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Journal of Cardiac Surgery

Volume 2023, Article ID 8887221, 12 pages
https://doi.org/10.1155/2023/8887221

Review Article
Efficiency and Safety of Temperatures Management in Aortic Arch
Surgery: A System Review and Meta-Analysis

Yang Yu, Zheng Ding, Enyi Shi, and Tianxiang Gu

Department of Cardiac Surgery, Te First Afliated Hospital of China Medical University, Shenyang, Liaoning, China

Correspondence should be addressed to Tianxiang Gu; sey2004@sina.com

Received 23 April 2023; Revised 21 May 2023; Accepted 22 June 2023; Published 25 August 2023

Academic Editor: Oktay Korun

Copyright © 2023 Yang Yu et al. Tis is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective. Te study evaluates the safety and efcacy of hypothermic cardiac arrest (HCA) at various temperatures in aortic arch
surgeries. Methods. We conducted a literature search in PubMed, Google Scholar, and Embase databases. For single proportion
assessments, we employed fxed-efect and random-efect models in the general linear mixture model and the inverse variance
model for other computations. We analyzed factors such as age, sex, operation time, and postoperative complications, with
subgroup and metaregression analyses. We used funnel plots to depict potential publication bias. Results. Our research in-
corporated 43 papers with 34,797 cases. HCA temperatures were divided into fve groups (A: 30–32°C, B: 28–30°C, C: 26–28°C, D:
24–26°C, and E: <24°C). Tere is no statistically signifcant diference in myocardial ischemia time (P = 0.90) and isolated cerebral
perfusion (ICP) time (P = 0.95). Groups A and C have the best performance in avoiding postoperative complications including
transient nerve injury (TNI), permanent nerve injury (PNI), renal failure (RF), and mortality occurrence rate. Group A has the
lowest occurrence rate in PNI (3%) and mortality (3%). Group C has the lowest RF incidence (5%). Conclusion. Maintaining
temperatures of 30–32°C in en bloc anastomosis or 26–28°C during arch replacement with separate grafts can signifcantly reduce
complications including PNI, RF, and in-hospital mortality.

1. Introduction [5–7], we seek to investigate the most efective temperature

Aortic arch surgery is a highly complex procedure within
cardiac surgery. Techniques such as hypothermic cardiac
arrest (HCA) and selective perfusion are critical in main-
taining circulation across multiple organs during open aortic
arch surgery. Traditionally, organs have been supported with
deep hypothermic cardiac arrest (DHCA) [1, 2]. However,
the optimal temperature to induce HCA remains a con-
tentious issue. Despite DHCA’s ability to decrease the
metabolic rate and oxygen consumption of primary organs,
it concurrently leads to functional impairment [3]. With
rapid advancements in cardiac surgery and hybrid tech-
niques, the duration of HCA has been progressively reduced.
Concurrently, our understanding and methodologies for
monitoring and safeguarding organ function have signif-
cantly improved [4].
With an increasing number of centers reporting satis-
factory results using moderate HCA in aortic surgeries
for HCA during aortic arch replacement. We aim to strike
a balance between reducing oxygen consumption and
mitigating low-temperature injury. A number of studies
have indicated that antegrade, retrograde, and bilateral
cerebral perfusion yield comparable outcomes [8–10].
Hence, we postulate that the operation time and cerebral
perfusion temperature play a pivotal role in determining the
results of HCA during aortic arch replacement. Our goal is
to ascertain the efcacy and safety of HCA at varying
temperatures during open aortic arch surgery. We believe
that the fndings from this investigation will provide valuable
guidance for clinical practice.
2. Materials and Methods
2.1. Literature Search Strategy. Te PubMed database,
Google Scholar database, and Embase database were
searched to fnd related articles. Ten, we used these search
2 Journal of Cardiac Surgery
terms: [(“total” OR “aortic”) AND (“arch replacement”)
AND (“temperature” OR “degree” OR “°C”)]. Te inclusion
time range began in 1990, and the fnal search was updated
until Sep. 2022, with English language only. We fltered
duplicated and other felds or types of literature. Finally, we
excluded meta-analyses, case reports, letters, reviews, or
articles with either too small of a sample size (less than 25) or
low quality, as determined by missing data, fawed design,
and an overall assessment of the journal’s impact.
2.2. Inclusion Criteria. Inclusion criteria specifed that pa-
tients in the studies must have undergone aortic arch re-
placement surgery, encompassing both total arch
replacement and hemiarch replacement, and that the sur-
gical procedure must involve a median sternotomy. Addi-
tional data points to be recorded included the proportion of
male patients, patient age and distribution, cardiopulmonary
bypass (CPB) time, myocardial ischemia time, isolated ce-
rebral perfusion (ICP) time, hypothermic circulatory arrest
(HCA) temperature, and complication rate.
2.3. Exclusion Criteria
(1) Lack of a detailed description of the operation time,
patients’ number, HCA temperature, or complica-
tion incidence
(2) Te article presented HCA-related parameters, yet
the operating procedures were not included aortic
arch replacement
2.4. Data Extraction. Two independent reviewers were in-
volved in data extraction, with a cardiac surgery specialist
available for consultation on specifc descriptions. Data were
organized and input into a form that included the following
categories: (a) author, (b) HCA classifcation (mild, mod-
erate, and deep) and HCA temperature (or core tempera-
ture), (c) number of patients, mean age, age standard
deviation (SD), male proportion, (d) CPB time, CPB SD,
cardiac ischemia time, cardiac ischemia time SD, ICP time,
ICP SD, (e) transient nerve injury (TNI) number and
proportion, permanent nerve injury (PNI) number and
proportion, renal failure (RF) number and proportion, mean
ventilation time and SD, mean 24-hour drainage volume and
SD, and mortality and proportion.
For the author’s naming convention, we adopted the
format of the author’s name followed by the year of publication
(e.g., He2019). If an article presented two or more temperature
comparisons, the sufxes “.1”, “.2”, and “.3” were employed for
distinction (e.g., Dong2020.1 and Dong2020.2). Furthermore,
we divided our data into fve groups (A: 30–32°C, B: 28–30°C,
C: 26–28°C, D: 24–26°C, and E: <24°C) based on the core
temperatures recorded during HCA. Core temperature, as
indicated by rectal, bladder, and nasopharyngeal measure-
ments, was considered. As nasopharyngeal temperature tends
to be higher in the same individual, any such reading was
assigned to the next higher group (e.g., a reading of 24–26
degrees would be classifed under group C).
In the analyzed articles, the cross-clamp time was treated
as cardiac ischemia time, and the circulatory arrest time was
considered as ICP time. If both ICP time and circulatory
arrest time were provided, we defaulted to using ICP time.
We included four types of complications and post-
operative evaluation parameters. Te complications con-
sidered were TNI, PNI, renal failure, and mortality. TNI
refers to largely reversible neurological complications
present before discharge, while PNI encompasses irrevers-
ible conditions such as stroke, paralysis, paraplegia, and
hemiplegia. Renal failure includes indications of kidney
replacement, acute kidney injury (AKI) stage 3, and
hemofltration. Mortality includes 30-day mortality, in-
hospital mortality, and intraoperative mortality. Ventila-
tion time and postoperative 24-hour drainage were extracted
as evaluation variables.
2.5. Statistical Analysis. In this study, we combined data on
gender, operation time, TNI, PNI, RF, and mortality to
quantify the impact of cerebral protection temperature
during HCA. We utilized complication and mortality rates
to refect the risk associated with the aortic arch replacement
procedure. To mitigate potential biases, such as those arising
from primary diseases (e.g., diabetes and hypertension) and
diagnoses (e.g., acute type A dissection, Marfan syndrome,
and degenerative aneurysm) that could afect certain pa-
rameters (such as complication or mortality rate), we used
the general linear mixture model (GLMM) for single pro-
portions and the inverse variance (IV) model for other
variables to analyze data distribution [11, 12]. We adjusted
the weights of the variables using both fxed-efects and
random-efects models in the IV approach to help capture
random attributes and decrease risk bias. Te
Knapp–Hartung adjustment was nested to lessen hetero-
geneity among the datasets, and maximum likelihood es-
timation was applied to constrain the model, deriving
optimal parameters and a wider 95% confdence
interval [13].
We quantifed heterogeneity using the inconsistency
index I2 (I2 > 25% suggests low heterogeneity; I2 > 50%,
moderate; and I2 > 75%, high) along with the Q statistic and
P value [14]. If P > 0.05 and I2 < 50%, we applied the fxed-
efect model; if not, we used the random-efects model to
prevent false positives due to high heterogeneity and low
sample quality, specifcally when P ≤ 0.05 and I2 > 50%
[15, 16]. We used funnel plots to visually assess publication
bias. For subsequent bias correction, we utilized the trim-
and-fll model following the Egger test for continuous
variables or the Peters test for binary proportion variables
[17]. If the postcorrection P value was greater than or equal
to the precorrection P value, we used the precorrection
results; otherwise, we used the postcorrection results. For
articles using median and quartile ranges in lieu of mean and
SD values, we used transformation tools developed by Luo
and Wang [18, 19].
Lastly, we conducted a subgroup analysis of all combined
efect sizes. Additionally, through a metaregression, we
sought to identify potential relationships between age,
Journal of Cardiac Surgery 3

