The efficacy and safety of fast track surgery (FTS) in patients after hip fracture surgery: a meta-analysis

Background Fast track surgery (FTS) has been gradually applied in perioperative management of orthopedic surgery, but there still some research suspected that the prognosis of patients is not as expected and the cost is high, the effect of the FTS still urgently needed for support by evidence-based medicine. Methods We retrieved RCTs from medical research literature databases. Risk ratios (RR), standard mean difference (SMD), and 95% confidence intervals (CI) were calculated to compare the primary and safety endpoints. Results Overall, a total of 8886 patients were retrieved from 57 articles, of which 4448 patients (50.06%) were randomized to experimental group whereas 4438 patients (49.94%) were randomized to control group. The result showed that FTS could significantly shorten the length of stay (LOS), decrease the visual analog scale (VAS), reduce the leaving bed time and the hospitalization costs, and improve Harris hip joint function score. The incidence of complications such as respiratory system infection, urinary system infection, venous thrombus embolism (VTE), pressure sore, incision infection, constipation, and prosthesis dislocation also has been decreased significantly. Meanwhile, FTS improved patients’ satisfaction apparently. Conclusions This meta-analysis reveals that FTS could significantly shorten the length of stay, alleviate the pain, reduce the leaving bed time and the hospitalization costs, and improve hip function. The incidence of complications also has been decreased significantly. Meanwhile, FTS has been spoken highly in patients in terms of nursing satisfaction. Its efficacy and safety were proved to be reliable. Supplementary Information The online version contains supplementary material available at 10.1186/s13018-021-02277-w.


Introduction
Hip fracture is a public health problem that could come with number of complications even threaten your life [1]. It could happen in any age and most common caused by falling [2]. Surgery is the most common treatment, and the rehabilitation therapy is being encouraged in order to avoid complications and resume routine activities of life. With the increase of age, the realization of rehabilitation plan is more limited. Especially with other basic diseases, the difficulty of rehabilitation increases, and the recovery of hip fracture may be limited [3].
Fast track surgery (FTS), also known as enhanced recovery after surgery (ERAS), is a new surgical concept aiming at early ambulation, discharge, and return to activities of daily living [4,5]. It uses a series of perioperative optimization measures confirmed by evidence-based medicine to eliminate the factors that delay postoperative recovery [6]. There are 3 parts of FTS: preoperative, intraoperative, and postoperative [7]. Psychological comfort and physical muscle training might reduce patients' response to psychological and surgical stress preoperative; intraoperative, optimizing anesthesia, and procedure (minimally invasive surgery, MIS), which can reduce pain and shorten recovery time; postoperative nutrition support and pain management are beneficial to improve organ dysfunction, and early rehabilitation exercise could prevent surgery-related complications [8][9][10][11][12][13].
Currently, the concept of FTS has been widely used in surgical malignant tumors and laparoscopic surgery (especially colorectal surgery), which is expected to be extended to other surgical specialties safely and effectively [14]. Though it is also gradually applied to the perioperative management of orthopedic surgery, the effect of perioperative in elderly patients with hip fracture is    [17]. The result that the incidence of adverse events (AEs) in FTS group was less than standard group has no statistical significance. According to the research conducted by Hansson et al., the FTS could shorten the time to operation, which is the only significant difference between FTS group and standard group, but there is no difference in the LOS or the incidence of AEs [18]. Haugan et al. also showed that there was no statistically significant difference in mortality and readmission rates between the FTS and the standard care models for firsttime admission [19]. All in all, the data of FTS in the rehabilitation and prognosis of elder patients did not meet the expectations.
The purpose of this article is to analyze the effect of nursing intervention based on FTS concept on perioperative pain management, postoperative length of stay and incidence of complications of hip fracture in the elderly by meta-analysis. It could provide effective evidence for perioperative nursing of hip fracture in the elderly.

