Introduction
Materials and methods
Case Mix Programme
Audit of DrotAA
Severe sepsis
Sample size calculation
Use of DrotAA
Nonrandomized comparison
Results
Participation
Use of DrotAA
Characteristic | All admissions receiving DrotAA (n = 1,292) | Admissions with severe sepsis and ≥2 organ systems failing receiving DrotAA (N = 1,079) | Admissions with severe sepsis and ≥2 organ systems failing not receiving DrotAA (n = 15,939) |
---|---|---|---|
Age (years; mean ± SD) | 58.8 ± 16.0 | 59.1 ± 16.1 | 63.3 ± 17.2 |
Sex (n [%]) | |||
Female | 638 (49.4) | 535 (49.6) | 7,333 (46.0) |
Male | 654 (50.6) | 544 (50.4) | 8,604 (54.0) |
Mechanical ventilation on admission or during first 24 hours of stay in critical care (n [%]) | 1,163 (90.0) | 998 (92.5) | 12,060 (75.7) |
APACHE II score (mean ± SD) | |||
Acute physiology score | 18.2 (6.5) | 18.8 (6.4) | 16.0 (6.5) |
Score | 21.9 (6.9) | 22.6 (6.7) | 20.7 (7.2) |
ICNARC model physiology score (mean ± SD) | 29.1 (9.0) | 30.4 (8.4) | 24.9 (9.4) |
Serious conditions in past medical historya (n [%]) | |||
Liver | 10 (0.8) | 9 (0.8) | 384 (2.4) |
Cardiovascular | 5 (0.4) | 5 (0.5) | 263 (1.7) |
Respiratory | 23 (1.8) | 23 (2.1) | 630 (4.0) |
Renal | 14 (1.1) | 12 (1.1) | 315 (2.0) |
Immunosuppressed | 92 (7.1) | 78 (7.2) | 1,545 (9.7) |
Admission typeb (n [%]) | |||
Medical | 939 (72.7) | 789 (73.1) | 11,375 (71.4) |
Elective surgical | 56 (4.3) | 32 (3.0) | 819 (5.1) |
Emergency surgical | 297 (23.0) | 258 (23.9) | 3,745 (23.5) |
Organ systems failing during first 24 hours of stay in critical care (n [%]) | |||
Cardiovascular | 1,235 (95.6) | 1,070 (99.2) | 15,136 (95.0) |
Respiratory | 1,166 (90.3) | 1,005 (93.1) | 13,722 (86.1) |
Renal | 480 (37.7) | 427 (40.0) | 4,274 (27.1) |
Haematological | 229 (17.7) | 199 (18.4) | 2,290 (14.4) |
Metabolic acidosis | 990 (76.6) | 872 (80.8) | 9,674 (60.7) |
Number of organ systems failing during first 24 hours of stay in critical care (n [%]) | |||
<2 | 60 (4.7) | N/A | N/A |
2 | 238 (18.4) | 198 (18.4) | 6,809 (42.7) |
3 | 498 (38.5) | 433 (40.1) | 5,664 (35.5) |
4 | 398 (30.8) | 362 (33.6) | 2,844 (17.8) |
5 | 98 (7.6) | 86 (8.0) | 622 (3.9) |
Primary site of infectionc (n [%]) | |||
Lung | 495 (41.9) | 423 (42.8) | N/R |
Abdomen | 478 (40.4) | 390 (39.5) | N/R |
Urinary tract | 57 (4.8) | 51 (5.2) | N/R |
Other | 158 (13.4) | 131 (13.3) | N/R |
Positive blood cultured (n [%]) | 438 (40.3) | 381 (42.1) | N/R |
Organisms cultured (n [%]) | |||
Any | 814 (64.6) | 692 (65.8) | N/R |
Gram-negative | 399 (49.0) | 331 (47.8) | N/R |
Gram-positive | 437 (53.7) | 382 (55.2) | N/R |
Fungus | 101 (12.4) | 81 (11.7) | N/R |
Deaths within 96 hours of unit admission (n [%]) | 166 (12.9) | 151 (14.0) | 3,315 (20.8) |
Mortality (deaths [%]) | |||
Unit | 449 (34.8) | 385 (35.7) | 5,404 (33.9) |
Hospitale | 567 (45.0) | 484 (45.4) | 7,438 (46.7) |
Location at 28-days (n [%]) | |||
Died | 463 (35.8) | 398 (36.9) | 6,541 (41.0) |
Unit | 240 (18.6) | 177 (16.4) | 888 (5.6) |
Hospital | 363 (28.1) | 312 (28.9) | 3,865 (24.3) |
Out of Hospitale | 226 (17.5) | 192 (17.8) | 4,645 (29.1) |
Unit length of stay (days; median [IQR]) | |||
Unit survivors | 14.2 (8.1–24.9) | 13.8 (8.0–23.2) | 5.0 (2.2–11.0) |
Unit nonsurvivors | 7.2 (2.3–16.3) | 6.4 (2.0–15.6) | 2.5 (1.0–7.4) |
Hospital length of stay (days; median [IQR])f | |||
Hospital survivors | 44 (25–69) | 44 (24–66) | 29 (16–52) |
Hospital nonsurvivors | 15 (6–31) | 14 (5–28) | 11 (4–25) |
Destination following discharge from hospital housing critical care unit (n [%]) | |||
Another acute hospital | 41 (6.5) | 29 (5.5) | 537 (6.8) |
Hospice or equivalent | 8 (1.3) | 8 (1.5) | 40 (0.5) |
Long-term institutional care | 13 (2.0) | 12 (2.3) | 126 (1.6) |
Rehabilitation unit | 43 (6.8) | 35 (6.6) | 549 (7.0) |
Normal residence | 531 (83.5) | 446 (84.2) | 6,652 (84.2) |
Infusion-related data | All admissions receiving DrotAA (n = 1,292) |
---|---|
Time from unit admission to start of infusion (hours; median [IQR]) | 19.5 (9.3–35.3) |
