Refractory Hypoxemia

Refractory Hypoxemia – Amelia Muhs


  • Inadequate arterial oxygenation despite high levels of inspired O2 or the development of barotrauma in mechanically ventilated pts
  • Generally start to consider the interventions below if needing FiO2 >80%
  • Differential:
    • Worsening underlying primary process (e.g. progressive ARDS)
    • PE
    • Pneumothorax
    • ET tube obstruction/malposition
    • Fluid overload
    • Ventilator-associated Pneumonia
    • New ARDS



  • Always get CXR STAT if pt has new or worsening O2 requirement
  • ABG is frequently very helpful as well
  • Can use POCUS to check for lung sliding (pneumothorax) or RV enlargement/septal bowing/McConnell’s sign (RV strain in PE)



  • Remember – if at any point the pt is rapidly decompensating, you can always disconnect them from the vent and bag them until they recover/while calling for help
  • Early consideration of ECMO consult in appropriate pts (discuss with MICU fellow)
    • After talking with the fellow/attending, you can start process by placing “Inpatient consult to ECMO adult” in Epic
  • Optimize fluid status consider diuresis/dialysis if not making urine
  • Consider higher PEEP strategy
    • Increased PEEP higher mean airway pressure, generally improves oxygenation especially with diffuse pulmonary pathologies
        • Exceptions may include certain focal/shunt pathologies (e.g. dense lobar PNA)
        • Worsening oxygenation may occur with overdistension of alveoli increase dead space ventilation; generally determined empirically at the bedside
    • Titrate up slowly; generally do not exceed PEEP 18
        • Limited by high plateau pressures/barotrauma, overdistension/dead space ventilation, decreased preload/venous return
    • ARDSnet FiO2/PEEP Tables: We usually use the Lower PEEP table


  • Other recruitment maneuvers
    • Reposition pt – can try elevating HOB or positioning so “good lung” is down
    • If concern for mucus plug, consider need for bronch
    • If concern for significant atelectasis can try recruitment maneuvers with the vent including sustained inflation (setting expiratory pressure to ~30 for ~30 seconds) and PEEP titration (setting PEEP to 20-25 and decreasing by 2cm at a time) – call the fellow before attempting


Management Algorithm:

1.  Inhaled vasodilators

  • VUMC formulary preference: inhaled epoprostenol (aka Flolan)
  • Alternatives: inhaled milrinone, inhaled nitric oxide
  • Data suggest improved PaO2/FiO2; large RCT without evidence for mortality benefit

2.  Deep sedation (RASS -4 or -5)

  • Promotes ventilator synchrony

3.  Neuromuscular blockade (paralysis) – call your fellow before doing this

  • Rationale: maximal vent synchrony (eliminates residual chest wall/diaphragm tone)
  • Pt MUST be RASS -5 (need analgesia + sedation, cannot achieve with dexmedetomidine alone, which does not have amnestic properties)
  • Trial one time IV push of vecuronium 0.1 mg/kg
  • If improved vent synchrony/oxygenation, consider cisatracurium (Nimbex) drip
  • Data are mixed ACURASYS 2010 (improved 90-day mortality but underpowered likely overestimating benefit); ROSE 2019 (no difference in 90-day mortality)

4.  Prone positioning (Need attending approval)

  • Pts with moderate to severe ARDS (PaO2/FiO2 ratio < 150)
  • At VUMC, we use regular ICU beds and manually flip pts; cycle prone 16 hrs/supine 8 hrs
  • When proning or supining a pt, always have a provider who can intubate in the room in case unplanned extubation occurs (anesthesia or pulm attending)
  • Considerations: need a team of people to reposition, high risk of ET tube malposition, difficult to access lines/perform procedures, high risk of pressure injuries
  • Data: PROSEVA 2013 proning improved 28-day mortality; study complicated by imbalances between groups

5.  Alternative ventilator modes (usually Pressure Control or APRV/BiLevel/BiVent)

  • Always ask for help from a fellow or attending before switching to a mode that you do not know how to trouble shoot!
  • APRV/BiVent should be avoided in people with bad obstructive lung disease, hemodynamic instability, refractory hypercarbia

6.  Venovenous (V-V) ECMO

  • Indications for hypoxemia:
    • PaO2/FiO2 < 50 with FiO2 >80% for >3 hrs OR
    • PaO2/FiO2 < 80 with FiO2 >80% for >6 hrs AND
    • Mechanical ventilation ≤ 1 week
  • Absolute Contraindications:
    • Poor short-term prognosis (e.g. metastatic cancer)
    • Irreversible, devastating neurologic pathology
    • Chronic respiratory insufficiency without the possibility for transplant
  • Goal must be clear upfront bridge to recovery, transplant, or transplant decision
  • Can calculate RESP score predicts in-hospital survival with ECMO
  • CONSULT EARLY if a pt may be a candidate; does not commit pt to procedure but allows ECMO team to assist with evaluation
  • Data:
    • CESAR 2009 improved 6-month survival without severe disability
    • EOLIA 2018 no mortality benefit but 28% crossover from control to ECMO arm dilutes potential effects