Perioperative Hypoalbuminemia is a Risk Factor for Wound Complications Following Posterior Lumbar Interbody Fusion

DOI: https://doi.org/10.21203/rs.3.rs-26106/v1

Abstract

Background: Although serum albumin levels are increasingly used as an indicator of nutritional status in the clinic, the relationship between perioperative hypoalbuminemia and wound complications after posterior lumbar interbody fusion in the treatment of lumbar degenerative disease remains ambiguous. The aim of this study was to evaluate perioperative serum albumin in relation to postoperative wound complications after posterior lumbar interbody fusion in the treatment of single-segment lumbar degenerative disease.

Material and methods : We reviewed patients who underwent single-segment posterior lumbar interbody fusion surgery from December 2014 to April 2017 in the Department of Orthopedics at the First Affiliated Hospital of Chongqing Medical University. Perioperative (preoperative and early postoperative) serum albumin levels were assessed in all patients and were used to quantify nutritional status. We divided the patients into a surgical wound dehiscence ( SWD ) group and a normal wound healing group, and into an surgical site infection(SSI)group and a non-SSI group. To evaluate the relationship between perioperative serum albumin level and postoperative wound complications, we conducted univariate and multiple logistic regression analyses.

Results: A total of 554 patients were enrolled in the study.The univariate and multiple logistic regression analysis of these differences showed that preoperative serum albumin <3.5 g/dl and postoperative serum albumin:<3.0 g/dl were significantly related to SWD (P<0.05). There were also significant differences between the surgical site infection (SSI) groups in terms of preoperative serum albumin <3.5 g/dl(P=0.001), postoperative serum albumin <3.5 g/dl (P<0.023) and <3.0 g/dl(P<0.001).Additionally, the increased hospitalization costs and length of hospitalization were statistically significant for patients with perioperative hypoproteinemia.

Conclusions: For patients who underwent single-segment posterior lumbar interbody fusion surgery, we need to pay more attention to steroid use,perioperative hypoalbuminemia, which are more likely to be associated with increased wound complications, hospitalization costs and length of hospitalization after surgery. Adequate assessment and management of these risk factors will help reduce wound complications and hospital stays for surgical patients and will save medical costs.

Background

Nutritional status is a key factor in patient prognosis in various medical contexts[14]. An estimated 4.3% of community-dwelling adults suffer from malnutrition, and the prevalence of malnutrition among medical inpatients ranges from 20–45%[511].Malnutrition can be identified in various ways, including serological marker evaluation, anthropometric measurements, and nutrition scoring tools. Among the numerous methods to define malnutrition, the one most frequently used is the serum albumin level. Albumin less than 3.5 g/dL is recognized as hypoalbuminemia (malnourished)[1214].

The perioperative malnutrition of surgical patients is related to various postoperative adverse outcomes, including infection, acute kidney injury (AKI) and mortality. Wound complications are the most common problems for surgeons, and understanding the impact of perioperative malnutrition on postoperative wound complications and outcomes is of great significance.

Lumbar fusion is one of the most common spinal procedures. Although this is a relatively safe operation with a high success rate, there is still a risk of postoperative complications and a need for revision surgery. The common wound complications are wound infection, wound dehiscence, wound hematoma and wound hernia. The incidence of complications after spinal fusion ranges from 1–20%[1516].Wound complications increase patient suffering, hospital length of stay, readmission rate, medical expenses, and mortality and places a heavy burden on patients' families and social health systems. Although progress has been made in the effective prevention of infection through antimicrobials, strengthening wound area management, strengthening operating room and instrument disinfection control, strict suturing during surgery, postoperative drainage and other methods reduce the possibility of complications, though it is still difficult to avoid wound complications in some spinal patients after surgery.

In recent years, with the gradual increase in patients with lumbar degenerative diseases, we found that perioperative malnutrition also increased year by year. Perioperative malnutrition may be linked to age, poor eating, pain, long-term bed rest and other factors. Obese patients who are overweight may still be malnourished[1719].Despite the growing body of literature on the effects of hypoalbuminemia on postoperative outcomes in other surgical fields, few studies to date have investigated the relationship between perioperative hypoalbuminemia and postoperative wound complications in patients following degenerative lumbar spine surgery. The authors analyzed 554 patients from the First Affiliated Hospital of Chongqing Medical University who underwent posterior lumbar interbody fusion to explore whether the perioperative albumin level can be used as an indicator to evaluate postoperative wound complications.