Identification of studies via databases and registers

Records identified from:

Identification
Pubmed (n = 8624)
Records removed before screening:
Google Scholar (n = 1688)
Duplicate records removed
Embase (n = 873)
(n = 2763)
Total
n = 11815

Records excluded on title &

abstract:
Title & abstract screened Not in the field of interest
(n = 9052) (n = 6997)
Case report (n = 1573)
Screening

Excluded on full text:

Not in the field of interest
Full text articles assessed for
(n = 424)
eligibility (n = 482)
Cases less than 25 (n = 10)
Low quality (n = 5)
Included

Articles eligible for meta-analysis

(n = 43)

Figure 1: Te main search process.

gender, and CPB time with the outcomes. All processes were 0.69; 0.73, P < 0.01). Te Egger test and Peters test for the
executed using R Studio software (version 1.4.1717) with the funnel plot revealed that the P value for age is 0.4423 and for
“meta”, “metafor”, “dmetar”, and “ggplot2′ packages sex is 0.2243, indicating no publication bias.
[20–23].

3. Result 3.3. Main Operation Time Presentation. We also performed

3.1. Literature Search. Te main search process is shown in
Figure 1. We searched 11815 papers, of which 43 papers and
34797 cases were selected [5–7, 24–63]. Te rest of them
include duplicated (2763), not in the feld of interest (7412),
case report (1573), case is less than 25 (10), and paper has low
quality (5). All articles, Newcastle–Ottawa Scale assessments,
and data availability are presented in the statement part.
3.2. Age and Sex Distribution. Te statistical analysis results
for age and male distribution (Figure 2) indicate that the
pooled age is 59.1 (95% confdence interval (CI): 56.5; 61.7),
exhibiting no statistically signifcant variation between
groups (P � 0.06). However, the proportion of males is
statistically signifcant (pooled proportion: 0.71, 95% CI:
the same pooled statistical analysis on CPB time, myocardial
ischemia time, and ICP time. Te results (Figure 3) showed
that CPB has intergroup diferences (P < 0.01,
A < C < B < D < E), while the others do not (P � 0.90 and
P � 0.95). Te pooled results showed that the mean value of
CPB is 189.27 (95% CI: 182.04; 196.5), myocardial ischemia
time is 113.89 (95% CI: 107.37; 120.36), and ICP time is 32.81
(95% CI: 28.33; 37.28). Te Egger test for the funnel plot
revealed that the P value for CPB is 0.8945, and no publi-
cation bias was detected.
3.4. Complications and Mortality. We used the random-
efect model to summarize the TNI, PNI, RF, and mortal-
ity, respectively. A pooled forest plot showed the main re-
sults of TNI and PNI proportion (Figure 4).
4 Journal of Cardiac Surgery

Study or Weight Mean Mean Study or

Mean SD Total Events Total GLMM, Random, 95% CI GLMM, Random, 95% CI
Subgroup (%) IV, Random, 95% CI IV, Random, 95% CI Subgroup
label = A= 30-32 °C label = A= 30-32 °C 0.0
He2019 51.30 10.9000 59 1.7 51.30[48.52; 54.08] He2019 47 59 0.80 [0.67; 0.89]
Toyama2009 68.90 10.7000 26 1.6 68.90 [64.79; 73.01] Toyama2009 14 26 0.54 [0.33; 0.73]
Urbanski2019 69.00 10.0000 46 1.7 69.00 [66.11;71.89] Urbanski2019 29 46 0.63 [0.48; 0.77]
Urbanski2012 63.00 13.0000 347 1.7 63.00 [61.63; 64.37] Urbanski2012 238 347 0.69 [0.63; 0.73] 0.5
Urbanski2013 66.00 11.0000 131 1.7 66.00 [64.12; 67.88] Urbanski2013 67 131 0.51 [0.42; 0.60]
Urbanski2020 63.00 12.0000 1000 1.7 63.00 [62.26; 63.74] Urbanski2020 700 1000 0.70 [0.67; 0.73]
Zierer2011 63.00 12.0000 245 1.7 63.00 [61.50; 64.50] Zierer2011 175 245 0.71 [0.65; 0.77]
Zierer2012a 64.00 14.0000 426 1.7 64.00 [62.67; 65.33] Zierer2012a 287 426 0.67 [0.63; 0.72] 1.0
Zierer2012b 62.00 14.0000 1002 1.7 62.00 [61.13; 62.87] Zierer2012b 663 1002 0.66 [0.63; 0.69]
Zierer2014.1 66.00 9.0000 246 1.7 66.00 [64.88; 67.12] Zierer2014.1 164 246 0.67 [0.60; 0.73]

