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Cited by 116Sepsis Diagnosis and TreatmentHemodynamic Monitoring and TherapyAbdominal Surgery and Complications

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Fluid resuscitation in sepsis: the great 30 mL per kg hoax

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Marik, Paul E., Byrne, Liam, van Haren, Frank·2020·Journal of Thoracic Disease
DOI 10.21037/jtd.2019.12.84PMC PMC7024756
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Abstract

Large volume fluid resuscitation is currently viewed as the cornerstone of the treatment of septic shock. The surviving sepsis campaign (SSC) guidelines provide a strong recommendation to rapidly administer a minimum of 30 mL/kg crystalloid solution intravenously in all patients with septic shock and those with elevated blood lactate levels. However, there is no credible evidence to support this recommendation. In fact, recent findings from experimental, observational and randomized clinical trials demonstrate improved outcomes with a more restrictive approach to fluid resuscitation. Accumulating evidence suggests that aggressive fluid resuscitation is harmful. Paradoxically, excess fluid administration may worsen shock. In this review, we critically evaluate the scientific evidence for a weight-based fluid resuscitation approach. Furthermore, the potential mechanisms and consequences of harm associated with fluid resuscitation are discussed. Finally, we recommend an individualized, conservative and physiologic guided approach to fluid resuscitation.

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  • The long-standing recommendation for an initial fixed-volume 30 mL/kg crystalloid bolus in septic shock has been increasingly challenged.

    “The long-standing recommendation for an initial fixed-volume 30 mL/kg crystalloid bolus in septic shock has been increasingly challenged.”

    From Artificial Intelligence to Facilitate SEP-1 Measure Compliance and Fluid Management in Sepsis (2026) · cites this paper as [20]

  • Critics argue that septic shock is not uniformly a hypovolemic state and that indiscriminate fluid loading may exacerbate vasoplegia, myocardial dysfunction, endothelial injury, and tissue edema, thereby impairing oxygen delivery despite increased intravascular volume.

    “Critics argue that septic shock is not uniformly a hypovolemic state and that indiscriminate fluid loading may exacerbate vasoplegia, myocardial dysfunction, endothelial injury, and tissue edema, thereby impairing oxygen delivery despite increased intravascular volume [20].”

    From Artificial Intelligence to Facilitate SEP-1 Measure Compliance and Fluid Management in Sepsis (2026) · cites this paper as [20]

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Research works printed but not linked: 66

