Septic and Aseptic Complications of Corticosteroid Injections: An Assessment of 278 Cases Reviewed by Expert Commissions and Mediation Boards From 2005 to 2009

Parenterally administered corticosteroids are used both for systemic treatment (by the intravenous or intramuscular route) and for local treatment (by infiltration or intra-articular injection). They are typically obtainable either in aqueous solution or in crystalloid suspension. These types of preparation are said to confer a longer-lasting effect (a “depot effect”).

Ever since the historical beginnings of local treatment by injection, complications have been recognized, including, for example, joint empyema (1, e1) and abscess formation. Sepsis is a not uncommon sequela of such complications; even death is a possible result. The local administration of steroids in the spine can be complicated by weakness of variable severity, ranging all the way to paraplegia.

Aseptic soft-tissue damage or infection that arises in association with, or in the aftermath of, corticosteroid injections can vary in severity from a small, slightly discolored indentation in the skin over an area of soft-tissue attenuation to extensive necrosis of multiple layers of soft tissue.

In this article, we discuss corticosteroid-related infection and aseptic tissue atrophy but omit any discussion of bony necrosis after intramuscular or intra-articular injection (2, 3, e2, e3). Other types of complication that are beyond the scope of this article include tendon rupture after corticosteroid infiltration (4, e4; a complication that has been recognized for many years), systemic side effects (5), very rare cases of secondary adrenal insufficiency (6), and injection-related Tachon syndrome (7).

Methods

The expert commissions and mediation boards of the medical associations of all states in the Federal Republic of Germany (hereinafter called the ”expert panels”) evaluated a total of 36 575 medicolegal cases from 2005 to 2009 (Table 1). 1528 cases involved complications of injections, of which 278 were found to have been local injections of corticosteroids. In these 278 cases, there were 223 instances of infection and 55 of aseptic tissue damage.

Table 1

Cases of infection or tissue atrophy ofter local corticosteroid injection that were reviewed by the expert commitees for medical malpractice claims and mediation boards across Germany from 2005 to 2009, as documented in MERS

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The expert panels enter their findings into a nationwide database called MERS (Medical Error Reporting System) using criteria that are uniform across Germany. Even though the selective data contained in MERS cannot be extrapolated to yield an estimate of the total number of injection-related adverse events that occur in Germany every year, they are certainly a good source of information on the cortisone injection–related complications and avoidable treatment errors.

In addition, we searched the literature for articles containing the terms “cortisone,” “injection,” and “infection” and looked for reports of the frequency of complications. This search also revealed further information about the efficacy of certain therapeutic procedures.

Alleged treatment errors

The expert panels evaluated patients’ allegations of treatment errors of the following types:

• inadequate diagnostic evaluation prior to injection
• faulty injection (in particular, inadequate aseptic technique)
• use of the wrong medication
• overtreatment
• failure to inform the patient of potential complications and non-invasive therapeutic alternatives
• delayed recognition of infection after injection.

Case illustrations

Case 1: multiple abscesses after paravertebral injections

A 74-year-old woman was treated in a neurosurgical group practice for “back pain radiating to the posterior aspect of the legs and cramps in the feet.” Nothing further about the patient’s history was documented. A computed tomogram (CT) of the lumbar spine that had been obtained nine years earlier was interpreted as showing “marked changes in the spinal joints.”

The patient was treated with a total of three “sacral blocks” in the space of four days. Five weeks later, because of “recurrent lumbar spinal pain,” she underwent four further paravertebral injections in the space of eight days. These injections were designated as “L3–S1 blocks.”

Only one physical examination was documented in the entire course of her treatment: “Lumbar spine stiff in fixed posture, no weakness, reflexes symmetric, sensation OK.”

All injections included both a local anesthetic and a corticosteroid. The physicians were later unable to say precisely what quantity was injected (probably a total of 240 mg of triamcinolone) or whether a fresh needle was used to inject the second side in each treatment. Patient information was documented by a standardized form.

