Impact of Hyponatremia

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Pathophysiology, impact, and management of hyponatremia

The high prevalence of hyponatremia in hospitalized patients has been recognized for decades. Published reports dating back to the 1960s indicate that serum sodium concentrations ([Na+]) tend to be lower in hospitalized patients than in outpatients in the community.1 Current estimates for the prevalence of hyponatremia in hospitalized patients range from 15% to nearly 40%.2, 3 Several factors account for this wide range. While most studies estimate the presence of hyponatremia based on International Classification of Diseases, Ninth Revision (ICD‐9) codes, accurate reporting varies widely from institution to institution.4 Furthermore, the definition of hyponatremia depends entirely on the cut‐off value of [Na+] used (generally, 136 mEq/L).3 In addition to patients who have hyponatremia present on admission, a significant proportion develop the condition during their hospital stay.3 Deficits in water excretion can develop or worsen during hospitalization as a result of several factors, combined with intake of hypotonic fluid.3 In a study of hyponatremia in intensive care unit (ICU) patients, as many as 80% demonstrated impaired urinary dilution during their ICU course.5

The prevalence of hyponatremia is significant in patients hospitalized for heart failure (HF), cirrhosis, and pneumonia.6 The prevalence of hyponatremiadefined as serum sodium 135 mEq/Lranges from 18% to 25% in patients admitted for congestive heart failure.79 Rates of hyponatremia in patients admitted with cirrhosis are even higher on average, ranging between 18% and 49%.1012 Hyponatremia is also common in patients with community‐acquired pneumonia (CAP), with prevalence estimates ranging from 8% to 28%.1315

Overall, hyponatremia in each of these disease states portends worse outcome.16 In a retrospective study of 71 adults with pneumonia, admission serum [Na+] 135 mEq/L was a risk factor for in‐hospital mortality.13 In each of these conditions, hyponatremia is associated with the need for ICU care and mechanical ventilation, increased hospital length of stay (LOS), and higher costs of care.17, 18

PATHOPHYSIOLOGY OF HYPONATREMIA

There are 2 primary stimuli for the secretion of antidiuretic hormone (ADH), otherwise known as arginine vasopressin (AVP). Osmoreceptors in the hypothalamus measure the osmolality of the plasma.19 When osmolality increases, AVP is secreted; alternatively, when plasma osmolality drops, secretion of AVP under normal circumstances will diminish. The other stimulus results from baroreceptors throughout the body. Decreased intravascular volume (manifested by lower blood pressure) causes activation of the renin‐angiotensin‐aldosterone system, the sympathetic nervous system, as well as AVP secretion.16, 20 In turn, AVP acts on vasopressin V2 receptors in the kidney to encourage water reapsorption, therefore impairing the patient's ability to excrete dilute urine.6

The mechanism by which hyponatremia develops varies according to disease state. Whereas neurohormonal activation predominates in those with HF and cirrhosis, inappropriate AVP secretion (and in some cases, a resetting of the osmostat) occurs in patients with CAP.10, 13, 17 In both HF and cirrhosis, the degree of neurohormonal activation correlates with the degree of hyponatremia.17

In healthy individuals, the mechanism for free water excretion is AVP suppression caused by a fall in plasma osmolality. Patients with hyponatremia, however, are unable to suppress AVP due to true volume depletion (eg, as a result of inadequate oral intake, gastrointestinal fluids loss from vomiting/diarrhea, or use of thiazide diuretics), effective volume depletion (reduced cardiac output in HF patients vs vasodilation in patients with cirrhosis), or an inappropriate increase in AVP secretion.19, 21, 22

RISK FACTORS

The risk factors for hyponatremia are numerous.2, 22 The ability to excrete water declines with increasing age and is exacerbated by chronic illness. Other risk factors include low body weight, low sodium diets, and residence in a chronic care facility.22, 23 Patients with a low baseline serum sodium concentration also appear to be at increased risk of developing hyponatremia. Although the mechanisms by which such patients develop hyponatremia are not always clear, they generally involve an impaired ability to excrete free water due to an inability to appropriately suppress AVP secretion. Medications commonly associated with the syndrome of inappropriate ADH secretion (SIADH) include selective serotonin reuptake inhibitors (SSRIs), psychotropic drugs, non‐steroidal anti‐inflammatory drugs (NSAIDs), opiates, proton pump inhibitors, as well as certain chemotherapeutics.21, 22 Other risk factors associated with SIADH include major abdominal or thoracic surgery, pain, nausea, and excessive administration of hypotonic intravenous fluids. Finally, diuretic use (in particular thiazides) places patients at risk to develop hyponatremia by increasing total urine volume and solute excretion without an appreciable increase in free water excretion.24

MORBIDITY

The morbidities associated with hyponatremia vary widely in severity. Serious sequelae may occur as a result of hyponatremia itself, as well as from complications that occur due to the challenging nature of effective management. Much of the symptomatology relates to the central nervous system (CNS). Patients presenting with extremely low serum [Na+] levels (eg, 115 mEq/L) often have severe neurologic symptoms, while those with lesser degrees of hyponatremia may be asymptomatic, or present with milder nonspecific symptoms, such as confusion.25, 26 It is important to note that the clinical presentation of hyponatremia very much depends on whether it is acute (occurring over 2448 hours) or chronic (>48 hours).

Water shifts between the intracellular and extracellular fluid compartments are the primary means by which the body equalizes osmolality. When serum sodium changes, the ability of the brain to compensate is limited, and may result in various forms of neurologic impairment due to cerebral edema.25, 26 Such patients may become disoriented, restless, unable to attend, or unable to process information cognitively. There may also be peripheral neurologic dysfunction, such as muscle weakness, blunted neuromuscular reflexes, and impaired gait. Such impairments can lead to delirium, falls, and fractures.25, 27

HYPONATREMIA AND COGNITIVE IMPAIRMENT

Renneboog and colleagues performed a case‐control study to assess the impact of mild chronic asymptomatic hyponatremia (mean serum [Na+] 126 5 mEq/L) in 122 patients compared with 244 matched controls (mean age 72 13 years).28 Hyponatremic patients had significantly longer mean response times on concentration tests. Interestingly, the changes in cognitive function in hyponatremic patients were similar to healthy volunteers purposefully intoxicated with alcohol.28 Patients with hyponatremia have also been shown to score lower on the mental component summary of the 36‐item Short‐Form (SF‐36) survey.29 With treatment aimed at improving serum sodium, these same patients demonstrated improved cognitive function,29 suggesting that treating even mild forms of hyponatremia can improve patient outcomes.30

HYPONATREMIA AND FALLS/FRACTURES

Renneboog and colleagues also demonstrated a markedly increased risk of falls in their patients with chronic hyponatremia compared to controls.28 Hyponatremia increases not only the risk of falls, but also the risk of fracture following a fall. In another recent case‐control study of 513 patients, the adjusted odds ratio for fracture after a fall in a patient with hyponatremia was 4.16 compared with an age‐matched control with normal serum sodium who sustained a similar fall.27 Of note, hyponatremia was mild and asymptomatic in all patients studied. Medications (36% diuretics, 17% SSRIs) were the most common precipitating cause of hyponatremia in this study, which is notable because such risk factors should be recognized and addressed.

Although falls and fractures lead to obvious increases in morbidity and cost, delirium has also been identified as a risk factor for increased hospital LOS.18 Delirious patients are less likely and able to mobilize and participate in physical therapy. As such, they are more often bed‐bound and at increased risk for aspiration and other preventable issues, including deep vein thrombosis, bed sores, and debility, all of which may increase their LOS and cost of care.

MORTALITY

Hyponatremia is associated with a significantly increased mortality risk not only during hospitalization, but also at 1 and 5 years following discharge.31 In a prospective cohort study of approximately 100,000 patients, even those with mild hyponatremia ([Na+] 130134 mEq/L) had a significantly higher mortality at 5 years. The adjusted odds ratio for mortality in patients with serum sodium less than 135 mEq/L was 1.47 during hospitalization (95% CI, 1.331.62), 1.38 at 1 year post‐discharge (1.321.46), and 1.25 at 5 years (1.211.30). The significance of hyponatremia varied according to the underlying clinical condition, with the greatest risk observed in patients with metastatic cancer, heart disease, and those who had undergone orthopedic surgery.31 While the association between hyponatremia and mortality is profound, most experts do not believe that hyponatremia directly causes mortality per se. Instead, hyponatremia is felt to be a marker for increased illness severity.

It is difficult to isolate the direct costs of hyponatremia in the acute care setting because the condition is rarely treated in isolation. However, in a study of a managed‐care claims database of nearly 1,300 patients (excluding Medicare patients), hyponatremia was a predictor of higher medical costs at 6 months and at 1 year.32

DIAGNOSIS

The most common presentation of hyponatremia involves nonspecific symptoms or a total lack of symptoms.19 Many patients have comorbid diseases, and symptoms of these illnesses often predominate at hospital admission. Patients with mild to moderate hyponatremia may present with nausea, weakness, malaise, headache, and/or impaired mobility. With more severe hyponatremia, more dangerous neurologic symptoms appear, including generalized seizures, lethargy, and coma.19 Once hyponatremia is identified, the next step is to determine its acuity and classify it.

Although several classification systems exist to describe hyponatremia, the most common scheme begins with assessment of plasma osmolality and volume status.19 The majority of hyponatremic patients present with hypotonic or hypo‐osmolar serum (eg, plasma osmolality 275 mOsm/kg). The primary causes of hyponatremia in patients with normal or high serum osmolality are hyperglycemia, pseudohyponatremia, and advanced renal failure. Marked hyperglycemia increases plasma osmolality, and as a result, water moves out of cells into plasma and lowers serum sodium concentration in the process. Pseudohyponatremia arises from hyperlipidemia or hyperproteinemia, in which high concentrations of lipids/proteins reduce the free water component of plasma, therefore reducing the sodium concentration per liter of plasma. These patients do not have true hyponatremia since the physiologically important sodium concentration per liter of plasma water is normal. Finally, patients with advanced renal failure develop hyponatremia due to the inability to excrete water.

The first step in the diagnosis of hyponatremia is to assess the plasma osmolality and rule out the aforementioned conditions that cause normal or elevated serum osmolality. Patients with hypotonic serum must then be evaluated clinically to determine their volume status. Appropriate classification here has important implications for management.

In addition to clinical history and physical examination, additional laboratory assessments should be carried out. Thyroid dysfunction and adrenal insufficiency should be ruled out on the basis of thyroid stimulating hormone (TSH) and plasma cortisol levels. In addition, urine sodium and urine osmolality should be checked, as they can often help confirm the assessment of the patient's volume status and assist in the classification of the hyponatremia.

Hypovolemic hyponatremia commonly results from either renal or gastrointestinal losses of solute (sodium and potassium).19, 33 Such patients will typically have urine sodium values below 25 mEq/L. Hypervolemic hyponatremia occurs when both solute and water are increased, with water increases that are out of proportion to solute. It is seen in patients with HF, cirrhosis, and nephrotic syndrome.19, 33 These patients often also demonstrate low urine sodium levels. Although plasma and extracellular volumes are increased in these states, patients with HF and cirrhosis experience effective arterial blood volume depletion due to reduced cardiac output and arterial vasodilatation, respectively.

In euvolemic patients, hyponatremia is most often due to the syndrome of inappropriate antidiuretic hormone secretion. Such patients typically have urine sodium levels above 40 mEq/L. Free water excretion is impaired in SIADH, as evidenced by urine osmolality levels greater than 100 mOsm/kg (and often much higher). SIADH is the most common cause of hyponatremia in hospitalized patients.22 The heterogeneity of conditions that can lead to SIADH is striking, including pulmonary and CNS diseases, cancer, and various forms of endocrinopathy.22, 23 Consequently, SIADH is often a diagnosis of exclusion.

Other important causes of hyponatremia in euvolemic patients include primary polydipsia and low dietary solute intake. Primary polydipsia most commonly affects those with psychiatric illness.34 Increased thirst is a common side effect of antipsychotic medications. If water intake is excessive, the ability of the kidney to excrete water is overwhelmed and hyponatremia develops. These patients manifest with low urine osmolality (less than 100 mOsm/kg). In contrast, beer drinkers and other malnourished patients often have reduced ability to excrete free water based on low solute intake.35 In order to maximize the kidney's ability to excrete free water, a basic level of solute intake is required. Severe alcoholics (in particular beer drinkers) often do not meet this minimum solute level since beer is very low in solute. The result is markedly impaired free water excretion. Such patients develop hyponatremia with low urine omolality (less than 100 mOsm/kg).

MANAGEMENT

Although effective management of hyponatremia can be challenging, it is important to recognize that even modest improvements in serum [Na+] are associated with survival benefits.22, 36 The most important treatment factors relate to the severity of hyponatremia, its acuity, and the patient's volume status.33, 36 The first steps in effective management are to optimize treatment of any underlying disease(s) and to discontinue any medications that may be contributing to hyponatremia.

In the severe group are patients who present with either a documented acute drop in serum [Na+] or neurologic symptoms that are not attributable to another disease process. The mainstay of therapy for this group is prompt administration of hypertonic saline to rapidly address neurologic symptoms or prevent their development. Experts recommend correcting serum [Na+] at a rate of 2 mEq/L per hour in patients with documented severe acute hyponatremia, with the assistance of a nephrologist.22 Slower correction rates (0.51 mEq/L per hour) should be used in symptomatic patients who develop severe hyponatremia in a subacute or chronic timeframe, so as to reduce the risk of osmotic demyelination, which confers irreversible damage to neurons and serious CNS sequelae. In both cases, an initial correction of 46 mEq/L is generally sufficient to address neurologic symptoms.37 Correcting the sodium by more than 10 mEq/L in the first 24‐hour period is widely felt to place the patient at risk for iatrogenic brain injury, and should therefore be avoided. Serum sodium must be monitored very frequently (up to every 2 hours) in such patients to ensure appropriate management.22

Management of patients with hyponatremia of uncertain duration and nonspecific symptoms is more common, as well as more challenging. A recently published algorithm recommends looking for and promptly treating hypovolemia if it exists, and then beginning correction at a more gradual rate with normal saline ( furosemide).22 Appropriate management of these patients addresses the sequelae of hyponatremia while at the same time minimizing the risk of iatrogenic injury. Experts recommend therapeutic goals of 6 to 8 mEq/L in 24 hours, 12 to 14 mEq/L in 48 hours, and 14 to 16 mEq/L in 72 hours.37

In asymptomatic patients with chronic hyponatremia, the aim of treatment is gradual correction of serum [Na+]. A significant number of SIADH patients fall into this category. A common mistake seen in the management of such patients is inaccurate assessment of volume status and a blind trial of normal saline infusion. Administration of normal saline to such patients will not improve the serum sodium concentration, and may, in fact, drive it lower. While SIADH patients have a normal ability to excrete sodium, their ability to excrete water is impaired. Therefore, normal saline infusion will lead to free water retention.

