Influence of Polypharmacy on Post-surgical Mortality in Elderly Adults With Hip Fracture

doi:10.21203/rs.3.rs-4821382/v1

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Research Article

Influence of Polypharmacy on Post-surgical Mortality in Elderly Adults With Hip Fracture

https://doi.org/10.21203/rs.3.rs-4821382/v1

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Purpose: Polypharmacy is a common problem in surgical patients with hip fractures. Their influence on the mortality is what we pretend to study, aiming to inform management strategies and reduce mortality risks.

Methods: A retrospective study was conducted at Hospital de la Ribera, Alzira, targeting patients aged ≥70 who underwent hip fracture surgery in 2017 and 2018. Data were extracted from electronic medical records, including demographic details, comorbidities, and medication use. Polypharmacy was defined as the use of five or more medications. Mortality rates were analyzed at 30 days, 6 months, 1 year, 2 years, and 5 years post-surgery using Kaplan-Meier survival curves and Cox regression analysis.

Results: Among 644 patients included, (mean age 84.5 years, 70.5%women), polypharmacy was present in 63.8%, and severe polypharmacy (≥10 medications) in 19.1% of patients. Polypharmacy significantly increased mortality at all time intervals: 30 days (10.6% severe polypharmacy vs 3.0% no polypharmacy, p=0.042), 6 months (22.7% vs 9.6%, p=0.003), 1 year (39.4% vs 11.9%, p<0.001), 2 years (51.5% vs 14.8%, p<0.001), and 5 years (76.2% vs 26.3%, p<0.001).It was also associated with higher rates of major complications and red cell transfusions. Hazard ratios for 5-year mortality were significantly elevated for patients on hypotensives, benzodiazepines, antidiabetics, opioids, neuroleptics, and anti-dementia drugs.

Conclusion: Polypharmacy significantly impacts postoperative mortality and morbidity in elderly hip fracture patients. Effective management, including medication review and deprescribing strategies, is crucial to improving outcomes. Comprehensive geriatric assessments and interdisciplinary approaches are recommended to optimize treatment and reduce the adverse effects of polypharmacy.

polypharmacy

postoperative mortality

hip fractures

medication management

geriatric assessment.

Aim: To describe the influence of polipharmacy ( ≥5 medications) on post-surgical mortality in elderly adults with hip fractures.

Findings: The study identified a significant association between polypharmacy and increased mortality at 30 days, 6 months, 1 year and 2 years. Additionally, the presence of polypharmacy in these patients increases the risk of major complications and transfusions.

Message: This study suggests that polypharmacy increases post-surgical mortality in elderly adults with hip fracture.

Global demographic aging is a phenomenon with profound social, economic, and public health implications. According to the World Health Organization [1], the global population aged ≥ 60 years, which accounted for 10% in 2023, is expected to increase to 16.7% by 2030, rising from 1 billion in 2020 to 1.4 billion. By 2050, this population will have doubled, and those aged ≥ 80 years will have tripled. In Spain, the National Institute of Statistics [2] reported that in 2022, 20.1% of the population was aged ≥ 65 years, a figure projected to reach 30.4% by 2050. This demographic shift is associated with a rise in chronic diseases and surgical procedures, presenting challenges in perioperative risks and postoperative morbidity and mortality.

Hip fractures represent a significant public health issue that frequently affects older adults. As the population ages, the prevalence of hip fractures rises, occurring in approximately 90% of cases in individuals aged ≥ 64 years [3]. Older adults with hip fractures are often characterized by the presence of frailty, functional and cognitive decline, malnutrition, and comorbidities, which adversely affect hospital morbidity, mortality and clinical outcomes [4, 5]. Frailty, marked by increased vulnerability due to physiological decline, significantly impacts postoperative complications and mortality in older adults undergoing hip fracture surgery [6]. Frail elderly patients face higher risks of hospital mortality, six-month mortality, prolonged hospital stays, and increased postoperative complications [7, 8]. The comprehensive geriatric assessment (CGA) is crucial for evaluating and managing older adults with hip fractures, addressing medical, functional, psychological, and social aspects [9, 10]. Preoperative nutritional support and physical rehabilitation are essential for improving outcomes.

Orthogeriatric units, which integrate orthopaedic and geriatric care, offer significant benefits by reducing postoperative complications, shortening hospital stays, and enhancing survival and functional recovery.

