Atopic dermatitis is becoming more prevalent in the industrialized world, along with other atopic disorders, including allergic rhinitis and asthma, according to Douglas W. Kress, MD, of the department of dermatology at the University of Pittsburgh.

Recent studies suggest that atopic dermatitis (AD) affects 10%-17% of the U.S. population, and 80%-90% of patients are diagnosed by the age of 5 years, Dr. Kress said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

“There seem to be multiple pathways, which initiate and perpetuate the cutaneous inflammation of AD including exposure to allergens, irritants, and physical trauma, infection, stress, extremes in temperature and humidity,” Dr. Kress said. In addition, foods and airborne allergens may trigger AD.

Many parents may believe that certain factors are associated with AD, but most of these perceptions are not supported by evidence, said Dr. Kress, who is also chief of the division of pediatric dermatology at the Children’s Hospital of Pittsburgh. AD appears to be a disorder of T cell dysregulation dominated by Th2 lesions in acute cases and Th1 inflammation in patients with chronic lesions.

No associations have been proven between the development of AD in the first 18 months of life and any maternal dietary restrictions, according to a recent Cochrane review, nor is there evidence for an association between AD and the introduction of solid foods, exposure to fish oil, or exposure to animals at a young age, he said. In addition, a study published in 2016 showed a lack of evidence to support the use of specific allergen immunotherapy for AD.

However, evidence does support an association between the presence of AD in children and certain other conditions, Dr. Kress said. “Other associations include an increased incidence of alopecia areata, a threefold increase in autism spectrum disorders, and a twofold increase in ADHD in children with atopic dermatitis.”

The only known food allergy linked to AD severity is egg whites; reducing egg white exposure has been shown to improve AD in children with both conditions, he noted.

Although many patients with AD experience annoying but relatively mild symptoms, health care providers should be alert to the potential for infections, particularly with Staphylococcus aureus, and remember that an active egg white allergy has been associated with staphylococcal superantigen sensitization, said Dr. Kress. The increased risk for S. aureus in children with AD may stem from a tendency to underuse antibiotics in AD children, which results in a delayed treatment until the infection becomes overt. In addition, the increased pH in patients with AD might promote the development of pathogenic strains of staph. However, ceramide-based moisturizers could help inhibit these strains by increasing skin acidity.

For patients who have poor AD control with standard therapy, antibiotics may be used as adjunctive therapy. “Consider bleach baths and/or staph decolonization with mupirocin, both of which led to significant improvement in eczema severity compared to placebo,” Dr. Kress said. “Bleach may also have an anti-inflammatory effect.”

Dr. Kress disclosed relationships with Pfizer, Amgen, and Sanofi/Regeneron. SDEF and this news organization are owned by Frontline Medical Communications.

Atopic dermatitis is becoming more prevalent in the industrialized world, along with other atopic disorders, including allergic rhinitis and asthma, according to Douglas W. Kress, MD, of the department of dermatology at the University of Pittsburgh.

Recent studies suggest that atopic dermatitis (AD) affects 10%-17% of the U.S. population, and 80%-90% of patients are diagnosed by the age of 5 years, Dr. Kress said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

“There seem to be multiple pathways, which initiate and perpetuate the cutaneous inflammation of AD including exposure to allergens, irritants, and physical trauma, infection, stress, extremes in temperature and humidity,” Dr. Kress said. In addition, foods and airborne allergens may trigger AD.

Many parents may believe that certain factors are associated with AD, but most of these perceptions are not supported by evidence, said Dr. Kress, who is also chief of the division of pediatric dermatology at the Children’s Hospital of Pittsburgh. AD appears to be a disorder of T cell dysregulation dominated by Th2 lesions in acute cases and Th1 inflammation in patients with chronic lesions.

No associations have been proven between the development of AD in the first 18 months of life and any maternal dietary restrictions, according to a recent Cochrane review, nor is there evidence for an association between AD and the introduction of solid foods, exposure to fish oil, or exposure to animals at a young age, he said. In addition, a study published in 2016 showed a lack of evidence to support the use of specific allergen immunotherapy for AD.

However, evidence does support an association between the presence of AD in children and certain other conditions, Dr. Kress said. “Other associations include an increased incidence of alopecia areata, a threefold increase in autism spectrum disorders, and a twofold increase in ADHD in children with atopic dermatitis.”

The only known food allergy linked to AD severity is egg whites; reducing egg white exposure has been shown to improve AD in children with both conditions, he noted.

Although many patients with AD experience annoying but relatively mild symptoms, health care providers should be alert to the potential for infections, particularly with Staphylococcus aureus, and remember that an active egg white allergy has been associated with staphylococcal superantigen sensitization, said Dr. Kress. The increased risk for S. aureus in children with AD may stem from a tendency to underuse antibiotics in AD children, which results in a delayed treatment until the infection becomes overt. In addition, the increased pH in patients with AD might promote the development of pathogenic strains of staph. However, ceramide-based moisturizers could help inhibit these strains by increasing skin acidity.

For patients who have poor AD control with standard therapy, antibiotics may be used as adjunctive therapy. “Consider bleach baths and/or staph decolonization with mupirocin, both of which led to significant improvement in eczema severity compared to placebo,” Dr. Kress said. “Bleach may also have an anti-inflammatory effect.”

Dr. Kress disclosed relationships with Pfizer, Amgen, and Sanofi/Regeneron. SDEF and this news organization are owned by Frontline Medical Communications.

Atopic dermatitis is becoming more prevalent in the industrialized world, along with other atopic disorders, including allergic rhinitis and asthma, according to Douglas W. Kress, MD, of the department of dermatology at the University of Pittsburgh.

Recent studies suggest that atopic dermatitis (AD) affects 10%-17% of the U.S. population, and 80%-90% of patients are diagnosed by the age of 5 years, Dr. Kress said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

“There seem to be multiple pathways, which initiate and perpetuate the cutaneous inflammation of AD including exposure to allergens, irritants, and physical trauma, infection, stress, extremes in temperature and humidity,” Dr. Kress said. In addition, foods and airborne allergens may trigger AD.

Many parents may believe that certain factors are associated with AD, but most of these perceptions are not supported by evidence, said Dr. Kress, who is also chief of the division of pediatric dermatology at the Children’s Hospital of Pittsburgh. AD appears to be a disorder of T cell dysregulation dominated by Th2 lesions in acute cases and Th1 inflammation in patients with chronic lesions.

No associations have been proven between the development of AD in the first 18 months of life and any maternal dietary restrictions, according to a recent Cochrane review, nor is there evidence for an association between AD and the introduction of solid foods, exposure to fish oil, or exposure to animals at a young age, he said. In addition, a study published in 2016 showed a lack of evidence to support the use of specific allergen immunotherapy for AD.

However, evidence does support an association between the presence of AD in children and certain other conditions, Dr. Kress said. “Other associations include an increased incidence of alopecia areata, a threefold increase in autism spectrum disorders, and a twofold increase in ADHD in children with atopic dermatitis.”

The only known food allergy linked to AD severity is egg whites; reducing egg white exposure has been shown to improve AD in children with both conditions, he noted.

Although many patients with AD experience annoying but relatively mild symptoms, health care providers should be alert to the potential for infections, particularly with Staphylococcus aureus, and remember that an active egg white allergy has been associated with staphylococcal superantigen sensitization, said Dr. Kress. The increased risk for S. aureus in children with AD may stem from a tendency to underuse antibiotics in AD children, which results in a delayed treatment until the infection becomes overt. In addition, the increased pH in patients with AD might promote the development of pathogenic strains of staph. However, ceramide-based moisturizers could help inhibit these strains by increasing skin acidity.

For patients who have poor AD control with standard therapy, antibiotics may be used as adjunctive therapy. “Consider bleach baths and/or staph decolonization with mupirocin, both of which led to significant improvement in eczema severity compared to placebo,” Dr. Kress said. “Bleach may also have an anti-inflammatory effect.”

Dr. Kress disclosed relationships with Pfizer, Amgen, and Sanofi/Regeneron. SDEF and this news organization are owned by Frontline Medical Communications.

ORLANDO – In patients with resectable hepatobiliary malignancies, percutaneous biliary drainage was associated with an increased risk of death or serious morbidity versus endoscopic drainage, results of a recent retrospective study show.

decade3d/thinkstockphotos.com

Patients undergoing percutaneous transhepatic biliary drainage did have more preoperative comorbidities, compared with those undergoing endoscopic biliary stenting, according researcher Q. Lina Hu, MD, an American College of Surgeons Clinical Scholar-in-Residence.

“Nevertheless, compared to endoscopic drainage, percutaneous drainage was associated with a significantly increased morbidity and mortality, even after adjustment for measured confounders,” Dr. Hu said a presentation at the American College of Surgeons Quality and Safety Conference.

Patients with resectable hepatobiliary malignancies often present with biliary obstruction, which may increase risk of perioperative morbidity and mortality, said Dr. Hu, a general surgery resident at University of California, Los Angeles.

“Preoperative biliary drainage is thought to reduce this risk by resolving cholestasis and preserving liver function,” she said.

However, the preferred drainage technique is not established, she added.

The endoscopic approach approximates normal physiologic drainage, she said, but is associated with complications including pancreatitis and cholangitis. By contrast, percutaneous drainage has a lower contamination risk and higher rate of success, but involves external catheters and has catheter-related complications.

To evaluate associations between preoperative drainage technique and postoperative outcomes, Dr. Hu and her colleagues queried the ACS National Surgical Quality Improvement Program (NSQIP) Procedure-Targeted Hepatectomy Database. They identified 527 patients who underwent preoperative biliary drainage prior to resection between 2014 and 2017, of whom about 80% underwent endoscopic drainage and 20% underwent percutaneous drainage. The primary outcome of their analysis was 30-day death or serious morbidity.

Patients who were selected for percutaneous drainage had significantly more preoperative comorbidities, including higher American Society of Anesthesiologists class, recent weight loss, and lower albumin levels, Dr. Hu said.

Death or serious morbidity occurred in 250 of the patients, or approximately 48% of the cohort.

In unadjusted analysis, the incidence of death or serious morbidity was significantly more frequent in the percutaneous group, compared with endoscopic group. The percutaneous group also had greater odds of surgical site infection, liver failure, bile leakage, and prolonged length of stay.

Those associations remained significant for death or serious morbidity and surgical site infection in both multivariable– and propensity score–adjusted models, Dr. Hu said.

In a propensity score–matched model, 93 patients who received percutaneous drainage were matched one-to-one to 93 patients who received endoscopic drainage based on relevant baseline characteristics. In that rigorous analysis, the odds ratio for death or serious morbidity was 2.17 (95% confidence interval, 1.16-4.09), according to the report.

“Death and serious morbidity was significantly associated with percutaneous drainage across all models, suggesting that patients receiving percutaneous drainage were more likely to experience an adverse event, compared to patients receiving endoscopic drainage,” Dr. Hu said.

However, Dr. Hu acknowledged the limitations of the retrospective study, noting that propensity score adjustment and matching accounts for measured confounders. “It obviously cannot account for any unmeasured confounders,” she said.

Dr. Hu reported funding from the Agency for Healthcare Research and Quality related to her position. She had no disclosures related to her presentation.

ORLANDO – In patients with resectable hepatobiliary malignancies, percutaneous biliary drainage was associated with an increased risk of death or serious morbidity versus endoscopic drainage, results of a recent retrospective study show.

decade3d/thinkstockphotos.com

Patients undergoing percutaneous transhepatic biliary drainage did have more preoperative comorbidities, compared with those undergoing endoscopic biliary stenting, according researcher Q. Lina Hu, MD, an American College of Surgeons Clinical Scholar-in-Residence.

“Nevertheless, compared to endoscopic drainage, percutaneous drainage was associated with a significantly increased morbidity and mortality, even after adjustment for measured confounders,” Dr. Hu said a presentation at the American College of Surgeons Quality and Safety Conference.

Patients with resectable hepatobiliary malignancies often present with biliary obstruction, which may increase risk of perioperative morbidity and mortality, said Dr. Hu, a general surgery resident at University of California, Los Angeles.

“Preoperative biliary drainage is thought to reduce this risk by resolving cholestasis and preserving liver function,” she said.

However, the preferred drainage technique is not established, she added.

The endoscopic approach approximates normal physiologic drainage, she said, but is associated with complications including pancreatitis and cholangitis. By contrast, percutaneous drainage has a lower contamination risk and higher rate of success, but involves external catheters and has catheter-related complications.

To evaluate associations between preoperative drainage technique and postoperative outcomes, Dr. Hu and her colleagues queried the ACS National Surgical Quality Improvement Program (NSQIP) Procedure-Targeted Hepatectomy Database. They identified 527 patients who underwent preoperative biliary drainage prior to resection between 2014 and 2017, of whom about 80% underwent endoscopic drainage and 20% underwent percutaneous drainage. The primary outcome of their analysis was 30-day death or serious morbidity.

Patients who were selected for percutaneous drainage had significantly more preoperative comorbidities, including higher American Society of Anesthesiologists class, recent weight loss, and lower albumin levels, Dr. Hu said.

Death or serious morbidity occurred in 250 of the patients, or approximately 48% of the cohort.

In unadjusted analysis, the incidence of death or serious morbidity was significantly more frequent in the percutaneous group, compared with endoscopic group. The percutaneous group also had greater odds of surgical site infection, liver failure, bile leakage, and prolonged length of stay.

Those associations remained significant for death or serious morbidity and surgical site infection in both multivariable– and propensity score–adjusted models, Dr. Hu said.

In a propensity score–matched model, 93 patients who received percutaneous drainage were matched one-to-one to 93 patients who received endoscopic drainage based on relevant baseline characteristics. In that rigorous analysis, the odds ratio for death or serious morbidity was 2.17 (95% confidence interval, 1.16-4.09), according to the report.

“Death and serious morbidity was significantly associated with percutaneous drainage across all models, suggesting that patients receiving percutaneous drainage were more likely to experience an adverse event, compared to patients receiving endoscopic drainage,” Dr. Hu said.

However, Dr. Hu acknowledged the limitations of the retrospective study, noting that propensity score adjustment and matching accounts for measured confounders. “It obviously cannot account for any unmeasured confounders,” she said.

Dr. Hu reported funding from the Agency for Healthcare Research and Quality related to her position. She had no disclosures related to her presentation.

ORLANDO – In patients with resectable hepatobiliary malignancies, percutaneous biliary drainage was associated with an increased risk of death or serious morbidity versus endoscopic drainage, results of a recent retrospective study show.

decade3d/thinkstockphotos.com

Patients undergoing percutaneous transhepatic biliary drainage did have more preoperative comorbidities, compared with those undergoing endoscopic biliary stenting, according researcher Q. Lina Hu, MD, an American College of Surgeons Clinical Scholar-in-Residence.

“Nevertheless, compared to endoscopic drainage, percutaneous drainage was associated with a significantly increased morbidity and mortality, even after adjustment for measured confounders,” Dr. Hu said a presentation at the American College of Surgeons Quality and Safety Conference.

Patients with resectable hepatobiliary malignancies often present with biliary obstruction, which may increase risk of perioperative morbidity and mortality, said Dr. Hu, a general surgery resident at University of California, Los Angeles.

“Preoperative biliary drainage is thought to reduce this risk by resolving cholestasis and preserving liver function,” she said.

However, the preferred drainage technique is not established, she added.

The endoscopic approach approximates normal physiologic drainage, she said, but is associated with complications including pancreatitis and cholangitis. By contrast, percutaneous drainage has a lower contamination risk and higher rate of success, but involves external catheters and has catheter-related complications.

To evaluate associations between preoperative drainage technique and postoperative outcomes, Dr. Hu and her colleagues queried the ACS National Surgical Quality Improvement Program (NSQIP) Procedure-Targeted Hepatectomy Database. They identified 527 patients who underwent preoperative biliary drainage prior to resection between 2014 and 2017, of whom about 80% underwent endoscopic drainage and 20% underwent percutaneous drainage. The primary outcome of their analysis was 30-day death or serious morbidity.

Patients who were selected for percutaneous drainage had significantly more preoperative comorbidities, including higher American Society of Anesthesiologists class, recent weight loss, and lower albumin levels, Dr. Hu said.

Death or serious morbidity occurred in 250 of the patients, or approximately 48% of the cohort.

In unadjusted analysis, the incidence of death or serious morbidity was significantly more frequent in the percutaneous group, compared with endoscopic group. The percutaneous group also had greater odds of surgical site infection, liver failure, bile leakage, and prolonged length of stay.

