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Perioperative Outcomes of Spinal Cord Stimulator Placement in Patients with Complex Regional Pain Syndrome Compared with Patients without Complex Regional Pain Syndrome
Journal Pre-proof Perioperative Outcomes of Spinal Cord Stimulator Placement in Patients with Complex Regional Pain Syndrome (CRPS) Compared to Patients Without CRPS Michael L. Martini, PhD, John M. Caridi, MD, Lawrence Zeldin, BA, Sean N. Neifert, BS, Dominic A. Nistal, BA, Jinseong D. Kim, BA, Yury Khelemsky, MD, Jonathan S. Gal, MD PII:
S1878-8750(20)30069-3
DOI:
https://doi.org/10.1016/j.wneu.2020.01.061
Reference:
WNEU 14091
To appear in:
World Neurosurgery
Received Date: 27 November 2019 Revised Date:
7 January 2020
Accepted Date: 8 January 2020
Please cite this article as: Martini ML, Caridi JM, Zeldin L, Neifert SN, Nistal DA, Kim JD, Khelemsky Y, Gal JS, Perioperative Outcomes of Spinal Cord Stimulator Placement in Patients with Complex Regional Pain Syndrome (CRPS) Compared to Patients Without CRPS, World Neurosurgery (2020), doi: https:// doi.org/10.1016/j.wneu.2020.01.061. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Elsevier Inc. All rights reserved.
Perioperative Outcomes of Spinal Cord Stimulator Placement in Patients with Complex Regional Pain Syndrome (CRPS) Compared to Patients Without CRPS Michael L. Martini, PhD1 John M. Caridi, MD1 Lawrence Zeldin, BA1 Sean N. Neifert, BS1 Dominic A. Nistal, BA1 Jinseong D. Kim, BA1 Yury Khelemsky, MD2 and Jonathan S. Gal, MD2 1
Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY
10029 2
Department of Anesthesiology, Icahn School of Medicine at Mount Sinai, New York,
NY 10029
Corresponding Author Contact Information: Jonathan S. Gal, MD, FASA Department of Anesthesiology Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1010 New York, NY 10029 (email: [email protected])
Keywords Complex Regional Pain Syndrome; Spinal Cord Stimulation; Perioperative Outcomes; Intraoperative Outcomes; Resource Utilization; Opioid Use; Numeric Rating Scale;
Running Head: CRPS Perioperative Outcomes
CRPS Perioperative Outcomes Introduction Complex Regional Pain Syndrome (CRPS) is a multifaceted disorder proposed to arise from an abnormal tissue injury response. CRPS is characterized by signs of neurogenic inflammation, maladaptive neuroplasticity, and vasomotor dysfunction, which result in chronic, severe pain and disability. Currently, CRPS can be further subdivided as CRPS-1 or CRPS-2, with the latter diagnosis featuring an identifiable nerve lesion. While the pathologic mechanism behind CRPS remains unclear, multiple treatments have been attempted, including physical and occupational therapy, steroids,1 sympathetic nerve blocks, and amputation of affected limbs 2,3. Most treatments, however, have less than favorable results 4,5. An increasingly utilized treatment, spinal cord stimulation (SCS) has been shown to be effective at managing multiple forms of chronic pain 6, including chronic radiculopathies and pain due to ischemia 7-10. It has also been used to minimize CRPS-induced pain,11,12 with prospective cohort studies showing it is more effective than physical therapy at minimizing pain in the affected limb and most patients are pleased with the outcome 13-15. Despite the increasing use of SCS in the treatment of CRPS and other chronic pain conditions, it remains unclear how CRPS status affects outcomes following SCS implantation surgery. Evidence exists of the effectiveness of SCS in CRPS treatment, with indications that over time it results in pain relief, reduction in pain scores, quality of life improvement, and patient satisfaction 16. Nevertheless, as with any invasive procedure, there are risks and costs associated with SCS procedures. As SCS use becomes more common, it becomes increasingly important to evaluate the patients for which the procedure would be most effective and to understand the drivers of outcomes and cost in various patient populations. To our knowledge, no study to date has examined the impact of CRPS on the perioperative outcomes of patients undergoing surgical implantation of an SCS or compared these outcomes to those of patients without CRPS undergoing SCS implantation. In this study, we seek to characterize the specific risks and outcomes of SCS implantation and determine how CRPS affects these outcomes relative to other chronic pain etiologies. We also provide a comprehensive literature review to supplement our study and provide context for where the field stands.
Methods
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CRPS Perioperative Outcomes
Data Source, Inclusion Criteria, and Patient Stratification
This retrospective study was approved by our institutional review board and informed consent was waived. Our records were retrospectively queried for all cases involving an SCS between 2008-2016 utilizing the ICD-10 diagnosis and procedure codes from the administrative claims data. This yielded 156 cases of SCS implantation and removal procedures performed in the inpatient and outpatient settings. SCS removal cases were excluded (N=21), as were cases performed in an outpatient setting because they lacked a complete set of variables for full analysis in this study, including pertinent outcome metrics (N=54). This yielded 81 cases of inpatient SCS implantation procedures (Figure 1). These cases were organized according to preoperative diagnosis, including 9 cases involving a CRPS diagnosis and 72 other cases performed for other indications (e.g. back pain, failed back syndrome, neuropathy). All cases were individually reviewed to confirm the correct clinical diagnoses and that standard diagnostic criteria were met. In the US, the only indications for SCS are pain syndromes. Therefore, it was confirmed that all patients in this study presented with symptoms of severe, intractable pain after failing conservative management. All patients underwent a neuropsychiatric evaluation prior to one-week trial of percutaneous stimulation and reported significant pain relief, confirming efficacy, before opting to undergo permanent implantation. Five surgeons at our institution performed the nine CRPS cases. All of the surgeons were fellowship-trained faculty with appointments in the Department of Neurosurgery. Review of the intraoperative reports confirmed that each of these cases followed the same general protocol, including details of patient positioning, instrumentation, methods for locating the spinal levels of interest, and methods for device placement.
Covariates
Demographic data was collected for each patient’s age, sex, race, body mass index (BMI), American Society of Anesthesiologists (ASA) status classification, comorbidities, primary insurance payer, and All Patients Refined Diagnosis Related Groups (APRDRG) scores for mortality risk and severity of illness. In addition, several intraoperative and perioperative
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CRPS Perioperative Outcomes variables were also obtained for each patient. These included the number of levels implanted, blood loss (measured as the output from all suction devices during surgery), method of anesthesia, total oral morphine equivalents received intraoperatively, total length of anesthesia time, total time in the operating room, surgery duration, and time to discharge from the postanesthesia care unit (PACU). Clinical variables pertaining to pain management in these patients were also obtained when available, including whether patients received chronic opioid therapy pre-operatively and if consultation with the inpatient pain service was pursued. In addition, preoperative and 24-hour post-operative Numeric Rating Scale (NRS) pain scores for each patient were noted.
Outcomes
Increased estimated blood loss, greater intraoperative opioid use, extended lengths of anesthetic or surgical times, extended hospitalization, extended time in the PACU, reduction in post-operative NRS pain scores, and higher direct costs were considered as clinical outcome variables. Each of these categorical outcomes were defined as cases greater than the 75th percentile across the entire study population for each category.
Statistical Analysis
R 3.4.1 (The R Foundation for Statistical Computing, 2016) was used for statistical analysis in this study. Chi-Squared tests were implemented to analyze categorical variables. Fisher’s Exact test was used for contingency tables containing an expected count less than one under the null hypothesis of independence. The means for any continuous variables were compared using two-sided, two-sample T tests. A two-way Analysis of Variance (ANOVA) was performed to analyze any interactions or effects between mulitple groups of two independent variables on a dependent variable and each other, such as CRPS status, time, and NRS pain scores. Univariate regression models were constructed to better understand the relationships between certain perioperative variables and various measures of clinical outcome. Finally, multivariable regression models were built to control for demographic and comorbidity variables significantly differing between the two groups or if they were previously known factors shown to
3
CRPS Perioperative Outcomes affect surgical outcomes. In this particular study, models controlled for age, sex, race, primary insurance payer, comorbidity burden, and number of spinal levels operated. A multivariate model was built for each intraoperative and resource utilization outcome of interest. A p value less than 0.05 was set for determining statistical significance. The variance inflation factor (VIF) evaluated multicollinearity in the models.
Results
Demographics
A total of 81 patients undergoing implantation of an SCS device in an inpatient setting were included in this study, of which nine patients (11.1%) carried a preoperative diagnosis of CRPS. Eight of the nine CRPS cases involved one or both of the lower extremities. As such, nearly all of the SCS implantation procedures involved the lower thoracic or upper lumbar regions of the spine. Only one of the CRPS cases involved the upper extremities. The patient cohorts generally shared very similar demographic characteristics, particularly with respect to age (p=0.0745), gender (p=0.7241), race (p=0.4736), BMI (p=0.9706), and number of comorbidities (p=0.1443) (Table 1). Both cohorts also displayed similar distributions in their APRDRG scores for mortality risk (p=0.8536) and disease severity (p=0.5365). Both groups also had similar numbers of spinal levels with SCS placement (p=0.6905) and experienced similar durations of surgery (p=0.9732), time in the operating room (p=0.9914), and time under anesthesia (p=0.9295) (Table 2). Though CRPS patients experienced greater mean times in the PACU until discharge (323.5 ± 77.8 minutes) compared to non-CRPS patients (277.8 ± 23.9 minutes), the difference was not statistically significant (p=0.6345). Although neither cohort experienced an intraoperative complication, the CRPS group, however, did experience significantly higher estimated blood loss during the procedure (p=0.0188), longer length of hospitalization (p=0.0044), and incurred greater direct costs (p=0.0437) on average compared to patients without CRPS. While CRPS patients did receive higher levels intraoperative oral morphine equivalents on average (113.3 ± 14.6) compared to all other patients (90.6 ± 6.7), this trend was not statistically significant (p=0.1832).
4
CRPS Perioperative Outcomes While every patient in both CRPS and non-CRPS cohorts had received pre-operative chronic opioid therapy prior to their procedure, non-CRPS patients were more likely to have had a perioperative consultation with the inpatient pain service (52.8%) compared to CRPS patients (33.3%), though this was not significant (p=0.2713) (Table 3). In addition, we compared the preoperative and 24 hour post-operative pain scores of patients in both cohorts. While CRPS patients generally experienced higher mean NRS scores compared to non-CRPS patients, these differences were not significant in the pre-operative (p=0.6745) or post-operative (p=0.6767) settings (Figure 1). Similarly, a two-way ANOVA showed that CRPS status did not significantly influence NRS scores over time (p=0.4363) nor was there an interaction effect between CRPS status and time on NRS scores (p=0.9538). We also examined if there were differences in the distributions of patients experiencing reductions in their NRS scores after SCS implantation. We found that 16.7% of CRPS patients experienced post-operative reductions in NRS scores by two or more points compared to 35.9% of non-CRPS patients. However, this difference also lacked statistical significance (p=0.3417).
