The use of bolus-dose vasopressors in anesthesiology and other areas of critical care medicine is well known. This common medical intervention, however, is not often employed in emergency medicine (EM). Bolus-dose vasopressors are defined as the administration of small bolus doses of vasopressor agents, such as epinephrine or phenylephrine, to patients with compromised perfusion who continue to have a pulse (ie, these patients are not in cardiac arrest). This intervention is considered as a temporizing measure for transient hypotension or as a bridge to more definitive therapy.

Clinical Application

Bolus-dose vasopressive therapy is also referred to as push-dose pressor (PDP) therapy—a term coined by Weingart.^1-3 Theoretically, any vasopressor could be used in a mini-dose, bolus fashion, though in current clinical practice, anesthesiologists primarily employ ephedrine, epinephrine, and phenylephrine. Two of these agents are likely more appropriate for the ED, including epinephrine and phenylephrine. Both of these agents have a short half-life and therefore an abbreviated period of effect. In addition, dosing and related administration of epinephrine and phenylephrine is relatively straightforward. Moreover, most emergency physicians and nurses are quite familiar with both agents.

With respect to ephedrine, due to its longer half-life, complex dosing regimen, and associated higher-incidence of cardiovascular (CV) complications, its use is likely not appropriate in the ED as a bolus-dose vasopressor.

Epinephrine and Phenylephrine

Epinephrine is a potent sympathomimetic agent with alpha- and beta-receptor activity. In addition to its vasopressor effects, epinephrine is also an inotropic and chronotropic agent, increasing cardiac output, heart rate (HR), and systemic vascular resistance, which can markedly improve perfusion. Epinephrine also can be given to patients with hypoperfusion and/or shock due to low-cardiac output with or without vasodilation, lacking significant tachycardia.

Phenylephrine is a pure alpha agonist and therefore does not appreciably affect cardiac output and HR, but does significantly increase systemic vascular resistance and thus systemic perfusion. Phenylephrine can be used to treat patients with hypoperfusion and/or shock states due to vasodilation with coexistent, significant tachycardia.

Preparation and Administration

The preparation and dosing of push-dose epinephrine and phenylephrine are not particularly complex. Many clinicians recommend the pre-mixed, manufacturer-prepared agents for PDP therapy. These premixed formulations not only facilitate administration, but also reduce the chance of a preparation error that can result in incorrect dosing.^3-5 If pre-mixed formulations are not available, clinicians can readily prepare epinephrine and phenylephrine for PDP use.

Push-Dose Epinephrine. Clinicians can prepare epinephrine for push-dose administration as follows:^1-3

• Obtain 1 mL of epinephrine 1:10,000 (ie, 0.1 mg/mL or 100 mcg/mL);
• Obtain a 10 mL syringe of normal saline and remove 1 mL;
• Inject the 1 mL of epinephrine 1:10,000 (100 mcg/mL) into this syringe containing 9 mL of normal saline; and
• Result: 10 mL of epinephrine (10 mcg/mL), with each 1 mL of this solution containing 10 mcg of epinephrine.

Administration of push-dose epinephrine (10 mcg/mL) produces effect within 1 minute of use with a duration of approximately 5 to 10 minutes. Dosing at this concentration ranges from 0.5 to 2.0 mL every 2 to 5 minutes, delivering 5 to 20 mcg.^1-3Push-Dose Phenylephrine. To prepare phenylephrine for push-dose administration, clinicians may use the following approach:^1-3

• Obtain 1 mL of phenylephrine (10 mg/mL concentration);
• Inject this 1 mL of phenylephrine (10 mg/mL) into a 100 mL bag of normal saline; and
• Result: 100 mL of phenylephrine (100 mcg/mL), with each 1 mL of this solution containing 100 mcg of phenylephrine.

Administration of push-dose phenylephrine (100 mcg/mL) produces effect within 1 minute of use with a duration of approximately 10 to 20 minutes. Dosing at this concentration ranges from 0.5 to 2.0 mL every 2 to 5 minutes, delivering 50 to 200 mcg.^1-3Alternative Push-Dose Preparations for Phenylephrine. Two other methods of preparing phenylephrine for bolus-dose administration include the following: (1) the addition of phenylephrine 20 mg to a bag of 250 cc of normal saline, resulting in an 80 mcg/mL concentration; and/or (2) phenylephrine (20 mg) is commercially available for continuous infusion in a 250 mL bag of normal saline, yielding the same concentration of 80 mcg/mL; in either case, medication can be drawn up and administered. Dosing at this concentration ranges from 0.5 to 2.5 mL every 2 to 5 minutes, delivering 40 to 200 mcg. Lastly, phenylephrine is also commercially available in pre-made mixtures, specifically manufactured for bolus-dose therapy.

Indications

Both epinephrine and phenylephrine can be considered in the management of significant transient or sustained hypoperfusion. Although the definition of significant hypotension is complex, Brunauer et al⁶ have suggested that a mean arterial pressure (MAP) of approximately 35 mm Hg is associated with a significant risk of CV collapse. Of course, a MAP of 40 to 50 mm Hg is also very concerning clinically, with significant risk of deterioration and CV collapse.

Procedural events, such as conscious sedation or rapid sequence intubation (RSI), can produce significant hypotension; PDP can rapidly correct hypotension. In other clinical scenarios in which sustained hypotension is likely and not transient (eg, sepsis with shock), PDP can be used as a bridge to definitive care (eg, volume replacement, continuous vasopressor infusion). It is important to note, however, that PDP administration must occur in conjunction with or after the patient has received other appropriate therapies such as a normal saline bolus and continuous vasopressor infusions. Push-dose pressors are not a replacement for these proven interventions, but rather are an important augmentation to these therapies.

Emergency Medicine Literature

As previously noted, the literature base describing and supporting the clinical use of PDP in EM is extremely limited. The few articles that comprise this literature base address significant hypotension in periendotracheal intubation intervention, post-return of spontaneous circulation (ROSC) management, and shock management with preload augmentation.^7-9In addition, there are several articles in the literature that address safety concerns surrounding the use of PDP in the ED.^4,5

Panchal et al¹⁰ investigated the use of phenylephrine in hypotensive patients undergoing RSI-assisted endotracheal intubation. The authors performed a 1-year retrospective review of hypotensive patients managed with endotracheal intubation for a range of clinical conditions that required clinical care intervention. In this study, 20 of the 119 patients received phenylephrine in the peri-intubation period. A range of clinical conditions requiring critical care intervention were encountered; in addition, almost three-quarters of these patients were receiving at least one other vasopressor infusion. Further differences were seen in the timing of PDP administration. In those patients receiving bolus-dose phenylephrine, blood pressure (BP) improved without change in HR. Panchal et al¹⁰ concluded that while push-dose phenylephrine improved hemodynamic status, there was significant variation among clinicians regarding dosing, timing of use, and overall clinical situation The significant variation in PDP management in this study was noted to be a potential source of medical error, thus increasing the chance of adverse clinical event.

Push-dose pressor therapy can be employed for significant hypotension while more definitive therapy is being readied and applied. For instance, patients with significant hypotension requiring continuous vasopressor infusion can be managed with PDP while appropriate venous access is established, intravenous fluids are administered, and medications are prepared. The immediate period after resuscitation from cardiac arrest can be complicated by shock of many types. In fact, hypotension following ROSC in the cardiac arrest patient is not uncommon and has been identified as a risk issue associated with poor outcome. Prompt treatment of this altered perfusion may improve outcome. Gottlieb⁸ described three patients with ROSC after cardiac arrest. All three patients experienced significant, sustained hypotension with systolic blood pressure reading in the 50 to 60 mm Hg range; bolus-dose epinephrine was administered with significant improvement in the hemodynamic status while central venous access was established.

In a related clinical scenario, Schwartz et al⁹ considered the impact of PDP on central venous line (CVL) placement with continuous vasopressor infusion. In this ED study, although patients experienced an increase in BP, this impact was transient with approximately half of these individuals ultimately requiring CVL. In addition, serious adverse effect was noted more commonly in the phenylephrine-treated patients with “reactive” hypertension and ventricular tachycardia occurring in study patients.

Patient-Safety Considerations

In addition to the limited literature base supporting PDP use in the ED, another major significant issue focuses on safety concerns and adverse effects. Extremely limited data is available describing adverse events related to ED-administered PDP. Extrapolating from other EM and critical care administrations of peripheral epinephrine, both local and systemic adverse effects have been reported.^11,12 The range of adverse events noted in these studies are considerable, including local skin and soft-tissue injury (necrosis), end-organ tissue ischemia (eg, digits, tip of nose), acute hypertension, cardiac ischemic events, and left ventricular (LV) dysfunction.^11,12

When comparing peripheral infusion with central infusion, the risk of extravasation with resultant local tissue injury is markedly greater with peripheral vasopressor administration. In a systematic review of this issue, Loubani and Green¹¹ noted that such local adverse events were much more commonly associated with peripheral administration.

In another report of vasopressor use in the ED, Kanwar et al¹² described apparent confusion with epinephrine dosing and route of administration, resulting in very significant, systemic CV maladies, including severe elevations in BP, acute LV dysfunction, and chest pain associated with ST segment elevation.

It must be stressed that the publications by Loubani and Green¹¹ and Kanwar et al¹² described peripheral vasopressor administration: neither study included PDP therapy. Therefore, as previously noted, the aforementioned statements are extrapolated from when applied to PDP strategy.

Acquisto et al⁴ describe several errors in medication administration of PDP in the ED and other critical care areas of the hospital. In this report, all treating physicians were present at the patients’ bedside, either administering the medication or directly supervising its use. Agents involved included epinephrine and phenylephrine, delivered at exceedingly high doses. In their study, the authors noted several issues which they believe contributed to medication errors, including heterogeneity of pathology treated in these patients, apparent “earlier-than-appropriate” use of vasopressors (ie, prior to giving an appropriate fluid bolus), and medication preparation at the bedside by clinicians who may not possess the experience and training to mix these agents.

From a patient-safety perspective, Holden et al⁵ noted the potential for dosing error with significant adverse medical consequence related to PDP, as well as several contributing issues. First, they highlight the lack of a solid literature base to support administration of PDP in the ED and the development of decision-making guidelines for use in the ED. They also observed an inconsistency in approach to patient selection, medication choice, agent preparation, dosing, and other therapies. As seen in the Acquisto et al⁴ report, the patient-care scenarios are high risk and quite dynamic.

Conclusion

Bolus-dose vasopressor therapy is a potentially very useful treatment in the ED and other emergency/critical care settings. However, despite its benefits in treating patients in shock or with hypoperfusion, PDP is not widely used in EM due to the lack of studies, reviews, and guidelines in the literature to support its use in the ED. Such a literature base is required to provide an appropriate, safe means of patient selection, medication choice, dosing, and administration. Continued educational and research efforts are needed to more fully explore the use of PDP therapy in the ED.

When used correctly and appropriately, PDP has promise to be an important aid in the management of shock in the ED. Although bolus-dose therapy is appropriate for select clinical scenarios involving significant shock states which have the potential for progression to complete CV collapse without timely therapy, it is an adjunct to, not a replacement for commonly employed and medically indicated therapies such as crystalloid bolus or continuous vasopressor infusions.

The use of bolus-dose vasopressors in anesthesiology and other areas of critical care medicine is well known. This common medical intervention, however, is not often employed in emergency medicine (EM). Bolus-dose vasopressors are defined as the administration of small bolus doses of vasopressor agents, such as epinephrine or phenylephrine, to patients with compromised perfusion who continue to have a pulse (ie, these patients are not in cardiac arrest). This intervention is considered as a temporizing measure for transient hypotension or as a bridge to more definitive therapy.

