Global Increased Permeability Syndrome

Revised and reviewed 12 July 2015

OVERVIEW

• Global Increased Permeability Syndrome (GIPS) “is characterised by high capillary leak index (CLI, expressed as the ratio of CRP over albumin x 100), excess interstitial fluid and persistent high extravascular lung water index (EVLWI), no late conservative fluid management (LCFM) achievement, and progression to organ failure” (Malbrain et al, 2014)
• aka capillary leak syndrome

PATHOPHYSIOLOGY

The “Three hit” model of critical illness

• first hit = acute injury/ insult (e.g. pneumonia resulting in septic shock)
• second hit = multi-organ dysfunction syndrome (MODS) (e.g. ischaemia-reperfusion, toxic oxygen metabolite generation, cell wall and enzyme injury leading to a loss of capillary endothelial barrier function)
• third hit = GIPS

Development of GIPS

• Successful response to an acute inflammatory insult tends to result in a crucial turning point on the third day after shock initiation
• cytokines and other pro-inflammatory mediators on  day 3 allows healing of the microcirculatory disruptions and ‘closure’ of capillary leakage.
• excess fluid administration results in oedema formation, polycompartment syndromes (when two or more anatomical compartments have elevated compartmental pressures), progression of organ failure and worse outcome.

MANAGEMENT

• As soon as haemodynamic stability is achieved during the resuscitation phase there should be a transition to conservative fluid management  and ‘late goal directed fluid removal’ (de-resuscitation) if appropriate
  • diuretics (e.g. frusemide boluses or infusions)
  • renal replacement therapy (e.g. net ultrafiltration to maintain a negative fluid balance)
• treat underlying cause
• Treat complications (e.g. widespread tissue and organ edema resulting in worsened organ dysfunction)

References and Links

Journal articles

• Malbrain ML, Marik PE, Witters I, Cordemans C, Kirkpatrick AW, Roberts DJ, Van Regenmortel N. Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice. Anaesthesiol Intensive Ther. 2014 Nov-Dec;46(5):361-80. doi: 10.5603/AIT.2014.0060. PMID: 25432556.