Negative Pressure Pulmonary Oedema

Reviewed and revised 12 May 2014


Negative pressure pulmonary edema (NPPE) is a form of noncardiogenic pulmonary edema (PE) that results from the generation of high negative intrathoracic pressure (NIP) needed to overcome upper airway obstruction

  • may occur in otherwise healthy individuals who can generate high NIP
  • typically resolves over 12-48 hours with appropriate care



  • any cause of upper airway obstruction
  • examples include laryngospasm or obstructed endotracheal tube (e.g. patient biting down)
  • high NIP from patient-ventilator dysnchrony may contribute to respiratory failure (e.g. ARDS patients) and extubation failure (high NIP against increased resistance)
  • Young healthy subjects can generate very high levels of NIP with a maximum of −140 cmH2O

Hydrostatic mechanism due to increased preload and increased LV afterload

  • high NIP augments venous return to the right side of the heart
    -> increased pulmonary venous pressures, while decreasing perivascular interstitial hydrostatic pressure
    -> movement of fluid from the pulmonary capillaries into the interstitium and alveolar spaces
  • hypoxia
    -> decreased myocardial contractility and increased pulmonary venous pressures through hypoxic vasoconstriction
  • sympathetic outflow
    -> increased venous return from venoconstriction, and increased afterload due to increased SVR (peripheral arterial vasoconstriction)
  • increased LV afterload due to NIP
    -> increased transmural pressure across LV wall
  • increased pulmonary capillary pressure due to decreased LV function

Mechanical stress mechanism

  • respiration against an obstructed upper airway
    -> increased transmural pulmonary capillary pressures
    -> disruption of the alveolar epithelial and pulmonary microvascular membranes
    -> increased pulmonary capillary permeability and protein-rich pulmonary edema


Clinical features

  • Pink frothy sputum
  • Crackles
  • Wheeze
  • Increased JVP/CVP
  • Liver engorgement
  • Increased airway P, HR, RR, CVP, PCWP
  • Decreased SpO2


  • CXR – basal shadowing, ULD, perihilar infiltrates, effusions, Kerley B lines, fluid in fissure, cardiomegaly
  • ECG – right heart strain, ischaemic change


Specific therapy

  • apply high FiO2 to keep SpO2 >94%
  • If awake – sit upright and apply CPAP
  • If intubated – IPPV + PEEP, head up positioning, aspirate fluid from endotracheal tube (may need frequent changes of HME filters)
  • no evidence for diuretics, and may exacerbate hypovolemia and hypoperfusion
  • consider preload reduction with GTN if adequate BP (e.g. SBP >100mmHg) —  may also have beneficial afterload lowering effects

References and Links


Journal articles

  • Lemyze M, Mallat J. Understanding negative pressure pulmonary edema. Intensive Care Med. 2014 May 6. PMID: 24797685. [Free Full Text]

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

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.