The United States is experiencing an epidemic of nonmedical opioid use. A concerted effort to better address pain increased the provision of prescription narcotics in the late 1990s and early 2000s.¹ Since then, there has been significant growth of opioid use and acorresponding increase in overdose-related deaths.^1-3 Public health officials have responded with initiatives to secure the opioid supply and improve outpatient treatment resources. However, the role of hospitalists in addressing opioid use disorder (OUD) is not well established. The inpatient needs for these individuals are complex and require a collaborative approach with input from outpatient clinicians, inpatient clinicians, addiction specialists, social workers, and case managers. Hospitals are often under-resourced to provide such comprehensive services. This frequently results in the hospitalist bearing significant responsibility for inpatient addiction management despite often insufficient addiction education or experience.^4,5

Therefore, there is a need for hospitalists to become leaders in the inpatient management of OUD. In this review, we will discuss the hospitalist’s role in the inpatient management of individuals with OUD.

Opioid use disorder is a medical illness resulting from neurobiological changes that cause drug tolerance, dependence, and cravings.⁶ It should be considered a treatable chronic medical condition, comparable to hypertension or diabetes,⁷ which requires a multifaceted treatment approach, including psychosocial, educational, and medical interventions.

Psychosocial Interventions

Individuals with OUD often have complicated social issues including stigmatization, involvement in the criminal justice system, unemployment, and homelessness,^5,8-10 in addition to frequent comorbid mental health issues.^11,12 Failure to address social or mental health barriers may lead to a lack of engagement in the treatment of OUD. The long-term management of OUD should involve outpatient psychotherapy and may include individual or group therapy, behavioral therapy, family counseling, or support groups.¹³ In the inpatient setting, hospitalists should use a collaborative approach to address psychosocial barriers. The authors recommend social work and case management consultations and consideration of psychiatric consultation when appropriate.

Management of Opioid Withdrawal

The prompt recognition and management of withdrawal is essential in hospitalized patients with OUD. The signs and symptoms of withdrawal can be evaluated by using the Clinical Opiate Withdrawal Scale or the Clinical Institute Narcotics Assessment, and may include lacrimation, rhinorrhea, diaphoresis, yawning, restlessness, insomnia, piloerection, myalgia, arthralgia, abdominal pain, nausea, vomiting, and diarrhea.⁴ Individuals using short-acting opioids, such as oxycodone or heroin, may develop withdrawal symptoms 8 to 12 hours after cessation of the opioid. Symptoms often peak on days 1 to 3 and can last for up to 10 days.¹⁴ Individuals taking long-acting opioids, such as methadone, may experience withdrawal symptoms for up to 21 days.¹⁴

While the goal of withdrawal treatment is to reduce the uncomfortable symptoms of withdrawal, there may be additional benefits. Around 16% of people who inject drugs will misuse drugs during their hospitalization, and 25% to 30% will be discharged against medical advice.^15,16 In hospitalizations when patients are administered methadone for management of withdrawal, there is a significant reduction in discharges against medical advice.¹⁶ This may suggest that treatment of withdrawal has the added benefit of preventing discharges against medical advice, and the authors postulate that treatment may decrease surreptitious drug use during hospitalizations, although this has not been studied.

There are 2 approaches to treating opioid withdrawal—opioid substitution treatment and alpha₂-adrenergic agonist treatment (Table 1).^4,17-20 Of note, opioid substitution treatment, especially when using buprenorphine, should be started only when a patient has at least mild withdrawal symptoms.²⁰

Medication-Assisted Treatment

It is important to recognize that treatment of withdrawal is not adequate to prevent long-term opioid misuse.²⁵ The optimal long-term management of OUD includes the use of medication-assisted treatment (MAT). The initiation and titration of MAT should always be done in conjunction with an addiction specialist or buprenorphine-waivered physician who will ensure continuation of MAT as an outpatient. This means that, while hospitalists may be critical in facilitating linkage to MAT, in general, they will not have a significant role in the long-term management of OUD. However, hospitalists should be knowledgeable about MAT because it is relatively common and can complicate hospitalizations.

There are two types of MAT: opioid-agonist treatment (OAT) and opioid-antagonist treatment. Opioid-agonist treatment involves the use of methadone, a long-acting opioid agonist, or buprenorphine, a long-acting partial opioid agonist. These medications decrease the amount and severity of cravings and limit the euphoric effects of subsequent opioid use.¹⁷ Compared to abstinence-based treatment, OAT has been associated with increased retention in addiction treatment and employment, and reductions in incarceration, human immunodeficiency virus transmission, illicit drug use, opioid-overdose events, and mortality.^26-32An alternative to OAT is naltrexone, an opioid antagonist. Naltrexone for OUD is administered as a monthly depot injection that prevents the user from experiencing opioid intoxication or dependence, and is associated with sustained abstinence.^17,33,34 The authors strongly recommend that hospitalists discuss the benefits of MAT with hospitalized individuals with OUD. In addition, when appropriate, patients should receive consultation with, or referral to, an addiction specialist.

Adverse Effects of Methadone, Buprenorphine, and Naltrexone

The benefits of MAT are substantial, but there are adverse effects, potential drug-to-drug interactions, and patient-specific characteristics that may impact the inpatient management of individuals on MAT. Selected adverse effects of OAT are listed in Table 1. The adverse effects of naltrexone include nausea, vomiting, and transaminitis. It should also be noted that the initiation of buprenorphine and naltrexone may induce opioid withdrawal when administered to an opioid-dependent patient with recent opioid use. To avoid precipitating withdrawal, buprenorphine should be used only in individuals who have at least mild withdrawal symptoms or have completed detoxification,²⁰ and naltrexone should be used only in patients who have abstained from opioids for at least 7 to 10 days.³⁵

Opioid-agonist treatments are primarily metabolized by the cytochrome P450 3A4 isoenzyme system. Medications that inhibit cytochrome P450 3A4 metabolism such as fluconazole can result in OAT toxicity, while medications that induce cytochrome P450 3A4 metabolism such as dexamethasone can lead to withdrawal symptoms.¹⁸ If these interactions are unavoidable, the dose of methadone or buprenorphine should be adjusted to prevent toxicity or withdrawal symptoms. The major drug interaction with naltrexone is ineffective analgesia from opioids.

Another major concern with MAT is the risk of overdose-related deaths. As an opioid agonist, large doses of methadone can result in respiratory depression, while buprenorphine alone, due to its partial agonist effect, is unlikely to result in respiratory depression. When methadone or buprenorphine are taken with other substances that cause respiratory depression, such as benzodiazepines or alcohol, the risk of respiratory depression and overdose is significantly increased.^36,37 Overdose-related death with naltrexone usually occurs after the medication has metabolized and results from a loss of opioid tolerance.³⁸

Special Populations

Medication-assisted treatment in individuals with acute pain. Maintenance treatment with OAT does not provide sufficient analgesia to treat episodes of acute pain.³⁹ In patients on methadone maintenance, the maintenance dose should be continued and adjunctive analgesia should be provided with nonopioid analgesics or short-acting opioids.³⁹ The management of acute pain in individuals on buprenorphine maintenance is more complicated since buprenorphine is a partial opioid agonist with high affinity to the opioid receptor, which limits the impact of adjunctive opioids. The options for analgesia in buprenorphine maintenance treatment include 1) continuing daily dosing of buprenorphine and providing nonopioid or opioid analgesics, 2) dividing buprenorphine dosing into a 3 or 4 times a day medication, 3) discontinuing buprenorphine and treating with opioid analgesics, 4) discontinuing buprenorphine and starting methadone with nonopioid or opioid analgesics.³⁹ In cases where buprenorphine is discontinued, it should be restarted before discharge upon resolution of the acute pain episode. An individual with acute pain on naltrexone may require nonopioid analgesia or regional blocks. In these patients, adequate pain control may be challenging and require the consultation of an acute pain specialist.

Pregnant or breastfeeding individuals. Opioid misuse puts the individual and fetus at risk of complications, and abrupt discontinuation can cause preterm labor, fetal distress, or fetal demise.⁴⁰ The current standard is to initiate methadone in consultation with an addiction specialist.⁴⁰ There is evidence that buprenorphine can be used during pregnancy; however, buprenorphine-naloxone is discouraged.^18,40 Of note, use of OAT in pregnancy can result in neonatal abstinence syndrome, an expected complication that can be managed by a pediatrician.⁴⁰

Methadone and buprenorphine can be found in low concentrations in breast milk.⁴¹ However, according to the Academy of Breastfeeding Medicine’s clinical guidelines, women on stable doses of methadone and buprenorphine should be encouraged to breastfeed.⁴¹ Naltrexone enters breast milk and has potential adverse effects for the newborn. Either the mother should discontinue naltrexone or should not breastfeed.³⁵

Treatment of polysubstance misuse. Individuals with OUD may also misuse other substances. The concomitant use of opioids and other central nervous system depressants, such as alcohol and benzodiazepines, is especially worrisome as they can potentiate respiratory depression. The presence of polysubstance misuse does not preclude the use of MAT for the treatment of OUD. In those with comorbid alcohol use disorder, the use of naltrexone may be appealing as it can treat both alcohol use disorder and OUD. Given the complexities of managing polysubstance misuse, addiction specialists should be involved in the care of these patients.⁴² In addition, patients should be educated on the risks of polysubstance misuse, especially when it involves 2 central nervous system depressants.

Comorbid medical disease. In general, medical comorbidities do not significantly affect the treatment of OUD; however, dysfunction of certain organ systems may necessitate a dose reduction or discontinuation of MAT. Severe liver disease may result in decreased hepatic metabolism of OAT.^35,42 Prolonged QTc, or history of arrhythmia, may preclude the use of methadone.^17,35,42 In addition, chronic hypercapnic respiratory failure or severe asthma may be contraindications for the use of methadone in an unmonitored setting.³⁵ Kidney failure is not known to be a contraindication to MAT, and there is no consensus on the need for dose reduction of MAT with decreasing glomerular filtration rate; however, some authors recommend a 25% to 50% dose reduction of methadone when the glomerular filtration rate is less than 10 milliliters per minute.⁴³ There is no such recommendation with buprenorphine, although it has not been adequately studied in individuals with renal failure. Close monitoring for evidence of toxicity is prudent in individuals on MAT with acute or chronic renal failure.³⁵

Rural or resource-limited areas. There is a significant shortage of addiction treatment options in many regions of the United States. As of 2012, there were an estimated 2.3 million individuals with OUD; however, more than 1 million of these individuals do not have access to treatment.⁴⁴ As a result, many addiction treatment programs have wait lists that can last months or even years.⁴⁵ These shortages are especially apparent in rural areas, where individuals with OUD are particularly reliant upon buprenorphine treatment because of prohibitive travel times to urban-based programs.⁴⁶ To address this problem, new models of care delivery are being developed, including models incorporating telemedicine to support rural primary care management of OUD.⁴⁷

The Future of Medication-Assisted Treatment

Currently, MAT is initiated and managed by outpatient addiction specialists. However, evidence supports initiation of MAT as an inpatient.⁴⁸ A recent study compared inpatient buprenorphine detoxification to inpatient buprenorphine induction, dose stabilization, and postdischarge linkage-of-care to outpatient opioid treatment clinics. Patients who received inpatient buprenorphine initiation and linkage-of-care had improved buprenorphine treatment retention and reported less illicit opioid use.⁴⁸ The development of partnerships between hospitals, inpatient clinicians, and outpatient addiction specialists is essential and could lead to significant advances in treating hospitalized patients with OUD.

The initiation of MAT in hospitalized patients with immediate linkage-of-care shows great promise; however, at this point, the initiation of MAT should be done only in conjunction with addiction specialists in patients with confirmed outpatient follow-up. In cases where inpatient MAT initiation is pursued, education of staff including nurses and pharmacists is essential.

