Albumin in sepsis and septic shock

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

According to the current edition of the SSC guidelines, treatment and resuscitation should begin immediately when sepsis or septic shock are recognised, and they recommend a low threshold for commencement in suspects¹. For example, some guidelines recommend that healthcare professionals ask, “Could this be sepsis?” when patients present with signs, symptoms or evidence of possible infection^18,19. Although based on observational studies, this recommendation is considered a best practice, as sepsis and septic shock are medical emergencies¹.

The SSC guidelines strongly recommend crystalloids as first-line fluid for resuscitation in adults with sepsis and septic shock (based on a moderate quality of evidence), and suggest balanced crystalloids over normal saline (low quality of evidence)¹. They suggest administration of ≥30 mL/kg of intravenous crystalloid fluid within the first 3 hours of resuscitation for patients with sepsis-induced hypoperfusion or septic shock (weak recommendation, low quality of evidence)¹, and suggest using dynamic measures such as a fluid bolus or a passive leg raise to guide fluid resuscitation rather than using static parameters or physical examination alone (weak recommendation, very low-quality evidence)¹. In addition, they suggest that resuscitation is guided such that serum lactate is decreased in patients with high lactate level, and suggest using capillary refill time as an adjunct to other perfusion measures to guide resuscitation (based on low quality evidence)¹.

The SSC guidelines suggest using albumin as a supplementary resuscitation fluid for haemodynamic management for patients who were administered crystalloids in large volumes^1,4. This is based on weak, moderate-quality evidence¹. Evidence demonstrates lower net fluid balance, higher static filling pressures and higher blood pressure at early and later time points with albumin, and limited data excludes a crystalloid infusion cut-off value, above which albumin could be considered as part of resuscitation¹. While theory suggests that albumin would be better at maintaining oncotic pressure, compared with crystalloids, clear benefit for its routine use is lacking, and albumin is more costly¹. However it should be noted that the use of human albumin solutions (HAS) for resuscitation require less fluid than using crystalloid solutions⁷.

While the SSC guidelines provide strong recommendations for crystalloids as the primary initial resuscitation fluid and albumin as a supplementary fluid, they do not provide clear recommendations regarding when to begin administration, the applicable population, optimal concentration or indications for albumin discontinuation^1,4, and do not provide guidance on when to move from crystalloid to colloid during resuscitation⁶. While the guidelines are associated with improved outcomes, gaps in the literature preclude them from making specific recommendations in all clinically relevant areas¹⁶. As a result, an expert consensus was convened by the Chinese Society of Critical Care Medicine to address these gaps and provide recommendations of their own⁴. In their publication, ‘Expert Consensus on the Use of Human Serum Albumin in Critically Ill Patients’, 11 clinical issues are outlined along with recommendations that use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology⁴.

In response to the use of HAS in sepsis and septic shock, the panel made five recommendations which are contained in Table 1⁴.

Table 1. Recommendations on the use of human serum albumin in sepsis and septic shock by an expert panel convened by the Chinese Society of Critical Care Medicine⁴. HAS, human albumin solution

In patients with persistent signs of hypoperfusion and volume depletion after initial resuscitation, the SSC guidelines do not make a recommendation on whether to use restrictive or liberal fluid strategies within the first 24 hours of resuscitation because there is insufficient evidence¹. However, they state that for most patients, continuous fluid administration will be required after initial resuscitation¹. This administration should be weighed against the risk of fluid accumulation and potential harm associated with fluid overload¹ – overload being defined as a 10% increase in fluid accumulation compared to baseline body weight³. Potential risks include: acute kidney injury progression, issues associated with prolonged ventilation, and increased mortality¹. 

When managing patients with complex sepsis, the SSC guidelines state the importance of conducting a detailed initial assessment and to continuously monitor and re-evaluate the patient’s response to treatment¹. By conducting careful assessment of the status of intravascular volume and organ perfusion, and using these levels to guide fluid administration following the initial resuscitation, over- and under-resuscitation may be avoided¹. In some settings, advanced haemodynamic monitoring may not be available. In such cases, other signs of tissue perfusion can be used, including skin mottling, capillary refill time and temperature of the extremities – all have been validated and demonstrated to be reproducible surrogates¹. If using capillary refill time during resuscitation, however, it is important to consider any underlying pathology or relevant pathological processes, and provide comprehensive and frequent patient evaluation to help predict/recognise fluid overload early¹.