Clinical Application

Bolus-dose vasopressive therapy is also referred to as push-dose pressor (PDP) therapy—a term coined by Weingart.^1-3 Theoretically, any vasopressor could be used in a mini-dose, bolus fashion, though in current clinical practice, anesthesiologists primarily employ ephedrine, epinephrine, and phenylephrine. Two of these agents are likely more appropriate for the ED, including epinephrine and phenylephrine. Both of these agents have a short half-life and therefore an abbreviated period of effect. In addition, dosing and related administration of epinephrine and phenylephrine is relatively straightforward. Moreover, most emergency physicians and nurses are quite familiar with both agents.

With respect to ephedrine, due to its longer half-life, complex dosing regimen, and associated higher-incidence of cardiovascular (CV) complications, its use is likely not appropriate in the ED as a bolus-dose vasopressor.

Epinephrine and Phenylephrine

Epinephrine is a potent sympathomimetic agent with alpha- and beta-receptor activity. In addition to its vasopressor effects, epinephrine is also an inotropic and chronotropic agent, increasing cardiac output, heart rate (HR), and systemic vascular resistance, which can markedly improve perfusion. Epinephrine also can be given to patients with hypoperfusion and/or shock due to low-cardiac output with or without vasodilation, lacking significant tachycardia.

Phenylephrine is a pure alpha agonist and therefore does not appreciably affect cardiac output and HR, but does significantly increase systemic vascular resistance and thus systemic perfusion. Phenylephrine can be used to treat patients with hypoperfusion and/or shock states due to vasodilation with coexistent, significant tachycardia.

Preparation and Administration

The preparation and dosing of push-dose epinephrine and phenylephrine are not particularly complex. Many clinicians recommend the pre-mixed, manufacturer-prepared agents for PDP therapy. These premixed formulations not only facilitate administration, but also reduce the chance of a preparation error that can result in incorrect dosing.^3-5 If pre-mixed formulations are not available, clinicians can readily prepare epinephrine and phenylephrine for PDP use.

Push-Dose Epinephrine. Clinicians can prepare epinephrine for push-dose administration as follows:^1-3

• Obtain 1 mL of epinephrine 1:10,000 (ie, 0.1 mg/mL or 100 mcg/mL);
• Obtain a 10 mL syringe of normal saline and remove 1 mL;
• Inject the 1 mL of epinephrine 1:10,000 (100 mcg/mL) into this syringe containing 9 mL of normal saline; and
• Result: 10 mL of epinephrine (10 mcg/mL), with each 1 mL of this solution containing 10 mcg of epinephrine.

Administration of push-dose epinephrine (10 mcg/mL) produces effect within 1 minute of use with a duration of approximately 5 to 10 minutes. Dosing at this concentration ranges from 0.5 to 2.0 mL every 2 to 5 minutes, delivering 5 to 20 mcg.^1-3Push-Dose Phenylephrine. To prepare phenylephrine for push-dose administration, clinicians may use the following approach:^1-3

• Obtain 1 mL of phenylephrine (10 mg/mL concentration);
• Inject this 1 mL of phenylephrine (10 mg/mL) into a 100 mL bag of normal saline; and
• Result: 100 mL of phenylephrine (100 mcg/mL), with each 1 mL of this solution containing 100 mcg of phenylephrine.

Administration of push-dose phenylephrine (100 mcg/mL) produces effect within 1 minute of use with a duration of approximately 10 to 20 minutes. Dosing at this concentration ranges from 0.5 to 2.0 mL every 2 to 5 minutes, delivering 50 to 200 mcg.^1-3Alternative Push-Dose Preparations for Phenylephrine. Two other methods of preparing phenylephrine for bolus-dose administration include the following: (1) the addition of phenylephrine 20 mg to a bag of 250 cc of normal saline, resulting in an 80 mcg/mL concentration; and/or (2) phenylephrine (20 mg) is commercially available for continuous infusion in a 250 mL bag of normal saline, yielding the same concentration of 80 mcg/mL; in either case, medication can be drawn up and administered. Dosing at this concentration ranges from 0.5 to 2.5 mL every 2 to 5 minutes, delivering 40 to 200 mcg. Lastly, phenylephrine is also commercially available in pre-made mixtures, specifically manufactured for bolus-dose therapy.

Indications

Both epinephrine and phenylephrine can be considered in the management of significant transient or sustained hypoperfusion. Although the definition of significant hypotension is complex, Brunauer et al⁶ have suggested that a mean arterial pressure (MAP) of approximately 35 mm Hg is associated with a significant risk of CV collapse. Of course, a MAP of 40 to 50 mm Hg is also very concerning clinically, with significant risk of deterioration and CV collapse.

Procedural events, such as conscious sedation or rapid sequence intubation (RSI), can produce significant hypotension; PDP can rapidly correct hypotension. In other clinical scenarios in which sustained hypotension is likely and not transient (eg, sepsis with shock), PDP can be used as a bridge to definitive care (eg, volume replacement, continuous vasopressor infusion). It is important to note, however, that PDP administration must occur in conjunction with or after the patient has received other appropriate therapies such as a normal saline bolus and continuous vasopressor infusions. Push-dose pressors are not a replacement for these proven interventions, but rather are an important augmentation to these therapies.

Emergency Medicine Literature

As previously noted, the literature base describing and supporting the clinical use of PDP in EM is extremely limited. The few articles that comprise this literature base address significant hypotension in periendotracheal intubation intervention, post-return of spontaneous circulation (ROSC) management, and shock management with preload augmentation.^7-9In addition, there are several articles in the literature that address safety concerns surrounding the use of PDP in the ED.^4,5

Panchal et al¹⁰ investigated the use of phenylephrine in hypotensive patients undergoing RSI-assisted endotracheal intubation. The authors performed a 1-year retrospective review of hypotensive patients managed with endotracheal intubation for a range of clinical conditions that required clinical care intervention. In this study, 20 of the 119 patients received phenylephrine in the peri-intubation period. A range of clinical conditions requiring critical care intervention were encountered; in addition, almost three-quarters of these patients were receiving at least one other vasopressor infusion. Further differences were seen in the timing of PDP administration. In those patients receiving bolus-dose phenylephrine, blood pressure (BP) improved without change in HR. Panchal et al¹⁰ concluded that while push-dose phenylephrine improved hemodynamic status, there was significant variation among clinicians regarding dosing, timing of use, and overall clinical situation The significant variation in PDP management in this study was noted to be a potential source of medical error, thus increasing the chance of adverse clinical event.

Push-dose pressor therapy can be employed for significant hypotension while more definitive therapy is being readied and applied. For instance, patients with significant hypotension requiring continuous vasopressor infusion can be managed with PDP while appropriate venous access is established, intravenous fluids are administered, and medications are prepared. The immediate period after resuscitation from cardiac arrest can be complicated by shock of many types. In fact, hypotension following ROSC in the cardiac arrest patient is not uncommon and has been identified as a risk issue associated with poor outcome. Prompt treatment of this altered perfusion may improve outcome. Gottlieb⁸ described three patients with ROSC after cardiac arrest. All three patients experienced significant, sustained hypotension with systolic blood pressure reading in the 50 to 60 mm Hg range; bolus-dose epinephrine was administered with significant improvement in the hemodynamic status while central venous access was established.

In a related clinical scenario, Schwartz et al⁹ considered the impact of PDP on central venous line (CVL) placement with continuous vasopressor infusion. In this ED study, although patients experienced an increase in BP, this impact was transient with approximately half of these individuals ultimately requiring CVL. In addition, serious adverse effect was noted more commonly in the phenylephrine-treated patients with “reactive” hypertension and ventricular tachycardia occurring in study patients.

Patient-Safety Considerations

In addition to the limited literature base supporting PDP use in the ED, another major significant issue focuses on safety concerns and adverse effects. Extremely limited data is available describing adverse events related to ED-administered PDP. Extrapolating from other EM and critical care administrations of peripheral epinephrine, both local and systemic adverse effects have been reported.^11,12 The range of adverse events noted in these studies are considerable, including local skin and soft-tissue injury (necrosis), end-organ tissue ischemia (eg, digits, tip of nose), acute hypertension, cardiac ischemic events, and left ventricular (LV) dysfunction.^11,12

When comparing peripheral infusion with central infusion, the risk of extravasation with resultant local tissue injury is markedly greater with peripheral vasopressor administration. In a systematic review of this issue, Loubani and Green¹¹ noted that such local adverse events were much more commonly associated with peripheral administration.

In another report of vasopressor use in the ED, Kanwar et al¹² described apparent confusion with epinephrine dosing and route of administration, resulting in very significant, systemic CV maladies, including severe elevations in BP, acute LV dysfunction, and chest pain associated with ST segment elevation.

It must be stressed that the publications by Loubani and Green¹¹ and Kanwar et al¹² described peripheral vasopressor administration: neither study included PDP therapy. Therefore, as previously noted, the aforementioned statements are extrapolated from when applied to PDP strategy.

Acquisto et al⁴ describe several errors in medication administration of PDP in the ED and other critical care areas of the hospital. In this report, all treating physicians were present at the patients’ bedside, either administering the medication or directly supervising its use. Agents involved included epinephrine and phenylephrine, delivered at exceedingly high doses. In their study, the authors noted several issues which they believe contributed to medication errors, including heterogeneity of pathology treated in these patients, apparent “earlier-than-appropriate” use of vasopressors (ie, prior to giving an appropriate fluid bolus), and medication preparation at the bedside by clinicians who may not possess the experience and training to mix these agents.

From a patient-safety perspective, Holden et al⁵ noted the potential for dosing error with significant adverse medical consequence related to PDP, as well as several contributing issues. First, they highlight the lack of a solid literature base to support administration of PDP in the ED and the development of decision-making guidelines for use in the ED. They also observed an inconsistency in approach to patient selection, medication choice, agent preparation, dosing, and other therapies. As seen in the Acquisto et al⁴ report, the patient-care scenarios are high risk and quite dynamic.

Conclusion

Bolus-dose vasopressor therapy is a potentially very useful treatment in the ED and other emergency/critical care settings. However, despite its benefits in treating patients in shock or with hypoperfusion, PDP is not widely used in EM due to the lack of studies, reviews, and guidelines in the literature to support its use in the ED. Such a literature base is required to provide an appropriate, safe means of patient selection, medication choice, dosing, and administration. Continued educational and research efforts are needed to more fully explore the use of PDP therapy in the ED.

When used correctly and appropriately, PDP has promise to be an important aid in the management of shock in the ED. Although bolus-dose therapy is appropriate for select clinical scenarios involving significant shock states which have the potential for progression to complete CV collapse without timely therapy, it is an adjunct to, not a replacement for commonly employed and medically indicated therapies such as crystalloid bolus or continuous vasopressor infusions.

The use of bolus-dose vasopressors in anesthesiology and other areas of critical care medicine is well known. This common medical intervention, however, is not often employed in emergency medicine (EM). Bolus-dose vasopressors are defined as the administration of small bolus doses of vasopressor agents, such as epinephrine or phenylephrine, to patients with compromised perfusion who continue to have a pulse (ie, these patients are not in cardiac arrest). This intervention is considered as a temporizing measure for transient hypotension or as a bridge to more definitive therapy.

Clinical Application

Bolus-dose vasopressive therapy is also referred to as push-dose pressor (PDP) therapy—a term coined by Weingart.^1-3 Theoretically, any vasopressor could be used in a mini-dose, bolus fashion, though in current clinical practice, anesthesiologists primarily employ ephedrine, epinephrine, and phenylephrine. Two of these agents are likely more appropriate for the ED, including epinephrine and phenylephrine. Both of these agents have a short half-life and therefore an abbreviated period of effect. In addition, dosing and related administration of epinephrine and phenylephrine is relatively straightforward. Moreover, most emergency physicians and nurses are quite familiar with both agents.

