Perioperative albumin drop is a marker for surgical stress and correlate with clinical outcomes in the elderly patients undergoing hip arthroplasty for femoral neck fractures

doi:10.21203/rs.3.rs-4040399/v1

Background

This single-center retrospective study investigated the correlation between the drop of perioperative albumin and clinical outcomes in the elderly patients undergoing hip arthroplasty for femoral neck fractures (FNF).

Methods

We investigated 278 patients 65 years of age or older who had undergone hip arthroplasty with FNF between January 2021 and March 2023. Albumin, C-reactive protein (CRP) and hemoglobin were monitored on preoperation, postoperative day-0, day-1 and day-7. The decrease of perioperative albumin (ΔAlb) was calculated by subtracting the value on day-0 from preoperation. Then patients were divided into two groups based on the ΔAlb values, with ΔAlb < 0.5 g/dL and ΔAlb ≥ 0.5 g/dL in group 1 and group 2, respectively.

Results

The albumin declined 0.8 g/dL from preoperation to day-1 and slowly increased by 0.3 g/dL from day-1 to day-7. The patients in group 2 had longer duration of surgery (75 minutes vs 65 minutes, P = 0.028), more intraoperative blood loss (246.7 ± 78.4 mL vs 201.5 ± 59.8 mL, P = 0.031) and changes of CRP (75.2 ± 48.1 mg/L vs 54.9 ± 44.9 mg/L, P = 0.003) comparing with the patients in group 1. Patients in group 2 had higher prevalences of postoperative complications (hypoalbuminemia: 94% vs 15%, moderate-severe anaemia: 60% vs 40%, P < 0.05) and longer postoperative length of stay (14 days vs 13 days, P = 0.045). The ΔAlb value was correlated with the duration of surgery (r= 0.3, P < 0.001), intraoperative blood loss (r = 0.2, P< 0.001), ΔCRP (r = 0.4, P < 0.001) and postoperative LOS (r= 0.2, P = 0.003).

Conclusions

The levels of albumin decreased significantly after surgery, while the CRP increased. Further, the perioperative albumin drop was a marker for surgical stress and correlated with adverse clinical outcomes.

Femoral neck fractures

Elderly patients

Hip arthroplasty

Length of stay

Perioper-ative monitoring

Femoral neck fractures (FNF) are a subset of hip fracture commonly encountered in orthopedic practice with significant morbidity and mortality [1]. Currently, this type of fracture is typically managed by arthroplasty (hemiarthroplasty or total hip arthroplasty), which avoids the risk of nonunion or femoral head necrosis, comparing to the reduction with internal fixation or conservative treatment [2].

With the promotion of the concept of enhanced recovery after surgery, more and more attention is paid to perioperative care aiming at modulating the surgical stress response [3]. A convenient and reliable biomarker representing surgical stress would be clinically important. C-reactive protein (CRP) is a widely used marker to assess postoperative inflammation [4]. Albumin, a widely used nutritional biomarker [5], is a negative acute phase protein that declines precipitously in surgical stress [6]. There has been growing interest in the use of albumin as an indicator of inflammatory activity [7]. However, the changes of these biomarkers during perioperative period of hip arthroplasty have not been fully clarified in the elderly with FNF.

Currently, a few studies used the drop of perioperative albumin level as a marker to explore its correlation with surgical stress and clinical outcomes in abdominal surgery [6, 8]. Previous studies have shown that hypoalbuminemia is associated with the worse outcomes in total hip and knee arthroplasty [9-11]. No study to date has assessed the correlation between the drop of perioperative albumin level and clinical outcomes in geriatric patients who had hip fractures. Therefore, the aim of this study was to analyze the changes of these biomarkers during the perioperative period, then figure out whether the drop of perioperative albumin level was correlated with surgical stress and clinical outcomes in geriatric patients undergoing hip arthroplasty for FNF.

