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. 2025 Dec 5;88(1):362–370. doi: 10.1097/MS9.0000000000004502

Rising mortality from electrolyte and acid–base imbalances in the United States (1999–2020): a joinpoint regression analysis of national trends and disparities

Zaima Afzaal a, Asma Chaudhary b, Inshal Uddin Khattak c, Saba Aliha d, Asad Khan e, Anas M Din Bashir f, Hameer Ali g, Amnah Khan h, Aizaz Anwar Khalid i, Wania Khan j, Touqeer Rehman k, Maryam Atif l, Areen Zia j, Mazia Mahnoor j, Rumman Javed m, Saad Ahmed Waqas j, Raheel Ahmed n, Somaiya Ahmed o,*
PMCID: PMC12767931  PMID: 41496914

Abstract

Background:

Electrolyte and acid–base imbalance (EABI) has emerged as a critical contributor to rising mortality rates worldwide. However, there is an inconsistency in the data on long-term mortality trends associated with EABI in the United States.

Objectives:

This study aims to evaluate nationwide mortality trends associated with EABI from 1999 to 2020.

Methods:

We utilized the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research database to retrieve EABI-associated mortality data among U.S. populations. We analyzed EABI-related deaths (ICD-10 codes E87.0–E87.8) across all ages, with subgroup analyses by EABI subcategory and common underlying causes: heart failure (I50), diabetes mellitus (E10–E14), sepsis (A41), and chronic kidney disease (N18). Age-adjusted mortality rates (AAMRs) were calculated per 100 000 persons, and annual percent changes (APCs) in mortality trends were determined using the joinpoint regression model with corresponding 95% confidence intervals. AAMRs were further stratified by race, sex, age, U.S. census region, and urbanization status.

Results:

Between 1999 and 2020, a total of 580 238 deaths occurred due to EABI. Overall, the AAMRs increased from 7.88 to 12.25 (AAPC: + 2.1533%; 95% CI: 0.87–3.43; P = 0.000817). Males exhibited consistently higher overall AAMRs as compared to females (8.58 vs 7.29). Among racial groups, Non-Hispanic Blacks had the highest AAMR (12.70), while Asians had the lowest (5.45). Regionally, the South reported the highest AAMR (8.70), followed by the Midwest (7.78), Northeast (7.35), and West (7.06). Non-metropolitan areas had notably higher AAMRs (9.73) than metropolitan counterparts (7.49). Subgroup analysis showed the highest AAMR for acidosis (2.88) and sepsis had the highest by cause (0.30).

Conclusion:

There is a prominent increase in EABI-linked mortality from 1999 to 2020, with significant disparities in various population groups. These findings warrant the instantaneous implementation of targeted interventions, such as improvement in electrolyte monitoring protocols and expanded access to specialist care, to control the rising burden.

Keywords: disparities, electrolytes, mortality, trends

Introduction

Electrolyte and acid–base imbalances (EABI) represent a spectrum of disorders involving sodium, potassium, calcium, magnesium, chloride, and pH homeostasis[1]. Electrolytes are essential for normal physiological function, and even minor deviations from their narrow range have consequences ranging from asymptomatic biochemical abnormalities to life-threatening organ dysfunction[1,2]. EABI are known to disrupt cardiac electrophysiology, increasing the risk of arrhythmias, and can exacerbate outcomes in critically ill patients[3,4]. A study reported that about 64% of critically ill patients experience acute metabolic acidosis[2]. Additionally, the burden of comorbid conditions such as diabetes mellitus (DM), heart failure (HF), cancer, and the recent COVID-19 pandemic has further underscored the fatal consequences of EABI[5–7]. Critically ill children, especially those with prolonged hospitalizations, face increased vulnerability to electrolyte emergencies[8]. Early recognition and prompt intervention are vital, as these disturbances are linked to extended hospital stays and higher in-hospital mortality.

