Sepsis: frontiers in supportive care, organisation and research

Intensive Care Medicine

Volumn 43, Issue 4, 2017, Pages 496-508

  Perner, Anders ^a   Rhodes, Andrew ^b   Venkatesh, Bala ^c,d   Angus, Derek C ^e   Martin loeches, Ignacio ^f,g,h   Preiser, Jean Charles ⁱ   Vincent, Jean Louis ⁱ   Marshall, John ^j   Reinhart, Konrad ^k   Joannidis, Michael ^l   Opal, Steven M ^m  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^c UNIVERSITY OF QUEENSLAND   (Australia)

^d UNIVERSITY OF SYDNEY   (Australia)

^e UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^f Multidisciplinary Intensive Care Research Organization (MICRO)   (Ireland)

^g ST JAMES S HOSPITAL   (Ireland)

^h INSTITUTO DE SALUD CARLOS III   (Spain)

ⁱ ERASME HOSPITAL   (Belgium)

^j ST MICHAEL'S HOSPITAL   (Canada)

^k JENA UNIVERSITY HOSPITAL   (Germany)

^l INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^m BROWN UNIVERSITY   (United States)

more..

Author keywords

Acute respiratory failure; Critical care medicine; Intensive care medicine; Renal failure; Sepsis; Shock

Indexed keywords

FUROSEMIDE; HORMONE;

ADULT RESPIRATORY DISTRESS SYNDROME; CLINICAL EFFECTIVENESS; CLINICAL RESEARCH; EPIDEMIOLOGY; EXTRACORPOREAL OXYGENATION; HEALTH CARE ORGANIZATION; HEALTH SERVICES RESEARCH; HORMONE BLOOD LEVEL; HUMAN; MEDIATOR; MEDICAL RESEARCH; NASAL CANNULA; NONHUMAN; NUTRITIONAL SUPPORT; OUTCOME ASSESSMENT; PERSONALIZED MEDICINE; PRACTICE GUIDELINE; RENAL REPLACEMENT THERAPY; RESUSCITATION; REVIEW; SEPSIS; COST OF ILLNESS; GLOBAL DISEASE BURDEN; HEALTH SERVICE; INCIDENCE; MORTALITY; ORGANIZATION AND MANAGEMENT; TREATMENT OUTCOME;

BIOMEDICAL RESEARCH; COST OF ILLNESS; GLOBAL BURDEN OF DISEASE; GUIDELINES AS TOPIC; HEALTH SERVICES ADMINISTRATION; HUMANS; INCIDENCE; OUTCOME AND PROCESS ASSESSMENT (HEALTH CARE); PRECISION MEDICINE; SEPSIS;

EID: 85010754928     PISSN: 03424642     EISSN: 14321238     Source Type: Journal    
DOI: 10.1007/s00134-017-4677-4     Document Type: Review

References (109)