Received complete 96-hour infusion (n [%]) | 896 (69.9) |
Reason for not receiving complete infusion (n [%]) | |
Deterioration/treatment withdrawn/died | 195 (50.8) |
Actual/possible bleeding | 91 (23.7) |
Patient improved/left ward | 34 (8.9) |
Other intervention/treatment outside unit | 16 (4.2) |
Criteria reassessed/incorrect | 9 (2.3) |
Timing error | 8 (2.1) |
Other intervention/treatment in unit | 5 (1.3) |
Macro/micro drug supply issues | 4 (1.0) |
Infused over shorter time period | 1 (0.3) |
No reason given/not known | 21 (5.5) |
Interruption in the infusion (n [%]) | 304 (24.0) |
Time from start of infusion to interruption (hours; median [IQR]) | 24.0 (13.2–49.0) |
Duration of interruption (hours; median [IQR]) | 5 (3–10) |
Reason for interruption (n [%]) | |
Lines/catheters/cannula/drain/dressing-inserted/changed/removed/re-sited/fell out | 144 (48.0) |
To theatre | 48 (16.0) |
Bleeding related (actual/suspected) | 35 (11.7) |
Intervention off unit | 15 (5.0) |
Tracheostomy | 15 (5.0) |
Intervention on unit | 11 (3.7) |
In error | 10 (3.3) |
Macro/micro drug supply issues | 10 (3.3) |
Patients condition improved/left unit | 1 (0.3) |
No reason given/not known | 11 (3.7) |
Characteristics | Admissions experiencing serious bleeding events (n = 80) |
---|---|
Site of serious bleeding event (n [%]) | |
Gastrointestinal | 29 (33.7) |
Skin or soft tissue | 19 (22.1) |
Intra-abdominal | 9 (10.5) |
Intracranial | 7 (8.1) |
Intrathoracic | 5 (5.8) |
Genitourinary | 3 (3.5) |
Retroperitoneal | 0 (0.0) |
Other (source identified)a | 6 (7.0) |
Other (source unidentified) | 5 (5.8) |
Age (years; mean ± SD) | 58.5 (14.9) |
APACHE II score (mean ± SD) | |
Acute physiology score | 19.6 (7.5) |
Score | 22.9 (7.6) |
ICNARC model physiology score (mean ± SD) | 30.5 (8.3) |
Serious conditions in past medical historyb (n [%]) | |
Liver | 1 (1.3) |
Cardiovascular | 0 (0.0) |
Respiratory | 0 (0.0) |
Renal | 1 (1.3) |
Immunosuppressed | 4 (5.0) |
Admission typec (n [%]) | |
Medical | 55 (68.8) |
Elective surgical | 3 (3.8) |
Emergency surgical | 22 (27.5) |
Organ systems failing during first 24 hours of stay in critical care (n [%]) | |
Cardiovascular | 79 (98.8) |
Respiratory | 72 (90.0) |
Renal | 32 (40.5) |
Haematological | 28 (35.0) |
Metabolic acidosis | 68 (85.0) |
Number of organ systems failing during first 24 hours of stay in critical care (n [%]) | |
<2 | 1 (1.3) |
2 | 5 (6.3) |
3 | 38 (47.5) |
4 | 26 (32.5) |
5 | 10 (12.5) |
Primary site of infectiond (n [%]) | |
Lung | 20 (27.0) |
Abdomen | 33 (44.6) |
Urinary tract | 5 (6.8) |
Other | 16 (21.6) |
Positive blood culturee (n [%]) | 26 (36.1) |
Organisms cultured (n [%]) | |
Any | 52 (65.8) |
Gram-negative | 22 (42.3) |
Gram-positive | 26 (50.0) |
Fungus | 12 (23.1) |
Mortality (n [%]) | |
Unit | 31 (3 8.8) |
Hospitalf | 39 (48.8) |
Location at 28 days (n [%]) | |
Died | 30 (37.5) |
Unit | 22 (27.5) |
Hospital | 22 (27.5) |
Out of Hospitalf | 6 (7.5) |
Unit length of stay (days; median [IQR]) | |
Unit survivors | 20.7 (12.7–28.5) |
Unit non-survivors | 9.8 (5.9–23.9) |
Hospitalg length of stay (days; median [IQR]) | |
Hospital survivors | 60 (43–105) |
Hospital nonsurvivors | 19 (8–32) |
Nonrandomized comparison
Discussion
Conclusion
Key messages
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The rate of use of DrotAA in the UK appears low and varies across critical care units.
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The nonrandomized evaluation of effectiveness of DrotAA on acute hospital mortality resulted in eight different point estimates, seven of which were consistent with the results of PROWESS.
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The need for further debate regarding whether 28 days is the optimum end-point for studies in severe sepsis was reinforced by our study
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Current guidelines for use of DrotAA should be revisited, as a priority, once new randomized data are available