25. Pacientes quirúrgicos en el Prowess : podemos saber más … Barie PS, et al. Am J Surg 2004; 188:212-220. Surgical N=474 Non-Surgical N=1216 p-Value Gender Male, n(%) 261 (55.1) 703 (57.8) Female, n(%) 213 (44.9) 513 (42.2) Age (years) Mean, SE 62.5 + 0.7 59.8 + 0.5 Median 66.2 62.3 0.002 APACHE II (Mean + SE) 23.5 + 0.36 25.3 + 0.22 0.001 Organ Dysfunctions (Mean + SE) 2.6 + 0.05 2.3 + 0.03 0.001
26. Fallos orgánicos pacientes quirúrgicos del PROWESS Barie PS, et al. Am J Surg 2004; 188:212-220. Barie PS, et al. Crit Care Med 2003; 30(S12 ):A102. Surgical (N=474) Non-Surgical (n=1216) Total p-Value Shock, n (%) Yes 347 (73.2) 853 (70.1) 1200 NS No 127 (26.8) 363 (29.9) 490 Vasopressors, n (%) Yes 315 (66.5) 742 (61.0) 1057 NS No 159 (33.5) 474 (39.0) 633 Ventilation, n (%) Yes 432 (91.1) 843 (69.3) 1275 0.001 No 42 (8.9) 373 (30.73) 415
27. Biomarcadores pacientes quirúrgicos del PROWESS Data on File, Lilly Research Laboratories, F1KNOV2005M. Barie PS, et al. Am J Surg 2004; 188:212-220. Surgical (N=474) Non-Surgical (n=1216) p-Value D-dimer (NL=0-0.39 mcg/ml) N=443 N=1107 <0.001 Median (IQR) 5.4 (3.1-9.3) 3.8 (1.9-7.7) IL-6 (NL=0.38-10.1 pg/ml) N=463 N=1172 <0.001 Median (IQR) 600 (228-2544) 418 (188-2589) Protein C Activity (NL= 81-173%) N=449 N=1125 <0.001 Median (IQR) 41 (27-59) 50 (34-69)
28. Edad y APACHE II en los quirúrgicos del PROWESS Barie PS, et al. Am J Surg 2004; 188:212-220. Surgical N=474 Non-Surgical N=1216 p-Value APACHE II Mean, SEM 23.5 + 0.36 25.3 + 0.22 <0.001 Acute Physiological Mean, SEM 19.1 + 0.33 20.8 + 0.22 <0.001 Chronic Health Mean, SEM 0.6 + 0.07 1.1 + 0.06 <0.001 Age (years) Mean, SEM 3.7 + 0.10 3.3 + 0.06 <0.002
29. Cirugía inicial en los pacientes quirúrgicos del PROWESS * Miscellaneous includes orthopedic, obstetrical, head and neck, neurological, and percutaneous device placement Barie PS, et al. Am J Surg 2004; 188:212-220. Surgical Category Placebo Drotrecogin alfa (activated) Total N=246 N=228 N=474 Intra-abdominal, n (%) 157 (63.8) 158 (69.3) 315 (66.5) Thoracic, n (%) 15 (6.1) 12 (5.3) 27 (5.7) Vascular, n (%) 13 (5.3) 13 (5.7) 26 (5.5) Skin, n (%) 11 (4.5) 13 (5.7) 24 (5.1) Cardiac, n (%) 12 (4.9) 5 (2.2) 17 (3.6) Genitourinary, n (%) 6 (2.4) 8 (3.5) 14 (2.9) Trauma, n (%) 7 (2.8) 3 (1.3) 10 (2.1) Miscellaneous * , n (%) 25 (10.2) 16 (7.0) 41 (8.6)
30. Infección pre o post cirugía Barie PS, et al. Am J Surg 2004; 188:212-220. Placebo N=246 Drotrecogin alfa (activated) N=228 Total N=474 Infection Present Prior to Surgery, n (%) Pre-op Severe Sepsis 121 (49.2) 129 (56.6) 250 (52.7) Surgery Prior to Infection, n (%) Post-op Severe Sepsis 125 (50.8) 99 (43.4) 224 (47.3)
31. Fuente primaria de infección * Miscellaneous includes central nervous system, head and neck, cardiac, pleural, bone, gynecologic, skin, other, and unknown Barie PS, et al. Am J Surg 2004; 188:212-220. Surgical N=468 Non-Surgical N=1171 p-Value Lung, n (%) 95 (20.3) 790 (67.5) <0.001 Intra-abdominal, n (%) 295 (63.0) 68 (5.8) <0.001 Urinary, n (%) 23 (4.9) 179 (15.3) <0.001 Miscellaneous * , n (%) 83 (17.7) 160 (13.7) 0.036