The management of medication use plays a crucial role in the recovery of older adults with hip fractures. The prevalence of potentially inappropriate medications (PIMs) and polypharmacy in this population is notably high, correlating with an increased risk of falls, subsequent fractures, and mortality [11]. Polypharmacy, typically defined as the concurrent use of five or more medications, is associated with adverse drug interactions and an increased burden of side effects. Implementing regular medication reviews and deprescribing strategies is essential to mitigate these risks and improve outcomes in this demographic [12–16].

Furthermore, the impact of polypharmacy on clinical outcomes among elderly patients with hip fractures encompasses more than just mortality rates. Research indicates that polypharmacy is associated with increased rates of hospital readmission, prolonged recovery periods, and diminished functional recuperation following surgery [17]. Elderly individuals with hip fractures often contend with intricate medication regimens due to multiple chronic conditions, which heightens the risk of confusion, non-adherence to prescribed medications, and a higher incidence of adverse drug reactions. Addressing polypharmacy in this population requirs a comprehensive approach that includes patient education, regular monitoring, and interdisciplinary collaboration among healthcare providers [18, 19].

Due to the complex interplay of polypharmacy and frailty in influencing the recovery and survival outcomes of older adults with hip fractures, it is crucial to delve deeper into these relationships [20, 21]. The existing evidence on this subject is currently sparse, demanding additional studies to validate findings. This research aims to investigate the association between polypharmacy and mortality among older adults with hip fractures, with the objective of providing empirical evidence to improve management strategies and reduce mortality risks in this vulnerable demographic.

Study Design

This retrospective study was carried out at Hospital de la Ribera in Alzira, Valencia. It specifically targeted patients aged 70 and above who underwent surgical treatment for hip fractures throughout the entire years of 2017 and 2018. Upon admission for a hip fracture, each patient was assigned a traumatologist, a geriatrician, and a nursing team. Pharmacologists reviewed their home medications for potential issues. The geriatrician and traumatologist evaluated the patients within the first 24 hours and daily thereafter. After surgery, rehabilitation began within 48 hours. The traumatologist assessed the surgical approach, while the geriatrician conducted a comprehensive geriatric assessment (CGA) covering various health aspects. Co-morbidities were evaluated to create a pre-operative treatment plan. For patients with cognitive impairments, information was gathered from caregivers. If needed, a social worker assessed the patient's social network to provide discharge support. Discharge decisions involved the traumatologist, geriatrician, and rehabilitation specialist. When considered necessary, rehabilitation was continued after hospital discharge at reference rehabilitation sites. This designed model attempted to provide early, integral care with an emphasis on early geriatric assessment, surgical procedure selection and the initiation of rehabilitation therapy to recover patient mobility in the shortest possible time following surgery [22].

Study Participants

All patients aged 70 years or older who underwent surgical intervention for hip fractures in either 2017 or 2018 were eligible for inclusion in this study. Inclusion criteria encompassed patients aged 70 or older who were admitted to the hospital specifically due to a hip fracture. Exclusion criteria included patients admitted with a diagnosis of polytrauma or pathological fracture, as well as those with an estimated life expectancy of less than six months from any cause.

Sample Size

All patients aged 70 years or older who were admitted to Hospital Universitario de La Ribera (Alzira, Valencia, Spain) for hip fractures between January 1, 2017, and December 31, 2018, were consecutively included, resulting in a sample size of 644 patients. The study's power analysis estimated a difference in 30-day post-discharge mortality among hip fracture patients at 16.9% [23], achieving a high-power level of 99.6%.

Outcome

The main objective of this study was to examine the correlation between polypharmacy and postoperative mortality. Polypharmacy was defined as the use of more than 5 medications, with severe polypharmacy categorized as 10 or more medications [24, 25]. The study aimed to assess the impact of polypharmacy on short-term (1 month), medium-term (6 months), and long-term (1, 2, and 5 years) mortality outcomes. Additionally, the research investigated the association between polypharmacy and the incidence of adverse events, length of hospital stays, and complications during hospitalization.

Study Variables

Data for this study were retrieved from the electronic medical records using SIAS© software version 20.7.7. Information was extracted from the medical records and hospital discharge summaries of patients diagnosed with hip fractures during the study period. Follow-up data were collected from outpatient records, emergency care episodes, and post-discharge hospital admissions. Survival information, including patient deaths within the hospital's care area, was obtained from updated medical records.