Epidemiologic research has provided valuable insights into the pathophysiology and diagnosis of acid–base disorders, along with comprehensive evaluations of electrolyte disturbances[1,8]. Prior studies have established the existence of marked sociodemographic disparities and health care inequities contributing to adverse outcomes[1,9–11]. However, the long-term mortality trends associated with EABI in the United States have not been systematically characterized. By quantifying two decades (1999–2020) of population-level mortality patterns using CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) data, and in compliance with TITAN guideline[12], our study builds on this foundational knowledge, translating awareness of disparities into concrete, temporal evidence. These data can guide targeted public health strategies, refine resource allocation, and support policies aimed at reducing inequities and improving outcomes for high-risk populations. Given that chronic diseases account for more than 90% of annual U.S. health care expenditures, understanding and addressing these mortality trends also has the potential to alleviate substantial economic burdens on the health care system through prevention, early intervention, and optimized care delivery.

Methods

Study setting and population

This retrospective study utilized de-identified death certificate data from the CDC WONDER database from 1999 to 2020[13]. We examined EABI-related death certificates across all age groups, using International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes E87.0 (hyperosmolality and hypernatremia), E87.1 (hypoosmolality and hyponatremia), E87.2 (acidosis), E87.3 (alkalosis), E87.4 (mixed disorders of acid-base balance), E87.5 (hyperkalaemia), E87.6 (hypokalaemia), E87.7 (fluid overload), and E87.8 (others) for EABI and its subcategories. Subgroup analyses were conducted for EABI and its subcategories, as well as for its common underlying causes: HF (I50), DM (E10–E14), sepsis (A41), and chronic kidney disease (CKD) (N18). EABI-related deaths were defined as those listing EABI as either a contributing or underlying cause. Analyses were conducted both individually by variable and collectively to assess national trends. This data set documented causes of mortality across all 50 states and the District of Columbia, using the Multiple Cause-of-Death Public Use files. Institutional review board approval was not required, as the study employed publicly available, de-identified data and adhered to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines[14].

Data abstraction

Data were abstracted and segmented based on population size, year, demographics, urban-rural classification, and geographic region. Demographic variables included sex, age, and race/ethnicity. Racial/ethnic categories were defined as Non-Hispanic (NH) White, NH Black or African American, Hispanic or Latino, NH American Indian or Alaskan Native, and NH Asian or Pacific Islander. Urban–rural classification followed the 2013 National Center for Health Statistics Urban–Rural Classification Scheme[15]. Geographic regions were categorized according to the U.S. Census Bureau’s definitions: Northeast, Midwest, South, and West[16].

HIGHLIGHTS

  • The AAMR for EABI-related deaths increased from 7.88 in 1999 to 12.25 in 2020, declining from 1999–2008, increasing from 2008–2018, and surging from 2018–2020.

  • The AAMR for men (8.58) was higher than that for women (7.29).

  • Among Racial groups and regions, the NH Black population and the Southern region had the highest AAMR, respectively.

  • Across EABI subcategories, the highest AAMR was for acidosis (2.88), followed by hyperkalemia (1.80).

  • AAMRs for EABI by underlying cause ranged from 0.13 (HF) to 0.30 (sepsis), with CKD and diabetes showing similar rates (0.28 each).

Statistical analysis

We analyzed mortality trends related to electrolyte imbalance from 1999 to 2020, reporting crude and age-adjusted mortality rates (AAMRs) per 100 000 population with 95% confidence intervals (CIs), stratified by year, sex, race/ethnicity, region, and urban-rural status. Crude mortality rates were calculated by dividing total EABI-related deaths by the corresponding annual U.S. population. AAMRs were standardized to the 2000 U.S. population to allow for temporal comparisons[17].

To assess annual trends, we used the Joinpoint Regression Program (version 5.3.0, National Cancer Institute)[18] to calculate annual percent changes (APCs) along with their 95% CI, employing the Monte Carlo permutation test for model selection. This software program points out changes in AAMRs to calculate APC by fitting a log-linear regression model where temporal variation appears. Average Annual Percentage Changes (AAPCs) over 1999–2020 were determined as the weighted average of APCs. Following guidelines, 0–4 joinpoints were tested, and the final model was applied. APC, AAPC, and CIs were calculated using the parametric method, with 4499 permutations for the permutation test. Moreover, APCs were classified as increasing or decreasing when the slope significantly differed from zero using two-tailed t-tests, with statistical significance set at P < 0.05.