Material And Methods

We retrospectively reviewed data that were collected for 787 consecutive patients with lumbar degenerative disease who underwent posterior lumbar interbody fusion (PLIF) between December 2014 and April 2017,all patients were followed up for at least 1 year.The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, Chongqing, China, and all patients provided informed consent concerning the use of their medical records.

The inclusion criteria for the patients were: 1) patients age 18 or above; 2) patients in good condition who can tolerate surgery; 3) only patients with a diagnosis of primary single-segment lumbar degenerative disease, lumbar disc herniation, lumbar spinal stenosis, or spondylolisthesis; 4) patients undergoing posterior lumbar interbody fusion (PLIF) surgery; and 5) patients with complete follow-up data.

The exclusion criteria for the patients were the following: 1) patients with multisegment lumbar degenerative disease, 2) patients with previous lumbar surgery, and 3) patients with incomplete laboratory data.

According to the above screening criteria, 554 patients were included in this study. There were 314 females and 240 males. The mean age of the patients was 58.5 years (range, 22–85), and at least 1 year of follow-up data were available for all patients. All operations were performed in standard vertical stratospheric operating rooms. We performed antibiotic prophylaxis 24 hours before and after the operation, and all patients were encouraged to wear braces after surgery. All operations were performed by the members of the same medical team (from the authors).

The preoperative baseline variables included albumin level, age, body mass index (BMI), sex, diabetes, tobacco use, and steroid use. Considering that early bed rest in patients with lumbar spondylolisthesis may lead to postoperative wound complications, we also included the preoperative diagnosis in the evaluation index.

We assessed two wound-related complications:SWD and SSI.For the purposes of research and statistics,SWD is defined as the rupturing or splitting apart of the margins of a wound closure[20].Wound dehiscence can be a superficial or deep tissue injury and according to the CDC[21]wound dehiscence can be associated with SSI,including patients with positive or negative drainage culture.Sixty-nine patients (12.5%) in our study were included in this group.

According to the Centers for Disease Control and Prevention criteria[21], superficial SSI was defined as:a) Purulent drainage from the superficial incision;b) Organism(s) identified from an aseptically-obtained specimen from the superficial incision or subcutaneous tissue by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment;c)the wound had at least one of the following signs of symptoms:localized pain or tenderness,localized swelling, erythema, or heat;d) Diagnosis of superficial incisional surgical site infection by the surgeon, attending doctor or other designee.

For deep SSI,the incision with at least one of the following:a)Purulent drainage from the deep incision;b) organism(s) identified from the deep soft tissues of the incision by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment, and when the patient has at least one of the following signs and symptoms: fever (> 38℃),localized pain or tenderness;c) An abscess or other evidence of infection involving the deep incision that is detected on gross anatomical or histopathologic exam, or imaging test.Patients meeting the above criteria were included in the SSI (n = 19; 3.4%) group in our study. During the hospital stay and follow-up, the surgeons remained vigilant for any signs of wound complications (drainage, atherosclerosis, skin necrosis, and dehiscence)in these patients. A surgical site infection occurring within 1 year after surgery was considered an infectious complication.

We attempted to explore the relationship between perioperative serum albumin levels and postoperative wound complications, so we included preoperative serum albumin and postoperative short-term albumin levels obtained within 7 days or surgery. Operative variables included operative time and intraoperative blood loss. Postoperative variables included postoperative drainage amount, length of hospital stay and hospitalization costs. Albumin less than 3.5 g/dL was recognized as hypoalbuminemia (malnourished); albumin less than 3.0 g/dL was recognized as malnourished to a level that required intravenous albumin supplementation[911].