Those associations remained significant for death or serious morbidity and surgical site infection in both multivariable– and propensity score–adjusted models, Dr. Hu said.

In a propensity score–matched model, 93 patients who received percutaneous drainage were matched one-to-one to 93 patients who received endoscopic drainage based on relevant baseline characteristics. In that rigorous analysis, the odds ratio for death or serious morbidity was 2.17 (95% confidence interval, 1.16-4.09), according to the report.

“Death and serious morbidity was significantly associated with percutaneous drainage across all models, suggesting that patients receiving percutaneous drainage were more likely to experience an adverse event, compared to patients receiving endoscopic drainage,” Dr. Hu said.

However, Dr. Hu acknowledged the limitations of the retrospective study, noting that propensity score adjustment and matching accounts for measured confounders. “It obviously cannot account for any unmeasured confounders,” she said.

Dr. Hu reported funding from the Agency for Healthcare Research and Quality related to her position. She had no disclosures related to her presentation.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are similar but distinct diabetic emergencies that are frequently encountered in the ED. Patients with DKA or HHS present with hyperglycemia and dehydration and frequently appear quite ill physically. In both syndromes, there is insufficient insulin levels to transport glucose into cells.

As previously noted, although DKA and HHS share similar characteristic signs and symptoms, they are two distinct conditions that must be differentiated in the clinical work-up. One characteristic that helps the emergency physician (EP) to distinguish between the two conditions is the patient age at symptom onset. Although both conditions can occur at any age, diabetic ketoacidosis typically develops in younger patients, less than 45 years, who have little or no endogenous insulin production, whereas HHS usually occurs in much older non-insulin-dependent patients (who are often greater than 60 years old). ^1-3 This review discusses the similarities and differences in the etiology, diagnosis, and treatment of DKA and HHS to guide evaluation and simplify management, highlighting practical tips and clinical pearls. When applicable, information has been organized into groups of five to facilitate retention and recall.

The Etiology of DKA Vs HHS

The fundamental underlying issue in both DKA and HHS is an absolute or relative lack of insulin that results in an increase in counter-regulatory hormones, including glucagon, cortisol, and catecholamines.

Insulin has five main actions: (1) to drive glucose into cells; (2) to drive potassium into cells; (3) to create an anabolic environment; (4) to inhibit breakdown of fat; and (5) to block the breakdown of proteins. (Table 1).

Diagnosis and Workup

Laboratory Evaluation

In addition to hyperglycemia, another key finding in DKA is elevated anion gap metabolic acidosis resulting from ketoacid production. Laboratory evaluation will demonstrate a pH less than 7.3 and serum bicarbonate level less than 18 mEq/L; urinalysis will be positive for ketones.

Though HHS patients also present with hyperglycemia, laboratory evaluation will demonstrate no, or only mild, acidosis, normal pH (typically >7.3), bicarbonate level greater than 18 mEq/L, and a high-serum osmolality (>350 mOsm/kg). While urinalysis may show low or no ketones, patients with HHS do not develop the marked ketoacidosis seen in DKA. Moreover, glucose values are more elevated in patients with HHS, frequently exceeding 1,000 mg/dL.

Signs and Symptoms

Patients with either of these hyperglycemic crises often present with fatigue, polyuria, and polydipsia. They appear dehydrated on examination with dry mucous membranes, tachycardia, and in severe cases, hypotension. Patients with HHS often present with altered mental status, seizures, and even coma, while patients with DKA typically only experience changes in mental status in the most severe cases (Table 2). As many as one-third of patients with a hyperglycemic crisis will have an overlapping DKA/HHS syndrome.^1-3 With respect to patient age, HHS tends to develop in older patients who have type 2 diabetes and several underlying comorbidities.²

Precipitating Causes of DKA and HHS

The five causes of DKA/HHS can be remembered as the “Five I’s”: (1) infection; (2) infarction; (3) infant (pregnancy), (4) indiscretion, and (5) [lack of] insulin (Table 3).

Infection. Infection is one of the most common precipitating factors in both DKA and HHS.¹ During the history intake, the EP should ask the patient if he or she has had any recent urinary and respiratory symptoms, as positive responses prompt further investigation with urinalysis and chest radiography. A thorough dermatological examination should be performed to assess for visible signs of infection, particularly in the extremities and intertriginous areas.

When assessing patients with DKA or HHS for signs of infection, body temperature to assess for the presence of fever is not always a reliable indicator. This is because many patients with DKA/HHS develop tachypnea, which can affect the efficacy of an oral thermometer. In such cases, the rectal temperature is more sensitive for detecting fever. It should be noted, however, that some patients with severe infection or immunocompromised state—regardless of the presence or absence of tachypnea—may be normothermic or even hypothermic due to peripheral vasodilation—a poor prognostic sign.³ Blood and urine cultures should be obtained for all patients in whom infection is suspected.

Laboratory evaluation of patients with DKA may demonstrate a mild leukocytosis, a very common finding in DKA even in the absence of infection; leukocytosis is believed to result from elevated stress hormones such as cortisol and epinephrine.³

Infarction. Infarction is another important underlying cause of DKA/HHS and one that must not be overlooked. Screening for acute coronary syndrome through patient history, electrocardiography, and cardiac biomarkers should be performed in all patients older than age 40 years and in patients in whom there is any suggestion of myocardial ischemia.

A thorough neurological examination should be performed to assess for deficits indicative of stroke. Although neurological deficits can be due to severe hyperglycemia, most patients with focal neurological deficits from hyperglycemia also have altered mental status. Focal neurological deficits without a change in mental status are more likely to represent an actual stroke.⁴

Infant (Pregnancy). Pregnant patients are at an increased risk of developing DKA for several reasons, most notably due to the increased production of insulin-antagonistic hormones, which can lead to higher insulin resistance and thus increased insulin requirements during pregnancy.⁵ A pregnancy test is therefore indicated for all female patients of child-bearing age.

Indiscretion. Non-compliance with diet, such as taking in too many calories without appropriate insulin correction, and the ingestion of significant amounts of alcohol can lead to DKA. Eating disorders, particularly in young patients, may also contribute to recurrent cases.³

[Lack of] Insulin. In insulin-dependent diabetes, skipped insulin doses or insulin pump failure can trigger DKA/HHS. In fact, missed insulin doses are becoming a more frequent cause of DKA than infections.¹

Both DKA and HHS are usually triggered by an underlying illness or event. Therefore, clinicians should always focus on identifying precipitating causes such as acute infection, stroke, or myocardial infarction, as some require immediate treatment. In fact, DKA or HHS is rarely the primary cause of death; patients are much more likely to die from the precipitating event that caused DKA or HHS.^1,3

Assessing Disease Severity

Mental status and pH and serum bicarbonate levels help clinicians determine the extent of disease severity, classifying patients as having mild, moderate, or severe DKA (Table 4).² Patients at the highest risk for poor outcomes include those at the extremes of age, who have severe comorbidities, who have underlying infection, and who are hypotensive and/or in a comatose state.³

Patients who have HHS are much more likely to present with altered mental status, including coma. There is a linear relationship between osmolality and degree of altered mental status. Thus, diabetic patients with major changes in mental status but without high serum osmolality warrant immediate workup for alternative causes of their altered mental status.³ In addition, seizures, especially focal seizures, are relatively common in severe cases of HHS. Finally, highly abnormal blood pressure, pulse, and respiratory rate can also provide additional clues regarding the severity of hyperglycemic crisis.

Arterial Blood Gas Assessment: To Stick or Not to Stick?

In the past, measuring arterial blood gases (ABG) has been considered a mainstay in the evaluation of patients with DKA. But does an arterial stick, which is associated with some risk, really add essential information? One study by Ma et al⁶ evaluated whether ABG results significantly alter how physicians manage patients with DKA. In the study, the authors evaluated 200 ED patients and found that ABG analysis only changed diagnosis in 1% of patients, altered treatment in 3.5% of patients, and changed disposition in only 1% of patients. Arterial stick partial pressure of oxygen and partial pressure of carbon dioxide altered treatment and disposition in only 1% of patients. Furthermore, the study results showed venous pH correlated very strongly with arterial pH (r = 0.95).⁶ These findings demonstrate that ABG measurements rarely affect or alter DKA management, and support the use of venous pH as an adequate substitute for ABG testing.

Euglycemia

Euglycemic DKA has been reported in patients with type 1 diabetes who had been fasting or vomiting or who had received exogenous insulin prior to presentation.¹Euglycemia has also been reported in pregnant patients with type I diabetes.¹ More recently, sodium glucose cotransporter 2 inhibitors (SGLT2) have been shown to cause euglycemic DKA. While the therapeutic mechanism of this drug class is to inhibit proximal tubular resorption of glucose, they can cause DKA by decreasing renal clearance of ketone bodies and increasing glucagon levels and promoting hepatic ketogenesis. Patients with DKA who are on SGLT2 inhibitors may present with only modestly elevated glucose levels (typically in the 200- to 300-mg/dL range), but have profound wide gap metabolic acidosis due to β-hydroxybutyrate acid and acetoacetate accumulation.⁷ When evaluating patients on SGLT2 inhibitors for DKA, EPs should not solely rely on glucose values but rather assess the patient’s overall clinical picture, including the physical examination, vital signs, and pH. Additionally, once resuscitation with intravenous (IV) fluids and insulin is initiated, it may take longer for patients who use SGLT2 inhibitors to clear ketoacids than patients with DKA who do not use these medications.⁸

Treatment

The goal of treatment for DKA and HHS is to correct volume deficits, hyperglycemia, and electrolyte abnormalities (Table 5). Three of the five therapies to manage DKA and HHS are mandatory: IV fluid resuscitation, IV insulin, and IV potassium. The other therapies, IV bicarbonate, and IV phosphate, should be considered, but are rarely required for DKA or HHS.

In general, management of HHS is less aggressive than that of DKA because HHS develops over a period of weeks—unlike DKA, which develops over only 1 to 2 days. Treatment of any underlying causes of HHS should occur simultaneously.

Intravenous Fluids

The goal of IV fluid therapy for patients with DKA is rehydration—not to “wash-out” ketones. Ketone elimination occurs through insulin-stimulated metabolism. When determining volume-replacement goals, it is helpful to keep in mind that patients with moderate-to-mild DKA typically have fluid deficiencies of 3 to 5 L, and patients with severe DKA have fluid deficiencies between 5 and 6 L. Patients with HHS present with significantly higher fluid deficiencies of around 9 to 12 L.

The initial goal of fluid management is to correct hypoperfusion with bolus fluids, followed by a more gradual repletion of remaining deficits. After bolus fluids are administered, the rate and type of subsequent IV fluid infusion varies depending on hemodynamics, hydration state, and serum sodium levels.^2,3

Nonaggressive Vs Aggressive Fluid Management. One study by Adrogué et al⁹ compared the effects of managing DKA with aggressive vs nonaggressive fluid repletion. In the study, one group of patients received normal saline at 1,000 mL per hour for 4 hours, followed by normal saline at 500 mL per hour for 4 hours. The other group of patients received normal saline at a more modest rate of 500 mL per hour for 4 hours, followed by normal saline at 250 mL per hour for 4 hours. The authors found that patients in the less aggressive volume therapy group achieved a prompt and adequate recovery and maintained higher serum bicarbonate levels.⁹

Current recommendations for patients with DKA are to first treat patients with an initial bolus of 1,000 mL or 20 cc/kg of normal saline. Patients without profound dehydration should then receive 500 cc of normal saline per hour for the first 4 hours of treatment, after which the flow rate may be reduced to 250 cc per hour. For patients with mild DKA, therapy can start at 250 cc per hour with a smaller bolus dose or no bolus dose. Patients with profound dehydration and poor perfusion, should receive crystalloid fluids wide open until perfusion has improved. Overall, volume resuscitation in HHS is similar to DKA. However, the EP should be cautious with respect to total fluid volume and infusion rates to avoid fluid overload, since many patients with HHS are elderly and may have congestive heart failure.

Crystalloid Fluid Type for Initial Resuscitation. Normal saline has been the traditional crystalloid fluid of choice for managing DKA and HHS. Recent studies, however, have shown some benefit to using balanced solutions (Ringer’s lactate or PlasmaLyte) instead of normal saline. A recently published large study by Semler et al¹⁰ compared balanced crystalloid, in most cases lactated Ringers solution, to normal saline in critically ill adult patients, some of whom were diagnosed with DKA. The study demonstrated decreased mortality (from any cause) in the group who received balanced crystalloid fluid therapy and reduced need for renal-replacement therapy and reduced incidence of persistent renal dysfunction. The findings by Semler et al¹⁰ and findings from other smaller studies, calls into question whether normal saline is the best crystalloid to manage DKA and HHS.^11,12 It remains to be seen what modification the American Diabetes Association (ADA) will make to its current recommendations for fluid therapy, which were last updated in 2009.

It appears that though the use of Ringers lactate or PlasmaLyte to treat DKA usually raises a patient’s serum bicarbonate level to 18 mEq/L at a more rapid rate than normal saline, the use of balanced solutions may result in longer time to lower blood glucose to 250 mg/dL.¹³ However, by using a balanced solution, the hyperchloremic metabolic acidosis often seen with normal saline treatment will be avoided.¹²

Half-Normal Saline. An initially normal or increased serum sodium level, despite significant hyperglycemia, suggests a substantial free-water deficit. Calculating a corrected serum sodium can help quantify the degree of free-water deficit.³ While isotonic fluids remain the standard for initial volume load, clinicians should consider switching patients to half-normal saline following initial resuscitation if the corrected serum sodium is elevated above normal. The simplest estimation to correct sodium levels in DKA is to expect a decrease in sodium levels at a rate of at least 2 mEq/L per 100-mg/dL increase in glucose levels above 100 mg/dL. For a more accurate calculation, providers can expect a drop in sodium of 1.6 mEq/L per 100 mg/dL increase of glucose up to a level of 400 mg/dL and then a fall of 2.4 mEq/L in sodium per every 100 mg/dL rise in glucose thereafter.¹⁴

Glucose. Patients with DKA require insulin therapy until ketoacidosis resolves. However, the average time to correct ketoacidosis from initiating treatment is about 12 hours compared to only 6 hours for correction of hyperglycemia. Since insulin therapy must be continued despite lower glucose levels, patients are at risk for developing hypoglycemia if glucose is not added to IV fluids. To prevent hypoglycemia and provide an energy source for ketone metabolism, patients should be switched to fluids containing dextrose when their serum glucose approaches 200 to 250 mg/dL.^1,3 Typically, 5% dextrose in half-normal saline at 150 to 250 cc per hour is usually adequate to achieve this goal.

Insulin

As previously noted, insulin therapy is required to treat hyperglycemic crises from DKA and HHS. In DKA there is an absolute insulin deficiency, whereas in HHS, there is a relative insulin deficiency. In HHS, there is not enough endogenous insulin to move glucose into the cells, but there is enough insulin to block a catabolic state. That is why the breakdown of fats and proteins does not occur, and why ketoacidosis and hyperkalemia are not seen in HHS. On the other hand, glucose elevations do occur, and are usually more extreme in HHS than DKA. There are five major therapeutic actions of insulin in DKA (Table 5), and it is imperative to determine serum potassium before starting an insulin infusion as insulin will drive potassium into the cell, worsening hypokalemia and promoting the development of life-threatening arrhythmias, including ventricular fibrillation, ventricular tachycardia, and torsades de pointes. The electrocardiogram does not accurately predict severity of hypokalemia and should not be used as a substitute for direct potassium measurement.