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

The 4 Ds of fluid therapy

According to the 4 Ds, healthcare professionals should consider the following aspects when considering the optimal fluid therapy for their patient⁵:

• Drug
  • The different compounds available (crystalloids versus colloids; balanced versus unbalanced; synthetic versus blood-derived; intravenous versus oral)
  • The pH, electrolyte composition, osmolality, tonicity and levels of other metabolically active compounds
  • The patients’ clinical factors (e.g. underlying conditions, liver or kidney failure)
  • The reason for fluid administration, of which there are four indications: resuscitation, maintenance, replacement and nutrition, or a combination
• Dose
  • There is a well-established risk of excessive fluid overload, so the dose decision should consider the fluid’s pharmacokinetics and pharmacodynamics
• Duration
  • The longer the delay in treatment, the greater the risk of microcirculatory hypoperfusion and subsequent organ damage from ischaemia-reperfusion injury
  • The best prognosis may lie in combining early adequate and late conservative fluid management, and late conservative fluid therapy may be more important than early adequate fluid therapy
• De-escalation
  • Fluid therapy duration should be as short as possible, and the volume tapered once shock is resolved
  • Without a trigger to stop fluid resuscitation there is a greater risk of fluid overload

ROSE concept

The second concept relevant to fluid selection in sepsis is that a different strategy is required for each phase of illness³. In sepsis, there are four dynamic phases of sepsis management, helpfully referred to as ‘ROSE’ (Figure 1)³.

Figure 1. The ROSE model (Adapted^3,5). The different fluid phases during shock image is licensed under CC BY 4.0 / image redrawn with detail added for clarity.

The figure illustrates the fluid phases during shock and shows how a patient’s cumulative fluid volume status evolves across the four phases of resuscitation: (1) resuscitation, (2) optimisation, (3) stabilisation and (4) evacuation. A fifth phase, hypoperfusion, may occur if de-resuscitation is overly aggressive⁵. HIT refers to the events that occur during shock: HIT 1 refers to the initiating event (e.g. sepsis, burns); HIT 2 refers to ischaemia and reperfusion; HIT 3 refers to a phase of de-resuscitation, which usually results from global increased permeability syndrome; HIT 4 refers to haemodynamic deterioration and hypoperfusion in patients who enter phase 5⁵.

Phases of sepsis management^3,5:

Resuscitation

• Aggressive resuscitation aimed at rescuing the patient’s life

Optimisation

• Diligent fluid titration to optimise organ perfusion

Stabilisation

• Aim to stabilise the fluid balance to a neutral daily balance

Evacuation

• Aim to evacuate fluids that may have accumulated without being too aggressive with fluid removal, to avoid phase 5

Watch the following video featuring Dr Christian Wiedermann, to learn about the different types of fluids, their functions and routes of administration. Dr Wiedermann also provides an overview of crystalloids and colloids and recommendations for their use.

There are three broad categories of fluid options: colloids, crystalloids and blood products. Colloids and crystalloids for resuscitation in sepsis patients, including recommendations for their use in sepsis and septic shock, are summarised in Tables 2 and 3, respectively.

Table 2. Colloid fluid options for resuscitation in sepsis including recommendations and key points^1,3,20–22. EMA, European Medicines Agency; PRAC, Pharmacovigilance Risk Assessment Committee; SSC, Surviving Sepsis Campaign. ^*Mekeirele et al., 2022; ^†Evans et al., 2022; ^‡Moeller et al., 2016; ^§Marx et al., 2021; ^**ClinicalTrials.gov. GENIUS. 2022. 

Table 3. Crystalloid fluid options for resuscitation in sepsis including recommendations and key points^1,3. EMA, European Medicines Agency; PRAC, Pharmacovigilance Risk Assessment Committee; SSC, Surviving Sepsis Campaign. ^*Evans et al., 2022.

Review human serum albumin products approved for use in fluid replacement therapy

Blood products are not usually administered as fluid resuscitation in septic shock³ and the Surviving Sepsis Campaign recommends blood transfusion only if haemoglobin levels fall below 7 g/dL, but transfusion practice should always be tailored to the patient’s individual needs¹.

Key considerations that may help guide optimal fluid choice include^3,5,16:

• Indications
• Reference to guideline recommendations
• Comparison between the options that are available
• Patient-specific factors
• Context-specific circumstances

Watch this video for Dr Wiedermann’s key take aways for healthcare professionals managing patients with sepsis and septic shock who require intravenous fluid therapy.

When considering the optimal resuscitation fluid, it is important that patients are given the opportunity to make informed decisions about their care and treatment in partnership with their clinician, when possible, with their individual needs and preferences considered²³. This extends to decisions post-intensive care and in hospital discharge planning¹. Goals of care and prognosis should be discussed with patients and their families, preferably with goals of care discussed within 72 hours of diagnosis, and palliative care principles should be integrated within the treatment plan when appropriate¹.

Learn about fluid needs and fluid selection in liver disease

References

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3. Mekeirele M, Vanhonacker D, Malbrain MLNG. Fluid Management in Sepsis. Springer Nature Singapore; 2022. p. 199-212.
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