Patients with inclusion and exclusion criteria

Patients aged 65 years and older who had undergone hemiarthroplasty or total hip arthroplasty for femoral neck fractures between January 2021 and March 2023 at our hospital were included. Patients who had any of the following situations were excluded:

Accompanied with other fractures.
Underwent orthopedic surgery previously.
Old femoral neck fracture or bilateral femoral neck fractures.
Concomitant cardiac, pulmonary or renal failure.
Conservative treatment or treated by internal fixation.

According to strict inclusion and exclusion, a total of 278 patients aged 65 years and older who underwent hip arthroplasty due to femoral neck fractures were included in this study (Figure 1).

Data collection and definition

The characteristics and other clinical data of patients, including age, sex, diagnosis, comorbidity, type of surgery, type of anesthesia, duration of surgery, the admission date and the discharge date, were obtained through the electronic case system of hospital. The intraoperative blood loss and transfusion of patients were carefully recorded from the systems of anesthesia and blood transfusion. The characteristics of patients in this study are summarized in Table 1.

Table 1 Demographic characteristics of the study population

Characteristics	Value
Patients (n = 278)
Age, median (range), years	81 (65-104)
Women, n (%)	203 (73)
Comorbidity, n (%)
Hypertension	155 (56)
Coronary heart disease	161 (58)
Type 2 diabetes	80 (29)
Old cerebral infarction	89 (32)
Osteoporosis	78 (28)
Type of surgery, n (%)
Hemiarthroplasty	174 (63)
Total hip arthroplasty	104 (37)
Type of anesthesia, n (%)
General anesthesia	12 (4)
Spinal anesthesia	12 (4)
Combined spinal-epidural anesthesia	166 (60)
Other anesthesia	88 (32)
Duration of surgery*, minutes	70 (60-90)
Intraoperative blood loss*, mL	200 (150-300)
Transfusion, n (%)	116 (42)
LOS*, days	18 (15-21)
Preoperative LOS*, days	5 (3-6)
Postoperative LOS*, days	14 (11-15)

*: median (inter-quartile range) ; LOS: length of stay.

The blood samples were tested preoperatively, on postoperative day-0, day-1 and day-7. No corresponding nutritional intervention had been implemented, such as albumin infusion. The decrease of perioperative albumin (ΔAlb) was calculated by subtracting the value on day-0 from the value during preoperation. Then patients were divided into two groups based on the ΔAlb values, with ΔAlb < 0.5 g/dL and ΔAlb ≥ 0.5 g/dL in group 1 and group 2, respectively. The changes of CRP were calculated by subtracting the value during preoperation from the value on day-1, as the changes on day-1 were more significant than day-0.

Hypoalbuminemia was defined as the value of serum albumin below 3.5 g/dL [11]. Anemia was defined as a blood hemoglobin level below 130 g/L for men and 120 g/L for women, sub-classified as mild ( hemoglobin ≥ 110 g/L), moderate (80-110 g/L), and severe (< 80 g/L) [12]. Length of stay (LOS) was counted from the day of admission to discharge, then, according to the date of surgery, it was divided into preoperative LOS and postoperative LOS.

Statistical analysis

Frequency and proportion were used for categorical variables, mean and standard deviation/median and inter-quartile range (IQR) or range were used for continuous variables. A repeated measures General Estimation Equation (GEE) model was employed to assess the overall trend in perioperative biomarkers over time. Pairwise comparisons of means between days were assessed and significance was adjusted using a Bonferroni correction for multiple testing by applying a lower critical value of 0.01 for pairwise P value. The comparison between groups used Chi-square for categorical variables and the Mann-Whitney U test or Kruskal-Wallis test for continuous variables because the distribution was non-normal. Partial correlation analysis was used to test the correlation between ΔAlb and surgical stress parameters and postoperative LOS. In the partial correlation analysis, we took age, preoperative albumin and preoperative LOS as the control variables, the other surgical stress parameters were also adjusted when analyzing one of these parameters.