Loading Dose and Drip Rate. When treating adult patients with DKA or HHS, the ADA recommends an IV push loading dose of 0.1 U/kg insulin, followed by an hourly maintenance dose of 0.1 U/kg. Alternatively, a continuous infusion of 0.16 U/kg/hr can be used without a bolus. The rationale behind a bolus is the rapid saturation of insulin receptors, followed by a drip to maintain saturation of receptors. However, a recent prospective observational cohort study by Goyal et al¹⁵ questions the utility of the initial insulin bolus. The study compared DKA patients who received an initial insulin bolus to those who did not. Both groups were similar at baseline and received equivalent IV fluids and insulin drips. They found no statistically significant differences in the incidence of hypoglycemia, rate of serum glucose change, anion gap change, or length of stay in the ED or hospital. The authors concluded that administration of an insulin bolus has no significant benefit to patients and does not change clinically relevant end-points.¹⁵ At this time, there is no proven benefit to giving DKA patients an IV insulin bolus; moreover, doing so may further increase hypoglycemia. The use of an insulin bolus is particularly not recommended for use in pediatric patients with DKA due to a higher incidence of hypoglycemia in this patient population.¹⁶

As with DKA, the ADA³ recommends giving HHS patients an insulin bolus of 0.1 U/ kg followed by a continuous infusion at 0.1 U/kg per hour. It is crucial to monitor patients closely to ensure glucose levels do not fall too rapidly. Glucose levels should be kept between 150 to 200 mg/dL for patients with DKA and 200 to 300 mg/dL for patients with HHS until the conditions resolve; this may necessitate lowering the infusion rate to 0.02 to 0.05 U/kg per hour. In addition to frequent glucose monitoring, a basic metabolic panel and venous pH should be obtained every 2 to 4 hours while a patient is on an insulin drip.³

Subcutaneous Vs Intravenous Insulin for DKA. Several small studies evaluating patients with mild-moderate DKA demonstrated similar outcomes when subcutaneous (SQ) insulin was used instead of IV insulin. However, SQ injections require more frequent dosing (every 1 to 2 hours) and still require close monitoring of blood glucose. This monitoring frequency is usually not feasible on a hospital floor, but may be feasible on step-down units, thus avoiding admission to the intensive care unit (ICU) for patients who do not otherwise require ICU-level of care.¹⁷ Subcutaneous insulin should not be given to patients with severe acidosis, hypotension, or altered mental status. The ADA consensus statement continues to recommend IV infusion of regular insulin as the preferred route due to its short half-life and easy titration.³

Determining When to Switch to Subcutaneous Insulin. Ideally, patients are not in the ED long enough to have their metabolic abnormalities corrected, as this usually requires several hours. In DKA, the insulin drip should continue until the blood glucose is less than 200 and at least two of the following conditions are met: the anion gap is less than 12, venous pH greater than 7.3, and serum bicarbonate >15. In HHS, osmolality and mental status should both return to normal prior to stopping the infusion. In both cases, subcutaneous insulin should be administered at least 1 to 2 hours before stopping the drip to prevent recurrent crisis.^1,3

Refractory Acidosis. First and foremost, refractory acidosis should prompt a diligent source for dead gut, abscess, and underlying sepsis. While vomiting and diffuse abdominal pain are common in DKA and are related to ketoacidosis, these symptoms are atypical of HHS and should raise suspicion for underlying pathology.³ Additionally, a lower than expected bicarbonate level can also occur from resuscitation with large volumes of normal saline, resulting in a hyperchloremic non-gap metabolic acidosis.

Potassium

Both DKA and HHS patients have total body potassium deficits due to osmotic diuresis that require careful repletion. Deficits can be substantial: The average total whole body potassium deficit in DKA is 3 to 5 mEq/kg.² Clinicians should exercise caution, however, since DKA patients may be hyperkalemic initially despite a total body potassium deficit. Early hyperkalemia is due to the transmembrane shift of potassium secondary to acidosis and insulin deficiency as well as hypertonicity. If initial potassium is greater than 5.2 mEq/L, potassium should not be administered but instead rechecked in 1 to 2 hours. If the potassium level is 4.0 to 5.2 mEq/L, then 10 mEq per hour is usually adequate. For levels between 3.3 and 4.0 mEq/L, administer potassium chloride at 20 mEq per hour. For levels less than 3.3 mEq/L, insulin should be held and potassium chloride should be aggressively repleted at 20 to 30 mEq per hour with continuous cardiac monitoring.^1-3 Failure to recognize and act on critical potassium levels is a known cause of unexpected death in DKA. During the first hour of DKA onset, patients are more likely to die from hyperkalemia. Later, while the patient is “stabilizing” on an insulin infusion, potassium levels will fall as insulin drives potassium back into cells.

Bicarbonate

Bicarbonate has many theoretical benefits but also has potential risks (Table 6).

Phosphate

Since there is no proven benefit to giving phosphate to adult patients with DKA, it is rarely used, except in specific situations other than pediatric DKA. Similar to potassium, initial serum phosphate levels do not reflect total body phosphate levels due to transmembrane shifts.^2,3 Phosphate repletionis most beneficial for patients who have cachexia, respiratory depression, anemia, cardiac dysfunction, or phosphate values lower than 1.0 to 1.5. If given, 20 to 30 mEq/L potassium phosphate (K₂PO₄) added to fluids is usually sufficient.³ Overly aggressive phosphate administration (>4.5 mmol/h or 1.5 mL/h potassium phosphate) can cause severe hypocalcemia and should be avoided.^1,3 In pediatric patients, up to one-half of potassium requirements are often given as potassium phosphate, but this may vary by institution.

Conclusion

Both DKA and HHS are diabetic emergencies that must be approached and managed systematically to correct underlying dehydration and metabolic abnormalities. Patient care begins by determining the etiology of these conditions, especially HHS. Once the cause has been identified, patients should be treated with bolus fluids to obtain adequate perfusion, followed by IV fluid infusion. Clinicians should carefully monitor the serum sodium level of patients with DKA or HHS to determine the ideal amount and type of fluid required, and also should measure potassium levels prior to starting patients on insulin. (Tables 7 and 8 summarize important clinical pearls when treating patients with DKA or HHS.)

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are similar but distinct diabetic emergencies that are frequently encountered in the ED. Patients with DKA or HHS present with hyperglycemia and dehydration and frequently appear quite ill physically. In both syndromes, there is insufficient insulin levels to transport glucose into cells.

As previously noted, although DKA and HHS share similar characteristic signs and symptoms, they are two distinct conditions that must be differentiated in the clinical work-up. One characteristic that helps the emergency physician (EP) to distinguish between the two conditions is the patient age at symptom onset. Although both conditions can occur at any age, diabetic ketoacidosis typically develops in younger patients, less than 45 years, who have little or no endogenous insulin production, whereas HHS usually occurs in much older non-insulin-dependent patients (who are often greater than 60 years old). ^1-3 This review discusses the similarities and differences in the etiology, diagnosis, and treatment of DKA and HHS to guide evaluation and simplify management, highlighting practical tips and clinical pearls. When applicable, information has been organized into groups of five to facilitate retention and recall.

The Etiology of DKA Vs HHS

The fundamental underlying issue in both DKA and HHS is an absolute or relative lack of insulin that results in an increase in counter-regulatory hormones, including glucagon, cortisol, and catecholamines.

Insulin has five main actions: (1) to drive glucose into cells; (2) to drive potassium into cells; (3) to create an anabolic environment; (4) to inhibit breakdown of fat; and (5) to block the breakdown of proteins. (Table 1).

Diagnosis and Workup

Laboratory Evaluation

In addition to hyperglycemia, another key finding in DKA is elevated anion gap metabolic acidosis resulting from ketoacid production. Laboratory evaluation will demonstrate a pH less than 7.3 and serum bicarbonate level less than 18 mEq/L; urinalysis will be positive for ketones.

Though HHS patients also present with hyperglycemia, laboratory evaluation will demonstrate no, or only mild, acidosis, normal pH (typically >7.3), bicarbonate level greater than 18 mEq/L, and a high-serum osmolality (>350 mOsm/kg). While urinalysis may show low or no ketones, patients with HHS do not develop the marked ketoacidosis seen in DKA. Moreover, glucose values are more elevated in patients with HHS, frequently exceeding 1,000 mg/dL.

Signs and Symptoms

Patients with either of these hyperglycemic crises often present with fatigue, polyuria, and polydipsia. They appear dehydrated on examination with dry mucous membranes, tachycardia, and in severe cases, hypotension. Patients with HHS often present with altered mental status, seizures, and even coma, while patients with DKA typically only experience changes in mental status in the most severe cases (Table 2). As many as one-third of patients with a hyperglycemic crisis will have an overlapping DKA/HHS syndrome.^1-3 With respect to patient age, HHS tends to develop in older patients who have type 2 diabetes and several underlying comorbidities.²

Precipitating Causes of DKA and HHS

The five causes of DKA/HHS can be remembered as the “Five I’s”: (1) infection; (2) infarction; (3) infant (pregnancy), (4) indiscretion, and (5) [lack of] insulin (Table 3).

Infection. Infection is one of the most common precipitating factors in both DKA and HHS.¹ During the history intake, the EP should ask the patient if he or she has had any recent urinary and respiratory symptoms, as positive responses prompt further investigation with urinalysis and chest radiography. A thorough dermatological examination should be performed to assess for visible signs of infection, particularly in the extremities and intertriginous areas.

When assessing patients with DKA or HHS for signs of infection, body temperature to assess for the presence of fever is not always a reliable indicator. This is because many patients with DKA/HHS develop tachypnea, which can affect the efficacy of an oral thermometer. In such cases, the rectal temperature is more sensitive for detecting fever. It should be noted, however, that some patients with severe infection or immunocompromised state—regardless of the presence or absence of tachypnea—may be normothermic or even hypothermic due to peripheral vasodilation—a poor prognostic sign.³ Blood and urine cultures should be obtained for all patients in whom infection is suspected.

Laboratory evaluation of patients with DKA may demonstrate a mild leukocytosis, a very common finding in DKA even in the absence of infection; leukocytosis is believed to result from elevated stress hormones such as cortisol and epinephrine.³

Infarction. Infarction is another important underlying cause of DKA/HHS and one that must not be overlooked. Screening for acute coronary syndrome through patient history, electrocardiography, and cardiac biomarkers should be performed in all patients older than age 40 years and in patients in whom there is any suggestion of myocardial ischemia.

A thorough neurological examination should be performed to assess for deficits indicative of stroke. Although neurological deficits can be due to severe hyperglycemia, most patients with focal neurological deficits from hyperglycemia also have altered mental status. Focal neurological deficits without a change in mental status are more likely to represent an actual stroke.⁴

Infant (Pregnancy). Pregnant patients are at an increased risk of developing DKA for several reasons, most notably due to the increased production of insulin-antagonistic hormones, which can lead to higher insulin resistance and thus increased insulin requirements during pregnancy.⁵ A pregnancy test is therefore indicated for all female patients of child-bearing age.

Indiscretion. Non-compliance with diet, such as taking in too many calories without appropriate insulin correction, and the ingestion of significant amounts of alcohol can lead to DKA. Eating disorders, particularly in young patients, may also contribute to recurrent cases.³

[Lack of] Insulin. In insulin-dependent diabetes, skipped insulin doses or insulin pump failure can trigger DKA/HHS. In fact, missed insulin doses are becoming a more frequent cause of DKA than infections.¹

Both DKA and HHS are usually triggered by an underlying illness or event. Therefore, clinicians should always focus on identifying precipitating causes such as acute infection, stroke, or myocardial infarction, as some require immediate treatment. In fact, DKA or HHS is rarely the primary cause of death; patients are much more likely to die from the precipitating event that caused DKA or HHS.^1,3

Assessing Disease Severity

Mental status and pH and serum bicarbonate levels help clinicians determine the extent of disease severity, classifying patients as having mild, moderate, or severe DKA (Table 4).² Patients at the highest risk for poor outcomes include those at the extremes of age, who have severe comorbidities, who have underlying infection, and who are hypotensive and/or in a comatose state.³

Patients who have HHS are much more likely to present with altered mental status, including coma. There is a linear relationship between osmolality and degree of altered mental status. Thus, diabetic patients with major changes in mental status but without high serum osmolality warrant immediate workup for alternative causes of their altered mental status.³ In addition, seizures, especially focal seizures, are relatively common in severe cases of HHS. Finally, highly abnormal blood pressure, pulse, and respiratory rate can also provide additional clues regarding the severity of hyperglycemic crisis.

Arterial Blood Gas Assessment: To Stick or Not to Stick?

In the past, measuring arterial blood gases (ABG) has been considered a mainstay in the evaluation of patients with DKA. But does an arterial stick, which is associated with some risk, really add essential information? One study by Ma et al⁶ evaluated whether ABG results significantly alter how physicians manage patients with DKA. In the study, the authors evaluated 200 ED patients and found that ABG analysis only changed diagnosis in 1% of patients, altered treatment in 3.5% of patients, and changed disposition in only 1% of patients. Arterial stick partial pressure of oxygen and partial pressure of carbon dioxide altered treatment and disposition in only 1% of patients. Furthermore, the study results showed venous pH correlated very strongly with arterial pH (r = 0.95).⁶ These findings demonstrate that ABG measurements rarely affect or alter DKA management, and support the use of venous pH as an adequate substitute for ABG testing.

Euglycemia

Euglycemic DKA has been reported in patients with type 1 diabetes who had been fasting or vomiting or who had received exogenous insulin prior to presentation.¹Euglycemia has also been reported in pregnant patients with type I diabetes.¹ More recently, sodium glucose cotransporter 2 inhibitors (SGLT2) have been shown to cause euglycemic DKA. While the therapeutic mechanism of this drug class is to inhibit proximal tubular resorption of glucose, they can cause DKA by decreasing renal clearance of ketone bodies and increasing glucagon levels and promoting hepatic ketogenesis. Patients with DKA who are on SGLT2 inhibitors may present with only modestly elevated glucose levels (typically in the 200- to 300-mg/dL range), but have profound wide gap metabolic acidosis due to β-hydroxybutyrate acid and acetoacetate accumulation.⁷ When evaluating patients on SGLT2 inhibitors for DKA, EPs should not solely rely on glucose values but rather assess the patient’s overall clinical picture, including the physical examination, vital signs, and pH. Additionally, once resuscitation with intravenous (IV) fluids and insulin is initiated, it may take longer for patients who use SGLT2 inhibitors to clear ketoacids than patients with DKA who do not use these medications.⁸

Treatment

The goal of treatment for DKA and HHS is to correct volume deficits, hyperglycemia, and electrolyte abnormalities (Table 5). Three of the five therapies to manage DKA and HHS are mandatory: IV fluid resuscitation, IV insulin, and IV potassium. The other therapies, IV bicarbonate, and IV phosphate, should be considered, but are rarely required for DKA or HHS.

In general, management of HHS is less aggressive than that of DKA because HHS develops over a period of weeks—unlike DKA, which develops over only 1 to 2 days. Treatment of any underlying causes of HHS should occur simultaneously.

Intravenous Fluids

The goal of IV fluid therapy for patients with DKA is rehydration—not to “wash-out” ketones. Ketone elimination occurs through insulin-stimulated metabolism. When determining volume-replacement goals, it is helpful to keep in mind that patients with moderate-to-mild DKA typically have fluid deficiencies of 3 to 5 L, and patients with severe DKA have fluid deficiencies between 5 and 6 L. Patients with HHS present with significantly higher fluid deficiencies of around 9 to 12 L.

The initial goal of fluid management is to correct hypoperfusion with bolus fluids, followed by a more gradual repletion of remaining deficits. After bolus fluids are administered, the rate and type of subsequent IV fluid infusion varies depending on hemodynamics, hydration state, and serum sodium levels.^2,3

Nonaggressive Vs Aggressive Fluid Management. One study by Adrogué et al⁹ compared the effects of managing DKA with aggressive vs nonaggressive fluid repletion. In the study, one group of patients received normal saline at 1,000 mL per hour for 4 hours, followed by normal saline at 500 mL per hour for 4 hours. The other group of patients received normal saline at a more modest rate of 500 mL per hour for 4 hours, followed by normal saline at 250 mL per hour for 4 hours. The authors found that patients in the less aggressive volume therapy group achieved a prompt and adequate recovery and maintained higher serum bicarbonate levels.⁹

Current recommendations for patients with DKA are to first treat patients with an initial bolus of 1,000 mL or 20 cc/kg of normal saline. Patients without profound dehydration should then receive 500 cc of normal saline per hour for the first 4 hours of treatment, after which the flow rate may be reduced to 250 cc per hour. For patients with mild DKA, therapy can start at 250 cc per hour with a smaller bolus dose or no bolus dose. Patients with profound dehydration and poor perfusion, should receive crystalloid fluids wide open until perfusion has improved. Overall, volume resuscitation in HHS is similar to DKA. However, the EP should be cautious with respect to total fluid volume and infusion rates to avoid fluid overload, since many patients with HHS are elderly and may have congestive heart failure.

Crystalloid Fluid Type for Initial Resuscitation. Normal saline has been the traditional crystalloid fluid of choice for managing DKA and HHS. Recent studies, however, have shown some benefit to using balanced solutions (Ringer’s lactate or PlasmaLyte) instead of normal saline. A recently published large study by Semler et al¹⁰ compared balanced crystalloid, in most cases lactated Ringers solution, to normal saline in critically ill adult patients, some of whom were diagnosed with DKA. The study demonstrated decreased mortality (from any cause) in the group who received balanced crystalloid fluid therapy and reduced need for renal-replacement therapy and reduced incidence of persistent renal dysfunction. The findings by Semler et al¹⁰ and findings from other smaller studies, calls into question whether normal saline is the best crystalloid to manage DKA and HHS.^11,12 It remains to be seen what modification the American Diabetes Association (ADA) will make to its current recommendations for fluid therapy, which were last updated in 2009.