Search strategy
Published articles were searched by two researchers for comparing the efficacy and safety of fast-track surgery (FTS) in elderly patients with hip fracture following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [20]. We have searched the RCTs systematically in the

Inclusion and exclusion criteria
The following inclusion criteria were used: (1) studies that assessed the efficacy and safety of FTS in elderly patients with hip fracture, (2) the study was a randomized controlled trial (RCT), (3) the study subjects were elderly patients undergoing hip fracture, (4) general information (e.g., gender, age, disease type) of the experimental group and the control group was not statistically different at baseline, (5) at least one of the evaluated groups was based on FTS, (6) included articles provide sufficient Fig. 3 Comparison of Harris hip joint function score between the experimental group and the control group. SMD standardized mean difference data for analysis, (7) language was limited to English or Chinese, and (8) the study was extracted from January 1, 2015, to August 1, 2020.
The following exclusion criteria were used: (1) nonclinical trials, case reports or series; (2) animal experiments; (3) semi-randomized controlled trials or nonrandomized trials; and (4) articles with incorrect or incomplete data, or articles whose data could not be extracted.

Endpoints
The primary endpoints for this study were length of stay (LOS), Harris hip joint function score, VAS, satisfaction.
The secondary endpoints for this study were the leaving bed time.

Data extraction
The two authors independently reviewed the contents of the retrieval research. The primary endpoints were extracted by two authors and verified by a third author. The extracted data included the following main information: first author's name, year of publication, sample size, sex ratio, average age, clinical diagnosis or operative type, FTS measures, follow-up time, and endpoints measured in each study. If the contents of the studies needed to be clarified, please contact the first author of the study. Disagreements were resolved through consensus or consultation with a third author.

Risk-of-bias assessments
The quality of the methodology in included studies was independently evaluated by the two authors according to the Cochrane Risk of Bias criteria. Each quality item was divided into low risk, high risk, and no obvious risk. The seven items used to estimate bias in each trial included randomization sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases.

Statistical analysis
Stata (version 12.0, Stata Corp, College Station, Texas) was used to analyse and pool the individual research results. Pooled results were recorded as risk ratios (RR) Standard mean difference (SMD) and 95% confidence intervals (CI) with two-sided P values. P values <0.05 were considered to be statistically significant. Heterogeneity was evaluated using the I 2 test. The heterogeneity was considered to be small when I 2 <50% and substantial when I 2 >50%. The fixed effect model was used when I 2 < 50%, while the random effect model was used when I 2 >50%. A funnel plot was generated to examine the publication bias and to explore the sources of heterogeneity if more than ten studies were included to assess this endpoint.

Studies retrieved and characteristics
A total of 16018 relevant studies were enrolled according to PRISMA guidelines. The titles and abstracts of the studies were screened to exclude irrelevant studies. Then, we further eliminated the unfit studies by reading the full text of the articles. Finally, 57 studies  were included according to the inclusion and exclusion criteria and they had a total of 8886 patients as shown in Fig. 1. In general, 4448 patients (50.06 %) were randomized to experimental group whereas 4438 patients (49.94 %) were randomized to control group. All studies included in this meta-analysis were RCTs. The basic characteristics of the individuals from the trials are described in Table 1.

Literature quality evaluation
The Cochrane Risk of Bias criteria was used to evaluate the quality of the retrieved studies by two authors. The included studies were all randomized controlled trials. Fiftyseven studies  described random sequence generation and allocation concealment. Four studies [53,57,66,72] described blinding of participants and personnel. Four studies [53,57,66,72] described blinding of outcome assessment. None of the studies described other biases. The literature quality score is shown in Table 2.