Outcomes
We constructed univariate linear models between all of the demographic and intraoperative variables, and two relevant measures of clinical outcome and resource utilization: length of hospitalization and direct cost of stay (Table 4). This analysis elucidated several important trends. First, a preoperative diagnosis of CRPS was associated with significantly longer lengths of stay compared to preoperative diagnoses of back pain (p=0.0041), failed back syndrome (p=0.0305), and neuropathy (p=0.0233). Similarly, CRPS was associated with significantly higher direct costs compared to neuropathy (p=0.0127) and a strong but nonsignificant trend towards lower costs compared to back pain (p=0.0910) and failed back syndrome (p=0.2480). Unlike the demographic variables examined in this study, several intraoperative variables were found to significantly impact clinical outcomes on a univariate level across the study population (Table 4). For example, patients receiving monitored anesthesia care for their procedure, rather than general anesthesia, had significantly shorted lengths of stay at the hospital (p=0.0092) but not lower direct costs for their visit (p=0.6112). Similarly, increased
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CRPS Perioperative Outcomes administration of intraoperative opioids (oral morphine equivalents) was associated with higher direct costs of stay (p=0.0586) and extended duration of hospitalization (p=0.1322) that strongly trended towards significance. NRS pain scores determined pre-operatively and 24 hours post-operatively did not have significant relationships with the direct costs or lengths of stay at the hospital. There was, however, a positive relationship between the time spent in the PACU until discharge and length of hospitalization (p=0.0338) as well as direct costs (p=0.0102). There was also a strong association between an extended time in the PACU and both hospitalization length (p=0.0188) and direct costs (p=0.0645). Multivariate analysis revealed CRPS patients did not experience significantly increased odds of any adverse intraoperative outcomes, including greater blood loss (OR 1.85; 95%CI 0.24-14.50; p=0.5431), higher intraoperative opioid administration (OR 2.04; 95%CI 0.28-15.76; p=0.4788), extended length of anesthesia (OR 1.69; 95%CI 0.18-1.27; p=0.6144), or extended length of surgery (OR 0.75; 95%CI 0.03-7.04; p=0.8193) (Table 5). Conversely, our models suggested CRPS patients did experience significantly higher odds of poorer resource utilization outcomes, including extended time to PACU discharge (OR 22.03; 95%CI 1.33-745.65; p=0.0406) and higher direct costs (OR 9.64; 95%CI 1.35-97.84; p=0.0326).
Discussion
This study provides a detailed retrospective analysis of SCS implantation cases at our institution to better understand the impact of CRPS on the perioperative outcomes following these procedures. As the clinical use of SCS increases, it becomes increasingly important to identify determinants associated with risks of adverse outcomes. This study was motivated by a deficit in the literature regarding how a CRPS diagnosis influences the risks and costs associated with SCS implantation for chronic pain treatment, as well as information on the perioperative characteristics and management of CRPS patients. In addition, given the general limited coverage of CRPS in the literature, we also provide a comprehensive literature review (Supplementary Materials) to allow readers to more fully understand where the field stands and to better assess the results of this study in the context of existing work in the field.
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CRPS Perioperative Outcomes Study Population Characteristics
Several interesting trends were observed in the demographic and intraoperative characteristics. First, the CRPS and non-CRPS groups did not differ significantly in terms of their distributions in any of the demographic variables examined, including age, sex, race, BMI, ASA status, number of comorbidities present on admission, primary insurance type, or APRDRG scores for mortality risk or disease severity (Table 1). While we did not see any differences in cohort sex distributions, previous epidemiological studies report that CRPS is three times more frequent in females than males 17. In general, both cohorts shared similar intraoperative characteristics (Table 2). This was expected given the relatively standardized nature of SCS implantation procedure. We did not observe any significant differences in the lengths of time in the operating room, under anesthesia, or in surgery between the two patient groups. Similarly, the vast majority of patients in both cohorts were discharged to home after their hospitalizations.
Blood Loss and Methods of Anesthesia
A significant difference was seen in length of hospital stay when comparing patients who underwent their procedure under general anesthesia versus monitored anesthesia care (MAC) (Table 4). Patients undergoing their procedure with MAC had a decreased length of hospital stay (p=0.0092), which was expected given previous studies suggesting MAC has shorter recovery times and lower cost 18,19. Direct comparison of the cohorts by CRPS status demonstrated CRPS patients experienced significantly greater mean estimated blood loss during SCS implantation (p=0.0188). Though multivariate regression analyses suggested CRPS patients did not face significantly greater odds of increased blood loss compared to non-CRPS patients, it is possible this result may be due to the low number of patients available for analysis. The risk of surgical blood loss in CRPS patients is worth further investigation in larger studies given the clinical pathophysiology of CRPS. While the pathologic mechanism of CRPS remains under study, it is known that CRPS patients have distinct changes in their vasculature, including excessive vasodilation 20. It is thus possible that impaired vasoconstriction might increase blood loss during
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CRPS Perioperative Outcomes surgery, may therefore represent an important risk that patients and providers should be aware of prior to pursuing surgical intervention.
Opioid Use and Pain
While there have not been any studies examining perioperative pain scores or opioid use in CRPS patients, several studies in the literature have demonstrated opioid use in the perioperative setting can have an important impact on post-operative outcomes and resource utilization following surgical procedures involving the spine 21-23. Given that opioid therapy is common in the management of patients with chronic pain opting to undergo SCS implantation, particularly those with CRPS 24, we conducted a detailed analysis of opioid use in our study population. We found that all of the patients in both cohorts received chronic opioid therapy prior to their procedure (Table 3). This was a notable finding with an important clinical bearing given that preoperative opioid use is known to impact complication rates, costs, and hospitalization length in patients undergoing surgery 21-23. Because it is known that patients on chronic opioid therapy develop tolerance over time thereby requiring higher medication doses to achieve similar amounts of analgesic relief, we sought to compare the amounts of intraoperative opioid administration (oral morphine equivalents) between the cohorts as a proxy measure for relative opioid use perioperatively. We found that while CRPS patients were administered higher amounts of opioids on average intraoperatively, this difference was not statistically significant (Table 2). Comparison of pre-operative NRS pain scores, which would be expected to trend in a similar direction as opioid use, showed a similar pattern suggesting higher mean pre-operative pain scores in CRPS patients that lacked statistical significance (Table 3). In examining the post-operative pain scores of our study cohorts, we noted two interesting trends. First, we noted a general mean increase in the NRS pain scores of both cohorts in the immediate 24-hour post-operative period. The mean pain scores of the CRPS cohort increased from 5.7 preoperatively to 6.0 postoperatively, while those of the non-CRPS cohort transitioned from 4.8 preoperatively to 5.2 in the postoperative setting (Figure 2). Second, we observed a difference in the proportion of patients in each cohort experiencing a meaningful reduction in their post-operative pain scores (defined as two points or greater). In particular,
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CRPS Perioperative Outcomes 35.9% of non-CRPS patients experienced a 24-hour post-operative reduction in their NRS pain scores, compared to only 16.7% of CRPS patients (Table 3). Previous studies have shown increased preoperative opioid use is associated with increased pain and pain perception, particularly in comparison to opioid naïve patients 25,26. In a study by Dagal et al. in which more than half of the study population was receiving chronic opioid therapy, patients with chronic opioid use prior to surgery reported they spent more time in severe pain 27. Other studies have reported similar findings, including evidence that perioperative opioid consumption is associated with increased acute pain after surgeries and increased postoperative opioid use prior to discharge 26,28. In a similar vein, our study found both patient cohorts experienced a general increase in their immediate postoperative pain scores after noting that every patient in this study population received chronic opioid therapy preoperatively. In addition, the CRPS cohort, which received more intraoperative opioids on average, had a smaller proportion of patients who experienced a meaningful reduction in their pain scores in postoperatively. Taken together, these findings suggest perioperative opioid use may have important implications for pain reduction and patient management in the immediate postoperative setting.
Resource Utilization Metrics
Detailed examination of the times spent in various stages of hospitalization is an important step in understanding the determinants of patient outcomes and improving the quality of care in the hospital. Initial comparison of mean hospitalization times revealed CRPS patients tended to have significantly longer hospitalizations during the course of SCS implantation compared to non-CRPS patients (Table 2). Similarly, univariate analyses revealed a strong trend suggesting that a preoperative diagnosis of CRPS was associated with significantly greater lengths of stay in the hospital relative to all other pre-operative diagnosis groups analyzed, including back pain (p=0.0041), failed back syndrome (p=0.0305), and neuropathy (p=0.0233). Interestingly, at the multivariate level, we found CRPS patients had significantly higher odds of an extended PACU stay (p=0.0406). One potential reason behind this finding might be that given the complex pathophysiology of their condition, CRPS patients require more time to recover from their procedure or that they might require additional time and care to manage their pain in
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CRPS Perioperative Outcomes the immediate postoperative setting. Given previous studies suggesting lower perioperative opioid consumption may lead to reduced time to readiness for discharge from the PACU 29, it is also possible that increased opioid consumption in the CRPS population might be a contributing driver of their extended times in the PACU. Direct costs of hospitalization represent another critical measure of resource utilization by a patient population. Initial analysis showed that CRPS patients had a significantly higher mean direct cost associated with their hospitalization compared to non-CRPS patients (p=0.0437; Table 2). Univariate analysis revealed that the direct costs for treating implanting a spinal cord stimulator in a CRPS patient were, on average $4,312 higher than for patients undergoing SCS for back pain, $3,572 higher than for patients with failed back syndrome, and $6,941 higher than for patients with neuropathy (Table 4). When pooling all patients by CRPS status and controlling for key demographic, intraoperative, and comorbidity variables, we still observed a robust trend suggesting that CRPS resulted in significantly higher odds of direct costs of hospitalization (p=0.0326; Table 5). Previous studies that examined the cost-effectiveness of SCS for different chronic pain etiologies have also reported that, while SCS did result in higher quality adjusted life years (QALYs) compared to medical management in CRPS patients (4.24 vs. 2.12), there was a relatively higher cost per QALY gained for CRPS patients compared to non-CRPS patients30. While the higher costs associated with CRPS might be related to the significantly extended times to PACU discharge observed in this cohort, it is also possible that a lack of power in this present study resulted in failure to detect significance in certain periprocedural outcomes that would influence cost or that this result was related to a periprocedural variable we could not reliably evaluate with our dataset, such as total postoperative opioid administration. Previous studies have noted that the increased acute postoperative pain experienced by patients with a history of preoperative chronic opioid therapy may ultimately contribute to poorer outcomes such as prolonged hospitalizations, higher direct costs, and increased readmission rates.31 Accordingly, in this present study, we conducted a univariate analysis across our entire study population to determine if a relationship existed between total intraoperative opioid administration and length of hospitalization and direct costs (Table 4). Interestingly, we found that total intraoperative opioid administration showed strong trends towards increased hospitalization length (p=0.1322) and direct costs (p=0.0586) that narrowly missed statistical significance. Given the clinical importance of this topic, we believe these findings warrant
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CRPS Perioperative Outcomes further investigation in larger prospective studies, as better treatment regimens for opioid management in these patient populations may represent opportunities for cost savings and improved resource utilization.