Two co-investigators, who were blinded to the study's design and objectives, were responsible for data collection. The study evaluated various sociodemographic variables such as age and sex, surgical delay, duration of hospital stay, comorbidities assessed using the Charlson Comorbidity Index (CCI) [26] and age-adjusted Charlson Comorbidity Index, clinical frailty assessed by the Clinical Frailty Scale (CFS) [27], nutritional status measured by the Control Nutritional (CONUT) scale [28], presence of geriatric syndromes like delirium, red blood cell transfusions, and both medical and surgical complications during hospital admission. Additionally, the study analysed mortality outcomes.

Data Collection

For this study, data were gathered from the electronic clinical records of hospitalized patients. Information was extracted by reviewing electronic medical histories recorded in outpatient prescription programs including Comunidad Valenciana's Abucasis® and the hospital prescription program NouSIS® at Hospital de la Ribera. Subsequently, all data were entered into an anonymized database for analysis.

Statistical Analysis

The statistical analysis was conducted using IBM SPSS Statistics® version 23. Categorical variables were summarized using frequencies, while quantitative variables were described using measures of central tendency (mean or median) and dispersion (standard deviation or interquartile range).

Normality of quantitative variables was assessed using the Kolmogorov-Smirnov test. If the data followed a normal distribution, they were described using means and standard deviations. For variables not conforming to normality, medians and interquartile ranges were used for description instead.

In the statistical analysis, categorical or qualitative variables were compared using the Pearson Chi-square test. Quantitative variables that exhibited a normal distribution were evaluated with the Fisher's exact test for dichotomous variables and ANOVA for variables with multiple categories. Furthermore, a 5-year survival analysis of patients was conducted using the non-parametric Kaplan-Meier method. The impact of polypharmacy on survival was assessed using the Log-Rank test. Lastly, a multivariate analysis was performed to examine the association between polypharmacy and mortality using Cox regression. This analysis included calculation of both crude hazard ratios (HR) and adjustments for sex, age, and Charlson Comorbidity Index (CCI). Statistical significance was defined as p < 0.05 for all tests.

Ethical Considerations

This study adheres to the principles outlined in the Declaration of Helsinki and complies with the regulations set forth in the Organic Law on the Protection of Personal Data and the Guarantee of Digital Rights (Organic Law 3/2018) for safeguarding personal data. Ethical approval for the study was obtained from the Ethics and Clinical Research Committee of HULR (reference code HULR23122022).

The study enrolled 644 elderly patients admitted to the hospital due to hip fractures, among whom 70.5% were women, with a mean age of 84.5 years (SD 6.1). Polypharmacy, defined as the use of 5 or more medications, was prevalent in 63.8% of patients, while severe polypharmacy, defined as 10 or more medications, was observed in 19.1% of cases.

Table 1 presents the baseline characteristics of patients categorized by the presence of polypharmacy, while Table 2 categorizes them based on the severity of polypharmacy.

