Introduction
Anterior Cervical Discectomy and Fusion (ACDF) is the most common spine procedure used for the management of cervical spondylolysis, with approximately 132,000 ACDFs performed each year (Kamalapathy et al. 2021; Saifi et al. 2018). Throughout the years, the parameters clinicians use to assess surgical outcomes have changed from objective physical metrics to subjective outcome measures grounded on patient perception, as commonly assessed by Patient Reported Outcome Measures (PROMs) (Finkelstein and Schwartz 2019; Deshpande et al. 2011; Field, Holmes, and Newell 2019). Commonly used PROMs for cervical spinal fusion surgery include: Visual Analog Scale (VAS) neck and arm, Neck Disability Index (NDI), 12-Item Short Form Survey (SF-12) Physical Composite Score (PCS), and Patient-Reported Outcome Measures Information System physical function (PROMIS-PF) (Finkelstein and Schwartz 2019; Vaishnav et al. 2020; Boody et al. 2018; Haws et al. 2019).
A drawback of PROM questionnaires is that they lack clinically significant meaning on their own (Parker et al. 2011; Mouelhi et al. 2020). To overcome this limitation, the concept of minimum clinically important difference (MCID) was developed (Parker et al. 2011; Mouelhi et al. 2020; Sedaghat 2019). MCID is defined as the minimum change in a patient reported outcome measure that is clinically significant and can justify implementation into medical practice (Parker et al. 2011; Paul et al. 2017). MCID values are unique to each individual PROM and spinal pathology (Parker et al. 2012).
Prior literature has demonstrated that the following preoperative risk factors can lead to poorer postoperative PROMs following ACDF: higher or lower age, increased duration of symptoms, depression, and comorbidity burden (determined by the Charlson Comorbidity Index (CCI) (Narain et al. 2019; Li et al. 2019; Rahman, Ibaseta, Reidler, et al. 2020; Omidi-Kashani, Ghayem Hasankhani, and Ghandehari 2014). While most patients achieve MCID for NDI and VAS neck following ACDF, a smaller subset of patients reach MCID for arm pain (Narain et al. 2019; Goldberg et al. 2002). Narain et al., one of few studies assessing the impact of preoperative variables on achievement of MCID, determined an association of increased CCI with failure to reach MCID for NDI (Narain et al. 2019). To better understand the long-term success of favorable postoperative outcomes, it is important to study how preoperative characteristics influence postoperative maintenance of previously attained MCID. The present study aims to identify risk factors for regressing below a level of meaningful clinical improvement for patients who already achieved MCID at an earlier time point following anterior cervical discectomy and fusion.
Methods
Patient Population
Informed patient consent and Institutional Review Board approval (ORA #14051301) were obtained prior to study onset. A prospectively maintained surgical registry was retrospectively reviewed to identify patients who received ACDF surgery between April 2008 and October 2020. All procedures were performed by a single attending spine surgeon at a single academic institution. Inclusion criteria were patients who underwent primary, elective, single- or multi-level ACDF. The following exclusion criteria were implemented: patients who did not complete preoperative PROM surveys or underwent surgery due to trauma, infection, or malignancy.
Data Collection
Patient demographics including age, gender, body mass index (BMI), smoking status, diabetic status, American Society of Anesthesiologists (ASA) score, Ageless Charlson Comorbidity Index (CCI), American Society of Anesthesiologists physical status classification (ASA), and insurance (workers compensation or non-workers compensation) were collected. PROM scores were collected preoperatively and at 6-week, 12-week, 6-month, 1-year, and 2-year postoperative time points for VAS neck, VAS arm, NDI, SF-12 PCS, and PROMIS-PF. Perioperative characteristics, including mean operative duration, mean estimated blood loss (EBL), mean hospital length of stay (LOS), and utilization of a stand-alone cage vs. additional anterior cervical plating were recorded for both single- and multi-level patient cohorts. Preoperative spinal pathologies of patients were recorded and included herniated nucleus pulposus, central stenosis, and myeloradiculopathy.
