Effects on Analgesia Use Following Percutaneous Spinal Augmentation and Cementoplasty: Sustained Significant Decrease

ABSTRACT: Introduction: Percutaneous spinal augmentation and cementoplasty (PSAC) is a minimally invasive procedure used to treat or prevent pathologic fractures and pain when other pain management is ineffective. Previous reports have demonstrated significant subjective pain and symptom relief through questionnaires and quality of life scoring frameworks, but no work has yet been performed focusing on the more objective measure of long-term analgesia use as a primary outcome. Materials and Methods: All patients who attended the preassessment vertebroplasty clinic at a tertiary referral center in the United Kingdom over a 1-year period (2011) were identified retrospectively using electronic hospital clinic records. Repeat prescription documentation was obtained from the patient’s general practitioner or inpatient hospital records and compared to preassessment analgesia documentation with statistical significance calculated using a Fisher exact test (P=.05). End points were set at early 2015 or natural death. Results: Forty-six patients (65% female, age range 26-88 years, median age 72 years) were assessed. Of these, 21 (46%) had a diagnosis of osteoporosis, and 25 (54%) had a cancer-related diagnosis. Twenty-seven (59%) had a PSAC procedure performed within a year of their preassessment and 19 (41%) were deemed unsuitable. Of the 27 patients who underwent a PSAC procedure, a statistically significant (P=.0188) decrease in analgesia use, as defined by the WHO pain ladder, was noted in 17 (63%) when compared with those who did not undergo the procedure. This was principally accounted for by a strongly significant decrease in the osteoporosis subset (P=.00752). There was no significant relationship to age or sex of patient. Conclusions: This study demonstrates that PSAC leads to a highly significant, long-term, sustained reduction in analgesia use in patients with osteoporotic lesions. 

Key words: analgesia, vertebroplasty, cementoplasty, pain, osteoporosis, palliation

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Percutaneous spinal augmentation and cementoplasty (PSAC), also called percutaneous vertebroplasty or cavity kyphoplasty, is a minimally invasive radiologic intervention procedure in which fluoroscopic radiologic guidance is used to inject high-viscosity bone cement into damaged spinal vertebrae to treat or prevent pathologic fractures and pain.^1,2 The procedure, in our institution, involves passing disposable bone trochar needles into the vertebral body using a bipedicular approach, under intravenous sedation and biplane fluoroscopy (Figures 1 and 2). A cavity is then created within the vertebral body, with a steerable MidLine Osteotome (DFINE) used to guide instillation of cement into vertebral bodies. Approximately 2 mL to 5 mL of high-viscosity cement (DFINE) is then slowly injected through a radiofrequency device, under constant radiological guidance, until a suitable fill of the vertebral body is achieved (Figures 3-5).^1,2 The procedure can be repeated to treat multiple vertebral bodies with the primary objective being to achieve the best possible fill. No other specific techniques to elevate the height of the vertebral body are used, and thus any elevation of the vertebral body achieved is a secondary effect of the high-viscosity cement instillation. Referral for a PSAC procedure is generally reserved as a second-line procedure for patients in whom optimal pain management using back bracing, bed rest, and analgesia is unsuccessful in controlling vertebral fracture pain.³

A number of open-label trials using patient questionnaire and quality of life scoring frameworks have suggested that PSAC can provide substantial subjective improvements to both quality of life and reduction in pain and disability.^4-6 These studies principally examined acute and chronic vertebral fractures secondary to osteoporosis. No study has yet been performed using the more objective measure of long-term analgesia use as a primary outcome following the procedure in chronic, painful vertebral fractures. This has direct clinical consequences with profound financial and service planning implications in health care system management. This study aimed to determine whether PSAC had a measurable and significant effect on long-term analgesia use in patients following the procedure.

Materials and Methods

All 46 patients (male-to-female ratio 16:30, age range 26-88, median 72, mean 69) who attended the preassessment PSAC clinic at a tertiary referral center in the United Kingdom from January 1, 2011, to December 31, 2011, were identified retrospectively using the internal hospital radiological administrative and reporting software (iCRIS). Collection of data through this clinic and informed consent for its use was obtained and approved by the Institution’s New Interventional Advisory Group (NIPAG). 

