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The Association Between Beta-Blocker Therapy and Mortality in Hip Fracture Patients
Örebro University, School of Medical Sciences.ORCID iD: 0000-0003-3436-1026
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hip fractures have been a major concern within the healthcare systems for many years. National efforts have been done to improve the overall outcomes during the last decades. Despite this, the mortality rates one year after hip fracture surgery are as high as 27% and have remained high the past 15 years. Patients that suffer from hip fractures are often elderly and have several comorbidities. The orthopaedic trauma and subsequent emergency surgery impose an activation of the sympathetic nervous system mediated through the release of catecholamines. This causes a hyper-adrenergic state, which can be harmful if prolonged, or if the patient already has a strain caused by comorbidities forgoing the injury, especially on the cardiovascular system. This gave rise to the thought of blocking the adrenergic receptor activation in hip fracture patients as an effort to reduce the mortality rates.

Papers I and II investigates the association between beta-blocker therapy and short-term mortality in hip fracture patients. In Paper I, (n=2443) patients operated in Orebro County between 2013 to 2017 were extracted from The National Quality Register for Hip Fractures (Rikshöft), to enable a more detailed review of the medical journals. The patients were divided into a betablocker cohort and a beta-blocker naive cohort. Results showed an 18% reduction in the risk of postoperative mortality within 90 days of surgery. In Paper II, all adults operated for traumatic hip fractures in Sweden between 2008 to 2017 were extracted from The National Quality Register for Hip Fractures and then cross-referenced with data from registers of The National Board of Health and Welfare. This resulted in a total of 134,915 patients eligible for analysis. The results demonstrated a 72% risk reduction in postoperative mortality within 30 days of surgery in the cohort with ongoing beta-blocker therapy.

Paper III explored if the effect seen in Paper I-II remains up to one year using the same database as Paper II. The results demonstrated that the association between beta-blocker therapy and reduction in the risk of mortality,extending up to one year postoperatively, with the main effect seen during the first postoperative period.

Paper IV investigates the interaction between the Revised Cardiac Risk Index and beta-blocker therapy related to 30-day post-operative mortality. This study concluded that all geriatric hip fracture patients could benefit from beta-blockers, but a more pronounced effect was seen in those with cardiac risk factors.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2022. , p. 69
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 252
Keywords [en]
Trauma, Hip Fracture, Beta-Blocker, Hyperadrenergic State, Stress, Mortality
National Category
Surgery
Identifiers
URN: urn:nbn:se:oru:diva-95781ISBN: 9789175294179 (print)OAI: oai:DiVA.org:oru-95781DiVA, id: diva2:1617725
Public defence
2022-02-25, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2021-12-07 Created: 2021-12-07 Last updated: 2024-03-06Bibliographically approved
List of papers
1. β-adrenergic blockade is associated with a reduced risk of 90-day mortality after surgery for hip fractures
Open this publication in new window or tab >>β-adrenergic blockade is associated with a reduced risk of 90-day mortality after surgery for hip fractures
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2020 (English)In: Trauma surgery & acute care open, ISSN 2397-5776, Vol. 5, no 1, article id e000533Article in journal (Refereed) Published
Abstract [en]

Background: There is a significant postoperative mortality risk in patients subjected to surgery for hip fractures. Adrenergic hyperactivity induced by trauma and subsequent surgery is thought to be an important contributor. By downregulating the effect of circulating catecholamines the increased risk of postoperative mortality may be reduced. The aim of the current study is to assess the association between regular β-blocker therapy and postoperative mortality.

Methods: This cohort study used the prospectively collected Swedish National Quality Registry for hip fractures to identify all patients over 40 years of age subjected to surgery for hip fractures between 2013 and 2017 in Örebro County, Sweden. Patients with ongoing β-blocker therapy at the time of surgery were allocated to the β-blocker-positive cohort. The primary outcome of interest was 90-day postoperative mortality. Risk factors for 90-day mortality were evaluated using Poisson regression analysis.

Results: A total of 2443 patients were included in this cohort of whom 900 (36.8%) had ongoing β-blocker therapy before surgery. The β-blocker positive group was significantly older, less fit for surgery based on their American Society of Anesthesiologists classification and had a higher prevalence of comorbidities. A significant risk reduction in 90-day mortality was detected in patients receiving β-blockers (adjusted incidence rate ratio=0.82, 95% CI 0.68 to 0.98, p=0.03).

