Universal symbols frequently associated with physicians are the stethoscope and the hypodermic syringe and needle. Early in the 19th century, scientists were able to purify and isolate active ingredients of several drugs, which would allow small quantities of the drugs to be administered to patients to get desired effects. Subsequently, physicians began searching for ways to administer these drugs so that the medications could be quickly absorbed into the bloodstream and not be altered or destroyed by digestive juices of the patients. Thus, the idea of administering drugs through the skin was conceived. As early as 1809, the French physiologist, Francois Magendie, coated wooden slivers with a drug and pushed it through the skin of his patients. The technique was successful, but unfortunately his patients died. The drug he administered was later found to be strychnine. The administration of medications by hypodermic injection, a term originating from two Greek words that mean "under the skin," was introduced by a Scottish physician, Alexander Wood, in 1853. He attempted to relieve the pain of patients with neuralgia by placing medication next to the involved nerves. The complete history of the development of hypodermic injection of medication can be found in the references.
IM Injection Complications
The first reported complication of the hypodermic injection of medication was reported by Dr. Charles Hunter, a London surgeon, in 1865. Two of his patients who received multiple morphine injections subsequently developed subcutaneous abscesses at the injection sites. At the time of his report, there was no sterilization of medications, syringes, or needles. It was not until 1867, twelve years after Dr. Wood introduced hypodermic injection of medication, that Dr. Joseph Lister published his work on surgical antisepsis and germs. Strangely, complications of hypodermic injection must have been exceedingly uncommon because Dr. Hunter, whose patients developed the first reported complications, said that "if the site of the injection was continually varied and the puncture was made with care and celerity, there was no fear of abscess or diffuse inflammation."
By 1880, complications from the technique were beginning to be recognized. In that year, Dr. H. H. Kane of the United States surveyed physicians worldwide and found all were seeing patients who suffered infectious complications due to hypodermic injection of medications. It was not until 1885 that the complications of this widely practiced procedure were acknowledged by the medical profession.
Today, the incidence of developing a complication from IM injections ranges from 0.4 percent3 to 19.3 percent of patients receiving the IM injection of a medication. The complications that can occur following this procedure are numerous, and some are surprising (Table 1). It has been suggested that most of the problems stemming from the procedure are related to local trauma of the injection itself or the irritating properties of the drug. Others suggest that inadequate training in the proper injection technique is responsible for many of the complications. In some cases, the true etiology of the problem is not immediately apparent.
Leakage. Leakage or seeping of the injected solution from the injection site after the needle is removed seems to be an insignificant problem but can result in erratic absorption of the medication and loss of the expected dose of the medication. This usually occurs in patients who have significant scarring at the injection site, which makes the tissue hard and less receptive to accepting the volume of fluid injected. Large amounts of simple edema fluid or lymphedema fluid at the injection site can result in erratic absorption of the medication and in medication loss since the injection tract cannot seal easily.
Bleeding. Bleeding from the injection site is not uncommon. Significant bleeding and hematoma formation can occur if blood vessels are injured. This can be a difficult problem in patients who have bleeding tendencies or are taking antiplatelet medications or anticoagulants. The person administering the IM injection should be adequately familiar with the anatomy of the region into which the medication is being given to avoid damage to blood vessels and subsequent bleeding complications. IM injections should be avoided in anticoagulated patients. Patients on antiplatelet agents should be watched closely following an IM injection to identify any bleeding problem.
Intravascular injections. None of the medications given by the IM route are safe to be given intraarterially. This is a significant problem seen in drug users who administer drugs into arteries instead of veins. Accidental intraarterial injection of medication during IM injection procedures was first reported in 1927 as a complication of bismuth injections in adults. The majority of the reported cases of inadvertent injection of medication into arteries during attempted IM injections occur in children receiving injections in the buttock region. The arteries most frequently involved are the inferior and superior gluteal arteries. The pressure exerted during the injection process can result in the medication being forced as far as the internal iliac artery to be redistributed throughout the leg. This results in a severe chemical injury to the vessels with vasospasm and thrombosis. Skin necrosis, neurological damage, and loss of limb can follow. Prompt recognition and vascular surgical consultation is imperative. Despite all therapy available, a good outcome is difficult to achieve. Having personally taken care of a child with this problem, this author can attest to the frustration of dealing with this complication. Unfortunately, aspirating the syringe prior to injection of the medication to see if there is blood return does not assure that this problem will not occur.