1. Kissoon N, Daniels R, van der Poll T et al (2016) Sepsis—the final common pathway to death from multiple organ failure in infection. Crit Care Med 44:e446. doi:10.1097/CCM.0000000000001582
2. Wang H, Naghavi M, Allen C et al (2015) Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the global burden of disease study. Lancet 388:1459–1544. doi:10.1016/S0140-6736(16)31012-1
3. Karlsson S, Ruokonen E, Varpula T et al (2009) Long-term outcome and quality-adjusted life years after severe sepsis. Crit Care Med 37:1268–1274. doi:10.1097/CCM.0b013e31819c13ac
4. Perner A, Haase N, Winkel P et al (2014) Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer’s acetate. Intensive Care Med 40:927–934. doi:10.1007/s00134-014-3311-y
5. Prescott HC, Langa KM, Liu V et al (2014) Increased 1-year healthcare use in survivors of severe sepsis. Am J Respir Crit Care Med 190:62–69. doi:10.1164/rccm.201403-0471OC
6. Perner A, Gordon AC, De Backer D et al (2016) Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med 42:1958–1969. doi:10.1007/s00134-016-4577-z
7. Martin-Loeches I, Levy MM, Artigas A (2015) Management of severe sepsis: advances, challenges, and current status. Drug Des Dev Ther 9:2079–2088. doi:10.2147/DDDT.S78757
8. Monro-Somerville T, Sim M, Ruddy J et al (2016) The effect of high-flow nasal cannula oxygen therapy on mortality and intubation rate in acute respiratory failure: a systematic review and meta-analysis. Crit Care Med. doi:10.1097/CCM.0000000000002091
9. Murias G, Lucangelo U, Blanch L (2016) Patient-ventilator asynchrony. Curr Opin Crit Care 22:53–59. doi:10.1097/MCC.0000000000000270
10. Blanch L, Villagra A, Sales B et al (2015) Asynchronies during mechanical ventilation are associated with mortality. Intensive Care Med 41:633–641. doi:10.1007/s00134-015-3692-6
11. Claesson J, Freundlich M, Gunnarsson I et al (2015) Scandinavian clinical practice guideline on mechanical ventilation in adults with the acute respiratory distress syndrome. Acta Anaesthesiol Scand 59:286–297. doi:10.1111/aas.12449
12. Claesson J, Freundlich M, Gunnarsson I et al (2016) Scandinavian clinical practice guideline on fluid and drug therapy in adults with acute respiratory distress syndrome. Acta Anaesthesiol Scand 60:697–709. doi:10.1111/aas.12713
13. Suzumura EA, Figueiró M, Normilio-Silva K et al (2014) Effects of alveolar recruitment maneuvers on clinical outcomes in patients with acute respiratory distress syndrome: a systematic review and meta-analysis. Intensive Care Med 40:1227–1240. doi:10.1007/s00134-014-3413-6
14. Amato MBP, Meade MO, Slutsky AS et al (2015) Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 372:747–755. doi:10.1056/NEJMsa1410639
15. Cheng A, Sun H-Y, Lee C-W et al (2013) Survival of septic adults compared with nonseptic adults receiving extracorporeal membrane oxygenation for cardiopulmonary failure: a propensity-matched analysis. J Crit Care 28:531.e1–531.e10. doi:10.1016/j.jcrc.2012.11.021
16. Schultz MJ, Juffermans NP, Matthay MA (2013) From protective ventilation to super-protective ventilation for acute respiratory distress syndrome. Intensive Care Med 39:963–965. doi:10.1007/s00134-012-2805-8
17. Clark PMS, Gordon K (2011) Challenges for the endocrine laboratory in critical illness. Best Pract Res Clin Endocrinol Metab 25:847–859. doi:10.1016/j.beem.2011.04.010
18. Venkatesh B, Cohen J (2011) Adrenocortical (dys)function in septic shock—a sick euadrenal state. Best Pract Res Clin Endocrinol Metab 25:719–733. doi:10.1016/j.beem.2011.04.007
19. Takala J, Ruokonen E, Webster NR et al (1999) Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 341:785–792. doi:10.1056/NEJM199909093411102
20. Finfer S, Chittock DR, NICE-SUGAR Study Investigators et al (2009) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 360:1283–1297. doi:10.1056/NEJMoa0810625
21. Volbeda M, Wetterslev J, Gluud C et al (2015) Glucocorticosteroids for sepsis: systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 41:1220–1234. doi:10.1007/s00134-015-3899-6