Limitations
Despite the thorough nature of our analyses, no statistical technique can eliminate certain types of bias inherent in retrospective data. We acknowledge that bias from selection, reporting, omitted variables, and even random chance could be influencing our statistical comparisons. We also acknowledge that the small sample size of patients in our analysis may have limited our ability to draw certain conclusions from the insights gained from these analyses. The sample size likely limited the power of the study and may have hindered the ability of our analyses to detect statistically significant differences between the study cohorts. This would play a particularly important role in variables with small effect sizes. Finally, our analyses were performed on data obtained from a single institution. As with other single-center studies, protocols and practices specific to the institution may influence certain outcomes and may limit the external generalizability. As such, the results from this single-center study should not be solely relied upon to enact protocols and payor policies for these patients and procedures. Future studies are necessary to follow up on the results from this study and further characterize the perioperative risk profile of CRPS patients in the setting of SCS implantation.
Conclusion
This study examined how CRPS status and other intraoperative variables influenced primary and secondary outcomes following SCS implantation procedures, and is the first to examine the impact of CRPS on the clinical outcomes and cost of SCS implantation in the inpatient setting. CRPS patients may face particularly difficult recoveries following spine surgery. The development of more effective protocols for managing these patients will require a better understanding of the unique problems and risks they may face in the perioperative period. This is important in light of the increasing use of SCS in the treatment of CRPS and other
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CRPS Perioperative Outcomes chronic pain conditions. Taken together, our results suggest CRPS may be an important determinant of primary and secondary outcomes following SCS implantation and poses certain risks physicians must be aware of when caring for this patient population.
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CRPS Perioperative Outcomes Acknowledgements: None
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CRPS Perioperative Outcomes References 1. 2.
3.
4. 5. 6. 7. 8. 9. 10. 11.
12. 13.
14.
15. 16.
17.
18.
Resmini G, Ratti C, Canton G, Murena L, Moretti A, Iolascon G. Treatment of complex regional pain syndrome. Clin Cases Miner Bone Metab. 2015;12(Suppl 1):26-30. Krans-Schreuder HK, Bodde MI, Schrier E, et al. Amputation for long-standing, therapyresistant type-I complex regional pain syndrome. J Bone Joint Surg Am. 2012;94(24):2263-2268. Bodde MI, Dijkstra PU, den Dunnen WF, Geertzen JH. Therapy-resistant complex regional pain syndrome type I: to amputate or not? J Bone Joint Surg Am. 2011;93(19):1799-1805. Schwartzman RJ, McLellan TL. Reflex sympathetic dystrophy. A review. Arch Neurol. 1987;44(5):555-561. Ochoa JL. Essence, investigation, and management of "neuropathic" pains: hopes from acknowledgment of chaos. Muscle Nerve. 1993;16(10):997-1008. Sundaraj SR, Johnstone C, Noore F, Wynn P, Castro M. Spinal cord stimulation: a sevenyear audit. J Clin Neurosci. 2005;12(3):264-270. Barolat G, Sharan AD. Future trends in spinal cord stimulation. Neurol Res. 2000;22(3):279-284. Deer TR. Current and future trends in spinal cord stimulation for chronic pain. Curr Pain Headache Rep. 2001;5(6):503-509. Kumar K, Rizvi S. Historical and present state of neuromodulation in chronic pain. Curr Pain Headache Rep. 2014;18(1):387. Kunnumpurath S, Srinivasagopalan R, Vadivelu N. Spinal cord stimulation: principles of past, present and future practice: a review. J Clin Monit Comput. 2009;23(5):333-339. Robaina FJ, Rodriguez JL, de Vera JA, Martin MA. Transcutaneous electrical nerve stimulation and spinal cord stimulation for pain relief in reflex sympathetic dystrophy. Stereotactic and functional neurosurgery. 1989;52(1):53-62. Kumar K, Nath RK, Toth C. Spinal cord stimulation is effective in the management of reflex sympathetic dystrophy. Neurosurgery. 1997;40(3):503-508; discussion 508-509. Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M. Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: five-year final follow-up of patients in a randomized controlled trial. J Neurosurg. 2008;108(2):292-298. Kemler MA, De Vet HC, Barendse GA, Van Den Wildenberg FA, Van Kleef M. The effect of spinal cord stimulation in patients with chronic reflex sympathetic dystrophy: two years' follow-up of the randomized controlled trial. Ann Neurol. 2004;55(1):13-18. Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med. 2000;343(9):618-624. Visnjevac O, Costandi S, Patel BA, et al. A Comprehensive Outcome-Specific Review of the Use of Spinal Cord Stimulation for Complex Regional Pain Syndrome. Pain Pract. 2017;17(4):533-545. Veldman PH, Reynen HM, Arntz IE, Goris RJ. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet. 1993;342(8878):10121016. Sohn HM, Ryu JH. Monitored anesthesia care in and outside the operating room. Korean J Anesthesiol. 2016;69(4):319-326.
14
CRPS Perioperative Outcomes 19.
20. 21.
22.
23.
24.
25.
26. 27.
28. 29.
30. 31.
Ben-Dor I, Looser PM, Maluenda G, et al. Transcatheter aortic valve replacement under monitored anesthesia care versus general anesthesia with intubation. Cardiovasc Revasc Med. 2012;13(4):207-210. Marinus J, Moseley GL, Birklein F, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10(7):637-648. Martini ML, Nistal DA, Deutsch BC, Caridi JM. Characterizing the risk and outcome profiles of lumbar fusion procedures in patients with opioid use disorders: a step toward improving enhanced recovery protocols for a unique patient population. Neurosurg Focus. 2019;46(4):E12. Cron DC, Englesbe MJ, Bolton CJ, et al. Preoperative Opioid Use is Independently Associated With Increased Costs and Worse Outcomes After Major Abdominal Surgery. Ann Surg. 2017;265(4):695-701. Jain N, Phillips FM, Weaver T, Khan SN. Preoperative Chronic Opioid Therapy: A Risk Factor for Complications, Readmission, Continued Opioid Use and Increased Costs After One- and Two-Level Posterior Lumbar Fusion. Spine (Phila Pa 1976). 2018;43(19):1331-1338. Bass C, Yates G. Complex regional pain syndrome type 1 in the medico-legal setting: High rates of somatoform disorders, opiate use and diagnostic uncertainty. Med Sci Law. 2018;58(3):147-155. Hina N, Fletcher D, Poindessous-Jazat F, Martinez V. Hyperalgesia induced by low-dose opioid treatment before orthopaedic surgery: An observational case-control study. Eur J Anaesthesiol. 2015;32(4):255-261. Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014;112(6):991-1004. Dagal A, Lesnik I, Bentov N, et al. Using a perioperative enhanced recovery care pathway for major spine surgery (PERMS) to improve pain management & patientreported outcomes. The Journal of Pain. 2016;17(4):S89. Myers J, Compton P. Addressing the Potential for Perioperative Relapse in Those Recovering from Opioid Use Disorder. Pain Med. 2018;19(10):1908-1915. Soffin EM, Wetmore DS, Beckman JD, et al. Opioid-free anesthesia within an enhanced recovery after surgery pathway for minimally invasive lumbar spine surgery: a retrospective matched cohort study. Neurosurg Focus. 2019;46(4):E8. Kumar K, Rizvi S. Cost-Effectiveness of Spinal Cord Stimulation Therapy in Management of Chronic Pain. Pain Medicine. 2013;14:1631-1649. Gupta A, Nizamuddin J, Elmofty D, et al. Opioid Abuse or Dependence Increases 30-day Readmission Rates after Major Operating Room Procedures: A National Readmissions Database Study. Anesthesiology. 2018;128(5):880-890.
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CRPS Perioperative Outcomes Figure Legends
Figure 1. Flowchart with inclusion and exclusion criteria that yielded the patient cases comprising the study population. CRPS= complex regional pain syndrome.
Figure 2. Comparison of pre- and post-operative pain scores by CRPS status (mean ± SEM). The CRPS cohort had higher scores on the NRS pain scale before and immediately after SCS implantation compared to non-CRPS patients. Both cohorts also had slightly higher mean pain scores in the immediate 24 hour post-operative period compared to their pre-operative baselines. CRPS= complex regional pain syndrome; NRS= numeric rating scale; SEM= standard error of the mean.
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Age (Mean ± SEM) Gender (%) Male Female Race (%) White Black Other BMI (Mean ± SEM) ASA Status (%) I II III IV Comorbidities (Mean ± SEM) Primary Insurance Type (%) Private Medicare Medicaid Other APRDRG Severity (%) Minor Loss of Function Moderate Loss of Function Major Loss of Function APRDRG Mortality (%) Minor Likelihood of Dying Moderate Likelihood of Dying Major Likelihood of Dying
CRPS (N=9) 44.00 ± 5.41
Non-CRPS (N=72) 54.54 ± 1.95
3 (33.33) 6 (66.67)
33 (45.83) 39 (54.17)
P Value 0.0745 0.7241
0.4736 3 (33.3) 2 (22.2) 4 (44.5) 29.2 ± 2.3
39 (54.2) 13 (18.1) 20 (27.8) 29.3 ± 0.9
1 (11.1) 3 (33.3) 4 (44.5) 1 (11.1) 1.2 ± 0.4
1 (1.4) 28 (38.9) 42 (58.3) 1 (1.4) 2.5 ± 0.3
5 (55.6) 1 (11.1) 0 (0) 3 (33.3) N=9 7 (77.8) 2 (22.2) 0 (0) N=9 8 (88.9) 1 (11.1) 0 (0)
21 (29.2) 34 (47.2) 4 (5.5) 13 (18.1) N=68 40 (58.8) 27 (39.7) 1 (1.5) N=68 57 (83.8) 9 (13.2) 2 (2.9)
0.9706 0.0912
0.1443 0.1331
0.5365
0.8536
Table 1. Demographics of the study population by CRPS status APRDRG= All Patients Refined Diagnosis Related Groups; ASA= American Society of Anesthesiologists physical status classification system; BMI= Body Mass Index; CRPS = Chronic Regional Pain Syndrome; SEM= Standard Error of the Mean. P<0.05 was used as a threshold for statistical significance.