For asymptomatic chronic hyponatremia patients, oral fluid restriction is the most simple and least toxic treatment. However, it is often difficult to calculate the actual fluid intake, since water present in food must be included. In addition, thirst often leads to patient nonadherence. Treatment with sodium chloride in the form of dietary salt or sodium chloride tablets is problematic in patients with hypertension, HF or cirrhosis.22 Demeclocycline is fairly well tolerated, but can cause nephrotoxicity and skin sensitivity. Urea, although effective, is available only as a powder that is bitter and difficult to tolerate.22

AVP‐receptor antagonists, commonly called vaptans, are the newest treatment option. Known as aquaretic drugs, they lead to free water excretion.38 Conivaptan and tolvaptan have been approved by the US Food and Drug Administration (FDA) for the treatment of hyponatremia. Conivaptan, available as an intravenous (IV) formulation only, is indicated for the acute treatment of euvolemic or hypervolemic hyponatremia in hospitalized patients for up to 4 days.21, 22, 38, 39 Due to its additional effects on the V1 receptor, this agent can cause vasodilation and resultant hypotension. In a randomized, placebo‐controlled study of patients with euvolemic or hypervolemic hyponatremia, a 4‐day IV infusion of conivaptan significantly increased serum [Na+] levels compared with placebo.40 Tolvaptan, available as an oral formulation, is more suitable for long‐term use, but must be started in the inpatient setting. Patients started on this agent must be followed closely after discharge. Based on the results of 2 multicenter, prospective, randomized, placebo‐controlled trials, tolvaptan is indicated for clinically significant euvolemic or hypervolemic hyponatremia (serum [Na+] 125 mEq/L, or less marked hyponatremia that is symptomatic and persistent, despite fluid restriction), in patients with HF, cirrhosis, and SIADH.22, 41, 42 The vaptans are contraindicated in hypovolemic patients because they can lead to hypotension and/or acute renal failure.38, 43 Fluid restrictions must also be relaxed in patients who are placed on a vaptan.

Long‐term clinical studies of these agents are needed to address their optimal duration of treatment, clinical outcomes, and comparative effectiveness to other treatment approaches. Although this is expected to change, vaptans are not included in current clinical practice guidelines for the management of hyponatremia.

SUMMARY

Hyponatremia is associated with significant morbidity and mortality in a variety of clinical scenarios. Prompt recognition and accurate diagnosis has the potential to improve patient outcomes, as even modest improvements in serum [Na+] are associated with survival benefits. The appropriate management of hyponatremia involves careful assessment of acuity, severity, and volume status. The recently approved vasopressin receptor antagonists show promise as a therapeutic option for this challenging clinical condition.

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References
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  2. Hawkins RC.Age and gender as risk factors for hyponatremia and hypernatremia.Clin Chim Acta.2003;337:169172.
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  10. Porcel A,Díaz F,Rendón P, et al.Dilutional hyponatremia in patients with cirrhosis and ascites.Arch Intern Med.2002;162:323328.
  11. Angeli P,Wong F,Watson H, et al.Hyponatremia in cirrhosis: results of a patient population survey.Hepatology.2006;44(6):15351542.
  12. Moini M,Hoseini‐Asl MK,Taghavi SA, et al.Hyponatremia a valuable predictor of early mortality in patients with cirrhosis listed for liver transplantation.Clin Transplant.2011;25(4):638645.
  13. Torres JM,Cardenas O,Wasquez A,Schlossberg D.Streptococcus pneumoniae bacteremia in a community hospital.Chest.1998;113:387390.
  14. Nair V,Niederman MS,Masani N, et al.Hyponatremia in community‐acquired pneumonia.Am J Nephrol.2007;27(2):184190.
  15. Zilberberg MD,Exuzides A,Spalding J, et al.Hyponatremia and hospital outcomes among patients with pneumonia: a retrospective cohort study.BMC Pulm Med.2008;8:16.
  16. Adrogué HJ.Consequences of inadequate management of hyponatremia.Am J Nephrol.2005;25:240249.
  17. Upadhyay A,Jaber BL,Madias NE.Incidence and prevalence of hyponatremia.Am J Med.2006;119:S30S35.
  18. Franco K,Litaker D,Locala J,Bronson D.The cost of delirium in the surgical patient.Psychosomatics.2001;42:6873.
  19. Kumar S,Berl T.Diseases of water metabolism. In: Schrier RW, series ed;Berl T,Bonventre JV, eds. Atlas of Diseases of the Kidney; vol 1. 1999;1–1.22. Available at: http://www.kidneyatlas.org/book1/ADK1_01.pdf. Accessed June 21,2011.
  20. Verbalis JG.Vasopressin V2 receptor antagonists.J Mol Endocrinol.2002;29:19.
  21. Ross E,Sigal SH.Managing hyponatremia in cirrhosis.J Hosp Med.2010;5:S8S17.
  22. Ellison DH,Berl T.The syndrome of inappropriate antidiuresis.N Engl J Med.2007;356:20642072.
  23. Wilkinson TJ,Begg EJ,Winter AC,Sainsbury R.Incidence and risk factors for hyponatremia following treatment with fluoxetine or paroxetine in elderly people.Br J Clin Pharmacol.1999;47:211217.
  24. Hix JK,Silver S,Sterns RH.Diuretic‐associated hyponatremia.Semin Nephrol.2011;31(6):553566.
  25. Adrogué HJ,Madias NE.Hyponatremia.N Engl J Med.2000;342:15811589.
  26. Nathan BR.Cerebral correlates of hyponatremia.Neurocrit Care.2007;6:7278.
  27. Kengne FG,Andres C,Sattar L,Melot C,Decaux G.Mild hyponatremia and risk of fracture in the ambulatory elderly.Q J Med.2008;101:583588.
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  29. Advisory Committee of the Cardiovascular and Renal Drugs Division of the US Food and Drug Administration. Treatment of Hyponatremia: Medical Utility of Vasopressin V2 Receptor Antagonism. Briefing Document. June 25, 2008. Available at: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008–4373b1–05.pdf. Accessed June 24,2011.
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  36. Lien YH,Shapiro JL.Hyponatremia: clinical diagnosis and management.Am J Med.2007;120:653658.
  37. Sterns RH,Nigwekar SU,Hix JK.The treatment of hyponatremia.Semin Nephrol.2009;29(3):282299.
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The high prevalence of hyponatremia in hospitalized patients has been recognized for decades. Published reports dating back to the 1960s indicate that serum sodium concentrations ([Na+]) tend to be lower in hospitalized patients than in outpatients in the community.1 Current estimates for the prevalence of hyponatremia in hospitalized patients range from 15% to nearly 40%.2, 3 Several factors account for this wide range. While most studies estimate the presence of hyponatremia based on International Classification of Diseases, Ninth Revision (ICD‐9) codes, accurate reporting varies widely from institution to institution.4 Furthermore, the definition of hyponatremia depends entirely on the cut‐off value of [Na+] used (generally, 136 mEq/L).3 In addition to patients who have hyponatremia present on admission, a significant proportion develop the condition during their hospital stay.3 Deficits in water excretion can develop or worsen during hospitalization as a result of several factors, combined with intake of hypotonic fluid.3 In a study of hyponatremia in intensive care unit (ICU) patients, as many as 80% demonstrated impaired urinary dilution during their ICU course.5

The prevalence of hyponatremia is significant in patients hospitalized for heart failure (HF), cirrhosis, and pneumonia.6 The prevalence of hyponatremiadefined as serum sodium 135 mEq/Lranges from 18% to 25% in patients admitted for congestive heart failure.79 Rates of hyponatremia in patients admitted with cirrhosis are even higher on average, ranging between 18% and 49%.1012 Hyponatremia is also common in patients with community‐acquired pneumonia (CAP), with prevalence estimates ranging from 8% to 28%.1315

Overall, hyponatremia in each of these disease states portends worse outcome.16 In a retrospective study of 71 adults with pneumonia, admission serum [Na+] 135 mEq/L was a risk factor for in‐hospital mortality.13 In each of these conditions, hyponatremia is associated with the need for ICU care and mechanical ventilation, increased hospital length of stay (LOS), and higher costs of care.17, 18

PATHOPHYSIOLOGY OF HYPONATREMIA

There are 2 primary stimuli for the secretion of antidiuretic hormone (ADH), otherwise known as arginine vasopressin (AVP). Osmoreceptors in the hypothalamus measure the osmolality of the plasma.19 When osmolality increases, AVP is secreted; alternatively, when plasma osmolality drops, secretion of AVP under normal circumstances will diminish. The other stimulus results from baroreceptors throughout the body. Decreased intravascular volume (manifested by lower blood pressure) causes activation of the renin‐angiotensin‐aldosterone system, the sympathetic nervous system, as well as AVP secretion.16, 20 In turn, AVP acts on vasopressin V2 receptors in the kidney to encourage water reapsorption, therefore impairing the patient's ability to excrete dilute urine.6

The mechanism by which hyponatremia develops varies according to disease state. Whereas neurohormonal activation predominates in those with HF and cirrhosis, inappropriate AVP secretion (and in some cases, a resetting of the osmostat) occurs in patients with CAP.10, 13, 17 In both HF and cirrhosis, the degree of neurohormonal activation correlates with the degree of hyponatremia.17

In healthy individuals, the mechanism for free water excretion is AVP suppression caused by a fall in plasma osmolality. Patients with hyponatremia, however, are unable to suppress AVP due to true volume depletion (eg, as a result of inadequate oral intake, gastrointestinal fluids loss from vomiting/diarrhea, or use of thiazide diuretics), effective volume depletion (reduced cardiac output in HF patients vs vasodilation in patients with cirrhosis), or an inappropriate increase in AVP secretion.19, 21, 22

RISK FACTORS

The risk factors for hyponatremia are numerous.2, 22 The ability to excrete water declines with increasing age and is exacerbated by chronic illness. Other risk factors include low body weight, low sodium diets, and residence in a chronic care facility.22, 23 Patients with a low baseline serum sodium concentration also appear to be at increased risk of developing hyponatremia. Although the mechanisms by which such patients develop hyponatremia are not always clear, they generally involve an impaired ability to excrete free water due to an inability to appropriately suppress AVP secretion. Medications commonly associated with the syndrome of inappropriate ADH secretion (SIADH) include selective serotonin reuptake inhibitors (SSRIs), psychotropic drugs, non‐steroidal anti‐inflammatory drugs (NSAIDs), opiates, proton pump inhibitors, as well as certain chemotherapeutics.21, 22 Other risk factors associated with SIADH include major abdominal or thoracic surgery, pain, nausea, and excessive administration of hypotonic intravenous fluids. Finally, diuretic use (in particular thiazides) places patients at risk to develop hyponatremia by increasing total urine volume and solute excretion without an appreciable increase in free water excretion.24

MORBIDITY

The morbidities associated with hyponatremia vary widely in severity. Serious sequelae may occur as a result of hyponatremia itself, as well as from complications that occur due to the challenging nature of effective management. Much of the symptomatology relates to the central nervous system (CNS). Patients presenting with extremely low serum [Na+] levels (eg, 115 mEq/L) often have severe neurologic symptoms, while those with lesser degrees of hyponatremia may be asymptomatic, or present with milder nonspecific symptoms, such as confusion.25, 26 It is important to note that the clinical presentation of hyponatremia very much depends on whether it is acute (occurring over 2448 hours) or chronic (>48 hours).

Water shifts between the intracellular and extracellular fluid compartments are the primary means by which the body equalizes osmolality. When serum sodium changes, the ability of the brain to compensate is limited, and may result in various forms of neurologic impairment due to cerebral edema.25, 26 Such patients may become disoriented, restless, unable to attend, or unable to process information cognitively. There may also be peripheral neurologic dysfunction, such as muscle weakness, blunted neuromuscular reflexes, and impaired gait. Such impairments can lead to delirium, falls, and fractures.25, 27

HYPONATREMIA AND COGNITIVE IMPAIRMENT

Renneboog and colleagues performed a case‐control study to assess the impact of mild chronic asymptomatic hyponatremia (mean serum [Na+] 126 5 mEq/L) in 122 patients compared with 244 matched controls (mean age 72 13 years).28 Hyponatremic patients had significantly longer mean response times on concentration tests. Interestingly, the changes in cognitive function in hyponatremic patients were similar to healthy volunteers purposefully intoxicated with alcohol.28 Patients with hyponatremia have also been shown to score lower on the mental component summary of the 36‐item Short‐Form (SF‐36) survey.29 With treatment aimed at improving serum sodium, these same patients demonstrated improved cognitive function,29 suggesting that treating even mild forms of hyponatremia can improve patient outcomes.30

HYPONATREMIA AND FALLS/FRACTURES

Renneboog and colleagues also demonstrated a markedly increased risk of falls in their patients with chronic hyponatremia compared to controls.28 Hyponatremia increases not only the risk of falls, but also the risk of fracture following a fall. In another recent case‐control study of 513 patients, the adjusted odds ratio for fracture after a fall in a patient with hyponatremia was 4.16 compared with an age‐matched control with normal serum sodium who sustained a similar fall.27 Of note, hyponatremia was mild and asymptomatic in all patients studied. Medications (36% diuretics, 17% SSRIs) were the most common precipitating cause of hyponatremia in this study, which is notable because such risk factors should be recognized and addressed.

Although falls and fractures lead to obvious increases in morbidity and cost, delirium has also been identified as a risk factor for increased hospital LOS.18 Delirious patients are less likely and able to mobilize and participate in physical therapy. As such, they are more often bed‐bound and at increased risk for aspiration and other preventable issues, including deep vein thrombosis, bed sores, and debility, all of which may increase their LOS and cost of care.

MORTALITY

Hyponatremia is associated with a significantly increased mortality risk not only during hospitalization, but also at 1 and 5 years following discharge.31 In a prospective cohort study of approximately 100,000 patients, even those with mild hyponatremia ([Na+] 130134 mEq/L) had a significantly higher mortality at 5 years. The adjusted odds ratio for mortality in patients with serum sodium less than 135 mEq/L was 1.47 during hospitalization (95% CI, 1.331.62), 1.38 at 1 year post‐discharge (1.321.46), and 1.25 at 5 years (1.211.30). The significance of hyponatremia varied according to the underlying clinical condition, with the greatest risk observed in patients with metastatic cancer, heart disease, and those who had undergone orthopedic surgery.31 While the association between hyponatremia and mortality is profound, most experts do not believe that hyponatremia directly causes mortality per se. Instead, hyponatremia is felt to be a marker for increased illness severity.

It is difficult to isolate the direct costs of hyponatremia in the acute care setting because the condition is rarely treated in isolation. However, in a study of a managed‐care claims database of nearly 1,300 patients (excluding Medicare patients), hyponatremia was a predictor of higher medical costs at 6 months and at 1 year.32

DIAGNOSIS

The most common presentation of hyponatremia involves nonspecific symptoms or a total lack of symptoms.19 Many patients have comorbid diseases, and symptoms of these illnesses often predominate at hospital admission. Patients with mild to moderate hyponatremia may present with nausea, weakness, malaise, headache, and/or impaired mobility. With more severe hyponatremia, more dangerous neurologic symptoms appear, including generalized seizures, lethargy, and coma.19 Once hyponatremia is identified, the next step is to determine its acuity and classify it.