Results

A total of 580 238 EABI-related deaths occurred among U.S. residents between 1999 and 2020 (Supplemental Digital Content Table 1, available at: http://links.lww.com/MS9/B47, Central Illustration). However, the location of death was known for 569 917 deaths. Of these, 76.46% were reported in medical facilities, 12.86% at nursing homes/long-term care facilities, 9.25% at homes, and 1.45% at hospices. (Supplemental Digital Content Table 2, available at: http://links.lww.com/MS9/B47).

Annual trends for EABI-related AAMR

The AAMR for EABI across all ages was 7.88 (95% CI: 7.78–7.99) in 1999 and peaked at 12.25 (95% CI: 12.14–12.36) in 2020. Initially, the AAMRs declined from 1999 to 2008 (APC: −2.73; 95% CI: −3.18 to −2.27), followed by a rising trend from 2008 to 2018 (APC: 4.44; 95% CI: 4.00–4.89). A marked increase was observed from 2018 to 2020 (APC: 12.08; 95% CI: 7.93–16.38) (Fig. 1, Supplemental Digital Content Table 3, available at: http://links.lww.com/MS9/B47, and Supplemental Digital Content Table 4, available at: http://links.lww.com/MS9/B47).

Figure 1.

Figure 1.

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Overall and sex-stratified EABI-related AAMRs per 100 000 in the United States, 1999–2020.

EABI-related AAMR stratified by sex

Our results disclosed that the absolute number of deaths from 1999 to 2020 was highest in women as compared to men (312 758 vs. 267 480) (Supplemental Digital Content Table 1, available at: http://links.lww.com/MS9/B47). Men exhibited a higher total overall AAMR than women (8.58 vs. 7.29), with both sexes peaking in 2020 (13.85 in men vs. 10.93 in women). Among men, AAMR declined from 1999 to 2007 (APC: −3.49; 95% CI: −4.17 to −2.79), then increased from 2007 to 2018 (APC: 4.16; 95% CI: 3.71–4.61), followed by a sharp rise between 2018 and 2020 (APC: 15.12; 95% CI: 10.35–20.09). Similarly among women, the AAMR decreased from 1999 to 2008 (APC: −2.63; 95% CI: −3.18 to −2.08), then rose steadily from 2008 to 2018 (APC: 4.29; 95% CI: 3.77–4.80), followed by a sharper increase from 2018 to 2020 (APC: 10.58; 95% CI: 5.72–15.65). Overall, mortality rates initially declined until the late 2000s before rising steadily, with a notable surge in recent years, especially among men (Fig. 1, Supplemental Digital Content Table 3, available at: http://links.lww.com/MS9/B47, and Supplemental Digital Content Table 1, available at: http://links.lww.com/MS9/B47).

EABI-related AAMR stratified by race

Our results also showed that the absolute number of deaths from 1999 to 2020 was highest in NH Whites (429 124), followed by NH Black or African Americans (87 253), Hispanic or Latinos (42 380), NH Asian or Pacific Islanders (14 999), and NH American Indian or Alaskan Natives (4909) (Supplemental Digital Content Table 1, available at: http://links.lww.com/MS9/B47).

Racial stratification revealed the highest AAMRs among Non-Hispanic (NH) Black/African Americans at 12.7 (95% CI: 12.61–12.79), followed by NH American Indian/Alaska Natives at 11.71 (95% CI: 11.36–12.06), NH Whites at 7.41 (95% CI: 7.39–7.43), Hispanic/Latinos at 7.22 (95% CI: 7.15–7.30), and NH Asian/Pacific Islanders at 5.45 (95% CI: 5.37–5.54). Among NH Black/African Americans, AAMRs declined from 1999 to 2008 (APC: −4.02; 95% CI: −4.60 to −3.42) before steadily rising until 2018 (APC: 3.59; 95% CI: 3.02–4.15), followed by a sharp increase from 2018 to 2020 (APC: 15.52; 95% CI: 10.38–20.89). Hispanic/Latino and NH White populations showed declines from 1999 to 2007 (Hispanic: APC: −3.46; 95% CI: −4.63 to −2.27; NH White: APC: −3.07; 95% CI: −3.83 to −2.30), then increases until 2018 (Hispanic: APC: 3.98; 95% CI: 3.31–4.63; NH White: APC: 4.20; 95% CI: 3.66–4.73), followed by steep rises through 2020 (Hispanic: APC: 25.70; 95% CI: 19.14–32.60; NH White: APC: 11.31; 95% CI: 5.73–17.16). NH American Indian/Alaska Natives experienced a steady increase from 1999 to 2018 (APC: 2.79; 95% CI: 1.95–3.62), with a marked rise from 2018 to 2020 (APC: 21.45; 95% CI: 2.58–43.78). NH Asian/Pacific Islanders saw a decline from 1999 to 2004 (APC: −5.63; 95% CI: −10.67 to −0.30), followed by a stable period until 2015, then a rapid increase through 2020 (APC: 9.19; 95% CI: 6.03–12.43) (Fig. 2, Supplemental Digital Content Table 4, available at: http://links.lww.com/MS9/B47, and Supplemental Digital Content Table 5, available at: http://links.lww.com/MS9/B47).

