SPINE Volume 30, Number 5, pp E118 –E122
`©2005, Lippincott Williams & Wilkins, Inc.
`
`Clinical Measurements of Cement Injection Pressure
`During Vertebroplasty
`
`Jo¨rg Krebs, DVM,* Stephen J. Ferguson, PhD,* Marc Bohner, PhD,† Gamal Baroud, PhD,‡
`Thomas Steffen, PhD, MD,§ and Paul F. Heini, MD储
`
`Study Design. Clinical study of injection pressure dur-
`ing vertebroplasty.
`Objectives. To investigate the range of injection pres-
`sures during conventional vertebroplasty interventions
`and to study the influence of syringe design and cement
`polymerization time on injection pressure.
`Summary of Background Data. Vertebroplasty is an
`efficient procedure for the treatment of painful vertebral
`fractures. However, cement leakage is a potentially seri-
`ous complication. Although injection pressure has been
`suggested as a factor for extravasation risk, to date, there
`are only anecdotal reports of pressure data for cement
`augmentation in the clinic.
`Methods. Using a syringe holder instrumented with
`load and displacement transducers,
`injection pressure
`and volume were recorded in vivo during conventional
`cement augmentation. Wide (3 mm opening) and normal
`(1.8 mm opening) syringes were alternated such that each
`type was evaluated for early (300 –500 seconds postmix-
`ing) and late (⬎500 seconds postmixing) cement poly-
`merization time. The influence of syringe type and poly-
`merization time on injection pressure was evaluated
`using a multifactorial analysis of variance followed by
`Scheffe´ post hoc comparison.
`Results. The maximum peak injection pressure mea-
`sured was 3215 kPa. The average pressure peaks for nor-
`mal and wide syringes were 1693 ⫾ 653 kPa and 1727 ⫾
`597 kPa, respectively. No statistically significant differ-
`ences were found between injection pressures with wide
`and normal syringes. Higher injection pressures were ob-
`served later in the polymerization process.
`Conclusions. High injection pressures approaching 20
`atmospheres are reached during conventional vertebro-
`plasty. Widening the syringe tip diameter did not signifi-
`cantly change injection pressures, whereas elapsed time
`did. Further research is needed to improve injection
`equipment and materials for vertebroplasty.
`Key words: vertebroplasty, osteoporotic compression
`fractures, polymethyl methacrylate,
`injection pressure.
`Spine 2005;30:E118 –E122
`
`From the *M. E. Mu¨ ller Institute for Surgical Technology and Biome-
`chanics, Bern, Switzerland, the †Robert Mathys Stiftung, Bettlach,
`Switzerland, ‡Laboratoire de Biomecanique, De´partement de Ge´nie
`Me´canique, Universite´ de Sherbrooke, Sherbrooke, Que´bec, Canada,
`§Orthopaedic Research Laboratory, McGill University, Montreal,
`Canada, and the 储Department of Orthopaedic Surgery, Inselspital,
`Bern, Switzerland.
`Supported by AO Spine International, Du¨ bendorf, Switzerland.
`Acknowledgment date: March 9, 2004. First revision date: June 30,
`2004. Acceptance date: July 23, 2004.
`The manuscript submitted does not contain information about medical
`device(s)/drug(s).
`Foundation funds were received in support of this work. No benefits in
`any form have been or will be received from a commercial party related
`directly or indirectly to the subject of this manuscript.
`Address correspondence and reprint requests to Dr. Jorg Krebs, MEM
`Research Center for Orthopaedic Surgery, Institute for Surgical Tech-
`nology and Biomechanics, University of Bern, Stauffacherstr. 78, 3014
`Bern, Switzerland; E-mail: jorg.krebs@MEMcenter.unibe.ch
`
`E118
`
`Vertebroplasty, the percutaneous augmentation of ver-
`tebral bodies with polymethyl methacrylate (PMMA), is
`reported to be an effective surgical procedure for provid-
`ing pain relief for patients suffering from osteoporotic
`compression fractures.1–3 The technique is therefore
`gaining increasing popularity with both physicians and
`patients.4 The reported rate of serious complications is
`low, but there is the concern that complications are un-
`derreported.5 The main complication is cement leakage
`into adjacent structures,3,6,7 which can lead to spinal
`cord or nerve root compression1,8,9 or pulmonary embo-
`lism.10 –12 The consequences of these leaks may be se-
`vere, i.e., paraplegia13 or death.14,15
`The reported incidence of cement leakage is approxi-
`mately 20% to 71% of augmented osteoporotic verte-
`bral bodies.1,2,6,16 –18 Cement leakage has occurred into
`paravertebral tissue, neural foramens, epidural space,
`and perivertebral veins. The risk of cement leakage has
`been observed to increase with the volume injected.6 Fur-
`thermore, the incidence of leakage was higher when lev-
`els above T7 were augmented. Other factors determining
`leakage risk include the choice of injection equipment,
`injection pressure,6,19,20 and cement viscosity.21,22 Al-
`though injection pressure has been suggested to affect
`extravasation, to date, only pressure data of isolated
`cases have been reported for cement augmentation in the
`clinic.23
`To better understand the vertebroplasty process and
`to facilitate the design of improved injection equipment
`and augmentation materials, the primary goal of this
`study was to determine the range of injection pressures
`during conventional vertebroplasty interventions. The
`secondary goal of the study was to determine the influ-
`ence of syringe design and cement polymerization time
`on injection pressure.
