Clinical Care Conundrums

Case

A 53-year-old woman with a history of a suprasellar meningioma resected nine years ago with recurrence of a 4.5x2 cm mass one year ago and recent ventriculoperitoneal (VP) shunt placement for hydrocephalus presented with altered mental status (AMS) and hallucinations. She was admitted for radiation therapy to the mass. The patient had little improvement in her mental status four weeks into a six-week, 4860 cGy course of photon therapy.

The internal medicine service was consulted for new onset tachycardia (103), hypotension (83/55), and fever (38.6 C). Laboratory data revealed a white blood cell count 4.8 x 109 cells/L, sodium 137 mmol/L, potassium 4.1 mmol/L, chloride 110 mmol/L, bicarbonate 28 mmol/L, blood urea nitrogen 3 mg/dl, creatinine 0.6 mg/dl, and glucose 91 mg/dl. Thyroid-stimulating hormone (TSH) was low at 0.38 mIU/mL. Urine specific gravity was 1.006. Workups for infectious and thromboembolic diseases were unremarkable.

Discussion

Hypopituitarism is a disorder of impaired hormone production from the anterior and, less commonly, posterior pituitary gland. The condition can originate from several broad categories of diseases affecting the hypothalamus, pituitary stalk, or pituitary gland. In adults, the etiology is often from the mass effect of tumors or from treatment with surgery or radiotherapy. Other causes include vascular, infectious, infiltrative, inflammatory, and idiopathic. Well-substantiated data on the incidence and prevalence of hypopituitarism is sparse. It has an estimated prevalence of 45.5 cases per 100,000 and incidence of 4.2 cases per 100,000 per year.¹

Clinical manifestations of hypopituitarism depend on the type and severity of hormone deficiency. The consequences of adrenal insufficiency (AI) range from smoldering and nonspecific findings (e.g. fatigue, lethargy, indistinct gastrointestinal symptoms, eosinophilia, fever) to full-fledged crisis (e.g. AMS, severe electrolyte abnormalities, hemodynamic compromise, shock). The presentation of central AI (i.e., arising from hypothalamic or pituitary pathology) is often more subtle than primary AI. In central AI, only glucocorticoid (GC) function is disrupted, leaving the renin-angiotensin-aldosterone system and mineralocorticoid (MC) function intact. This is in stark contrast to primary AI resulting from direct adrenal gland injury, which nearly always disrupts both GC and MC function, leading to more profound circulatory collapse and electrolyte disturbance.²

Aside from orthostatic blood pressure or possible low-grade fever, few physical exam features are associated with central AI. Hyperpigmentation is not seen due to the lack of anterior pituitary-derived melanocortins that stimulate melanocytes and induce pigmentation. As for laboratory findings, hyperkalemia is a feature of primary AI (due to hypoaldosteronism) but is not seen in central AI. Hyponatremia occurs in both types of AI and is vasopressin-mediated. Hyponatremia is more common in primary AI, resulting from appropriate vasopressin release that occurs due to hypotension. Hyponatremia also occurs in secondary AI because of increased vasopressin secretion mediated directly by hypocortisolemia.^3,4

In summary, hyperpigmentation and the electrolyte pattern of hyponatremia and hyperkalemia are distinguishing clinical characteristics of primary AI, occurring in up to 90% of cases, but these features would not be expected with central AI.⁵

In the hospitalized patient with multiple active acute illnesses and infectious risk factors, it can be difficult to recognize the diagnosis of AI or hypopituitarism. Not only do signs and symptoms frequently overlap, but concomitant acute illness is usually a triggering event. Crisis should be suspected in the setting of unexplained fever, dehydration, or shock out of proportion to severity of current illness.⁵

Not surprisingly, high rates of partial or complete hypopituitarism are seen in patients following surgical removal of pituitary tumors or nearby neoplasms (e.g. craniopharyngiomas). Both surgery and radiotherapy for non-pituitary brain tumors are also major risk factors for development of hypopituitarism, occurring in up to 38% and 41% of patients, respectively.⁶ The strongest predictors of hormone failure are higher radiation doses, proximity to the pituitary-hypothalamus, and longer time interval after completion of radiotherapy. Within 10 years after a median dose of 5000 rad (50Gy) directed at the skull base, nasopharynx, or cranium, up to three-fourths of patients will develop some degree of pituitary insufficiency. Later onset of hormone failure usually reflects hypothalamic injury, whereas higher irradiation doses can lead to earlier onset pituitary damage.⁵

Not all hormone-secreting cells of the hypothalamus or pituitary are equally susceptible to injury; there is a characteristic sequence of hormonal failure. The typical order of hormone deficiency from pituitary compression or destruction is as follows: growth hormone (GH) > follicle-stimulating hormone (FSH) > luteinizing hormone (LH) > TSH > adrenocorticotropic hormone (ACTH) > vasopressin. A similar pattern is seen following brain irradiation: GH > FSH and LH > ACTH > TSH. A recent systematic review of 18 studies with 813 patients receiving cranial radiotherapy for non-pituitary tumors found pituitary dysfunction was 45% for GH deficiency, compared to 22% for ACTH deficiency.⁷

Biochemical diagnosis of hypopituitarism consists of measuring the various pituitary and target hormone levels as well as provocation testing. When interpreting these tests, whether to identify excess or deficient states, it is important to remember the individual values are part of the broader hypothalamic-pituitary axis feedback loops. Thus, it can be more useful designating if a high or low test value is appropriately or inappropriately high or low. In the presented case, low TSH level could be misinterpreted as excess thyroid hormone supplementation. An appropriately elevated free T4 level would confirm this, but an inappropriately low free T4 would raise suspicion of central hypothalamic-pituitary dysfunction.

With high enough clinical suspicion of hypopituitarism, empiric treatment with thyroid supplementation and corticosteroids should be started before confirmation of the diagnosis, to prevent secondary organ dysfunction and improve morbidity and mortality.² Rapid administration with intravenous levothyroxine can be given in severe hypothyroidism or myxedema.

“Stress-dose” steroids are generally recommended for patients who are also administered levothyroxine, as the desired increased in metabolic rate can deplete existing pituitary-adrenocortical hormone reserves, precipitating adrenal crisis.⁵ Stress-dose corticosteroids also ensure recruitment of a mineralocorticoid response. Cortisol has both GC and MC stimulating effects but is rapidly metabolized to cortisone, which lacks MC stimulating effects. Thus, high doses overwhelm this conversion step and allow remaining cortisol to stimulate MC receptors.² These high doses may not be necessary in secondary AI (i.e., preserved MC function) but would be reasonable in an unstable patient or until confirmation is made with an inappropriately low ACTH.

Back to the Case

Morning cortisol returned undetectable, and ACTH was 14 pg/mL (6-58). Past records revealed a down-trending TSH from 1.12 to 0.38 mIU/mL, which had inappropriately prompted a levothyroxine dose reduction from 50 mcg to 25 mcg. A free thyroxine (T4) was low at 0.67 ng/dL (0.89-1.76). Estradiol, FSH, and LH were undetectable. Prolactin was 23 ng/mL (3-27). She was started on prednisone, 5 mg daily, and her levothyroxine was adjusted to a weight-based dose. Her fever resolved with the initiation of prednisone, and all cultures remained negative. Over two weeks, she improved back to her baseline, was discharged to a rehabilitation center, and eventually returned home.

Dr. Inman is a hospitalist at St. Mary’s Hospital and Regional Medical Center in Grand Junction, Colo. Dr. Bridenstine is an endocrinologist at the University of Colorado Denver. Dr. Cumbler is a hospitalist at the University of Colorado Denver.

References

1. Regal M, Pàramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol. 2001;55(6):735-740.
2. Bouillon R. Acute adrenal insufficiency. Endocrinol Metab Clin North Am. 2006;35(4):767-75, ix.
3. Raff H. Glucocorticoid inhibition of neurohypophysial vasopressin secretion. Am J Physiol. 1987;252(4 Pt 2):R635-644.
4. Erkut ZA, Pool C, Swaab DF. Glucocorticoids suppress corticotropin-releasing hormone and vasopressin expression in human hypothalamic neurons. J Clin Endocrinol Metab. 1998;83(6):2066-2073.
5. Melmed S, Polonski KS, Reed Larsen P, Kronenberg HM. Williams Textbook of Endocrinology. 12th ed. Philadelphia, Pa.: Saunders/Elsevier; 2012.
6. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK, Ghigo E. Hypopituitarism. Lancet. 2007;369(9571):1461-1470.
7. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metabol. 2011;96(8):2330-2340.

Case

A 53-year-old woman with a history of a suprasellar meningioma resected nine years ago with recurrence of a 4.5x2 cm mass one year ago and recent ventriculoperitoneal (VP) shunt placement for hydrocephalus presented with altered mental status (AMS) and hallucinations. She was admitted for radiation therapy to the mass. The patient had little improvement in her mental status four weeks into a six-week, 4860 cGy course of photon therapy.

The internal medicine service was consulted for new onset tachycardia (103), hypotension (83/55), and fever (38.6 C). Laboratory data revealed a white blood cell count 4.8 x 109 cells/L, sodium 137 mmol/L, potassium 4.1 mmol/L, chloride 110 mmol/L, bicarbonate 28 mmol/L, blood urea nitrogen 3 mg/dl, creatinine 0.6 mg/dl, and glucose 91 mg/dl. Thyroid-stimulating hormone (TSH) was low at 0.38 mIU/mL. Urine specific gravity was 1.006. Workups for infectious and thromboembolic diseases were unremarkable.

Discussion

Hypopituitarism is a disorder of impaired hormone production from the anterior and, less commonly, posterior pituitary gland. The condition can originate from several broad categories of diseases affecting the hypothalamus, pituitary stalk, or pituitary gland. In adults, the etiology is often from the mass effect of tumors or from treatment with surgery or radiotherapy. Other causes include vascular, infectious, infiltrative, inflammatory, and idiopathic. Well-substantiated data on the incidence and prevalence of hypopituitarism is sparse. It has an estimated prevalence of 45.5 cases per 100,000 and incidence of 4.2 cases per 100,000 per year.¹

Clinical manifestations of hypopituitarism depend on the type and severity of hormone deficiency. The consequences of adrenal insufficiency (AI) range from smoldering and nonspecific findings (e.g. fatigue, lethargy, indistinct gastrointestinal symptoms, eosinophilia, fever) to full-fledged crisis (e.g. AMS, severe electrolyte abnormalities, hemodynamic compromise, shock). The presentation of central AI (i.e., arising from hypothalamic or pituitary pathology) is often more subtle than primary AI. In central AI, only glucocorticoid (GC) function is disrupted, leaving the renin-angiotensin-aldosterone system and mineralocorticoid (MC) function intact. This is in stark contrast to primary AI resulting from direct adrenal gland injury, which nearly always disrupts both GC and MC function, leading to more profound circulatory collapse and electrolyte disturbance.²

Aside from orthostatic blood pressure or possible low-grade fever, few physical exam features are associated with central AI. Hyperpigmentation is not seen due to the lack of anterior pituitary-derived melanocortins that stimulate melanocytes and induce pigmentation. As for laboratory findings, hyperkalemia is a feature of primary AI (due to hypoaldosteronism) but is not seen in central AI. Hyponatremia occurs in both types of AI and is vasopressin-mediated. Hyponatremia is more common in primary AI, resulting from appropriate vasopressin release that occurs due to hypotension. Hyponatremia also occurs in secondary AI because of increased vasopressin secretion mediated directly by hypocortisolemia.^3,4

In summary, hyperpigmentation and the electrolyte pattern of hyponatremia and hyperkalemia are distinguishing clinical characteristics of primary AI, occurring in up to 90% of cases, but these features would not be expected with central AI.⁵

In the hospitalized patient with multiple active acute illnesses and infectious risk factors, it can be difficult to recognize the diagnosis of AI or hypopituitarism. Not only do signs and symptoms frequently overlap, but concomitant acute illness is usually a triggering event. Crisis should be suspected in the setting of unexplained fever, dehydration, or shock out of proportion to severity of current illness.⁵

Not surprisingly, high rates of partial or complete hypopituitarism are seen in patients following surgical removal of pituitary tumors or nearby neoplasms (e.g. craniopharyngiomas). Both surgery and radiotherapy for non-pituitary brain tumors are also major risk factors for development of hypopituitarism, occurring in up to 38% and 41% of patients, respectively.⁶ The strongest predictors of hormone failure are higher radiation doses, proximity to the pituitary-hypothalamus, and longer time interval after completion of radiotherapy. Within 10 years after a median dose of 5000 rad (50Gy) directed at the skull base, nasopharynx, or cranium, up to three-fourths of patients will develop some degree of pituitary insufficiency. Later onset of hormone failure usually reflects hypothalamic injury, whereas higher irradiation doses can lead to earlier onset pituitary damage.⁵

Not all hormone-secreting cells of the hypothalamus or pituitary are equally susceptible to injury; there is a characteristic sequence of hormonal failure. The typical order of hormone deficiency from pituitary compression or destruction is as follows: growth hormone (GH) > follicle-stimulating hormone (FSH) > luteinizing hormone (LH) > TSH > adrenocorticotropic hormone (ACTH) > vasopressin. A similar pattern is seen following brain irradiation: GH > FSH and LH > ACTH > TSH. A recent systematic review of 18 studies with 813 patients receiving cranial radiotherapy for non-pituitary tumors found pituitary dysfunction was 45% for GH deficiency, compared to 22% for ACTH deficiency.⁷

Biochemical diagnosis of hypopituitarism consists of measuring the various pituitary and target hormone levels as well as provocation testing. When interpreting these tests, whether to identify excess or deficient states, it is important to remember the individual values are part of the broader hypothalamic-pituitary axis feedback loops. Thus, it can be more useful designating if a high or low test value is appropriately or inappropriately high or low. In the presented case, low TSH level could be misinterpreted as excess thyroid hormone supplementation. An appropriately elevated free T4 level would confirm this, but an inappropriately low free T4 would raise suspicion of central hypothalamic-pituitary dysfunction.

With high enough clinical suspicion of hypopituitarism, empiric treatment with thyroid supplementation and corticosteroids should be started before confirmation of the diagnosis, to prevent secondary organ dysfunction and improve morbidity and mortality.² Rapid administration with intravenous levothyroxine can be given in severe hypothyroidism or myxedema.

“Stress-dose” steroids are generally recommended for patients who are also administered levothyroxine, as the desired increased in metabolic rate can deplete existing pituitary-adrenocortical hormone reserves, precipitating adrenal crisis.⁵ Stress-dose corticosteroids also ensure recruitment of a mineralocorticoid response. Cortisol has both GC and MC stimulating effects but is rapidly metabolized to cortisone, which lacks MC stimulating effects. Thus, high doses overwhelm this conversion step and allow remaining cortisol to stimulate MC receptors.² These high doses may not be necessary in secondary AI (i.e., preserved MC function) but would be reasonable in an unstable patient or until confirmation is made with an inappropriately low ACTH.

Back to the Case

Morning cortisol returned undetectable, and ACTH was 14 pg/mL (6-58). Past records revealed a down-trending TSH from 1.12 to 0.38 mIU/mL, which had inappropriately prompted a levothyroxine dose reduction from 50 mcg to 25 mcg. A free thyroxine (T4) was low at 0.67 ng/dL (0.89-1.76). Estradiol, FSH, and LH were undetectable. Prolactin was 23 ng/mL (3-27). She was started on prednisone, 5 mg daily, and her levothyroxine was adjusted to a weight-based dose. Her fever resolved with the initiation of prednisone, and all cultures remained negative. Over two weeks, she improved back to her baseline, was discharged to a rehabilitation center, and eventually returned home.

Dr. Inman is a hospitalist at St. Mary’s Hospital and Regional Medical Center in Grand Junction, Colo. Dr. Bridenstine is an endocrinologist at the University of Colorado Denver. Dr. Cumbler is a hospitalist at the University of Colorado Denver.

References

1. Regal M, Pàramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol. 2001;55(6):735-740.
2. Bouillon R. Acute adrenal insufficiency. Endocrinol Metab Clin North Am. 2006;35(4):767-75, ix.
3. Raff H. Glucocorticoid inhibition of neurohypophysial vasopressin secretion. Am J Physiol. 1987;252(4 Pt 2):R635-644.
4. Erkut ZA, Pool C, Swaab DF. Glucocorticoids suppress corticotropin-releasing hormone and vasopressin expression in human hypothalamic neurons. J Clin Endocrinol Metab. 1998;83(6):2066-2073.
5. Melmed S, Polonski KS, Reed Larsen P, Kronenberg HM. Williams Textbook of Endocrinology. 12th ed. Philadelphia, Pa.: Saunders/Elsevier; 2012.
6. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK, Ghigo E. Hypopituitarism. Lancet. 2007;369(9571):1461-1470.
7. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metabol. 2011;96(8):2330-2340.

Case

A 53-year-old woman with a history of a suprasellar meningioma resected nine years ago with recurrence of a 4.5x2 cm mass one year ago and recent ventriculoperitoneal (VP) shunt placement for hydrocephalus presented with altered mental status (AMS) and hallucinations. She was admitted for radiation therapy to the mass. The patient had little improvement in her mental status four weeks into a six-week, 4860 cGy course of photon therapy.

The internal medicine service was consulted for new onset tachycardia (103), hypotension (83/55), and fever (38.6 C). Laboratory data revealed a white blood cell count 4.8 x 109 cells/L, sodium 137 mmol/L, potassium 4.1 mmol/L, chloride 110 mmol/L, bicarbonate 28 mmol/L, blood urea nitrogen 3 mg/dl, creatinine 0.6 mg/dl, and glucose 91 mg/dl. Thyroid-stimulating hormone (TSH) was low at 0.38 mIU/mL. Urine specific gravity was 1.006. Workups for infectious and thromboembolic diseases were unremarkable.

Discussion

Hypopituitarism is a disorder of impaired hormone production from the anterior and, less commonly, posterior pituitary gland. The condition can originate from several broad categories of diseases affecting the hypothalamus, pituitary stalk, or pituitary gland. In adults, the etiology is often from the mass effect of tumors or from treatment with surgery or radiotherapy. Other causes include vascular, infectious, infiltrative, inflammatory, and idiopathic. Well-substantiated data on the incidence and prevalence of hypopituitarism is sparse. It has an estimated prevalence of 45.5 cases per 100,000 and incidence of 4.2 cases per 100,000 per year.¹

Clinical manifestations of hypopituitarism depend on the type and severity of hormone deficiency. The consequences of adrenal insufficiency (AI) range from smoldering and nonspecific findings (e.g. fatigue, lethargy, indistinct gastrointestinal symptoms, eosinophilia, fever) to full-fledged crisis (e.g. AMS, severe electrolyte abnormalities, hemodynamic compromise, shock). The presentation of central AI (i.e., arising from hypothalamic or pituitary pathology) is often more subtle than primary AI. In central AI, only glucocorticoid (GC) function is disrupted, leaving the renin-angiotensin-aldosterone system and mineralocorticoid (MC) function intact. This is in stark contrast to primary AI resulting from direct adrenal gland injury, which nearly always disrupts both GC and MC function, leading to more profound circulatory collapse and electrolyte disturbance.²

Aside from orthostatic blood pressure or possible low-grade fever, few physical exam features are associated with central AI. Hyperpigmentation is not seen due to the lack of anterior pituitary-derived melanocortins that stimulate melanocytes and induce pigmentation. As for laboratory findings, hyperkalemia is a feature of primary AI (due to hypoaldosteronism) but is not seen in central AI. Hyponatremia occurs in both types of AI and is vasopressin-mediated. Hyponatremia is more common in primary AI, resulting from appropriate vasopressin release that occurs due to hypotension. Hyponatremia also occurs in secondary AI because of increased vasopressin secretion mediated directly by hypocortisolemia.^3,4

In summary, hyperpigmentation and the electrolyte pattern of hyponatremia and hyperkalemia are distinguishing clinical characteristics of primary AI, occurring in up to 90% of cases, but these features would not be expected with central AI.⁵

In the hospitalized patient with multiple active acute illnesses and infectious risk factors, it can be difficult to recognize the diagnosis of AI or hypopituitarism. Not only do signs and symptoms frequently overlap, but concomitant acute illness is usually a triggering event. Crisis should be suspected in the setting of unexplained fever, dehydration, or shock out of proportion to severity of current illness.⁵

Not surprisingly, high rates of partial or complete hypopituitarism are seen in patients following surgical removal of pituitary tumors or nearby neoplasms (e.g. craniopharyngiomas). Both surgery and radiotherapy for non-pituitary brain tumors are also major risk factors for development of hypopituitarism, occurring in up to 38% and 41% of patients, respectively.⁶ The strongest predictors of hormone failure are higher radiation doses, proximity to the pituitary-hypothalamus, and longer time interval after completion of radiotherapy. Within 10 years after a median dose of 5000 rad (50Gy) directed at the skull base, nasopharynx, or cranium, up to three-fourths of patients will develop some degree of pituitary insufficiency. Later onset of hormone failure usually reflects hypothalamic injury, whereas higher irradiation doses can lead to earlier onset pituitary damage.⁵

Not all hormone-secreting cells of the hypothalamus or pituitary are equally susceptible to injury; there is a characteristic sequence of hormonal failure. The typical order of hormone deficiency from pituitary compression or destruction is as follows: growth hormone (GH) > follicle-stimulating hormone (FSH) > luteinizing hormone (LH) > TSH > adrenocorticotropic hormone (ACTH) > vasopressin. A similar pattern is seen following brain irradiation: GH > FSH and LH > ACTH > TSH. A recent systematic review of 18 studies with 813 patients receiving cranial radiotherapy for non-pituitary tumors found pituitary dysfunction was 45% for GH deficiency, compared to 22% for ACTH deficiency.⁷

Biochemical diagnosis of hypopituitarism consists of measuring the various pituitary and target hormone levels as well as provocation testing. When interpreting these tests, whether to identify excess or deficient states, it is important to remember the individual values are part of the broader hypothalamic-pituitary axis feedback loops. Thus, it can be more useful designating if a high or low test value is appropriately or inappropriately high or low. In the presented case, low TSH level could be misinterpreted as excess thyroid hormone supplementation. An appropriately elevated free T4 level would confirm this, but an inappropriately low free T4 would raise suspicion of central hypothalamic-pituitary dysfunction.

