Stroke Alert to the PACU

Non-contrast head CT of CAGE patient who became obtunded following dialysis

CAGE can occur as a complication from many procedures, with the more common culprits listed below in descending order of prevalence as reported by Hatling et al.

1. Cardiopulmonary bypass
2. Central venous catheter
3. Lung biopsy
4. ERCP
5. Hemodialysis
6. Mechanical ventilation
7. Angiography

Classic teaching was to place patients with suspected CAGE in the Trendelenburg position in an effort to displace bubbles from cerebral circulation; however, this is no longer recommended given the deleterious effects of increased intracranial pressure caused by the Trendelenburg position.  In extreme cases of CAGE, cardiac arrest can occur as a result of a large volume of intra-cardiac air causing “vapor lock” and cessation of forwarding circulation of blood.  

Ischemia and Intimal Injury

Much of what we know regarding CAGE comes from historical research in submarine escape training (from which subjects unfortunately frequently had CAGE) and from animal models.2  In addition to the overt ischemia caused by bubble emboli, delayed injuries occur from a shearing effect that bubbles have on cerebrovascular intimal layers and from ischemia reperfusion injury.  The mechanical shearing effect bubbles have on vascular endothelial cells leads to a cascade in which there is an opening of transient receptor potential vanilloid (TRPV) channels, calcium influx, mitochondrial dysfunction, and subsequent cell death.  Not dissimilar from the “lucid interval” classically described with epidural hematoma, patients with CAGE often have transient improvement which is followed by a worsening decline in the hours thereafter.  This is thought to be due to progressive focal edema following the initial insult as well as ischemia-reperfusion injury.  Considering this, it is important to still pursue appropriate treatment in a suspected CAGE patient even with apparent spontaneous resolution of symptoms.    

Crushing Bubbles and CAGE Treatment

Treatment for iatrogenic CAGE is the same as for CAGE occurring in SCUBA divers, which is hyperbaric oxygen therapy (HBOT) to be initiated as soon as possible (immediate is ideal but patient may still benefit out to 24h).  The potential benefits a CAGE patient can gain from HBOT are as follows: 

• Crushing bubbles-Following the inescapable laws of physics (Boyle’s Law in this case), bubble burden size is reduced during HBOT

• Off gassing-The 100% O2 used in HBOT creates a gradient such that bubble size will also be reduced by off gassing to tissues.  In this vein, oxygen via facemask as an immediate, more accessible measure can also help, but to a lesser degree.

• Oxygen for ischemic tissues-restoration of oxygenation to ischemic tissues

• Blunting ischemia-reperfusion injury-Via pathways involving reactive oxygen species, neutrophil adhesion, and local vasoconstriction, HBOT has an overall blunting effect on ischemia-reperfusion injury

It is also of critical importance in the anesthetized patient to stop any inhaled nitrous, as this can cause bubbles to continue to grow even after the initial insult!

Of the previously explored adjunctive therapies (lidocaine, aspirin, NSAIDs, anticoagulation, steroids), lidocaine is the only therapy with reasonable data in support of its use.  It is not considered standard of care in CAGE, but a single dose of 1-2mg/kg IV can be considered.  

Lastly, just as in other types of major CNS injuries, it is important to avoid hyperthermia or hyperglycemia