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01-12-2016 | Review

Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy

Authors: Anders Perner, Anthony C. Gordon, Daniel De Backer, George Dimopoulos, James A. Russell, Jeffrey Lipman, Jens-Ulrik Jensen, John Myburgh, Mervyn Singer, Rinaldo Bellomo, Timothy Walsh

Published in: Intensive Care Medicine | Issue 12/2016

Abstract

Sepsis is a major growing global burden and a major challenge to intensive care clinicians, researchers, guideline committee members and policy makers, because of its high and increasing incidence and great pathophysiological, molecular, genetic and clinical complexity. In spite of recent progress, short-term mortality remains high and there is growing evidence of long-term morbidity and increased long-term mortality in survivors of sepsis both in developed and developing countries. Further improvement in the care of patients with sepsis will impact upon global health. In this narrative review, invited experts describe the expected challenges and progress to be made in the near future. We focus on diagnosis, resuscitation (fluids, vasopressors, inotropes, blood transfusion and hemodynamic targets) and infection (antibiotics and infection biomarkers), as these areas are key, if initial management and subsequent outcomes are to be improved in patients with sepsis.

Fleischmann C, Scherag A, Adhikari NK et al (2015) Assessment of Global Incidence and Mortality of Hospital-treated sepsis—current estimates and limitations. Am J Respir Crit Care Med. doi:10.1164/rccm.201504-0781OC

Levy MM, Fink MP, Marshall JC et al (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 29:530–538. doi:10.1007/s00134-003-1662-x CrossRefPubMed

Bone RC, Balk RA, Cerra FB et al (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655CrossRefPubMed

Singer M, Deutschman CS, Seymour CW et al (2016) The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:801–810. doi:10.1001/jama.2016.0287 CrossRefPubMedPubMedCentral

Gaieski DF, Edwards JM, Kallan MJ, Carr BG (2013) Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med 41:1167–1174. doi:10.1097/CCM.0b013e31827c09f8 CrossRefPubMed

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 CrossRefPubMed

Rhee C, Gohil S, Klompas M (2014) Regulatory mandates for sepsis care—reasons for caution. N Engl J Med 370:1673–1676. doi:10.1056/NEJMp1400276 CrossRefPubMedPubMedCentral

Kaukonen K-M, Bailey M, Pilcher D et al (2015) Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med 372:1629–1638. doi:10.1056/NEJMoa1415236 CrossRefPubMed

Shankar-Hari M, Phillips GS, Levy ML et al (2016) Developing a new definition and assessing new clinical criteria for septic shock: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:775–787. doi:10.1001/jama.2016.0289 CrossRefPubMedPubMedCentral

10.

Seymour CW, Liu VX, Iwashyna TJ et al (2016) Assessment of clinical criteria for sepsis: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315:762–774. doi:10.1001/jama.2016.0288 CrossRefPubMed

11.

Ferreira FL, Bota DP, Bross A et al (2001) Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 286:1754–1758CrossRefPubMed

12.

Tang BMP, Eslick GD, Craig JC, McLean AS (2007) Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 7:210–217. doi:10.1016/S1473-3099(07)70052-X CrossRefPubMed

13.

Travaglino F, De Berardinis B, Magrini L et al (2012) Utility of procalcitonin (PCT) and mid regional pro-adrenomedullin (MR-proADM) in risk stratification of critically ill febrile patients in Emergency Department (ED). A comparison with APACHE II score. BMC Infect Dis 12:184. doi:10.1186/1471-2334-12-184 CrossRefPubMedPubMedCentral

14.

Burillo A, Bouza E (2014) Use of rapid diagnostic techniques in ICU patients with infections. BMC Infect Dis 14:593. doi:10.1186/s12879-014-0593-1 CrossRefPubMedPubMedCentral

15.

Liesenfeld O, Lehman L, Hunfeld K-P, Kost G (2014) Molecular diagnosis of sepsis: new aspects and recent developments. Eur J Microbiol Immunol 4:1–25. doi:10.1556/EuJMI.4.2014.1.1 CrossRef

16.

Leli C, Cenci E, Cardaccia A et al (2013) Rapid identification of bacterial and fungal pathogens from positive blood cultures by MALDI-TOF MS. Int J Med Microbiol 303:205–209. doi:10.1016/j.ijmm.2013.03.002 CrossRefPubMed

17.

Vincent J-L, Brealey D, Libert N et al (2015) Rapid diagnosis of infection in the critically ill, a multicenter study of molecular detection in bloodstream infections, pneumonia, and sterile site infections. Crit Care Med 43:2283–2291. doi:10.1097/CCM.0000000000001249 CrossRefPubMedPubMedCentral

18.