With high enough clinical suspicion of hypopituitarism, empiric treatment with thyroid supplementation and corticosteroids should be started before confirmation of the diagnosis, to prevent secondary organ dysfunction and improve morbidity and mortality.² Rapid administration with intravenous levothyroxine can be given in severe hypothyroidism or myxedema.

“Stress-dose” steroids are generally recommended for patients who are also administered levothyroxine, as the desired increased in metabolic rate can deplete existing pituitary-adrenocortical hormone reserves, precipitating adrenal crisis.⁵ Stress-dose corticosteroids also ensure recruitment of a mineralocorticoid response. Cortisol has both GC and MC stimulating effects but is rapidly metabolized to cortisone, which lacks MC stimulating effects. Thus, high doses overwhelm this conversion step and allow remaining cortisol to stimulate MC receptors.² These high doses may not be necessary in secondary AI (i.e., preserved MC function) but would be reasonable in an unstable patient or until confirmation is made with an inappropriately low ACTH.

Back to the Case

Morning cortisol returned undetectable, and ACTH was 14 pg/mL (6-58). Past records revealed a down-trending TSH from 1.12 to 0.38 mIU/mL, which had inappropriately prompted a levothyroxine dose reduction from 50 mcg to 25 mcg. A free thyroxine (T4) was low at 0.67 ng/dL (0.89-1.76). Estradiol, FSH, and LH were undetectable. Prolactin was 23 ng/mL (3-27). She was started on prednisone, 5 mg daily, and her levothyroxine was adjusted to a weight-based dose. Her fever resolved with the initiation of prednisone, and all cultures remained negative. Over two weeks, she improved back to her baseline, was discharged to a rehabilitation center, and eventually returned home.

Dr. Inman is a hospitalist at St. Mary’s Hospital and Regional Medical Center in Grand Junction, Colo. Dr. Bridenstine is an endocrinologist at the University of Colorado Denver. Dr. Cumbler is a hospitalist at the University of Colorado Denver.

References

1. Regal M, Pàramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol. 2001;55(6):735-740.
2. Bouillon R. Acute adrenal insufficiency. Endocrinol Metab Clin North Am. 2006;35(4):767-75, ix.
3. Raff H. Glucocorticoid inhibition of neurohypophysial vasopressin secretion. Am J Physiol. 1987;252(4 Pt 2):R635-644.
4. Erkut ZA, Pool C, Swaab DF. Glucocorticoids suppress corticotropin-releasing hormone and vasopressin expression in human hypothalamic neurons. J Clin Endocrinol Metab. 1998;83(6):2066-2073.
5. Melmed S, Polonski KS, Reed Larsen P, Kronenberg HM. Williams Textbook of Endocrinology. 12th ed. Philadelphia, Pa.: Saunders/Elsevier; 2012.
6. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK, Ghigo E. Hypopituitarism. Lancet. 2007;369(9571):1461-1470.
7. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metabol. 2011;96(8):2330-2340.

4/8/15

HM15 Presenter: Tammie Quest, MD

Summation: Heroics- a set of medical actions that attempt to prolong life with a low likelihood of success.

Palliative care- an approach of care provided to patients and families suffering from serious and/or life limiting illness; focus on physical, spiritual, psychological and social aspects of distress.

Hospice care- intense palliative care provided when the patient has terminal illness with a prognosis of 6 months or less if the disease runs its usual course.

We underutilize Palliative and Hospice care in the US. Here in the US fewer than 50% of all persons receive hospice care at EOL, of those who receive hospice care more than half receive care for less than 20 days, and 1 in 5 patients die in an ICU. Palliative Care can/should co-exist with life prolonging care following the diagnosis of serious illness.

Common therapies/interventions to be contemplated and discussed with patient at end of life: cpr, mechanical ventilation, central venous/arterial access, renal replacement therapy, surgical procedures, valve therapies, ventricular assist devices, continuous infusions, IV fluids, supplemental oxygen, artificial nutrition, antimicrobials, blood products, cancer directed therapy, antithrombotics, anticoagulation.

Practical Elements of Palliative Care: pain and symptom management, advance care planning, communication/goals of care, truth-telling, social support, spiritual support, psychological support, risk/burden assessment of treatments.

Key Points/HM Takeaways:

1-Palliative Care Bedside Talking Points-

• Cardiac arrest is the moment of death, very few people survive an attempt at reversing death
• If you are one of the few who survive to discharge, you may do well but few will survive to discharge
• Antibiotics DO improve survival, antibiotics DO NOT improve comfort
• No evidence to show that dying from pneumonia, or other infection, is painful
• Allowing natural death includes permitting the body to shut itself down through natural mechanisms, including infection
• Dialysis may extend life, but there will be progressive functional decline

2-Goals of Care define what therapies are indicated. Balance prolongation of life with illness experience.

Julianna Lindsey is a hospitalist and physician leader based in the Dallas-Fort Worth Metroplex. Her focus is patient safety/quality and physician leadership. She is a member of TeamHospitalist.

4/8/15

HM15 Presenter: Tammie Quest, MD

Summation: Heroics- a set of medical actions that attempt to prolong life with a low likelihood of success.

Palliative care- an approach of care provided to patients and families suffering from serious and/or life limiting illness; focus on physical, spiritual, psychological and social aspects of distress.

Hospice care- intense palliative care provided when the patient has terminal illness with a prognosis of 6 months or less if the disease runs its usual course.

We underutilize Palliative and Hospice care in the US. Here in the US fewer than 50% of all persons receive hospice care at EOL, of those who receive hospice care more than half receive care for less than 20 days, and 1 in 5 patients die in an ICU. Palliative Care can/should co-exist with life prolonging care following the diagnosis of serious illness.

Common therapies/interventions to be contemplated and discussed with patient at end of life: cpr, mechanical ventilation, central venous/arterial access, renal replacement therapy, surgical procedures, valve therapies, ventricular assist devices, continuous infusions, IV fluids, supplemental oxygen, artificial nutrition, antimicrobials, blood products, cancer directed therapy, antithrombotics, anticoagulation.

Practical Elements of Palliative Care: pain and symptom management, advance care planning, communication/goals of care, truth-telling, social support, spiritual support, psychological support, risk/burden assessment of treatments.

Key Points/HM Takeaways:

1-Palliative Care Bedside Talking Points-

• Cardiac arrest is the moment of death, very few people survive an attempt at reversing death
• If you are one of the few who survive to discharge, you may do well but few will survive to discharge
• Antibiotics DO improve survival, antibiotics DO NOT improve comfort
• No evidence to show that dying from pneumonia, or other infection, is painful
• Allowing natural death includes permitting the body to shut itself down through natural mechanisms, including infection
• Dialysis may extend life, but there will be progressive functional decline

2-Goals of Care define what therapies are indicated. Balance prolongation of life with illness experience.

Julianna Lindsey is a hospitalist and physician leader based in the Dallas-Fort Worth Metroplex. Her focus is patient safety/quality and physician leadership. She is a member of TeamHospitalist.

4/8/15

HM15 Presenter: Tammie Quest, MD

Summation: Heroics- a set of medical actions that attempt to prolong life with a low likelihood of success.

Palliative care- an approach of care provided to patients and families suffering from serious and/or life limiting illness; focus on physical, spiritual, psychological and social aspects of distress.

Hospice care- intense palliative care provided when the patient has terminal illness with a prognosis of 6 months or less if the disease runs its usual course.

We underutilize Palliative and Hospice care in the US. Here in the US fewer than 50% of all persons receive hospice care at EOL, of those who receive hospice care more than half receive care for less than 20 days, and 1 in 5 patients die in an ICU. Palliative Care can/should co-exist with life prolonging care following the diagnosis of serious illness.

Common therapies/interventions to be contemplated and discussed with patient at end of life: cpr, mechanical ventilation, central venous/arterial access, renal replacement therapy, surgical procedures, valve therapies, ventricular assist devices, continuous infusions, IV fluids, supplemental oxygen, artificial nutrition, antimicrobials, blood products, cancer directed therapy, antithrombotics, anticoagulation.

Practical Elements of Palliative Care: pain and symptom management, advance care planning, communication/goals of care, truth-telling, social support, spiritual support, psychological support, risk/burden assessment of treatments.

Key Points/HM Takeaways:

1-Palliative Care Bedside Talking Points-

• Cardiac arrest is the moment of death, very few people survive an attempt at reversing death
• If you are one of the few who survive to discharge, you may do well but few will survive to discharge
• Antibiotics DO improve survival, antibiotics DO NOT improve comfort
• No evidence to show that dying from pneumonia, or other infection, is painful
• Allowing natural death includes permitting the body to shut itself down through natural mechanisms, including infection
• Dialysis may extend life, but there will be progressive functional decline

2-Goals of Care define what therapies are indicated. Balance prolongation of life with illness experience.

Julianna Lindsey is a hospitalist and physician leader based in the Dallas-Fort Worth Metroplex. Her focus is patient safety/quality and physician leadership. She is a member of TeamHospitalist.

Case

A 70-year-old woman was brought to the ED by ambulance with slurred speech after a fall. She arrived in the ED three hours and 29 minutes after the last time she was known to be normal. On initial examination, she had a National Institutes of Health Stroke Scale (NIHSS) score of 13, with a left facial droop, left hemiplegia, and right gaze deviation. Her acute noncontrast head computed tomography (CT), CT angiogram, and CT perfusion scans are shown in Figure 1.

How should this patient’s acute stroke be managed at this time?

Overview

Pathophysiology/Epidemiology: Stroke is the fourth most common cause of death in the United States and the main cause of disability, resulting in substantial healthcare expenditures.¹ Ischemic stroke accounts for about 85% of all stroke cases and has several subtypes. The most common causes of ischemic stroke are small vessel thrombosis, large vessel thromboembolism, and cardioembolism. Both small vessel thrombosis and large vessel thromboembolism often are related to typical atherosclerotic risk factors, and cardioembolism is most often related to atrial fibrillation/flutter.

Minimizing death and disability from stroke is dependent on prevention measures, as well as early response to the onset of symptoms. The typical patient loses 1.9 million neurons for every minute a stroke is untreated—hence the popular adage “Time is Brain.”² Although the appropriate management and time window of stroke treatment have been somewhat controversial, the acuity of treatment is now undisputed. Intravenous thrombolysis with tPA, also known as alteplase, has been an FDA-approved treatment for stroke since 1996, yet, as of 2006, only 2.4% of patients hospitalized for ischemic stroke were treated with IV tPA.³

The etiology of stroke, in most cases, does not change management in the hyperacute period, when thrombolysis is appropriate regardless of etiology.

Timely evaluation: Although recognition of stroke symptoms by the public and pre-hospital management is a barrier in the treatment of acute stroke, this article will focus on appropriate ED and in-hospital treatment of stroke. Given the urgent need for management of acute ischemic stroke, it is critical that hospitals have an efficient process for identifying possible strokes and beginning treatment early. In order to accomplish these objectives, the National Institute of Neurological Disorders and Stroke (NINDS) has established goals for time frames of evaluation and management of patients with stroke in the ED (see Table 1).⁴

The role of the hospitalist: Hospitalists can play critical roles both as part of a primary stroke team and in identifying missed strokes. Some acute stroke teams have included hospitalists due to their ability to help with medical management, identify mimics, and assess medical contraindications to thrombolytic therapy. In addition, hospitalists may be the first to recognize a stroke in the ED when evaluating a patient with symptoms confused with a medical condition, or when a stroke occurs in an inpatient. In both of these situations, as first responders, hospitalists have knowledge of stroke evaluation and treatment that is crucial in beginning the evaluation and triggering a stroke alert.

Diagnostic tools: The initial evaluation of a patient with a possible stroke includes a brief but thorough history of current symptoms, as well as past medical and medication histories. The most critical piece of information to obtain from patients, family members, or bystanders is the time of symptom onset, or the time the patient was last known normal, so that the options for treatment can be evaluated early.

After basic stabilization of ABCs—airway maintenance, breathing and ventilation, and circulation— a brief but thorough neurologic examination is critical to define severity of neurologic injury and to help localize injury. Some standardized tools help with rapid assessment, including the NIHSS. The NIHSS is a standardized and reproducible evaluation that can be performed by many different specialties and levels of healthcare providers and provides information about stroke severity, localization, and prognosis.⁵ NIHSS offers free online certification.

Imaging: Early brain imaging and interpretation is another important piece of the acute evaluation of stroke. The most commonly used first-line imaging is noncontrast head CT, which is widely available and quickly performed. This type of imaging is sensitive for intracranial hemorrhage and can help distinguish nonvascular causes of symptoms such as tumor. CT is not sensitive for early signs of infarct, and, most often, initial CT findings are normal in early ischemic stroke. In patients who are candidates for intravenous fibrinolysis, ruling out hemorrhage is the main priority. Noncontrast head CT is the only imaging necessary to make decisions regarding IV thrombolytic treatment.

For further treatment decisions beyond IV tPA, intracranial and extracranial vascular imaging can help with decision making. All patients with stroke should have extracranial vascular imaging to help determine the etiology of stroke and evaluate the need for carotid endarterectomy or stenting for symptomatic stenosis in the days to weeks after stroke. More acutely, vascular imaging can be used to identify large vessel occlusions, in consideration of endovascular intervention (discussed in further detail below). CT angiography, magnetic resonance (MR) angiography, and conventional angiography are all options for evaluating the vasculature, though the first two are generally used as a noninvasive first step. Carotid ultrasound is often considered but only evaluates the extracranial anterior circulation; posterior circulation vessel abnormalities (like dissection) and intracranial abnormalities (like stenosis) may be missed. Although tPA decisions are not based upon these imaging modalities, secondary stroke prevention decisions may be altered by the findings.⁴

Perfusion imaging is the newest addition to acute stroke imaging, but its utility in guiding decision making remains unclear. Perfusion imaging provides hemodynamic information, ideally to identify areas of infarct versus ischemic penumbra, an area at risk of becoming ischemic. The use of perfusion imaging to identify good candidates for reperfusion (with IV tPA or with interventional techniques) is controversial.⁹ It is clear that perfusion imaging should not delay the time to treatment for IV tPA within the 4.5-hour window.

Windows: Current guidelines for administration of IV tPA for acute stroke are based in large part on two pivotal studies—the NINDS tPA Stroke Trial and the European Cooperative Acute Stroke Study III (ECASS III).^6,7 IV alteplase for the treatment of acute stroke was approved by the FDA in 1996 following publication of the NINDS tPA Stroke Trial. This placebo-controlled randomized trial of 624 patients within three hours of ischemic stroke onset found that treatment with IV alteplase improved the odds of minimal or no disability at three months by approximately 30%. The rate of symptomatic intracranial hemorrhage was higher in the tPA group (6.4%) compared to the placebo group (0.6%), but mortality was not significantly different at three months. Though the benefit of IV tPA was clear in the three-hour window, subgroup analyses and further studies have clarified that treatment earlier in the window provides further benefit.

Given the difficulty of achieving treatment in short time windows, further studies have aimed to evaluate the utility of IV thrombolysis beyond the three-hour time window. While early studies found no clear benefit in extending the window, pooled analyses suggested a benefit in the three to 4.5-hour window, and ECASS III was designed to evaluate this window. This randomized placebo-controlled study used similar inclusion criteria to the NINDS study, with the exception of the time window, and excluded patients more than 80 years old, with large stroke (NIHSS score greater than 25), on anticoagulation (regardless of INR [international normalized ratio]), and with a history of prior stroke and diabetes. Again, in line with prior findings of time-dependent response to tPA, the study found that the IV tPA group were more likely than the placebo group to have good functional outcomes at three months, but the magnitude of this effect was lower than the one seen in the studies of the zero- to three-hour window. The rate of symptomatic intracranial hemorrhage in the 4.5-hour window was 7.9% using the NINDS tPA Stroke Trial criteria.

The American Heart Association/American Stroke Association (AHA/ASA) guidelines now recommend the use of IV tPA for patients within three hours of onset of ischemic stroke, with treatment initiated as quickly as possible (Class I; Level A). Although it has not been FDA approved, IV tPA treatment of eligible patients within the three to 4.5-hour window is recommended as Class I-Level B evidence with exclusions as in the ECASS study.4 Inclusion and exclusion criteria for tPA according to AHA/ASA guidelines can be found in Table 2.

IA thrombolysis/thrombectomy: Over the last two decades, there has been great interest in endovascular treatment of acute ischemic stroke and large advances in the numbers and types of treatments available. The FDA has approved multiple devices developed for mechanical thrombectomy based on their ability to recanalize vessels; however, to date, there is no clear evidence that thrombectomy improves patient outcomes. Several studies of endovascular therapy were recently published, including the Interventional Management of Stroke III (IMS 3) study, the Mechanical Retrieval and Recanalization of Stroke Clots using Embolectomy (MR RESCUE) study, and the SYNTHESIS Expansion study.^8,9,10 None of these studies showed a benefit to endovascular treatment; however, critics have pointed out many flaws in these studies, including protracted time to treatment and patient selection. Furthermore, the most recent devices, like Solitaire and Trevo, were not used in most patients.

Three more recent trials found promising results for interventional treatment.^11-13 The trials ranged from 70 to 500 patients with anterior circulation strokes with a large vessel occlusion; each study found a statistically significant improvement in functional independence at three months in the intervention group.^12,13 Intravenous tPA was given in 72.7% to 100% of patients.^11,12 Intervention to reperfusion was very quick in each study.

Some possible reasons for the more successful outcomes include the high proportion of newer devices for thrombectomy used and rapid treatment of symptoms, with symptom onset to groin puncture medians ranging from 185 minutes to 260 minutes.^11,13 It remains clear that careful patient selection should occur, and those who are not candidates for intravenous therapy who present inside an appropriate time window could be considered. Time from symptom onset continues to be an important piece of making decisions about candidates for interventional treatment, but some advocate for the use of advanced imaging modalities, such as DWI imaging on MRI, or MR, or CT perfusion imaging, to help decide who could be a candidate.

Back to the Case

IV tPA was given to the patient 30 minutes after presentation. She met all inclusion and exclusion criteria for treatment and received the best-proven therapy for acute ischemic stroke. Due to her severe symptoms, the neurointerventional team was consulted for possible thrombectomy. This decision is controversial, as there is no proven benefit to intraarterial therapy. She was a possible candidate because of her time to presentation, large vessel occlusion, and substantial penumbra with CT imaging (see Figure 1).

About 20 minutes after treatment, she began to improve, now lifting her left arm and leg against gravity and showing less dysarthria. The decision was made to perform a conventional angiogram to reevaluate her blood vessels and to consider thrombectomy based upon the result. The majority of her middle cerebral artery had recanalized, so no further interventions were needed.

Bottom Line

Intravenous tPA (alteplase) is indicated for patients presenting within 4.5 hours of last known normal. Careful patient selection should occur if additional therapies are considered.

Drs. Poisson and Simpson are a neurohospitalists in the department of neurology at the University of Colorado Denver in Aurora.

References

1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28-e292.
2. Saver JL. Time is brain–quantified. Stroke. 2006;37(1):263-266.
3. Fang MC, Cutler DM, Rosen AB. Trends in thrombolytic use for ischemic stroke in the United States. J Hosp Med. 2010;5(7):406-409.
4. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870-947. Lyden P, Raman R, Liu L, Emr M, Warren M, Marler
5. J. National Institutes of Health Stroke Scale certification is reliable across multiple venues. Stroke. 2009;40(7):2507-2511.
6. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581-1587.
7. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. Broderick JP, Palesch YY, Demchuk AM, et al Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368(10):893-903.
8. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;368(10):914-923.
9. Ciccone A, Valvassori L, Nichelatti M, et al. SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013;368(10):904-913.
10. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019-1030.
11. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009-1018.
12. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20.

Case

A 70-year-old woman was brought to the ED by ambulance with slurred speech after a fall. She arrived in the ED three hours and 29 minutes after the last time she was known to be normal. On initial examination, she had a National Institutes of Health Stroke Scale (NIHSS) score of 13, with a left facial droop, left hemiplegia, and right gaze deviation. Her acute noncontrast head computed tomography (CT), CT angiogram, and CT perfusion scans are shown in Figure 1.