Harm Reduction Interventions

Ideally, management of OUD results in abstinence from opioid misuse; however, some individuals are not ready for treatment or, despite MAT, have relapses of opioid misuse. Given this, a secondary goal in the management of OUD is the reduction of harm that can result from opioid misuse.

Many individuals inject opioids, which is associated with increased rates of viral and bacterial infections secondary to nonsterile injection practices.⁴⁹ Educating patients on sterile injection methods (Table 2),⁵⁰ including the importance of sterile-injecting equipment and water, and cleaning the skin prior to injection, may mitigate the risk of infections and should be provided for all hospitalized people who inject drugs.

Syringe-exchange programs provide sterile-injecting equipment in exchange for used needles, with a goal of increasing access to sterile supplies and removing contaminated syringes from circulation.⁵¹ While controversial, these programs may reduce the incidence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus.⁵¹

In addition, syringe-exchange programs often provide addiction treatment referrals, counseling, testing, and prevention education for human immunodeficiency virus, hepatitis C virus, and sexually transmitted infections.⁴⁹ In the United States, there are 226 programs in 33 states (see https://nasen.org/directory for a list of programs and locations. Inpatient clinicians should provide a list of local resources including syringe-exchange programs at the time of discharge for any people who inject drugs. In addition, individuals with OUD are at increased risk for overdose, especially in the postdischarge setting due to decreased opioid tolerance.⁵² In 2014, there were 28,647 opioid overdose-related deaths in the United States.² To address this troubling epidemic, opioid overdose education and naloxone distribution has been championed to educate patients at risk of opioid overdose and potential first responders on how to counteract an overdose by using naloxone, an opioid antagonist (see Table 2 for more information on opioid overdose education). The use of opioid overdose education and naloxone distribution has been observed to reduce opioid overdose-related death rates.⁵³

Hospitalists should provide opioid overdose education and naloxone to all individuals at risk of opioid overdose (including those with OUD), as well as potential first responders where the law allows (more information including individual state laws can be found at http://prescribetoprevent.org).²⁰

Considerations at Discharge

There are a number of considerations for the hospitalist at discharge (see Table 3 for a recommended discharge checklist). In addition, it is important to appreciate, and minimize, the ways that hospitalists contribute to the opioid epidemic. For instance, prescribing opioids at discharge in opioid-naïve patients increases the risk of chronic opioid use.⁵⁴ It is also essential to recognize that increased doses of opioids are associated with increased rates of opioid overdose-related deaths.⁵⁵ As such, hospitalists should maximize the use of nonopioid analgesics, prescribe opioids only when necessary, use the smallest effective dose of opioids, limit the number of opioid pills distributed to patients, and check prescription-monitoring programs for evidence of misuse.

Hospitalization serves as an important opportunity to address addiction in individuals with OUD. In addressing addiction, hospitalists should identify and intervene on psychosocial and mental health barriers, treat opioid withdrawal, and propagate harm reduction strategies. In addition, there is a growing role for hospitalists to be involved in the initiation of MAT and linkage-of-care to outpatient addiction treatment. If hospitalists become leaders in the inpatient management of OUD, they will significantly improve the care provided to this vulnerable patient population.

Disclosure

The authors report no financial conflicts of interest.

The United States is experiencing an epidemic of nonmedical opioid use. A concerted effort to better address pain increased the provision of prescription narcotics in the late 1990s and early 2000s.¹ Since then, there has been significant growth of opioid use and acorresponding increase in overdose-related deaths.^1-3 Public health officials have responded with initiatives to secure the opioid supply and improve outpatient treatment resources. However, the role of hospitalists in addressing opioid use disorder (OUD) is not well established. The inpatient needs for these individuals are complex and require a collaborative approach with input from outpatient clinicians, inpatient clinicians, addiction specialists, social workers, and case managers. Hospitals are often under-resourced to provide such comprehensive services. This frequently results in the hospitalist bearing significant responsibility for inpatient addiction management despite often insufficient addiction education or experience.^4,5

Therefore, there is a need for hospitalists to become leaders in the inpatient management of OUD. In this review, we will discuss the hospitalist’s role in the inpatient management of individuals with OUD.

Opioid use disorder is a medical illness resulting from neurobiological changes that cause drug tolerance, dependence, and cravings.⁶ It should be considered a treatable chronic medical condition, comparable to hypertension or diabetes,⁷ which requires a multifaceted treatment approach, including psychosocial, educational, and medical interventions.

Psychosocial Interventions

Individuals with OUD often have complicated social issues including stigmatization, involvement in the criminal justice system, unemployment, and homelessness,^5,8-10 in addition to frequent comorbid mental health issues.^11,12 Failure to address social or mental health barriers may lead to a lack of engagement in the treatment of OUD. The long-term management of OUD should involve outpatient psychotherapy and may include individual or group therapy, behavioral therapy, family counseling, or support groups.¹³ In the inpatient setting, hospitalists should use a collaborative approach to address psychosocial barriers. The authors recommend social work and case management consultations and consideration of psychiatric consultation when appropriate.

Management of Opioid Withdrawal

The prompt recognition and management of withdrawal is essential in hospitalized patients with OUD. The signs and symptoms of withdrawal can be evaluated by using the Clinical Opiate Withdrawal Scale or the Clinical Institute Narcotics Assessment, and may include lacrimation, rhinorrhea, diaphoresis, yawning, restlessness, insomnia, piloerection, myalgia, arthralgia, abdominal pain, nausea, vomiting, and diarrhea.⁴ Individuals using short-acting opioids, such as oxycodone or heroin, may develop withdrawal symptoms 8 to 12 hours after cessation of the opioid. Symptoms often peak on days 1 to 3 and can last for up to 10 days.¹⁴ Individuals taking long-acting opioids, such as methadone, may experience withdrawal symptoms for up to 21 days.¹⁴

While the goal of withdrawal treatment is to reduce the uncomfortable symptoms of withdrawal, there may be additional benefits. Around 16% of people who inject drugs will misuse drugs during their hospitalization, and 25% to 30% will be discharged against medical advice.^15,16 In hospitalizations when patients are administered methadone for management of withdrawal, there is a significant reduction in discharges against medical advice.¹⁶ This may suggest that treatment of withdrawal has the added benefit of preventing discharges against medical advice, and the authors postulate that treatment may decrease surreptitious drug use during hospitalizations, although this has not been studied.

There are 2 approaches to treating opioid withdrawal—opioid substitution treatment and alpha₂-adrenergic agonist treatment (Table 1).^4,17-20 Of note, opioid substitution treatment, especially when using buprenorphine, should be started only when a patient has at least mild withdrawal symptoms.²⁰

Medication-Assisted Treatment

It is important to recognize that treatment of withdrawal is not adequate to prevent long-term opioid misuse.²⁵ The optimal long-term management of OUD includes the use of medication-assisted treatment (MAT). The initiation and titration of MAT should always be done in conjunction with an addiction specialist or buprenorphine-waivered physician who will ensure continuation of MAT as an outpatient. This means that, while hospitalists may be critical in facilitating linkage to MAT, in general, they will not have a significant role in the long-term management of OUD. However, hospitalists should be knowledgeable about MAT because it is relatively common and can complicate hospitalizations.

There are two types of MAT: opioid-agonist treatment (OAT) and opioid-antagonist treatment. Opioid-agonist treatment involves the use of methadone, a long-acting opioid agonist, or buprenorphine, a long-acting partial opioid agonist. These medications decrease the amount and severity of cravings and limit the euphoric effects of subsequent opioid use.¹⁷ Compared to abstinence-based treatment, OAT has been associated with increased retention in addiction treatment and employment, and reductions in incarceration, human immunodeficiency virus transmission, illicit drug use, opioid-overdose events, and mortality.^26-32An alternative to OAT is naltrexone, an opioid antagonist. Naltrexone for OUD is administered as a monthly depot injection that prevents the user from experiencing opioid intoxication or dependence, and is associated with sustained abstinence.^17,33,34 The authors strongly recommend that hospitalists discuss the benefits of MAT with hospitalized individuals with OUD. In addition, when appropriate, patients should receive consultation with, or referral to, an addiction specialist.

Adverse Effects of Methadone, Buprenorphine, and Naltrexone

The benefits of MAT are substantial, but there are adverse effects, potential drug-to-drug interactions, and patient-specific characteristics that may impact the inpatient management of individuals on MAT. Selected adverse effects of OAT are listed in Table 1. The adverse effects of naltrexone include nausea, vomiting, and transaminitis. It should also be noted that the initiation of buprenorphine and naltrexone may induce opioid withdrawal when administered to an opioid-dependent patient with recent opioid use. To avoid precipitating withdrawal, buprenorphine should be used only in individuals who have at least mild withdrawal symptoms or have completed detoxification,²⁰ and naltrexone should be used only in patients who have abstained from opioids for at least 7 to 10 days.³⁵

Opioid-agonist treatments are primarily metabolized by the cytochrome P450 3A4 isoenzyme system. Medications that inhibit cytochrome P450 3A4 metabolism such as fluconazole can result in OAT toxicity, while medications that induce cytochrome P450 3A4 metabolism such as dexamethasone can lead to withdrawal symptoms.¹⁸ If these interactions are unavoidable, the dose of methadone or buprenorphine should be adjusted to prevent toxicity or withdrawal symptoms. The major drug interaction with naltrexone is ineffective analgesia from opioids.

Another major concern with MAT is the risk of overdose-related deaths. As an opioid agonist, large doses of methadone can result in respiratory depression, while buprenorphine alone, due to its partial agonist effect, is unlikely to result in respiratory depression. When methadone or buprenorphine are taken with other substances that cause respiratory depression, such as benzodiazepines or alcohol, the risk of respiratory depression and overdose is significantly increased.^36,37 Overdose-related death with naltrexone usually occurs after the medication has metabolized and results from a loss of opioid tolerance.³⁸

Special Populations

Medication-assisted treatment in individuals with acute pain. Maintenance treatment with OAT does not provide sufficient analgesia to treat episodes of acute pain.³⁹ In patients on methadone maintenance, the maintenance dose should be continued and adjunctive analgesia should be provided with nonopioid analgesics or short-acting opioids.³⁹ The management of acute pain in individuals on buprenorphine maintenance is more complicated since buprenorphine is a partial opioid agonist with high affinity to the opioid receptor, which limits the impact of adjunctive opioids. The options for analgesia in buprenorphine maintenance treatment include 1) continuing daily dosing of buprenorphine and providing nonopioid or opioid analgesics, 2) dividing buprenorphine dosing into a 3 or 4 times a day medication, 3) discontinuing buprenorphine and treating with opioid analgesics, 4) discontinuing buprenorphine and starting methadone with nonopioid or opioid analgesics.³⁹ In cases where buprenorphine is discontinued, it should be restarted before discharge upon resolution of the acute pain episode. An individual with acute pain on naltrexone may require nonopioid analgesia or regional blocks. In these patients, adequate pain control may be challenging and require the consultation of an acute pain specialist.

