Author's summary
There are limited data on sex differences in clinical outcomes of patients with severe cardiogenic shock (CS) treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). Therefore, our study aimed to compare the clinical outcomes between male and female patients undergoing VA-ECMO. A total of 1,328 patients receiving VA-ECMO were selected from either Samsung Medical Center or the multicenter CS registry, SMART RESCUE. In our study, no significant sex difference was found in in-hospital mortality. However, procedure-related complications showed significant differences between males and females, and female sex was identified as an independent risk factor for extracorporeal membrane oxygenation-related complications.
Keywords: Cardiogenic shock, Sex, Female
Abstract
Background and objectives
Limited data are available on sex differences in clinical outcomes of patients with profound cardiogenic shock (CS) receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). Therefore, our study sought to compare clinical pictures and outcomes between male and female patients treated with VA-ECMO.
Methods
A total of 1,328 patients receiving VA-ECMO were selected from either the Samsung Medical Center or a multicenter CS registry named the SMART RESCUE study. The study population was divided into men (n=903) and women (n=425). The primary outcome was in-hospital mortality, and the secondary outcome was procedure-related complications, which included limb ischemia, extracorporeal membrane oxygenation (ECMO) site bleeding and infection, and wound dehiscence.
Results
There was no significant difference in in-hospital mortality (men vs. women, 46.4% vs. 45.6%; adjusted odds ratio [OR], 0.78; 95% confidence interval [CI], 0.58–1.05; p=0.106) based on multivariable analysis. Women showed higher rates of procedure-related complication than men (18.7% vs. 25.9%; adjusted OR, 1.82; 95% CI, 1.29–2.57; p=0.001) mainly driven by higher incidence of limb ischemia (7.1% vs. 12.9%; adjusted OR, 2.32; 95% CI, 1.42–3.78; p=0.001) On multivariable logistic regression analysis, female sex was an independent predictor of procedure-related complications (adjusted OR, 1.68; 95% CI, 1.13–2.49; p=0.009).
Conclusions
Although no significant difference in either in-hospital or mid-term mortality was found between men and women, female sex is an independent factor for ECMO-related complications.
Trial Registration
ClinicalTrials.gov Identifier: NCT02985008
Graphical Abstract
INTRODUCTION
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a temporary mechanical circulatory support approach that assists with cardiac function recovery following the onset of cardiogenic shock (CS) and is applicable in non-cardiac conditions requiring circulatory support for cardiopulmonary function.1),2) Peripheral VA-ECMO is a viable choice for refractory CS and cardiac arrest because it improves hemodynamics quickly and can be initiated rapidly.1)
In CS, substantial evidence exists supporting the existence of sex differences in etiology, with men more frequently presenting with acute myocardial infarction and women more often experiencing CS from non-ischemic causes, respectively.3) However, controversies about mortality persist and may result in conflicting reports about how sex differences influence clinical presentation and treatment outcomes.4),5),6) Previous studies have demonstrated that the mortality rate among women with CS is higher, possibly as a result of their older age at presentation, less aggressive treatment, and associations with lower socioeconomic status.5),7),8) However, other studies suggest there is no difference in mortality between men and women with CS.9) Furthermore, the association between sex and clinical outcomes, such as mortality and complication, has not yet been fully elucidated in CS patients receiving VA-ECMO, which is initiated in an advanced stage of CS.
Therefore, we aimed to investigate whether sex differences in clinical presentation and disease severity among critically ill patients receiving VA-ECMO exist and whether there is an association between sex and clinical outcomes such as complications using data from 2 large-scale CS registries.
METHODS
Ethical statement
The Institutional Review Board (IRB) of the Samsung Medical Center approved this study and waived the requirement for written informed consent due to the study's retrospective nature. This study was conducted in accordance with the Declaration of Helsinki, as revised in 2013 (IRB No. 2020-10-102). Patient data was anonymized and de-identified before analysis.