Table 1

Bivariate Analysis of variables present at hospital admission and during hospital stay.
Variable	No Polypharmacy N = 232	Polypharmacy N = 412	p-Value
Age (years), m (SD)	76.0 ( 12.1)	80.6 (10.7)	0.004
Male sex, n (%)	57 (24.6%)	133 (32.3%)	0.039
CCI score (SD)	4.0 (2.8)	4.2 (3.3)	0.364
CONUT at hospital admission	152 (72.7%)	268 (79.5%)	0.067
CONUT at hospital discharge	119 (60.7%)	208 (68.6%)	0.069
Hx of IHD	10 (4.3%)	51 (12.4%)	0.001
Hx of HF	6 (2.6%)	40 (9.7%)	0.001
Hx of COPD	22 (9.5%)	59 (14.3%)	0.076
Hx of CVA	3 (1.3%)	20 (4.9%)	0.019
Hx of Dementia	28 (12.1%)	58 (14.1%)	0.472
Hx of RF	12 (5.2%)	46 (11.2%)	0.011
Hx of Diabetes	48 (20.7%)	146 (35.4%)	< 0.001
Table 1b. Bivariate Analysis of variables analysed during hospital stay
ICU	2 (0.9%)	8 (1.9%)	0.287
Mortality rate	5 (2.2%)	14 (3.4%)	0.371
Total complications	92 (39.7%)	233 (56.6%)	< 0.001
Major complications	87 (37.5%)	225 (54.6%)	< 0.001
Delirium	19 (8.2%)	30 (7.3%)	0.676
AE Cardiac	12 (5.2%)	32 (7.8%)	0.210
AE Anemia	19 (8.2%)	42 (10.2%)	0.399
AE UTI	6 (2.6%)	9 (2.2%)	0.746
AE Digestive Issues	0 (0.0%)	5 (1.2%)	0.092
AE Respiratory	7 (3.0%)	23 (5.6%)	0.138
Surgery Delay of 48 Hours	167 (72.0%)	261 (63.3%)	0.026
Surgery Delay of 72 Hours	205 (88.4%)	354 (85.9%)	0.380
Trasfusions	119 (51.3%)	256 (62.1%)	0.007
Initial Hb, m (SD)	12.7 (1.7)	12.2 (1.6)	0.000
Final Hb, m (SD)	10.3 (1.1)	10.4 (1.2)	0.307
Glomerular Filtration(ml/min), m (SD)	70.1 (22.1)	61. 8 (24.8)	< 0.001
30-Day Mortality	9 (3.9%)	37 (9.0%)	0.016
180-Day Mortality	25 (10.8%)	88 (21.4%)	0.001
365-Day Mortality	27 (11.6%)	118 (28.6%)	< 0.001
2-Year Mortality	33 (14.2%)	169 (41.0%)	< 0.001
5-Year Mortality	61 (26.3%)	292 (70.9%)	< 0.001
Hospital Stay (days)	7.7 (3.0)	8.3 (3.8)	0.033
Legend CCI: score Charlson Index score, Hx of IHD: History of Ischemic Heart Disease, Hx of HF: History of Heart Failure, Hx of COPD: History of Chronic Obstructive Pulmonary Disease, Hx of CVA: History of Cerebrovascular Accident, Hx of RF: History of Renal Failure. ICU: intensive care unit, AE: adverse event, AE UTI: adverse event of Urinary Tract Infection.

Table 2

Bivariate Analysis of variables present at hospital admission and during hospital stay.
Variable	No Polypharmacy N = 232	Polypharmacy N = 286	Severe Polypharmacy N = 126	p-Value
Age (years), m (SD)	83.2 (6.3)	84.3 ( 6.0)	85.5 (6.0)	< 0.001
Male sex, n (%)	57 (24.6%)	82 (28.7%)	51 (40.5%)	0.006
CCI score, m (SD)	1.7 (1.8)	2.7 ( 2.1)	3.3 (2.6)	< 0.001
CONUT at hospital admission	152 (72.7%)	182 (78.1%)	86 (82.7%)	0.122
CONUT at hospital discharge	119 (60.7%)	143 (67.5%)	65 (71.4%)	0.153
Hx of IHD	10 (4.3%)	26 (9.1%)	25 (19.8%)	< 0.001
Hx of HF	6 (2.6%)	29 (10.1%)	11 (8.7%)	0.003
Hx of COPD	22 (9.5%)	30 (10.5%)	29 (23.0%)	< 0.001
Hx of CVA	3 (1.3%)	17 (5.9%)	3 (2.4%)	0.013
Hx of Dementia	28 (12.1%)	43 (15.0%)	15 (11.9%)	0.533
Hx of RF	12 (5.2%)	27 (9.4%)	19 (15.1%)	0.007
Hx of Diabetes	48 (20.7%)	78 (27.3%)	68 (54.0%)	< 0.001
Table 2b. Bivariate Analysis of variables analysed during hospital stay.
ICU	2 (0.9%)	4 (1.4%)	4 (3.2%)	0.230
Mortality rate	5(2.2%)	7 (2.4%)	7 (5.6%)	0.153
Complications	92(39.7%)	159 (55.6%)	74 (58.7%)	< 0.001
Major complications	87 (37.5%)	152 (53.1%)	73 (57.9%)	< 0.001
Delirium	19 (8.2%)	18 (6.3%)	12 (9.5%)	0.479
AE Cardiac	12 (5.2%)	19 (6.6%)	13 (10.3%)	0.180
AE Anemia	19 (8.2%)	28 (9.8%)	14 (11.1%)	0.644
AE UTI	6 (2.6%)	7 (2.4%)	2 (1.6%)	0.823
AE Digestive Issues	0 (0.0%)	3 (1.0%)	2 (1.6%)	0.205
AE Respiratory	7 (3.0%)	15 (5.2%)	8 (6.3%)	0.295
Surgery Delay of 48 Hours	167 (72.0%)	184 (64.3%)	77 (61.1%)	0.068
Surgery Delay of 72 Hours	205 (88.4%)	248 (86.7%)	106 (84.1%)	0.527
Trasfusions	119 (51.3%)	178 (62.2%)	78 (61.9%)	0.028
Initial Hb, m (SD)	12.8 (1.7)	12.2 (1.7)	12.3 (1.5)	< 0.001
Final Hb, m (SD)	10.3 (1.1)	10.4 (1.2)	10.3 (1.2)	0.526
Glomerular Filtration (mil/min), m (SD)	70.1 (22.1)	63.5(25.1)	58.0 (23.8)	< 0.001
30-Day Mortality	9 (3.9%)	24 (8.4%)	13 (10.3%)	0.043
180-Day Mortality	25 (10.8%)	61 (21.3%)	27 (21.4%)	0.003
365-Day Mortality	27 (11.6%)	76 (26.6%)	42 (33.3%)	< 0.001
2-Year Mortality	33 (14.2%)	111 (38.8%)	58 (46.0%)	< 0.001
5-Year Mortality	61 (26.3%)	196 (68.5%)	96 (76.2%)	< 0.001
Hospital Stay (days)	7.7 (3.0)	8.2 (3.5)	8.5 (3.8)	0.082
Legend CCI: score Charlson Index score, Hx of IHD: History of Ischemic Heart Disease, Hx of HF: History of Heart Failure, Hx of COPD: History of Chronic Obstructive Pulmonary Disease, Hx of CVA: History of Cerebrovascular Accident, Hx of RF: History of Renal Failure. ICU: intensive care unit, AE: adverse event, AE UTI: adverse event of Urinary Tract Infection.