Conclusions: β-blocker therapy is associated with a significant reduction in 90-day postoperative mortality after hip fracture surgery. Further investigation into this finding is warranted.

Level of evidence: Therapeutic study, level III; prognostic study, level II.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2020
Keywords
Emergency treatment, femoral fractures, hip fractures, mortality
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-86590 (URN)10.1136/tsaco-2020-000533 (DOI)000672553900081 ()32789190 (PubMedID)2-s2.0-85101842310 (Scopus ID)
Available from: 2020-10-26 Created: 2020-10-26 Last updated: 2024-03-06Bibliographically approved
2. A nationwide observational cohort study of the relationship between beta-blockade and survival after hip fracture surgery
Open this publication in new window or tab >>A nationwide observational cohort study of the relationship between beta-blockade and survival after hip fracture surgery
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2022 (English)In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941, Vol. 48, no 2, p. 743-751Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Despite advances in the care of hip fractures, this area of surgery is associated with high postoperative mortality. Downregulating circulating catecholamines, released as a response to traumatic injury and surgical trauma, is believed to reduce the risk of death in noncardiac surgical patients. This effect has not been studied in hip fractures. This study aims to assess whether survival benefits are gained by reducing the effects of the hyper-adrenergic state with beta-blocker therapy in patients undergoing emergency hip fracture surgery.

METHODS: This is a retrospective nationwide observational cohort study. All adults [Formula: see text] 18 years were identified from the prospectively collected national quality register for hip fractures in Sweden during a 10-year period. Pathological fractures were excluded. The cohort was subdivided into beta-blocker users and non-users. Poisson regression with robust standard errors and adjustments for confounders was used to evaluate 30-day mortality.

RESULTS: 134,915 patients were included of whom 38.9% had ongoing beta-blocker therapy at the time of surgery. Beta-blocker users were significantly older and less fit for surgery. Crude 30-day all-cause mortality was significantly increased in non-users (10.0% versus 3.7%, p < 0.001). Beta-blocker therapy resulted in a 72% relative risk reduction in 30-day all-cause mortality (incidence rate ratio 0.28, 95% CI 0.26-0.29, p < 0.001) and was independently associated with a reduction in deaths of cardiovascular, respiratory, and cerebrovascular origin and deaths due to sepsis or multiorgan failure.

CONCLUSIONS: Beta-blockers are associated with significant survival benefits when undergoing emergency hip fracture surgery. Outlined results strongly encourage an interventional design to validate the observed relationship.

Place, publisher, year, edition, pages
Urban und Vogel Medien und Medizin Verlagsgesellsc, 2022
Keywords
Beta-blockers, Hip fractures, Mortality
National Category
Orthopaedics
Identifiers
urn:nbn:se:oru:diva-89079 (URN)10.1007/s00068-020-01588-7 (DOI)000612583000001 ()33507317 (PubMedID)2-s2.0-85099985820 (Scopus ID)
Note

Funding Agency:

Örebro University  

Available from: 2021-01-29 Created: 2021-01-29 Last updated: 2024-03-06Bibliographically approved
3. Beta-Blocker Therapy Is Associated With Increased 1-Year Survival After Hip Fracture Surgery: A Retrospective Cohort Study
Open this publication in new window or tab >>Beta-Blocker Therapy Is Associated With Increased 1-Year Survival After Hip Fracture Surgery: A Retrospective Cohort Study
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2021 (English)In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 133, no 5, p. 1225-1234Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The high mortality rates seen within the first postoperative year after hip fracture surgery have remained relatively unchanged in many countries for the past 15 years. Recent investigations have shown an association between beta-blocker (BB) therapy and a reduction in risk-adjusted mortality within the first 90 days after hip fracture surgery. We hypothesized that preoperative, and continuous postoperative, BB therapy may also be associated with a decrease in mortality within the first year after hip fracture surgery.

