Increased 30-Day Readmission Rates in Total Knee Arthroplasty Patients Using Hypoallergenic Implants

Abstract

Introduction:

Metal hypersensitivity has emerged as a notable concern in the context of total knee arthroplasty (TKA), leading to the development of hypoallergenic implants. Current studies assessing hypoallergenic TKA implants suggest a decrease in quality of life and patient-reported outcome measures when compared with TKA with standard implants. This study seeks to compare clinical outcomes, including readmission and medical complications between patients undergoing TKA with hypoallergenic versus standard implants.

Methods:

A retrospective review of our institution's prospective Mayo Clinic Joint Replacement Database was conducted to identify all patients aged 18 years and older who underwent unilateral TKA between January 2019 and August 2022 using either hypoallergenic or standard implants. Cohorts were compared based on factors, such as age, heart disease, diabetes, alcohol use, smoking history, BMI, allergies, and ASA classification. Clinical outcomes included 30-day readmission, ED visits within 30 days, and medical complications. Statistical analysis was done using multiple logistic regression, chi-square, and paired t-tests.

Results:

6954 TKAs (6626 standard and 320 hypoallergenic) were identified through retrospective review. Hypoallergenic implant patients were associated with higher 30-readmission (2.19% vs. 0.74%, P < 0.001, 95% confidence interval, 1.052 to 1.132). No notable association was found between hypoallergenic TKA and BMI, ASA, heart disease, diabetes, alcohol, smoking incidence, or medical complications (all P > 0.05).

Conclusion:

There is a notable difference in 30-day readmission rates between patients undergoing TKA with hypoallergenic implants and those with standard implants, underscoring the need for heightened vigilance in this patient population.

Total knee arthroplasty (TKA) stands as one of the most frequently performed procedures in the United States, with a projected surge of 673% in cases to reach 3.48 million procedures by 2030.¹ Despite its widespread adoption, TKA is not without challenges, as evidenced by a reported revision rate between 3 to 5% at the 5-year mark.² This trend underscores the growing necessity for superior implants and improved outcomes in response to the escalating procedural demand.

Metal hypersensitivity, affecting between 10 to 17%^3-8 of the general population, has emerged as a notable concern, particularly in the context of TKA. The key metals implicated in hypersensitivity reactions include nickel, chromium, and cobalt.^9,10 This heightened awareness among patients undergoing TKA has led to the development of hypoallergenic implants. Nickel-free hypoallergenic implants consist of cobalt-chromium-molybdenum and titanium alloys.¹¹ The hypoallergenic options encompass a variety of designs, including coated implants (with Titanium Nitride or Zirconia Nitride), ceramic implants (oxonium and oxidized zirconium), pure titanium implants, and all-polyethylene tibial implants.^4,12

Confirming metal allergy as the root cause of implant failure following TKA remains challenging due to the lack of a standardized diagnostic approach. The reliability of common diagnostic tests for metal hypersensitivity, including contact skin patch testing (SPT), lymphocyte blood testing, and synovial biopsies,⁴ has all been called into question.^13-16 Reported allergic reactions to the metal components of TKA implants include dermatitis, inflammation, and implant loosening¹⁷; however, these symptoms can also be caused by several other etiologies. Consequently, the identification of metal allergies in the context of TKA⁴ is often inconclusive, complicating patient management.

Studies assessing hypoallergenic TKA implants have produced conflicting results, ranging from markedly worse^18-20 to no notable difference^21-23 in clinical outcomes when compared with TKA with standard implants. Despite these studies on implants, there remains a paucity of literature evaluating patients with suspected metal hypersensitivity who undergo TKA; current research suggests a decrease in quality of life and patient-reported outcome measures but are limited by low sample sizes and short follow-up periods.^18,19,22 In addition, only one previous study has compared readmission rates in patients undergoing TKA using hypoallergenic or standard implants.²¹

This study seeks to compare the clinical outcomes, including 30-day readmission rates, ED visits within 72 hours, ED visits within 7 days, ED visits within 30 days, and medical complications, between patients undergoing TKA with either hypoallergenic or standard implants.

Methods

Following institutional review board approval, a retrospective review was conducted to examine all patients aged 18 years and older who underwent unilateral TKA between January 2019 and August 2022 at a high-volume orthopedic specialty hospital. Hypoallergenic implants used in the study included Smith and Nephew Oxinium, Zimmer NextGen Tivanium, and Zimmer Persona Ti-Nidium. Patients who received simultaneous bilateral TKAs were excluded from the study. Collected patient information included demographic data and comorbidities, such as heart disease, diabetes, alcohol use, smoking use, TXA use, BMI, allergies, ASA classification, and length of stay. Clinical outcomes included 30-day readmission rates, ED visits within 30 days, ED visits within 7 days, ED visits within 72 hours, and medical complications.

Paired t-tests were conducted to assess statistical differences in patient characteristics between the hypoallergenic and standard implant cohorts. Multiple logistic regression analyses were run on demographics, comorbidities, use of hypoallergenic implants, and clinical outcomes. Chi-square analyses were conducted for cross-tabulations.