This clinic is run weekly by 1 of 2 consultant radiologists with more than 10 years of PSAC experience, and it is split between new patient referrals and 1-month postoperative follow-up. A decision to treat with PSAC or discharge with conservative management is made in the clinic for all new patients following a thorough clinical history, spinal physical examination, and review of the preclinic imaging with the most recent MRI. Patients who choose not to proceed, those determined to be high risk for the procedure, or those who do not require the procedure are discharged back to their referrer. Their risk for osteoporosis and medications are reviewed. Appropriate guidance is given to the referrer regarding future referral to an osteoporosis specialist or assessment for osteoporotic status if not considered. As part of the preassessment, data regarding the patients’ age, symptoms, diagnosis, and regular analgesia were recorded, in addition to review of most recent spinal imaging (CT or MRI). 

All patients referred to the preassessment clinic had symptoms warranting their referral. These included pain and vertebral body collapse such as that found in osteoporosis, or significant vertebral body disease such as that found in oncologic and hematologic diagnoses (e.g., myeloma, vertebral metastases). A procedure was performed on 1 patient who did not have any pain on presentation. This patient was a young female patient suffering from aggressive metastatic breast cancer with vertebral deposits for which she was due to undergo radical radiotherapy. As such the procedure was used more to provide stability to her spine and prevent future fracture and pain rather than primarily as an analgesic procedure.

Analgesia requirements – both regular and pro re nata – were available on the patient’s electronic medical records via clinic letters. Analgesic status was also recorded, at fixed end points of early 2015 or at the time of the patient’s natural death. For those still alive in early 2015, the most recent repeat analgesia prescription was obtained from the patient’s general practitioner (GP). For those who had passed away, a final repeat prescription was obtained from the patient’s GP or the most recent hospital inpatient discharge summary was used. Repeat prescription information was obtained for all patients who attended the clinic. For 37 patients this was their latest repeat prescription, obtained from their GP. For the remaining 9, all of whom had passed away, data were obtained from the most recent discharge summary on the internal hospital discharge summary system. In all cases, this was within the last 3 months of their life. Pain and quality of life scoring frameworks such as the EQ-5D and visual analogue scales were completed for those attending the clinic who were potential candidates for the procedure. These scores were repeated at intervals following the procedure to assess effectiveness of the procedure.

Referring diagnosis was broadly split into two categories after preassessment; osteoporosis (n=21, 46%) and a cancer-related diagnosis (n=25, 54%). Twenty-seven patients (59%) underwent a PSAC procedure within a year of their preassessment, and the remaining 19 patients (41%) were deemed not suitable for the procedure either at preassessment or on the day of the procedure. On review of the medical records in early 2015, 26 patients (57%) were still alive, 20 of whom (43%) had undergone a PSAC procedure (Figure 6). 

A reduction in analgesia between preassessment and end point was defined as either a reduction in dose or frequency of a previously taken medication, or, when medications were of different types, a reduction in number of medications taken or potency of medications as defined using the widely accepted World Health Organisation Analgesia Ladder.⁷ This concept comprises a tiered scale of medications starting, at the bottom, with nonsteroidal anti-inflammatory medications (e.g., aspirin, acetaminophen) and increasing as necessary to mild opioids (e.g., codeine) and finally strong opioids (e.g., morphine).

The primary outcome measured in this study was reduction in analgesia as defined above. Data analysis was performed using Microsoft Excel 2010, with a Fisher exact test and a P value of .05 (SPSS 15.0 for Windows and online GraphPad software).⁸

Results

A change in analgesia regime was noted in 36 (78%) patients (Tables 1 and 2). An increase in analgesia was noted in 14 (30%) patients with a decrease in 22 (48%) patients. 10 patients (22%) had no change in their analgesia medications. In the patients with a decrease in analgesia, 17 (77%) had a PSAC procedure performed with a statistically significant (P=.0188) reduction in analgesia (Table 3). Six patients who had a PSAC procedure performed had an increase in analgesia, with no significant difference (P=.1988) demonstrated (Table 4). Eleven patients were completely analgesia free at the end point, 9 of whom had had a PSAC procedure performed (asterisks in Tables 1 and 2). This demonstrated a further highly significant difference between the 2 groups (P=.0008). 