A P value of < 0.05 was considered significant for all except for pairwise comparisons, which were adjusted for multiple comparisons using a lower critical value of 0.01 for P value. All analyses were produced using SPSS Statistics (Version 27.0, IBM Corp).

Changes in biomarkers during perioperation

The results from the GEE model revealed that the values of CRP increased from preoperation to day-1 (overall increase: 69.2 mg/L) and decreased to 36.7 mg/L on day-7 (Table 2, Figure 2A). The serum albumin declined from preoperation to day-1 (overall drop: 0.8 g/dL), with a slow increase of 0.3 g/dL from day-1 to day-7 (Table 2, Figure 2B). Specifically, the value of albumin dropped precipitously after surgery on day-0 (Figure 2B).

Table2 Predicted CRP and albumin values from the GEE model over time

Times	CRP (mg/L)			P-value	Albumin (g/dL)			P-value
Times	n	Mean ± SD	changes*	P-value	n	Mean ± SD	changes*	P-value
Preoperation	273	32.9 ± 1.6	-	-	278	3.8 ± 0.0	-	-
Day-0	253	37.8 ± 2.4	5.0	0.035	278	3.1 ± 0.0	-0.7	0.000
Day-1	260	102.1 ± 3.4	64.2	0.000	128	3.0 ± 0.0	-0.1	0.006
Day-7	252	36.7 ± 1.9	-65.4	0.000	278	3.3 ± 0.0	0.3	0.000

CRP: C-reactive protein; SD: standard deviation; *: Compared to the previous point of time.

Comparison of related parameters between two groups based on ΔAlb

There were 47 patients (ΔAlb < 0.5 g/dL) in group 1 and 231 patients (ΔAlb ≥ 0.5 g/dL) in group 2 (Table 3). The median age in group 1 was 77 years, while patients in group 2 were older, with a median age of 82 years (P = 0.007). The median preoperative LOS was 4 days in group 1 and 5 days in group 2 (P = 0.002). Patients in group 2 had a higher prevalence of hypertension (59% vs 38%) and coronary heart disease (62% vs 40%) than those in group 1. Further, there were no significant differences in surgical stress parameters and clinical outcomes between the hypertension group and the non-hypertensive group (Supplementary Table 1), as well as the coronary heart disease group and the non-coronary heart disease group (Supplementary Table 2).

Table 3 Compared characteristics between Group 1 and Group 2

Characteristics	Group 1 (n = 47)	Group 2 (n = 231)	P-value
Age, median (range), years	77 (71-84)	82 (74-86)	0.007
Women, n (%)	37 (79)	166 (72)	0.334
Comorbidity, n (%)
Hypertension	18 (38)	137 (59)	0.008
Coronary heart disease	19 (40)	142 (62)	0.008
Type 2 diabetes	10 (21)	70 (30)	0.213
Old cerebral infarction	12 (26)	77 (33)	0.296
Osteoporosis	12 (26)	66 (29)	0.672
Preoperative laboratories, (Mean ± SD)
CRP, (mg/L)	34.7 ± 33.6	38.9 ± 39.6	0.447
Hemoglobin, (g/L)	121.3 ± 19.4	119.3 ± 15.9	0.378
Hemiarthroplasty, n (%)	24 (51)	150 (65)	0.073
Combined spinal-epidural anesthesia, n (%)	31 (66)	135 (58)	0.594
Transfusion, n (%)	19 (40)	97 (42)	0.843
Preoperative hypoalbuminemia	4 (9)	36 (16)	0.208
Preoperative LOS, median (IQR), days	4 (3-5)	5 (3-7)	0.002

SD: standard deviation; CRP: C-reactive protein; TLC: total lymphocyte count.

