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Experience of Using Activated Protein C in a Patient With Emphysematous Pyelonephritis Receiving Percutaneous Nephrostomy Drainage
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CASE REPORT
EXPERIENCE OF USING ACTIVATED PROTEIN C IN A PATIENT WITH EMPHYSEMATOUS PYELONEPHRITIS RECEIVING PERCUTANEOUS NEPHROSTOMY DRAINAGE Yueh-Hung Lin1, Shou-Chuan Shih2, Chien-Liang Wu3,4, Yi-Chou Chen5, Yu-Wei Chen4,5, Shih-Yi Lee3,4* 1
Department of Internal Medicine, Mackay Memorial Hospital, 2Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mackay Memorial Hospital, 4Mackay Medicine, Nursing and Management College, 5Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
SUMMARY Drotrecogin alfa, a type of recombinant human activated protein C, has potential to reduce the mortality in severe sepsis, but may simultaneously increase the risk of serious bleeding events. Here, we report an 81-yearold female suffering from emphysematous pyelonephritis who recovered after appropriate management, including antibiotics, percutaneous nephrostomy drainage and administration of activated protein C. This case showed that percutaneous nephrostomy drainage is not an absolute contraindication in the prescribing of activated protein C in patients with severe sepsis. [International Journal of Gerontology 2010; 4(3): 161–164] Key Words: emphysema, hemorrhage, nephritis, protein C, severe sepsis
Introduction Activated protein C is a well known anti-inflammatory, anti-apoptotic, and coagulation modulatory medication for severe sepsis. However, use of drotrecogin alfa, a type of recombinant human activated protein C, is still of major concern in practice because it may induce serious hemorrhagic events. Although several contraindications have been listed in the guidelines, its application before or after invasive procedures in patients with severe sepsis has not been fully defined.
*Correspondence to: Dr Shih-Yi Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei, Taiwan. E-mail: [email protected] Accepted: June 23, 2009
International Journal of Gerontology | September 2010 | Vol 4 | No 3 © 2010 Taiwan Society of Geriatric Emergency & Critical Care Medicine.
We report a case of an elderly woman with emphysematous nephritis receiving drotrecogin alfa 24 hours after percutaneous nephrostomy drainage. She did not suffer from procedure-related bleeding. It is safe to use drotrecogin alfa in patients with severe sepsis, even in those undergoing post-percutaneous nephrostomy drainage.
Case Report An 81-year-old female presented with type 2 diabetes mellitus. She had been taking metformin 300 mg twice a day and pioglitazone 15 mg daily for the past 10 years. She was admitted to our hospital because of right lower abdominal pain, low urine output, and swollen legs for 6 days. The pain was dull, intermittent, and progressively increasing in intensity. There was no referral pain or any aggravating factors. There was no fever, 161
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Figure 1. Renal stone (arrow) at the right ureteropelvic junction and right hydronephrosis with multifocal air collection within the renal pelvis.
nausea, vomiting, change in bowel habit, urinary frequency or urgency, burning sensation, or vaginal discharge. She had no history of abdominal surgery or abdominal trauma. In the emergency department, her temperature was 37.4°C, pulse 82 beats/minute, respiration 20 breaths/ minute, and blood pressure 136/79 mmHg. The physical examination was normal except for a right costovertebral knocking tenderness and 2 + leg edema. Her hematocrit was 35.6%, hemoglobin 11.8 g/dL, white blood count 14,900 with neutrophils 85%, band forms 0%, creatinine 1.5 mg/dL, and blood urea nitrogen 27 mg/dL. Plain abdominal radiography revealed paralytic ileus and stool impaction. An abdominal computed tomography scan showed a right renal stone, pyelonephritis involving the right kidney with gas collection in the renal pelvis and extension to the perirenal and pararenal spaces (Figure 1). These findings were compatible with emphysematous pyelonephritis. We then prescribed a parenteral antibiotic, flomoxef, 1 g every 8 hours. Emergency computed tomography—guided percutaneous nephrostomy drainage was performed (Figure 2). In spite of aggressive medical intervention, her body temperature increased to 40°C and septic shock occurred while she was being cared for in the intensive care unit (ICU). One day later, disseminated intravascular coagulation developed with a platelet count drop from 12,100/μL to 6,500/μL, prothrombin time increased to 18.3 seconds, with activated partial thromboplastin time of 162
■
Figure 2. A 22-gauge, fine metallic needle was used to puncture and opacify the right renal pelvis. Filling defects were noted in the right renal pelvis representing pelvic stones and right side percutaneous nephrostomy with drainage catheter insertion for continuous urine drainage.