Statistical Analysis
Data analysis was conducted with Stata 16.0 (StataCorp LP, College Station, TX). Mean PROM values were calculated, after which delta PROMs were computed as the improvement in PROMs from preoperative to each postoperative time point. Delta PROMs were used to calculate the proportion of patients achieving MCID by comparison to previously established threshold values: 2.6 for VAS neck (Parker et al. 2013), 4.1 for VAS arm (Parker et al. 2013), 8.5 for NDI (Parker et al. 2013), 8.1 for SF-12 PCS (Parker et al. 2013), and 4.5 for PROMIS PF (Steinhaus et al. 2019). MCID “drop-off” for each PROM was calculated as the proportion of patients who achieved MCID postoperatively but then failed to maintain clinical improvement at any subsequent time point till 2-years. Poisson regression with robust error variance was employed to evaluate the relative risk of each collected demographic and perioperative variable for all PROMs. A p-value ≤ 0.05 was used as a marker for statistical significance in all analyses performed.
Results
Descriptive Analysis
351 patients who underwent either single-level or multi-level ACDF were studied (Table 1). Majority were male (57.3%), with an average age of 49.9 years and an average BMI of 29.3 kg/m2 (Table 1). Within the single-level ACDF cohort, the most commonly observed spinal pathology was herniated nucleus pulposus (92.2%), followed by myeloradiculopathy (73.5%) and central stenosis (29.4%). Of the patients undergoing multi-level fusion, spinal pathologies were seen more uniformly, with 71.4% of patients with herniated nucleus pulposus, 76.2% with myeloradiculopathy, and 71.4% with central stenosis (Table 2).
The mean operative duration for single-level ACDF was 55.4 minutes with an average estimated blood loss of 40.0 mL (Table 2). Multi-level fusions took approximately 80.5 minutes to perform with an average estimated blood loss of 43.9 mL. Patients with both single- and multi-level ACDF experienced a hospital stay of one day or less (Table 2).
In each ACDF procedure, either a conventional stand-alone cage or additional anterior cervical plate was used. Within single-level ACDF procedures, 96 patients received a stand-alone cage and 108 patients received the cage-plate. On the contrary, nearly all multi-level patients received the cage-plate (139), while only 8 patients received a stand-alone cage (Table 2).
Primary Outcome Measures
The proportion of patients achieving MCID across PROMs was highest for VAS neck at 12-weeks (56.5%), VAS arm at 6-months (38.5%), NDI at 6-months (68.1%), SF-12 PCS at 6-months (45.1%), and PROMIS-PF at 1-year (69.0%) (Table 3). MCID drop-off rates were highest for VAS arm (26.8%), followed by VAS neck (26.2%), SF-12 PCS (18.6%), NDI (17.0%), and PROMIS PF (16.3%) (Table 3).
Preoperative PHQ-9 (RR 1.1, p=0.011) significantly predicted MCID drop-off for VAS neck, while anterior plating (RR 0.6, p=0.029) was a significant protector of preventing drop-off for VAS neck (Table 4). Smoking status (RR 2.2, p=0.038) and preoperative VAS arm (RR 1.2, p=0.001) were significant risk factors for MCID drop-off for VAS arm (Table 5). No significant risk factors for MCID drop-off were observed in NDI (Table 6). Male sex was a significant protector of preventing MCID drop-off for SF-12 PCS (RR 0.4, p=0.025) (Table 7). BMI was a significant risk factor of MCID drop-off for PROMIS-PF (RR 1.1, p=0.006) (Table 8).
Discussion
Spinal surgery has primarily turned to patient reported outcome measures (PROMs) to assess the effectiveness of surgical procedures, including anterior cervical discectomy and fusion (ACDF) (Staartjes et al. 2019). Translating PROMs into clinical significance has proved more complex, with Jaeschke et al. noting a disconnect between statistically significant PROMs and clinical significance (Parker et al. 2011, 2012; Jaeschke, Singer, and Guyatt 1989; Jenkins et al. 2020). Minimally important clinical difference (MCID) was created to address this discrepancy and evaluate progression of PROMs following spinal surgery in a clinically significant context. Nonetheless, many times MCID is achieved at one time point, yet this achievement may not be maintained at successive time points. Our study aims to assess the predictive capability of preoperative and perioperative characteristics on a patient’s ability to maintain a previously attained MCID at subsequent time points following ACDF.