With respect to ephedrine, due to its longer half-life, complex dosing regimen, and associated higher-incidence of cardiovascular (CV) complications, its use is likely not appropriate in the ED as a bolus-dose vasopressor.

Epinephrine and Phenylephrine

Epinephrine is a potent sympathomimetic agent with alpha- and beta-receptor activity. In addition to its vasopressor effects, epinephrine is also an inotropic and chronotropic agent, increasing cardiac output, heart rate (HR), and systemic vascular resistance, which can markedly improve perfusion. Epinephrine also can be given to patients with hypoperfusion and/or shock due to low-cardiac output with or without vasodilation, lacking significant tachycardia.

Phenylephrine is a pure alpha agonist and therefore does not appreciably affect cardiac output and HR, but does significantly increase systemic vascular resistance and thus systemic perfusion. Phenylephrine can be used to treat patients with hypoperfusion and/or shock states due to vasodilation with coexistent, significant tachycardia.

Preparation and Administration

The preparation and dosing of push-dose epinephrine and phenylephrine are not particularly complex. Many clinicians recommend the pre-mixed, manufacturer-prepared agents for PDP therapy. These premixed formulations not only facilitate administration, but also reduce the chance of a preparation error that can result in incorrect dosing.^3-5 If pre-mixed formulations are not available, clinicians can readily prepare epinephrine and phenylephrine for PDP use.

Push-Dose Epinephrine. Clinicians can prepare epinephrine for push-dose administration as follows:^1-3

• Obtain 1 mL of epinephrine 1:10,000 (ie, 0.1 mg/mL or 100 mcg/mL);
• Obtain a 10 mL syringe of normal saline and remove 1 mL;
• Inject the 1 mL of epinephrine 1:10,000 (100 mcg/mL) into this syringe containing 9 mL of normal saline; and
• Result: 10 mL of epinephrine (10 mcg/mL), with each 1 mL of this solution containing 10 mcg of epinephrine.

Administration of push-dose epinephrine (10 mcg/mL) produces effect within 1 minute of use with a duration of approximately 5 to 10 minutes. Dosing at this concentration ranges from 0.5 to 2.0 mL every 2 to 5 minutes, delivering 5 to 20 mcg.^1-3Push-Dose Phenylephrine. To prepare phenylephrine for push-dose administration, clinicians may use the following approach:^1-3

• Obtain 1 mL of phenylephrine (10 mg/mL concentration);
• Inject this 1 mL of phenylephrine (10 mg/mL) into a 100 mL bag of normal saline; and
• Result: 100 mL of phenylephrine (100 mcg/mL), with each 1 mL of this solution containing 100 mcg of phenylephrine.

Administration of push-dose phenylephrine (100 mcg/mL) produces effect within 1 minute of use with a duration of approximately 10 to 20 minutes. Dosing at this concentration ranges from 0.5 to 2.0 mL every 2 to 5 minutes, delivering 50 to 200 mcg.^1-3Alternative Push-Dose Preparations for Phenylephrine. Two other methods of preparing phenylephrine for bolus-dose administration include the following: (1) the addition of phenylephrine 20 mg to a bag of 250 cc of normal saline, resulting in an 80 mcg/mL concentration; and/or (2) phenylephrine (20 mg) is commercially available for continuous infusion in a 250 mL bag of normal saline, yielding the same concentration of 80 mcg/mL; in either case, medication can be drawn up and administered. Dosing at this concentration ranges from 0.5 to 2.5 mL every 2 to 5 minutes, delivering 40 to 200 mcg. Lastly, phenylephrine is also commercially available in pre-made mixtures, specifically manufactured for bolus-dose therapy.

Indications

Both epinephrine and phenylephrine can be considered in the management of significant transient or sustained hypoperfusion. Although the definition of significant hypotension is complex, Brunauer et al⁶ have suggested that a mean arterial pressure (MAP) of approximately 35 mm Hg is associated with a significant risk of CV collapse. Of course, a MAP of 40 to 50 mm Hg is also very concerning clinically, with significant risk of deterioration and CV collapse.

Procedural events, such as conscious sedation or rapid sequence intubation (RSI), can produce significant hypotension; PDP can rapidly correct hypotension. In other clinical scenarios in which sustained hypotension is likely and not transient (eg, sepsis with shock), PDP can be used as a bridge to definitive care (eg, volume replacement, continuous vasopressor infusion). It is important to note, however, that PDP administration must occur in conjunction with or after the patient has received other appropriate therapies such as a normal saline bolus and continuous vasopressor infusions. Push-dose pressors are not a replacement for these proven interventions, but rather are an important augmentation to these therapies.

Emergency Medicine Literature

As previously noted, the literature base describing and supporting the clinical use of PDP in EM is extremely limited. The few articles that comprise this literature base address significant hypotension in periendotracheal intubation intervention, post-return of spontaneous circulation (ROSC) management, and shock management with preload augmentation.^7-9In addition, there are several articles in the literature that address safety concerns surrounding the use of PDP in the ED.^4,5

Panchal et al¹⁰ investigated the use of phenylephrine in hypotensive patients undergoing RSI-assisted endotracheal intubation. The authors performed a 1-year retrospective review of hypotensive patients managed with endotracheal intubation for a range of clinical conditions that required clinical care intervention. In this study, 20 of the 119 patients received phenylephrine in the peri-intubation period. A range of clinical conditions requiring critical care intervention were encountered; in addition, almost three-quarters of these patients were receiving at least one other vasopressor infusion. Further differences were seen in the timing of PDP administration. In those patients receiving bolus-dose phenylephrine, blood pressure (BP) improved without change in HR. Panchal et al¹⁰ concluded that while push-dose phenylephrine improved hemodynamic status, there was significant variation among clinicians regarding dosing, timing of use, and overall clinical situation The significant variation in PDP management in this study was noted to be a potential source of medical error, thus increasing the chance of adverse clinical event.

Push-dose pressor therapy can be employed for significant hypotension while more definitive therapy is being readied and applied. For instance, patients with significant hypotension requiring continuous vasopressor infusion can be managed with PDP while appropriate venous access is established, intravenous fluids are administered, and medications are prepared. The immediate period after resuscitation from cardiac arrest can be complicated by shock of many types. In fact, hypotension following ROSC in the cardiac arrest patient is not uncommon and has been identified as a risk issue associated with poor outcome. Prompt treatment of this altered perfusion may improve outcome. Gottlieb⁸ described three patients with ROSC after cardiac arrest. All three patients experienced significant, sustained hypotension with systolic blood pressure reading in the 50 to 60 mm Hg range; bolus-dose epinephrine was administered with significant improvement in the hemodynamic status while central venous access was established.

In a related clinical scenario, Schwartz et al⁹ considered the impact of PDP on central venous line (CVL) placement with continuous vasopressor infusion. In this ED study, although patients experienced an increase in BP, this impact was transient with approximately half of these individuals ultimately requiring CVL. In addition, serious adverse effect was noted more commonly in the phenylephrine-treated patients with “reactive” hypertension and ventricular tachycardia occurring in study patients.

Patient-Safety Considerations

In addition to the limited literature base supporting PDP use in the ED, another major significant issue focuses on safety concerns and adverse effects. Extremely limited data is available describing adverse events related to ED-administered PDP. Extrapolating from other EM and critical care administrations of peripheral epinephrine, both local and systemic adverse effects have been reported.^11,12 The range of adverse events noted in these studies are considerable, including local skin and soft-tissue injury (necrosis), end-organ tissue ischemia (eg, digits, tip of nose), acute hypertension, cardiac ischemic events, and left ventricular (LV) dysfunction.^11,12

When comparing peripheral infusion with central infusion, the risk of extravasation with resultant local tissue injury is markedly greater with peripheral vasopressor administration. In a systematic review of this issue, Loubani and Green¹¹ noted that such local adverse events were much more commonly associated with peripheral administration.

In another report of vasopressor use in the ED, Kanwar et al¹² described apparent confusion with epinephrine dosing and route of administration, resulting in very significant, systemic CV maladies, including severe elevations in BP, acute LV dysfunction, and chest pain associated with ST segment elevation.

It must be stressed that the publications by Loubani and Green¹¹ and Kanwar et al¹² described peripheral vasopressor administration: neither study included PDP therapy. Therefore, as previously noted, the aforementioned statements are extrapolated from when applied to PDP strategy.

Acquisto et al⁴ describe several errors in medication administration of PDP in the ED and other critical care areas of the hospital. In this report, all treating physicians were present at the patients’ bedside, either administering the medication or directly supervising its use. Agents involved included epinephrine and phenylephrine, delivered at exceedingly high doses. In their study, the authors noted several issues which they believe contributed to medication errors, including heterogeneity of pathology treated in these patients, apparent “earlier-than-appropriate” use of vasopressors (ie, prior to giving an appropriate fluid bolus), and medication preparation at the bedside by clinicians who may not possess the experience and training to mix these agents.

From a patient-safety perspective, Holden et al⁵ noted the potential for dosing error with significant adverse medical consequence related to PDP, as well as several contributing issues. First, they highlight the lack of a solid literature base to support administration of PDP in the ED and the development of decision-making guidelines for use in the ED. They also observed an inconsistency in approach to patient selection, medication choice, agent preparation, dosing, and other therapies. As seen in the Acquisto et al⁴ report, the patient-care scenarios are high risk and quite dynamic.

Conclusion

Bolus-dose vasopressor therapy is a potentially very useful treatment in the ED and other emergency/critical care settings. However, despite its benefits in treating patients in shock or with hypoperfusion, PDP is not widely used in EM due to the lack of studies, reviews, and guidelines in the literature to support its use in the ED. Such a literature base is required to provide an appropriate, safe means of patient selection, medication choice, dosing, and administration. Continued educational and research efforts are needed to more fully explore the use of PDP therapy in the ED.

When used correctly and appropriately, PDP has promise to be an important aid in the management of shock in the ED. Although bolus-dose therapy is appropriate for select clinical scenarios involving significant shock states which have the potential for progression to complete CV collapse without timely therapy, it is an adjunct to, not a replacement for commonly employed and medically indicated therapies such as crystalloid bolus or continuous vasopressor infusions.

The likelihood that a trauma or acute care surgeon will encounter or treat a transgender patient in an emergency setting is increasing every year.

The number of patients who self-identify as transgender and who have undergone both medical and/or surgical gender-affirming treatment is on the rise. The trend has accelerated since private insurers, Medicare, and Medicaid are now covering some of the costs (JAMA Surg. 2018 Feb 28. doi: 10.1001/jamasurg.2017.6231).

Privacy concerns can be of particular sensitivity. “Care must be taken to maintain privacy for the patient, as others outside of the hospital may not know they are transgender. Consultation with the patient’s primary care provider may be beneficial to determine the extent of gender-affirmation and the patient’s disclosure to family and friends,” the investigator advised. In addition, the clinician needs to establish which if any nonmedical interventions the transgender patients has had. These may include nonprescription hormone therapy and silicone injections.

The encounter should include an evaluation for injury to genitalia. “Transgender patients may have significant dysphoria associated with their preoperative genitals,” Dr. Mandell and his coauthors said. In these cases, “involvement of providers experienced with examination of transgender patients should be sought, if possible.” These patients should be screened for potential abuse by a companion or self-injury, the investigators suggested.