43.5 seconds, fibrin-fibrinogen degradation products greater than 32 μg/mL, D-dimer 5907 ng/mL, and lactic dehydrogenase 334 μg/mL. We changed the parenteral antibiotic to meropenem (1 g every 8 hours). Activated protein C was then prescribed for 96 hours. Three days after administration of activated protein C, follow-up white blood count, diffentnt count, C-reactive protein, platelet count, prothrombin time, and activated partial thromboplastin time values all improved. There were no signs of bleeding, despite the presence of percutaneous nephrostomy drainage. After 3 days she was transferred to a regular ward and was then discharged home 15 days after admission.
Discussion Emphysematous pyelonephritis, first reported in 1898, is a rare and life-threatening, gas-producing infection of the renal parenchyma and/or perirenal tissue. This disease is predominantly seen in women and especially those with diabetes mellitus1–8. It may present with fever, chills, abdominal pain, nausea, vomiting and hematuria. Apart from appropriate use of antibiotics, surgical intervention is curative for emphysematous pyelonephritis. Percutaneous nephrostomy drainage is indicated in mild emphysematous pyelonephritis or in patients with contraindication for nephrectomy4,5,9. In this case, the degree of emphysematous pyelonephritis was not so extensive according to the location of the gas collection6. However, the
International Journal of Gerontology | September 2010 | Vol 4 | No 3
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Activated Protein C in Emphysematous Pyelonephritis
patient still developed refractory septic shock and even underwent percutaneous nephrostomy drainage instead of nephrectomy. Protein C synthesis in the liver is reduced during severe sepsis. It is also degraded by elastase secreted by either leukocytes or pathogens. The decline of the concentration of activated protein C results in a state of hypercoagulation and hyperinflammation. Of these patients, 20–40% will suffer from organ dysfunction and death10. The anticoagulatory, anti-inflammatory, and anti-apoptotic effects of activated protein C could break the viscous cycle between inflammation and disseminated intravascular coagulopathy in severe sepsis11,12. Activated protein C, an important modulator of coagulation, is converted from the protein C zymogen by the thrombin-thrombomodulin complex. It can inactivate coagulation factors Va and VIIIa, which inhibit thrombin generation. Activated protein C can also be a profibrinolytic factor because it promotes fibrinolysis by inhibiting plasminogen activator inhibitor-110,13. In addition to its role as an anticoagulant, a number of anti-inflammatory effects and anti-apoptotic properties have been described13. It has a role in the inhibition of neutrophil chemotaxis and in maintaining endothelial integrity after binding to endothelial protein C receptors. Its cytoprotective effects are mediated by intracellular signaling, which results in interaction with an adjacent protease-activated receptor via the S1P1-, Rac1-, PI3-kinase-, and Akt-dependent sphingosine 1-phosphate pathway10,14,15. Drotrecogin alfa is recombinant human activated protein C that has significantly reduced the mortality in patients with severe sepsis12,16. However, it may increase the risk of bleeding12,17. The risk-benefit ratio has to be considered in clinical practice18–20. In elderly patients with severe sepsis, drotrecogin alfa also increases short-term and long-term survival rates, and vasopressor-free, ventilator-free, ICU-free and hospitalfree days without increasing the incidence of adverse events of severe sepsis, including serious hemorrhagic events21. In previous studies, drotrecogin alfa has been reported to have been safely applied in several elective and emergency invasive procedures; however, an identical case study for percutaneous nephrostomy drainage is not available12,22. In our case, because of septic shock and disseminated intravascular coagulation, we used drotrecogin alfa for 96 hours and no bleeding was noted. Our case could be an example of
International Journal of Gerontology | September 2010 | Vol 4 | No 3
■
the safety of drotrecogin alfa in percutaneous nephrostomy drainage in the elderly patient with emphysematous pyelonephritis.