CRPS (N=9) 1.5 ± 0.2
Non-CRPS (N=72) 1.6 ± 0.1
2 (22.2) 7 (77.8)
39 (54.2) 33 (45.8)
113.3 ± 14.6
90.6 ± 6.7
8 (88.9) 0 (0) 1 (11.1)
70 (97.2) 1 (1.4) 1 (1.4)
Direct Costs (Mean ± SEM)
39286 ± 2266
34320 ± 808
0.0437
Length of Anesthesia, minutes (Mean ± SEM)
217.2 ± 17.46
215.4 ± 7.02
0.9295
Time in OR, minutes (Mean ± SEM)
204.6 ± 17.99
204.8 ± 6.94
0.9914
Length of Surgery, minutes (Mean ± SEM)
131.7 ± 10.16
132.1 ± 4.48
0.9732
Estimated Blood Loss (Mean ± SEM)
98.33 ± 76.01
28.13 ± 4.94
0.0188
3.44 ± 1.54
1.57 ± 0.13
0.0044
CRPS (N=4) 323.5 ± 77.8
Non-CRPS (N=61) 277.8 ± 23.9
P Value 0.6345
2 (50)
15 (24.6)
0.2783
Number of Levels Implanted (Mean ± SEM) Method of Anesthesia (%) Monitored Anesthesia Care General Intraoperative Opioid Administration, Oral Morphine Equivalents (Mean ± SEM) Discharge Disposition (%) Home Skilled Nursing Facility Other
Length of Hospital Stay, days (Mean ± SEM)
Time to PACU Discharge, minutes (Mean ± SEM) Extended Time in PACU (%)
P Value 0.6905 0.0877
0.1832 0.1974
Table 2. Perioperative characteristics of the study population by CRPS status CRPS = Chronic Regional Pain Syndrome; OR= Operating Room; SEM= Standard Error of the Mean. P<0.05 was used as a threshold for statistical significance.
CRPS (N=9) 9 (100)
Non-CRPS (N=72) 72 (100)
P Value >0.9999
3 (33.3)
38 (52.8)
0.2713
CRPS (N=6) 5.7 ± 1.6
Non-CRPS (N=64) 4.8 ± 0.4
P Value 0.6745
24-hour Post-Operative VAS Pain Scores (Mean ± SEM)
6.0 ± 0.9
5.2 ± 0.4
0.6767
Post-Operative Reduction in VAS Score ε2
1 (16.7)
23 (35.9)
0.3417
Pre-Operative Chronic Opioid Therapy (%) Pain Consult Rates (%)
Pre-Operative VAS Pain Scores (Mean ± SEM)
Table 3. Pre- and post-operative pain characteristics of the study population by CRPS status CRPS = Chronic Regional Pain Syndrome; PACU= Post-Anesthesia Care Unit; SEM= Standard Error of the Mean; VAS= Visual Analogue Scale for Pain. P<0.05 was used as a threshold for statistical significance.
Length of Hospital Stay
Age
Direct Costs Coefficient P Value (95%CI)
Coefficient (95%CI)
P Value
-0.02 (-0.04 - 0.01)
0.1451
8.9 (-84.7-102.4)
0.8508
-0.15 (-1.00 - 0.70)
0.7251
-1316 (-4432 - 1801)
0.4032
Gender (Reference: Female) Male Race (Reference: White) Black Other
-0.11 (-1.26 - 1.03) 0.29 (-0.69 - 1.26) 0.03 (-0.04 - 0.09)
BMI
0.8436 0.5603
0.4032
2043 (-2147 - 6232) 2139 (-1425 - 5703) 162.4 (-62.2 - 386.9)
0.3352 0.2366
0.1541
ASA Status (Reference: I) II III IV
1.00 (-1.78 - 3.78) 0.67 (-2.08 - 3.43) 0.50 (-3.31 - 4.31)
0.4765 0.6288 0.7957
-2293 (-12447 - 7860) -1006 (-11058 - 9046) -9042 (-22959 - 4875)
0.6540 0.8437 0.2004
Preoperative Diagnosis (Reference: CRPS) Back Pain Failed Back Syndrome Neuropathy
Number of Comorbidities
-1.99 (-3.34 - -0.65) -1.81 (-3.44 - -0.17) -1.68 (-3.13 - 0.23) 0.02 (-0.1 - 0.2)
0.0041 0.0305 0.0233
0.7832
-4312 (-9328 - 704) -3572 (-9683 - 2539) -6941 (-12358 - 1523)
0.2480
316.9 (-299.5 - 933.2)
0.3093
0.0910
0.0127
APRDRG Severity (Reference: Minor Functional Loss) Moderate Functional Loss Major Functional Loss APRDRG Mortality (Reference: Minor)
-0.20 (-1.12 - 0.73) -0.85 (-4.80 - 3.10)
0.6732 0.6694
-1863 (-5017 - 1290) -1594 (-15090 - 11902)
0.2432 0.8156
Moderate Likelihood of Dying Major Likelihood of Dying
-0.10 (-1.43 - 1.23) -0.80 (-3.60 - 2.00)
0.8816 0.5721
-512 (-5088 - 4064) -1032 (-10704 - 8639)
0.8249 0.8327
Primary Insurance Type (Reference: Private) Medicare Medicaid Other
-0.26 (-1.24 - 0.71) -0.81 (-2.83 - 1.21) 0.63 (-0.57 - 1.82)
0.5907 0.4284 0.2975
-3780 (-7296 - -265) 2050 (-5242 - 9342) 24.7 (-4289 - 4339)
0.0354 0.5773 0.9909
-0.12 (-0.74 - 0.49)
0.6918
-481.5 (-3227.0 - 2264.1)
0.7272
-1.08 (-1.89 - -0.28)
0.0092
-796.4 (-3902 - 2310)
0.6112
Total Intraoperative Opioid Administration (Oral Morphine Equivalents)
0.006 (-0.002 - 0.013)
0.1322
26.3 (-0.9 – 53.6)
0.0586
Length of Anesthesia
0.003 (-0.005 - 0.010)
0.4983
-13.0 (-39.5 - 13.6)
0.3351
Time in OR
0.002 (-0.005 - 0.009)
0.5699
-14.5 (-41.2 - 12.3)
0.2852
Length of Surgery
0.003 (-0.008 - 0.014)
0.6005
-36.3 (-77.8 – 5.1)
0.0849
Estimated Blood Loss
0.001 (-0.004 - 0.006)
0.5977
-2.7 (-21.0 - 15.7)
0.7745
Received Pain Consult
-0.225 (-0.755 – 0.305)
0.4013
3335 (-2127 – 8798)
0.2278
Pre-Operative VAS Pain Scores
0.036 (-0.039 – 0.111)
0.3411
46.4 (-399.0 – 491.7)
0.8361
Post-Operative VAS Pain Scores
-0.009 (-0.090 – 0.073)
0.8280
-347.8 (-821.1 – 125.6)
0.1472
Time in PACU Until Discharge
0.002 (0.0001 – 0.003)
0.0338
6.4 (-2.7 – 15.4)
0.1651
0.73 (0.12 – 1.33)
0.0188
3499 (-216 – 7215)
0.0645
Number of Levels Implanted Method of Anesthesia (Reference: General) Monitored Anesthesia Care
Extended Time in PACU
Table 4. Univariate regression models evaluating the relationship between certain perioperative variables and various measures of clinical outcome in the total study population undergoing spinal cord stimulator implantation. APRDRG= All Patients Refined Diagnosis Related Groups; ASA= American Society of Anesthesiologists physical status classification system; BMI= Body Mass Index; CI = Confidence Interval; CRPS = Chronic Regional Pain Syndrome; PACU= Post-Anesthesia Care Unit; VAS= Visual Analogue Scale for Pain. P<0.05 was used as a threshold for statistical significance.
Intraoperative Outcomes Outcome Greater Blood Loss Higher Intraoperative Opioid Administration (Morphine Equivalents) Extended Length of Anesthesia Extended Length of Surgery
OR (95%CI) 1.85 (0.24-14.50) 2.04 (0.28-15.76) 1.69 (0.18-1.27) 0.75 (0.03-7.04)
Secondary Outcomes and Resource Utilization Metrics Outcome OR (95%CI) Extended Hospitalization 2.42 (0.40-1.46) 22.03 (1.33Extended PACU Discharge 745.65) Reduced 24 Hour Post-Operative VAS Pain Score 1.21 (0.11-10.58) Higher Direct Costs 9.64 (1.35-97.84)
P Value 0.5431 0.4788 0.6144 0.8193
P Value 0.3261 0.0406 0.8645 0.0326
Table 5. Multivariate logistic regression models evaluating the impact of CRPS status on relevant intraoperative and resource utilization measures Models control for demographic variables, including age, sex, race, BMI, primary payer status, spinal levels and comorbidities, which included smoking history, alcohol use, anemia, arthritis, heart failure, chronic lung disease, hyperlipidemia, depression, diabetes mellitus, drug abuse, hypertension, hypothyroid, liver disease, lymphoma, metastatic disease, obesity, cardiovascular disease, renal failure, weight loss, sleep apnea, osteoporosis, and other neurological disorders. BMI= Body Mass Index; CI= Confidence Interval; CRPS= Chronic Regional Pain Syndrome; PACU= Post-Anesthesia Care Unit; OR= Odds Ratio; VAS= Visual Analogue Scale for Pain. P<0.05 was used as a threshold for statistical significance.
