DISCUSSION
The optimal cerebral protection strategy during aortic arch surgery remains controversial. The main finding of this network meta-analysis is that the application of moderate and mild hypothermia in combination with selective cerebral perfusion is associated with lower incidence of postoperative stroke, when compared with DHCA alone or in combination with any selective cerebral perfusion strategy. To the best of our knowledge, this is the first network meta-analysis on the three most commonly used hypothermia levels.
Historically, the implementation of DHCA seemed to be safe under 40 minutes 16. The general impression exists among the surgeons that lower temperatures are safer. Despite well-recognized complications of deep and profound hypothermia, wide-ranged implementation of moderate temperatures is not fully adopted. This emerges from concerns that still exist due to suboptimal organ protection of non-DHCA approaches, even with the addition of selective cerebral perfusion 17.
Recently the collaborative efforts of the ARCH registry have resulted in more published global data on this topic. Keeling and colleagues18 reported the outcomes of 3265 patients from the ARCH International aortic database who underwent total aortic arch replacement with either MHCA or DHCA in conjunction with ACP. Comparing the results of 669 propensity-score matched pairs, despite shorter CPB, ACC and cerebral perfusion times in MHCA group, no significant differences in operative mortality and postoperative neurological complications were found.
The collaborative effort of the same investigators resulted in the meta-analysis by Tian and colleagues 4 in which they included 9 studies comparing DHCA with MHCA in conjunction with ACP. In line with our findings, they reported significantly higher permanent neurological dysfunction in the DHCA group compared with MHCA in combination with ACP. A more recent pairwise meta-analysis by Tian et al. 5 compared “cold” with “warm” hypothermic circulatory arrest groups in conjunction with ACP. Mean hypothermic circulatory arrest temperatures were 20.3 ⁰C and 26.5⁰C in the cold and warm groups, respectively. Significantly more emergent cases were in the “cold” hypothermia group. At the same time, the proportion of total aortic arch replacements and bilateral ACP were similar. In line with our founding, warmer temperatures showed significantly reduced perioperative mortality. Furthermore, they found a significant reduction in transient neurologic dysfunction, postoperative dialysis, ventilation duration and intensive care unit stay compared with colder hypothermic circulatory arrest. No significant reduction in postoperative stroke was found.
Our sensitivity analysis of solely RCT and PSM studies revealed that DHCA is associated with sustained higher postoperative risk of stroke when compared with MHCA and mild HCA in combination with selective cerebral perfusion. There was also a sustained significantly higher risk of operative mortality for MHCA when compared with mild HCA. Though further differences between DHCA, MHCA and mild HCA for the outcome operative mortality are not holding up. Reason behind this result could be underpowered analysis or the adjusted confounding associated with the network meta-analysis in unadjusted observational studies.
There is sparse published data on the effect of hypothermia level on postoperative spinal, renal and liver function. Recently, Liang et al. compared the impact of MHCA with DHCA on postoperative renal function by performing a pairwise meta-analysis of 14 observational studies6. They concluded that MHCA significantly reduced the postoperative incidence of renal failure and the need for renal replacement therapy. Unfortunately, we were unable to find any differences in the postoperative occurrence of AKI.
The shift towards warmer temperatures persists but is not uniform17. The same restraint exists in the adaptation of more evolved selective cerebral perfusion techniques, such as unilateral cerebral perfusion 19. Skeptics advocate that it might not sufficiently supply the contralateral hemisphere and cause undetectable transient neurological injuries by conventional imaging methods 20.
As the debate about optimal cerebral protection continues, this comprehensive network-meta analysis incorporating the existing data illustrates that despite the current concerns about warm cooling temperatures, moderate and mild hypothermic circulatory arrests in conjunction with selective cerebral perufsion provide improved data are that may support daily practice as well as direct designs of future multicentric randomized controlled trials in this regard.