32. Tipo de infección según el GRAM Note: Type of infection determined by the PROWESS Clinical Evaluation Committee Barie PS, et al. Am J Surg 2004; 188:212-220. Surgical N=474 Non-Surgical N=1216 Pure Gram +, n (%) 72 (15.2) 354 (29.1) Pure Gram -, n (%) 105 (22.1) 297 (24.4) Mixed Gram, n (%) And other organisms 109 (23.0) 110 (9.1) Fungal, n (%) 38 (8.0) 24 (2.0) Unknown/none, n (%) 150 (31.6) 431 (35.4)
33. Estado de la coagulación el los pacientes quirúrgicos del PROWESS Data on File, Lilly Research Laboratories, F1KNOV2005O. Barie PS, et al. Am J Surg 2004; 188:212-220. Surgical N=474 Non-Surgical N=1216 p-Value aPTT (sec) n=446 n=1115 <0.001 Median (IQR) 44.6 (38.3 – 52.2) 41.9 (35.5 – 49.6) PT (sec) n=446 n=1112 <0.001 Median (IQR) 20.1 (17.5 – 23.9) 18.1 (16.2 – 21.3) Platelets (10 3 /mm 3 ) n=407 n=1012 NS Median (IQR) 188 (124-272) 180 (114-242)
34. Mortalidad subgrupos quirúrgicos en el PROWESS Mortality Rate Other Surg 159 32.6% 42.0% -10.3 0.5 0.6 0.7 0.8 1 1.25 1.67 2 0.9 Relative Risk of Death (Point Estimate and 95% CI) PROWESS Overall Surgical Cohort 1690 30.8% 24.7% 6.1 474 31.3% 28.1% 3.2 N Placebo DrotAA Non-Surgical Cohort 1216 30.6% 23.5% 7.1 Data on File, Lilly Research Laboratories, F1KNOV2005P. Barie P, et al. Crit Care Med 2003; 30(S12):A102. Barie PS, et al. Am J Surg 2004; 188:212-220. Intra-abd 315 30.6% 21.5% 9.1 Absolute Risk Reduction
35. PROWESS: Subgroup Mortality 0.5 0.6 0.7 0.8 1 1.25 1.67 2 0.9 Relative Risk of Death (Point Estimate and 95% CI) PROWESS Overall 1690 30.8% 24.7% 6.1 APACHE II < 25 278 20.0% 22.5% -2.5 APACHE II 25 196 46.2% 36.7% 9.5 Surgical Cohort 474 31.3% 28.1% 3.2 Organ Dysf <2 94 19.6% 22.9% -3.3 Organ Dysf 2 380 34.0% 29.4% 4.6 N Placebo DrotAA Mortality Rate Data on File, Lilly Research Laboratories, F1KNOV2005Q. Barie PS, et al. Am J Surg 2004; 188:212-220. Absolute Risk Reduction
36. PROWESS: Treatment Emergent Bleeding Events by Treatment and Surgical Status (SEC) During Infusion (n=19) (n=38) (n=49) (n=39) (n=122) (n=72) (n=163) (n=110) (n=228) (n=246) (n=228) (n=246) (n=622) (n=594) (n=622) (n=594) During Infusion 28-Day 28-Day Surgical Patients Non - Surgical Patients p=0.0028 p=0.0004 p=0.0013 p-value from Pearson’s chi square Percent of Patients Data on File, Lilly Research Laboratories, F1KNOV2005R. Barie PS, et al. Am J Surg 2004; 188:212-220.
37. PROWESS: Serious Adverse Bleeding Events (SEC) (n=8) (n=20) (n=7) (n=0) (n=8) (n=13) (n=17) (n=30) (n=4) (n=8) (n=13) (n=22) (n=840) (n=850) (n=246) (n=228) (n=594) (n=622) (n=840) (n=850) (n=246) (n=228) (n=594) (n=622) All Prowess Surgical Non-Surgical All Prowess Surgical Non-Surgical Drug Infusion Period 28 Day Study Period p=0.024 p=0.006 p=0.060 Percent of Patients Percent of Patients Data on File, Lilly Research Laboratories, F1KNOV2005S. Barie PS, et al. Am J Surg 2004; 188:212-220.