Salimnia H, Fairfax MR, Lephart PR et al (2016) Evaluation of the filmarray blood culture identification panel: results of a multicenter controlled trial. J Clin Microbiol 54:687–698. doi:10.1128/JCM.01679-15 CrossRefPubMedPubMedCentral

19.

Cercenado E, Marín M, Burillo A et al (2012) Rapid detection of Staphylococcus aureus in lower respiratory tract secretions from patients with suspected ventilator-associated pneumonia: evaluation of the Cepheid Xpert MRSA/SA SSTI assay. J Clin Microbiol 50:4095–4097. doi:10.1128/JCM.02409-12 CrossRefPubMedPubMedCentral

20.

Sinclair A, Xie X, Teltscher M, Dendukuri N (2013) Systematic review and meta-analysis of a urine-based pneumococcal antigen test for diagnosis of community-acquired pneumonia caused by Streptococcus pneumoniae. J Clin Microbiol 51:2303–2310. doi:10.1128/JCM.00137-13 CrossRefPubMedPubMedCentral

21.

de Ory F, Minguito T (2009) Comparison of five commercial assays for the detection of Legionella pneumophila antigens in urine. Enferm Infecc Microbiol Clín 27:81–84. doi:10.1016/j.eimc.2008.03.002 CrossRefPubMed

22.

Emmadi R, Boonyaratanakornkit JB, Selvarangan R et al (2011) Molecular methods and platforms for infectious diseases testing a review of FDA-approved and cleared assays. J Mol Diagn 13:583–604. doi:10.1016/j.jmoldx.2011.05.011 CrossRefPubMedPubMedCentral

23.

Schelenz S, Barnes RA, Barton RC et al (2015) British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis 15:461–474. doi:10.1016/S1473-3099(15)70006-X CrossRefPubMed

24.

Bouadma L, Luyt C-E, Tubach F et al (2010) Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 375:463–474. doi:10.1016/S0140-6736(09)61879-1 CrossRefPubMed

25.

de Jong E, van Oers JA, Beishuizen A et al (2016) Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 16:819–827. doi:10.1016/S1473-3099(16)00053-0 CrossRefPubMed

26.

Jensen JU, Hein L, Lundgren B et al (2011) Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 39:2048–2058. doi:10.1097/CCM.0b013e31821e8791 CrossRefPubMed

27.

Sweeney TE, Shidham A, Wong HR, Khatri P (2015) A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set. Sci Transl Med 7:287ra71. doi:10.1126/scitranslmed.aaa5993 CrossRefPubMedPubMedCentral

28.

McHugh L, Seldon TA, Brandon RA et al (2015) A molecular host response assay to discriminate between sepsis and infection-negative systemic inflammation in critically ill patients: discovery and validation in independent cohorts. PLoS Med 12:e1001916. doi:10.1371/journal.pmed.1001916 CrossRefPubMedPubMedCentral

29.

Garcia-Simon M, Morales JM, Modesto-Alapont V et al (2015) Prognosis biomarkers of Severe Sepsis and Septic Shock by 1H nmr urine metabolomics in the intensive care unit. Plos ONE 10:e0140993. doi:10.1371/journal.pone.0140993 CrossRefPubMedPubMedCentral

30.

Lin S-M, Wang Y-M, Lin H-C et al (2008) Serum thrombomodulin level relates to the clinical course of disseminated intravascular coagulation, multiorgan dysfunction syndrome, and mortality in patients with sepsis. Crit Care Med 36:683–689. doi:10.1097/CCM.0B013E31816537D8 CrossRefPubMed

31.

Ware LB, Koyama T, Zhao Z et al (2013) Biomarkers of lung epithelial injury and inflammation distinguish severe sepsis patients with acute respiratory distress syndrome. Crit Care 17:R253. doi:10.1186/cc13080 CrossRefPubMedPubMedCentral

32.

Madonna R, Jiang J, Geng Y-J (2012) Attenuated expression of gelsolin in association with induction of aquaporin-1 and nitric oxide synthase in dysfunctional hearts of aging mice exposed to endotoxin. Int J Immunopathol Pharmacol 25:911–922PubMed

33.

Armand-Lefèvre L, Angebault C, Barbier F et al (2013) Emergence of imipenem-resistant gram-negative bacilli in intestinal flora of intensive care patients. Antimicrob Agents Chemother 57:1488–1495. doi:10.1128/AAC.01823-12 CrossRefPubMedPubMedCentral

34.