Pregnant or breastfeeding individuals. Opioid misuse puts the individual and fetus at risk of complications, and abrupt discontinuation can cause preterm labor, fetal distress, or fetal demise.⁴⁰ The current standard is to initiate methadone in consultation with an addiction specialist.⁴⁰ There is evidence that buprenorphine can be used during pregnancy; however, buprenorphine-naloxone is discouraged.^18,40 Of note, use of OAT in pregnancy can result in neonatal abstinence syndrome, an expected complication that can be managed by a pediatrician.⁴⁰

Methadone and buprenorphine can be found in low concentrations in breast milk.⁴¹ However, according to the Academy of Breastfeeding Medicine’s clinical guidelines, women on stable doses of methadone and buprenorphine should be encouraged to breastfeed.⁴¹ Naltrexone enters breast milk and has potential adverse effects for the newborn. Either the mother should discontinue naltrexone or should not breastfeed.³⁵

Treatment of polysubstance misuse. Individuals with OUD may also misuse other substances. The concomitant use of opioids and other central nervous system depressants, such as alcohol and benzodiazepines, is especially worrisome as they can potentiate respiratory depression. The presence of polysubstance misuse does not preclude the use of MAT for the treatment of OUD. In those with comorbid alcohol use disorder, the use of naltrexone may be appealing as it can treat both alcohol use disorder and OUD. Given the complexities of managing polysubstance misuse, addiction specialists should be involved in the care of these patients.⁴² In addition, patients should be educated on the risks of polysubstance misuse, especially when it involves 2 central nervous system depressants.

Comorbid medical disease. In general, medical comorbidities do not significantly affect the treatment of OUD; however, dysfunction of certain organ systems may necessitate a dose reduction or discontinuation of MAT. Severe liver disease may result in decreased hepatic metabolism of OAT.^35,42 Prolonged QTc, or history of arrhythmia, may preclude the use of methadone.^17,35,42 In addition, chronic hypercapnic respiratory failure or severe asthma may be contraindications for the use of methadone in an unmonitored setting.³⁵ Kidney failure is not known to be a contraindication to MAT, and there is no consensus on the need for dose reduction of MAT with decreasing glomerular filtration rate; however, some authors recommend a 25% to 50% dose reduction of methadone when the glomerular filtration rate is less than 10 milliliters per minute.⁴³ There is no such recommendation with buprenorphine, although it has not been adequately studied in individuals with renal failure. Close monitoring for evidence of toxicity is prudent in individuals on MAT with acute or chronic renal failure.³⁵

Rural or resource-limited areas. There is a significant shortage of addiction treatment options in many regions of the United States. As of 2012, there were an estimated 2.3 million individuals with OUD; however, more than 1 million of these individuals do not have access to treatment.⁴⁴ As a result, many addiction treatment programs have wait lists that can last months or even years.⁴⁵ These shortages are especially apparent in rural areas, where individuals with OUD are particularly reliant upon buprenorphine treatment because of prohibitive travel times to urban-based programs.⁴⁶ To address this problem, new models of care delivery are being developed, including models incorporating telemedicine to support rural primary care management of OUD.⁴⁷

The Future of Medication-Assisted Treatment

Currently, MAT is initiated and managed by outpatient addiction specialists. However, evidence supports initiation of MAT as an inpatient.⁴⁸ A recent study compared inpatient buprenorphine detoxification to inpatient buprenorphine induction, dose stabilization, and postdischarge linkage-of-care to outpatient opioid treatment clinics. Patients who received inpatient buprenorphine initiation and linkage-of-care had improved buprenorphine treatment retention and reported less illicit opioid use.⁴⁸ The development of partnerships between hospitals, inpatient clinicians, and outpatient addiction specialists is essential and could lead to significant advances in treating hospitalized patients with OUD.

The initiation of MAT in hospitalized patients with immediate linkage-of-care shows great promise; however, at this point, the initiation of MAT should be done only in conjunction with addiction specialists in patients with confirmed outpatient follow-up. In cases where inpatient MAT initiation is pursued, education of staff including nurses and pharmacists is essential.

Harm Reduction Interventions

Ideally, management of OUD results in abstinence from opioid misuse; however, some individuals are not ready for treatment or, despite MAT, have relapses of opioid misuse. Given this, a secondary goal in the management of OUD is the reduction of harm that can result from opioid misuse.

Many individuals inject opioids, which is associated with increased rates of viral and bacterial infections secondary to nonsterile injection practices.⁴⁹ Educating patients on sterile injection methods (Table 2),⁵⁰ including the importance of sterile-injecting equipment and water, and cleaning the skin prior to injection, may mitigate the risk of infections and should be provided for all hospitalized people who inject drugs.

Syringe-exchange programs provide sterile-injecting equipment in exchange for used needles, with a goal of increasing access to sterile supplies and removing contaminated syringes from circulation.⁵¹ While controversial, these programs may reduce the incidence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus.⁵¹

In addition, syringe-exchange programs often provide addiction treatment referrals, counseling, testing, and prevention education for human immunodeficiency virus, hepatitis C virus, and sexually transmitted infections.⁴⁹ In the United States, there are 226 programs in 33 states (see https://nasen.org/directory for a list of programs and locations. Inpatient clinicians should provide a list of local resources including syringe-exchange programs at the time of discharge for any people who inject drugs. In addition, individuals with OUD are at increased risk for overdose, especially in the postdischarge setting due to decreased opioid tolerance.⁵² In 2014, there were 28,647 opioid overdose-related deaths in the United States.² To address this troubling epidemic, opioid overdose education and naloxone distribution has been championed to educate patients at risk of opioid overdose and potential first responders on how to counteract an overdose by using naloxone, an opioid antagonist (see Table 2 for more information on opioid overdose education). The use of opioid overdose education and naloxone distribution has been observed to reduce opioid overdose-related death rates.⁵³

Hospitalists should provide opioid overdose education and naloxone to all individuals at risk of opioid overdose (including those with OUD), as well as potential first responders where the law allows (more information including individual state laws can be found at http://prescribetoprevent.org).²⁰

Considerations at Discharge

There are a number of considerations for the hospitalist at discharge (see Table 3 for a recommended discharge checklist). In addition, it is important to appreciate, and minimize, the ways that hospitalists contribute to the opioid epidemic. For instance, prescribing opioids at discharge in opioid-naïve patients increases the risk of chronic opioid use.⁵⁴ It is also essential to recognize that increased doses of opioids are associated with increased rates of opioid overdose-related deaths.⁵⁵ As such, hospitalists should maximize the use of nonopioid analgesics, prescribe opioids only when necessary, use the smallest effective dose of opioids, limit the number of opioid pills distributed to patients, and check prescription-monitoring programs for evidence of misuse.

Hospitalization serves as an important opportunity to address addiction in individuals with OUD. In addressing addiction, hospitalists should identify and intervene on psychosocial and mental health barriers, treat opioid withdrawal, and propagate harm reduction strategies. In addition, there is a growing role for hospitalists to be involved in the initiation of MAT and linkage-of-care to outpatient addiction treatment. If hospitalists become leaders in the inpatient management of OUD, they will significantly improve the care provided to this vulnerable patient population.

Disclosure

The authors report no financial conflicts of interest.

The United States is experiencing an epidemic of nonmedical opioid use. A concerted effort to better address pain increased the provision of prescription narcotics in the late 1990s and early 2000s.¹ Since then, there has been significant growth of opioid use and acorresponding increase in overdose-related deaths.^1-3 Public health officials have responded with initiatives to secure the opioid supply and improve outpatient treatment resources. However, the role of hospitalists in addressing opioid use disorder (OUD) is not well established. The inpatient needs for these individuals are complex and require a collaborative approach with input from outpatient clinicians, inpatient clinicians, addiction specialists, social workers, and case managers. Hospitals are often under-resourced to provide such comprehensive services. This frequently results in the hospitalist bearing significant responsibility for inpatient addiction management despite often insufficient addiction education or experience.^4,5

Therefore, there is a need for hospitalists to become leaders in the inpatient management of OUD. In this review, we will discuss the hospitalist’s role in the inpatient management of individuals with OUD.

Opioid use disorder is a medical illness resulting from neurobiological changes that cause drug tolerance, dependence, and cravings.⁶ It should be considered a treatable chronic medical condition, comparable to hypertension or diabetes,⁷ which requires a multifaceted treatment approach, including psychosocial, educational, and medical interventions.

Psychosocial Interventions

Individuals with OUD often have complicated social issues including stigmatization, involvement in the criminal justice system, unemployment, and homelessness,^5,8-10 in addition to frequent comorbid mental health issues.^11,12 Failure to address social or mental health barriers may lead to a lack of engagement in the treatment of OUD. The long-term management of OUD should involve outpatient psychotherapy and may include individual or group therapy, behavioral therapy, family counseling, or support groups.¹³ In the inpatient setting, hospitalists should use a collaborative approach to address psychosocial barriers. The authors recommend social work and case management consultations and consideration of psychiatric consultation when appropriate.

Management of Opioid Withdrawal

The prompt recognition and management of withdrawal is essential in hospitalized patients with OUD. The signs and symptoms of withdrawal can be evaluated by using the Clinical Opiate Withdrawal Scale or the Clinical Institute Narcotics Assessment, and may include lacrimation, rhinorrhea, diaphoresis, yawning, restlessness, insomnia, piloerection, myalgia, arthralgia, abdominal pain, nausea, vomiting, and diarrhea.⁴ Individuals using short-acting opioids, such as oxycodone or heroin, may develop withdrawal symptoms 8 to 12 hours after cessation of the opioid. Symptoms often peak on days 1 to 3 and can last for up to 10 days.¹⁴ Individuals taking long-acting opioids, such as methadone, may experience withdrawal symptoms for up to 21 days.¹⁴

While the goal of withdrawal treatment is to reduce the uncomfortable symptoms of withdrawal, there may be additional benefits. Around 16% of people who inject drugs will misuse drugs during their hospitalization, and 25% to 30% will be discharged against medical advice.^15,16 In hospitalizations when patients are administered methadone for management of withdrawal, there is a significant reduction in discharges against medical advice.¹⁶ This may suggest that treatment of withdrawal has the added benefit of preventing discharges against medical advice, and the authors postulate that treatment may decrease surreptitious drug use during hospitalizations, although this has not been studied.

There are 2 approaches to treating opioid withdrawal—opioid substitution treatment and alpha₂-adrenergic agonist treatment (Table 1).^4,17-20 Of note, opioid substitution treatment, especially when using buprenorphine, should be started only when a patient has at least mild withdrawal symptoms.²⁰

Medication-Assisted Treatment

It is important to recognize that treatment of withdrawal is not adequate to prevent long-term opioid misuse.²⁵ The optimal long-term management of OUD includes the use of medication-assisted treatment (MAT). The initiation and titration of MAT should always be done in conjunction with an addiction specialist or buprenorphine-waivered physician who will ensure continuation of MAT as an outpatient. This means that, while hospitalists may be critical in facilitating linkage to MAT, in general, they will not have a significant role in the long-term management of OUD. However, hospitalists should be knowledgeable about MAT because it is relatively common and can complicate hospitalizations.

There are two types of MAT: opioid-agonist treatment (OAT) and opioid-antagonist treatment. Opioid-agonist treatment involves the use of methadone, a long-acting opioid agonist, or buprenorphine, a long-acting partial opioid agonist. These medications decrease the amount and severity of cravings and limit the euphoric effects of subsequent opioid use.¹⁷ Compared to abstinence-based treatment, OAT has been associated with increased retention in addiction treatment and employment, and reductions in incarceration, human immunodeficiency virus transmission, illicit drug use, opioid-overdose events, and mortality.^26-32An alternative to OAT is naltrexone, an opioid antagonist. Naltrexone for OUD is administered as a monthly depot injection that prevents the user from experiencing opioid intoxication or dependence, and is associated with sustained abstinence.^17,33,34 The authors strongly recommend that hospitalists discuss the benefits of MAT with hospitalized individuals with OUD. In addition, when appropriate, patients should receive consultation with, or referral to, an addiction specialist.