56. Objective: To determine the incidence and outcome of severe sepsis in the adult Finnish population and to evaluate how treatment guidelines in severe sepsis are applied in clinical practice. Study design: A prospective study in 24 closed multidisciplinary ICUs in 21 hospitals (4 university and 17 tertiary hospitals) in Finland. Patients: All 4,500 consecutive ICU admission episodes were screened for severe sepsis during a 4-month period (1 November 2004 – 28 February 2005). The referral population was 3,743,225.
59. Treatment compliance with the Sepsis Management Bundle's guidelines was poor. Recommended low-dose corticosteroid treatment was administered to fewer than one-half of the patients with septic shock. Treatment with aPC was given to only one-third of the patients with indications according to Finnish recommendations published in 2003. Blood cultures were absent nearly in one-third of patients. Ventilating acute lung injury/acute respiratory distress syndrome patients with low tidal volumes according to ARDSnet recommendations was poor
60. Recent studies have reported difficulty in implementing clinical guidelines in practice. Young MP, (2004) Ventilation of patients with acute lung injury and acute respiratory distress syndrome: has new evidence changed clinical practice? Crit Care Med 32:1260–1265 Rubenfeld GD, (2004) Barriers to providing lung-protective ventilation to patients with acute lung injury. Crit Care Med 32:1289–1293 Cabana MD, (1999) Why don't physicians follow clinical practise guidelines? A framework for improvement. JAMA 282:1458–1465
61. 101 consecutive adult patients with severe sepsis or septic shock The main outcome measures were: The rate of compliance with 6-hour and 24-hour sepsis care bundles adapted from the Surviving Sepsis Campaign guidelines on patients' clinical care. Difference in hospital mortality between the compliant and the non-compliant groups.
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66. Compliance with 24-hour sepsis bundle and hospital mortality 71 critical care patients 69 (98%) were qualified for the 24-hour sepsis bundle for clinical care. 64% received glucose control < 8.3 mmol/ 43% had low-dose steroids given when requiring continued use of vasopressors Activated protein C was considered in only 30% of patients Plateau pressures were maintained < 30 cm H2O in 85% of ventilated patients. Rate of compliance was 30%. Hospital mortality was increased in the non-compliant group from 29% to 50%
67. Patients with severe sepsis who did not receive the 6-hour sepsis bundle for their early management had a twofold increase in hospital mortality The association between the use of a group of evidence-based interventions, improved outcomes. Efforts to improve hospital mortality from severe sepsis should focus on increasing compliance with these evidence-based interventions in appropriate patients.
Age Mean SE p-value = 0.002 (from 2-way ANOVA model) In essence, there is a difference in age but this age difference is not related to treatment with Xigris. This is a baseline age.
P-value is from Pearson’s chi-square. NS= Non Significant
P value from two-way ANOVA IQR = Interquartile range
P value is from 2-way ANOVA SEM = Standard Error of the Mean
Important Note: The Intraabdominal group is over 10 times the size of any other group. Initial Surgery=the first operative procedure performed in the 30 days prior to enrollment in PROWESS Explanation of “Other” Xigris Placebo Anorectal 1 (0.4) 0 (0.0) Esophageal 3 (1.3) 4 (1.6) All procedures including those with multiple procedures performed
The site of infection was either documented or suspected on the basis of clinical findings. To meet the suspected infection criteria, patients had to have one of the following: White blood cells in a normally sterile body fluid Perforated viscus Chest x-ray consistent with pneumonia and associated with purulent sputum production Clinical syndrome associated with a high risk of infection (eg ascending cholangitis) The number of patients with an infection in a particular site was similar in both treatment groups. The lungs and the abdomen were the most common sites of infection, accounting for 53.6% and 19.9% of patients, respectively, in the two treatment groups combined. Other sites of infection included the blood, skin, central nervous system, bones and joints, cardiac system and reproductive organs.
IQR = Interquartile range
The Xigris label specifies the Absolute Risk Reduction in rounded numbers as: 2%, 5%, 8%, and 11% for organ failures.
Treatment Emergent Bleeding includes both serious adverse bleeding and non-serious adverse bleeding events.
-Surgical patients receiving drotrecogin alfa (activated) had more serious bleeding during the infusion period compared to those on placebo, however, none of these bleeding events were fatal. -Six of the 7 serious bleeding events occurring during the infusion of drotrecogin alfa (activated) occurred following placement of a chest tube or drain or an operative procedure -The rate of serious bleeding in surgical patients during the 28-days was similar between the placebo and the drotrecogin alfa (activated) groups -Serious bleeding in surgical patients during infusion and the 28 days was similar to that of all PROWESS patients
This data is not adjusted for survival. There are more survivors in the drotrecogin alfa (activated) group. P-Value from Pearson’s chi square
