Community‐associated methicillin‐resistant Staphylococcus aureus (MRSA) infection is an evolving disease that is changing medical practice. MRSA has become the most frequent cause of skin and soft‐tissue infections presenting to most emergency departments in the United States.1 In comparison with methicillin‐sensitive S. aureus, community‐associated MRSA is more likely to present as soft‐tissue abscesses or necrotizing pneumonia.2 In 2005 alone, 94,360 invasive MRSA infections were estimated to have occurred in the United States, most of which were associated with MRSA bacteremia.3 In the hospital, MRSA infections are associated with greater lengths of stay, higher mortality, and increased costs.3

We report a patient with persistent MRSA bacteremia due to a prostatic abscess. Prostatitis or prostatic abscess with MRSA has rarely been reported. Resolution of the bacteremia was achieved only after drainage of the abscess. This case highlights the importance of recognizing this clinical condition and draining any MRSA‐associated abscesses. In addition, the abscess‐forming characteristics of MRSA may suggest that the incidence of prostatic abscess due to this microbe is on the rise.

CASE REPORT

A 40‐year‐old human immunodeficiency viruspositive man presented with a 10‐day history of intermittent fever, urinary hesitancy, weak urinary stream, and intermittent abdominal pain relieved following urination. He denied dysuria, hematuria, chest pain, dyspnea, nausea, weight loss, diarrhea, or decreased functional status. His last CD4 count was 528/L on highly active antiretroviral therapy 1 year prior to presentation; however, he had run out of medications several months prior to presentation. His medical history was also significant for incision and drainage of skin abscesses with unknown microbiology several months prior to presentation. He currently used tobacco but denied illicit drug use. He was sexually abstinent for over a year prior to presentation but had a history of having unprotected sex with men.

On physical examination, his vital signs were as follows: temperature, 37.8C; blood pressure, 133/84 mm Hg; heart rate, 107 beats/minute; respiration rate, 16 breaths/minute; and oxygen saturation, 100% on room air. He was under no distress. His heart sound was tachycardic and regular with no murmur noted. Lung sounds were clear. Abdominal examination revealed no tenderness or organomegaly. His prostate was boggy, minimally tender, and slightly enlarged. The rest of his physical examination was normal. The white blood cell count was 7.5 10⁹/L with 79% neutrophils. The serum chemistry was normal. The prostate‐specific antigen level was 2.9 ng/mL. A repeat CD4 count was 140/L. Urinalysis revealed large leukocyte esterase, no nitrites, and 60 white blood cells per high‐power field. He was diagnosed with prostatitis and discharged on levofloxacin.

The subsequent day, he returned to the emergency department with an inability to void. A Foley catheter was placed with resolution of his symptoms. Later that day, blood cultures from his initial admission grew MRSA in 2 out of 4 bottles, and he was admitted to the hospital. A review of the prior urine culture showed no growth. Computed tomography (CT) of the abdomen and pelvis showed an enlarged prostate with multiple noncommunicating peripherally enhancing hypodensities consistent with prostatic abscesses (arrows in Figure 1). These abscesses were associated with periprostatic fat stranding, edematous seminal vesicles, diffuse urinary bladder wall thickening, and mild inguinal adenopathy. Therapy with intravenous vancomycin was initiated.

Figure 1

Over the next 6 days, the patient continued to have intermittent fevers. Blood cultures continued to grow MRSA. Gentamicin was added for possible synergy on hospital day 3 without improvement. A transesophageal echocardiogram was normal. On hospital day 6, repeat CT showed no change in the size of the prostatic abscesses but an increased capsular bulge along the right mid gland. The urology service was consulted. They performed bedside transperineal drainage of the largest abscess with transrectal ultrasound guidance. No indwelling drain was placed. A culture of the purulent drainage grew MRSA. Three days after the surgical drainage, the patient was afebrile, urinary symptoms had resolved, and serial blood cultures remained negative. He was discharged on hospital day 13 to complete a 4‐week course of intravenous vancomycin. The patient missed an appointment for follow‐up imaging.

DISCUSSION

We report a case of community‐associated MRSA bacteremia secondary to a prostatic abscess, as confirmed by cultures from serum and of the abscess. S. aureus bacteremia often stems from infections of the respiratory tract, skin, and soft tissues, endocarditis, or infections of indwelling devices.4S. aureus can then create embolic foci, including in the prostate, which can serve as sources of persistent bacteremia. However, new evidence suggests community‐associated MRSA might be sexually transmitted among men who have sex with men.5 An MRSA prostatic abscess could then potentially be related to an ascending urinary tract infection or translocation from the gastrointestinal tract.

The vast majority of prostatitis cases prostatic abscesses are caused by Escherichia coli and other gram‐negative bacilli.6 Staphylococcus species are less common, and MRSA isolates have been described as a rare etiologic agent. Only four other case reports describing MRSA bacteremia associated with prostatitis or prostatic abscesses have been published.710 Both our patient and the three other case reports in the literature with prostatic abscesses and MRSA bacteremia required drainage of the abscess as well as antibiotics for resolution. The other reported cases involved drainage by transurethral resection of the prostate,79 whereas our case used transperineal drainage of the prostatic abscess via transrectal ultrasound guidance. In addition to intravenous antibiotics, drainage appears to be a key therapeutic measure for resolution of MRSA prostatic abscesses.

With the increasing incidence of community‐associated and healthcare‐associated MRSA infections, the incidence of prostatitis or prostatic abscesses secondary to MRSA may be increasing. MRSA seems to have a specific predilection for abscess formation in skin and soft‐tissue infections and pneumonia.2 Clinicians must be alert to a potentially higher frequency of MRSA as a cause of prostatic abscesses and prostatitis.

In the evaluation of a patient with persistent MRSA bacteremia, the potential for the prostate as a source of infection should be considered. Urinary symptoms may be subtle. Clinicians should have a low threshold for imaging studies such as CT to evaluate for a possible source of MRSA bacteremia. If a prostatic abscess is found, prompt surgical drainage or debridement is necessary for cure.

Community‐associated methicillin‐resistant Staphylococcus aureus (MRSA) infection is an evolving disease that is changing medical practice. MRSA has become the most frequent cause of skin and soft‐tissue infections presenting to most emergency departments in the United States.1 In comparison with methicillin‐sensitive S. aureus, community‐associated MRSA is more likely to present as soft‐tissue abscesses or necrotizing pneumonia.2 In 2005 alone, 94,360 invasive MRSA infections were estimated to have occurred in the United States, most of which were associated with MRSA bacteremia.3 In the hospital, MRSA infections are associated with greater lengths of stay, higher mortality, and increased costs.3

We report a patient with persistent MRSA bacteremia due to a prostatic abscess. Prostatitis or prostatic abscess with MRSA has rarely been reported. Resolution of the bacteremia was achieved only after drainage of the abscess. This case highlights the importance of recognizing this clinical condition and draining any MRSA‐associated abscesses. In addition, the abscess‐forming characteristics of MRSA may suggest that the incidence of prostatic abscess due to this microbe is on the rise.

