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Bedside frailty assessment can determine when CPR will be nonbeneficial
Background: Although average survival after in-hospital cardiac arrest is 17%-20%, many clinicians feel that survival is lower in older patients or patients with multiple comorbidities. The Clinical Frailty Scale (CFS) is a simple bedside visual tool that encapsulates patients’ mobility and functional status, with a score greater than 4 indicating frailty. How this measure of frailty correlates with outcomes after in-hospital cardiac arrest is unknown.
Study design: Retrospective review.
Setting: Tertiary referral center in England.
Synopsis: The study included patients over 60 years old who received CPR between May 2017 and December 2018. CFS was retroactively applied based on available chart data. The patients’ median age was 77 years old, and 71% were male. The initial cardiac rhythm was nonshockable in 82% of cases, and overall in-hospital mortality was 86%. Frailty was independently associated with increased mortality when controlling for age, comorbidities, and rhythm. No frail patients survived to hospital discharge, while 26% of patients with CFS greater than 4 survived. Although patients with a shockable rhythm had a better chance of survival overall, compared with those with a nonshockable rhythm (92% vs. 23%, P less than .001), 15% of frail patients had a shockable rhythm, and none survived to discharge. Limitations of the study include relatively small sample size and the possibility of confounding variables, such as comorbid conditions.
Bottom line: When adjusted for age and rhythm, no frail patients older than 60 who received CPR for cardiac arrest survived to hospital discharge. Clinicians should discuss the limited chance of survival and potential burdens of resuscitation with frail patients and their families to avoid inappropriate CPR at the end of life.
Citation: Ibitoye SE et al. Frailty status predicts futility of cardiopulmonary resuscitation in older adults. Age Ageing. 2020 Jun 5;[e-pub]. doi: doi.org/10.1093/ageing/afaa104.
Dr. Chokshi is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.
Background: Although average survival after in-hospital cardiac arrest is 17%-20%, many clinicians feel that survival is lower in older patients or patients with multiple comorbidities. The Clinical Frailty Scale (CFS) is a simple bedside visual tool that encapsulates patients’ mobility and functional status, with a score greater than 4 indicating frailty. How this measure of frailty correlates with outcomes after in-hospital cardiac arrest is unknown.
Study design: Retrospective review.
Setting: Tertiary referral center in England.
Synopsis: The study included patients over 60 years old who received CPR between May 2017 and December 2018. CFS was retroactively applied based on available chart data. The patients’ median age was 77 years old, and 71% were male. The initial cardiac rhythm was nonshockable in 82% of cases, and overall in-hospital mortality was 86%. Frailty was independently associated with increased mortality when controlling for age, comorbidities, and rhythm. No frail patients survived to hospital discharge, while 26% of patients with CFS greater than 4 survived. Although patients with a shockable rhythm had a better chance of survival overall, compared with those with a nonshockable rhythm (92% vs. 23%, P less than .001), 15% of frail patients had a shockable rhythm, and none survived to discharge. Limitations of the study include relatively small sample size and the possibility of confounding variables, such as comorbid conditions.
Bottom line: When adjusted for age and rhythm, no frail patients older than 60 who received CPR for cardiac arrest survived to hospital discharge. Clinicians should discuss the limited chance of survival and potential burdens of resuscitation with frail patients and their families to avoid inappropriate CPR at the end of life.
Citation: Ibitoye SE et al. Frailty status predicts futility of cardiopulmonary resuscitation in older adults. Age Ageing. 2020 Jun 5;[e-pub]. doi: doi.org/10.1093/ageing/afaa104.
Dr. Chokshi is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.
Background: Although average survival after in-hospital cardiac arrest is 17%-20%, many clinicians feel that survival is lower in older patients or patients with multiple comorbidities. The Clinical Frailty Scale (CFS) is a simple bedside visual tool that encapsulates patients’ mobility and functional status, with a score greater than 4 indicating frailty. How this measure of frailty correlates with outcomes after in-hospital cardiac arrest is unknown.
Study design: Retrospective review.
Setting: Tertiary referral center in England.
Synopsis: The study included patients over 60 years old who received CPR between May 2017 and December 2018. CFS was retroactively applied based on available chart data. The patients’ median age was 77 years old, and 71% were male. The initial cardiac rhythm was nonshockable in 82% of cases, and overall in-hospital mortality was 86%. Frailty was independently associated with increased mortality when controlling for age, comorbidities, and rhythm. No frail patients survived to hospital discharge, while 26% of patients with CFS greater than 4 survived. Although patients with a shockable rhythm had a better chance of survival overall, compared with those with a nonshockable rhythm (92% vs. 23%, P less than .001), 15% of frail patients had a shockable rhythm, and none survived to discharge. Limitations of the study include relatively small sample size and the possibility of confounding variables, such as comorbid conditions.