Rubinstein E, Keynan Y (2013) Short-course therapy for severe infections. Int J Antimicrob Agents 42(Suppl):S22–S24. doi:10.1016/j.ijantimicag.2013.04.013 CrossRefPubMed

35.

Klompas M (2012) What can we learn from international ventilator-associated pneumonia rates? Crit Care Med 40:3303–3304. doi:10.1097/CCM.0b013e31826bf3a5 CrossRefPubMed

36.

Sugianto TD, Chan H-K (2015) Inhaled antibiotics in the treatment of non-cystic fibrosis bronchiectasis: clinical and drug delivery perspectives. Expert Opin Drug Deliv. doi:10.1517/17425247.2015.1078309 PubMed

37.

Wong G, Brinkman A, Benefield RJ et al (2014) An international, multicentre survey of β-lactam antibiotic therapeutic drug monitoring practice in intensive care units. J Antimicrob Chemother 69:1416–1423. doi:10.1093/jac/dkt523 CrossRefPubMed

38.

Bergen P, Bulitta J, Kirkpatrick C et al (2016) Effect of different renal function on anti-bacterial effects of piperacillin against Pseudomonas aeruginosa evaluated via the hollow fibre infection model and mechanism-based modelling. J Antimicrob Chemother. doi:10.1093/jac/dkw153

39.

Vincent J-L, De Backer D (2014) My paper 20 years later: effects of dobutamine on the VO₂/DO₂ relationship. Intensive Care Med 40:1643–1648. doi:10.1007/s00134-014-3472-8 CrossRefPubMed

40.

Ronco JJ, Fenwick JC, Tweeddale MG et al (1993) Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans. JAMA 270:1724–1730CrossRefPubMed

41.

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 CrossRefPubMed

42.

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 CrossRefPubMed

43.

De Backer D, Vincent J-L (2016) Early goal-directed therapy: do we have a definitive answer? Intensive Care Med 42:1048–1050. doi:10.1007/s00134-016-4295-6 CrossRefPubMed

44.

Ospina-Tascón GA, Umaña M, Bermúdez WF et al (2015) Can venous-to-arterial carbon dioxide differences reflect microcirculatory alterations in patients with septic shock? Intensive Care Med. doi:10.1007/s00134-015-4133-2

45.

Vallée F, Vallet B, Mathe O et al (2008) Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock? Intensive Care Med 34:2218–2225. doi:10.1007/s00134-008-1199-0 CrossRefPubMed

46.

Ospina-Tascón GA, Bautista-Rincón DF, Umaña M et al (2013) Persistently high venous-to-arterial carbon dioxide differences during early resuscitation are associated with poor outcomes in septic shock. Crit Care 17:R294. doi:10.1186/cc13160 CrossRefPubMedPubMedCentral

47.

Monnet X, Julien F, Ait-Hamou N et al (2013) Lactate and venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio, but not central venous oxygen saturation, predict increase in oxygen consumption in fluid responders. Crit Care Med 41:1412–1420. doi:10.1097/CCM.0b013e318275cece CrossRefPubMed

48.

De Backer D, Creteur J, Preiser J-C et al (2002) Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 166:98–104CrossRefPubMed

49.

De Backer D, Donadello K, Sakr Y et al (2013) Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med 41:791–799. doi:10.1097/CCM.0b013e3182742e8b CrossRefPubMed

50.

Perner A, Haase N, Guttormsen AB et al (2012) Hydroxyethyl starch 130/0.42 vs. Ringer’s acetate in severe sepsis. N Engl J Med 367:124–134. doi:10.1056/NEJMoa1204242 CrossRefPubMed

51.

Myburgh JA, Finfer S, Bellomo R et al (2012) Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 367:1901–1911. doi:10.1056/NEJMoa1209759 CrossRefPubMed

52.

Haase N, Perner A, Hennings LI et al (2013) Hydroxyethyl starch 130/0.38-0.45 vs. crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis. BMJ 346:f839CrossRefPubMedPubMedCentral

53.

Perner A, Junttila E, Haney M et al (2015) Scandinavian clinical practice guideline on choice of fluid in resuscitation of critically ill patients with acute circulatory failure. Acta Anaesthesiol Scand 59:274–285. doi:10.1111/aas.12429 CrossRefPubMed

54.

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 CrossRefPubMedPubMedCentral

55.

SAFE Study Investigators, Finfer S, McEvoy S et al (2011) Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med 37:86–96. doi:10.1007/s00134-010-2039-6 CrossRef

56.