Although several classification systems exist to describe hyponatremia, the most common scheme begins with assessment of plasma osmolality and volume status.19 The majority of hyponatremic patients present with hypotonic or hypo‐osmolar serum (eg, plasma osmolality 275 mOsm/kg). The primary causes of hyponatremia in patients with normal or high serum osmolality are hyperglycemia, pseudohyponatremia, and advanced renal failure. Marked hyperglycemia increases plasma osmolality, and as a result, water moves out of cells into plasma and lowers serum sodium concentration in the process. Pseudohyponatremia arises from hyperlipidemia or hyperproteinemia, in which high concentrations of lipids/proteins reduce the free water component of plasma, therefore reducing the sodium concentration per liter of plasma. These patients do not have true hyponatremia since the physiologically important sodium concentration per liter of plasma water is normal. Finally, patients with advanced renal failure develop hyponatremia due to the inability to excrete water.

The first step in the diagnosis of hyponatremia is to assess the plasma osmolality and rule out the aforementioned conditions that cause normal or elevated serum osmolality. Patients with hypotonic serum must then be evaluated clinically to determine their volume status. Appropriate classification here has important implications for management.

In addition to clinical history and physical examination, additional laboratory assessments should be carried out. Thyroid dysfunction and adrenal insufficiency should be ruled out on the basis of thyroid stimulating hormone (TSH) and plasma cortisol levels. In addition, urine sodium and urine osmolality should be checked, as they can often help confirm the assessment of the patient's volume status and assist in the classification of the hyponatremia.

Hypovolemic hyponatremia commonly results from either renal or gastrointestinal losses of solute (sodium and potassium).19, 33 Such patients will typically have urine sodium values below 25 mEq/L. Hypervolemic hyponatremia occurs when both solute and water are increased, with water increases that are out of proportion to solute. It is seen in patients with HF, cirrhosis, and nephrotic syndrome.19, 33 These patients often also demonstrate low urine sodium levels. Although plasma and extracellular volumes are increased in these states, patients with HF and cirrhosis experience effective arterial blood volume depletion due to reduced cardiac output and arterial vasodilatation, respectively.

In euvolemic patients, hyponatremia is most often due to the syndrome of inappropriate antidiuretic hormone secretion. Such patients typically have urine sodium levels above 40 mEq/L. Free water excretion is impaired in SIADH, as evidenced by urine osmolality levels greater than 100 mOsm/kg (and often much higher). SIADH is the most common cause of hyponatremia in hospitalized patients.22 The heterogeneity of conditions that can lead to SIADH is striking, including pulmonary and CNS diseases, cancer, and various forms of endocrinopathy.22, 23 Consequently, SIADH is often a diagnosis of exclusion.

Other important causes of hyponatremia in euvolemic patients include primary polydipsia and low dietary solute intake. Primary polydipsia most commonly affects those with psychiatric illness.34 Increased thirst is a common side effect of antipsychotic medications. If water intake is excessive, the ability of the kidney to excrete water is overwhelmed and hyponatremia develops. These patients manifest with low urine osmolality (less than 100 mOsm/kg). In contrast, beer drinkers and other malnourished patients often have reduced ability to excrete free water based on low solute intake.35 In order to maximize the kidney's ability to excrete free water, a basic level of solute intake is required. Severe alcoholics (in particular beer drinkers) often do not meet this minimum solute level since beer is very low in solute. The result is markedly impaired free water excretion. Such patients develop hyponatremia with low urine omolality (less than 100 mOsm/kg).

MANAGEMENT

Although effective management of hyponatremia can be challenging, it is important to recognize that even modest improvements in serum [Na+] are associated with survival benefits.22, 36 The most important treatment factors relate to the severity of hyponatremia, its acuity, and the patient's volume status.33, 36 The first steps in effective management are to optimize treatment of any underlying disease(s) and to discontinue any medications that may be contributing to hyponatremia.

In the severe group are patients who present with either a documented acute drop in serum [Na+] or neurologic symptoms that are not attributable to another disease process. The mainstay of therapy for this group is prompt administration of hypertonic saline to rapidly address neurologic symptoms or prevent their development. Experts recommend correcting serum [Na+] at a rate of 2 mEq/L per hour in patients with documented severe acute hyponatremia, with the assistance of a nephrologist.22 Slower correction rates (0.51 mEq/L per hour) should be used in symptomatic patients who develop severe hyponatremia in a subacute or chronic timeframe, so as to reduce the risk of osmotic demyelination, which confers irreversible damage to neurons and serious CNS sequelae. In both cases, an initial correction of 46 mEq/L is generally sufficient to address neurologic symptoms.37 Correcting the sodium by more than 10 mEq/L in the first 24‐hour period is widely felt to place the patient at risk for iatrogenic brain injury, and should therefore be avoided. Serum sodium must be monitored very frequently (up to every 2 hours) in such patients to ensure appropriate management.22

Management of patients with hyponatremia of uncertain duration and nonspecific symptoms is more common, as well as more challenging. A recently published algorithm recommends looking for and promptly treating hypovolemia if it exists, and then beginning correction at a more gradual rate with normal saline ( furosemide).22 Appropriate management of these patients addresses the sequelae of hyponatremia while at the same time minimizing the risk of iatrogenic injury. Experts recommend therapeutic goals of 6 to 8 mEq/L in 24 hours, 12 to 14 mEq/L in 48 hours, and 14 to 16 mEq/L in 72 hours.37

In asymptomatic patients with chronic hyponatremia, the aim of treatment is gradual correction of serum [Na+]. A significant number of SIADH patients fall into this category. A common mistake seen in the management of such patients is inaccurate assessment of volume status and a blind trial of normal saline infusion. Administration of normal saline to such patients will not improve the serum sodium concentration, and may, in fact, drive it lower. While SIADH patients have a normal ability to excrete sodium, their ability to excrete water is impaired. Therefore, normal saline infusion will lead to free water retention.

For asymptomatic chronic hyponatremia patients, oral fluid restriction is the most simple and least toxic treatment. However, it is often difficult to calculate the actual fluid intake, since water present in food must be included. In addition, thirst often leads to patient nonadherence. Treatment with sodium chloride in the form of dietary salt or sodium chloride tablets is problematic in patients with hypertension, HF or cirrhosis.22 Demeclocycline is fairly well tolerated, but can cause nephrotoxicity and skin sensitivity. Urea, although effective, is available only as a powder that is bitter and difficult to tolerate.22

AVP‐receptor antagonists, commonly called vaptans, are the newest treatment option. Known as aquaretic drugs, they lead to free water excretion.38 Conivaptan and tolvaptan have been approved by the US Food and Drug Administration (FDA) for the treatment of hyponatremia. Conivaptan, available as an intravenous (IV) formulation only, is indicated for the acute treatment of euvolemic or hypervolemic hyponatremia in hospitalized patients for up to 4 days.21, 22, 38, 39 Due to its additional effects on the V1 receptor, this agent can cause vasodilation and resultant hypotension. In a randomized, placebo‐controlled study of patients with euvolemic or hypervolemic hyponatremia, a 4‐day IV infusion of conivaptan significantly increased serum [Na+] levels compared with placebo.40 Tolvaptan, available as an oral formulation, is more suitable for long‐term use, but must be started in the inpatient setting. Patients started on this agent must be followed closely after discharge. Based on the results of 2 multicenter, prospective, randomized, placebo‐controlled trials, tolvaptan is indicated for clinically significant euvolemic or hypervolemic hyponatremia (serum [Na+] 125 mEq/L, or less marked hyponatremia that is symptomatic and persistent, despite fluid restriction), in patients with HF, cirrhosis, and SIADH.22, 41, 42 The vaptans are contraindicated in hypovolemic patients because they can lead to hypotension and/or acute renal failure.38, 43 Fluid restrictions must also be relaxed in patients who are placed on a vaptan.

Long‐term clinical studies of these agents are needed to address their optimal duration of treatment, clinical outcomes, and comparative effectiveness to other treatment approaches. Although this is expected to change, vaptans are not included in current clinical practice guidelines for the management of hyponatremia.

SUMMARY

Hyponatremia is associated with significant morbidity and mortality in a variety of clinical scenarios. Prompt recognition and accurate diagnosis has the potential to improve patient outcomes, as even modest improvements in serum [Na+] are associated with survival benefits. The appropriate management of hyponatremia involves careful assessment of acuity, severity, and volume status. The recently approved vasopressin receptor antagonists show promise as a therapeutic option for this challenging clinical condition.

The high prevalence of hyponatremia in hospitalized patients has been recognized for decades. Published reports dating back to the 1960s indicate that serum sodium concentrations ([Na+]) tend to be lower in hospitalized patients than in outpatients in the community.1 Current estimates for the prevalence of hyponatremia in hospitalized patients range from 15% to nearly 40%.2, 3 Several factors account for this wide range. While most studies estimate the presence of hyponatremia based on International Classification of Diseases, Ninth Revision (ICD‐9) codes, accurate reporting varies widely from institution to institution.4 Furthermore, the definition of hyponatremia depends entirely on the cut‐off value of [Na+] used (generally, 136 mEq/L).3 In addition to patients who have hyponatremia present on admission, a significant proportion develop the condition during their hospital stay.3 Deficits in water excretion can develop or worsen during hospitalization as a result of several factors, combined with intake of hypotonic fluid.3 In a study of hyponatremia in intensive care unit (ICU) patients, as many as 80% demonstrated impaired urinary dilution during their ICU course.5

The prevalence of hyponatremia is significant in patients hospitalized for heart failure (HF), cirrhosis, and pneumonia.6 The prevalence of hyponatremiadefined as serum sodium 135 mEq/Lranges from 18% to 25% in patients admitted for congestive heart failure.79 Rates of hyponatremia in patients admitted with cirrhosis are even higher on average, ranging between 18% and 49%.1012 Hyponatremia is also common in patients with community‐acquired pneumonia (CAP), with prevalence estimates ranging from 8% to 28%.1315

Overall, hyponatremia in each of these disease states portends worse outcome.16 In a retrospective study of 71 adults with pneumonia, admission serum [Na+] 135 mEq/L was a risk factor for in‐hospital mortality.13 In each of these conditions, hyponatremia is associated with the need for ICU care and mechanical ventilation, increased hospital length of stay (LOS), and higher costs of care.17, 18

PATHOPHYSIOLOGY OF HYPONATREMIA

There are 2 primary stimuli for the secretion of antidiuretic hormone (ADH), otherwise known as arginine vasopressin (AVP). Osmoreceptors in the hypothalamus measure the osmolality of the plasma.19 When osmolality increases, AVP is secreted; alternatively, when plasma osmolality drops, secretion of AVP under normal circumstances will diminish. The other stimulus results from baroreceptors throughout the body. Decreased intravascular volume (manifested by lower blood pressure) causes activation of the renin‐angiotensin‐aldosterone system, the sympathetic nervous system, as well as AVP secretion.16, 20 In turn, AVP acts on vasopressin V2 receptors in the kidney to encourage water reapsorption, therefore impairing the patient's ability to excrete dilute urine.6

The mechanism by which hyponatremia develops varies according to disease state. Whereas neurohormonal activation predominates in those with HF and cirrhosis, inappropriate AVP secretion (and in some cases, a resetting of the osmostat) occurs in patients with CAP.10, 13, 17 In both HF and cirrhosis, the degree of neurohormonal activation correlates with the degree of hyponatremia.17

In healthy individuals, the mechanism for free water excretion is AVP suppression caused by a fall in plasma osmolality. Patients with hyponatremia, however, are unable to suppress AVP due to true volume depletion (eg, as a result of inadequate oral intake, gastrointestinal fluids loss from vomiting/diarrhea, or use of thiazide diuretics), effective volume depletion (reduced cardiac output in HF patients vs vasodilation in patients with cirrhosis), or an inappropriate increase in AVP secretion.19, 21, 22

RISK FACTORS

The risk factors for hyponatremia are numerous.2, 22 The ability to excrete water declines with increasing age and is exacerbated by chronic illness. Other risk factors include low body weight, low sodium diets, and residence in a chronic care facility.22, 23 Patients with a low baseline serum sodium concentration also appear to be at increased risk of developing hyponatremia. Although the mechanisms by which such patients develop hyponatremia are not always clear, they generally involve an impaired ability to excrete free water due to an inability to appropriately suppress AVP secretion. Medications commonly associated with the syndrome of inappropriate ADH secretion (SIADH) include selective serotonin reuptake inhibitors (SSRIs), psychotropic drugs, non‐steroidal anti‐inflammatory drugs (NSAIDs), opiates, proton pump inhibitors, as well as certain chemotherapeutics.21, 22 Other risk factors associated with SIADH include major abdominal or thoracic surgery, pain, nausea, and excessive administration of hypotonic intravenous fluids. Finally, diuretic use (in particular thiazides) places patients at risk to develop hyponatremia by increasing total urine volume and solute excretion without an appreciable increase in free water excretion.24

MORBIDITY

The morbidities associated with hyponatremia vary widely in severity. Serious sequelae may occur as a result of hyponatremia itself, as well as from complications that occur due to the challenging nature of effective management. Much of the symptomatology relates to the central nervous system (CNS). Patients presenting with extremely low serum [Na+] levels (eg, 115 mEq/L) often have severe neurologic symptoms, while those with lesser degrees of hyponatremia may be asymptomatic, or present with milder nonspecific symptoms, such as confusion.25, 26 It is important to note that the clinical presentation of hyponatremia very much depends on whether it is acute (occurring over 2448 hours) or chronic (>48 hours).

Water shifts between the intracellular and extracellular fluid compartments are the primary means by which the body equalizes osmolality. When serum sodium changes, the ability of the brain to compensate is limited, and may result in various forms of neurologic impairment due to cerebral edema.25, 26 Such patients may become disoriented, restless, unable to attend, or unable to process information cognitively. There may also be peripheral neurologic dysfunction, such as muscle weakness, blunted neuromuscular reflexes, and impaired gait. Such impairments can lead to delirium, falls, and fractures.25, 27

HYPONATREMIA AND COGNITIVE IMPAIRMENT

Renneboog and colleagues performed a case‐control study to assess the impact of mild chronic asymptomatic hyponatremia (mean serum [Na+] 126 5 mEq/L) in 122 patients compared with 244 matched controls (mean age 72 13 years).28 Hyponatremic patients had significantly longer mean response times on concentration tests. Interestingly, the changes in cognitive function in hyponatremic patients were similar to healthy volunteers purposefully intoxicated with alcohol.28 Patients with hyponatremia have also been shown to score lower on the mental component summary of the 36‐item Short‐Form (SF‐36) survey.29 With treatment aimed at improving serum sodium, these same patients demonstrated improved cognitive function,29 suggesting that treating even mild forms of hyponatremia can improve patient outcomes.30

HYPONATREMIA AND FALLS/FRACTURES

Renneboog and colleagues also demonstrated a markedly increased risk of falls in their patients with chronic hyponatremia compared to controls.28 Hyponatremia increases not only the risk of falls, but also the risk of fracture following a fall. In another recent case‐control study of 513 patients, the adjusted odds ratio for fracture after a fall in a patient with hyponatremia was 4.16 compared with an age‐matched control with normal serum sodium who sustained a similar fall.27 Of note, hyponatremia was mild and asymptomatic in all patients studied. Medications (36% diuretics, 17% SSRIs) were the most common precipitating cause of hyponatremia in this study, which is notable because such risk factors should be recognized and addressed.

