Background

Hip fractures (i.e. fractures of the proximal femur), which are often a result of low-energy trauma, are serious injuries commonly experienced by older individuals.1,2 These injuries have a major impact on not only older individuals' long-term health but also their families, health services and the community.3 In older individuals living at home, sustaining a hip fracture can reduce life expectancy by 25%.4 Globally, the 30-day mortality after a neck of femur fracture is between 7% and 9% and the one-year mortality ranges from 21.6% to 30%.5,6 Hip fractures also pose a considerable burden to the healthcare system because of the associated increase in morbidity. According to a report released by Osteoporosis Australia in 2013, approximately 23,000 Australians had a hip fracture in 2012, costing approximately AUS$731 million dollars in total direct fracture cost including informal care.7 According to a study by Stephens et al.8 the number of hip fractures is predicted to increase by around 100% over the next two decades.

Elderly individuals with hip fractures are admitted to the hospital for fixation of the broken hip. These patients are at risk of developing complications including functional, physical and mental impairments.3 Poor general health, older age, cognitive impairment and decreased activity level have been identified to further increase the risk of complications associated with hip fractures.9,10 Studies have identified delirium as the most frequent complication among the hospitalized elderly, particularly among those undergoing orthopedic surgical interventions following hip fracture.11-13 Delirium is a complex neuropsychiatric syndrome characterized by acute and fluctuating onset, inattention, altered level of consciousness and evidence of disorganized thinking.14 Marcantonio et al.15 reported that 35% to 65% of patients who have undergone surgery for a neck of femur fracture repair suffered delirium postoperatively. Many studies observed that patients presenting with delirium during the hospital stay have a worse prognosis, stay longer in the hospital and have higher mortality rates, worse functional recovery and higher institutionalization rates after hospital discharge.16-18 Inouye et al.19 reported that although this condition is known to be associated with poor clinical outcomes, and health service planners and practitioners have hugely ignored its existence.

The exact mechanisms and causative factors of delirium are not well understood. A number of neurotransmitters have been postulated to lead to the development of delirium, including an elevation in dopamine level and deficiencies in acetylcholine, serotonin and gamma-aminobutyric acid.20 Some researchers proposed that impaired cholinergic transmission, inflammation and impaired oxidative metabolism may explain the pathogenesis of delirium.21 There are also a variety of potential risk factors associated with this condition, many of which are avoidable or treatable.22 Delirium is considered to be a result of the interactions between patient vulnerabilities and precipitating factors.23 Advancing old age and cognitive impairment have been identified as the most consistent predictor of postoperative delirium.24,25 The amount of blood lost intra-operatively has been identified as another correlate of postoperative delirium. Greater intra-operative blood loss, more blood transfusions and a postoperative hematocrit <30% are associated with a higher incidence of delirium.26 The physical hospital environment has also been identified as an aggravating factor for the onset of delirium.27 Hip fracture patients are subject to emergency room wait times and are therefore exposed to stressful factors often characterized by multiple staff encounters, disturbed sleep and discomfort.28,29 Hip fracture is also associated with considerable pain30 and undertreated pain is a significant risk factor for delirium.31 The literature suggests that hip fracture surgery confers higher risks for delirium compared to other surgical procedures.32 Moreover, compared to older, non-surgical patients, hip fracture repair patients have a different set of precipitating risk factors for delirium including time between admission and surgery, type of surgery, type of anesthesia, duration of surgery and anesthesia and complications during surgery.33

A number of studies have investigated various interventions to prevent delirium, which can be grouped into multi-component therapies and single interventions.34-37 The majority of single intervention studies focus on the impact of pharmacological interventions.34-36 Effectiveness studies on the use of pharmacological interventions for delirium prevention show mixed results.34-36 A randomized, placebo-controlled trial investigated the effectiveness of haloperidol prophylaxis on postoperative delirium in elderly hip fracture patients from a large general hospital.34 Low-dose haloperidol treatment (i.e. 1.5 mg/d started preoperatively and up to three days postoperatively) decreased hospital length of stay and improved delirium severity; however, it did not decrease the incidence of delirium.34 Another multi-centre, double-blind randomized controlled trial (RCT) examined the effectiveness of melatonin on the incidence of delirium among patients with hip fractures.36 This study showed that treatment with 3 mg of melatonin did not reduce the incidence of delirium.36 On the other hand, studies exploring multi-component therapies showed promising results.37 Multi-component interventions/therapies refer to more than one strategy to address the range of risk factors associated with delirium that can include pharmacological as well as non-pharmacological interventions. A quasi-experimental study that included elderly patients with hip fracture showed a 35% reduction in the incidence of delirium following the implementation of a multi-factorial program that consisted of intense prehospital and perioperative treatment and care.37 The multi-factorial program comprised oxygen therapy, fluid intake management, pain relief management, delirium screening, avoidance of polypharmacy, and a select choice of perioperative drugs and anesthetic interventions.37 Similar results were described in a systematic review of RCTs and prospective studies which identified effective strategies for delirium prevention in critical care patients (e.g. critically ill, general medicine patients and post-surgical patients).38 This review suggested that multi-component programs targeting known risk factors for delirium appear to be more beneficial than single-intervention programs.

