Global Increased Permeability Syndrome

Revised and reviewed 12 July 2015


  • 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


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.


  • 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.

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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