Albumin in sepsis and septic shock

Fluid needs in sepsis and septic shock

Introduction to albumin use in sepsis

Watch this video featuring Dr Christian Wiedermann, a medical research consultant, to learn about the roles of albumin in sepsis. Dr Wiedermann also discusses the SAFE Study and the ALBIOS trial.

Globally, sepsis and septic shock affect millions of people every year, killing one-sixth to one-third of those affected¹

Sepsis is defined as a life-threatening organ dysfunction caused by the body’s dysregulated infection response, while septic shock is a subset in which the underlying abnormalities are severe enough to lead to increased mortality². Fluid loss is a major factor in organ damage³.

To improve patient outcomes, sepsis must be identified early and managed appropriately in the first hours after development¹. In patients with sepsis and septic shock, fluid management is an essential part of haemodynamic resuscitation⁴. Fast and effective fluid resuscitation is necessary to stabilise tissue hypoperfusion caused by sepsis¹. Tissue hypoxia can then be corrected and organ function maintained when plasma volume is restored quickly and effectively⁴. However, haemodynamic resuscitation with fluid administration remains a therapeutic challenge with regard to the risk of fluid overload, questions about the most effective type and dose of fluid, and timing of resuscitation⁵.

There has been extensive research into the use of intravenous fluid therapy to treat sepsis and septic shock, with albumin solution being extensively reviewed for its use as a resuscitation fluid and to prevent hypoalbuminaemia⁶.

Albumin’s range of pharmacological effects, including its regulation of oncotic pressure, contributes to its role in critical care⁷. It is hypothesised that the potential clinical benefits of albumin use in sepsis are also related to anti-inflammatory and immunomodulatory effects, endothelial stabilisation and antibiotic transportation⁷. While albumin transports a range of drugs typically administered in critically ill people, in patients with hypoalbuminaemia the binding ability of albumin is often diminished, thereby potentially leading to suboptimal treatment⁷.

The antioxidant properties of albumin reduce re-oxygenation injury, which is of particular importance in sepsis⁷. In fact, most of the research into the administration of albumin combines a degree of resuscitation with a degree of supplementation or maintenance of albumin⁷.

Albumin derived from human plasma has a range of therapeutic applications, but the question of whether the use of human serum albumin improves the clinical prognosis of critically ill patients has been contentious because of conflicting results of meta-analyses⁸. Practice was largely influenced by a meta-analysis published by the Cochrane Injuries Group in 1998, which included 32 studies with a total of 1,419 patients. The study reported increased mortality rates in patients who received albumin treatment,⁹ which led to a significant decrease in the use of albumin¹⁰. Interestingly, a Cochrane review published in 2018 that compared crystalloids and colloids, including albumin, concluded that either choice probably makes little to no difference to mortality¹¹.

The conflicting results of meta-analyses on the use of albumin in critically ill patients may have been due to the inclusion of heterogenous populations, including patients with traumatic brain injury, in whom albumin is associated with worse outcomes and should be avoided^8,10,12

Access our full range of information to deepen your understanding of how to manage sepsis and septic shock by registering for a free Medthority account today, or by logging into your existing account. By logging in, you will discover the features of different intravenous fluids, learn the recommendations for managing sepsis and septic shock, and find out the evidence behind recommendations for fluid management.

Guidelines for fluid management in sepsis and septic shock

In this video Dr Christian Wiedermann, a medical research consultant, discusses guideline recommendations for fluid use in sepsis and sepsis shock. He notes that some aspects of fluid management remain under discussion.

In patients with traumatic brain injury, albumin has been shown to increase mortality; in patients with peripheral oedema during the recovery phase, albumin may be beneficial; and in patients with sepsis, albumin has been shown to be beneficial⁸

The latest version of the global guidelines for adult sepsis management, published by the Surviving Sepsis Campaign (SSC) in October 2021, states that recommendations and guidelines cannot substitute for a clinician’s decision-making in the context of a patient’s unique clinical circumstances¹.

The SSC is an initiative by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine (USA), with its goal being to improve mortality from sepsis¹⁶.

The 2021 version of the SSC guidelines was updated to represent broader gender and geographic diversity, and provides greater emphasis on improving after-patient care to address the challenges inherent when treating patients for the long-term impacts of sepsis¹⁷. These challenges include¹:

• Long stays in the intensive care unit
• Physical rehabilitation
• Cognitive and emotional issues
• Care coordination for patients and their families that align with their goals

Learn more about SSC guideline recommendations by logging in or registering for a free Medthority account

Fluid selection in sepsis and septic shock

In this video Dr Christian Wiedermann, a medical research consultant, discusses key considerations and challenges when managing patients with sepsis or septic shock who require intravenous fluid therapy. He outlines the risks of fluid overload, the evidence for increased mortality risk and highlights the importance of attempting to reduce overaccumulation when administering fluid for resuscitation.