Adverse Effects of Methadone, Buprenorphine, and Naltrexone

The benefits of MAT are substantial, but there are adverse effects, potential drug-to-drug interactions, and patient-specific characteristics that may impact the inpatient management of individuals on MAT. Selected adverse effects of OAT are listed in Table 1. The adverse effects of naltrexone include nausea, vomiting, and transaminitis. It should also be noted that the initiation of buprenorphine and naltrexone may induce opioid withdrawal when administered to an opioid-dependent patient with recent opioid use. To avoid precipitating withdrawal, buprenorphine should be used only in individuals who have at least mild withdrawal symptoms or have completed detoxification,²⁰ and naltrexone should be used only in patients who have abstained from opioids for at least 7 to 10 days.³⁵

Opioid-agonist treatments are primarily metabolized by the cytochrome P450 3A4 isoenzyme system. Medications that inhibit cytochrome P450 3A4 metabolism such as fluconazole can result in OAT toxicity, while medications that induce cytochrome P450 3A4 metabolism such as dexamethasone can lead to withdrawal symptoms.¹⁸ If these interactions are unavoidable, the dose of methadone or buprenorphine should be adjusted to prevent toxicity or withdrawal symptoms. The major drug interaction with naltrexone is ineffective analgesia from opioids.

Another major concern with MAT is the risk of overdose-related deaths. As an opioid agonist, large doses of methadone can result in respiratory depression, while buprenorphine alone, due to its partial agonist effect, is unlikely to result in respiratory depression. When methadone or buprenorphine are taken with other substances that cause respiratory depression, such as benzodiazepines or alcohol, the risk of respiratory depression and overdose is significantly increased.^36,37 Overdose-related death with naltrexone usually occurs after the medication has metabolized and results from a loss of opioid tolerance.³⁸

Special Populations

Medication-assisted treatment in individuals with acute pain. Maintenance treatment with OAT does not provide sufficient analgesia to treat episodes of acute pain.³⁹ In patients on methadone maintenance, the maintenance dose should be continued and adjunctive analgesia should be provided with nonopioid analgesics or short-acting opioids.³⁹ The management of acute pain in individuals on buprenorphine maintenance is more complicated since buprenorphine is a partial opioid agonist with high affinity to the opioid receptor, which limits the impact of adjunctive opioids. The options for analgesia in buprenorphine maintenance treatment include 1) continuing daily dosing of buprenorphine and providing nonopioid or opioid analgesics, 2) dividing buprenorphine dosing into a 3 or 4 times a day medication, 3) discontinuing buprenorphine and treating with opioid analgesics, 4) discontinuing buprenorphine and starting methadone with nonopioid or opioid analgesics.³⁹ In cases where buprenorphine is discontinued, it should be restarted before discharge upon resolution of the acute pain episode. An individual with acute pain on naltrexone may require nonopioid analgesia or regional blocks. In these patients, adequate pain control may be challenging and require the consultation of an acute pain specialist.

Pregnant or breastfeeding individuals. Opioid misuse puts the individual and fetus at risk of complications, and abrupt discontinuation can cause preterm labor, fetal distress, or fetal demise.⁴⁰ The current standard is to initiate methadone in consultation with an addiction specialist.⁴⁰ There is evidence that buprenorphine can be used during pregnancy; however, buprenorphine-naloxone is discouraged.^18,40 Of note, use of OAT in pregnancy can result in neonatal abstinence syndrome, an expected complication that can be managed by a pediatrician.⁴⁰

Methadone and buprenorphine can be found in low concentrations in breast milk.⁴¹ However, according to the Academy of Breastfeeding Medicine’s clinical guidelines, women on stable doses of methadone and buprenorphine should be encouraged to breastfeed.⁴¹ Naltrexone enters breast milk and has potential adverse effects for the newborn. Either the mother should discontinue naltrexone or should not breastfeed.³⁵

Treatment of polysubstance misuse. Individuals with OUD may also misuse other substances. The concomitant use of opioids and other central nervous system depressants, such as alcohol and benzodiazepines, is especially worrisome as they can potentiate respiratory depression. The presence of polysubstance misuse does not preclude the use of MAT for the treatment of OUD. In those with comorbid alcohol use disorder, the use of naltrexone may be appealing as it can treat both alcohol use disorder and OUD. Given the complexities of managing polysubstance misuse, addiction specialists should be involved in the care of these patients.⁴² In addition, patients should be educated on the risks of polysubstance misuse, especially when it involves 2 central nervous system depressants.

Comorbid medical disease. In general, medical comorbidities do not significantly affect the treatment of OUD; however, dysfunction of certain organ systems may necessitate a dose reduction or discontinuation of MAT. Severe liver disease may result in decreased hepatic metabolism of OAT.^35,42 Prolonged QTc, or history of arrhythmia, may preclude the use of methadone.^17,35,42 In addition, chronic hypercapnic respiratory failure or severe asthma may be contraindications for the use of methadone in an unmonitored setting.³⁵ Kidney failure is not known to be a contraindication to MAT, and there is no consensus on the need for dose reduction of MAT with decreasing glomerular filtration rate; however, some authors recommend a 25% to 50% dose reduction of methadone when the glomerular filtration rate is less than 10 milliliters per minute.⁴³ There is no such recommendation with buprenorphine, although it has not been adequately studied in individuals with renal failure. Close monitoring for evidence of toxicity is prudent in individuals on MAT with acute or chronic renal failure.³⁵

Rural or resource-limited areas. There is a significant shortage of addiction treatment options in many regions of the United States. As of 2012, there were an estimated 2.3 million individuals with OUD; however, more than 1 million of these individuals do not have access to treatment.⁴⁴ As a result, many addiction treatment programs have wait lists that can last months or even years.⁴⁵ These shortages are especially apparent in rural areas, where individuals with OUD are particularly reliant upon buprenorphine treatment because of prohibitive travel times to urban-based programs.⁴⁶ To address this problem, new models of care delivery are being developed, including models incorporating telemedicine to support rural primary care management of OUD.⁴⁷

The Future of Medication-Assisted Treatment

Currently, MAT is initiated and managed by outpatient addiction specialists. However, evidence supports initiation of MAT as an inpatient.⁴⁸ A recent study compared inpatient buprenorphine detoxification to inpatient buprenorphine induction, dose stabilization, and postdischarge linkage-of-care to outpatient opioid treatment clinics. Patients who received inpatient buprenorphine initiation and linkage-of-care had improved buprenorphine treatment retention and reported less illicit opioid use.⁴⁸ The development of partnerships between hospitals, inpatient clinicians, and outpatient addiction specialists is essential and could lead to significant advances in treating hospitalized patients with OUD.

The initiation of MAT in hospitalized patients with immediate linkage-of-care shows great promise; however, at this point, the initiation of MAT should be done only in conjunction with addiction specialists in patients with confirmed outpatient follow-up. In cases where inpatient MAT initiation is pursued, education of staff including nurses and pharmacists is essential.

Harm Reduction Interventions

Ideally, management of OUD results in abstinence from opioid misuse; however, some individuals are not ready for treatment or, despite MAT, have relapses of opioid misuse. Given this, a secondary goal in the management of OUD is the reduction of harm that can result from opioid misuse.

Many individuals inject opioids, which is associated with increased rates of viral and bacterial infections secondary to nonsterile injection practices.⁴⁹ Educating patients on sterile injection methods (Table 2),⁵⁰ including the importance of sterile-injecting equipment and water, and cleaning the skin prior to injection, may mitigate the risk of infections and should be provided for all hospitalized people who inject drugs.

Syringe-exchange programs provide sterile-injecting equipment in exchange for used needles, with a goal of increasing access to sterile supplies and removing contaminated syringes from circulation.⁵¹ While controversial, these programs may reduce the incidence of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus.⁵¹

In addition, syringe-exchange programs often provide addiction treatment referrals, counseling, testing, and prevention education for human immunodeficiency virus, hepatitis C virus, and sexually transmitted infections.⁴⁹ In the United States, there are 226 programs in 33 states (see https://nasen.org/directory for a list of programs and locations. Inpatient clinicians should provide a list of local resources including syringe-exchange programs at the time of discharge for any people who inject drugs. In addition, individuals with OUD are at increased risk for overdose, especially in the postdischarge setting due to decreased opioid tolerance.⁵² In 2014, there were 28,647 opioid overdose-related deaths in the United States.² To address this troubling epidemic, opioid overdose education and naloxone distribution has been championed to educate patients at risk of opioid overdose and potential first responders on how to counteract an overdose by using naloxone, an opioid antagonist (see Table 2 for more information on opioid overdose education). The use of opioid overdose education and naloxone distribution has been observed to reduce opioid overdose-related death rates.⁵³

Hospitalists should provide opioid overdose education and naloxone to all individuals at risk of opioid overdose (including those with OUD), as well as potential first responders where the law allows (more information including individual state laws can be found at http://prescribetoprevent.org).²⁰

Considerations at Discharge

There are a number of considerations for the hospitalist at discharge (see Table 3 for a recommended discharge checklist). In addition, it is important to appreciate, and minimize, the ways that hospitalists contribute to the opioid epidemic. For instance, prescribing opioids at discharge in opioid-naïve patients increases the risk of chronic opioid use.⁵⁴ It is also essential to recognize that increased doses of opioids are associated with increased rates of opioid overdose-related deaths.⁵⁵ As such, hospitalists should maximize the use of nonopioid analgesics, prescribe opioids only when necessary, use the smallest effective dose of opioids, limit the number of opioid pills distributed to patients, and check prescription-monitoring programs for evidence of misuse.

Hospitalization serves as an important opportunity to address addiction in individuals with OUD. In addressing addiction, hospitalists should identify and intervene on psychosocial and mental health barriers, treat opioid withdrawal, and propagate harm reduction strategies. In addition, there is a growing role for hospitalists to be involved in the initiation of MAT and linkage-of-care to outpatient addiction treatment. If hospitalists become leaders in the inpatient management of OUD, they will significantly improve the care provided to this vulnerable patient population.

Disclosure

The authors report no financial conflicts of interest.

Up to 40% of Americans experience chronic pain of some kind.¹ In the United States, opioid analgesics are the most prescribed class of medications,² with 245 million prescriptions filled in 2014 alone. Thirty-five percent of these prescriptions were for long-term therapy.³ It is now apparent that opioid pain medication use presents serious risks. In 2014, 10.3 million persons reported using prescription opioids for nonmedical reasons.⁴ Between 1999 and 2014, more than 165,000 people in the United States died of overdose related to opioid medication.⁵ In addition, heroin use in the United States has increased over the past decade.⁶ Opioid agonist maintenance therapy is also increasingly used to treat patients with opioid use disorder.

Given the prevalence of opioid use in the United States, it is important for hospitalists to be able to appropriately and safely manage acute pain in patients who have been exposed long-term to opioids, whether it is therapeutic or non-medical in origin. Although nonopioid medications and nondrug treatments are essential components of managing all acute pain, opioids continue to be the mainstay of treatment for severe acute pain in both opioid-naïve and opioid-dependent patients.

Given the paucity of published trials meeting the typical criteria, we did not perform a structured meta-analysis but, instead, a case-based narrative review of the relevant published literature. Our goal in performing this review is to guide hospitalists in the appropriate and safe use of opioid analgesics in treating acute pain in hospitalized patients who are opioid-dependent.

When managing acute pain in patients with opioid dependence it is important to have a clear understanding of the definitions related to opioid use. Addiction, physical dependence and tolerance have been defined by a joint consensus statement of the American Society of Addiction Medicine, American Academy of Pain Medicine, and American Pain Society⁷: Addiction is a primary, chronic, biological disease, with genetic, psychosocial and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.

Physical Dependence is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.

Tolerance is the state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time.