How should this patient’s acute stroke be managed at this time?

Overview

Pathophysiology/Epidemiology: Stroke is the fourth most common cause of death in the United States and the main cause of disability, resulting in substantial healthcare expenditures.¹ Ischemic stroke accounts for about 85% of all stroke cases and has several subtypes. The most common causes of ischemic stroke are small vessel thrombosis, large vessel thromboembolism, and cardioembolism. Both small vessel thrombosis and large vessel thromboembolism often are related to typical atherosclerotic risk factors, and cardioembolism is most often related to atrial fibrillation/flutter.

Minimizing death and disability from stroke is dependent on prevention measures, as well as early response to the onset of symptoms. The typical patient loses 1.9 million neurons for every minute a stroke is untreated—hence the popular adage “Time is Brain.”² Although the appropriate management and time window of stroke treatment have been somewhat controversial, the acuity of treatment is now undisputed. Intravenous thrombolysis with tPA, also known as alteplase, has been an FDA-approved treatment for stroke since 1996, yet, as of 2006, only 2.4% of patients hospitalized for ischemic stroke were treated with IV tPA.³

The etiology of stroke, in most cases, does not change management in the hyperacute period, when thrombolysis is appropriate regardless of etiology.

Timely evaluation: Although recognition of stroke symptoms by the public and pre-hospital management is a barrier in the treatment of acute stroke, this article will focus on appropriate ED and in-hospital treatment of stroke. Given the urgent need for management of acute ischemic stroke, it is critical that hospitals have an efficient process for identifying possible strokes and beginning treatment early. In order to accomplish these objectives, the National Institute of Neurological Disorders and Stroke (NINDS) has established goals for time frames of evaluation and management of patients with stroke in the ED (see Table 1).⁴

The role of the hospitalist: Hospitalists can play critical roles both as part of a primary stroke team and in identifying missed strokes. Some acute stroke teams have included hospitalists due to their ability to help with medical management, identify mimics, and assess medical contraindications to thrombolytic therapy. In addition, hospitalists may be the first to recognize a stroke in the ED when evaluating a patient with symptoms confused with a medical condition, or when a stroke occurs in an inpatient. In both of these situations, as first responders, hospitalists have knowledge of stroke evaluation and treatment that is crucial in beginning the evaluation and triggering a stroke alert.

Diagnostic tools: The initial evaluation of a patient with a possible stroke includes a brief but thorough history of current symptoms, as well as past medical and medication histories. The most critical piece of information to obtain from patients, family members, or bystanders is the time of symptom onset, or the time the patient was last known normal, so that the options for treatment can be evaluated early.

After basic stabilization of ABCs—airway maintenance, breathing and ventilation, and circulation— a brief but thorough neurologic examination is critical to define severity of neurologic injury and to help localize injury. Some standardized tools help with rapid assessment, including the NIHSS. The NIHSS is a standardized and reproducible evaluation that can be performed by many different specialties and levels of healthcare providers and provides information about stroke severity, localization, and prognosis.⁵ NIHSS offers free online certification.

Imaging: Early brain imaging and interpretation is another important piece of the acute evaluation of stroke. The most commonly used first-line imaging is noncontrast head CT, which is widely available and quickly performed. This type of imaging is sensitive for intracranial hemorrhage and can help distinguish nonvascular causes of symptoms such as tumor. CT is not sensitive for early signs of infarct, and, most often, initial CT findings are normal in early ischemic stroke. In patients who are candidates for intravenous fibrinolysis, ruling out hemorrhage is the main priority. Noncontrast head CT is the only imaging necessary to make decisions regarding IV thrombolytic treatment.

For further treatment decisions beyond IV tPA, intracranial and extracranial vascular imaging can help with decision making. All patients with stroke should have extracranial vascular imaging to help determine the etiology of stroke and evaluate the need for carotid endarterectomy or stenting for symptomatic stenosis in the days to weeks after stroke. More acutely, vascular imaging can be used to identify large vessel occlusions, in consideration of endovascular intervention (discussed in further detail below). CT angiography, magnetic resonance (MR) angiography, and conventional angiography are all options for evaluating the vasculature, though the first two are generally used as a noninvasive first step. Carotid ultrasound is often considered but only evaluates the extracranial anterior circulation; posterior circulation vessel abnormalities (like dissection) and intracranial abnormalities (like stenosis) may be missed. Although tPA decisions are not based upon these imaging modalities, secondary stroke prevention decisions may be altered by the findings.⁴

Perfusion imaging is the newest addition to acute stroke imaging, but its utility in guiding decision making remains unclear. Perfusion imaging provides hemodynamic information, ideally to identify areas of infarct versus ischemic penumbra, an area at risk of becoming ischemic. The use of perfusion imaging to identify good candidates for reperfusion (with IV tPA or with interventional techniques) is controversial.⁹ It is clear that perfusion imaging should not delay the time to treatment for IV tPA within the 4.5-hour window.

Windows: Current guidelines for administration of IV tPA for acute stroke are based in large part on two pivotal studies—the NINDS tPA Stroke Trial and the European Cooperative Acute Stroke Study III (ECASS III).^6,7 IV alteplase for the treatment of acute stroke was approved by the FDA in 1996 following publication of the NINDS tPA Stroke Trial. This placebo-controlled randomized trial of 624 patients within three hours of ischemic stroke onset found that treatment with IV alteplase improved the odds of minimal or no disability at three months by approximately 30%. The rate of symptomatic intracranial hemorrhage was higher in the tPA group (6.4%) compared to the placebo group (0.6%), but mortality was not significantly different at three months. Though the benefit of IV tPA was clear in the three-hour window, subgroup analyses and further studies have clarified that treatment earlier in the window provides further benefit.

Given the difficulty of achieving treatment in short time windows, further studies have aimed to evaluate the utility of IV thrombolysis beyond the three-hour time window. While early studies found no clear benefit in extending the window, pooled analyses suggested a benefit in the three to 4.5-hour window, and ECASS III was designed to evaluate this window. This randomized placebo-controlled study used similar inclusion criteria to the NINDS study, with the exception of the time window, and excluded patients more than 80 years old, with large stroke (NIHSS score greater than 25), on anticoagulation (regardless of INR [international normalized ratio]), and with a history of prior stroke and diabetes. Again, in line with prior findings of time-dependent response to tPA, the study found that the IV tPA group were more likely than the placebo group to have good functional outcomes at three months, but the magnitude of this effect was lower than the one seen in the studies of the zero- to three-hour window. The rate of symptomatic intracranial hemorrhage in the 4.5-hour window was 7.9% using the NINDS tPA Stroke Trial criteria.

The American Heart Association/American Stroke Association (AHA/ASA) guidelines now recommend the use of IV tPA for patients within three hours of onset of ischemic stroke, with treatment initiated as quickly as possible (Class I; Level A). Although it has not been FDA approved, IV tPA treatment of eligible patients within the three to 4.5-hour window is recommended as Class I-Level B evidence with exclusions as in the ECASS study.4 Inclusion and exclusion criteria for tPA according to AHA/ASA guidelines can be found in Table 2.

IA thrombolysis/thrombectomy: Over the last two decades, there has been great interest in endovascular treatment of acute ischemic stroke and large advances in the numbers and types of treatments available. The FDA has approved multiple devices developed for mechanical thrombectomy based on their ability to recanalize vessels; however, to date, there is no clear evidence that thrombectomy improves patient outcomes. Several studies of endovascular therapy were recently published, including the Interventional Management of Stroke III (IMS 3) study, the Mechanical Retrieval and Recanalization of Stroke Clots using Embolectomy (MR RESCUE) study, and the SYNTHESIS Expansion study.^8,9,10 None of these studies showed a benefit to endovascular treatment; however, critics have pointed out many flaws in these studies, including protracted time to treatment and patient selection. Furthermore, the most recent devices, like Solitaire and Trevo, were not used in most patients.

Three more recent trials found promising results for interventional treatment.^11-13 The trials ranged from 70 to 500 patients with anterior circulation strokes with a large vessel occlusion; each study found a statistically significant improvement in functional independence at three months in the intervention group.^12,13 Intravenous tPA was given in 72.7% to 100% of patients.^11,12 Intervention to reperfusion was very quick in each study.

Some possible reasons for the more successful outcomes include the high proportion of newer devices for thrombectomy used and rapid treatment of symptoms, with symptom onset to groin puncture medians ranging from 185 minutes to 260 minutes.^11,13 It remains clear that careful patient selection should occur, and those who are not candidates for intravenous therapy who present inside an appropriate time window could be considered. Time from symptom onset continues to be an important piece of making decisions about candidates for interventional treatment, but some advocate for the use of advanced imaging modalities, such as DWI imaging on MRI, or MR, or CT perfusion imaging, to help decide who could be a candidate.

Back to the Case

IV tPA was given to the patient 30 minutes after presentation. She met all inclusion and exclusion criteria for treatment and received the best-proven therapy for acute ischemic stroke. Due to her severe symptoms, the neurointerventional team was consulted for possible thrombectomy. This decision is controversial, as there is no proven benefit to intraarterial therapy. She was a possible candidate because of her time to presentation, large vessel occlusion, and substantial penumbra with CT imaging (see Figure 1).

About 20 minutes after treatment, she began to improve, now lifting her left arm and leg against gravity and showing less dysarthria. The decision was made to perform a conventional angiogram to reevaluate her blood vessels and to consider thrombectomy based upon the result. The majority of her middle cerebral artery had recanalized, so no further interventions were needed.

Bottom Line

Intravenous tPA (alteplase) is indicated for patients presenting within 4.5 hours of last known normal. Careful patient selection should occur if additional therapies are considered.

Drs. Poisson and Simpson are a neurohospitalists in the department of neurology at the University of Colorado Denver in Aurora.

References

1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28-e292.
2. Saver JL. Time is brain–quantified. Stroke. 2006;37(1):263-266.
3. Fang MC, Cutler DM, Rosen AB. Trends in thrombolytic use for ischemic stroke in the United States. J Hosp Med. 2010;5(7):406-409.
4. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870-947. Lyden P, Raman R, Liu L, Emr M, Warren M, Marler
5. J. National Institutes of Health Stroke Scale certification is reliable across multiple venues. Stroke. 2009;40(7):2507-2511.
6. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581-1587.
7. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. Broderick JP, Palesch YY, Demchuk AM, et al Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368(10):893-903.
8. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;368(10):914-923.
9. Ciccone A, Valvassori L, Nichelatti M, et al. SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013;368(10):904-913.
10. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019-1030.
11. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009-1018.
12. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20.

Case

A 70-year-old woman was brought to the ED by ambulance with slurred speech after a fall. She arrived in the ED three hours and 29 minutes after the last time she was known to be normal. On initial examination, she had a National Institutes of Health Stroke Scale (NIHSS) score of 13, with a left facial droop, left hemiplegia, and right gaze deviation. Her acute noncontrast head computed tomography (CT), CT angiogram, and CT perfusion scans are shown in Figure 1.

How should this patient’s acute stroke be managed at this time?

Overview

Pathophysiology/Epidemiology: Stroke is the fourth most common cause of death in the United States and the main cause of disability, resulting in substantial healthcare expenditures.¹ Ischemic stroke accounts for about 85% of all stroke cases and has several subtypes. The most common causes of ischemic stroke are small vessel thrombosis, large vessel thromboembolism, and cardioembolism. Both small vessel thrombosis and large vessel thromboembolism often are related to typical atherosclerotic risk factors, and cardioembolism is most often related to atrial fibrillation/flutter.

Minimizing death and disability from stroke is dependent on prevention measures, as well as early response to the onset of symptoms. The typical patient loses 1.9 million neurons for every minute a stroke is untreated—hence the popular adage “Time is Brain.”² Although the appropriate management and time window of stroke treatment have been somewhat controversial, the acuity of treatment is now undisputed. Intravenous thrombolysis with tPA, also known as alteplase, has been an FDA-approved treatment for stroke since 1996, yet, as of 2006, only 2.4% of patients hospitalized for ischemic stroke were treated with IV tPA.³

The etiology of stroke, in most cases, does not change management in the hyperacute period, when thrombolysis is appropriate regardless of etiology.

Timely evaluation: Although recognition of stroke symptoms by the public and pre-hospital management is a barrier in the treatment of acute stroke, this article will focus on appropriate ED and in-hospital treatment of stroke. Given the urgent need for management of acute ischemic stroke, it is critical that hospitals have an efficient process for identifying possible strokes and beginning treatment early. In order to accomplish these objectives, the National Institute of Neurological Disorders and Stroke (NINDS) has established goals for time frames of evaluation and management of patients with stroke in the ED (see Table 1).⁴

The role of the hospitalist: Hospitalists can play critical roles both as part of a primary stroke team and in identifying missed strokes. Some acute stroke teams have included hospitalists due to their ability to help with medical management, identify mimics, and assess medical contraindications to thrombolytic therapy. In addition, hospitalists may be the first to recognize a stroke in the ED when evaluating a patient with symptoms confused with a medical condition, or when a stroke occurs in an inpatient. In both of these situations, as first responders, hospitalists have knowledge of stroke evaluation and treatment that is crucial in beginning the evaluation and triggering a stroke alert.

Diagnostic tools: The initial evaluation of a patient with a possible stroke includes a brief but thorough history of current symptoms, as well as past medical and medication histories. The most critical piece of information to obtain from patients, family members, or bystanders is the time of symptom onset, or the time the patient was last known normal, so that the options for treatment can be evaluated early.

After basic stabilization of ABCs—airway maintenance, breathing and ventilation, and circulation— a brief but thorough neurologic examination is critical to define severity of neurologic injury and to help localize injury. Some standardized tools help with rapid assessment, including the NIHSS. The NIHSS is a standardized and reproducible evaluation that can be performed by many different specialties and levels of healthcare providers and provides information about stroke severity, localization, and prognosis.⁵ NIHSS offers free online certification.

Imaging: Early brain imaging and interpretation is another important piece of the acute evaluation of stroke. The most commonly used first-line imaging is noncontrast head CT, which is widely available and quickly performed. This type of imaging is sensitive for intracranial hemorrhage and can help distinguish nonvascular causes of symptoms such as tumor. CT is not sensitive for early signs of infarct, and, most often, initial CT findings are normal in early ischemic stroke. In patients who are candidates for intravenous fibrinolysis, ruling out hemorrhage is the main priority. Noncontrast head CT is the only imaging necessary to make decisions regarding IV thrombolytic treatment.

For further treatment decisions beyond IV tPA, intracranial and extracranial vascular imaging can help with decision making. All patients with stroke should have extracranial vascular imaging to help determine the etiology of stroke and evaluate the need for carotid endarterectomy or stenting for symptomatic stenosis in the days to weeks after stroke. More acutely, vascular imaging can be used to identify large vessel occlusions, in consideration of endovascular intervention (discussed in further detail below). CT angiography, magnetic resonance (MR) angiography, and conventional angiography are all options for evaluating the vasculature, though the first two are generally used as a noninvasive first step. Carotid ultrasound is often considered but only evaluates the extracranial anterior circulation; posterior circulation vessel abnormalities (like dissection) and intracranial abnormalities (like stenosis) may be missed. Although tPA decisions are not based upon these imaging modalities, secondary stroke prevention decisions may be altered by the findings.⁴

Perfusion imaging is the newest addition to acute stroke imaging, but its utility in guiding decision making remains unclear. Perfusion imaging provides hemodynamic information, ideally to identify areas of infarct versus ischemic penumbra, an area at risk of becoming ischemic. The use of perfusion imaging to identify good candidates for reperfusion (with IV tPA or with interventional techniques) is controversial.⁹ It is clear that perfusion imaging should not delay the time to treatment for IV tPA within the 4.5-hour window.

Windows: Current guidelines for administration of IV tPA for acute stroke are based in large part on two pivotal studies—the NINDS tPA Stroke Trial and the European Cooperative Acute Stroke Study III (ECASS III).^6,7 IV alteplase for the treatment of acute stroke was approved by the FDA in 1996 following publication of the NINDS tPA Stroke Trial. This placebo-controlled randomized trial of 624 patients within three hours of ischemic stroke onset found that treatment with IV alteplase improved the odds of minimal or no disability at three months by approximately 30%. The rate of symptomatic intracranial hemorrhage was higher in the tPA group (6.4%) compared to the placebo group (0.6%), but mortality was not significantly different at three months. Though the benefit of IV tPA was clear in the three-hour window, subgroup analyses and further studies have clarified that treatment earlier in the window provides further benefit.

Given the difficulty of achieving treatment in short time windows, further studies have aimed to evaluate the utility of IV thrombolysis beyond the three-hour time window. While early studies found no clear benefit in extending the window, pooled analyses suggested a benefit in the three to 4.5-hour window, and ECASS III was designed to evaluate this window. This randomized placebo-controlled study used similar inclusion criteria to the NINDS study, with the exception of the time window, and excluded patients more than 80 years old, with large stroke (NIHSS score greater than 25), on anticoagulation (regardless of INR [international normalized ratio]), and with a history of prior stroke and diabetes. Again, in line with prior findings of time-dependent response to tPA, the study found that the IV tPA group were more likely than the placebo group to have good functional outcomes at three months, but the magnitude of this effect was lower than the one seen in the studies of the zero- to three-hour window. The rate of symptomatic intracranial hemorrhage in the 4.5-hour window was 7.9% using the NINDS tPA Stroke Trial criteria.

The American Heart Association/American Stroke Association (AHA/ASA) guidelines now recommend the use of IV tPA for patients within three hours of onset of ischemic stroke, with treatment initiated as quickly as possible (Class I; Level A). Although it has not been FDA approved, IV tPA treatment of eligible patients within the three to 4.5-hour window is recommended as Class I-Level B evidence with exclusions as in the ECASS study.4 Inclusion and exclusion criteria for tPA according to AHA/ASA guidelines can be found in Table 2.

IA thrombolysis/thrombectomy: Over the last two decades, there has been great interest in endovascular treatment of acute ischemic stroke and large advances in the numbers and types of treatments available. The FDA has approved multiple devices developed for mechanical thrombectomy based on their ability to recanalize vessels; however, to date, there is no clear evidence that thrombectomy improves patient outcomes. Several studies of endovascular therapy were recently published, including the Interventional Management of Stroke III (IMS 3) study, the Mechanical Retrieval and Recanalization of Stroke Clots using Embolectomy (MR RESCUE) study, and the SYNTHESIS Expansion study.^8,9,10 None of these studies showed a benefit to endovascular treatment; however, critics have pointed out many flaws in these studies, including protracted time to treatment and patient selection. Furthermore, the most recent devices, like Solitaire and Trevo, were not used in most patients.

Three more recent trials found promising results for interventional treatment.^11-13 The trials ranged from 70 to 500 patients with anterior circulation strokes with a large vessel occlusion; each study found a statistically significant improvement in functional independence at three months in the intervention group.^12,13 Intravenous tPA was given in 72.7% to 100% of patients.^11,12 Intervention to reperfusion was very quick in each study.

Some possible reasons for the more successful outcomes include the high proportion of newer devices for thrombectomy used and rapid treatment of symptoms, with symptom onset to groin puncture medians ranging from 185 minutes to 260 minutes.^11,13 It remains clear that careful patient selection should occur, and those who are not candidates for intravenous therapy who present inside an appropriate time window could be considered. Time from symptom onset continues to be an important piece of making decisions about candidates for interventional treatment, but some advocate for the use of advanced imaging modalities, such as DWI imaging on MRI, or MR, or CT perfusion imaging, to help decide who could be a candidate.

Back to the Case

IV tPA was given to the patient 30 minutes after presentation. She met all inclusion and exclusion criteria for treatment and received the best-proven therapy for acute ischemic stroke. Due to her severe symptoms, the neurointerventional team was consulted for possible thrombectomy. This decision is controversial, as there is no proven benefit to intraarterial therapy. She was a possible candidate because of her time to presentation, large vessel occlusion, and substantial penumbra with CT imaging (see Figure 1).

About 20 minutes after treatment, she began to improve, now lifting her left arm and leg against gravity and showing less dysarthria. The decision was made to perform a conventional angiogram to reevaluate her blood vessels and to consider thrombectomy based upon the result. The majority of her middle cerebral artery had recanalized, so no further interventions were needed.

Bottom Line

Intravenous tPA (alteplase) is indicated for patients presenting within 4.5 hours of last known normal. Careful patient selection should occur if additional therapies are considered.

Drs. Poisson and Simpson are a neurohospitalists in the department of neurology at the University of Colorado Denver in Aurora.

References

1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28-e292.
2. Saver JL. Time is brain–quantified. Stroke. 2006;37(1):263-266.
3. Fang MC, Cutler DM, Rosen AB. Trends in thrombolytic use for ischemic stroke in the United States. J Hosp Med. 2010;5(7):406-409.
4. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870-947. Lyden P, Raman R, Liu L, Emr M, Warren M, Marler
5. J. National Institutes of Health Stroke Scale certification is reliable across multiple venues. Stroke. 2009;40(7):2507-2511.
6. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581-1587.
7. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. Broderick JP, Palesch YY, Demchuk AM, et al Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368(10):893-903.
8. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;368(10):914-923.
9. Ciccone A, Valvassori L, Nichelatti M, et al. SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013;368(10):904-913.
10. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019-1030.
11. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009-1018.
12. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20.