Dr. Mandell and his coauthors also discussed some of the nuances of trauma care for this population. For example, transgender women may need a smaller endotracheal tube for establishing an airway as intubation to avoid damaging surgically altered vocal chords. Other craniofacial alterations can get in the way of establishing an airway. Clinicians also should keep in mind the increased likelihood of a venous thromboembolism from estrogen hormone therapy in immobilized transgender patients in the trauma setting. Implants and surgical alterations can add a layer of complexity to reading images. Anatomical rearrangement can make catheterization challenging.

Dr. Mandell and his coauthors concluded, “Further research is needed on the appropriate management of cross-gender hormones, dosing of medications and nutrition, and the special considerations for injury patterns and risks in transgender patients. Development of a system for quickly determining the state of gender-affirmation of the patient in regards to hormone therapy, surgeries, and social aspects may prove beneficial to providers in the setting of trauma, but involvement of the transgender population in the development of any such system is crucial.”

Eileen M. Bulger, MD, FACS, Chair ACS Committee on Trauma and one of the coauthors of the study, views the findings as potentially useful to meet the training deficit on transgender trauma issues. “As trauma surgeons, we strive to provide optimal care by attending to the physical, psychological, and social needs of our patients. This review raises awareness of critical issues to consider when caring for transgender patients and should be included in our educational programs for trauma fellowship training and used as a resource to raise awareness in our trauma centers.”

Dr. Mandell and his coauthors reported having no financial disclosures.

The likelihood that a trauma or acute care surgeon will encounter or treat a transgender patient in an emergency setting is increasing every year.

The number of patients who self-identify as transgender and who have undergone both medical and/or surgical gender-affirming treatment is on the rise. The trend has accelerated since private insurers, Medicare, and Medicaid are now covering some of the costs (JAMA Surg. 2018 Feb 28. doi: 10.1001/jamasurg.2017.6231).

Privacy concerns can be of particular sensitivity. “Care must be taken to maintain privacy for the patient, as others outside of the hospital may not know they are transgender. Consultation with the patient’s primary care provider may be beneficial to determine the extent of gender-affirmation and the patient’s disclosure to family and friends,” the investigator advised. In addition, the clinician needs to establish which if any nonmedical interventions the transgender patients has had. These may include nonprescription hormone therapy and silicone injections.

The encounter should include an evaluation for injury to genitalia. “Transgender patients may have significant dysphoria associated with their preoperative genitals,” Dr. Mandell and his coauthors said. In these cases, “involvement of providers experienced with examination of transgender patients should be sought, if possible.” These patients should be screened for potential abuse by a companion or self-injury, the investigators suggested.

Dr. Mandell and his coauthors also discussed some of the nuances of trauma care for this population. For example, transgender women may need a smaller endotracheal tube for establishing an airway as intubation to avoid damaging surgically altered vocal chords. Other craniofacial alterations can get in the way of establishing an airway. Clinicians also should keep in mind the increased likelihood of a venous thromboembolism from estrogen hormone therapy in immobilized transgender patients in the trauma setting. Implants and surgical alterations can add a layer of complexity to reading images. Anatomical rearrangement can make catheterization challenging.

Dr. Mandell and his coauthors concluded, “Further research is needed on the appropriate management of cross-gender hormones, dosing of medications and nutrition, and the special considerations for injury patterns and risks in transgender patients. Development of a system for quickly determining the state of gender-affirmation of the patient in regards to hormone therapy, surgeries, and social aspects may prove beneficial to providers in the setting of trauma, but involvement of the transgender population in the development of any such system is crucial.”

Eileen M. Bulger, MD, FACS, Chair ACS Committee on Trauma and one of the coauthors of the study, views the findings as potentially useful to meet the training deficit on transgender trauma issues. “As trauma surgeons, we strive to provide optimal care by attending to the physical, psychological, and social needs of our patients. This review raises awareness of critical issues to consider when caring for transgender patients and should be included in our educational programs for trauma fellowship training and used as a resource to raise awareness in our trauma centers.”

Dr. Mandell and his coauthors reported having no financial disclosures.

The likelihood that a trauma or acute care surgeon will encounter or treat a transgender patient in an emergency setting is increasing every year.

The number of patients who self-identify as transgender and who have undergone both medical and/or surgical gender-affirming treatment is on the rise. The trend has accelerated since private insurers, Medicare, and Medicaid are now covering some of the costs (JAMA Surg. 2018 Feb 28. doi: 10.1001/jamasurg.2017.6231).

Privacy concerns can be of particular sensitivity. “Care must be taken to maintain privacy for the patient, as others outside of the hospital may not know they are transgender. Consultation with the patient’s primary care provider may be beneficial to determine the extent of gender-affirmation and the patient’s disclosure to family and friends,” the investigator advised. In addition, the clinician needs to establish which if any nonmedical interventions the transgender patients has had. These may include nonprescription hormone therapy and silicone injections.

The encounter should include an evaluation for injury to genitalia. “Transgender patients may have significant dysphoria associated with their preoperative genitals,” Dr. Mandell and his coauthors said. In these cases, “involvement of providers experienced with examination of transgender patients should be sought, if possible.” These patients should be screened for potential abuse by a companion or self-injury, the investigators suggested.

Dr. Mandell and his coauthors also discussed some of the nuances of trauma care for this population. For example, transgender women may need a smaller endotracheal tube for establishing an airway as intubation to avoid damaging surgically altered vocal chords. Other craniofacial alterations can get in the way of establishing an airway. Clinicians also should keep in mind the increased likelihood of a venous thromboembolism from estrogen hormone therapy in immobilized transgender patients in the trauma setting. Implants and surgical alterations can add a layer of complexity to reading images. Anatomical rearrangement can make catheterization challenging.

Dr. Mandell and his coauthors concluded, “Further research is needed on the appropriate management of cross-gender hormones, dosing of medications and nutrition, and the special considerations for injury patterns and risks in transgender patients. Development of a system for quickly determining the state of gender-affirmation of the patient in regards to hormone therapy, surgeries, and social aspects may prove beneficial to providers in the setting of trauma, but involvement of the transgender population in the development of any such system is crucial.”

Eileen M. Bulger, MD, FACS, Chair ACS Committee on Trauma and one of the coauthors of the study, views the findings as potentially useful to meet the training deficit on transgender trauma issues. “As trauma surgeons, we strive to provide optimal care by attending to the physical, psychological, and social needs of our patients. This review raises awareness of critical issues to consider when caring for transgender patients and should be included in our educational programs for trauma fellowship training and used as a resource to raise awareness in our trauma centers.”

Dr. Mandell and his coauthors reported having no financial disclosures.

CHICAGO – Women who have treatment for breast cancer seldom talk about the costs of care with their medical team, but a study out of Duke University has found that more than one-third reported having a financial burden from their breast cancer treatment, even among women with health insurance, according to a report presented at the Society of Surgical Oncology Annual Cancer Symposium.

“The financial harm associated with cancer treatment is now known as ‘financial toxicity,’ ” Rachel A. Greenup, MD, MPH, said in reporting the results of an 88-item survey completed by 654 adult women who had treatment for breast cancer. The women were recruited through the Army of Women of the Dr. Susan Love Research Foundation and The Sister’s Network of North Carolina, an African-American breast cancer survivors’ organization.

Overall, 69% of survey respondents had private insurance and 26% had Medicare. Of the patients surveyed, 94% had breast cancer surgery: 40.6% lumpectomy, 23.7% mastectomy, and 29.7% bilateral mastectomy; 34% also had breast reconstruction. Among those surveyed, 43% reported considering costs in their treatment decision. Of these, 29% considered costs when making surgical treatment decisions, including 14% who reported that costs were “extremely” important.

Despite the high levels of insurance coverage, 35% of the study participants reported a financial burden resulting from cancer treatment, ranging from “somewhat” burdensome to “catastrophic.” The median out-of-pocket cost for the study participants was $4,000, and 5% exceeded $40,000 in such costs, Dr. Greenup said. “The risk of financial harm and increased out-of-pocket costs to patients differed by surgery type,” with higher financial burdens seen in women who underwent bilateral mastectomy.

Cost was one of many factors survey participants reported considering when making surgical treatment decisions, but the most important factors were the opinions and advice of the medical team and the individual patient’s fear of recurrence. However, in lower-income women, cost factored more significantly in decision making. “In a subset of women who reported an annual income of $45,000 a year or less, cost of treatment gained importance and, interestingly, became more important than many variables we routinely discuss – for example, appearance of the breast, sexuality, avoiding radiation, and breast preservation,” Dr. Greenup said. “An income of $74,000 a year was the tipping point at which women reported incorporating costs into their cancer treatment decisions.”

She added that younger, minority women who did not have Medicare coverage were more likely to consider costs in breast cancer treatment decisions.

Most women surveyed (79%) said they preferred to know their out-of-pocket costs before they begin treatment, Dr. Greenup said, “and 40% believed that we as physicians should be considering out-of-pocket costs while making medical decisions.” However, 78% of those surveyed said they never discussed costs with their cancer team – despite American Society of Clinical Oncologists guidelines, she pointed out – and 35% said their treatment costs were higher than expected.

Dr. Greenup described the study population as “well engaged … with good insurance and strong educational background that likely does not reflect the general population.” The results may not be generalizable. “We expect that in a general cohort of women, our findings would be even more exaggerated,” she said.

The study points out the need to better understand how cost transparency may affect breast cancer treatment decisions, Dr. Greenup said. “As eligible women with breast cancer choose between surgical options, it’s important that we consider the potential risk of financial harm as we guide them through these difficult treatment decisions,” she said.

Dr. Greenup and her study coauthors reported having no financial disclosures.

[email protected]

SOURCE: Greenup RA. SSO 2018, Abstract No. 24.

CHICAGO – Women who have treatment for breast cancer seldom talk about the costs of care with their medical team, but a study out of Duke University has found that more than one-third reported having a financial burden from their breast cancer treatment, even among women with health insurance, according to a report presented at the Society of Surgical Oncology Annual Cancer Symposium.

“The financial harm associated with cancer treatment is now known as ‘financial toxicity,’ ” Rachel A. Greenup, MD, MPH, said in reporting the results of an 88-item survey completed by 654 adult women who had treatment for breast cancer. The women were recruited through the Army of Women of the Dr. Susan Love Research Foundation and The Sister’s Network of North Carolina, an African-American breast cancer survivors’ organization.

Overall, 69% of survey respondents had private insurance and 26% had Medicare. Of the patients surveyed, 94% had breast cancer surgery: 40.6% lumpectomy, 23.7% mastectomy, and 29.7% bilateral mastectomy; 34% also had breast reconstruction. Among those surveyed, 43% reported considering costs in their treatment decision. Of these, 29% considered costs when making surgical treatment decisions, including 14% who reported that costs were “extremely” important.

Despite the high levels of insurance coverage, 35% of the study participants reported a financial burden resulting from cancer treatment, ranging from “somewhat” burdensome to “catastrophic.” The median out-of-pocket cost for the study participants was $4,000, and 5% exceeded $40,000 in such costs, Dr. Greenup said. “The risk of financial harm and increased out-of-pocket costs to patients differed by surgery type,” with higher financial burdens seen in women who underwent bilateral mastectomy.

Cost was one of many factors survey participants reported considering when making surgical treatment decisions, but the most important factors were the opinions and advice of the medical team and the individual patient’s fear of recurrence. However, in lower-income women, cost factored more significantly in decision making. “In a subset of women who reported an annual income of $45,000 a year or less, cost of treatment gained importance and, interestingly, became more important than many variables we routinely discuss – for example, appearance of the breast, sexuality, avoiding radiation, and breast preservation,” Dr. Greenup said. “An income of $74,000 a year was the tipping point at which women reported incorporating costs into their cancer treatment decisions.”

She added that younger, minority women who did not have Medicare coverage were more likely to consider costs in breast cancer treatment decisions.