Nerve injury. Nerve injury is another serious complication of IM injections and occurs more frequently than originally thought. During a five-year period from 1958 to 1963, an average of one case of nerve injury after IM injection was reported every three weeks to a medical liability insurance company. Any nerve in the vicinity of the chosen injection site is likely to be damaged. The radial nerve is likely to be injured with injections in the deltoid or upper arm areas. The sciatic nerve is commonly injured by gluteal injections, especially in children. In the past, children with foot drops were thought to have had "missed" cases of polio when in fact they had suffered injuries to their sciatic nerves with IM injections given during infancy. These injuries were reported as early as the 1940s.[11,12] Sciatic nerve injury following injection is commonly manifested by paresis in the sciatic distribution followed by a causalgia or burning pain in the extremity several hours or days later. Damage to motor function can be more severe, and recovery may be less complete.[14,15] One group reported that the diagnosis of sciatic palsy was made an average of 3.8 months following the intragluteal injection. Radial nerve injury at the shoulder may be manifested by paresthesias in the distribution of the radial nerve and wrist drop. Recent information has shown there is no specific medication that is neurotoxic when injected close to a nerve, but all will result in complete transverse necrosis of the nerve with extention of the necrosis to the exit of the nerve from the spinal cord if injected directly into any nerve.
Pain. Pain during an IM injection generally is to be expected. Persistent pain, however, at the injection site is not an expected event. One series reports that persistent pain may occur in 23 percent of the patients who have complications. The prolonged pain is usually due to irritation or chemical neuritis of a nerve; however, local muscle spasm due to the presence of the irritating medication has been faulted. Continued pain at an IM injection site must be investigated to ensure it is not a symptom of an underlying abscess or other local problem. Many times this requires an MRI scan of the area as illustrated by Case 1 of this article. It is of interest that neither needle size nor needle length influence the degree of pain experienced at the time of the injection or the incidence of post-injection persistent pain.[4,6]
Abscess formation. Abscess formation at the site of an IM injection was the first recorded complication of the procedure. It was the most common complication of IM injections in one study, occurring in 31 percent of patients who developed complications. Infectious abscesses following IM injections are caused by the inoculation of the site with bacteria from the needle, syringe, or the medication. The bacteria can be carried to the tissues because of poor site preparation. Inadequately sterilized equipment and medications also can be responsible for inoculation of the area. The majority of these complications present with red, hot masses surrounding the previous injection sites. Occasionally, an abscess will rupture, and the site will be draining pus and liquid fat. Incision and drainage of the area will result in marked improvement in the discomfort and will allow for cultures to be obtained to direct antibiotic therapy. The majority of these cases are seen within a few days to a few weeks following the injection; however, in some cases, an abscess clinically may not be apparent for years after the injection as illustrated by Case 3 of this article. A high index of suspicion must be maintained for uncommon infectious problems after an injection, especially in the immunocompromised patient. For example, there is a report of a leukemia patient with no history of infectious problems who developed a localized mucormycosis infection at the site of an IM corticosteroid injection.
More commonly, the abscesses that are seen at IM injection sites are sterile abscesses. These are nodules of liquefied fat and muscle resulting from necrosis of the involved tissues. Their development has been blamed on a hypersensitivity to the injected medication, but more detailed research has shown that the problem develops when a caustic medication is injected in an inappropriate location. When the medication is injected into the subcutaneous tissues rather than the muscle, absorption is delayed, which allows for a greater tissue reaction to the medication. This reaction is manifested by local tissue necrosis and liquefaction with a surrounding area of intense inflammation. Thus, a painful nodule filled with sterile, liquefied tissue remains at the site. Many times this problem is caused by not using a needle of sufficient length to reach the muscle.