Opioid use disorder (OUD) is defined as a problematic pattern of opioid use leading to clinically significant impairment or distress with symptoms including a strong desire for opioids, inability to control or reduce use of opioids, continued use despite adverse consequences, and development of tolerance and withdrawal symptoms.⁸

Physical dependence and tolerance are common consequences of long-term opioid use. In contrast, OUD has been reported to affect only 2% to 6% of individuals exposed to opioids.⁹ The underlying mechanisms that lead an individual to abuse or become addicted to opioids largely due to the effects opioids have on endogenous μ-opioid receptors. As analgesics, opioids exert their effects by binding primarily to these μ-opioid receptors, with a large concentration in the brain regions regulating pain perception.^10,11 There is also a large concentration of μ-opioid receptors in the brain reward regions, leading to perceptions of pleasure and euphoria. Repeated administration of opioids conditions the brain to a learned association between receiving the opiate and euphoria.^12,13 This association becomes stronger as the frequency and duration of administration increases over time, ultimately leading to the desire or craving of the opioid’s effect.

The effect of tolerance also contributes to the pathophysiology of opioid abuse as it leads to a decrease in opioid potency with repeated administration.^14-16 To achieve analgesia as well as the reward effect, opioid dosage and/or frequency must be increased, strengthening the association between receipt of opioid and reward. Tolerance to the reward effect occurs quickly, whereas tolerance to respiratory depression occurs much more slowly.¹⁷ This mismatch in tolerance of effect may lead to increase in opioid doses to maintain analgesia or euphoria, and also places patients at a higher risk of overdose.¹⁸

Clinical Example: Heroin User

A 47-year-old man is admitted with fever, chills, and severe mid-back pain and receives a diagnosis of sepsis. The patient admits to using intravenous heroin 500 mg (five 100 mg “bags”) on a daily basis. He is admitted, fluid resuscitated and started on broad spectrum antibiotics. Blood cultures quickly grow Staphylococcus aureus. Magnetic resonance imaging of the spine shows cervical vertebral osteomyelitis. On examination, the patient is diaphoretic and complains of diffuse myalgias and diarrhea. The patient’s back pain is so severe that he cannot ambulate. What is the best way to manage this patient’s acute pain and communicate with him about his pain management?

Managing acute pain in a patient using heroin can be challenging for many reasons. First, both physicians and pharmacists report a lack of confidence in their ability to prescribe opioids safely or to treat patients with a history of opioid abuse.¹⁹ Second, there is a paucity of evidence in treating acute pain in heroin users. Finally, due to the clandestine manufacturing of illicit drugs, the actual purity of the drug is often unknown making it difficult to assess the dose of opioids in heroin users. Drug Enforcement Agency seizure data indicate a wide range of heroin purity: 30% to 70%.²⁰

In the hospital setting, acute pain is often undertreated in patients with a history of active opioid abuse. This may be due to providers’ misconceptions regarding pain and behavior in opioid addicts, including worrying that the patient’s pain is exaggerated in order to obtain drugs, thinking that a regular opioid habit eliminates pain, believing that opioid therapy is not effective in drug addicts, or worrying that prescribing opioids will exacerbate drug addiction.²¹ Data demonstrates that the presence of opioid addiction seems to worsen the experience of acute pain.²² These patients also often have a higher tolerance and thus require higher dosages and more frequent dosing of opioids to adequately treat their pain.²³

Converting daily heroin use to morphine equivalents is necessary to establish a baseline analgesic requirement and to prevent withdrawal. It is challenging to convert illicit heroin to morphine equivalents however, as one must take into account the wide variation in purity and understand that the stated use of heroin (e.g. 500 mg daily) reflects weight and not dosage of heroin.²⁰

In these patients, treatment of acute pain should be individualized according to presenting illness and comorbidities. Previous data and an average purity of 40% suggest that the parenteral morphine equivalent to a bag of heroin (100 mg) is 15 to 30 mg.^20,24,25 Common equianalgesic doses of opioid medications are listed in Table 1. Because of increased tolerance, the frequency of administration should be shortened, from every 4 hours to every 2 or 3 hours. Except for a shorter onset of action, there has not been a difference shown in superiority between oral and parenteral routes of administration. Finally, patients should receive both long-acting basal and short-acting as-needed analgesics based on their daily use of opioids.²³

Clinical Example: Patient on Chronic Opioid Therapy for Chronic Pain

A 64 year-old man was involved in a motorcycle accident and suffered a right distal tibia-fibula fracture and several broken ribs with a secondary pneumothorax. The patient’s past medical history is significant for chronic low back pain for which he states he takes morphine sustained release 30 mg orally every 8 hours and morphine immediate release 15 mg orally four times daily for breakthrough pain. The patient states his pain is much worse than prior to the accident. Trauma surgery requests recommendations on appropriate pain management. What is the best way to manage this patient’s acute pain and communicate with him about his pain management?

When treating acute pain in patients with chronic pain on opioid therapy, it is vital to establish the patient’s baseline pain level and to accurately reconcile the patient’s outpatient daily opioid use. The patient’s prescription record should be verified in the state’s prescription drug monitoring program. On admission, a urine drug test should be obtained to assess for use of other potential illicit substances (eg, cocaine). Patients who test positive for illicit substances are at high risk for a substance use disorder. Management and discharge plans should be as outlined in the above case. It is important to know that the first-tier immunoassay urine toxicology screens used by hospitals test for natural opioids (morphine, codeine, heroin). Semi-synthetic (example, oxycodone) or synthetic (example, fentanyl) opioids are unlikely to be detected and thus the urine drug screen may not be helpful to determine adherence to certain prescription opioids. Gas chromatography/mass spectrometry is the most sensitive and specific type of urine screen and can be ordered to confirm a prescribed opioid if needed.²⁶

Pain management should begin with calculating the TDD of oral opioids that the patient was taking prior to admission, and converting to morphine equivalents. For moderate acute pain, TDD can be increased by 25% to 50%. The revised TDD can then be prescribed as a long-acting opioid every 8 to 12 hours to provide basal analgesia. The dose of additional immediate-release medication available throughout the day to manage breakthrough pain is determined by dividing the new TDD into every 3 to 4 hours as-needed dosing (Table 2).

If severe pain is anticipated, patient controlled analgesia (PCA) is an effective alternative to deliver opioids. The use of PCA allows self-titration, on demand analgesia, and minimizes the likelihood of under-dosing the patient.²⁷ The revised TDD is a useful starting point when calculating the PCA dosage regimen. Ideally, the revised TDD should be prescribed as a long acting oral opioid medication every 8 to 12 hours for basal analgesia, with PCA administered as an as-needed bolus. If a patient cannot tolerate oral medications, PCA can provide continuous infusion of medication to provide basal analgesia, though the risk of oversedation and respiratory depression is increased.²⁸

For our clinical example, we recommend increasing the preadmission TDD of opioids (180 mg morphine equivalents) by 25% (225 mg) and administering as morphine 75 mg sustained-release every 8 hours to provide baseline analgesia and prevent withdrawal symptoms. The acute pain can be managed by initiating morphine PCA without continuous infusion at 0.5 mg bolus every 8 minutes as needed for breakthrough pain or oral morphine 30 mg immediate-release tablets every 3 hours as needed for pain. The patient should be assessed frequently, and naloxone kept readily available. In addition, nonopioid and nondrug treatments should be optimized.

When communicating with patients with underlying chronic pain on chronic opioid therapy, it is important to discuss the treatment plan early, including addressing that they will likely not be pain free during their hospitalization, but rather goals of pain relief and improved function should be established. The plan to change to oral opioid analgesics as soon as possible and importance of multi-modal treatment should be emphasized. The patient should be informed that medication changes are for the short-term only and that the underlying chronic pain will likely remain unchanged.

Clinical Example: Patient on Medication-Assisted Therapy

A 42-year-old woman presents with acute epigastric pain and receives a diagnosis of acute gallstone pancreatitis. She states that her pain is very severe and appears uncomfortable. Her past medical history is significant for heroin addiction, but she has been successfully treated for opioid-use disorder with buprenorphine 16 mg daily for the past three years. What is the best way to manage this patient’s acute pain and communicate with her about her pain management?

Medication-assisted therapies (MATs) for treatment of opioid abuse, which include methadone and buprenorphine (Table 3), have been shown to be effective in helping patients recover in opioid-use disorder, are cost-effective and reduce the risk of opioid overdose.²⁹ However, treatment for acute pain in patients who are receiving methadone or buprenorphine MAT is a challenge because of pharmacokinetic changes that occur with prolonged use. It is important to know that patients receiving opioid agonist MAT are usually treated with 1 dose every 24 to 48 hours and do not receive sustained analgesia.³⁰

• Continue maintenance therapy with buprenorphine and treat acute pain with short acting opioid agonists. Higher doses of opioid agonists and more frequent dosing may be needed to provide adequate pain relief since they compete with buprenorphine at the mu receptor. Opioids with higher affinity for the mu receptor (morphine, hydromorphone, fentanyl) may be more efficacious.
• Discontinue buprenorphine and treat the patient with scheduled full opioid analgesics, titrating the dose initially to try to avoid withdrawal and then to provide pain relief. The partial agonism of the mu-receptor from buprenorphine and the blockade of other opioids can persist for as long as 72 hours. During this period, close monitoring and keeping naloxone available are important. When acute pain resolves, discontinue full opioid agonist therapy and resume buprenorphine using an induction protocol.

For our clinical example, we recommend continuing buprenorphine at 16 mg daily, optimizing nonopioid treatment strategies, and using a higher dose parenteral full opioid agonist every 3 hours as needed to achieve adequate analgesia. The patient should be frequently monitored for adverse effects, and naloxone kept available. Full opioid analgesics should be tapered and discontinued as the acute pain resolves. The patient should be reassured that there is no evidence that using opioids to treat acute pain episodes increases the risk of relapse and that untreated acute pain is a more likely trigger for relapse. The patient’s buprenorphine provider should be contacted at admission to verify dose as well as at discharge.

Early discharge planning is essential for appropriate and safe management of acute pain in hospitalized patients with opioid dependence. The major goals are to treat acute pain effectively, improve function, and return care to the patient’s usual treating physician or methadone clinic. Patients on chronic opioid therapy often have a written opioid treatment agreement specifying only 1 prescriber. Therefore, verbal communication with the patient’s authorized prescriber at admission and at discharge is essential, particularly given that the discharge summary may not be available at follow-up. Additional or higher doses of opioids should not be prescribed at discharge unless discussed with the patient’s authorized prescriber. If it is believed necessary to provide opioid medication at discharge it should only be provided for a short period: 3 to 7 days.³⁵ Patients with OUD should be referred for addiction treatment, including MAT, and should be educated on harm-reduction strategies, including safe injecting, obtaining clean needles, and recognizing, avoiding, and treating opioid overdose. Prescribing intranasal naloxone should be strongly considered for patients with OUD and for patients who are taking more than 50 mg oral morphine equivalents for chronic pain.³⁴

Management of acute pain in opioid-dependent patients is a complex and increasingly common problem encountered by hospitalists. In addition, given the OUD epidemic in the United States, safe opioid prescribing has become a paramount goal for all physicians. Although acute pain management will be individualized and will encompass clinical judgment, this review provides an evidence-based guide to effective and safe acute pain management and optimal opioid prescribing for hospitalized opioid-dependent patients.

Disclosure

Nothing to report.

Up to 40% of Americans experience chronic pain of some kind.¹ In the United States, opioid analgesics are the most prescribed class of medications,² with 245 million prescriptions filled in 2014 alone. Thirty-five percent of these prescriptions were for long-term therapy.³ It is now apparent that opioid pain medication use presents serious risks. In 2014, 10.3 million persons reported using prescription opioids for nonmedical reasons.⁴ Between 1999 and 2014, more than 165,000 people in the United States died of overdose related to opioid medication.⁵ In addition, heroin use in the United States has increased over the past decade.⁶ Opioid agonist maintenance therapy is also increasingly used to treat patients with opioid use disorder.