Most women surveyed (79%) said they preferred to know their out-of-pocket costs before they begin treatment, Dr. Greenup said, “and 40% believed that we as physicians should be considering out-of-pocket costs while making medical decisions.” However, 78% of those surveyed said they never discussed costs with their cancer team – despite American Society of Clinical Oncologists guidelines, she pointed out – and 35% said their treatment costs were higher than expected.

Dr. Greenup described the study population as “well engaged … with good insurance and strong educational background that likely does not reflect the general population.” The results may not be generalizable. “We expect that in a general cohort of women, our findings would be even more exaggerated,” she said.

The study points out the need to better understand how cost transparency may affect breast cancer treatment decisions, Dr. Greenup said. “As eligible women with breast cancer choose between surgical options, it’s important that we consider the potential risk of financial harm as we guide them through these difficult treatment decisions,” she said.

Dr. Greenup and her study coauthors reported having no financial disclosures.

[email protected]

SOURCE: Greenup RA. SSO 2018, Abstract No. 24.

CHICAGO – Women who have treatment for breast cancer seldom talk about the costs of care with their medical team, but a study out of Duke University has found that more than one-third reported having a financial burden from their breast cancer treatment, even among women with health insurance, according to a report presented at the Society of Surgical Oncology Annual Cancer Symposium.

“The financial harm associated with cancer treatment is now known as ‘financial toxicity,’ ” Rachel A. Greenup, MD, MPH, said in reporting the results of an 88-item survey completed by 654 adult women who had treatment for breast cancer. The women were recruited through the Army of Women of the Dr. Susan Love Research Foundation and The Sister’s Network of North Carolina, an African-American breast cancer survivors’ organization.

Overall, 69% of survey respondents had private insurance and 26% had Medicare. Of the patients surveyed, 94% had breast cancer surgery: 40.6% lumpectomy, 23.7% mastectomy, and 29.7% bilateral mastectomy; 34% also had breast reconstruction. Among those surveyed, 43% reported considering costs in their treatment decision. Of these, 29% considered costs when making surgical treatment decisions, including 14% who reported that costs were “extremely” important.

Despite the high levels of insurance coverage, 35% of the study participants reported a financial burden resulting from cancer treatment, ranging from “somewhat” burdensome to “catastrophic.” The median out-of-pocket cost for the study participants was $4,000, and 5% exceeded $40,000 in such costs, Dr. Greenup said. “The risk of financial harm and increased out-of-pocket costs to patients differed by surgery type,” with higher financial burdens seen in women who underwent bilateral mastectomy.

Cost was one of many factors survey participants reported considering when making surgical treatment decisions, but the most important factors were the opinions and advice of the medical team and the individual patient’s fear of recurrence. However, in lower-income women, cost factored more significantly in decision making. “In a subset of women who reported an annual income of $45,000 a year or less, cost of treatment gained importance and, interestingly, became more important than many variables we routinely discuss – for example, appearance of the breast, sexuality, avoiding radiation, and breast preservation,” Dr. Greenup said. “An income of $74,000 a year was the tipping point at which women reported incorporating costs into their cancer treatment decisions.”

She added that younger, minority women who did not have Medicare coverage were more likely to consider costs in breast cancer treatment decisions.

Most women surveyed (79%) said they preferred to know their out-of-pocket costs before they begin treatment, Dr. Greenup said, “and 40% believed that we as physicians should be considering out-of-pocket costs while making medical decisions.” However, 78% of those surveyed said they never discussed costs with their cancer team – despite American Society of Clinical Oncologists guidelines, she pointed out – and 35% said their treatment costs were higher than expected.

Dr. Greenup described the study population as “well engaged … with good insurance and strong educational background that likely does not reflect the general population.” The results may not be generalizable. “We expect that in a general cohort of women, our findings would be even more exaggerated,” she said.

The study points out the need to better understand how cost transparency may affect breast cancer treatment decisions, Dr. Greenup said. “As eligible women with breast cancer choose between surgical options, it’s important that we consider the potential risk of financial harm as we guide them through these difficult treatment decisions,” she said.

Dr. Greenup and her study coauthors reported having no financial disclosures.

[email protected]

SOURCE: Greenup RA. SSO 2018, Abstract No. 24.

SILVER SPRING, MD.  – Members of the Food and Drug Administration Psychopharmacologic Drugs Advisory Committee voted 11 to 1 to recommend approval of lofexidine as the first nonopioid treatment option for the symptomatic treatment of opioid withdrawal.

Opioid withdrawal symptoms are the largest barrier to discontinuing opioid use, according to Louis Baxter, MD, executive medical director of the Professional Assistance Program in Princeton, N.J., who presented on behalf of U.S. WorldMeds, which plans to market lofexidine as Lucemyra.

Lofexidine, a selective alpha2-adrenergic receptor agonist that regulates norepinephrine release has been approved for management of opioid withdrawal in the United Kingdom since 1992.

The advisory committee voted to recommend lofexidine on the strength of the results of two randomized, double-blind, and placebo controlled phase 3 studies on the safety and efficacy of lofexidine for symptomatic treatment of opioid withdrawal between days 1 through 7. One study randomized 264 patients to lofexidine (134) or placebo (130), with patients in the treatment arm received 3.2 mg of lofexidine on days 1-5, then placebo until day 7. The second study randomized 603 patients to three groups, comparing high dose (3.2 mg/day) and low dose (2.4 mg/day) regimens of lofexidine to placebo; patients in the treatment arms took four smaller doses of lofexidine throughout the day to achieve the cumulative dose.

Researchers enrolled heavy users of short-acting opioids; heroin was the predominant agent. Both studies were conducted in the scenario of abrupt withdrawal, or the most intense withdrawal situation.

Symptomatic benefit was measured using the Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop), a patient reported outcome. Patients were asked to rank their symptoms as none, mild, moderate or severe across measures like feeling sick, stomach cramps, and heart pounding among other symptoms.  

Lofexidine increased completion of withdrawal treatment compared to placebo. Patients in the first study had a 5-day completion rate of 53%, compared to 35% for the placebo group. Researchers observed similar results in the 7-day completion rates the second study, with low and high dose completion rates of 42% and 40%, respectively, both of which were much higher than placebo (28%).

Lofexidine also reduced patient withdrawal symptoms, according to SOWS-Gossop scores during peak withdrawal. In the first study, SOWS-Gossop scores were 2-4 points lower in the lofexidine group compared to placebo. Similarly, the scores were significantly better in both lofexidine groups in the second study, compared to placebo, particularly on days 1 to 4. Decreasing withdrawal symptoms during this period is particularly important because this is the most vulnerable window for patient dropout, briefing documents from US WorldMeds.

Several notable adverse events occurred during the study, particularly at higher doses of lofexidine. The risk of bradycardia and hypotension are prominent in patients taking lofexidine, but these are risks associated with this class of drug, according to Mark Pirner, MD, senior medical director at US WorldMeds, who noted that “the lower dose, if that’s what ultimately gets approved [by the FDA], is safe and effective too.”

Development of lofexidine was conducted in collaboration with the National Institute on Drug Abuse and the FDA, according to briefing documents from US WorldMeds.

The Prescription Drug User Fee Act (PDUFA) for lofexidine is May 26; FDA actions on new drug applications often occur at near the PDUFA date.

The FDA is not obligated to follow the recommendations of its advisory committees.

[email protected]

SILVER SPRING, MD.  – Members of the Food and Drug Administration Psychopharmacologic Drugs Advisory Committee voted 11 to 1 to recommend approval of lofexidine as the first nonopioid treatment option for the symptomatic treatment of opioid withdrawal.

Opioid withdrawal symptoms are the largest barrier to discontinuing opioid use, according to Louis Baxter, MD, executive medical director of the Professional Assistance Program in Princeton, N.J., who presented on behalf of U.S. WorldMeds, which plans to market lofexidine as Lucemyra.

Lofexidine, a selective alpha2-adrenergic receptor agonist that regulates norepinephrine release has been approved for management of opioid withdrawal in the United Kingdom since 1992.

The advisory committee voted to recommend lofexidine on the strength of the results of two randomized, double-blind, and placebo controlled phase 3 studies on the safety and efficacy of lofexidine for symptomatic treatment of opioid withdrawal between days 1 through 7. One study randomized 264 patients to lofexidine (134) or placebo (130), with patients in the treatment arm received 3.2 mg of lofexidine on days 1-5, then placebo until day 7. The second study randomized 603 patients to three groups, comparing high dose (3.2 mg/day) and low dose (2.4 mg/day) regimens of lofexidine to placebo; patients in the treatment arms took four smaller doses of lofexidine throughout the day to achieve the cumulative dose.

Researchers enrolled heavy users of short-acting opioids; heroin was the predominant agent. Both studies were conducted in the scenario of abrupt withdrawal, or the most intense withdrawal situation.

Symptomatic benefit was measured using the Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop), a patient reported outcome. Patients were asked to rank their symptoms as none, mild, moderate or severe across measures like feeling sick, stomach cramps, and heart pounding among other symptoms.  

Lofexidine increased completion of withdrawal treatment compared to placebo. Patients in the first study had a 5-day completion rate of 53%, compared to 35% for the placebo group. Researchers observed similar results in the 7-day completion rates the second study, with low and high dose completion rates of 42% and 40%, respectively, both of which were much higher than placebo (28%).

Lofexidine also reduced patient withdrawal symptoms, according to SOWS-Gossop scores during peak withdrawal. In the first study, SOWS-Gossop scores were 2-4 points lower in the lofexidine group compared to placebo. Similarly, the scores were significantly better in both lofexidine groups in the second study, compared to placebo, particularly on days 1 to 4. Decreasing withdrawal symptoms during this period is particularly important because this is the most vulnerable window for patient dropout, briefing documents from US WorldMeds.

Several notable adverse events occurred during the study, particularly at higher doses of lofexidine. The risk of bradycardia and hypotension are prominent in patients taking lofexidine, but these are risks associated with this class of drug, according to Mark Pirner, MD, senior medical director at US WorldMeds, who noted that “the lower dose, if that’s what ultimately gets approved [by the FDA], is safe and effective too.”

Development of lofexidine was conducted in collaboration with the National Institute on Drug Abuse and the FDA, according to briefing documents from US WorldMeds.

The Prescription Drug User Fee Act (PDUFA) for lofexidine is May 26; FDA actions on new drug applications often occur at near the PDUFA date.

The FDA is not obligated to follow the recommendations of its advisory committees.

[email protected]

SILVER SPRING, MD.  – Members of the Food and Drug Administration Psychopharmacologic Drugs Advisory Committee voted 11 to 1 to recommend approval of lofexidine as the first nonopioid treatment option for the symptomatic treatment of opioid withdrawal.

Opioid withdrawal symptoms are the largest barrier to discontinuing opioid use, according to Louis Baxter, MD, executive medical director of the Professional Assistance Program in Princeton, N.J., who presented on behalf of U.S. WorldMeds, which plans to market lofexidine as Lucemyra.

Lofexidine, a selective alpha2-adrenergic receptor agonist that regulates norepinephrine release has been approved for management of opioid withdrawal in the United Kingdom since 1992.

The advisory committee voted to recommend lofexidine on the strength of the results of two randomized, double-blind, and placebo controlled phase 3 studies on the safety and efficacy of lofexidine for symptomatic treatment of opioid withdrawal between days 1 through 7. One study randomized 264 patients to lofexidine (134) or placebo (130), with patients in the treatment arm received 3.2 mg of lofexidine on days 1-5, then placebo until day 7. The second study randomized 603 patients to three groups, comparing high dose (3.2 mg/day) and low dose (2.4 mg/day) regimens of lofexidine to placebo; patients in the treatment arms took four smaller doses of lofexidine throughout the day to achieve the cumulative dose.