Standard Error
Zierer2014.2 65.00 11.0000 246 1.7 65.00 [63.63; 66.37] Zierer2014.2 156 246 0.63 [0.57; 0.69]
Total (95% CI) 3774 18.4 63.70 [60.60; 66.81] Total (95% CI) 3774 0.67 [0.63; 0.70] 1.5
Heterogeneity: tau2 = 19.2394; chi2 = 139.46, df = 10 (P < 0.01); I2 = 93% Heterogeneity: tau2 = 0.0312; chi2 = 29.13, df = 10 (P < 0.01); I2 = 66%
label = B= 28-30 °C label = B= 28-30 °C
Dong2020.1 50.60 12.0000 25 1.6 50.60 [45.90; 55.30] Dong2020.1 20 25 0.80 [0.59; 0.93] 2.0
Dong2021.2 46.90 12.2000 41 1.6 46.90 [43.17; 50.63] Dong2021.2 31 41 0.76 [0.60; 0.88]
EI–Sayed2018 59.00 15.0000 63 1.6 59.00 [55.30; 62.70] EI–Sayed2018 39 63 0.62 [0.49; 0.74]
EI–Sayed2017 68.00 16.000 587 1.7 68.00 [66.71; 69.29] EI–Sayed2017 405 587 0.69 [0.65; 0.73]
EI–Sayed2019 62.00 15.0000 38 1.6 62.00 [57.23; 66.77] EI–Sayed2019 25 38 0.66 [0.49; 0.80] 2.5
Kamiya2007 59.60 11.9000 31 1.6 59.60 [55.41; 63.79] Kamiya2007 24 31 0.77 [0.59; 0.90]
Leshnower2012.257.70 14.1000 277 1.7 57.70 [56.04; 59.36] Leshnower2012.2 181 277 0.65 [0.59; 0.71]
Li_Y_Yan2020.1 48.84 12.2000 130 1.7 48.84 [46.74; 50.94] Li_Y_Yan2020.1 99 130 0.76 [0.68; 0.83]
Li_Y_Yan2020.2 78.00 10.3000 230 1.7 78.00 [76.67; 73.11] Li_Y_Yan2020.2 173 230 0.75 [0.69; 0.81] 3.0
Minatoya2018.3 70.40 11.3000 67 1.7 70.40 [67.69; 73.11] Minatoya2018.3 46 67 0.69 [0.56; 0.79]
Numata2015.2 66.00 12.0000 39 1.6 66.00 [62.23; 69.77] Numata2015.2 28 39 0.72 [0.55; 0.85]
Zhang2020.1 49.80 12.5000 100 1.7 49.80 [47.35; 52.25] Zhang2020.1 75 100 0.75 [0.65; 0.83]
Zierer2017 67.00 13.0000 453 1.7 67.00 [65.80; 68.20] Zierer2017 298 453 0.66 [0.61; 0.70]
Total (95% CI) 2081 21.5 60.36 [54.61; 66.11] Total (95% CI) 2081 0.70 [0.67; 0.73] 30 40 50 60 70 80
Heterogeneity: tau2 = 88.7543; chi2 = 1007.6, df = 2 (P < 0.01); I2 = 99% Heterogeneity: tau2 = 0.0173; chi2 = 17.76, df = 12 (P = 0.12); I2 = 32% Mean
label = C= 26-28 °C label = C= 26-28 °C = group A = group D
Jassar2016 63.00 13.0000 100 1.7 63.00 [60.45; 65.55] Jassar2016 72 100 0.72 [0.62; 0.81] = group B = group E
Gong2016.2 48.60 10.7000 39 1.6 48.60 [45.24; 51.96] Gong2016.2 30 39 0.77 [0.61; 0.89]
Leshnower2014.228.40 15.7000 23 1.5 28.40 [21.98; 34.82] Leshnower2014.2 15 23 0.65 [0.43; 0.84] = group C
Li_Y_Guo2020.2 50.00 12.1000 80 1.7 50.00 [47.35; 52.65] Li_Y_Guo2020.2 60 80 0.75 [0.64; 0.84]
Shen2020.2 47.40 11.4000 37 1.6 47.40 [43.73; 51.07] Shen2020.2 30 37 0.81 [0.65; 0.92]
Suzuki2013 72.00 13.2000 105 1.7 72.00 [69.48; 74.52] Suzuki2013 85 105 0.81 [0.72; 0.88] (c)
Zhang2020.2 46.40 9.6000 147 1.7 46.40 [44.85; 47.95] Zhang2020.2 113 147 0.77 [0.69; 0.83]
Total (95% CI) 531 11.5 50.98 [38.34; 63.63] Total (95% CI) 531 0.76 [0.71; 0.80]
Heterogeneity: tau2 = 181.4922; chi2 = 423.1, df = 6 (P < 0.01); I2 = 99% Heterogeneity: tau2 = 0; chi2 = 4.35, df = 6 (P = 0.63); I2 = 0%
0.0
label = D= 24-26 °C label = D= 24-26 °C
Dong2020.2 49.80 11.0000 36 1.6 49.80 [46.21; 53.39] Dong2020.2 30 36 0.83 [0.67; 0.94]
Dong2021.1 47.00 9.9000 47 1.7 47.00 [44.17; 49.83] Dong2021.1 40 47 0.85 [0.72; 0.94]
Fang2019.2 46.10 11.0000 287 1.7 46.10 [44.83; 47.37] Fang2019.2 224 287 0.78 [0.73; 0.83]
Keeling2018.2 61.00 4.0000 2586 1.7 61.00 [60.85; 61.15] Keeling2018.2 1830 2586 0.71 [0.69; 0.73] 0.1
Kasama2019 80.00 3.0000 48 1.7 80.00 [79.15; 80.85] Kasama2019 40 48 0.83 [0.70; 0.93]
Leontyev2013 69.00 10.0000 51 1.7 69.00 [66.26; 71.74] Leontyev2013 27 51 0.53 [0.38; 0.67]
Leshnower2014.158.50 13.4000 122 1.7 58.50 [56.12; 60.88] Leshnower2014.1 78 122 0.64 [0.55; 0.72]
Leshnower2012.157.90 14.1000 223 1.7 57.90 [56.05; 59.75] Leshnower2012.1 160 223 0.72 [0.65;0.78]
Liu2020 53.80 11.5000 300 1.7 53.80 [52.50; 55.10] Liu2020 237 300 0.79 [0.74; 0.83]
Minatoya2018.2 71.10 8.4000 81 1.7 71.10 [69.27; 72.93] Minatoya2018.2 55 81 0.68 [0.57; 0.78] 0.2