22. Van den Berghe G, Wilmer A, Hermans G et al (2006) Intensive insulin therapy in the medical ICU. N Engl J Med 354:449–461. doi:10.1056/NEJMoa052521
23. Annane D, Sébille V, Charpentier C et al (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871
24. Sprung CL, Annane D, Keh D et al (2008) Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111–124. doi:10.1056/NEJMoa071366
25. Keh D, Trips E, Marx G et al (2016) Effect of hydrocortisone on development of shock among patients with severe sepsis: the HYPRESS randomized clinical trial. JAMA 316:1775–1785. doi:10.1001/jama.2016.14799
26. Venkatesh B, Myburgh J, Finfer S et al (2013) The ADRENAL study protocol: adjunctive corticosteroid treatment in critically ill patients with septic shock. Crit Care Resusc 15:83–88
27. Amrein K, Schnedl C, Holl A et al (2014) Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial. JAMA 312:1520–1530. doi:10.1001/jama.2014.13204
28. Wong HR, Cvijanovich NZ, Anas N et al (2015) Developing a clinically feasible personalized medicine approach to pediatric septic shock. Am J Respir Crit Care Med 191:309–315. doi:10.1164/rccm.201410-1864OC
29. Cohen J, Pretorius CJ, Ungerer JPJ et al (2016) Glucocorticoid sensitivity is highly variable in critically ill patients with septic shock and is associated with disease severity. Crit Care Med 44:1034–1041. doi:10.1097/CCM.0000000000001633
30. Plummer MP, Bellomo R, Cousins CE et al (2014) Dysglycaemia in the critically ill and the interaction of chronic and acute glycaemia with mortality. Intensive Care Med 40:973–980. doi:10.1007/s00134-014-3287-7
31. Hoste EAJ, Bagshaw SM, Bellomo R et al (2015) Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 41:1411–1423. doi:10.1007/s00134-015-3934-7
32. Gomez H, Ince C, De Backer D et al (2014) A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock 41:3–11. doi:10.1097/SHK.0000000000000052
33. Pettilä V, Bellomo R (2014) Understanding acute kidney injury in sepsis. Intensive Care Med 40:1018–1020. doi:10.1007/s00134-014-3313-9
34. Kashani K, Al-Khafaji A, Ardiles T et al (2013) Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 17:R25. doi:10.1186/cc12503
35. Mårtensson J, Bell M, Oldner A et al (2010) Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Med 36:1333–1340. doi:10.1007/s00134-010-1887-4
36. Honore PM, Nguyen HB, Gong M et al (2016) Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 for risk stratification of acute kidney injury in patients with sepsis. Crit Care Med 44:1851–1860. doi:10.1097/CCM.0000000000001827
37. Cecconi M, Hofer C, Teboul J-L et al (2015) Fluid challenges in intensive care: the FENICE study: a global inception cohort study. Intensive Care Med 41:1529–1537. doi:10.1007/s00134-015-3850-x
38. Asfar P, Meziani F, Hamel J-F et al (2014) High versus low blood-pressure target in patients with septic shock. N Engl J Med 370:1583–1593. doi:10.1056/NEJMoa1312173
39. Saito S, Uchino S, Takinami M et al (2016) Postoperative blood pressure deficit and acute kidney injury progression in vasopressor-dependent cardiovascular surgery patients. Crit Care 20:74. doi:10.1186/s13054-016-1253-1
40. Molitoris BA, Reilly ES (2016) Quantifying glomerular filtration rates in acute kidney injury: a requirement for translational success. Semin Nephrol 36:31–41. doi:10.1016/j.semnephrol.2016.01.008
41. Dellinger RP, Levy MM, Rhodes A et al (2013) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39:165–228. doi:10.1007/s00134-012-2769-8
42. Hjortrup PB, Haase N, Bundgaard H et al (2016) Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med. doi:10.1007/s00134-016-4500-7
43. Legrand M, Dupuis C, Simon C et al (2013) Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study. Crit Care 17:R278. doi:10.1186/cc13133
44. Jones SL, Tanaka A, Eastwood GM et al (2015) Bioelectrical impedance vector analysis in critically ill patients: a prospective, clinician-blinded investigation. Crit Care 19:290. doi:10.1186/s13054-015-1009-3