It appears that though the use of Ringers lactate or PlasmaLyte to treat DKA usually raises a patient’s serum bicarbonate level to 18 mEq/L at a more rapid rate than normal saline, the use of balanced solutions may result in longer time to lower blood glucose to 250 mg/dL.¹³ However, by using a balanced solution, the hyperchloremic metabolic acidosis often seen with normal saline treatment will be avoided.¹²

Half-Normal Saline. An initially normal or increased serum sodium level, despite significant hyperglycemia, suggests a substantial free-water deficit. Calculating a corrected serum sodium can help quantify the degree of free-water deficit.³ While isotonic fluids remain the standard for initial volume load, clinicians should consider switching patients to half-normal saline following initial resuscitation if the corrected serum sodium is elevated above normal. The simplest estimation to correct sodium levels in DKA is to expect a decrease in sodium levels at a rate of at least 2 mEq/L per 100-mg/dL increase in glucose levels above 100 mg/dL. For a more accurate calculation, providers can expect a drop in sodium of 1.6 mEq/L per 100 mg/dL increase of glucose up to a level of 400 mg/dL and then a fall of 2.4 mEq/L in sodium per every 100 mg/dL rise in glucose thereafter.¹⁴

Glucose. Patients with DKA require insulin therapy until ketoacidosis resolves. However, the average time to correct ketoacidosis from initiating treatment is about 12 hours compared to only 6 hours for correction of hyperglycemia. Since insulin therapy must be continued despite lower glucose levels, patients are at risk for developing hypoglycemia if glucose is not added to IV fluids. To prevent hypoglycemia and provide an energy source for ketone metabolism, patients should be switched to fluids containing dextrose when their serum glucose approaches 200 to 250 mg/dL.^1,3 Typically, 5% dextrose in half-normal saline at 150 to 250 cc per hour is usually adequate to achieve this goal.

Insulin

As previously noted, insulin therapy is required to treat hyperglycemic crises from DKA and HHS. In DKA there is an absolute insulin deficiency, whereas in HHS, there is a relative insulin deficiency. In HHS, there is not enough endogenous insulin to move glucose into the cells, but there is enough insulin to block a catabolic state. That is why the breakdown of fats and proteins does not occur, and why ketoacidosis and hyperkalemia are not seen in HHS. On the other hand, glucose elevations do occur, and are usually more extreme in HHS than DKA. There are five major therapeutic actions of insulin in DKA (Table 5), and it is imperative to determine serum potassium before starting an insulin infusion as insulin will drive potassium into the cell, worsening hypokalemia and promoting the development of life-threatening arrhythmias, including ventricular fibrillation, ventricular tachycardia, and torsades de pointes. The electrocardiogram does not accurately predict severity of hypokalemia and should not be used as a substitute for direct potassium measurement.

Loading Dose and Drip Rate. When treating adult patients with DKA or HHS, the ADA recommends an IV push loading dose of 0.1 U/kg insulin, followed by an hourly maintenance dose of 0.1 U/kg. Alternatively, a continuous infusion of 0.16 U/kg/hr can be used without a bolus. The rationale behind a bolus is the rapid saturation of insulin receptors, followed by a drip to maintain saturation of receptors. However, a recent prospective observational cohort study by Goyal et al¹⁵ questions the utility of the initial insulin bolus. The study compared DKA patients who received an initial insulin bolus to those who did not. Both groups were similar at baseline and received equivalent IV fluids and insulin drips. They found no statistically significant differences in the incidence of hypoglycemia, rate of serum glucose change, anion gap change, or length of stay in the ED or hospital. The authors concluded that administration of an insulin bolus has no significant benefit to patients and does not change clinically relevant end-points.¹⁵ At this time, there is no proven benefit to giving DKA patients an IV insulin bolus; moreover, doing so may further increase hypoglycemia. The use of an insulin bolus is particularly not recommended for use in pediatric patients with DKA due to a higher incidence of hypoglycemia in this patient population.¹⁶

As with DKA, the ADA³ recommends giving HHS patients an insulin bolus of 0.1 U/ kg followed by a continuous infusion at 0.1 U/kg per hour. It is crucial to monitor patients closely to ensure glucose levels do not fall too rapidly. Glucose levels should be kept between 150 to 200 mg/dL for patients with DKA and 200 to 300 mg/dL for patients with HHS until the conditions resolve; this may necessitate lowering the infusion rate to 0.02 to 0.05 U/kg per hour. In addition to frequent glucose monitoring, a basic metabolic panel and venous pH should be obtained every 2 to 4 hours while a patient is on an insulin drip.³

Subcutaneous Vs Intravenous Insulin for DKA. Several small studies evaluating patients with mild-moderate DKA demonstrated similar outcomes when subcutaneous (SQ) insulin was used instead of IV insulin. However, SQ injections require more frequent dosing (every 1 to 2 hours) and still require close monitoring of blood glucose. This monitoring frequency is usually not feasible on a hospital floor, but may be feasible on step-down units, thus avoiding admission to the intensive care unit (ICU) for patients who do not otherwise require ICU-level of care.¹⁷ Subcutaneous insulin should not be given to patients with severe acidosis, hypotension, or altered mental status. The ADA consensus statement continues to recommend IV infusion of regular insulin as the preferred route due to its short half-life and easy titration.³

Determining When to Switch to Subcutaneous Insulin. Ideally, patients are not in the ED long enough to have their metabolic abnormalities corrected, as this usually requires several hours. In DKA, the insulin drip should continue until the blood glucose is less than 200 and at least two of the following conditions are met: the anion gap is less than 12, venous pH greater than 7.3, and serum bicarbonate >15. In HHS, osmolality and mental status should both return to normal prior to stopping the infusion. In both cases, subcutaneous insulin should be administered at least 1 to 2 hours before stopping the drip to prevent recurrent crisis.^1,3

Refractory Acidosis. First and foremost, refractory acidosis should prompt a diligent source for dead gut, abscess, and underlying sepsis. While vomiting and diffuse abdominal pain are common in DKA and are related to ketoacidosis, these symptoms are atypical of HHS and should raise suspicion for underlying pathology.³ Additionally, a lower than expected bicarbonate level can also occur from resuscitation with large volumes of normal saline, resulting in a hyperchloremic non-gap metabolic acidosis.

Potassium

Both DKA and HHS patients have total body potassium deficits due to osmotic diuresis that require careful repletion. Deficits can be substantial: The average total whole body potassium deficit in DKA is 3 to 5 mEq/kg.² Clinicians should exercise caution, however, since DKA patients may be hyperkalemic initially despite a total body potassium deficit. Early hyperkalemia is due to the transmembrane shift of potassium secondary to acidosis and insulin deficiency as well as hypertonicity. If initial potassium is greater than 5.2 mEq/L, potassium should not be administered but instead rechecked in 1 to 2 hours. If the potassium level is 4.0 to 5.2 mEq/L, then 10 mEq per hour is usually adequate. For levels between 3.3 and 4.0 mEq/L, administer potassium chloride at 20 mEq per hour. For levels less than 3.3 mEq/L, insulin should be held and potassium chloride should be aggressively repleted at 20 to 30 mEq per hour with continuous cardiac monitoring.^1-3 Failure to recognize and act on critical potassium levels is a known cause of unexpected death in DKA. During the first hour of DKA onset, patients are more likely to die from hyperkalemia. Later, while the patient is “stabilizing” on an insulin infusion, potassium levels will fall as insulin drives potassium back into cells.

Bicarbonate

Bicarbonate has many theoretical benefits but also has potential risks (Table 6).

Phosphate

Since there is no proven benefit to giving phosphate to adult patients with DKA, it is rarely used, except in specific situations other than pediatric DKA. Similar to potassium, initial serum phosphate levels do not reflect total body phosphate levels due to transmembrane shifts.^2,3 Phosphate repletionis most beneficial for patients who have cachexia, respiratory depression, anemia, cardiac dysfunction, or phosphate values lower than 1.0 to 1.5. If given, 20 to 30 mEq/L potassium phosphate (K₂PO₄) added to fluids is usually sufficient.³ Overly aggressive phosphate administration (>4.5 mmol/h or 1.5 mL/h potassium phosphate) can cause severe hypocalcemia and should be avoided.^1,3 In pediatric patients, up to one-half of potassium requirements are often given as potassium phosphate, but this may vary by institution.

Conclusion

Both DKA and HHS are diabetic emergencies that must be approached and managed systematically to correct underlying dehydration and metabolic abnormalities. Patient care begins by determining the etiology of these conditions, especially HHS. Once the cause has been identified, patients should be treated with bolus fluids to obtain adequate perfusion, followed by IV fluid infusion. Clinicians should carefully monitor the serum sodium level of patients with DKA or HHS to determine the ideal amount and type of fluid required, and also should measure potassium levels prior to starting patients on insulin. (Tables 7 and 8 summarize important clinical pearls when treating patients with DKA or HHS.)

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are similar but distinct diabetic emergencies that are frequently encountered in the ED. Patients with DKA or HHS present with hyperglycemia and dehydration and frequently appear quite ill physically. In both syndromes, there is insufficient insulin levels to transport glucose into cells.

As previously noted, although DKA and HHS share similar characteristic signs and symptoms, they are two distinct conditions that must be differentiated in the clinical work-up. One characteristic that helps the emergency physician (EP) to distinguish between the two conditions is the patient age at symptom onset. Although both conditions can occur at any age, diabetic ketoacidosis typically develops in younger patients, less than 45 years, who have little or no endogenous insulin production, whereas HHS usually occurs in much older non-insulin-dependent patients (who are often greater than 60 years old). ^1-3 This review discusses the similarities and differences in the etiology, diagnosis, and treatment of DKA and HHS to guide evaluation and simplify management, highlighting practical tips and clinical pearls. When applicable, information has been organized into groups of five to facilitate retention and recall.

The Etiology of DKA Vs HHS

The fundamental underlying issue in both DKA and HHS is an absolute or relative lack of insulin that results in an increase in counter-regulatory hormones, including glucagon, cortisol, and catecholamines.

Insulin has five main actions: (1) to drive glucose into cells; (2) to drive potassium into cells; (3) to create an anabolic environment; (4) to inhibit breakdown of fat; and (5) to block the breakdown of proteins. (Table 1).

Diagnosis and Workup

Laboratory Evaluation

In addition to hyperglycemia, another key finding in DKA is elevated anion gap metabolic acidosis resulting from ketoacid production. Laboratory evaluation will demonstrate a pH less than 7.3 and serum bicarbonate level less than 18 mEq/L; urinalysis will be positive for ketones.

Though HHS patients also present with hyperglycemia, laboratory evaluation will demonstrate no, or only mild, acidosis, normal pH (typically >7.3), bicarbonate level greater than 18 mEq/L, and a high-serum osmolality (>350 mOsm/kg). While urinalysis may show low or no ketones, patients with HHS do not develop the marked ketoacidosis seen in DKA. Moreover, glucose values are more elevated in patients with HHS, frequently exceeding 1,000 mg/dL.

Signs and Symptoms

Patients with either of these hyperglycemic crises often present with fatigue, polyuria, and polydipsia. They appear dehydrated on examination with dry mucous membranes, tachycardia, and in severe cases, hypotension. Patients with HHS often present with altered mental status, seizures, and even coma, while patients with DKA typically only experience changes in mental status in the most severe cases (Table 2). As many as one-third of patients with a hyperglycemic crisis will have an overlapping DKA/HHS syndrome.^1-3 With respect to patient age, HHS tends to develop in older patients who have type 2 diabetes and several underlying comorbidities.²

Precipitating Causes of DKA and HHS

The five causes of DKA/HHS can be remembered as the “Five I’s”: (1) infection; (2) infarction; (3) infant (pregnancy), (4) indiscretion, and (5) [lack of] insulin (Table 3).

Infection. Infection is one of the most common precipitating factors in both DKA and HHS.¹ During the history intake, the EP should ask the patient if he or she has had any recent urinary and respiratory symptoms, as positive responses prompt further investigation with urinalysis and chest radiography. A thorough dermatological examination should be performed to assess for visible signs of infection, particularly in the extremities and intertriginous areas.

When assessing patients with DKA or HHS for signs of infection, body temperature to assess for the presence of fever is not always a reliable indicator. This is because many patients with DKA/HHS develop tachypnea, which can affect the efficacy of an oral thermometer. In such cases, the rectal temperature is more sensitive for detecting fever. It should be noted, however, that some patients with severe infection or immunocompromised state—regardless of the presence or absence of tachypnea—may be normothermic or even hypothermic due to peripheral vasodilation—a poor prognostic sign.³ Blood and urine cultures should be obtained for all patients in whom infection is suspected.

Laboratory evaluation of patients with DKA may demonstrate a mild leukocytosis, a very common finding in DKA even in the absence of infection; leukocytosis is believed to result from elevated stress hormones such as cortisol and epinephrine.³

Infarction. Infarction is another important underlying cause of DKA/HHS and one that must not be overlooked. Screening for acute coronary syndrome through patient history, electrocardiography, and cardiac biomarkers should be performed in all patients older than age 40 years and in patients in whom there is any suggestion of myocardial ischemia.

A thorough neurological examination should be performed to assess for deficits indicative of stroke. Although neurological deficits can be due to severe hyperglycemia, most patients with focal neurological deficits from hyperglycemia also have altered mental status. Focal neurological deficits without a change in mental status are more likely to represent an actual stroke.⁴

Infant (Pregnancy). Pregnant patients are at an increased risk of developing DKA for several reasons, most notably due to the increased production of insulin-antagonistic hormones, which can lead to higher insulin resistance and thus increased insulin requirements during pregnancy.⁵ A pregnancy test is therefore indicated for all female patients of child-bearing age.

Indiscretion. Non-compliance with diet, such as taking in too many calories without appropriate insulin correction, and the ingestion of significant amounts of alcohol can lead to DKA. Eating disorders, particularly in young patients, may also contribute to recurrent cases.³

[Lack of] Insulin. In insulin-dependent diabetes, skipped insulin doses or insulin pump failure can trigger DKA/HHS. In fact, missed insulin doses are becoming a more frequent cause of DKA than infections.¹

Both DKA and HHS are usually triggered by an underlying illness or event. Therefore, clinicians should always focus on identifying precipitating causes such as acute infection, stroke, or myocardial infarction, as some require immediate treatment. In fact, DKA or HHS is rarely the primary cause of death; patients are much more likely to die from the precipitating event that caused DKA or HHS.^1,3

Assessing Disease Severity

Mental status and pH and serum bicarbonate levels help clinicians determine the extent of disease severity, classifying patients as having mild, moderate, or severe DKA (Table 4).² Patients at the highest risk for poor outcomes include those at the extremes of age, who have severe comorbidities, who have underlying infection, and who are hypotensive and/or in a comatose state.³

Patients who have HHS are much more likely to present with altered mental status, including coma. There is a linear relationship between osmolality and degree of altered mental status. Thus, diabetic patients with major changes in mental status but without high serum osmolality warrant immediate workup for alternative causes of their altered mental status.³ In addition, seizures, especially focal seizures, are relatively common in severe cases of HHS. Finally, highly abnormal blood pressure, pulse, and respiratory rate can also provide additional clues regarding the severity of hyperglycemic crisis.

Arterial Blood Gas Assessment: To Stick or Not to Stick?

In the past, measuring arterial blood gases (ABG) has been considered a mainstay in the evaluation of patients with DKA. But does an arterial stick, which is associated with some risk, really add essential information? One study by Ma et al⁶ evaluated whether ABG results significantly alter how physicians manage patients with DKA. In the study, the authors evaluated 200 ED patients and found that ABG analysis only changed diagnosis in 1% of patients, altered treatment in 3.5% of patients, and changed disposition in only 1% of patients. Arterial stick partial pressure of oxygen and partial pressure of carbon dioxide altered treatment and disposition in only 1% of patients. Furthermore, the study results showed venous pH correlated very strongly with arterial pH (r = 0.95).⁶ These findings demonstrate that ABG measurements rarely affect or alter DKA management, and support the use of venous pH as an adequate substitute for ABG testing.

