“Mastering the Fluid Balance: Navigating Sepsis, Capillary Leak, and Critical Illness in the ICU"

Prof. Dr. Manu Malbrain

President IFA | Book author | Internist Intensivist | Medisch Adviseur AZ Oudenaarde | Healthcare Consultant | Crisis and Change Management | CMO Medaman | Research professor Medical University Lublin | Keynote speaker

AZ Oudenaarde KU Leuven Bierbeek, Flemish Region, Belgium

Clinical Vignette

A 55-year-old male presents to the ICU with sepsis and septic shock secondary to bacterial pneumonia. Despite initial fluid resuscitation and vasopressor support, he remains hypotensive. Over the next 24 hours, the patient develops hypoalbuminemia and exhibits signs of fluid overloadaccumulation, including peripheral oedema and worsening oxygenation, while maintaining a normal CVP. 

A chest X-ray reveals bilateral infiltrates, and there is a progressive increase in interstitial fluid accumulation. Given his deteriorating condition, capillary leak syndrome is suspected. The clinical team must now reassess the fluid management strategy, carefully balancing the need for adequate perfusion against the risk of exacerbating fluid overloadaccumulation.

Key Questions at the Bedside

(Click / Tap on Questions to Reveal Content)

  • It is important to note that fluid resuscitation and vasopressor support are not mutually exclusive; both play crucial roles in managing septic shock.
  • Vasopressors should be considered early when there is evidence of low SVR (vasoplegia), low diastolic pressure, or high diastolic shock index (DSI), which is calculated as the ratio of heart rate (HR) to diastolic arterial pressure (DAP).
  • In this case, the patient exhibits signs of vasoplegia, which means early vasopressor administration can help stabilize blood pressure without exacerbating fluid accumulation.
  • Vasopressors can be initiated at low doses, even before central venous access (CVA) is established, especially when waiting for central venous catheter placement. This early use can allow for adequate perfusion with fewer fluids.
  • Fluid Challenge: A common misconception is that vasopressors should only be introduced after administering 30 ml/kg of fluids. In fact, the decision to start vasopressors should not be delayed until this threshold is reached.
 
Understanding Fluid Responsiveness vs. Fluid Tolerance:
 
It is essential to distinguish between fluid responsiveness and fluid tolerance, as these concepts are often confused but are critically important in managing sepsis and septic shock.
  1. Fluid Responsiveness refers to a patient’s ability to increase cardiac output (CO) by at least 15% after a fluid challenge. This can be assessed by measuring hemodynamic parameters before and after fluid administration.
  2. Fluid Tolerance is the maximum amount of fluid a patient can safely receive without causing harm or worsening organ dysfunction.
 
These concepts are not mutually exclusive and can coexist in various combinations:
  • A patient can be euvolemic (normal blood volume), fluid responsive, and fluid intolerant—meaning they respond to fluids but can only tolerate a limited amount before adverse effects occur.
  • Conversely, a patient can also be hypovolemic (low blood volume), fluid unresponsive, and fluid tolerant—meaning they do not benefit from additional fluids but can tolerate some fluid load without severe complications.
 
Understanding these nuances is crucial for effective fluid management in critically ill patients.

They play a very important role. Most of the fluids are intracellular (66%) while 33% are extracellular. Of the extracellular fluids only 25% constitute the intravascular fluids while interstitial fluids account for 75%. All fluids are lost to the interstitial space at some point, it is just a matter of time. After 1 hour only 8% of hypotonic solutions and 25-30% of isotonic solutions will remain intravascularly. The lymphatics are very well performing machinery that take the interstitial fluids back to the central circulation via the ductus thoracicus. Some conditions eg like PEEP ventilation or intra-abdominal hypertension may impede lymphatic return and thereby increase pulmonary edema. Recent discussions are questioning the old Starling equation and advocate the revised Starling mechanisms where there is filtration toward interstitial space but no re-absorption back (as this is taken care of by the lymphatics). In this process the endothelial glycocalyx layer plays a pivotal role.

This is very tricky as fluids may leak as they are administered. The fact that a capillary leak persists should be seen as a biomarker or a warning sign that source control is sub-optimal and one should do ultrasound or CT to search for abscess, discuss with surgeon or change the antibiotics after cultures. An edematous patient that is fluid responsive can be very challenging and further fluid accumulation (and fluid accumulation syndrome) should be avoided. This can be done with restriction, de-escalation or de-resuscitation of fluids and the use of hyperoncotic abumin 20% with (combination) diuretics or CVVH with UF.

  • The 6S and CHEST trials launched the PRAC recommendations by the EMEA after which starch solutions have been banned in Europe although there has been much criticism on the study methodology.
  • Is there data to support that colloids would have a larger volume expansion effect? None, in fact as long there is infusion of either colloids or crystalloids there will be a volume expansion effect. In shocked patients the studies by Hahn showed that the volume expansion effect of colloids and crystalloids is similar in shocked patients because excretion and distribution is slow. The volume expansion effect of crystalloids to colloids is not 1:4 as suspected but rather 1:1.2-1.3.
  • Again a very good point as patients with cardiac failure can also have sepsis and be fluid responsive. Is it really sepsis vs cardiogenic shock? Is the patient not congested from the beginning?
  • Fluids can be administered to cardiac patients with sepsis if it is confirmed to be sepsis and they are not congestive from the outset. It is important to consider a component of cardiogenic shock before proceeding with treatment for sepsis. Early norepinephrine may be appropriate, as there is no strong evidence suggesting harm in cardiac patients. Early hemodynamic monitoring should also be considered and inotropes when indicated. We should aim for personalized or better individualized patient care rather than protocolized.
  • The bottomline is that recent studies RELIEF, CLASSIC, CLOVERS,… show no difference in outcomes. Said otherwise less may be more. Problem is that many studies do not achieve a nice separation between study group and controls and what is standard in one study may be liberal in another. The RADAR 2 trial was one of the few studies where a clear separation in cumulative fluid balance was observed.
  • Speed of fluid administration-Bolus vs Infusion!! o In burn patients continuous IV fluids are administered – it looks like this is better for the EGL however after an insult the EGL may be gone within minutes. It makes sense to use continuous infusion (to have ongoing volume expansion effect) with bolus fluids whenever fluid responsiveness increases (PPV, PLR,..)

Everyting you need to know is summarized in 2 recent papers:

  • 1Pfortmueller CA, Dabrowski W, Wise R, van Regenmortel N, Malbrain MLNG. Fluid accumulation syndrome in sepsis and septic shock: pathophysiology, relevance and treatment-a comprehensive review. Ann Intensive Care. 2024 Jul 20;14(1):115. doi: 10.1186/s13613-024-01336-9. PMID: 39033219; PMCID: PMC11264678.
  • Malbrain MLNG, Martin G, Ostermann M. Everything you need to know about deresuscitation. Intensive Care Med. 2022 Dec;48(12):1781-1786. doi: 10.1007/s00134-022-06761-7. Epub 2022 Aug 6. PMID: 35932335; PMCID: PMC9362613
  • Effective methods for fluid removal in critically ill patients.
  • Medical: start with furosemide stress test, use loop diuretics or combination treatment
  • Mechanical: CVVH with UF and/or compression stockings

A concise 3-line overview of fluid management in the ICU setting.

Fluids are drugs, that come with indications, contra-indications and potential adverse effects. Use the 10D framework: Definitions – diagnosis – distribution – drug – dose – duration – de-escalation – documentation – diligence – discussion. The best fluid is the one that has not been given unnecessarily

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