Two days after the last injection, the patient was admitted to the hospital via the emergency room and remained hospitalized for four weeks. She underwent three operations for the treatment of abscesses in the paraspinal musculature, in a psoas muscle, and inside the spinal canal. The causative organism was identified as Staphylococcus aureus. The patient was paraparetic; her weakness resolved slowly during the period of inpatient rehabilitation that followed.

The main treatment error was judged to have been that too much corticosteroid was injected at too short intervals, elevating the risk of infection. A reprimand was issued because of the absence of documentation of the patient’s history and the failure to mention alternative treatments that clearly would have been feasible options in this case.

Case 2: extensive necrosis after intragluteal injection for back pain

An obese 49-year-old woman who was said to be suffering from a “chronic, recurrent spinal syndrome” received multiple intragluteal injections of 4 mg of dexamethasone dihydrogen phosphate, 4 mg of dexamethasone, and diclofenac. About six weeks after the last injection of one of these substances, she required surgery for the removal of 500 g of necrotic skin and subcutaneous fat from the buttock. An infection that arose at the resection site necessitated multiple further hospitalizations.

The expert panel determined that there were two treatment errors: injection into adipose tissue, rather than into the deeper-lying musculature (prima facie evidence, see Box), and the repeated parenteral application of the substances, instead of a switch to oral administration.

Box

Prima facie evidence

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Findings

The distribution of complications (infections and aseptic tissue damage) by site of application, in both absolute numbers and percentages, is shown in Table 1.

Roughly half of the 55 cases of tissue atrophy after corticosteroid injections involved intramuscular depot injections, mainly for the treatment of allergy. Treatment errors were especially common in this situation.

The type and dose of the corticosteroid used could not always be ascertained from the medical record, as they were sometimes not documented. As far as can be determined, the most commonly used corticosteroid was triamcinolone.

The expert panels’ explanations for the individual treatment errors that they judged to have occurred, as documented in the MERS database, are shown for the infectious cases in Table 2 and for the cases of aseptic tissue damage in Table 3. The most common errors were:

Table 3

Treatment errors that were determined to have occurred in cases of tissue atrophy after corticosteroid injection

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• delayed recognition of infection (24 cases)
• lack of indication (19 cases)
• faulty aseptic technique (18 cases)
• too superficial gluteal injection (14 cases)
• injection at too short intervals (14 cases).

Patients were found to have been inadequately informed of the risks of treatment in 20 cases; in nine of these cases, the treatment was judged to have been properly conducted in other respects. Whenever legally valid informed consent is lacking, the physician is liable for all adverse effects of the injection on the patient’s health.

Discussion

The injection of corticosteroids into inflamed joints is a method of treatment that has been used with good effect for decades (e5–e7). Unfortunately, it can also be complicated by intra-articular infection, sometimes leading to severe sepsis. Another complication that has been known and feared for decades is abscess formation after intramuscular injection; necrotizing fasciitis is a severe variant of this problem (8, e8). The reported frequencies of joint infection after intra-articular injection range from 1 in 3000 to 1 in 100 000 (9, e2, e6, e9–e12). Faulty aseptic technique at the time of injection is thought to be the main cause. Expert panels generally consider infection to be no more than the random expression of a small risk inherent to the procedure if it is found to have occurred despite proper aseptic precautions. In such cases, infection is thought to be due to pathogenic organisms that were present in deeper-lying parts of the skin not accessible to aseptic disinfection (9, e1, e13).

It has likewise been known for at least 50 years that locally injected corticosteroids can damage the skin (10–12, e14–e18). Moreover, corticosteroid-related soft-tissue damage has been reported in the eye (e19), the hairy scalp (e20), the mandible, and the sole of the foot (e21). Soft-tissue damage can also be a complication of injections into tendon spaces (12) and of injections that were intended to be intra-articular (e22).

Most of these individual case reports involved mild, primarily cosmetic complications. Some involved more extensive ones taking the form of embolia cutis medicamentosa (e23) or even very extensive and severe tissue necrosis in Nicolau syndrome (13, e24–e28).