Delirium is a serious geriatric condition that is largely prevalent in hospitalized older patients and is associated with adverse long-term consequences. Therefore, early intervention to prevent its onset is of critical importance for patients, their families and the health system. The use of multi-component interventions appears to be the most promising approach to delirium prevention. A preliminary search of the JBI Database of Systematic Reviews and Implementation Reports, the Cochrane Database of Systematic Reviews, and MEDLINE revealed a number of systematic reviews on multi-component interventions for delirium. A Cochrane review published in 2007 examined interventions for preventing delirium in various older patient groups including those needing elective hip surgery, hip or knee arthroplasty, hip fracture repair and surgery secondary to gastric or colorectal cancer. The findings of this review relevant to hip fracture repair were based on a single study that suggested that proactive geriatric consultation can reduce incidence and severity of delirium.39 In 2013, Thomas et al. published a systematic review on the effectiveness of non-pharmacological multi-component interventions for delirium prevention; participants in the study comprised any elderly patient admitted to a non-intensive care unit. The findings of this review suggested that multi-component interventions have a potential to reduce risk of delirium.40 More recently, two systematic reviews were undertaken on the same interventions but involving elderly patients with various conditions such as orthopedic ward patients with hip fractures, patients in medical wards and coronary care patients; findings of both reviews suggested that multi-component interventions are effective in reducing incidence of delirium.41,42 None of these reviews, however, are specific to hip fracture patients and given that this patient group has a higher level of risk and a different set of precipitating risk factors for delirium (as described above) and may therefore require a distinct set of interventions compared to other older patient groups, a systematic review specifically investigating this population is warranted.

Inclusion criteria

Types of participants

The current review will consider studies that include hospitalized patients aged 65 years and over, who sustained a hip fracture, irrespective of the mechanism of injury.

Types of interventions

The current review will consider studies that evaluate effect of multi-component interventions on incidence of delirium. A multi-component intervention refers to the use of more than one strategy that can include but is not limited to the use of specialized clinical staff/volunteers, geriatric/psychiatric consultation, staff education, patient orientation, addressing visual and hearing needs, sleep enhancement, medication review, hydration and nutrition, early mobilization, pain management, addressing bowel and bladder functions and prevention and treatment of medical complications. Some of these issues are addressed by pharmacological interventions. This review will not exclude studies based on the dose (e.g. intensity, frequency and duration) of intervention or who delivered the intervention.

Types of comparators

The current review will consider studies where multi-component interventions have been compared to single interventions or usual care or no intervention. Studies with any comparator interventions are also eligible for inclusion in the review.

Outcomes

The current review will consider studies that measure incidence of delirium as a primary outcome. Only studies that have determined the presence of delirium using standardized criteria or a validated tool such as, but not limited to, the Confusion Assessment Method, Mental Status Questionnaires and Mini Mental State Examination will be included. Where reported, other outcomes such as discharge destination, length of stay, cognitive function, functional ability and readmission will also be considered in the review.

Types of studies

The current review will consider experimental studies including randomized controlled trials, non-randomized controlled trials, quasi-experimental, and before and after studies. This review will also consider observational studies such as prospective and retrospective cohort studies and case-control studies.

Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Third, the reference list of all identified articles will be searched for additional studies. Only studies published in English will be considered for inclusion in this review. The search will be limited to studies published between 1990 and the present as multi-component intervention strategies for the prevention of delirium began to appear in the published literature during this time.43-47

The databases to be searched via EBSCO and Ovid platforms will include:

* MEDLINE

* CINAHL

* PsycINFO

* Cochrane Central Register of Controlled Trials

* Embase

* Web of Science.

The search for unpublished studies will include:

* Clinicaltrial.gov

* NZ Research.org

* National Clearing House

* ProQuest Dissertations and Theses.

The following initial keywords will be used:

Delirium: delirium, acute confusion, acute confusional state, acute altered mental state.

Hospitalized: medical surgical inpatients, in-patient, hospitalization, non-ICU, non-critical care.

Elderly: older adults, elderly, aged.

Prevention: prevention, interventions, multi-component intervention, nursing care.

Hip fracture: hip fracture, neck of femur fracture, pertrochanteric fracture, subtrochanteric fracture.

Assessment of methodological quality

Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.

Data extraction

Data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the populations, interventions (e.g. type, intensity and duration), outcomes and study methods. In addition, attempts will be made to obtain missing data from the study report(s) by contacting the authors of the included studies. Data extraction will be carried out by one reviewer with verification by another reviewer to minimize bias and potential errors in data extraction.

Data synthesis

Quantitative data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard chi-square and where appropriate also explored using subgroup analyses based on the different study designs included in this review. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.

Appendix I: Appraisal Instruments

MAStARI appraisal instrument

Appendix II: Data extraction instruments

MAStARI data extraction instrument

REFERENCES