Sapienza, Università di Roma
Ospedale Sant’Andrea
Dipartimento di Cardiochirurgia
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
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
Sapienza, Università di Roma
Ospedale Sant’Andrea
Dipartimento di Cardiochirurgia
Objective
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)
Sapienza, Università di Roma
Ospedale Sant’Andrea
Dipartimento di Cardiochirurgia
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
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
Results
• A total of 136 studies were identified, and only 35 were finally included
136 papers
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)
35 papers
Sapienza, Università di Roma
Ospedale Sant’Andrea
Dipartimento di Cardiochirurgia
Results
Study population
uACP
bACP
Time frame, years
2002-2011
1998-2011
na
Patients, n
1761
3791
na
Age, years
59.8±2.6
62.2±5.6
0.35
Male sex, n (%)
926 (54.6)
2422 (63.9)
0.92
CPB time, mins
181.5±45.7
203.9±40.6
0.16
Xclamp time, mins
124.8±37.9
121.6±35.9
0.84
CA time, mins
40.6±14.5
42.9±18.6
0.71
CA temp, celsius°
24.2±2.6
26.2±3.8
0.12
Emergency, n (%)
751 (55.4)*
1415 (48.9)**
0.53
* Total of 1355 pts
** Total of 2895 pts
p value
Sapienza, Università di Roma
Ospedale Sant’Andrea
Dipartimento di Cardiochirurgia
Results
Meta-analysis of outcomes
8.0% (95CI 6.3-10.1)
Mortality
p=0.92
PND
p=0.37
TND
p=0.03
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)
Sapienza, Università di Roma
Ospedale Sant’Andrea
Dipartimento di Cardiochirurgia
Results
• Meta-regression analysis showed that age, emergency, CPB time, CA time,
and CA temperature did not influence effect size estimates
Regression
of CAtime
time
Mortality
Regression
of ACC
onfor
Logit
event rate
Regression
oftime
CA time
for TND
Regression
of ACC
on Logit
event rate
2,00
4,00
1,00
2,80
0,00
1,60
-1,00
Logit event rate
Logit event rate
0,40
-0,80
-2,00
-3,20
-2,00
-3,00
-4,00
-5,00
-4,40
Q-model 0.06
p=0.74
-6,00
-5,60
Q-model 0.16
p=0.43
-6,80
-8,00
3,30
12,54
21,78
31,02
40,26
49,50
58,74
67,98
77,22
86,46
-7,00
-8,00
4,40
13,52
22,64
31,76
40,88
95,70
50,00
59,12
68,24
77,36
86,48
95,60
ACC time
Regression
of ACC
Logit
event rate
ACCon
time
Regression
of CAtemp
temp
for
Mortality
Regression
oftemp
CA temp
for TND
Regression
of ACC
on Logit
event rate
4,00
2,00
2,80
1,00
1,60
0,00
-1,00
Logit event rate
Logit event rate
0,40
-0,80
-2,00
-3,20
-4,40
-2,00
-3,00
-4,00
-5,00
Q-model 0.07
p=0.79
-5,60
-6,80
Q-model 0.08
p=0.66
-6,00
-7,00
-8,00
-8,00
18,40
20,32
22,24
24,16
26,08
28,00
ACC temp
29,92
31,84
33,76
35,68
37,60
18,40
20,32
22,24
24,16
26,08
28,00
ACC temp
29,92
31,84
33,76
35,68
37,60
Sapienza, Università di Roma
Ospedale Sant’Andrea
Dipartimento di Cardiochirurgia
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
Regression of CA time for PND
Regression of ACC time on Logit event rate
Regression of CA temp for PND
Regression of ACC temp on Logit event rate
1,00
1,00
Q-model 42.0
p<0.0001
0,10
-0,80
0,10
-0,80
-1,70
Logit event rate
Logit event rate
-1,70
-2,60
-3,50
-4,40
-2,60
-3,50
-4,40
-5,30
-5,30
-6,20
-6,20
-7,10
-7,10
-8,00
Q-model 16.5
P<0.0001
-8,00
3,30
12,54
21,78
31,02
40,26
49,50
ACC time
58,74
67,98
77,22
86,46
95,70
18,40
20,32
22,24
24,16
26,08
28,00
29,92
31,84
33,76
35,68
37,60
ACC temp
• Egger’s test excluded publication bias for mortality (p=0.36), PND (p=0.31),
and TND (p=0.48)
Sapienza, Università di Roma
Ospedale Sant’Andrea
Dipartimento di Cardiochirurgia
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
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