CASE REPORT

A 40‐year‐old human immunodeficiency viruspositive man presented with a 10‐day history of intermittent fever, urinary hesitancy, weak urinary stream, and intermittent abdominal pain relieved following urination. He denied dysuria, hematuria, chest pain, dyspnea, nausea, weight loss, diarrhea, or decreased functional status. His last CD4 count was 528/L on highly active antiretroviral therapy 1 year prior to presentation; however, he had run out of medications several months prior to presentation. His medical history was also significant for incision and drainage of skin abscesses with unknown microbiology several months prior to presentation. He currently used tobacco but denied illicit drug use. He was sexually abstinent for over a year prior to presentation but had a history of having unprotected sex with men.

On physical examination, his vital signs were as follows: temperature, 37.8C; blood pressure, 133/84 mm Hg; heart rate, 107 beats/minute; respiration rate, 16 breaths/minute; and oxygen saturation, 100% on room air. He was under no distress. His heart sound was tachycardic and regular with no murmur noted. Lung sounds were clear. Abdominal examination revealed no tenderness or organomegaly. His prostate was boggy, minimally tender, and slightly enlarged. The rest of his physical examination was normal. The white blood cell count was 7.5 10⁹/L with 79% neutrophils. The serum chemistry was normal. The prostate‐specific antigen level was 2.9 ng/mL. A repeat CD4 count was 140/L. Urinalysis revealed large leukocyte esterase, no nitrites, and 60 white blood cells per high‐power field. He was diagnosed with prostatitis and discharged on levofloxacin.

The subsequent day, he returned to the emergency department with an inability to void. A Foley catheter was placed with resolution of his symptoms. Later that day, blood cultures from his initial admission grew MRSA in 2 out of 4 bottles, and he was admitted to the hospital. A review of the prior urine culture showed no growth. Computed tomography (CT) of the abdomen and pelvis showed an enlarged prostate with multiple noncommunicating peripherally enhancing hypodensities consistent with prostatic abscesses (arrows in Figure 1). These abscesses were associated with periprostatic fat stranding, edematous seminal vesicles, diffuse urinary bladder wall thickening, and mild inguinal adenopathy. Therapy with intravenous vancomycin was initiated.

Figure 1

Over the next 6 days, the patient continued to have intermittent fevers. Blood cultures continued to grow MRSA. Gentamicin was added for possible synergy on hospital day 3 without improvement. A transesophageal echocardiogram was normal. On hospital day 6, repeat CT showed no change in the size of the prostatic abscesses but an increased capsular bulge along the right mid gland. The urology service was consulted. They performed bedside transperineal drainage of the largest abscess with transrectal ultrasound guidance. No indwelling drain was placed. A culture of the purulent drainage grew MRSA. Three days after the surgical drainage, the patient was afebrile, urinary symptoms had resolved, and serial blood cultures remained negative. He was discharged on hospital day 13 to complete a 4‐week course of intravenous vancomycin. The patient missed an appointment for follow‐up imaging.

DISCUSSION

We report a case of community‐associated MRSA bacteremia secondary to a prostatic abscess, as confirmed by cultures from serum and of the abscess. S. aureus bacteremia often stems from infections of the respiratory tract, skin, and soft tissues, endocarditis, or infections of indwelling devices.4S. aureus can then create embolic foci, including in the prostate, which can serve as sources of persistent bacteremia. However, new evidence suggests community‐associated MRSA might be sexually transmitted among men who have sex with men.5 An MRSA prostatic abscess could then potentially be related to an ascending urinary tract infection or translocation from the gastrointestinal tract.

The vast majority of prostatitis cases prostatic abscesses are caused by Escherichia coli and other gram‐negative bacilli.6 Staphylococcus species are less common, and MRSA isolates have been described as a rare etiologic agent. Only four other case reports describing MRSA bacteremia associated with prostatitis or prostatic abscesses have been published.710 Both our patient and the three other case reports in the literature with prostatic abscesses and MRSA bacteremia required drainage of the abscess as well as antibiotics for resolution. The other reported cases involved drainage by transurethral resection of the prostate,79 whereas our case used transperineal drainage of the prostatic abscess via transrectal ultrasound guidance. In addition to intravenous antibiotics, drainage appears to be a key therapeutic measure for resolution of MRSA prostatic abscesses.

With the increasing incidence of community‐associated and healthcare‐associated MRSA infections, the incidence of prostatitis or prostatic abscesses secondary to MRSA may be increasing. MRSA seems to have a specific predilection for abscess formation in skin and soft‐tissue infections and pneumonia.2 Clinicians must be alert to a potentially higher frequency of MRSA as a cause of prostatic abscesses and prostatitis.

In the evaluation of a patient with persistent MRSA bacteremia, the potential for the prostate as a source of infection should be considered. Urinary symptoms may be subtle. Clinicians should have a low threshold for imaging studies such as CT to evaluate for a possible source of MRSA bacteremia. If a prostatic abscess is found, prompt surgical drainage or debridement is necessary for cure.

Community‐associated methicillin‐resistant Staphylococcus aureus (MRSA) infection is an evolving disease that is changing medical practice. MRSA has become the most frequent cause of skin and soft‐tissue infections presenting to most emergency departments in the United States.1 In comparison with methicillin‐sensitive S. aureus, community‐associated MRSA is more likely to present as soft‐tissue abscesses or necrotizing pneumonia.2 In 2005 alone, 94,360 invasive MRSA infections were estimated to have occurred in the United States, most of which were associated with MRSA bacteremia.3 In the hospital, MRSA infections are associated with greater lengths of stay, higher mortality, and increased costs.3

We report a patient with persistent MRSA bacteremia due to a prostatic abscess. Prostatitis or prostatic abscess with MRSA has rarely been reported. Resolution of the bacteremia was achieved only after drainage of the abscess. This case highlights the importance of recognizing this clinical condition and draining any MRSA‐associated abscesses. In addition, the abscess‐forming characteristics of MRSA may suggest that the incidence of prostatic abscess due to this microbe is on the rise.

CASE REPORT

A 40‐year‐old human immunodeficiency viruspositive man presented with a 10‐day history of intermittent fever, urinary hesitancy, weak urinary stream, and intermittent abdominal pain relieved following urination. He denied dysuria, hematuria, chest pain, dyspnea, nausea, weight loss, diarrhea, or decreased functional status. His last CD4 count was 528/L on highly active antiretroviral therapy 1 year prior to presentation; however, he had run out of medications several months prior to presentation. His medical history was also significant for incision and drainage of skin abscesses with unknown microbiology several months prior to presentation. He currently used tobacco but denied illicit drug use. He was sexually abstinent for over a year prior to presentation but had a history of having unprotected sex with men.

On physical examination, his vital signs were as follows: temperature, 37.8C; blood pressure, 133/84 mm Hg; heart rate, 107 beats/minute; respiration rate, 16 breaths/minute; and oxygen saturation, 100% on room air. He was under no distress. His heart sound was tachycardic and regular with no murmur noted. Lung sounds were clear. Abdominal examination revealed no tenderness or organomegaly. His prostate was boggy, minimally tender, and slightly enlarged. The rest of his physical examination was normal. The white blood cell count was 7.5 10⁹/L with 79% neutrophils. The serum chemistry was normal. The prostate‐specific antigen level was 2.9 ng/mL. A repeat CD4 count was 140/L. Urinalysis revealed large leukocyte esterase, no nitrites, and 60 white blood cells per high‐power field. He was diagnosed with prostatitis and discharged on levofloxacin.