Statistical Analysis

Statistical analyses were performed using SPSS 24.0 for Windows. Data are shown as the mean ± standard deviation (SD) and median (interquartile range, IQR). Logistic regression analysis was conducted to analyze the risk factors for SWD and SSI. Univariate logistic regression found factors with p < 0.05 that were added to multivariate logistic regression analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined when statistically significant differences (p < 0.05) were found. All p-values were two-sided.

Results

A total of 554 patients were included in this study. There were 237 men and 317 women (women outnumbered men in this study population), and the mean age was 56.9 years. The incidence of SWD after lumbar spine fusion was 12.45% (69/554), and the incidence of SSI was 3.43% (19/554), which is consistent with other related reports. Microorganisms were isolated from all 19 patients with SSI by open debridement, ultrasound-guided biopsy, superficial exudate, and drainage culture (Table 1.2). There were 13 (2.4%) patients with malnutrition before surgery (preoperative albumin < 3.5 g/dL), 314 (56.4%) patients with albumin < 3.5 g/dL within 7 days after surgery, and 114 (20.6%) patients with albumin < 3.0 g/dL within 7 days after surgery.

Table 1.2 summarizes the univariate analysis results for age, body mass index (BMI), sex, preoperative diagnosis of diabetes, smoking, chronic steroid use, preoperative serum albumin, diagnosis, operation time, bleeding volume, postoperative serum albumin, and postoperative drainage. As shown in Table 1, steroid use (P < 0.001), preoperative albumin level < 3.5 g/dl (P = 0.001), postoperative albumin level < 3.5 g/dl (P = 0.023), postoperative albumin level < 3.0 g/dl (P = 0.001) were significantly correlated with the incidence of SWD(P < 0.05). Although p value of postoperative drainage (P = 0.003) was less than 0.05, OR value was close to 1 infinitely, so there was no statistical significance.

Table 2 shows that age (P = 0.010), steroid use (P = 0.003), preoperative albumin level < 3.5 g/dl (P = 0.001), a spondylolisthesis diagnosis (P = 0.001), postoperative albumin level < 3.5 g/dl (P < 0.001),postoperative albumin level < 3.0 g/dl (P < 0.001), length of stay (P < 0.001), and hospitalization expenses (P < 0.001) were significantly correlated with the incidence of SSI (P < 0.05).

The results above were included in the multivariate logistic regression, and there were statistically significant findings for preoperative hypoalbuminemia (p = 0.024, OR = 4.16 95% CI 1.203–14.44) and postoperative hypoalbuminemia (p < 0.001 OR = 5.22 95% CI 2.84–9.58) (Table 3, Fig. 1) indicating that both were risk factors for SWD.Multivariate logistic regression also found that preoperative hypoproteinemia (p = 0.040 OR = 5.69 95% CI 1.08–29.88) and steroid use (p < 0.001 OR = 20.20 95% CI 4.43–92.16)were statistically significant (Table 4, Fig. 2) risk factors for SSI.

The average hospital stay length was 11 (9–14) days overall; it was 17 (13-22.5) days in the SWD group, and 11 (9–13) days in the normal wound healing group. The difference between the two groups was statistically significant (P < 0.001). The hospital length of stay in the SSI group was 22 (14–32) days, and in the non-SSI group, was 11 (9–14) days; the difference between the two groups was statistically significant (P < 0.001);The average patient expenditure during hospitalization was 25.6 (± 8.7) thousand RMB overall; it was 35.0 (± 17.5) thousand RMB in the SWD group, and it was 24.2 (± 5.5) thousand RMB in the normal wound healing group (P<0.001); the average patient expenditure during hospitalization in the SSI group was 43.9 (± 21.3) thousand RMB, and in the non-SSI group, it was 24.9 (± 7.2) thousand RMB (P < 0.001).

