Carolyn Kim and Christopher Gharibo
Corticosteroids have been a mainstay in the area of interventional pain management because of their clinical effectiveness in treating numerous inflammatory subacute and chronic pain conditions. These conditions often include significant inflammatory components as seen in certain neuraxial, intra-articular and extra-articular disorders.
INDICATIONS FOR CORTICOSTEROIDS IN INTERVENTIONAL PAIN MANAGEMENT
Hollander introduced the concept that injected corticosteroids can have a positive effect on inflammatory pain conditions in 1950. Since Hollander’s study, the role of corticosteroids has expanded into treating many other types of acute and chronic pain conditions such as degenerative and inflammatory conditions of the peripheral joints and the spine.6
The common indications for corticosteroids in interventional pain medicine can be broadly divided into the following categories:
Epidural steroids were introduced into the United States in the 1960s and are the most commonly performed spinal interventions in the United States with an annual estimated Medicare spending of 175 million dollars in 2001. Studies have shown that epidural steroid can be effective in the treatment of painful radiculopathy from:
Other diseases that may benefit from corticosteroid injections include:
CONTRAINDICATIONS FOR CORTICOSTEROIDS IN INTERVENTIONAL PAIN MANAGEMENT
The contraindications are more a function of the specific injection being performed rather than whether if cortisone should be included in the injectate. Active infection at the needle insertion site must be considered before all injections although this at times may prove difficult to differentiate from noninfectious arthropathies. Bleeding disorders are especially important in neuraxial procedures as they can lead to paralysis if the physician is not appropriately vigilant. The absolute and relative contraindications for corticosteroid injections are listed in Table 6-1.
TABLE 6-1. Absolute and Relative Contraindications to Corticosteroid Injection
PHYSIOLOGY
PHARMACOLOGY
Cortisol has a half-life of about 90 minutes and is metabolized in the liver by its conversion to a water-soluble compound that can be excreted by the kidney. Any change in the physical structure of the compound, such as with the commonly used particulate preparations of steroids, will result in slower metabolism of the product and thus a longer half-life and duration of action.
The role of corticosteroids in interrupting the inflammatory pathway is shown in Figure 6-1.
Figure 6-1. Inflammatory pathway.
Pain relief after injection of a neuroma with corticosteroids can be due to:
Corticosteroids act at the nerve fibers and affect the transmission of pain. A study in which the sciatic nerves of rats were ligated and then treated with either triamcinolone hexacetonide, triamcinolone diacetate, or dexamethasone demonstrated a statistically significant reduction in the incidence of spontaneous discharge of the A beta fibers in a neuroma compared to the saline control. The application of corticosteroids to the cut nerves prevented ectopic neuroma hyperexcitability and decreased the discharge in active neuromas that had been present for 3 to 10 days postoperatively. A study by Johnasson of corticosteroids on exposed rat nerves interestingly suggested that its application reduced the transmission of normal unmyelinated C-fibers that carry nociceptive impulses.33
With inflammatory, neuralgic, and paresthetic pain, the initial insult results in:
COMPLICATIONS OF CHRONIC CORTICOSTEROID THERAPY
Adrenal Insufficiency
Adrenal Insufficiency is a significant concern with frequent exogenous corticosteroid administration because of the interaction with the HPA axis which functions on a feedback mechanism. Symptoms include:
The degree of adrenal suppression is affected by the dose, frequency, chronicity and intervals between glucocorticoid administration. However, an acute suppression of ACTH after a single dose of epidural trimacinolone and suppression of cortisol levels following an intra-articular and intramuscular injection have also been shown. Prompt recognition and treatment are essential. The duration of adrenal suppression with the commonly used depot corticosteroids is shown in Table 6-2. Adrenal suppression has been reported to take up to 9 to 12 months to recover after chronic use of supraphysiologic doses of glucocorticoids.
TABLE 6-2. Adrenal Suppression and Depot Corticosteroids16
Hyperglycemia
There are conflicting reports regarding the effect of intra-articular and epidural steroid injections on glucose levels. Significant hyperglycemia may occur and is secondary to:
This fact is even more relevant due to the fact that lumbar spinal stenosis is more prevalent in patients with diabetes, thus highlighting the need for patient education and vigilance on this matter. Furthermore, elevated glucose levels have been shown to be an important risk factor in postoperative infection after spinal surgery and the same risk may hold for spinal injections as well.
Cushing syndrome has also been described following repeated epidural steroid administrations. This condition manifests as:
Therefore, it is important to have the patient’s diabetes optimized before the injection followed by postinjection glucose vigilance.