Abbreviation List: ANOVA - Analysis of Variance APRDRG - All Patients Refined Diagnosis Related Groups ASA - American Society of Anesthesiologists BMI - Body mass index CRPS - Complex Regional Pain Syndrome MAC - Monitored anesthesia care NRS - Numeric Rating Scale PACU - Post-anesthesia care unit QALY – Quality Adjusted Life Year SCS - Spinal cord stimulation VIF - Variance inflation factor
Abbreviation List: Michael Martini: Conceptualization, Methodology, Formal Analysis, Visualization, WritingOriginal Draft. John Caridi: Writing- Reviewing and Editing. Lawrence Zeldin: Data Curation, Formal Analysis, Writing- Original Draft. Sean Neifert: Data Curation, Writing- Reviewing and Editing. Dominic Nistal: Writing- Reviewing and Editing. Jinseong Kim: Data Curation, Formal Analysis. Yury Khelemsky: Writing- Reviewing and Editing. Jonathan Gal: WritingReviewing and Editing
S1878-8750(20)30069-3
DOI:
https://doi.org/10.1016/j.wneu.2020.01.061
Reference:
WNEU 14091
To appear in:
World Neurosurgery
Received Date: 27 November 2019 Revised Date:
7 January 2020
Accepted Date: 8 January 2020
Please cite this article as: Martini ML, Caridi JM, Zeldin L, Neifert SN, Nistal DA, Kim JD, Khelemsky Y, Gal JS, Perioperative Outcomes of Spinal Cord Stimulator Placement in Patients with Complex Regional Pain Syndrome (CRPS) Compared to Patients Without CRPS, World Neurosurgery (2020), doi: https:// doi.org/10.1016/j.wneu.2020.01.061. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Elsevier Inc. All rights reserved.
Perioperative Outcomes of Spinal Cord Stimulator Placement in Patients with Complex Regional Pain Syndrome (CRPS) Compared to Patients Without CRPS Michael L. Martini, PhD1 John M. Caridi, MD1 Lawrence Zeldin, BA1 Sean N. Neifert, BS1 Dominic A. Nistal, BA1 Jinseong D. Kim, BA1 Yury Khelemsky, MD2 and Jonathan S. Gal, MD2 1
Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY
10029 2
Department of Anesthesiology, Icahn School of Medicine at Mount Sinai, New York,
NY 10029
Corresponding Author Contact Information: Jonathan S. Gal, MD, FASA Department of Anesthesiology Icahn School of Medicine at Mount Sinai One Gustave L. Levy Place, Box 1010 New York, NY 10029 (email: [email protected])
Keywords Complex Regional Pain Syndrome; Spinal Cord Stimulation; Perioperative Outcomes; Intraoperative Outcomes; Resource Utilization; Opioid Use; Numeric Rating Scale;
Running Head: CRPS Perioperative Outcomes
CRPS Perioperative Outcomes Introduction Complex Regional Pain Syndrome (CRPS) is a multifaceted disorder proposed to arise from an abnormal tissue injury response. CRPS is characterized by signs of neurogenic inflammation, maladaptive neuroplasticity, and vasomotor dysfunction, which result in chronic, severe pain and disability. Currently, CRPS can be further subdivided as CRPS-1 or CRPS-2, with the latter diagnosis featuring an identifiable nerve lesion. While the pathologic mechanism behind CRPS remains unclear, multiple treatments have been attempted, including physical and occupational therapy, steroids,1 sympathetic nerve blocks, and amputation of affected limbs 2,3. Most treatments, however, have less than favorable results 4,5. An increasingly utilized treatment, spinal cord stimulation (SCS) has been shown to be effective at managing multiple forms of chronic pain 6, including chronic radiculopathies and pain due to ischemia 7-10. It has also been used to minimize CRPS-induced pain,11,12 with prospective cohort studies showing it is more effective than physical therapy at minimizing pain in the affected limb and most patients are pleased with the outcome 13-15. Despite the increasing use of SCS in the treatment of CRPS and other chronic pain conditions, it remains unclear how CRPS status affects outcomes following SCS implantation surgery. Evidence exists of the effectiveness of SCS in CRPS treatment, with indications that over time it results in pain relief, reduction in pain scores, quality of life improvement, and patient satisfaction 16. Nevertheless, as with any invasive procedure, there are risks and costs associated with SCS procedures. As SCS use becomes more common, it becomes increasingly important to evaluate the patients for which the procedure would be most effective and to understand the drivers of outcomes and cost in various patient populations. To our knowledge, no study to date has examined the impact of CRPS on the perioperative outcomes of patients undergoing surgical implantation of an SCS or compared these outcomes to those of patients without CRPS undergoing SCS implantation. In this study, we seek to characterize the specific risks and outcomes of SCS implantation and determine how CRPS affects these outcomes relative to other chronic pain etiologies. We also provide a comprehensive literature review to supplement our study and provide context for where the field stands.
Methods
1
CRPS Perioperative Outcomes
Data Source, Inclusion Criteria, and Patient Stratification
This retrospective study was approved by our institutional review board and informed consent was waived. Our records were retrospectively queried for all cases involving an SCS between 2008-2016 utilizing the ICD-10 diagnosis and procedure codes from the administrative claims data. This yielded 156 cases of SCS implantation and removal procedures performed in the inpatient and outpatient settings. SCS removal cases were excluded (N=21), as were cases performed in an outpatient setting because they lacked a complete set of variables for full analysis in this study, including pertinent outcome metrics (N=54). This yielded 81 cases of inpatient SCS implantation procedures (Figure 1). These cases were organized according to preoperative diagnosis, including 9 cases involving a CRPS diagnosis and 72 other cases performed for other indications (e.g. back pain, failed back syndrome, neuropathy). All cases were individually reviewed to confirm the correct clinical diagnoses and that standard diagnostic criteria were met. In the US, the only indications for SCS are pain syndromes. Therefore, it was confirmed that all patients in this study presented with symptoms of severe, intractable pain after failing conservative management. All patients underwent a neuropsychiatric evaluation prior to one-week trial of percutaneous stimulation and reported significant pain relief, confirming efficacy, before opting to undergo permanent implantation. Five surgeons at our institution performed the nine CRPS cases. All of the surgeons were fellowship-trained faculty with appointments in the Department of Neurosurgery. Review of the intraoperative reports confirmed that each of these cases followed the same general protocol, including details of patient positioning, instrumentation, methods for locating the spinal levels of interest, and methods for device placement.
Covariates
Demographic data was collected for each patient’s age, sex, race, body mass index (BMI), American Society of Anesthesiologists (ASA) status classification, comorbidities, primary insurance payer, and All Patients Refined Diagnosis Related Groups (APRDRG) scores for mortality risk and severity of illness. In addition, several intraoperative and perioperative
2
CRPS Perioperative Outcomes variables were also obtained for each patient. These included the number of levels implanted, blood loss (measured as the output from all suction devices during surgery), method of anesthesia, total oral morphine equivalents received intraoperatively, total length of anesthesia time, total time in the operating room, surgery duration, and time to discharge from the postanesthesia care unit (PACU). Clinical variables pertaining to pain management in these patients were also obtained when available, including whether patients received chronic opioid therapy pre-operatively and if consultation with the inpatient pain service was pursued. In addition, preoperative and 24-hour post-operative Numeric Rating Scale (NRS) pain scores for each patient were noted.
Outcomes
Increased estimated blood loss, greater intraoperative opioid use, extended lengths of anesthetic or surgical times, extended hospitalization, extended time in the PACU, reduction in post-operative NRS pain scores, and higher direct costs were considered as clinical outcome variables. Each of these categorical outcomes were defined as cases greater than the 75th percentile across the entire study population for each category.
Statistical Analysis
R 3.4.1 (The R Foundation for Statistical Computing, 2016) was used for statistical analysis in this study. Chi-Squared tests were implemented to analyze categorical variables. Fisher’s Exact test was used for contingency tables containing an expected count less than one under the null hypothesis of independence. The means for any continuous variables were compared using two-sided, two-sample T tests. A two-way Analysis of Variance (ANOVA) was performed to analyze any interactions or effects between mulitple groups of two independent variables on a dependent variable and each other, such as CRPS status, time, and NRS pain scores. Univariate regression models were constructed to better understand the relationships between certain perioperative variables and various measures of clinical outcome. Finally, multivariable regression models were built to control for demographic and comorbidity variables significantly differing between the two groups or if they were previously known factors shown to
3
CRPS Perioperative Outcomes affect surgical outcomes. In this particular study, models controlled for age, sex, race, primary insurance payer, comorbidity burden, and number of spinal levels operated. A multivariate model was built for each intraoperative and resource utilization outcome of interest. A p value less than 0.05 was set for determining statistical significance. The variance inflation factor (VIF) evaluated multicollinearity in the models.
Results
Demographics
A total of 81 patients undergoing implantation of an SCS device in an inpatient setting were included in this study, of which nine patients (11.1%) carried a preoperative diagnosis of CRPS. Eight of the nine CRPS cases involved one or both of the lower extremities. As such, nearly all of the SCS implantation procedures involved the lower thoracic or upper lumbar regions of the spine. Only one of the CRPS cases involved the upper extremities. The patient cohorts generally shared very similar demographic characteristics, particularly with respect to age (p=0.0745), gender (p=0.7241), race (p=0.4736), BMI (p=0.9706), and number of comorbidities (p=0.1443) (Table 1). Both cohorts also displayed similar distributions in their APRDRG scores for mortality risk (p=0.8536) and disease severity (p=0.5365). Both groups also had similar numbers of spinal levels with SCS placement (p=0.6905) and experienced similar durations of surgery (p=0.9732), time in the operating room (p=0.9914), and time under anesthesia (p=0.9295) (Table 2). Though CRPS patients experienced greater mean times in the PACU until discharge (323.5 ± 77.8 minutes) compared to non-CRPS patients (277.8 ± 23.9 minutes), the difference was not statistically significant (p=0.6345). Although neither cohort experienced an intraoperative complication, the CRPS group, however, did experience significantly higher estimated blood loss during the procedure (p=0.0188), longer length of hospitalization (p=0.0044), and incurred greater direct costs (p=0.0437) on average compared to patients without CRPS. While CRPS patients did receive higher levels intraoperative oral morphine equivalents on average (113.3 ± 14.6) compared to all other patients (90.6 ± 6.7), this trend was not statistically significant (p=0.1832).
4
CRPS Perioperative Outcomes While every patient in both CRPS and non-CRPS cohorts had received pre-operative chronic opioid therapy prior to their procedure, non-CRPS patients were more likely to have had a perioperative consultation with the inpatient pain service (52.8%) compared to CRPS patients (33.3%), though this was not significant (p=0.2713) (Table 3). In addition, we compared the preoperative and 24 hour post-operative pain scores of patients in both cohorts. While CRPS patients generally experienced higher mean NRS scores compared to non-CRPS patients, these differences were not significant in the pre-operative (p=0.6745) or post-operative (p=0.6767) settings (Figure 1). Similarly, a two-way ANOVA showed that CRPS status did not significantly influence NRS scores over time (p=0.4363) nor was there an interaction effect between CRPS status and time on NRS scores (p=0.9538). We also examined if there were differences in the distributions of patients experiencing reductions in their NRS scores after SCS implantation. We found that 16.7% of CRPS patients experienced post-operative reductions in NRS scores by two or more points compared to 35.9% of non-CRPS patients. However, this difference also lacked statistical significance (p=0.3417).
