This study was performed to detect the risk factors for complications in patients with RA who underwent all types of cervical spine surgeries. The prevalence of complications was 20.1% in the present study. We newly found that 1) short height, 2) high ASA-PS, 3) short disease duration of RA, and 4) long fusion procedures could be risk factors for perioperative complications. In addition, when focused on severe complications, 5) high-dose prednisolone administration , 6) existence of SAS, and 7) OC fusion and long fusion were suggested to be risk factors.
Patients with RA have been shown to experience a variety of complications after spine surgery more frequently than patients without RA (18,28,29). On the other hand, there was a report that RA itself was not a risk factor for complications after cervical spine surgery (30). Comorbidities could be among the risk factors correlated with perioperative complications after spine surgery, since patients with RA have a higher incidence of not only perioperative complications but also comorbidities than patients without RA (18). Regarding cervical spine surgery, significantly higher incidences of major medical complications and postoperative infection were observed in patients with RA over 65 years old who underwent anterior cervical fusion (19). In addition, the existence of cervical spine lesions by RA was suggested to be a risk factor for SSI (17).
Both the existence of SAS and the long fusion procedures were detected as risk factors for severe perioperative complications after cervical spine surgery for patients with RA. Cervical spine lesions with RA generally start at the atlantoaxial joint, and they progress from AAS to VS and then SAS (31,32). Patients with SAS are expected to have progressive systemic joint damage (32,33), resulting in multiple comorbidities (34). In the present study, only SAS lesions were not associated with ASA-PS, and the patients with VS or SAS were significantly associated with higher ASA-PS than patients with AAS or without cervical spine lesions [OR: 2.276, 95% CI: 1.130-4.588, p=0.0214]. In addition to the risks associated with systemic conditions before surgery, operative procedures for SAS were also related to perioperative complications. Treatment for symptomatic SAS usually requires a long fusion procedure, which fixes many vertebrae and places a much greater burden on the patient’s body than laminoplasty or C1-2 fusion (3). In fact, long fusion was associated with significantly longer operation time [laminoplasty: 114 min, C1-2 fusion: 137 min, OC fusion: 168 min, long fusion: 214 min] and heavily bleeding volume [laminoplasty: 69 g C1-2 fusion: 52 g, OC fusion: 75 g, long fusion: 248 g] than the other procedures in the present study. Thus, the presence of preoperative comorbidities and an increase in surgical burden may be associated with perioperative complications in patients with SAS lesions who underwent long fusion. In addition, OC fusion was also detected as a risk factor for severe complications. OC fusion required longer surgery times than laminoplasty and C1-2 fusion, although there was no differences in the amount of bleeding, as shown in the previous discussion. This result suggested that OC fusion placed a moderate surgical burden on the patients but not as much as long fusion. Otherwise, poor general condition or highly invasive OC fusion procedures might influence the incidence of severe complications but not mild/moderate complications.
ASA-PS was generally associated with perioperative complications, such that as the class increased, the risk of complications increased (35). In adult spine surgery, ASA-PS class higher than class III was shown to be a significant risk factor for any complications compared to class II and lower (36,37). Although there was no significant difference, ASA-PS class III or higher also tended to increase the risk for perioperative complications compared to class II and lower [odds ratio: 2.265, 95% CI: 0.974-5.265, p=0.058] in the present study. In addition, the mean value of ASA-PS was significantly higher in patients with perioperative complications than in patients with no complications. ASA-PS has been suggested to be one of the predictors of perioperative complications in patients with RA after all cervical spine surgeries. On the other hand, the CCI was not correlated with perioperative complications of cervical spine surgery in patients with RA, although previous reports have suggested that the CCI could be useful to predict perioperative complications in spine surgery(38,39). A previous report also showed a significant correlation between the CCI and ASA-PS (39), whereas there was no correlation in the present study. The CCI represents the simple sum of comorbidities weighted based on adjusted risk of mortality or resource use in the future. The ASA-PS are determined by anaesthesiologists considering not only types of comorbidity but also severity, which suggests that the ASA-PS could reflect the comorbidity status in more detail and more accurately than the CCI. The subtle differences between these two criteria concepts might make a difference in the strength of their relevance to complications depending on the underlying disease.