`
`Methods
`Patient Population. Twenty patients (17 female, 3 male; aged
`54 – 84 years, mean 71.7) were randomly allocated for injection
`pressure measurements. Candidates were selected from pa-
`tients admitted to the Orthopedic Department of the Inselspital
`Bern for vertebroplasty due to osteoporotic vertebral compres-
`sion fractures. Patients selected for pressure measurements had
`sustained between 1 and 3 (mean 1.67) vertebral compression
`fractures.
`
`Surgical Technique. Vertebroplasty was carried out accord-
`ing to the technique described by Heini et al.2 Unipedicular
`augmentation of vertebral bodies (3–7 vertebral bodies per pa-
`tient, mean 4.77) was performed using standard 2 mL (no mea-
`surements) or 5 mL (pressure measurements) syringes contain-
`
`STRYKER EXHIBIT 1012, pg. 1
`
`STRYKER CORPORATION v. ORTHOPHOENIX, LLC
`
`IPR2014-01433
`
`

`

`Cement Injection Pressure • Krebs et al
`
`E119
`
`Figure 1. Syringe holder instrumented with load and displacement
`transducers (arrow) connected to the data acquisition system and
`palm computer.
`
`ing Vertebroplastic™ cement (DePuy AcroMed, Raynham,
`MA). Cement was injected through standard bone marrow bi-
`opsy needles (8 gauge, MD Tech, Gainesville, FL) under fluo-
`roscopic control. Cement injection was commenced following
`visual appraisal of cement viscosity. Cement injection was per-
`formed until a satisfactory vertebral body filling was achieved
`or until limited by the viscosity changes throughout the poly-
`merization process or by any signs of extravasation. Not only
`collapsed but also intact adjacent vertebral bodies were aug-
`mented.2,24 –27
`
`Measurements. Using a syringe holder instrumented with
`load and displacement transducers (Figure 1), the injection
`pressure and cement injection volume were recorded in vivo
`during conventional manual cement augmentation of 50 osteo-
`porotic, nonfractured vertebral bodies (T7–L5). For most ver-
`tebral bodies, several measurements were taken, with pauses
`due to leakage (Figure 2) or changing of syringes. Data were
`collected at a frequency of 4 Hz with a data acquisition system
`(MyCorder, DAS-1206, Datastick Systems, Santa Clara, CA)
`and stored on a Palm handheld computer (Palm III, Palm
`Corp., Milpitas, CA). Data were later transferred to a PC.
`
`Figure 3. Injection pressure (circles) and volume injected (solid
`line) during PMMA augmentation of a vertebral body.
`
`The influence of the syringe tip diameter was evaluated by
`expanding the standard 5 mL syringe tip (diameter 1.8 mm) to
`a diameter of 3 mm using a sterile drill before filling. In each
`patient, injection pressures during the augmentation of at least
`2 vertebral bodies were measured. During the augmentation of
`each vertebral body, we attempted to take measurements for
`both syringe types. However, this was not possible in all cases
`due to the clinical situation (e.g., termination due to extrava-
`sation, complete filling, technical error). As cement viscosity
`increases with polymerization time, wide and normal syringes
`were alternated such that each type was equally evaluated for
`the early (300 –500 seconds postmixing) and late (⬎500 sec-
`onds postmixing) polymerization phase.
`Statistical Analysis. Based on previously determined calibra-
`tion curves, force and displacement measurements were con-
`verted to maximum pressure and total injection volume. Data
`were calculated and presented as mean ⫾ standard deviation of
`the mean. The influence of syringe type (wide and normal),
`polymerization phase (early and late), and flow rate on injec-
`tion pressure was evaluated using a multifactorial analysis of
`variance (ANOVA) followed by Scheffe´ post hoc comparison,
`with a significance level of P ⫽ 0.05.
`
`Results
`
`Representative curves for the injection of 1 syringe into a
`vertebral body are presented in Figure 3. In a typical
`injection process, a fairly constant injection pressure is
`
`Figure 2. Fluoroscopic images
`(left lateral view/right anteropos-
`terior view) showing extravasa-
`tion of cement (arrow).
