Abstract
Introduction
Sex disparities in access to health care in low-resource settings have been demonstrated. Still, there has been little research on the effect of sex on postoperative outcomes. We evaluated the relationship between sex and mortality after emergency abdominal surgery.
Methods
We performed a retrospective cohort study using the acute care surgery database at Kamuzu Central Hospital (KCH) in Malawi. We included patients who underwent emergency abdominal surgery between 2013 and 2021. We created a propensity score weighted Cox proportional hazards model to assess the relationship between sex and inpatient survival.
Results
We included 2052 patients in the study, and 76% were males. The most common admission diagnosis in both groups was bowel obstruction. Females had a higher admission shock index than males (0.91 vs. 0.81, p < 0.001) and a longer delay from admission until surgery (1.47 vs. 0.79 days, p < 0.001). Females and males had similar crude postoperative mortality (16.3% vs. 15.3%, p = 0.621). The final Cox proportional hazards regression model was based on the propensity-weighted cohort. The mortality hazard ratio was 0.65 among females compared to males (95% CI 0.46–0.92, p = 0.014).
Conclusions
Our results show a survival advantage among female patients undergoing emergency abdominal surgery despite sex-based disparities in access to surgical care that favors males. Further research is needed to understand the mechanisms underlying these findings.
Introduction
Worldwide, females face significant disparities in the form of sex-based discrimination leading to inferior social status, lower levels of educational attainment, and economic vulnerability [1]. These disparities are also evident within the health care system, particularly in low-resource settings [2]. Women in low- and middle-income countries (LMICs) present to a health care facility less frequently when compared to men in similar medical circumstances, with studies reporting male-to-female ratios of 2.2 for emergency abdominal surgeries and 1.4 for general admissions, excluding obstetric care [3, 4].
The 2019 Lancet series on Gender Equality, Norms, and Health documents how traditional gender norms focusing on women as caregivers and men as providers can impact health [5]. As a result, females in LMICs frequently experience barriers to surgical care. For example, compared to males, female patients report more difficulty navigating the health care system, securing funds for surgery, and finding someone to care for them after a procedure [6, 7]. Females are less likely to seek care for an illness, dismissing their health needs in favor of their husbands or male children [6]. They are also more likely to report fear of surgery or mistrust of the health care system [7, 8]. In some settings, female patients cannot even access health services without being accompanied by a male relative [9]. Women in low- and middle-income countries (LMICs) present to a health care facility less frequently when compared to men in similar medical circumstances [4, 10, 11].
Despite these inequalities, the female sex is not universally associated with worse surgical outcomes. Female patients have consistently been found to be at lower risk of sepsis, organ failure, and mortality after sustaining traumatic injuries [12–14]. They also have lower mortality after hip fracture admission and after revascularization or amputation for peripheral artery disease [15, 16]. Conversely, females have higher mortality after open or endovascular abdominal aortic aneurysm (AAA) repair and after coronary artery bypass grafting (CABG) [17, 18]. The mechanisms underlying these conflicting outcomes are poorly understood but are attributed to the combined effects of multiple biological, behavioral, and social factors [19].
In resource-limited settings, though female sex is an independent predictor of delayed presentation and delayed surgery, the potential effect of sex on postoperative outcomes is not well delineated. We, therefore, sought to evaluate the relationship between sex and postoperative in-hospital survival after emergency abdominal surgery in Malawi. We hypothesized that female patients would have inferior survival compared to male patients.
Methods
Setting
Malawi is a low-income country in Sub-Saharan Africa and has a population of 19 million people. This study occurred at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. KCH is a 900-bed tertiary care center in Malawi’s central region, with a catchment population of approximately 7.5 million persons. Its facilities include a 4-bed 24-h casualty department, a 4-bed high dependency unit (HDU), a 6-bed intensive care unit (ICU), and six operating rooms in the main operating theaters, with one dedicated to emergency general surgery and available 24 h per day. KCH Surgery department is staffed by six attending general surgeons, surgery residents, and the anesthesia department has one anesthesiologist and 15 anesthetic clinical officers.
Data collection
The University of North Carolina, in collaboration with KCH, developed and implemented a prospectively maintained acute care surgery (ACS) registry at KCH in 2013. All patients with emergency general surgery complaints are entered into the registry upon arrival at KCH and followed for the duration of their hospitalization. The registry data variables include patient demographics, admission vitals and diagnoses, treatment, and outcomes. The registry does not include patients with traumatic injuries or obstetric/gynecologic diagnoses. We performed a retrospective cohort study of the KCH ACS registry from September 2013 until July 2021.
