Diagnostic Dilemma: Intramuscular Injection Site Injuries Masquerading As Pressure Ulcers

Presentation Case 1. A 47-year-old Caucasian woman was referred to the author’s facility for the treatment of “bed sores.” Five months prior to being seen at the author’s facility, the patient suffered a fracture of the right hip, which was treated with a hip prosthesis. Postoperatively, she developed a small area of skin breakdown on the right posterio-lateral buttock area. Hospital records showed that this was a stage 1 pressure ulceration of the right hip. It was treated with moist wound care and healed. Despite healing of the skin, the area of the breakdown continued to be painful and hard. Examination showed an area of induration of the right buttock at the site of the previous skin disruption. The hardness was at least 2cm below the surface of the skin. There was no overlying skin defect. No redness of the skin or other problems were noted. Magnetic resonance imaging (MRI) scan was interpreted as showing an abscess in the subcutaneous tissues of the right buttock just to the right of the midline (Figure 1). There was evidence of surrounding edema. Extending superiorly from the lesion was a track that involved the posterior medial aspect of the gluteus maximus and the posterior right sacrum. These findings were suspicious for a right gluteal abscess and osteomyelitis of the sacrum. A bone scan showed only mild increased activity in the right sacrum; this activity was not intense enough to be osteomyelitis but suggested a low-grade infection. The patient had a diagnostic aspiration of the mass. No abscess was found, and cultures were negative. The patient was treated with antibiotic medication and had some relief of her symptoms. As soon as the antibiotic medication was stopped, the discomfort recurred and the subcutaneous mass enlarged to 4cm in diameter. Case 2. An 81-year-old Caucasian woman with multiple medical problems was referred to the author’s clinic for treatment of a “pressure ulcer” of her right presacral area, which had been present for nearly four months. Home health nurses had been treating the ulcer with hydrogel dressings. At the time of the author’s evaluation, the patient had a painful stage 4 ulceration of the right ileal area that was 5cm in diameter and full of necrotic tissue (Figure 2). Case 3. A 57-year-old Caucasian woman came to the author’s clinic for treatment of an abscess of her right iliac fossa area. Over the years she had developed multiple “hard knots” on her hips, which were occasionally painful and would drain pus. The patient noted that, at times, one of the areas would open and a hard “rock” would come out after which the area would become less tender. Examination showed that the patient had multiple areas of subcutaneous calcification on both lateral hip areas. There was a subcutaneous abscess on the right hip with a surrounding area of cellulitis (Figures 3A and B). Diagnosis Case 1. A review of the patient’s hospital record at the time of her hip operation revealed that she had received an intramuscular (IM) injection of promethazine in the right buttock area in the postoperative period for symptoms of nausea. Case 2. On close questioning of the patient, it was discovered that the “ulcer” had occurred at the site of an IM injection of an antibiotic she had received for treatment of cellulitis of her right leg. The type of antibiotic and the dosage were not known. Case 3. The patient related that she had severe migraine headaches thirty years previously at the time of a family disaster. She had been treated by her physician with multiple IM injections of pentazocine. These had been given repeatedly at the site of the current problem. Diagnosis. Each patient was diagnosed as having complications due to IM injections of medication. Discussion 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.[1] 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.[1] 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.[1] The complete history of the development of hypodermic injection of medication can be found in the references.[1] IM injection complications. The first reported complication of the hypodermic injection of medication was reported by Dr. Charles Hunter, a London surgeon, in 1865.[2] 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.”[2] 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.[1] Today, the incidence of developing a complication from IM injections ranges from 0.4 percent3 to 19.3 percent[4] 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.[3] Others suggest that inadequate training in the proper injection technique is responsible for many of the complications.[5] 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,[3] 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.[6] 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.[6] Intravascular injections. None of the medications given by the IM route are safe to be given intraarterially.[7] This is a significant problem seen in drug users who administer drugs into arteries instead of veins.[8] Accidental intraarterial injection of medication during IM injection procedures was first reported in 1927 as a complication of bismuth injections in adults.[9] 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.[10] 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.[10] 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.[4] 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.[10] 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.[10] 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.[13] 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.[16] Radial nerve injury at the shoulder may be manifested by paresthesias in the distribution of the radial nerve and wrist drop.[4] 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.[4] 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.[3] 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.[13] 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.[2] It was the most common complication of IM injections in one study, occurring in 31 percent of patients who developed complications.[3] 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.[4] 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;[4] 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.[17] 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,[18] but more detailed research has shown that the problem develops when a caustic medication is injected in an inappropriate location.[19] 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.[19] 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.