Bottom line: When adjusted for age and rhythm, no frail patients older than 60 who received CPR for cardiac arrest survived to hospital discharge. Clinicians should discuss the limited chance of survival and potential burdens of resuscitation with frail patients and their families to avoid inappropriate CPR at the end of life.
Citation: Ibitoye SE et al. Frailty status predicts futility of cardiopulmonary resuscitation in older adults. Age Ageing. 2020 Jun 5;[e-pub]. doi: doi.org/10.1093/ageing/afaa104.
Dr. Chokshi is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.
How do you manage common inpatient oncologic emergencies?
Three routinely encountered emergencies in the inpatient setting
In 2016, there were an estimated 15,338,988 people living with cancer in the United States.1 As such, it is important that hospitalists be proficient in managing oncologic emergencies that can arise during the natural history of cancer or from its treatment. This article will review three emergencies that are routinely encountered in the inpatient setting: malignant spinal cord compression (MSCC), hypercalcemia of malignancy (HCM), and febrile neutropenia (FN).
Case
Mr. Williams is a 56-year-old man with newly diagnosed metastatic prostate cancer, diabetes mellitus, peptic ulcer disease, and hypertension. He is admitted with back pain and lower extremity weakness worsening over 2 weeks. He denies loss of sensation or bowel and bladder incontinence and can walk. MRI confirms cord compression at T10. What initial and subsequent steroid doses would be of most benefit to administer?
Malignant spinal cord compression
Treatment of MSCC usually aims to preserve function rather than reverse established deficits. MSCC from epidural tumor metastasis develops in 5%-14% of all cancer cases,2 with back pain as the most common symptom. Nearly 60%-85% of patients have weakness at the time of diagnosis,3 and unfortunately, nearly two-thirds of patients will be nonambulatory at presentation.
While timely steroid administration in addition to definitive treatment may maintain ambulatory capacity at 1 year after therapy,4 there is no consensus on the optimal loading and maintenance dose and duration of steroids.
Overview of the data
Although there are no formal guidelines on optimal steroid dosing for MSCC, it is common practice for dexamethasone to be initially dosed at 10 mg followed by 4 mg every 4-6 hours.5 The use of higher doses of dexamethasone may result in improvement in neurologic deficits, but has higher risks for toxicity and is not universally supported in the literature.
A study conducted by Vecht and colleagues demonstrated few differences between initial high-dose and low-dose dexamethasone.6 Intravenous administration of either 10 mg or 100 mg dexamethasone, both followed by total 16 mg of dexamethasone orally per day, showed no significant difference in mobility or survival between the groups.
In a prospective study by Heimdal and colleagues that evaluated the relationship between dexamethasone dose and toxicity, higher doses of steroids had no meaningful impact on neurological symptoms and resulted in more severe side effects.7 Patients were either given 96-mg IV loading dose, gradually tapered over 2 weeks, or enrolled in the low-dose group in which they received 4-mg IV dexamethasone four times per day with a taper over 2 weeks. The high-dose group experienced side effects in 28.6% of patients, with 14.3% experiencing serious side effects. Meanwhile, 7.9% of the low-dose group exhibited some side effects, with none experiencing serious adverse effects.The high-dose group did not experience a significant increase in mobility (57.1 vs. 57.9%).
Key takeaways
Dexamthasone 10-mg oral or IV followed by 4 mg every 4-6 hours until definitive treatment is started is associated with improved neurologic outcomes and minimal adverse side effects. Higher doses of steroids are unlikely to offer more benefit. In patients with paraplegia or autonomic dysfunction, the ability to restore neurologic function is reduced and the burdens of steroid treatment may outweigh its benefits.5
Case continued
Mr. Williams completed treatment for MSCC but was still complaining of extreme lethargy and noticed an increase in thirst and no bowel movement in 5 days. His serum calcium was 14 mg/dL.
Hypercalcemia of malignancy
HCM is the most common paraneoplastic syndrome, observed in nearly 30% of patients with advanced cancer. It is a poor prognostic indicator, and approximately half of all patients with HCM will die within 30 days.8 Cancer is the most common reason for hypercalcemia in the inpatient setting9 and is most often associated with multiple myeloma, non–small cell lung cancer, breast cancer, renal cell carcinoma, non-Hodgkins lymphoma, and leukemia.
Hypercalcemia most often presents with cognitive changes and lethargy, anorexia, nausea, constipation, polyuria and polydipsia, and renal failure. Bradycardia and shortened QT interval are seen more with severe hypercalcemia.
Management of hypercalcemia of malignancy
Management of HCM depends on corrected calcium or ionized calcium levels, chronicity, degree of symptoms, and presence of renal failure. In general, mild asymptomatic hypercalcemia can be managed with outpatient care. Serum calcium greater than 14 mg/dL should be treated regardless of symptoms (Table 1).