Although falls and fractures lead to obvious increases in morbidity and cost, delirium has also been identified as a risk factor for increased hospital LOS.18 Delirious patients are less likely and able to mobilize and participate in physical therapy. As such, they are more often bed‐bound and at increased risk for aspiration and other preventable issues, including deep vein thrombosis, bed sores, and debility, all of which may increase their LOS and cost of care.

MORTALITY

Hyponatremia is associated with a significantly increased mortality risk not only during hospitalization, but also at 1 and 5 years following discharge.31 In a prospective cohort study of approximately 100,000 patients, even those with mild hyponatremia ([Na+] 130134 mEq/L) had a significantly higher mortality at 5 years. The adjusted odds ratio for mortality in patients with serum sodium less than 135 mEq/L was 1.47 during hospitalization (95% CI, 1.331.62), 1.38 at 1 year post‐discharge (1.321.46), and 1.25 at 5 years (1.211.30). The significance of hyponatremia varied according to the underlying clinical condition, with the greatest risk observed in patients with metastatic cancer, heart disease, and those who had undergone orthopedic surgery.31 While the association between hyponatremia and mortality is profound, most experts do not believe that hyponatremia directly causes mortality per se. Instead, hyponatremia is felt to be a marker for increased illness severity.

It is difficult to isolate the direct costs of hyponatremia in the acute care setting because the condition is rarely treated in isolation. However, in a study of a managed‐care claims database of nearly 1,300 patients (excluding Medicare patients), hyponatremia was a predictor of higher medical costs at 6 months and at 1 year.32

DIAGNOSIS

The most common presentation of hyponatremia involves nonspecific symptoms or a total lack of symptoms.19 Many patients have comorbid diseases, and symptoms of these illnesses often predominate at hospital admission. Patients with mild to moderate hyponatremia may present with nausea, weakness, malaise, headache, and/or impaired mobility. With more severe hyponatremia, more dangerous neurologic symptoms appear, including generalized seizures, lethargy, and coma.19 Once hyponatremia is identified, the next step is to determine its acuity and classify it.

Although several classification systems exist to describe hyponatremia, the most common scheme begins with assessment of plasma osmolality and volume status.19 The majority of hyponatremic patients present with hypotonic or hypo‐osmolar serum (eg, plasma osmolality 275 mOsm/kg). The primary causes of hyponatremia in patients with normal or high serum osmolality are hyperglycemia, pseudohyponatremia, and advanced renal failure. Marked hyperglycemia increases plasma osmolality, and as a result, water moves out of cells into plasma and lowers serum sodium concentration in the process. Pseudohyponatremia arises from hyperlipidemia or hyperproteinemia, in which high concentrations of lipids/proteins reduce the free water component of plasma, therefore reducing the sodium concentration per liter of plasma. These patients do not have true hyponatremia since the physiologically important sodium concentration per liter of plasma water is normal. Finally, patients with advanced renal failure develop hyponatremia due to the inability to excrete water.

The first step in the diagnosis of hyponatremia is to assess the plasma osmolality and rule out the aforementioned conditions that cause normal or elevated serum osmolality. Patients with hypotonic serum must then be evaluated clinically to determine their volume status. Appropriate classification here has important implications for management.

In addition to clinical history and physical examination, additional laboratory assessments should be carried out. Thyroid dysfunction and adrenal insufficiency should be ruled out on the basis of thyroid stimulating hormone (TSH) and plasma cortisol levels. In addition, urine sodium and urine osmolality should be checked, as they can often help confirm the assessment of the patient's volume status and assist in the classification of the hyponatremia.

Hypovolemic hyponatremia commonly results from either renal or gastrointestinal losses of solute (sodium and potassium).19, 33 Such patients will typically have urine sodium values below 25 mEq/L. Hypervolemic hyponatremia occurs when both solute and water are increased, with water increases that are out of proportion to solute. It is seen in patients with HF, cirrhosis, and nephrotic syndrome.19, 33 These patients often also demonstrate low urine sodium levels. Although plasma and extracellular volumes are increased in these states, patients with HF and cirrhosis experience effective arterial blood volume depletion due to reduced cardiac output and arterial vasodilatation, respectively.

In euvolemic patients, hyponatremia is most often due to the syndrome of inappropriate antidiuretic hormone secretion. Such patients typically have urine sodium levels above 40 mEq/L. Free water excretion is impaired in SIADH, as evidenced by urine osmolality levels greater than 100 mOsm/kg (and often much higher). SIADH is the most common cause of hyponatremia in hospitalized patients.22 The heterogeneity of conditions that can lead to SIADH is striking, including pulmonary and CNS diseases, cancer, and various forms of endocrinopathy.22, 23 Consequently, SIADH is often a diagnosis of exclusion.

Other important causes of hyponatremia in euvolemic patients include primary polydipsia and low dietary solute intake. Primary polydipsia most commonly affects those with psychiatric illness.34 Increased thirst is a common side effect of antipsychotic medications. If water intake is excessive, the ability of the kidney to excrete water is overwhelmed and hyponatremia develops. These patients manifest with low urine osmolality (less than 100 mOsm/kg). In contrast, beer drinkers and other malnourished patients often have reduced ability to excrete free water based on low solute intake.35 In order to maximize the kidney's ability to excrete free water, a basic level of solute intake is required. Severe alcoholics (in particular beer drinkers) often do not meet this minimum solute level since beer is very low in solute. The result is markedly impaired free water excretion. Such patients develop hyponatremia with low urine omolality (less than 100 mOsm/kg).

MANAGEMENT

Although effective management of hyponatremia can be challenging, it is important to recognize that even modest improvements in serum [Na+] are associated with survival benefits.22, 36 The most important treatment factors relate to the severity of hyponatremia, its acuity, and the patient's volume status.33, 36 The first steps in effective management are to optimize treatment of any underlying disease(s) and to discontinue any medications that may be contributing to hyponatremia.

In the severe group are patients who present with either a documented acute drop in serum [Na+] or neurologic symptoms that are not attributable to another disease process. The mainstay of therapy for this group is prompt administration of hypertonic saline to rapidly address neurologic symptoms or prevent their development. Experts recommend correcting serum [Na+] at a rate of 2 mEq/L per hour in patients with documented severe acute hyponatremia, with the assistance of a nephrologist.22 Slower correction rates (0.51 mEq/L per hour) should be used in symptomatic patients who develop severe hyponatremia in a subacute or chronic timeframe, so as to reduce the risk of osmotic demyelination, which confers irreversible damage to neurons and serious CNS sequelae. In both cases, an initial correction of 46 mEq/L is generally sufficient to address neurologic symptoms.37 Correcting the sodium by more than 10 mEq/L in the first 24‐hour period is widely felt to place the patient at risk for iatrogenic brain injury, and should therefore be avoided. Serum sodium must be monitored very frequently (up to every 2 hours) in such patients to ensure appropriate management.22

Management of patients with hyponatremia of uncertain duration and nonspecific symptoms is more common, as well as more challenging. A recently published algorithm recommends looking for and promptly treating hypovolemia if it exists, and then beginning correction at a more gradual rate with normal saline ( furosemide).22 Appropriate management of these patients addresses the sequelae of hyponatremia while at the same time minimizing the risk of iatrogenic injury. Experts recommend therapeutic goals of 6 to 8 mEq/L in 24 hours, 12 to 14 mEq/L in 48 hours, and 14 to 16 mEq/L in 72 hours.37

In asymptomatic patients with chronic hyponatremia, the aim of treatment is gradual correction of serum [Na+]. A significant number of SIADH patients fall into this category. A common mistake seen in the management of such patients is inaccurate assessment of volume status and a blind trial of normal saline infusion. Administration of normal saline to such patients will not improve the serum sodium concentration, and may, in fact, drive it lower. While SIADH patients have a normal ability to excrete sodium, their ability to excrete water is impaired. Therefore, normal saline infusion will lead to free water retention.

For asymptomatic chronic hyponatremia patients, oral fluid restriction is the most simple and least toxic treatment. However, it is often difficult to calculate the actual fluid intake, since water present in food must be included. In addition, thirst often leads to patient nonadherence. Treatment with sodium chloride in the form of dietary salt or sodium chloride tablets is problematic in patients with hypertension, HF or cirrhosis.22 Demeclocycline is fairly well tolerated, but can cause nephrotoxicity and skin sensitivity. Urea, although effective, is available only as a powder that is bitter and difficult to tolerate.22

AVP‐receptor antagonists, commonly called vaptans, are the newest treatment option. Known as aquaretic drugs, they lead to free water excretion.38 Conivaptan and tolvaptan have been approved by the US Food and Drug Administration (FDA) for the treatment of hyponatremia. Conivaptan, available as an intravenous (IV) formulation only, is indicated for the acute treatment of euvolemic or hypervolemic hyponatremia in hospitalized patients for up to 4 days.21, 22, 38, 39 Due to its additional effects on the V1 receptor, this agent can cause vasodilation and resultant hypotension. In a randomized, placebo‐controlled study of patients with euvolemic or hypervolemic hyponatremia, a 4‐day IV infusion of conivaptan significantly increased serum [Na+] levels compared with placebo.40 Tolvaptan, available as an oral formulation, is more suitable for long‐term use, but must be started in the inpatient setting. Patients started on this agent must be followed closely after discharge. Based on the results of 2 multicenter, prospective, randomized, placebo‐controlled trials, tolvaptan is indicated for clinically significant euvolemic or hypervolemic hyponatremia (serum [Na+] 125 mEq/L, or less marked hyponatremia that is symptomatic and persistent, despite fluid restriction), in patients with HF, cirrhosis, and SIADH.22, 41, 42 The vaptans are contraindicated in hypovolemic patients because they can lead to hypotension and/or acute renal failure.38, 43 Fluid restrictions must also be relaxed in patients who are placed on a vaptan.

Long‐term clinical studies of these agents are needed to address their optimal duration of treatment, clinical outcomes, and comparative effectiveness to other treatment approaches. Although this is expected to change, vaptans are not included in current clinical practice guidelines for the management of hyponatremia.

SUMMARY

Hyponatremia is associated with significant morbidity and mortality in a variety of clinical scenarios. Prompt recognition and accurate diagnosis has the potential to improve patient outcomes, as even modest improvements in serum [Na+] are associated with survival benefits. The appropriate management of hyponatremia involves careful assessment of acuity, severity, and volume status. The recently approved vasopressin receptor antagonists show promise as a therapeutic option for this challenging clinical condition.