The locally injected drug is usually a combination of a local anesthetic with a corticosteroid; intramuscular injections are usually of a corticosteroid alone, or else of a corticosteroid combined with an analgesic (by intragluteal injection, as described in Case 2, above). Intra-articular corticosteroid injections are usually performed without any other admixed drugs, or else after local anesthetization of the needle trajectory. Sometimes the corticosteroid is given in combination with a so-called cartilage-production promoter.

The most common applications of corticosteroids other than in the joints (which we will designate as “injections into the soft tissues”) are infiltrations of

• muscle, tendon, and ligament origins and attachments
• synovial tissue and tendon spaces
• the carpal tunnel
• mucosa-lined pouches (bursae), particularly subacromial bursae (in rotator-cuff defects—which are more common from age 50 years onward—subacromial infiltration inevitably becomes intraarticular injection) and trochanteric bursae.

Such injections are always performed to treat a presumed state of inflammation that is diagnosed on the basis of the patient’s symptoms and physical findings. Examples include humeral epicondylopathy, de Quervain’s tendovaginitis, and achillodynia involving the synovial tissue.

Paravertebral infiltrations and injections are very common as well. They are generally performed in the vicinity of nerve roots. Facet infiltration is also a type of nerve-root infiltration, as it is intended to block the posterior branch that emerges directly from the spinal nerve (14, 15, e29–e31). Injections performed without image guidance are often soft-tissue infiltrations rather than nerve-root infiltrations. Infection after paravertebral injections is a less widely known complication than infections at other sites, even though it can have very severe consequences.

Superficial atrophy of skin and adipose tissue, with central discoloration of the skin, is attributed to a combination of the following factors:

• an inhibitory effect on fibroblasts that lowers protein synthesis;
• blockage of lymphatic pathways;
• displacement of tissue fluid.

In about half of all cases (as far as can be determined from an overview of case reports), the affected area returns to normal over a few months to years. The duration of this process seems to be a function of the cortisone dose.

It has been pointed out time and again—and rightly so!—that all patients should be informed in advance of this potential complication.

Nicolau syndrome is a rare entity that has been observed as a complication of the types of treatments that we have been discussing. It is caused by acute arterial thrombosis or spasm upon the intravascular injection of an insoluble drug, leading to ischemic soft-tissue damage in the distribution of the vessel in question. Severe pain and livid discoloration of the skin usually arise right after the injection. Nicolau syndrome can cause small central or more extensive necrosis, nerve damage, compartment syndrome, and gangrene. Corticosteroid injections without any other precipitating cause account for only a small minority of the reported cases. Superficial infiltration can cause more extensive damage (embolia cutis medicamentosa).

Overview

A thorough discussion of the pharmacological properties of the various types of glucocorticosteroid would be beyond the scope of this article. For more information on the half-life, crystal size, parenteral effects, and threshold doses of each type of corticosteroid, as well as the recommended temporal intervals between repeated injections at a single site, the reader is referred to the specialized literature (16) and to manufacturer-supplied information.

Overtreatment is certainly a problem in German medicine in general, particularly with respect to invasive treatments (17, e48). Many such treatments have turned out not to meet the high expectations originally placed on them when their effects were later subjected to careful study, e.g., in Cochrane Reviews (18–22, e32–e36). Clearly, some patients are being endangered where there is no justification for doing so.

The diagnosis of “facet syndrome,” for example, is often assigned in cases of nonspecific, chronic back pain, an entity whose proper treatment certainly does not involve serial injections (17, 23, e22, e46). As stated in the statistical report of the German Institute for Hospital Reimbursement (Institut für das Entgeltsystem im Krankenhaus) for the year 2010, “[...] interventional treatments for pain are carried out about ten times more often in Germany than in other countries, even though their lasting efficacy has not been demonstrated and despite the considerable danger of long-term patient dependency.”

Infection after corticosteroid injections is relatively common; there would be far fewer severe complications and complications overall if injections were performed only when strictly indicated.