  1. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med 2018;44:925-8.
  2. Byrne L, Van Haren F. Fluid resuscitation in human sepsis: Time to rewrite history? Ann Intensive Care 2017;7:4.
  3. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011;364:2483-95.
  4. Boyd JH, Forbes J, Nakada TA, et al. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 2011;39:259-65.
  5. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.
  6. Angus DC, Barnato AE, Bell D, et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators. Intensive Care Med 2015;41:1549-60.
  7. Vandervelden S, Malbrain ML. Initial resuscitation from severe sepsis: one size does not fit all. Anaesthesiol Intensive Ther 2015;47:s44-55.
  8. Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371:1496-506.
  9. Rhodes A, Phillips G, Beale R, et al. The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). Intensive Care Med 2015;41:1620-8.
  10. Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med 2015;43:3-12.
  11. Marik PE, Linde-Zwirble WT, Bittner EA, et al. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med 2017;43:625-32.
  12. Hendershot KM, Robinson L, Roland J, et al. Estimated height, weight and body mass index: Implications for research and patient safety. J Am Coll Surg 2006;203:887-93.
  13. Maskin LP, Attie S, Setten M, et al. Accuracy of weight and height estimation in an intensive care unit. Anaesth Intensive Care 2010;38:930-4.
  14. Bloomfield R, Steel E, MacLennan G, et al. Accuracy of weight and height estimation in an intensive care unit: Implications for clinical practice and research. Crit Care Med 2006;34:2153-7.
  15. van Haren F. Personalised fluid resuscitation in the ICU: still a fluid concept? Crit Care 2017;21:313.
  16. Truong TN, Dunn AS, McCardle K, et al. Adherence to fluid resuscitation guidelines and outcomes in patients with septic shock: Reassessing the "one-size-fits-all" approach. J Crit Care 2019;51:94-8.
  17. Marik PE, Malbrain M. The SEP-1 quality mandate may be harmful: How to drown a patient with 30 mL per kg fluid! Anaesthesiol Intensive Ther 2017;49:323-8.
  18. Ognibene FP, Parker MM, Natanson C, et al. Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock. Chest 1988;93:903-10.
  19. Hernández G, Ospina-Tascon GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA 2019;321:654-64.
  20. Rehberg S, Yamamoto Y, Sousse L, et al. Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis. Am J Physiol Heart Circ Physiol 2012;303:H1245-54.
  21. Maitland K, George EC, Evans JA, et al. Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Med 2013;11:68.
  22. Byrne L, Obonyo NG, Diab SD, et al. Unintended Consequences; Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia. Am J Respir Crit Care Med 2018;198:1043-54.
  23. Byrne L, Obonyo NG, Diab S, et al. An Ovine Model of Hyperdynamic Endotoxemia and Vital Organ Metabolism. Shock 2018;49:99-107.
  24. Cholley BP, Lang RM, Berger DS, et al. Alterations in systemic arterial mechanical properties during septic shock: role of fluid resuscitation. Am J Physiol 1995;269:H375-84.
  25. Ricard-Hibon A, Losser MR, Kong R, et al. Systemic pressure-flow reactivity to norepinephrine in rabbits: impact of endotoxin and fluid loading. Intensive Care Med 1998;24:959-66.
  26. Losser MR, Forget AP, Payen D. Nitric oxide involvement in the hemodynamic response to fluid resuscitation in endotoxic shock in rats. Crit Care Med 2006;34:2426-31.
  27. Monge García MI, González PG, Romero MG, et al. Effects of fluid administration on arterial load in septic shock patients. Intensive Care Med 2015;41:1247-55.
  28. Pierrakos C, Velissaris D, Scolletta S, et al. Can changes in arterial pressure be used to detect changes in cardiac index during fluid challenge in patients with septic shock? Intensive Care Med 2012;38:422-8.
  29. Monge García MI, Guijo Gonzalez P, Gracia Romero M, et al. Effects of arterial load variations on dynamic arterial elastance: an experimental study. Br J Anaesth 2017;118:938-46.
  30. Pohl U, De Wit C, Gloe T. Large arterioles in the control of blood flow: role of endothelium-dependent dilation. Acta Physiol Scand 2000;168:505-10.
  31. Hennig T, Mogensen C, Kirsch J, et al. Shear stress induces the release of an endothelial elastase: role in integrin alpha(v)beta(3)-mediated FGF-2 release. J Vasc Res 2011;48:453-64.
  32. Maeder M, Fehr T, Rickli H, et al. Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides. Chest 2006;129:1349-66.
  33. Bessière F, Khenifer S, Dubourg J, et al. Prognostic value of troponins in sepsis: a meta-analysis. Intensive Care Med 2013;39:1181-9.
  34. Neri M, Cerretani D, Fiaschi AI, et al. Correlation between cardiac oxidative stress and myocardial pathology due to acute and chronic norepinephrine administration in rats. J Cell Mol Med 2007;11:156-70.
  35. Haileselassie B, Su E, Pozios I, et al. Myocardial oxidative stress correlates with left ventricular dysfunction on strain echocardiography in a rodent model of sepsis. Intensive Care Med Exp 2017;5:21.
  36. Henrich M, Gruss M, Weigand MA. Sepsis- induced degradation of endothelial glycocalix. ScientificWorldJournal 2010;10:917-23.
  37. von Geldern TW, Budzik GP, Dillon TP, et al. Atrial natriuretic peptide antagonists: biological evaluation and structural correlations. Mol Pharmacol 1990;38:771-8.
  38. Bruegger D, Jacob M, Rehm M, et al. Atrial natriuretic peptide induces shedding of endothelial glycocalyx in coronary vascular bed of guinea pig hearts. Am J Physiol- Heart Circ Physiol 2005;289:H1993-9.
  39. Chen C, Chappell D, Annecke T, et al. Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study. Hypoxia 2016;4:81-90.
