heart failure, myocardial infarction, obesity, diabetes mellitus, chronic obstructive pulmonary disease, dementia, human immunodeficiency virus infection, paralysis, chronic liver disease, chronic kidney disease, and metastatic or hematologic malignancy), acute organ failures (renal, respiratory, hematologic, metabolic,neurologic, hepatic), procedures (mechanical ventilation, dialysis, pulmonary artery catheter, arterial catheter), infection site (respiratory, urinary tract, abdominal, skin or soft tissue), pathogen (gram positive, gram negative or unspecified), and hospital characteristics (region, rural/urban location, teaching status, bed size.
bAdjusted for demographics,comorbid conditions, hospital characteristics and payer.
cAdjustedfor same covariates as model a, with exception of mechanical ventilation.
Pvalue forinteraction betweenearly central venous catheter, year, and hospital mortality < 0.05 for all sensitivity analyses.
Supplemental Figure 1: Flow chart of septic shock cohort case selection in Nationwide Inpatient Sample 1998-2009
1