The following conclusions can be drawn from the material provided by the expert panels:

Intra-articular corticosteroid injections should come into consideration only when there is a diagnosis of an “inflammatory state in a joint,” i.e., activated arthrosis with swelling and effusion. The quantity and formulation of the drug should be chosen in relation to the size of the joint, and the manufacturer’s instructions should be strictly followed. Moreover, repeated injections should be performed only after an adequate interval, and the total quantity injected in one year should not exceed the allowable limit.

The relevant guidelines (AWMF Guideline Registry 029/006: Intraartikuläre Punktion und Injektionen [Intra-Articular Punctures and Injections] [24, e37–e39]) state that aseptic technique should be used. This implies, among other things, that the physician must invariably have an assistant when performing joint punctures and injections or paravertebral infiltrations (e40). Furthermore, expert panels generally cannot assess the methods that physicians claim to have employed to ensure asepsis, because the panels are not judicial bodies and cannot examine witnesses. Thus, panels must proceed from the assumption that the injection was performed in adherence to the specifications for standard aseptic technique, without any violation. Statements to the contrary by the complainant cannot be used as the basis for the panel’s judgment. In any case, there should be standardized specifications for aseptic technique and instructions for treatment personnel in any institution or practice where such treatments are performed.

Missed infections (e41, e42) were judged several times to have been treatment errors (Table 2). On the slightest suspicion of infection after an injection, the appropriate diagnostic tests should be ordered at once (laboratory tests, ultrasonography, magnetic resonance imaging) and the patient should be followed up at short intervals, or, if necessary, hospitalized. Joint fluid obtained by puncture should be sent for bacteriological testing on the slightest suspicion of an intra-articular infection.

Table 2

Treatment errors that were determined to have occurred in cases of infection after corticosteroid injection

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The indication for treatment should always be documented in the medical record in such a way that it can be critically evaluated by others. Corticosteroids should be used for facet injections only when a prior test injection of local anesthetic has led to clear improvement. As the manufacturers’ instructions point out, repeated injections at short intervals should be strenuously avoided.

The intramuscular injection of depot corticosteroids is held to be contraindicated because of the risk of characteristic adverse effects due to suppression of the hypothalamic-pituitary-adrenocortical axis. This mode of corticosteroid administration was designated as obsolete many years ago (e43–e47). Even though the “Red List” in Germany still permits the intramuscular administration of depot corticosteroids for certain indications (according to information from a small number of manufacturers), the physician can nonetheless be held liable for any complications that arise, as it is the long-established judgment of general medical opinion that such treatments should not be performed.

In all cases of extensive tissue necrosis, particularly in the buttocks, it can be assumed that the injection failed to reach the musculature because the needle used for it was too short. According to the juridical principles of prima facie evidence (Box), this can substantiate the determination that a treatment error has occurred.

Superficial tissue atrophy is likewise caused, in most cases, by crystal deposition outside the intended target of injection, and less commonly by partial backward flow of the injected fluid. If the corticosteroid is mixed with local anesthetic and the injection is begun as soon as the needle perforates the skin in order to diminish the pain of the procedure, partial deposition of crystals in subcutaneous tissue is inevitable. It is, therefore, safer to infiltrate the needle trajectory with pure local anesthetic first, and only then to inject the corticosteroid.

All injections carry a risk of side effects of the injected drug as well as other risks related to the injection per se (infection, vascular injury, nerve injury). To assure patient safety, the indication for the injection should always be critically assessed, and the patient should be fully informed about all risks and therapeutic alternatives (e.g., oral corticosteroid administration instead of depot injection) (25).

Physicians should decline to perform any injection that is not medically indicated, even if the patient requests it. Whenever a proper indication is lacking, the physician can be be held liable for any complications that arise.

Conflict of interest statement
Mr. Smentkowski has received lecture honoraria and reimbursement of travel expenses from Bayer AG. Prof. Holland, Mr. Jaeger, Dr. Weber, and Dr. Otto declare that they have no conflict of interest.

Manuscript received on 1 September 2011, revised version accepted on

2 February 2012.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Christian Holland
Ärztekammer Nordrhein, Tersteegenstr. 9
40474 Düsseldorf, Germany
gak@aekno.de

@For eReferences please refer to:
www.aerzteblatt-international.de/ref2412