Log in | Register

Sepsis: frontiers in supportive care, organisation and research

Anders Perner| Andrew Rhodes| Bala Venkatesh| Derek C. Angus| Ignacio Martin-loeches| Jean-Charles Preiser| Jean-Louis Vincent| John Marshall| Konrad Reinhart| Michael Joannidis| Steven M. Opal
Review
Volume 43, Issue 4 / April , 2017

Pages 496 - 508

Abstract

Because of its high incidence and clinical complexity, sepsis is a major challenge to clinicians and researchers and a global burden to healthcare systems and society. Despite recent progress, short- and long-term morbidity, mortality and costs remain high in both developed and developing countries. Thus, further improvements in supportive interventions and organisation of care are likely to have a substantial impact upon global health. In this narrative review, invited experts describe the challenges and progress to be made in sepsis research and care in the near future. We focus on supportive care (pulmonary, endocrine, renal, and nutritional support, mediator modulation and precision medicine), organisational themes (guidelines, outcome measures and stakeholder involvement) and clinical research as key areas to improving the care and outcomes of patients with sepsis.

Keywords

References

  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  78. Rimmelé T, Kellum JA (2011) Clinical review: blood purification for sepsis. Crit Care 15:205. doi:10.1186/cc9411
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  81. Hotchkiss RS, Moldawer LL, Opal SM et al (2016) Sepsis and septic shock. Nat Rev Dis Primer 2:16045
    • View reference on publisher's website
  82. Hotchkiss RS, Moldawer LL (2014) Parallels between cancer and infectious disease. N Engl J Med 371:380–383. doi:10.1056/NEJMcibr1404664
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  95. Siegel JP (2002) Biotechnology and clinical trials. J Infect Dis 185(Suppl 1):S52–S57. doi:10.1086/338061
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
  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
    • View reference on PubMed
    • View reference on publisher's website
  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
    • View reference on PubMed
    • View reference on publisher's website
  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

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement