Abraham Kayal1; Tharun
Rajasekar2 ; Amer Harky3
1. Department of General Surgery, St George’s University Hospital,
London, UK
2. School of Medicine, Faculty of health and life science, University of
Liverpool, Liverpool, UK
4. Department of Cardiothoracic surgery, Liverpool Heart and Chest
Hospital,
Liverpool, UK
Corresponding author
Amer Harky
MRCS, MSc
Department of Cardiothoracic Surgery
Liverpool Heart and Chest Hospital
Liverpool, UK
L14 3PE
e-mail: amer.harky@lhch.nhs.uk
tel: +44-151-600-1616
Conflict of interest: None
Funding: None
Key words: aorta, cardiac surgery, outcome, post-operative
Acute type A Aortic Dissection (AAAD) is a catastrophic disorder and a
surgical emergency associated with a high mortality rate when no
intervention is performed in the acute setting (1). Several schools
exist for managing this lethal pathology, depending on the extent of the
disease; this could range from an interposition graft to replacing the
ascending aorta to aortic root replacement and total arch replacement
with the frozen elephant trunk (FET) in a more extensive approach.
However, the novel Triple Branched Stent Graft (TBSG) implantation
approach has been proven to shorten intraoperative parameters such as
cardiopulmonary bypass time, aortic cross-clamp time, circulation arrest
time and the duration of ventilator-assisted breathing (2). TBSG
implantation was first described by Chen et al (3) in 2010 and is
effective in the treatment of type A aortic dissections, however, the
procedure, as with most cardiac surgeries is not without risk. Risks
associated with this technique include occlusion and disruption of the
aorta, paraplegia, and hypoxaemia (4,5).
Wang and colleagues (6) attempted to develop a predictive nomographic
model to identify postoperative hypoxic risk factors in patients
following TBSG implant surgery. A population of 97 patients were
included in this study, all of whom underwent TBSG implantation at
Fujian Union Hospital in the Fujian Province of China within a 3-month
window. The predictive nomogram was based on the result of their study,
being that postoperative lactic acid, creatinine, intraoperative and
aortic occlusion time were all independent risk factors for hypoxemia,
and that age, sex and body mass index (BMI) were clinically relevant for
predicting postoperative hypoxemia. (6) The methodology Wang et al. (6)
utilise, although practical in approach, is not without its limitations.
When involving patients in the sample population, Wang et al (6) failed
to report their individual demographics. In patients with aortic
dissections, certain demographic features could be considered
independent risk factors for morbidity and mortality. For example, in
the United States of America, acute type B aortic dissections occur more
frequently in the black population (7). As a result of this, applying
the results of the predictive nomogram developed by Wang et al (6) to an
international population will not be possible. To be reliable, the
application of such models should be demonstrated on varied validation
datasets in the same setting. Furthermore, the imbalance of the male to
female ratio (75% to 25%) of the sample population affects the
generalisation and applicability of the results, as the female sex is a
known risk factor in cardiac surgery, mainly coronary and valve surgery
(8). Although these criticisms are true, the population used was
homogenous, supporting the validation of the dataset.
As postoperative hypoxemia is the focus of this study (6), it is
expected that the variables collected should pertain to the precise
definition of hypoxia. However, Wang et al (6) refer to hypoxemia in the
context of ARDS with a PaO2/FiO2 ratio of less than or equal to 200
mmHg, not coinciding with the Berlin Definition of a PaO2/FiO2 ratio of
equal to or less than 300 mmHg (6,9). Additionally, there was no mention
of the different severities of hypoxia, as hypoxemia is classified into
mild hypoxemia for PaO2/FiO2 ratios between 300 and 201 mmHg, moderate
hypoxemia for PaO2/FiO2 ratios between 200 and 101 mmHg, and severe
hypoxemia for PaO2/FiO2 ratios below or equal to 100 mmHg (10).
