Comparison of Efficacy Transforaminal epidural injection of autologous platelet rich plasma vs triamcinolone in patients of lumbar disc herniation with radicular pain: A Prospective Randomized control study

INTRODUCTION

Low back pain is one ofthe most difficult conditions to manage for doctors, patients, andpolicymakers. Not only does it limit physical activity, life quality is alsogreatly reduced alongside additional social and economic burden. The pointprevalence of low back pain is 12%, with its one-year prevalence being 38% andthe lifetime prevalence being approximately 40%1. Aging population leads to therising number of individuals affected by low back pain. Lumbar disc herniationhas been identified as the common etiology of low back pain2. The treatments for lumbar discherniation vary from conservative to surgical management, which includeanalgesics, traction, physical therapy, manipulation, and psychotherapy.However, not all patients are able to be relieved from pain through thesetreatments.

For over 30 years, epidural steroidinjection has been widely used as a treatment for lumbar disc herniation3, 4, with its effectiveness proven bymultiple research5–7. It works in anti-inflammation, painrelief, and functional improvement. There are three routes for steroidinjection: interlaminar, transforaminal, and caudal routes. The transforaminalroute fared better than the other two because it could reach the targetedsites, namely, spinal nerve, anterior epidural space, and the dorsal rootganglion, to counteract the inflammation secondary to compression.5However,there are still concerns about the safety of epidural steroid injection. Basedon literature, several complications related to epidural steroid injection havebeen pointed out, including neurotoxicity, pharmacologic effect of steroid(hypercorticism, adrenal suppression, and hyperglycemia), and neurologic injury6,7.Besides, the contraindications of steroid use (allergy, diabetes, severeosteoporosis, pregnancy, severe hypertension, infection, etc.) limit the usageof epidural steroid injection.

Autologous platelet-rich plasma is ablood-derived product obtained through centrifugation, when plateletconcentrations are three times higher than baseline in plasma. This procedureallows the degradation of platelet α-granules and the release of severalimportant growth factors such as platelet-derived growth factor ([PDGF-αα],[PDGF-αβ], [PDGF] -ββ]), endothelial growth factor (VEGF), two transforminggrowth factor-β ([TGF-β1] [TGF-β2]) and epithelial growth factor (EGF). MostlyPRP has been used for chronic tendinopathy and enthesopathy, including kneeosteoarthritis. It has become an important tool for use of pain physicianbecause of low cost, ease of use and its apparent safety.8,9

Platelet-rich plasma (PRP), abiological product from the centrifugation of autologous blood with a highnumber of platelets in a small volume of plasma, has a positive effect on painrelief in some musculoskeletal diseases, especially osteoarthritis, tendinosis,and ligament tears10. PRP contains high concentration ofgrowth factors (GFs) and cytokines that play important roles inanti-inflammatory, antiapoptotic, and proliferative effects on the neurons andfibroblasts11. Although the role of PRP in painrelief looks promising, the effect of transforaminal PRP injection in lumbardisc herniation with radicular pain remains unclear.

AIMSAND OBJECTIVES

AIM :

·        To compare theefficacy and safety of autologous platelet rich plasma injection versus Triamcinolonein lumbar disc herniation with radicular pain through C-arm guided technique.

Primary Objective :

–    To comparepain relief with PRP Vs Triamcinolone in transforminal epidural for radicularpain due to lumbar disc herniation via VAS.

Secondary objective:

–    To comparepatients satisfaction with PRP vsTriamcinolone

–     To compare safety and side effects of PRP vsTriamcinolone

 MATERIALAND METHODS

Studysetting:

The study willbe conducted in Pain OT, Department of Anesthesiology, King George’s MedicalUniversity, Lucknow after written informed consent will be obtained from eitherof the patients/Guardian

**Studyduration :**One year

Studydesign:

Prospective Randomized control study

Samplesize:

60 cases(30 in each group)

Inclusion Criteria:

·        Patientsgiving written consent will be taken

·        Patient in theage group of 20 to 60 years.

