Gas Gangrene From Subcutaneous insulin Administration RACHEL L. CHIN, MD, RICARDO MARTINEZ, MD, GUS GARMEL, MD A case of gas gangrene that caused intractable shoulder pain refractory to narcotics in an immunocompromised host is presented. Gas gangrene has been associated with severe trauma involving penetrating wounds, compound fractures, extensive soft-tissue injury, intramuscular injection of epinephrine, and interruption of arterial blood supply. This case de- scribes an elderly insulin-dependent diabetic woman who developed gas gangrene In her arm and leg at the site of her subcutaneous insulin injections. The responsible organism was Closfritfium sepficum. Emer- gency medicine physicians must consider gas gangrene Closfridium in- fection in immunocompromised individuals without evidence of trauma who present with localized and intractable pain. (Am J Emerg Med 1993; 11:622-626. Copyrighl 0 1993 by W.6. Saunders Company) Gas gangrene has remained a major cause of morbidity and mortality despite advances in antibiotics and monitoring techniques. Etiologies other than trauma account for ap- proximately one half of the reported cases in a 20-year col- lective review.’ Clostridium septicum is a major cause of spontaneous, nontraumatic gas gangrene. It is relatively aerotolerant and thus is more capable of initiating infection in the absence of obvious tissue damage. Diabetes and leu- kopenia are common predisposing conditions; compromise of vital host responses may facilitate proliferation of those organisms that seed the tissues.* This case report emphasizes the importance of considering gas gangrene in immunocompromised individuals receiving intramuscular (IM) injections with localized pain in the ab- sence of trauma. CASE REPORT An 88-year old insulin-dependent diabetic woman arrived by am- bulance to the emergency department (ED) for intermittent left shoulder pain. This pain began 3 days before admission, but had steadily increased during the previous 12 hours. The patient stated that this pain was worse than the “pinched nerve” she had in the past, which usually responded to oxycodone. She denied any heavy lifting, unusual stretching, or trauma. She further denied any chest pain, shortness of breath, fevers, chills, dizziness, nausea, or vom- iting. Her medical history included insulin-dependent diabetes mel- litus, cerebral vascular accident, hypertension, gout, and pinched nerve. She had been administering her NPH insulin subcutaneously into her left lateral subdeltoid arm and left medial upper thigh, and denied reusing her needles. From the Stanford/Kaiser Emergency Medicine Residency Program, and the Division of Emergency Medicine at Stanford University Hospital, Palo Alto, CA. Manuscript received March 26, 1993; accepted April 3, 1993. Address reprints requests to Dr Chin, Emergency Medicine Stanford University Medical Center H-1249, Stanford, CA 94305. Key Words: Clostridium septicurn, subcutaneous insulin, im- munocompromised host. Copyright 0 1993 by W.B. Saunders Company 07356757/93/l 106-0018$500/O 622 The patient was alert, oriented, and cooperative. Her vital signs were stable with a blood pressure of 180/96 mm Hg, a regular heart rate of 100 beats/min, unlabored respirations of 24 breaths/min, and an oral temperature of 37.X. On physical examination, she was a well-groomed, obese woman in moderate discomfort. Her head and neck examinations were normal. The patient’s lungs were clear and her heart was without murmurs. Her abdominal and rectal exami- nations were unremarkable. Her extremities were symmetrical with excess skin folds, warm with good capillary refill, and without any evidence of ecchymosis, erythema, or violaceous skin discoloration. She had nonlocalizable tenderness in her left shoulder associated with neck and arm motion. Her right arm had full range of motion (ROM) without distress. Radial pulses were equal bilaterally. The remainder of her neuro- logical examination was unremarkable. In the ED, the patient received oxygen by nasal cannula, and a chemstrip estimated her blood glucose at 153 mg/dL. Her oxygen saturation was 95% on room air. An electrocardiogram (ECG) showed a normal sinus rhythm with left ventricular hypertrophy. Her left shoulder radiograph showed minimal degenerative joint dis- ease (Figure 1). The complete blood cell count was remarkable for a white blood cell count of 6.6 with 53 polys, 40 bands, and 1 lymph. Her pain management in the ED consisted of 60 mg of ketorolac IM in her right thigh, which provided no relief, followed by 50 mg of meperidine and 25 mg of phenergan IM 25 minutes later in the same area that also provided no pain relief. A final attempt at pain relief was made with 6 mg of betamethasone with 1 mL of 1% lidocaine without epinephrine injected anteriorly into the left subacromial space; no improvement was noted. Four hours after presentation to the ED a 5 mm x 8 mm purple bullous swelling developed along the distal medial aspect of her left upper arm. Her left upper extremity had become tender and slightly enlarged with respect to the right upper extremity. Tissue