The use of high-dose prednisolone was also detected as a risk factor for severe perioperative complications. A few reports have investigated the correlation of prednisolone administration with perioperative complications in patients in studies that were not limited to RA (40–42). Prednisolone use and its dose did not affect the incidence of perioperative complications in patients with Crohn’s disease (42) or cause infections, including SSIs, in patients with RA who underwent cervical spine and prosthesis surgery (40,41). However, the use of prednisolone correlated with severe perioperative complications in the present study. Considering the background of the patients who were taking high-dose prednisolone for RA, these patients are expected to have high disease activity and a limited drug selection due to comorbidities. Administration of high-dose prednisolone might only identify a population prone to perioperative complications, and the increased risk for complications may not be an effect of the drug itself.
Infections were one of the considerable perioperative complications in patients with RA, since almost all patients took immunomodulatory reagents. In a US nationwide analysis, infection was the most common complication of spine surgery (18) and was the leading cause of readmission after cervical fusion surgery in patients with RA (43). Among DMARDs, biologics, JAK inhibitors and high doses of glucocorticoids have been associated with an increased risk of infections (44,45). However, conflicting results of biological DMARDs, mainly tumour necrosis factor antagonists, have been reported in many studies, including both increased and unchanged risks of superimposed infections after surgery (46). Regarding spinal surgery, the use of biologic DMARDs or prednisolone did not increase the risk of infection (41). The present study also revealed that postoperative infection, including SSI, was the most common complication but did not increase with any particular medication, such as biologics, JAK inhibitors or prednisolone, after cervical spine surgery. Among the identified risk factors for perioperative complications in this study, only OC fusion was significantly associated with infectious complications [vs. laminoplasty: OR: 4.72, 95% CI: 1.795-48.0, p=0.0079].
Physical constitution could affect perioperative complications and anaesthesia management. In fact, obesity correlates with not only comorbidities in patients with RA (47) but also perioperative complications after many types of surgery (48–52). However, there have been only a few reports that shorter patients were at higher risk for perioperative complications, which were shown in coronal and carotid endarterectomy (53,54). Body size was suggested to have a direct impact on technical issues related to the surgery, such as limited access to the surgical field, since both BSA and height have been shown to correlate closely with the diameter of the common carotid artery (55). Surgery in a small, limited field might affect certain kinds of surgical techniques, resulting in an increase in perioperative complications. However, it was difficult to substantiate this possibility with cervical spine surgery because there were no significant inverse correlations between short height and operation time or bleeding volume in the present study.
A shorter duration of RA in the patients with perioperative complications than in the patients without complications was shown in the present study. However, the mean disease duration of RA at the time of cervical spine surgery was 20.2 years in the complication group and 17.6 years in the no-complication group. It is difficult to determine the clinical meaning of this 2.5 year difference over such a long disease duration. A possible reason might be related to the features of cervical spine lesions in patients with RA. Most studies have reported that cervical spine lesions are a feature of longstanding rather than early disease, which are generally apparent ten years into the natural history of RA(56,57). On the other hand, cervical spine lesions have also been associated with the severity of peripheral radiographic joint damage (8,58), and the extent of progression at cervical spine lesions was well correlated with the number of erosive joints in the hand and foot (32,33). In addition, an increasing number of comorbidities were associated with poorer values for tender joint count and swollen joint count (34). These findings suggested that patients with uncontrollable inflammatory arthritis in the systemic joint progressed to cervical spine lesions early (i.e., with a short disease duration) and tended to have more comorbidities, which resulted in increased perioperative complications after cervical spine surgery.
There were two limitations in the present study. First, there could have been heterogeneity in the background conditions over time. The patients enrolled in the present study were enrolled over the last 20 years. During this 20-year period, the general condition of patients with RA and the pathophysiology of cervical spine lesions has changed, as pharmacological treatment for RA has changed dramatically after the emergence of biologics and JAK inhibitors. Considering that most patients used prednisolone and a few patients used biologics, the patient group in the present study seemed to be a distinct population with relatively progressed RA and some comorbidities. In addition, instruments for fixation have advanced or been modified year after year. These biases could have resulted in an underestimate or overestimate in the analysis. The second limitation was data deficiency. Physical examinations or questionnaires assessing disease activity or physiological function in the patients with RA could not be investigated. Anti-citrullinated protein antibodies, rheumatoid factor or matrix metalloproteinase-3 were not detected in some cases. In addition, many patients did not have radiographs available except for the cervical spine. These data deficiencies limited the ability to directly investigate correlations of perioperative complications with disease activity or progression of RA, biomarker contributions and the existence of systemic joint destruction.