The subsequent day, he returned to the emergency department with an inability to void. A Foley catheter was placed with resolution of his symptoms. Later that day, blood cultures from his initial admission grew MRSA in 2 out of 4 bottles, and he was admitted to the hospital. A review of the prior urine culture showed no growth. Computed tomography (CT) of the abdomen and pelvis showed an enlarged prostate with multiple noncommunicating peripherally enhancing hypodensities consistent with prostatic abscesses (arrows in Figure 1). These abscesses were associated with periprostatic fat stranding, edematous seminal vesicles, diffuse urinary bladder wall thickening, and mild inguinal adenopathy. Therapy with intravenous vancomycin was initiated.

Figure 1

Over the next 6 days, the patient continued to have intermittent fevers. Blood cultures continued to grow MRSA. Gentamicin was added for possible synergy on hospital day 3 without improvement. A transesophageal echocardiogram was normal. On hospital day 6, repeat CT showed no change in the size of the prostatic abscesses but an increased capsular bulge along the right mid gland. The urology service was consulted. They performed bedside transperineal drainage of the largest abscess with transrectal ultrasound guidance. No indwelling drain was placed. A culture of the purulent drainage grew MRSA. Three days after the surgical drainage, the patient was afebrile, urinary symptoms had resolved, and serial blood cultures remained negative. He was discharged on hospital day 13 to complete a 4‐week course of intravenous vancomycin. The patient missed an appointment for follow‐up imaging.

DISCUSSION

We report a case of community‐associated MRSA bacteremia secondary to a prostatic abscess, as confirmed by cultures from serum and of the abscess. S. aureus bacteremia often stems from infections of the respiratory tract, skin, and soft tissues, endocarditis, or infections of indwelling devices.4S. aureus can then create embolic foci, including in the prostate, which can serve as sources of persistent bacteremia. However, new evidence suggests community‐associated MRSA might be sexually transmitted among men who have sex with men.5 An MRSA prostatic abscess could then potentially be related to an ascending urinary tract infection or translocation from the gastrointestinal tract.

The vast majority of prostatitis cases prostatic abscesses are caused by Escherichia coli and other gram‐negative bacilli.6 Staphylococcus species are less common, and MRSA isolates have been described as a rare etiologic agent. Only four other case reports describing MRSA bacteremia associated with prostatitis or prostatic abscesses have been published.710 Both our patient and the three other case reports in the literature with prostatic abscesses and MRSA bacteremia required drainage of the abscess as well as antibiotics for resolution. The other reported cases involved drainage by transurethral resection of the prostate,79 whereas our case used transperineal drainage of the prostatic abscess via transrectal ultrasound guidance. In addition to intravenous antibiotics, drainage appears to be a key therapeutic measure for resolution of MRSA prostatic abscesses.

With the increasing incidence of community‐associated and healthcare‐associated MRSA infections, the incidence of prostatitis or prostatic abscesses secondary to MRSA may be increasing. MRSA seems to have a specific predilection for abscess formation in skin and soft‐tissue infections and pneumonia.2 Clinicians must be alert to a potentially higher frequency of MRSA as a cause of prostatic abscesses and prostatitis.

In the evaluation of a patient with persistent MRSA bacteremia, the potential for the prostate as a source of infection should be considered. Urinary symptoms may be subtle. Clinicians should have a low threshold for imaging studies such as CT to evaluate for a possible source of MRSA bacteremia. If a prostatic abscess is found, prompt surgical drainage or debridement is necessary for cure.

A 38‐year‐old woman with juvenile dermatomyositis (JDM) and calcinosis universalis presented with 3 days of drainage from a lesion on her right elbow. An examination of the elbow revealed diffuse and firm subcutaneous nodules with overlying erythema. X‐rays illustrated soft‐tissue calcifications in the forearm and elbow without evidence of osteomyelitis (Figure 1). Wound cultures grew Staphylococcus aureus, and the patient was started on intravenous antibiotics for abscess treatment.

Figure 1

Calcinosis universalis is soft‐tissue calcification presenting as a complication of JDM. It is often detected in childhood in 30% to 70% of patients. It is hypothesized that calcinosis is due to chronic tissue inflammation, as seen in JDM, leading to muscle damage, releasing calcium, and inducing mineralization. Calcinosis universalis often presents as calcified nodules and plaques in areas of repeated trauma, such as joints, extremities, and buttocks (Figures 13). Calcification is localized in subcutaneous tissue, fascial planes, tendons, or intramuscular areas. It can cause debilitating secondary complications such as skin ulcerations expressing calcified material, superimposed infections of skin lesions, joint contractures with severe arthralgias, and muscle atrophy. Calcinosis has been correlated with severity of JDM with presence of cardiac involvement and use of more than one immunosuppression medication.1 It has also been associated with the degree of vasculopathy and delay in initiation of therapy for controlling inflammation in JDM.2

Soft‐tissue calcification can be classified into 5 categories:

• 1

  Dystrophic calcification occurs in injured tissues with normal calcium, phosphorus, and parathyroid hormone levels, as seen in this patient. Calcified nodules or plaques occur in the extremities and buttocks. This is most often seen in JDM, scleroderma, and systemic lupus erythematosus.

• 2

  Metastatic calcification affects normal tissues with abnormal levels of calcium and phosphorus. It is seen in large joints as well as arteries and visceral organs. It is associated with hyperparathyroidism, hypervitaminosis D, and malignancies.

• 3

  Calciphylaxis with abnormal calcium and phosphorus metabolism causes small‐vessel calcification in patients with chronic renal failure.

• 4

  Tumoral calcification is a familial condition with normal calcium levels but elevated phosphorus levels. Large subcutaneous calcifications are seen near high‐pressure areas and joints.

• 5

  Idiopathic calcification is seen in healthy children and young adults with normal calcium metabolism and appears as multiple subcutaneous calcifications.2

Figure 2

Figure 3

Although multiple therapeutic options have been tried for the management or prevention of calcinosis, there is currently no accepted standard of treatment. In patients with calcinosis, warfarin, probenecid, colchicine, bisphosphonates, minocycline, diltiazem, aluminum hydroxide, corticosteroids, and salicylate have been attempted with variable results. Other therapeutic options include carbon dioxide laser treatments and surgical excision of large plaques. Decreasing muscle inflammation with aggressive treatment of JDM may improve outcomes and decrease the incidence of calcification.3 Unfortunately, once calcinosis has occurred, it is highly refractory to medical therapy.

Calcinosis universalis can lead to severe functional impairment. It can be distinguished from other types of calcinosis by diffuse involvement of muscle and fascia in connective tissue disease with normal calcium and phosphorus levels. New management modalities such as cyclosporine, intravenous immunoglobulin, and tumor necrosis factor alpha inhibitors are currently being evaluated.