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 CrossRefPubMed

57.

Patel A, Laffan MA, Waheed U, Brett SJ (2014) Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality. BMJ 349:g4561CrossRefPubMedPubMedCentral

58.

Yunos NM, Bellomo R, Glassford N et al (2015) Chloride-liberal vs. chloride-restrictive intravenous fluid administration and acute kidney injury: an extended analysis. Intensive Care Med 41:257–264. doi:10.1007/s00134-014-3593-0 CrossRefPubMed

59.

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 CrossRefPubMed

60.

Boyd JH, Forbes J, Nakada T et al (2011) Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 39:259–265. doi:10.1097/CCM.0b013e3181feeb15 CrossRefPubMed

61.

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 CrossRefPubMed

62.

Maybauer MO, Maybauer DM, Enkhbaatar P et al (2014) The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis. Crit Care Med 42:e525–e533. doi:10.1097/CCM.0000000000000300 CrossRefPubMedPubMedCentral

63.

Walkey AJ, Wiener RS, Ghobrial JM et al (2011) Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis. JAMA 306:2248–2254. doi:10.1001/jama.2011.1615 CrossRefPubMedPubMedCentral

64.

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 CrossRefPubMed

65.

Linder A, Lee T, Fisher J et al (2016) Short-term organ dysfunction is associated with long-term (10-year) mortality of septic shock. Crit Care Med 44:e728–e736. doi:10.1097/CCM.0000000000001843 CrossRefPubMed

66.

Chawla LS, Busse L, Brasha-Mitchell E et al (2014) Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care 18:534. doi:10.1186/s13054-014-0534-9 CrossRefPubMedPubMedCentral

67.

Kirov MY, Evgenov OV, Evgenov NV et al (2001) Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med 29:1860–1867CrossRefPubMed

68.

Donati A, Conti G, Loggi S et al (2002) Does methylene blue administration to septic shock patients affect vascular permeability and blood volume? Crit Care Med 30:2271–2277. doi:10.1097/01.CCM.0000029185.70149.5F CrossRefPubMed

69.

Wang Z, Lambden S, Taylor V et al (2014) Pharmacological inhibition of DDAH1 improves survival, haemodynamics and organ function in experimental septic shock. Biochem J 460:309–316. doi:10.1042/BJ20131666 CrossRefPubMed

70.

Russell JA (2016) Genomics and pharmacogenomics of sepsis: so close and yet so far. Crit Care 20:185. doi:10.1186/s13054-016-1374-6 CrossRefPubMedPubMedCentral

71.

Nakada T-A, Russell JA, Boyd JH et al (2010) beta2-Adrenergic receptor gene polymorphism is associated with mortality in septic shock. Am J Respir Crit Care Med 181:143–149. doi:10.1164/rccm.200903-0332OC CrossRefPubMed

72.

Nakada T, Russell JA, Wellman H et al (2011) Leucyl/cystinyl aminopeptidase gene variants in septic shock. Chest 139:1042–1049. doi:10.1378/chest.10-2517 CrossRefPubMed

73.

Lasker MV, Leventhal SM, Lim D et al (2015) Hyperactive human glucocorticoid receptor isoforms and their implications for the stress response. Shock 43:228–232. doi:10.1097/SHK.0000000000000289 CrossRefPubMed

74.

Bentzer P, Fjell C, Walley KR et al (2016) Plasma cytokine levels predict response to corticosteroids in septic shock. Intensive Care Med. doi:10.1007/s00134-016-4338-z PubMed

75.

Nakada T, Russell JA, Boyd JH et al (2011) Association of angiotensin II type 1 receptor-associated protein gene polymorphism with increased mortality in septic shock. Crit Care Med 39:1641–1648. doi:10.1097/CCM.0b013e318218665a CrossRefPubMed

76.

Health C for D and R In Vitro Diagnostics—Companion Diagnostics. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm407297.htm. Accessed 14 Sep 2016

77.

Research C for DE and Genomics—Table of Pharmacogenomic Biomarkers in Drug Labeling. http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm. Accessed 14 Sep 2016

78.

Walley KR, Thain KR, Russell JA et al (2014) PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci Transl Med 6:258ra143. doi:10.1126/scitranslmed.3008782 CrossRefPubMedPubMedCentral

79.

Morelli A, Ertmer C, Westphal M et al (2013) Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 310:1683–1691. doi:10.1001/jama.2013.278477 CrossRefPubMed

80.