References
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  15. Zilberberg MD,Exuzides A,Spalding J, et al.Hyponatremia and hospital outcomes among patients with pneumonia: a retrospective cohort study.BMC Pulm Med.2008;8:16.
  16. Adrogué HJ.Consequences of inadequate management of hyponatremia.Am J Nephrol.2005;25:240249.
  17. Upadhyay A,Jaber BL,Madias NE.Incidence and prevalence of hyponatremia.Am J Med.2006;119:S30S35.
  18. Franco K,Litaker D,Locala J,Bronson D.The cost of delirium in the surgical patient.Psychosomatics.2001;42:6873.
  19. Kumar S,Berl T.Diseases of water metabolism. In: Schrier RW, series ed;Berl T,Bonventre JV, eds. Atlas of Diseases of the Kidney; vol 1. 1999;1–1.22. Available at: http://www.kidneyatlas.org/book1/ADK1_01.pdf. Accessed June 21,2011.
  20. Verbalis JG.Vasopressin V2 receptor antagonists.J Mol Endocrinol.2002;29:19.
  21. Ross E,Sigal SH.Managing hyponatremia in cirrhosis.J Hosp Med.2010;5:S8S17.
  22. Ellison DH,Berl T.The syndrome of inappropriate antidiuresis.N Engl J Med.2007;356:20642072.
  23. Wilkinson TJ,Begg EJ,Winter AC,Sainsbury R.Incidence and risk factors for hyponatremia following treatment with fluoxetine or paroxetine in elderly people.Br J Clin Pharmacol.1999;47:211217.
  24. Hix JK,Silver S,Sterns RH.Diuretic‐associated hyponatremia.Semin Nephrol.2011;31(6):553566.
  25. Adrogué HJ,Madias NE.Hyponatremia.N Engl J Med.2000;342:15811589.
  26. Nathan BR.Cerebral correlates of hyponatremia.Neurocrit Care.2007;6:7278.
  27. Kengne FG,Andres C,Sattar L,Melot C,Decaux G.Mild hyponatremia and risk of fracture in the ambulatory elderly.Q J Med.2008;101:583588.
  28. Renneboog B,Musch W,Vandemergel X, et al.Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits.Am J Med.2006;119:71.e171.e8.
  29. Advisory Committee of the Cardiovascular and Renal Drugs Division of the US Food and Drug Administration. Treatment of Hyponatremia: Medical Utility of Vasopressin V2 Receptor Antagonism. Briefing Document. June 25, 2008. Available at: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008–4373b1–05.pdf. Accessed June 24,2011.
  30. Sherlock M,Thompson CJ.The syndrome of inappropriate antidiuretic hormone: current and future management options.Eur J Endocrinol.2010;162(suppl 1):S13S18.
  31. Waikar SS,Mount DB,Curhan GC.Mortality after hospitalization with mild, moderate, and severe hyponatremia.Am J Med.2009;122:857865.
  32. Shea AM,Hammill BG,Curtis LH,Szczech LA,Schulman KA.Medical costs of abnormal serum levels.J Am Soc Nephrol.2008;19:764770.
  33. Verbalis JG,Goldsmith SR,Greenberg A,Schrier RW,Sterns RH.Hyponatremia treatment guidelines 2007: expert panel recommendations.Am J Med.2007;120:S1S21.
  34. Hariprasad MK,Eisinger RP,Nadler IM, et al.Hyponatremia in psychogenic polydipsia.Arch Intern Med.1980;140(12):16391642.
  35. Thaler SM,Teitelbaum I,Berl T.“Beer potomania” in non‐beer drinkers: effect of low dietary solute intake.Am J Kidney Dis.1998;31(6):10281031.
  36. Lien YH,Shapiro JL.Hyponatremia: clinical diagnosis and management.Am J Med.2007;120:653658.
  37. Sterns RH,Nigwekar SU,Hix JK.The treatment of hyponatremia.Semin Nephrol.2009;29(3):282299.
  38. Zietse R,van der Lubbe N,Hoorn EJ.Current and future treatment options in SIADH.NDT Plus.2009;2(suppl 3):iii12iii19.
  39. Vaprisol (conivaptan hydrochloride injection). Prescribing information.Deerfield, IL:Astellas Pharma US, Inc; October2008.
  40. Zeltser D,Rosansky S,Van Rensburg H, et al.Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia.Am J Nephrol.2007;27:447457.
  41. Samsca™ (oral selective vasopressin antagonist). Prescribing information.Rockville, MD:Otsuka America Pharmaceutical, Inc; November2009.
  42. Schrier RW,Gheorghiade M,Berl T, et al.Tolvaptan, a selective oral vasopressin V2‐receptor antagonist, for hyponatremia.N Engl J Med.2006;355:20992112.
  43. Rozen‐Zvi B,Yahav D,Gheorghiade M, et al.Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta‐analysis.Am J Kidney Dis.2010;56:325337.
References
  1. Owen JA,Campbell DG.A comparison of plasma electrolyte and urea values in healthy persons and in hospital patients.Clin Chim Acta.1968;22:611618.
  2. Hawkins RC.Age and gender as risk factors for hyponatremia and hypernatremia.Clin Chim Acta.2003;337:169172.
  3. Hoorn EJ,Lindemans J,Zietse R.Development of severe hyponatremia in hospitalized patients: treatment‐related risk factors and inadequate management.Nephrol Dial Transplant.2006;21:7076.
  4. Movig KL,Leufkens HG,Lenderink AW,Egberts AC.Validity of hospital discharge International Classification of Diseases (ICD) codes for identifying patients with hyponatremia.J Clin Epidemiol.2003;56:530535.
  5. DeVita MV,Gardenswartz MH,Konecky A,Zabetakis PM.Incidence and etiology of hyponatremia in an intensive care unit.Clin Nephrol.1990;34:163166.
  6. Upadhyay A,Jaber BL,Madias NE.Epidemiology of hyponatremia.Semin Nephrol.2009;29:227238.
  7. Lee SI,Honiden S,Fain EB, et al.Severe hyponatremia caused by an instrasellar carotid artery aneurysm.Med Health R I.2003;86(2):5255.
  8. Gheorghiade M,Rossi JS,Cotts W, et al.Characterization and prognostic value of persistent hyponatremia in patients with severe heart failure in the ESCAPE trial.Arch Intern Med.2007;167:19982005.
  9. Choi JS,Kim CS,Park JW, et al.Hyponatremia in a patient with a sellar mass.Chonnam Med J.2011;47(2):122123.
  10. Porcel A,Díaz F,Rendón P, et al.Dilutional hyponatremia in patients with cirrhosis and ascites.Arch Intern Med.2002;162:323328.
  11. Angeli P,Wong F,Watson H, et al.Hyponatremia in cirrhosis: results of a patient population survey.Hepatology.2006;44(6):15351542.
  12. Moini M,Hoseini‐Asl MK,Taghavi SA, et al.Hyponatremia a valuable predictor of early mortality in patients with cirrhosis listed for liver transplantation.Clin Transplant.2011;25(4):638645.
  13. Torres JM,Cardenas O,Wasquez A,Schlossberg D.Streptococcus pneumoniae bacteremia in a community hospital.Chest.1998;113:387390.
  14. Nair V,Niederman MS,Masani N, et al.Hyponatremia in community‐acquired pneumonia.Am J Nephrol.2007;27(2):184190.
  15. Zilberberg MD,Exuzides A,Spalding J, et al.Hyponatremia and hospital outcomes among patients with pneumonia: a retrospective cohort study.BMC Pulm Med.2008;8:16.
  16. Adrogué HJ.Consequences of inadequate management of hyponatremia.Am J Nephrol.2005;25:240249.
  17. Upadhyay A,Jaber BL,Madias NE.Incidence and prevalence of hyponatremia.Am J Med.2006;119:S30S35.
  18. Franco K,Litaker D,Locala J,Bronson D.The cost of delirium in the surgical patient.Psychosomatics.2001;42:6873.
  19. Kumar S,Berl T.Diseases of water metabolism. In: Schrier RW, series ed;Berl T,Bonventre JV, eds. Atlas of Diseases of the Kidney; vol 1. 1999;1–1.22. Available at: http://www.kidneyatlas.org/book1/ADK1_01.pdf. Accessed June 21,2011.
  20. Verbalis JG.Vasopressin V2 receptor antagonists.J Mol Endocrinol.2002;29:19.
  21. Ross E,Sigal SH.Managing hyponatremia in cirrhosis.J Hosp Med.2010;5:S8S17.
  22. Ellison DH,Berl T.The syndrome of inappropriate antidiuresis.N Engl J Med.2007;356:20642072.
  23. Wilkinson TJ,Begg EJ,Winter AC,Sainsbury R.Incidence and risk factors for hyponatremia following treatment with fluoxetine or paroxetine in elderly people.Br J Clin Pharmacol.1999;47:211217.
  24. Hix JK,Silver S,Sterns RH.Diuretic‐associated hyponatremia.Semin Nephrol.2011;31(6):553566.
  25. Adrogué HJ,Madias NE.Hyponatremia.N Engl J Med.2000;342:15811589.
  26. Nathan BR.Cerebral correlates of hyponatremia.Neurocrit Care.2007;6:7278.
  27. Kengne FG,Andres C,Sattar L,Melot C,Decaux G.Mild hyponatremia and risk of fracture in the ambulatory elderly.Q J Med.2008;101:583588.
  28. Renneboog B,Musch W,Vandemergel X, et al.Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits.Am J Med.2006;119:71.e171.e8.
  29. Advisory Committee of the Cardiovascular and Renal Drugs Division of the US Food and Drug Administration. Treatment of Hyponatremia: Medical Utility of Vasopressin V2 Receptor Antagonism. Briefing Document. June 25, 2008. Available at: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008–4373b1–05.pdf. Accessed June 24,2011.
  30. Sherlock M,Thompson CJ.The syndrome of inappropriate antidiuretic hormone: current and future management options.Eur J Endocrinol.2010;162(suppl 1):S13S18.
  31. Waikar SS,Mount DB,Curhan GC.Mortality after hospitalization with mild, moderate, and severe hyponatremia.Am J Med.2009;122:857865.
  32. Shea AM,Hammill BG,Curtis LH,Szczech LA,Schulman KA.Medical costs of abnormal serum levels.J Am Soc Nephrol.2008;19:764770.
  33. Verbalis JG,Goldsmith SR,Greenberg A,Schrier RW,Sterns RH.Hyponatremia treatment guidelines 2007: expert panel recommendations.Am J Med.2007;120:S1S21.
  34. Hariprasad MK,Eisinger RP,Nadler IM, et al.Hyponatremia in psychogenic polydipsia.Arch Intern Med.1980;140(12):16391642.
  35. Thaler SM,Teitelbaum I,Berl T.“Beer potomania” in non‐beer drinkers: effect of low dietary solute intake.Am J Kidney Dis.1998;31(6):10281031.
  36. Lien YH,Shapiro JL.Hyponatremia: clinical diagnosis and management.Am J Med.2007;120:653658.
  37. Sterns RH,Nigwekar SU,Hix JK.The treatment of hyponatremia.Semin Nephrol.2009;29(3):282299.
  38. Zietse R,van der Lubbe N,Hoorn EJ.Current and future treatment options in SIADH.NDT Plus.2009;2(suppl 3):iii12iii19.
  39. Vaprisol (conivaptan hydrochloride injection). Prescribing information.Deerfield, IL:Astellas Pharma US, Inc; October2008.
  40. Zeltser D,Rosansky S,Van Rensburg H, et al.Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia.Am J Nephrol.2007;27:447457.
  41. Samsca™ (oral selective vasopressin antagonist). Prescribing information.Rockville, MD:Otsuka America Pharmaceutical, Inc; November2009.
  42. Schrier RW,Gheorghiade M,Berl T, et al.Tolvaptan, a selective oral vasopressin V2‐receptor antagonist, for hyponatremia.N Engl J Med.2006;355:20992112.
  43. Rozen‐Zvi B,Yahav D,Gheorghiade M, et al.Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta‐analysis.Am J Kidney Dis.2010;56:325337.
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APA Symposium Will Focus on Combining Modalities

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Ms. Suarez, a 48-year-old married Hispanic woman, came to her appointment at the outpatient psychiatry clinic asking for a second opinion. She told the admitting resident that she had had depression for years, and that nothing had helped. She said she had tried many medications and individual therapy, and she was feeling hopeless and frustrated. She worried that her husband would leave her. She was still working, but felt that the quality of her work was poor.

The psychiatric resident wondered whether to put her in the psychopharmacology clinic or in the psychotherapy clinic. What should the resident do? The American Psychiatric Association Symposium No. 81, from 9 a.m. to noon on May 8 in Philadelphia, will answer this question.

The symposium is called "Improving Quality of Care for Patients with Psychiatric Illness: Combining and Integrating Psychopharmacological, Individual, and Family Therapy." I will be presenting the symposium with Dr. Alan F. Schatzberg, Dr. Glen O. Gabbard, and Dr. Gabor I. Keitner as panelists, and Dr. Ira D. Glick as the discussant. We’ll be looking at the following topics:

• Dr. Schatzberg will discuss "Combining Pharmacotherapy With Other Modalities."

Psychopharmacology has become a major approach in the treatment of patients with psychiatric disorders. The discipline has evolved from its humble beginnings with a limited number of classes of agents that had a relatively narrow range of mechanisms of action, to the current host of classes and agents, many with disparate effects. This development demands considerable knowledge of the basic biology of the disorder, as well as the specific pharmacology of specific agents.

The development of this field, however, is not the only one in psychiatric treatment. Rather, parallel developments have taken place in the psychotherapies – as well as in devices – such that the practitioner needs to be able to incorporate advances in all of them to most optimally help his or her patient.

As models of other areas in psychiatry, recent developments in psychopharmacology and stimulatory device treatment of major depression will be reviewed, with data from studies on the biology of early abuse and cognitive deficits in depression and with an eye toward understanding how these various approaches can be integrated optimally to treating particular patients.

Early child abuse is associated with an increased risk for developing increased responsiveness to stress, as well as major depression in adulthood, and this risk interacts with specific genetic vulnerability. These patients might respond to medication, but do best when medications are combined with psychotherapy. Optimally, effective treatment outcomes will require the sophisticated application of knowledge of biology, pharmacology, and psychotherapy. In addition, training and education need to incorporate such approaches.

• Dr. Gabbard will discuss "Combining Individual Therapy With Other Modalities."

In the practice of general psychiatry, it inevitably becomes necessary to combine medication and psychotherapy techniques. However, this combination is undertheorized in our literature. In this presentation, the practice of combining individual therapy strategies and pharmacotherapy will be systematically considered from the standpoint of adherence, meanings of medication, enhancement of outcome, and different modes of therapeutic action. This presentation will address the practical matter of sequencing of the two modalities overall and within sessions.

• Dr. Keitner will discuss "Family Intervention by Psychiatrists as a Routine Component of Patient Care."

Illnesses begin and evolve in a social context, and affect friends and relatives of the ill person. The ways in which the patient’s significant others, in turn, deal with the illness influence its course and outcome.

It is necessary, therefore, to involve the families of patients in the assessment and treatment process. Family interventions can be stand-alone treatments or adjuncts to pharmacotherapy and psychotherapy. Numerous family-assessment and family-therapy models have been tested for use in many different illnesses. In general, family interventions have been found to be useful in the management of many chronic medical conditions as well as in major depression, bipolar disorder, anxiety disorders, schizophrenia, and substance abuse.

Most psychiatrists are not comfortable with or skilled in working with families, despite the evidence for its usefulness. This presentation will outline ways in which psychiatrists can systematically involve the families of patients in their assessment and treatment, and ways to combine and integrate family interventions with pharmacotherapy and psychotherapy.

For many decades, a biopsychosocial approach to patient care has meant a comprehensive assessment of the patient and the family environment. However, little discussion has occurred regarding what follows. What should follow is an extensive discussion with the patient and family about treatment. Clinical decision making should be done with the patient and the family, and should include a discussion of the biopsychosocial components that contribute to the illness, followed by a discussion of treatment options. The expected changes for each modality must be provided to the patient and family.

 

 

This symposium will address how to combine modalities, and how to discuss doing so with the patient and family. Each panelist will discuss how to combine modalities and will apply their expertise to Ms. Suarez’s situation.

Bring your clinical cases and questions, and pose them to the experts! See you there!

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Ms. Suarez, a 48-year-old married Hispanic woman, came to her appointment at the outpatient psychiatry clinic asking for a second opinion. She told the admitting resident that she had had depression for years, and that nothing had helped. She said she had tried many medications and individual therapy, and she was feeling hopeless and frustrated. She worried that her husband would leave her. She was still working, but felt that the quality of her work was poor.

The psychiatric resident wondered whether to put her in the psychopharmacology clinic or in the psychotherapy clinic. What should the resident do? The American Psychiatric Association Symposium No. 81, from 9 a.m. to noon on May 8 in Philadelphia, will answer this question.

The symposium is called "Improving Quality of Care for Patients with Psychiatric Illness: Combining and Integrating Psychopharmacological, Individual, and Family Therapy." I will be presenting the symposium with Dr. Alan F. Schatzberg, Dr. Glen O. Gabbard, and Dr. Gabor I. Keitner as panelists, and Dr. Ira D. Glick as the discussant. We’ll be looking at the following topics:

• Dr. Schatzberg will discuss "Combining Pharmacotherapy With Other Modalities."

Psychopharmacology has become a major approach in the treatment of patients with psychiatric disorders. The discipline has evolved from its humble beginnings with a limited number of classes of agents that had a relatively narrow range of mechanisms of action, to the current host of classes and agents, many with disparate effects. This development demands considerable knowledge of the basic biology of the disorder, as well as the specific pharmacology of specific agents.

The development of this field, however, is not the only one in psychiatric treatment. Rather, parallel developments have taken place in the psychotherapies – as well as in devices – such that the practitioner needs to be able to incorporate advances in all of them to most optimally help his or her patient.

As models of other areas in psychiatry, recent developments in psychopharmacology and stimulatory device treatment of major depression will be reviewed, with data from studies on the biology of early abuse and cognitive deficits in depression and with an eye toward understanding how these various approaches can be integrated optimally to treating particular patients.

Early child abuse is associated with an increased risk for developing increased responsiveness to stress, as well as major depression in adulthood, and this risk interacts with specific genetic vulnerability. These patients might respond to medication, but do best when medications are combined with psychotherapy. Optimally, effective treatment outcomes will require the sophisticated application of knowledge of biology, pharmacology, and psychotherapy. In addition, training and education need to incorporate such approaches.

• Dr. Gabbard will discuss "Combining Individual Therapy With Other Modalities."

In the practice of general psychiatry, it inevitably becomes necessary to combine medication and psychotherapy techniques. However, this combination is undertheorized in our literature. In this presentation, the practice of combining individual therapy strategies and pharmacotherapy will be systematically considered from the standpoint of adherence, meanings of medication, enhancement of outcome, and different modes of therapeutic action. This presentation will address the practical matter of sequencing of the two modalities overall and within sessions.

• Dr. Keitner will discuss "Family Intervention by Psychiatrists as a Routine Component of Patient Care."

Illnesses begin and evolve in a social context, and affect friends and relatives of the ill person. The ways in which the patient’s significant others, in turn, deal with the illness influence its course and outcome.

It is necessary, therefore, to involve the families of patients in the assessment and treatment process. Family interventions can be stand-alone treatments or adjuncts to pharmacotherapy and psychotherapy. Numerous family-assessment and family-therapy models have been tested for use in many different illnesses. In general, family interventions have been found to be useful in the management of many chronic medical conditions as well as in major depression, bipolar disorder, anxiety disorders, schizophrenia, and substance abuse.

Most psychiatrists are not comfortable with or skilled in working with families, despite the evidence for its usefulness. This presentation will outline ways in which psychiatrists can systematically involve the families of patients in their assessment and treatment, and ways to combine and integrate family interventions with pharmacotherapy and psychotherapy.

