Identification of risk factors for 1-year mortality among elderly and critically ill patients with hip fractures surgery: A single medical center retrospective study

doi:10.21203/rs.3.rs-1735964/v1

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Identification of risk factors for 1-year mortality among elderly and critically ill patients with hip fractures surgery: A single medical center retrospective study

https://doi.org/10.21203/rs.3.rs-1735964/v1

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AIM: The aim of this study is to examine potential risk factors for 1-year mortality after hip fracture surgery.

METHODS: We reviewed 591 elderly and critically ill patients who underwent hip surgery at our institution from January 2018 to April 2021 retrospectively. The baseline demographic, clinical data and 1-year survival status in both groups were collected through the medical record system and follow-up phone calls. Patients were divided into survival group and death group according to the survival status within the first postoperative year.

RESULTS: According to the results from 1year follow-up, 117 cases were classified into the death group while 474 cases were in the survival group, and it was calculated that the 1-year mortality rate of elderly and critically ill patients with hip fracture was 19.8% (117/591) in our hospital. The identified risk factors for 1-year mortality were advanced age (HR:1.04, 95%:1.01- 1.06), preoperative arrhythmia (HR: 1.95, 95%: 1.26 - 2.70), high level of NLR (HR:1.03, 95%:1.01 - 1.06), respiratory failure (HR: 2.63, 95%:1.32 - 5.23) and acute cardiovascular events (HR: 1.65, 95%:1.05 - 2.59).

CONCLUSION: Advanced age, preoperative comorbid arrhythmias, preoperative high level of NLR, respiratory failure and acute cardiovascular events postoperatively were independently associated with increased risk of 1-year mortality rate of critically ill elderly patients with hip fracture. Laboratory tests such as high level of NLR preoperative can be used as important indicators to determine the prognosis of patients.

hip fracture surgery

elderly

mortality

NLR

arrhythmia

respiratory failure

With the increasing aging population, the number of hip fractures among the elderly continues to reach new highs. Zhang et al[1] showed the absolute number of patients with hip fracture in China increased fourfold in 2016 compared to with 2012, and the per capita hospitalization cost increased to 1.59 times. Geriatric hip fractures are becoming an increasingly prominent problem that cannot be ignored. In recent years, with the rapid improvement of surgical types, anesthesia methods and perioperative management, most of the patients with low risk of basic diseases can obtain good surgical results; however, the risk of pulmonary infection, acute cardiovascular events, and acute kidney injury is still high in high-risk patients with severe comorbidities during the perioperative period, which seriously affects the early postoperative activities and rehabilitation training. Its high rate of disability and fatality increases the social and economic burden, and may lead to a drain on public health resources [2, 3].

Several studies have reported a mortality rate of up to 20% at 1 year after hip fracture in the elderly[4, 5], but there are fewer prognostic studies related to critically ill elderly patients with hip fractures (ASA ≥ III or Nottingham score ≥ 5). All critically ill patients with ASA ≥ III or Nottingham score ≥ 5 in our hospital were transferred to ICU for observation or treatment after surgery. Based on the latest status of domestic and international studies, we retrospectively collected all patients transferred to the ICU after surgery in our hospital from January 2018 to April 2021. By comparing their basic information, perioperative treatment and postoperative survival status, we analyzed the risk factors affecting the long-term survival of elderly and critically ill patients with hip fracture, and provided valuable guidance for clinical practice.

The studies involving human participants were reviewed and approved by the Institutional Review Board of the Beijing Jishuitan Hospital. This is a retrospective anonymous data analysis, the requirement for informed consent was therefore waived. All methods were carried out in accordance with relevant guidelines and regulations[6]. Patients who underwent hip surgery at our hospital from 2018 to April 2021 were selected. Inclusion criteria were (1) age ≥ 65 years, (2) fracture duration ≤ 21 days, (3) unilateral fracture, (4) low-energy injury, and (5) ASA > grade III or Nottingham score ≥ 5. Exclusion criteria were: (1) patients lacked relevant clinical data, (2) old or pathological fractures, (3) high-energy injuries, (4) multiple traumas.

All data were collected through electronic medical records and telephone follow-up. Data collected through our electronic medical record system included age, gender, BMI, ASA classification, comorbidities, type of hip fracture, length of surgical wait, type of surgical procedure, type of anesthesia, intraoperative adverse events, length of hospital stay, preoperative creatinine, neutrophil/lymphocyte ratio (NLR), albumin, hemoglobin, C-reactive protein, NT- proBNP, perioperative AKI (KDIGO guidelines diagnostic criteria[7]), pulmonary infections and circulatory complications. Follow-up phone calls were made at 365 days postoperatively a team of study investigators.