45. Dubois M-J, Orellana-Jimenez C, Melot C et al (2006) Albumin administration improves organ function in critically ill hypoalbuminemic patients: a prospective, randomized, controlled, pilot study. Crit Care Med 34:2536–2540. doi:10.1097/01.CCM.0000239119.57544.0C
46. Caironi P, Tognoni G, Masson S et al (2014) Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 370:1412–1421. doi:10.1056/NEJMoa1305727
47. Haase N, Perner A, Hennings LI et al (2013) Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis. BMJ 346:f839
48. Moeller C, Fleischmann C, Thomas-Rueddel D et al (2016) How safe is gelatin? A systematic review and meta-analysis of gelatin-containing plasma expanders vs crystalloids and albumin. J Crit Care 35:75–83. doi:10.1016/j.jcrc.2016.04.011
49. Perner A, Haase N, Guttormsen AB et al (2012) Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med 367:124–134. doi:10.1056/NEJMoa1204242
50. Raghunathan K, Shaw A, Nathanson B et al (2014) Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med 42:1585–1591. doi:10.1097/CCM.0000000000000305
51. Young P, Bailey M, Beasley R et al (2015) Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care Unit: the SPLIT randomized clinical trial. JAMA 314:1701–1710. doi:10.1001/jama.2015.12334
52. Grissom CK, Hirshberg EL, Dickerson JB et al (2015) Fluid management with a simplified conservative protocol for the acute respiratory distress syndrome. Crit Care Med 43:288–295. doi:10.1097/CCM.0000000000000715
53. Koyner JL, Davison DL, Brasha-Mitchell E et al (2015) Furosemide stress test and biomarkers for the prediction of AKI severity. J Am Soc Nephrol 26:2023–2031. doi:10.1681/ASN.2014060535
54. Legrand M, Darmon M, Joannidis M, Payen D (2013) Management of renal replacement therapy in ICU patients: an international survey. Intensive Care Med 39:101–108. doi:10.1007/s00134-012-2706-x
55. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2:1–138
56. KDIGO (2016) KDIGO clinical practice guideline for acute kidney injury http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline.pdf. Accessed 11 Oct 2016
57. Ostermann M, Joannidis M, Pani A et al (2016) Patient selection and timing of continuous renal replacement therapy. Blood Purif 42:224–237. doi:10.1159/000448506
58. Payen D, Mateo J, Cavaillon JM et al (2009) Impact of continuous venovenous hemofiltration on organ failure during the early phase of severe sepsis: a randomized controlled trial. Crit Care Med 37:803–810. doi:10.1097/CCM.0b013e3181962316
59. Gaudry S, Hajage D, Schortgen F et al (2016) Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med 375:122–133. doi:10.1056/NEJMoa1603017
60. Lehner GF, Wiedermann CJ, Joannidis M (2014) High-volume hemofiltration in critically ill patients: a systematic review and meta-analysis. Minerva Anestesiol 80:595–609
61. Casaer MP, Mesotten D, Hermans G et al (2011) Early versus late parenteral nutrition in critically ill adults. N Engl J Med 365:506–517. doi:10.1056/NEJMoa1102662
62. Arabi YM, Aldawood AS, Haddad SH et al (2015) Permissive underfeeding or standard enteral feeding in critically ill adults. N Engl J Med 372:2398–2408. doi:10.1056/NEJMoa1502826
63. Preiser J-C, Ichai C, Orban J-C, Groeneveld ABJ (2014) Metabolic response to the stress of critical illness. Br J Anaesth 113:945–954. doi:10.1093/bja/aeu187
64. Fivez T, Kerklaan D, Mesotten D et al (2016) Early versus late parenteral nutrition in critically ill children. N Engl J Med 374:1111–1122. doi:10.1056/NEJMoa1514762
65. Heyland D, Muscedere J, Wischmeyer PE et al (2013) A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 368:1489–1497. doi:10.1056/NEJMoa1212722
66. van Zanten ARH, Sztark F, Kaisers UX et al (2014) High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial. JAMA 312:514–524. doi:10.1001/jama.2014.7698
67. Doig GS, Simpson F, Heighes PT et al (2015) Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. Lancet Respir Med 3:943–952. doi:10.1016/S2213-2600(15)00418-X