Study population
We selected patients from 2 large-scale registries, specifically the Samsung Medical Center extracorporeal membrane oxygenation (ECMO) registry and a separate dedicated CS registry in a study known as SMART RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients with CS) (ClinicalTrials.gov identifier: NCT02985008), from which we only enrolled those patients who received VA-ECMO. First, medical records were retrospectively reviewed to identify adult patients at the Samsung Medical Center who received VA-ECMO support for acute cardiorespiratory failure between January 2012 and April 2023. Initially, 973 patients were considered; after excluding cases of failed ECMO insertion with an initial flow of <1.0 L/min and cannulation failure, 957 patients were included in the present analysis. Separately, a total of 1,247 patients were enrolled from 12 tertiary centers between January 2014 and December 2018 in the SMART RESCUE study, including 496 individuals who underwent ECMO insertion. After excluding duplicate patients enrolled in the VA-ECMO registry of Samsung Medical Center, 371 patients from the SMART RESCUE were included in the present analysis. Consequently, 1,328 patients were finally analyzed (Figure 1).
Figure 1. Study flow of patient inclusion and exclusion with propensity score matching.
VA-ECMO = venoarterial extracorporeal membrane oxygenation.
Data collection and outcomes
Data on patient demographics, baseline clinical presentation, treatments, and follow-up outcomes were collected from electronic medical records available in the Samsung Medical Center registry or using a web-based case record form in the SMART RESCUE registry.
The primary outcome was in-hospital all-cause mortality, while the secondary outcome was procedure-related complications, which are defined as a composite of limb ischemia, ECMO site bleeding, wound dehiscence, and site infection.
Procedure and definitions
The cardiovascular surgeons or interventional cardiologists implanted the peripheral VA-ECMO at the patient’s bedside or in a catheterization laboratory or operating room. The choice of perfusion catheter and drainage catheter and the decisions regarding venting and distal perfusion were made at the operator’s discretion and according to the patient’s condition. In this study, distal perfusion was specified as the pre-emptive distal perfusion, and a 6- or 7-French sheath was inserted distal to the cannulation site for limb perfusion. Failed ECMO system implantation was defined by a low initial pump flow (<1 L/min) and cannulation failure until the end of cardiopulmonary resuscitation (CPR). Successful weaning was defined as patient disconnection from the ECMO system without reinsertion or death within 30 days.10),11) We categorized cases requiring VA-ECMO insertion based on four distinct etiologies: acute myocardial infarction, heart failure (of ischemic origin and non-ischemic origin, respectively), or other. Procedure-related complications of interest included limb ischemia, ECMO site bleeding, infections related to the ECMO site, and wound dehiscence. Limb ischemia was defined as a condition necessitating major amputation, operation, or intervention due to a sudden decrease in limb perfusion and threat to limb viability. ECMO site bleeding was defined as bleeding at the cannulation site, persisting for 24 hours despite compression, excluding oozing. Stroke was defined as an ischemic or hemorrhagic cerebral event. Bleeding refers to any bleeding event except bleeding from the ECMO site or cranial hemorrhage. We defined sepsis as a positive result on a blood culture test.
Statistical analysis
Categorical variables are presented as numbers and relative frequencies (percentages), and continuous variables are presented as mean ± standard deviation values. Student’s t-test and the χ2 test were used to compare continuous and categorical variables, respectively. In multivariable models, covariates suggested to be relevant with a p<0.2 in univariate analysis or clinically relevant were initially considered candidate independent predictors of clinical events. Adjusted ORs and 95% CIs for clinical outcomes according to sex were obtained using a covariate including age, body surface area, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, peripheral vascular disease, cerebral vascular accident, current smoking status, history of percutaneous coronary intervention, coronary artery bypass graft, etiology, extracorporeal CPR (ECPR), arterial cannula size, venous cannular size, and preemptive distal perfusion. Univariable logistic regression and multivariable logistic regression were used to identify independent predictors of in-hospital mortality, procedure-related complications, and limb ischemia; results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Kaplan–Meier survival curves and Cox proportional hazard modeling were used to evaluate overall survival rates, including mortality after discharge. Hazard ratios (HRs) and 95% CIs were calculated using a Cox proportional hazards model to compare the adverse event risk between men and women. p<0.05 was considered statistically significant. Statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria).
