February 25, 2019 P.M. Fornasari
A task force of regenerative medicine experts established by the American Society of Interventional Pain Physicians (ASIPP) has formulated new guidelines for the safe and effective use of biologics in the management of low back pain. The guidelines, published in Pain Physician, are based on a review of the literature on the use of regenerative injections for the management of chronic noncancer low back pain or pain in the lower extremities.
The expert panel focused on articles in which the efficacy and safety outcomes of biologic therapies were examined. A set of 10 key clinical questions were used to identify studies for the review. Evidence grading was based on randomized controlled trials (RCTs), observational studies, and several other clinical reports.
Informed Decision Making
It is recommended that clinicians include the patient as a “partner” in an effort to achieve a shared decision-making process. To this end, healthcare professionals should engage with patients and educate them about treatment-related studies, in particular, on clinical benefits and adverse events associated with a treatment, until the patient fully understands and can make an informed decision regarding their treatment strategy. Physicians should provide information regarding the diagnosis, nature and purpose of recommendations, burdens, risks, and expected benefits of every available option.
Preprocedural, Intraprocedural, and Postprocedural Considerations
Prior to receiving biologics for the management of low back pain, patients should undergo imaging (eg, magnetic resonance imaging [MRI], computed tomography [CT] scan, ultrasound, or radiographs) to identify the underlying pathology of the pain. In addition, patients should avoid using corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) for 2 to 3 weeks and 1 week, respectively, prior to the procedure, and anticoagulation precautions are recommended, ahead of the procedure.
In addition, a platelet concentration in the injectate should be ≥2.5 times than the baseline plasma concentration to be clinically effective. All biologics should undergo minimal manipulations and should be homologous, as recommended in the US Food and Drug Administration draft guidelines, and all cells should be used within a 24-hour period of thawing from frozen medium, as proliferation is thought to be highest 24 hours after thawing. Injections should be performed under direct visualization with ultrasound, fluoroscopy, CT, MRI, or arthroscopic/endoscopic guidance. After injections, patients should avoid taking anti-inflammatory medications for several weeks, and follow-up should be scheduled every 2 to 4 weeks.
Protein-rich plasma is centrifuged concentrated whole blood that is used to obtain plasma comprised of platelets with accompanying growth factors (ie, endothelial growth factor, platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor). Growth factors contained within the plasma facilitate healing by increasing the metabolic activity of fibroblasts and/or osteoblast and reducing cell death. These factors also promote angiogenesis and enhance the expression of the procollagen and collagen-derived growth factor genes. Several studies indicate that injection of platelet-rich plasma may be safe and effective for the treatment of intervertebral disk degeneration for up to 2 years.
Risks Associated With the Use of Biologics
Bleedings risk is low with bone marrow aspiration, intraarticular/soft tissue injections, and low-dose NSAIDs, but injections in the central nervous system and meninges have a high risk for bleeding. Medications (eg, selective serotonin reuptake inhibitors) or supplements (eg, fish oil, garlic) that may increase the bleeding risk should be evaluated prior to using biologics. Antithrombotic therapies should be discontinued, either temporarily or permanently, for the safe and efficient administration of regenerative medicine, and the thromboembolic risk should be assessed to evaluate the necessity of heparin bridging.
Adverse Events and Complications
Several aspects of therapies, including their risks, benefits, and indications, should be disclosed to patients before administration. Treatments using platelet-rich plasma are an example: they are known to be associated with localized inflammation, which can worsen pain and pressure sensations before the healing process.
“The survival of the clinical use of biologics depends on the standardization of their use, the consistency of outcomes, and on the documentation of an overall decrease in healthcare costs. This can be achieved by the publication of high-quality studies which will increase the predictability in the use of biologic therapy,” concluded the guideline authors. “These efforts, on behalf of our patients and to ensure the future of regenerative medicine, will require dedication on the part of all stakeholders to move the science and technology of biologic therapy forward.”
Navani A, Manchikanti L, Albers SL, et al. Responsible, safe, and effective use of biologics in the management of low back pain: American Society of Interventional Pain Physicians (ASIPP) guidelines. Pain Physician. 2019;22(1S):S1-S74.