For mild to moderate HCM, management involves saline administration to achieve euvolemia and calcitonin, which has temporizing effects. Early administration of IV bisphosphonates for moderate to severe HCM is beneficial because onset of action is 24-48 hours. Furosemide for management of HCM has fallen out of favor unless the patient develops hypervolemia. Denosumab has been Food and Drug Administration–approved for HCM refractory to bisphosphonate therapy and can manage HCM in 64% of patients who did not respond adequately to bisphosphonate therapy.10 Because it can be used in advanced renal failure without dose adjustment, it is first-line therapy in this population, although the risk for hypocalcemia is increased in renal failure. For patients with serum calcium greater than 18 mg/dL, worsening renal failure, or inability to tolerate IV fluids, dialysis with a low-calcium bath should be considered (Table 2).
Zoledronic acid versus pamidronate
A single dose of zoledronic acid normalizes the serum calcium concentration in 88% of patients, compared with 70% of those who received pamidronate, in a pooled analysis of two phase 3 trials.11 The median duration of normocalcemia was longer for those receiving zoledronic acid (32-43 days vs. 18 days). The efficacy of the 4-mg and 8-mg zoledronic acid doses were similar, but the 4-mg dose was recommended because of renal toxicity and increased mortality associated with the higher dose.Despite this data, many specialists maintain that pamidronate, which is less expensive, is of similar clinical efficacy to ZA.12
Key takeaways
Management of HCM should be determined by the severity of the calcium level. The mainstay of treatment includes hydration with normal saline, calcitonin ,and bisphosphonate therapy; zoledronic acid is preferred over pamidronate. For patients refractory to bisphosphonates or patients with renal insufficiency, denosumab should be used.
Case continued: Febrile neutropenia
Febrile neutropenia is defined as a single oral temperature of 100.9° F or a temperature of 100.4° F sustained over a 1-hour period in a patient with absolute neutrophil count (ANC) less than 1,000 cells/mL or ANC expected to decrease to less than 500 cells/mL within a 48-hour period.13 Up to 30% of patients with solid tumors develop febrile neutropenia after chemotherapy, and nearly 80% of patients with hematologic malignancy or after hematopoietic stem cell therapy (HSCT) experience it.
Even though an infectious etiology is identified in only 30%-40% of cases, all patients with febrile neutropenia should initially receive at least empiric gram-negative coverage. The mortality rate is nearly 70% in neutropenic patients who do not receive empiric antibiotics and is reduced to 4%-20% with antibiotics.14
Risk stratification for febrile neutropenia and early discharge
Talcott’s Rules, the Multinational Association for Supportive Care in Cancer (MASCC) score, and the Clinical Index of Stable Febrile Neutropenia (CISNE) are validated tools to determine low-risk febrile neutropenia patients (Tables 3 and 4). The Infectious Diseases Society of America guidelines validated the use of MASCC in 2002 but found that CISNE had better performance than other tools. Coyne and colleagues conducted a retrospective cohort study to assess these two risk stratification tools in the ED and found that the CISNE was 98.3% specific for identifying adverse outcomes, whereas the MASCC was 54.2% specific.15
A study by Talcott and colleagues used Talcott’s Rules to identify low-risk febrile neutropenia patients, who were randomized to early discharge with home intravenous antibiotics versus continued inpatient management. There were no significant differences in the primary outcomes, defined as any change in clinical status requiring medical evaluation.16 Another study suggested that discharge after 24 hours based on clinical stability with outpatient oral antibiotics were noninferior to standard inpatient and intravenous antibiotic therapy.17 A Cochrane review in 2013 of 22 randomized controlled trials determined that oral antibiotics were an acceptable treatment for low-risk patients.18
Key takeaways
Though the MASCC is highly sensitive in identifying low-risk febrile neutropenia patients, it should be used with clinical caution because up to 11% of patients characterized as low risk developed severe complications.19 If a low-risk patient with solid tumor malignancy has adequate home support, lives within an hour of the hospital, and has access to follow-up within 72 hours, oral antibiotics and early discharge can be considered.
Dr. Chokshi is assistant professor in the division of hospital medicine at Mount Sinai Hospital, New York. Dr. Smith is associate professor in the division of hematology/oncology at Mount Sinai Hospital.
QUIZ
Mrs. Smith is a 64-year-old woman with endometrial cancer with temperature of 100.4° F at home. She takes no antibiotics, has no other medical history, and was sent in from clinic and admitted for further management. She feels well, and preliminary infectious workup is negative. She has been afebrile for more than 24 hours, and her ANC is 600 cells/mL.
Her son’s soccer game is tomorrow, and she would like to be present. Her family is involved in her care. Under what conditions can she be discharged?
A. She should not be discharged until full course of empiric intravenous antibiotics is completed.
B. Consider discharge in another 24 hours if she remains afebrile.
C. Discharge if low risk by MASCC or CISNE, with oral doses of levofloxacin or moxifloxacin or oral ciprofloxacin and amoxicillin/clavulanic acid.