For many decades, a biopsychosocial approach to patient care has meant a comprehensive assessment of the patient and the family environment. However, little discussion has occurred regarding what follows. What should follow is an extensive discussion with the patient and family about treatment. Clinical decision making should be done with the patient and the family, and should include a discussion of the biopsychosocial components that contribute to the illness, followed by a discussion of treatment options. The expected changes for each modality must be provided to the patient and family.

 

 

This symposium will address how to combine modalities, and how to discuss doing so with the patient and family. Each panelist will discuss how to combine modalities and will apply their expertise to Ms. Suarez’s situation.

Bring your clinical cases and questions, and pose them to the experts! See you there!

Ms. Suarez, a 48-year-old married Hispanic woman, came to her appointment at the outpatient psychiatry clinic asking for a second opinion. She told the admitting resident that she had had depression for years, and that nothing had helped. She said she had tried many medications and individual therapy, and she was feeling hopeless and frustrated. She worried that her husband would leave her. She was still working, but felt that the quality of her work was poor.

The psychiatric resident wondered whether to put her in the psychopharmacology clinic or in the psychotherapy clinic. What should the resident do? The American Psychiatric Association Symposium No. 81, from 9 a.m. to noon on May 8 in Philadelphia, will answer this question.

The symposium is called "Improving Quality of Care for Patients with Psychiatric Illness: Combining and Integrating Psychopharmacological, Individual, and Family Therapy." I will be presenting the symposium with Dr. Alan F. Schatzberg, Dr. Glen O. Gabbard, and Dr. Gabor I. Keitner as panelists, and Dr. Ira D. Glick as the discussant. We’ll be looking at the following topics:

• Dr. Schatzberg will discuss "Combining Pharmacotherapy With Other Modalities."

Psychopharmacology has become a major approach in the treatment of patients with psychiatric disorders. The discipline has evolved from its humble beginnings with a limited number of classes of agents that had a relatively narrow range of mechanisms of action, to the current host of classes and agents, many with disparate effects. This development demands considerable knowledge of the basic biology of the disorder, as well as the specific pharmacology of specific agents.

The development of this field, however, is not the only one in psychiatric treatment. Rather, parallel developments have taken place in the psychotherapies – as well as in devices – such that the practitioner needs to be able to incorporate advances in all of them to most optimally help his or her patient.

As models of other areas in psychiatry, recent developments in psychopharmacology and stimulatory device treatment of major depression will be reviewed, with data from studies on the biology of early abuse and cognitive deficits in depression and with an eye toward understanding how these various approaches can be integrated optimally to treating particular patients.

Early child abuse is associated with an increased risk for developing increased responsiveness to stress, as well as major depression in adulthood, and this risk interacts with specific genetic vulnerability. These patients might respond to medication, but do best when medications are combined with psychotherapy. Optimally, effective treatment outcomes will require the sophisticated application of knowledge of biology, pharmacology, and psychotherapy. In addition, training and education need to incorporate such approaches.

• Dr. Gabbard will discuss "Combining Individual Therapy With Other Modalities."

In the practice of general psychiatry, it inevitably becomes necessary to combine medication and psychotherapy techniques. However, this combination is undertheorized in our literature. In this presentation, the practice of combining individual therapy strategies and pharmacotherapy will be systematically considered from the standpoint of adherence, meanings of medication, enhancement of outcome, and different modes of therapeutic action. This presentation will address the practical matter of sequencing of the two modalities overall and within sessions.

• Dr. Keitner will discuss "Family Intervention by Psychiatrists as a Routine Component of Patient Care."

Illnesses begin and evolve in a social context, and affect friends and relatives of the ill person. The ways in which the patient’s significant others, in turn, deal with the illness influence its course and outcome.

It is necessary, therefore, to involve the families of patients in the assessment and treatment process. Family interventions can be stand-alone treatments or adjuncts to pharmacotherapy and psychotherapy. Numerous family-assessment and family-therapy models have been tested for use in many different illnesses. In general, family interventions have been found to be useful in the management of many chronic medical conditions as well as in major depression, bipolar disorder, anxiety disorders, schizophrenia, and substance abuse.

Most psychiatrists are not comfortable with or skilled in working with families, despite the evidence for its usefulness. This presentation will outline ways in which psychiatrists can systematically involve the families of patients in their assessment and treatment, and ways to combine and integrate family interventions with pharmacotherapy and psychotherapy.

For many decades, a biopsychosocial approach to patient care has meant a comprehensive assessment of the patient and the family environment. However, little discussion has occurred regarding what follows. What should follow is an extensive discussion with the patient and family about treatment. Clinical decision making should be done with the patient and the family, and should include a discussion of the biopsychosocial components that contribute to the illness, followed by a discussion of treatment options. The expected changes for each modality must be provided to the patient and family.

 

 

This symposium will address how to combine modalities, and how to discuss doing so with the patient and family. Each panelist will discuss how to combine modalities and will apply their expertise to Ms. Suarez’s situation.

Bring your clinical cases and questions, and pose them to the experts! See you there!

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Wachter Highlights New Era for Hospitalists

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When Robert Wachter, MD, MHM, graduated from medical school in 1983, he thought he knew what a great doctor was. When he gave the penultimate address to a packed house at the Society of Hospital Medicine’s annual meeting in San Diego on Wednesday, he said that definition has changed—and will continue to evolve as hospitalists tackle the challenges of delivering high-value, cost-conscious care in an age of healthcare reform.

“We need to be great team players, but we also need to be great leaders,” said Dr. Wachter, professor and chief of the division of hospital medicine. chief of the medical service at the University of California San Francisco Medical Center and chair-elect for the American Board of Internal Medicine. “We need to embrace useful technology, but we can’t be slaves to it … improve systems of care, but welcome personal and group accountability. Strive for a balanced life but remember medicine is more a calling than a job. And think about the patients’ needs before our own. These are core and enduring values even as we move into this new era.”

Dr. Wachter’s plenary, titled “The Great Physician, Circa 2012: How Hospitalists Must Lead Efforts to Identify and Become This New Breed,” highlighted the balance HM practitioners must find in an increasingly complex healthcare system. He suggested hospitalists view themselves as technologically savvy “lifelong learners” whose reputation for systems improvement positions them perfectly to champion reform.

“We have big targets on us and I think they are appropriate,” said Dr. Wachter. “There are others who should have targets as well, but the main target has to be us. Change is impossible if we don’t embrace change.”

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When Robert Wachter, MD, MHM, graduated from medical school in 1983, he thought he knew what a great doctor was. When he gave the penultimate address to a packed house at the Society of Hospital Medicine’s annual meeting in San Diego on Wednesday, he said that definition has changed—and will continue to evolve as hospitalists tackle the challenges of delivering high-value, cost-conscious care in an age of healthcare reform.

“We need to be great team players, but we also need to be great leaders,” said Dr. Wachter, professor and chief of the division of hospital medicine. chief of the medical service at the University of California San Francisco Medical Center and chair-elect for the American Board of Internal Medicine. “We need to embrace useful technology, but we can’t be slaves to it … improve systems of care, but welcome personal and group accountability. Strive for a balanced life but remember medicine is more a calling than a job. And think about the patients’ needs before our own. These are core and enduring values even as we move into this new era.”

Dr. Wachter’s plenary, titled “The Great Physician, Circa 2012: How Hospitalists Must Lead Efforts to Identify and Become This New Breed,” highlighted the balance HM practitioners must find in an increasingly complex healthcare system. He suggested hospitalists view themselves as technologically savvy “lifelong learners” whose reputation for systems improvement positions them perfectly to champion reform.

“We have big targets on us and I think they are appropriate,” said Dr. Wachter. “There are others who should have targets as well, but the main target has to be us. Change is impossible if we don’t embrace change.”

When Robert Wachter, MD, MHM, graduated from medical school in 1983, he thought he knew what a great doctor was. When he gave the penultimate address to a packed house at the Society of Hospital Medicine’s annual meeting in San Diego on Wednesday, he said that definition has changed—and will continue to evolve as hospitalists tackle the challenges of delivering high-value, cost-conscious care in an age of healthcare reform.

“We need to be great team players, but we also need to be great leaders,” said Dr. Wachter, professor and chief of the division of hospital medicine. chief of the medical service at the University of California San Francisco Medical Center and chair-elect for the American Board of Internal Medicine. “We need to embrace useful technology, but we can’t be slaves to it … improve systems of care, but welcome personal and group accountability. Strive for a balanced life but remember medicine is more a calling than a job. And think about the patients’ needs before our own. These are core and enduring values even as we move into this new era.”

Dr. Wachter’s plenary, titled “The Great Physician, Circa 2012: How Hospitalists Must Lead Efforts to Identify and Become This New Breed,” highlighted the balance HM practitioners must find in an increasingly complex healthcare system. He suggested hospitalists view themselves as technologically savvy “lifelong learners” whose reputation for systems improvement positions them perfectly to champion reform.

“We have big targets on us and I think they are appropriate,” said Dr. Wachter. “There are others who should have targets as well, but the main target has to be us. Change is impossible if we don’t embrace change.”

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Engineering Can Help Hospitalists Solve Scheduling Dilemmas

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Could engineering processes and techniques help hospitalists with some of the inherent frustrations of their practice—scheduling, staffing, admission surges, prioritizing which patients to see first?

Jonathan Turner, PhD, an industrial engineer who works as a healthcare engineer with the division of hospital medicine at Northwestern University Medical Center in Chicago, led a workshop on applying techniques such as queuing principles to hospitalist practice on Wednesday morning at the Society of Hospital Medicine’s annual meeting, HM12.

One of those principles is Little's Law which, applied to hospitals, calculates length of stay as the hospital’s census divided by its admission rate, reflecting the rates in and out and waiting times within the hospital.

“A lot of hospital administrators talk about reducing lengths of stay, when what they really want to do is increase admissions without increasing beds,” said Dr. Turner. You could reduce length of stay without actually affecting admissions, he added, which would result in unused capacity. At the same time, as capacity approaches 100% percent, negative consequences such as longer wait times and reduced quality may dilute the gains in efficiency. A better target, he said, may be closer to 85% percent of capacity.

One workshop participant relayed how his hospital struggled with delays in processing admissions. He took Little’s Law to his administration and made the case for additional staffing. The administration agreed to an additional hospitalist FTE, since the alternative was back-ups, and shifts were adjusted to times of greatest need. Currently, on 85% of days at the hospital, there are no delays in admissions.

“We talked about how difficult it is to predict caseload,” said Turner at the end of the workshop. “We can look at spikes and seasonal differences, but it may be easier to see patterns if you start peeling off subsets of your patient population.”

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Could engineering processes and techniques help hospitalists with some of the inherent frustrations of their practice—scheduling, staffing, admission surges, prioritizing which patients to see first?

Jonathan Turner, PhD, an industrial engineer who works as a healthcare engineer with the division of hospital medicine at Northwestern University Medical Center in Chicago, led a workshop on applying techniques such as queuing principles to hospitalist practice on Wednesday morning at the Society of Hospital Medicine’s annual meeting, HM12.

One of those principles is Little's Law which, applied to hospitals, calculates length of stay as the hospital’s census divided by its admission rate, reflecting the rates in and out and waiting times within the hospital.

“A lot of hospital administrators talk about reducing lengths of stay, when what they really want to do is increase admissions without increasing beds,” said Dr. Turner. You could reduce length of stay without actually affecting admissions, he added, which would result in unused capacity. At the same time, as capacity approaches 100% percent, negative consequences such as longer wait times and reduced quality may dilute the gains in efficiency. A better target, he said, may be closer to 85% percent of capacity.

One workshop participant relayed how his hospital struggled with delays in processing admissions. He took Little’s Law to his administration and made the case for additional staffing. The administration agreed to an additional hospitalist FTE, since the alternative was back-ups, and shifts were adjusted to times of greatest need. Currently, on 85% of days at the hospital, there are no delays in admissions.

“We talked about how difficult it is to predict caseload,” said Turner at the end of the workshop. “We can look at spikes and seasonal differences, but it may be easier to see patterns if you start peeling off subsets of your patient population.”

Could engineering processes and techniques help hospitalists with some of the inherent frustrations of their practice—scheduling, staffing, admission surges, prioritizing which patients to see first?

Jonathan Turner, PhD, an industrial engineer who works as a healthcare engineer with the division of hospital medicine at Northwestern University Medical Center in Chicago, led a workshop on applying techniques such as queuing principles to hospitalist practice on Wednesday morning at the Society of Hospital Medicine’s annual meeting, HM12.

One of those principles is Little's Law which, applied to hospitals, calculates length of stay as the hospital’s census divided by its admission rate, reflecting the rates in and out and waiting times within the hospital.

“A lot of hospital administrators talk about reducing lengths of stay, when what they really want to do is increase admissions without increasing beds,” said Dr. Turner. You could reduce length of stay without actually affecting admissions, he added, which would result in unused capacity. At the same time, as capacity approaches 100% percent, negative consequences such as longer wait times and reduced quality may dilute the gains in efficiency. A better target, he said, may be closer to 85% percent of capacity.

One workshop participant relayed how his hospital struggled with delays in processing admissions. He took Little’s Law to his administration and made the case for additional staffing. The administration agreed to an additional hospitalist FTE, since the alternative was back-ups, and shifts were adjusted to times of greatest need. Currently, on 85% of days at the hospital, there are no delays in admissions.

“We talked about how difficult it is to predict caseload,” said Turner at the end of the workshop. “We can look at spikes and seasonal differences, but it may be easier to see patterns if you start peeling off subsets of your patient population.”

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HM12 Session Analysis: Using IT Systems to Address Quality, Safety Imperatives

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Clinical decision support (CDS) can be defined very broadly as “a process for enhancing health-related decisions and actions with pertinent, organized clinical knowledge and patient information to improve health and healthcare delivery.” However, it's important to remember that simply deploying CDS does not automatically equate to performance improvement (PI), said Jerome Osheroff, MD, during a Wednesday morning session at HM12.

Dr. Osheroff is a leader in CDS and a key editor of the new HIMSS publication "Improving Outcomes with CDS: An Implementer's Guide." SHM co-sponsored the publication, and hospitalist Kendall Rogers was an editor.

Dr. Osheroff advised hospitalists to keep in mind the five "rights" of CDS: the right information, to the right people, in the right intervention formats, through the right channels, and at the right points in workflow. He also stressed the importance of workflow analysis, solid governance and management, and strategic plan development when initiating a hospital-based CDS program.

He finished the discussion by stressing the importance of collaboration, and described the "CDS/PI Collaborative," a multi-stakeholder national movement bringing CDS tools to caregivers and healthcare organizations.

"The screws are getting tighter and tighter" in healthcare, he said, and CDS collaboration needs to act as the screwdriver. In a show of hands during the session, the majority of attendees would participate in this approach, especially with SHM support.

Takeaways

  • Apply the "CDS Five Rights" when implementing the CDS process.
  • CDS deployment does not equate to performance improvement.
  • The CDS/PI Collaborative can provide tools to healthcare organizations.
  • Consider the Zen saying: A poor farmer produces weeds, a good farmer produces crops, a wise farmer produces soil.
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Clinical decision support (CDS) can be defined very broadly as “a process for enhancing health-related decisions and actions with pertinent, organized clinical knowledge and patient information to improve health and healthcare delivery.” However, it's important to remember that simply deploying CDS does not automatically equate to performance improvement (PI), said Jerome Osheroff, MD, during a Wednesday morning session at HM12.