Additionally, regarding the exclusion and inclusion criteria, the
decision to exclude patients from the study who had severe preoperative
pulmonary insufficiency was adequate in this context, however, such
exclusion should have been extended to include preoperative inflammatory
conditions. This is true as it could severely affect intraoperative
systemic inflammatory degree during aortic dissection surgery (11). The
preoperative inflammatory state relates directly to postoperative
hypoxaemia due to the physiology of postoperative hypoxaemia: alveolar
accumulation and activation of macrophages and neutrophils occur due to
the release of pro-inflammatory cytokines, leading to the release of
toxic mediators and proteolytic enzymes which allow the permeability of
epithelial and endothelial cells, pulmonary vascular pressures, affect
the alveolar surfactant function, impair the oxygenation function, and
cause postoperative hypoxaemia (12). This serves to be another
significant limitation recognized from this study, causing a diagnosis
purity bias to be present in the data collection.
The absence of imperative operative variables is apparent when
considering risk factors for postoperative hypoxia. Such variables
include the circulatory arrest time, known to affect neurological
outcomes of the FET for acute type A aortic dissection, and may
therefore also influence the outcomes of the TBSG implantation.
Furthermore, there was no consideration of prolonged bypass time,
disease severity, and neurological status. Both the performance and
length of time that the patient is under cardiopulmonary bypass are
important factors which influence the occurrence of postoperative
hypoxemia in aortic dissection patients undergoing surgery. This is
evidenced in a retrospective single-centre study by Wang et al (13)
which highlighted the fact that 12.2-27% of patients undergoing
cardiopulmonary bypass experienced postoperative hypoxemia. Failure to
consider the neurological status of patients further limits the study,
as an observational study by Lin et al (5) concluded that hypoxaemia
following the insertion of a TBSG increases the risk of postoperative
delirium, calling to attention its significance. Still, as mentioned by
Wang et al (6), there exists a scarcity of studies assessing the risk
factors of postoperative hypoxemia after TBSG implantation.
Further limitations of the study exist in the exclusion of postoperative
interventions. Wang and colleagues neglected to mention any oxygen
supplementation provided to the patients within the 6-hour interval of
blood collection. Such an intervention could either prove beneficial or
detrimental to the patient, significantly affecting the results of this
study. Moreover, the 6-hour postoperative duration of blood collection
was not justified. Providing a lack of insight into this time interval
allows for speculation into the varying laboratory values such as lactic
acid which is Wang et al’s (6) primary predictive factor of hypoxemia
(14). Despite the limitations described above, the study does provide
valuable insight into the independent risk factors which may affect the
occurrence of hypoxemia postoperatively.
Statistically, Wang et al. provided reliable analysis and interpretation
of the data collected in their study. Internal validation was performed
via bootstrapping and a concordance index was utilised to measure the
predictive ability of the nomogram graph. This resulted in a value of
0.76 which suggests that the validation was between a good (C-index:
0.7) and a strong level (C-index: 0.8), corroborating the efficacy of
the study (15). Using univariate and multivariate logistic regression to
screen independent risk factors also provided localised rather than
generalised results. Finally, the utilisation of decision curve analysis
(DCA) in the study was appropriate due to the relatively high incidence
and significant volume of information available on aortic dissections
(16,17).
Overall, it can be concluded that Wang et al. have provided valuable
insights into the relatively new procedure of triple branched stent
graft implantation for type A aortic dissections. Developing a
predictive model for the risk factors of postoperative hypoxemia will
carve a path for other studies to follow. This work was strengthened by
a strong internal validity and the reproducibility of its results due to
the clear description of his methods. However, the lack of a more
extensive list of operative variables, omission of data regarding levels
of hypoxemia, and insufficient justification of follow-up time limits
the applicability of the study. The authors need a more extensive
approach to the perioperative state of the patient, along with a
long-term follow-up to heighten its suitability for more widespread use.
The study serves as a stepping stone for further investigation into the
risk factors and confounding variables for postoperative hypoxaemia,
providing the scope for larger multi-centred studies and developing an
international risk model.
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