  40. Chappell D, Bruegger D, Potzel J, et al. Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx. Crit Care 2014;18:538.
  41. Berg S, Engman A, Hesselvik JF, et al. Crystalloid infusion increases plasma hyaluronan. Crit Care Med 1994;22:1563-7.
  42. Jacob M, Saller T, Chappell D, et al. Physiological levels of A-, B-and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability. Basic Res Cardiol 2013;108:347.
  43. Hippensteel JA, Uchimido R, Tyler PD, et al. Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation. Crit Care 2019;23:259.
  44. Rivers EP, Kruse JA, Jacobsen G, et al. The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med 2007;35:2016-24.
  45. Dorresteijn MJ, van Eijk LT, Netea MG, et al. Iso-osmolar prehydration shifts the cytokine response towards a more anti-inflammatory balance in human endotoxemia. J Endotoxin Res 2005;11:287-93.
  46. Rhee P, Wang D, Ruff P, et al. Human neutrophil activation and increased adhesion by various resuscitation fluids. Crit Care Med 2000;28:74-8.
  47. Lee SH, Seo E-H, Park HJ, et al. The effects of crystalloid versus synthetic colloid in vitro on immune cells, co- cultured with mouse splenocytes. Scientific Reports 2018;8:4794.
  48. van Haren FM, Sleigh J, Cursons R, et al. The effects of hypertonic fluid administration on the gene expression of inflammatory mediators in circulating leucocytes in patients with septic shock: a preliminary study. Ann Intensive Care 2011;1:44.
  49. Vincent JL, Pinsky MR. We should avoid the term "fluid overload". Crit Care 2018;22:214.
  50. Malbrain ML, Marik PE, Witters I, et al. Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice. Anaesthesiol Intensive Ther 2014;46:361-80.
  51. Sadaka F, Juarez M, Naydenov S, et al. Fluid resuscitation in septic shock: the effect of increasing fluid balance on mortality. J Intensive Care Med 2014;29:213-7.
  52. Smith SH, Perner A. Higher vs. lower fluid volume for septic shock: clinical characteristics and outcome in unselected patients in a prospective, multicenter cohort. Crit Care 2012;16:R76.
  53. Samoni S, Vigo V, Resendiz LI, et al. Impact of hyperhydration on the mortality risk in critically ill patients admitted in intensive care units: comparison between bioelectrical impedance vector analysis and cumulative fluid balance recording. Crit Care 2016;20:95.
  54. Prowle JR, Echeverri JE, Ligabo EV, et al. Fluid balance and acute kidney injury. Nat Rev Nephrol. 2010;6:107-15.
  55. Prowle JR, Kirwan CJ, Bellomo R. Fluid management for the prevention and attenuation of acute kidney injury. Nat Rev Nephrol. 2014;10:37-47.
  56. Hilton AK, Bellomo R. A critique of fluid bolus resuscitation in severe sepsis. Crit Care 2012;16:302.
  57. Vellinga NA, Ince C, Boerma EC. Elevated central venous pressure is associated with impairment of microcirculatory blood flow in sepsis: a hypothesis generating post hoc analysis. BMC Anesthesiol 2013;13:17.
  58. Rohn DA, Stewart RH, Elk JR, et al. Renal lymphatic function following venous pressure elevation. Lymphology1996;29:67-75.
  59. Van Regenmortel N, Verbrugghe W, Roelant E, et al. Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population. Intensive Care Med 2018;44:409-17.
  60. Van Regenmortel N, Hendrickx S, Roelant E, et al. 154 compared to 54 mmol per liter of sodium in intravenous maintenance fluid therapy for adult patients undergoing major thoracic surgery (TOPMAST): a single-center randomized controlled double-blind trial. Intensive Care Med 2019;45:1422-32.
  61. Malbrain ML, Chiumello D, Pelosi P, et al. Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study. Crit Care Med 2005;33:315-22.
  62. Kirkpatrick AW, Roberts DJ, De Waele J, et al. Intra- abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med 2013;39:1190-206.
  63. Dalfino L, Tullo L, Donadio I, et al. Intra-abdominal hypertension and acute renal failure in critically ill patients. Intensive Care Med 2008;34:707-13.
  64. Diebel LN, Wilson RF, Dulchavsky SA, et al. Effect of increased intra-abdominal pressure on hepatic arterial, portal venous, and hepatic microcirculatory blood flow. J Trauma 1992;33:279-82.
  65. Silversides JA, Perner A, Malbrain M. Liberal versus restrictive fluid therapy in critically ill patients. Intensive Care Med 2019;45:1440-2.
  66. MacGillivray N. Dr Latta of Leith: pioneer in the treatment of cholera by intravenous saline infusion. J R Coll Physicians Edinb 2006; 36:80-5.

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Metadata

Authors
Marik, P. E., Byrne, L., & van Haren, F.
Affiliations
  • Eastern Virginia Medical School (US)
  • Australian National University (AU)
Corresponding author
Marik, Paul E.
ORCID
Venue
Journal of Thoracic Disease
Publisher
AME Publishing Company
Published
2020-02
Volume
12
Issue
S1
Pages
S37-S47
ISSN
  • 2072-1439 (ISSN-L)
  • 2077-6624
DOI
10.21037/jtd.2019.12.84
PMC
PMC7024756
OpenAlex
W3000726620
Cited by
116
References
5
Citations by year
2026: 11 · 2025: 13 · 2024: 20 · 2023: 14 · 2022: 26 · 2021: 19 · 2020: 12
FWCI
2.59
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of Thoracic Disease (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • ANU Open Research (Australian National University) (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
  • Health Sciences › Medicine › Surgery › Abdominal Surgery and Complications
Keywords
fluid resuscitation, septic shock, sepsis, crystalloid administration, restrictive fluid therapy, Surviving Sepsis Campaign guidelines, blood lactate, fluid overload, physiological monitoring

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