·        ASA grade I& II

·        Lowback pain more than 3 months and unilateral lower limb with radicular pain

·        Posterolaterallumbar disc herniation of L4/L5 or L5/S1 segment on CT and correspondingclinical symptoms and signs

·        Painlevel on VAS â‰¥5

·        Nosymptoms of severe nerve damage include motor paralysis, muscle atrophy andcauda equine syndrome

·        Nohistory of spinal surgery

Exclusion Criteria:

·        Patients notgiving informed consent

·        ASA grade IIIto IV

·        Infection

·        Prior epidural injection in the past 3 months, such as nerveroot injection and caudal injection

·        Spinal tumors or tuberculosis

·        Multi-segmentallumbar disc herniation, spinal deformity, or spinal stenosis

·        Allergicto the drug used in this study

·        Symptomsof severe nerve damage including motor paralysis, muscle atrophy, and caudaequinasyndrome.

Ethicalapproval:

·        It will be taken from the Institutional EthicsCommittee of the university.

Methodology:

•      Patients will be divided randomlyin two groups:

–     Group A: Patients administered transforaminalepidural injection of platelet rich plasma (4ml).

–     Group B: Patients administeredtransforaminal epidural injection of steroid (2mltriamcelone+ 2ml 0.9% normal saline)

Sample size

On the basis of previous study, the changes in the mean d OSS scores between the PRP (16.2 ) and corticosteroid groups (25.0)at 6-month follow-up was8.8 and the population variance (σ2)was 10.2 (Thepsoparn et al., 2021).11The sample size (n) = 2 (Zα/2 + Z [1-β])2× σ2/( μ1−μ2)2,assuming 0.05 level significance (Zα/2 =1.96), and 90% power (Z [1-β])=1.28) was 28.20 in each group. Considering anydropouts, we had enrolled 30 patients in each group. 11

2 (Zα/2 + Z [1-β])2 × σ2

n=

(μ1−μ2)2

 2 (1.96 + 1.28)2 × 10.22

n=

(25-16.2)2

 n=28.20

Procedure

The patients enrolled to this study underwent physical examination,neurological examination, and laboratory tests. The operationwill be  performed at the Pain OT,Department of Anaesthesiology,KGMU, Lucknow

The procedure of PRP preparation will be follows: 18 ml blood samplewill be drawn from the anterior elbow vein and mixed with 2 ml of 3.8%(w/v) sodium citrate (total 20 ml). The blood sample willbe centrifuged at 1600 rpm for 10 min at room temperature(23 Â°C) under aseptic condition to divide the sample into 3 layers. Thelower layers, composed of red blood cells, will be subsequently removed. Theremaining sample will be transferred into a new centrifuge tube and wascentrifuged again at 3200 rpm for 10 min at room temperature.4 ml was collected from the lower part which contains PRP.

Technique of transforaminal PRP injection: thepatient lied prone, under localanesthesia. To determine the point for injection: 3–5 cmfrom midline, depending on the side with corresponding symptoms, check theright segment below the C-arm. Align the C-arm head in the diagonal directionuntil the superior articularsurface ofthe lowervertebrae isin the middle of the disc space. Insert the 22G Spine needle in the directionof the lamp head, gently until it passes the outer edge of the superior joint.Adjust the lamp head in the front and back direction, determine that the needletip is on the inter-peduncle seam. Align the lamp head in the lateraldirection; locate the needle tip at the lower back of the conjugate hole.Gently withdraw the syringe to check for blood orcerebrospinalfluid. Inject 1 ml of Omnipaque300 contrast agent, check theC-arm to see if the drug spreads along the path of the nerve roots into theepidural area. Inject 4 ml Platelet Rich Plasma. Withdraw the needle andapply a sterile bandage at the injectionsite.Check vital signs after the procedure. Same procedure will be done for group Bpatients

Patients will be evaluated after 1 h of procedure anddischarged with advice to avoid too much bending, lifting heavy weight orwalking long distances and asked to follow-up at 1 week, 2 weeks, 1 month and 3months. VAS score, and likert scale will be recorded at all times.Neurological check-up of lower limb included motor examination in form tone,muscle strength, reflexes and sensory examination as well as side effects ofprocedure will be evaluated.