Table 3

Cox Regression. Crude and Adjusted Rate of Polypharmacy and Severe Polypharmacy. a) Crude Rate of Polypharmacy and Severe Polypharmacy
Variable	Hazard Ratio	95%CI	p-Value
Polypharmacy 5–9 drugs	3.61	2.71–4.82	< 0.001
Polypharmacy ≥ 10 drugs	4.47	3.24–6.17	< 0.001
Table 3b. Adjusted Rate of Polypharmacy and Severe Polypharmacy
Variable	Hazard Ratio	95%CI	p-Value
Polypharmacy 5–9 drugs	2.90	2.15–3.91	< 0.001
Polypharmacy ≥ 10 drugs	3.33	2.37–4.68	< 0.001
Adjustment variables: sex, age and comorbidity through the Charlson Index

The study identified a significant association between polypharmacy and increased mortality across all analysed intervals: 30 days (10.6% severe polypharmacy vs 10.1% polypharmacy vs 3.0% no polypharmacy; p = 0.042), 6 months (22.7% vs 25.2% vs 9.6%; p = 0.003), 1 year (39.4% vs 32.4% vs 11.9%; p < 0.001), and 2 years (51.5% vs 41.0% vs 14.8%; p < 0.001).

Additionally, severe polypharmacy and polypharmacy were associated with an increase in the incidence of red cell transfusions (62.1% severe polypharmacy vs 64.0% polypharmacy vs 49.6% no polypharmacy; p = 0.040), total complications (63.6% vs 54.0% vs 38.5%; p = 0.002), and major complications (62.1% vs 51.1% vs 35.6%; p = 0.001). These groups also showed higher Charlson Comorbidity Index scores (3.83 ± 2.63 severe polypharmacy vs 3.34 ± 2.62 polypharmacy vs 1.75 ± 1.72 no polypharmacy; p < 0.001). Significantly, despite these associations, polypharmacy did not result in prolonged hospital stays, delayed hip surgeries, or increased incidence of adverse events such as delirium during hospitalization.

Regarding the medications analysed, hypotensive were the most commonly prescribed, with a prevalence of 64.1% among the patients. Benzodiazepines and hypnotics followed closely, prescribed to 41.6% of the patients. Antidiabetic medications were also frequently used, prescribed in 24.4% of cases. Opioids were utilized by 15.1% of the patients, while neuroleptics had a prevalence of 13.4%. Anti-dementia drugs were the least prescribed, with a frequency of 7.3%.