RESULTS
Baseline and procedural characteristics
Ultimately, the study population comprised 903 male patients (68.0%) and 425 female patients (32.0%). Baseline clinical characteristics according to sex are described in Table 1. No significant age or body surface area difference was observed between the enrolled male and female patients. However, male patients had higher incidence rates of diabetes mellitus, a previous history of percutaneous coronary intervention, and a greater prevalence rate of current smoking. Concerning etiology, men more frequently initially presented with acute myocardial infarction (men vs. women, 53.7% vs. 35.1%; p<0.001), whereas women were more likely to present with non-ischemic heart failure (24.8% vs. 39.5%; p<0.001). Considering procedural characteristics, the two groups had no significant difference in the venous cannula size, use of venting, or implementation of distal perfusion. However, men required a larger arterial cannula size than women (16.1±1.7 vs. 15.9±1.7; p=0.042) (Table 1).
Table 1. Baseline characteristics.
| Characteristics | Overall population | |||
|---|---|---|---|---|
| Male (n=903) | Female (n=425) | p value | ||
| Demographic factors | ||||
| Age (years) | 59.3±14.2 | 59.2±17.6 | 0.910 | |
| Body mass index (kg/m2) | 24.1±3.5 | 23.7±4.2 | 0.109 | |
| Risk factors & medical history | ||||
| Current smoker | 284 (31.5) | 16 (3.8) | <0.001 | |
| Hypertension | 397 (44.0) | 189 (44.5) | 0.264 | |
| Diabetes mellitus | 343 (38.0) | 125 (29.4) | 0.003 | |
| Dyslipidemia | 171 (18.9) | 69 (16.2) | 0.264 | |
| Chronic kidney disease | 101 (11.2) | 38 (8.9) | 0.250 | |
| Peripheral vascular disease | 33 (3.7) | 14 (3.3) | 0.863 | |
| Cerebral vascular accident | 83 (9.2) | 30 (7.1) | 0.232 | |
| History of PCI | 249 (27.6) | 61 (14.4) | <0.001 | |
| History of CABG | 64 (7.1) | 23 (5.4) | 0.302 | |
| Etiology | <0.001 | |||
| AMI related CS | 485 (53.7) | 149 (35.1) | ||
| HF-related CS, ischemic | 94 (10.4) | 34 (8.0) | ||
| HF-related CS, non-ischemic | 224 (24.8) | 168 (39.5) | ||
| Other | 100 (11.1) | 74 (17.4) | ||
| Procedural characteristics | ||||
| ECPR | 450 (49.8) | 192 (45.2) | 0.127 | |
| Initial pump flow (L/min) | 3.1±0.9 | 2.9±0.8 | <0.001 | |
| Pump on time (min) | 35.9±27.8 | 37.0±40.6 | 0.764 | |
| Arterial cannula size (Fr) | 16.1±1.7 | 15.9±1.7 | 0.042 | |
| Venous cannula size (Fr) | 21.7±2.1 | 21.5±2.2 | 0.095 | |
| Venting | 141 (15.6) | 69 (16.2) | 0.835 | |
| Distal perfusion | 383 (42.4) | 186 (43.8) | 0.686 | |
| Mechanical ventilation | 764 (84.8) | 346 (81.6) | 0.165 | |
| CRRT | 403 (44.6) | 176 (41.4) | 0.297 | |
| Vasopressor | 583 (90.4) | 274 (87.8) | 0.270 | |
| Preemptive distal perfusion | 383 (42.4) | 186 (43.8) | 0.686 | |
Data are presented as mean ± standard deviation or number (%).