68. Angstwurm MWA, Engelmann L, Zimmermann T et al (2007) Selenium in intensive care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med 35:118–126. doi:10.1097/01.CCM.0000251124.83436.0E
69. Bloos F, Trips E, Nierhaus A et al (2016) Effect of sodium selenite administration and procalcitonin-guided therapy on mortality in patients with severe sepsis or septic shock: a randomized clinical trial. JAMA Intern Med 176:1266–1276. doi:10.1001/jamainternmed.2016.2514
70. Puskarich MA, Kline JA, Krabill V et al (2014) Preliminary safety and efficacy of L-carnitine infusion for the treatment of vasopressor-dependent septic shock: a randomized control trial. JPEN J Parenter Enter Nutr 38:736–743. doi:10.1177/0148607113495414
71. Zeng J, Wang C-T, Zhang F-S et al (2016) Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial. Intensive Care Med 42:1018–1028. doi:10.1007/s00134-016-4303-x
72. Hotchkiss RS, Opal S (2010) Immunotherapy for sepsis—a new approach against an ancient foe. N Engl J Med 363:87–89. doi:10.1056/NEJMcibr1004371
73. Rouphael NG, Talati NJ, Vaughan C et al (2007) Infections associated with haemophagocytic syndrome. Lancet Infect Dis 7:814–822. doi:10.1016/S1473-3099(07)70290-6
74. Miettunen PM, Narendran A, Jayanthan A et al (2011) Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients. Rheumatology (Oxford) 50:417–419. doi:10.1093/rheumatology/keq218
75. Bulger EM, Maier RV, Sperry J et al (2014) A novel drug for treatment of necrotizing soft-tissue infections: a randomized clinical trial. JAMA Surg 149:528–536. doi:10.1001/jamasurg.2013.4841
76. Peters E, van Elsas A, Heemskerk S et al (2013) Alkaline phosphatase as a treatment of sepsis-associated acute kidney injury. J Pharmacol Exp Ther 344:2–7. doi:10.1124/jpet.112.198226
77. Peters E, Mehta RL, Murray PT et al (2016) Study protocol for a multicentre randomised controlled trial: safety, tolerability, efficacy and quality of life Of a human recombinant alkaline phosphatase in patients with sepsis-associated acute kidney injury (STOP-AKI). BMJ Open 6:e012371. doi:10.1136/bmjopen-2016-012371
78. Rimmelé T, Kellum JA (2011) Clinical review: blood purification for sepsis. Crit Care 15:205. doi:10.1186/cc9411
79. Kang JH, Super M, Yung CW et al (2014) An extracorporeal blood-cleansing device for sepsis therapy. Nat Med 20:1211–1216. doi:10.1038/nm.3640
80. Shindo Y, Unsinger J, Burnham C-A et al (2015) Interleukin-7 and anti-programmed cell death 1 antibody have differing effects to reverse sepsis-induced immunosuppression. Shock 43:334–343. doi:10.1097/SHK.0000000000000317
81. Hotchkiss RS, Moldawer LL, Opal SM et al (2016) Sepsis and septic shock. Nat Rev Dis Primer 2:16045
82. Hotchkiss RS, Moldawer LL (2014) Parallels between cancer and infectious disease. N Engl J Med 371:380–383. doi:10.1056/NEJMcibr1404664
83. Chahin A, Opal SM, Zorzopulos J et al (2015) The novel immunotherapeutic oligodeoxynucleotide IMT504 protects neutropenic animals from fatal Pseudomonas aeruginosa bacteremia and sepsis. Antimicrob Agents Chemother 59:1225–1229. doi:10.1128/AAC.03923-14
84. Mathias B, Szpila BE, Moore FA et al (2015) A review of GM-CSF therapy in sepsis. Medicine (Baltimore) 94:e2044. doi:10.1097/MD.0000000000002044
85. Wu J, Zhou L, Liu J et al (2013) The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care 17:R8. doi:10.1186/cc11932
86. Bloos F, Trips E, Nierhaus A et al (2016) Effect of sodium selenite administration and procalcitonin-guided therapy on mortality in patients with severe sepsis or septic shock: a randomized clinical trial. JAMA Intern Med 176:1266–1276. doi:10.1001/jamainternmed.2016.2514
87. Reinhart K, Bauer M, Riedemann NC, Hartog CS (2012) New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev 25:609–634. doi:10.1128/CMR.00016-12
88. Davenport EE, Burnham KL, Radhakrishnan J et al (2016) Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med 4:259–271. doi:10.1016/S2213-2600(16)00046-1
