28 T. Rath et al.: J Extra Corpor Technol 2026, 58, 19 – 31
transmission. Using glycerin, matched to a blood hematocrit of 25 %, showed more GME transmission when compared with crystalloid, but still less compared to bovine blood. These findings align with similar work by Harea et al., supporting the hypothesis that blood proteins may facilitate GME transmission [ 41 ].
Another potential mechanism contributing to GME transmission occurs at the reservoir’ s air-blood interface. The reservoir design may explain discrepancies in GME count when comparing manufacturer reservoirs. It speaks to the reservoir’ s ability to promote bubble buoyancy, keep big bubbles big, and remove or filter the air. At this interface, inadvertent mixing of blood and air creates a foam that ruptures, generating numerous smaller bubbles into the circuit [ 40 ]. CPB circuits are designed to remove macro-air effectively but are less efficient with micro-air. The air-blood interface remains an unavoidable factor when utilizing open venous reservoirs. In the future, we hope to compare manufacturer reservoirs and explore how reservoir design might play a role in GME transmission.
While there are many potential mechanisms behind GME transmission, improving procedural practices can help reduce the amount of GME transmitted to the patient. By refining techniques to minimize these contributing factors, it may be possible to reduce GME exposure during CPB and improve patient outcomes.
Clinical implications
Introducing large air bubbles into the arterial circulation is a well-established iatrogenic cause of cerebral ischemia, which can result in multifocal ischemic injury or even death [ 42, 43 ]. While various CPB techniques and equipment, such as level sensors and gross air detectors, are employed to prevent the transmission of large air bubbles, small, unfiltered air bubbles may still pose a risk. The clinical question that needs to be answered is whether GME harms the patient. Unfortunately, the literature on this issue is divided, and the GME load required to produce neurologic impairment in humans is difficult to establish. Current research is focused on determining how GME load can affect potential occlusion of critical capillary beds, endothelial irritation, and the inflammatory response.
Managing iatrogenic risks of GME introduction remains challenging, and the process may be more patient-dependent and multifactorial than previously thought [ 44 ]. GME, fat, and other microemboli can deform within the brain, disrupting the blood-brain barrier and contributing to neurological injury [ 45 ]. Other organs are also impacted by the systemic effects of microemboli [ 14, 45 – 47 ]. These smaller bubbles can directly block capillaries or coalesce into larger bubbles, thereby increasing the risk of vascular obstruction. Most in vivo studies investigating the pathological effects of air bubbles introduce known volumes of air; however, the size( diameter) of the bubbles is often not specified, which is crucial when examining GME [ 48 ]. Moreover, air can be introduced into the venous circulation, compromising pulmonary function, or paradoxically enter the arterial circulation through atrial septal defects [ 43 ].
Aside from stroke risk, postoperative cognitive dysfunction( POCD) remains a significant concern. As with air introduction,
POCD is multifactorial and patient dependent. Contributing factors include the number, volume, and type( lipid or air) of emboli [ 43, 49 ]. These complex and varied causes make it challenging to establish a clear threshold of GME that leads to neurological impairment [ 43, 45 ].
Growing evidence suggests that neurological complications following CPB are not always due to significant ischemic events but instead to endothelial irritation and inflammation caused by microemboli [ 45, 46 ]. GME is a potent endothelial irritant that triggers an inflammatory cascade. When a GME contacts the endothelial surface, an inflammatory response is prompted since it is perceived as a foreign insult. As CPB progresses, inflammatory markers accumulate throughout the body, contributing to a systemic inflammatory response associated with increased morbidity and mortality. However, some studies have failed to demonstrate a significant relationship between GME and inflammatory biomarkers [ 50 ]. In addition to increased GME, another problem related to using a cardiotomy suction reservoir is the blood suctioned from the surgical field. This blood contains vasoactive cytokines and inflammatory markers, which are not filtered before being reintroduced into the patient. Once reintroduced, these substances exacerbate endothelial inflammation, contributing to further complications [ 9, 51 – 53 ].
Whether or not the evidence suggests that tiny bubbles may cause harm to a patient, it seems logical to take practical steps to minimize perioperative GME exposure. Our study found that GME load can be reduced by implementing easily implemented protocols, such as maintaining safe suction speeds and reservoir levels.
Limitations of the study
It is noteworthy that this study measured GME for only 3 min. In preparation for this study, we performed several test runs lasting over an hour with continuous aerated pump suction. We found that the same level of GME activity was maintained throughout the entire period. A typical CPB case may last significantly longer, suggesting that the amount of GME passing through the circuit and then to the patient could be substantial. We also only utilized one sucker. Perfusionists often have multiple suction and vent pumps running simultaneously, which would also increase the GME count beyond our findings. The amount of air injected into the sucker flow in this study was 0.20 L / min for all the runs. It would be difficult to determine how much air gets entrained from pump suction during a clinical case, but the rate we chose was similar to that seen on CPB. Although our results indicate that the blood suction flow rate affects GME transmission, it would be interesting to see if varying the airflow would increase GME count or if GME depended more on the suction blood flow rate.
Due to the study design, we were unable to compare the differences between reservoir and oxygenator manufacturers. To compare different reservoirs and oxygenators accurately, we should have tested all three manufacturers’ circuits using the same biological replicate( a pail of bovine blood). Therefore, we pooled the results of all reservoir and oxygenator manufacturers.