An analysis of the impact of the underlying diagnosis on the decrease in analgesia following PSAC was conducted. Of the 21 osteoporosis patients, 13 PSAC procedures were performed, with 10 patients experiencing a decrease in analgesia. This was of high statistical significance (P=.00752) with a decrease in analgesia in those osteoporosis patients who had undergone the procedure (Table 5). In the 25 cancer-related patients, 14 PSAC procedures were performed, with 7 patients experiencing a decrease in analgesia (Table 6). This group did not see a significant decrease in analgesia medications following the procedure (P=.688). When this analysis was extended to sex and age using the median as a division, no significant differences were observed (Two-tailed t test P=.6919 and P=.2365, respectively).

Discussion

As a tertiary referral center situated in a large teaching hospital trust, the PSAC service at our institution provides specialist care to a catchment area of more than 1 million people. The PSAC clinic has been accepting referrals from both primary and secondary care sources since 2006 and assesses approximately 50 patients per year, 25 or more will undergo a PSAC procedure. The majority of referrals are from secondary care sources, with myeloma and osteoporosis the principal conditions prompting consideration for assessment (see Tables 1 and 2). Multiple previous studies4-6 have demonstrated this procedure to be beneficial in alleviating pain for such diagnoses through the use of long-term follow-up qualitative questionnaires; however, little was known about the effect on long-term analgesia in these patients.

This study demonstrates quantitatively that a PSAC procedure leads to a significant, sustained, long-term reduction in analgesia use. One-third (9/27) of the patients who had a PSAC procedure performed were analgesia-free at the end point. The greatest benefit from the procedure was seen in osteoporosis patients, in whom a highly statistically significant decrease in analgesia was recorded (P=.00752); this decrease was not replicated in cancer patients (P=.688). There was no significant association between age at presentation, nor gender in the reduction in analgesia observed. In the minority of cases where an increase in analgesia was noted, this was not significantly related to the PSAC procedure. 

Some previous high-profile reports in the literature have cast doubt on the effectiveness of PSAC for painful osteoporotic fractures, suggesting through the use of sham procedures that the pain reduction observed following the procedure is not significantly different between intervention and control group.^9,10 Although conducted with a larger patient population than our cohort, the methods employed in these studies differ markedly from our own. The most noticeable difference is our use of an osteotome to create a cavity within the vertebra and create channels to direct placement of cement. Furthermore, our selection of up to 3 symptomatic vertebral levels is by percussion of the spinous processes under real-time fluoroscopy and MR imaging correlation. The follow-up of patients was also limited to a maximum of 6 months and relied on mailed patient questionnaires. This did not include face-to-face assessments and telephone follow-up of patients after the procedure, a feature which seems unique to our center. As such, our methods would more resemble recent large trials that have demonstrated significant improvement in qualitative pain scores as a result of the procedure.^4,11 

One of the limitations of this study was the high morbidity of the patients referred, possibly due to their underlying disease and their age at the time of referral, not allowing a single time point of analysis of a year. Despite this, a significant association between reduction in analgesia and intervention was observed in our cohort. In addition, given the chronic, non-self-limiting, and progressive nature of the underlying diagnoses, any improvement in analgesia noted is likely to be related to the procedure.

Although the numbers in this study are small, the strength of the statistical significance of PSAC for reduction of analgesia in osteoporosis patients found would suggest a clear link between the procedure and a decrease in analgesic medications. This cannot purely be explained by confounding factors such as age and the natural history of osteoporotic fractures. The data would suggest that conventional understanding of spontaneous healing of osteoporotic fractures with oral analgesia could be challenged, at least in our cohort. In fact, 88% (7/8) of osteoporosis patients who did not have PSAC demonstrated no decrease in their analgesia medications over the follow-up period. 