Presenter: Julia Ragland, MD, FHM

Summation: Discussion of Prognosis in Advance Illness is a key component of informed decision-making and should be undertaken during a “Sentinel Hospitalization” and at times of other “triggers”.  End-of-Life discussions are critical for providing the best care for patients with advanced diseases.

A Sentinel Hospitalization is a hospitalization in the patient’s disease course that heralds a need to reassess prognosis, patient understanding, treatment options and intensities, and goals of care.

Other triggers for discussing prognosis: new diagnosis of serious illness, major medical decision with uncertain outcome, frequent hospitalizations for advanced disease, patient/family query prognosis, patient/family request treatment inconsistent with good clinical judgment (futile care), patient actively dying, “No” answer to “Surprise Question” (“would you be surprised if this patient died in the next year?”)

How can we prognosticate? Data from studies, Clinical intuition and experience, Prognostic indices, Key indicators of worsening prognosis (declining functional status, weight loss/malnutrition, co-morbidities, frequent hospitalizations)

Resources for Prognostication: ePrognosis, Seattle Heart Failure Model, MELD, Charlson Comorbidity Index, MJHSpalliativeinstitute.org/e-learning, Palliative Care Fast Facts mobile app

Ask-Tell-Ask method for communicating prognosis

• ASK: if they want to talk about prognosis and what they already know
• TELL: give information in small amounts, build on what they already know, use simple straight-forward language
• ASK: repeat understanding of what has been said, if they would like to hear more

Key Points/HM Takeaways:

• Estimating and discussing prognosis are core competencies for hospitalists and should be utilized during a “sentinel hospitalization”
• Prognostic awareness in advanced illness is key for:

  • Informed decision making (CPR, procedures, chemo, et al)
  • Determining realistic goals of care
  • Providing patient centered care

• Most patients and families want prognostic information, but not always- must ask to know. Give the patient the option not to discuss prognosis.
• Ask-Tell-Ask approach for discussing prognosis is effective

Presenter: Julia Ragland, MD, FHM

Summation: Discussion of Prognosis in Advance Illness is a key component of informed decision-making and should be undertaken during a “Sentinel Hospitalization” and at times of other “triggers”.  End-of-Life discussions are critical for providing the best care for patients with advanced diseases.

A Sentinel Hospitalization is a hospitalization in the patient’s disease course that heralds a need to reassess prognosis, patient understanding, treatment options and intensities, and goals of care.

Other triggers for discussing prognosis: new diagnosis of serious illness, major medical decision with uncertain outcome, frequent hospitalizations for advanced disease, patient/family query prognosis, patient/family request treatment inconsistent with good clinical judgment (futile care), patient actively dying, “No” answer to “Surprise Question” (“would you be surprised if this patient died in the next year?”)

How can we prognosticate? Data from studies, Clinical intuition and experience, Prognostic indices, Key indicators of worsening prognosis (declining functional status, weight loss/malnutrition, co-morbidities, frequent hospitalizations)

Resources for Prognostication: ePrognosis, Seattle Heart Failure Model, MELD, Charlson Comorbidity Index, MJHSpalliativeinstitute.org/e-learning, Palliative Care Fast Facts mobile app

Ask-Tell-Ask method for communicating prognosis

• ASK: if they want to talk about prognosis and what they already know
• TELL: give information in small amounts, build on what they already know, use simple straight-forward language
• ASK: repeat understanding of what has been said, if they would like to hear more

Key Points/HM Takeaways:

• Estimating and discussing prognosis are core competencies for hospitalists and should be utilized during a “sentinel hospitalization”
• Prognostic awareness in advanced illness is key for:

  • Informed decision making (CPR, procedures, chemo, et al)
  • Determining realistic goals of care
  • Providing patient centered care

• Most patients and families want prognostic information, but not always- must ask to know. Give the patient the option not to discuss prognosis.
• Ask-Tell-Ask approach for discussing prognosis is effective

Presenter: Julia Ragland, MD, FHM

Summation: Discussion of Prognosis in Advance Illness is a key component of informed decision-making and should be undertaken during a “Sentinel Hospitalization” and at times of other “triggers”.  End-of-Life discussions are critical for providing the best care for patients with advanced diseases.

A Sentinel Hospitalization is a hospitalization in the patient’s disease course that heralds a need to reassess prognosis, patient understanding, treatment options and intensities, and goals of care.

Other triggers for discussing prognosis: new diagnosis of serious illness, major medical decision with uncertain outcome, frequent hospitalizations for advanced disease, patient/family query prognosis, patient/family request treatment inconsistent with good clinical judgment (futile care), patient actively dying, “No” answer to “Surprise Question” (“would you be surprised if this patient died in the next year?”)

How can we prognosticate? Data from studies, Clinical intuition and experience, Prognostic indices, Key indicators of worsening prognosis (declining functional status, weight loss/malnutrition, co-morbidities, frequent hospitalizations)

Resources for Prognostication: ePrognosis, Seattle Heart Failure Model, MELD, Charlson Comorbidity Index, MJHSpalliativeinstitute.org/e-learning, Palliative Care Fast Facts mobile app

Ask-Tell-Ask method for communicating prognosis

• ASK: if they want to talk about prognosis and what they already know
• TELL: give information in small amounts, build on what they already know, use simple straight-forward language
• ASK: repeat understanding of what has been said, if they would like to hear more

Key Points/HM Takeaways:

• Estimating and discussing prognosis are core competencies for hospitalists and should be utilized during a “sentinel hospitalization”
• Prognostic awareness in advanced illness is key for:

  • Informed decision making (CPR, procedures, chemo, et al)
  • Determining realistic goals of care
  • Providing patient centered care

• Most patients and families want prognostic information, but not always- must ask to know. Give the patient the option not to discuss prognosis.
• Ask-Tell-Ask approach for discussing prognosis is effective

Kathleen Finn, MD, FHM and Jeffrey Greenwald, MD, SFHM engaged the audience with their playful banter while reviewing medical literature of clinical significance for the hospitalist in Update in Hospital Medicine. The studies presented were high-quality, practical and addressed questions that arise in our day-to-day practice. A wide variety of topics were addressed and key points are summarized below.

Key takeaways

• In the PARADIGM-HF study, Angiotensin Receptor Blocker (ARB) + Neprilysin Inhibitor decreased cardiovascular mortality and reduced CHF hospitalization by 20% when compared to Enalapril alone in heart failure patients. The combination drug is an alternative choice to ACE inhibitors. FDA approval is forthcoming.
• Is the risk of contrast-induced nephrotoxicity really as great as we have come to believe? Review of propensity matched studies suggests that AKI, 30 day need for emergent hemodi

  

  alysis and death are unrelated to contrast. If CT with contrast makes a difference to the patient, consider using it if GFR>30 ml/min.
• SAGES trial and Project Recovery developed a delirium screening method in hospitalized patients. The CAM (Confusion Assessment Method) scoring system assesses delirium severity in elderly patients (70+). Hospital and post-hospital outcomes in delirious vs. non-delirious patients showed that the more severe the delirium, the longer the patient stayed in the hospital. Further, the rate of new SNF placement and 90 day mortality was higher in the delirious group. The CAM score correlates with prognosis in medical patients. Addressing long-term goals of care in this patient population may be warranted.
• A randomized placebo-controlled trail looked at the preventive effects of Ramelteon (melatonin receptor agonist) on delirium. Ramelteon 8mg was given to patients at 9pm for 7 days (or d/c). Although this was a small and short study, Ramelteon appears to reduce incident delirium in medical and non-intubated ICU patients.
• The HELP randomized clinical trial compared Lactulose vs. Polyethylene Glycol (PEG) electrolyte solution for treatment of overt hepatic encephalopathy. Patients received either PEG (4L in 4 hours) or Lactulose (20-30g 3+doses/24hrs). Primary outcome was an improvement in HESA (Hepatic Encephalopathy Scoring Algorithm ) score by 1 at 24 hours. HESA score improved and patients had a shorter length of stay in the PEG group. In addition, patients requested PEG at discharge because it tasted better.
• A retrospective study looked at Nonselective beta blockers (NSBB) in patients with Spontaneous Bacterial Peritonitis (SBP). It suggests that the use of NSBB after SBP onset increases the risk of AKI, Hepatorenal Syndrome and mortality by 58%. NSBB appear beneficial before SBP onset suggesting that as cirrhosis becomes more severe, NSBB may not be effective.
• A retrospective cohort trial (Michigan Hospital Medicine Safety Consortium) assessed hospital performance of VTE prophylaxis. The rate of clinically evident, confirmed VTE was measured. There was no difference in VTE occurrence during hospitalization, 90 day VTE rates and PE vs. DVT rates. No clear benefit was evident from VTE prophylaxis for medical patients. This could indicate the need to risk stratify patients’ VTE risk.
• Direct oral anticoagulants (DOACs) were compared with Vitamin K antagonists (VKA) for treatment of acute VTE in a meta-analysis reviewed by the speakers. Death, safety and bleeding were assessed. DOACs seem to work as well as VKAs for VTE. They also had a better safety profile. In cancer patients, DOACs vs. LMWH study is still needed. In patients with atrial fibrillation (AF), DOACs prevent AF-associated strokes better than VKAs. They also reduce hemorrhagic stroke and intracranial hemorrhage.

  

  In the elderly (75 or older) patient, DOACs are as safe as VKAs and LMWH for AF and VTE treatment.
• Randomized control trails compared once weekly Dalbavancin or single-dose Oritavancin vs. daily conventional therapy for acute bacterial skin infections (cellulitis, major abscess, wound infection, 75cm² erythema). Outcomes measured were cessation of spread of erythema and no fever X3 readings in 48-72 hours. Dalbavancin once weekly was non-inferior to Vancomycin in safety profile and outcome measures. Direct cost of Dalbavancin was higher although patients on this drug had shorter length of stays which is cost effective. FDA approved for skin infections.
• The presence of family during CPR decreased PTSD, anxiety and depression symptoms in family members. Outcomes were similar when participants were assesses at 90 days and 1 year. While this study was conducted in an out of hospital setting, it may be worthwhile to assess if it is applicable to patients who code in the hospital.

Kathleen Finn, MD, FHM and Jeffrey Greenwald, MD, SFHM engaged the audience with their playful banter while reviewing medical literature of clinical significance for the hospitalist in Update in Hospital Medicine. The studies presented were high-quality, practical and addressed questions that arise in our day-to-day practice. A wide variety of topics were addressed and key points are summarized below.

Key takeaways

• In the PARADIGM-HF study, Angiotensin Receptor Blocker (ARB) + Neprilysin Inhibitor decreased cardiovascular mortality and reduced CHF hospitalization by 20% when compared to Enalapril alone in heart failure patients. The combination drug is an alternative choice to ACE inhibitors. FDA approval is forthcoming.
• Is the risk of contrast-induced nephrotoxicity really as great as we have come to believe? Review of propensity matched studies suggests that AKI, 30 day need for emergent hemodi

  

  alysis and death are unrelated to contrast. If CT with contrast makes a difference to the patient, consider using it if GFR>30 ml/min.
• SAGES trial and Project Recovery developed a delirium screening method in hospitalized patients. The CAM (Confusion Assessment Method) scoring system assesses delirium severity in elderly patients (70+). Hospital and post-hospital outcomes in delirious vs. non-delirious patients showed that the more severe the delirium, the longer the patient stayed in the hospital. Further, the rate of new SNF placement and 90 day mortality was higher in the delirious group. The CAM score correlates with prognosis in medical patients. Addressing long-term goals of care in this patient population may be warranted.
• A randomized placebo-controlled trail looked at the preventive effects of Ramelteon (melatonin receptor agonist) on delirium. Ramelteon 8mg was given to patients at 9pm for 7 days (or d/c). Although this was a small and short study, Ramelteon appears to reduce incident delirium in medical and non-intubated ICU patients.
• The HELP randomized clinical trial compared Lactulose vs. Polyethylene Glycol (PEG) electrolyte solution for treatment of overt hepatic encephalopathy. Patients received either PEG (4L in 4 hours) or Lactulose (20-30g 3+doses/24hrs). Primary outcome was an improvement in HESA (Hepatic Encephalopathy Scoring Algorithm ) score by 1 at 24 hours. HESA score improved and patients had a shorter length of stay in the PEG group. In addition, patients requested PEG at discharge because it tasted better.
• A retrospective study looked at Nonselective beta blockers (NSBB) in patients with Spontaneous Bacterial Peritonitis (SBP). It suggests that the use of NSBB after SBP onset increases the risk of AKI, Hepatorenal Syndrome and mortality by 58%. NSBB appear beneficial before SBP onset suggesting that as cirrhosis becomes more severe, NSBB may not be effective.
• A retrospective cohort trial (Michigan Hospital Medicine Safety Consortium) assessed hospital performance of VTE prophylaxis. The rate of clinically evident, confirmed VTE was measured. There was no difference in VTE occurrence during hospitalization, 90 day VTE rates and PE vs. DVT rates. No clear benefit was evident from VTE prophylaxis for medical patients. This could indicate the need to risk stratify patients’ VTE risk.
• Direct oral anticoagulants (DOACs) were compared with Vitamin K antagonists (VKA) for treatment of acute VTE in a meta-analysis reviewed by the speakers. Death, safety and bleeding were assessed. DOACs seem to work as well as VKAs for VTE. They also had a better safety profile. In cancer patients, DOACs vs. LMWH study is still needed. In patients with atrial fibrillation (AF), DOACs prevent AF-associated strokes better than VKAs. They also reduce hemorrhagic stroke and intracranial hemorrhage.

  

  In the elderly (75 or older) patient, DOACs are as safe as VKAs and LMWH for AF and VTE treatment.
• Randomized control trails compared once weekly Dalbavancin or single-dose Oritavancin vs. daily conventional therapy for acute bacterial skin infections (cellulitis, major abscess, wound infection, 75cm² erythema). Outcomes measured were cessation of spread of erythema and no fever X3 readings in 48-72 hours. Dalbavancin once weekly was non-inferior to Vancomycin in safety profile and outcome measures. Direct cost of Dalbavancin was higher although patients on this drug had shorter length of stays which is cost effective. FDA approved for skin infections.
• The presence of family during CPR decreased PTSD, anxiety and depression symptoms in family members. Outcomes were similar when participants were assesses at 90 days and 1 year. While this study was conducted in an out of hospital setting, it may be worthwhile to assess if it is applicable to patients who code in the hospital.

Kathleen Finn, MD, FHM and Jeffrey Greenwald, MD, SFHM engaged the audience with their playful banter while reviewing medical literature of clinical significance for the hospitalist in Update in Hospital Medicine. The studies presented were high-quality, practical and addressed questions that arise in our day-to-day practice. A wide variety of topics were addressed and key points are summarized below.

Key takeaways

• In the PARADIGM-HF study, Angiotensin Receptor Blocker (ARB) + Neprilysin Inhibitor decreased cardiovascular mortality and reduced CHF hospitalization by 20% when compared to Enalapril alone in heart failure patients. The combination drug is an alternative choice to ACE inhibitors. FDA approval is forthcoming.
• Is the risk of contrast-induced nephrotoxicity really as great as we have come to believe? Review of propensity matched studies suggests that AKI, 30 day need for emergent hemodi

  

  alysis and death are unrelated to contrast. If CT with contrast makes a difference to the patient, consider using it if GFR>30 ml/min.
• SAGES trial and Project Recovery developed a delirium screening method in hospitalized patients. The CAM (Confusion Assessment Method) scoring system assesses delirium severity in elderly patients (70+). Hospital and post-hospital outcomes in delirious vs. non-delirious patients showed that the more severe the delirium, the longer the patient stayed in the hospital. Further, the rate of new SNF placement and 90 day mortality was higher in the delirious group. The CAM score correlates with prognosis in medical patients. Addressing long-term goals of care in this patient population may be warranted.
• A randomized placebo-controlled trail looked at the preventive effects of Ramelteon (melatonin receptor agonist) on delirium. Ramelteon 8mg was given to patients at 9pm for 7 days (or d/c). Although this was a small and short study, Ramelteon appears to reduce incident delirium in medical and non-intubated ICU patients.
• The HELP randomized clinical trial compared Lactulose vs. Polyethylene Glycol (PEG) electrolyte solution for treatment of overt hepatic encephalopathy. Patients received either PEG (4L in 4 hours) or Lactulose (20-30g 3+doses/24hrs). Primary outcome was an improvement in HESA (Hepatic Encephalopathy Scoring Algorithm ) score by 1 at 24 hours. HESA score improved and patients had a shorter length of stay in the PEG group. In addition, patients requested PEG at discharge because it tasted better.
• A retrospective study looked at Nonselective beta blockers (NSBB) in patients with Spontaneous Bacterial Peritonitis (SBP). It suggests that the use of NSBB after SBP onset increases the risk of AKI, Hepatorenal Syndrome and mortality by 58%. NSBB appear beneficial before SBP onset suggesting that as cirrhosis becomes more severe, NSBB may not be effective.
• A retrospective cohort trial (Michigan Hospital Medicine Safety Consortium) assessed hospital performance of VTE prophylaxis. The rate of clinically evident, confirmed VTE was measured. There was no difference in VTE occurrence during hospitalization, 90 day VTE rates and PE vs. DVT rates. No clear benefit was evident from VTE prophylaxis for medical patients. This could indicate the need to risk stratify patients’ VTE risk.
• Direct oral anticoagulants (DOACs) were compared with Vitamin K antagonists (VKA) for treatment of acute VTE in a meta-analysis reviewed by the speakers. Death, safety and bleeding were assessed. DOACs seem to work as well as VKAs for VTE. They also had a better safety profile. In cancer patients, DOACs vs. LMWH study is still needed. In patients with atrial fibrillation (AF), DOACs prevent AF-associated strokes better than VKAs. They also reduce hemorrhagic stroke and intracranial hemorrhage.

  

  In the elderly (75 or older) patient, DOACs are as safe as VKAs and LMWH for AF and VTE treatment.
• Randomized control trails compared once weekly Dalbavancin or single-dose Oritavancin vs. daily conventional therapy for acute bacterial skin infections (cellulitis, major abscess, wound infection, 75cm² erythema). Outcomes measured were cessation of spread of erythema and no fever X3 readings in 48-72 hours. Dalbavancin once weekly was non-inferior to Vancomycin in safety profile and outcome measures. Direct cost of Dalbavancin was higher although patients on this drug had shorter length of stays which is cost effective. FDA approved for skin infections.
• The presence of family during CPR decreased PTSD, anxiety and depression symptoms in family members. Outcomes were similar when participants were assesses at 90 days and 1 year. While this study was conducted in an out of hospital setting, it may be worthwhile to assess if it is applicable to patients who code in the hospital.

Case

A 66-year-old homeless man with a history of smoking and cirrhosis due to alcoholism presents to the hospital with a productive cough and fever for one month. He has traveled around Arizona and New Mexico but has never left the country. His complete blood count (CBC) is notable for a white blood cell count of 13,000. His chest X-ray reveals a 1.7-cm right upper lobe cavitary lung lesion (see Figure 1). What is the best approach to this patient’s cavitary lung lesion?

Overview

Cavitary lung lesions are relatively common findings on chest imaging and often pose a diagnostic challenge to the hospitalist. Having a standard approach to the evaluation of a cavitary lung lesion can facilitate an expedited workup.

A lung cavity is defined radiographically as a lucent area contained within a consolidation, mass, or nodule.¹ Cavities usually are accompanied by thick walls, greater than 4 mm. These should be differentiated from cysts, which are not surrounded by consolidation, mass, or nodule, and are accompanied by a thinner wall.²

The differential diagnosis of a cavitary lung lesion is broad and can be delineated into categories of infectious and noninfectious etiologies (see Figure 2). Infectious causes include bacterial, fungal, and, rarely, parasitic agents. Noninfectious causes encompass malignant, rheumatologic, and other less common etiologies such as infarct related to pulmonary embolism.

The clinical presentation and assessment of risk factors for a particular patient are of the utmost importance in delineating next steps for evaluation and management (see Table 1). For those patients of older age with smoking history, specific occupational or environmental exposures, and weight loss, the most common etiology is neoplasm. Common infectious causes include lung abscess and necrotizing pneumonia, as well as tuberculosis. The approach to diagnosis should be based on a composite of the clinical presentation, patient characteristics, and radiographic appearance of the cavity.

Guidelines for the approach to cavitary lung lesions are lacking, yet a thorough understanding of the initial approach is important for those practicing hospital medicine. Key components in the approach to diagnosis of a solitary cavitary lesion are outlined in this article.

Diagnosis of Infectious Causes

In the initial evaluation of a cavitary lung lesion, it is important to first determine if the cause is an infectious process. The infectious etiologies to consider include lung abscess and necrotizing pneumonia, tuberculosis, and septic emboli. Important components in the clinical presentation include presence of cough, fever, night sweats, chills, and symptoms that have lasted less than one month, as well as comorbid conditions, drug or alcohol abuse, and history of immunocompromise (e.g. HIV, immunosuppressive therapy, or organ transplant).

Given the public health considerations and impact of treatment, tuberculosis (TB) will be discussed in its own category.