Standard Error
Numata2015.1 67.00 10.0000 70 1.7 67.00 [64.66; 69.34] Numata2015.1 29 70 0.41 [0.30; 0.54]
Okada2012 69.80 13.3000 321 1.7 69.80 [68.35; 71.25] Okada2012 234 321 0.73 [0.68; 0.78]
Okita2015.1 70.50 10.1000 7038 1.7 70.50 [70.26; 70.74] Okita2015.1 5102 7038 0.72 [0.71;0.74]
Preventza2016 59.40 13.5000 118 1.7 59.40 [56.96; 61.84] Preventza2016 94 118 0.80 [0.71; 0.87]
Shen2020.1 47.50 8.9000 52 1.7 47.50 [45.08; 49.92] Shen2020.1 42 52 0.81 [0.67; 0.90] 0.3
Wang2020 47.00 2.3700 1708 1.7 47.00 [46.89; 47.11] Wang2020 1282 1708 0.75 [0.73; 0.77]
Wu2021.2 52.30 11.7000 438 1.7 52.30 [51.20; 53.40] Wu2021.2 313 438 0.71 [0.67; 0.76]
Total (95% CI) 13526 28.5 59.30 [53.92; 64.67] Total (95% CI) 13526 0.73 [0.68; 0.77]
Heterogeneity: tau2 = 108.5795; chi2 = 46306.81, df = 16 (P = 0); I2 = 100% Heterogeneity: tau2 = 0.1627; chi2 = 77.51, df = 16 (P < 0.01); I2 = 79%
label = E: <24 °C label = E: <24 °C 0.4
Fang2019.1 47.20 10.1000 340 1.7 47.20 [ 46.13; 48.27] Fang2019.1 252 340 0.74 [0.69; 0.79]
Gong2016.1 46.70 8.7000 35 1.7 46.70 [43.82; 49.58] Gong2016.1 24 35 0.69 [0.51; 0.83]
Huang2010 48.00 12.8000 46 1.6 48.00 [44.30; 51.70] Huang2010 36 46 0.78 [0.64; 0.89]
Keeling2018.1 65.00 3.2000 679 1.7 65.00 [64.76; 65.24] Keeling2018.1 421 679 0.62 [0.58; 0.66]
Li_Y_Guo2020.1 47.40 9.7000 1225 1.7 47.40 [ 46.86; 47.94] Li_Y_Guo2020.1 966 1225 0.79 [0.76; 0.81]
Minatoya2018.1 70.80 9.7000 81 1.7 70.80 [68.69; 72.91] Minatoya2018.1 55 81 0.68 [0.57; 0.78] 0.5
Ghoreishi2020 60.00 3.3000 7353 1.7 60.00 [59.92; 60.08] Ghoreishi2020 4846 7353 0.66 [0.65; 0.67]
OHara2020 60.00 13.4000 2950 1.7 60.00 [59.92; 60.08] OHara2020 1993 2950 0.68 [0.66; 0.69]
Okita2015.2 68.30 11.6000 1141 1.7 68.30 [67.63; 68.97] Okita2015.2 821 1141 0.72 [0.69; 0.75] 0.0 0.5 1.0 1.5 2.0
Sasaki2007 70.50 26.1000 305 1.7 70.50 [67.57; 73.43] Sasaki2007 238 305 0.78 [0.73; 0.83] Logit Transformed Proportion
Spielvogel2007 63.00 14.0000 150 1.7 63.00 [60.76; 65.24] Spielvogel2007 91 150 0.61 [0.52; 0.69]
Wu2021.1 46.70 10.7000 580 1.7 46.70 [45.83; 47.57] Wu2021.1 447 580 0.77 [0.73; 0.80] = group A = group D
Total (95% CI) 14885 20.1 57.81 [51.49; 64.13] Total (95% CI) 14885 0.71 [0.67; 0.75] = group B = group E
Heterogeneity: tau = 97.8930; chi = 6007, df = 11 (P = 0); I2 = 100%
2 2 Heterogeneity: tau2 =0.0761; chi2 = 145.72, df = 11 (P < 0.01); I2 = 92% = group C
Total (95% CI) 34797 100.0 59.10 [56.50; 61.70] Total (95% CI) 34797 0.71 [0.69; 0.73]
Heterogeneity: tau2 = 98.6109; chi2 = 65537.89, df = 59 (P = 0); I2 = 100%
Test for subgroup diferences: chi2 = 9.18, df = 4 (P = 0.06) 30 40 50 60 70
Heterogeneity: tau2 = 0.0831; chi2 = 359.59, df = 59 (P < 0.01); I2 = 84%
80 Test for subgroup diferences: chi2 = 16.24, df = 4 (P < 0.01) 0.3 0.4 0.5 0.6 0.7 0.8 0.9
(d)

(a) (b)
Figure 2: Age and male pooled proportion subgroup data.

Te subgroup analysis indicated that the P values for 3.5. Metaregression Analysis. We conducted a metare-
statistical diferences between the TNI and PNI groups were gression analysis with age, sex, and cardiopulmonary bypass
0.14 and 0.02, respectively. Te incidences of TNI and PNI (CPB) time as independent variables and TNI, PNI, RF, and
were signifcantly lower in groups A (4% and 3%) and C (2% mortality as dependent variables. Te primary outcomes
and 4%) compared to the other groups. Furthermore, RF and include age, which was not statistically signifcant with any
in-hospital mortality rates were also compiled into forest of the results. Statistically signifcant fndings include that
plots, as depicted in Figure 5. Te pooled results showed an sex was signifcantly associated with TNI (P � 0.0456, esti-
8% incidence of RF (P � 0.01, 95% CI: 0.06; 0.10) and a 6% mate value � −0.0001) and mortality (P � 0.0398, estimate
in-hospital mortality rate (P � 0.05, 95% CI: 0.05; 0.07). Te value � 0.0002); CPB time was signifcantly associated with
best subgroup analysis outcomes were observed in group C mortality (P � 0.0232, estimate value � 0.0067). A Q statistic
for RF (5%) and in group A for in-hospital mortality (3%). (QE) test showed signifcant heterogeneity for all results
We conducted the Peters test for the funnel plot which (P < 0.0001).
revealed a P value for PNI of 0.2434, for RF of 0.5059, and for
mortality of 0.1175 indicating no publication bias. However, 4. Discussion
the P value for TNI was <0.0001, prompting us to use the
trim-and-fll model for correction. Nevertheless, the sig- DHCA has long been the gold standard for aortic arch
nifcance after correction was unchanged from the pre-trim- surgeries. Despite DHCA’s recognized ability to lower cel-
and-fll model analysis. Consequently, we believe that our lular metabolism rates and safeguard organs in a hypo-
study is not afected by publication bias, and all the pooled thermic environment, it also can induce neural system
results are shown in Table 1. damage and coagulation anomalies, among other detriments
Journal of Cardiac Surgery
(a)
Figure 3: Pooled operation time in aortic arch replacement with subgroup analysis.
[64, 65]. Prior research suggests that optimal brain pro-
tection temperatures range from 32 to 34 degrees Celsius,
while kidney protection is best achieved between 28 and 32
degrees Celsius [66–69]. In this study, we have grouped
temperatures in two-degree intervals to illustrate the re-
lationship between decreased temperature and increased
tissue damage, mindful of the 32-degree boundary. Tis
methodology elucidates why Group A manifests the least
neural complications, and Group C exhibits diminished
renal complications. However, given that clinical treatments
often encompass multiple primary diseases, our systemic
review amalgamates data from various centers to provide
more robust evidence for clinical decisions.
Our meta-analysis and systematic review encompassed 43
articles, 60 groups, and 34,797 cases. Statistically, Groups A
and C showcased the best results through subgroup com-
parison. Group A, which maintains temperatures between 30
and 32 degrees Celsius, had the lowest rates of peripheral
neuropathy injury (PNI) (3%) and mortality (3%), illustrating
a signifcant statistical diference. Conversely, Group C, where
temperatures were kept within the 26–28 degrees Celsius
range, had the lowest incidence of renal failure (RF) (5%). For
other parameters, such as age (P � 0.06), myocardial ischemia
time (P � 0.90), ICP time (P � 0.95), and traumatic neural
injury (TNI) occurrence rate (P � 0.06), no signifcant sta-
tistical diference was observed. Similarly, the male pro-
portion (P < 0.01) and CPB time (P � 0.01) showed no
5
(b) (c)
statistical diference. Accordingly, we suggest that main-
taining the temperature at 30–32 degrees Celsius or 26–28
degrees Celsius during HCA is safe and efectively decreases
the incidence rate of each type of complication. Furthermore,
our funnel plots reveal no signifcant publication bias, and this
conclusion is supported by our center’s experience [70].
Due to current state-of-the-art techniques in cardiac sur-
gery, such as advancements in suture devices and anastomosis
methods, the time and bleeding involved in arch replacement
procedures have signifcantly reduced. As a result, the need for
low-temperature protection has also decreased. In our research,
we found that some articles had ICP times of just a few
minutes, which was achieved using a debranch hybrid aortic
replacement surgery method that reduces the operation time
and simplifes the surgery. Most of our sample population had
type A aortic dissection, but surgical techniques varied among
medical centers. Nevertheless, en bloc anastomosis and HCA
techniques remained commonly used in these procedures. Te
fndings of this research may aid in decision-making when
clinicians need to induce CA in dissection patients.
From our perspective, the perfusion strategy is a crucial
factor during ICP. By monitoring the organs’ function,
guided perfusion strategies can make organs tolerant of
transient hypoxia during HCA [71]. During HCA, main-
taining balanced cardiac and cerebral perfusion pressure is
essential. Tough there have been controversial discussions
on antegrade, retrograde, and bilateral cerebral perfusion
6 Journal of Cardiac Surgery