PROMIS PF drop-off: BMI
An increased body mass index (BMI) has been associated with development of degenerative disc disease due to greater mechanical load and stimulation of chronic inflammatory pathways, leading to increased risk for cervical myelopathy and radiculopathy (Zhang et al. 2020; Fatima et al. 2020). Interestingly, BMI has not significantly impacted postoperative PROMs, attainment of MCID across PROMs, patient satisfaction, narcotics consumption, length of hospital stay, or healthcare costs following ACDF (Narain et al. 2018; Sielatycki et al. 2016). Nevertheless, greater BMI has predicted significantly decreased Patient-Reported Outcomes Measurement Information System physical function (PROMIS-PF) scores following other surgical procedures, suggesting a potential relationship among the two variables (Katakam et al. 2021; Blanchett et al. 2019). Katakam et al. established that for each one-unit increase in BMI, there was an additional 2% risk of failure to attain MCID following total joint arthroplasty (Katakam et al. 2021). Our findings uniquely demonstrated that higher BMI is significantly associated with failure to maintain previously achieved MCID for PROMIS-PF. For this reason, surgeons should acknowledge the increased possibility of lack of maintainance of clinically meaningful physical funciton improvement among obese ACDF candidates. Early weight management education in the preoperative period may allow for obese patients to have a better chance of maintaining clinically meaningful improvements in their postoperative physical health.
VAS Arm MCID drop-off: Preoperative VAS arm, Smoking Status
Patients with cervical radiculopathy often experience unilateral neck pain, arm pain, or a combination of both due to impingement of a nerve from a herniated disc or bony spurs (Eubanks 2010; Eubanks et al. 2011; Iyer and Kim 2016). Several studies have demonstrated a significant reduction in arm pain, measured by VAS arm, following ACDF (Massel et al. 2017; Laratta et al. 2018). Carreon et al. concluded that patients with a three-point decrease in arm pain achieved MCID, while those with a four-point decrease reached substantial clinical benefit (SCB) following cervical fusion (Carreon et al. 2010). Our findings uniquely demonstrate higher preoperative arm pain as a significant risk factor for loss of previously attained MCID for VAS arm. Therefore, patients with more severe baseline arm pain should be informed that they will be more prone to losing previously achieved clinically significant long-term pain improvements. As alignment of provider and patient expectations has been associated with improved satisfaction (and thus clinical outcomes), relaying this evidence-based trend to this patient population is crucial, especially among those presenting with arm pain as their predominant symptom (Tabibian et al. 2017). To counteract this unfavorable trend, postoperative treatment modalities such as structured physiotherapy may be considered to increase expectation fulfillment, an association demonstrated by Wibault et al. (2018).
It is commonly understood that smoking is a risk factor for incomplete bone healing in spinal fusion procedures (Berman et al. 2017; Echt et al. 2018). Mangan et al. showed smokers had significantly decreased fusion rates compared to non-smokers, while other studies found similar fusion rates among the two cohorts following ACDF (Goldberg et al. 2002; Samartzis et al. 2005; Luszczyk et al. 2013). Nevertheless, clinical findings including fusion rates may not align with patients’ perceived health status as measured by PROMs (Jaeschke, Singer, and Guyatt 1989). Our findings identified preoperative smoking as a significant predictor for loss of previously attained MCID for VAS arm following ACDF. In an effort to improve long-term clinical outcomes following ACDF for smokers, implementation of preoperative education and recommendation of pre/postoperative smoking cessation resources may be beneficial. Preoperative medical education may include consultations with patients to inform them of the long-term postoperative implications of smoking on ACDF. Likewise, resources for smoking cessation can be discussed preoperatively and postoperatively to encourage patients to quit behaviors that may impede maintenance of clinical recovery in arm pain following ACDF.
SF-12 PCS MCID drop-off: Male Sex
The incidence of cervical radiculopathies is higher in males compared to females, putting them at greater risk for requiring ACDF management (Radhakrishnan et al. 1994; Robinson et al. 2014). Prior literature has also demonstrated that male sex is associated with a significantly greater risk for any adverse event and numerous specific adverse events (e.g. pneumonia, sepsis, death) following ACDF (Radhakrishnan et al. 1994; Basques et al. 2018). While aforementioned studies have evaluated the impact of sex on incidence and surgical complications of ACDF, the relationship between sex and PROMs or MCID achievement/drop-off across PROMs has yet to be assessed. Our study found that male sex was a significant protective factor for regression of previously attained MCID for SF-12 PCS. While males are more prone to cervical radiculopathy and post-surgical complications following ACDF, improved physical functioning is likely to remain through a minimum of 2-years following fusion, which may provide comfort and positively influence a patient’s decision to undergo surgery. Further studies on the impact of male vs. female sex on PROMs, MCID attainment, and MCID drop-off in patients undergoing cervical fusions would add invaluable insight on the relationship between sex and postoperative success following ACDF. Future implications of these findings will allow for appropriate preoperative and postoperative measures to be taken so that optimal patient outcomes following ACDF can be achieved for both genders.