Outcomes
We constructed univariate linear models between all of the demographic and intraoperative variables, and two relevant measures of clinical outcome and resource utilization: length of hospitalization and direct cost of stay (Table 4). This analysis elucidated several important trends. First, a preoperative diagnosis of CRPS was associated with significantly longer lengths of stay compared to preoperative diagnoses of back pain (p=0.0041), failed back syndrome (p=0.0305), and neuropathy (p=0.0233). Similarly, CRPS was associated with significantly higher direct costs compared to neuropathy (p=0.0127) and a strong but nonsignificant trend towards lower costs compared to back pain (p=0.0910) and failed back syndrome (p=0.2480). Unlike the demographic variables examined in this study, several intraoperative variables were found to significantly impact clinical outcomes on a univariate level across the study population (Table 4). For example, patients receiving monitored anesthesia care for their procedure, rather than general anesthesia, had significantly shorted lengths of stay at the hospital (p=0.0092) but not lower direct costs for their visit (p=0.6112). Similarly, increased
5
CRPS Perioperative Outcomes administration of intraoperative opioids (oral morphine equivalents) was associated with higher direct costs of stay (p=0.0586) and extended duration of hospitalization (p=0.1322) that strongly trended towards significance. NRS pain scores determined pre-operatively and 24 hours post-operatively did not have significant relationships with the direct costs or lengths of stay at the hospital. There was, however, a positive relationship between the time spent in the PACU until discharge and length of hospitalization (p=0.0338) as well as direct costs (p=0.0102). There was also a strong association between an extended time in the PACU and both hospitalization length (p=0.0188) and direct costs (p=0.0645). Multivariate analysis revealed CRPS patients did not experience significantly increased odds of any adverse intraoperative outcomes, including greater blood loss (OR 1.85; 95%CI 0.24-14.50; p=0.5431), higher intraoperative opioid administration (OR 2.04; 95%CI 0.28-15.76; p=0.4788), extended length of anesthesia (OR 1.69; 95%CI 0.18-1.27; p=0.6144), or extended length of surgery (OR 0.75; 95%CI 0.03-7.04; p=0.8193) (Table 5). Conversely, our models suggested CRPS patients did experience significantly higher odds of poorer resource utilization outcomes, including extended time to PACU discharge (OR 22.03; 95%CI 1.33-745.65; p=0.0406) and higher direct costs (OR 9.64; 95%CI 1.35-97.84; p=0.0326).
Discussion
This study provides a detailed retrospective analysis of SCS implantation cases at our institution to better understand the impact of CRPS on the perioperative outcomes following these procedures. As the clinical use of SCS increases, it becomes increasingly important to identify determinants associated with risks of adverse outcomes. This study was motivated by a deficit in the literature regarding how a CRPS diagnosis influences the risks and costs associated with SCS implantation for chronic pain treatment, as well as information on the perioperative characteristics and management of CRPS patients. In addition, given the general limited coverage of CRPS in the literature, we also provide a comprehensive literature review (Supplementary Materials) to allow readers to more fully understand where the field stands and to better assess the results of this study in the context of existing work in the field.
6
CRPS Perioperative Outcomes Study Population Characteristics
Several interesting trends were observed in the demographic and intraoperative characteristics. First, the CRPS and non-CRPS groups did not differ significantly in terms of their distributions in any of the demographic variables examined, including age, sex, race, BMI, ASA status, number of comorbidities present on admission, primary insurance type, or APRDRG scores for mortality risk or disease severity (Table 1). While we did not see any differences in cohort sex distributions, previous epidemiological studies report that CRPS is three times more frequent in females than males 17. In general, both cohorts shared similar intraoperative characteristics (Table 2). This was expected given the relatively standardized nature of SCS implantation procedure. We did not observe any significant differences in the lengths of time in the operating room, under anesthesia, or in surgery between the two patient groups. Similarly, the vast majority of patients in both cohorts were discharged to home after their hospitalizations.
Blood Loss and Methods of Anesthesia
A significant difference was seen in length of hospital stay when comparing patients who underwent their procedure under general anesthesia versus monitored anesthesia care (MAC) (Table 4). Patients undergoing their procedure with MAC had a decreased length of hospital stay (p=0.0092), which was expected given previous studies suggesting MAC has shorter recovery times and lower cost 18,19. Direct comparison of the cohorts by CRPS status demonstrated CRPS patients experienced significantly greater mean estimated blood loss during SCS implantation (p=0.0188). Though multivariate regression analyses suggested CRPS patients did not face significantly greater odds of increased blood loss compared to non-CRPS patients, it is possible this result may be due to the low number of patients available for analysis. The risk of surgical blood loss in CRPS patients is worth further investigation in larger studies given the clinical pathophysiology of CRPS. While the pathologic mechanism of CRPS remains under study, it is known that CRPS patients have distinct changes in their vasculature, including excessive vasodilation 20. It is thus possible that impaired vasoconstriction might increase blood loss during
7
CRPS Perioperative Outcomes surgery, may therefore represent an important risk that patients and providers should be aware of prior to pursuing surgical intervention.
Opioid Use and Pain
While there have not been any studies examining perioperative pain scores or opioid use in CRPS patients, several studies in the literature have demonstrated opioid use in the perioperative setting can have an important impact on post-operative outcomes and resource utilization following surgical procedures involving the spine 21-23. Given that opioid therapy is common in the management of patients with chronic pain opting to undergo SCS implantation, particularly those with CRPS 24, we conducted a detailed analysis of opioid use in our study population. We found that all of the patients in both cohorts received chronic opioid therapy prior to their procedure (Table 3). This was a notable finding with an important clinical bearing given that preoperative opioid use is known to impact complication rates, costs, and hospitalization length in patients undergoing surgery 21-23. Because it is known that patients on chronic opioid therapy develop tolerance over time thereby requiring higher medication doses to achieve similar amounts of analgesic relief, we sought to compare the amounts of intraoperative opioid administration (oral morphine equivalents) between the cohorts as a proxy measure for relative opioid use perioperatively. We found that while CRPS patients were administered higher amounts of opioids on average intraoperatively, this difference was not statistically significant (Table 2). Comparison of pre-operative NRS pain scores, which would be expected to trend in a similar direction as opioid use, showed a similar pattern suggesting higher mean pre-operative pain scores in CRPS patients that lacked statistical significance (Table 3). In examining the post-operative pain scores of our study cohorts, we noted two interesting trends. First, we noted a general mean increase in the NRS pain scores of both cohorts in the immediate 24-hour post-operative period. The mean pain scores of the CRPS cohort increased from 5.7 preoperatively to 6.0 postoperatively, while those of the non-CRPS cohort transitioned from 4.8 preoperatively to 5.2 in the postoperative setting (Figure 2). Second, we observed a difference in the proportion of patients in each cohort experiencing a meaningful reduction in their post-operative pain scores (defined as two points or greater). In particular,
8
CRPS Perioperative Outcomes 35.9% of non-CRPS patients experienced a 24-hour post-operative reduction in their NRS pain scores, compared to only 16.7% of CRPS patients (Table 3). Previous studies have shown increased preoperative opioid use is associated with increased pain and pain perception, particularly in comparison to opioid naïve patients 25,26. In a study by Dagal et al. in which more than half of the study population was receiving chronic opioid therapy, patients with chronic opioid use prior to surgery reported they spent more time in severe pain 27. Other studies have reported similar findings, including evidence that perioperative opioid consumption is associated with increased acute pain after surgeries and increased postoperative opioid use prior to discharge 26,28. In a similar vein, our study found both patient cohorts experienced a general increase in their immediate postoperative pain scores after noting that every patient in this study population received chronic opioid therapy preoperatively. In addition, the CRPS cohort, which received more intraoperative opioids on average, had a smaller proportion of patients who experienced a meaningful reduction in their pain scores in postoperatively. Taken together, these findings suggest perioperative opioid use may have important implications for pain reduction and patient management in the immediate postoperative setting.
Resource Utilization Metrics
Detailed examination of the times spent in various stages of hospitalization is an important step in understanding the determinants of patient outcomes and improving the quality of care in the hospital. Initial comparison of mean hospitalization times revealed CRPS patients tended to have significantly longer hospitalizations during the course of SCS implantation compared to non-CRPS patients (Table 2). Similarly, univariate analyses revealed a strong trend suggesting that a preoperative diagnosis of CRPS was associated with significantly greater lengths of stay in the hospital relative to all other pre-operative diagnosis groups analyzed, including back pain (p=0.0041), failed back syndrome (p=0.0305), and neuropathy (p=0.0233). Interestingly, at the multivariate level, we found CRPS patients had significantly higher odds of an extended PACU stay (p=0.0406). One potential reason behind this finding might be that given the complex pathophysiology of their condition, CRPS patients require more time to recover from their procedure or that they might require additional time and care to manage their pain in
9
CRPS Perioperative Outcomes the immediate postoperative setting. Given previous studies suggesting lower perioperative opioid consumption may lead to reduced time to readiness for discharge from the PACU 29, it is also possible that increased opioid consumption in the CRPS population might be a contributing driver of their extended times in the PACU. Direct costs of hospitalization represent another critical measure of resource utilization by a patient population. Initial analysis showed that CRPS patients had a significantly higher mean direct cost associated with their hospitalization compared to non-CRPS patients (p=0.0437; Table 2). Univariate analysis revealed that the direct costs for treating implanting a spinal cord stimulator in a CRPS patient were, on average $4,312 higher than for patients undergoing SCS for back pain, $3,572 higher than for patients with failed back syndrome, and $6,941 higher than for patients with neuropathy (Table 4). When pooling all patients by CRPS status and controlling for key demographic, intraoperative, and comorbidity variables, we still observed a robust trend suggesting that CRPS resulted in significantly higher odds of direct costs of hospitalization (p=0.0326; Table 5). Previous studies that examined the cost-effectiveness of SCS for different chronic pain etiologies have also reported that, while SCS did result in higher quality adjusted life years (QALYs) compared to medical management in CRPS patients (4.24 vs. 2.12), there was a relatively higher cost per QALY gained for CRPS patients compared to non-CRPS patients30. While the higher costs associated with CRPS might be related to the significantly extended times to PACU discharge observed in this cohort, it is also possible that a lack of power in this present study resulted in failure to detect significance in certain periprocedural outcomes that would influence cost or that this result was related to a periprocedural variable we could not reliably evaluate with our dataset, such as total postoperative opioid administration. Previous studies have noted that the increased acute postoperative pain experienced by patients with a history of preoperative chronic opioid therapy may ultimately contribute to poorer outcomes such as prolonged hospitalizations, higher direct costs, and increased readmission rates.31 Accordingly, in this present study, we conducted a univariate analysis across our entire study population to determine if a relationship existed between total intraoperative opioid administration and length of hospitalization and direct costs (Table 4). Interestingly, we found that total intraoperative opioid administration showed strong trends towards increased hospitalization length (p=0.1322) and direct costs (p=0.0586) that narrowly missed statistical significance. Given the clinical importance of this topic, we believe these findings warrant
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CRPS Perioperative Outcomes further investigation in larger prospective studies, as better treatment regimens for opioid management in these patient populations may represent opportunities for cost savings and improved resource utilization.