Study or GLMM, Random, GLMM, Random, Study or GLMM, Random, GLMM, Random,
Events Total Events Total
Subgroup 95% CI 95% CI Subgroup 95% CI 95% CI
0.0
label = A: 30-32 °C
label = A: 30-32 °C He2019 6 59 0.10 [0.04; 0.21]
He2019 1 59 0.02 [0.00; 0.09] Toyama2009 2 26 0.08 [0.01; 0.25]
Toyama2009 0 26 0.00 [0.00; 0.13] Urbanski2019 1 46 0.02 [0.00; 0.12] 0.2
Urbanski2019 6 46 0.13 [0.05; 0.26] Urbanski2012 3 347 0.01 [0.00; 0.03]
Urbanski2012 8 347 0.02 [0.01; 0.04] Urbanski2013 1 131 0.01 [0.00; 0.04]
Urbanski2020 10 1000 0.01 [0.00; 0.02]
Urbanski2013 6 131 0.05 [0.02; 0.10] Zierer2011 14 0.06 [0.03; 0.09] 0.4
Urbanski2020 49 1000 0.05 [0.04; 0.06] Zierer2012a 25 245 0.06 [0.04; 0.09]
Zierer2011 12 245 0.05 [0.03; 0.08] Zierer2012b 28 426 0.03 [0.02; 0.04]
Zierer2014.1 5 1002 0.02 [0.01; 0.05]
Zierer2012a 20 426 0.05 [0.03; 0.07] 0.06 [0.03; 0.09]
14 246

Standard Error
Zierer2014.2 0.6
Zierer2012b 42 1002 0.04 [0.03; 0.06]
Total (95% CI) 3774 0.03 [0.02; 0.05]
Zierer2014.1 12 246 0.05 [0.03; 0.08] Heterogeneity: tau2 = 0.5572; chi2 = 49.57, df = 10 (P < 0.01) ; I² = 80%
Zierer2014.2 10 246 0.04 [0.02; 0.07]
Total (95% CI) 3774 0.04 [0.04; 0.05] label B: 28-30 °C 0.8
Dong2020.1 1 25 0.04 [0.00; 0.20]
Heterogeneity: tau = 0; chi = 12.59, df = 10 (P = 0.25) ; I2 = 21%
2 2
Dong2021.2 0 41 0.00 [0.00; 0.09]
EI–Sayed2018 5 63 0.08 [0.03; 0.18]
label = B: 28-30 °C EI–Sayed2017 34 587 0.06 [0.04; 0.08] 1.0
Dong2020.1 2 25 0.08 [0.01; 0.26] EI–Sayed2019 2 38 0.05 [0.01; 0.18]
Dong2021.2 3 41 0.07 [0.02; 0.20] Kamiya2007 2 31 0.06 [0.01; 0.21]
EI–Sayed2018 6 63 0.10 [0.04; 0.20] Leshnower2012.2 7 277 0.03 [0.01; 0.05]
Li_Y_Yan2020.1 14 130 0.11 [0.06; 0.17] 1.2
EI–Sayed2017 29 587 0.05 [0.03; 0.07] Li Y Yan2020.2 230 0.14 [0.10; 0.19]
32
EI–Sayed2019 3 38 0.08 [0.02; 0.21] Minatoya2018.3 6 67 0.09 [0.03; 0.18]
Kamiya2007 1 31 0.03 [0.00; 0.17] Numata2015.2 5 39 0.13 [0.04; 0.27]
Leshnower2012.2 12 277 0.04 [0.02; 0.07] Zhang2020.1 100 0.07 [0.03; 0.14] 1.4
7
Zierer2017 453 0.06 [0.04; 0.09]
Li_Y_Yan2020.1 3 130 0.02 [0.00; 0.07] 27
Total (95% CI) 2081 0.07 [0.05; 0.09]
Li_Y_Yan2020.2 10 230 0.04 [0.02; 0.08] Heterogeneity: tau2 = 0.1899; chi2 = 30.43, df = 12 (P < 0.01); I2 =61%
Minatoya2018.3 4 67 0.06 [0.02; 0.15] -5 -4 -3 -2 -1 0
Zierer2017 31 453 0.07 [0.05; 0.10] label = C: 26-28 °C
Jassar2016 2 100 0.02 [0.00; 0.07] Logit Transformed Proportion
Total (95% CI) 1942 0.05 [0.04; 0.07]
Gong2016.2 5 39 0.13 [0.04; 0.27]
Heterogeneity: tau = 0; chi = 8.79, df = 10 (P = 0.55); I2 =0%
2 2
Leshnower2014.2 1 23 0.04 [0.00; 0.22]
Li Y Guo2020.2 4 80 0.05 [0.01; 0.12] = group A = group D
label = C: 26-28 °C Shen2020.2 0 37 0.00 [0.00; 0.09]
Jassar2016 1 100 0.01 [0.00; 0.05] Suzuki2013 3 105 0.03 [0.01; 0.08] = group B = group E
Leshnower2014.2 1 23 0.04 [0.00; 0.22] Zhang2020.2 10 147 0.07 [0.03; 0.12] = group C
Shen2020.2
Suzuki2013
1
3
37
105
0.03 [0.00; 0.14]
0.03 [0.01; 0.08]
Total (95% CI) 531 0.04 [0.02; 0.09]
Heterogeneity: tau2 = 0.1577; chi2 = 7.73, df = 6 (P = 0.26); I2 = 22% (c)
Total (95% CI) 265 0.02 [0.01; 0.08] label = D: 24-26 °C
Heterogeneity: tau2 = 0; chi2 = 1.23, df = 3 (P = 0.75); I2 = 0% Dong2020.2 5 36 0.14 [0.05; 0.29]
Dong2021.1 4 47 0.09 [0.02; 0.20] 0.0
Fang2019.2 22 287 0.08 [0.05; 0.11]
label D: 24-26 °C Keeling2018.2 167 2586 0.06 [0.06; 0.07]
Dong2020.2 5 36 0.14 [0.05; 0.29] Kasama2019 0 48 0.00 (0.00; 0.07]
Dong2021.1 3 47 0.06 [0.01; 0.18] Leontyev2013 6 51 0.12 [0.04; 0.24] 0.2
Keeling2018.2 117 2586 0.05 [0.04; 0.05] Leshnower2014.1 3 122 0.02 [0.01; 0.07]
Kasama2019 3 48 0.06 [0.01; 0.17] Leshnower2012.1 16 223 0.07 [0.04; 0.11]
Liu2020 12 300 0.04 [0.02; 0.07]
Leontyev2013 5 51 0.10 [0.03; 0.21] Minatoya2018.2 7 81 0.09 [0.04; 0.17] 0.4
Leshnower2014.1 7 122 0.06 [0.02; 0.11] Numata2015.1 10 70 0.14 [0.07; 0.25]
Leshnower2012.1 14 223 0.06 [0.03; 0.10] Okada2012 2 321 0.01 [0.00; 0.02]
Minatoya2018.2 9 81 0.11 [0.05; 0.20] Okita2015.1 767 7038 0.11 [0.10; 0.12]

