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Eur J Cardiothorac Surg 2005;28:102-103
© 2005 Elsevier Science NL

Editorial comment

R.S. Bonser * , D.K. Harrington

University Hospital Birmingham NHS Trust, Birmingham, UK

* Corresponding author. Address: Cardiothoracic Surgery Unit, Queen Elizabeth Medical Centre, University Hospital, Edgbaston, B15 3RB Birmingham, UK. Tel.: +44 1214 721311; fax: +44 1216 272542. (Email: r.s.bonser{at}bham.ac.uk).

In an era in which mortality risk for complex cardiac surgery is reducing, there is an increased focus on reducing morbidity. Brain injury following cardiac surgery remains important and represents a spectrum through grave irrecoverable global injury, focal irreversible and reversible neurological deficit, transient post-operative neurological dysfunction and more subtle neurocognitive change [1,2]. In this issue, Miyairi et al. [3], report neurocognitive outcomes in two series of patients, 28 undergoing coronary artery bypass surgery (CABG) and 46 undergoing aortic arch surgery utilizing retrograde cerebral perfusion (RCP), of which 19 underwent RCP for durations >60min. This study is the first of its kind to compare neurocognitive outcome between RCP and a standard CABG group, i.e. a group undergoing cardiopulmonary bypass but not requiring a period of hypothermic circulatory arrest. From our own experience [4,5] thoracic aortic patients are a difficult group to study neurocognitively and this cohort of 46 aortic patients is the largest group of RCP patients to be studied so far. The authors are, therefore, to be congratulated on the performance of a difficult clinical task. Moreover, their study demonstrates no mortality and no reported stroke or transient neurological dysfunction.

The authors report a significantly worse neurocognitive outcome in patients undergoing RCP >60min compared to CABG and equivalent outcome to CABG in patients undergoing shorter RCP durations. These data lead to two important inferences; first, we might infer that RCP <60min is neurologically safe and causes no more brain injury than a standard CABG procedure, and second, we can infer that RCP cannot afford extended brain protection during hypothermic circulatory arrest (HCA) and that like HCA alone, the risk of brain injury following RCP increases after 60min of arrest/RCP duration.

Is the first inference correct? Miyairi et al. present their data as the difference in mean Z-scores between pre- and post-operative performance for each test performed. They do not report the group incidence of significant neurocognitive change by accepted criteria (e.g. >20% or >1 SD decline in 2 or more tests.), the group change in raw scores for each test or an overall neurocognitive change score based on the Z score analysis. A cursory inspection of the early testing interval for CABG and short-RCP groups suggest that the S-RCP group either deteriorated more or improved less in 9 of 11 tests and that overall neurocognitive deterioration was greater than for CABG (Fig. 1 ). Thus, the reason for failing to detect a difference at the early interval in S-RCP patients probably represents a type II statistical error in an underpowered study.



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  		Fig. 1. Mean overall Z score changes (±SD) in each group (data derived from Miyairi et al.).

 
Despite this reservation, there appears to be very little true difference, if any, in neurocognitive outcomes between CABG and S-RCP at 4–6 months. There is a clear suggestion that early change has improved in the S-RCP group but persists in the L-RCP group and may be irreversible; a finding supported by previous studies [4–6]. The study by Miyairi et al. is limited by the absence of a hypothermic circulatory arrest group and the authors acknowledge this. Thus, their data cannot contribute to the debate of whether RCP can augment the brain protection afforded by HCA [7].

There is now increasing evidence of the failure of RCP to provide brain metabolic benefit during aortic surgery. Theoretically, RCP may better maintain intracranial hypothermia, flush out toxic catabolites and embolic debris and provide oxygen and metabolic substrate support during an otherwise ischaemic period. Its main potential disadvantage is intracranial venous hypertension and edema. Although, canine studies suggest metabolic benefit and reversed brain perfusion has been demonstrated in humans [8–10] and despite non-randomized clinical series reporting reduced mortality and morbidity [11–14], the weight of evidence is shifting against RCP as a brain protection adjunct. Experimentally and clinically, the true reversal of brain blood flow in humans and comparable species is miniscule and fails to provide effective metabolic support [9,15–17]. If RCP flows are increased, intracranial venous hypertension ensues, increasing brain edema and compromising outcome [16]. The data supporting a role for maintenance of intracranial hypothermia and embolic protection is also unconvincing [17–19]. This non-benefit has been similarly reflected in more recent clinical reports [6,20]. No studies have demonstrated a neurocognitive benefit of RCP over HCA alone and some suggest a worse outcome [4,6,21]. These studies have also demonstrated a high incidence of early neurocognitive deterioration improving over time analogous to the changes seen in Miyairi's study.

The duration of HCA and RCP have both been previously identified as risk factors for stroke and transient neurological injury [22]. The current study demonstrates that this increasing risk also extends to neurocognitive deterioration.

Overall, RCP appears to provide no benefit over standard HCA in clinical practice and does not extend the safe duration of HCA to the time necessary to complete a complex arch repair. As suggested by the authors of this paper, attention is now focused upon the use of selective antegrade cerebral perfusion (SACP) as a protective adjunct, particularly for longer durations of circulatory arrest [5,23,24].

In conclusion, the contribution of Miyairi et al. is an important addition to the literature regarding RCP and clearly demonstrates the inadequacy of RCP to augment brain protection when arrest durations >60min are required. Rigorous investigation of alternatives, especially SACP, remains necessary to improve brain outcomes in aortic arch surgery.


   References
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