Tuberculosis. Given the fact that TB patients require airborne isolation, the disease must be considered early in the evaluation of a cavitary lung lesion. Patients with TB often present with more chronic symptoms, such as fevers, night sweats, weight loss, and hemoptysis. Immunocompromised state, travel to endemic regions, and incarceration increase the likelihood of TB. Nontuberculous mycobacterium (i.e., M. kansasii) should also be considered in endemic areas.

For those patients in whom TB is suspected, airborne isolation must be initiated promptly. The provider should obtain three sputum samples for acid-fast bacillus (AFB) smear and culture when risk factors are present. Most patients with reactivation TB have abnormal chest X-rays, with approximately 20% of those patients having air-fluid levels and the majority of cases affecting the upper lobes.³ Cavities may be seen in patients with primary or reactivation TB.³

Lung abscess and necrotizing pneumonia. Lung abscesses are cavities associated with necrosis caused by a microbial infection. The term necrotizing pneumonia typically is used when there are multiple smaller (smaller than 2 cm) associated lung abscesses, although both lung abscess and necrotizing pneumonia represent a similar pathophysiologic process and are along the same continuum. Lung abscess is suspected with the presence of predisposing risk factors to aspiration (e.g. alcoholism) and poor dentition. History of cough, fever, putrid sputum, night sweats, and weight loss may indicate subacute or chronic development of a lung abscess. Physical examination might be significant for signs of pneumonia and gingivitis.

Organisms that cause lung abscesses include anaerobes (most common), TB, methicillin-resistant Staphylococcus aureus (MRSA), post-influenza illness, endemic fungi, and Nocardia, among others.⁴ In immunocompromised patients, more common considerations include TB, Mycobacterium avium complex, other mycobacteria, Pseudomonas aeruginosa, Nocardia, Cryptococcus, Aspergillus, endemic fungi (e.g. Coccidiodes in the Southwest and Histoplasma in the Midwest), and, less commonly, Pneumocystis jiroveci.⁴ The likelihood of each organism is dependent on the patient’s risk factors. Initial laboratory testing includes sputum and blood cultures, as well as serologic testing for endemic fungi, especially in immunocompromised patients.

Imaging may reveal a cavitary lesion in the dependent pulmonary segments (posterior segments of the upper lobes or superior segments of the lower lobes), at times associated with a pleural effusion or infiltrate. The most common appearance of a lung abscess is an asymmetric cavity with an air-fluid level and a wall with a ragged or smooth border. CT scan is often indicated when X-rays are equivocal and when cases are of uncertain cause or are unresponsive to antibiotic therapy. Bronchoscopy is reserved for patients with an immunocompromising condition, atypical presentation, or lack of response to treatment.

For those cavitary lesions in which there is a high degree of suspicion for lung abscess, empiric treatment should include antibiotics active against anaerobes and MRSA if the patient has risk factors. Patients often receive an empiric trial of antibiotics prior to biopsy unless there are clear indications that the cavitary lung lesion is related to cancer. Lung abscesses typically drain spontaneously, and transthoracic or endobronchial drainage is not usually recommended as initial management due to risk of pneumothorax and formation of bronchopleural fistula.

Lung abscesses should be followed to resolution with serial chest imaging. If the lung abscess does not resolve, it would be appropriate to consult thoracic surgery, interventional radiology, or pulmonary, depending on the location of the abscess and the local expertise with transthoracic or endobronchial drainage and surgical resection.

Septic emboli. Septic emboli are a less common cause of cavitary lung lesions. This entity should be considered in patients with a history of IV drug use or infected indwelling devices (central venous catheters, pacemaker wires, and right-sided prosthetic heart valves). Physical examination should include an assessment for signs of endocarditis and inspection for infected indwelling devices. In patients with IV drug use, the likely pathogen is S. aureus.

Oropharyngeal infection or indwelling catheters may predispose patients to septic thrombophlebitis of the internal jugular vein, also known as Lemierre’s syndrome, a rare but important cause of septic emboli.⁵ Laboratory testing includes culture for sputum and blood and culture of the infected device if applicable. On chest X-ray, septic emboli commonly appear as nodules located in the lung periphery. CT scan is more sensitive for detecting cavitation associated with septic emboli.

Diagnosis of Noninfectious Causes

Upon identification of a cavitary lung lesion, noninfectious etiologies must also be entertained. Noninfectious etiologies include malignancy, rheumatologic diseases, pulmonary embolism, and other causes. Important components in the clinical presentation include the presence of constitutional symptoms (fevers, weight loss, night sweats), smoking history, family history, and an otherwise complete review of systems. Physical exam should include evaluation for lymphadenopathy, cachexia, rash, clubbing, and other symptoms pertinent to the suspected etiology.

Malignancy. Perhaps most important among noninfectious causes of cavitary lung lesions is malignancy, and a high index of suspicion is warranted given that it is commonly the first diagnosis to consider overall.² Cavities can form in primary lung cancers (e.g. bronchogenic carcinomas), lung tumors such as lymphoma or Kaposi’s sarcoma, or in metastatic disease. Cavitation has been detected in 7%-11% of primary lung cancers by plain radiography and in 22% by computed tomography.⁵ Cancers of squamous cell origin are the most likely to cavitate; this holds true for both primary lung tumors and metastatic tumors.⁶ Additionally, cavitation portends a worse prognosis.⁷

Clinicians should review any available prior chest imaging studies to look for a change in the quality or size of a cavitary lung lesion. Neoplasms are typically of variable size with irregular thick walls (greater than 4 mm) on CT scan, with higher specificity for neoplasm in those with a wall thickness greater than 15 mm.²

When the diagnosis is less clear, the decision to embark on more advanced diagnostic methods, such as biopsy, should rest on the provider’s clinical suspicion for a certain disease process. When a lung cancer is suspected, consultation with pulmonary and interventional radiology should be obtained to determine the best approach for biopsy.

Rheumatologic. Less common causes of cavitary lesions include those related to rheumatologic diseases (e.g. granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis). One study demonstrated that cavitary lung nodules occur in 37% of patients with granulomatosis with polyangiitis.⁸

Although uncommon, cavitary nodules can also be seen in rheumatoid arthritis and sarcoidosis. Given that patients with rheumatologic diseases are often treated with immunosuppressive agents, infection must remain high on the differential. Suspicion of a rheumatologic cause should prompt the clinician to obtain appropriate serologic testing and consultation as needed.

Pulmonary embolism. Although often not considered in the evaluation of cavitary lung lesions, pulmonary embolism (PE) can lead to infarction and the formation of a cavitary lesion. Pulmonary infarction has been reported to occur in as many as one third of cases of PE.⁹ Cavitary lesions also have been described in chronic thromboembolic disease.¹⁰

Other. Uncommon causes of cavitary lesions include bronchiolitis obliterans with organizing pneumonia, Langerhans cell histiocytosis, and amyloidosis, among others. The hospitalist should keep a broad differential and involve consultants if the diagnosis remains unclear after initial diagnostic evaluation.

Back to the Case

The patient’s fever and productive cough, in combination with recent travel and location of the cavitary lesion, increase his risk for tuberculosis and endemic fungi, such as Coccidioides. This patient was placed on respiratory isolation with AFBs obtained to rule out TB, with Coccidioides antibodies, Cyptococcal antigen titers, and sputum for fungus sent to evaluate for an endemic fungus. He had a chest CT, which revealed a 17-mm cavitary mass within the right upper lobe that contained an air-fluid level indicating lung abscess. Coccidioides, cryptococcal, fungal sputum, and TB studies were negative.

The patient was treated empirically with clindamycin given the high prevalence of anaerobes in lung abscess. He was followed as an outpatient and had a chest X-ray showing resolution of the lesion at six months. The purpose of the X-ray was two-fold: to monitor the effect of antibiotic treatment and to evaluate for persistence of the cavitation given the neoplastic risk factors of older age and smoking.

Bottom Line

The best approach to a patient with a cavitary lung lesion includes assessing the clinical presentation and risk factors, differentiating infectious from noninfectious causes, and then utilizing this information to further direct the diagnostic evaluation. Consultation with a subspecialist or further testing such as biopsy should be considered if the etiology remains undefined after the initial evaluation.

Drs. Rendon, Pizanis, Montanaro, and Kraai are hospitalists in the department of internal medicine at the University of New Mexico School of Medicine in Albuquerque.

References

1. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246(3):697-722.
2. Ryu JH, Swensen SJ. Cystic and cavitary lung diseases: focal and diffuse. Mayo Clin Proc. 2003;78(6):744-752.
3. Barnes PF, Verdegem TD, Vachon LA, Leedom JM, Overturf GD. Chest roentgenogram in pulmonary tuberculosis. New data on an old test. Chest. 1988;94(2):316-320.
4. Yazbeck MF, Dahdel M, Kalra A, Browne AS, Pratter MR. Lung abscess: update on microbiology and management. Am J Ther. 2012;21(3):217-221. doi: 10.1097/MJT.0b013e3182383c9b.
5. Gadkowski LB, Stout JE. Cavitary pulmonary disease. Clin Microbiol Rev. 2008;21(2):305-333.
6. Chiu FT. Cavitation in lung cancers. Aust N Z J Med. 1975;5(6):523-530.
7. Kolodziejski LS, Dyczek S, Duda K, Góralczyk J, Wysocki WM, Lobaziewicz W. Cavitated tumor as a clinical subentity in squamous cell lung cancer patients. Neoplasma. 2003;50(1):66-73.
8. Cordier JF, Valeyre D, Guillevin L, Loire R, Brechot JM. Pulmonary Wegener’s granulomatosis. A clinical and imaging study of 77 cases. Chest. 1990;97(4):906-912.
9. He H, Stein MW, Zalta B, Haramati LB. Pulmonary infarction: spectrum of findings on multidetector helical CT. J Thorac Imaging. 2006;21(1):1-7.
10. Harris H, Barraclough R, Davies C, Armstrong I, Kiely DG, van Beek E Jr. Cavitating lung lesions in chronic thromboembolic pulmonary hypertension. J Radiol Case Rep. 2008;2(3):11-21.
11. Woodring JH, Fried AM, Chuang VP. Solitary cavities of the lung: diagnostic implications of cavity wall thickness. AJR Am J Roentgenol. 1980;135(6):1269-1271.

Case

A 66-year-old homeless man with a history of smoking and cirrhosis due to alcoholism presents to the hospital with a productive cough and fever for one month. He has traveled around Arizona and New Mexico but has never left the country. His complete blood count (CBC) is notable for a white blood cell count of 13,000. His chest X-ray reveals a 1.7-cm right upper lobe cavitary lung lesion (see Figure 1). What is the best approach to this patient’s cavitary lung lesion?

Overview

Cavitary lung lesions are relatively common findings on chest imaging and often pose a diagnostic challenge to the hospitalist. Having a standard approach to the evaluation of a cavitary lung lesion can facilitate an expedited workup.

A lung cavity is defined radiographically as a lucent area contained within a consolidation, mass, or nodule.¹ Cavities usually are accompanied by thick walls, greater than 4 mm. These should be differentiated from cysts, which are not surrounded by consolidation, mass, or nodule, and are accompanied by a thinner wall.²

The differential diagnosis of a cavitary lung lesion is broad and can be delineated into categories of infectious and noninfectious etiologies (see Figure 2). Infectious causes include bacterial, fungal, and, rarely, parasitic agents. Noninfectious causes encompass malignant, rheumatologic, and other less common etiologies such as infarct related to pulmonary embolism.

The clinical presentation and assessment of risk factors for a particular patient are of the utmost importance in delineating next steps for evaluation and management (see Table 1). For those patients of older age with smoking history, specific occupational or environmental exposures, and weight loss, the most common etiology is neoplasm. Common infectious causes include lung abscess and necrotizing pneumonia, as well as tuberculosis. The approach to diagnosis should be based on a composite of the clinical presentation, patient characteristics, and radiographic appearance of the cavity.

Guidelines for the approach to cavitary lung lesions are lacking, yet a thorough understanding of the initial approach is important for those practicing hospital medicine. Key components in the approach to diagnosis of a solitary cavitary lesion are outlined in this article.

Diagnosis of Infectious Causes

In the initial evaluation of a cavitary lung lesion, it is important to first determine if the cause is an infectious process. The infectious etiologies to consider include lung abscess and necrotizing pneumonia, tuberculosis, and septic emboli. Important components in the clinical presentation include presence of cough, fever, night sweats, chills, and symptoms that have lasted less than one month, as well as comorbid conditions, drug or alcohol abuse, and history of immunocompromise (e.g. HIV, immunosuppressive therapy, or organ transplant).

Given the public health considerations and impact of treatment, tuberculosis (TB) will be discussed in its own category.

Tuberculosis. Given the fact that TB patients require airborne isolation, the disease must be considered early in the evaluation of a cavitary lung lesion. Patients with TB often present with more chronic symptoms, such as fevers, night sweats, weight loss, and hemoptysis. Immunocompromised state, travel to endemic regions, and incarceration increase the likelihood of TB. Nontuberculous mycobacterium (i.e., M. kansasii) should also be considered in endemic areas.

For those patients in whom TB is suspected, airborne isolation must be initiated promptly. The provider should obtain three sputum samples for acid-fast bacillus (AFB) smear and culture when risk factors are present. Most patients with reactivation TB have abnormal chest X-rays, with approximately 20% of those patients having air-fluid levels and the majority of cases affecting the upper lobes.³ Cavities may be seen in patients with primary or reactivation TB.³

Lung abscess and necrotizing pneumonia. Lung abscesses are cavities associated with necrosis caused by a microbial infection. The term necrotizing pneumonia typically is used when there are multiple smaller (smaller than 2 cm) associated lung abscesses, although both lung abscess and necrotizing pneumonia represent a similar pathophysiologic process and are along the same continuum. Lung abscess is suspected with the presence of predisposing risk factors to aspiration (e.g. alcoholism) and poor dentition. History of cough, fever, putrid sputum, night sweats, and weight loss may indicate subacute or chronic development of a lung abscess. Physical examination might be significant for signs of pneumonia and gingivitis.

Organisms that cause lung abscesses include anaerobes (most common), TB, methicillin-resistant Staphylococcus aureus (MRSA), post-influenza illness, endemic fungi, and Nocardia, among others.⁴ In immunocompromised patients, more common considerations include TB, Mycobacterium avium complex, other mycobacteria, Pseudomonas aeruginosa, Nocardia, Cryptococcus, Aspergillus, endemic fungi (e.g. Coccidiodes in the Southwest and Histoplasma in the Midwest), and, less commonly, Pneumocystis jiroveci.⁴ The likelihood of each organism is dependent on the patient’s risk factors. Initial laboratory testing includes sputum and blood cultures, as well as serologic testing for endemic fungi, especially in immunocompromised patients.

Imaging may reveal a cavitary lesion in the dependent pulmonary segments (posterior segments of the upper lobes or superior segments of the lower lobes), at times associated with a pleural effusion or infiltrate. The most common appearance of a lung abscess is an asymmetric cavity with an air-fluid level and a wall with a ragged or smooth border. CT scan is often indicated when X-rays are equivocal and when cases are of uncertain cause or are unresponsive to antibiotic therapy. Bronchoscopy is reserved for patients with an immunocompromising condition, atypical presentation, or lack of response to treatment.

For those cavitary lesions in which there is a high degree of suspicion for lung abscess, empiric treatment should include antibiotics active against anaerobes and MRSA if the patient has risk factors. Patients often receive an empiric trial of antibiotics prior to biopsy unless there are clear indications that the cavitary lung lesion is related to cancer. Lung abscesses typically drain spontaneously, and transthoracic or endobronchial drainage is not usually recommended as initial management due to risk of pneumothorax and formation of bronchopleural fistula.

Lung abscesses should be followed to resolution with serial chest imaging. If the lung abscess does not resolve, it would be appropriate to consult thoracic surgery, interventional radiology, or pulmonary, depending on the location of the abscess and the local expertise with transthoracic or endobronchial drainage and surgical resection.

Septic emboli. Septic emboli are a less common cause of cavitary lung lesions. This entity should be considered in patients with a history of IV drug use or infected indwelling devices (central venous catheters, pacemaker wires, and right-sided prosthetic heart valves). Physical examination should include an assessment for signs of endocarditis and inspection for infected indwelling devices. In patients with IV drug use, the likely pathogen is S. aureus.

Oropharyngeal infection or indwelling catheters may predispose patients to septic thrombophlebitis of the internal jugular vein, also known as Lemierre’s syndrome, a rare but important cause of septic emboli.⁵ Laboratory testing includes culture for sputum and blood and culture of the infected device if applicable. On chest X-ray, septic emboli commonly appear as nodules located in the lung periphery. CT scan is more sensitive for detecting cavitation associated with septic emboli.

Diagnosis of Noninfectious Causes

Upon identification of a cavitary lung lesion, noninfectious etiologies must also be entertained. Noninfectious etiologies include malignancy, rheumatologic diseases, pulmonary embolism, and other causes. Important components in the clinical presentation include the presence of constitutional symptoms (fevers, weight loss, night sweats), smoking history, family history, and an otherwise complete review of systems. Physical exam should include evaluation for lymphadenopathy, cachexia, rash, clubbing, and other symptoms pertinent to the suspected etiology.

Malignancy. Perhaps most important among noninfectious causes of cavitary lung lesions is malignancy, and a high index of suspicion is warranted given that it is commonly the first diagnosis to consider overall.² Cavities can form in primary lung cancers (e.g. bronchogenic carcinomas), lung tumors such as lymphoma or Kaposi’s sarcoma, or in metastatic disease. Cavitation has been detected in 7%-11% of primary lung cancers by plain radiography and in 22% by computed tomography.⁵ Cancers of squamous cell origin are the most likely to cavitate; this holds true for both primary lung tumors and metastatic tumors.⁶ Additionally, cavitation portends a worse prognosis.⁷

Clinicians should review any available prior chest imaging studies to look for a change in the quality or size of a cavitary lung lesion. Neoplasms are typically of variable size with irregular thick walls (greater than 4 mm) on CT scan, with higher specificity for neoplasm in those with a wall thickness greater than 15 mm.²

When the diagnosis is less clear, the decision to embark on more advanced diagnostic methods, such as biopsy, should rest on the provider’s clinical suspicion for a certain disease process. When a lung cancer is suspected, consultation with pulmonary and interventional radiology should be obtained to determine the best approach for biopsy.

Rheumatologic. Less common causes of cavitary lesions include those related to rheumatologic diseases (e.g. granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis). One study demonstrated that cavitary lung nodules occur in 37% of patients with granulomatosis with polyangiitis.⁸

Although uncommon, cavitary nodules can also be seen in rheumatoid arthritis and sarcoidosis. Given that patients with rheumatologic diseases are often treated with immunosuppressive agents, infection must remain high on the differential. Suspicion of a rheumatologic cause should prompt the clinician to obtain appropriate serologic testing and consultation as needed.

Pulmonary embolism. Although often not considered in the evaluation of cavitary lung lesions, pulmonary embolism (PE) can lead to infarction and the formation of a cavitary lesion. Pulmonary infarction has been reported to occur in as many as one third of cases of PE.⁹ Cavitary lesions also have been described in chronic thromboembolic disease.¹⁰

Other. Uncommon causes of cavitary lesions include bronchiolitis obliterans with organizing pneumonia, Langerhans cell histiocytosis, and amyloidosis, among others. The hospitalist should keep a broad differential and involve consultants if the diagnosis remains unclear after initial diagnostic evaluation.

Back to the Case

The patient’s fever and productive cough, in combination with recent travel and location of the cavitary lesion, increase his risk for tuberculosis and endemic fungi, such as Coccidioides. This patient was placed on respiratory isolation with AFBs obtained to rule out TB, with Coccidioides antibodies, Cyptococcal antigen titers, and sputum for fungus sent to evaluate for an endemic fungus. He had a chest CT, which revealed a 17-mm cavitary mass within the right upper lobe that contained an air-fluid level indicating lung abscess. Coccidioides, cryptococcal, fungal sputum, and TB studies were negative.

The patient was treated empirically with clindamycin given the high prevalence of anaerobes in lung abscess. He was followed as an outpatient and had a chest X-ray showing resolution of the lesion at six months. The purpose of the X-ray was two-fold: to monitor the effect of antibiotic treatment and to evaluate for persistence of the cavitation given the neoplastic risk factors of older age and smoking.

Bottom Line

The best approach to a patient with a cavitary lung lesion includes assessing the clinical presentation and risk factors, differentiating infectious from noninfectious causes, and then utilizing this information to further direct the diagnostic evaluation. Consultation with a subspecialist or further testing such as biopsy should be considered if the etiology remains undefined after the initial evaluation.

Drs. Rendon, Pizanis, Montanaro, and Kraai are hospitalists in the department of internal medicine at the University of New Mexico School of Medicine in Albuquerque.

