1. Unilateral versus Bilateral Antegrade Cerebral Protection During Circulatory Arrest in Aortic Surgery: A Meta-Analysis of 5462 patients Emiliano Angeloni, Umberto Benedetto, Ivan Stigliano, Simone Refice, Giovanni Melina, and Riccardo Sinatra Department of Cardiac Surgery, “Sapienza” University of Rome, S. Andrea Hospital, Rome, Italy Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia

2. Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia Background During complex aortic surgery cerebral protection can be achieved with different strategies In the current practice hypothermic circulatory arrest (CA) associated to cerebral perfusion is widely used Antegrade cerebral perfusion (ACP) has been reported to grant longer “safe period” and lowest rates of postoperative mortality and neurologic events In this setting, the use of bilateral (b-ACP) or unilateral (u-ACP) cannulation of the supra-aortic vessels remains controversial

3. To determine whether cerebral protection achieved by means of bACP or uACP results in different clinical outcomes in terms of Mortality, Permanent Neurologic Disease (PND), and Transient Neurologic Disease (TND) Objective Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia

4. Methods A systematic review and meta-analysis was performed with the use of the Meta-analysis of Observational Studies in Epidemiology guidelines PubMed, Embase and Cochrane library were searched for studies reporting on postoperative mortality, permanent neurologic disease and transient neurologic disease after aortic surgery performed with the use of ACP QUORUM on 17/07/2011: antegrade[All Fields] AND ("cerebrum"[MeSH Terms] OR "cerebrum"[All Fields] OR "cerebral"[All Fields] OR "brain"[MeSH Terms] OR "brain"[All Fields]) AND ("perfusion"[MeSH Terms] OR "perfusion"[All Fields]) AND protection[All Fields] Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia

5. Methods Comparison between bACP and uACP by means of analysis of heterogeneity (Cochrane Q-statistic) Causes for heterogeneity explored throughout subgroup analyses Publication bias detected by Egger’s regression test Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia

6. Results A total of 136 studies were identified, and only 35 were finally included Case reports (n=11) Pediatric papers (n=2) Multiple publications (n=33) Data not available (n=14) Animal studies (n=18) Review articles (n=16) Alternative techniques (n=7) 136 papers 35 papers Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia

7. Results Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia uACPbACPp value Time frame, years2002-20111998-2011na Patients, n17613791na Age, years59.8±2.662.2±5.60.35 Male sex, n (%)926 (54.6)2422 (63.9)0.92 CPB time, mins181.5±45.7203.9±40.60.16 Xclamp time, mins124.8±37.9121.6±35.90.84 CA time, mins40.6±14.542.9±18.60.71 CA temp, celsius°24.2±2.626.2±3.80.12 Emergency, n (%)751 (55.4)*1415 (48.9)**0.53 * Total of 1355 pts ** Total of 2895 pts Study population

8. Results Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia Mortalityp=0.92 PNDp=0.37 TNDp=0.03 8.0% (95CI 6.3-10.1) 7.8% (95CI 5.4-11.2) 7.1% (95CI 4.2-11.8) 4.5% (95CI 1.9-10.6) 12.1% (95CI 7.7-18.5) 4.5% (95CI 1.9-10.1) Meta-analysis of outcomes

9. Results Meta-regression analysis showed that age, emergency, CPB time, CA time, and CA temperature did not influence effect size estimates Regression of CA time for Mortality Regression of CA temp for Mortality Regression of CA time for TND Regression of CA temp for TND Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia Q-model 0.07 p=0.79 Q-model 0.16 p=0.43 Q-model 0.08 p=0.66 Q-model 0.06 p=0.74

10. Regression of CA temp for PND Results As expected, longer CA times and lower CA temperatures were associated with higher rates of PND, but as shown in Table 1 there was no difference in their prevalence between uACP and bACP groups Egger’s test excluded publication bias for mortality (p=0.36), PND (p=0.31), and TND (p=0.48) Regression of CA time for PND Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia Q-model 42.0 p<0.0001 Q-model 16.5 P<0.0001

11. Conclusions This meta-analysis shows that both bACP and uACP have similar postoperative mortality and PND rates following CA for complex aortic surgery The statistically significant lower rate of TND shown in uACP group may be due to the different definitions adopted to make diagnosis of such a heterogeneous cohort of neurologic alterations Grade of hypothermia, CA time, CPB time, age, and emergency status did not affect results Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia

12. Conclusions Even if resulting from an accurate, large meta-analysis, these findings should be interpreted with some caution because the design of the studies analyzed lacks of random allocation and the indication for the different ACP strategies is not univocal Sapienza, Università di Roma Ospedale Sant’Andrea Dipartimento di Cardiochirurgia