Euglycemia

Euglycemic DKA has been reported in patients with type 1 diabetes who had been fasting or vomiting or who had received exogenous insulin prior to presentation.¹Euglycemia has also been reported in pregnant patients with type I diabetes.¹ More recently, sodium glucose cotransporter 2 inhibitors (SGLT2) have been shown to cause euglycemic DKA. While the therapeutic mechanism of this drug class is to inhibit proximal tubular resorption of glucose, they can cause DKA by decreasing renal clearance of ketone bodies and increasing glucagon levels and promoting hepatic ketogenesis. Patients with DKA who are on SGLT2 inhibitors may present with only modestly elevated glucose levels (typically in the 200- to 300-mg/dL range), but have profound wide gap metabolic acidosis due to β-hydroxybutyrate acid and acetoacetate accumulation.⁷ When evaluating patients on SGLT2 inhibitors for DKA, EPs should not solely rely on glucose values but rather assess the patient’s overall clinical picture, including the physical examination, vital signs, and pH. Additionally, once resuscitation with intravenous (IV) fluids and insulin is initiated, it may take longer for patients who use SGLT2 inhibitors to clear ketoacids than patients with DKA who do not use these medications.⁸

Treatment

The goal of treatment for DKA and HHS is to correct volume deficits, hyperglycemia, and electrolyte abnormalities (Table 5). Three of the five therapies to manage DKA and HHS are mandatory: IV fluid resuscitation, IV insulin, and IV potassium. The other therapies, IV bicarbonate, and IV phosphate, should be considered, but are rarely required for DKA or HHS.

In general, management of HHS is less aggressive than that of DKA because HHS develops over a period of weeks—unlike DKA, which develops over only 1 to 2 days. Treatment of any underlying causes of HHS should occur simultaneously.

Intravenous Fluids

The goal of IV fluid therapy for patients with DKA is rehydration—not to “wash-out” ketones. Ketone elimination occurs through insulin-stimulated metabolism. When determining volume-replacement goals, it is helpful to keep in mind that patients with moderate-to-mild DKA typically have fluid deficiencies of 3 to 5 L, and patients with severe DKA have fluid deficiencies between 5 and 6 L. Patients with HHS present with significantly higher fluid deficiencies of around 9 to 12 L.

The initial goal of fluid management is to correct hypoperfusion with bolus fluids, followed by a more gradual repletion of remaining deficits. After bolus fluids are administered, the rate and type of subsequent IV fluid infusion varies depending on hemodynamics, hydration state, and serum sodium levels.^2,3

Nonaggressive Vs Aggressive Fluid Management. One study by Adrogué et al⁹ compared the effects of managing DKA with aggressive vs nonaggressive fluid repletion. In the study, one group of patients received normal saline at 1,000 mL per hour for 4 hours, followed by normal saline at 500 mL per hour for 4 hours. The other group of patients received normal saline at a more modest rate of 500 mL per hour for 4 hours, followed by normal saline at 250 mL per hour for 4 hours. The authors found that patients in the less aggressive volume therapy group achieved a prompt and adequate recovery and maintained higher serum bicarbonate levels.⁹

Current recommendations for patients with DKA are to first treat patients with an initial bolus of 1,000 mL or 20 cc/kg of normal saline. Patients without profound dehydration should then receive 500 cc of normal saline per hour for the first 4 hours of treatment, after which the flow rate may be reduced to 250 cc per hour. For patients with mild DKA, therapy can start at 250 cc per hour with a smaller bolus dose or no bolus dose. Patients with profound dehydration and poor perfusion, should receive crystalloid fluids wide open until perfusion has improved. Overall, volume resuscitation in HHS is similar to DKA. However, the EP should be cautious with respect to total fluid volume and infusion rates to avoid fluid overload, since many patients with HHS are elderly and may have congestive heart failure.

Crystalloid Fluid Type for Initial Resuscitation. Normal saline has been the traditional crystalloid fluid of choice for managing DKA and HHS. Recent studies, however, have shown some benefit to using balanced solutions (Ringer’s lactate or PlasmaLyte) instead of normal saline. A recently published large study by Semler et al¹⁰ compared balanced crystalloid, in most cases lactated Ringers solution, to normal saline in critically ill adult patients, some of whom were diagnosed with DKA. The study demonstrated decreased mortality (from any cause) in the group who received balanced crystalloid fluid therapy and reduced need for renal-replacement therapy and reduced incidence of persistent renal dysfunction. The findings by Semler et al¹⁰ and findings from other smaller studies, calls into question whether normal saline is the best crystalloid to manage DKA and HHS.^11,12 It remains to be seen what modification the American Diabetes Association (ADA) will make to its current recommendations for fluid therapy, which were last updated in 2009.

It appears that though the use of Ringers lactate or PlasmaLyte to treat DKA usually raises a patient’s serum bicarbonate level to 18 mEq/L at a more rapid rate than normal saline, the use of balanced solutions may result in longer time to lower blood glucose to 250 mg/dL.¹³ However, by using a balanced solution, the hyperchloremic metabolic acidosis often seen with normal saline treatment will be avoided.¹²

Half-Normal Saline. An initially normal or increased serum sodium level, despite significant hyperglycemia, suggests a substantial free-water deficit. Calculating a corrected serum sodium can help quantify the degree of free-water deficit.³ While isotonic fluids remain the standard for initial volume load, clinicians should consider switching patients to half-normal saline following initial resuscitation if the corrected serum sodium is elevated above normal. The simplest estimation to correct sodium levels in DKA is to expect a decrease in sodium levels at a rate of at least 2 mEq/L per 100-mg/dL increase in glucose levels above 100 mg/dL. For a more accurate calculation, providers can expect a drop in sodium of 1.6 mEq/L per 100 mg/dL increase of glucose up to a level of 400 mg/dL and then a fall of 2.4 mEq/L in sodium per every 100 mg/dL rise in glucose thereafter.¹⁴

Glucose. Patients with DKA require insulin therapy until ketoacidosis resolves. However, the average time to correct ketoacidosis from initiating treatment is about 12 hours compared to only 6 hours for correction of hyperglycemia. Since insulin therapy must be continued despite lower glucose levels, patients are at risk for developing hypoglycemia if glucose is not added to IV fluids. To prevent hypoglycemia and provide an energy source for ketone metabolism, patients should be switched to fluids containing dextrose when their serum glucose approaches 200 to 250 mg/dL.^1,3 Typically, 5% dextrose in half-normal saline at 150 to 250 cc per hour is usually adequate to achieve this goal.

Insulin

As previously noted, insulin therapy is required to treat hyperglycemic crises from DKA and HHS. In DKA there is an absolute insulin deficiency, whereas in HHS, there is a relative insulin deficiency. In HHS, there is not enough endogenous insulin to move glucose into the cells, but there is enough insulin to block a catabolic state. That is why the breakdown of fats and proteins does not occur, and why ketoacidosis and hyperkalemia are not seen in HHS. On the other hand, glucose elevations do occur, and are usually more extreme in HHS than DKA. There are five major therapeutic actions of insulin in DKA (Table 5), and it is imperative to determine serum potassium before starting an insulin infusion as insulin will drive potassium into the cell, worsening hypokalemia and promoting the development of life-threatening arrhythmias, including ventricular fibrillation, ventricular tachycardia, and torsades de pointes. The electrocardiogram does not accurately predict severity of hypokalemia and should not be used as a substitute for direct potassium measurement.

Loading Dose and Drip Rate. When treating adult patients with DKA or HHS, the ADA recommends an IV push loading dose of 0.1 U/kg insulin, followed by an hourly maintenance dose of 0.1 U/kg. Alternatively, a continuous infusion of 0.16 U/kg/hr can be used without a bolus. The rationale behind a bolus is the rapid saturation of insulin receptors, followed by a drip to maintain saturation of receptors. However, a recent prospective observational cohort study by Goyal et al¹⁵ questions the utility of the initial insulin bolus. The study compared DKA patients who received an initial insulin bolus to those who did not. Both groups were similar at baseline and received equivalent IV fluids and insulin drips. They found no statistically significant differences in the incidence of hypoglycemia, rate of serum glucose change, anion gap change, or length of stay in the ED or hospital. The authors concluded that administration of an insulin bolus has no significant benefit to patients and does not change clinically relevant end-points.¹⁵ At this time, there is no proven benefit to giving DKA patients an IV insulin bolus; moreover, doing so may further increase hypoglycemia. The use of an insulin bolus is particularly not recommended for use in pediatric patients with DKA due to a higher incidence of hypoglycemia in this patient population.¹⁶

As with DKA, the ADA³ recommends giving HHS patients an insulin bolus of 0.1 U/ kg followed by a continuous infusion at 0.1 U/kg per hour. It is crucial to monitor patients closely to ensure glucose levels do not fall too rapidly. Glucose levels should be kept between 150 to 200 mg/dL for patients with DKA and 200 to 300 mg/dL for patients with HHS until the conditions resolve; this may necessitate lowering the infusion rate to 0.02 to 0.05 U/kg per hour. In addition to frequent glucose monitoring, a basic metabolic panel and venous pH should be obtained every 2 to 4 hours while a patient is on an insulin drip.³

Subcutaneous Vs Intravenous Insulin for DKA. Several small studies evaluating patients with mild-moderate DKA demonstrated similar outcomes when subcutaneous (SQ) insulin was used instead of IV insulin. However, SQ injections require more frequent dosing (every 1 to 2 hours) and still require close monitoring of blood glucose. This monitoring frequency is usually not feasible on a hospital floor, but may be feasible on step-down units, thus avoiding admission to the intensive care unit (ICU) for patients who do not otherwise require ICU-level of care.¹⁷ Subcutaneous insulin should not be given to patients with severe acidosis, hypotension, or altered mental status. The ADA consensus statement continues to recommend IV infusion of regular insulin as the preferred route due to its short half-life and easy titration.³

Determining When to Switch to Subcutaneous Insulin. Ideally, patients are not in the ED long enough to have their metabolic abnormalities corrected, as this usually requires several hours. In DKA, the insulin drip should continue until the blood glucose is less than 200 and at least two of the following conditions are met: the anion gap is less than 12, venous pH greater than 7.3, and serum bicarbonate >15. In HHS, osmolality and mental status should both return to normal prior to stopping the infusion. In both cases, subcutaneous insulin should be administered at least 1 to 2 hours before stopping the drip to prevent recurrent crisis.^1,3

Refractory Acidosis. First and foremost, refractory acidosis should prompt a diligent source for dead gut, abscess, and underlying sepsis. While vomiting and diffuse abdominal pain are common in DKA and are related to ketoacidosis, these symptoms are atypical of HHS and should raise suspicion for underlying pathology.³ Additionally, a lower than expected bicarbonate level can also occur from resuscitation with large volumes of normal saline, resulting in a hyperchloremic non-gap metabolic acidosis.

Potassium

Both DKA and HHS patients have total body potassium deficits due to osmotic diuresis that require careful repletion. Deficits can be substantial: The average total whole body potassium deficit in DKA is 3 to 5 mEq/kg.² Clinicians should exercise caution, however, since DKA patients may be hyperkalemic initially despite a total body potassium deficit. Early hyperkalemia is due to the transmembrane shift of potassium secondary to acidosis and insulin deficiency as well as hypertonicity. If initial potassium is greater than 5.2 mEq/L, potassium should not be administered but instead rechecked in 1 to 2 hours. If the potassium level is 4.0 to 5.2 mEq/L, then 10 mEq per hour is usually adequate. For levels between 3.3 and 4.0 mEq/L, administer potassium chloride at 20 mEq per hour. For levels less than 3.3 mEq/L, insulin should be held and potassium chloride should be aggressively repleted at 20 to 30 mEq per hour with continuous cardiac monitoring.^1-3 Failure to recognize and act on critical potassium levels is a known cause of unexpected death in DKA. During the first hour of DKA onset, patients are more likely to die from hyperkalemia. Later, while the patient is “stabilizing” on an insulin infusion, potassium levels will fall as insulin drives potassium back into cells.

Bicarbonate

Bicarbonate has many theoretical benefits but also has potential risks (Table 6).

Phosphate

Since there is no proven benefit to giving phosphate to adult patients with DKA, it is rarely used, except in specific situations other than pediatric DKA. Similar to potassium, initial serum phosphate levels do not reflect total body phosphate levels due to transmembrane shifts.^2,3 Phosphate repletionis most beneficial for patients who have cachexia, respiratory depression, anemia, cardiac dysfunction, or phosphate values lower than 1.0 to 1.5. If given, 20 to 30 mEq/L potassium phosphate (K₂PO₄) added to fluids is usually sufficient.³ Overly aggressive phosphate administration (>4.5 mmol/h or 1.5 mL/h potassium phosphate) can cause severe hypocalcemia and should be avoided.^1,3 In pediatric patients, up to one-half of potassium requirements are often given as potassium phosphate, but this may vary by institution.

Conclusion

Both DKA and HHS are diabetic emergencies that must be approached and managed systematically to correct underlying dehydration and metabolic abnormalities. Patient care begins by determining the etiology of these conditions, especially HHS. Once the cause has been identified, patients should be treated with bolus fluids to obtain adequate perfusion, followed by IV fluid infusion. Clinicians should carefully monitor the serum sodium level of patients with DKA or HHS to determine the ideal amount and type of fluid required, and also should measure potassium levels prior to starting patients on insulin. (Tables 7 and 8 summarize important clinical pearls when treating patients with DKA or HHS.)

In the wild world of health care rankings, a year can make a big difference … or not.

After finishing eighth last year, Vermont’s health care system moved up to first in personal finance website WalletHub’s rankings for 2018 and Hawaii, which took the top spot in 2017, dropped to fifth. Iowa fell from second to ninth over the course of the last year while Connecticut and South Dakota moved out of the top 10 to make way for Colorado and Maryland, according to WalletHub.

There was less movement at the other end of the rankings, however, with no change at all in the bottom five: Louisiana finished 51st again (the rankings include the District of Columbia), preceded by fellow repeaters Mississippi (50), Alaska (49), Arkansas (48), and North Carolina (47). Texas and Nevada did manage to move on up out of the bottom 11 – to 38th and 40th, respectively – at the expense of Oklahoma and Tennessee, WalletHub reported.

For 2018, the company compared the states and D.C. “across 40 measures of cost, accessibility and outcome,” which is five more measures than last year and a possible explanation for the changes at the top. The cost dimension’s five metrics included cost of medical visits and share of high out-of-pocket medical spending. The accessibility dimension consisted of 21 metrics, including average emergency department wait time and share of insured children. The outcomes dimension included 14 metrics, among them maternal mortality rate and share of adults with type 2 diabetes.

Vermont did well in both the outcomes (first) and cost (third) dimensions but only middle of the pack (23rd) in access. The District of Columbia was ranked first in cost and Maine was the leader in access. The lowest-ranked states in each category were Alaska (cost), Texas (access), and Mississippi (outcomes), according to the WalletHub analysis, which was based on data from such sources as the Centers for Disease Control and Prevention, the Health Resources & Services Administration, and the United Health Foundation.

[email protected]

In the wild world of health care rankings, a year can make a big difference … or not.

After finishing eighth last year, Vermont’s health care system moved up to first in personal finance website WalletHub’s rankings for 2018 and Hawaii, which took the top spot in 2017, dropped to fifth. Iowa fell from second to ninth over the course of the last year while Connecticut and South Dakota moved out of the top 10 to make way for Colorado and Maryland, according to WalletHub.

There was less movement at the other end of the rankings, however, with no change at all in the bottom five: Louisiana finished 51st again (the rankings include the District of Columbia), preceded by fellow repeaters Mississippi (50), Alaska (49), Arkansas (48), and North Carolina (47). Texas and Nevada did manage to move on up out of the bottom 11 – to 38th and 40th, respectively – at the expense of Oklahoma and Tennessee, WalletHub reported.

For 2018, the company compared the states and D.C. “across 40 measures of cost, accessibility and outcome,” which is five more measures than last year and a possible explanation for the changes at the top. The cost dimension’s five metrics included cost of medical visits and share of high out-of-pocket medical spending. The accessibility dimension consisted of 21 metrics, including average emergency department wait time and share of insured children. The outcomes dimension included 14 metrics, among them maternal mortality rate and share of adults with type 2 diabetes.

Vermont did well in both the outcomes (first) and cost (third) dimensions but only middle of the pack (23rd) in access. The District of Columbia was ranked first in cost and Maine was the leader in access. The lowest-ranked states in each category were Alaska (cost), Texas (access), and Mississippi (outcomes), according to the WalletHub analysis, which was based on data from such sources as the Centers for Disease Control and Prevention, the Health Resources & Services Administration, and the United Health Foundation.