When categorizing patients based on the presence of polypharmacy, the use of these medications was associated with an increased risk of 5-year mortality. Specifically, the hazard ratios (HR) for hypotensive [HR = 3.70 (2.75–4.98)], benzodiazepines/hypnotics [HR = 3.62 (2.72–4.84)], antidiabetics [HR = 3.57 (2.69–4.74)], opioids [HR = 3.85 (2.90–5.11)], neuroleptics [HR = 3.68 (2.78–4.86)], and anti-dementia drugs [HR = 3.74 (2.83–4.95)] were significantly elevated. These findings underscore the association between the use of multiple medications and heightened mortality risk over a 5-year period among elderly patients with hip fractures.

The study found that the 5-year mortality risk was markedly higher among patients with polypharmacy, regardless of its severity, compared to those without polypharmacy (p < 0.001). Specifically, the hazard ratios (HR) were 3.61 (95% CI 2.71–4.82) for patients using 5 or more drugs and 4.47 (95% CI 3.24–6.17) for those using 10 or more drugs.

The Kaplan-Meier survival analysis revealed a significantly lower 5-year survival rate among patients with polypharmacy compared to those without. This finding was further supported by multivariate Cox regression analysis, which demonstrated that patients without polypharmacy had a significantly longer 5-year survival duration (66.21 ± 1.99 months) compared to those with polypharmacy using 5 or more drugs (47.60 ± 2.41 months) and those with severe polypharmacy (36.95 ± 2.94 months) (see Fig. 1).

Figure 2 illustrates that there were no significant differences in mortality rates at 30 days, 6 months, 1 year, 2 years, and 5 years based on the severity of polypharmacy. This suggests that while polypharmacy overall was associated with reduced long-term survival, the degree of polypharmacy did not significantly influence short-term mortality outcomes within these specific time frames.

The findings of this study highlight polypharmacy, defined as the concurrent use of five or more medications, as a significant contributor to postoperative morbidity and mortality among older adults with hip fractures. The prevalence of polypharmacy in the study sample was notably high, and there was a clear and robust association between the severity of polypharmacy and an increased incidence of both major and total complications during hospitalization. Furthermore, patients with polypharmacy exhibited elevated mortality rates across short-, medium-, and long-term follow-ups.

These results underscore the critical importance of meticulous medication management in this vulnerable patient population to enhance clinical outcomes. They are consistent with numerous studies in the scientific literature that have similarly demonstrated the detrimental impact of polypharmacy on health outcomes in older adults [11, 12, 16, 17, 23, 29].

The impact of polypharmacy on clinical outcomes has been extensively studied and documented [30–33], demonstrating effects that extend beyond immediate postoperative risks to encompass long-term health complications [34]. In our study sample, the prevalence of global polypharmacy was 63.8%, with a clear correlation observed between the severity of polypharmacy and increases in both Charlson Comorbidity Index (CCI) scores and the incidence of major and total complications during hospitalization.

Furthermore, existing research has highlighted the heightened likelihood and risk of neck of femur fractures associated with polypharmacy, along with its link to elevated postoperative mortality rates [20, 35]. These findings underscore the critical need for comprehensive management strategies to mitigate the adverse effects of polypharmacy in older adults, particularly those undergoing surgical interventions for hip fractures.

These findings underscore the complexity of managing patients with polypharmacy and emphasize the necessity for vigilant monitoring to prevent and promptly address associated complications [16, 18, 19]. These complications may encompass requirements for red blood cell transfusions, falls, infections, and cardiovascular events, all contributing to heightened morbidity and prolonged recovery periods.

Interestingly, our study did not find a significant difference in the length of hospital stay, suggesting that the severity of complications, rather than the duration of hospitalization, may be a critical factor influenced by polypharmacy. This underscores the potential role of specialized care from geriatricians within orthogeriatric units in attenuating the impact of hospital admission duration on patient outcomes.

In this context, this study underscores the crucial role of comprehensive geriatric assessment (CGA) in managing elderly patients with hip fractures. CGA facilitates early identification of frailty, comorbidities, and specific patient needs [6, 9]. By implementing CGA, healthcare providers can optimize pharmacological treatment, thereby reducing the burden of polypharmacy and enhancing clinical outcomes.