Measurement of outcome

Patients’characteristics comprise of gender, age and baseline data upon admission.Baseline data will be collected including visual analogue scale (VAS), and Likertscale. Randomization will be done as computer generated random number table.

Firstly,the visual analogue scale (VAS) will be a method to evaluate the degree ofpain. A 10 cm line as an indicator presented one end meaning no pain,while the other end meaning the most severe pain. The patient will be asked toindicate the point on the line which could represent patient’s pain level.

VAS:before injection and after injection for 1 week, 2 weeks, 4 weeks and 12 weeks.To define as effective in pain relief, pain level post-op had to be smallerthan pre-op at least 2.5 points and had to decrease ≥50% compared to pre-op,according to VAS.

Likert scale assumes that the strength/intensity of an attitude is linear,i.e. on a continuum from strongly agree to strongly disagree, and makes theassumption that attitudes can be measured.

Statisticalanalysis:

Data will be entered in Microsoftexcel and analyzed using statistical software SPSS version25( Chicago, IL,  USA). Student’s t test willbe used to analyze parametric data, while the Mann-Whitney U testwas applied to non-parametric data and Fisher’s test to categorical data. Pvalues < 0.05 will be considered statistically significant.

REVIEW OF LITERATURE

Bodoretal. [2014] studied 35 patients who were given 47 disc injections of PRP inthe lumbar and thoracic spine (28). Two-thirds of the patients showed positive outcomes. Theauthors also presented a detailed case series of five patients with discogenicback pain treated with PRP injections. The follow-up period ranged from tendays to 10 months, in which patients exhibited substantial improvements in painthat enabled them to return to normal physical activities. Despite two patientshaving vasovagal episodes, there were no complications or side effects relatedto this treatment.12

In 2016,Levi *et al.*13 published data from a prospective clinicaltrial on 22 patients examining the effect of intradiscal PRP injection ondiscogenic back pain (35). No complications or serious side effects were reported.Back pain was measured using a visual analogue scale (VAS) and OswestryDisability Index (ODI). After a 6-month follow-up period, 47% of patientsreported at least a 50% improvement in pain and a 30% improvement in their ODIscore. The authors speculate that the time frame required for the treatment totake effect, possible adverse effects from the anesthetics and antibiotics usedduring the procedure, and the PRP preparation method used, account for the lackof a significant positive outcome in this study. In another study by Navani andHames [2015],14 six patients were given a single injection of 1.5–3mL of autologous PRP (36). At a 24-week follow-up, patients reported a 50% decreasein pain according to the verbal pain scale (VPS), with no adverse effectsreported.

In 2016,Hussein and Hussein performed a clinical trial on 104 patients with chronic lowback pain. Unlike the studies mentioned earlier in this section, plateletleucocyte-rich plasma (PLRP) was used instead of PRP, owing to the phagocyticnature of leucocytes. Injections were carried out weekly for 6 weeks. Themethod was proven to be a safe and effective method for relieving chronic lowback pain, with a success rate of 71.2% reported by the authors. No adverseeffects or complications were reported other than short-term pain at theinjection site.15