Results

A total of 6986 patients were identified to have undergone primary TKA between January 2019 and August 2022. The average age was 69.23 ± 9.14 (range 21 to 95) years in the standard cohort and 68.62 ± 7.55 (46 to 89) years in the hypoallergenic implant cohort (P = 0.220). Overall, there were 3677 women (55.49%) in the standard cohort and 287 women (89.68%) in the hypoallergenic cohort (P < 0.0001). The standard implant cohort had an average length of stay (LOS) of 0.97 ± 0.82 days and 1.14 ± 0.96 days in the hypoallergenic implant cohort (P = 0.002). Chi-square tests found no notable association between hypoallergenic implant TKA and BMI, heart disease, alcohol use, diabetes, TXA use and smoking use (all P > 0.05) but found notable association between hypoallergenic implant TKA and ASA score (Table 1).

Table 1.

Patient Demographics

	Standard Implant (n = 6626)	Hypoallergenic Implant (n = 320)	P
Age (yr), mean ± SD (range)	69.23 ± 9.14 (21 to 95)	68.62 ± 7.55 (46 to 89)	0.220
Females, n (%)	3677 (55.49)	287 (89.68)	<0.001
BMI, mean ± SD (range)	29.56 ± 5.28 (14.5 to 53.6)	29.81 ± 5.61 (18.7 to 58.2)	0.189
Heart disease, n (%)	4708 (71.05)	215 (67.19)	0.074
Diabetes, n (%)	1027 (15.5)	47 (14.69)	0.672
Alcohol use, n (%)	28 (0.42)	0 (0)	0.238
Smoking use, n (%)	1902 (28.7)	88 (27.5)	0.707
TXA use, n (%)	6206 (93.7)	302 (94.4)	0.331
Length of stay (days), mean ± SD	0.97 ± 0.82	1.14 ± 0.96	0.002
ASA, n (%)			0.069
1	150 (2.26)	4 (1.25)
2	4428 (66.8)	240 (75)
3	2029 (30.6)	83 (25.9)
4	15 (0.23)	0 (0)

Significance for bold entries was P value ≤ 0.05. ASA = American Society of Anesthesiologists, BMI = body mass index

The 30-day readmission rate in the standard implant cohort was 0.74% (n = 49 patients) and 2.19% (n = 7 patients) in the hypoallergenic cohort (P = 0.005). No notable difference exist in ED visits within 72 hours, ED visits within 7 days, and ED visits within 30 days between the standard and hypoallergenic implant cohorts (all P > 0.05). No notable differences were found in both superficial and complex SSI between the two cohorts (both P > 0.05) (Table 2).

Table 2.

Outcomes Table

	Standard Implant, n (%)	Hypoallergenic Implant, n (%)	P
Readmission
ED visits < 72 hours	108 (1.63)	8 (2.5)	0.154
ED visits < 7 days	116 (1.75)	8 (2.5)	0.296
ED visits < 30 days	108 (1.63)	9 (2.81)	0.127
30-day readmission	49 (0.74)	7 (2.19)	0.005
SSI
Superficial SSI	6 (0.09)	0 (0)	0.223
Complex SSI	8 (0.12)	0 (0)	0.860

Significance for bold entries was P value ≤ 0.05. ED = emergency department

Reasons for 30-day readmission in the hypoallergenic cohort include acute pulmonary edema (n = 1), pulmonary embolism (n = 3), sepsis (n = 2), nausea and vomiting (n = 1), and wound infection (n = 1). Reasons for 30-day readmission in the standard cohort include acute kidney failure (n = 2), acute respiratory failure (n = 2), cellulitis of the lower limb (n = 2), gastrointestinal hemorrhage (n = 3), heart failure (n = 3), infection and inflammation due to knee prosthesis (n = 3), noninfective gastroenteritis and colitis (n = 2), sepsis (n = 3), unspecified abdominal pain (n = 2), and unspecified internal obstruction (n = 2).

All other readmission reasons for the standard implant cohort include single instances of acute cystitis, disorientation, disruption of wound, diverticulosis, enterocolitis, fecal impaction, hyperosmolality and hypernatremia, hypo-osmolality and hyponatremia, infection due to urethral catheter, neurological complication, orthostatic hypotension, nonspecified complication of procedures, spondylosis with myelopathy in the cervical region, knee pain, paroxysmal atrial fibrillation, pneumonia, accidental opioid poisoning, postprocedural hematoma of skin, left quadricep strain, supraventricular tachycardia, toxic encephalopathy, osteoarthritis of the knee, and unspecified fracture of the upper end of the right tibia.

Logistic regression analysis found hypoallergenic implant TKA to be a notable predictor of 30-day readmission (P = 0.005). Age was found to be a notable predictor of 30-day readmission rate (P < 0.0001) and ED visits < 30 days (P = 0.001) (Table 3).

Table 3.