METHODS: In this retrospective cohort study, all adults who underwent primary emergency hip fracture surgery in Sweden, between January 1, 2008 and December 31, 2017, were included. Patients with pathological fractures and conservatively managed hip fractures were excluded. Patients who filled a prescription within the year before and after surgery were defined as having ongoing BB therapy. The primary outcome of interest was postoperative mortality within the first year. To reduce the effects of confounding from covariates due to nonrandomization in the current study, the inverse probability of treatment weighting (IPTW) method was used. Subsequently, Cox proportional hazards models were fitted to the weighted cohorts. These analyses were repeated while excluding patients who died within the first 30 days postoperatively. This reduces the effect of early deaths due to surgical and anesthesiologic complications as well as the higher degree of advanced directives present in the study population compared to the general population, which allowed for the evaluation of the long-term association between BB therapy and mortality in isolation. Results are reported as hazard ratios (HR) with 95% confidence intervals (CI). Statistical significance was defined as a 2-sided P value <.05.

RESULTS: A total of 134,915 cases were included in the study. After IPTW, BB therapy was associated with a 42% reduction the risk of mortality within the first postoperative year (adjusted HR = 0.58, 95% CI, 0.57-0.60; P < .001). After excluding patients who died within the first 30 days postoperatively, BB therapy was associated with a 27% reduction in the risk of mortality (adjusted HR = 0.73, 95% CI, 0.71-0.75; P < .001).

CONCLUSIONS: A significant reduction in the risk of mortality in the first year following hip fracture surgery was observed in patients with ongoing BB therapy. Further investigations into this finding are warranted.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2021
National Category
Orthopaedics
Identifiers
urn:nbn:se:oru:diva-93336 (URN)10.1213/ANE.0000000000005659 (DOI)000708283100027 ()34260428 (PubMedID)
Available from: 2021-08-01 Created: 2021-08-01 Last updated: 2024-03-06Bibliographically approved
4. The interaction between pre-admission β-blocker therapy, the Revised Cardiac Risk Index, and mortality in geriatric hip fracture patients
Open this publication in new window or tab >>The interaction between pre-admission β-blocker therapy, the Revised Cardiac Risk Index, and mortality in geriatric hip fracture patients
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2022 (English)In: Journal of Trauma and Acute Care Surgery, ISSN 2163-0755, E-ISSN 2163-0763, Vol. 92, no 1, p. 49-56Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: An association between beta-blocker (BB) therapy and a reduced risk of major cardiac events and mortality in patients undergoing surgery for hip fractures has previously been demonstrated. Furthermore, a relationship between an increased Revised Cardiac Risk Index (RCRI) score and a higher risk of postoperative mortality has also been detected. The purpose of the current study was to investigate the interaction between BB therapy and RCRI in relation to 30-day postoperative mortality in geriatric patients after hip fracture surgery.

METHODS: All patients over 65 years of age who underwent primary emergency hip fracture surgery in Sweden between January 1, 2008 and December 31, 2017, except for pathological fractures, were included in this retrospective cohort study. Patients were divided into cohorts based on their RCRI score (RCRI 1, 2, 3, and ≥ 4) and whether they had ongoing BB therapy at the time of admission. A Poisson regression model with robust standard errors of variance was used, while adjusting for confounders, to evaluate the association between BB therapy, RCRI, and 30-day mortality.

RESULTS: A total of 126,934 cases met the study inclusion criteria. Beta-blocker therapy was associated with a 65% decrease in the risk of 30-day postoperative mortality in the whole study population [adj. IRR (95% CI): 0.35 (0.32-0.38), p < 0.001]. The use of BB also resulted in a significant reduction in 30-day postoperative mortality within all RCRI cohorts. However, the most pronounced effect of beta-blocker therapy was seen in patients with an RCRI score greater than 0.

CONCLUSIONS: Beta-blocker therapy is associated with a reduction in 30-day postoperative mortality, irrespective of RCRI score. Furthermore, patients with an elevated cardiac risk appear to have a greater benefit of beta-blocker therapy.

LEVEL OF EVIDENCE: Level II, Therapeutic / Care Management.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2022
Keywords
beta-Blocker therapy, hip fracture, Revised Cardiac Risk Index, mortality
National Category
Orthopaedics
Identifiers
urn:nbn:se:oru:diva-93478 (URN)10.1097/TA.0000000000003358 (DOI)000731994300013 ()34252058 (PubMedID)
Available from: 2021-08-12 Created: 2021-08-12 Last updated: 2024-03-06Bibliographically approved

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Mohammad Ismail, Ahmad

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