AMI = acute myocardial infarction; CABG = coronary artery bypass graft; CRRT = continuous renal replacement therapy; CS = cardiogenic shock; ECPR = extracorporeal cardiopulmonary resuscitation; HF = heart failure; PCI = percutaneous coronary intervention.
In-hospital complications and clinical outcomes
There was no significant difference in in-hospital mortality (46.4% vs. 45.6%; unadjusted OR, 0.97; 95% CI, 0.77–1.22; p=0.797) or mid-term mortality between men and women during the follow-up period, which lasted for a median of 11 months (unadjusted HR, 0.98; 95% CI, 0.84–1.14; p=0.078). Independent predictors of in-hospital mortality included age, diabetes mellitus, current smoking, chronic kidney disease, ECPR, and preemptive distal perfusion. Female sex was not included (Supplementary Table 1). Compared to male patients, female patients showed a significantly higher rate of procedure-related complications (18.7% vs. 25.9%; unadjusted OR, 1.52; 95% CI, 1.15–1.99; p=0.003), including limb ischemia (7.1% vs. 12.9%; unadjusted OR, 1.95; 95% CI, 1.33–2.85; p<0.001) and ECMO site bleeding (11.3% vs. 12.7%; unadjusted OR, 1.50; 95% CI, 1.10–2.04; p=0.013). The incidence of stroke was also higher in women than in men (4.9% vs. 8.0%; unadjusted OR, 1.70; 95% CI, 1.06–2.69; p=0.025). After adjustment for baseline differences, a similar trend in both in-hospital mortality (46.4% vs. 45.6%; adjusted OR, 0.78; 95% CI, 0.58–1.05; p=0.106) and mid-term mortality was observed between the sexes during the follow-up period, with a median of 339 days (adjusted HR, 0.85; 95% CI, 0.71–1.02; p=0.077) (Figure 2). Procedure-related complications (18.7% vs. 25.9%; adjusted OR, 1.82; 95% CI, 1.29–2.57; p=0.001) were more frequent among women than among men, as was limb ischemia (7.1% vs. 12.9%; adjusted OR, 2.32; 95% CI, 1.42–3.78; p=0.001) which is an important portion of procedure-related complications. However, the two groups had no significant difference in ECMO site bleeding or infection related to the ECMO, wound dehiscence, or stroke. Additionally, the weaning success rate also showed no difference between the groups (Table 2).
Figure 2. Kaplan–Meier curve for all-cause mortality according to sex.
CI = confidence interval; HR = hazard ratio.
Table 2. In-hospital clinical outcomes.
| Variables | Event rates | Unadjusted | Adjusted* | ||||
|---|---|---|---|---|---|---|---|
| Men (n=903) | Women (n=425) | OR (95% CI) | p value | OR (95% CI) | p value | ||
| In-hospital mortality | 419 (46.4) | 194 (45.6) | 0.97 (0.77–1.22) | 0.797 | 0.78 (0.58–1.05) | 0.106 | |
| Weaning success | 607 (67.2) | 291 (68.5) | 1.06 (0.83–1.36) | 0.650 | 1.22 (0.89–1.68) | 0.213 | |
| Procedure–related complication | 169 (18.7) | 110 (25.9) | 1.52 (1.15–1.99) | 0.003 | 1.82 (1.29–2.57) | 0.001 | |
| Limb ischemia | 64 (7.1) | 55 (12.9) | 1.95 (1.33–2.85) | <0.001 | 2.32 (1.42–3.78) | 0.001 | |
| ECMO site bleeding | 102 (11.3) | 54 (12.7) | 1.50 (1.10–2.04) | 0.013 | 1.45 (0.94–2.25) | 0.093 | |
| Infection related to the ECMO | 11 (1.2) | 10 (2.4) | 1.95 (0.81–4.67) | 0.129 | 1.87 (0.65–5.41) | 0.242 | |
| Wound dehiscence | 11 (1.2) | 15 (3.5) | 2.97 (1.36–6.68) | <0.001 | 2.62 (0.98–7.27) | 0.058 | |
| Stroke | 44 (4.9) | 34 (8.0) | 1.70 (1.06–2.69) | 0.025 | 1.57 (0.96–1.92) | 0.058 | |
| Bleeding | 68 (7.5) | 37 (8.7) | 1.17 (0.76–1.77) | 0.459 | 1.26 (0.75–2.11) | 0.378 | |
| Sepsis | 42 (4.7) | 27 (6.4) | 1.39 (0.84–2.27) | 0.194 | 1.10 (0.60–1.99) | 0.759 | |
Data presented as number (%).