The differences in surgical stress parameters between the two groups are shown in Table 4. The preoperative albumin was 4.0 ± 0.3 g/dL in group 1 and 3.8 ± 0.4 g/dL in group 2 (P < 0.001). After surgery, the albumin in group 2 was significantly lower than that in group 1 (3.0 ± 0.3 g/dL vs 3.7 ± 0.2 g/dL, P < 0.001). The median duration of surgery in group 2 was longer than that in group 1 (75 minutes vs 65 minutes, P = 0.028). The intraoperative blood loss in group 2 was more than that in group 1 (246.7 ± 78.4 mL vs 201.5 ± 59.8 mL, P = 0.031). The ΔCRP in group 2 was 75.2 ± 48.1 mg/L, more than that in group 1, which was 54.9 ± 44.9 mg/L (P = 0.003).

Table 4 Compared surgical stress parameters and clinical outcomes between Group 1 and Group 2

Characteristics	Group 1 (n = 47)	Group 2 (n = 231)	P-value
Preoperative Albumin, (g/dL)	4.0 ± 0.3	3.8 ± 0.4	< 0.001
Albumin on Day-0, g/dL	3.7 ± 0.2	3.0 ± 0.3	< 0.001
Duration of surgery, median (IQR), minutes	65 (60-84)	75 (60-90)	0.028
Intraoperative blood loss, (Mean ± SD), mL	201.5 ± 59.8	246.7 ± 78.4	0.031
ΔCRP, (mg/L)	54.9 ± 44.9	75.2 ± 48.1	0.003
Postoperative hypoalbuminemia	7 (15)	216 (94)	< 0.001
Postoperative moderate-severe anaemia	19 (40)	139 (60)	0.013
Postoperative LOS, median (IQR), days	13 (10-14)	14 (11-15)	0.045

IQR: inter-quartile range; SD: standard deviation; CRP: C-reactive protein; LOS: length of stay.

The differences in clinical outcomes between the two groups are also shown in Table 4. The prevalences of hypoalbuminemia and moderate-severe anaemia in group 2 were higher than that in group 1 (94% vs 15%, 60% vs 40%, P < 0.05). The postoperative LOS in group 2 was longer than that in group 1 (14 days vs 13 days, P = 0.045).

ΔAlb was correlated with surgical stress parameters and postoperative LOS

The results revealed that ΔAlb was correlated with the duration of surgery (r = 0.3, P < 0.001), intraoperative blood loss (r = 0.2, P < 0.001), ΔCRP (r = 0.4, P < 0.001) and postoperative LOS (r = 0.2, P = 0.003), adjusted for control variables (Table 5).

Table 5 The correlation between ΔAlb and surgical stress and clinical outcomes with several control variables

Parameters	n	correlation	P-value
Duration of surgery, median (IQR), minutes	278	0.3	< 0.001
Intraoperative blood loss, median (IQR), mL	278	0.2	0.005
ΔCRP, mg/L	258	0.4	< 0.001
Postoperative LOS, median (IQR), days	278	0.2	0.003

IQR: inter-quartile range; CRP: C-reactive protein; LOS: length of stay.

The present study showed that the levels of albumin in patients significantly decreased after surgery, meanwhile, the CRP increased until day-1. Our study evaluated the drop of perioperative albumin as a marker for surgical stress and a predictor for adverse postoperative outcomes in the elderly patients undergoing hip arthroplasty for FNF. The findings of this study suggest that the drop of perioperative albumin reliably quantifies the magnitude of surgery stress and may be used as a biomarker for clinical outcomes.

The albumin was used as a nutritional screening tool in many studies, and these literature is mainly limited to describe the hypoalbuminemia [13, 14]. The dynamic change of albumin during the perioperative period have not been elucidated. In the present study, combined with the changes of CRP, it was highly likely that inflammatory activity was manifest [7]. In the setting of inflammatory conditions, the effectiveness of albumin for the diagnosis of malnutrition is relatively poor [15]. Hübner M et al. indicated that postoperative albumin drop was a marker for surgical stress [8]. CRP is a protein of the acute systemic inflammation and is, therefore, a prime marker of inflammation [16]. In the present study, the ΔAlb was correlated with ΔCRP and the results from the GEE model showed that the changes of albumin were more rapid than those of CRP after surgery. Also, ΔAlb was correlated with duration of surgery and intraoperative blood loss. The patients in group 2 had longer duration of surgery, more intraoperative blood loss and changes of CRP. These results indicated that the drop of albumin was a marker of surgery stress.