Answer: C. The patient has a solid tumor malignancy, is low risk by both MASCC and CISNE, and can most likely be discharged if she is clinically stable or improved. A 7-day course of antibiotics is recommended with close follow-up.
References
1. SEER. Cancer of Any Site - Cancer Stat Facts. https://seer.cancer.gov/statfacts/html/all.html. Accessed 2019 Jul 17.
2. Kwok Y et al. Clinical Approach to Metastatic Epidural Spinal Cord Compression. Hematol Oncol Clin North Am. 2006;20(6):1297-305.
3. Helweg-Larsen S et al. Prognostic factors in metastatic spinal cord compression: a prospective study using multivariate analysis of variables influencing survival and gait function in 153 patients. Int J Radiat Oncol Biol Phys. 2000;46(5):1163-9.
4. Sørensen P et al. Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: A randomised trial. Eur J Cancer. 1994;30(1):22-7.
5. Skeoch G et al. Corticosteroid treatment for metastatic spinal cord compression: A review. Global Spine J. 2017;7(3):272-9.
6. Vecht C et al. Initial bolus of conventional versus high-dose dexamethasone in metastatic spinal cord compression. Neurology. 1989;39(9):1255-7.
7. Heimdal K et al. High incidence of serious side effects of high-dose dexamethasone treatment in patients with epidural spinal cord compression. J Neurooncol. 1992;12(2):141-4.
8. Ralston S et al. Cancer-associated hypercalcemia: Morbidity and mortality. Clinical experience in 126 treated patients. Ann Intern Med. 1990;112(7):499-504.
9. Lindner G et al. Hypercalcemia in the ED: Prevalence, etiology, and outcome. Am J Emerg Med. 2013;31(4):657-60.
10. Hu M et al. Denosumab for patients with persistent or relapsed hypercalcemia of malignancy despite recent bisphosphonate treatment. J Natl Cancer Inst. 2013;105(18):1417-20.
11. Major P et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: A pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. 2001;19(2):558-67.
12. Stewart A. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373-9.
13. Freifeld A et al. Executive summary: Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):427-31.
14. Baden L et al. Prevention and treatment of cancer-related infections, version 2.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2016;14(7):882-913.
15. Coyne C et al. Application of the MASCC and CISNE risk-stratification scores to identify low-risk febrile neutropenic patients in the emergency department. Ann Emerg Med. 2017;69(6):755-64.
16. Talcott J et al. Safety of early discharge for low-risk patients with febrile neutropenia: a multicenter randomized controlled trial. J Clin Oncol. 2011;29(30):3977-83.
17. Innes H et al. Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: A prospective randomised controlled single centre study. Br J Cancer. 2003;89(1):43-9.
18. Vidal L, et al. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst. Rev. 2013.
19. Taplitz RA et al. Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America clinical practice guideline update. J Clin Oncol. 2018;36(14):1443-53.
Three routinely encountered emergencies in the inpatient setting
Three routinely encountered emergencies in the inpatient setting
In 2016, there were an estimated 15,338,988 people living with cancer in the United States.1 As such, it is important that hospitalists be proficient in managing oncologic emergencies that can arise during the natural history of cancer or from its treatment. This article will review three emergencies that are routinely encountered in the inpatient setting: malignant spinal cord compression (MSCC), hypercalcemia of malignancy (HCM), and febrile neutropenia (FN).
Case
Mr. Williams is a 56-year-old man with newly diagnosed metastatic prostate cancer, diabetes mellitus, peptic ulcer disease, and hypertension. He is admitted with back pain and lower extremity weakness worsening over 2 weeks. He denies loss of sensation or bowel and bladder incontinence and can walk. MRI confirms cord compression at T10. What initial and subsequent steroid doses would be of most benefit to administer?
Malignant spinal cord compression
Treatment of MSCC usually aims to preserve function rather than reverse established deficits. MSCC from epidural tumor metastasis develops in 5%-14% of all cancer cases,2 with back pain as the most common symptom. Nearly 60%-85% of patients have weakness at the time of diagnosis,3 and unfortunately, nearly two-thirds of patients will be nonambulatory at presentation.
While timely steroid administration in addition to definitive treatment may maintain ambulatory capacity at 1 year after therapy,4 there is no consensus on the optimal loading and maintenance dose and duration of steroids.
Overview of the data
Although there are no formal guidelines on optimal steroid dosing for MSCC, it is common practice for dexamethasone to be initially dosed at 10 mg followed by 4 mg every 4-6 hours.5 The use of higher doses of dexamethasone may result in improvement in neurologic deficits, but has higher risks for toxicity and is not universally supported in the literature.
A study conducted by Vecht and colleagues demonstrated few differences between initial high-dose and low-dose dexamethasone.6 Intravenous administration of either 10 mg or 100 mg dexamethasone, both followed by total 16 mg of dexamethasone orally per day, showed no significant difference in mobility or survival between the groups.