Given the prevalence of opioid use in the United States, it is important for hospitalists to be able to appropriately and safely manage acute pain in patients who have been exposed long-term to opioids, whether it is therapeutic or non-medical in origin. Although nonopioid medications and nondrug treatments are essential components of managing all acute pain, opioids continue to be the mainstay of treatment for severe acute pain in both opioid-naïve and opioid-dependent patients.

Given the paucity of published trials meeting the typical criteria, we did not perform a structured meta-analysis but, instead, a case-based narrative review of the relevant published literature. Our goal in performing this review is to guide hospitalists in the appropriate and safe use of opioid analgesics in treating acute pain in hospitalized patients who are opioid-dependent.

When managing acute pain in patients with opioid dependence it is important to have a clear understanding of the definitions related to opioid use. Addiction, physical dependence and tolerance have been defined by a joint consensus statement of the American Society of Addiction Medicine, American Academy of Pain Medicine, and American Pain Society⁷: Addiction is a primary, chronic, biological disease, with genetic, psychosocial and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.

Physical Dependence is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.

Tolerance is the state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time.

Opioid use disorder (OUD) is defined as a problematic pattern of opioid use leading to clinically significant impairment or distress with symptoms including a strong desire for opioids, inability to control or reduce use of opioids, continued use despite adverse consequences, and development of tolerance and withdrawal symptoms.⁸

Physical dependence and tolerance are common consequences of long-term opioid use. In contrast, OUD has been reported to affect only 2% to 6% of individuals exposed to opioids.⁹ The underlying mechanisms that lead an individual to abuse or become addicted to opioids largely due to the effects opioids have on endogenous μ-opioid receptors. As analgesics, opioids exert their effects by binding primarily to these μ-opioid receptors, with a large concentration in the brain regions regulating pain perception.^10,11 There is also a large concentration of μ-opioid receptors in the brain reward regions, leading to perceptions of pleasure and euphoria. Repeated administration of opioids conditions the brain to a learned association between receiving the opiate and euphoria.^12,13 This association becomes stronger as the frequency and duration of administration increases over time, ultimately leading to the desire or craving of the opioid’s effect.

The effect of tolerance also contributes to the pathophysiology of opioid abuse as it leads to a decrease in opioid potency with repeated administration.^14-16 To achieve analgesia as well as the reward effect, opioid dosage and/or frequency must be increased, strengthening the association between receipt of opioid and reward. Tolerance to the reward effect occurs quickly, whereas tolerance to respiratory depression occurs much more slowly.¹⁷ This mismatch in tolerance of effect may lead to increase in opioid doses to maintain analgesia or euphoria, and also places patients at a higher risk of overdose.¹⁸

Clinical Example: Heroin User

A 47-year-old man is admitted with fever, chills, and severe mid-back pain and receives a diagnosis of sepsis. The patient admits to using intravenous heroin 500 mg (five 100 mg “bags”) on a daily basis. He is admitted, fluid resuscitated and started on broad spectrum antibiotics. Blood cultures quickly grow Staphylococcus aureus. Magnetic resonance imaging of the spine shows cervical vertebral osteomyelitis. On examination, the patient is diaphoretic and complains of diffuse myalgias and diarrhea. The patient’s back pain is so severe that he cannot ambulate. What is the best way to manage this patient’s acute pain and communicate with him about his pain management?

Managing acute pain in a patient using heroin can be challenging for many reasons. First, both physicians and pharmacists report a lack of confidence in their ability to prescribe opioids safely or to treat patients with a history of opioid abuse.¹⁹ Second, there is a paucity of evidence in treating acute pain in heroin users. Finally, due to the clandestine manufacturing of illicit drugs, the actual purity of the drug is often unknown making it difficult to assess the dose of opioids in heroin users. Drug Enforcement Agency seizure data indicate a wide range of heroin purity: 30% to 70%.²⁰

In the hospital setting, acute pain is often undertreated in patients with a history of active opioid abuse. This may be due to providers’ misconceptions regarding pain and behavior in opioid addicts, including worrying that the patient’s pain is exaggerated in order to obtain drugs, thinking that a regular opioid habit eliminates pain, believing that opioid therapy is not effective in drug addicts, or worrying that prescribing opioids will exacerbate drug addiction.²¹ Data demonstrates that the presence of opioid addiction seems to worsen the experience of acute pain.²² These patients also often have a higher tolerance and thus require higher dosages and more frequent dosing of opioids to adequately treat their pain.²³

Converting daily heroin use to morphine equivalents is necessary to establish a baseline analgesic requirement and to prevent withdrawal. It is challenging to convert illicit heroin to morphine equivalents however, as one must take into account the wide variation in purity and understand that the stated use of heroin (e.g. 500 mg daily) reflects weight and not dosage of heroin.²⁰

In these patients, treatment of acute pain should be individualized according to presenting illness and comorbidities. Previous data and an average purity of 40% suggest that the parenteral morphine equivalent to a bag of heroin (100 mg) is 15 to 30 mg.^20,24,25 Common equianalgesic doses of opioid medications are listed in Table 1. Because of increased tolerance, the frequency of administration should be shortened, from every 4 hours to every 2 or 3 hours. Except for a shorter onset of action, there has not been a difference shown in superiority between oral and parenteral routes of administration. Finally, patients should receive both long-acting basal and short-acting as-needed analgesics based on their daily use of opioids.²³

Clinical Example: Patient on Chronic Opioid Therapy for Chronic Pain

A 64 year-old man was involved in a motorcycle accident and suffered a right distal tibia-fibula fracture and several broken ribs with a secondary pneumothorax. The patient’s past medical history is significant for chronic low back pain for which he states he takes morphine sustained release 30 mg orally every 8 hours and morphine immediate release 15 mg orally four times daily for breakthrough pain. The patient states his pain is much worse than prior to the accident. Trauma surgery requests recommendations on appropriate pain management. What is the best way to manage this patient’s acute pain and communicate with him about his pain management?

When treating acute pain in patients with chronic pain on opioid therapy, it is vital to establish the patient’s baseline pain level and to accurately reconcile the patient’s outpatient daily opioid use. The patient’s prescription record should be verified in the state’s prescription drug monitoring program. On admission, a urine drug test should be obtained to assess for use of other potential illicit substances (eg, cocaine). Patients who test positive for illicit substances are at high risk for a substance use disorder. Management and discharge plans should be as outlined in the above case. It is important to know that the first-tier immunoassay urine toxicology screens used by hospitals test for natural opioids (morphine, codeine, heroin). Semi-synthetic (example, oxycodone) or synthetic (example, fentanyl) opioids are unlikely to be detected and thus the urine drug screen may not be helpful to determine adherence to certain prescription opioids. Gas chromatography/mass spectrometry is the most sensitive and specific type of urine screen and can be ordered to confirm a prescribed opioid if needed.²⁶

Pain management should begin with calculating the TDD of oral opioids that the patient was taking prior to admission, and converting to morphine equivalents. For moderate acute pain, TDD can be increased by 25% to 50%. The revised TDD can then be prescribed as a long-acting opioid every 8 to 12 hours to provide basal analgesia. The dose of additional immediate-release medication available throughout the day to manage breakthrough pain is determined by dividing the new TDD into every 3 to 4 hours as-needed dosing (Table 2).

If severe pain is anticipated, patient controlled analgesia (PCA) is an effective alternative to deliver opioids. The use of PCA allows self-titration, on demand analgesia, and minimizes the likelihood of under-dosing the patient.²⁷ The revised TDD is a useful starting point when calculating the PCA dosage regimen. Ideally, the revised TDD should be prescribed as a long acting oral opioid medication every 8 to 12 hours for basal analgesia, with PCA administered as an as-needed bolus. If a patient cannot tolerate oral medications, PCA can provide continuous infusion of medication to provide basal analgesia, though the risk of oversedation and respiratory depression is increased.²⁸

For our clinical example, we recommend increasing the preadmission TDD of opioids (180 mg morphine equivalents) by 25% (225 mg) and administering as morphine 75 mg sustained-release every 8 hours to provide baseline analgesia and prevent withdrawal symptoms. The acute pain can be managed by initiating morphine PCA without continuous infusion at 0.5 mg bolus every 8 minutes as needed for breakthrough pain or oral morphine 30 mg immediate-release tablets every 3 hours as needed for pain. The patient should be assessed frequently, and naloxone kept readily available. In addition, nonopioid and nondrug treatments should be optimized.

When communicating with patients with underlying chronic pain on chronic opioid therapy, it is important to discuss the treatment plan early, including addressing that they will likely not be pain free during their hospitalization, but rather goals of pain relief and improved function should be established. The plan to change to oral opioid analgesics as soon as possible and importance of multi-modal treatment should be emphasized. The patient should be informed that medication changes are for the short-term only and that the underlying chronic pain will likely remain unchanged.

Clinical Example: Patient on Medication-Assisted Therapy

A 42-year-old woman presents with acute epigastric pain and receives a diagnosis of acute gallstone pancreatitis. She states that her pain is very severe and appears uncomfortable. Her past medical history is significant for heroin addiction, but she has been successfully treated for opioid-use disorder with buprenorphine 16 mg daily for the past three years. What is the best way to manage this patient’s acute pain and communicate with her about her pain management?

Medication-assisted therapies (MATs) for treatment of opioid abuse, which include methadone and buprenorphine (Table 3), have been shown to be effective in helping patients recover in opioid-use disorder, are cost-effective and reduce the risk of opioid overdose.²⁹ However, treatment for acute pain in patients who are receiving methadone or buprenorphine MAT is a challenge because of pharmacokinetic changes that occur with prolonged use. It is important to know that patients receiving opioid agonist MAT are usually treated with 1 dose every 24 to 48 hours and do not receive sustained analgesia.³⁰

• Continue maintenance therapy with buprenorphine and treat acute pain with short acting opioid agonists. Higher doses of opioid agonists and more frequent dosing may be needed to provide adequate pain relief since they compete with buprenorphine at the mu receptor. Opioids with higher affinity for the mu receptor (morphine, hydromorphone, fentanyl) may be more efficacious.
• Discontinue buprenorphine and treat the patient with scheduled full opioid analgesics, titrating the dose initially to try to avoid withdrawal and then to provide pain relief. The partial agonism of the mu-receptor from buprenorphine and the blockade of other opioids can persist for as long as 72 hours. During this period, close monitoring and keeping naloxone available are important. When acute pain resolves, discontinue full opioid agonist therapy and resume buprenorphine using an induction protocol.

For our clinical example, we recommend continuing buprenorphine at 16 mg daily, optimizing nonopioid treatment strategies, and using a higher dose parenteral full opioid agonist every 3 hours as needed to achieve adequate analgesia. The patient should be frequently monitored for adverse effects, and naloxone kept available. Full opioid analgesics should be tapered and discontinued as the acute pain resolves. The patient should be reassured that there is no evidence that using opioids to treat acute pain episodes increases the risk of relapse and that untreated acute pain is a more likely trigger for relapse. The patient’s buprenorphine provider should be contacted at admission to verify dose as well as at discharge.