Conclusion Although drotrecogin alfa may induce serious hemorrhagic events, its application before or after invasive procedures in patients with severe sepsis has not been fully defined. This case provides useful information of an elderly woman with emphysematous nephritis, a disease which even increases the risk of hematuria, who received drotrecogin alfa 24 hours after percutaneous nephrostomy drainage but did not suffer from procedure-related bleeding. This encourages us to use drotrecogin alfa in patients with severe sepsis, even in those who have undergone post percutaneous nephrostomy drainage.
References 1. 2.
3.
4.
5.
6.
7.
8.
9.
Michaeli J, Mogle P, Perlberg S, et al. Emphysematous pyelonephritis. J Urol 1984; 131: 203–8. Evanoff GV, Thompson CS, Foley R, et al. Spectrum of gas within the kidney. Emphysematous pyelonephritis and emphysematous pyelitis. Am J Med 1987; 83: 149–54. Pontin AR, Barnes RD, Joffe J, et al. Emphysematous pyelonephritis in diabetic patients. Br J Urol 1995; 75: 71–4. Chen MT, Huang CN, Chou YH, et al. Percutaneous drainage in the treatment of emphysematous pyelonephritis: 10-year experience. J Urol 1997; 157: 1569–73. Shokeir AA, El-Azab M, Mohsen T, et al. Emphysematous pyelonephritis: a 15-year experience with 20 cases. Urology 1997; 49: 343–6. Huang JJ, Tseng CC. Emphysematous pyelonephritis: clinicoradiological classification, management, prognosis, and pathogenesis. Arch Intern Med 2000; 160: 797–805. Tahir H, Thomas G, Sheerin N, et al. Successful medical treatment of acute bilateral emphysematous pyelonephritis. Am J Kidney Dis 2000; 36: 1267–70. Kumar, A. Turney JH, Brownjohn AM, et al. Unusual bacterial infections of the urinary tract in diabetic patients— rare but frequently lethal. Nephrol Dial Transplant 2001; 16: 1062–5. McHugh TP, Albanna SE, Stewart NJ. Bilateral emphysematous pyelonephritis. Am J Emerg Med 1998; 16: 166–9.
163
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10. Vangerow B, Shorr AF, Wyncoll D, et al. The protein C pathway: implications for the design of the RESPOND study. Crit Care 2007; 11 (Suppl 5): S4. 11. Esmon CT. The protein C anticoagulant pathway. Arterioscler Thromb 1992; 12: 135–45. 12. Bernard G, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699–709. 13. Macias WL, Yan SB, Williams MD, et al. New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated). Crit Care 2005; 9 Suppl 4: S38–45. 14. Finigan JH, Dudek SM, Singleton PA, et al. Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation. J Biol Chem 2005; 280: 17286–93. 15. Mosnier LO, Zlokovic BV, Griffin JH. The cytoprotective protein C pathway. Blood 2007; 109: 3161–72. 16. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of
164
17. 18.
19.
20. 21.
22.
■ severe sepsis and septic shock: 2008. Crit Care Med 2008; 36: 296–327. Laterre PF. Clinical trials in severe sepsis with drotrecogin alfa (activated). Crit Care 2007; 11 (Suppl 5): S5. Barie PS, Hydo LJ, Shou J, et al. Efficacy and safety of drotrecogin alfa (activated) for the therapy of surgical patients with severe sepsis. Surg Infect (Larchmt) 2006; 7 (Suppl 2): S77–80. Camporota L, Wyncoll D. Practical aspects of treatment with drotrecogin alfa (activated). Crit Care 2007; 11 (Suppl 5): S7. Fumagalli R, Mignini MA. The safety profile of drotrecogin alfa (activated). Crit Care 2007; 11 (Suppl 5): S6. Ely EW, Angus DC, Williams MD, et al. Drotrecogin alfa (activated) treatment of older patients with severe sepsis. Clin Infect Dis 2003; 37: 187–95. Laterre PF, Wittebole X. Clinical review: drotrecogin alfa (activated) as adjunctive therapy for severe sepsis— practical aspects at the bedside and patient identification. Crit Care 2003; 7: 445–50.
