Understanding Potential Complications Of Epidural Steroid Injections

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Corticosteroids are a common component of nearly all therapeutic injections for pain management that physicians perform. Whether they are used in a trigger-point injection performed by a primary care physician in an office or in a precision cervical epidural injection performed under fluoroscopic guidance, steroids have become one of the most commonly used injectable pain medications in the United States.

Despite the indisputable rise in the number of pain interventions, little has been written about the potential side effects of administering steroids into the epidural space. In fact, many premier textbooks allocate only a couple of pages to exploring glucocorticoid mechanism of action and then only briefly mention potential side effects.1 This lack of understanding has led many practitioners to naïvely view steroids as benign drugs without fully comprehending the broad scope of potential side effects that can occur when steroids are injected into the epidural space.

Undoubtedly, adverse effects from epidural steroid injections are not usually lethal, but they can carry significant morbidity and may be very disconcerting to patients. To understand the full scope of complications that can arise from epidural administration of glucocorticoids, it is necessary not only to understand the technical/mechanical complications that occur with needle placement, but also to grasp the role of pharmacokinetics, steroid particulate size, and, most importantly, how glucocorticoids affect nearly every organ system.


Glucocorticoids have slowly and steadily become more common in the pharmacologic toolbox of the modern physician. In the early 1900s, as medicine grew in its understanding of the inflammatory cascade, so, too, grew the role for steroids as a treatment modality to modulate and downregulate excess inflammation. In 1950, the Nobel Prize in Physiology or Medicine was awarded jointly to three researchers, Edward Calvin Kendall, Tadeus Reichstein, and Philip Showalter Hench, “for their discoveries relating to the hormones of the adrenal cortex, their structure, and biological effects.”2

Corticosteroids were first administered into the epidural space in the 1950s to treat sciatica, with the thought that direct deposition of medications at the site of inflammation would have a more pronounced and longer duration of action.3 Since that time, we have developed a greater understanding of how corticosteroids administered in the epidural space can modulate epidural radiculitis. There are numerous histologic and biochemical studies that have shown that there is an upregulation of substance P, calcitonin gene-related peptide (CGRP), N-methyl-d-aspartate (NMDA), and glucocorticoid receptors in lamina 1 and 2 of the dorsal horn, a key location where first-order sensory neurons synapse onto second-order sensory neurons.4 The presence of glucocorticoid receptors at that key synapse suggests that glucocorticoids modulate sensory/pain transmission either through their anti-inflammatory properties or by serving as reversible local anesthetics. Despite these basic science studies elucidating potential mechanisms of action when corticosteroids are administered into the epidural space, the complete mechanisms are still not clearly known.

Endogenous cortisol is a lipophilic, 6-ring carbon structure produced by the adrenal glands. In a nonstressed person, normal production of cortisol is 10 to 20 mg per day. Glucocorticoids are derivatives of cortisol and have numerous physiologic effects, primarily immunologic and metabolic. In the 60 years since steroid pathways were elucidated, various synthetic glucocorticoid preparations have been created, usually by substituting the outer carbon moieties on the primary 6-ring steroid structure. These synthetic glucocorticoids are more potent than cortisol, dramatically potentiating the immunologic and metabolic effects while minimizing but not fully eliminating mineral corticoid activity.

Synthetic glucocorticoids have higher receptor binding affinities for the glucocorticoid receptor and alter endogenous cortisol function by taking over the hypothalamic–pituitary–adrenal (HPA) axis. Once attached to the receptor, glucocorticoids function to induce numerous cellular changes by altering nuclear transcription (see Figure 1).

Figure 1. Chemical structure of endogenous cortisol (left), dexamethasone (right)

After glucocorticoids are injected into the epidural potential space, they can function as a medication depot, exerting prolonged anti-inflammatory action and pain/sensory signal modulation. Inevitably, the glucocorticoids are absorbed though the epidural venous plexus into systemic circulation, where they can cause numerous side effects. Finally, the agents are metabolized and eliminated from circulation by the liver. Seemingly every tissue including skin, neuronal tissue, muscle, and bone alter their function in some way when exposed to the glucocorticoid signal (see Figure 2).

Figure 2. Diagram of hypothalamic–pituitary–adrenal axis.

Cutaneous Changes

In addition to local depigmentation, skin fragility, easy bruising, and development of telangiectasia, facial flushing can be a very common side effect after an epidural steroid injection. Although not a lethal reaction, the appearance and feeling can be uncomfortable for many patients. The mechanism of steroid-induced flushing is thought to be from both immunoglobulin E (IgE) and histamine release; it is independent of route of administration and has been seen with a variety of steroid preparations.5

Commonly cited incidence numbers in many textbooks have ranged from 0.1% to 11%.6,7 Yet a recent prospective study by Kim et al aimed to further elucidate this issue.8 Kim and his team enrolled 150 patients who underwent interlaminar epidural corticosteroid injections with 16 mg of dexamethasone. They reported that 42 of the 150 patients (28%) experienced self-reported flushing, most of which occurred after discharge (30 of 42). Interestingly, 67% of those who reported flushing were female; all events resolved within 48 hours of onset.

First published on: May 1, 2011