In a prospective study by Heimdal and colleagues that evaluated the relationship between dexamethasone dose and toxicity, higher doses of steroids had no meaningful impact on neurological symptoms and resulted in more severe side effects.7 Patients were either given 96-mg IV loading dose, gradually tapered over 2 weeks, or enrolled in the low-dose group in which they received 4-mg IV dexamethasone four times per day with a taper over 2 weeks. The high-dose group experienced side effects in 28.6% of patients, with 14.3% experiencing serious side effects. Meanwhile, 7.9% of the low-dose group exhibited some side effects, with none experiencing serious adverse effects.The high-dose group did not experience a significant increase in mobility (57.1 vs. 57.9%).
Key takeaways
Dexamthasone 10-mg oral or IV followed by 4 mg every 4-6 hours until definitive treatment is started is associated with improved neurologic outcomes and minimal adverse side effects. Higher doses of steroids are unlikely to offer more benefit. In patients with paraplegia or autonomic dysfunction, the ability to restore neurologic function is reduced and the burdens of steroid treatment may outweigh its benefits.5
Case continued
Mr. Williams completed treatment for MSCC but was still complaining of extreme lethargy and noticed an increase in thirst and no bowel movement in 5 days. His serum calcium was 14 mg/dL.
Hypercalcemia of malignancy
HCM is the most common paraneoplastic syndrome, observed in nearly 30% of patients with advanced cancer. It is a poor prognostic indicator, and approximately half of all patients with HCM will die within 30 days.8 Cancer is the most common reason for hypercalcemia in the inpatient setting9 and is most often associated with multiple myeloma, non–small cell lung cancer, breast cancer, renal cell carcinoma, non-Hodgkins lymphoma, and leukemia.
Hypercalcemia most often presents with cognitive changes and lethargy, anorexia, nausea, constipation, polyuria and polydipsia, and renal failure. Bradycardia and shortened QT interval are seen more with severe hypercalcemia.
Management of hypercalcemia of malignancy
Management of HCM depends on corrected calcium or ionized calcium levels, chronicity, degree of symptoms, and presence of renal failure. In general, mild asymptomatic hypercalcemia can be managed with outpatient care. Serum calcium greater than 14 mg/dL should be treated regardless of symptoms (Table 1).
For mild to moderate HCM, management involves saline administration to achieve euvolemia and calcitonin, which has temporizing effects. Early administration of IV bisphosphonates for moderate to severe HCM is beneficial because onset of action is 24-48 hours. Furosemide for management of HCM has fallen out of favor unless the patient develops hypervolemia. Denosumab has been Food and Drug Administration–approved for HCM refractory to bisphosphonate therapy and can manage HCM in 64% of patients who did not respond adequately to bisphosphonate therapy.10 Because it can be used in advanced renal failure without dose adjustment, it is first-line therapy in this population, although the risk for hypocalcemia is increased in renal failure. For patients with serum calcium greater than 18 mg/dL, worsening renal failure, or inability to tolerate IV fluids, dialysis with a low-calcium bath should be considered (Table 2).
Zoledronic acid versus pamidronate
A single dose of zoledronic acid normalizes the serum calcium concentration in 88% of patients, compared with 70% of those who received pamidronate, in a pooled analysis of two phase 3 trials.11 The median duration of normocalcemia was longer for those receiving zoledronic acid (32-43 days vs. 18 days). The efficacy of the 4-mg and 8-mg zoledronic acid doses were similar, but the 4-mg dose was recommended because of renal toxicity and increased mortality associated with the higher dose.Despite this data, many specialists maintain that pamidronate, which is less expensive, is of similar clinical efficacy to ZA.12
Key takeaways
Management of HCM should be determined by the severity of the calcium level. The mainstay of treatment includes hydration with normal saline, calcitonin ,and bisphosphonate therapy; zoledronic acid is preferred over pamidronate. For patients refractory to bisphosphonates or patients with renal insufficiency, denosumab should be used.
Case continued: Febrile neutropenia
Febrile neutropenia is defined as a single oral temperature of 100.9° F or a temperature of 100.4° F sustained over a 1-hour period in a patient with absolute neutrophil count (ANC) less than 1,000 cells/mL or ANC expected to decrease to less than 500 cells/mL within a 48-hour period.13 Up to 30% of patients with solid tumors develop febrile neutropenia after chemotherapy, and nearly 80% of patients with hematologic malignancy or after hematopoietic stem cell therapy (HSCT) experience it.