International Journal of Gerontology | September 2010 | Vol 4 | No 3
CASE REPORT
EXPERIENCE OF USING ACTIVATED PROTEIN C IN A PATIENT WITH EMPHYSEMATOUS PYELONEPHRITIS RECEIVING PERCUTANEOUS NEPHROSTOMY DRAINAGE Yueh-Hung Lin1, Shou-Chuan Shih2, Chien-Liang Wu3,4, Yi-Chou Chen5, Yu-Wei Chen4,5, Shih-Yi Lee3,4* 1
Department of Internal Medicine, Mackay Memorial Hospital, 2Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mackay Memorial Hospital, 4Mackay Medicine, Nursing and Management College, 5Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
SUMMARY Drotrecogin alfa, a type of recombinant human activated protein C, has potential to reduce the mortality in severe sepsis, but may simultaneously increase the risk of serious bleeding events. Here, we report an 81-yearold female suffering from emphysematous pyelonephritis who recovered after appropriate management, including antibiotics, percutaneous nephrostomy drainage and administration of activated protein C. This case showed that percutaneous nephrostomy drainage is not an absolute contraindication in the prescribing of activated protein C in patients with severe sepsis. [International Journal of Gerontology 2010; 4(3): 161–164] Key Words: emphysema, hemorrhage, nephritis, protein C, severe sepsis
Introduction Activated protein C is a well known anti-inflammatory, anti-apoptotic, and coagulation modulatory medication for severe sepsis. However, use of drotrecogin alfa, a type of recombinant human activated protein C, is still of major concern in practice because it may induce serious hemorrhagic events. Although several contraindications have been listed in the guidelines, its application before or after invasive procedures in patients with severe sepsis has not been fully defined.
*Correspondence to: Dr Shih-Yi Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei, Taiwan. E-mail: [email protected] Accepted: June 23, 2009
International Journal of Gerontology | September 2010 | Vol 4 | No 3 © 2010 Taiwan Society of Geriatric Emergency & Critical Care Medicine.
We report a case of an elderly woman with emphysematous nephritis receiving drotrecogin alfa 24 hours after percutaneous nephrostomy drainage. She did not suffer from procedure-related bleeding. It is safe to use drotrecogin alfa in patients with severe sepsis, even in those undergoing post-percutaneous nephrostomy drainage.
Case Report An 81-year-old female presented with type 2 diabetes mellitus. She had been taking metformin 300 mg twice a day and pioglitazone 15 mg daily for the past 10 years. She was admitted to our hospital because of right lower abdominal pain, low urine output, and swollen legs for 6 days. The pain was dull, intermittent, and progressively increasing in intensity. There was no referral pain or any aggravating factors. There was no fever, 161
■
Y.H. Lin et al
Figure 1. Renal stone (arrow) at the right ureteropelvic junction and right hydronephrosis with multifocal air collection within the renal pelvis.
nausea, vomiting, change in bowel habit, urinary frequency or urgency, burning sensation, or vaginal discharge. She had no history of abdominal surgery or abdominal trauma. In the emergency department, her temperature was 37.4°C, pulse 82 beats/minute, respiration 20 breaths/ minute, and blood pressure 136/79 mmHg. The physical examination was normal except for a right costovertebral knocking tenderness and 2 + leg edema. Her hematocrit was 35.6%, hemoglobin 11.8 g/dL, white blood count 14,900 with neutrophils 85%, band forms 0%, creatinine 1.5 mg/dL, and blood urea nitrogen 27 mg/dL. Plain abdominal radiography revealed paralytic ileus and stool impaction. An abdominal computed tomography scan showed a right renal stone, pyelonephritis involving the right kidney with gas collection in the renal pelvis and extension to the perirenal and pararenal spaces (Figure 1). These findings were compatible with emphysematous pyelonephritis. We then prescribed a parenteral antibiotic, flomoxef, 1 g every 8 hours. Emergency computed tomography—guided percutaneous nephrostomy drainage was performed (Figure 2). In spite of aggressive medical intervention, her body temperature increased to 40°C and septic shock occurred while she was being cared for in the intensive care unit (ICU). One day later, disseminated intravascular coagulation developed with a platelet count drop from 12,100/μL to 6,500/μL, prothrombin time increased to 18.3 seconds, with activated partial thromboplastin time of 162
■
Figure 2. A 22-gauge, fine metallic needle was used to puncture and opacify the right renal pelvis. Filling defects were noted in the right renal pelvis representing pelvic stones and right side percutaneous nephrostomy with drainage catheter insertion for continuous urine drainage.