The firstdouble-blind randomized controlled trial (RCT) of intradiscal PRP therapy wasperformed by Tuakli-Wosornuet al. in 2016 on 47 participants withchronic lumbar discogenic pain. Participants with a history of chronic axiallow back pain were recruited and were randomly allocated to treatment orcontrol groups at a 2:1 ratio, respectively. At an 8-week follow-up, outcomeswere measured by Functional Rating Index (FRI), Numeric Rating Scale (NRS)-bestpain, the Short Form (SF)-36, and modified North American Spine Society (NASS)satisfaction scores. The study found statistically significant improvements inthe treatment group, and the effects of PRP were sustained for a period of atleast 1 year according to FRI scores. No complications were reported.16

In a pilotstudy performed on ten patients in 2016 by Bhatia and Chopra, PRP injectionswere shown to improve pain. Patients suffering from chronic prolapsedintervertebral discs were given single 5 mL injections of autologous PRP andwere followed up after 3 months. Improvement in pain was evaluated using VAS,the Modified Oswestry Disability Questionnaire (MODQ) index and Straight LegRaising Test (SLRT). All patients had a gradual improvement in symptoms thatpersisted for at least three months without any complications.17

In 2017,Akedaet al. conducted a clinical study investigating the safety andfeasibility of autologous PRP releasate injections for discogenic low backpain. PRP releasate is a form of bioactive soluble factors isolated fromactivated PRP that can stimulate tissue repair. The authors implicated that theplatelets were isolated by the buffy coat (BC) method and therefore containedlower concentrations of pro-inflammatory cytokines; hence, the sample wasconsidered as “pure PRPâ€. This prospective, preliminary clinical study wascarried out in 14 patients with lumbar discogenic low back pain for a period of10 months. Seventy-one percent of patients showed a 50% reduction in pain asmeasured by VAS scores; however, low back pain returned in two patients. Incontrast to the VAS scores, physical disability scores [Roland-MorrisDisability Questionnaire (RDQ)] were significantly reduced in 79% of patients.Apart from temporary leg numbness in two patients, no other notable adverseevents were reported. In summary, this study proved the safety, feasibility andefficacy of PRP in the treatment of lumbar discogenic back pain.18

A singlecase report by Lutz [2017] reported on the effectiveness of intradiscal PRPinjection for improving low back pain and function. The patient was diagnosedwith a degenerated disc and had received an ineffective caudal epidural steroidinjection and physical therapy. The patient was given a single PRP injectionand showed considerable improvement in pain and motion after 6 weeks. At a1-year follow-up, there was remarkable improvement in low back pain and thepatient was able to return to athletic activities.19

Theclinical studies discussed so far in this review demonstrate the efficacy ofautologous PRP when applied alone in the treatment of chronic back pain.Therefore, a report which shows the effect of PRP injection together withanother agent [stromal vascular fraction (SVF)] is particularly interesting.Comellaet al. investigated the safety and efficacy of PRP in combinationwith SVF delivered into the disc nucleus of patients with degenerative discdisease. SVF is a mixture of adipose-derived stem cells (ADSCs) and growthfactors. The study proved to be safe and successful with significantimprovements in flexion, VAS, and pain scores according to the Present PainIntensity (PPI) scale, SF-12 and Dallas Pain Questionnaires (DPQ). The majorityof patients reported remarkable reductions in pain compared to baseline over aperiod of 6 months post-injection. The only side effects reported were sorenessin the abdomen from liposuction (for SVF) and soreness in the back from the PRPinjection, both of which resolved within 1 week.20

MohammedS  et al (2018) conducted a study thatAutologous platelet-rich plasma (PRP) injections have been investigated in recentyears as an emerging therapy for various musculoskeletal conditions, includinglumbar degenerative disc disease. Although PRP has received increasingattention from medical science experts, comprehensive clinical reports of itsefficacy are limited to those treating knee osteoarthritis and epicondylitis.Use of PRP is gaining popularity in the area of degenerative disc disease, butthere is a clear need for reliable clinical evidence of its applications andeffectiveness. In this article, we review the current literature on PRP therapyand its potential use in the treatment of chronic discogenic low back pain,with a focus on evidence from clinical trials.21

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