A 38‐year‐old woman with juvenile dermatomyositis (JDM) and calcinosis universalis presented with 3 days of drainage from a lesion on her right elbow. An examination of the elbow revealed diffuse and firm subcutaneous nodules with overlying erythema. X‐rays illustrated soft‐tissue calcifications in the forearm and elbow without evidence of osteomyelitis (Figure 1). Wound cultures grew Staphylococcus aureus, and the patient was started on intravenous antibiotics for abscess treatment.

Figure 1

Calcinosis universalis is soft‐tissue calcification presenting as a complication of JDM. It is often detected in childhood in 30% to 70% of patients. It is hypothesized that calcinosis is due to chronic tissue inflammation, as seen in JDM, leading to muscle damage, releasing calcium, and inducing mineralization. Calcinosis universalis often presents as calcified nodules and plaques in areas of repeated trauma, such as joints, extremities, and buttocks (Figures 13). Calcification is localized in subcutaneous tissue, fascial planes, tendons, or intramuscular areas. It can cause debilitating secondary complications such as skin ulcerations expressing calcified material, superimposed infections of skin lesions, joint contractures with severe arthralgias, and muscle atrophy. Calcinosis has been correlated with severity of JDM with presence of cardiac involvement and use of more than one immunosuppression medication.1 It has also been associated with the degree of vasculopathy and delay in initiation of therapy for controlling inflammation in JDM.2

Soft‐tissue calcification can be classified into 5 categories:

• 1

  Dystrophic calcification occurs in injured tissues with normal calcium, phosphorus, and parathyroid hormone levels, as seen in this patient. Calcified nodules or plaques occur in the extremities and buttocks. This is most often seen in JDM, scleroderma, and systemic lupus erythematosus.

• 2

  Metastatic calcification affects normal tissues with abnormal levels of calcium and phosphorus. It is seen in large joints as well as arteries and visceral organs. It is associated with hyperparathyroidism, hypervitaminosis D, and malignancies.

• 3

  Calciphylaxis with abnormal calcium and phosphorus metabolism causes small‐vessel calcification in patients with chronic renal failure.

• 4

  Tumoral calcification is a familial condition with normal calcium levels but elevated phosphorus levels. Large subcutaneous calcifications are seen near high‐pressure areas and joints.

• 5

  Idiopathic calcification is seen in healthy children and young adults with normal calcium metabolism and appears as multiple subcutaneous calcifications.2

Figure 2

Figure 3

Although multiple therapeutic options have been tried for the management or prevention of calcinosis, there is currently no accepted standard of treatment. In patients with calcinosis, warfarin, probenecid, colchicine, bisphosphonates, minocycline, diltiazem, aluminum hydroxide, corticosteroids, and salicylate have been attempted with variable results. Other therapeutic options include carbon dioxide laser treatments and surgical excision of large plaques. Decreasing muscle inflammation with aggressive treatment of JDM may improve outcomes and decrease the incidence of calcification.3 Unfortunately, once calcinosis has occurred, it is highly refractory to medical therapy.

Calcinosis universalis can lead to severe functional impairment. It can be distinguished from other types of calcinosis by diffuse involvement of muscle and fascia in connective tissue disease with normal calcium and phosphorus levels. New management modalities such as cyclosporine, intravenous immunoglobulin, and tumor necrosis factor alpha inhibitors are currently being evaluated.

A 38‐year‐old woman with juvenile dermatomyositis (JDM) and calcinosis universalis presented with 3 days of drainage from a lesion on her right elbow. An examination of the elbow revealed diffuse and firm subcutaneous nodules with overlying erythema. X‐rays illustrated soft‐tissue calcifications in the forearm and elbow without evidence of osteomyelitis (Figure 1). Wound cultures grew Staphylococcus aureus, and the patient was started on intravenous antibiotics for abscess treatment.

Figure 1

Calcinosis universalis is soft‐tissue calcification presenting as a complication of JDM. It is often detected in childhood in 30% to 70% of patients. It is hypothesized that calcinosis is due to chronic tissue inflammation, as seen in JDM, leading to muscle damage, releasing calcium, and inducing mineralization. Calcinosis universalis often presents as calcified nodules and plaques in areas of repeated trauma, such as joints, extremities, and buttocks (Figures 13). Calcification is localized in subcutaneous tissue, fascial planes, tendons, or intramuscular areas. It can cause debilitating secondary complications such as skin ulcerations expressing calcified material, superimposed infections of skin lesions, joint contractures with severe arthralgias, and muscle atrophy. Calcinosis has been correlated with severity of JDM with presence of cardiac involvement and use of more than one immunosuppression medication.1 It has also been associated with the degree of vasculopathy and delay in initiation of therapy for controlling inflammation in JDM.2

Soft‐tissue calcification can be classified into 5 categories:

• 1

  Dystrophic calcification occurs in injured tissues with normal calcium, phosphorus, and parathyroid hormone levels, as seen in this patient. Calcified nodules or plaques occur in the extremities and buttocks. This is most often seen in JDM, scleroderma, and systemic lupus erythematosus.

• 2

  Metastatic calcification affects normal tissues with abnormal levels of calcium and phosphorus. It is seen in large joints as well as arteries and visceral organs. It is associated with hyperparathyroidism, hypervitaminosis D, and malignancies.

• 3

  Calciphylaxis with abnormal calcium and phosphorus metabolism causes small‐vessel calcification in patients with chronic renal failure.

• 4

  Tumoral calcification is a familial condition with normal calcium levels but elevated phosphorus levels. Large subcutaneous calcifications are seen near high‐pressure areas and joints.

• 5

  Idiopathic calcification is seen in healthy children and young adults with normal calcium metabolism and appears as multiple subcutaneous calcifications.2

Figure 2

Figure 3

Although multiple therapeutic options have been tried for the management or prevention of calcinosis, there is currently no accepted standard of treatment. In patients with calcinosis, warfarin, probenecid, colchicine, bisphosphonates, minocycline, diltiazem, aluminum hydroxide, corticosteroids, and salicylate have been attempted with variable results. Other therapeutic options include carbon dioxide laser treatments and surgical excision of large plaques. Decreasing muscle inflammation with aggressive treatment of JDM may improve outcomes and decrease the incidence of calcification.3 Unfortunately, once calcinosis has occurred, it is highly refractory to medical therapy.

Calcinosis universalis can lead to severe functional impairment. It can be distinguished from other types of calcinosis by diffuse involvement of muscle and fascia in connective tissue disease with normal calcium and phosphorus levels. New management modalities such as cyclosporine, intravenous immunoglobulin, and tumor necrosis factor alpha inhibitors are currently being evaluated.