Even though an infectious etiology is identified in only 30%-40% of cases, all patients with febrile neutropenia should initially receive at least empiric gram-negative coverage. The mortality rate is nearly 70% in neutropenic patients who do not receive empiric antibiotics and is reduced to 4%-20% with antibiotics.14
Risk stratification for febrile neutropenia and early discharge
Talcott’s Rules, the Multinational Association for Supportive Care in Cancer (MASCC) score, and the Clinical Index of Stable Febrile Neutropenia (CISNE) are validated tools to determine low-risk febrile neutropenia patients (Tables 3 and 4). The Infectious Diseases Society of America guidelines validated the use of MASCC in 2002 but found that CISNE had better performance than other tools. Coyne and colleagues conducted a retrospective cohort study to assess these two risk stratification tools in the ED and found that the CISNE was 98.3% specific for identifying adverse outcomes, whereas the MASCC was 54.2% specific.15
A study by Talcott and colleagues used Talcott’s Rules to identify low-risk febrile neutropenia patients, who were randomized to early discharge with home intravenous antibiotics versus continued inpatient management. There were no significant differences in the primary outcomes, defined as any change in clinical status requiring medical evaluation.16 Another study suggested that discharge after 24 hours based on clinical stability with outpatient oral antibiotics were noninferior to standard inpatient and intravenous antibiotic therapy.17 A Cochrane review in 2013 of 22 randomized controlled trials determined that oral antibiotics were an acceptable treatment for low-risk patients.18
Key takeaways
Though the MASCC is highly sensitive in identifying low-risk febrile neutropenia patients, it should be used with clinical caution because up to 11% of patients characterized as low risk developed severe complications.19 If a low-risk patient with solid tumor malignancy has adequate home support, lives within an hour of the hospital, and has access to follow-up within 72 hours, oral antibiotics and early discharge can be considered.
Dr. Chokshi is assistant professor in the division of hospital medicine at Mount Sinai Hospital, New York. Dr. Smith is associate professor in the division of hematology/oncology at Mount Sinai Hospital.
QUIZ
Mrs. Smith is a 64-year-old woman with endometrial cancer with temperature of 100.4° F at home. She takes no antibiotics, has no other medical history, and was sent in from clinic and admitted for further management. She feels well, and preliminary infectious workup is negative. She has been afebrile for more than 24 hours, and her ANC is 600 cells/mL.
Her son’s soccer game is tomorrow, and she would like to be present. Her family is involved in her care. Under what conditions can she be discharged?
A. She should not be discharged until full course of empiric intravenous antibiotics is completed.
B. Consider discharge in another 24 hours if she remains afebrile.
C. Discharge if low risk by MASCC or CISNE, with oral doses of levofloxacin or moxifloxacin or oral ciprofloxacin and amoxicillin/clavulanic acid.
Answer: C. The patient has a solid tumor malignancy, is low risk by both MASCC and CISNE, and can most likely be discharged if she is clinically stable or improved. A 7-day course of antibiotics is recommended with close follow-up.
References
1. SEER. Cancer of Any Site - Cancer Stat Facts. https://seer.cancer.gov/statfacts/html/all.html. Accessed 2019 Jul 17.
2. Kwok Y et al. Clinical Approach to Metastatic Epidural Spinal Cord Compression. Hematol Oncol Clin North Am. 2006;20(6):1297-305.
3. Helweg-Larsen S et al. Prognostic factors in metastatic spinal cord compression: a prospective study using multivariate analysis of variables influencing survival and gait function in 153 patients. Int J Radiat Oncol Biol Phys. 2000;46(5):1163-9.
4. Sørensen P et al. Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: A randomised trial. Eur J Cancer. 1994;30(1):22-7.
5. Skeoch G et al. Corticosteroid treatment for metastatic spinal cord compression: A review. Global Spine J. 2017;7(3):272-9.
6. Vecht C et al. Initial bolus of conventional versus high-dose dexamethasone in metastatic spinal cord compression. Neurology. 1989;39(9):1255-7.
7. Heimdal K et al. High incidence of serious side effects of high-dose dexamethasone treatment in patients with epidural spinal cord compression. J Neurooncol. 1992;12(2):141-4.
8. Ralston S et al. Cancer-associated hypercalcemia: Morbidity and mortality. Clinical experience in 126 treated patients. Ann Intern Med. 1990;112(7):499-504.
9. Lindner G et al. Hypercalcemia in the ED: Prevalence, etiology, and outcome. Am J Emerg Med. 2013;31(4):657-60.
10. Hu M et al. Denosumab for patients with persistent or relapsed hypercalcemia of malignancy despite recent bisphosphonate treatment. J Natl Cancer Inst. 2013;105(18):1417-20.
11. Major P et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: A pooled analysis of two randomized, controlled clinical trials. J Clin Oncol. 2001;19(2):558-67.
12. Stewart A. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373-9.
13. Freifeld A et al. Executive summary: Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):427-31.
14. Baden L et al. Prevention and treatment of cancer-related infections, version 2.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2016;14(7):882-913.
15. Coyne C et al. Application of the MASCC and CISNE risk-stratification scores to identify low-risk febrile neutropenic patients in the emergency department. Ann Emerg Med. 2017;69(6):755-64.
16. Talcott J et al. Safety of early discharge for low-risk patients with febrile neutropenia: a multicenter randomized controlled trial. J Clin Oncol. 2011;29(30):3977-83.