Patients were eligible for inclusion if they were ≥ 12 years of age and underwent emergency abdominal surgery for an acute abdomen diagnosis. The age cutoff was chosen because the adult general surgery service manages all patients 12 years of age and older. We excluded patients with hernias, as most in this database are inguinal hernias, which are significantly more common in males than females. We also excluded patients with missing data on sex, length of stay, or outcome.
Statistical analysis
We used bivariable analysis to compare patient characteristics by sex. We used the Student’s T test to assess differences in means and Pearson’s Chi-square test to evaluate differences in proportions. We then performed a propensity score weighted analysis. The two groups (male and female) were weighted on the following variables: age, transfer from another facility to KCH versus direct admission, transport mechanism, admission diagnosis, shock index (Heart rate/Systolic blood pressure), admission AVPU score (an acronym from "alert, verbal, pain, unresponsive"), and days from arrival at KCH until surgery. Propensity matching was estimated using a logistic regression model that included all potential confounders (age, transfer status, type of transport, shock index, AVPU, and days from presenting to KCH until surgery).
The percentage of missing data values ranged from 0% for some demographics variables to as high as 20% for shock index. Data were missing completely at random due to the inconsistencies of vital sign collection and documentation in a resource-limited setting. We address the problem of missing data using multiple imputation (MI) technique including all variables. To account for missing data, we performed MI for heart rate and systolic blood pressure. The imputation modeling was performed using STATA (release 17, College Station, TX: StataCorp LLC) package mi impute command. The variables used in the imputation phase include death, age, transfer status, AVPU, diagnosis, and time from presentation at KCH until surgery and generated 20 imputed datasets. Imputed values compare reasonably to observed values, and results using listwise deletion are similar to MI, so imputed results are presented.
To control for baseline differences between the two treatment groups on the multiply imputed dataset, we weighted the cohort using inverse probability of treatment weights (IPTW) derived from the propensity score. We used IPTW to avoid losing study subjects, which could occur during the matching process, to allow us to perform balance diagnostics after applying the propensity score, and to confirm the equalization of differences in baseline covariates between the males and females. We then performed a balance assessment of our IPTW samples using mean standardized differences and visually inspected the weights using overlap plots of the propensity scores between males and females [20, 21]. Appendix Fig. 3
Fig. 3.
Overlap plot for assessment of balance following inverse probability treatment weighting
We created a Cox proportional hazards model to assess the relationship between sex and survival based on the imputed and propensity-weighted cohort. A Kaplan–Meier survival curve was used to display our results, including a risk table over the length of stay. Statistical tests based on the scaled Schoenfeld residuals assessed the proportional hazards assumption [22].
Results
Over the study period, 6,733 patients were entered into the registry. After excluding patients with non-abdominal diagnoses (N = 2659), patients with hernias (N = 547), patients who were treated nonoperatively or with elective surgery (N = 1422), patients under 12 years of age (N = 39), and patients missing length of stay data (N = 14), the final study population was 2,052 (Fig. 1). None of the remaining patients were missing sex or outcome data.
Fig. 1.
Flow diagram of patient selection
The study population included 1566 males (76.3%) and 486 females (23.7%) (Table 1). There were no statistically significant differences between males and females in age, proportion transferred to KCH from another facility, and proportion transported by ambulances. Bowel obstructions were the most common diagnosis in both groups but were more common in females than in males (59.3% and 48.0%, respectively). Males had a higher proportion of generalized peritonitis and volvulus than females. Females waited longer than males from arrival at KCH until surgery (1.5 (SD 5.1) versus 0.8 (SD 2.2) days, p < 0.0001). The median time from arrival to surgery was 1 day (IQR 0–1) among females and 0 days (IQR 0–1) among males. Females also had a longer mean length of stay (10.8 (SD 10.1) versus 8.9 (SD 9.9) days, p = 0.002). The median length of stay was 7 days (IQR 5–12) among females and 6 days (IQR 4–10) among males. Postoperative mortality in the overall cohort was 15.6%. Crude postoperative mortality was similar in females compared to males (16.3% versus 15.3%, p = 0.62).
Table 1.