CI = confidence interval; ECMO = extracorporeal membrane oxygenation; OR = odds ratio.
*Adjusted variables included age, body surface area, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, peripheral vascular disease, cerebral vascular accident, current smoking status, history of percutaneous coronary intervention, history of coronary artery bypass graft, etiology, extracorporeal cardiopulmonary resuscitation, return cannular size, drainage cannular size, and preemptive distal perfusion.
Factors associated with procedure-related complications and limb ischemia
Female sex (adjusted OR, 1.68; 95% CI, 1.13–2.49; p=0.009), ECPR (adjusted OR, 1.42; 95% CI, 1.03–1.97; p=0.003), and preemptive distal perfusion (adjusted OR, 0.71; 95% CI, 0.52–0.98; p=0.037) were independent predictors of procedure-related complications (Table 3). Additionally, the female sex (adjusted OR, 2.60; 95% CI, 1.50–4.54; p<0.001) and the implementation of a pre-emptive catheterization for distal limb perfusion (adjusted OR, 0.47; 95% CI, 0.30–0.74; p=0.001) were also identified as independent predictors of limb ischemia (Supplementary Table 2). In patients who received preemptive distal perfusion, there were no significant differences in clinical outcomes between men and women (5.5% vs. 9.7%; p=0.093). However, in patients who did not receive preemptive distal perfusion, females had higher limb ischemia rates than males (8.3% vs. 15.5%; p=0.004). In patients who did not receive preemptive distal perfusion, female sex was a predictor of limb ischemia (adjusted OR, 2.26; 95% CI, 1.23–4.18; p=0.008). Both women (preemptive distal perfusion vs. without preemptive distal perfusion, 45.4% vs. 32.7%; adjusted OR, 0.53; 95% CI, 0.28–0.98; p=0.046) and men (43.1% vs. 32.8%; adjusted OR, 0.62; 95% CI, 0.35–1.08; p=0.098) tended to have a lower incidence of the limb ischemia in preemptive distal perfusion compared to those without it, without significant interaction (p for interaction=0.872) (Figure 3).
Table 3. Independent predictors of procedure-related complications.
| Variables | Unadjusted OR (95% CI) | p value | Adjusted* OR (95% CI) | p value | |
|---|---|---|---|---|---|
| Female sex | 1.52 (1.15–1.99) | 0.003 | 1.68 (1.13–2.49) | 0.009 | |
| Age (years) | 0.99 (0.98–1.00) | 0.043 | 1.00 (0.98–1.01) | 0.553 | |
| Body surface area (m2) | 1.02 (0.98–1.05) | 0.391 | 1.54 (0.61–3.85) | 0.360 | |
| Diabetes mellitus | 0.76 (0.57–1.01) | 0.061 | 0.93 (0.64–1.34) | 0.685 | |
| Hypertension | 0.81 (0.62–1.06) | 0.132 | 0.91 (0.63–1.31) | 0.612 | |
| Dyslipidemia | 1.18 (0.84–1.64) | 0.329 | 1.32 (0.85–2.00) | 0.206 | |
| Current smoker | 0.92 (0.67–1.26) | 0.626 | 1.07 (0.69–1.62) | 0.763 | |
| Chronic kidney disease | 0.99 (0.63–1.51) | 0.964 | 1.00 (0.59–1.64) | 0.994 | |
| Peripheral vascular disease | 0.87 (0.40–1.78) | 0.750 | 0.43 (0.12–1.17) | 0.134 | |
| Cerebral vascular accident | 1.14 (0.71–1.77) | 0.586 | 1.07 (0.59–1.87) | 0.811 | |
| History of PCI | 1.05 (0.76–1.42) | 0.766 | 1.14 (0.75–1.73) | 0.534 | |
| History of CABG | 1.21 (0.71–1.98) | 0.459 | 1.31 (0.73–2.28) | 0.342 | |
| Ischemic etiology | |||||
| AMI-related CS | Reference | Reference | |||
| HF-related CS, ischemic | 1.08 (0.66–1.71) | 0.748 | 1.05 (0.59–1.80) | 0.862 | |
| HF-related CS, non-ischemic | 1.49 (1.10–2.01) | 0.009 | 1.49 (0.96–2.31) | 0.075 | |
| Other | 0.88 (0.56–1.36) | 0.581 | 0.72 (0.41–1.26) | 0.255 | |
