Page 25 - ANZCP Gazette NOVEMBER 2022

Jabur et al.
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Table 4. Comparisons of the gaseous, solid and total embolic counts in the right versus left middle cerebral arteries.
Emboli
All operations Gaseous
Solid
Total
Closed chamber operations
Gaseous Solid Total
Open chamber operations Gaseous
Solid Total
aMiddle cerebral artery. bInterquartile range.
Right MCA,a Median (IQRb)
804 (343–2186) 64 (16–217)
985 (397–2422)
650 (271–1110) 22 (11–64)
683 (295–1201)
1275 (570–3628) 130 (68–416)
1515 (654–4089)
Left MCA,a Median (IQRb)
331 (174–676) 41 (23–96)
376 (198–769)
192 (120–331) 26 (15–34)
206 (144–378)
517 (335–1476) 96 (44–190)
621 (376–1727)
p-Value
<0.001 0.029 <0.001
<0.001 0.985 <0.001
<0.001 0.013 <0.001
Thus, although it is unarguable that large bubbles entering the cerebral vasculature are capable of obstruct- ing flow and causing multifocal ischaemic injury,16 small bubbles in the size range typically seen in cardiac sur- gery will not do this. This is not to say that exposure to small arterial bubbles is benign. Indeed, there is sub- stantial evidence that non-obstructing exposure of the arterial or arteriolar endothelium to the passage of bub- bles may have relevant pathophysiological effects. For example, the passage of bubbles through cerebral vessels can disrupt the blood-brain barrier17 and activate leuko- cytes with consequent reduction of cerebral perfusion.18 In decompression sickness, the passage of microbubbles through the skin microcirculation has been associated with the appearance of a florid inflammatory rash in the overlying skin.19
In keeping with these examples of bubble induced physical and inflammatory injuries to blood vessels, there is related interest in disruption of endothelial phys- iology. The vascular endothelium has a critical role in mediating vasoreactivity through autocrine and parac- rine functions that can mediate vasoconstriction and vasodilation. There is evidence from multiple studies that bubble interactions with endothelium may damage endothelium20–22 and impair these functions.6,7,23 Some of these studies arise in the context of diving where the intravascular inert gas bubbles formed during decom- pression are similar in size24 to those recorded in the cer- ebral vessels during cardiac surgery. It is therefore plausible that exposure to small bubbles during cardiac surgery may cause damage to the endothelium and hin- der cerebral endothelial function (such as blood flow autoregulation), thereby rendering the brain more sus- ceptible to harm from other (perhaps multiple) injurious events, such as low cerebral perfusion pressures, that might otherwise be tolerated. A recent study by Ono et al.,5 which incorporated measurement of cerebral
autoregulation in real-time during cardiopulmonary bypass found a higher incidence of stroke in patients who became dysautoregulated than those who did not. The cause of cerebral dysautoregulation in their cohort of patients was not elucidated and, although likely multi- factorial, it is plausible that bubble exposure could play an as-yet uninvestigated role.
While there has been a substantial focus on reduc- ing the embolic load from the bypass circuit,25 emboli generated from the surgical field have received less attention. Numerous emboli can reach the brain if there is inadequate de-airing of the heart chambers before the resumption of cardiac output, particularly in open-chamber procedures.3,26,27 Our results con- firm that the introduction of comparatively high numbers of bubbles to the arterial circulation after open-chamber procedures still occurs in the modern era, reflecting the fundamental difficulty of completely "de-airing" the heart in these operations. It may also reflect reticence among surgeons to invest more time in the process given that there is yet to be a convincing demonstration that reducing exposure to small bub- bles matters. Correlating emboli numbers against post- operative cognitive function has resulted in conflicting results.1,2 However, the implicit assumption that serial administration of neurocognitive tests in relatively small studies is sensitive enough to detect cognitive deficits explicitly caused by just one of many potential contributors may be flawed.2 An alternative approach to which the present analysis is a prelude is to investi- gate the role of bubble exposure in causing cerebrovas- cular dysfunction identified by others5 as a significant risk factor for neurological injury in cardiac surgery. Thus, the next step is to use the widely differing bubble exposure in closed- versus open-chamber surgery patients, confirmed in the present study, as a natural human experimental setting for evaluating the effect of
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