CGA involves a thorough evaluation of medical, functional, psychological, and social factors, enabling the development of personalized care plans that address all aspects of a patient's health. Effective coordination between geriatricians and other specialists is essential for managing polypharmacy and mitigating its associated complications [18, 36]. This approach ensures comprehensive care tailored to the unique needs of elderly patients with hip fractures, ultimately improving their overall health outcomes.

The analysis reveals that patients with polypharmacy exhibit elevated mortality rates at 30 days, 6 months, 1 year, 2 years, and 5 years post-surgery compared to those without polypharmacy. Specifically, severe polypharmacy (≥ 10 drugs) was associated with an even greater increase in mortality. These findings align with previous studies indicating that the use of multiple medications increases the risk of death in geriatric patients [5, 21, 25].

The relationship between the number of medications and mortality may be explained by the higher probability of adverse drug interactions, the increased complexity and burden of comorbidities, and heightened frailty due to cumulative drug side effects [17]. These factors underscore the critical importance of meticulously managing polypharmacy in elderly patients, emphasizing the necessity for strategies that mitigate these risks and enhance overall patient outcomes.

The study underscores the impact of hypotensive drugs, benzodiazepines/hypnotics, antidiabetics, opioids, neuroleptics, and anti-dementia drugs on five-year mortality. While these medications are beneficial for specific conditions, they pose a high-risk profile in geriatric patients due to their side effects and potential to exacerbate frailty [13, 20].

Managing these medications in older patients should be prioritized, emphasizing deprescription strategies and regular review of medication regimens to mitigate risks [11, 12]. This approach necessitates a multidisciplinary effort involving primary care physicians, pharmacists, and specialists to ensure that each patient's medication plan is optimized for safety and efficacy. Comprehensive medication management is essential, advocating for regular reviews and deprescribing protocols in orthogeriatric units. Tools like STOPP/START criteria or Beers Criteria can help identify inappropriate medications.

Deprescribing should be approached cautiously, involving patients and caregivers in the decision-making process. Educating them about the risks of polypharmacy and the benefits of reducing medication can enhance adherence to deprescribing plans and improve satisfaction with care. Patient-centered deprescribing interventions have been shown to effectively reduce medication use and improve health outcomes [12].

A multidisciplinary team approach involving geriatricians, pharmacists, primary care physicians, and surgeons is crucial to consider all health aspects in medication decisions. Regular interdisciplinary case conferences can enhance patient outcomes through collaborative management [14].

There are no differences in comorbidity estimated by the CCI, although the results may be confounded by the higher prevalence of ischemic heart disease, heart failure, stroke, chronic kidney failure, and diabetes.

It is essential to acknowledge several limitations of this study. Firstly, its retrospective design introduces the potential for bias in data collection. Furthermore, while this study can establish associations, it cannot determine causality. Despite controlling for variables such as age, sex, and comorbidities, there remains a possibility that unconsidered factors may have influenced the observed results. Additionally, although the loss rate was relatively low at 7%, it could potentially impact the study's findings. In addition, no potential adverse effects of the prescribed medication at home were recorded. The number of modified START/STOPP criteria and the number of medications discontinued at discharge were not collected.

Moving forward, future prospective and multicentre studies are warranted to validate these findings assess specific deprescribing interventions on clinical outcomes. Incorporating comprehensive geriatric assessments (CGA) into routine care for elderly hip fracture patients is essential for identifying frailty and comorbidities, leading to individualized care plans that optimize treatment and reduce polypharmacy [10]. Additionally, leveraging health information technology can help monitor polypharmacy and prevent adverse drug events through real-time alerts for healthcare providers. Future research should focus on integrating these technological tools in geriatric care settings.

Polypharmacy significantly influences post-surgical morbidity and mortality among elderly patients with hip fractures. Proactively identifying and managing this factor can markedly enhance clinical outcomes in this vulnerable population. This study underscores the critical importance of implementing a multidisciplinary and personalized management approach, with a focus on deprescription and ongoing review of medication regimens for older adults. These strategies are crucial for optimizing treatment efficacy and minimizing the risks associated with polypharmacy, thereby improving overall patient care and outcomes.

The authors declare that they have not received any type of internal or external funding to carry out the research.

Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and was approved by the HULR Ethics and Clinical Research Committee (registration code HULR23122022).

Conflicts of Interest: The author declares no conflict of interest.

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Influence of Polypharmacy on Post-surgical Mortality in Elderly Adults With Hip Fracture

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