TABLE 1. Patients’ demographic characteristics

Variable

Total(N=554)

Poor wound healing (n =69)

Normal wound healing (n =485)

P value

Preoperative baseline variables

Age at surgery, mean (SD)

56.9(13.4)

60.8(14.2)

56.4(13.2)

0.950

BMI, mean (SD)

24.1(3.1)

24.2(3.8)

24.1(3.0)

0.731

Male

237(43)

30(43.5)

207(42.7)

0.076

Diabetes

60(10.8)

9(13.0)

51(10.5)

0.965

Smoker

144(26.0)

22(31.9)

120(25.2)

0.573

Steroid use

11(1.99)

5(7.25)

6(1.24)

<0.001

Albumin level<3.5g/dl

13(2.35)

6(8.70)

7(1.44)

0.001

Diagnose

Herniation

270(48.7)

33(47.8)

237(48.9)

-

Stenosis

86(15.5)

12(17.4)

74(15.3)

0.053

Spondylolisthesis

198(35.7)

24(34.8)

174(35.8)

0.397

Operative variables

Operative time, mean (SD), min

160.8(43.9)

154.4(48.5)

161.8(43.2)

0.593

Bleeding volume, mean (SD) mL

318.5(90.8)

284.1(30.4)

311.4(89.6)

0.662

Postoperative variables

Albumin level<3.5g/dl

314(56.7)

56(81.2)

258(53.2)

0.023

Albumin level<3.0g/dl

110(19.9)

36(52.2)

74(15.3)

0.001

Postoperative drainage median,ml, (IQR)

223.5(151.0-309.0)

205.0(120.0-300.0)

231.0(154.5-310.5)

0.003

Length of stay, day, median (SD)

11.0(9.0-14.0)

17.0(13.0-22.5)

11.0(9.0-13.0)

<0.001

Hospitalization expenses mean (SD)

25.6(8.7)

35.0(17.5)

24.2(5.5)

<0.001

*Statistically significant (P 0.05).

BMI indicates body mass index; SD, standard deviation.

  

 

 

TABLE 2. Patients’ demographic characteristics

Variable

Total(N=554)

SSI (n =19)

No-SSI (n =535)

P value

Preoperative baseline variables

Age at surgery, mean (SD)

56.9(13.4)

56.7(16.0)

56.9(13.3)

0.010

BMI, mean (SD)

24.1(3.1)

23.9(3.9)

24.1(3.1)

0.750

Male

237(43)

12(63.2)

225(42.1)

0.900

Diabetes

60(10.8)

2(10.5)

58(10.8)

0.300

Smoker

144(26.0)

6(31.6)

138(25.8)

0.235

Steroid use

11(1.99)

5(26.3)

6(1.1)

0.003

Albumin level<3.5g/dl

13(2.35)

3(15.8)

10(1.9)

0.001

Diagnose

Herniation

270(48.7)

6(31.6)

264(49.3)

-

Stenosis

86(15.5)

6(31.6)

80(15.0)

0.180

Spondylolisthesis

198(35.7)

7(36.8)

191(35.7)

0.001

Operative variables

Operative time, mean (SD), min

160.8(43.9)

155.5(48.2)

161.0(43.8)

0.178

Bleeding volume, mean (SD) mL

318.5(90.8)

321.1(105.7)

311.9(89.2)

0.537

Postoperative variables

Albumin level<3.5g/dl

314(56.7)

16(84.2)

298 (55.7)

<0.001

Albumin level<3.0g/dl

110(19.9)

10(52.6)

100(18.7)

<0.001

Postoperative drainage median,ml,(IQR)

223.5(151.0-309.0)

148(93.0-188.0)

231(154.0-312.0)

0.116

Length of stay, day, median (SD)

11.0(9.0-14.0)

22.0(14.0-32.0)

11.0(9.0-14.0)

<0.001

Hospitalization expenses mean (SD)

25.6(8.7)

43.9(21.3)

24.9(7.2)

<0.001

*Statistically significant (P 0.05).

BMI indicates body mass index; SD, standard deviation.

