Increased Rates of Septic Shock, Cardiac Arrest, and Mortality Associated With Chronic Steroid Use Following Anterior Cervical Discectomy and Fusion for Cervical Stenosis

INTRODUCTION

Cervical spondylosis encompasses multiple degenerative changes of the cervical spine resulting in myelopathy and/or radiculopathy and has been classically associated with advancing age.^1,2 With the incidence of cervical spondylosis and subsequent degenerative cervical myelopathy/radiculopathy expected to increase in the coming decades due to an aging population, the number of patients undergoing cervical spinal surgery is also expected to increase.^3,4 For example, degenerative cervical myelopathy (DCM) is a strong indication for early operative intervention because patients can decline progressively in a predictable, stepwise fashion. Surgical management of DCM has also been shown to be cost-effective and to vastly improve patients' quality of life.⁵

Many patients with degenerative cervical spine disease are on or have tried steroids to control inflammation and control symptoms.⁶ Although anterior cervical discectomy and fusion (ACDF) has been validated as an effective surgical modality for treating degenerative cervical spine disease with favorable postoperative outcomes,⁷ complication rates associated with the ACDF approach have not been studied in immunosuppressed patient populations. Many immunosuppressants, such as steroids and calcineurin inhibitors, have been linked with decreases in bone mineral density,⁸ potentially increasing risks of complications or failure after a cervical procedure. This study will analyze the effects of chronic steroid/immunosuppressant use for chronic conditions on postoperative complications in ACDF for the treatment of cervical spondylosis resulting in cervical spinal stenosis. Because surgeons use arthrodesis to treat a significant portion of patients with inflammatory degenerative cervical diseases, it is important to understand how steroid/immunosuppressant use affects complication and success rates in ACDF in this specific population so that surgeons can take proper preoperative and postoperative measures to optimize outcomes and patient satisfaction. We hypothesize that chronic steroid/immunosuppression therapy will predispose patients to various postoperative complications, particularly infectious complications.

MATERIALS AND METHODS

RESULTS

Among the 38 645 ACDF patients analyzed, 5377 (13.91%) patients had a postoperative diagnosis of cervical stenosis; of these, 198 (3.68%) had a history of steroid use in the management of a chronic condition in the 30-day preoperative period. In the initial univariate analyses, the steroid cohort was significantly older (59.78 years vs 56.09 years, P < .001) and had a larger proportion of female patients (58.59% vs 49.53%, P = .012) than the control cohort (Table 1). Patients using steroids were more likely than those without a history of steroid use to present with dyspnea (10.61% vs 5.41%, P = .007), COPD (8.08% vs 4.69%, P = .029), hypertension requiring medication management (59.60% vs 46.89%, P = .001), acute renal failure (0.51% vs 0.00%, P < .001), dialysis dependence (1.01% vs 0.23%, P = .035), disseminated cancer (1.01% vs 0.08%, P < .001), and an open wound or wound infection preoperatively (1.01% vs 0.23%, P = .035) in the unmatched analysis (Table 1).

In the propensity-matched analysis, the steroid cohort had significantly higher rates of dyspnea (10.61% vs 6.16%, P = .032), acute renal failure (0.51% vs 0.00%, P = .025), and disseminated cancer preoperatively (1.01% vs 0.10%, P = .020), with no differences in age, gender, race/ethnicity, or BMI (Table 1).

Patients with a history of steroid use experienced a significantly longer length of total hospital stay (1.61 days vs 2.16 days, P = .007) and a significantly longer delay from admission to operation (0.05 days vs 0.44 days, P = .009) when compared with the propensity-generated control cohort. A larger proportion of the steroid cohort (61.62%) was assigned an ASA class of 3 or higher than was the propensity-matched control cohort (50.00%, P < .001; Table 2).

Those on steroids had higher postoperative complication rates when compared with the propensity-adjusted patients, including PEs (0.51% vs 0.00%, P = .025), cardiac arrest requiring resuscitation (1.01% vs 0.10%, P = .020), septic shock (0.51% vs 0.00%, P = .025), and mortality (1.52% vs 0.20%, P = .009) in the 30-day period following ACDF (Table 3). Similar trends were seen in complication rates when comparing steroid users in the propensity-matched cohorts, stratified by 1- and 2-level ACDF versus 3-level or higher ACDF. Similar complication rates were observed in the 1- and 2-level ACDF cohort, specifically (Table 4).

DISCUSSION

In the United States, a move towards bundled payments/risk sharing makes understanding the factors that affect rates of complications and LOS crucial. This study has analyzed chronic presurgical steroid use and associated comorbidities. The results of this study demonstrate that steroid use for chronic medical conditions is associated with a number of preoperative morbidities and also with higher rates of multiple postoperative complications. Consideration of these results may make the surgeon adverse to surgical intervention, but not all surgical management for cervical spinal stenosis is elective. As such, these data should be used to inform those creating bundled payment plans with hospitals and insurers.