Patient characteristics by sex
| Total N = 2,052 | Male N = 1566 (76.3%) | Female N = 486 (23.7%) | P-value | |
|---|---|---|---|---|
| Age in years: Mean (SD) | 39.2 (17.0) | 39.5 (17.1) | 38.0 (16.8) | P = 0.09 |
| Transferred to from another facility: N(%) | 1807 (88.2%) | 1373 (87.9%) | 434 (89.3%) | P = 0.40 |
| Ambulance Transport: N(%) | 1667 (82.3%) | 1270 (82.0%) | 397 (83.1%) | P = 0.61 |
| Admission dx: N(%) | ||||
| Generalized peritonitis | 517 (25.2%) | 408 (26.1%) | 109 (22.4%) | |
| Appendicitis | 221 (10.8%) | 166 (10.6%) | 55 (11.3%) | |
| Bowel obstruction | 1040 (50.7%) | 752 (48.0%) | 288 (59.3%) | |
| Volvulus | 274 (13.4%) | 240 (15.3%) | 34 (7.0%) | P < 0.0001 |
| Admission HR: Mean (SD) | 98.7 (22.6) | 96.7 (21.9) | 105.3(23.6) | P < 0.0001 |
| Admission SBP: Mean (SD) | 123.8 (21.3) | 124.8 (21.4) | 120.4 (20.4) | P = 0.001 |
| Admission Shock Index: Mean(SD) | 0.8 (0.3) | 0.8 (0.3) | 0.9 (0.3) | P < 0.0001 |
| Admission AVPU: N(%) | ||||
| Alert/voice | 1952 (95.9%) | 1494 (96.3%) | 458 (94.6%) | |
| Pain/unresponsive | 83 (4.1%) | 57 (3.7%) | 26 (5.4%) | P = 0.09 |
| Days from arrival at KCH until surgery: Mean (SD) | 0.95 (3.2) | 0.79 (2.2) | 1.47 (5.1) | |
| Median (IQR) | 0 (0–1) | 0 (0–1) | 0 (0–1) | P < 0.0001 |
| Length of stay in days: Mean (SD) | 9.4 (10.0) | 8.9 (9.9) | 10.8 (10.1) | |
| Median (IQR) | 6 (4–10) | 6 (4–9) | 7 (5–12) | P = 0.0002 |
| Postoperative length of stay: Mean (SD) | 8.5 (9.7) | 8.2 (9.6) | 9.6 (10.0) | |
| Median (IQR) | 6 (4–9) | 6 (5–11) | 7 (5–11) | P = 0.05 |
| Postoperative death: N(%) | 319 (15.6%) | 240 (15.3%) | 79 (16.3%) | P = 0.62 |
After propensity weighting of the sample, weighted logistic regression analysis revealed that the groups were well balanced across the included variables (Table 2), and there were no statistically significant differences in standardized mean differences in the weighted and unweighted covariates. Figure 2 shows the overlap plots after matching, showing good balance. The unadjusted Cox proportional hazards regression model revealed a mortality hazard ration of 0.65 among females compared to male patients (95% CI 0.46–0.92, p = 0.014) (Table 3). Survival curves by sex is shown in Fig. 2. The proportional hazards assumption using Schoenfeld residuals showed a test statistic of 0.3 and a p-value of 0.58, suggesting that the proportional hazards assumption is not violated.
Table 2.
Logistic regression model predicting female sex before and after propensity matching
| Unweighted logistic regression | Weighted logistic regression | ||||||
|---|---|---|---|---|---|---|---|
| OR | 95% CI | P-value | OR | 95% CI | P-value | ||
| Age | 1.01 | 1.00–1.01 | < 0.001 | 1.00 | 1.00–1.00 | 0.761 | |
| Transferred from another facility to KCH | 0.88 | 0.73–1.05 | 0.16 | 0.99 | 0.82–1.19 | 0.90 | |
| Ambulance transport | 1.50 | 1.28–1.75 | < 0.001 | 1.06 | 0.90–1.24 | 0.52 | |
| Admission diagnosis | Reference: Peritonitis | – | – | – | – | – | – |
| Appendicitis | 1.15 | 0.98–1.34 | 0.08 | 1.02 | 0.90–1.20 | 0.81 | |
| Bowel obstruction | 1.35 | 1.21–1.51 | < 0.001 | 0.99 | 0.89–1.11 | 0.92 | |
| Volvulus | 0.53 | 0.44–0.63 | < 0.001 | 0.97 | 0.80–1.18 | 0.78 | |
| Shock index | 2.89 | 2.47–3.38 | < 0.001 | 0.92 | 0.74–1.15 | 0.48 | |
| Admission AVPU | Pain/unresponsive | 1.34 | 1.11–1.61 | 0.002 | 1.01 | 0.89–1.32 | 0.45 |
| Days from arrival at KCH until surgery | 1.04 | 1.03–1.06 | < 0.001 | 1.01 | 1.00–1.02 | 0.22 | |
Fig. 2.