`
`STRYKER EXHIBIT 1012, pg. 2
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`

`

`E120 Spine • Volume 30 • Number 5 • 2005
`
`Table 1. Injection Pressure Data of Normal and Wide
`Syringes During Vertebroplasty
`
`Polymerization Time
`
`Phase 1 (300–500 s)
`
`Phase 2 (501–800 s)
`
`Average
`Pressure
`(kPa)
`
`1391 ⫾ 520
`1394 ⫾ 388
`1943 ⫾ 654
`1968 ⫾ 622
`
`Peak
`Pressure
`(kPa)
`
`2493
`2142
`3215
`3178
`
`Syringe
`
`Normal
`Wide
`Normal
`Wide
`
`N
`
`24
`23
`29
`27
`
`The values are given as the mean ⫾ the standard deviation.
`N ⫽ number of measurements.
`
`produced using a hand-held syringe, and a constant flow
`rate of cement is obtained. Resting periods during the
`injection can be recognized. Injections were performed at
`an average flow rate of 0.09 ⫾ 0.04 mL/s (range 0.03–
`0.2 mL/s). There was no correlation between flow rate
`and injection pressure. During each measuring period,
`an average of 1.9 ⫾ 0.9 mL cement was injected. The
`average elapsed time after mixing during the early (300 –
`500 seconds) and later (501– 800 seconds) polymeriza-
`tion phase was 450 ⫾ 43 seconds and 616 ⫾ 89 seconds,
`respectively.
`Injection pressure data are summarized in Table 1.
`The average pressure peaks for all measurements (n ⫽
`103) was 1698 ⫾ 624 kPa, and the maximum injection
`pressure recorded during the study was 3215 kPa, which
`was measured with a normal syringe. The highest pres-
`sure recorded with wide syringes was 2178 kPa. The
`average pressure peak for measurements of normal (n ⫽
`53) and wide (n ⫽ 50) syringes were 1693 ⫾ 653 kPa and
`1704 ⫾ 597 kPa, respectively. No statistically significant
`differences were found between injection pressures of
`wide and normal syringes. Higher injection pressures
`were observed later in the polymerization process (P ⬍
`0.001). For injections during the early and late phase of
`cement polymerization, the average pressure peaks were
`1392 ⫾ 455 kPa and 1955 ⫾ 633 kPa, respectively.
`In 2 atypical cases, only a limited volume of cement
`could be injected (⬍2 mL) despite high injection pres-
`sures exceeding 2000 kPa.
`Discussion
`
`During conventional vertebroplasty injection, pressure
`peaks approached, on average, 2000 kPa (approximately
`20 atmospheres). Pressure peaks as high as 3215 kPa
`were observed. Absolute injection pressure peaks for
`wide syringes were lower compared to normal syringes;
`however, the differences were not statistically significant.
`There was no difference in average pressure peaks be-
`tween normal and wide syringes. Injection pressure in-
`creased with polymerization time.
`Until now, only injection pressure data of isolated
`cases were available for vertebroplasty in the clinical sit-
`uation.23 In the present study, injection pressure was
`equivalent to approximately 40 kg being applied onto
`the 5 mL syringe plunger (area: ⬃200 mm2). For the 2
`
`mL syringe (plunger area: ⬃130 mm2), which is rou-
`tinely used for vertebroplasty, the measured pressure
`would be equivalent to approximately 26 kg. This force
`is necessary to push the cement through the syringe and
`the cannula into the bone. Injection pressure data pro-
`vided by the present study will aid in the development of
`automated injection equipment or devices for vertebro-
`plasty that employ a mechanical advantage. However, it
`remains to be determined how well injection pressure
`correlates with intravertebral pressure. It was not feasi-
`ble in the present study to measure intravertebral pres-
`sure. Baroud et al28 reported that intravertebral pressure
`was 2 orders of magnitude lower than injection pressure
`in vitro due to the friction between the cement and the
`cannula wall. Using this ratio, intravertebral pressures in
`the present study may have approached 150 mm Hg. An
`experimental study of vertebroplasty in nonosteoporotic
`sheep reported intravertebral pressures averaging 400
`mm Hg during cement injection into intact nonosteopo-
`rotic vertebrae using conventional 3 mL syringes without
`cannulas.30
`It has been suggested that the risk of leakage increases
`with high injection pressures and consequently increased
`intravertebral pressures using current cements.6,20 How-
`ever, there may be no correlation between extravasation
`risk and intravertebral pressure. Extravasation is mostly
`determined by the viscosity of the cement and the perme-
`ability of the vertebral body at and around the injection
`point.21 High injection pressures and consequently in-
`creased intravertebral pressures during vertebroplasty
`may also increase the extravasation of bone marrow con-
`tents, leading to embolization in the lungs20,31 as re-
`ported during arthroplasty.32–34 In arthroplasty, drilling
`a vent hole with or without additional vacuum has been
`shown to allay intraosseous pressure increase and there-
`fore embolic events.32–35 During vertebroplasty, a bi-