Hyperglycemia and insulin resistance are common occurrences in critically ill patients, even those without a past medical history of diabetes.1, 2 This hyperglycemic state is associated with adverse outcomes, including severe infections, polyneuropathy, multiple‐organ failure, and death.3 Several studies have shown benefit in keeping patients' blood glucose (BG) tightly controlled.37 In a randomized controlled study, strict BG control (80‐110 mg/dL) with an insulin drip significantly reduced morbidity and mortality in critically ill patients.3 A recent meta‐analysis concluded that avoiding BG levels >150 mg/dL appeared to be crucial to reducing mortality in a mixed medical and surgical intensive care unit (ICU) population.7

The Diabetes Mellitus Insulin‐Glucose Infusion in Acute Myocardial Infarction study addressed the issue of tight glycemic control both acutely and chronically in 620 diabetic patients postmyocardial infarction. Patients were randomized to tight glycemic control (126‐180 mg/dL) followed by a transition to maintenance insulin or to standard care. This intervention demonstrated a sustained mortality reduction of 7.5% at 1 year.8 In contrast, the CREATE‐ECLA study showed a neutral mortality benefit of a short‐term (24‐hour) insulin infusion in postmyocardial infarction patients.9 These data demonstrate the need for clinicians to consider insulin requirements throughout the hospital stay and after discharge. To date, there are no published studies evaluating glycemic control following discontinuation of an intensive insulin protocol (IIP). Therefore, the current study was conducted to compare BG control during the use of an IIP and for the 5 days following intensive insulin therapy.

METHODS

RESULTS

A total of 171 patients received the IIP during the study period. Ninety‐seven patients did not meet inclusion criteria because they received the IIP for less than 24 hours. Of the 74 patients meeting inclusion criteria, 9 were excluded (5 had insufficient glucose data, 3 were cared for by an endocrinologist, and 1 died while receiving the IIP). Thus, 65 patients were included in the study.

Table 1 lists the baseline demographics for all patients and those with and without a history of diabetes mellitus (DM). The majority of the patients (n = 49) underwent a surgical procedure, with the most common procedure being coronary artery bypass graft (n = 38). Patients undergoing coronary artery bypass graft had the IIP included in their standard postoperative order set. The majority of patients were considered stable during the 12 hours prior to discontinuation of the IIP, including 23 patients with a history of DM. Of the 65 patients who were included in the study, 25 (38.5%) received a scheduled insulin order following discontinuation of the IIP, whereas 38 (58.5%) received some form of sliding‐scale insulin (SSI). Additionally, 2 (3%) patients did not receive any form of insulin order after stopping the IIP. Of those receiving scheduled insulin, 15 (60%) received neutral protamine Hagedorn, 5 (20%) received glargine, 5 (20%) received 70/30, and 1 (4%) received regular insulin. Of those receiving SSI only, the prescribed frequency was as follows: every 4 hours for 17 (45%), before meals and at bedtime for 15 (39%), every 6 hours for 5 (13%), and every 2 hours for 1 (3%).

A total of 562 glucose measurements were collected during the last 12 hours on the IIP, whereas 201 were collected during the first 12 hours immediately following the IIP. Patients demonstrated a significant increase in BG (mean standard deviation) during the first 12 hours of the follow‐up period versus the last 12 hours of the IIP (168 50 mg/dL versus 123 26 mg/dL, P < 0.001). This corresponded to a significant decrease in the median (interquartile range) insulin administered during the first 12 hours of the follow‐up period versus the last 12 hours of the IIP [8 (0‐18) units versus 40 (22‐65) units, P < 0.001; Figure 1]. A total of 1914 BG measurements were collected during the follow‐up period. Figure 2 shows mean BG values for all patients on the IIP compared to mean BG values for each day of the follow‐up period. There was a significant increase in mean BG measurements when the IIP was compared to each day of the follow‐up period, but there was no difference between days of the follow‐up period. Table 2 shows the proportion of patients experiencing at least 1 episode of hyperglycemia (BG > 150 mg/dL), significant hyperglycemia (BG > 200 mg/dL), severe hyperglycemia (BG > 300 mg/dL), or hypoglycemia (BG < 60 mg/dL) while receiving the IIP and during the follow‐up period. When comparing the IIP to the follow‐up period, we found a significant increase in the proportion of patients with at least 1 BG > 150 mg/dL. This was also true for patients with a BG of > 200 mg/dL.

Figure 1

Figure 2

The only independent predictor of a greater than 30% change in mean BG was the requirement for more than 20 units of insulin (>1.7 units/hour) during the last 12 hours on the IIP. The odds of a greater than 30% change was 4.62 times higher (95% confidence interval: 1.1718.17) in patients requiring more than 20 units during the last 12 hours on IIP after adjustments for stability on the protocol and past medical history of diabetes. Stability on the protocol was not identified as an independent predictor, with an adjusted odds ratio of 2.40 (95% confidence interval: 0.797.32).

DISCUSSION

This is the first study to describe glycemic control following the transition from an IIP to subcutaneous insulin. We observed that during the 5 days following discontinuation of an IIP, patients had significantly elevated mean BG values. These data are highlighted by the fact that patients received significantly less insulin during the first 12 hours of the follow‐up period versus the last 12 hours of the IIP. Additionally, a larger than expected proportion of patients exhibited at least 1 episode of hyperglycemia during the follow‐up period. We also found that an increased insulin requirement of >1.7 units/hour during the last 12 hours of the IIP was an independent risk factor for a greater than 30% increase in mean BG on day 1 of the follow‐up period.

Increasing evidence demonstrates that the development of hyperglycemia in the hospital setting is a marker of poor clinical outcome and mortality. In fact, hyperglycemia has been associated with prolonged hospital stay, infection, disability after discharge, and death in patients on general surgical and medical wards.1012 This makes the increase in mean BG found in our study following discontinuation of the IIP a concern.

SSI with subcutaneous short‐acting insulin has been used for inpatients as the standard of care for many years. However, evidence supporting the effectiveness of SSI alone is lacking, and it is not recommended by the American Diabetes Association.13 Queale et al.14 showed that SSI regimens when used alone were associated with suboptimal glycemic control and a 3‐fold higher risk of hyperglycemic episodes.1 Two retrospective studies have also demonstrated that SSI is less effective and widely variable in comparison with proactive preventative therapy.15, 16 In the current study, 58.5% of patients received SSI alone during the follow‐up period. As indicated in Figure 1, there was a significant increase in mean BG during this time interval. The choice of an inappropriate insulin regimen might be a contributing factor to poor glycemic control.

Because only 38.5% of patients were transitioned to scheduled insulin in our study, one possible strategy to help improve glycemic control would be to transition patients to a scheduled insulin regimen. Umpierrez et al.12 conducted a prospective, multicenter randomized trial to compare the efficacy and safety of a basal‐bolus insulin regimen with that of SSI in hospitalized type 2 diabetics. These authors found that patients treated with insulin glargine and glulisine had greater improvement in glycemic control than those treated with SSI (P < 0.01).12 Interestingly, the basal‐bolus method provides a maintenance insulin regimen that is aggressively titrated upward as well as an adjustable SSI based on insulin sensitivity. Patients in the current study may have benefited from a similar approach as many did not have their scheduled insulin adjusted despite persistent hyperglycemia.