Kaplan–Meier survival curve by sex. Test of proportional hazards assumption = 0.3
Table 3.
Propensity weighted cox proportional hazard model for mortality
| Hazard ratio | 95% Confidence interval | P-value | |
|---|---|---|---|
| Female sex | 0.65 | 0.46–0.92 | 0.014 |
Number of observation in the analysis -1977
Discussion
In this propensity-matched cohort of patients undergoing emergency abdominal surgery in Malawi, we found that female patients had statistically significant better survival than males. We expected females to have higher mortality based on prior research reporting disproportionate barriers to timely surgical care among females. Our results contradict our hypothesis. Females did wait an average of 0.7 days longer than males for surgery, a time difference that could be clinically significant for patients requiring urgent surgical intervention, but this did not affect their outcomes negatively.
The results of prior studies on this topic are conflicting. Two extensive studies from Canada and Poland reported statistically significantly lower mortality among females across various surgical procedures [23, 24]. An American study also found significantly lower postoperative sepsis rates among females, but the relationship between sex and mortality was not evaluated [25]. On the other hand, Rucker et al. in a different Canadian study that only included patients undergoing emergency abdominal surgery found no statistically significant differences in mortality by sex. However, males did have higher rates of major respiratory complications [26]. An essential commonality between these studies and our own is that patients who did not receive surgery were excluded, and it is certainly possible that this influenced results. Indeed, a study of the World Health Organization Global Burn Registry, which included patients regardless of surgical status, found that female patients had lower rates of surgical treatment and higher mortality rates than males [10].
It has been suggested that the female survival advantage after surgery may be attributable to better health-seeking behaviors among females than among males [23]. In Kenya, among patients with elevated blood pressure, females are more likely than males to have attended an outpatient visit in the last 12 months and be taking prescription antihypertensive medication [27]. In a Malawian household survey, too, females were more likely than males to report seeking care for an illness [28]. However, the potential relationship between contact with the health care system and postoperative outcomes has not specifically been studied. In addition, it is unclear how to reconcile this phenomenon with the fact that only 25% of the patients in our cohort were female, even though we excluded sex-specific diagnoses. This finding may again be related to a possible discrepancy between those who seek surgical care and those who receive surgery, an area that warrants further research.
Studies have shown improved survival among female patients following traumatic injury, which may be attributable to sex-based biological differences [13, 14, 29]. In particular, estrogen has been found to have a protective effect on macrophage and T cell function, reducing the degree of post-trauma immunosuppression and potentially lowering the risk of sepsis and mortality [14]. Interestingly, differences in immune function between men and women have also been cited as a reason for the survival benefit among females with COVID-19 [30, 31]. It is plausible that similar biologic effects, in combination with other social, economic, cultural, and behavioral factors, play a role in the improved survival among females after emergent abdominal surgery as well.
This study has several limitations, including but not limited to the retrospective methodology. Covariates that may be important and not accounted for in the adjustment model may have affected our results. In particular, we did not have data on comorbidities, ASA score, or illness severity (other than admission vitals, which allowed us to calculate shock index). To compensate for this, we only included patients who had an indication for emergent surgery. In addition, we lacked information on the time from symptom onset to presentation. A future prospective study would be able to eliminate confounding by these variables. Finally, as discussed previously, there may have been a survival bias among those patients who survived until surgical intervention. It is possible that this bias was more pronounced among females, as they waited longer than males for surgery. Nonetheless, we believe that our results are an essential contribution to the literature on sex differences in postoperative survival.
Conclusions
Among patients undergoing emergency abdominal surgery in Malawi, females have significantly better postoperative survival than males. Additional research is needed to better understand the reasons for this survival advantage and determine whether there are differences in mortality when patients who do not survive until surgery are included.
Acknowledgements
We wish to thank all our collaborators and partners at Kamuzu Central Hospital.
Appendix
See Fig. 3.
Funding
This study was funded by the NIH Fogarty International Center (Avital Yohann: Grant #D43TW009340).
Declarations
Conflict of interest
None.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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