Patients were divided into survival and death groups based on follow-up results. For continuous variables, data were expressed as mean ± standard deviation or median (interquartile range), and for categorical variables, data were expressed as numbers (percentages). We performed group comparisons using the independent-samples t-test or Mann-Whitney U test for quantitative variables and chi-squared test for categorical variables. Analyses for 1-year survival were performed using the Kaplan-Meier method. We performed univariate and multivariate analyses to identify independent risk factors for 1-year mortality. All variables with p < 0.05 in the univariate model were included in the multivariate model Cox regression models were used for all survival analyses to compare outcomes between study groups and to identify predictors of mortality. SPSS 24.0 software was used for all statistical analysis. All tests were two-sided, and P < 0.05 was considered a statistically significant difference.

A total of 641 elderly and critically ill patients with hip fractures were enrolled in the study from January 2018 to April 2021, and the final number of patients included in the study statistics was 591. 50 cases were excluded from the study as they did not meet the non-inclusion criteria (11 cases of old fractures, 1 case of multiple fractures, and 38 cases lost to follow-up). According to the follow-up results, there were 117 cases in the death group and 474 cases in the survival group, with a 1-year mortality rate of 19.8% (117/591). (as shown in Figure 1).

The difference in age between the two groups was statistically significant (P < 0.05); preoperative chronic heart failure, arrhythmia, chronic kidney disease and Nottingham scores were significantly higher in the death group than in the survival group (P < 0.05); in terms of laboratory tests, Scr, NLR and NT-BNP were significantly higher in the death group than in the survival group (P < 0.05), and the use of general anesthesia was higher in the death group (P < 0.05) ( See Table 1).

Table 1 Characteristics of hip fracture patients classified by survival status within 1 year
	ALL （n=591）	Death group (n=117)	Survival group (n=474)	P
Age(year)	86.0(80.0,91.0)	88.0(83.0,91.0)	85.0(80.0,90.0)	0.006
Gender(M/F)	188/403	149/325	39/78	0.693
ASA(II/III/IV)	81/391/119	16/72/29	65/319/90	0.361
BMI	22.3±4.1	21.5±3.9	22.5±4.1	0.013
Complications
Hypertension	350(59.2%)	64（54.7%)	286(60.3)	0.267
Diabetes	163(27.6%)	32（27.4%)	131(27.6%)	0.950
CHD	200(33.8%)	35（29.9%)	165(34.8%)	0.316
Arrhythmia^a	151(25.5%)	46(39.3%)	105(22.2%)	0.000
CHF	87(14.7%)	25(21.4%)	62(13.1%)	0.023
Pulmonary disease	173(29.3%)	45(38.5%)	128(27.0%)	0.015
CKD	162(27.4%)	42(35.9%)	120(25.3%)	0.022
Anemia	121(20.5%)	25(21.4%）	96(20.3%)	0.789
Alzheimer's	94(15.9%)	19(16.2%)	75(15.8%)	0.912
Time to surgery(≥ 2 d)	567(80.2%)	93(81.1%)	381(80.0%)	0.774
Type of fracture
Intertrochanteric	352(59.6%)	71(60.7%)	281(59.2%)	0.149
Femoral neck	224(37.9%)	46(39.3%)	178(37.6%)
Subtrochanteric	15(2.5%)	0(0%)	15(3.2%)
Type of anesthesia
General	47(8%)	3(2.6%)	44(9.3%)	0.016
Spinal	544(92%)	114(97.4%)	430(90.7%)	0.016
Laboratory examination
Hemoglobin	111.3±20.9	110.9±21.2	111.9±19.8	0.649
NT-proBNP	577.1(272.6,1544.0)	918.0(418.0,3183.5)	519.2(248.7,1292.3)	0.000
NLR	9.8±6.4	11.1±7.0	9.5±6.2	0.014
CRP	39.1±50.0	39.1±42.4	39.1±51.7	0.999
SCr	65.0(52.0,86.0)	71.0(56.5,102,5)	64.0(51.0,84.0)	0.024
Albumin	38.3±4.5	37.9±3.9	38.3±4.6	0.299
Nottingham score	5.5±0.9	5.6±1.0	5.4±0.9	0.026
a including atrial fibrillation, tachycardia, atrioventricular block and sick sinus node syndrome; ASA, American Society of Anesthesiologists; CHD, coronary heart disease; CHF, chronic heart failure; CKD, chronic kidney disease; NT-proBNP, NT-proB-type Natriuretic Peptide; NLR, neutrophil-lymphocyte ratio; CRP, C-reaction protein; SCr, serum creatinine.