With the increasing evidence for tight glycemic control in the ICU, a standardized transition from an intensive insulin infusion to a subcutaneous basal‐bolus regimen or other scheduled regimen is needed. To date, the current study is the first to describe this transition. Based on these data, recommendations for transitioning patients off an IIP provided by Furnary and Braithwaite17 should be considered by clinicians. In fact, one of their proposed predictors for unsuccessful transition was an insulin requirement of 2 units/hour. Indeed, the only independent risk factor for poor glycemic control identified in the current study was a requirement of >20 units (>1.7 units/hour) during the last 12 hours of the IIP. Further research is required to verify the other predictors suggested by Furnary and Braithwaite. They recommended using a standardized conversion protocol to transition patients off an IIP.

More recently, Kitabchi et al.18 recommended that a BG target of less than 180 mg/dL be maintained for the hospitalized patient.18 Although our study showed a mean BG less than 180 mg/dL during the follow‐up period, the variability in these values raises concerns for individual patients.

The current study is limited by its size and retrospective nature. As with all retrospective studies, the inability to control the implementation and discontinuation of the IIP may confound the results. However, this study demonstrates a real world experience with an IIP and illustrates the difficulties with transitioning patients to a subcutaneous regimen. BG values and administered insulin were collected only for the last 12 hours on the IIP. This duration is considered appropriate as this time period is used clinically at MUH, and previous recommendations for transitioning patients suggest using a time period of 6 to 8 hours to guide the transition insulin regimen.17 In addition, data regarding the severity of illness and new onset of infections were not collected for patients in the study. Both could affect glucose control. All patients had to be in an ICU to receive the IIP, but their location during the follow‐up period varied. Although these data were not available, control of BG is a problem that should be addressed whether the patient is in the ICU or not. Another possible limitation of the study was the identification of patients with or without a past medical history of DM. The inability to identify new‐onset or previously undiagnosed DM may have affected analyses based on this variable.

CONCLUSIONS

This study demonstrated a significant increase in mean BG following discontinuation of an IIP; this corresponded to a significant decrease in the amount of insulin administered. This increase was sustained for a period of at least 5 days. Additionally, an independent risk factor for poor glycemic control immediately following discontinuation of an IIP was an insulin requirement of >1.7 units/hour during the previous 12 hours. Further study into transitioning off an IIP is warranted.

Hyperglycemia and insulin resistance are common occurrences in critically ill patients, even those without a past medical history of diabetes.1, 2 This hyperglycemic state is associated with adverse outcomes, including severe infections, polyneuropathy, multiple‐organ failure, and death.3 Several studies have shown benefit in keeping patients' blood glucose (BG) tightly controlled.37 In a randomized controlled study, strict BG control (80‐110 mg/dL) with an insulin drip significantly reduced morbidity and mortality in critically ill patients.3 A recent meta‐analysis concluded that avoiding BG levels >150 mg/dL appeared to be crucial to reducing mortality in a mixed medical and surgical intensive care unit (ICU) population.7

The Diabetes Mellitus Insulin‐Glucose Infusion in Acute Myocardial Infarction study addressed the issue of tight glycemic control both acutely and chronically in 620 diabetic patients postmyocardial infarction. Patients were randomized to tight glycemic control (126‐180 mg/dL) followed by a transition to maintenance insulin or to standard care. This intervention demonstrated a sustained mortality reduction of 7.5% at 1 year.8 In contrast, the CREATE‐ECLA study showed a neutral mortality benefit of a short‐term (24‐hour) insulin infusion in postmyocardial infarction patients.9 These data demonstrate the need for clinicians to consider insulin requirements throughout the hospital stay and after discharge. To date, there are no published studies evaluating glycemic control following discontinuation of an intensive insulin protocol (IIP). Therefore, the current study was conducted to compare BG control during the use of an IIP and for the 5 days following intensive insulin therapy.

METHODS

RESULTS

A total of 171 patients received the IIP during the study period. Ninety‐seven patients did not meet inclusion criteria because they received the IIP for less than 24 hours. Of the 74 patients meeting inclusion criteria, 9 were excluded (5 had insufficient glucose data, 3 were cared for by an endocrinologist, and 1 died while receiving the IIP). Thus, 65 patients were included in the study.

Table 1 lists the baseline demographics for all patients and those with and without a history of diabetes mellitus (DM). The majority of the patients (n = 49) underwent a surgical procedure, with the most common procedure being coronary artery bypass graft (n = 38). Patients undergoing coronary artery bypass graft had the IIP included in their standard postoperative order set. The majority of patients were considered stable during the 12 hours prior to discontinuation of the IIP, including 23 patients with a history of DM. Of the 65 patients who were included in the study, 25 (38.5%) received a scheduled insulin order following discontinuation of the IIP, whereas 38 (58.5%) received some form of sliding‐scale insulin (SSI). Additionally, 2 (3%) patients did not receive any form of insulin order after stopping the IIP. Of those receiving scheduled insulin, 15 (60%) received neutral protamine Hagedorn, 5 (20%) received glargine, 5 (20%) received 70/30, and 1 (4%) received regular insulin. Of those receiving SSI only, the prescribed frequency was as follows: every 4 hours for 17 (45%), before meals and at bedtime for 15 (39%), every 6 hours for 5 (13%), and every 2 hours for 1 (3%).

A total of 562 glucose measurements were collected during the last 12 hours on the IIP, whereas 201 were collected during the first 12 hours immediately following the IIP. Patients demonstrated a significant increase in BG (mean standard deviation) during the first 12 hours of the follow‐up period versus the last 12 hours of the IIP (168 50 mg/dL versus 123 26 mg/dL, P < 0.001). This corresponded to a significant decrease in the median (interquartile range) insulin administered during the first 12 hours of the follow‐up period versus the last 12 hours of the IIP [8 (0‐18) units versus 40 (22‐65) units, P < 0.001; Figure 1]. A total of 1914 BG measurements were collected during the follow‐up period. Figure 2 shows mean BG values for all patients on the IIP compared to mean BG values for each day of the follow‐up period. There was a significant increase in mean BG measurements when the IIP was compared to each day of the follow‐up period, but there was no difference between days of the follow‐up period. Table 2 shows the proportion of patients experiencing at least 1 episode of hyperglycemia (BG > 150 mg/dL), significant hyperglycemia (BG > 200 mg/dL), severe hyperglycemia (BG > 300 mg/dL), or hypoglycemia (BG < 60 mg/dL) while receiving the IIP and during the follow‐up period. When comparing the IIP to the follow‐up period, we found a significant increase in the proportion of patients with at least 1 BG > 150 mg/dL. This was also true for patients with a BG of > 200 mg/dL.

Figure 1

Figure 2

The only independent predictor of a greater than 30% change in mean BG was the requirement for more than 20 units of insulin (>1.7 units/hour) during the last 12 hours on the IIP. The odds of a greater than 30% change was 4.62 times higher (95% confidence interval: 1.1718.17) in patients requiring more than 20 units during the last 12 hours on IIP after adjustments for stability on the protocol and past medical history of diabetes. Stability on the protocol was not identified as an independent predictor, with an adjusted odds ratio of 2.40 (95% confidence interval: 0.797.32).