[email protected]

In the wild world of health care rankings, a year can make a big difference … or not.

After finishing eighth last year, Vermont’s health care system moved up to first in personal finance website WalletHub’s rankings for 2018 and Hawaii, which took the top spot in 2017, dropped to fifth. Iowa fell from second to ninth over the course of the last year while Connecticut and South Dakota moved out of the top 10 to make way for Colorado and Maryland, according to WalletHub.

There was less movement at the other end of the rankings, however, with no change at all in the bottom five: Louisiana finished 51st again (the rankings include the District of Columbia), preceded by fellow repeaters Mississippi (50), Alaska (49), Arkansas (48), and North Carolina (47). Texas and Nevada did manage to move on up out of the bottom 11 – to 38th and 40th, respectively – at the expense of Oklahoma and Tennessee, WalletHub reported.

For 2018, the company compared the states and D.C. “across 40 measures of cost, accessibility and outcome,” which is five more measures than last year and a possible explanation for the changes at the top. The cost dimension’s five metrics included cost of medical visits and share of high out-of-pocket medical spending. The accessibility dimension consisted of 21 metrics, including average emergency department wait time and share of insured children. The outcomes dimension included 14 metrics, among them maternal mortality rate and share of adults with type 2 diabetes.

Vermont did well in both the outcomes (first) and cost (third) dimensions but only middle of the pack (23rd) in access. The District of Columbia was ranked first in cost and Maine was the leader in access. The lowest-ranked states in each category were Alaska (cost), Texas (access), and Mississippi (outcomes), according to the WalletHub analysis, which was based on data from such sources as the Centers for Disease Control and Prevention, the Health Resources & Services Administration, and the United Health Foundation.

[email protected]

Marked differences were seen in the composition of hepatitis C virus hypervariable region 1 (HVR1) when comparing HIV-coinfected (CIP) with HCV-monoinfected (MIP) individuals, according to the results of a genetic analysis of nearly 300 patients.

Courtesy NIH

Intrahost HCV HVR1 evolution varies between these two groups, which suggests that HIV-inflicted changes in the host environment exact a strong HCV genetic response, according to a report published online in Infection, Genetics, and Evolution.

“A high prevalence of HIV-HCV coinfection and its impact on mortality among such populations groups as PWID [people who inject drugs] and MSM [men who have sex with men] is of major concern to public health,” according to the researchers.

Previous studies using the Global Hepatitis Outbreak and Surveillance Technology, a Web-based system for the detection of HCV transmission developed by the researchers, analyzed sequences of intrahost variants of the HVR1 region using next-generation sequencing. They found that genetic variation in the HVR1 of intrahost HCV variants was strongly associated with host sex and ethnicity, resistance to interferon, and stages of HCV infection.

In this particular study, the researchers assessed 28,622 nucleotide sequences of intrahost HCV HVR1 variants from 113 CIP and 176 MIP individuals.

They examined 148 physical-chemical indexes of DNA nucleotide dimers and found that there were significant differences in the means and frequency distributions of seven physical-chemical properties between HVR1 variants from both groups.

The significant majority of these profiles (98%-99%) were found to be specific to CIP or MIP, indicating that coevolution among HVR1 sites reflects HCV adaptation to HIV among coinfected individuals. “This observation suggests substantial differences in fitness between HVR1 variants circulating in infected hosts in the presence or absence of HIV, according to the researchers from the Centers for Disease Control and Prevention.

“HCV strains circulating in high-risk groups need to be carefully monitored for the identification of potentially new traits of clinical and public health relevance,” the researchers concluded.

This study was supported by CDC intramural funding. The authors reported that they had no disclosures.

[email protected]

SOURCE: Lara J et al. doi: 10.1016/j.meegid.2018.07.039.

Marked differences were seen in the composition of hepatitis C virus hypervariable region 1 (HVR1) when comparing HIV-coinfected (CIP) with HCV-monoinfected (MIP) individuals, according to the results of a genetic analysis of nearly 300 patients.

Courtesy NIH

Intrahost HCV HVR1 evolution varies between these two groups, which suggests that HIV-inflicted changes in the host environment exact a strong HCV genetic response, according to a report published online in Infection, Genetics, and Evolution.

“A high prevalence of HIV-HCV coinfection and its impact on mortality among such populations groups as PWID [people who inject drugs] and MSM [men who have sex with men] is of major concern to public health,” according to the researchers.

Previous studies using the Global Hepatitis Outbreak and Surveillance Technology, a Web-based system for the detection of HCV transmission developed by the researchers, analyzed sequences of intrahost variants of the HVR1 region using next-generation sequencing. They found that genetic variation in the HVR1 of intrahost HCV variants was strongly associated with host sex and ethnicity, resistance to interferon, and stages of HCV infection.

In this particular study, the researchers assessed 28,622 nucleotide sequences of intrahost HCV HVR1 variants from 113 CIP and 176 MIP individuals.

They examined 148 physical-chemical indexes of DNA nucleotide dimers and found that there were significant differences in the means and frequency distributions of seven physical-chemical properties between HVR1 variants from both groups.

The significant majority of these profiles (98%-99%) were found to be specific to CIP or MIP, indicating that coevolution among HVR1 sites reflects HCV adaptation to HIV among coinfected individuals. “This observation suggests substantial differences in fitness between HVR1 variants circulating in infected hosts in the presence or absence of HIV, according to the researchers from the Centers for Disease Control and Prevention.

“HCV strains circulating in high-risk groups need to be carefully monitored for the identification of potentially new traits of clinical and public health relevance,” the researchers concluded.

This study was supported by CDC intramural funding. The authors reported that they had no disclosures.

[email protected]

SOURCE: Lara J et al. doi: 10.1016/j.meegid.2018.07.039.

Marked differences were seen in the composition of hepatitis C virus hypervariable region 1 (HVR1) when comparing HIV-coinfected (CIP) with HCV-monoinfected (MIP) individuals, according to the results of a genetic analysis of nearly 300 patients.

Courtesy NIH

Intrahost HCV HVR1 evolution varies between these two groups, which suggests that HIV-inflicted changes in the host environment exact a strong HCV genetic response, according to a report published online in Infection, Genetics, and Evolution.

“A high prevalence of HIV-HCV coinfection and its impact on mortality among such populations groups as PWID [people who inject drugs] and MSM [men who have sex with men] is of major concern to public health,” according to the researchers.

Previous studies using the Global Hepatitis Outbreak and Surveillance Technology, a Web-based system for the detection of HCV transmission developed by the researchers, analyzed sequences of intrahost variants of the HVR1 region using next-generation sequencing. They found that genetic variation in the HVR1 of intrahost HCV variants was strongly associated with host sex and ethnicity, resistance to interferon, and stages of HCV infection.

In this particular study, the researchers assessed 28,622 nucleotide sequences of intrahost HCV HVR1 variants from 113 CIP and 176 MIP individuals.

They examined 148 physical-chemical indexes of DNA nucleotide dimers and found that there were significant differences in the means and frequency distributions of seven physical-chemical properties between HVR1 variants from both groups.

The significant majority of these profiles (98%-99%) were found to be specific to CIP or MIP, indicating that coevolution among HVR1 sites reflects HCV adaptation to HIV among coinfected individuals. “This observation suggests substantial differences in fitness between HVR1 variants circulating in infected hosts in the presence or absence of HIV, according to the researchers from the Centers for Disease Control and Prevention.

“HCV strains circulating in high-risk groups need to be carefully monitored for the identification of potentially new traits of clinical and public health relevance,” the researchers concluded.

This study was supported by CDC intramural funding. The authors reported that they had no disclosures.

[email protected]

SOURCE: Lara J et al. doi: 10.1016/j.meegid.2018.07.039.

PARIS – Use of the Sapien 3 transcatheter heart valve led to similarly favorable short-term and 1-year outcomes in a propensity-matched comparison of patients with bicuspid versus tricuspid aortic stenosis, with one glaring exception: The total stroke rate was significantly higher in the bicuspid group.

But the higher stroke rate isn’t necessarily a deal breaker for efforts to develop transcatheter aortic valve replacement (TAVR) as an option for patients with bicuspid aortic stenosis, according to Rajendra Makkar, MD, who presented the study results at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Dr. Makkar noted that “75% of the strokes in the bicuspid aortic stenosis group occurred in the periprocedural time period, and these are all heavily calcified valves.” “So I would make the argument that, in young bicuspid patients where you decide to treat using TAVR, the safety gain from using an embolic protection device may be even more [than in most tricuspid patients]. I say that should be the way to do it. I think carefully selected patients with bicuspid aortic stenosis can be managed with TAVR with an embolic protection device very safely.”

He presented the results of this comparison of TAVR outcomes using the Sapien 3 valve in patients with native bicuspid versus tricuspid valves; all patients had enrolled in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry between June 2015 and February 2018. The initial analysis included 1,792 Sapien 3 recipients with severely symptomatic bicuspid aortic stenosis and 55,023 with severely symptomatic tricuspid aortic stenosis.

As TAVR increasingly becomes an option for younger and healthier patients with symptomatic aortic stenosis, operators will encounter more patients with congenital bicuspid valves. Outcomes using early-generation TAVR valves in such patients were poor, so pivotal randomized trials of the Sapien 3 and other contemporary TAVR valves – including the ongoing trials of TAVR versus surgery in patients with low surgical risk – have excluded those with bicuspid aortic stenosis.

As a result, there has been little clinical data to guide interventionalists, so there was an impetus for a study like this one, explained Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center in Los Angeles.

In the registry analysis, the unadjusted 1-year all-cause mortality rate was 10.4% in the bicuspid patients and 15% in the tricuspid patients, for a significant 22% relative risk reduction. The 1-year total stroke rates were nearly identical at 3.4% in the bicuspid patients and 3.3% in the tricuspid patients. However, the two groups differed in many key ways. The bicuspid patients were on average 8 years younger, and their mean Society of Thoracic Surgeons risk score was 5.1 versus 6.7 in the tricuspid patients. The bicuspid patients also had less atrial fibrillation, peripheral artery disease, and prior revascularization.

Because of these differences, Dr. Makkar and his coinvestigators carefully propensity-matched the 1,792 bicuspid aortic stenosis who received the Sapien 3 valve at 386 U.S. sites with an equal number of tricuspid aortic stenosis patients treated at 424 sites. This yielded two populations that were virtually identical in terms of age, Society of Thoracic Surgeons score, and 22 other baseline characteristics. Of the patients in both groups, 93%had transfemoral access, 38% had conscious sedation, and the device success rate was in 97%.

Thirty-day outcomes in the two groups didn’t differ significantly except for the total stroke rate: 2.5% in the bicuspid group versus 0.9% in the tricuspid group (see graphic). The 1-year mortality rates didn’t differ significantly: 10.4% in the bicuspid group and 10.8% in the patients with tricuspid disease. However, the 1-year total stroke rate remained significantly higher in the bicuspid group by a margin of 3.4%-2.7%.

The reduction in aortic valve mean gradient and increase in aortic valve area were similar in both groups through 1 year of follow-up, as was the increase in left ventricular ejection fraction. Rates of significant paravalvular leak were similarly low in both groups.

Quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed what Dr. Makkar called “remarkable” improvement in both groups: There was an average 30-point improvement from baseline at 30 days after TAVR that was sustained through 1 year, at which point the average gain over baseline was 32 points.

Dr. Makkar drew attention to the impressively low rates of major procedural complications in both groups: Conversion to open-heart surgery took place in 0.9% of the bicuspid and 0.4% of the tricuspid group; annulus rupture occurred in 0.3% of bicuspid TAVR patients and none of the tricuspid group; the aortic dissection rates were 0.3% and 0.1%, respectively; coronary obstruction occurred in 0.4% and 0.1%; and a second valve was needed in 0.6% of the bicuspid group and 0.1% of the tricuspid group. The fact that each of those adverse events happened in fewer than 1% of the bicuspid recipients of the Sapien 3 valve stands in striking contrast to the far higher rates when earlier-generation devices were used in TAVR for bicuspid aortic valves.

“I think our data suggest that in patients with bicuspid aortic stenosis who are at high or intermediate surgical risk, it is really reasonable to actually use TAVR as one of the treatment modalities. And I would make the argument that based on these data it is very reasonable to enroll carefully selected low–surgical risk bicuspid patients in ongoing TAVR versus surgery clinical trials,” the cardiologist said.

Session cochair Alain Cribier, MD, was put off by the higher total stroke rate in the bicuspid group.

“I think, really, that in young patients with a true congenital calcific bicuspid aortic valve, these patients should remain in the hands of the surgeons. In the future, this will be one of the remaining indications for surgery if TAVR works in low-risk patients,” predicted Dr. Cribier, professor of medicine at the University of Rouen (France) and a TAVR pioneer.

Dr. Makkar reported receiving research grants from and serving as a consultant to Edwards Lifesciences, which sponsored the study, as well as from Abbott Laboratories, Pfizer, Medtronic, and Claret Medical.

[email protected]

PARIS – Use of the Sapien 3 transcatheter heart valve led to similarly favorable short-term and 1-year outcomes in a propensity-matched comparison of patients with bicuspid versus tricuspid aortic stenosis, with one glaring exception: The total stroke rate was significantly higher in the bicuspid group.

But the higher stroke rate isn’t necessarily a deal breaker for efforts to develop transcatheter aortic valve replacement (TAVR) as an option for patients with bicuspid aortic stenosis, according to Rajendra Makkar, MD, who presented the study results at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Dr. Makkar noted that “75% of the strokes in the bicuspid aortic stenosis group occurred in the periprocedural time period, and these are all heavily calcified valves.” “So I would make the argument that, in young bicuspid patients where you decide to treat using TAVR, the safety gain from using an embolic protection device may be even more [than in most tricuspid patients]. I say that should be the way to do it. I think carefully selected patients with bicuspid aortic stenosis can be managed with TAVR with an embolic protection device very safely.”

He presented the results of this comparison of TAVR outcomes using the Sapien 3 valve in patients with native bicuspid versus tricuspid valves; all patients had enrolled in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry between June 2015 and February 2018. The initial analysis included 1,792 Sapien 3 recipients with severely symptomatic bicuspid aortic stenosis and 55,023 with severely symptomatic tricuspid aortic stenosis.

As TAVR increasingly becomes an option for younger and healthier patients with symptomatic aortic stenosis, operators will encounter more patients with congenital bicuspid valves. Outcomes using early-generation TAVR valves in such patients were poor, so pivotal randomized trials of the Sapien 3 and other contemporary TAVR valves – including the ongoing trials of TAVR versus surgery in patients with low surgical risk – have excluded those with bicuspid aortic stenosis.

As a result, there has been little clinical data to guide interventionalists, so there was an impetus for a study like this one, explained Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center in Los Angeles.

In the registry analysis, the unadjusted 1-year all-cause mortality rate was 10.4% in the bicuspid patients and 15% in the tricuspid patients, for a significant 22% relative risk reduction. The 1-year total stroke rates were nearly identical at 3.4% in the bicuspid patients and 3.3% in the tricuspid patients. However, the two groups differed in many key ways. The bicuspid patients were on average 8 years younger, and their mean Society of Thoracic Surgeons risk score was 5.1 versus 6.7 in the tricuspid patients. The bicuspid patients also had less atrial fibrillation, peripheral artery disease, and prior revascularization.

Because of these differences, Dr. Makkar and his coinvestigators carefully propensity-matched the 1,792 bicuspid aortic stenosis who received the Sapien 3 valve at 386 U.S. sites with an equal number of tricuspid aortic stenosis patients treated at 424 sites. This yielded two populations that were virtually identical in terms of age, Society of Thoracic Surgeons score, and 22 other baseline characteristics. Of the patients in both groups, 93%had transfemoral access, 38% had conscious sedation, and the device success rate was in 97%.

Thirty-day outcomes in the two groups didn’t differ significantly except for the total stroke rate: 2.5% in the bicuspid group versus 0.9% in the tricuspid group (see graphic). The 1-year mortality rates didn’t differ significantly: 10.4% in the bicuspid group and 10.8% in the patients with tricuspid disease. However, the 1-year total stroke rate remained significantly higher in the bicuspid group by a margin of 3.4%-2.7%.

The reduction in aortic valve mean gradient and increase in aortic valve area were similar in both groups through 1 year of follow-up, as was the increase in left ventricular ejection fraction. Rates of significant paravalvular leak were similarly low in both groups.

Quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed what Dr. Makkar called “remarkable” improvement in both groups: There was an average 30-point improvement from baseline at 30 days after TAVR that was sustained through 1 year, at which point the average gain over baseline was 32 points.