Some of the other complications reported with chronic administration of corticosteroid are:
COMMERCIALLY AVAILABLE PREPARATIONS
Although various corticosteroids preparations are available for several different modes of administration, the injected depot form is most commonly utilized in pain medicine due to their sustained effect in the treated area. The most commonly used depot steroid preparations are:
Although data on comparative efficacy is lacking, it can be beneficial to understand the physical properties, solubility, duration of action, particulate size, and presence of additives in individual preparations.
Solubility is a critical component since corticosteroids with a lower solubility will theoretically result in a longer therapeutic action with less systemic effects than that of a compound with a high solubility. However, it should be noted that this may or may not correlate with the clinical effect. For example, when triamcinolone hexacetonide, a compound with a lower solubility, was compared with methylprednisolone acetate, the triamcinolone had a lesser clinical effect than methylprednisolone acetate when used in the treatment of osteoarthritic knees.
The duration of action differs significantly among the corticosteroids. This is a highly variable value and can range from 6 to 90 days. The following chart (Table 6-3) reviews the basic characteristics of the different corticosteroids that are commonly used in interventional pain medicine.
TABLE 6-3. Characteristics of Corticosteroids5,20
The preservatives found in corticosteroid formulations play a role in their selection as well since there have been case reports of adverse effects attributed to the preservatives alone. A case report of flaccid paraparesis for 16 months following an epidural was linked to the benzyl alcohol preservative that was in the saline solution injected through the epidural catheter. Benzyl alcohol is effective against both gram-positive and gram-negative bacteria which can be found in epidural abscesses. Another potential culprit is polyethylene glycol which was shown to be neurolytic and produced degeneration of rat nerves. It has also been shown that concentrations of greater than 20% of polyethylene glycol can diminish the action potentials of myelinated alpha, beta, and unmyelinated C-fibers. This neurotoxic risk has led to the practice of dilution of the corticosteroid preparation in order to lessen the risk from the concentrated preservatives as well as improve the spread of the injectate.
PARTICULATE VERSUS NONPARTICULATE CORTICOSTEROIDS
Particle size in corticosteroids has posed an important debate in the treatment of chronic pain. Solutions with larger particles would seem to be preferred given their longer duration of action. The risk of embolization has been brought up as a hypothetical concern with particulate solutions. Although all synthetic corticosteroids have long biological half lives (36-72 hours), this duration can be further prolonged by a particulate formulation that can slowly release into the localized area. However, multiple case reports of paraplegia, conus infarction, quadriparesis, cerebellar infarction, and death have been cited, primarily after cervical transforaminal injections.
The exact mechanism of neural injury is uncertain in many of these cases. The cause of injury may be due to one or more of the following factors:
Almost all the cases of lumbar transforaminal epidural steroids resulting in spinal cord infarction were patients who had prior lumbar spine surgery. Although less likely, an intraosseous injection (due to osteopenia) with a particulate steroid has been demonstrated to travel to the inferior vena cava. It is questionable whether such communication can occur with the arterial circulation leading to cerebrovascular or spinal embolization or whether venous embolism of steroid particles would be of sufficient caliber to result in neural damage.
The pathogenesis of the final injury may be due to any one of the above factors alone or a combination of them. There has been much discussion of types of steroids injected in the epidural space and specific focus on particulate steroid size in relation to the inner blood vessel diameter in the region. However, when the particulate steroid embolization is put into perspective, it is only one of many potential explanations for neural injury.
The highly variable vascular anatomy of the spinal cord presents a certain amount of inherent risk during any spinal injection. The steroid particles have been analyzed and measured under a high-power microscope to characterize their physical properties more accurately. Both methylprednisolone and triamcinolone could aggregate to greater than 100 micrometers which could contribute to occlusion. The different particle characteristics are shown in Figure 6-2.
Figure 6-2. Microscopic appearance of corticosteroids.5 (Reproduced with permission from The Spine Journal 2004; 4: 468-474.
Derby et al in a corollary experiment used the size of a red blood cell (7.5 × 7.8 μm in diameter) as the reference point for a blood vessel and compared it to the sizes of the particulate matter of the corticosteroid preparations.30 Derby’s observations are shown in Table 6-4.
TABLE 6-4. Size of Steroid Particles Compared to RBC (7.5-7. μm)
There is no conclusive evidence that compares the efficacy of particulate versus nonparticulate steroids. Most studies with positive results for epidural steroids injections have been performed with particulate steroids suggesting that the use of nonparticulate steroids based on a theoretical risk may not be comparably efficacious.
Suggested Reading
Hollander J et al. Hydrocortisone and cortisone injected into arthritic joints. JAMA. 1951;147:1629-1635.
Kushnerik V, Altman G, Gozenput P. Pharmacology of steroids used during epidural steroid injections. Tech Regl Anesth Pain Manag. 2009;13:212-216.
Manchikanti L. Role of neuroaxial steroids in interventional pain management. Pain Physician 2002;5:182-199.
References