Diabetes mellitus is an epidemic. 19 More than one million new cases are diagnosed each year. The prevalence has more than tripled since 1970 with the disease affecting 17 million Americans (6.2% of the United States population). By the year 2050, the prevalence is expected to increase by another 165%. Unfortunately, 1/3 of these patients remain undiagnosed. Furthermore, within the common age groups for joint arthroplasty, the prevalence increases (20.1% of all people age 65 years and older). 1 Because of this alarming rate of growth and the multiple acute and chronic medical complications associated with diabetes, the annual direct and indirect costs attributable to diabetes are estimated to be approximately 100 billion dollars per year. 1
Yet, as the prevalence of diabetes 1 and the number of TKRs done each year increase, 13 few reports are available that review the results of TKA in patients with diabetes mellitus. 3,5,16,18,22 The results have been less than uniform. Some authors have reported an increased deep infection rate in this population, 3,5,18,22 others have reported a higher incidence of postoperative neuropathy, 18 and others have raised concern over wound complications. 5,16,18,22 In addition, a recent prospective randomized study showed that the addition of cefuroxime-impregnated cement was effective in preventing deep infection after TKR in patients with diabetes mellitus. 3
The purpose of the current study was to review the clinical and radiographic results including complications and survivorship of cemented TKR using cefuroxime-impregnated cement in patients with diabetes mellitus, and to determine whether patients with diabetes achieve inferior results, with respect to these variables, after TKR.
MATERIALS AND METHODS
Between June 1987 and November 1999, 5220 primary cemented AGC (Anatomic Graduated Components, Biomet, Warsaw, IN) posterior cruciate-retaining TKRs were done at our institution. From this consecutive series, 329 TKRs (6%) were done in 291 patients with diabetes. Forty-three patients (13% of knees) had bilateral simultaneous TKRs. One hundred eighteen TKRs (36%) were implanted in patients with insulin-dependent diabetes and 211 TKRs (64%) were implanted in patients with noninsulin-dependent diabetes. During the same period, 4891 TKRs were done in 3228 patients without diabetes (Table 1).
All knees were approached through a standard medial parapatellar incision. All-PE patellas were used in every patient and all components were cemented. During this period, 750 mg of cefuroxime (Kefurox, Lilly, Indianapolis, IN) was added routinely to each 40-g package of bone cement (Simplex, Howmedica, East Rutherford, NJ). In the study group, 31 TKRs (9%) were implanted in patients with an allergy to penicillin or a cephalosporin, or both. Therefore, 17 of these 31 TKRs (5% of study group) were implanted with no antibiotics in the bone cement. All patients received the same DVT prophylaxis using 1000 to 1500 units intravenous heparin sodium (Elkins-Sinn, Cherry Hill, NJ) during surgery. All patients received perioperative antibiotics. One or more of the clean-air measures, 2 including laminar air flow, ultraviolet lights, and body exhaust suits were used in every case. Full weightbearing ambulation was started on the first postoperative day and ROM was started on the second postoperative day. An indwelling urinary catheter was placed at the time of operation and usually was removed 2 days later unless otherwise indicated.
Patients were evaluated preoperatively and postoperatively at 8 weeks, 6 months, 1 year, and then every 2 to 3 years thereafter according to the Knee Society clinical 9 and radiographic 6 scoring system. Complications also were recorded including perioperative urinary tract infections, cerebrovascular infarctions (resulting in a residual neurologic deficit), and myocardial infarctions. Manipulations, early (0–6 months postoperative) deep infection, late (> 6 months postoperative) deep infection, neuropathy (sensory or motor loss, or both) and gastrointestinal complications also were recorded including bleeding and postoperative ileus. Patients were screened clinically for DVT and the diagnosis was confirmed with doppler ultrasonography. These data were recorded prospectively.
A chart review of the study group then was done to determine the diabetic diagnosis (insulin- or noninsulin-dependent) and the presence of any wound complications. Superficial wound complications included skin necrosis, superficial infections, and wound dehiscence whether a debridement or delayed primary closure was done. The current study represented a retrospective review of these data. Institution review board approval was obtained from our institution for a retrospective review of TKR.
The followup averaged 52 months (range, 2 months – 12 years) in patients with diabetes and 58 months (range, 0 – 13 months) in patients without diabetes. Because perioperative complications were considered, patients followed up for less than 2 years were not excluded from either study group.
Statistical analysis was done including two-way ANOVA, the nonparametric Friedman’s and the Wilcoxon tests, and chi square test. Kaplan-Meier survival analysis 10 up to 7 years (63 in patients with diabetes and 830 in patients without diabetes) was determined because 10-year followup information on only 15 knees in patients with diabetes and 191 knees in patients without diabetes was available. Failure was defined as revision of any component for any reason or loosening of any component. Computation was done with the aid of the Statistical Analysis System (Cary, NC). Power analysis revealed a probability for a Type 2 error (incorrectly accepting the null hypothesis) of less than 10% (standard,< 20%).