The present study demonstrated longer LOS for those on preoperative chronic steroid therapy undergoing ACDF for cervical stenosis than their propensity-matched cohorts. These findings are in line with the current literature, given that White et al¹⁰ previously reported similar increases in LOS for patients on preoperative chronic steroids for anterior lumbar fusion. It is likely that patients on steroid therapy are medically more complex and may understandably require resources at the time of surgery. For example, chronic steroid use suppresses the hypothalamic-pituitary-adrenal axis and can lead to subsequent adrenal insufficiency. Glucocorticoid stress dosing to prevent adrenal crisis may be one of many such considerations regarding chronic steroid therapy that may be responsible for increasing the duration from admission to operation for these medically complex patients. However, there is a lack of consensus and ongoing debate regarding the use of perioperative stress dosing.^11,12

In line with the current literature, this study demonstrated increased rates of PE in patients on steroid/immunosuppressive therapy undergoing ACDF for cervical stenosis. Previous analyses of nationwide databases and pharmacological registries have demonstrated increased rates of PE in patients on chronic steroid therapy in the general population.^13,14 Chronic steroid therapy has also demonstrated increased PE risk in the 30-day postoperative period for neurosurgical procedures.¹⁵ Experimental evidence suggests that glucocorticoids may increase levels of coagulation factors that could contribute to these increased rates of thromboembolic events.^16,17 In light of the increased rates of PE, it is not unreasonable to have a lower threshold of suspicion for PE and consideration of appropriate chemical prophylaxis in patients on chronic steroid therapy undergoing ACDF.

The present study demonstrated increased rates of septic shock in the steroid cohort compared with the nonsteroid cohort following ACDF for cervical stenosis. Steroid use is known to have negative effects on immunological defense mechanisms, causing secondary immunodeficiency by way of altering immune cell trafficking/functions and decreasing cytokine production.¹⁸ Steroids bind to glucocorticoid receptors, altering cellular physiology by inhibiting or stimulating gene expression to overall inhibit inflammation.^19–21 In addition, chronic immunosuppressive therapy can lead to severe lymphopenia and predispose individuals to septic shock.²² Prior studies^23,24 have demonstrated that preoperative steroid use independently increased the risk for infectious complications. Glucocorticoids are widely used to noninvasively treat inflammatory and autoimmune conditions of the spine.²¹ Therefore, with steroid use being commonly implicated in inflammatory spinal conditions, it is important to factor the impacts of prior immunosuppressant therapy in subsequent surgical management.

The rate of these postoperative complications increased by chronic steroid use are most likely contributing to an overall increase in rates of mortality as well. Prior studies^25,26 have demonstrated increased mortality risk for patients on chronic steroid therapy for various intra-abdominal surgeries. However, there is a lack of literature demonstrating this increased relationship in spinal procedures. In light of the increased rates of mortality, orthopedic surgeons and neurosurgeons should carefully weigh the risks and benefits of potential ACDF to treat cervical stenosis for patients on chronic steroid therapy. Nonoperative treatment options should be thoroughly discussed, and the patient's overall quality of health must be carefully considered. Surgeons may wish to carefully consider the decision to place patients on steroids preoperatively to control radicular and myelopathic symptoms, because the results of our study suggest that there is an increased risk of various postoperative complications.

There are various limitations to this current retrospective study. Although baseline differences in demographics and preoperative comorbidities were controlled for using propensity-score matching, steroid users may have presented with worse overall health for which the database could not account. Although propensity-score matching is a widely accepted method of matching, the demographics and preoperative comorbidities provided by the ACS NSQIP database do not capture the entire medical history of each of these patients, highlighting a limitation in the granularity of information provided by the database. The increased rates of complications seen in steroid users may be explained by the presence of other medical conditions, such as rheumatoid arthritis and inflammatory bowel disease. Although we attempted to control for baseline differences in demographics and comorbidities to the best of our ability with the information provided by the database, this limitation underscores the need for future research to truly elucidate the impact of chronic steroid usage in outcomes following ACDF for cervical stenosis. In addition, the ACS NSQIP database does not include information as to which specific immunosuppressants were used in each surgical case. Although steroid use is the most common modality of immunosuppression, more targeted immunosuppressants are continuously being developed. It is possible that not differentiating the specific type of immunosuppression used can introduce confounding variables to this study. Furthermore, the ACS NSQIP database does not provide the medical condition for which patients were prescribed immunosuppressive therapy. Finally, the lack of differences seen in complication rates between 1- and 2-level ACDF and 3-level ACDF may be better explained by a significantly smaller sample size in the multilevel fusion cohort. The number of levels fused may serve as a proxy for complexity of the procedure, and one may presume that patients undergoing multilevel fusions would be at a higher risk for complications. However, our results do not support this presumption and must be considered in light of the small sample size within the propensity-matched cohort. Future research with larger cohorts may shed additional insight on the impact of chronic steroid usage on outcomes following ACDF involving 3 or more levels.

CONCLUSION

It is important to consider the preoperative history of steroid/immunosuppressant use when evaluating candidate patients for ACDF to treat cervical stenosis. Previous literature has reported the association between steroid use in various surgical and spinal procedures and infectious complications. This study demonstrated increased rates for PEs, septic shock, cardiac events, and mortality in patients on chronic steroid therapy. Future research may investigate steroid tapering protocols that reduce the rate or risk of infection and other postoperative complications in the subset of immunosuppressed ACDF patients. The risks and benefits of surgery should be carefully weighed, and nonoperative management options should be thoroughly discussed prior to operative intervention. Presurgical involvement of cardiology, consideration of postoperative DVT chemoprophylaxis, and inpatient monitoring of these patients is recommended. Furthermore, consideration of these data will be crucial in determining bundled payment plans in the United States.