References

1. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246(3):697-722.
2. Ryu JH, Swensen SJ. Cystic and cavitary lung diseases: focal and diffuse. Mayo Clin Proc. 2003;78(6):744-752.
3. Barnes PF, Verdegem TD, Vachon LA, Leedom JM, Overturf GD. Chest roentgenogram in pulmonary tuberculosis. New data on an old test. Chest. 1988;94(2):316-320.
4. Yazbeck MF, Dahdel M, Kalra A, Browne AS, Pratter MR. Lung abscess: update on microbiology and management. Am J Ther. 2012;21(3):217-221. doi: 10.1097/MJT.0b013e3182383c9b.
5. Gadkowski LB, Stout JE. Cavitary pulmonary disease. Clin Microbiol Rev. 2008;21(2):305-333.
6. Chiu FT. Cavitation in lung cancers. Aust N Z J Med. 1975;5(6):523-530.
7. Kolodziejski LS, Dyczek S, Duda K, Góralczyk J, Wysocki WM, Lobaziewicz W. Cavitated tumor as a clinical subentity in squamous cell lung cancer patients. Neoplasma. 2003;50(1):66-73.
8. Cordier JF, Valeyre D, Guillevin L, Loire R, Brechot JM. Pulmonary Wegener’s granulomatosis. A clinical and imaging study of 77 cases. Chest. 1990;97(4):906-912.
9. He H, Stein MW, Zalta B, Haramati LB. Pulmonary infarction: spectrum of findings on multidetector helical CT. J Thorac Imaging. 2006;21(1):1-7.
10. Harris H, Barraclough R, Davies C, Armstrong I, Kiely DG, van Beek E Jr. Cavitating lung lesions in chronic thromboembolic pulmonary hypertension. J Radiol Case Rep. 2008;2(3):11-21.
11. Woodring JH, Fried AM, Chuang VP. Solitary cavities of the lung: diagnostic implications of cavity wall thickness. AJR Am J Roentgenol. 1980;135(6):1269-1271.

Case

A 66-year-old homeless man with a history of smoking and cirrhosis due to alcoholism presents to the hospital with a productive cough and fever for one month. He has traveled around Arizona and New Mexico but has never left the country. His complete blood count (CBC) is notable for a white blood cell count of 13,000. His chest X-ray reveals a 1.7-cm right upper lobe cavitary lung lesion (see Figure 1). What is the best approach to this patient’s cavitary lung lesion?

Overview

Cavitary lung lesions are relatively common findings on chest imaging and often pose a diagnostic challenge to the hospitalist. Having a standard approach to the evaluation of a cavitary lung lesion can facilitate an expedited workup.

A lung cavity is defined radiographically as a lucent area contained within a consolidation, mass, or nodule.¹ Cavities usually are accompanied by thick walls, greater than 4 mm. These should be differentiated from cysts, which are not surrounded by consolidation, mass, or nodule, and are accompanied by a thinner wall.²

The differential diagnosis of a cavitary lung lesion is broad and can be delineated into categories of infectious and noninfectious etiologies (see Figure 2). Infectious causes include bacterial, fungal, and, rarely, parasitic agents. Noninfectious causes encompass malignant, rheumatologic, and other less common etiologies such as infarct related to pulmonary embolism.

The clinical presentation and assessment of risk factors for a particular patient are of the utmost importance in delineating next steps for evaluation and management (see Table 1). For those patients of older age with smoking history, specific occupational or environmental exposures, and weight loss, the most common etiology is neoplasm. Common infectious causes include lung abscess and necrotizing pneumonia, as well as tuberculosis. The approach to diagnosis should be based on a composite of the clinical presentation, patient characteristics, and radiographic appearance of the cavity.

Guidelines for the approach to cavitary lung lesions are lacking, yet a thorough understanding of the initial approach is important for those practicing hospital medicine. Key components in the approach to diagnosis of a solitary cavitary lesion are outlined in this article.

Diagnosis of Infectious Causes

In the initial evaluation of a cavitary lung lesion, it is important to first determine if the cause is an infectious process. The infectious etiologies to consider include lung abscess and necrotizing pneumonia, tuberculosis, and septic emboli. Important components in the clinical presentation include presence of cough, fever, night sweats, chills, and symptoms that have lasted less than one month, as well as comorbid conditions, drug or alcohol abuse, and history of immunocompromise (e.g. HIV, immunosuppressive therapy, or organ transplant).

Given the public health considerations and impact of treatment, tuberculosis (TB) will be discussed in its own category.

Tuberculosis. Given the fact that TB patients require airborne isolation, the disease must be considered early in the evaluation of a cavitary lung lesion. Patients with TB often present with more chronic symptoms, such as fevers, night sweats, weight loss, and hemoptysis. Immunocompromised state, travel to endemic regions, and incarceration increase the likelihood of TB. Nontuberculous mycobacterium (i.e., M. kansasii) should also be considered in endemic areas.

For those patients in whom TB is suspected, airborne isolation must be initiated promptly. The provider should obtain three sputum samples for acid-fast bacillus (AFB) smear and culture when risk factors are present. Most patients with reactivation TB have abnormal chest X-rays, with approximately 20% of those patients having air-fluid levels and the majority of cases affecting the upper lobes.³ Cavities may be seen in patients with primary or reactivation TB.³

Lung abscess and necrotizing pneumonia. Lung abscesses are cavities associated with necrosis caused by a microbial infection. The term necrotizing pneumonia typically is used when there are multiple smaller (smaller than 2 cm) associated lung abscesses, although both lung abscess and necrotizing pneumonia represent a similar pathophysiologic process and are along the same continuum. Lung abscess is suspected with the presence of predisposing risk factors to aspiration (e.g. alcoholism) and poor dentition. History of cough, fever, putrid sputum, night sweats, and weight loss may indicate subacute or chronic development of a lung abscess. Physical examination might be significant for signs of pneumonia and gingivitis.

Organisms that cause lung abscesses include anaerobes (most common), TB, methicillin-resistant Staphylococcus aureus (MRSA), post-influenza illness, endemic fungi, and Nocardia, among others.⁴ In immunocompromised patients, more common considerations include TB, Mycobacterium avium complex, other mycobacteria, Pseudomonas aeruginosa, Nocardia, Cryptococcus, Aspergillus, endemic fungi (e.g. Coccidiodes in the Southwest and Histoplasma in the Midwest), and, less commonly, Pneumocystis jiroveci.⁴ The likelihood of each organism is dependent on the patient’s risk factors. Initial laboratory testing includes sputum and blood cultures, as well as serologic testing for endemic fungi, especially in immunocompromised patients.

Imaging may reveal a cavitary lesion in the dependent pulmonary segments (posterior segments of the upper lobes or superior segments of the lower lobes), at times associated with a pleural effusion or infiltrate. The most common appearance of a lung abscess is an asymmetric cavity with an air-fluid level and a wall with a ragged or smooth border. CT scan is often indicated when X-rays are equivocal and when cases are of uncertain cause or are unresponsive to antibiotic therapy. Bronchoscopy is reserved for patients with an immunocompromising condition, atypical presentation, or lack of response to treatment.

For those cavitary lesions in which there is a high degree of suspicion for lung abscess, empiric treatment should include antibiotics active against anaerobes and MRSA if the patient has risk factors. Patients often receive an empiric trial of antibiotics prior to biopsy unless there are clear indications that the cavitary lung lesion is related to cancer. Lung abscesses typically drain spontaneously, and transthoracic or endobronchial drainage is not usually recommended as initial management due to risk of pneumothorax and formation of bronchopleural fistula.

Lung abscesses should be followed to resolution with serial chest imaging. If the lung abscess does not resolve, it would be appropriate to consult thoracic surgery, interventional radiology, or pulmonary, depending on the location of the abscess and the local expertise with transthoracic or endobronchial drainage and surgical resection.

Septic emboli. Septic emboli are a less common cause of cavitary lung lesions. This entity should be considered in patients with a history of IV drug use or infected indwelling devices (central venous catheters, pacemaker wires, and right-sided prosthetic heart valves). Physical examination should include an assessment for signs of endocarditis and inspection for infected indwelling devices. In patients with IV drug use, the likely pathogen is S. aureus.

Oropharyngeal infection or indwelling catheters may predispose patients to septic thrombophlebitis of the internal jugular vein, also known as Lemierre’s syndrome, a rare but important cause of septic emboli.⁵ Laboratory testing includes culture for sputum and blood and culture of the infected device if applicable. On chest X-ray, septic emboli commonly appear as nodules located in the lung periphery. CT scan is more sensitive for detecting cavitation associated with septic emboli.

Diagnosis of Noninfectious Causes

Upon identification of a cavitary lung lesion, noninfectious etiologies must also be entertained. Noninfectious etiologies include malignancy, rheumatologic diseases, pulmonary embolism, and other causes. Important components in the clinical presentation include the presence of constitutional symptoms (fevers, weight loss, night sweats), smoking history, family history, and an otherwise complete review of systems. Physical exam should include evaluation for lymphadenopathy, cachexia, rash, clubbing, and other symptoms pertinent to the suspected etiology.

Malignancy. Perhaps most important among noninfectious causes of cavitary lung lesions is malignancy, and a high index of suspicion is warranted given that it is commonly the first diagnosis to consider overall.² Cavities can form in primary lung cancers (e.g. bronchogenic carcinomas), lung tumors such as lymphoma or Kaposi’s sarcoma, or in metastatic disease. Cavitation has been detected in 7%-11% of primary lung cancers by plain radiography and in 22% by computed tomography.⁵ Cancers of squamous cell origin are the most likely to cavitate; this holds true for both primary lung tumors and metastatic tumors.⁶ Additionally, cavitation portends a worse prognosis.⁷

Clinicians should review any available prior chest imaging studies to look for a change in the quality or size of a cavitary lung lesion. Neoplasms are typically of variable size with irregular thick walls (greater than 4 mm) on CT scan, with higher specificity for neoplasm in those with a wall thickness greater than 15 mm.²

When the diagnosis is less clear, the decision to embark on more advanced diagnostic methods, such as biopsy, should rest on the provider’s clinical suspicion for a certain disease process. When a lung cancer is suspected, consultation with pulmonary and interventional radiology should be obtained to determine the best approach for biopsy.

Rheumatologic. Less common causes of cavitary lesions include those related to rheumatologic diseases (e.g. granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis). One study demonstrated that cavitary lung nodules occur in 37% of patients with granulomatosis with polyangiitis.⁸

Although uncommon, cavitary nodules can also be seen in rheumatoid arthritis and sarcoidosis. Given that patients with rheumatologic diseases are often treated with immunosuppressive agents, infection must remain high on the differential. Suspicion of a rheumatologic cause should prompt the clinician to obtain appropriate serologic testing and consultation as needed.

Pulmonary embolism. Although often not considered in the evaluation of cavitary lung lesions, pulmonary embolism (PE) can lead to infarction and the formation of a cavitary lesion. Pulmonary infarction has been reported to occur in as many as one third of cases of PE.⁹ Cavitary lesions also have been described in chronic thromboembolic disease.¹⁰

Other. Uncommon causes of cavitary lesions include bronchiolitis obliterans with organizing pneumonia, Langerhans cell histiocytosis, and amyloidosis, among others. The hospitalist should keep a broad differential and involve consultants if the diagnosis remains unclear after initial diagnostic evaluation.

Back to the Case

The patient’s fever and productive cough, in combination with recent travel and location of the cavitary lesion, increase his risk for tuberculosis and endemic fungi, such as Coccidioides. This patient was placed on respiratory isolation with AFBs obtained to rule out TB, with Coccidioides antibodies, Cyptococcal antigen titers, and sputum for fungus sent to evaluate for an endemic fungus. He had a chest CT, which revealed a 17-mm cavitary mass within the right upper lobe that contained an air-fluid level indicating lung abscess. Coccidioides, cryptococcal, fungal sputum, and TB studies were negative.

The patient was treated empirically with clindamycin given the high prevalence of anaerobes in lung abscess. He was followed as an outpatient and had a chest X-ray showing resolution of the lesion at six months. The purpose of the X-ray was two-fold: to monitor the effect of antibiotic treatment and to evaluate for persistence of the cavitation given the neoplastic risk factors of older age and smoking.

Bottom Line

The best approach to a patient with a cavitary lung lesion includes assessing the clinical presentation and risk factors, differentiating infectious from noninfectious causes, and then utilizing this information to further direct the diagnostic evaluation. Consultation with a subspecialist or further testing such as biopsy should be considered if the etiology remains undefined after the initial evaluation.

Drs. Rendon, Pizanis, Montanaro, and Kraai are hospitalists in the department of internal medicine at the University of New Mexico School of Medicine in Albuquerque.

References

1. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246(3):697-722.
2. Ryu JH, Swensen SJ. Cystic and cavitary lung diseases: focal and diffuse. Mayo Clin Proc. 2003;78(6):744-752.
3. Barnes PF, Verdegem TD, Vachon LA, Leedom JM, Overturf GD. Chest roentgenogram in pulmonary tuberculosis. New data on an old test. Chest. 1988;94(2):316-320.
4. Yazbeck MF, Dahdel M, Kalra A, Browne AS, Pratter MR. Lung abscess: update on microbiology and management. Am J Ther. 2012;21(3):217-221. doi: 10.1097/MJT.0b013e3182383c9b.
5. Gadkowski LB, Stout JE. Cavitary pulmonary disease. Clin Microbiol Rev. 2008;21(2):305-333.
6. Chiu FT. Cavitation in lung cancers. Aust N Z J Med. 1975;5(6):523-530.
7. Kolodziejski LS, Dyczek S, Duda K, Góralczyk J, Wysocki WM, Lobaziewicz W. Cavitated tumor as a clinical subentity in squamous cell lung cancer patients. Neoplasma. 2003;50(1):66-73.
8. Cordier JF, Valeyre D, Guillevin L, Loire R, Brechot JM. Pulmonary Wegener’s granulomatosis. A clinical and imaging study of 77 cases. Chest. 1990;97(4):906-912.
9. He H, Stein MW, Zalta B, Haramati LB. Pulmonary infarction: spectrum of findings on multidetector helical CT. J Thorac Imaging. 2006;21(1):1-7.
10. Harris H, Barraclough R, Davies C, Armstrong I, Kiely DG, van Beek E Jr. Cavitating lung lesions in chronic thromboembolic pulmonary hypertension. J Radiol Case Rep. 2008;2(3):11-21.
11. Woodring JH, Fried AM, Chuang VP. Solitary cavities of the lung: diagnostic implications of cavity wall thickness. AJR Am J Roentgenol. 1980;135(6):1269-1271.

Case

A 51-year-old male with known hepatocellular carcinoma (HCC) recently underwent successful transarterial chemoembolization of a segment VII liver lesion. The patient was admitted to the hospitalist service for overnight observation. Soon after being sent to the floor, he developed a large mass in his right groin, with associated erythema and tenderness. Upon examination, the radiology resident on call found a 3-cm round red hematoma near the arterial puncture site.

Manual pressure was reapplied for 15 minutes, and the mass was circled with a marker. The patient was monitored for an additional day in the hospital with serial blood counts that were stable. Prior to discharge, the hematoma was 1 cm and disappeared by his follow-up, five days later.

Current State of Liver Malignancies

Liver malignancies have increased in incidence over the last decade, from 7.1 to 8.4 per 100,000 people.¹ HCC is the most common form of primary liver cancer, with more than one million new cases worldwide each year. While generally more prevalent in countries where hepatitis B is endemic (i.e., China and sub-Saharan Africa), prevalence is increasing in the United States and Europe due to chronic hepatitis C, nonalcoholic steatohepatitis (NASH), and alcoholic cirrhosis. HCC traditionally has had few treatment options, with surgical resection or liver transplantation providing the only potential cures; however, only a minority of patients (10%-15%) are surgical candidates.^2,3

Similarly, liver metastasis due to cancers from the gastrointestinal tract and breast are on the rise in developing and developed countries. The National Cancer Institute (NCI) estimates that approximately 50% of patients with colon cancer will have liver metastases at some point in the course of their disease, and only a small number of patients will be candidates for surgical resection.⁴

In light of the limited treatment options for liver malignancies, alternative treatments continue to be an area of intense research, namely transarterial therapies, the most common of which are briefly described in Table 1.

Puncture Site Complications

Hematoma. Puncture site hematoma is the most common complication of arterial access, with an estimated incidence of 5%-23%.⁵ The main clinical findings are erythema and swelling at the puncture site, with a palpable hardening of the skin. Pain and decreased range of motion in the affected extremity are common. Severe cases can result in hypotension and tachycardia with an acute drop in hemoglobin. Initial management will involve marking the site to evaluate for change in size as well as applying pressure. Patients should remain in bed, and serial blood counts should be monitored. Simple hematomas may resolve with time; however, more severe cases may require surgical intervention.^6,7

Pseudoaneurysm formation. The incidence of pseudoaneurysm after arterial puncture is 0.5%-9%. These primarily arise from difficulty with cannulation of the artery and inadequate compression after vascular sheath removal. Signs of pseudoaneurysm are similar to those associated with hematoma; however, these will present with a palpable thrill or possibly a bruit on auscultation. Ultrasound is used for diagnosis. As with hematoma, bed rest and close monitoring are important. More severe cases may require surgical intervention or thrombin injection.^5,8

Infection: Puncture site infection is rare, with incidence around 1%. Pain, swelling, and erythema, in combination with fever and leukocytosis, should raise suspicion for infection. Treatment typically involves antibiotics.

Nerve damage: Another rare occurrence is damage to surrounding nerves when performing initial puncture or post-procedural compression. The incidence of nerve damage is <0.5%, and symptoms include numbness and tingling at the access site, along with limb weakness. Treatment involves symptomatic management and physical therapy. Nerve damage may also arise secondary to nerve sheath compression from a hematoma.^5,9

Thrombosis of the artery. Arterial thrombosis can occur at the site of sheath entry; however, this can be avoided by administering anticoagulation during the procedure. Classic symptoms include the “5 P’s”: pain, pallor, parasthesia, pulselessness, and paralysis. Treatment depends on clot burden, with small clots potentially dissolving and larger clots requiring possible thrombolysis, embolectomy, or surgery.^5,10

Systemic Considerations

Postembolization syndrome: This syndrome is characterized by fever, leukocytosis, and pain; while not a true complication, this issue must be addressed, as it is an expected event in post-procedural care. The reported incidence is as high as 90%-95%, with 81% of patients reporting nausea, vomiting, malaise, and myalgias; 42% experience low-grade fever. Typically, the symptoms peak around five days post-procedure and last about 10 days. Although this syndrome is mostly self-limited, it is important to rule out concurrent infection in patients with prolonged symptoms and/or fever outside of the expected time frame.¹¹

Delayed hypersensitivity to contrast. Contrast reactions can occur anywhere from one hour to seven days after administration. The most common symptoms are pruritis, maculopapular rash, and urticaria; however, more severe reactions may involve respiratory distress and cardiovascular collapse.

Risk factors for delayed reactions include prior contrast reaction, history of drug allergy, and chronic renal impairment. Ideally, high risk patients should avoid contrast medium, if possible; if contrast is necessary, premedication should be provided.

For treatment of a delayed reaction, use the patient’s symptoms as a guide on how to proceed. If the reaction is mild (pruritis or rash), secure IV access, have oxygen on standby, begin IV fluids, and consider administering diphenhydramine 50 mg IV or PO. Hydrocortisone 200 mg IV can be substituted if the patient has a diphenhydramine allergy. In severe reactions, epinephrine (1:1,000 IM or 1:10,000 IV) should be administered immediately.

Hypersensitivity to embolizing agents. Frequently in chemoembolization, iodized oil is used both as contrast and as an occluding agent. This lipiodol suspension is combined with the chemotherapy drug of choice and injected into the vessel of interest. The most common hypersensitivity reaction experienced with this technique is dyspnea. Patients also can experience pruritis, urticaria, bronchospasm, or altered mental status in lower frequencies.

One study showed a 3.2% occurrence of hypersensitivity to the frequently used combination of lipiodol and cisplatin.¹² The most common reactions were dyspnea and urticaria (observed in 57% of patients); bronchospasm, altered mental status, and pruritus were observed in lower frequencies. Treatment involves corticosteroids and antihistamines, with blood pressure support using vasopressors as needed.¹²

Contrast-induced nephropathy (CIN). CIN is defined as a 25% rise in serum creatinine from baseline after exposure to iodinated contrast agents. Patients particularly at risk for this complication include those with preexisting renal impairment, diabetes mellitus, or acute renal failure due to dehydration. Other risk factors include age, preexisting cardiovascular disease, and hepatic impairment. Prophylactic strategies primarily rely on intravenous hydration prior to exposure. The use of N-acetylcysteine can be considered; however, its effectiveness is controversial and it is not routinely recommended.^13,14

Bottom Line

Transarterial liver tumor therapies offer treatment options to patients who would otherwise have none. With these presented considerations in mind, the hospitalist will be prepared to address common issues when and if they arise.

Drs. Sandeep and Archana Laroia are clinical assistant professors in the department of radiology at the University of Iowa Hospitals and Clinics, Iowa City. Dr. Morales is a radiology resident at UIHC.