Logistic Regression Results^a

Dependent Variables	30-Day Readmission	ED Visits < 30 Days	ED Visits < 72 Hours	ED Visits < 7 Days
ASA	—	—	—	—
Age	1.091 [1.052–1.132]***	1.042 [1.017–1.067]***	1.016 [0.980–1.052]	1.010 [0.987–1.033]
Sex	—	—	—	—
BMI	1.003 [0.948–1.062]	0.996 [0.959–1.035]	0.969 [0.915–1.027]	0.979 [0.943–1.017]
Hypoallergenic implant	3.300 [1.442–7.553]**	1.727 [0.856–3.486]	1.987 [0.773–5.111]	1.481 [0.709–3.094]
Heart disease	0.990 [0.492–1.992]	1.364 [0.829–2.243]	1.330 [0.652–2.712]	1.600 [0.989–2.587]
Diabetes	0.772 [0.354–1.683]	0.727 [0.420–1.258]	1.130 [0.532–2.402]	1.032 [0.630–1.690]
Alcohol use	4.377 [0.564–33.954]	2.060 [0.274–15.506]	0.000 [0.000–0.000]	0.000 [0.000–0.000]
Smoking use	1.599 [0.929–2.754]	1.139 [0.769–1.688]	0.998 [0.541–1.844]	0.990 [0.667–1.469]

Significance for bold entries was P value ≤ 0.05. ASA = American Society of Anesthesiologists; BMI = body mass index; ED = emergency department

^aValues written as odds ratio [95% confidence interval].

*P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001.

Discussion

The estimated prevalence of metal hypersensitivity ranges from 15% to 20% of patients who undergo TKA,^5,6 and it is important to evaluate the potential risks that this patient population may face when compared with those who receive standard implants. This large study of more than 6000 cases in a high-volume, private practice, orthopedic hospital found that those with a reported metal hypersensitivity who received hypoallergenic implants were more likely to be readmitted within 30 days compared with those who received standard implants (2.19% vs. 0.74%, P < 0.001). Of note, however, besides postoperative wound infection (n = 1), no other readmission diagnoses appeared to be related to metal hypersensitivity or hypoallergenic implant use; these included postoperative nausea and emesis (n = 1), pulmonary edema (n = 1), pulmonary embolism (n = 2), sepsis (n = 2), and heart failure (n = 1). No notable differences in age, BMI, or medical complication rates were found between the two cohorts.

The growing volume of total joint arthroplasty in the United States has made curbing early readmission a target for cost containment.²⁴ Despite this scrutiny, previous reports on readmission rates following TKA using hypoallergenic implants are restricted to one propensity-matched study by Tidd et al comparing 452 standard patients and 151 hypoallergenic implant patients, which found no notable difference in 90-day readmission rates (10.7% vs. 11.1%, P = 0.893).¹⁸ This contradicts the findings of this study. Although reasons for 90-day readmission were not recorded in either cohort, patients in the study of Tidd et al predominantly received one hypoallergenic implant material (Oxinium); this may limit the generalizability of the study to others that use a more diverse range of hypoallergenic implants.

Markedly more women were there in the hypoallergenic cohort than in the standard cohort (89.5% vs. 55.5%, P < 0.0001). However, logistic regression found no notable difference in 30-day readmissions based on sex in this study (P = 0.869). The role that gender plays in readmission following TKA remains unclear, with studies either finding no notable association^25,26 or quoting male gender^27,28 as a risk factor for readmission. The findings of this study suggest that readmission following hypoallergenic implant TKA was not confounded by patient sex.

In addition to hypoallergenic implant use, this study found age to be a notable predictor for readmission at 30 days (P < 0.001), a finding that is corroborated by many studies in the literature. Older age is a known risk factor for 30-day readmission following TKA.^27,29-31 However, this finding is not relevant to this study because no notable difference was found in age between the hypoallergenic and standard implant cohorts (P > 0.05). Despite BMI being historically noted as a predictor for readmission following TKA,³² no notable difference was found in BMI between the cohorts in this study (P > 0.05).

Several limitations exist. Because of its retrospective nature, this study is subject to potential selection bias through nonrandomization. In addition, only patients who were readmitted to the study's hospital were flagged. Metal hypersensitivity was largely self-reported. Additional insight may be gathered from longer-term follow-up. Radiological outcomes were not assessed and compared between the groups, which would be a suggestion for future research. Patient-reported outcome measures were not assessed and compared due inconsistency in collection. Because of the constraints of the data pull system, which was used, the use of DMARDS or steroids, heavy blood thinners, implant type (cemented vs. Noncemented), and implant configuration was not assessed between the cohorts. Greater insight on readmission reasons may be gathered from the inclusion of such information.

Conclusion

There is a notable difference in 30-day readmission rates between patients undergoing TKA with hypoallergenic implants and those with standard implants, underscoring the need for heightened vigilance in this patient population and adding to the growing attention toward the benefit of hypoallergenic implants in TKA. Understanding the notable health and financial implications associated with hypoallergenic implants can lead to important discussions between physician and patient. Further research, particularly with longer follow-up and more comprehensive diagnostic criteria for metal hypersensitivity, are necessary to better understand the clinical outcomes and to develop more effective strategies for managing this subset of TKA patients.