Figure 2.

Figure 2.

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Electrolyte and acid–base imbalance AAMRs per 100 000 stratified by race in the United States, 1999–2020.

EABI-related AAMR stratified by census region

The study identified notable regional disparities in AAMRs, with the highest total AAMR observed in the South (8.70; 95% CI: 8.67–8.74), followed by the Midwest (7.78; 95% CI: 7.73–7.82), Northeast (7.35; 95% CI: 7.30–7.39), and West (7.06; 95% CI: 7.01–7.10). From 1999 until the late 2000s, AAMRs declined across all regions: Northeast (until 2008, APC: −3.20; 95% CI: −3.94 to −2.44), Midwest (until 2009, APC: −2.91; 95% CI: −3.67 to −2.14), South (until 2007, APC: −2.66; 95% CI: −3.39 to −1.92), and West (until 2010, APC: −1.90; 95% CI: −2.89 to −0.90). Subsequently, AAMRs increased in all regions through 2020 (Central Illustration, Supplemental Digital Content Table 6, available at: http://links.lww.com/MS9/B47).

EABI-related AAMR stratified by geographic regions

Throughout the study period, non-metropolitan areas consistently exhibited higher EABI-related AAMRs than metropolitan areas (9.73; 95% CI: 9.67–9.78 vs. 7.49; 95% CI: 7.47–7.51). AAMRs in large central metropolitan and non-core non-metropolitan areas declined from 1999 to 2009 (APC: −3.35; 95% CI: −4.48 to −2.21 and—1.87; 95% CI: −3.09 to −0.63, respectively), followed by a steady increase through 2020 (APC: 5.32; 95% CI: 4.41–6.24 and 5.66; 95% CI: 4.68–6.65). Similarly, AAMRs in large fringe, medium metro, and micropolitan non-metro areas declined from 1999 to 2008 (APC range: −2.07 to −2.90), rose steadily through 2018 (APC range: 3.92 to 4.72), and then sharply increased through 2020 (APC range: 11.97 to 15.67). Small metropolitan areas also showed a decline from 1999 to 2008 (APC: −1.68; 95% CI: −3.18 to −0.17), followed by a rise through 2020 (APC: 5.52; 95% CI: 4.68 to 6.37) (Fig. 3, Supplemental Digital Content Table 4, available at: http://links.lww.com/MS9/B47, Supplemental Digital Content Table 7, available at: http://links.lww.com/MS9/B47).

Figure 3.

Figure 3.

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Electrolyte and acid–base imbalance AAMRs per 100 000 stratified by metropolitan and non-metropolitan in the United States, 1999–2020.

Subgroup Analysis

EABI-related AAMR stratified by Sub-categories

AAMRs were also analyzed across EABI subcategories. The highest overall AAMR was observed for acidosis (2.88; 95% CI: 2.87 to 2.89), followed by hyperkalemia (1.80; 95% CI: 1.79 to 1.81), other electrolyte/fluid disorders not elsewhere classified (1.05; 95% CI: 1.05–1.06), hypo-osmolality and hyponatremia (0.91; 95% CI: 0.90–0.92), hyperosmolality and hypernatremia (0.84; 95% CI: 0.83–0.85), hypokalemia (0.38; 95% CI: 0.38–0.39), fluid overload (0.35; 95% CI: 0.35–0.36), and alkalosis (0.02; 95% CI: 0.02–0.02) (Fig. 4, Supplemental Digital Content Table 8, available at: http://links.lww.com/MS9/B47).

Central illustration.

Central illustration.