References

1. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. Available at: http://seer.cancer.gov/archive/csr/1975_2010/. Accessed January 11, 2015.
2. Llovet JM. Treatment of hepatocellular carcinoma. Curr Treat Options Gastroenterol. 2004;7(6):431-441.
3. Sasson AR, Sigurdson ER. Surgical treatment of liver metastases. Semin Oncol. 2002;29(2):107-118.
4. National Cancer Institute. Colon Cancer Treatment (PDQ). Available at: http://cancer.gov/cancertopics/pdq/treatment/colon/HealthProfessional. Accessed January 11, 2015.
5. Merriweather N, Sulzbach-Hoke LM. Managing risk of complications at femoral vascular access sites in percutaneous coronary intervention. Crit Care Nurse. 2012;32(5):16-29.
6. Sigstedt B, Lunderquist A. Complications of angiographic examinations. AJR Am J Roentgenol. 1978;130(3):455-460.
7. Clark TW. Complications of hepatic chemoembolization. Semin Intervent Radiol. 2006;23(2):119-125.
8. Webber GW, Jang J, Gustavson S, Olin JW. Contemporary management of postcatheterization pseudoaneurysms. Circulation. 2007;115(20):2666-2674.
9. Tran DD, Andersen CA. Axillary sheath hematomas causing neurologic complications following arterial access. Ann Vasc Surg. 2011;25(5):697 e5-8.
10. Hall R. Vascular injuries resulting from arterial puncture of catheterization. Br J Surg. 1971;58(7):513-516.
11. Leung DA, Goin JE, Sickles C, Raskay BJ, Soulen MC. Determinants of postembolization syndrome after hepatic chemoembolization. J Vasc Interv Radiol. 2001;12(3):321-326.
12. Kawaoka T, Aikata H, Katamura Y, et al. Hypersensitivity reactions to transcatheter chemoembolization with cisplatin and Lipiodol suspension for unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2010;21(8):1219-1225.
13. Barrett BJ, Parfrey PS. Clinical practice. Preventing nephropathy induced by contrast medium. N Engl J Med. 2006;354(4):379-386.
14. McCullough PA, Adam A, Becker CR, et al. Risk prediction of contrast-induced nephropathy. Am J Cardiol. 2006;98(6A):27K-36K.

Case

A 51-year-old male with known hepatocellular carcinoma (HCC) recently underwent successful transarterial chemoembolization of a segment VII liver lesion. The patient was admitted to the hospitalist service for overnight observation. Soon after being sent to the floor, he developed a large mass in his right groin, with associated erythema and tenderness. Upon examination, the radiology resident on call found a 3-cm round red hematoma near the arterial puncture site.

Manual pressure was reapplied for 15 minutes, and the mass was circled with a marker. The patient was monitored for an additional day in the hospital with serial blood counts that were stable. Prior to discharge, the hematoma was 1 cm and disappeared by his follow-up, five days later.

Current State of Liver Malignancies

Liver malignancies have increased in incidence over the last decade, from 7.1 to 8.4 per 100,000 people.¹ HCC is the most common form of primary liver cancer, with more than one million new cases worldwide each year. While generally more prevalent in countries where hepatitis B is endemic (i.e., China and sub-Saharan Africa), prevalence is increasing in the United States and Europe due to chronic hepatitis C, nonalcoholic steatohepatitis (NASH), and alcoholic cirrhosis. HCC traditionally has had few treatment options, with surgical resection or liver transplantation providing the only potential cures; however, only a minority of patients (10%-15%) are surgical candidates.^2,3

Similarly, liver metastasis due to cancers from the gastrointestinal tract and breast are on the rise in developing and developed countries. The National Cancer Institute (NCI) estimates that approximately 50% of patients with colon cancer will have liver metastases at some point in the course of their disease, and only a small number of patients will be candidates for surgical resection.⁴

In light of the limited treatment options for liver malignancies, alternative treatments continue to be an area of intense research, namely transarterial therapies, the most common of which are briefly described in Table 1.

Puncture Site Complications

Hematoma. Puncture site hematoma is the most common complication of arterial access, with an estimated incidence of 5%-23%.⁵ The main clinical findings are erythema and swelling at the puncture site, with a palpable hardening of the skin. Pain and decreased range of motion in the affected extremity are common. Severe cases can result in hypotension and tachycardia with an acute drop in hemoglobin. Initial management will involve marking the site to evaluate for change in size as well as applying pressure. Patients should remain in bed, and serial blood counts should be monitored. Simple hematomas may resolve with time; however, more severe cases may require surgical intervention.^6,7

Pseudoaneurysm formation. The incidence of pseudoaneurysm after arterial puncture is 0.5%-9%. These primarily arise from difficulty with cannulation of the artery and inadequate compression after vascular sheath removal. Signs of pseudoaneurysm are similar to those associated with hematoma; however, these will present with a palpable thrill or possibly a bruit on auscultation. Ultrasound is used for diagnosis. As with hematoma, bed rest and close monitoring are important. More severe cases may require surgical intervention or thrombin injection.^5,8

Infection: Puncture site infection is rare, with incidence around 1%. Pain, swelling, and erythema, in combination with fever and leukocytosis, should raise suspicion for infection. Treatment typically involves antibiotics.

Nerve damage: Another rare occurrence is damage to surrounding nerves when performing initial puncture or post-procedural compression. The incidence of nerve damage is <0.5%, and symptoms include numbness and tingling at the access site, along with limb weakness. Treatment involves symptomatic management and physical therapy. Nerve damage may also arise secondary to nerve sheath compression from a hematoma.^5,9

Thrombosis of the artery. Arterial thrombosis can occur at the site of sheath entry; however, this can be avoided by administering anticoagulation during the procedure. Classic symptoms include the “5 P’s”: pain, pallor, parasthesia, pulselessness, and paralysis. Treatment depends on clot burden, with small clots potentially dissolving and larger clots requiring possible thrombolysis, embolectomy, or surgery.^5,10

Systemic Considerations

Postembolization syndrome: This syndrome is characterized by fever, leukocytosis, and pain; while not a true complication, this issue must be addressed, as it is an expected event in post-procedural care. The reported incidence is as high as 90%-95%, with 81% of patients reporting nausea, vomiting, malaise, and myalgias; 42% experience low-grade fever. Typically, the symptoms peak around five days post-procedure and last about 10 days. Although this syndrome is mostly self-limited, it is important to rule out concurrent infection in patients with prolonged symptoms and/or fever outside of the expected time frame.¹¹

Delayed hypersensitivity to contrast. Contrast reactions can occur anywhere from one hour to seven days after administration. The most common symptoms are pruritis, maculopapular rash, and urticaria; however, more severe reactions may involve respiratory distress and cardiovascular collapse.

Risk factors for delayed reactions include prior contrast reaction, history of drug allergy, and chronic renal impairment. Ideally, high risk patients should avoid contrast medium, if possible; if contrast is necessary, premedication should be provided.

For treatment of a delayed reaction, use the patient’s symptoms as a guide on how to proceed. If the reaction is mild (pruritis or rash), secure IV access, have oxygen on standby, begin IV fluids, and consider administering diphenhydramine 50 mg IV or PO. Hydrocortisone 200 mg IV can be substituted if the patient has a diphenhydramine allergy. In severe reactions, epinephrine (1:1,000 IM or 1:10,000 IV) should be administered immediately.

Hypersensitivity to embolizing agents. Frequently in chemoembolization, iodized oil is used both as contrast and as an occluding agent. This lipiodol suspension is combined with the chemotherapy drug of choice and injected into the vessel of interest. The most common hypersensitivity reaction experienced with this technique is dyspnea. Patients also can experience pruritis, urticaria, bronchospasm, or altered mental status in lower frequencies.

One study showed a 3.2% occurrence of hypersensitivity to the frequently used combination of lipiodol and cisplatin.¹² The most common reactions were dyspnea and urticaria (observed in 57% of patients); bronchospasm, altered mental status, and pruritus were observed in lower frequencies. Treatment involves corticosteroids and antihistamines, with blood pressure support using vasopressors as needed.¹²

Contrast-induced nephropathy (CIN). CIN is defined as a 25% rise in serum creatinine from baseline after exposure to iodinated contrast agents. Patients particularly at risk for this complication include those with preexisting renal impairment, diabetes mellitus, or acute renal failure due to dehydration. Other risk factors include age, preexisting cardiovascular disease, and hepatic impairment. Prophylactic strategies primarily rely on intravenous hydration prior to exposure. The use of N-acetylcysteine can be considered; however, its effectiveness is controversial and it is not routinely recommended.^13,14

Bottom Line

Transarterial liver tumor therapies offer treatment options to patients who would otherwise have none. With these presented considerations in mind, the hospitalist will be prepared to address common issues when and if they arise.

Drs. Sandeep and Archana Laroia are clinical assistant professors in the department of radiology at the University of Iowa Hospitals and Clinics, Iowa City. Dr. Morales is a radiology resident at UIHC.

References

1. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. Available at: http://seer.cancer.gov/archive/csr/1975_2010/. Accessed January 11, 2015.
2. Llovet JM. Treatment of hepatocellular carcinoma. Curr Treat Options Gastroenterol. 2004;7(6):431-441.
3. Sasson AR, Sigurdson ER. Surgical treatment of liver metastases. Semin Oncol. 2002;29(2):107-118.
4. National Cancer Institute. Colon Cancer Treatment (PDQ). Available at: http://cancer.gov/cancertopics/pdq/treatment/colon/HealthProfessional. Accessed January 11, 2015.
5. Merriweather N, Sulzbach-Hoke LM. Managing risk of complications at femoral vascular access sites in percutaneous coronary intervention. Crit Care Nurse. 2012;32(5):16-29.
6. Sigstedt B, Lunderquist A. Complications of angiographic examinations. AJR Am J Roentgenol. 1978;130(3):455-460.
7. Clark TW. Complications of hepatic chemoembolization. Semin Intervent Radiol. 2006;23(2):119-125.
8. Webber GW, Jang J, Gustavson S, Olin JW. Contemporary management of postcatheterization pseudoaneurysms. Circulation. 2007;115(20):2666-2674.
9. Tran DD, Andersen CA. Axillary sheath hematomas causing neurologic complications following arterial access. Ann Vasc Surg. 2011;25(5):697 e5-8.
10. Hall R. Vascular injuries resulting from arterial puncture of catheterization. Br J Surg. 1971;58(7):513-516.
11. Leung DA, Goin JE, Sickles C, Raskay BJ, Soulen MC. Determinants of postembolization syndrome after hepatic chemoembolization. J Vasc Interv Radiol. 2001;12(3):321-326.
12. Kawaoka T, Aikata H, Katamura Y, et al. Hypersensitivity reactions to transcatheter chemoembolization with cisplatin and Lipiodol suspension for unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2010;21(8):1219-1225.
13. Barrett BJ, Parfrey PS. Clinical practice. Preventing nephropathy induced by contrast medium. N Engl J Med. 2006;354(4):379-386.
14. McCullough PA, Adam A, Becker CR, et al. Risk prediction of contrast-induced nephropathy. Am J Cardiol. 2006;98(6A):27K-36K.

Case

A 51-year-old male with known hepatocellular carcinoma (HCC) recently underwent successful transarterial chemoembolization of a segment VII liver lesion. The patient was admitted to the hospitalist service for overnight observation. Soon after being sent to the floor, he developed a large mass in his right groin, with associated erythema and tenderness. Upon examination, the radiology resident on call found a 3-cm round red hematoma near the arterial puncture site.

Manual pressure was reapplied for 15 minutes, and the mass was circled with a marker. The patient was monitored for an additional day in the hospital with serial blood counts that were stable. Prior to discharge, the hematoma was 1 cm and disappeared by his follow-up, five days later.

Current State of Liver Malignancies

Liver malignancies have increased in incidence over the last decade, from 7.1 to 8.4 per 100,000 people.¹ HCC is the most common form of primary liver cancer, with more than one million new cases worldwide each year. While generally more prevalent in countries where hepatitis B is endemic (i.e., China and sub-Saharan Africa), prevalence is increasing in the United States and Europe due to chronic hepatitis C, nonalcoholic steatohepatitis (NASH), and alcoholic cirrhosis. HCC traditionally has had few treatment options, with surgical resection or liver transplantation providing the only potential cures; however, only a minority of patients (10%-15%) are surgical candidates.^2,3

Similarly, liver metastasis due to cancers from the gastrointestinal tract and breast are on the rise in developing and developed countries. The National Cancer Institute (NCI) estimates that approximately 50% of patients with colon cancer will have liver metastases at some point in the course of their disease, and only a small number of patients will be candidates for surgical resection.⁴

In light of the limited treatment options for liver malignancies, alternative treatments continue to be an area of intense research, namely transarterial therapies, the most common of which are briefly described in Table 1.

Puncture Site Complications

Hematoma. Puncture site hematoma is the most common complication of arterial access, with an estimated incidence of 5%-23%.⁵ The main clinical findings are erythema and swelling at the puncture site, with a palpable hardening of the skin. Pain and decreased range of motion in the affected extremity are common. Severe cases can result in hypotension and tachycardia with an acute drop in hemoglobin. Initial management will involve marking the site to evaluate for change in size as well as applying pressure. Patients should remain in bed, and serial blood counts should be monitored. Simple hematomas may resolve with time; however, more severe cases may require surgical intervention.^6,7

Pseudoaneurysm formation. The incidence of pseudoaneurysm after arterial puncture is 0.5%-9%. These primarily arise from difficulty with cannulation of the artery and inadequate compression after vascular sheath removal. Signs of pseudoaneurysm are similar to those associated with hematoma; however, these will present with a palpable thrill or possibly a bruit on auscultation. Ultrasound is used for diagnosis. As with hematoma, bed rest and close monitoring are important. More severe cases may require surgical intervention or thrombin injection.^5,8

Infection: Puncture site infection is rare, with incidence around 1%. Pain, swelling, and erythema, in combination with fever and leukocytosis, should raise suspicion for infection. Treatment typically involves antibiotics.

Nerve damage: Another rare occurrence is damage to surrounding nerves when performing initial puncture or post-procedural compression. The incidence of nerve damage is <0.5%, and symptoms include numbness and tingling at the access site, along with limb weakness. Treatment involves symptomatic management and physical therapy. Nerve damage may also arise secondary to nerve sheath compression from a hematoma.^5,9

Thrombosis of the artery. Arterial thrombosis can occur at the site of sheath entry; however, this can be avoided by administering anticoagulation during the procedure. Classic symptoms include the “5 P’s”: pain, pallor, parasthesia, pulselessness, and paralysis. Treatment depends on clot burden, with small clots potentially dissolving and larger clots requiring possible thrombolysis, embolectomy, or surgery.^5,10

Systemic Considerations

Postembolization syndrome: This syndrome is characterized by fever, leukocytosis, and pain; while not a true complication, this issue must be addressed, as it is an expected event in post-procedural care. The reported incidence is as high as 90%-95%, with 81% of patients reporting nausea, vomiting, malaise, and myalgias; 42% experience low-grade fever. Typically, the symptoms peak around five days post-procedure and last about 10 days. Although this syndrome is mostly self-limited, it is important to rule out concurrent infection in patients with prolonged symptoms and/or fever outside of the expected time frame.¹¹

Delayed hypersensitivity to contrast. Contrast reactions can occur anywhere from one hour to seven days after administration. The most common symptoms are pruritis, maculopapular rash, and urticaria; however, more severe reactions may involve respiratory distress and cardiovascular collapse.

Risk factors for delayed reactions include prior contrast reaction, history of drug allergy, and chronic renal impairment. Ideally, high risk patients should avoid contrast medium, if possible; if contrast is necessary, premedication should be provided.

For treatment of a delayed reaction, use the patient’s symptoms as a guide on how to proceed. If the reaction is mild (pruritis or rash), secure IV access, have oxygen on standby, begin IV fluids, and consider administering diphenhydramine 50 mg IV or PO. Hydrocortisone 200 mg IV can be substituted if the patient has a diphenhydramine allergy. In severe reactions, epinephrine (1:1,000 IM or 1:10,000 IV) should be administered immediately.

Hypersensitivity to embolizing agents. Frequently in chemoembolization, iodized oil is used both as contrast and as an occluding agent. This lipiodol suspension is combined with the chemotherapy drug of choice and injected into the vessel of interest. The most common hypersensitivity reaction experienced with this technique is dyspnea. Patients also can experience pruritis, urticaria, bronchospasm, or altered mental status in lower frequencies.

One study showed a 3.2% occurrence of hypersensitivity to the frequently used combination of lipiodol and cisplatin.¹² The most common reactions were dyspnea and urticaria (observed in 57% of patients); bronchospasm, altered mental status, and pruritus were observed in lower frequencies. Treatment involves corticosteroids and antihistamines, with blood pressure support using vasopressors as needed.¹²

Contrast-induced nephropathy (CIN). CIN is defined as a 25% rise in serum creatinine from baseline after exposure to iodinated contrast agents. Patients particularly at risk for this complication include those with preexisting renal impairment, diabetes mellitus, or acute renal failure due to dehydration. Other risk factors include age, preexisting cardiovascular disease, and hepatic impairment. Prophylactic strategies primarily rely on intravenous hydration prior to exposure. The use of N-acetylcysteine can be considered; however, its effectiveness is controversial and it is not routinely recommended.^13,14

Bottom Line

Transarterial liver tumor therapies offer treatment options to patients who would otherwise have none. With these presented considerations in mind, the hospitalist will be prepared to address common issues when and if they arise.

Drs. Sandeep and Archana Laroia are clinical assistant professors in the department of radiology at the University of Iowa Hospitals and Clinics, Iowa City. Dr. Morales is a radiology resident at UIHC.

References

1. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. Available at: http://seer.cancer.gov/archive/csr/1975_2010/. Accessed January 11, 2015.
2. Llovet JM. Treatment of hepatocellular carcinoma. Curr Treat Options Gastroenterol. 2004;7(6):431-441.
3. Sasson AR, Sigurdson ER. Surgical treatment of liver metastases. Semin Oncol. 2002;29(2):107-118.
4. National Cancer Institute. Colon Cancer Treatment (PDQ). Available at: http://cancer.gov/cancertopics/pdq/treatment/colon/HealthProfessional. Accessed January 11, 2015.
5. Merriweather N, Sulzbach-Hoke LM. Managing risk of complications at femoral vascular access sites in percutaneous coronary intervention. Crit Care Nurse. 2012;32(5):16-29.
6. Sigstedt B, Lunderquist A. Complications of angiographic examinations. AJR Am J Roentgenol. 1978;130(3):455-460.
7. Clark TW. Complications of hepatic chemoembolization. Semin Intervent Radiol. 2006;23(2):119-125.
8. Webber GW, Jang J, Gustavson S, Olin JW. Contemporary management of postcatheterization pseudoaneurysms. Circulation. 2007;115(20):2666-2674.
9. Tran DD, Andersen CA. Axillary sheath hematomas causing neurologic complications following arterial access. Ann Vasc Surg. 2011;25(5):697 e5-8.
10. Hall R. Vascular injuries resulting from arterial puncture of catheterization. Br J Surg. 1971;58(7):513-516.
11. Leung DA, Goin JE, Sickles C, Raskay BJ, Soulen MC. Determinants of postembolization syndrome after hepatic chemoembolization. J Vasc Interv Radiol. 2001;12(3):321-326.
12. Kawaoka T, Aikata H, Katamura Y, et al. Hypersensitivity reactions to transcatheter chemoembolization with cisplatin and Lipiodol suspension for unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2010;21(8):1219-1225.
13. Barrett BJ, Parfrey PS. Clinical practice. Preventing nephropathy induced by contrast medium. N Engl J Med. 2006;354(4):379-386.
14. McCullough PA, Adam A, Becker CR, et al. Risk prediction of contrast-induced nephropathy. Am J Cardiol. 2006;98(6A):27K-36K.

Case

A 31-year-old male with a history of asthma is admitted with an asthma exacerbation. He has no regular outpatient provider. He denies tobacco use and reports that he is in a monogamous relationship with his girlfriend. On rounds, a medical student mentions that new HIV screening guidelines have been released recently and asks whether this patient should be screened for HIV.

Background

By the mid-2000s, approximately one to 1.2 million people in the United States were infected with HIV.¹ Approximately one quarter of these patients are estimated to be unaware of their HIV status, and this subgroup is believed responsible for a disproportionately higher percentage of new HIV infections each year.¹

While older HIV screening recommendations focused on screening patients who were deemed to be at high risk for HIV infection, there has been a paradigm change in recent years toward universal screening of all patients.^2,3 The ultimate goal is for earlier identification of infected patients, which will, in turn, lead to earlier treatment and better prevention efforts.