The incidence of postoperative respiratory failure and acute cardiovascular events was higher in the death group than survival group (P < 0.05); more people required ventilator-assisted ventilation and mask ventilation in the death group than in the survival group(P < 0.05); and the duration of ICU stay was significantly longer in the death group than in the survival group (P < 0.05) (see Table 2).

Table 2 Postoperative complications and ICU interventions
	ALL （n=591）	Death group (n=117)	Survival group (n=474)	P
Complications
Pulmonary Infection	67(11.3%)	17(14.5%)	50(10.5%)	0.224
Respiratory failure	22(3.7%)	9(7.7%)	13(2.7%)	0.024
Acute cardiovascular events^b	77(13.0%)	25(21.4%)	52(11.%%)	0.003
AKI	24(4.1%)	8(6.8%)	16(3.4%)	0.113
Delirium	20(3.4%)	7(6.0%)	13(2.7%)	0.090
length of hospital (d)	5.0(4.0,7.0)	5.0(4.0,7.0)	5.0(4.0,7.0)	0.081
length of ICU (d)	1.0(1.0,2.0)	1.0(1.0,3.0)	1.0(1.0,2.0)	0.002
ICU interventions
Ventilator ventilation	7(1.2%)	4(3.4%)	3(0.6%)	0.031
Mask ventilation	18(3%)	8(6.8%)	10(2.1%)	0.014
Antihypertensive	100(16.9%)	23(19.7%)	77(16.2%)	0.378
Hypertensive	33(5.6%)	6(5.1%)	27(5.7%)	0.811
Anti-arrhythmias	63(10.7%)	18(15.4%)	45(9.5%)	0.064
b including acute coronary syndrome, acute exacerbation of chronic heart failure, malignant cardiac arrhythmia. AKI, acute renal insufficiency.

Kaplan-Meier survival curves are shown in Fig. 2. Figure 2A shows the lowest survival probability associated with age ≥86; Figure 2B, 2D, 2E , 2C shows a better survival associated without arrythmia, acute cardiovascular events, respiratory failure and low NLR level, respectively.

The Cox's regression analysis model showed that advanced age, preoperative comorbid arrhythmias, postoperative occurrence of respiratory failure, and acute cardiovascular events were risk factors for 1-year survival in elderly and critically ill patients with hip fracture (as shown in Table 3).

Table 3 Predictive factors for 1-year mortality among hip fracture patients: multivariate analysis
Variables	HR	95% CI	p
Age	1.04	1.01- 1.06	0.011
Preoperative arrhythmias	1.95	1.26 - 2.70	0.002
Preoperative NLR	1.03	1.01 - 1.06	0.004
Respiratory failure	2.63	1.32 – 5.23	0.006
Acute cardiovascular events	1.65	1.05 – 2.59	0.029

In this observational, single-center, retrospective cohort study, the 1-year mortality rate and loss to follow-up rate were 19.8% (117/591), and 6.0% (38/629), respectively. Using multivariate Cox proportional hazards regression analysis, we found that advanced age, preoperative arrhythmias, high level of NLR, respiratory failure and acute cardiovascular events postoperatively were independent risk factors for survival within the first postoperative year.

There is consensus that advanced age is an independent risk factor for postoperative survival in elderly hip fracture patients[8, 9]. Cui et al[10] reported the 1-year mortality of elderly hip fractures in China from 2000 to 2018, and they found that mortality increased simultaneously with age, with a 1-year mortality rate of more than 23.4% in hip fracture patients over 90 years of age. Elderly patients often have more comorbidities and decreased organ function that cannot effectively resist perioperative surgical and anesthetic stimuli. Therefore, effective elimination of adverse perioperative stimuli can improve postoperative survival in elderly patients [11].

The heart in elderly patients is often associated with pathological changes such as myocardial hypertrophy, fibrosis, inflammation and persistent stiffness[12], and the sinoatrial node and conduction system of the heart are often affected by pathological changes. Clinically, it may present as bradyarrhythmia, tachyarrhythmia or tachycardia-bradycardia syndrome. Several studies have reported that bradyarrhythmia, tachyarrhythmia or tachycardia-bradycardia syndrome are associated with higher postoperative mortality[13-15]. Adunsky et al [16]found a 1-fold increase in mortality in elderly hip fractures with atrial fibrillation compared with patients without atrial fibrillation for at least 365 days; Frenkel et al [17]investigated 701 elderly hip fractures patients who over 90 years， and showed that the median survival was 201 days in patients with atrial fibrillation and 377 day in patients without atrial fibrillation; Härstedt et al [18]found that pathological bradycardia was also an independent risk factor for mid- to long-term survival in elderly patients with hip fracture. Our multivariate Cox proportional hazards regression analysis found that preoperative combined with arrhythmias were also an independent risk factor for 1-year survival time in elderly and critically ill patients with hip fracture, and 1-year mortality was 1.95 times higher in hip fracture patients with arrhythmias than in patients without arrhythmias. Therefore, a comprehensive preoperative evaluation of patients with arrhythmias should be performed to reduce the impact of adverse factors such as perioperative pain, anemia, and volume overload. This will prevent aggravation or worsening of arrhythmias and reduce the incidence of acute postoperative cardiovascular events. Because our study also suggested that postoperative acute cardiovascular events were associated with a 1.65-fold increase in 1-year mortality (95CI: 1.05 – 2.59).