Dr. Osheroff is a leader in CDS and a key editor of the new HIMSS publication "Improving Outcomes with CDS: An Implementer's Guide." SHM co-sponsored the publication, and hospitalist Kendall Rogers was an editor.

Dr. Osheroff advised hospitalists to keep in mind the five "rights" of CDS: the right information, to the right people, in the right intervention formats, through the right channels, and at the right points in workflow. He also stressed the importance of workflow analysis, solid governance and management, and strategic plan development when initiating a hospital-based CDS program.

He finished the discussion by stressing the importance of collaboration, and described the "CDS/PI Collaborative," a multi-stakeholder national movement bringing CDS tools to caregivers and healthcare organizations.

"The screws are getting tighter and tighter" in healthcare, he said, and CDS collaboration needs to act as the screwdriver. In a show of hands during the session, the majority of attendees would participate in this approach, especially with SHM support.

Takeaways

  • Apply the "CDS Five Rights" when implementing the CDS process.
  • CDS deployment does not equate to performance improvement.
  • The CDS/PI Collaborative can provide tools to healthcare organizations.
  • Consider the Zen saying: A poor farmer produces weeds, a good farmer produces crops, a wise farmer produces soil.

Clinical decision support (CDS) can be defined very broadly as “a process for enhancing health-related decisions and actions with pertinent, organized clinical knowledge and patient information to improve health and healthcare delivery.” However, it's important to remember that simply deploying CDS does not automatically equate to performance improvement (PI), said Jerome Osheroff, MD, during a Wednesday morning session at HM12.

Dr. Osheroff is a leader in CDS and a key editor of the new HIMSS publication "Improving Outcomes with CDS: An Implementer's Guide." SHM co-sponsored the publication, and hospitalist Kendall Rogers was an editor.

Dr. Osheroff advised hospitalists to keep in mind the five "rights" of CDS: the right information, to the right people, in the right intervention formats, through the right channels, and at the right points in workflow. He also stressed the importance of workflow analysis, solid governance and management, and strategic plan development when initiating a hospital-based CDS program.

He finished the discussion by stressing the importance of collaboration, and described the "CDS/PI Collaborative," a multi-stakeholder national movement bringing CDS tools to caregivers and healthcare organizations.

"The screws are getting tighter and tighter" in healthcare, he said, and CDS collaboration needs to act as the screwdriver. In a show of hands during the session, the majority of attendees would participate in this approach, especially with SHM support.

Takeaways

  • Apply the "CDS Five Rights" when implementing the CDS process.
  • CDS deployment does not equate to performance improvement.
  • The CDS/PI Collaborative can provide tools to healthcare organizations.
  • Consider the Zen saying: A poor farmer produces weeds, a good farmer produces crops, a wise farmer produces soil.
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Society of Hospital Medicine Announces Annual Research, Innovation, and Clinical Vignette Poster Winners

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Four hospitalist research teams were announced as winners of the 2012 Research, Innovation, and Clinical Vignette poster competition at HM12 in San Diego. More than 500 posters were judged this year, the most in competition history.

Research

Title: Veterans Administration Acute Care 30-Day Mortality Model: Development, Validation, and Performance Variation

Team: Eduard Vasilevskis, MD, Annette Christianson, MS, James Deddens, PhD, Siva Sivaganesin, PhD3, Ron Freyberg, MS, Timothy Hofer, MD, MSc, Peter Almenoff, MD, Marta Render, MD; VA Tennessee Valley Healthcare System, Nashville, Tenn.; Department of Veterans Affairs, Cincinnati, University of Cincinnati, Cincinnati, Ohio, Department of Veterans Affairs, Ann Arbor, Mich., Veterans Affairs Medical Center, Kansas City, Mo.

Click here to view the abstract.

Innovation

Title: Accountable Care Unit on a Medical Ward in a Teaching Hospital: A New Care Model Designed To Improve Patient and Hospital Outcomes

Team: Christina Payne, MD, Dapo Odetoyinbo, MD, Bryan Castle, RN, MBA, Amanda Methvin, MD, John Vazquez, MD, Molly Burleson, RN, Dustin Smith, MD, Daniel Dressler, MD, MSc, Jason Stein, MD; Emory University Hospital, Atlanta, Ga., Veterans’ Affairs Medical Center, Atlanta, Ga.

Click here to view the abstract.

Clinical Vignette – Adult

Title: Moo Is the Clue

Team: Rafina Khateeb, MD, Min Jiang, MD, Tejal Gandhi, MD; University of Michigan Health System, Ann Arbor, Mich

Click here to view the abstract.

Clinical Vignette - Pediatric

Title: Rare Cause of Lack of Expected Weight Gain in an Infant

Team: Jonathan Chiles, MD, Christrine Hrach, MD; Washington University, St. Louis, Mo.

Click here to view the abstract.

View all of the 2012 RIV abstracts via the HM12 at Hand app.

Jason Carris is editor of The Hospitalist.

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Four hospitalist research teams were announced as winners of the 2012 Research, Innovation, and Clinical Vignette poster competition at HM12 in San Diego. More than 500 posters were judged this year, the most in competition history.

Research

Title: Veterans Administration Acute Care 30-Day Mortality Model: Development, Validation, and Performance Variation

Team: Eduard Vasilevskis, MD, Annette Christianson, MS, James Deddens, PhD, Siva Sivaganesin, PhD3, Ron Freyberg, MS, Timothy Hofer, MD, MSc, Peter Almenoff, MD, Marta Render, MD; VA Tennessee Valley Healthcare System, Nashville, Tenn.; Department of Veterans Affairs, Cincinnati, University of Cincinnati, Cincinnati, Ohio, Department of Veterans Affairs, Ann Arbor, Mich., Veterans Affairs Medical Center, Kansas City, Mo.

Click here to view the abstract.

Innovation

Title: Accountable Care Unit on a Medical Ward in a Teaching Hospital: A New Care Model Designed To Improve Patient and Hospital Outcomes

Team: Christina Payne, MD, Dapo Odetoyinbo, MD, Bryan Castle, RN, MBA, Amanda Methvin, MD, John Vazquez, MD, Molly Burleson, RN, Dustin Smith, MD, Daniel Dressler, MD, MSc, Jason Stein, MD; Emory University Hospital, Atlanta, Ga., Veterans’ Affairs Medical Center, Atlanta, Ga.

Click here to view the abstract.

Clinical Vignette – Adult

Title: Moo Is the Clue

Team: Rafina Khateeb, MD, Min Jiang, MD, Tejal Gandhi, MD; University of Michigan Health System, Ann Arbor, Mich

Click here to view the abstract.

Clinical Vignette - Pediatric

Title: Rare Cause of Lack of Expected Weight Gain in an Infant

Team: Jonathan Chiles, MD, Christrine Hrach, MD; Washington University, St. Louis, Mo.

Click here to view the abstract.

View all of the 2012 RIV abstracts via the HM12 at Hand app.

Jason Carris is editor of The Hospitalist.

Four hospitalist research teams were announced as winners of the 2012 Research, Innovation, and Clinical Vignette poster competition at HM12 in San Diego. More than 500 posters were judged this year, the most in competition history.

Research

Title: Veterans Administration Acute Care 30-Day Mortality Model: Development, Validation, and Performance Variation

Team: Eduard Vasilevskis, MD, Annette Christianson, MS, James Deddens, PhD, Siva Sivaganesin, PhD3, Ron Freyberg, MS, Timothy Hofer, MD, MSc, Peter Almenoff, MD, Marta Render, MD; VA Tennessee Valley Healthcare System, Nashville, Tenn.; Department of Veterans Affairs, Cincinnati, University of Cincinnati, Cincinnati, Ohio, Department of Veterans Affairs, Ann Arbor, Mich., Veterans Affairs Medical Center, Kansas City, Mo.

Click here to view the abstract.

Innovation

Title: Accountable Care Unit on a Medical Ward in a Teaching Hospital: A New Care Model Designed To Improve Patient and Hospital Outcomes

Team: Christina Payne, MD, Dapo Odetoyinbo, MD, Bryan Castle, RN, MBA, Amanda Methvin, MD, John Vazquez, MD, Molly Burleson, RN, Dustin Smith, MD, Daniel Dressler, MD, MSc, Jason Stein, MD; Emory University Hospital, Atlanta, Ga., Veterans’ Affairs Medical Center, Atlanta, Ga.

Click here to view the abstract.

Clinical Vignette – Adult

Title: Moo Is the Clue

Team: Rafina Khateeb, MD, Min Jiang, MD, Tejal Gandhi, MD; University of Michigan Health System, Ann Arbor, Mich

Click here to view the abstract.

Clinical Vignette - Pediatric

Title: Rare Cause of Lack of Expected Weight Gain in an Infant

Team: Jonathan Chiles, MD, Christrine Hrach, MD; Washington University, St. Louis, Mo.

Click here to view the abstract.

View all of the 2012 RIV abstracts via the HM12 at Hand app.

Jason Carris is editor of The Hospitalist.

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Slowed Infusions Cut Hypersensitivity Reactions in Rituximab Desensitization

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ORLANDO – A slowed, rate-controlled infusion of rituximab during a desensitization protocol significantly reduced the number of hypersensitivity reactions compared with faster, standard-rate desensitization infusions.

"The safety of rituximab desensitization was improved using rate-controlled protocols," said Dr. Caroline L. Sokol, who discussed a review of 16 patients who underwent 103 desensitizations at a single U.S. center. The findings prompted her division to switch to rate-controlled infusions for all rituximab desensitization protocols, said Dr. Sokol of the division of allergy and immunology at Massachusetts General Hospital, Boston (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB371).

Dr. Caroline L. Sokol

Hypersensitivity reactions to rituximab primarily occur among patients who receive the drug to treat cancer. Patients who receive rituximab for other indications, such as rheumatoid diseases, rarely have hypersensitivity reactions. The explanation for this difference isn’t clear, Dr. Sokol said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In the series she reviewed, 15 patients received rituximab for cancer and one patient received it to treat multiple sclerosis.

She and her associates also plan to assess the safety of rate-controlled infusions for desensitization to other drugs, including other types of monoclonal antibodies and platinum-containing cancer chemotherapy drugs.

They compared the safety of standard and rate-controlled infusions with rituximab because some cancer patients who receive the drug experience hypersensitivity reactions that are not controllable with antihistamine or steroid pretreatment. These patients must therefore undergo desensitization, a step that usually needs to be repeated every time they start a new course of the drug.

To compare the two infusion protocols, the researchers reviewed the Massachusetts General experience using the rate-control method during 2006-2008 as well as in 2011-2012. Those results were compared against the outcomes using a standard-infusion protocol during 2008-2011.

Among the 103 total rituximab desensitization procedures done on 16 patients during 2006-2012, 75 protocols used the rate-controlled method with a fixed infusion rate that delivered no more than 200 mg/hr of rituximab and 28 used a standard protocol that delivered a fixed fluid volume with varying rituximab concentrations that finished at 320 mg/hr. Most patients underwent desensitization with each of the two methods at some point during the 6 years included in the review. The average age of the 16 patients was 51 years, and they were equally split between men and women.

The 75 rate-controlled desensitizations resulted in 13 hypersensitivity reactions (17%), including 6 mild reactions, 5 moderate, and 2 severe. The 28 standard desensitizations produced eight reactions (29%), a statistically significant difference compared with the rate-control incidence, and included two mild, five moderate, and one severe reaction, Dr. Sokol reported.

The reaction rate was highest in three patients who converted from rituximab skin-test negative to skin-test positive during the course of their 28 desensitization protocols. Hypersensitivity reactions occurred in nine of these 28 protocols (32%). In contrast, the reaction rate was 19% in patients who remained skin-test negative throughout their desensitizations. Among those who remained consistently skin-test positive, the reaction rate was 16%, she said.

Dr. Sokol said that she had no disclosures.

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ORLANDO – A slowed, rate-controlled infusion of rituximab during a desensitization protocol significantly reduced the number of hypersensitivity reactions compared with faster, standard-rate desensitization infusions.

"The safety of rituximab desensitization was improved using rate-controlled protocols," said Dr. Caroline L. Sokol, who discussed a review of 16 patients who underwent 103 desensitizations at a single U.S. center. The findings prompted her division to switch to rate-controlled infusions for all rituximab desensitization protocols, said Dr. Sokol of the division of allergy and immunology at Massachusetts General Hospital, Boston (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB371).

Dr. Caroline L. Sokol

Hypersensitivity reactions to rituximab primarily occur among patients who receive the drug to treat cancer. Patients who receive rituximab for other indications, such as rheumatoid diseases, rarely have hypersensitivity reactions. The explanation for this difference isn’t clear, Dr. Sokol said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In the series she reviewed, 15 patients received rituximab for cancer and one patient received it to treat multiple sclerosis.

She and her associates also plan to assess the safety of rate-controlled infusions for desensitization to other drugs, including other types of monoclonal antibodies and platinum-containing cancer chemotherapy drugs.

They compared the safety of standard and rate-controlled infusions with rituximab because some cancer patients who receive the drug experience hypersensitivity reactions that are not controllable with antihistamine or steroid pretreatment. These patients must therefore undergo desensitization, a step that usually needs to be repeated every time they start a new course of the drug.

To compare the two infusion protocols, the researchers reviewed the Massachusetts General experience using the rate-control method during 2006-2008 as well as in 2011-2012. Those results were compared against the outcomes using a standard-infusion protocol during 2008-2011.

Among the 103 total rituximab desensitization procedures done on 16 patients during 2006-2012, 75 protocols used the rate-controlled method with a fixed infusion rate that delivered no more than 200 mg/hr of rituximab and 28 used a standard protocol that delivered a fixed fluid volume with varying rituximab concentrations that finished at 320 mg/hr. Most patients underwent desensitization with each of the two methods at some point during the 6 years included in the review. The average age of the 16 patients was 51 years, and they were equally split between men and women.

The 75 rate-controlled desensitizations resulted in 13 hypersensitivity reactions (17%), including 6 mild reactions, 5 moderate, and 2 severe. The 28 standard desensitizations produced eight reactions (29%), a statistically significant difference compared with the rate-control incidence, and included two mild, five moderate, and one severe reaction, Dr. Sokol reported.

The reaction rate was highest in three patients who converted from rituximab skin-test negative to skin-test positive during the course of their 28 desensitization protocols. Hypersensitivity reactions occurred in nine of these 28 protocols (32%). In contrast, the reaction rate was 19% in patients who remained skin-test negative throughout their desensitizations. Among those who remained consistently skin-test positive, the reaction rate was 16%, she said.

Dr. Sokol said that she had no disclosures.

ORLANDO – A slowed, rate-controlled infusion of rituximab during a desensitization protocol significantly reduced the number of hypersensitivity reactions compared with faster, standard-rate desensitization infusions.

"The safety of rituximab desensitization was improved using rate-controlled protocols," said Dr. Caroline L. Sokol, who discussed a review of 16 patients who underwent 103 desensitizations at a single U.S. center. The findings prompted her division to switch to rate-controlled infusions for all rituximab desensitization protocols, said Dr. Sokol of the division of allergy and immunology at Massachusetts General Hospital, Boston (J. Allergy Clin. Immunol. 2012;129[suppl.]:AB371).