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Trends in demographics and disparities in electrolyte imbalances-related mortality in the United States, 1999 to 2020 (AAMR = age-adjusted mortality rate).

Figure 4.

Figure 4.

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Electrolyte and acid–base imbalance AAMRs per 100 000 stratified by sub-categories, 1999–2020.

EABI-related AAMR stratified by underlying cause of death

The overall AAMRs for EABI varied across different diseases as the underlying cause of death. Individuals with HF had the lowest AAMR (0.13; 95% CI: 0.12–0.13), while the highest AAMR was observed in individuals with sepsis (0.3; 95% CI: 0.3–0.31). The overall AAMR for CKD patients and diabetic patients was very similar (0.28; 95% CI: 0.27–0.28 and 0.28; 95% CI: 0.28–0.29, respectively). These findings highlight the variation in mortality risk associated with electrolyte imbalance across different conditions (Central Illustration, Supplemental Digital Content Table 9, available at: http://links.lww.com/MS9/B47).

EABI-related crude mortality rates stratified by ten-year age group

Among EABI-related deaths, 1.77% occurred in individuals ≤24 years, 11.4% in those aged 25–54, and 86.82% in those >54 years. The highest number of deaths was observed in the ≥55 age group (n = 503 751; 86.82%), while the lowest was in children aged 1–14 years (n = 1919; 0.33%). The highest crude mortality rate (CMR) was recorded in the ≥85 age group (139.49 per 100 000; 95% CI: 138.82–140.16), while the lowest CMR was observed in the ≤24 age group (0.45; 95% CI: 0.44–0.46) (Supplemental Digital Content Table 10, available at: http://links.lww.com/MS9/B47).

Discussion

This study offers a comprehensive evaluation of EABI-related mortality in the U.S. from 1999 to 2020 using CDC WONDER data. The overall AAMR rose from 7.88 in 1999 to 12.25 in 2020. Geographically, mortality was highest in the Southern region and non-metropolitan areas. Demographically, older adults, males, and NH Black/African American populations experienced the highest AAMRs. Among EABI subtypes, acidosis had the highest AAMR, while alkalosis had the lowest. Furthermore, sepsis emerged as the most common underlying cause of EABI-related death, while HF was the least common.

The annual AAMRs displayed a biphasic trend – initially declining until 2008, followed by a sustained rise, and finally a sharp increase from 2018 to 2020. This trend was observed in both men and women, though men experienced a more pronounced increase in recent years, most likely as a result of sex-based discrepancies in acid-base and electrolyte regulation. Due to lower baseline bicarbonate levels, less compensatory respiratory alkalosis, and increased lactate production under stress, men are more prone to severe metabolic acidosis (such as that caused by sepsis, renal failure, or diabetic ketoacidosis). Furthermore, androgens can aggravate organ dysfunction by increasing the release of pro-inflammatory cytokines (such as TNF-α and IL-6) during acidosis. Women’s X-chromosome-linked genes (such as GPR4 and OGR1) improve endothelial resilience and pH sensing, providing superior defense against acidotic insults[19].

The recent surge in mortality may, in part, reflect the impact of the COVID-19 pandemic, which aggravated EABI through fluid shifts brought on by aggressive resuscitation protocols, renal dysfunction from viral tropism for ACE2 receptors in the kidneys, and widespread use of diuretics and corticosteroids that upset potassium and pH homeostasis[20]. The pandemic produced favorable conditions for complications from EABI: hospital overcrowding postponed vital ABG monitoring, and hypoxemia-induced lactate production and RAAS activation (through ACE2 binding) often resulted in complex acid-base disorders, from metabolic alkalosis to anion gap acidosis[21].

Accurate diagnosis of these imbalances is crucial, and clinical laboratories rely on techniques like flame photometry, enzymatic assays for sodium/potassium measurement, and ion-selective electrodes (ISE, the gold standard). Although enzymatic approaches offer automation-friendly alternatives to ISE, they differ slightly from ISE in terms of accuracy and resistance to sample interference (such as hemolysis)[19].