The ΔAlb was correlated with postoperative LOS. Of note, lower preoperative albumin was found in patients who had ΔAlb ≥ 0.5g/dL, which was different from the research of Rahman RA et al. in children [6]. A previous study estimated that 77% of the postoperative albumin decrease was due to redistribution, while 18% and 6% were attributed to blood loss and catabolism, respectively [17]. The albumin decreased amount in group 1 is less than the one in group 2, which might indicate that in group 1, perioperative nutrition reduced albumin loss by decreasing the loss in the extravascular space [18]. This result also suggested that early identification of patients at risk was important, as preoperative carbohydrates could be considered in patients undergoing surgery to reduce stress [19]. Meanwhile, the patients in group 2 (ΔAlb ≥ 0.5 g/dL) had longer preoperative LOS. Delayed surgery was associated with adverse outcomes in patients undergoing hip arthroplasty for hip fractures [20]. Therefore, we took the preoperative LOS as a control variable in the partial correlation when the other parameter was analysed. In addition, the prevalences of postoperative hypoalbuminemia and moderate-severe anaemia were higher in patients who had ΔAlb ≥ 0.5 g/dL. Several studies had indicated that hypoalbuminemia was associated with increased short-term mortality and complications 13[14, 21]. Perioperative anemia was associated with significant adverse clinical outcomes, such as decreased physical function [22], increased transfusions [23], complications and mortality [24, 25]. These results indicated that the drop of albumin was a predictor for adverse postoperative outcomes in the elderly patients with FNF undergoing hip arthroplasty.

Besides the important findings mentioned above, there are some limitations in our study. Although preoperative LOS was used as a control variable in partial correlation analysis, measured preoperative indicators on the day of surgery were more accurately. In addition, the limitation lies in its retrospective nature and the level of evidence is low. Unfortunately, the database only included in-hospital information, so the long-term outcomes are not examined.

The levels of albumin in elderly patients undergoing hip arthroplasty for femoral neck fractures decreased significantly after surgery, meanwhile, the CRP increased. The drop of perioperative albumin was a marker of surgery stress and correlated with worse clinical outcomes. Our findings could be of clinical importance, since nutritional and pharmacological interventions can be implemented to reduce perioperative stress response. We will conduct a randomized controlled study to confirm this hypothesis in aged patients who had hip fractures in the near future.

CRP: C-reactive protein; FNF: Femoral neck fractures; GEE: General Estimation Equation; IQR: Inter-quartile range; LOS: Length of stay.

Acknowledgments

We are grateful to our colleagues and friends for their help in terms of surgical details and statistical analysis.

Author contributions

YQW is the principal investigator, as she conceived the study and provided critical input for the manuscript. WWL contributed to the data collection, the critical analysis of findings and the writing of the first draft of the manuscript. BL contributed to the data collection and the editing of this manuscript. XW designed the study and made key revisions to the manuscript. All authors have contributed significantly, and all authors agree with the content of the manuscript.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

This study was conducted according to the guidelines in the 2013 Helsinki declaration, and all procedures involving study participants were approved by the hospital’s Institutional Review Board (2022-011). Because the study was retrospective, patient consent was waived and all data was anonymized prior to analysis.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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No competing interests reported.

SupplementaryTables.docx

Perioperative albumin drop is a marker for surgical stress and correlate with clinical outcomes in the elderly patients undergoing hip arthroplasty for femoral neck fractures

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Abstract

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Introduction

Materials and methods

Results

Discussion

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