Multicenter studies with increased numbers and regular follow-up and assessment could be undertaken to determine whether the findings are widely representative of the procedure itself or related to our specific pathway and practice. This could be used as supportive evidence to standardize referral pathways through appropriate patient selection. Future health economic analysis of the impact on the National Health Service and other national health care systems could be performed, related to the effect of a reduction in long-term analgesia. These could include both specific costs of the medications and more diverse and wide-ranging costs such as decrease in clinic attendance and other short- and longer-term measures, such as improvement in quality of life, disability scores, pain scores, morbidity, and psychosocial well-being.

Conclusions

Our study demonstrates that a PSAC procedure leads to a highly significant, long-term, sustained reduction in analgesia use in patients with osteoporotic lesions. It is hoped that this finding will be used to strengthen access to this procedure, in addition to providing the platform for further work in the area into the financial implications of such a reduction, thus informing both planning and provision services.

The lack of statistical significance in cancer patients may be due to small numbers in this study, the early morbidity, and associated bone pain due to the tumor burden. It is of note that half the cohort of cancer patients experienced a reduction in pain following PSAC in this study.

Editor’s note: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no financial relationships or conflicts of interest regarding the content herein.

Manuscript received June 20, 2016; provisional acceptance given July 13, 2016; manuscript accepted August 8, 2016. 

Address for correspondence: Winston J. Rennie, MSc, FRCR. University Hospitals of Leicester, Leicester Royal Infirmary, Infirmary Square, Leicester LE15WW, United Kingdom. Email: winston.rennie@uhl-tr.nhs.uk.

Suggested citation: Street D, Morlese JF, Shah A, Morgan S, Garg M, Rennie WJ. Effects on analgesia use following percutaneous spinal augmentation and cementoplasty: sustained significant decrease. Intervent Oncol 360. 2016;4(9):E146-E156.

References

1. Stevenson M, Gomersall T, Lloyd Jones M, et al. Percutaneous vertebroplasty and percutaneous balloon kyphoplasty for the treatment of osteoporotic vertebral fractures: a systematic review and cost-effectiveness analysis. Health Technol Assess. 2014;18(17):1-290.
2. Katsanos K, Sabharwal T, Adam A. Percutaneous cementoplasty. Semin Intervent Radiol. 2010;27(2):137-147.
3. Percutaneous vertebroplasty and percutaneous balloon kyphoplasty for treating osteoporotic vertebral compression fractures. National Institute for Health and Care Excellence. https://www.nice.org.uk/guidance/ta279. Accessed March 16, 2015.
4. Blasco J, Martinez-Ferrer A, Macho J, et al. Effect of vertebroplasty on pain relief, quality of life and the incidence of new vertebral fractures. A 12-month randomised follow-up, controlled trial. J Bone Miner Res. 2012;27(5):1159-1166.
5. Rousing R, Andersen MO, Jespersen SM, Thomsen K, Lauritsen J. Percutaneous vertebroplasty compared to conservative treatment in patients with painful acute or subacute osteoporotic vertebral fractures. Three-months follow-up in a clinical randomized study. Spine. 2009;34(13):1349-1354.
6. Voormolen MHJ, Mali WP, Lohle PN, et al. Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study. AJNR Am J Neuroradiol. 2007;28(3):555-560.
7. WHO’s cancer pain ladder for adults. World Health Organization. https://www.who.int/cancer/palliative/painladder/en/. Accessed March 16, 2015.
8. Analyse a 2x2 contingency table. GraphPad Software. https://graphpad.com/quickcalcs/contingency1.cfm. Accessed February 11, 2015.
9. Buchbinder R, Osborne RH, Ebeling PR, et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med. 2009;361(6):557-568. 
10. Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med. 2009;361(6):569-579. 
11. Klazen CAH, Lohle PN, de Vries J, et al. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial. Lancet. 2010;376(9746):1085-1092.