The average Knee Society knee scores were statistically higher (p = 0.0016) in the patients with diabetes preoperatively and postoperatively at each followup up to 7 years. Similarly, average pain scores were uniformly higher (p = 0.0053) in the patients with diabetes before and after TKR. In contrast, Knee Society function scores were, on the average, statistically lower (p = 0.0001), preoperatively and postoperatively at each followup in the patients with diabetes (Table 2).
The rate of aseptic loosening of the femoral and tibial components was statistically higher (p < 0.05) in the patients with diabetes (3.6%) compared with the patients without diabetes (0.4%). In each case, revision TKR was done. The rates of urinary tract infections, DVT, gastrointestinal complications, myocardial infarctions, and manipulations were not statistically different (Table 3). Nine new postoperative neuropathies were observed in the patients with diabetes. No new cases were identified in the patients without diabetes (p < 0.05). The rate of cerebrovascular infarctions also was higher (p = 0.0409) in the patients with diabetes.
The deep infection rate was slightly higher in the patients with diabetes but this difference was not significant (p > 0.05). Four deep infections (1.2%) occurred in the patients with diabetes versus 35 deep infections in the patients without diabetes (0.7%). All of the four patients with diabetes received cefuroxime-impregnated cement. Twenty-six (74%) of the 35 patients without diabetes who had an infection received cefuroxime in the bone cement. Six (17%) of the deep infections in the patients without diabetes occurred beyond 6 months postoperatively (average, 2.3 years; range, 1–5 years). The remaining infections (83%) in the 29 patients without diabetes occurred at an average of 5.7 weeks after surgery (range, 1–26 weeks). Conversely, all four deep infections in the patients with diabetes occurred early, at an average of 8.5 weeks after surgery (range, 3–18 weeks).
The survival rate at 7 years was slightly higher in the patients without diabetes (0.9819 versus 0.9752), this difference was not statistically significant (p = 0.4942). Fourteen (0.3%) of the patients without diabetes and one patient with diabetes (0.3%) died within the first 6 months after TKR (Fig 1).
There was no statistical difference between the patients with insulin-dependent and noninsulin-dependent diabetes with respect to the average preoperative or postoperative Knee Society knee (p = 0.5588) and pain scores (p = 0.6995). Function scores, however, were lower (p = 0.0022), on the average, in patients with insulin-dependent diabetes before and after TKR (Table 4).
In the study group, all deep infections, urinary tract infections, and new cases of postoperative neuropathy occurred in the patients with insulin-dependent diabetes (p < 0.05). The rate of manipulation also was higher (p < 0.05) in the patients with insulin-dependent diabetes (2.5% versus 0.5%). The rates of revision and the number of wound complications in both subgroups, were not significantly different (Table 5).
The Kaplan-Meier prosthesis survival rates in the patients with insulin-dependent and noninsulin-dependent diabetes up to 7 years postoperatively were not statistically different (p = 0.9550). Therefore, although all deep infections in the patients with insulin-dependent diabetes, the overall prosthetic survival, including aseptic loosening of any component for any reason, was no different (Fig 2).
The current study was developed because evidence suggests that the addition of cefuroxime-impregnated cement is effective in preventing deep infection after TKR in patients with diabetes mellitus. 3 One limitation of the current study is that it is not prospective or randomized with respect to the addition of cefuroxime in the bone cement. However, unlike previous reports, 5,16,18,22 it does represent a large number of cemented TKR done in patients with diabetes where cefuroxime-impregnated cement was used (Table 6).
The deleterious effects of diabetes mellitus on fracture healing and bone remodeling, 4,11,12,20 are well-documented. In addition, sensory and autonomic diabetic neuropathy may occur even at subclinical levels. 8 When sensation is diminished, the loss of proprioception and pain perception allows for repeated trauma to the extremity. 8 One or more of these factors may have contributed to the increased aseptic loosening rate seen in the patients with diabetes. With the exception of the report by Chiu et al, 3, a higher than expected aseptic loosening rate in patients with diabetes has been documented by other authors. 5,16,18,22 Similarly, the loss of pain perception may have contributed to the higher Knee Society knee and pain scores seen in the patients with diabetes.
Not surprisingly, Knee Society function scores were significantly lower in the patients with diabetes and ever lower, on the average, in the patients with insulin-dependent diabetes. It is likely that the recognized chronic complications of diabetes mellitus, including vasculopathy, nephropathy, retinopathy, neuropathy, myopathy (amyotrophy), dermopathy, and arthropathy, all may have an adverse effect on patient function and mobility.