Universal screening has been supported by a number of different professional societies and screening guidelines.⁴

2013 Guideline

In 2013, the United States Preventive Services Task Force (USPSTF) issued new recommendations regarding HIV screening. Although the previous USPSTF guidelines (released in 2005) recommended screening patients who were believed to be at increased risk for contracting HIV, the 2013 guidelines now recommend screening all patients aged 15 to 65.⁴

Screening patients outside of this age range is recommended if the patient is deemed to be at increased risk for contracting HIV.⁴ The USPSTF provides criteria for identifying patients who are at increased risk of contracting HIV. These include:

• Men who have sex with men;
• People having unprotected vaginal or anal intercourse;
• People using injection drugs;
• People exchanging sex for drugs or money; and
• People requesting testing for other sexually transmitted diseases (STDs).⁴

Patients are also considered to be high risk if their sexual partners are infected with HIV, are bisexual, or use injection drugs.⁴

The shift toward universal HIV screening has been a trend for many years, because risk-based targeting of HIV screening will miss a significant number of HIV infections.² In fact, the 2013 recommendations bring the USPSTF guidelines into agreement with current CDC guidelines, which were released in 2006.²

The CDC, in its 2006 guidelines, recommended screening for all patients 13 to 64 years old unless HIV prevalence in the patient population has been found to be less than 0.1%, the minimum prevalence deemed necessary for HIV screening to be cost-effective.² The CDC guidelines also recommend HIV screening for all patients starting treatment for tuberculosis, patients being screened for STDs, and patients visiting STD clinics regardless of chief complaint.² They recommend that HIV screening be performed in an “opt-out” fashion, meaning that patients are informed that screening will be performed unless they decline.² Furthermore, they recommend against the need for a separate written consent form for HIV screening, as well as the prior requirement that pre-screening counseling be performed, because these requirements were felt to create potential time constraint barriers that prevented providers from screening patients.²

The CDC and the USPSTF are less conclusive with regard to frequency of rescreening for HIV infection. Both recommend rescreening patients considered high risk for HIV infection, but the interval for rescreening has not been concretely defined.^2,4 The guidelines urge providers to use clinical judgment in deciding when to rescreen for HIV infection.² For example, one reason for rescreening cited by the CDC would be the initiation of a new sexual relationship.²

In the 2013 guidelines, the USPSTF also recommends screening all pregnant women, including those presenting in labor without a known HIV status.⁴ This stance is supported by the American College of Gynecologists and Obstetricians.³ In high-risk patients with a negative screening test early in pregnancy, consideration should be given to repeat testing in the third trimester.³ Routinely screening pregnant women for HIV and starting appropriate therapy in positive patients has lowered the incidence of perinatal HIV transmission dramatically.²

Rationale

There are several reasons behind the shift to universal HIV screening, regardless of risk. First, providers often do not accurately identify patients’ HIV risk, often because patients are not aware of their actual risk or are uncomfortable discussing their high-risk behaviors with healthcare providers.² Using risk factors as a basis of screening will miss a significant number of HIV-positive patients.⁴

Additionally, screening all patients will result in the detection of HIV infection in a greater number of patients during the early asymptomatic phase, rather than when they later become symptomatic from HIV or AIDS.^2,4 Recent data has led the International Antiviral Society—USA Panel to issue updated recommendations advising initiation of antiretroviral therapy at all CD4 levels.⁵ Studies and observational data suggest that this could result in reduced AIDS complications and death rates.⁴

Early detection of HIV infection also has the potential of reducing spread of the virus.^2,4 It has been suggested that early initiation of antiretroviral therapy could reduce risk of transmission to noninfected partners by lowering viral load in the infected patient.² Knowledge of HIV status has also been shown to reduce high-risk behaviors.⁴

Moreover, by facilitating earlier detection of HIV, universal screening will allow for earlier and better counseling for infected patients.⁴ This has the potential to further alter behaviors and possibly reduce transmission of HIV and/or other sexually transmitted diseases.⁴ Additionally, routine screening of pregnant women allows for better detection of HIV-infected mothers.³ With appropriate interventions during pregnancy, including antiretroviral therapy, rates of mother-to-child transmission have decreased significantly.⁴

On the other hand, potential harms from HIV screening were considered during the USPSTF analysis, including risk of false positive test results, as well as the side effects of antiretroviral medications.⁴ Although there are known short-term and long-term side effects of antiretroviral medications, some of these side effects can be avoided by changing drug regimens.⁴ For many other side effects, the benefits appeared to outweigh the risks of these medications.⁴

Studies have also shown some potential side effects in infants exposed to antiretroviral medications, but the overall evidence is not strong.⁴ In the end, thorough analysis performed by the USPSTF resulted in the opinion that the benefits of HIV screening far outweigh the associated risks.⁴

Challenges for Hospitalists

Several potential drawbacks to universal HIV screening are relatively unique to hospitalists and other providers of hospital-based care.6 First, hospitalists must be prepared to counsel patients regarding their test results, particularly if patients are hospitalized for another issue. Second, hospitalists must be able to communicate these test results to primary care providers in a timely fashion, a challenge that is not unique to HIV testing.

The biggest concern for hospitalists is what to do with HIV test results that are still pending at the time of hospital discharge. Hospitalists will likely face this issue more as increasing numbers of patients are screened in a growing number of medical settings, including the ED and inpatient admissions. Hospitalists who plan to screen inpatients for HIV testing must ensure that these issues have been worked out prior to screening.

Back to the Case

Looking back to the initial case discussion, based on the 2006 CDC and 2013 USPSTF guidelines, this patient should be offered HIV screening if he has not been tested previously. Although the patient states that he is in a monogamous relationship and does not report any high-risk behaviors, patients often do not recognize the true risk associated with their behaviors and fail to accurately report them.² Additionally, patients often are embarrassed by high-risk behaviors and may not report them completely to providers.²

The patient has admitted that he does not seek medical care on a regular basis. This inpatient admission may be his only interaction with the medical field for some time, and thus his only opportunity to undergo screening. But, prior to screening the patient, the hospitalist must ensure that he or she will be able to counsel the patient regarding test results, will be able to communicate those results to the patient’s primary care physician, and will be able to handle pending results if the patient is discharged before the test results are returned.

Drs. Gwyn, Carbo and Li are hospitalists at Beth Israel Deaconess Medical Center in Boston.

References

1. Branson B. Current HIV epidemiology and revised recommendations for HIV testing in health-care settings. J Med Virol. 2007;79 Suppl 1:S6-S10.
2. Moyer VA; U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2013;159(1):51-60.
3. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1-17.
4. Clark J, Lampe MA, Jamieson DJ. Testing women for human immunodeficiency virus infection: who, when, and how? Clin Obstet Gynceol. 2008;51(3):507-517.
5. Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society–USA Panel. JAMA. 2012;308(4):387-402.
6. Arbelaez C, Wright EA, Losina E, et al. Emergency provider attitudes and barriers to universal HIV testing in the emergency department. J Emerg Med. 2012;42(1):7-14.

Case

A 31-year-old male with a history of asthma is admitted with an asthma exacerbation. He has no regular outpatient provider. He denies tobacco use and reports that he is in a monogamous relationship with his girlfriend. On rounds, a medical student mentions that new HIV screening guidelines have been released recently and asks whether this patient should be screened for HIV.

Background

By the mid-2000s, approximately one to 1.2 million people in the United States were infected with HIV.¹ Approximately one quarter of these patients are estimated to be unaware of their HIV status, and this subgroup is believed responsible for a disproportionately higher percentage of new HIV infections each year.¹

While older HIV screening recommendations focused on screening patients who were deemed to be at high risk for HIV infection, there has been a paradigm change in recent years toward universal screening of all patients.^2,3 The ultimate goal is for earlier identification of infected patients, which will, in turn, lead to earlier treatment and better prevention efforts.

Universal screening has been supported by a number of different professional societies and screening guidelines.⁴

2013 Guideline

In 2013, the United States Preventive Services Task Force (USPSTF) issued new recommendations regarding HIV screening. Although the previous USPSTF guidelines (released in 2005) recommended screening patients who were believed to be at increased risk for contracting HIV, the 2013 guidelines now recommend screening all patients aged 15 to 65.⁴

Screening patients outside of this age range is recommended if the patient is deemed to be at increased risk for contracting HIV.⁴ The USPSTF provides criteria for identifying patients who are at increased risk of contracting HIV. These include:

• Men who have sex with men;
• People having unprotected vaginal or anal intercourse;
• People using injection drugs;
• People exchanging sex for drugs or money; and
• People requesting testing for other sexually transmitted diseases (STDs).⁴

Patients are also considered to be high risk if their sexual partners are infected with HIV, are bisexual, or use injection drugs.⁴

The shift toward universal HIV screening has been a trend for many years, because risk-based targeting of HIV screening will miss a significant number of HIV infections.² In fact, the 2013 recommendations bring the USPSTF guidelines into agreement with current CDC guidelines, which were released in 2006.²

The CDC, in its 2006 guidelines, recommended screening for all patients 13 to 64 years old unless HIV prevalence in the patient population has been found to be less than 0.1%, the minimum prevalence deemed necessary for HIV screening to be cost-effective.² The CDC guidelines also recommend HIV screening for all patients starting treatment for tuberculosis, patients being screened for STDs, and patients visiting STD clinics regardless of chief complaint.² They recommend that HIV screening be performed in an “opt-out” fashion, meaning that patients are informed that screening will be performed unless they decline.² Furthermore, they recommend against the need for a separate written consent form for HIV screening, as well as the prior requirement that pre-screening counseling be performed, because these requirements were felt to create potential time constraint barriers that prevented providers from screening patients.²

The CDC and the USPSTF are less conclusive with regard to frequency of rescreening for HIV infection. Both recommend rescreening patients considered high risk for HIV infection, but the interval for rescreening has not been concretely defined.^2,4 The guidelines urge providers to use clinical judgment in deciding when to rescreen for HIV infection.² For example, one reason for rescreening cited by the CDC would be the initiation of a new sexual relationship.²

In the 2013 guidelines, the USPSTF also recommends screening all pregnant women, including those presenting in labor without a known HIV status.⁴ This stance is supported by the American College of Gynecologists and Obstetricians.³ In high-risk patients with a negative screening test early in pregnancy, consideration should be given to repeat testing in the third trimester.³ Routinely screening pregnant women for HIV and starting appropriate therapy in positive patients has lowered the incidence of perinatal HIV transmission dramatically.²

Rationale

There are several reasons behind the shift to universal HIV screening, regardless of risk. First, providers often do not accurately identify patients’ HIV risk, often because patients are not aware of their actual risk or are uncomfortable discussing their high-risk behaviors with healthcare providers.² Using risk factors as a basis of screening will miss a significant number of HIV-positive patients.⁴

Additionally, screening all patients will result in the detection of HIV infection in a greater number of patients during the early asymptomatic phase, rather than when they later become symptomatic from HIV or AIDS.^2,4 Recent data has led the International Antiviral Society—USA Panel to issue updated recommendations advising initiation of antiretroviral therapy at all CD4 levels.⁵ Studies and observational data suggest that this could result in reduced AIDS complications and death rates.⁴

Early detection of HIV infection also has the potential of reducing spread of the virus.^2,4 It has been suggested that early initiation of antiretroviral therapy could reduce risk of transmission to noninfected partners by lowering viral load in the infected patient.² Knowledge of HIV status has also been shown to reduce high-risk behaviors.⁴

Moreover, by facilitating earlier detection of HIV, universal screening will allow for earlier and better counseling for infected patients.⁴ This has the potential to further alter behaviors and possibly reduce transmission of HIV and/or other sexually transmitted diseases.⁴ Additionally, routine screening of pregnant women allows for better detection of HIV-infected mothers.³ With appropriate interventions during pregnancy, including antiretroviral therapy, rates of mother-to-child transmission have decreased significantly.⁴

On the other hand, potential harms from HIV screening were considered during the USPSTF analysis, including risk of false positive test results, as well as the side effects of antiretroviral medications.⁴ Although there are known short-term and long-term side effects of antiretroviral medications, some of these side effects can be avoided by changing drug regimens.⁴ For many other side effects, the benefits appeared to outweigh the risks of these medications.⁴

Studies have also shown some potential side effects in infants exposed to antiretroviral medications, but the overall evidence is not strong.⁴ In the end, thorough analysis performed by the USPSTF resulted in the opinion that the benefits of HIV screening far outweigh the associated risks.⁴

Challenges for Hospitalists

Several potential drawbacks to universal HIV screening are relatively unique to hospitalists and other providers of hospital-based care.6 First, hospitalists must be prepared to counsel patients regarding their test results, particularly if patients are hospitalized for another issue. Second, hospitalists must be able to communicate these test results to primary care providers in a timely fashion, a challenge that is not unique to HIV testing.

The biggest concern for hospitalists is what to do with HIV test results that are still pending at the time of hospital discharge. Hospitalists will likely face this issue more as increasing numbers of patients are screened in a growing number of medical settings, including the ED and inpatient admissions. Hospitalists who plan to screen inpatients for HIV testing must ensure that these issues have been worked out prior to screening.

Back to the Case

Looking back to the initial case discussion, based on the 2006 CDC and 2013 USPSTF guidelines, this patient should be offered HIV screening if he has not been tested previously. Although the patient states that he is in a monogamous relationship and does not report any high-risk behaviors, patients often do not recognize the true risk associated with their behaviors and fail to accurately report them.² Additionally, patients often are embarrassed by high-risk behaviors and may not report them completely to providers.²

The patient has admitted that he does not seek medical care on a regular basis. This inpatient admission may be his only interaction with the medical field for some time, and thus his only opportunity to undergo screening. But, prior to screening the patient, the hospitalist must ensure that he or she will be able to counsel the patient regarding test results, will be able to communicate those results to the patient’s primary care physician, and will be able to handle pending results if the patient is discharged before the test results are returned.

Drs. Gwyn, Carbo and Li are hospitalists at Beth Israel Deaconess Medical Center in Boston.

References

1. Branson B. Current HIV epidemiology and revised recommendations for HIV testing in health-care settings. J Med Virol. 2007;79 Suppl 1:S6-S10.
2. Moyer VA; U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2013;159(1):51-60.
3. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1-17.
4. Clark J, Lampe MA, Jamieson DJ. Testing women for human immunodeficiency virus infection: who, when, and how? Clin Obstet Gynceol. 2008;51(3):507-517.
5. Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society–USA Panel. JAMA. 2012;308(4):387-402.
6. Arbelaez C, Wright EA, Losina E, et al. Emergency provider attitudes and barriers to universal HIV testing in the emergency department. J Emerg Med. 2012;42(1):7-14.

Case

A 31-year-old male with a history of asthma is admitted with an asthma exacerbation. He has no regular outpatient provider. He denies tobacco use and reports that he is in a monogamous relationship with his girlfriend. On rounds, a medical student mentions that new HIV screening guidelines have been released recently and asks whether this patient should be screened for HIV.

Background

By the mid-2000s, approximately one to 1.2 million people in the United States were infected with HIV.¹ Approximately one quarter of these patients are estimated to be unaware of their HIV status, and this subgroup is believed responsible for a disproportionately higher percentage of new HIV infections each year.¹

While older HIV screening recommendations focused on screening patients who were deemed to be at high risk for HIV infection, there has been a paradigm change in recent years toward universal screening of all patients.^2,3 The ultimate goal is for earlier identification of infected patients, which will, in turn, lead to earlier treatment and better prevention efforts.

Universal screening has been supported by a number of different professional societies and screening guidelines.⁴

2013 Guideline

In 2013, the United States Preventive Services Task Force (USPSTF) issued new recommendations regarding HIV screening. Although the previous USPSTF guidelines (released in 2005) recommended screening patients who were believed to be at increased risk for contracting HIV, the 2013 guidelines now recommend screening all patients aged 15 to 65.⁴

Screening patients outside of this age range is recommended if the patient is deemed to be at increased risk for contracting HIV.⁴ The USPSTF provides criteria for identifying patients who are at increased risk of contracting HIV. These include:

• Men who have sex with men;
• People having unprotected vaginal or anal intercourse;
• People using injection drugs;
• People exchanging sex for drugs or money; and
• People requesting testing for other sexually transmitted diseases (STDs).⁴

Patients are also considered to be high risk if their sexual partners are infected with HIV, are bisexual, or use injection drugs.⁴

The shift toward universal HIV screening has been a trend for many years, because risk-based targeting of HIV screening will miss a significant number of HIV infections.² In fact, the 2013 recommendations bring the USPSTF guidelines into agreement with current CDC guidelines, which were released in 2006.²

The CDC, in its 2006 guidelines, recommended screening for all patients 13 to 64 years old unless HIV prevalence in the patient population has been found to be less than 0.1%, the minimum prevalence deemed necessary for HIV screening to be cost-effective.² The CDC guidelines also recommend HIV screening for all patients starting treatment for tuberculosis, patients being screened for STDs, and patients visiting STD clinics regardless of chief complaint.² They recommend that HIV screening be performed in an “opt-out” fashion, meaning that patients are informed that screening will be performed unless they decline.² Furthermore, they recommend against the need for a separate written consent form for HIV screening, as well as the prior requirement that pre-screening counseling be performed, because these requirements were felt to create potential time constraint barriers that prevented providers from screening patients.²

The CDC and the USPSTF are less conclusive with regard to frequency of rescreening for HIV infection. Both recommend rescreening patients considered high risk for HIV infection, but the interval for rescreening has not been concretely defined.^2,4 The guidelines urge providers to use clinical judgment in deciding when to rescreen for HIV infection.² For example, one reason for rescreening cited by the CDC would be the initiation of a new sexual relationship.²

In the 2013 guidelines, the USPSTF also recommends screening all pregnant women, including those presenting in labor without a known HIV status.⁴ This stance is supported by the American College of Gynecologists and Obstetricians.³ In high-risk patients with a negative screening test early in pregnancy, consideration should be given to repeat testing in the third trimester.³ Routinely screening pregnant women for HIV and starting appropriate therapy in positive patients has lowered the incidence of perinatal HIV transmission dramatically.²

Rationale

There are several reasons behind the shift to universal HIV screening, regardless of risk. First, providers often do not accurately identify patients’ HIV risk, often because patients are not aware of their actual risk or are uncomfortable discussing their high-risk behaviors with healthcare providers.² Using risk factors as a basis of screening will miss a significant number of HIV-positive patients.⁴

Additionally, screening all patients will result in the detection of HIV infection in a greater number of patients during the early asymptomatic phase, rather than when they later become symptomatic from HIV or AIDS.^2,4 Recent data has led the International Antiviral Society—USA Panel to issue updated recommendations advising initiation of antiretroviral therapy at all CD4 levels.⁵ Studies and observational data suggest that this could result in reduced AIDS complications and death rates.⁴

Early detection of HIV infection also has the potential of reducing spread of the virus.^2,4 It has been suggested that early initiation of antiretroviral therapy could reduce risk of transmission to noninfected partners by lowering viral load in the infected patient.² Knowledge of HIV status has also been shown to reduce high-risk behaviors.⁴

Moreover, by facilitating earlier detection of HIV, universal screening will allow for earlier and better counseling for infected patients.⁴ This has the potential to further alter behaviors and possibly reduce transmission of HIV and/or other sexually transmitted diseases.⁴ Additionally, routine screening of pregnant women allows for better detection of HIV-infected mothers.³ With appropriate interventions during pregnancy, including antiretroviral therapy, rates of mother-to-child transmission have decreased significantly.⁴

On the other hand, potential harms from HIV screening were considered during the USPSTF analysis, including risk of false positive test results, as well as the side effects of antiretroviral medications.⁴ Although there are known short-term and long-term side effects of antiretroviral medications, some of these side effects can be avoided by changing drug regimens.⁴ For many other side effects, the benefits appeared to outweigh the risks of these medications.⁴

Studies have also shown some potential side effects in infants exposed to antiretroviral medications, but the overall evidence is not strong.⁴ In the end, thorough analysis performed by the USPSTF resulted in the opinion that the benefits of HIV screening far outweigh the associated risks.⁴

Challenges for Hospitalists

Several potential drawbacks to universal HIV screening are relatively unique to hospitalists and other providers of hospital-based care.6 First, hospitalists must be prepared to counsel patients regarding their test results, particularly if patients are hospitalized for another issue. Second, hospitalists must be able to communicate these test results to primary care providers in a timely fashion, a challenge that is not unique to HIV testing.

The biggest concern for hospitalists is what to do with HIV test results that are still pending at the time of hospital discharge. Hospitalists will likely face this issue more as increasing numbers of patients are screened in a growing number of medical settings, including the ED and inpatient admissions. Hospitalists who plan to screen inpatients for HIV testing must ensure that these issues have been worked out prior to screening.

Back to the Case

Looking back to the initial case discussion, based on the 2006 CDC and 2013 USPSTF guidelines, this patient should be offered HIV screening if he has not been tested previously. Although the patient states that he is in a monogamous relationship and does not report any high-risk behaviors, patients often do not recognize the true risk associated with their behaviors and fail to accurately report them.² Additionally, patients often are embarrassed by high-risk behaviors and may not report them completely to providers.²

The patient has admitted that he does not seek medical care on a regular basis. This inpatient admission may be his only interaction with the medical field for some time, and thus his only opportunity to undergo screening. But, prior to screening the patient, the hospitalist must ensure that he or she will be able to counsel the patient regarding test results, will be able to communicate those results to the patient’s primary care physician, and will be able to handle pending results if the patient is discharged before the test results are returned.

Drs. Gwyn, Carbo and Li are hospitalists at Beth Israel Deaconess Medical Center in Boston.

References

1. Branson B. Current HIV epidemiology and revised recommendations for HIV testing in health-care settings. J Med Virol. 2007;79 Suppl 1:S6-S10.
2. Moyer VA; U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2013;159(1):51-60.
3. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1-17.
4. Clark J, Lampe MA, Jamieson DJ. Testing women for human immunodeficiency virus infection: who, when, and how? Clin Obstet Gynceol. 2008;51(3):507-517.
5. Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society–USA Panel. JAMA. 2012;308(4):387-402.
6. Arbelaez C, Wright EA, Losina E, et al. Emergency provider attitudes and barriers to universal HIV testing in the emergency department. J Emerg Med. 2012;42(1):7-14.