Dr. Makkar drew attention to the impressively low rates of major procedural complications in both groups: Conversion to open-heart surgery took place in 0.9% of the bicuspid and 0.4% of the tricuspid group; annulus rupture occurred in 0.3% of bicuspid TAVR patients and none of the tricuspid group; the aortic dissection rates were 0.3% and 0.1%, respectively; coronary obstruction occurred in 0.4% and 0.1%; and a second valve was needed in 0.6% of the bicuspid group and 0.1% of the tricuspid group. The fact that each of those adverse events happened in fewer than 1% of the bicuspid recipients of the Sapien 3 valve stands in striking contrast to the far higher rates when earlier-generation devices were used in TAVR for bicuspid aortic valves.

“I think our data suggest that in patients with bicuspid aortic stenosis who are at high or intermediate surgical risk, it is really reasonable to actually use TAVR as one of the treatment modalities. And I would make the argument that based on these data it is very reasonable to enroll carefully selected low–surgical risk bicuspid patients in ongoing TAVR versus surgery clinical trials,” the cardiologist said.

Session cochair Alain Cribier, MD, was put off by the higher total stroke rate in the bicuspid group.

“I think, really, that in young patients with a true congenital calcific bicuspid aortic valve, these patients should remain in the hands of the surgeons. In the future, this will be one of the remaining indications for surgery if TAVR works in low-risk patients,” predicted Dr. Cribier, professor of medicine at the University of Rouen (France) and a TAVR pioneer.

Dr. Makkar reported receiving research grants from and serving as a consultant to Edwards Lifesciences, which sponsored the study, as well as from Abbott Laboratories, Pfizer, Medtronic, and Claret Medical.

[email protected]

PARIS – Use of the Sapien 3 transcatheter heart valve led to similarly favorable short-term and 1-year outcomes in a propensity-matched comparison of patients with bicuspid versus tricuspid aortic stenosis, with one glaring exception: The total stroke rate was significantly higher in the bicuspid group.

But the higher stroke rate isn’t necessarily a deal breaker for efforts to develop transcatheter aortic valve replacement (TAVR) as an option for patients with bicuspid aortic stenosis, according to Rajendra Makkar, MD, who presented the study results at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Dr. Makkar noted that “75% of the strokes in the bicuspid aortic stenosis group occurred in the periprocedural time period, and these are all heavily calcified valves.” “So I would make the argument that, in young bicuspid patients where you decide to treat using TAVR, the safety gain from using an embolic protection device may be even more [than in most tricuspid patients]. I say that should be the way to do it. I think carefully selected patients with bicuspid aortic stenosis can be managed with TAVR with an embolic protection device very safely.”

He presented the results of this comparison of TAVR outcomes using the Sapien 3 valve in patients with native bicuspid versus tricuspid valves; all patients had enrolled in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry between June 2015 and February 2018. The initial analysis included 1,792 Sapien 3 recipients with severely symptomatic bicuspid aortic stenosis and 55,023 with severely symptomatic tricuspid aortic stenosis.

As TAVR increasingly becomes an option for younger and healthier patients with symptomatic aortic stenosis, operators will encounter more patients with congenital bicuspid valves. Outcomes using early-generation TAVR valves in such patients were poor, so pivotal randomized trials of the Sapien 3 and other contemporary TAVR valves – including the ongoing trials of TAVR versus surgery in patients with low surgical risk – have excluded those with bicuspid aortic stenosis.

As a result, there has been little clinical data to guide interventionalists, so there was an impetus for a study like this one, explained Dr. Makkar, director of interventional cardiology and the cardiac catheterization laboratory at Cedars-Sinai Medical Center in Los Angeles.

In the registry analysis, the unadjusted 1-year all-cause mortality rate was 10.4% in the bicuspid patients and 15% in the tricuspid patients, for a significant 22% relative risk reduction. The 1-year total stroke rates were nearly identical at 3.4% in the bicuspid patients and 3.3% in the tricuspid patients. However, the two groups differed in many key ways. The bicuspid patients were on average 8 years younger, and their mean Society of Thoracic Surgeons risk score was 5.1 versus 6.7 in the tricuspid patients. The bicuspid patients also had less atrial fibrillation, peripheral artery disease, and prior revascularization.

Because of these differences, Dr. Makkar and his coinvestigators carefully propensity-matched the 1,792 bicuspid aortic stenosis who received the Sapien 3 valve at 386 U.S. sites with an equal number of tricuspid aortic stenosis patients treated at 424 sites. This yielded two populations that were virtually identical in terms of age, Society of Thoracic Surgeons score, and 22 other baseline characteristics. Of the patients in both groups, 93%had transfemoral access, 38% had conscious sedation, and the device success rate was in 97%.

Thirty-day outcomes in the two groups didn’t differ significantly except for the total stroke rate: 2.5% in the bicuspid group versus 0.9% in the tricuspid group (see graphic). The 1-year mortality rates didn’t differ significantly: 10.4% in the bicuspid group and 10.8% in the patients with tricuspid disease. However, the 1-year total stroke rate remained significantly higher in the bicuspid group by a margin of 3.4%-2.7%.

The reduction in aortic valve mean gradient and increase in aortic valve area were similar in both groups through 1 year of follow-up, as was the increase in left ventricular ejection fraction. Rates of significant paravalvular leak were similarly low in both groups.

Quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed what Dr. Makkar called “remarkable” improvement in both groups: There was an average 30-point improvement from baseline at 30 days after TAVR that was sustained through 1 year, at which point the average gain over baseline was 32 points.

Dr. Makkar drew attention to the impressively low rates of major procedural complications in both groups: Conversion to open-heart surgery took place in 0.9% of the bicuspid and 0.4% of the tricuspid group; annulus rupture occurred in 0.3% of bicuspid TAVR patients and none of the tricuspid group; the aortic dissection rates were 0.3% and 0.1%, respectively; coronary obstruction occurred in 0.4% and 0.1%; and a second valve was needed in 0.6% of the bicuspid group and 0.1% of the tricuspid group. The fact that each of those adverse events happened in fewer than 1% of the bicuspid recipients of the Sapien 3 valve stands in striking contrast to the far higher rates when earlier-generation devices were used in TAVR for bicuspid aortic valves.

“I think our data suggest that in patients with bicuspid aortic stenosis who are at high or intermediate surgical risk, it is really reasonable to actually use TAVR as one of the treatment modalities. And I would make the argument that based on these data it is very reasonable to enroll carefully selected low–surgical risk bicuspid patients in ongoing TAVR versus surgery clinical trials,” the cardiologist said.

Session cochair Alain Cribier, MD, was put off by the higher total stroke rate in the bicuspid group.

“I think, really, that in young patients with a true congenital calcific bicuspid aortic valve, these patients should remain in the hands of the surgeons. In the future, this will be one of the remaining indications for surgery if TAVR works in low-risk patients,” predicted Dr. Cribier, professor of medicine at the University of Rouen (France) and a TAVR pioneer.

Dr. Makkar reported receiving research grants from and serving as a consultant to Edwards Lifesciences, which sponsored the study, as well as from Abbott Laboratories, Pfizer, Medtronic, and Claret Medical.

[email protected]

Manufacturers developing the next generation of drugs to help combat opioid use disorder could have a broader set of outcome measures to target when bringing their products before the Food and Drug Administration for approval.

[email protected]

Manufacturers developing the next generation of drugs to help combat opioid use disorder could have a broader set of outcome measures to target when bringing their products before the Food and Drug Administration for approval.

[email protected]

Manufacturers developing the next generation of drugs to help combat opioid use disorder could have a broader set of outcome measures to target when bringing their products before the Food and Drug Administration for approval.

[email protected]

Cardiologists in states with payment limits for medical malpractice claims practice less defensive medicine, a study suggests.

Steven A. Farmer, MD, PhD, of George Washington University, Washington, and his colleagues studied the coronary artery disease (CAD) testing practices of 36,647 doctors in nine states that have noneconomic damages caps for medical liability payouts and compared them with the testing practices of 39,154 doctors in 20 no-cap states. (The investigators studied only states that enacted damage limits between 2002 and 2005.) They studied physicians who ordered or performed two or more angiographies on a 5% random sample of Medicare fee-for-service beneficiaries between 1999 and 2013 who were 65 years or older.

Findings showed that in the cap states, doctors ordered 24% fewer angiographies as a first diagnostic test, compared with control physicians (relative change, −24%; 95% confidence interval, −40% to −7%; P = .005), but cap-state doctors also ordered 8% more noninvasive stress tests (7.8%; 95% CI, −3.6% to 19. P = .17), the authors reported in JAMA Cardiology.

Physicians in damages cap states referred 21% fewer patients for angiography following stress testing (−21%; 95% CI, −40% to −2%; P = .03) and fewer of their patients progressed from evaluation to revascularization. Changes in overall ischemic evaluation rates were similar for new-cap and no-cap physicians, the study found.

The authors noted that the decreased tendency for patients of cap-state physicians to progress from ischemic evaluation to revascularization had three possible channels: fewer initial angiographies, less progression from stress testing to angiography, and less progression from angiography to revascularization. The first two channels are statistically significant, while the third is directionally consistent, according to the study.

The overall results show a direct link between damage caps and cardiac care decisions, Dr. Framer wrote, adding that physicians are willing to tolerate greater clinical uncertainty in CAD testing if they face lower malpractice risk. The authors said the analysis builds on previous research showing that 12% of percutaneous coronary interventions for nonacute indications are inappropriate, and that CAD testing and treatments may be overused in the Medicare fee-for-service setting.

“Curtailing marginal or unnecessary angiography and revascularization spares patients invasive procedures and associated risk and saves resources,” Dr. Farmer wrote. “In addition, both the Department of Health and Human Services and commercial payers are moving rapidly toward alternate payment models. A core issue for these models is provider resistance to changing established practice patterns. Our study suggests that physicians who face lower malpractice risk may be less concerned with that risk, and thus more receptive to new care delivery strategies associated with alternate payment models.”

The study is believed to be the first to demonstrate changes in clinical behavior in the CAD testing and treatment setting after damages cap adoption.

SOURCE: Farmer et al. JAMA Cardiol. 2018 Jun 6 doi: 10.1001/jamacardio.2018.1360.

Cardiologists in states with payment limits for medical malpractice claims practice less defensive medicine, a study suggests.

Steven A. Farmer, MD, PhD, of George Washington University, Washington, and his colleagues studied the coronary artery disease (CAD) testing practices of 36,647 doctors in nine states that have noneconomic damages caps for medical liability payouts and compared them with the testing practices of 39,154 doctors in 20 no-cap states. (The investigators studied only states that enacted damage limits between 2002 and 2005.) They studied physicians who ordered or performed two or more angiographies on a 5% random sample of Medicare fee-for-service beneficiaries between 1999 and 2013 who were 65 years or older.

Findings showed that in the cap states, doctors ordered 24% fewer angiographies as a first diagnostic test, compared with control physicians (relative change, −24%; 95% confidence interval, −40% to −7%; P = .005), but cap-state doctors also ordered 8% more noninvasive stress tests (7.8%; 95% CI, −3.6% to 19. P = .17), the authors reported in JAMA Cardiology.

Physicians in damages cap states referred 21% fewer patients for angiography following stress testing (−21%; 95% CI, −40% to −2%; P = .03) and fewer of their patients progressed from evaluation to revascularization. Changes in overall ischemic evaluation rates were similar for new-cap and no-cap physicians, the study found.

The authors noted that the decreased tendency for patients of cap-state physicians to progress from ischemic evaluation to revascularization had three possible channels: fewer initial angiographies, less progression from stress testing to angiography, and less progression from angiography to revascularization. The first two channels are statistically significant, while the third is directionally consistent, according to the study.

The overall results show a direct link between damage caps and cardiac care decisions, Dr. Framer wrote, adding that physicians are willing to tolerate greater clinical uncertainty in CAD testing if they face lower malpractice risk. The authors said the analysis builds on previous research showing that 12% of percutaneous coronary interventions for nonacute indications are inappropriate, and that CAD testing and treatments may be overused in the Medicare fee-for-service setting.

“Curtailing marginal or unnecessary angiography and revascularization spares patients invasive procedures and associated risk and saves resources,” Dr. Farmer wrote. “In addition, both the Department of Health and Human Services and commercial payers are moving rapidly toward alternate payment models. A core issue for these models is provider resistance to changing established practice patterns. Our study suggests that physicians who face lower malpractice risk may be less concerned with that risk, and thus more receptive to new care delivery strategies associated with alternate payment models.”

The study is believed to be the first to demonstrate changes in clinical behavior in the CAD testing and treatment setting after damages cap adoption.

SOURCE: Farmer et al. JAMA Cardiol. 2018 Jun 6 doi: 10.1001/jamacardio.2018.1360.

Cardiologists in states with payment limits for medical malpractice claims practice less defensive medicine, a study suggests.

Steven A. Farmer, MD, PhD, of George Washington University, Washington, and his colleagues studied the coronary artery disease (CAD) testing practices of 36,647 doctors in nine states that have noneconomic damages caps for medical liability payouts and compared them with the testing practices of 39,154 doctors in 20 no-cap states. (The investigators studied only states that enacted damage limits between 2002 and 2005.) They studied physicians who ordered or performed two or more angiographies on a 5% random sample of Medicare fee-for-service beneficiaries between 1999 and 2013 who were 65 years or older.

Findings showed that in the cap states, doctors ordered 24% fewer angiographies as a first diagnostic test, compared with control physicians (relative change, −24%; 95% confidence interval, −40% to −7%; P = .005), but cap-state doctors also ordered 8% more noninvasive stress tests (7.8%; 95% CI, −3.6% to 19. P = .17), the authors reported in JAMA Cardiology.

Physicians in damages cap states referred 21% fewer patients for angiography following stress testing (−21%; 95% CI, −40% to −2%; P = .03) and fewer of their patients progressed from evaluation to revascularization. Changes in overall ischemic evaluation rates were similar for new-cap and no-cap physicians, the study found.

The authors noted that the decreased tendency for patients of cap-state physicians to progress from ischemic evaluation to revascularization had three possible channels: fewer initial angiographies, less progression from stress testing to angiography, and less progression from angiography to revascularization. The first two channels are statistically significant, while the third is directionally consistent, according to the study.

The overall results show a direct link between damage caps and cardiac care decisions, Dr. Framer wrote, adding that physicians are willing to tolerate greater clinical uncertainty in CAD testing if they face lower malpractice risk. The authors said the analysis builds on previous research showing that 12% of percutaneous coronary interventions for nonacute indications are inappropriate, and that CAD testing and treatments may be overused in the Medicare fee-for-service setting.

“Curtailing marginal or unnecessary angiography and revascularization spares patients invasive procedures and associated risk and saves resources,” Dr. Farmer wrote. “In addition, both the Department of Health and Human Services and commercial payers are moving rapidly toward alternate payment models. A core issue for these models is provider resistance to changing established practice patterns. Our study suggests that physicians who face lower malpractice risk may be less concerned with that risk, and thus more receptive to new care delivery strategies associated with alternate payment models.”

The study is believed to be the first to demonstrate changes in clinical behavior in the CAD testing and treatment setting after damages cap adoption.

SOURCE: Farmer et al. JAMA Cardiol. 2018 Jun 6 doi: 10.1001/jamacardio.2018.1360.

When the American Medical Association – one of the nation’s most powerful health care groups – met in Chicago this June, its medical student caucus seized an opportunity for change.

Though they had tried for years to advance a resolution calling on the organization to drop its decades-long opposition to single-payer health care, this was the first time it got a full hearing. The debate grew heated – older physicians warned their pay would decrease, calling younger advocates naive to single-payer’s consequences. But this time, by the meeting’s end, the AMA’s older members had agreed to at least study the possibility of changing its stance.

“We believe health care is a human right, maybe more so than past generations,” said Brad Zehr, MD, a pathology resident at Ohio State University, who was part of the debate. “There’s a generational shift happening, where we see universal health care as a requirement.”

The ins and outs of the AMA’s policymaking may sound like inside baseball. But this year’s youth uprising at the nexus of the medical establishment speaks to a cultural shift in the medical profession, and one with big political implications.

Amid Republican attacks on the Affordable Care Act, an increasing number of Democrats – both candidates and Congress members – are putting forth proposals that would vastly increase the government’s role in running the health system. These include single-payer, Medicare-for-all, or an option for anyone to buy in to the Medicare program. At least 70 House Democrats have signed on to the new “Medicare-for-all” caucus.