`opsy needle in the contralateral pedicle may be used to
`decompress the vertebral body during injection.29,31 The
`preformation of a cavity for injection has also been sug-
`gested to reduce the required injection pressure20; how-
`ever, laboratory testing and computational models have
`demonstrated that the bottleneck for PMMA cement in-
`jection is the geometry of conventional syringes and can-
`nulas used for injection, rather than the inherent perme-
`ability of the vertebral body itself.36,37 It appears that the
`best way of decreasing the risk of cement leakage is to use
`high viscosity cement.21,22 The injection of high viscosity
`cement will involve higher injection pressures. Sugges-
`tions have been made to use screw-driven injection sys-
`tems to mechanically exert the extremely high pressures
`required for cement injection.19 Due to the inherent in-
`ertia of the cement and the deformation of the injection
`system, however, the cement flow cannot be immediately
`halted.21 The use of automated injection equipment or
`devices that employ a mechanical advantage should
`therefore be reviewed with caution. However, the in-
`jection of high viscosity cement may increase the ex-
`travasation of bone marrow contents (i.e., fat) from
`
`STRYKER EXHIBIT 1012, pg. 3
`
`

`

`the vertebral bodies.22 Secondly, there is a clear need
`for injectable materials that maintain a constant and
`optimal viscosity throughout the duration of the injec-
`tion process.
`No significant differences between wide and normal
`syringes could be demonstrated in the present series of
`measurements. This is in contrast to laboratory experi-
`ments that have demonstrated a trend towards lower
`injection pressures with wider syringes (Bohner et al,
`unpublished data). In these experiments, the inner part
`of the Luer lock of a 5 mLsyringe was removed by
`drilling a 4.5-mm hole into the frontal part. Using the
`modified syringe, the cement flowed directly from the
`syringe into a 7-gauge (⬇4.5 mm; present study: 8
`gauge ⬇ 4.1 mm) cannula, whereas with the nonmodi-
`fied syringe, it first flowed into the syringe tip (diameter
`⬃2 mm) and then into the cannula. The difference in
`injection pressure between modified and nonmodified sy-
`ringes was significant at P ⬍ 0.03. In the present study,
`the difference in diameter between the normal and wide
`syringe (difference: 1.2 mm) may have been too small to
`have a substantial influence on injection resistance and
`thus pressure. Different factors influence cement viscos-
`ity and thus injection pressure. Laboratory experiments
`have shown that time after mixing had the largest effect
`on the injection force (Bohner et al, unpublished data).
`The present study therefore analyzed injection pressure
`according to elapsed time after mixing. However, cement
`viscosity is also influenced by the ambient temperature,
`cement composition, liquid to powder ratio, and mixing
`time.38,39 Cement was used and mixed according to the
`manufacturer’s instructions. However, the mixing pro-
`cess (intensity and duration) in the clinical situation is
`variable. Baroud et al40 have shown that the variability
`in the viscosity for vertebroplastic cement is 30% higher
`after manual mixing compared to oscillatory mixing.
`Furthermore, the ambient temperature was not con-
`trolled in the present study. This may have masked a
`potential difference in injection pressure between normal
`and wide syringes. It was not feasible to measure cement
`viscosity in the present study.
`In conclusion, high injection pressures (approaching
`20 atmospheres) are reached during manual augmenta-
`tion of vertebral bodies with cement. Widening the sy-
`ringe tip diameter did not significantly influence injection
`pressures, whereas polymerization time did. There is a
`clear need to improve injection equipment and injectable
`materials for vertebroplasty to allow better control of the
`injection process and to minimize the risk of cement ex-
`travasation. Widening the cannula may decrease injec-
`tion pressure. Injection devices can provide the force
`needed to injection high viscosity cement; however, it is
`imperative that the operator is able to stop the advance
`of cement immediately at impending leakage. Injectable
`materials should maintain a constant and optimal viscos-
`ity throughout the duration of the injection process.
`
`Cement Injection Pressure • Krebs et al
`
`E121
`
`Key Points
`
`● Peak injection pressures during conventional
`vertebroplasty approached on average 2000 kPa
`(20 atmospheres).
`● The syringe tip diameter did not significantly af-
`fect injection pressure.
`● Injection pressure increased with cement poly-
`merization time.
`● Further research is needed to improve injection
`equipment and injectable materials for
`vertebroplasty.
`
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