17. Innes H et al. Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: A prospective randomised controlled single centre study. Br J Cancer. 2003;89(1):43-9.
18. Vidal L, et al. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst. Rev. 2013.
19. Taplitz RA et al. Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America clinical practice guideline update. J Clin Oncol. 2018;36(14):1443-53.
In 2016, there were an estimated 15,338,988 people living with cancer in the United States.1 As such, it is important that hospitalists be proficient in managing oncologic emergencies that can arise during the natural history of cancer or from its treatment. This article will review three emergencies that are routinely encountered in the inpatient setting: malignant spinal cord compression (MSCC), hypercalcemia of malignancy (HCM), and febrile neutropenia (FN).
Case
Mr. Williams is a 56-year-old man with newly diagnosed metastatic prostate cancer, diabetes mellitus, peptic ulcer disease, and hypertension. He is admitted with back pain and lower extremity weakness worsening over 2 weeks. He denies loss of sensation or bowel and bladder incontinence and can walk. MRI confirms cord compression at T10. What initial and subsequent steroid doses would be of most benefit to administer?
Malignant spinal cord compression
Treatment of MSCC usually aims to preserve function rather than reverse established deficits. MSCC from epidural tumor metastasis develops in 5%-14% of all cancer cases,2 with back pain as the most common symptom. Nearly 60%-85% of patients have weakness at the time of diagnosis,3 and unfortunately, nearly two-thirds of patients will be nonambulatory at presentation.
While timely steroid administration in addition to definitive treatment may maintain ambulatory capacity at 1 year after therapy,4 there is no consensus on the optimal loading and maintenance dose and duration of steroids.
Overview of the data
Although there are no formal guidelines on optimal steroid dosing for MSCC, it is common practice for dexamethasone to be initially dosed at 10 mg followed by 4 mg every 4-6 hours.5 The use of higher doses of dexamethasone may result in improvement in neurologic deficits, but has higher risks for toxicity and is not universally supported in the literature.
A study conducted by Vecht and colleagues demonstrated few differences between initial high-dose and low-dose dexamethasone.6 Intravenous administration of either 10 mg or 100 mg dexamethasone, both followed by total 16 mg of dexamethasone orally per day, showed no significant difference in mobility or survival between the groups.
In a prospective study by Heimdal and colleagues that evaluated the relationship between dexamethasone dose and toxicity, higher doses of steroids had no meaningful impact on neurological symptoms and resulted in more severe side effects.7 Patients were either given 96-mg IV loading dose, gradually tapered over 2 weeks, or enrolled in the low-dose group in which they received 4-mg IV dexamethasone four times per day with a taper over 2 weeks. The high-dose group experienced side effects in 28.6% of patients, with 14.3% experiencing serious side effects. Meanwhile, 7.9% of the low-dose group exhibited some side effects, with none experiencing serious adverse effects.The high-dose group did not experience a significant increase in mobility (57.1 vs. 57.9%).
Key takeaways
Dexamthasone 10-mg oral or IV followed by 4 mg every 4-6 hours until definitive treatment is started is associated with improved neurologic outcomes and minimal adverse side effects. Higher doses of steroids are unlikely to offer more benefit. In patients with paraplegia or autonomic dysfunction, the ability to restore neurologic function is reduced and the burdens of steroid treatment may outweigh its benefits.5
Case continued
Mr. Williams completed treatment for MSCC but was still complaining of extreme lethargy and noticed an increase in thirst and no bowel movement in 5 days. His serum calcium was 14 mg/dL.
Hypercalcemia of malignancy
HCM is the most common paraneoplastic syndrome, observed in nearly 30% of patients with advanced cancer. It is a poor prognostic indicator, and approximately half of all patients with HCM will die within 30 days.8 Cancer is the most common reason for hypercalcemia in the inpatient setting9 and is most often associated with multiple myeloma, non–small cell lung cancer, breast cancer, renal cell carcinoma, non-Hodgkins lymphoma, and leukemia.
Hypercalcemia most often presents with cognitive changes and lethargy, anorexia, nausea, constipation, polyuria and polydipsia, and renal failure. Bradycardia and shortened QT interval are seen more with severe hypercalcemia.
Management of hypercalcemia of malignancy
Management of HCM depends on corrected calcium or ionized calcium levels, chronicity, degree of symptoms, and presence of renal failure. In general, mild asymptomatic hypercalcemia can be managed with outpatient care. Serum calcium greater than 14 mg/dL should be treated regardless of symptoms (Table 1).
For mild to moderate HCM, management involves saline administration to achieve euvolemia and calcitonin, which has temporizing effects. Early administration of IV bisphosphonates for moderate to severe HCM is beneficial because onset of action is 24-48 hours. Furosemide for management of HCM has fallen out of favor unless the patient develops hypervolemia. Denosumab has been Food and Drug Administration–approved for HCM refractory to bisphosphonate therapy and can manage HCM in 64% of patients who did not respond adequately to bisphosphonate therapy.10 Because it can be used in advanced renal failure without dose adjustment, it is first-line therapy in this population, although the risk for hypocalcemia is increased in renal failure. For patients with serum calcium greater than 18 mg/dL, worsening renal failure, or inability to tolerate IV fluids, dialysis with a low-calcium bath should be considered (Table 2).