Researchers enrolled heavy users of short-acting opioids; heroin was the predominant agent. Both studies were conducted in the scenario of abrupt withdrawal, or the most intense withdrawal situation.

Symptomatic benefit was measured using the Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop), a patient reported outcome. Patients were asked to rank their symptoms as none, mild, moderate or severe across measures like feeling sick, stomach cramps, and heart pounding among other symptoms.  

Lofexidine increased completion of withdrawal treatment compared to placebo. Patients in the first study had a 5-day completion rate of 53%, compared to 35% for the placebo group. Researchers observed similar results in the 7-day completion rates the second study, with low and high dose completion rates of 42% and 40%, respectively, both of which were much higher than placebo (28%).

Lofexidine also reduced patient withdrawal symptoms, according to SOWS-Gossop scores during peak withdrawal. In the first study, SOWS-Gossop scores were 2-4 points lower in the lofexidine group compared to placebo. Similarly, the scores were significantly better in both lofexidine groups in the second study, compared to placebo, particularly on days 1 to 4. Decreasing withdrawal symptoms during this period is particularly important because this is the most vulnerable window for patient dropout, briefing documents from US WorldMeds.

Several notable adverse events occurred during the study, particularly at higher doses of lofexidine. The risk of bradycardia and hypotension are prominent in patients taking lofexidine, but these are risks associated with this class of drug, according to Mark Pirner, MD, senior medical director at US WorldMeds, who noted that “the lower dose, if that’s what ultimately gets approved [by the FDA], is safe and effective too.”

Development of lofexidine was conducted in collaboration with the National Institute on Drug Abuse and the FDA, according to briefing documents from US WorldMeds.

The Prescription Drug User Fee Act (PDUFA) for lofexidine is May 26; FDA actions on new drug applications often occur at near the PDUFA date.

The FDA is not obligated to follow the recommendations of its advisory committees.

[email protected]

On March 15, 2018, I had the opportunity to present on behalf of the ACS at a roundtable discussion on Capitol Hill to members of the House Ways and Means Committee on the topic of Medicare red tape relief

The roundtable provided members of this key committee of jurisdiction over Medicare policy the opportunity to hear from representatives from a variety of health care professional organizations on how Congress can improve Medicare to work more effectively and efficiently for both patients and providers. Each group was allotted just three minutes for their presentation. A summary of my presentation is included below:
 

E/M Documentation Guidelines

The ACS has significant concerns regarding Evaluation and Management (E/M) Documentation Guidelines. Though CMS created the E/M documentation guidelines 23 years ago with the laudable goal of adding structure to the various levels of E/M services, and in an effort to create a sense of equivalency of E/M services across the multitude of specialties, ACS believes the time has come to re-examine and revise these guidelines to be more appropriate in the modern digital information era.

US House Ways and Means Committee

Meaningful Measurement of Surgical Quality

I also addressed concerns relative to the meaningful measurement of surgical quality. Despite having expended significant human and financial resources toward helping Fellows succeed in MIPS, the College is becoming increasingly concerned that MIPS is not actually measuring surgical quality, and therefore, is not a quality program for surgery and serves primarily as a payment program.

As evidence, the most recent quality metric data available (from the 2015 Physician Quality Reporting System) show that many of the CMS quality measures reported by surgeons have little to do with improving the quality of the actual surgical care provided to patients. For general surgeons, the two most commonly reported measures were the documentation of a patient’s medications in the medical record and tobacco use screening. While no one would deny the importance of either of these activities, neither is of much real value in the effort to measure the quality of surgical care provided. In another, perhaps even more illustrative example, one of the most common quality measures reported by urologists was inquiring of their patients whether they had received a pneumovax. This obviously has little to do with why one would see an urologist, much less the quality of care provided.

As an organization, the ACS and its members are absolutely dedicated to improving the quality of care they provide to their patients. However, the quality measures forming the basis of the assessment of their care must first be relevant to the surgical care they provide, and second be achievable. Fellows are increasingly expressing concerns about the burdens imposed by the Quality component of MIPS and believe their efforts to participate do little to meaningfully measure the quality of surgical care they provide. I asked that the Ways and Means Committee hold a hearing specifically addressing issues relative to the Quality component of MIPS.
 

Standardizing Electronic Prior Authorization for Safe Prescribing Act

I expressed ACS’ support for the Standardizing Electronic Prior Authorization for Safe Prescribing Act, H.R. 4841, which would allow for electronic prior authorization under Medicare Part D and allow for the creation of technical standards for the electronic transmission of prior authorization. While the College believes this legislation is a good first step for electronic prior authorization, I asked that the scope of the legislation be expanded to include all medical services, supplies, and prescription drugs covered by the Medicare program, and also requested prior authorization policies be standardized across all insurers and that prior authorization requests, decisions, and appeals processes be automated through uniform electronic transaction portals for all services and supplies.

As evidence, I provided data from a 2017 ACS survey of nearly 300 surgeons and their staff, which indicated that, on average, a medical practice receives approximately 37 prior authorization requests per provider, per week. Action on these requests requires 25 hours to complete. This exorbitant expenditure of time and resources required for prior authorization is largely due to a lack of automated prior authorization processes that integrate with current electronic health record systems. The ACS is committed to working with the bill’s sponsors and the Ways and Means Committee toward a goal of swift passage.

Questions from and discussion with members of the Ways and Means Committee were truncated because of votes on the House floor. We look forward to continuing the dialogue in the coming weeks when the roundtable is reconvened.

Until next month ….

On March 15, 2018, I had the opportunity to present on behalf of the ACS at a roundtable discussion on Capitol Hill to members of the House Ways and Means Committee on the topic of Medicare red tape relief

The roundtable provided members of this key committee of jurisdiction over Medicare policy the opportunity to hear from representatives from a variety of health care professional organizations on how Congress can improve Medicare to work more effectively and efficiently for both patients and providers. Each group was allotted just three minutes for their presentation. A summary of my presentation is included below:
 

E/M Documentation Guidelines

The ACS has significant concerns regarding Evaluation and Management (E/M) Documentation Guidelines. Though CMS created the E/M documentation guidelines 23 years ago with the laudable goal of adding structure to the various levels of E/M services, and in an effort to create a sense of equivalency of E/M services across the multitude of specialties, ACS believes the time has come to re-examine and revise these guidelines to be more appropriate in the modern digital information era.

US House Ways and Means Committee

Meaningful Measurement of Surgical Quality

I also addressed concerns relative to the meaningful measurement of surgical quality. Despite having expended significant human and financial resources toward helping Fellows succeed in MIPS, the College is becoming increasingly concerned that MIPS is not actually measuring surgical quality, and therefore, is not a quality program for surgery and serves primarily as a payment program.

As evidence, the most recent quality metric data available (from the 2015 Physician Quality Reporting System) show that many of the CMS quality measures reported by surgeons have little to do with improving the quality of the actual surgical care provided to patients. For general surgeons, the two most commonly reported measures were the documentation of a patient’s medications in the medical record and tobacco use screening. While no one would deny the importance of either of these activities, neither is of much real value in the effort to measure the quality of surgical care provided. In another, perhaps even more illustrative example, one of the most common quality measures reported by urologists was inquiring of their patients whether they had received a pneumovax. This obviously has little to do with why one would see an urologist, much less the quality of care provided.

As an organization, the ACS and its members are absolutely dedicated to improving the quality of care they provide to their patients. However, the quality measures forming the basis of the assessment of their care must first be relevant to the surgical care they provide, and second be achievable. Fellows are increasingly expressing concerns about the burdens imposed by the Quality component of MIPS and believe their efforts to participate do little to meaningfully measure the quality of surgical care they provide. I asked that the Ways and Means Committee hold a hearing specifically addressing issues relative to the Quality component of MIPS.
 

Standardizing Electronic Prior Authorization for Safe Prescribing Act

I expressed ACS’ support for the Standardizing Electronic Prior Authorization for Safe Prescribing Act, H.R. 4841, which would allow for electronic prior authorization under Medicare Part D and allow for the creation of technical standards for the electronic transmission of prior authorization. While the College believes this legislation is a good first step for electronic prior authorization, I asked that the scope of the legislation be expanded to include all medical services, supplies, and prescription drugs covered by the Medicare program, and also requested prior authorization policies be standardized across all insurers and that prior authorization requests, decisions, and appeals processes be automated through uniform electronic transaction portals for all services and supplies.

As evidence, I provided data from a 2017 ACS survey of nearly 300 surgeons and their staff, which indicated that, on average, a medical practice receives approximately 37 prior authorization requests per provider, per week. Action on these requests requires 25 hours to complete. This exorbitant expenditure of time and resources required for prior authorization is largely due to a lack of automated prior authorization processes that integrate with current electronic health record systems. The ACS is committed to working with the bill’s sponsors and the Ways and Means Committee toward a goal of swift passage.

Questions from and discussion with members of the Ways and Means Committee were truncated because of votes on the House floor. We look forward to continuing the dialogue in the coming weeks when the roundtable is reconvened.

Until next month ….

On March 15, 2018, I had the opportunity to present on behalf of the ACS at a roundtable discussion on Capitol Hill to members of the House Ways and Means Committee on the topic of Medicare red tape relief

The roundtable provided members of this key committee of jurisdiction over Medicare policy the opportunity to hear from representatives from a variety of health care professional organizations on how Congress can improve Medicare to work more effectively and efficiently for both patients and providers. Each group was allotted just three minutes for their presentation. A summary of my presentation is included below:
 

E/M Documentation Guidelines

The ACS has significant concerns regarding Evaluation and Management (E/M) Documentation Guidelines. Though CMS created the E/M documentation guidelines 23 years ago with the laudable goal of adding structure to the various levels of E/M services, and in an effort to create a sense of equivalency of E/M services across the multitude of specialties, ACS believes the time has come to re-examine and revise these guidelines to be more appropriate in the modern digital information era.

US House Ways and Means Committee

Meaningful Measurement of Surgical Quality

I also addressed concerns relative to the meaningful measurement of surgical quality. Despite having expended significant human and financial resources toward helping Fellows succeed in MIPS, the College is becoming increasingly concerned that MIPS is not actually measuring surgical quality, and therefore, is not a quality program for surgery and serves primarily as a payment program.

As evidence, the most recent quality metric data available (from the 2015 Physician Quality Reporting System) show that many of the CMS quality measures reported by surgeons have little to do with improving the quality of the actual surgical care provided to patients. For general surgeons, the two most commonly reported measures were the documentation of a patient’s medications in the medical record and tobacco use screening. While no one would deny the importance of either of these activities, neither is of much real value in the effort to measure the quality of surgical care provided. In another, perhaps even more illustrative example, one of the most common quality measures reported by urologists was inquiring of their patients whether they had received a pneumovax. This obviously has little to do with why one would see an urologist, much less the quality of care provided.

As an organization, the ACS and its members are absolutely dedicated to improving the quality of care they provide to their patients. However, the quality measures forming the basis of the assessment of their care must first be relevant to the surgical care they provide, and second be achievable. Fellows are increasingly expressing concerns about the burdens imposed by the Quality component of MIPS and believe their efforts to participate do little to meaningfully measure the quality of surgical care they provide. I asked that the Ways and Means Committee hold a hearing specifically addressing issues relative to the Quality component of MIPS.
 

