Capillary leak syndrome with tamponade

A 70-year-old male was admitted to our intensive care unit (ICU) with severe shock and multi-organ dysfunction. His history included moderate aortic stenosis, minor coronary artery disease and hypertension. The provisional diagnosis was sepsis of unknown origin given the history of low-grade fevers and hypotension. His preliminary treatment included broad-spectrum antibiotics and vasopressors. The rapid progression of his multi-organ failure subsequently necessitated intubation, ventilation and renal replacement therapy.

Initially, the patient’s haemodynamic status proved volume-responsive. This was determined both on clinical grounds and the recordings of an advanced haemodynamic monitoring device (PiCCO®, Pulsion Medical Systems, Germany). The total fluid volume administered was extremely high, with the patient receiving 22.6 L of crystalloid in the first 48 hours of ICU admission. Of note, his haemoglobin after 5 L of fluid resuscitation rose from 195 to 203 g/L.

Echocardiography performed after a dramatic rise in vasopressor support revealed a large pericardial effusion with complete right atrial collapse. An emergent pericardiocentesis significantly decreased his vasopressor requirement. Pericardial fluid continued to drain for 24 hours with a total output of 1150 mL. He also developed bilateral, moderate-sized pleural effusions and significant generalised oedema. A creatine kinase level of 60,000 units (U)/L (reference range 0–250 U/L) was attributed to severe muscle oedema and a resultant widespread compartment syndrome.

The ongoing need for large-volume fluid resuscitation with multiple sites of third-spaced fluid and haemoconcentration prompted the consideration of systemic capillary leak syndrome (CLS), or Clarkson’s syndrome. In addition to hydrocortisone, 2 g/kg body weight of intravenous (IV) immunoglobulin (Ig) was administered whilst further confirmatory tests were processed.

The final diagnosis was CLS induced by influenza B, subsequently confirmed on molecular testing. A paraprotein (IgG lambda, 2.0 g/L) was also identified.

CLS is a rare syndrome, characterised by plasma and plasma proteins leaking from capillaries. There are < 500 cases reported in the literature. The pathophysiology is poorly understood but transient endothelial dysfunction is a major component. It is thought to be immune-mediated and may involve an interaction between paraproteins, vascular endothelial growth factor and cytokine release. ¹

Early differentiation of CLS from the normal capillary leak of critical illness relies on both the clinical course and investigations. A paraprotein is a consistent association in ∼67% of cases. Cases associated with both autoimmune diseases and drugs such as oxaliplatin have been described. ² The median age of patients diagnosed with CLS in one series was 55 years. ¹

CLS presents as recurrent episodes of shock and anasarca. The syndrome is characterised by three different stages; a flu-like prodrome, transient leakage of fluid and proteins at a capillary level, and finally resolution. ¹ The second stage is characterised by hypotension and oedema, and can mimic septic shock. ³ Angioedema and anaphylaxis, which have plasma leakage as part of their pathophysiology, should also be considered in the differential diagnosis. ⁴

Although CLS is a clinical diagnosis, a paraprotein may be present between attacks. ¹ Initial investigations will reveal intravascular hypovolaemia, haemoconcentration and hypoalbuminaemia.^4,5 Proteinuria is absent. ¹

Fluid can accumulate in any organ or potential space, causing a range of complications: respiratory failure (from pulmonary oedema or pleural effusions), shock (from hypovolaemia or cardiac tamponade), mesenteric ischaemia (from severe oedema of the gut and hepatic congestion) and, as in this case, compartment syndrome and rhabdomyolysis (from muscle oedema). ¹

In the acute phase, IVIg is recommended to decrease mortality. ⁶ The use of plasmapheresis has been described. ¹

Judicious fluid therapy in the early resuscitation period is important. Monitoring various measures of intravascular filling with invasive haemodynamic monitoring maybe helpful given the difficulty in maintaining an effective circulatory volume. ⁵ Diuresis may be needed in the resolution stage.

Despite its severity, 76% of patients identified with CLS will survive to five years. ¹ This case is a reminder to seek a broader differential for the capillary leak evident in many forms of critical illness and to consider CLS, as the treatment is distinct and effective.

Written consent was obtained from the patient for publication.