Early discharge planning is essential for appropriate and safe management of acute pain in hospitalized patients with opioid dependence. The major goals are to treat acute pain effectively, improve function, and return care to the patient’s usual treating physician or methadone clinic. Patients on chronic opioid therapy often have a written opioid treatment agreement specifying only 1 prescriber. Therefore, verbal communication with the patient’s authorized prescriber at admission and at discharge is essential, particularly given that the discharge summary may not be available at follow-up. Additional or higher doses of opioids should not be prescribed at discharge unless discussed with the patient’s authorized prescriber. If it is believed necessary to provide opioid medication at discharge it should only be provided for a short period: 3 to 7 days.³⁵ Patients with OUD should be referred for addiction treatment, including MAT, and should be educated on harm-reduction strategies, including safe injecting, obtaining clean needles, and recognizing, avoiding, and treating opioid overdose. Prescribing intranasal naloxone should be strongly considered for patients with OUD and for patients who are taking more than 50 mg oral morphine equivalents for chronic pain.³⁴

Management of acute pain in opioid-dependent patients is a complex and increasingly common problem encountered by hospitalists. In addition, given the OUD epidemic in the United States, safe opioid prescribing has become a paramount goal for all physicians. Although acute pain management will be individualized and will encompass clinical judgment, this review provides an evidence-based guide to effective and safe acute pain management and optimal opioid prescribing for hospitalized opioid-dependent patients.

Disclosure

Nothing to report.

Up to 40% of Americans experience chronic pain of some kind.¹ In the United States, opioid analgesics are the most prescribed class of medications,² with 245 million prescriptions filled in 2014 alone. Thirty-five percent of these prescriptions were for long-term therapy.³ It is now apparent that opioid pain medication use presents serious risks. In 2014, 10.3 million persons reported using prescription opioids for nonmedical reasons.⁴ Between 1999 and 2014, more than 165,000 people in the United States died of overdose related to opioid medication.⁵ In addition, heroin use in the United States has increased over the past decade.⁶ Opioid agonist maintenance therapy is also increasingly used to treat patients with opioid use disorder.

Given the prevalence of opioid use in the United States, it is important for hospitalists to be able to appropriately and safely manage acute pain in patients who have been exposed long-term to opioids, whether it is therapeutic or non-medical in origin. Although nonopioid medications and nondrug treatments are essential components of managing all acute pain, opioids continue to be the mainstay of treatment for severe acute pain in both opioid-naïve and opioid-dependent patients.

Given the paucity of published trials meeting the typical criteria, we did not perform a structured meta-analysis but, instead, a case-based narrative review of the relevant published literature. Our goal in performing this review is to guide hospitalists in the appropriate and safe use of opioid analgesics in treating acute pain in hospitalized patients who are opioid-dependent.

When managing acute pain in patients with opioid dependence it is important to have a clear understanding of the definitions related to opioid use. Addiction, physical dependence and tolerance have been defined by a joint consensus statement of the American Society of Addiction Medicine, American Academy of Pain Medicine, and American Pain Society⁷: Addiction is a primary, chronic, biological disease, with genetic, psychosocial and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.

Physical Dependence is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.

Tolerance is the state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time.

Opioid use disorder (OUD) is defined as a problematic pattern of opioid use leading to clinically significant impairment or distress with symptoms including a strong desire for opioids, inability to control or reduce use of opioids, continued use despite adverse consequences, and development of tolerance and withdrawal symptoms.⁸

Physical dependence and tolerance are common consequences of long-term opioid use. In contrast, OUD has been reported to affect only 2% to 6% of individuals exposed to opioids.⁹ The underlying mechanisms that lead an individual to abuse or become addicted to opioids largely due to the effects opioids have on endogenous μ-opioid receptors. As analgesics, opioids exert their effects by binding primarily to these μ-opioid receptors, with a large concentration in the brain regions regulating pain perception.^10,11 There is also a large concentration of μ-opioid receptors in the brain reward regions, leading to perceptions of pleasure and euphoria. Repeated administration of opioids conditions the brain to a learned association between receiving the opiate and euphoria.^12,13 This association becomes stronger as the frequency and duration of administration increases over time, ultimately leading to the desire or craving of the opioid’s effect.

The effect of tolerance also contributes to the pathophysiology of opioid abuse as it leads to a decrease in opioid potency with repeated administration.^14-16 To achieve analgesia as well as the reward effect, opioid dosage and/or frequency must be increased, strengthening the association between receipt of opioid and reward. Tolerance to the reward effect occurs quickly, whereas tolerance to respiratory depression occurs much more slowly.¹⁷ This mismatch in tolerance of effect may lead to increase in opioid doses to maintain analgesia or euphoria, and also places patients at a higher risk of overdose.¹⁸

Clinical Example: Heroin User

A 47-year-old man is admitted with fever, chills, and severe mid-back pain and receives a diagnosis of sepsis. The patient admits to using intravenous heroin 500 mg (five 100 mg “bags”) on a daily basis. He is admitted, fluid resuscitated and started on broad spectrum antibiotics. Blood cultures quickly grow Staphylococcus aureus. Magnetic resonance imaging of the spine shows cervical vertebral osteomyelitis. On examination, the patient is diaphoretic and complains of diffuse myalgias and diarrhea. The patient’s back pain is so severe that he cannot ambulate. What is the best way to manage this patient’s acute pain and communicate with him about his pain management?

Managing acute pain in a patient using heroin can be challenging for many reasons. First, both physicians and pharmacists report a lack of confidence in their ability to prescribe opioids safely or to treat patients with a history of opioid abuse.¹⁹ Second, there is a paucity of evidence in treating acute pain in heroin users. Finally, due to the clandestine manufacturing of illicit drugs, the actual purity of the drug is often unknown making it difficult to assess the dose of opioids in heroin users. Drug Enforcement Agency seizure data indicate a wide range of heroin purity: 30% to 70%.²⁰

In the hospital setting, acute pain is often undertreated in patients with a history of active opioid abuse. This may be due to providers’ misconceptions regarding pain and behavior in opioid addicts, including worrying that the patient’s pain is exaggerated in order to obtain drugs, thinking that a regular opioid habit eliminates pain, believing that opioid therapy is not effective in drug addicts, or worrying that prescribing opioids will exacerbate drug addiction.²¹ Data demonstrates that the presence of opioid addiction seems to worsen the experience of acute pain.²² These patients also often have a higher tolerance and thus require higher dosages and more frequent dosing of opioids to adequately treat their pain.²³

Converting daily heroin use to morphine equivalents is necessary to establish a baseline analgesic requirement and to prevent withdrawal. It is challenging to convert illicit heroin to morphine equivalents however, as one must take into account the wide variation in purity and understand that the stated use of heroin (e.g. 500 mg daily) reflects weight and not dosage of heroin.²⁰

In these patients, treatment of acute pain should be individualized according to presenting illness and comorbidities. Previous data and an average purity of 40% suggest that the parenteral morphine equivalent to a bag of heroin (100 mg) is 15 to 30 mg.^20,24,25 Common equianalgesic doses of opioid medications are listed in Table 1. Because of increased tolerance, the frequency of administration should be shortened, from every 4 hours to every 2 or 3 hours. Except for a shorter onset of action, there has not been a difference shown in superiority between oral and parenteral routes of administration. Finally, patients should receive both long-acting basal and short-acting as-needed analgesics based on their daily use of opioids.²³

Clinical Example: Patient on Chronic Opioid Therapy for Chronic Pain

A 64 year-old man was involved in a motorcycle accident and suffered a right distal tibia-fibula fracture and several broken ribs with a secondary pneumothorax. The patient’s past medical history is significant for chronic low back pain for which he states he takes morphine sustained release 30 mg orally every 8 hours and morphine immediate release 15 mg orally four times daily for breakthrough pain. The patient states his pain is much worse than prior to the accident. Trauma surgery requests recommendations on appropriate pain management. What is the best way to manage this patient’s acute pain and communicate with him about his pain management?

When treating acute pain in patients with chronic pain on opioid therapy, it is vital to establish the patient’s baseline pain level and to accurately reconcile the patient’s outpatient daily opioid use. The patient’s prescription record should be verified in the state’s prescription drug monitoring program. On admission, a urine drug test should be obtained to assess for use of other potential illicit substances (eg, cocaine). Patients who test positive for illicit substances are at high risk for a substance use disorder. Management and discharge plans should be as outlined in the above case. It is important to know that the first-tier immunoassay urine toxicology screens used by hospitals test for natural opioids (morphine, codeine, heroin). Semi-synthetic (example, oxycodone) or synthetic (example, fentanyl) opioids are unlikely to be detected and thus the urine drug screen may not be helpful to determine adherence to certain prescription opioids. Gas chromatography/mass spectrometry is the most sensitive and specific type of urine screen and can be ordered to confirm a prescribed opioid if needed.²⁶

Pain management should begin with calculating the TDD of oral opioids that the patient was taking prior to admission, and converting to morphine equivalents. For moderate acute pain, TDD can be increased by 25% to 50%. The revised TDD can then be prescribed as a long-acting opioid every 8 to 12 hours to provide basal analgesia. The dose of additional immediate-release medication available throughout the day to manage breakthrough pain is determined by dividing the new TDD into every 3 to 4 hours as-needed dosing (Table 2).

If severe pain is anticipated, patient controlled analgesia (PCA) is an effective alternative to deliver opioids. The use of PCA allows self-titration, on demand analgesia, and minimizes the likelihood of under-dosing the patient.²⁷ The revised TDD is a useful starting point when calculating the PCA dosage regimen. Ideally, the revised TDD should be prescribed as a long acting oral opioid medication every 8 to 12 hours for basal analgesia, with PCA administered as an as-needed bolus. If a patient cannot tolerate oral medications, PCA can provide continuous infusion of medication to provide basal analgesia, though the risk of oversedation and respiratory depression is increased.²⁸

For our clinical example, we recommend increasing the preadmission TDD of opioids (180 mg morphine equivalents) by 25% (225 mg) and administering as morphine 75 mg sustained-release every 8 hours to provide baseline analgesia and prevent withdrawal symptoms. The acute pain can be managed by initiating morphine PCA without continuous infusion at 0.5 mg bolus every 8 minutes as needed for breakthrough pain or oral morphine 30 mg immediate-release tablets every 3 hours as needed for pain. The patient should be assessed frequently, and naloxone kept readily available. In addition, nonopioid and nondrug treatments should be optimized.

When communicating with patients with underlying chronic pain on chronic opioid therapy, it is important to discuss the treatment plan early, including addressing that they will likely not be pain free during their hospitalization, but rather goals of pain relief and improved function should be established. The plan to change to oral opioid analgesics as soon as possible and importance of multi-modal treatment should be emphasized. The patient should be informed that medication changes are for the short-term only and that the underlying chronic pain will likely remain unchanged.

Clinical Example: Patient on Medication-Assisted Therapy

A 42-year-old woman presents with acute epigastric pain and receives a diagnosis of acute gallstone pancreatitis. She states that her pain is very severe and appears uncomfortable. Her past medical history is significant for heroin addiction, but she has been successfully treated for opioid-use disorder with buprenorphine 16 mg daily for the past three years. What is the best way to manage this patient’s acute pain and communicate with her about her pain management?

Medication-assisted therapies (MATs) for treatment of opioid abuse, which include methadone and buprenorphine (Table 3), have been shown to be effective in helping patients recover in opioid-use disorder, are cost-effective and reduce the risk of opioid overdose.²⁹ However, treatment for acute pain in patients who are receiving methadone or buprenorphine MAT is a challenge because of pharmacokinetic changes that occur with prolonged use. It is important to know that patients receiving opioid agonist MAT are usually treated with 1 dose every 24 to 48 hours and do not receive sustained analgesia.³⁰

• Continue maintenance therapy with buprenorphine and treat acute pain with short acting opioid agonists. Higher doses of opioid agonists and more frequent dosing may be needed to provide adequate pain relief since they compete with buprenorphine at the mu receptor. Opioids with higher affinity for the mu receptor (morphine, hydromorphone, fentanyl) may be more efficacious.
• Discontinue buprenorphine and treat the patient with scheduled full opioid analgesics, titrating the dose initially to try to avoid withdrawal and then to provide pain relief. The partial agonism of the mu-receptor from buprenorphine and the blockade of other opioids can persist for as long as 72 hours. During this period, close monitoring and keeping naloxone available are important. When acute pain resolves, discontinue full opioid agonist therapy and resume buprenorphine using an induction protocol.