According to research, the type of intravenous fluid administered during resuscitation impacts a patient's outcomes³

Selection of fluid should be grounded in the concept of treating fluids as drugs: each with indications, contraindications and possible side effects³. This concept has been labelled ‘the 4 Ds of fluid therapy’⁵.

The 4 Ds of fluid therapy⁵:

• Drug
• Dose
• Duration
• De-escalation

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References

1. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Critical Care Medicine. 2022.
2. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801.
3. Mekeirele M, Vanhonacker D, Malbrain MLNG. Fluid Management in Sepsis. Springer Nature Singapore; 2022. p. 199-212.
4. Yu Y-T, Liu J, Hu B, Wang R-L, Yang X-H, Shang X-L, et al. Expert consensus on the use of human serum albumin in critically ill patients. Chinese Medical Journal. 2021;134(14).
5. Malbrain MLNG, Van Regenmortel N, Saugel B, De Tavernier B, Van Gaal P-J, Joannes-Boyau O, et al. Principles of fluid management and stewardship in septic shock: it is time to consider the four D’s and the four phases of fluid therapy. Annals of Intensive Care. 2018;8(1).
6. Melia D, Post B. Human albumin solutions in intensive care: A review. Journal of the Intensive Care Society. 2021;22(3):248-254.
7. Ferrer R, Mateu X, Maseda E, Yébenes JC, Aldecoa C, De Haro C, et al. Non-oncotic properties of albumin. A multidisciplinary vision about the implications for critically ill patients. Expert Review of Clinical Pharmacology. 2018;11(2):125-137.
8. Caironi P, Gattinoni L. The clinical use of albumin: the point of view of a specialist in intensive care. Blood Transfus. 2009;7(4):259-267.
9. Cochrane Injuries Group Albumin Reviewers Why albumin may not work. BMJ. 1998;317.
10. Vincent J-L, Russell JA, Jacob M, Martin G, Guidet B, Wernerman J, et al. Albumin administration in the acutely ill: what is new and where next? Critical Care. 2014;18(4):231.
11. Lewis SR, Pritchard MW, Evans DJ, Butler AR, Alderson P, Smith AF, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database of Systematic Reviews. 2018.
12. Wiedermann CJ. Phases of fluid management and the roles of human albumin solution in perioperative and critically ill patients. Current Medical Research and Opinion. 2020;36(12):1961-1973.
13. The SAFE Study Investigators. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit. N Eng J Med. 2004;350(22):2247-2256.
14. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, et al. Albumin Replacement in Patients with Severe Sepsis or Septic Shock. New England Journal of Medicine. 2014;370(15):1412-1421.
15. Piotti A, Novelli D, Meessen JMTA, Ferlicca D, Coppolecchia S, Marino A, et al. Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS. Critical Care. 2021;25(1).
16. Lat I, Coopersmith CM, De Backer D. The Surviving Sepsis Campaign: Fluid Resuscitation and Vasopressor Therapy Research Priorities in Adult Patients. Critical Care Medicine. 2021;49(4).
17. Treatment of Sepsis. https://www.australiansepsisnetwork.net.au/healthcare-providers/treatment-sepsis. Accessed 1 July 2022.
18. Sepsis in adults - Symptoms, diagnosis and treatment | BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/3000098. Accessed 21 October 2022.
19. NICE. Recommendations | Sepsis: recognition, diagnosis and early management | Guidance | NICE. https://www.nice.org.uk/guidance/NG51/chapter/Recommendations#identifying-people-with-suspected-sepsis. Accessed 21 October 2022.
20. Moeller C, Fleischmann C, Thomas-Rueddel D, Vlasakov V, Rochwerg B, Theurer P, et al. How safe is gelatin? A systematic review and meta-analysis of gelatin-containing plasma expanders vs crystalloids and albumin. 2016(1557-8615 (Electronic)).
21. Marx G, Zacharowski K, Ichai C, Asehnoune K, Černý V, Dembinski R, et al. Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomiz. Trials. 2021;22(1).
22. NCT02715466. Gelatin in ICU and Sepsis (GENIUS). 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT02715466?term=NCT02715466&draw=2&rank=1. Accessed July 2022.
23. NICE. Patient-centred care | Intravenous fluid therapy in adults in hospital | Guidance | NICE. https://www.nice.org.uk/guidance/cg174/chapter/Patient-centred-care. Accessed 2 Jul 2022.