Standard Error
Preventza2016 16 118 0.14 [0.08; 0.21] 0.6
Okada2012 2 321 0.01 [0.00; 0.02]
Shen2020.1 6 52 0.12 [0.04; 0.23]
Okita2015.1 267 7038 0.04 [0.03; 0.04] Wang2020 82 1708 0.05 [0.04; 0.06]
Preventza2016 1 118 0.01 [0.00; 0.05] Wu2021.2 22 438 0.05 [0.03; 0.08] 0.8
Shen2020.1 11 52 0.21 [0.11; 0.35] Total (95% CI) 13526 0.06 [0.04; 0.09]
Total (95% CI) 10723 0.05 [0.03; 0.09] Heterogeneity: tau2 = 0.3968; chi2 = 132.42, df = 16 (P < 0.01); I2 = 88%
Heterogeneity: tau = 0.6761; chi = 65.17, df = 11 (P < 0.01); I2= 83%
2 2
label = E: <24 °C
Fang2019.1 16 35 0.05 [0.03; 0.08] 1.0
label = E: <24 °C Gong2016.1 5 340 0.14 [0.05; 0.30]
Huang2010 0 46 0.00 [0.00; 0.08]
Huang2010 5 46 0.11 [0.04; 0.24] 679
Keeling2018.1 52 0.08 [0.06; 0.10]
Keeling2018.1 44 679 0.06 [0.05; 0.09] Li_Y_Guo2020.1 220 1225 0.18 [0.16; 0.20] 1.2
Minatoya2018.1 7 81 0.09 [0.04; 0.17] Minatoya2018.1 10 81 0.12 [0.06; 0.22]
OHara2020 105 2950 0.04 [0.03; 0.04] Ghoreishi2020 945 7353 0.13 [0.12; 0.14]
Okita2015.2 50 1141 0.04 [0.03; 0.06] OHara2020 369 2950 0.13 [0.11; 0.14]
Okita2015.2 140 1141 0.12 [0.10; 0.14] 1.4
Sasaki2007 20 305 0.07 [0.04; 0.10]
Sasaki2007 5 305 0.02 [0.01; 0.04]
Spielvogel2007 7 150 0.05 [0.02; 0.09] Spielvogel2007 6 150 0.04 [0.01; 0.09]
Total (95% CI) 5352 0.05 [0.04; 0.07] Wu2021.1 41 580 0.07 [0.05; 0.09] -5 -4 -3 -2 -1 0
Heterogeneity: tau2 = 0.0636; chi2= 22.14, df = 6 (P < 0.01); I2 = 73% Total (95% CI) 14885 0.08 [0.05; 0.12]
Heterogeneity: tau2 = 0.4826; chi2 = 111.66, df = 11 Logit Transformed Proportion
Total (95% CI) 22056 0.05 [0.04; 0.06] (P < 0.01); I2 = 90%
Heterogeneity: tau2 = 0.1506; chi2 = 117.09, df = 44 Total (95% CI) 0.06 [0.04; 0.07]
0 0.05 0.1 0.15 0.2 0.25 0.3 Heterogeneity: tau2 = 0.5424; chi2 = 581.15, df = 59 = group A = group D
(P < 0.01); I2 = 62% 0 0.05 0.1 0.15 0.2 0.25 0.3
Test for subgroup differences: chi = 6.84, df = 4 (P = 0.14)
2 (P < 0.01); I2 = 90% = group B = group E
Test for subgroup differences: chi2 = 11.25, df = 4 (P = 0.02)
= group C

(a) (b) (d)

Figure 4: Pooled TNI and PNI complication results with subgroup analysis.

strategies, single-center studies or meta-analyses showed no Aortic arch replacement is a complex procedure, and
signifcant diferences [8–10]. We believe that this may be various surgical techniques are currently in use. Some of the
related to the routine use of near-infrared spectroscopy research analyzed in this study was performed by the same
(NIRS) monitoring. In cases where there is abnormal ce- operators, which might result in potential bias. Additionally,
rebral oxygen saturation monitoring, changing the perfusion imbalanced distributions of valve diseases, cerebral in-
strategy and implementing local cooling methods can pre- fractions, and other diseases that could infuence the results
dict and help to avoid peripheral neuropathy injury (PNI). were observed in some of the samples, potentially resulting
Improvements in CPB, such as acid-base management in heterogeneity in all analyses. We understand that factors
(alpha-stat and PH-stat management), can retain homeo- such as operator experience and sample diferences can be
stasis and the goal-guided perfusion strategies, resulting in responsible for this heterogeneity, making it impossible for
better performance in maintaining DO2/VO2 balance our models to address all related problems. Consequently,
during CPB and reducing damage to critical organs [72–74]. this is the main limitation of our study.
Journal of Cardiac Surgery 7

Study or GLMM, Random, GLMM, Random,

Study or GLMM, Random, GLMM, Random, Events Total
Events Total Subgroup 95% CI 95% CI
Subgroup 95% CI 95% CI
label = A : 30-32 °C 0.0
label = A: 30-32 °C He2019 2 59 0.03 [0.00; 0.12]
He2019 20 59 0.34 [0.22; 0.47] Toyama2009 1 26 0.04 [0.00; 0.20]
Toyama2009 5 26 0.19 [0.07; 0.39] Urbanski2019 0 46 0.00 [0.00; 0.08]
Zierer2012a 34 426 0.08 [0.06; 0.11] Urbanski2012 3 347 0.01 [0.00; 0.03] 0.2
Urbanski2013 3 131 0.02 [0.00; 0.07]
Zierer2012b 38 1002 0.04 [0.03; 0.05] Urbanski2020 21 1000 0.02 [0.01; 0.03]
Zierer2014.1 13 246 0.05 [0.03; 0.09] Zierer2011 20 245 0.08 [0.05; 0.12]
Zierer2014.2 9 246 0.04 [0.02; 0.07] Zierer2012a 34 426 0.08 [0.06; 0.11] 0.4
Total (95% CI) 2005 0.08 [0.03; 0.20] Zierer2012b 52 1002 0.05 [0.04; 0.07]
Zierer2014.1 9 246 0.04 [0.02; 0.07]
Heterogeneity: tau2 = 0.8342; chi2 = 75.11, df = 5 (P < 0.01); I2 = 93% Zierer2014.2 11 246 0.04 [0.02; 0.08]
Total (95% CI) 3774 0.03 [0.02; 0.06] 0.6