Harris Hip Joint Function Score
Harris hip joint function score scale is a widely used method to evaluate hip function. The higher the total score, the stronger the function. Harris hip joint function score was reported in 25 studies [21, 23, 25, 27-29, 33-35, 38, 41, 43, 48-51, 55, 56, 63, 65, 70, 72-74, 77]. 2441 patients were involved in all, wherein 1232 were assigned to the experimental group and 1209 were assigned to control group. The result showed that patients' score in experimental group was significantly greater than that in control group (SMD: 2.22, 95% CI 1.73 to 2.71, I 2 =95.9%) as shown in Fig. 3. The random effect model was applied. Subgroup analysis was performed according to the follow-up period and divided into 1 month after surgery, 6 months after surgery, and not applicable three group. The result of follow-up time subgroup showed that patients' Harris hip joint function score 6 months after surgery in experimental group was significantly higher than that in control group, though the not applicable group is the highest. (SMD: 1.50, 95% CI 0.88 to 2.13; SMD: 2.20, 95% CI 1.27 to 3.12; SD, 95% CI 2.21 to 4.34) as shown in Fig. 4.

VAS
Visual analog scale (VAS) was used to score the pain degree of patients, which the score was in direct proportion to the pain degree. It was reported by 13 studies [25,27,28,37,40,41,44,51,56,58,70,72,76] included 1293 patients, wherein 649 were assigned to the experimental group and 644 were assigned to control group. The result showed that FTS could reduce VAS significantly in experimental group than control group (SMD: −2.38, 95% CI −3.26 to −1.49, I 2 =97.4%) as shown in Fig. 5. The random effect Fig. 7 Comparison of satisfaction between the experimental group and the control group. RR risk ratio model was applied. Subgroup analysis was performed according to the follow-up time and divided into 1 month after surgery and others' group. The result of follow-up subgroup was showed that the VAS in experimental group was significantly less than that in control group in 1 month after surgery subgroup (SMD: −2.76, 95% CI −3.79 to −1.73; SMD: −1.93, 95% CI −3.38 to −0.47) as shown in Fig. 6.