Zoledronic acid versus pamidronate
A single dose of zoledronic acid normalizes the serum calcium concentration in 88% of patients, compared with 70% of those who received pamidronate, in a pooled analysis of two phase 3 trials.11 The median duration of normocalcemia was longer for those receiving zoledronic acid (32-43 days vs. 18 days). The efficacy of the 4-mg and 8-mg zoledronic acid doses were similar, but the 4-mg dose was recommended because of renal toxicity and increased mortality associated with the higher dose.Despite this data, many specialists maintain that pamidronate, which is less expensive, is of similar clinical efficacy to ZA.12
Key takeaways
Management of HCM should be determined by the severity of the calcium level. The mainstay of treatment includes hydration with normal saline, calcitonin ,and bisphosphonate therapy; zoledronic acid is preferred over pamidronate. For patients refractory to bisphosphonates or patients with renal insufficiency, denosumab should be used.
Case continued: Febrile neutropenia
Febrile neutropenia is defined as a single oral temperature of 100.9° F or a temperature of 100.4° F sustained over a 1-hour period in a patient with absolute neutrophil count (ANC) less than 1,000 cells/mL or ANC expected to decrease to less than 500 cells/mL within a 48-hour period.13 Up to 30% of patients with solid tumors develop febrile neutropenia after chemotherapy, and nearly 80% of patients with hematologic malignancy or after hematopoietic stem cell therapy (HSCT) experience it.
Even though an infectious etiology is identified in only 30%-40% of cases, all patients with febrile neutropenia should initially receive at least empiric gram-negative coverage. The mortality rate is nearly 70% in neutropenic patients who do not receive empiric antibiotics and is reduced to 4%-20% with antibiotics.14
Risk stratification for febrile neutropenia and early discharge
Talcott’s Rules, the Multinational Association for Supportive Care in Cancer (MASCC) score, and the Clinical Index of Stable Febrile Neutropenia (CISNE) are validated tools to determine low-risk febrile neutropenia patients (Tables 3 and 4). The Infectious Diseases Society of America guidelines validated the use of MASCC in 2002 but found that CISNE had better performance than other tools. Coyne and colleagues conducted a retrospective cohort study to assess these two risk stratification tools in the ED and found that the CISNE was 98.3% specific for identifying adverse outcomes, whereas the MASCC was 54.2% specific.15
A study by Talcott and colleagues used Talcott’s Rules to identify low-risk febrile neutropenia patients, who were randomized to early discharge with home intravenous antibiotics versus continued inpatient management. There were no significant differences in the primary outcomes, defined as any change in clinical status requiring medical evaluation.16 Another study suggested that discharge after 24 hours based on clinical stability with outpatient oral antibiotics were noninferior to standard inpatient and intravenous antibiotic therapy.17 A Cochrane review in 2013 of 22 randomized controlled trials determined that oral antibiotics were an acceptable treatment for low-risk patients.18
Key takeaways
Though the MASCC is highly sensitive in identifying low-risk febrile neutropenia patients, it should be used with clinical caution because up to 11% of patients characterized as low risk developed severe complications.19 If a low-risk patient with solid tumor malignancy has adequate home support, lives within an hour of the hospital, and has access to follow-up within 72 hours, oral antibiotics and early discharge can be considered.
Dr. Chokshi is assistant professor in the division of hospital medicine at Mount Sinai Hospital, New York. Dr. Smith is associate professor in the division of hematology/oncology at Mount Sinai Hospital.
QUIZ
Mrs. Smith is a 64-year-old woman with endometrial cancer with temperature of 100.4° F at home. She takes no antibiotics, has no other medical history, and was sent in from clinic and admitted for further management. She feels well, and preliminary infectious workup is negative. She has been afebrile for more than 24 hours, and her ANC is 600 cells/mL.
Her son’s soccer game is tomorrow, and she would like to be present. Her family is involved in her care. Under what conditions can she be discharged?
A. She should not be discharged until full course of empiric intravenous antibiotics is completed.
B. Consider discharge in another 24 hours if she remains afebrile.
C. Discharge if low risk by MASCC or CISNE, with oral doses of levofloxacin or moxifloxacin or oral ciprofloxacin and amoxicillin/clavulanic acid.
Answer: C. The patient has a solid tumor malignancy, is low risk by both MASCC and CISNE, and can most likely be discharged if she is clinically stable or improved. A 7-day course of antibiotics is recommended with close follow-up.
References
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17. Innes H et al. Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: A prospective randomised controlled single centre study. Br J Cancer. 2003;89(1):43-9.
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