With advances in the management of acute and chronic conditions, life expectancy has increased, leading to greater susceptibility to chronic diseases, including EABI[22]. Our analysis confirms that advancing age is significantly associated with increased AAMR, which is consistent with prior studies[23,24]. Unlike other conditions where mortality has either stabilized or declined, EABI-related mortality has risen, particularly in the last decade and among adults aged > 25 years. This increase is likely multifactorial. Potential contributors include systemic health care limitations such as the Hospital Readmissions Reduction Program, polypharmacy, underdiagnosis or misdiagnosis of EABI, and greater travel burdens in rural areas. Polypharmacy, in particular, has been linked to adverse drug reactions, medication non-adherence, functional decline, geriatric syndromes, and increased mortality[25–27].

Our findings also reveal significant variation across EABI subtypes, with acidosis showing the highest AAMR and alkalosis the lowest. Lactic acidosis, a common finding in critically ill patients, is strongly associated with increased mortality[28]. Among electrolyte disorders, hyponatremia is the most frequently observed imbalance, affecting up to 30% of hospitalized patients in its mild form (serum sodium: 130–135 mEq/L)[29]. Hyponatremia is particularly associated with increased in-hospital mortality in older adults[30,31], yet remains underdiagnosed. Notably, only 53.2% of hospitalized patients show any improvement in sodium levels, and approximately 25% fail to achieve levels ≥ 130 mEq/L[32]. Hypernatremia increases mortality risk sevenfold[33], while hyponatremia doubles the risk compared to normonatremic peers[34], underscoring the prognostic importance of sodium imbalances, irrespective of direction. Additionally, dyskalemia in patients with HF and DM is associated with increased mortality, as it predisposes to life-threatening arrhythmias, flaccid paralysis, respiratory failure, tetany, and rhabdomyolysis[35,36].

Poorer outcomes among NH Black individuals likely stem from multiple factors, including social determinants of health such as geographic location, socioeconomic status, and health care access[9]. State-level disparities in service accessibility and affordability may further exacerbate these outcomes[37]. Broader systemic issues, including uneven health care policy implementation and access to care, also play a significant role[10]. Although limited access to endocrinology services affects all groups, its impact is particularly pronounced among racial and ethnic populations that face a higher burden of endocrine disorders[11].

Significant geographical disparities were evident, with the Southern region and non-metropolitan areas having the highest AAMRs. This disparity may be linked to limited access to health care services, fewer specialists, and socioeconomic challenges faced by rural populations. One concerning factor is the ongoing decline in primary care providers in nonmetropolitan areas, which may have contributed to worse health outcomes for patients with electrolyte imbalances. A 2012 report showed that nearly 99% of urban adults had access to at least one endocrinologist, compared to much lower access in rural areas[5]. Rural regions also lack the infrastructure for managing complex conditions like electrolyte imbalances, which require timely nephrology and critical care[38].

Mortality rates from EABI in older adults with comorbidities such as CKD[39], DM[40], HF[41], and sepsis[42] have risen, likely due to improved detection, clinical awareness, and changes in ICD-10 coding[42]. Electrolyte disturbances such as hyperkalemia, hyponatremia, metabolic acidosis, and fluid overload are common in these patients and contribute to poor outcomes[43,44]. CKD patients, especially those in marginalized communities, also face challenges in accessing care and adhering to treatment[45]. Hyperkalemia is a common electrolyte imbalance, and it can be deadly in people with CKD, HF, DM, or high blood pressure. Studies show that in individuals having hypokalemia, CKD progresses faster than in the average person[39]. In the general population, the reported incidence is between 2.6% and 7%, while in patients with CKD, the rate can be as high as 73%. In DM, hyperkalemia can happen when there isn’t enough insulin, when blood sugar levels are too high, or when there isn’t enough renin or aldosterone. In the same way, people with cardiovascular (CV) disease, especially HF, are more likely to get hyperkalemia if they have less sodium delivered through their tubules and take drugs that block the renin–angiotensin–aldosterone axis[46].

Addressing these disparities is critical to improving care for high-risk groups. Reducing EABI-related mortality requires better preventive care, increased access to specialists in underserved areas, and culturally tailored interventions. Telemedicine and care coordination can improve chronic disease management in rural settings. Medication safety is key; long-term proton pump inhibitor (PPI) use has been linked to kidney damage and electrolyte imbalances[47]. Raising awareness among health care providers about the risks associated with prolonged PPI use and optimizing medication regimens could contribute to better patient outcomes. Studies on electrolyte and acid-base disorders in emergency critical care settings have emphasized the importance of early detection and intervention, which could inform future public health strategies[47]. Additionally, research into the long-term effects of post-hospitalization electrolyte disturbances on mortality rates could enhance clinical and public health interventions.