Standard Error
label = B: 28-30 °C Heterogeneity: tau2 = 0.3628; chi2 = 42.36, df = 10 (P < 0.01); I2 = 76%
Dong2020.1 0 25 0.00 [0.00; 0.14] label = B : 28-30 °C
Dong2021.2 0 41 0.00 [0.00; 0.09] Dong2020.1 0 25 0.00 [0.00, 0.14] 0.8
EI–Sayed2018 5 63 0.08 [0.03; 0.18] Dong2021.2 1 41 0.02 [0.00; 0.13]
EI–Sayed2017 49 587 0.08 [0.06; 0.11] EI–Sayed2018 7 63 0.11 [0.05; 0.22]
EI–Sayed2017 36 587 0.06 [0.04; 0.08]
EI–Sayed2019 3 38 0.08 [0.02; 0.21] EI–Sayed2019 6 38 0.16 [0.06; 0.31]
Leshnower2012.2 11 277 0.04 [0.02; 0.07] Kamiya2007 1 31 0.03 [0.00; 0.17] 1.0
Numata2015.2 3 39 0.08 [0.02; 0.21] Leshnower2012.2 14 277 0.05 [0.03; 0.08]
Zhang2020.1 11 100 0.11 [0.06; 0.19] Li_Y_Yan2020.1 6 130 0.05 [0.02; 0.10]
Li_Y_Yan2020.2 18 230 0.08 [0.05; 0.12]
Zierer2017 24 453 0.05 [0.03; 0.08] Minatoya2018.3 1 67 0.01 [0.00; 0.08] 1.2
Total (95% CI) 1623 0.06 [0.04; 0.09] Numata2015.2 4 39 0.10 [0.03; 0.24]
Heterogeneity: tau2 = 0.0747; chi2 = 9.96, df = 8 (P = 0.27); I2 = 20% Zhang2020.1 3 100 0.03 [0.01; 0.09]
Zierer2017 32 453 0.07 [0.05; 0.10]
label = C: 26-28 °C Total (95% CI) 2081 0.06 [0.05; 0.07] 1.4

Jassar2016 1 100 0.01 [0.00; 0.05] Heterogeneity: tau2 = 0; chi2 = 16.39, df = 12 (P = 0.17); I2 = 27%
Gong2016.2 3 39 0.08 [0.02; 0.21] label = C: 26-28 °C
Jassar2016 1 100 0.01 [0.00; 0.05] -5 -4 -3 -2 -1 0
Leshnower2014.2 2 23 0.09 [0.01; 0.28]
Gong2016.2 4 39 0.10 [0.03; 0.24]
Li_Y_Guo2020.2 5 80 0.06 [0.02; 0.14] Leshnower2014.2 2 23 0.09 [0.01; 0.28] Logit Transformed Proportion
Suzuki2013 2 105 0.02 [0.00; 0.07] Li_Y_Guo2020.2 5 80 0.06 [0.02; 0.14]
Shen2020.2 2 37 0.05 [0.01, 0.18] = group A = group D
Zhang2020.2 19 147 0.13 [0.08; 0.19]
Suzuki2013 3 105 0.03 [0.01; 0.08] = group B = group E
Total (95% CI) 494 0.05 [0.02; 0.13] Zhang2020.2 7 147 0.05 [0.02; 0.10]
Heterogeneity: tau2 = 0.5307; chi2 = 13.85, df = 5 (P = 0.02); I2 = 64% Total (95% CI) 531 0.05 [0.03; 0.07] = group C
Heterogeneity: tau = 0.0109; chi = 6.68, df = 6 (P = 0.35); I2 = 10%
2 2

label = D : 24-26 °C
Dong2020.2 5 36 0.14 [0.05; 0.29]
label = D: 24-26 °C (c)
Dong2020.2 3 36 0.08 [0.02; 0.22]
Dong2021.1 6 47 0.13 [0.05; 0.26] Dong2021.1 4 47 0.09 [0.02; 0.20]
Fang2019.2 46 287 0.16 [0.12; 0.21] Fang2019.2 7 287 0.02 [0.01; 0.05] 0.0
Keeling2018.2 300 2586 0.12 [0.10; 0.13] Keeling2018.2 260 2586 0.10 [0.09; 0.11]
Kasama2019 1 48 0.02 [0.00; 0.11]
Kasama2019 1 48 0.02 [0.00; 0.11] Leontyev2013 4 51 0.08 [0.02; 0.19]
Leontyev2013 13 51 0.25 [0.14; 0.40] Leshnower2014.1 12 122 0.10 [0.05; 0.17]
Leshnower2012.1 16 223 0.07 [0.04; 0.11] 0.2
Leshnower2014.1 4 122 0.03 [0.01; 0.08]
Leshnower2012.1 9 223 0.04 [0.02; 0.08] Liu2020 20 300 0.07 [0.04; 0.10]
Minatoya2018.2 0 81 0.00 [0.00; 0.04]
Liu2020 70 300 0.23 [0.19; 0.29] Numata2015.1 10 70 0.14 [0.07; 0.25]
Numata2015.1 12 70 0.17 [0.09; 0.28] Okada2012 14 321 0.04 [0.02; 0.07] 0.4
Okada2012 10 321 0.03 [0.02; 0.06] Okita2015.1 415 7038 0.06 [0.05; 0.06]
Preventza2016 27 118 0.23 [0.16; 0.32] Preventza2016 12 118 0.10 [0.05; 0.17]
Shen2020.1 7 52 0.13 [0.06; 0.26]
Wang2020 135 1708 0.08 [0.07; 0.09] 0.6

Standard Error
Wang2020 112 1708 0.07 [0.05; 0.08]
Wu2021.2 31 438 0.07 [0.05; 0.10] Wu2021.2 23 438 0.05 [0.03; 0.08]
Total (95% CI) 6355 0.10 [0.06; 0.15] Total (95% CI) 13526 0.07 [0.05; 0.08]
Heterogeneity: tau = 0.5773; chi = 139.99, df = 5 (P < 0.01); I2 = 91%
2 2 Heterogeneity: tau2 = 0.1477; chi2 = 77.58, df = 16 (P < 0.01); I2 = 79%
0.8
label = E: <24 °C
label = E: <24 °C Fang2019.1 6 340 0.02 [0.01; 0.04]
Fang2019.1 73 340 0.21 [0.17; 0.26] Gong2016.1 5 35 0.14 [0.05; 0.30]
Huang2010 3 46 0.07 [0.01; 0.18] 1.0
Gong2016.1 5 35 0.14 [0.05; 0.30] Keeling2018.1 90 679 0.13 [0.11; 0.16]
Huang2010 1 46 0.02 [0.00; 0.12] Li_Y_Guo2020.1 118 1225 0.10 [0.08; 0.11]
Keeling2018.1 71 679 0.10 [0.08; 0.13] Minatoya2018.1 3 81 0.04 [0.01; 0.10]
Li_Y_Guo2020.1 132 1225 0.11 [0.09; 0.13] Ghoreishi2020 1234 7353 0.17 [0.16; 0.18] 1.2
OHara2020 466 2950 0.16 [0.14; 0.17]
OHara2020 443 2950 0.15 [0.14; 0.16] Okita2015.2 82 1141 0.07 [0.06; 0.09]
Wu2021.1 54 580 0.09 [0.07; 0.12] Sasaki2007 7 305 0.02 [0.01; 0.05]
Total (95% CI) 5855 0.12 [0.08; 0.17] Spielvogel2007 7 150 0.05 [0.02; 0.09] 1.4
Wu2021.1 49 580 0.08 [0.06; 0.11]
Heterogeneity: tau2 = 0.1327; chi2 = 49.15, df = 6 (P < 0.01); I2 = 88% Total (95% CI) 14885 0.07 [0.05; 0.12]
Heterogeneity: tau = 0.5112; chi = 196.81, df = 11 (P < 0.01); I2 = 94%
2 2
Total (95% CI) 16332 0.08 [0.06; 0.10] -5 -4 -3 -2 -1 0
Heterogeneity: tau2 = 0.5553; chi2 = 374.18, df = 41 (P < 0.01); Total (95% CI) 34797 0.06 [0.05; 0.07]
I2 = 89% 0 0.1 0.2 0.3 0.4 Heterogeneity: tau2 = 0.3695; chi2 = 897.48, df = 59 Logit Transformed Proportion
(P < 0.01); I2 = 93% 0 0.05 0.1 0.15 0.2 0.25 0.3
Test for subgroup differences: chi2 = 1277, df = 4 (P = 0.01)
Test for subgroup differences: chi2 = 9.73, df = 4 (P = 0.05)
= group A = group D
= group B = group E
= group C