Shahul S, Gulati G, Hacker MR et al (2015) Detection of myocardial dysfunction in septic shock: a speckle-tracking echocardiography study. Anesth Analg 121:1547–1554. doi:10.1213/ANE.0000000000000943 CrossRefPubMed

81.

Vieillard-Baron A, Slama M, Cholley B et al (2008) Echocardiography in the intensive care unit: from evolution to revolution? Intensive Care Med 34:243–249. doi:10.1007/s00134-007-0923-5 CrossRefPubMed

82.

Hayes MA, Timmins AC, Yau EH et al (1994) Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 330:1717–1722. doi:10.1056/NEJM199406163302404 CrossRefPubMed

83.

Schmittinger CA, Torgersen C, Luckner G et al (2012) Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study. Intensive Care Med 38:950–958. doi:10.1007/s00134-012-2531-2 CrossRefPubMed

84.

Wang Q, Yokoo H, Takashina M et al (2015) Anti-inflammatory profile of levosimendan in cecal ligation-induced septic mice and in lipopolysaccharide-stimulated macrophages. Crit Care Med 43:e508–e520. doi:10.1097/CCM.0000000000001269 CrossRefPubMed

85.

Koster G, Wetterslev J, Gluud C et al (2015) Effects of levosimendan for low cardiac output syndrome in critically ill patients: systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 41:203–221. doi:10.1007/s00134-014-3604-1 CrossRefPubMed

86.

Zangrillo A, Putzu A, Monaco F et al (2015) Levosimendan reduces mortality in patients with severe sepsis and septic shock: a meta-analysis of randomized trials. J Crit Care. doi:10.1016/j.jcrc.2015.05.017 PubMed

87.

Orme RML, Perkins GD, McAuley DF et al (2014) An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): protocol for a randomized controlled trial. Trials 15:199. doi:10.1186/1745-6215-15-199 CrossRefPubMedPubMedCentral

88.

Perner A, Myburgh J (2015) Ten “short-lived” beliefs in intensive care medicine. Intensive Care Med 41:1703–1706. doi:10.1007/s00134-015-3733-1 CrossRefPubMed

89.

Ibrahim-Zada I, Rhee P, Gomez CT et al (2014) Inhibition of sepsis-induced inflammatory response by β1-adrenergic antagonists. J Trauma Acute Care Surg 76:320–327. doi:10.1097/TA.0000000000000113 CrossRefPubMed

90.

Ruchala P, Nemeth E (2014) The pathophysiology and pharmacology of hepcidin. Trends Pharmacol Sci 35:155–161. doi:10.1016/j.tips.2014.01.004 CrossRefPubMedPubMedCentral

91.

Pieracci FM, Stovall RT, Jaouen B et al (2014) A multicenter, randomized clinical trial of IV iron supplementation for anemia of traumatic critical illness. Crit Care Med 42:2048–2057. doi:10.1097/CCM.0000000000000408 CrossRefPubMed

92.

Rohde JM, Dimcheff DE, Blumberg N et al (2014) Health care-associated infection after red blood cell transfusion: a systematic review and meta-analysis. JAMA 311:1317–1326. doi:10.1001/jama.2014.2726 CrossRefPubMedPubMedCentral

93.

Lacroix J, Hébert PC, Fergusson DA et al (2015) Age of transfused blood in critically ill adults. N Engl J Med 372:1410–1418. doi:10.1056/NEJMoa1500704 CrossRefPubMed

94.

Steiner ME, Ness PM, Assmann SF et al (2015) Effects of red-cell storage duration on patients undergoing cardiac surgery. N Engl J Med 372:1419–1429. doi:10.1056/NEJMoa1414219 CrossRefPubMed

95.

Holst LB, Petersen MW, Haase N et al (2015) Restrictive versus liberal transfusion strategy for red blood cell transfusion: systematic review of randomised trials with meta-analysis and trial sequential analysis. BMJ 350:h1354CrossRefPubMedPubMedCentral

96.

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 CrossRefPubMed

97.

Docherty AB, O’Donnell R, Brunskill S et al (2016) Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis. BMJ 352:i1351CrossRefPubMedPubMedCentral

Title: Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy
Authors: Anders Perner
Anthony C. Gordon
Daniel De Backer
George Dimopoulos
James A. Russell
Jeffrey Lipman
Jens-Ulrik Jensen
John Myburgh
Mervyn Singer
Rinaldo Bellomo
Timothy Walsh
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: Intensive Care Medicine / Issue 12/2016
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-016-4577-z

At a glance: The STEP trials

Springer Medicine

Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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