Standardizing Electronic Prior Authorization for Safe Prescribing Act

I expressed ACS’ support for the Standardizing Electronic Prior Authorization for Safe Prescribing Act, H.R. 4841, which would allow for electronic prior authorization under Medicare Part D and allow for the creation of technical standards for the electronic transmission of prior authorization. While the College believes this legislation is a good first step for electronic prior authorization, I asked that the scope of the legislation be expanded to include all medical services, supplies, and prescription drugs covered by the Medicare program, and also requested prior authorization policies be standardized across all insurers and that prior authorization requests, decisions, and appeals processes be automated through uniform electronic transaction portals for all services and supplies.

As evidence, I provided data from a 2017 ACS survey of nearly 300 surgeons and their staff, which indicated that, on average, a medical practice receives approximately 37 prior authorization requests per provider, per week. Action on these requests requires 25 hours to complete. This exorbitant expenditure of time and resources required for prior authorization is largely due to a lack of automated prior authorization processes that integrate with current electronic health record systems. The ACS is committed to working with the bill’s sponsors and the Ways and Means Committee toward a goal of swift passage.

Questions from and discussion with members of the Ways and Means Committee were truncated because of votes on the House floor. We look forward to continuing the dialogue in the coming weeks when the roundtable is reconvened.

Until next month ….

NEW ORLEANS – Pelvic radiation was as effective for producing recurrence-free survival as vaginal cuff brachytherapy plus chemotherapy but with less acute toxicity and fewer local recurrences in women with high-risk stage I or stage II endometrial cancer in a multicenter, randomized trial with 601 patients.

These findings should result in wider use of pelvic radiation as the preferred treatment for these patients, Marcus E. Randall, MD, said at the annual meeting of the Society of Gynecologic Oncology. “It will change practice,” he predicted.

Dr. Randall and his colleagues from the Gynecologic Oncology Group (which recently became part of NRG Oncology) designed the trial, GOG-0249, to address recent interest in using vaginal cuff brachytherapy plus chemotherapy with carboplatin and paclitaxel as an alternative to the more standard approach of pelvic radiation for treating women with either high-risk stage I or stage II endometrial cancers. Clinicians had considered the brachytherapy plus chemotherapy approach a reasonable option by “extrapolating from studies with advanced” endometrial cancer, but with no direct evidence to support this alternative, Dr. Randall explained in a video interview.

To generate evidence, the researchers enrolled 601 patients at several participating U.S. centers and followed them for a median of 53 months (4.4 years), with 259 patients treated and followed in the pelvic radiation arm and 268 patients treated and followed in the brachytherapy plus chemotherapy arm. Clinicians administered the complete planned treatment regimen to 91% of patients assigned to pelvic radiation and to 87% of those assigned to brachytherapy plus chemotherapy. Three quarters of enrolled patients had high-risk stage I disease, and the entire study group averaged about 62 years old.

The trial’s primary endpoint was recurrence-free survival, which occurred in 78% of the pelvic radiation patients and 79% of brachytherapy plus chemotherapy patients after 5 years when analyzed on an intention-to-treat basis. The two subgroups also showed similar rates of overall survival during follow-up.

Although the two treatments produced essentially identical outcomes for the primary result, they showed two important differences on secondary outcomes, reported Dr. Randall, professor and chair of radiation medicine at the University of Kentucky in Lexington.

Acute adverse effects rated as grade 3 severity or higher occurred in 11% of the pelvic radiation patients and in 64% of the brachytherapy plus chemotherapy patients, although late toxicities occurred at similar rates (13% and 12%, respectively) in the two subgroups.

Local pelvic and para-aortic nodal recurrences occurred in 4% of the pelvic radiation patients and in 9% of the brachytherapy plus chemotherapy patients, a 53% relative risk reduction with pelvic radiation. The difference in the nodal recurrences was apparent within the first year of follow-up, and the difference in rates continued to steadily widen over time after that. However the rates of both vaginal and distant recurrences were very similar in the two treatment arms. Distant recurrences were the most common type of treatment failure, occurring in about 18% of patients in both subgroups during complete follow-up.

“Pelvic radiation therapy remains an appropriate and preferable treatment for high-risk, early stage endometrial carcinoma,” Dr. Randall concluded.

[email protected]

SOURCE: Randall ME et al. SGO 2018.
 

NEW ORLEANS – Pelvic radiation was as effective for producing recurrence-free survival as vaginal cuff brachytherapy plus chemotherapy but with less acute toxicity and fewer local recurrences in women with high-risk stage I or stage II endometrial cancer in a multicenter, randomized trial with 601 patients.

These findings should result in wider use of pelvic radiation as the preferred treatment for these patients, Marcus E. Randall, MD, said at the annual meeting of the Society of Gynecologic Oncology. “It will change practice,” he predicted.

Dr. Randall and his colleagues from the Gynecologic Oncology Group (which recently became part of NRG Oncology) designed the trial, GOG-0249, to address recent interest in using vaginal cuff brachytherapy plus chemotherapy with carboplatin and paclitaxel as an alternative to the more standard approach of pelvic radiation for treating women with either high-risk stage I or stage II endometrial cancers. Clinicians had considered the brachytherapy plus chemotherapy approach a reasonable option by “extrapolating from studies with advanced” endometrial cancer, but with no direct evidence to support this alternative, Dr. Randall explained in a video interview.

To generate evidence, the researchers enrolled 601 patients at several participating U.S. centers and followed them for a median of 53 months (4.4 years), with 259 patients treated and followed in the pelvic radiation arm and 268 patients treated and followed in the brachytherapy plus chemotherapy arm. Clinicians administered the complete planned treatment regimen to 91% of patients assigned to pelvic radiation and to 87% of those assigned to brachytherapy plus chemotherapy. Three quarters of enrolled patients had high-risk stage I disease, and the entire study group averaged about 62 years old.

The trial’s primary endpoint was recurrence-free survival, which occurred in 78% of the pelvic radiation patients and 79% of brachytherapy plus chemotherapy patients after 5 years when analyzed on an intention-to-treat basis. The two subgroups also showed similar rates of overall survival during follow-up.

Although the two treatments produced essentially identical outcomes for the primary result, they showed two important differences on secondary outcomes, reported Dr. Randall, professor and chair of radiation medicine at the University of Kentucky in Lexington.

Acute adverse effects rated as grade 3 severity or higher occurred in 11% of the pelvic radiation patients and in 64% of the brachytherapy plus chemotherapy patients, although late toxicities occurred at similar rates (13% and 12%, respectively) in the two subgroups.

Local pelvic and para-aortic nodal recurrences occurred in 4% of the pelvic radiation patients and in 9% of the brachytherapy plus chemotherapy patients, a 53% relative risk reduction with pelvic radiation. The difference in the nodal recurrences was apparent within the first year of follow-up, and the difference in rates continued to steadily widen over time after that. However the rates of both vaginal and distant recurrences were very similar in the two treatment arms. Distant recurrences were the most common type of treatment failure, occurring in about 18% of patients in both subgroups during complete follow-up.

“Pelvic radiation therapy remains an appropriate and preferable treatment for high-risk, early stage endometrial carcinoma,” Dr. Randall concluded.

[email protected]

SOURCE: Randall ME et al. SGO 2018.
 

NEW ORLEANS – Pelvic radiation was as effective for producing recurrence-free survival as vaginal cuff brachytherapy plus chemotherapy but with less acute toxicity and fewer local recurrences in women with high-risk stage I or stage II endometrial cancer in a multicenter, randomized trial with 601 patients.

These findings should result in wider use of pelvic radiation as the preferred treatment for these patients, Marcus E. Randall, MD, said at the annual meeting of the Society of Gynecologic Oncology. “It will change practice,” he predicted.

Dr. Randall and his colleagues from the Gynecologic Oncology Group (which recently became part of NRG Oncology) designed the trial, GOG-0249, to address recent interest in using vaginal cuff brachytherapy plus chemotherapy with carboplatin and paclitaxel as an alternative to the more standard approach of pelvic radiation for treating women with either high-risk stage I or stage II endometrial cancers. Clinicians had considered the brachytherapy plus chemotherapy approach a reasonable option by “extrapolating from studies with advanced” endometrial cancer, but with no direct evidence to support this alternative, Dr. Randall explained in a video interview.

To generate evidence, the researchers enrolled 601 patients at several participating U.S. centers and followed them for a median of 53 months (4.4 years), with 259 patients treated and followed in the pelvic radiation arm and 268 patients treated and followed in the brachytherapy plus chemotherapy arm. Clinicians administered the complete planned treatment regimen to 91% of patients assigned to pelvic radiation and to 87% of those assigned to brachytherapy plus chemotherapy. Three quarters of enrolled patients had high-risk stage I disease, and the entire study group averaged about 62 years old.

The trial’s primary endpoint was recurrence-free survival, which occurred in 78% of the pelvic radiation patients and 79% of brachytherapy plus chemotherapy patients after 5 years when analyzed on an intention-to-treat basis. The two subgroups also showed similar rates of overall survival during follow-up.

Although the two treatments produced essentially identical outcomes for the primary result, they showed two important differences on secondary outcomes, reported Dr. Randall, professor and chair of radiation medicine at the University of Kentucky in Lexington.

Acute adverse effects rated as grade 3 severity or higher occurred in 11% of the pelvic radiation patients and in 64% of the brachytherapy plus chemotherapy patients, although late toxicities occurred at similar rates (13% and 12%, respectively) in the two subgroups.

Local pelvic and para-aortic nodal recurrences occurred in 4% of the pelvic radiation patients and in 9% of the brachytherapy plus chemotherapy patients, a 53% relative risk reduction with pelvic radiation. The difference in the nodal recurrences was apparent within the first year of follow-up, and the difference in rates continued to steadily widen over time after that. However the rates of both vaginal and distant recurrences were very similar in the two treatment arms. Distant recurrences were the most common type of treatment failure, occurring in about 18% of patients in both subgroups during complete follow-up.

“Pelvic radiation therapy remains an appropriate and preferable treatment for high-risk, early stage endometrial carcinoma,” Dr. Randall concluded.

[email protected]

SOURCE: Randall ME et al. SGO 2018.
 

The total direct and indirect costs of diabetes jumped over 25% from 2012 to 2017, which was enough to make it “the most costly chronic illness in the country,” the American Diabetes Association said.

The estimated total economic burden of diabetes went from an inflation-adjusted estimate of $261 billion in 2012 to $327 billion – $237 billion in direct medical costs and $90 billion in indirect costs such as absenteeism, reduced productivity, and premature mortality – in 2017, according to a new report from the ADA published in Diabetes Care.

“One of every four health care dollars is incurred by someone with diagnosed diabetes, and one of every seven health care dollars is spent directly treating diabetes and its complications,” the ADA said in a written statement.

The study used data from a large number of sources, including the American Community Survey, the OptumInsight de-identified Normative Health Information database, the Medical Expenditure Panel Survey, and the Medicare 5% sample Standard Analytical Files. All cost estimates were extrapolated to the 2017 U.S. population and adjusted to 2017 dollars.

[email protected]

SOURCE: Diabetes Care. 2018 Mar 22. doi: 10.2337/dci18-0007.

The total direct and indirect costs of diabetes jumped over 25% from 2012 to 2017, which was enough to make it “the most costly chronic illness in the country,” the American Diabetes Association said.

The estimated total economic burden of diabetes went from an inflation-adjusted estimate of $261 billion in 2012 to $327 billion – $237 billion in direct medical costs and $90 billion in indirect costs such as absenteeism, reduced productivity, and premature mortality – in 2017, according to a new report from the ADA published in Diabetes Care.

“One of every four health care dollars is incurred by someone with diagnosed diabetes, and one of every seven health care dollars is spent directly treating diabetes and its complications,” the ADA said in a written statement.