(a) (b) (d)

Figure 5: Pooled RF and mortality results with subgroup analysis.

Table 1: Pooled outcomes with subgroup analysis.

Temperature Patients’ Heterogeneity Interaction-p
Variables Group Events Estimate P value
(degrees Celsius) numbers (I square) (%) (subgroup-P value)
63.70
A 30–32 3774 NA 93 <0.01 0.06
[60.60; 66.81]
60.36
B 28–30 2081 NA 99 <0.01
[54.61; 66.11]
50.98
C 26–28 531 NA 99 <0.01
[38.34; 63.63]
Age
59.30
D 24–26 13526 NA 100 <0.001
[53.92; 64.67]
57.81
E <24 14885 NA 100 <0.001
[51.49; 64.13]
Pooled 59.10 [56.50;
34797 NA 100 <0.001
outcome 61.70]
8 Journal of Cardiac Surgery

Table 1: Continued.
Temperature Patients’ Heterogeneity Interaction-p
Variables Group Events Estimate P value
(degrees Celsius) numbers (I square) (%) (subgroup-P value)
0.67 [0.63;
A 30–32 3774 2540 66 <0.01 <0.01
0.70]
0.70 [0.67;
B 28–30 2081 1444 32 0.12
0.73]
0.76 [0.71;
C 26–28 531 405 0 0.63
0.80]
Sex (male)
0.73 [0.68;
D 24–26 13526 9817 79 <0.01
0.77]
0.71 [0.67;
E <24 14485 10190 92 <0.01
0.73]
Pooled 0.71 [0.69;
34797 4386 84 <0.01
outcome 0.73]
170.11
A 30–32 3774 NA [154.74; 96 <0.01 <0.01
185.49]
184.05
B 28–30 2081 NA [171.27; 91 <0.01
196.84]
180.59
C 26–28 531 NA [155.29; 90 <0.01
CPB time 205.90]
(minutes) 197.22
D 24–26 13526 NA [184.11; 100 <0.001
210.33]
206.25
E <24 11935 NA [185.50; 100 <0.001
227.01]
189. 7
Pooled
31847 NA [18 .04; 100 <0.001
outcome
196.50]
0.04 [0.04;
A 30–32 3774 166 21 0.25 0.14
0.05]
0.05 [0.04;
B 28–30 1942 104 0 0.55
0.07]
0.02 [0.01;
C 26–28 265 6 0 0.75
0.08]
TNI
0.05 [0.03;
D 24–26 10723 444 83 <0.01
0.09]
0.05 [0.04;
E <24 5352 238 73 <0.01
0.07]
Pooled 0.05 [0.04;
056 958 6 <0.01
outcome 0.06]
0.03 [0.02;
A 30–32 3774 109 80 <0.01 0.02
0.05]
0.07 [0.05;
B 28–30 2081 142 61 <0.01
0.09]
0.04 [0.02;
C 26–28 531 25 22 0.26
0.09]
PNI
0.06 [0.04;
D 24–26 13526 1147 88 <0.01
0.09]
0.08 [0.05;
E <24 14885 1809 90 <0.01
0.12]
Pooled 0.06 [0.04;
34797 3 3 90 <0.01
outcome 0.07]
Journal of Cardiac Surgery 9

Table 1: Continued.
Temperature Patients’ Heterogeneity Interaction-p
Variables Group Events Estimate P value
(degrees Celsius) numbers (I square) (%) (subgroup-P value)
0.08 [0.03;
A 30–32 2005 119 93 <0.01 0.01
0.20]
0.06 [0.04;
B 28–30 1623 106 20 0.27
0.09]
0.05 [0.02;
C 26–28 494 32 64 0.02
0.13]
RF
0.10 [0.06;
D 24–26 6355 669 91 <0.01
0.15]
0.12 [0.08;
E <24 5855 779 88 <0.01
0.17]
Pooled 0.08 [0.06;
1633 1705 89 <0.01
outcome 0.10]
0.03 [0.02;
A 30–32 3774 156 76 <0.01 0.05
0.06]
0.06 [0.05;
B 28–30 2081 129 27 0.17
0.07]
0.05 [0.03;
C 26–28 531 24 10 0.35
0.07]
Mortality
0.07 [0.05;
D 24–26 13526 920 79 <0.01
0.08]
0.07 [0.05;
E <24 14885 2070 94 <0.01
0.12]
Pooled 0.06 [0.05;
34797 330 93 <0.01
outcome 0.07]
For the age variable, the pooled outcome is statistically signifcant with a P value <0.001. However, it is also worth noting the high heterogeneity (I2 � 100%),
which suggests that there is a lot of variability in the results across the diferent age groups. And for the sex variable, the pooled proportion of males across all
groups is 0.71, and this result is statistically signifcant with a P value <0.01. However, there is signifcant heterogeneity in the results across the groups
(I2 � 84%). Besides, for CPB time, the pooled outcome is 189.27 minutes with a 95% confdence interval of (182.04 and 196.50), and the P value for the pooled
outcome’s heterogeneity is <0.001, indicating that the heterogeneity is statistically signifcant. Finally, in all complication variables, including PNI, TNI, RF,
and mortality, all suggest that there is a lot of variability in the results across the diferent groups with a P value <0.01.

However, based on our study, maintaining a tempera- Acknowledgments

ture of 30–32°C during en bloc anastomosis or 26–28°C
during longer HCA time operation, such as in total arch
replacement, is safe and signifcantly reduces the incidence
rate of complications such as stroke, hemiplegia, or neural
system complications, RF, and in-hospital mortality.
Data Availability
Te data supporting this meta-analysis are from previously
reported studies and datasets, which have been cited. Te
processed data are available from the corresponding author
upon request.
Conflicts of Interest
Te authors declare that there are no conficts of interest.
Authors’ Contributions
GTX, YY, and DZ designed the study; SEY and YY cali-
brated the datasheet and design parameters; DZ collected
the data and carried out the computation and generated
fgures; YY and DZ analyzed the data and wrote the
manuscript. Yang Yu and Zheng Ding contributed equally
to this work.
We appreciate all faculties in our department for their active
work, support, and help.
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