[19] 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.[1] It has been found that necrosis of the muscle will occur after any IM injection no matter what medication is injected.[4] 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.[20] 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,[4] but the long-acting injectable medications have recently become the prime offenders.[5] 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.[4] 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.[23] The losses to the meat producers runs into the millions of dollars annually.[23] 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.[24] 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.[27] Repeated IM injections causes damage to the muscle with development of the fibrosis.[27] 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.[27] 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.[27] 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. Treatment The treatment of each of these complications should be individualized to the particular complication. The problems that appear as open wounds should be treated as any wound would be treated. Debridement is needed for necrotic open wounds followed by good moist wound care. Painful nodules occurring soon after injection should be treated expectantly to see if they will resolve with time. Infectious complications will require treatment with incision and drainage and appropriate antibiotic medication. For the other complications, prompt specialty referral will be the best approach. Since all IM injections cause necrosis of the tissues and some type of reaction,[4] avoiding the technique completely if possible would be best. If an IM injection must be done, the appropriate technique for carrying out the procedure must be observed. Table 2 is a list of the ways to avoid potential complications.[4] To avoid complications due to vascular and nerve injury, the approved landmarks for the injection site should be identified whether in the deltoid region, the gluteal region, or the thigh region. It has been recommended that the deltoid region be avoided if possible because of the small area available for safe injection, especially in children.4 These landmarks are described in standard textbooks of nursing and numerous articles and their descriptions are beyond the scope of this discussion. Avoidance of infection at the injection site can be minimized by cleansing the skin thoroughly prior to the injection. The use of disposable needles and syringes reduces the chance of inadequate sterilization of the equipment. Using single-dose medication vials will help prevent contamination of the medication. It is imperative that a needle of appropriate size and length be used to avoid injecting the medication into the subcutaneous tissues. This will minimize the chance of necrosis of the overlying skin.[3,4] As previously mentioned, the length or size of the needle does not affect post-injection pain.[4,6] The technique of injecting as the needle is advanced through the tissues is not recommended.[3] This technique results in the medication being distributed along the needle track and in multiple tissues, which causes erratic absorption of the medication as well as injection into the subcutaneous tissues.[3] Avoiding intravascular injection with this technique is impossible. Techniques to avoid inadvertent intravascular injection of medications have not been routinely successful. The standard technique is to insert the needle to the chosen depth then aspirate to see if blood is withdrawn. If blood is withdrawn, the needle tip is in the vessel, and the needle should be repositioned. That is the best technique available but is not foolproof. The needle could be within the vessel lumen but against the distal wall, which seals the needle tip during aspiration. However, once injection begins, the medication unfortunately can be easily deposited within the lumen of the vessel. Repositioning of the needle tip after aspiration and before injection can result in inadvertently entering the lumen of an adjacent vessel. Care must be taken to make all reasonable efforts to avoid this complication since the results can be devastating. Alternating the injection site can prevent complications from tissue necrosis. Repeated injection of any medication into the same area will increase the size of the necrotic lesion.[3,4] Conclusion Utilizing the proper technique when giving an IM injection will help minimize the possibility of a complication. If a complication occurs, the true etiology of the injury must be made so that appropriate treatment can be given. Treatment of the necrosis or infections proceeds along standard treatment lines. One must be aware that the necrotic or infectious lesion on a buttock or thigh might not be a pressure ulceration but a pretender. Patient Management Case 1. Operative intervention was undertaken in the anticipation of finding an abscess or other inflammatory process. At the time of operation, a solid mass was found in the subcutaneous tissues with no surrounding tracking. The area was completely excised and the wound was closed primarily. Postoperatively, the patient’s symptoms resolved. She has had no further problems. Pathology report showed only an area of fat necrosis and fibrosis (Figure 4). Case 2. The necrotic tissue was debrided and the wound was treated with an enzymatic debriding agent. With appropriate offloading and nutritional support, the ulceration began to improve but required repeated surgical debridements. Pathologic evaluation of the debridement specimen revealed only acutely inflamed granulation tissue. After the granulation tissue appeared in the ulcer, the treatment was changed to silver-plated fabric dressing and a secondary dressing that were changed every 3 to 4 days depending on the patient’s wound drainage. The patient was readmitted to the hospital on two occasions during the course of her treatment for other medical problems, but the ulceration continued slow improvement. The wound was healed 10 months after first being seen by the author (Figure 5). Case 3. The abscess was drained removing the purulent and necrotic, calcified material. The patient was treated with silver sulfadiazine cream on the local area and oral antibiotic medication. After the infection resolved, the entire area of calcium-containing skin and subcutaneous tissue was excised and the wound was closed primarily. The pathology report showed dystrophic calcification of the subcutaneous tissues with abscess formation. The patient will have the other hip treated with excision in the near future.