Discussion
Fast track surgery (FTS), also named as enhanced recovery after surgery (ERAS), improved or reselected partially perioperative steps of traditional hip arthroplasty in order to reduce the direct surgical injury, surgical stress response, and operation-related complication and achieve the purpose of promoting the rapid rehabilitation of patients, which could shorten the length of stay and reduce the cost of hospitalization [78][79][80]. The ultimate objective of FTS is to achieve "painless and risk-free surgery," which has attracted worldwide attention [81].
Kehlet published an article to describe "fast-track surgery" (also known as enhanced recovery after surgery, ERAS) in 2001 first. The ERAS society, a nonprofit and multidisciplinary medical association, was founded later that same year, aimed to help worldwide to carry through ERAS Social Guidelines systematically, and it has remained a challenge to monitor patient compliance and follow-up the rehabilitation outcomes [82]. The UK's National Hip Fracture Database (NHFD), which collected information about fractured neck of femur, was established in 2007 and the most recent report supported early rehabilitation exercise [83]. NHFD has been focus on orthogeriatric assessment recently, an assessment before operation similar to the ERAS principles [84].
Nowadays, preoperative management of diabetes and anemia, personalized risk assessment, path sharing between enhanced recovery and hospitals, individualized pain management, multimodal anesthesia strategies, and the great differences in nursing in different area and so on still have room for improvement, which limited the promotion of FTS in worldwide [85]. Meanwhile, the research on ERAS has gradually shifted from standard indicators such as mortality, morbidity, and readmission rate to patient-reported outcome measures (PROMs).
The results we got consist with Husted et al.'s [86] (a prospective study), Larsson et al.'s [13] (a retrospective pilot study), and Bao et al.'s ( a meta-analysis), which suggested that patients could leave bed, recover the function of hip joint faster, suffer less pain, and reduce Fig. 9 Comparison of cost between the experimental group and the control group. SMD standardized mean difference the incidence of postoperative complications, which could achieve the purpose of leaving hospital as soon as possible in addition after FTS. The novel nursing care delivery system also has a better satisfaction. However, the focus of their RCTs was to shorten the preparation time and nursing time, which means the results they come to may be influenced by shorter waiting times for surgery and cannot be attributed solely to the improvement of the chains of nursing. Bao et al. included a portion of studies with a lower quality, which might be measurement bias and selective bias, besides, the metaanalysis only analyzed the perioperative pain management of FTS [87]. Pollmann et al. [88] suggested that although the introduction of fast-track care for hip fractures significantly reduced length of stay, duration of surgery and risk of reoperation within 30 days, there was no significant different in 30-day, 90-day, or 1-year mortality rates. The data of the study were obtained retrospectively from electronic hospital records so that we could not identified that whether the patients follow the nursing protocol strictly. About half of the data on the admission are unclear, the others were admitted through fast-track admission pathway, which may have an influence on the outcome of mortality. The study by Amlie et al. reported that compared with the standard THA patients, patients with FTS regimen had an increased risk of postoperative revision surgery due to deep infection [89]. Therefore, there is still a controversial about whether FTS is effective and safe enough in the perioperative period for elderly patients with hip fracture.
At the time of assessment of the primary end point, a subgroup analysis was performed based on follow-up time. Subgroup analysis is performed only if each subgroup has more than two experimental comparisons. The result of follow-up time subgroup showed that patients' Harris hip joint function score 6 months after surgery in the experimental group was significantly higher than that in control group, though the not applicable group is the highest. It could be concluded that FTS improves the long-term functional recovery of patients after hip replacement. The VAS in experimental group was significantly less than that in the control group 1 month after surgery.
As the primary endpoint, we evaluated was highly heterogeneous, and we did sensitivity analyses to decompose it. The results showed that after excluding Jia et al.'s article [59], and the overall effect of LOS has been affected significantly. We speculated that that the control group in research also offer a guidance of fracture functional exercise postoperative. There is also a great deal of influence of the overall effect of respiratory, VTE, and pressure sores after excluding Borges et al.'s article [72]. However, the RCT focused on accelerated surgical treatment (within 6 h), so that the waiting time for surgery is shorter than that of other patients, which may lead to heterogeneity.
The potential clinical implications of this metaanalysis are as follows: (1) 57 RCTs were retrieved which included a large sample size of 8886 participants compared to previous studies. (2) Subgroup analyses were performed according to the follow-up period to explain the influence of different factors on the overall effect. (3) We evaluated 12 indicators, including length of stay (LOS), Harris hip joint function score, VAS, satisfaction, the leaving bed time, respiratory system infection, urinary system infection, VTE, pressure sore, incision infection, constipation, and prosthesis dislocation, which were more comprehensive than previous articles.
The limitations of this study are as follows: (1) Most of the elderly patients with hip fractures were associated with risk factors (such as elder age, smoking), other complications (such as diabetes, Fig. 11 Incidence of urinary tract infection between the experimental group and the control group. RR risk ratio hypertension), or some drug use history, which were adverse to incision healing. The influence of these baseline factors was not excluded and may lead to mixed bias. (2) We use the outcomes from reported events retrieved to integrate the results of this metaanalysis, so it is difficult to assess the impact of these baseline characteristics on the result. (3) Due to the limitations of the included study, this study was unable to explore the interaction between subgroup analyses. (4) The detail of the intervention measures in the control group (or standard track group) was not acceptable in most articles. (5) Only 3 of the retrieved articles were published in English journals and 54 in Chinese journals. Therefore, we have correctly attempt to address this problem by assessing the quality of the studies retrieved and rating most of them B.
This meta-analysis reveals that FTS could significantly shorten the LOS and reduce VAS, the leaving bed time, and the hospitalization costs and improve hip function. The incidence of complications (such as respiratory system infection, urinary system infection, VTE, pressure sore, incision infection, constipation, and prosthesis dislocation) also has been decreased significantly. Meanwhile, FTS improved patients' satisfaction apparently. Its efficacy and safety were proved to be reliable.  Due to individual differences of every patient, the fast track should be adjusted clinically so that patients with special needs or high co-morbidity burden should be transferred to a safe and effective FTS [84]. A peopleoriented approach is an important factor in optimizing care from surgical decisions to rehabilitation [85].
In the future, the perioperative strategy of rapid rehabilitation surgery in total hip replacement will need to extract more large samples of high quality for evidencebased analysis under a more perfect unified standard, so as to conduct more safe and effective multidisciplinary cooperation.