Dr. Caroline L. Sokol

Hypersensitivity reactions to rituximab primarily occur among patients who receive the drug to treat cancer. Patients who receive rituximab for other indications, such as rheumatoid diseases, rarely have hypersensitivity reactions. The explanation for this difference isn’t clear, Dr. Sokol said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In the series she reviewed, 15 patients received rituximab for cancer and one patient received it to treat multiple sclerosis.

She and her associates also plan to assess the safety of rate-controlled infusions for desensitization to other drugs, including other types of monoclonal antibodies and platinum-containing cancer chemotherapy drugs.

They compared the safety of standard and rate-controlled infusions with rituximab because some cancer patients who receive the drug experience hypersensitivity reactions that are not controllable with antihistamine or steroid pretreatment. These patients must therefore undergo desensitization, a step that usually needs to be repeated every time they start a new course of the drug.

To compare the two infusion protocols, the researchers reviewed the Massachusetts General experience using the rate-control method during 2006-2008 as well as in 2011-2012. Those results were compared against the outcomes using a standard-infusion protocol during 2008-2011.

Among the 103 total rituximab desensitization procedures done on 16 patients during 2006-2012, 75 protocols used the rate-controlled method with a fixed infusion rate that delivered no more than 200 mg/hr of rituximab and 28 used a standard protocol that delivered a fixed fluid volume with varying rituximab concentrations that finished at 320 mg/hr. Most patients underwent desensitization with each of the two methods at some point during the 6 years included in the review. The average age of the 16 patients was 51 years, and they were equally split between men and women.

The 75 rate-controlled desensitizations resulted in 13 hypersensitivity reactions (17%), including 6 mild reactions, 5 moderate, and 2 severe. The 28 standard desensitizations produced eight reactions (29%), a statistically significant difference compared with the rate-control incidence, and included two mild, five moderate, and one severe reaction, Dr. Sokol reported.

The reaction rate was highest in three patients who converted from rituximab skin-test negative to skin-test positive during the course of their 28 desensitization protocols. Hypersensitivity reactions occurred in nine of these 28 protocols (32%). In contrast, the reaction rate was 19% in patients who remained skin-test negative throughout their desensitizations. Among those who remained consistently skin-test positive, the reaction rate was 16%, she said.

Dr. Sokol said that she had no disclosures.

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FROM THE ANNUAL MEETING OF THE AMERICAN ACADEMY OF ALLERGY, ASTHMA, AND IMMUNOLOGY

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Inside the Article

Vitals

Major Finding: Rituximab desensitization by standard infusion resulted in a 29% hypersensitivity-reaction rate, but rate-controlled infusion produced a 17% reaction rate.

Data Source: In a single-center review, 16 patients underwent 103 rituximab desensitization protocols during 2006-2012.

Disclosures: Dr. Sokol said that she had no disclosures.

HM12 Session Analysis: Variation in Medical Practice

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All hospitalists have seen the phenomenon of "surgical signature," when different surgeons appear to have different rates of surgical intervention. Residents know different physicians often treat a single condition in varying ways. The losers in practice variation are the patients, learners, and the overall healthcare system.

Mark Shen, MD, the pediatric editor for The Hospitalist and presenter of this Tuesday afternoon session at HM12, said he has gone through the five stages of grief in the past when dealing with different care plans in a hospital setting, finally settling on acceptance. Now, he said it is important to move past acceptance and recognize variations in physician practice. Further, it's critical to understand the unintended consequences of unwarranted variation.

There are many factors in variation, said Dr. Shen. Examples include preference-sensitive care, in which a physician has a particular model that she or he follows that is specific to that physician, and supply-sensitive care, the trend where certain procedures are more frequently utilized when they are more readily available. A specific example of variation is the rate of tonsillectomy between surgeons.

Variation arises easily in medicine because of inherent uncertainty in medicine. Uncertainty arises because of the challenges of defining disease, making a diagnosis, selecting a procedure, observing outcomes, and assessing preferences.

Variation can be mitigated by formal protocols individualized to each patient. An example of successful protocols is modern pediatric oncology, which has dramatically improved patient outcomes.

Takeaways

  • Hospitalists must recognize variation in care.
  • Addressing variation improves patient care and offers improved utilization of limited healthcare resources.
  • There are several approaches to mitigate variation, including practice guidelines.
  • Shared decision making with the patient and family will also improve individual patient care.
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All hospitalists have seen the phenomenon of "surgical signature," when different surgeons appear to have different rates of surgical intervention. Residents know different physicians often treat a single condition in varying ways. The losers in practice variation are the patients, learners, and the overall healthcare system.

Mark Shen, MD, the pediatric editor for The Hospitalist and presenter of this Tuesday afternoon session at HM12, said he has gone through the five stages of grief in the past when dealing with different care plans in a hospital setting, finally settling on acceptance. Now, he said it is important to move past acceptance and recognize variations in physician practice. Further, it's critical to understand the unintended consequences of unwarranted variation.

There are many factors in variation, said Dr. Shen. Examples include preference-sensitive care, in which a physician has a particular model that she or he follows that is specific to that physician, and supply-sensitive care, the trend where certain procedures are more frequently utilized when they are more readily available. A specific example of variation is the rate of tonsillectomy between surgeons.

Variation arises easily in medicine because of inherent uncertainty in medicine. Uncertainty arises because of the challenges of defining disease, making a diagnosis, selecting a procedure, observing outcomes, and assessing preferences.

Variation can be mitigated by formal protocols individualized to each patient. An example of successful protocols is modern pediatric oncology, which has dramatically improved patient outcomes.

Takeaways

  • Hospitalists must recognize variation in care.
  • Addressing variation improves patient care and offers improved utilization of limited healthcare resources.
  • There are several approaches to mitigate variation, including practice guidelines.
  • Shared decision making with the patient and family will also improve individual patient care.

All hospitalists have seen the phenomenon of "surgical signature," when different surgeons appear to have different rates of surgical intervention. Residents know different physicians often treat a single condition in varying ways. The losers in practice variation are the patients, learners, and the overall healthcare system.

Mark Shen, MD, the pediatric editor for The Hospitalist and presenter of this Tuesday afternoon session at HM12, said he has gone through the five stages of grief in the past when dealing with different care plans in a hospital setting, finally settling on acceptance. Now, he said it is important to move past acceptance and recognize variations in physician practice. Further, it's critical to understand the unintended consequences of unwarranted variation.

There are many factors in variation, said Dr. Shen. Examples include preference-sensitive care, in which a physician has a particular model that she or he follows that is specific to that physician, and supply-sensitive care, the trend where certain procedures are more frequently utilized when they are more readily available. A specific example of variation is the rate of tonsillectomy between surgeons.

Variation arises easily in medicine because of inherent uncertainty in medicine. Uncertainty arises because of the challenges of defining disease, making a diagnosis, selecting a procedure, observing outcomes, and assessing preferences.

Variation can be mitigated by formal protocols individualized to each patient. An example of successful protocols is modern pediatric oncology, which has dramatically improved patient outcomes.

Takeaways

  • Hospitalists must recognize variation in care.
  • Addressing variation improves patient care and offers improved utilization of limited healthcare resources.
  • There are several approaches to mitigate variation, including practice guidelines.
  • Shared decision making with the patient and family will also improve individual patient care.
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HM12 Session Analysis: Economics of Hospital Medicine and the Changing Value Proposition

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The key word in the title of this Tuesday session at HM12 was "change." In 50 years, healthcare expenditures will consume 50% of the U.S. national GDP. Change in hospital medicine has to happen to accommodate this.

Robert Bessler, a former economics graduate, kept the talk interesting and simple enough even for a non-financial physician like myself. As everyone knows, the cost of health care is rapidly rising and will likely be unsustainable. Bressler described hospital medicine economic management as being made up of "three legs of a stool": These legs are the cost of healthcare, the quality of healthcare, and access to healthcare.

Two important occurrences that complicate quality are the aging baby boomers and the obesity epidemic hitting Americans. Access represents the second leg of the "stool," and it's extremely shaky. The demand for care will eventually exceed the professionals ability to provide it, as more patients become insured and some hospitals go bankrupt (an estimated 15% will do so in the next eight years), said Bressler.

Hospitalists will play a major role in the future in the financial health of medical institutions, the third leg of the stool. Bessler called hospitalists the "pit crew leaders" and our turf encompasses "accountable" acute-care episodes.

Takeaways

  • The cost of healthcare is unsustainable.
  • Quality will play a key role in decreasing costs.
  • Access to healthcare will be constrained.
  • Accountable acute-care episodes are on hospitalist "turf."
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The key word in the title of this Tuesday session at HM12 was "change." In 50 years, healthcare expenditures will consume 50% of the U.S. national GDP. Change in hospital medicine has to happen to accommodate this.

Robert Bessler, a former economics graduate, kept the talk interesting and simple enough even for a non-financial physician like myself. As everyone knows, the cost of health care is rapidly rising and will likely be unsustainable. Bressler described hospital medicine economic management as being made up of "three legs of a stool": These legs are the cost of healthcare, the quality of healthcare, and access to healthcare.

Two important occurrences that complicate quality are the aging baby boomers and the obesity epidemic hitting Americans. Access represents the second leg of the "stool," and it's extremely shaky. The demand for care will eventually exceed the professionals ability to provide it, as more patients become insured and some hospitals go bankrupt (an estimated 15% will do so in the next eight years), said Bressler.

Hospitalists will play a major role in the future in the financial health of medical institutions, the third leg of the stool. Bessler called hospitalists the "pit crew leaders" and our turf encompasses "accountable" acute-care episodes.

Takeaways

  • The cost of healthcare is unsustainable.
  • Quality will play a key role in decreasing costs.
  • Access to healthcare will be constrained.
  • Accountable acute-care episodes are on hospitalist "turf."

The key word in the title of this Tuesday session at HM12 was "change." In 50 years, healthcare expenditures will consume 50% of the U.S. national GDP. Change in hospital medicine has to happen to accommodate this.

Robert Bessler, a former economics graduate, kept the talk interesting and simple enough even for a non-financial physician like myself. As everyone knows, the cost of health care is rapidly rising and will likely be unsustainable. Bressler described hospital medicine economic management as being made up of "three legs of a stool": These legs are the cost of healthcare, the quality of healthcare, and access to healthcare.

Two important occurrences that complicate quality are the aging baby boomers and the obesity epidemic hitting Americans. Access represents the second leg of the "stool," and it's extremely shaky. The demand for care will eventually exceed the professionals ability to provide it, as more patients become insured and some hospitals go bankrupt (an estimated 15% will do so in the next eight years), said Bressler.

Hospitalists will play a major role in the future in the financial health of medical institutions, the third leg of the stool. Bessler called hospitalists the "pit crew leaders" and our turf encompasses "accountable" acute-care episodes.

Takeaways

  • The cost of healthcare is unsustainable.
  • Quality will play a key role in decreasing costs.
  • Access to healthcare will be constrained.
  • Accountable acute-care episodes are on hospitalist "turf."
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Society of Hospital Medicine (SHM) President Stresses Accountability, Genuine Results in Inaugural Address

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The future of hospital medicine is rooted in the accountability of its practitioners, the new SHM president said Tuesday morning at the Society of Hospital Medicine’s annual meeting.

Shaun Frost, MD, SFHM, FACP, chief medical officer for the Northeast region for Cogent HMG, used his inaugural address at the HM12 award ceremony as a clarion call for HM leaders to view personal and professional accountability as a challenge.

“Delivering genuine results is now what we definitely must do, because the train that is healthcare reform has clearly left the station,” he said. “If we don’t jump aboard this train by delivering tangible and measurable results through true quality performance improvements and honest cost containment, I’m afraid that the consequences could be disastrous for our hospitals, for our communities, for us individually, and for the profession of hospital medicine.”

Dr. Frost said that providing evidence-based improvements will solidify the specialty’s status as a “successful historical improvement to the practice of medicine.” HM leaders who have prided themselves on leading the push for quality have done an admirable job of becoming change agents at their institutions over the past 15 years, said Dr. Frost. And now, he added, the field's reputation is staked to the next wave of reform.

“It’s time for each of us to put our money where our mouths have been,” he said.

Adds outgoing society president Joseph Ming-Wah Li, MD, SFHM: “Expectations are higher than ever for hospital medicine and for SHM … can we meet those expectations? What’s the story that’s going to be told about hospital medicine and SHM five, 10 years from now?”

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The future of hospital medicine is rooted in the accountability of its practitioners, the new SHM president said Tuesday morning at the Society of Hospital Medicine’s annual meeting.

Shaun Frost, MD, SFHM, FACP, chief medical officer for the Northeast region for Cogent HMG, used his inaugural address at the HM12 award ceremony as a clarion call for HM leaders to view personal and professional accountability as a challenge.

“Delivering genuine results is now what we definitely must do, because the train that is healthcare reform has clearly left the station,” he said. “If we don’t jump aboard this train by delivering tangible and measurable results through true quality performance improvements and honest cost containment, I’m afraid that the consequences could be disastrous for our hospitals, for our communities, for us individually, and for the profession of hospital medicine.”

Dr. Frost said that providing evidence-based improvements will solidify the specialty’s status as a “successful historical improvement to the practice of medicine.” HM leaders who have prided themselves on leading the push for quality have done an admirable job of becoming change agents at their institutions over the past 15 years, said Dr. Frost. And now, he added, the field's reputation is staked to the next wave of reform.

“It’s time for each of us to put our money where our mouths have been,” he said.

Adds outgoing society president Joseph Ming-Wah Li, MD, SFHM: “Expectations are higher than ever for hospital medicine and for SHM … can we meet those expectations? What’s the story that’s going to be told about hospital medicine and SHM five, 10 years from now?”

The future of hospital medicine is rooted in the accountability of its practitioners, the new SHM president said Tuesday morning at the Society of Hospital Medicine’s annual meeting.

Shaun Frost, MD, SFHM, FACP, chief medical officer for the Northeast region for Cogent HMG, used his inaugural address at the HM12 award ceremony as a clarion call for HM leaders to view personal and professional accountability as a challenge.

“Delivering genuine results is now what we definitely must do, because the train that is healthcare reform has clearly left the station,” he said. “If we don’t jump aboard this train by delivering tangible and measurable results through true quality performance improvements and honest cost containment, I’m afraid that the consequences could be disastrous for our hospitals, for our communities, for us individually, and for the profession of hospital medicine.”

Dr. Frost said that providing evidence-based improvements will solidify the specialty’s status as a “successful historical improvement to the practice of medicine.” HM leaders who have prided themselves on leading the push for quality have done an admirable job of becoming change agents at their institutions over the past 15 years, said Dr. Frost. And now, he added, the field's reputation is staked to the next wave of reform.

“It’s time for each of us to put our money where our mouths have been,” he said.

Adds outgoing society president Joseph Ming-Wah Li, MD, SFHM: “Expectations are higher than ever for hospital medicine and for SHM … can we meet those expectations? What’s the story that’s going to be told about hospital medicine and SHM five, 10 years from now?”

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