crepitus was detected on palpation and auscultation of the left upper arm. Pitting edema was present diffusely over her left upper extremity. Repeat radiographs of the patient’s left arm demonstrated a large amount of soft tissue air not present on initial radiographs (Figure 2). The patient was given 2 million units of penicillin G and 3.1 g of ticarcillin clavulanate intravenously and taken to the operating room for surgical debridement of her left arm. In the operating room, both her blood pressure and pulse de- creased precipitously after amputation of her left arm at the glenoid humoral joint. Postoperatively, she continued to have hemodynamic instability in the intensive care unit. Approximately 18 hours after she presented to the ED, she developed several small bullae on the medial aspect of her left thigh, at the site of previous insulin injec- tions. A radiograph of her left thigh showed a small gas pattern around the area of the ecchymotic skin lesions. Within 1 hour, the entire posterior medial aspect of her left leg developed a confluent hemorrhagic bullae similar to the one in her amputated arm, which continued to spread rapidly (Figure 3). The patient died 4 hours later in the intensive care unit despite continued aggressive antibiotic therapy. Clostridium septicum was identified by gram stain and cul- tures in the surgical specimens as well as in her blood. Her autopsy did not show occult malignancy. Culture of her insulin bottle from home produced no growth. The patient’s own syringes and needles were not available to culture.
Transcript
Gas Gangrene From Subcutaneous insulin Administration
RACHEL L. CHIN, MD, RICARDO MARTINEZ, MD, GUS GARMEL, MD
A case of gas gangrene that caused intractable shoulder pain refractory to narcotics in an immunocompromised host is presented. Gas gangrene has been associated with severe trauma involving penetrating wounds, compound fractures, extensive soft-tissue injury, intramuscular injection of epinephrine, and interruption of arterial blood supply. This case de- scribes an elderly insulin-dependent diabetic woman who developed gas gangrene In her arm and leg at the site of her subcutaneous insulin injections. The responsible organism was Closfritfium sepficum. Emer- gency medicine physicians must consider gas gangrene Closfridium in- fection in immunocompromised individuals without evidence of trauma who present with localized and intractable pain. (Am J Emerg Med 1993; 11:622-626. Copyrighl 0 1993 by W.6. Saunders Company)
Gas gangrene has remained a major cause of morbidity and mortality despite advances in antibiotics and monitoring techniques. Etiologies other than trauma account for ap- proximately one half of the reported cases in a 20-year col- lective review.’ Clostridium septicum is a major cause of spontaneous, nontraumatic gas gangrene. It is relatively aerotolerant and thus is more capable of initiating infection in the absence of obvious tissue damage. Diabetes and leu- kopenia are common predisposing conditions; compromise of vital host responses may facilitate proliferation of those organisms that seed the tissues.*
This case report emphasizes the importance of considering gas gangrene in immunocompromised individuals receiving intramuscular (IM) injections with localized pain in the ab- sence of trauma.
CASE REPORT
An 88-year old insulin-dependent diabetic woman arrived by am- bulance to the emergency department (ED) for intermittent left shoulder pain. This pain began 3 days before admission, but had steadily increased during the previous 12 hours. The patient stated that this pain was worse than the “pinched nerve” she had in the past, which usually responded to oxycodone. She denied any heavy lifting, unusual stretching, or trauma. She further denied any chest pain, shortness of breath, fevers, chills, dizziness, nausea, or vom- iting. Her medical history included insulin-dependent diabetes mel- litus, cerebral vascular accident, hypertension, gout, and pinched nerve. She had been administering her NPH insulin subcutaneously into her left lateral subdeltoid arm and left medial upper thigh, and denied reusing her needles.
From the Stanford/Kaiser Emergency Medicine Residency Program, and the Division of Emergency Medicine at Stanford University Hospital, Palo Alto, CA.
Manuscript received March 26, 1993; accepted April 3, 1993. Address reprints requests to Dr Chin, Emergency Medicine
Stanford University Medical Center H-1249, Stanford, CA 94305. Key Words: Clostridium septicurn, subcutaneous insulin, im-
munocompromised host. Copyright 0 1993 by W.B. Saunders Company 07356757/93/l 106-0018$500/O
622
The patient was alert, oriented, and cooperative. Her vital signs were stable with a blood pressure of 180/96 mm Hg, a regular heart rate of 100 beats/min, unlabored respirations of 24 breaths/min, and an oral temperature of 37.X. On physical examination, she was a well-groomed, obese woman in moderate discomfort. Her head and neck examinations were normal. The patient’s lungs were clear and her heart was without murmurs. Her abdominal and rectal exami- nations were unremarkable.