Organized medicine, and previous generations of doctors, had for the most part staunchly opposed any such plan. The AMA has thwarted public health insurance proposals since the 1930s and long been considered one of the policy’s most powerful opponents.

But the battle lines are shifting as younger doctors flip their views, a change that will likely assume greater significance as the next generation of physicians takes on leadership roles. The AMA did not make anyone available for comment.

Many younger physicians are “accepting of single-payer,” said Christian Pean, MD, a third-year orthopedic surgery resident at New York University.

In prior generations, “intelligent, motivated, quantitative” students pursued medicine, both for the income and because of the workplace independence – running practices with minimal government interference, said Steven Schroeder, MD, professor of medicine at the University of California, San Francisco.

In his 50 years of teaching, students’ attitudes have changed, he said. “The ‘Oh, keep government out of my work’ feeling is not as strong as it was with maybe older cohorts,” said Dr. Schroeder. “Students come in saying, ‘We want to make a difference through social justice. That’s why we’re here.’ ”

Though single-payer health care long has been dismissed as a left-wing pipe dream, polling suggests a slim majority of Americans now support the idea – though it is not clear people know what the term means.

A full single-payer system means everyone gets coverage from the same insurance plan, usually sponsored by the government. “Medicare for all,” a phrase that gained currency with the presidential campaign of Sen. Bernie Sanders (I-Vt.), means everyone gets Medicare, but, depending on the proposal, it may or may not allow private insurers to offer Medicare as well. (Sen. Sanders’ plan, which eliminates deductibles and expands benefits, would get rid of private insurers.)

Meanwhile, lots of countries achieve universal health care – everyone is covered somehow – but the method can vary. For example, France requires all citizens purchase coverage, which is sold through nonprofits. In Germany, most people get insurance from a government-run “public option,” while others purchase private plans. In England, health care is provided through the tax-funded National Health System.

American skeptics often use the phrase “socialized medicine” pejoratively to describe all of these models.

“Few really understand what you mean when you say single-payer,” said Frank Opelka, MD, medical director of quality and health policy for the American College of Surgeons, which opposes such a policy. “What they mean is, ‘I don’t think the current system is working.’ ”

But the willingness to explore previously unthinkable ideas is evident in young doctors’ ranks.

Recent surveys through LinkedIn, Merritt Hawkins, and NEJM Catalyst indicate growing support. In the March NEJM Catalyst survey, 61% of 607 respondents said single-payer would make it easier to deliver cost-effective, quality health care.

Delving further, that survey shows support is stronger among younger physicians, said Namita Mohta, MD, a hospitalist at Brigham and Women’s Hospital, Boston, and clinical editor at NEJM Catalyst.

But it’s unclear whether these findings reflect young doctors’ feelings about the policy or whether they are tapping in to broader frustrations with the American health system.

Much like the general public, doctors often use terms like single-payer, Medicare for all, and universal health care interchangeably.

“Our younger generation is less afraid to come out and say we want universal health care,” said Anna Yap, MD, an emergency medicine resident at UCLA, who served as a medical student delegate to the AMA until this past June. “But how? It’s different in what forms we see.”

Younger doctors also pointed to growing concern about how best to keep patients healthy. They cited research that broadly suggests having health insurance tracks with better health outcomes.

“Medical students, I would say, are very interested in public health and improving social determinants of health – one of them being access to health insurance,” said Jerome Jeevarajan, MD, a neurology resident at the University of Texas–Houston, referring to nonmedical factors that improve health, such as food or housing.

Some of the shift in opinion has to do with the changing realities of medical practice. Doctors now are more likely to end up working for large health systems or hospitals, rather than starting a practice. Combined with the increasing complexity of billing private insurance, many said, that means contracting with the government may feel like less of an intrusion.

The debate is, at this point, still theoretical. Republicans – who control the White House and both houses of Congress – sharply oppose single-payer. Meanwhile, single-state efforts in California, Colorado, and New York have fallen flat.

Also, doctors represent only one part of the sprawling health care industrial complex. Other health care interests – including private insurance, the drug industry, and hospital trade groups – have been slower to warm to catchphrases like single-payer or universal health care, all of which would likely mean a drop in income.

But increasingly physicians seem to be switching sides in the debate, and young physicians want to be part of the discussion.

“There’s tremendous potential ... to be at the table if single-payer becomes a significant part of the political discourse, and create a system that is more equitable,” Dr. Pean said.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

When the American Medical Association – one of the nation’s most powerful health care groups – met in Chicago this June, its medical student caucus seized an opportunity for change.

Though they had tried for years to advance a resolution calling on the organization to drop its decades-long opposition to single-payer health care, this was the first time it got a full hearing. The debate grew heated – older physicians warned their pay would decrease, calling younger advocates naive to single-payer’s consequences. But this time, by the meeting’s end, the AMA’s older members had agreed to at least study the possibility of changing its stance.

“We believe health care is a human right, maybe more so than past generations,” said Brad Zehr, MD, a pathology resident at Ohio State University, who was part of the debate. “There’s a generational shift happening, where we see universal health care as a requirement.”

The ins and outs of the AMA’s policymaking may sound like inside baseball. But this year’s youth uprising at the nexus of the medical establishment speaks to a cultural shift in the medical profession, and one with big political implications.

Amid Republican attacks on the Affordable Care Act, an increasing number of Democrats – both candidates and Congress members – are putting forth proposals that would vastly increase the government’s role in running the health system. These include single-payer, Medicare-for-all, or an option for anyone to buy in to the Medicare program. At least 70 House Democrats have signed on to the new “Medicare-for-all” caucus.

Organized medicine, and previous generations of doctors, had for the most part staunchly opposed any such plan. The AMA has thwarted public health insurance proposals since the 1930s and long been considered one of the policy’s most powerful opponents.

But the battle lines are shifting as younger doctors flip their views, a change that will likely assume greater significance as the next generation of physicians takes on leadership roles. The AMA did not make anyone available for comment.

Many younger physicians are “accepting of single-payer,” said Christian Pean, MD, a third-year orthopedic surgery resident at New York University.

In prior generations, “intelligent, motivated, quantitative” students pursued medicine, both for the income and because of the workplace independence – running practices with minimal government interference, said Steven Schroeder, MD, professor of medicine at the University of California, San Francisco.

In his 50 years of teaching, students’ attitudes have changed, he said. “The ‘Oh, keep government out of my work’ feeling is not as strong as it was with maybe older cohorts,” said Dr. Schroeder. “Students come in saying, ‘We want to make a difference through social justice. That’s why we’re here.’ ”

Though single-payer health care long has been dismissed as a left-wing pipe dream, polling suggests a slim majority of Americans now support the idea – though it is not clear people know what the term means.

A full single-payer system means everyone gets coverage from the same insurance plan, usually sponsored by the government. “Medicare for all,” a phrase that gained currency with the presidential campaign of Sen. Bernie Sanders (I-Vt.), means everyone gets Medicare, but, depending on the proposal, it may or may not allow private insurers to offer Medicare as well. (Sen. Sanders’ plan, which eliminates deductibles and expands benefits, would get rid of private insurers.)

Meanwhile, lots of countries achieve universal health care – everyone is covered somehow – but the method can vary. For example, France requires all citizens purchase coverage, which is sold through nonprofits. In Germany, most people get insurance from a government-run “public option,” while others purchase private plans. In England, health care is provided through the tax-funded National Health System.

American skeptics often use the phrase “socialized medicine” pejoratively to describe all of these models.

“Few really understand what you mean when you say single-payer,” said Frank Opelka, MD, medical director of quality and health policy for the American College of Surgeons, which opposes such a policy. “What they mean is, ‘I don’t think the current system is working.’ ”

But the willingness to explore previously unthinkable ideas is evident in young doctors’ ranks.

Recent surveys through LinkedIn, Merritt Hawkins, and NEJM Catalyst indicate growing support. In the March NEJM Catalyst survey, 61% of 607 respondents said single-payer would make it easier to deliver cost-effective, quality health care.

Delving further, that survey shows support is stronger among younger physicians, said Namita Mohta, MD, a hospitalist at Brigham and Women’s Hospital, Boston, and clinical editor at NEJM Catalyst.

But it’s unclear whether these findings reflect young doctors’ feelings about the policy or whether they are tapping in to broader frustrations with the American health system.

Much like the general public, doctors often use terms like single-payer, Medicare for all, and universal health care interchangeably.

“Our younger generation is less afraid to come out and say we want universal health care,” said Anna Yap, MD, an emergency medicine resident at UCLA, who served as a medical student delegate to the AMA until this past June. “But how? It’s different in what forms we see.”

Younger doctors also pointed to growing concern about how best to keep patients healthy. They cited research that broadly suggests having health insurance tracks with better health outcomes.

“Medical students, I would say, are very interested in public health and improving social determinants of health – one of them being access to health insurance,” said Jerome Jeevarajan, MD, a neurology resident at the University of Texas–Houston, referring to nonmedical factors that improve health, such as food or housing.

Some of the shift in opinion has to do with the changing realities of medical practice. Doctors now are more likely to end up working for large health systems or hospitals, rather than starting a practice. Combined with the increasing complexity of billing private insurance, many said, that means contracting with the government may feel like less of an intrusion.

The debate is, at this point, still theoretical. Republicans – who control the White House and both houses of Congress – sharply oppose single-payer. Meanwhile, single-state efforts in California, Colorado, and New York have fallen flat.

Also, doctors represent only one part of the sprawling health care industrial complex. Other health care interests – including private insurance, the drug industry, and hospital trade groups – have been slower to warm to catchphrases like single-payer or universal health care, all of which would likely mean a drop in income.

But increasingly physicians seem to be switching sides in the debate, and young physicians want to be part of the discussion.

“There’s tremendous potential ... to be at the table if single-payer becomes a significant part of the political discourse, and create a system that is more equitable,” Dr. Pean said.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

When the American Medical Association – one of the nation’s most powerful health care groups – met in Chicago this June, its medical student caucus seized an opportunity for change.

Though they had tried for years to advance a resolution calling on the organization to drop its decades-long opposition to single-payer health care, this was the first time it got a full hearing. The debate grew heated – older physicians warned their pay would decrease, calling younger advocates naive to single-payer’s consequences. But this time, by the meeting’s end, the AMA’s older members had agreed to at least study the possibility of changing its stance.

“We believe health care is a human right, maybe more so than past generations,” said Brad Zehr, MD, a pathology resident at Ohio State University, who was part of the debate. “There’s a generational shift happening, where we see universal health care as a requirement.”

The ins and outs of the AMA’s policymaking may sound like inside baseball. But this year’s youth uprising at the nexus of the medical establishment speaks to a cultural shift in the medical profession, and one with big political implications.

Amid Republican attacks on the Affordable Care Act, an increasing number of Democrats – both candidates and Congress members – are putting forth proposals that would vastly increase the government’s role in running the health system. These include single-payer, Medicare-for-all, or an option for anyone to buy in to the Medicare program. At least 70 House Democrats have signed on to the new “Medicare-for-all” caucus.

Organized medicine, and previous generations of doctors, had for the most part staunchly opposed any such plan. The AMA has thwarted public health insurance proposals since the 1930s and long been considered one of the policy’s most powerful opponents.

But the battle lines are shifting as younger doctors flip their views, a change that will likely assume greater significance as the next generation of physicians takes on leadership roles. The AMA did not make anyone available for comment.

Many younger physicians are “accepting of single-payer,” said Christian Pean, MD, a third-year orthopedic surgery resident at New York University.

In prior generations, “intelligent, motivated, quantitative” students pursued medicine, both for the income and because of the workplace independence – running practices with minimal government interference, said Steven Schroeder, MD, professor of medicine at the University of California, San Francisco.

In his 50 years of teaching, students’ attitudes have changed, he said. “The ‘Oh, keep government out of my work’ feeling is not as strong as it was with maybe older cohorts,” said Dr. Schroeder. “Students come in saying, ‘We want to make a difference through social justice. That’s why we’re here.’ ”

Though single-payer health care long has been dismissed as a left-wing pipe dream, polling suggests a slim majority of Americans now support the idea – though it is not clear people know what the term means.

A full single-payer system means everyone gets coverage from the same insurance plan, usually sponsored by the government. “Medicare for all,” a phrase that gained currency with the presidential campaign of Sen. Bernie Sanders (I-Vt.), means everyone gets Medicare, but, depending on the proposal, it may or may not allow private insurers to offer Medicare as well. (Sen. Sanders’ plan, which eliminates deductibles and expands benefits, would get rid of private insurers.)

Meanwhile, lots of countries achieve universal health care – everyone is covered somehow – but the method can vary. For example, France requires all citizens purchase coverage, which is sold through nonprofits. In Germany, most people get insurance from a government-run “public option,” while others purchase private plans. In England, health care is provided through the tax-funded National Health System.

American skeptics often use the phrase “socialized medicine” pejoratively to describe all of these models.

“Few really understand what you mean when you say single-payer,” said Frank Opelka, MD, medical director of quality and health policy for the American College of Surgeons, which opposes such a policy. “What they mean is, ‘I don’t think the current system is working.’ ”

But the willingness to explore previously unthinkable ideas is evident in young doctors’ ranks.

Recent surveys through LinkedIn, Merritt Hawkins, and NEJM Catalyst indicate growing support. In the March NEJM Catalyst survey, 61% of 607 respondents said single-payer would make it easier to deliver cost-effective, quality health care.

Delving further, that survey shows support is stronger among younger physicians, said Namita Mohta, MD, a hospitalist at Brigham and Women’s Hospital, Boston, and clinical editor at NEJM Catalyst.

But it’s unclear whether these findings reflect young doctors’ feelings about the policy or whether they are tapping in to broader frustrations with the American health system.

Much like the general public, doctors often use terms like single-payer, Medicare for all, and universal health care interchangeably.

“Our younger generation is less afraid to come out and say we want universal health care,” said Anna Yap, MD, an emergency medicine resident at UCLA, who served as a medical student delegate to the AMA until this past June. “But how? It’s different in what forms we see.”

Younger doctors also pointed to growing concern about how best to keep patients healthy. They cited research that broadly suggests having health insurance tracks with better health outcomes.

“Medical students, I would say, are very interested in public health and improving social determinants of health – one of them being access to health insurance,” said Jerome Jeevarajan, MD, a neurology resident at the University of Texas–Houston, referring to nonmedical factors that improve health, such as food or housing.

Some of the shift in opinion has to do with the changing realities of medical practice. Doctors now are more likely to end up working for large health systems or hospitals, rather than starting a practice. Combined with the increasing complexity of billing private insurance, many said, that means contracting with the government may feel like less of an intrusion.

The debate is, at this point, still theoretical. Republicans – who control the White House and both houses of Congress – sharply oppose single-payer. Meanwhile, single-state efforts in California, Colorado, and New York have fallen flat.

Also, doctors represent only one part of the sprawling health care industrial complex. Other health care interests – including private insurance, the drug industry, and hospital trade groups – have been slower to warm to catchphrases like single-payer or universal health care, all of which would likely mean a drop in income.

But increasingly physicians seem to be switching sides in the debate, and young physicians want to be part of the discussion.

“There’s tremendous potential ... to be at the table if single-payer becomes a significant part of the political discourse, and create a system that is more equitable,” Dr. Pean said.

Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Background: Rhythm control with medical therapy has been shown to not be superior to rate control for patients with both heart failure and AF. Rhythm control by ablation has been associated with positive outcomes in this same population, but its effectiveness, compared with medical therapy for patient-centered outcomes, has not been demonstrated.

Citation: Marrouche N et al. Catheter ablation for atrial fibrillation with heart failure. N Eng J Med. 2018 Feb 1; 378:417-27.

Dr. Salber is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.

Background: Rhythm control with medical therapy has been shown to not be superior to rate control for patients with both heart failure and AF. Rhythm control by ablation has been associated with positive outcomes in this same population, but its effectiveness, compared with medical therapy for patient-centered outcomes, has not been demonstrated.

Citation: Marrouche N et al. Catheter ablation for atrial fibrillation with heart failure. N Eng J Med. 2018 Feb 1; 378:417-27.

Dr. Salber is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.

Background: Rhythm control with medical therapy has been shown to not be superior to rate control for patients with both heart failure and AF. Rhythm control by ablation has been associated with positive outcomes in this same population, but its effectiveness, compared with medical therapy for patient-centered outcomes, has not been demonstrated.

Citation: Marrouche N et al. Catheter ablation for atrial fibrillation with heart failure. N Eng J Med. 2018 Feb 1; 378:417-27.

Dr. Salber is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.