Limitations
Despite the thorough nature of our analyses, no statistical technique can eliminate certain types of bias inherent in retrospective data. We acknowledge that bias from selection, reporting, omitted variables, and even random chance could be influencing our statistical comparisons. We also acknowledge that the small sample size of patients in our analysis may have limited our ability to draw certain conclusions from the insights gained from these analyses. The sample size likely limited the power of the study and may have hindered the ability of our analyses to detect statistically significant differences between the study cohorts. This would play a particularly important role in variables with small effect sizes. Finally, our analyses were performed on data obtained from a single institution. As with other single-center studies, protocols and practices specific to the institution may influence certain outcomes and may limit the external generalizability. As such, the results from this single-center study should not be solely relied upon to enact protocols and payor policies for these patients and procedures. Future studies are necessary to follow up on the results from this study and further characterize the perioperative risk profile of CRPS patients in the setting of SCS implantation.
Conclusion
This study examined how CRPS status and other intraoperative variables influenced primary and secondary outcomes following SCS implantation procedures, and is the first to examine the impact of CRPS on the clinical outcomes and cost of SCS implantation in the inpatient setting. CRPS patients may face particularly difficult recoveries following spine surgery. The development of more effective protocols for managing these patients will require a better understanding of the unique problems and risks they may face in the perioperative period. This is important in light of the increasing use of SCS in the treatment of CRPS and other
11
CRPS Perioperative Outcomes chronic pain conditions. Taken together, our results suggest CRPS may be an important determinant of primary and secondary outcomes following SCS implantation and poses certain risks physicians must be aware of when caring for this patient population.
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CRPS Perioperative Outcomes Acknowledgements: None
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CRPS Perioperative Outcomes References 1. 2.
3.
4. 5. 6. 7. 8. 9. 10. 11.
12. 13.
14.
15. 16.
17.
18.
Resmini G, Ratti C, Canton G, Murena L, Moretti A, Iolascon G. Treatment of complex regional pain syndrome. Clin Cases Miner Bone Metab. 2015;12(Suppl 1):26-30. Krans-Schreuder HK, Bodde MI, Schrier E, et al. Amputation for long-standing, therapyresistant type-I complex regional pain syndrome. J Bone Joint Surg Am. 2012;94(24):2263-2268. Bodde MI, Dijkstra PU, den Dunnen WF, Geertzen JH. Therapy-resistant complex regional pain syndrome type I: to amputate or not? J Bone Joint Surg Am. 2011;93(19):1799-1805. Schwartzman RJ, McLellan TL. Reflex sympathetic dystrophy. A review. Arch Neurol. 1987;44(5):555-561. Ochoa JL. Essence, investigation, and management of "neuropathic" pains: hopes from acknowledgment of chaos. Muscle Nerve. 1993;16(10):997-1008. Sundaraj SR, Johnstone C, Noore F, Wynn P, Castro M. Spinal cord stimulation: a sevenyear audit. J Clin Neurosci. 2005;12(3):264-270. Barolat G, Sharan AD. Future trends in spinal cord stimulation. Neurol Res. 2000;22(3):279-284. Deer TR. Current and future trends in spinal cord stimulation for chronic pain. Curr Pain Headache Rep. 2001;5(6):503-509. Kumar K, Rizvi S. Historical and present state of neuromodulation in chronic pain. Curr Pain Headache Rep. 2014;18(1):387. Kunnumpurath S, Srinivasagopalan R, Vadivelu N. Spinal cord stimulation: principles of past, present and future practice: a review. J Clin Monit Comput. 2009;23(5):333-339. Robaina FJ, Rodriguez JL, de Vera JA, Martin MA. Transcutaneous electrical nerve stimulation and spinal cord stimulation for pain relief in reflex sympathetic dystrophy. Stereotactic and functional neurosurgery. 1989;52(1):53-62. Kumar K, Nath RK, Toth C. Spinal cord stimulation is effective in the management of reflex sympathetic dystrophy. Neurosurgery. 1997;40(3):503-508; discussion 508-509. Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M. Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: five-year final follow-up of patients in a randomized controlled trial. J Neurosurg. 2008;108(2):292-298. Kemler MA, De Vet HC, Barendse GA, Van Den Wildenberg FA, Van Kleef M. The effect of spinal cord stimulation in patients with chronic reflex sympathetic dystrophy: two years' follow-up of the randomized controlled trial. Ann Neurol. 2004;55(1):13-18. Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med. 2000;343(9):618-624. Visnjevac O, Costandi S, Patel BA, et al. A Comprehensive Outcome-Specific Review of the Use of Spinal Cord Stimulation for Complex Regional Pain Syndrome. Pain Pract. 2017;17(4):533-545. Veldman PH, Reynen HM, Arntz IE, Goris RJ. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet. 1993;342(8878):10121016. Sohn HM, Ryu JH. Monitored anesthesia care in and outside the operating room. Korean J Anesthesiol. 2016;69(4):319-326.
14
CRPS Perioperative Outcomes 19.
20. 21.
22.
23.
24.
25.
26. 27.
28. 29.
30. 31.
Ben-Dor I, Looser PM, Maluenda G, et al. Transcatheter aortic valve replacement under monitored anesthesia care versus general anesthesia with intubation. Cardiovasc Revasc Med. 2012;13(4):207-210. Marinus J, Moseley GL, Birklein F, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10(7):637-648. Martini ML, Nistal DA, Deutsch BC, Caridi JM. Characterizing the risk and outcome profiles of lumbar fusion procedures in patients with opioid use disorders: a step toward improving enhanced recovery protocols for a unique patient population. Neurosurg Focus. 2019;46(4):E12. Cron DC, Englesbe MJ, Bolton CJ, et al. Preoperative Opioid Use is Independently Associated With Increased Costs and Worse Outcomes After Major Abdominal Surgery. Ann Surg. 2017;265(4):695-701. Jain N, Phillips FM, Weaver T, Khan SN. Preoperative Chronic Opioid Therapy: A Risk Factor for Complications, Readmission, Continued Opioid Use and Increased Costs After One- and Two-Level Posterior Lumbar Fusion. Spine (Phila Pa 1976). 2018;43(19):1331-1338. Bass C, Yates G. Complex regional pain syndrome type 1 in the medico-legal setting: High rates of somatoform disorders, opiate use and diagnostic uncertainty. Med Sci Law. 2018;58(3):147-155. Hina N, Fletcher D, Poindessous-Jazat F, Martinez V. Hyperalgesia induced by low-dose opioid treatment before orthopaedic surgery: An observational case-control study. Eur J Anaesthesiol. 2015;32(4):255-261. Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014;112(6):991-1004. Dagal A, Lesnik I, Bentov N, et al. Using a perioperative enhanced recovery care pathway for major spine surgery (PERMS) to improve pain management & patientreported outcomes. The Journal of Pain. 2016;17(4):S89. Myers J, Compton P. Addressing the Potential for Perioperative Relapse in Those Recovering from Opioid Use Disorder. Pain Med. 2018;19(10):1908-1915. Soffin EM, Wetmore DS, Beckman JD, et al. Opioid-free anesthesia within an enhanced recovery after surgery pathway for minimally invasive lumbar spine surgery: a retrospective matched cohort study. Neurosurg Focus. 2019;46(4):E8. Kumar K, Rizvi S. Cost-Effectiveness of Spinal Cord Stimulation Therapy in Management of Chronic Pain. Pain Medicine. 2013;14:1631-1649. Gupta A, Nizamuddin J, Elmofty D, et al. Opioid Abuse or Dependence Increases 30-day Readmission Rates after Major Operating Room Procedures: A National Readmissions Database Study. Anesthesiology. 2018;128(5):880-890.
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CRPS Perioperative Outcomes Figure Legends
Figure 1. Flowchart with inclusion and exclusion criteria that yielded the patient cases comprising the study population. CRPS= complex regional pain syndrome.
Figure 2. Comparison of pre- and post-operative pain scores by CRPS status (mean ± SEM). The CRPS cohort had higher scores on the NRS pain scale before and immediately after SCS implantation compared to non-CRPS patients. Both cohorts also had slightly higher mean pain scores in the immediate 24 hour post-operative period compared to their pre-operative baselines. CRPS= complex regional pain syndrome; NRS= numeric rating scale; SEM= standard error of the mean.
16
Age (Mean ± SEM) Gender (%) Male Female Race (%) White Black Other BMI (Mean ± SEM) ASA Status (%) I II III IV Comorbidities (Mean ± SEM) Primary Insurance Type (%) Private Medicare Medicaid Other APRDRG Severity (%) Minor Loss of Function Moderate Loss of Function Major Loss of Function APRDRG Mortality (%) Minor Likelihood of Dying Moderate Likelihood of Dying Major Likelihood of Dying
CRPS (N=9) 44.00 ± 5.41
Non-CRPS (N=72) 54.54 ± 1.95
3 (33.33) 6 (66.67)
33 (45.83) 39 (54.17)
P Value 0.0745 0.7241
0.4736 3 (33.3) 2 (22.2) 4 (44.5) 29.2 ± 2.3
39 (54.2) 13 (18.1) 20 (27.8) 29.3 ± 0.9
1 (11.1) 3 (33.3) 4 (44.5) 1 (11.1) 1.2 ± 0.4
1 (1.4) 28 (38.9) 42 (58.3) 1 (1.4) 2.5 ± 0.3
5 (55.6) 1 (11.1) 0 (0) 3 (33.3) N=9 7 (77.8) 2 (22.2) 0 (0) N=9 8 (88.9) 1 (11.1) 0 (0)
21 (29.2) 34 (47.2) 4 (5.5) 13 (18.1) N=68 40 (58.8) 27 (39.7) 1 (1.5) N=68 57 (83.8) 9 (13.2) 2 (2.9)
0.9706 0.0912
0.1443 0.1331
0.5365
0.8536
Table 1. Demographics of the study population by CRPS status APRDRG= All Patients Refined Diagnosis Related Groups; ASA= American Society of Anesthesiologists physical status classification system; BMI= Body Mass Index; CRPS = Chronic Regional Pain Syndrome; SEM= Standard Error of the Mean. P<0.05 was used as a threshold for statistical significance.