Her extremities were symmetrical with excess skin folds, warm with good capillary refill, and without any evidence of ecchymosis, erythema, or violaceous skin discoloration. She had nonlocalizable tenderness in her left shoulder associated with neck and arm motion. Her right arm had full range of motion (ROM) without distress. Radial pulses were equal bilaterally. The remainder of her neuro- logical examination was unremarkable.
In the ED, the patient received oxygen by nasal cannula, and a chemstrip estimated her blood glucose at 153 mg/dL. Her oxygen saturation was 95% on room air. An electrocardiogram (ECG) showed a normal sinus rhythm with left ventricular hypertrophy. Her left shoulder radiograph showed minimal degenerative joint dis- ease (Figure 1). The complete blood cell count was remarkable for a white blood cell count of 6.6 with 53 polys, 40 bands, and 1 lymph. Her pain management in the ED consisted of 60 mg of ketorolac IM in her right thigh, which provided no relief, followed by 50 mg of meperidine and 25 mg of phenergan IM 25 minutes later in the same area that also provided no pain relief. A final attempt at pain relief was made with 6 mg of betamethasone with 1 mL of 1% lidocaine without epinephrine injected anteriorly into the left subacromial space; no improvement was noted.
Four hours after presentation to the ED a 5 mm x 8 mm purple bullous swelling developed along the distal medial aspect of her left upper arm. Her left upper extremity had become tender and slightly enlarged with respect to the right upper extremity. Tissue crepitus was detected on palpation and auscultation of the left upper arm. Pitting edema was present diffusely over her left upper extremity. Repeat radiographs of the patient’s left arm demonstrated a large amount of soft tissue air not present on initial radiographs (Figure 2). The patient was given 2 million units of penicillin G and 3.1 g of ticarcillin clavulanate intravenously and taken to the operating room for surgical debridement of her left arm.
In the operating room, both her blood pressure and pulse de- creased precipitously after amputation of her left arm at the glenoid humoral joint. Postoperatively, she continued to have hemodynamic instability in the intensive care unit. Approximately 18 hours after she presented to the ED, she developed several small bullae on the medial aspect of her left thigh, at the site of previous insulin injec- tions. A radiograph of her left thigh showed a small gas pattern around the area of the ecchymotic skin lesions. Within 1 hour, the entire posterior medial aspect of her left leg developed a confluent hemorrhagic bullae similar to the one in her amputated arm, which continued to spread rapidly (Figure 3). The patient died 4 hours later in the intensive care unit despite continued aggressive antibiotic therapy. Clostridium septicum was identified by gram stain and cul- tures in the surgical specimens as well as in her blood. Her autopsy did not show occult malignancy. Culture of her insulin bottle from home produced no growth. The patient’s own syringes and needles were not available to culture.
CHIN ET AL n GAS GANGRENE FROM SUBCUTANEOUS INSUL .IN
FIGURE 1. Initial radiograph of left upper extremity.
DISCUSSION
Infections in diabetics are common and can be life- threatening. Even minor infections have been reported to result in limb loss. Diabetics have an increased incidence of accelerated arteriosclerosis, which may lead to low oxygen tension in the peripheral vasculature. Diabetics also have impaired phagocytosis and intracellular bactericidal activity. All of these processes delay tissue healing and promote op- portunist infections.
Clostridium species are gram-positive, sporulating, spin- dle-shaped rod. Clostridium perfringens has been thought to be responsible for the majority of gas gangrene associated with trauma. Unlike C perfringens, C septicum is often as- sociated with spontaneous nontraumatic gas gangrene and may even be the initial presentation of an occult tumor. The association of clostridial infection and malignancy, espe- cially colon cancer, has been described in several reports. IT5
Clostridium organisms thrive in tissues with low oxygen tension. Diabetics with impaired oxygen delivery caused by both microvascular and macrovascular disease present an ideal environment for the multiplication of anaerobic organ- isms. Anaerobic organisms introduced by minor trauma into the subcutaneous tissues of a diabetic patient find them- selves in oxygen-deficient culture medium. Bacterial prolif- eration in the absence of effective immunological responses, and the release of tissue-toxic substances, lead to the devel- opment of massive interstitial edema, which further compro- mises the regional blood supply and availability of leuko- cytes. The result is extensive malignant tissue necrosis and infection.
A case of C septicum gas gangrene after subcutaneous
FIGURE 2. Repeat radiograph of left upper extremity with sub- cutaneous air identified.