The occurrence of respiratory failure in the perioperative period is also an important risk factor affecting the prognosis of hip fractures in the elderly[19]. The causes of respiratory failure in elderly patients are mainly as follows: first, the elderly patients would have degenerative physiological changes in lung compliance, respiratory mucosa, cilia movement, lung volume and respiratory rate with aging[20]. With a progressive decline in systemic immunity, the respiratory tract was susceptible to lung infections from bacterial and viral invasion, which subsequently developed into respiratory failure in severe cases; Secondly, trauma, pain and other stimuli could result in a state of systemic stress, and lead to an increase in oxygen demand and respiratory muscle work, which might develop respiratory muscle weakness and respiratory failure[21]; Finally, respiratory failure could also occur in elderly patients with existing diseases under traumatic stimulation. Chen et al [22] found that elderly hip fracture patients preoperative combined with hypertension, obstructive lung disease, bronchiectasis, and a history of respiratory failure were significantly more likely to develop respiratory failure postoperatively. Wang et al [23] showed that the occurrence of postoperative respiratory failure was an independent risk factor for survival within 1 and 2 postoperative years after following up 144 intertrochanteric fracture patients. Our study also found that the occurred of respiratory failure in the perioperative period was also an important risk factor for survival in the 1-year postoperative period. Patients who developed respiratory failure had 1.95 fold (95CI: 1.26 - 2.70) mortality in 1 year than those who did not. Therefore, reducing the occurrence of perioperative respiratory failure was beneficial in reducing postoperative mortality.

The neutrophil-lymphocyte ratio (NLR) was a potential indicator of dysregulated immune homeostasis and systemic inflammatory response in the body [24].Vaughan-Shaw et al [25]found that NLR was a good predictor of 30-day mortality, six-month mortality, and 1-year mortality after emergency abdominal surgery in the elderly. Zhou et al [26] found that when the NLR ratio was more than 6.939, patients had significantly increased mortality within 1 year. The results of our study also suggest that high preoperative NLR increases postoperative mortality within 1 year. The level of NLR reflects the patient's systemic stress state, which increases the likelihood of perioperative pulmonary complications, acute cardiovascular events, and acute kidney injury at high intensity[27, 28]. Therefore, we need to pay more attention to prevent acute adverse events in patients with high perioperative NLR values.

Reviewing the entire study, we still have many limitations. First, although we performed postoperative follow-up, many family members kept the causes postoperative patient death confidential or could not describe them accurately, preventing us from conducting an in-depth summary in-depth summary and analysis of the causes of postoperative death; second, as a single-center retrospective study with a moderate sample size, it was not yet possible to adequately compare the effects of type of anesthesia and ICU interventions on postoperative survival time in elderly and critically ill patients with hip fracture.

The results of this study showed that advanced age, preoperative combined arrhythmias, high preoperative NLR levels, and postoperative acute cardiovascular events were independent risk factors for 1-year survival in elderly patients with critical hip fractures. Preoperative NLR high level and other tests can be used as important indicators to determine the prognosis of patients.

Data Availability Statement: The datasets generated for this study are available on request to the corresponding author.

Ethics Statement: The studies involving human participants were reviewed and approved by the Institutional Review Board of the Beijing Jishuitan Hospital.

Author Contributions: Each author has made an important scientific contribution to the study and is thoroughly familiar with the primary data. All authors listed have read the complete manuscript and have approved submission of the paper.

Consent for publication: Not applicable.

Funding: This study was supported by Capital’s Funds for Health Improvement and Research [2018-1-2071], and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201813].

Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments: The authors thank all the medical staff in the Department of Anesthesiology, Traumatic Orthopedics, and ICU in Beijing Jishuitan Hospital for their support to this clinical trial.

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No competing interests reported.

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Identification of risk factors for 1-year mortality among elderly and critically ill patients with hip fractures surgery: A single medical center retrospective study

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