Necrosis. Necrosis of the surrounding tissue following IM installation of a medication was not thought to occur unless the patient was allergic to the medication. It has been found that necrosis of the muscle will occur after any IM injection no matter what medication is injected. The only variable is the size of the necrotic lesion and the severity of it. Forceful placement of a volume of fluid into a closed space will cause damage. In other words, the surrounding muscle and tissues in the immediate area of the needle tip are subjected to the pressure of the mass of fluid that has been instilled into the area, which causes pressure necrosis. The toxicity of the medication, the volume injected, and even the speed at which the injection is given also will influence the size of the necrotic lesion.
Numerous medications have gained notoriety for causing complications at IM injection sites. The significance and magnitude of the damage can be predicted by measuring the serum creatine phosphokinase activity following the injection.[21,22] Cephalothin sodium and tetracycline hydrochloride were the most frequent offenders in one study, but the long-acting injectable medications have recently become the prime offenders. Despite these reports it has been stated that the incidence of complications after administration of any specific agent is generally related to a medication's popularity.
Scar formation. The significance of the necrosis may be negligible when few injections are given, but if multiple injections are given, especially in the same area over a protracted period of time, the areas of necrosis may become quite large and result in large areas of fibrosis of the tissues. This may be manifested by hard nodules felt deep in the tissues and even sunken areas of scar tissue seen on the surface of the skin. Dystrophic calcification of the scar tissue can occur with time resulting in even more painful areas. This is shown in Case 3 of this article. Once this occurs, operative excision of the area is the only therapy.
The muscle fibrosis from IM injections is a significant problem for veterinarians as well. The fibrotic scar that occurs in cattle following IM injection of medications may result in meat that is not suitable for the consumer and makes the remainder of the meat tough. The losses to the meat producers runs into the millions of dollars annually. It is apparent that the damage from IM injections is not just suffered by man.
Contracture of joints. Numerous reports have shown that in humans fibrosis of the extremity muscles following IM injections can result in contracture of joints. The local damage caused by the injected medication plus the local pressure necrosis causes the muscles to scar and shorten. This causes the extremity to be held in an abnormal position, prevents normal range of motion, and can dislocate an extremity. This problem has been reported in the shoulder due to deltoid fibrosis,[24-28] the hip due to gluteal fibrosis,[16,28] and the knee due to quadriceps fibrosis.[29-31] In a thorough review of the subject of muscle fibrosis, Brodersen concludes that the majority of the muscle fibrotic complications and contractures were not apparent until the advent and widespread use of IM injections. Repeated IM injections causes damage to the muscle with development of the fibrosis. Treatment of these problems requires operative release of the fibrotic contractures and intensive postoperative physical therapy.[24,27] Treatment with physical therapy, use of nonsteroidal agents, and stretching are not effective. It is of interest that, according to Ogawa, et al. (as quoted by Brodersen) no new cases of deltoid contracture in Japan have been reported since the dangers of IM injection were pointed out in 1975.
Malignancy. Despite the severity of the previously discussed problems, a far more disturbing complication has been reported following IM injections -- the development of malignancies at injection sites.[32,33] The reported tumors have all been forms of sarcoma. There has not been a common medication injected in patients who developed the malignancies. Even though the incidences must be extremely low, any patient who has had an IM injection and continues to complain of a painful nodule at the injection site well after the injection should be thoroughly examined.
Figure 1. An MRI showed an abscess in the subcutaneous tissues of the patient's right buttock.
Figure 2. The patient had a 5cm necrotic wound that was diagnosed as a pressure ulcer.
Figure 3. (A), This patient developed a nonhealing abscessed wound on the right hip (A: iliac crest indicated by green arrows). (B), Closer view of the hip abscess.Tables
Table 1. Complications of IM injections
Seeping of injected solution
Bleeding from the injection site
Necrosis of tissue
Contracture of joints
Table 2. Avoidance of IM injection site complications
Clean skin thoroughly before inserting needleUse disposable syringes
Use needle of adequate length
Use needle of adequate length
Inject medication only into muscle, not fat
Avoid injecting during needle insertion
Aspirate syringe prior to injectingAvoid repeated injections into the same site