CRPS (N=9) 1.5 ± 0.2
Non-CRPS (N=72) 1.6 ± 0.1
2 (22.2) 7 (77.8)
39 (54.2) 33 (45.8)
113.3 ± 14.6
90.6 ± 6.7
8 (88.9) 0 (0) 1 (11.1)
70 (97.2) 1 (1.4) 1 (1.4)
Direct Costs (Mean ± SEM)
39286 ± 2266
34320 ± 808
0.0437
Length of Anesthesia, minutes (Mean ± SEM)
217.2 ± 17.46
215.4 ± 7.02
0.9295
Time in OR, minutes (Mean ± SEM)
204.6 ± 17.99
204.8 ± 6.94
0.9914
Length of Surgery, minutes (Mean ± SEM)
131.7 ± 10.16
132.1 ± 4.48
0.9732
Estimated Blood Loss (Mean ± SEM)
98.33 ± 76.01
28.13 ± 4.94
0.0188
3.44 ± 1.54
1.57 ± 0.13
0.0044
CRPS (N=4) 323.5 ± 77.8
Non-CRPS (N=61) 277.8 ± 23.9
P Value 0.6345
2 (50)
15 (24.6)
0.2783
Number of Levels Implanted (Mean ± SEM) Method of Anesthesia (%) Monitored Anesthesia Care General Intraoperative Opioid Administration, Oral Morphine Equivalents (Mean ± SEM) Discharge Disposition (%) Home Skilled Nursing Facility Other
Length of Hospital Stay, days (Mean ± SEM)
Time to PACU Discharge, minutes (Mean ± SEM) Extended Time in PACU (%)
P Value 0.6905 0.0877
0.1832 0.1974
Table 2. Perioperative characteristics of the study population by CRPS status CRPS = Chronic Regional Pain Syndrome; OR= Operating Room; SEM= Standard Error of the Mean. P<0.05 was used as a threshold for statistical significance.
CRPS (N=9) 9 (100)
Non-CRPS (N=72) 72 (100)
P Value >0.9999
3 (33.3)
38 (52.8)
0.2713
CRPS (N=6) 5.7 ± 1.6
Non-CRPS (N=64) 4.8 ± 0.4
P Value 0.6745
24-hour Post-Operative VAS Pain Scores (Mean ± SEM)
6.0 ± 0.9
5.2 ± 0.4
0.6767
Post-Operative Reduction in VAS Score ε2
1 (16.7)
23 (35.9)
0.3417
Pre-Operative Chronic Opioid Therapy (%) Pain Consult Rates (%)
Pre-Operative VAS Pain Scores (Mean ± SEM)
Table 3. Pre- and post-operative pain characteristics of the study population by CRPS status CRPS = Chronic Regional Pain Syndrome; PACU= Post-Anesthesia Care Unit; SEM= Standard Error of the Mean; VAS= Visual Analogue Scale for Pain. P<0.05 was used as a threshold for statistical significance.
Length of Hospital Stay
Age
Direct Costs Coefficient P Value (95%CI)
Coefficient (95%CI)
P Value
-0.02 (-0.04 - 0.01)
0.1451
8.9 (-84.7-102.4)
0.8508
-0.15 (-1.00 - 0.70)
0.7251
-1316 (-4432 - 1801)
0.4032
Gender (Reference: Female) Male Race (Reference: White) Black Other
-0.11 (-1.26 - 1.03) 0.29 (-0.69 - 1.26) 0.03 (-0.04 - 0.09)
BMI
0.8436 0.5603
0.4032
2043 (-2147 - 6232) 2139 (-1425 - 5703) 162.4 (-62.2 - 386.9)
0.3352 0.2366
0.1541
ASA Status (Reference: I) II III IV
1.00 (-1.78 - 3.78) 0.67 (-2.08 - 3.43) 0.50 (-3.31 - 4.31)
0.4765 0.6288 0.7957
-2293 (-12447 - 7860) -1006 (-11058 - 9046) -9042 (-22959 - 4875)
0.6540 0.8437 0.2004
Preoperative Diagnosis (Reference: CRPS) Back Pain Failed Back Syndrome Neuropathy
Number of Comorbidities
-1.99 (-3.34 - -0.65) -1.81 (-3.44 - -0.17) -1.68 (-3.13 - 0.23) 0.02 (-0.1 - 0.2)
0.0041 0.0305 0.0233
0.7832
-4312 (-9328 - 704) -3572 (-9683 - 2539) -6941 (-12358 - 1523)
0.2480
316.9 (-299.5 - 933.2)
0.3093
0.0910
0.0127
APRDRG Severity (Reference: Minor Functional Loss) Moderate Functional Loss Major Functional Loss APRDRG Mortality (Reference: Minor)
-0.20 (-1.12 - 0.73) -0.85 (-4.80 - 3.10)
0.6732 0.6694
-1863 (-5017 - 1290) -1594 (-15090 - 11902)
0.2432 0.8156
Moderate Likelihood of Dying Major Likelihood of Dying
-0.10 (-1.43 - 1.23) -0.80 (-3.60 - 2.00)
0.8816 0.5721
-512 (-5088 - 4064) -1032 (-10704 - 8639)
0.8249 0.8327
Primary Insurance Type (Reference: Private) Medicare Medicaid Other
-0.26 (-1.24 - 0.71) -0.81 (-2.83 - 1.21) 0.63 (-0.57 - 1.82)
0.5907 0.4284 0.2975
-3780 (-7296 - -265) 2050 (-5242 - 9342) 24.7 (-4289 - 4339)
0.0354 0.5773 0.9909
-0.12 (-0.74 - 0.49)
0.6918
-481.5 (-3227.0 - 2264.1)
0.7272
-1.08 (-1.89 - -0.28)
0.0092
-796.4 (-3902 - 2310)
0.6112
Total Intraoperative Opioid Administration (Oral Morphine Equivalents)
0.006 (-0.002 - 0.013)
0.1322
26.3 (-0.9 – 53.6)
0.0586
Length of Anesthesia
0.003 (-0.005 - 0.010)
0.4983
-13.0 (-39.5 - 13.6)
0.3351
Time in OR
0.002 (-0.005 - 0.009)
0.5699
-14.5 (-41.2 - 12.3)
0.2852
Length of Surgery
0.003 (-0.008 - 0.014)
0.6005
-36.3 (-77.8 – 5.1)
0.0849
Estimated Blood Loss
0.001 (-0.004 - 0.006)
0.5977
-2.7 (-21.0 - 15.7)
0.7745
Received Pain Consult
-0.225 (-0.755 – 0.305)
0.4013
3335 (-2127 – 8798)
0.2278
Pre-Operative VAS Pain Scores
0.036 (-0.039 – 0.111)
0.3411
46.4 (-399.0 – 491.7)
0.8361
Post-Operative VAS Pain Scores
-0.009 (-0.090 – 0.073)
0.8280
-347.8 (-821.1 – 125.6)
0.1472
Time in PACU Until Discharge
0.002 (0.0001 – 0.003)
0.0338
6.4 (-2.7 – 15.4)
0.1651
0.73 (0.12 – 1.33)
0.0188
3499 (-216 – 7215)
0.0645
Number of Levels Implanted Method of Anesthesia (Reference: General) Monitored Anesthesia Care
Extended Time in PACU
Table 4. Univariate regression models evaluating the relationship between certain perioperative variables and various measures of clinical outcome in the total study population undergoing spinal cord stimulator implantation. APRDRG= All Patients Refined Diagnosis Related Groups; ASA= American Society of Anesthesiologists physical status classification system; BMI= Body Mass Index; CI = Confidence Interval; CRPS = Chronic Regional Pain Syndrome; PACU= Post-Anesthesia Care Unit; VAS= Visual Analogue Scale for Pain. P<0.05 was used as a threshold for statistical significance.
Intraoperative Outcomes Outcome Greater Blood Loss Higher Intraoperative Opioid Administration (Morphine Equivalents) Extended Length of Anesthesia Extended Length of Surgery
OR (95%CI) 1.85 (0.24-14.50) 2.04 (0.28-15.76) 1.69 (0.18-1.27) 0.75 (0.03-7.04)
Secondary Outcomes and Resource Utilization Metrics Outcome OR (95%CI) Extended Hospitalization 2.42 (0.40-1.46) 22.03 (1.33Extended PACU Discharge 745.65) Reduced 24 Hour Post-Operative VAS Pain Score 1.21 (0.11-10.58) Higher Direct Costs 9.64 (1.35-97.84)
P Value 0.5431 0.4788 0.6144 0.8193
P Value 0.3261 0.0406 0.8645 0.0326
Table 5. Multivariate logistic regression models evaluating the impact of CRPS status on relevant intraoperative and resource utilization measures Models control for demographic variables, including age, sex, race, BMI, primary payer status, spinal levels and comorbidities, which included smoking history, alcohol use, anemia, arthritis, heart failure, chronic lung disease, hyperlipidemia, depression, diabetes mellitus, drug abuse, hypertension, hypothyroid, liver disease, lymphoma, metastatic disease, obesity, cardiovascular disease, renal failure, weight loss, sleep apnea, osteoporosis, and other neurological disorders. BMI= Body Mass Index; CI= Confidence Interval; CRPS= Chronic Regional Pain Syndrome; PACU= Post-Anesthesia Care Unit; OR= Odds Ratio; VAS= Visual Analogue Scale for Pain. P<0.05 was used as a threshold for statistical significance.
Abbreviation List: ANOVA - Analysis of Variance APRDRG - All Patients Refined Diagnosis Related Groups ASA - American Society of Anesthesiologists BMI - Body mass index CRPS - Complex Regional Pain Syndrome MAC - Monitored anesthesia care NRS - Numeric Rating Scale PACU - Post-anesthesia care unit QALY – Quality Adjusted Life Year SCS - Spinal cord stimulation VIF - Variance inflation factor
Abbreviation List: Michael Martini: Conceptualization, Methodology, Formal Analysis, Visualization, WritingOriginal Draft. John Caridi: Writing- Reviewing and Editing. Lawrence Zeldin: Data Curation, Formal Analysis, Writing- Original Draft. Sean Neifert: Data Curation, Writing- Reviewing and Editing. Dominic Nistal: Writing- Reviewing and Editing. Jinseong Kim: Data Curation, Formal Analysis. Yury Khelemsky: Writing- Reviewing and Editing. Jonathan Gal: WritingReviewing and Editing