624 AMERICAN JOURNAL OF EME iRGENCY MEDICINE H Volume 11, Number 6 n November 1993
FIGURE 3. Development of hemorrhagic bullae in the left leg.
injection of insulin was not found in a review of the litera- ture. A recent case of C perfringens myonecrosis after sub- cutaneous epinephrine injection in the right upper arm has been reported.6 Gas gangrene has been identified in the fore- arm of a diet-controlled diabetic after an IM Influvac influ- enza booster.’ Adrenaline mutate injection causes vasocon- striction and lowers oxygen tension to a point that enables anaerobic organisms to grow.’ Injections of as little as 2 kg of adrenaline into the thigh muscles of guinea pigs enhanced such infection at that site 100,000-fold.9 Diabetics are known to have poor perfusion and lower oxygen tension, therefore, placing them at high risk for developing clostridial gas gan- grene. lo
A high index of suspicion and early recognition can sig- nificantly decrease the morbidity and mortality of Clostrid- ium gas infections. Our patient became septic without re- markably abnormal vital signs a few hours after presentation to the ED. Often the onset of disease presents with a sensa- tion of increasing weight of the involved area followed by either extraordinary or excruciating pain unrelieved by non- steroidal antiinflammatory drugs or narcotics. Initially, gas is often absent, and there is a profuse serosanguineous dis- charge that has a sweet odor and contains many organisms. It changes color very rapidly from red, yellow, brown, or black, and the affected area is then covered by hemorrhagic blebs and bullae.” Extremely rapid progression of gangrene may follow. The skin around these bullae became ecchy- motic, perhaps reflecting vascular compromise, which re- sults from diffusion of bacterial toxins into surrounding tis- sues.” These changes develop rapidly when the disease is fulminant. Laboratory studies often show a metabolic aci- dosis, leukocytosis, thrombocytopenia, coagulopathy, renal and liver function abnormalities, myoglobinemia, and myo- globinuria. l2
Aggressive treatment of gas gangrene is necessary and includes antibiotics in conjunction with surgical debridement and hyperbaric oxygen. The mortality in previous reports of spontaneous gas gangrene has ranged from 67% to 100%. Early recognition and aggressive surgical debridement is es- sential to patient survival.
Nineteen strains of C septicum were uniformly sensitive (100%) to all antibiotics tested by Brazier et a1.13 Agents
used were penicillin, tetracycline, erythromycin, clindamy- tin, chloramphenicol, metronidazole, and amoxicillin/ clavulanic acid. Of the 28 clostridial species studied, only C dijjkile showed a high degree of resistance to penicillin and clindamycin.
Hyperbaric oxygen has been a beneficial adjunct in the treatment of clostridial myonecrosis. Since Brummelkamp et al reported the successful treatment of gas gangrene with hyperbaric oxygen at 3 atm absolute pressure, hyperbaric oxygen has been recommended as part of the treatment of gas gangrene. l4 Demello et al compared combinations of sur- gical debridement, antibiotics, and hyperbaric oxygen in a dog model. A survival rate of 95% was achieved by a com- bination of surgery, antibiotics, and hyperbaric oxygen, when compared with surgery and antibiotics alone (70%), surgery alone (O%), or hyperbaric oxygen alone (0%). Anti- biotics alone resulted in only 50% survival rate.15
Mechanically, hyperbaric oxygen enhances the bacterial killing of polymorphonuclear leukocytes by increasing the availability of oxygen substrate for the production of bacte- ricidal-free radicals. Hyperbaric oxygen has a direct bacte- ricidal effect on most Clostridium species and inhibits the further production of Clostridium a-toxin.16 Its use in the treatment of the species C septicum infection has not been studied adequately. Theoretically, hyperbaric oxygen should protect the viability of healthy tissue surrounding an area of progressive vascular necrosis. This may help to slow the progression of the disease and to reduce the amount of sub- sequent surgical debridement. In the case presented, the pa- tient was never hemodynamically stable enough to permit transfer to a hyperbaric oxygen facility.
SUMMARY
Clostridial gas gangrene is a major cause of limb loss and death despite aggressive therapy, including antibiotics, sur- gery, and hyperbaric oxygen. Delays in diagnosis and con- current medical problems are contributing factors to the morbidity and mortality of this limb-threatening infection. Immunocompromised hosts should be admitted with early surgical consultation if they present with localized intracta- ble pain refractory to narcotics. Aggressive treatment in- cluding clostridialcidal antibiotics and arrangements for hy- perbaric oxygen should be instituted.
The authors thank Dr Marc Nelson for reviewing the manuscript and for his dedication to residency teaching in emergency med- icine.
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CHIN ET AL n GAS GANGRENE FROM SUBCUTANEOUS INSULIN 625
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