89. Cohen J, Vincent J-L, Adhikari NKJ et al (2015) Sepsis: a roadmap for future research. Lancet Infect Dis 15:581–614. doi:10.1016/S1473-3099(15)70112-X
90. Vincent J-L, Opal SM, Marshall JC (2010) Ten reasons why we should NOT use severity scores as entry criteria for clinical trials or in our treatment decisions. Crit Care Med 38:283–287. doi:10.1097/CCM.0b013e3181b785a2
91. ClinicalTrials.gov (2016) Phase 3 safety and efficacy study of ART-123 in subjects with severe sepsis and coagulopathy. https://clinicaltrials.gov/ct2/show/NCT01598831. Accessed 12 Oct 2016
92. ClinicalTrials.gov (2016) GM-CSF to decrease ICU acquired infections. https://clinicaltrials.gov/ct2/show/NCT02361528?term=NCT02361528&rank=1. Accessed 12 Oct 2016
93. Levy MM, Rhodes A, Phillips GS et al (2014) Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Intensive Care Med 40:1623–1633. doi:10.1007/s00134-014-3496-0
94. Marshall JC, Vincent J-L, Guyatt G et al (2005) Outcome measures for clinical research in sepsis: a report of the 2nd Cambridge Colloquium of the international sepsis forum. Crit Care Med 33:1708–1716
95. Siegel JP (2002) Biotechnology and clinical trials. J Infect Dis 185(Suppl 1):S52–S57. doi:10.1086/338061
96. Bagshaw SM, Uchino S, Bellomo R et al (2007) Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2:431–439. doi:10.2215/CJN.03681106
97. Afshari A, Brok J, Møller AM, Wetterslev J (2011) Inhaled nitric oxide for acute respiratory distress syndrome and acute lung injury in adults and children: a systematic review with meta-analysis and trial sequential analysis. Anesth Analg 112:1411–1421. doi:10.1213/ANE.0b013e31820bd185
98. Yende S, Austin S, Rhodes A et al (2016) Long-term quality of life among survivors of severe sepsis: analyses of two international trials. Crit Care Med 44:1461–1467. doi:10.1097/CCM.0000000000001658
99. Ferguson ND, Scales DC, Pinto R et al (2013) Integrating mortality and morbidity outcomes: using quality-adjusted life years in critical care trials. Am J Respir Crit Care Med 187:256–261. doi:10.1164/rccm.201206-1057OC
100. Fleischmann C, Scherag A, Adhikari NKJ et al (2016) Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med 193:259–272. doi:10.1164/rccm.201504-0781OC
101. Fleischmann C, Thomas-Rueddel DO, Hartmann M et al (2016) Hospital incidence and mortality rates of sepsis. Dtsch Ärztebl Int 113:159–166. doi:10.3238/arztebl.2016.0159
102. Angus DC, Barnato AE, Bell D et al (2015) A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe investigators. Intensive Care Med 41:1549–1560. doi:10.1007/s00134-015-3822-1
103. Rhodes A, Phillips G, Beale R et al (2015) The Surviving Sepsis Campaign bundles and outcome: results from the international multicentre prevalence study on sepsis (the IMPreSS study). Intensive Care Med 41:1620–1628. doi:10.1007/s00134-015-3906-y
104. Kaukonen K-M, Bailey M, Suzuki S et al (2014) Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA 311:1308–1316. doi:10.1001/jama.2014.2637
105. Shankar-Hari M, Harrison DA, Rowan KM (2016) Differences in Impact of definitional elements on mortality precludes international comparisons of sepsis epidemiology-a cohort study illustrating the need for standardized reporting. Crit Care Med. doi:10.1097/CCM.0000000000001876
106. SepNet Critical Care Trials Group (2016) Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study. Intensive Care Med 42:1980–1989. doi:10.1007/s00134-016-4504-3
107. Brunkhorst FM, Engel C, Bloos F et al (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358:125–139. doi:10.1056/NEJMoa070716
108. Holst LB, Haase N, Wetterslev J et al (2014) Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 371:1381–1391. doi:10.1056/NEJMoa1406617
109. Hammond NE, Taylor C, Saxena M et al (2015) Resuscitation fluid use in Australian and New Zealand Intensive Care Units between 2007 and 2013. Intensive Care Med 41:1611–9. doi:10.1007/s00134-015-3878-y