VAS Neck MCID drop-off: PHQ-9, Anterior Plate Fixation
In 2016, neck and back pain accounted for the largest amount of healthcare expenditure at $134.5 billion, with neck pain affecting over 20% of the representative population in the US (Dieleman et al. 2020; Genebra et al. 2017). Multiple studies have confirmed the effectiveness of ACDF in significantly improving several PROMs, including neck pain, through extended follow-ups (Massel et al. 2017; Oliver et al. 2018; Song et al. 2009). Recent advancements in ACDF have led to an increase in use of anterior plate fixation in addition to conventional stand-alone interbody cage for enhanced stability (Cheung et al. 2019). While the anterior plating can significantly improve radiographic outcomes following fusion by restoring lordosis and decreasing subsidence, a meta-analysis by Cheung et al. demonstrated no differences among cage-plate vs. cage-only cohorts for PROMs, including Odom’s criteria, VAS neck, VAS arm, Japanese Orthopaedic Association (JOA) score, and NDI (Oliver et al. 2018; Cheung et al. 2019). Notably, the cage-plate cohort demonstrated increased surgical complications, including dysphagia and adjacent segment disease, highlighting potential drawbacks of anterior fixation (Cheung et al. 2019). Prior research has yet to evaluate the impact of anterior plating on MCID achievement and drop-off for PROMs, including VAS neck. Our study established that anterior plating was protective against the loss of previously gained MCID in patients with neck pain. While there are many potential benefits to using anterior plate fixation technique during ACDF, there are numerous risks. Physicians ought to discuss the evidence-based advantages and disadvantages of anterior plating with patients considering ACDF treatment (Viswanathan and Manoharan 2017).
Prior literature has demonstrated chronic neck pain as a significant risk indicator for preoperative depression, which in turn is a well-established predictor of poorer postoperative outcomes following ACDF (Elbinoune et al. 2016; Harris et al. 2020; Phan et al. 2017). Alvin et al. found that increasing preoperative PHQ-9 was significantly associated with inferior Quality-of-Life (QOL) outcomes following ACDF (Alvin et al. 2016). Our results distinctly highlight preoperative PHQ-9 as a significant risk factor for loss of previously achieved MCID for neck pain. Appreciation of this finding emphasizes the interrelatedness of mental health and postoperative surgical outcomes. In an effort to allow for greater longevity of neck pain improvement following ACDF, it may be beneficial for surgeons to preoperatively console patients about the importance of depression management and recommend guidance from mental health providers.
Limitations
There are numerous limitations to this study. External validity was weakened due to all fusions being performed at one academic center by a single surgeon. Our results were based on outcomes collected from patient perception and thus prone to subjectivity and recall bias. Many individuals did not complete PROMs to full follow-up at 2-years, resulting in selection bias that skewed results to represent outcomes of remaining patients more accurately. Finally, the lack of control in the number of levels for ACDFs studied (single- and multi-level included) may introduce a confounder and limit the generalizability of our findings.
Conclusion
Our findings revealed a number of risk factors predictive of regression from initially achieved MCID for various PROMs following ACDF including: higher BMI, greater preoperative arm pain, smoking, and depression. Interestingly, male sex and anterior plating were significant protective factors for long-term retention of clinically significant improvements following ACDF. By identifying and addressing preoperative risk-inducing and protective factors for MCID drop-off, providers can help patients achieve greater longevity of benefits associated with cervical fusion. Furthermore, by communicating these evidence-based trends to patients in the preoperative period, surgeon and patient expectations may become better aligned, allowing for greater likelihood of patient satisfaction.
Correspondence:
Kern Singh, MD
Professor
Department of Orthopaedic Surgery
Rush University Medical Center
1611 W. Harrison St, Suite #300
Chicago, IL 60612
Phone: 312-432-2373
Fax: 708-409-5179
E-mail: kern.singh@rushortho.com
Disclosure
No funds were received in support of this work. No benefits in any form have been or will be received from any commercial party related directly or indirectly to the subject of this manuscript.
IRB Approval
ORA #14051301