43.5 seconds, fibrin-fibrinogen degradation products greater than 32 μg/mL, D-dimer 5907 ng/mL, and lactic dehydrogenase 334 μg/mL. We changed the parenteral antibiotic to meropenem (1 g every 8 hours). Activated protein C was then prescribed for 96 hours. Three days after administration of activated protein C, follow-up white blood count, diffentnt count, C-reactive protein, platelet count, prothrombin time, and activated partial thromboplastin time values all improved. There were no signs of bleeding, despite the presence of percutaneous nephrostomy drainage. After 3 days she was transferred to a regular ward and was then discharged home 15 days after admission.
Discussion Emphysematous pyelonephritis, first reported in 1898, is a rare and life-threatening, gas-producing infection of the renal parenchyma and/or perirenal tissue. This disease is predominantly seen in women and especially those with diabetes mellitus1–8. It may present with fever, chills, abdominal pain, nausea, vomiting and hematuria. Apart from appropriate use of antibiotics, surgical intervention is curative for emphysematous pyelonephritis. Percutaneous nephrostomy drainage is indicated in mild emphysematous pyelonephritis or in patients with contraindication for nephrectomy4,5,9. In this case, the degree of emphysematous pyelonephritis was not so extensive according to the location of the gas collection6. However, the
International Journal of Gerontology | September 2010 | Vol 4 | No 3
■
Activated Protein C in Emphysematous Pyelonephritis
patient still developed refractory septic shock and even underwent percutaneous nephrostomy drainage instead of nephrectomy. Protein C synthesis in the liver is reduced during severe sepsis. It is also degraded by elastase secreted by either leukocytes or pathogens. The decline of the concentration of activated protein C results in a state of hypercoagulation and hyperinflammation. Of these patients, 20–40% will suffer from organ dysfunction and death10. The anticoagulatory, anti-inflammatory, and anti-apoptotic effects of activated protein C could break the viscous cycle between inflammation and disseminated intravascular coagulopathy in severe sepsis11,12. Activated protein C, an important modulator of coagulation, is converted from the protein C zymogen by the thrombin-thrombomodulin complex. It can inactivate coagulation factors Va and VIIIa, which inhibit thrombin generation. Activated protein C can also be a profibrinolytic factor because it promotes fibrinolysis by inhibiting plasminogen activator inhibitor-110,13. In addition to its role as an anticoagulant, a number of anti-inflammatory effects and anti-apoptotic properties have been described13. It has a role in the inhibition of neutrophil chemotaxis and in maintaining endothelial integrity after binding to endothelial protein C receptors. Its cytoprotective effects are mediated by intracellular signaling, which results in interaction with an adjacent protease-activated receptor via the S1P1-, Rac1-, PI3-kinase-, and Akt-dependent sphingosine 1-phosphate pathway10,14,15. Drotrecogin alfa is recombinant human activated protein C that has significantly reduced the mortality in patients with severe sepsis12,16. However, it may increase the risk of bleeding12,17. The risk-benefit ratio has to be considered in clinical practice18–20. In elderly patients with severe sepsis, drotrecogin alfa also increases short-term and long-term survival rates, and vasopressor-free, ventilator-free, ICU-free and hospitalfree days without increasing the incidence of adverse events of severe sepsis, including serious hemorrhagic events21. In previous studies, drotrecogin alfa has been reported to have been safely applied in several elective and emergency invasive procedures; however, an identical case study for percutaneous nephrostomy drainage is not available12,22. In our case, because of septic shock and disseminated intravascular coagulation, we used drotrecogin alfa for 96 hours and no bleeding was noted. Our case could be an example of
International Journal of Gerontology | September 2010 | Vol 4 | No 3
■
the safety of drotrecogin alfa in percutaneous nephrostomy drainage in the elderly patient with emphysematous pyelonephritis.