DISCUSSION

This is the first study to describe glycemic control following the transition from an IIP to subcutaneous insulin. We observed that during the 5 days following discontinuation of an IIP, patients had significantly elevated mean BG values. These data are highlighted by the fact that patients received significantly less insulin during the first 12 hours of the follow‐up period versus the last 12 hours of the IIP. Additionally, a larger than expected proportion of patients exhibited at least 1 episode of hyperglycemia during the follow‐up period. We also found that an increased insulin requirement of >1.7 units/hour during the last 12 hours of the IIP was an independent risk factor for a greater than 30% increase in mean BG on day 1 of the follow‐up period.

Increasing evidence demonstrates that the development of hyperglycemia in the hospital setting is a marker of poor clinical outcome and mortality. In fact, hyperglycemia has been associated with prolonged hospital stay, infection, disability after discharge, and death in patients on general surgical and medical wards.1012 This makes the increase in mean BG found in our study following discontinuation of the IIP a concern.

SSI with subcutaneous short‐acting insulin has been used for inpatients as the standard of care for many years. However, evidence supporting the effectiveness of SSI alone is lacking, and it is not recommended by the American Diabetes Association.13 Queale et al.14 showed that SSI regimens when used alone were associated with suboptimal glycemic control and a 3‐fold higher risk of hyperglycemic episodes.1 Two retrospective studies have also demonstrated that SSI is less effective and widely variable in comparison with proactive preventative therapy.15, 16 In the current study, 58.5% of patients received SSI alone during the follow‐up period. As indicated in Figure 1, there was a significant increase in mean BG during this time interval. The choice of an inappropriate insulin regimen might be a contributing factor to poor glycemic control.

Because only 38.5% of patients were transitioned to scheduled insulin in our study, one possible strategy to help improve glycemic control would be to transition patients to a scheduled insulin regimen. Umpierrez et al.12 conducted a prospective, multicenter randomized trial to compare the efficacy and safety of a basal‐bolus insulin regimen with that of SSI in hospitalized type 2 diabetics. These authors found that patients treated with insulin glargine and glulisine had greater improvement in glycemic control than those treated with SSI (P < 0.01).12 Interestingly, the basal‐bolus method provides a maintenance insulin regimen that is aggressively titrated upward as well as an adjustable SSI based on insulin sensitivity. Patients in the current study may have benefited from a similar approach as many did not have their scheduled insulin adjusted despite persistent hyperglycemia.

With the increasing evidence for tight glycemic control in the ICU, a standardized transition from an intensive insulin infusion to a subcutaneous basal‐bolus regimen or other scheduled regimen is needed. To date, the current study is the first to describe this transition. Based on these data, recommendations for transitioning patients off an IIP provided by Furnary and Braithwaite17 should be considered by clinicians. In fact, one of their proposed predictors for unsuccessful transition was an insulin requirement of 2 units/hour. Indeed, the only independent risk factor for poor glycemic control identified in the current study was a requirement of >20 units (>1.7 units/hour) during the last 12 hours of the IIP. Further research is required to verify the other predictors suggested by Furnary and Braithwaite. They recommended using a standardized conversion protocol to transition patients off an IIP.

More recently, Kitabchi et al.18 recommended that a BG target of less than 180 mg/dL be maintained for the hospitalized patient.18 Although our study showed a mean BG less than 180 mg/dL during the follow‐up period, the variability in these values raises concerns for individual patients.

The current study is limited by its size and retrospective nature. As with all retrospective studies, the inability to control the implementation and discontinuation of the IIP may confound the results. However, this study demonstrates a real world experience with an IIP and illustrates the difficulties with transitioning patients to a subcutaneous regimen. BG values and administered insulin were collected only for the last 12 hours on the IIP. This duration is considered appropriate as this time period is used clinically at MUH, and previous recommendations for transitioning patients suggest using a time period of 6 to 8 hours to guide the transition insulin regimen.17 In addition, data regarding the severity of illness and new onset of infections were not collected for patients in the study. Both could affect glucose control. All patients had to be in an ICU to receive the IIP, but their location during the follow‐up period varied. Although these data were not available, control of BG is a problem that should be addressed whether the patient is in the ICU or not. Another possible limitation of the study was the identification of patients with or without a past medical history of DM. The inability to identify new‐onset or previously undiagnosed DM may have affected analyses based on this variable.

CONCLUSIONS

This study demonstrated a significant increase in mean BG following discontinuation of an IIP; this corresponded to a significant decrease in the amount of insulin administered. This increase was sustained for a period of at least 5 days. Additionally, an independent risk factor for poor glycemic control immediately following discontinuation of an IIP was an insulin requirement of >1.7 units/hour during the previous 12 hours. Further study into transitioning off an IIP is warranted.

Hyperglycemia and insulin resistance are common occurrences in critically ill patients, even those without a past medical history of diabetes.1, 2 This hyperglycemic state is associated with adverse outcomes, including severe infections, polyneuropathy, multiple‐organ failure, and death.3 Several studies have shown benefit in keeping patients' blood glucose (BG) tightly controlled.37 In a randomized controlled study, strict BG control (80‐110 mg/dL) with an insulin drip significantly reduced morbidity and mortality in critically ill patients.3 A recent meta‐analysis concluded that avoiding BG levels >150 mg/dL appeared to be crucial to reducing mortality in a mixed medical and surgical intensive care unit (ICU) population.7

The Diabetes Mellitus Insulin‐Glucose Infusion in Acute Myocardial Infarction study addressed the issue of tight glycemic control both acutely and chronically in 620 diabetic patients postmyocardial infarction. Patients were randomized to tight glycemic control (126‐180 mg/dL) followed by a transition to maintenance insulin or to standard care. This intervention demonstrated a sustained mortality reduction of 7.5% at 1 year.8 In contrast, the CREATE‐ECLA study showed a neutral mortality benefit of a short‐term (24‐hour) insulin infusion in postmyocardial infarction patients.9 These data demonstrate the need for clinicians to consider insulin requirements throughout the hospital stay and after discharge. To date, there are no published studies evaluating glycemic control following discontinuation of an intensive insulin protocol (IIP). Therefore, the current study was conducted to compare BG control during the use of an IIP and for the 5 days following intensive insulin therapy.

METHODS

RESULTS

A total of 171 patients received the IIP during the study period. Ninety‐seven patients did not meet inclusion criteria because they received the IIP for less than 24 hours. Of the 74 patients meeting inclusion criteria, 9 were excluded (5 had insufficient glucose data, 3 were cared for by an endocrinologist, and 1 died while receiving the IIP). Thus, 65 patients were included in the study.

Table 1 lists the baseline demographics for all patients and those with and without a history of diabetes mellitus (DM). The majority of the patients (n = 49) underwent a surgical procedure, with the most common procedure being coronary artery bypass graft (n = 38). Patients undergoing coronary artery bypass graft had the IIP included in their standard postoperative order set. The majority of patients were considered stable during the 12 hours prior to discontinuation of the IIP, including 23 patients with a history of DM. Of the 65 patients who were included in the study, 25 (38.5%) received a scheduled insulin order following discontinuation of the IIP, whereas 38 (58.5%) received some form of sliding‐scale insulin (SSI). Additionally, 2 (3%) patients did not receive any form of insulin order after stopping the IIP. Of those receiving scheduled insulin, 15 (60%) received neutral protamine Hagedorn, 5 (20%) received glargine, 5 (20%) received 70/30, and 1 (4%) received regular insulin. Of those receiving SSI only, the prescribed frequency was as follows: every 4 hours for 17 (45%), before meals and at bedtime for 15 (39%), every 6 hours for 5 (13%), and every 2 hours for 1 (3%).