| ECPR | 1.29 (0.99–1.69) | 0.057 | 1.42 (1.03–1.97) | 0.033 | |
| Vasopressor use | 1.10 (0.67–1.87) | 0.711 | 1.12 (0.67–1.92) | 0.676 | |
| Preemptive distal perfusion | 0.94 (0.72–1.22) | <0.001 | 0.71 (0.52–0.98) | 0.037 | |
AMI = acute myocardial infarction; CABG = coronary artery bypass graft; CI = confidence interval; CS = cardiogenic shock; ECPR = extracorporeal cardiopulmonary resuscitation; HF = heart failure; OR = odds ratio; PCI = percutaneous coronary intervention.
*Adjusted variables are sex, age, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, current smoking habit, peripheral vascular disease, cerebral vascular accident, history of percutaneous coronary intervention, history of coronary artery bypass graft, etiology, extracorporeal cardiopulmonary resuscitation, vasopressor, and preemptive distal perfusion.
Figure 3. ORs for limb ischemia by subgroup analysis.
Adjusted according to sex, age, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, current smoking habit, peripheral vascular disease, cerebral vascular accident, history of percutaneous coronary intervention, history of coronary artery bypass graft, etiology, extracorporeal cardiopulmonary resuscitation, and arterial cannular size.
CI = confidence interval; OR = odds ratio.
DISCUSSION
In this study, we investigated whether sex-related differences in clinical outcomes exist among patients with CS from 2 large registries receiving VA-ECMO support. The main findings were as follows. First, in unadjusted and adjusted analyses, the in-hospital and follow-up mortality rates were similar between men and women. Second, women were more likely to experience procedure-related complications, including limb ischemia. Third, female sex was a significant predictor of limb ischemia as well as pre-emptive distal perfusion catheterization.
Numerous studies have evaluated sex differences in cardiovascular disease; however, limited data are available from CS patients, especially those receiving VA-ECMO. In previous studies, female CS patients showed a higher mortality rate than male CS patients.8),12) These results have been attributed to the fact that women tend to present at an older age with atypical symptoms and more underlying risk factors, and they more often do not receive adequate treatment due to a low socioeconomic status.13),14),15) Furthermore, more recently, a few studies have included other etiologies, including non-ischemic–related heart failure and Ton et al.5) found that women with heart failure–related CS experienced worse in-hospital mortality than men with heart failure–related CS. However, Wang et al.4) also reported no difference in in-hospital mortality between men and women after ECMO implantation in patients with CS, including those undergoing ECPR.16) In this study, a variety of patients with both ischemic- and non-ischemic–related CS were included, and we found no significant difference in mortality between women and men. Importantly, there is some discrepancy in the results of previous studies, especially concerning the application of VA-ECMO. However, this could be attributed to the varying severity of the disease, with mechanical circulatory support required in only more severe cases. Even if there was a sex difference, an increase in disease severity may mitigate this difference, resulting in a more minor sex effect.