Conclusion Although drotrecogin alfa may induce serious hemorrhagic events, its application before or after invasive procedures in patients with severe sepsis has not been fully defined. This case provides useful information of an elderly woman with emphysematous nephritis, a disease which even increases the risk of hematuria, who received drotrecogin alfa 24 hours after percutaneous nephrostomy drainage but did not suffer from procedure-related bleeding. This encourages us to use drotrecogin alfa in patients with severe sepsis, even in those who have undergone post percutaneous nephrostomy drainage.
References 1. 2.
3.
4.
5.
6.
7.
8.
9.
Michaeli J, Mogle P, Perlberg S, et al. Emphysematous pyelonephritis. J Urol 1984; 131: 203–8. Evanoff GV, Thompson CS, Foley R, et al. Spectrum of gas within the kidney. Emphysematous pyelonephritis and emphysematous pyelitis. Am J Med 1987; 83: 149–54. Pontin AR, Barnes RD, Joffe J, et al. Emphysematous pyelonephritis in diabetic patients. Br J Urol 1995; 75: 71–4. Chen MT, Huang CN, Chou YH, et al. Percutaneous drainage in the treatment of emphysematous pyelonephritis: 10-year experience. J Urol 1997; 157: 1569–73. Shokeir AA, El-Azab M, Mohsen T, et al. Emphysematous pyelonephritis: a 15-year experience with 20 cases. Urology 1997; 49: 343–6. Huang JJ, Tseng CC. Emphysematous pyelonephritis: clinicoradiological classification, management, prognosis, and pathogenesis. Arch Intern Med 2000; 160: 797–805. Tahir H, Thomas G, Sheerin N, et al. Successful medical treatment of acute bilateral emphysematous pyelonephritis. Am J Kidney Dis 2000; 36: 1267–70. Kumar, A. Turney JH, Brownjohn AM, et al. Unusual bacterial infections of the urinary tract in diabetic patients— rare but frequently lethal. Nephrol Dial Transplant 2001; 16: 1062–5. McHugh TP, Albanna SE, Stewart NJ. Bilateral emphysematous pyelonephritis. Am J Emerg Med 1998; 16: 166–9.
163
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10. Vangerow B, Shorr AF, Wyncoll D, et al. The protein C pathway: implications for the design of the RESPOND study. Crit Care 2007; 11 (Suppl 5): S4. 11. Esmon CT. The protein C anticoagulant pathway. Arterioscler Thromb 1992; 12: 135–45. 12. Bernard G, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699–709. 13. Macias WL, Yan SB, Williams MD, et al. New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated). Crit Care 2005; 9 Suppl 4: S38–45. 14. Finigan JH, Dudek SM, Singleton PA, et al. Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation. J Biol Chem 2005; 280: 17286–93. 15. Mosnier LO, Zlokovic BV, Griffin JH. The cytoprotective protein C pathway. Blood 2007; 109: 3161–72. 16. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of
164
17. 18.
19.
20. 21.
22.
■ severe sepsis and septic shock: 2008. Crit Care Med 2008; 36: 296–327. Laterre PF. Clinical trials in severe sepsis with drotrecogin alfa (activated). Crit Care 2007; 11 (Suppl 5): S5. Barie PS, Hydo LJ, Shou J, et al. Efficacy and safety of drotrecogin alfa (activated) for the therapy of surgical patients with severe sepsis. Surg Infect (Larchmt) 2006; 7 (Suppl 2): S77–80. Camporota L, Wyncoll D. Practical aspects of treatment with drotrecogin alfa (activated). Crit Care 2007; 11 (Suppl 5): S7. Fumagalli R, Mignini MA. The safety profile of drotrecogin alfa (activated). Crit Care 2007; 11 (Suppl 5): S6. Ely EW, Angus DC, Williams MD, et al. Drotrecogin alfa (activated) treatment of older patients with severe sepsis. Clin Infect Dis 2003; 37: 187–95. Laterre PF, Wittebole X. Clinical review: drotrecogin alfa (activated) as adjunctive therapy for severe sepsis— practical aspects at the bedside and patient identification. Crit Care 2003; 7: 445–50.
International Journal of Gerontology | September 2010 | Vol 4 | No 3