Wound healing also has long been recognized to be a problem in patients with diabetes, 7 and it also is a concern after TKR. 3,5,16,18,22 Surgical wound complication rates have ranged from 1.2% (current study) to as high as 12%. 5 The number of wound problems in the current study was determined by chart review. Therefore, it is possible this rate even was higher. Furthermore, the charts of all the patients without diabetes (3228) were not reviewed. Therefore, the actual rate of wound problems in the comparison group was not determined. However, the rate of wound complications in the patients with insulin-dependent diabetes was approximately two times the rate (1.7% versus 0.9%) of the patients with noninsulin-dependent diabetes. With the numbers available, no statistical difference was observed.
The relative increased risk of deep infection in patients with diabetes is a concern after THR 14,21 and TKR. 3,5,18,22 With the exception of the study of Papagelopoulos et al, 16 a higher than average rate of deep infection after TKR has been reported. 3,5,18,22 In a prospective and randomized study evaluating cefuroxime-impregnated cement at TKR in patients with diabetes, Chiu et al 3 reported no deep infections in 41 TKRs implanted with cefuroxime in the bone cement and five deep infections in 37 TKRs (13.5%) in the control group. The authors concluded that this technique was effective in preventing deep infection. In another report from the same institution, 2 cefuroxime-impregnated cement was shown to be effective in preventing deep infection after TKR in the patients without diabetes. Interestingly, England et al 5 suggested that, “consideration should be given to the use of antibiotic-impregnated cement in these patients.” Serna et al 18 did not report whether antibiotic-impregnated cement was used. In addition, 30 of the 53 knees studied (57%) were uncemented. Yang et al 22 reported that 88% of the 78 knees studied received no antibiotic in the bone cement. Therefore, in all three of these later studies reporting an increased incidence of deep infection, antibiotic-impregnated cement was not used routinely. In the current study, cefuroxime, was used in 95% (312) of the knee arthroplasties. Although the infection rate was slightly higher in the patients with diabetes (1.2% versus 0.7%) this difference was not statistically significant. It would seem that cefuroxime-impregnated cement is useful in preventing deep infection after TKR in patients with diabetes mellitus. However, the routine use of prophylactic intravenous antibiotics and clean-air measures 2 such as laminar air-flow, ultraviolet lights, body exhaust suits, or a combination thereof, may have contributed to a lower infection rate. Of interest, Moeckel et al 15 reported no postoperative infections after THR in patients with diabetes when clean-air measures were used.
Cefuroxime is prepared as a fine white powder and mixes well with PMMA. It was chosen at our institution because of availability and thermal stability. 2 Furthermore, as reported by Chiu et al, 2 as much as 2 g of power may be mixed with a 40-g package of cement without substantially changing the static tensile and compressive strength of cement. 2
The most common of the diabetic neuropathic syndromes is polyneuropathy. 8 Although sensation may be diminished, extremity pain actually may increase. 8 Similar to the current report, Serna et al 18 reported five of 53 (9%) new cases of postoperative neuropathy. All five cases involved unexplained pain. Conversely, Papagelopoulos et al 16 reported no new cases of postoperative neuropathy. In the current study, a tourniquet was used in every patients with diabetes. Whether avoiding a tourniquet in patients with diabetes would affect the rate of postoperative neuropathy is unknown.
Patellar component failure was considered in the survival analysis. It was not, however, considered separately when comparing the patients with and without diabetes because the rate of lateral retinacular release was not consistent in either group.
In a previous report from our institution, 17 lateral retinacular release was significantly associated with loosening of the patella. In that report, 4.2% (180 of 4913 knees) of the all-PE patellar components became loose. However, only 15 (8% of loose patellas) were revised. 17 During the period of the current report, there was a significant advancement in the understanding of the importance of rotational alignment of the femoral component that led to a dramatic reduction in the need for lateral retinacular release. 17
All deep infections in the patients with diabetes occurred in patients with insulin-dependent diabetes. Therefore, patients with a more advanced or chronic form of diabetes may be at an increased risk for postoperative deep infection. Similarly, Knee Society function scores were lower in patients with insulin-dependent diabetes compared with patients with noninsulin-dependent diabetes possibly because of the presence of more comorbid conditions associated with a more chronic form of the disease.
Finally, diabetes mellitus is a heterogeneous disease that varies in severity. This fact must be considered when comparing patient outcomes within and between studies. Interestingly, three patients without diabetes (0.09%) had diabetes develop during the followup period. None of the knees in these patients became infected.
Patients with diabetes mellitus, as a group, had less pain and higher scores after TKR when compared with patients without diabetes. With the routine use of cefuroxime-impregnated cement, the deep infection rate only was slightly greater in the patients with diabetes (1.2% versus 0.7%). However, the rate of aseptic loosening was higher in the patients with diabetes. Patients with insulin-dependent diabetes seem to be particularly susceptible to deep infection, postoperative neuropathy, manipulations, and concomitant urinary tract infections. Although the combination of cefuroxime-impregnated cement and the use of clean-air measures may minimized the risk of infection at TKR in patients with diabetes, the patient and the surgeon should be aware of the relative increased risk of aseptic loosening as compared with the risk of aseptic loosening in patients without diabetics.
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