In the present study, procedure-related complications were more common in women, which is driven by the greater incidence of limb ischemia in women. Limb ischemia is a representative complication related to ECMO cannulation, resulting in reduced perfusion to the limb below the arterial cannula's insertion point.5),17),18) In their study, Ton et al.5) similarly identified higher rates of vascular complications, including limb ischemia, among women compared to men. The mechanisms behind such adverse events are often multifactorial, including suboptimal arterial perfusion and hemodynamic instability due to the underlying disease, peripheral vascular disease, and placement of cannulas that nearly occlude the vessel.17) Limb ischemia impacts in-hospital mortality and quality of life.19) In some cases, intervention or surgery may be required, and amputation may be necessary in severe cases. Therefore, it is crucial to prevent limb ischemia by the preventive insertion of a distal perfusion catheter.20),21) In our study, women had a higher incidence of limb ischemia, and their smaller peripheral artery diameter relative to that in men may be a contributing factor19),22) This smaller diameter makes it easier to puncture the artery multiple times, which can lead to vascular injury, such as dissection or perforation, resulting in limb ischemia. Furthermore, postmenopausal women have greater arterial stiffness than age-matched men,23) and there is evidence that patients with critical limb ischemia have high arterial stiffness.24) In the present study, 3-quarters of the included women were postmenopausal, which may be related to the greater rate of limb ischemia in women. In the present study, there were 55 cases of limb ischemia among women, of which 18 underwent distal perfusion and 37 did not. In patients who did not receive distal perfusion, there was a sex difference in limb ischemia. More importantly, preemptive distal perfusion was associated with a lower incidence of limb ischemia in both men and women, with no significant interaction between sex and the intervention. These results support that preemptive distal perfusion would provide prognostic benefits compared to not using it, regardless of sex. These findings suggest that pre-emptive cannulation of distal perfusion catheters should be considered to prevent ECMO-related limb ischemia, especially among women.16),25)
This study has several limitations. First, since it was a retrospective study, residual or unmeasured confounding factors may have influenced the results. However, our data revealed statistically significant differences in outcomes between women and men. Second, although we hypothesized that the reasons for the higher incidence of limb ischemia in women were vessel size and peripheral arterial disease, we lacked data on vessel size. Third, we did not consider other factors that may contribute to the higher mortality rate in women, such as differences in socioeconomic status or medical compliance. Numerous previous studies have shown that individuals with lower socioeconomic status and poor medical compliance tend to have poorer clinical outcomes in the intensive care unit, attributed to higher baseline severity of illness, a more significant burden of comorbidities, and limited access to healthcare resources.26),27) Fourth, in our study, patients with CS were presented with variable etiologies, which could influence mortality outcomes. Therefore, we included the etiology variable as a covariate in multivariable analysis to minimize such biases. Fifth, we did not adjust for the patient’s condition before ECMO insertion, including factors such as ECPR and the quality and duration of CPR. These factors may have influenced outcomes, representing potential limitations in our analysis.
Although there was no significant difference in in-hospital or mid-term mortality between men and women, being female was an independent risk factor for procedure-related complications, mainly driven by the greater rate of limb ischemia among women. These findings suggest that more caution should be taken when implanting ECMO, especially in women.
Footnotes
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest: The authors have no financial conflicts of interest.
Data Sharing Statement: The data generated in this study is available from the corresponding author upon reasonable request.
- Conceptualization: Kim O, Choi KH.
- Data curation: Yang JH.
- Formal analysis: Kim O.
- Investigation: Hong D, Choi KH, Lee JM, Park TK, Song YB, Hahn JY, Choi SH, Cho YH, Gwon HC, Yang JH.
- Methodology: Yang JH.
- Supervision: Yang JH.
- Visualization: Yang JH.
- Writing - original draft: Kim O.
- Writing - review & editing: Yang JH.
SUPPLEMENTARY MATERIALS
Independent predictors of in-hospital mortality
Independent predictors of limb ischemia
References
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Supplementary Materials
Independent predictors of in-hospital mortality
Independent predictors of limb ischemia