Limitations

Several limitations should be noted in this study while analyzing our findings. First, using death certificate data carries risks of coding errors and misclassification, which may underrepresent electrolyte imbalances as a cause of death. Second, changes in coding practices over time may have influenced the observed trends. Third, this analysis lacks individual-level data on socioeconomic status, health care utilization, and specific comorbidities that could affect mortality. Fourth, this study only included data up to 2020, with no analysis of subsequent years. Also, information about clinical variables such as vital signs, labs, ventilator settings, genetic data, or medical therapy details was not available. Furthermore, we excluded those codes in which data were unreliable such as E87.4 (Mixed disorder of acid-base balance) and for sepsis, only ICD code A41 (other septicemia) was used, as A40 (streptococcal septicemia) mortality data were unreliable in multiple years. Due to statistical instability and privacy protections, CDC WONDER suppresses mortality data with <20 deaths and marks rates as “unreliable” when the relative standard error exceeds 30%. Because of this, some subgroup analyses (like those of rare causes of death or small demographic/geographic populations) may not be accurate or may not be done at all. However, we opt to use this database due to its comprehensive nature as compared with others available at the time. Previous studies also validate employment of this database.

Conclusion

The initial decline from 1999 to 2008 in our results was followed by an upward trend with a steeper increase from 2018 to 2020 in the AAMR for the mortality trends related to EABI. The NH African Americans, men, the south region of the United States, and nonmetropolitan areas observed the highest AAMRs across all age groups. Understanding these trends is essential for designing health care services that cater to this expanding population. Future research should explore these factors in greater detail and assess the impact of health care policies and the COVID-19 pandemic on electrolyte-related mortality.

Acknowledgements

Not applicable.

Footnotes

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal’s website, www.lww.com/annals-of-medicine-and-surgery.

Published online 5 December 2025

Contributor Information

Zaima Afzaal, Email: zaimaafzaal123@gmail.com.

Asma Chaudhary, Email: annieshahid9x@gmail.com.

Inshal Uddin Khattak, Email: inshalk2004@gmail.com.

Saba Aliha, Email: sabaaliha22@gmail.com.

Asad Khan, Email: khad900063@gmail.com.

Hameer Ali, Email: hameer.alimd@gmail.com.

Amnah Khan, Email: khad900063@gmail.com.

Aizaz Anwar Khalid, Email: khad900063@gmail.com.

Wania Khan, Email: wania.khan2002@gmail.com.

Touqeer Rehman, Email: callmetouqeer19@gmail.com.

Maryam Atif, Email: maryam.atif365@gmail.com.

Areen Zia, Email: areenzia32@gmail.com.

Mazia Mahnoor, Email: maziamahnoor9@gmail.com.

Rumman Javed, Email: javedrumman@gmail.com.

Saad Ahmed Waqas, Email: ahsaad404@gmail.com.

Raheel Ahmed, Email: r.ahmed21@imperial.ac.uk.

Somaiya Ahmed, Email: somaiyaahmed1996@gmail.com.

Ethical approval

These data were taken from Centers for Disease Control and Prevention.

Consent

We used de-identified data for which no consent was required.

Sources of funding

No source of funding.

Author contributions

Z.A.: Study concept, Writing the paper. A.C.: Study concept, Data analysis or interpretation, Writing the paper. I.U.K.: Study concept, Data analysis or interpretation, Writing the paper. S.A.: Writing the paper, Data analysis or interpretation, Data collection, Study concept. A.K.: Writing the paper. A.M.D.B.: Writing the paper. H.A.: Writing the paper. A.Kh.: Writing the paper. A.A.K.: Writing the paper. W.K.: Writing the paper. T.R.: Writing the paper. M.A.: Writing the paper. A.Z.: Writing the paper. M.M.: Writing the paper. R.J.: Writing the paper. S.A.W.: Contributor. R.A.: Supervisor. S.Am.: Corresponding author.

Conflicts of interest disclosure

No conflicts of interest.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Somaiya Ahmed.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

No data set generated or analyzed.

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