The study used data from a large number of sources, including the American Community Survey, the OptumInsight de-identified Normative Health Information database, the Medical Expenditure Panel Survey, and the Medicare 5% sample Standard Analytical Files. All cost estimates were extrapolated to the 2017 U.S. population and adjusted to 2017 dollars.

[email protected]

SOURCE: Diabetes Care. 2018 Mar 22. doi: 10.2337/dci18-0007.

The total direct and indirect costs of diabetes jumped over 25% from 2012 to 2017, which was enough to make it “the most costly chronic illness in the country,” the American Diabetes Association said.

The estimated total economic burden of diabetes went from an inflation-adjusted estimate of $261 billion in 2012 to $327 billion – $237 billion in direct medical costs and $90 billion in indirect costs such as absenteeism, reduced productivity, and premature mortality – in 2017, according to a new report from the ADA published in Diabetes Care.

“One of every four health care dollars is incurred by someone with diagnosed diabetes, and one of every seven health care dollars is spent directly treating diabetes and its complications,” the ADA said in a written statement.

The study used data from a large number of sources, including the American Community Survey, the OptumInsight de-identified Normative Health Information database, the Medical Expenditure Panel Survey, and the Medicare 5% sample Standard Analytical Files. All cost estimates were extrapolated to the 2017 U.S. population and adjusted to 2017 dollars.

[email protected]

SOURCE: Diabetes Care. 2018 Mar 22. doi: 10.2337/dci18-0007.

BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.

An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.

SOURCE: Martinez MA et al. CROI 2018, abstract 639.

BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.

An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.

SOURCE: Martinez MA et al. CROI 2018, abstract 639.

BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.

An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.

SOURCE: Martinez MA et al. CROI 2018, abstract 639.

Answer to “What’s your diagnosis?”  Chilaiditi syndrome

Abdominal CT images display the Chilaiditi sign, which is the radiographic term used to describe interposition of the colon, usually at the hepatic flexure, with the liver and right diaphragm.1 This is considered an incidental radiographic finding and is generally asymptomatic; however, when one develops clinical symptoms such as abdominal pain, bloating or distension, anorexia, constipation, or nausea it is called Chilaiditi syndrome.

First described by Greek radiologist Demetrius Chilaiditi in 1910, Chilaiditi syndrome is a rare occurrence with an incidence rate of 0.25%-0.28% in the general population.2 The etiology of Chilaiditi syndrome is felt to be congenital or acquired with predisposing congenital abnormalities such as absent suspensory or falciform ligaments, redundant colon, malposition of the colon, dolichocolon, and paralysis of the right diaphragm. Other risk factors for development of Chilaiditi syndrome include chronic constipation, cirrhosis, ascites, and obesity. Men are times times as likely as women to develop Chilaiditi syndrome and it is more common in the elderly, occurring in 1% of the elderly population.3 Chilaiditi sign is diagnosed with radiographic imaging meeting the following criteria: the right hemidiaphragm must be elevated above the liver by the intestine, the bowel must be distended by air to illustrate pseudopneumoperitoneum, and the superior margin of the liver must be depressed below the level of the left hemidiaphragm.1

Chilaiditi syndrome is managed conservatively with close observation. Recurrent symptoms can be treated with colopexy. This syndrome has been known to cause severe complications including volvulus of the cecum, splenic flexure, or transverse colon, cecal perforation, and subdiaphragmatic perforated appendicitis, which all require surgical intervention.3 It is important to recognize Chilaiditi syndrome on presentation to prevent unnecessary diagnostic studies and unwarranted surgical intervention.

References
1. Uygungul, E., Uygungul, D., Ayrik, C., et al. Chilaiditi sign: why are clinical findings more important in ED?. Am J Emerg Med. 2015;33:733.e1-733.e2.
2. Ho, M.P., Cheung, W.K., Tsai, K.C., et al. Chilaiditi syndrome mimicking subdiaphragmatic free air in an elderly adult. J Am Geriatr Soc. 2014;62:2019-21.
3. Kang, D., Pan, A.S., Lopez, M.A., et al. Acute abdominal pain secondary to Chilaiditi syndrome. Case Rep Surg. 2013;2013:756590.

Answer to “What’s your diagnosis?”  Chilaiditi syndrome

Abdominal CT images display the Chilaiditi sign, which is the radiographic term used to describe interposition of the colon, usually at the hepatic flexure, with the liver and right diaphragm.1 This is considered an incidental radiographic finding and is generally asymptomatic; however, when one develops clinical symptoms such as abdominal pain, bloating or distension, anorexia, constipation, or nausea it is called Chilaiditi syndrome.

First described by Greek radiologist Demetrius Chilaiditi in 1910, Chilaiditi syndrome is a rare occurrence with an incidence rate of 0.25%-0.28% in the general population.2 The etiology of Chilaiditi syndrome is felt to be congenital or acquired with predisposing congenital abnormalities such as absent suspensory or falciform ligaments, redundant colon, malposition of the colon, dolichocolon, and paralysis of the right diaphragm. Other risk factors for development of Chilaiditi syndrome include chronic constipation, cirrhosis, ascites, and obesity. Men are times times as likely as women to develop Chilaiditi syndrome and it is more common in the elderly, occurring in 1% of the elderly population.3 Chilaiditi sign is diagnosed with radiographic imaging meeting the following criteria: the right hemidiaphragm must be elevated above the liver by the intestine, the bowel must be distended by air to illustrate pseudopneumoperitoneum, and the superior margin of the liver must be depressed below the level of the left hemidiaphragm.1

Chilaiditi syndrome is managed conservatively with close observation. Recurrent symptoms can be treated with colopexy. This syndrome has been known to cause severe complications including volvulus of the cecum, splenic flexure, or transverse colon, cecal perforation, and subdiaphragmatic perforated appendicitis, which all require surgical intervention.3 It is important to recognize Chilaiditi syndrome on presentation to prevent unnecessary diagnostic studies and unwarranted surgical intervention.

References
1. Uygungul, E., Uygungul, D., Ayrik, C., et al. Chilaiditi sign: why are clinical findings more important in ED?. Am J Emerg Med. 2015;33:733.e1-733.e2.
2. Ho, M.P., Cheung, W.K., Tsai, K.C., et al. Chilaiditi syndrome mimicking subdiaphragmatic free air in an elderly adult. J Am Geriatr Soc. 2014;62:2019-21.
3. Kang, D., Pan, A.S., Lopez, M.A., et al. Acute abdominal pain secondary to Chilaiditi syndrome. Case Rep Surg. 2013;2013:756590.

Answer to “What’s your diagnosis?”  Chilaiditi syndrome

Abdominal CT images display the Chilaiditi sign, which is the radiographic term used to describe interposition of the colon, usually at the hepatic flexure, with the liver and right diaphragm.1 This is considered an incidental radiographic finding and is generally asymptomatic; however, when one develops clinical symptoms such as abdominal pain, bloating or distension, anorexia, constipation, or nausea it is called Chilaiditi syndrome.

First described by Greek radiologist Demetrius Chilaiditi in 1910, Chilaiditi syndrome is a rare occurrence with an incidence rate of 0.25%-0.28% in the general population.2 The etiology of Chilaiditi syndrome is felt to be congenital or acquired with predisposing congenital abnormalities such as absent suspensory or falciform ligaments, redundant colon, malposition of the colon, dolichocolon, and paralysis of the right diaphragm. Other risk factors for development of Chilaiditi syndrome include chronic constipation, cirrhosis, ascites, and obesity. Men are times times as likely as women to develop Chilaiditi syndrome and it is more common in the elderly, occurring in 1% of the elderly population.3 Chilaiditi sign is diagnosed with radiographic imaging meeting the following criteria: the right hemidiaphragm must be elevated above the liver by the intestine, the bowel must be distended by air to illustrate pseudopneumoperitoneum, and the superior margin of the liver must be depressed below the level of the left hemidiaphragm.1

Chilaiditi syndrome is managed conservatively with close observation. Recurrent symptoms can be treated with colopexy. This syndrome has been known to cause severe complications including volvulus of the cecum, splenic flexure, or transverse colon, cecal perforation, and subdiaphragmatic perforated appendicitis, which all require surgical intervention.3 It is important to recognize Chilaiditi syndrome on presentation to prevent unnecessary diagnostic studies and unwarranted surgical intervention.

References
1. Uygungul, E., Uygungul, D., Ayrik, C., et al. Chilaiditi sign: why are clinical findings more important in ED?. Am J Emerg Med. 2015;33:733.e1-733.e2.
2. Ho, M.P., Cheung, W.K., Tsai, K.C., et al. Chilaiditi syndrome mimicking subdiaphragmatic free air in an elderly adult. J Am Geriatr Soc. 2014;62:2019-21.
3. Kang, D., Pan, A.S., Lopez, M.A., et al. Acute abdominal pain secondary to Chilaiditi syndrome. Case Rep Surg. 2013;2013:756590.

SAN DIEGO – Although the intrusion of private equity in the ownership and operation of U.S. dermatology practices that has been snowballing for a little under a decade is often bemoaned by dermatologists, at least some physicians in the field may see it as a positive development.

“I think private equity investment is good for dermatology,” Clifford Perlis, MD, said at the annual meeting of the American Academy of Dermatology. “Dermatologists should be thrilled that private equity is here.” Investment by private equity companies into dermatology practices “adds value to practices, creates more practice options, enhances advocacy, and better manages the complexity” of practices, claimed Dr. Perlis, a dermatologist and Mohs surgeon who practices in King of Prussia, Pa. The debate on this topic was presented during a forum on dermatoethics at the meeting, structured as a pro and con conversation. The organizers, including Dr. Perlis and Jane Grant-Kels, MD., chose the topics and assigned positions to each presenter, which do not necessarily represent their personal views.*

Mitchel L. Zoler/MDedge News

*This article was updated on April 4, 2018.

[email protected]

SAN DIEGO – Although the intrusion of private equity in the ownership and operation of U.S. dermatology practices that has been snowballing for a little under a decade is often bemoaned by dermatologists, at least some physicians in the field may see it as a positive development.

“I think private equity investment is good for dermatology,” Clifford Perlis, MD, said at the annual meeting of the American Academy of Dermatology. “Dermatologists should be thrilled that private equity is here.” Investment by private equity companies into dermatology practices “adds value to practices, creates more practice options, enhances advocacy, and better manages the complexity” of practices, claimed Dr. Perlis, a dermatologist and Mohs surgeon who practices in King of Prussia, Pa. The debate on this topic was presented during a forum on dermatoethics at the meeting, structured as a pro and con conversation. The organizers, including Dr. Perlis and Jane Grant-Kels, MD., chose the topics and assigned positions to each presenter, which do not necessarily represent their personal views.*

Mitchel L. Zoler/MDedge News

*This article was updated on April 4, 2018.

[email protected]

SAN DIEGO – Although the intrusion of private equity in the ownership and operation of U.S. dermatology practices that has been snowballing for a little under a decade is often bemoaned by dermatologists, at least some physicians in the field may see it as a positive development.

“I think private equity investment is good for dermatology,” Clifford Perlis, MD, said at the annual meeting of the American Academy of Dermatology. “Dermatologists should be thrilled that private equity is here.” Investment by private equity companies into dermatology practices “adds value to practices, creates more practice options, enhances advocacy, and better manages the complexity” of practices, claimed Dr. Perlis, a dermatologist and Mohs surgeon who practices in King of Prussia, Pa. The debate on this topic was presented during a forum on dermatoethics at the meeting, structured as a pro and con conversation. The organizers, including Dr. Perlis and Jane Grant-Kels, MD., chose the topics and assigned positions to each presenter, which do not necessarily represent their personal views.*

Mitchel L. Zoler/MDedge News

*This article was updated on April 4, 2018.

[email protected]