  

 

TABLE 3. Multivariate logistic regression analysis(PWH)

Variable

B

SD

OR

95% CI

P value

Albumin level<3.5g/dl(pre)

1.427

0.634

4.168

1.203-14.442

0.024

Albumin level<3.5g/dl(post)

0.540

0.364

1.716

0.841-3.503

0.138

Albumin level<3.0g/dl(post)

1.652

0.310

5.219

2.843-9.580

<0.001

Age

0.016

0.011

1.017

0.995-1.039

0.133

Steroid use

1.378

0.722

3.967

0.965-16.317

0.056

 

 

TABLE 4. Multivariate logistic regression analysis(SSI)

Variable

B

SD

OR

95% CI

P value

Albumin level<3.5g/dl(pre)

1.738

0.846

5.687

1.082-29.880

0.040

Albumin level<3.5g/dl(post)

0.886

0.717

2.425

0.595-9.889

0.217

Albumin level<3.0g/dl(post)

0.695

0.576

2.003

0.647-6.196

0.228

Drainage

-0.008

0.003

0.993

0.986-0.999

0.023

Steroid use

3.006

0.774

20.203

4.429-92.155

<0.001

 

Discussion

Understanding perioperative malnutrition is important for postoperative complications and outcomes. In fact, postoperative complications of the lumbar spine can lead to devastating sequelae. Although there may be a direct link between perioperative malnutrition and postoperative wound complications, there is no consensus[2227].Serum albumin is one of the biochemical indicators of total protein depletion in patients. Our study further confirmed that preoperative hypoproteinemia and postoperative hypoproteinemia are important risk factors for wound complications following single-segment PLIF surgery.

Based on previous reports of wound complications of posterior lumbar surgery, we performed a univariate logistic analysis to investigate the impact of related risk factors. With the subsequent multivariate logistic analysis, we were able to identify 2 independent factors of SWD (preoperative serum albumin < 3.5 g/dl, postoperative serum albumin < 3.0 g/dl) and 2 independent factors of SSI (preoperative serum albumin < 3.5 g/dl, steroid use).

Previous studies have reported that various markers of preoperative malnutrition are associated with surgical site infection following various types of surgery[28].Cross MB et al pointed out that superficial and deep SSI after orthopedic spinal surgery was associated with several markers of malnutrition, such as serological laboratory values, DM, hyperglycemia and obesity[29].Bohl DD et al investigated the relationship between preoperative hypoalbuminemia (a sign of malnutrition) and complications within 30 days after total joint replacement. Compared with patients with normal albumin concentrations, patients with hypoalbuminemia had a higher risk of surgical site infection, pneumonia, prolonged hospital stay, and readmission[30].Similarly, they retrospectively reviewed data prospectively collected by the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) to investigate the relationship between preoperative hypoproteinemia (a sign of malnutrition) and complications after 30 days of posterior lumbar fusion. They pointed out that malnutrition was an independent risk factor for infection and wound complications after posterior lumbar fusion, and it was also associated with increased length of stay and readmission[31].

Our data showed that preoperative low serum albumin (< 3.5 g/dL) was significantly associated with an increased risk of postoperative SWD(P = 0.024) and SSI (P = 0.040). We combined the results of these data with previous literature and concluded that, although serum albumin concentration is used to measure nutritional status, hypoalbuminemia may be more closely related to pathological inflammatory status.

In addition, early postoperative hypoproteinemia has also been reported as a risk factor for serious postoperative complications[3235].Lee JI et al investigated 337 patients with major oropharyngeal squamous cell carcinoma (OSCC) who underwent clean and contaminated surgery and monitored serum albumin, glucose, and hemoglobin levels during the perioperative period. The results showed that early postoperative hypoproteinemia < 2.5 g/dl was an independent risk factor for SSI in patients who underwent oral cancer surgery[36].Bohl DD et al. also reported that malnutrition increased the risk of periprosthetic joint infection (PJI) following total joint arthroplasty (TJA)[37].

We also found that low postoperative serum albumin (< 3.0 g/dL) was significantly associated with an increased risk of postoperative SWD(P < 0.001). However, low postoperative albumin is affected by many factors. Ge X et al noted that the stress response, perioperative fluid overload, hemodilution, albumin redistribution, a breakdown of metabolism and other comprehensive factors cause postoperative albumin decline[38].Despite this, we still need to be wary of hypoalbuminemia with albumin levels < 3.0 g/dl after surgery.