A total of 562 glucose measurements were collected during the last 12 hours on the IIP, whereas 201 were collected during the first 12 hours immediately following the IIP. Patients demonstrated a significant increase in BG (mean standard deviation) during the first 12 hours of the follow‐up period versus the last 12 hours of the IIP (168 50 mg/dL versus 123 26 mg/dL, P < 0.001). This corresponded to a significant decrease in the median (interquartile range) insulin administered during the first 12 hours of the follow‐up period versus the last 12 hours of the IIP [8 (0‐18) units versus 40 (22‐65) units, P < 0.001; Figure 1]. A total of 1914 BG measurements were collected during the follow‐up period. Figure 2 shows mean BG values for all patients on the IIP compared to mean BG values for each day of the follow‐up period. There was a significant increase in mean BG measurements when the IIP was compared to each day of the follow‐up period, but there was no difference between days of the follow‐up period. Table 2 shows the proportion of patients experiencing at least 1 episode of hyperglycemia (BG > 150 mg/dL), significant hyperglycemia (BG > 200 mg/dL), severe hyperglycemia (BG > 300 mg/dL), or hypoglycemia (BG < 60 mg/dL) while receiving the IIP and during the follow‐up period. When comparing the IIP to the follow‐up period, we found a significant increase in the proportion of patients with at least 1 BG > 150 mg/dL. This was also true for patients with a BG of > 200 mg/dL.

Figure 1

Figure 2

The only independent predictor of a greater than 30% change in mean BG was the requirement for more than 20 units of insulin (>1.7 units/hour) during the last 12 hours on the IIP. The odds of a greater than 30% change was 4.62 times higher (95% confidence interval: 1.1718.17) in patients requiring more than 20 units during the last 12 hours on IIP after adjustments for stability on the protocol and past medical history of diabetes. Stability on the protocol was not identified as an independent predictor, with an adjusted odds ratio of 2.40 (95% confidence interval: 0.797.32).

DISCUSSION

This is the first study to describe glycemic control following the transition from an IIP to subcutaneous insulin. We observed that during the 5 days following discontinuation of an IIP, patients had significantly elevated mean BG values. These data are highlighted by the fact that patients received significantly less insulin during the first 12 hours of the follow‐up period versus the last 12 hours of the IIP. Additionally, a larger than expected proportion of patients exhibited at least 1 episode of hyperglycemia during the follow‐up period. We also found that an increased insulin requirement of >1.7 units/hour during the last 12 hours of the IIP was an independent risk factor for a greater than 30% increase in mean BG on day 1 of the follow‐up period.

Increasing evidence demonstrates that the development of hyperglycemia in the hospital setting is a marker of poor clinical outcome and mortality. In fact, hyperglycemia has been associated with prolonged hospital stay, infection, disability after discharge, and death in patients on general surgical and medical wards.1012 This makes the increase in mean BG found in our study following discontinuation of the IIP a concern.

SSI with subcutaneous short‐acting insulin has been used for inpatients as the standard of care for many years. However, evidence supporting the effectiveness of SSI alone is lacking, and it is not recommended by the American Diabetes Association.13 Queale et al.14 showed that SSI regimens when used alone were associated with suboptimal glycemic control and a 3‐fold higher risk of hyperglycemic episodes.1 Two retrospective studies have also demonstrated that SSI is less effective and widely variable in comparison with proactive preventative therapy.15, 16 In the current study, 58.5% of patients received SSI alone during the follow‐up period. As indicated in Figure 1, there was a significant increase in mean BG during this time interval. The choice of an inappropriate insulin regimen might be a contributing factor to poor glycemic control.

Because only 38.5% of patients were transitioned to scheduled insulin in our study, one possible strategy to help improve glycemic control would be to transition patients to a scheduled insulin regimen. Umpierrez et al.12 conducted a prospective, multicenter randomized trial to compare the efficacy and safety of a basal‐bolus insulin regimen with that of SSI in hospitalized type 2 diabetics. These authors found that patients treated with insulin glargine and glulisine had greater improvement in glycemic control than those treated with SSI (P < 0.01).12 Interestingly, the basal‐bolus method provides a maintenance insulin regimen that is aggressively titrated upward as well as an adjustable SSI based on insulin sensitivity. Patients in the current study may have benefited from a similar approach as many did not have their scheduled insulin adjusted despite persistent hyperglycemia.

With the increasing evidence for tight glycemic control in the ICU, a standardized transition from an intensive insulin infusion to a subcutaneous basal‐bolus regimen or other scheduled regimen is needed. To date, the current study is the first to describe this transition. Based on these data, recommendations for transitioning patients off an IIP provided by Furnary and Braithwaite17 should be considered by clinicians. In fact, one of their proposed predictors for unsuccessful transition was an insulin requirement of 2 units/hour. Indeed, the only independent risk factor for poor glycemic control identified in the current study was a requirement of >20 units (>1.7 units/hour) during the last 12 hours of the IIP. Further research is required to verify the other predictors suggested by Furnary and Braithwaite. They recommended using a standardized conversion protocol to transition patients off an IIP.

More recently, Kitabchi et al.18 recommended that a BG target of less than 180 mg/dL be maintained for the hospitalized patient.18 Although our study showed a mean BG less than 180 mg/dL during the follow‐up period, the variability in these values raises concerns for individual patients.

The current study is limited by its size and retrospective nature. As with all retrospective studies, the inability to control the implementation and discontinuation of the IIP may confound the results. However, this study demonstrates a real world experience with an IIP and illustrates the difficulties with transitioning patients to a subcutaneous regimen. BG values and administered insulin were collected only for the last 12 hours on the IIP. This duration is considered appropriate as this time period is used clinically at MUH, and previous recommendations for transitioning patients suggest using a time period of 6 to 8 hours to guide the transition insulin regimen.17 In addition, data regarding the severity of illness and new onset of infections were not collected for patients in the study. Both could affect glucose control. All patients had to be in an ICU to receive the IIP, but their location during the follow‐up period varied. Although these data were not available, control of BG is a problem that should be addressed whether the patient is in the ICU or not. Another possible limitation of the study was the identification of patients with or without a past medical history of DM. The inability to identify new‐onset or previously undiagnosed DM may have affected analyses based on this variable.

CONCLUSIONS

This study demonstrated a significant increase in mean BG following discontinuation of an IIP; this corresponded to a significant decrease in the amount of insulin administered. This increase was sustained for a period of at least 5 days. Additionally, an independent risk factor for poor glycemic control immediately following discontinuation of an IIP was an insulin requirement of >1.7 units/hour during the previous 12 hours. Further study into transitioning off an IIP is warranted.