Chronic steroid users (steroid usage for more than 10 days preoperatively) have reportedly increased their risk of infection by two- to three-fold after surgery. Singla A et al reported chronic steroid usage to be a significant risk factor for SSI in their database analysis of 360,005 patients over 65 years of age[39].Similarly, chronic steroid usage was reported to be associated with a higher risk of SSI (OR 20.20, 95% CI 4.43–92.16, P < 0.001).

In our univariate logistic analysis, we found that poor drainage after surgery can lead to SWD (P = 0.003). This may be related to the poor placement of the drainage tube and blockage of the drainage tube. Irregular drainage after surgery is prone to deep congestion and hematoma,SWD and increased risk of infection.However, the OR value is infinitely close to 1,which may be related to the small sample size of SSI group,expanding the sample size is helpful for further research.We also analyzed the increased risk of SSI in those diagnosed with lumbar spondylolisthesis (P = 0.001), which might be related to short-term bed rest after surgery. The elderly patients also needed to be alert to SSI after the operation (P = 0.010). However, this should be further evaluated in future prospective experiments with increased sample sizes.

When malnutrition is detected, timely nutritional supplementation is beneficial to patients' postoperative recovery. Oral nutritional supplements have been shown to be effective in improving nutrient intake, and they can also be given intravenously. Avenell A et al proved that oral non-protein energy, protein, vitamin and mineral supplements can prevent complications after hip fracture in the elderly[40].

The strengths of this study include the use of the same surgical procedure (PLIF) for lumbar fusion and internal fixation. Only single-segment fusion patients were included to reduce the impact of surgical procedures on the results of the study. In future research, it will be important to further explore, elucidate, and establish potential links between malnutrition and adverse incision outcomes after spinal fusion surgery.

The study was limited by the inherent problems of retrospective studies. First, as a retrospective, single institution study, all data on patient characteristics, laboratory test results, medical interventions directly related to abnormal laboratory values, and patient clinical symptoms were dependent on the inherent limitations of the files in the electronic medical record system. Second, the sample size of patients with preoperative hypoalbuminemia (13 cases) was relatively small, and a larger sample size may have been helpful for the statistical analysis. Although the serum albumin value is a valuable tool for assessing nutritional status, it is affected by many perioperative factors, so it cannot be a comprehensive assessment of the nutritional status of patients.

Conclusions

The current study showed that lower preoperative (< 3.5 g/dl) and postoperative (< 3.0 g/dl) serum albumin values were associated with SWD, and lower preoperative (< 3.5 g/dl) serum albumin levels and chronic steroid use were associated with SSI after posterior lumbar interbody fusion in the treatment of single-segment lumbar degenerative disease. More attention should be paid to the nutritional status of patients to ensure they are supplemented in a timely manner and to reduce hospitalization time and costs.

Abbreviations

SSI:Surgical Site Infection;SWD:surgical wound dehiscence;AKI: Acute kidney injury;PLIF:Posterior lumbar interbody fusion;BMI:body mass index; ACS-NSQIP: American College of Surgeons National Surgical Quality Improvement Program; SD:standard deviation;IQR:Postoperative drainage median;OSCC:oropharyngeal squamous cell carcinoma;PJI:periprosthetic joint infection;TJA:following total joint arthroplasty;

Declarations

Acknowledgements

Not applicable.

Authors’ contributions

ZYH and BS contributed to the study design of this retrospective study.ZXQ, KT, BS,WYZ and ZYH performed the surgery.KZ and ZYH collected the data.KZ and ZYH analyzed the data. ZYH wrote the manuscript. All authors read and approved the final manuscript.

Funding: There is no funding source.

Availability of data and materials

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

Ethics approval and consent to participate

This study is a retrospective clinical study and has been approved by The First Hospital of Chongqing Medical University Ethics Committee.All patients had signed the consent form.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Author details

1 Department of Orthopedics,The Seventh Affiliated Hospital,Sun Yat-sen University, Guangming District, Shenzhen,518000 China

2 Department of Orthopedics,the First Affiliated Hospital of Chongqing Medical University,Yuanjiagang, Yuzhong District, Chongqing, China

Zhongyuan He and Kai Zhou are co-first authors.

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