For our clinical example, we recommend continuing buprenorphine at 16 mg daily, optimizing nonopioid treatment strategies, and using a higher dose parenteral full opioid agonist every 3 hours as needed to achieve adequate analgesia. The patient should be frequently monitored for adverse effects, and naloxone kept available. Full opioid analgesics should be tapered and discontinued as the acute pain resolves. The patient should be reassured that there is no evidence that using opioids to treat acute pain episodes increases the risk of relapse and that untreated acute pain is a more likely trigger for relapse. The patient’s buprenorphine provider should be contacted at admission to verify dose as well as at discharge.

Early discharge planning is essential for appropriate and safe management of acute pain in hospitalized patients with opioid dependence. The major goals are to treat acute pain effectively, improve function, and return care to the patient’s usual treating physician or methadone clinic. Patients on chronic opioid therapy often have a written opioid treatment agreement specifying only 1 prescriber. Therefore, verbal communication with the patient’s authorized prescriber at admission and at discharge is essential, particularly given that the discharge summary may not be available at follow-up. Additional or higher doses of opioids should not be prescribed at discharge unless discussed with the patient’s authorized prescriber. If it is believed necessary to provide opioid medication at discharge it should only be provided for a short period: 3 to 7 days.³⁵ Patients with OUD should be referred for addiction treatment, including MAT, and should be educated on harm-reduction strategies, including safe injecting, obtaining clean needles, and recognizing, avoiding, and treating opioid overdose. Prescribing intranasal naloxone should be strongly considered for patients with OUD and for patients who are taking more than 50 mg oral morphine equivalents for chronic pain.³⁴

Management of acute pain in opioid-dependent patients is a complex and increasingly common problem encountered by hospitalists. In addition, given the OUD epidemic in the United States, safe opioid prescribing has become a paramount goal for all physicians. Although acute pain management will be individualized and will encompass clinical judgment, this review provides an evidence-based guide to effective and safe acute pain management and optimal opioid prescribing for hospitalized opioid-dependent patients.

Disclosure

Nothing to report.

In this issue of the Journal of Hospital Medicine, Lusica et al.¹ discuss the utility of urine eosinophils (UEs) in evaluating for acute interstitial nephritis (AIN) in patients with acute kidney injury (AKI), an important and oft-confused concern in medicine. I can’t think of a more appropriate topic for the “Things We Do for No Reason” (TWDFNR) series. Numerous tests are ordered in the evaluation of AKI.² Many, such as batteries of serological tests, are unnecessary and add little diagnostic information. Some, such as UEs and fractional excretion of sodium (FENa), provide misinformation. And others, such as contrast-enhanced computed tomography scans, are potentially harmful.² In a previous TWDFNR article, the limitations of FENa in the evaluation of AKI were reviewed.³ There are common threads linking the shortcomings of UEs and FENa and even new diagnostic tests. What are the lessons from these studies, and how might clinicians best apply them in their practice?

As reviewed in this issue, UE testing is employed in AKI to evaluate for hospital-acquired AIN. Small initial studies led to widespread use of this test, despite methodological flaws.⁴ A later, definitive study involving 566 patients who had both UEs and kidney biopsies performed within the same week demonstrated that UEs offered no diagnostic value in AKI.⁵ The same pattern occurred in the increased use of FENa to distinguish prerenal azotemia from acute tubular necrosis in AKI patients.³ Small studies in highly select patients supported its use for this purpose.⁶ Subsequently, larger studies in more diverse populations noted that FENa was associated with many false positive and negative results,⁶ likely due to more widespread use of this test in disease states such as cirrhosis, congestive heart failure, chronic kidney disease, and diabetes, which were not included in initial studies.

It is apparent that clinicians have been led astray by small, flawed positive studies employed in highly selected populations. These initial positive studies based on excessively large effect size estimates were subsequently shown to be negative in larger studies with more plausible effect sizes. Examples of this error are seen in publications involving prophylactic measures to reduce contrast nephrotoxicity.⁷ Early studies on N-acetylcysteine administration prior to radiocontrast exposure showed positive results. Examination of these studies, however, demonstrates 2 key problems: 1) inclusion of small numbers of patients due to power calculations based on excessively large effect sizes, and 2) use of clinically unimportant endpoints such as serum creatinine changes.⁷ The same issue complicates studies evaluating isotonic sodium bicarbonate vs. normal saline for contrast prophylaxis.⁷

The past 10-plus years have seen a proliferation of studies evaluating the utility of novel biomarkers for early diagnosis and prognosis in AKI. Have we fallen down the same rabbit hole in evaluating these new diagnostic tests for AKI? There is reason for concern if we examine published studies of novel biomarkers in other areas of medicine. To this point, many highly cited novel biomarker studies used for various diagnostic purposes (eg, cancer, infection, cardiovascular disease) employed excessively large effect size estimates for postulated associations that resulted in small, underpowered studies with initially positive results.⁸ Subsequent large studies and meta-analyses reported negative or modestly positive test results when examining these same associations.⁸ But we may be moving in the right direction. An early urine biomarker publication from a small, single center study⁹ revealed overly optimistic results (area under the curve [AUC], 0.998; sensitivity, 100%; specificity, 98%) for AKI prediction. Subsequent large, multicenter biomarker studies showed only modest improvement in their discriminative value when compared with traditional clinical models.¹⁰ These results precluded U.S. Food and Drug Administration (FDA) approval of most novel biomarkers for clinical practice and they were not adopted. In 2014, the FDA approved the point-of-care urinary biomarker TIMP-2/IGFBP7 (NephroCheck^®) for predicting risk of AKI based on fairly rigorous testing using larger numbers of patients, heterogeneous populations, and important clinical endpoints.¹¹ In a 522-patient discovery cohort, this biomarker had an AUC of 0.80 for AKI prediction, which was validated in a 722-patient cohort and subsequently followed by a 420-patient multicenter cohort study revealing similar test characteristics (AUC, 0.82; sensitivity, 92%; specificity, 46%).¹¹ A study involving 382 critically ill AKI patients noted that this biomarker had a hazard ratio of 2.16 (95% confidence interval [CI] 1.32 to 3.53) for predicting dialysis requirement or death.¹¹ And while this test has yet to find its clinical niche, its operating characteristics are well-studied and likely valid. While predicting AKI earlier does not currently result in effective therapy, it may allow more timely discontinuation or avoidance of potentially nephrotoxic medications, ultimately reducing the severity of AKI and its consequences.

In summary, clinicians should be aware of the strengths and limitations of diagnostic tests ordered in AKI patients, as seen with the overly optimistic results in small, flawed UE and FENa studies. While we have taken a step in the right direction with diagnostic and prognostic biomarkers for AKI, we must apply rigorous study design to diagnostic tests under evaluation before adopting them into clinical practice. Only then can we move the field forward and improve patient care.

Disclosure

Nothing to report.

In this issue of the Journal of Hospital Medicine, Lusica et al.¹ discuss the utility of urine eosinophils (UEs) in evaluating for acute interstitial nephritis (AIN) in patients with acute kidney injury (AKI), an important and oft-confused concern in medicine. I can’t think of a more appropriate topic for the “Things We Do for No Reason” (TWDFNR) series. Numerous tests are ordered in the evaluation of AKI.² Many, such as batteries of serological tests, are unnecessary and add little diagnostic information. Some, such as UEs and fractional excretion of sodium (FENa), provide misinformation. And others, such as contrast-enhanced computed tomography scans, are potentially harmful.² In a previous TWDFNR article, the limitations of FENa in the evaluation of AKI were reviewed.³ There are common threads linking the shortcomings of UEs and FENa and even new diagnostic tests. What are the lessons from these studies, and how might clinicians best apply them in their practice?

As reviewed in this issue, UE testing is employed in AKI to evaluate for hospital-acquired AIN. Small initial studies led to widespread use of this test, despite methodological flaws.⁴ A later, definitive study involving 566 patients who had both UEs and kidney biopsies performed within the same week demonstrated that UEs offered no diagnostic value in AKI.⁵ The same pattern occurred in the increased use of FENa to distinguish prerenal azotemia from acute tubular necrosis in AKI patients.³ Small studies in highly select patients supported its use for this purpose.⁶ Subsequently, larger studies in more diverse populations noted that FENa was associated with many false positive and negative results,⁶ likely due to more widespread use of this test in disease states such as cirrhosis, congestive heart failure, chronic kidney disease, and diabetes, which were not included in initial studies.

It is apparent that clinicians have been led astray by small, flawed positive studies employed in highly selected populations. These initial positive studies based on excessively large effect size estimates were subsequently shown to be negative in larger studies with more plausible effect sizes. Examples of this error are seen in publications involving prophylactic measures to reduce contrast nephrotoxicity.⁷ Early studies on N-acetylcysteine administration prior to radiocontrast exposure showed positive results. Examination of these studies, however, demonstrates 2 key problems: 1) inclusion of small numbers of patients due to power calculations based on excessively large effect sizes, and 2) use of clinically unimportant endpoints such as serum creatinine changes.⁷ The same issue complicates studies evaluating isotonic sodium bicarbonate vs. normal saline for contrast prophylaxis.⁷

The past 10-plus years have seen a proliferation of studies evaluating the utility of novel biomarkers for early diagnosis and prognosis in AKI. Have we fallen down the same rabbit hole in evaluating these new diagnostic tests for AKI? There is reason for concern if we examine published studies of novel biomarkers in other areas of medicine. To this point, many highly cited novel biomarker studies used for various diagnostic purposes (eg, cancer, infection, cardiovascular disease) employed excessively large effect size estimates for postulated associations that resulted in small, underpowered studies with initially positive results.⁸ Subsequent large studies and meta-analyses reported negative or modestly positive test results when examining these same associations.⁸ But we may be moving in the right direction. An early urine biomarker publication from a small, single center study⁹ revealed overly optimistic results (area under the curve [AUC], 0.998; sensitivity, 100%; specificity, 98%) for AKI prediction. Subsequent large, multicenter biomarker studies showed only modest improvement in their discriminative value when compared with traditional clinical models.¹⁰ These results precluded U.S. Food and Drug Administration (FDA) approval of most novel biomarkers for clinical practice and they were not adopted. In 2014, the FDA approved the point-of-care urinary biomarker TIMP-2/IGFBP7 (NephroCheck^®) for predicting risk of AKI based on fairly rigorous testing using larger numbers of patients, heterogeneous populations, and important clinical endpoints.¹¹ In a 522-patient discovery cohort, this biomarker had an AUC of 0.80 for AKI prediction, which was validated in a 722-patient cohort and subsequently followed by a 420-patient multicenter cohort study revealing similar test characteristics (AUC, 0.82; sensitivity, 92%; specificity, 46%).¹¹ A study involving 382 critically ill AKI patients noted that this biomarker had a hazard ratio of 2.16 (95% confidence interval [CI] 1.32 to 3.53) for predicting dialysis requirement or death.¹¹ And while this test has yet to find its clinical niche, its operating characteristics are well-studied and likely valid. While predicting AKI earlier does not currently result in effective therapy, it may allow more timely discontinuation or avoidance of potentially nephrotoxic medications, ultimately reducing the severity of AKI and its consequences.

In summary, clinicians should be aware of the strengths and limitations of diagnostic tests ordered in AKI patients, as seen with the overly optimistic results in small, flawed UE and FENa studies. While we have taken a step in the right direction with diagnostic and prognostic biomarkers for AKI, we must apply rigorous study design to diagnostic tests under evaluation before adopting them into clinical practice. Only then can we move the field forward and improve patient care.

Disclosure

Nothing to report.

In this issue of the Journal of Hospital Medicine, Lusica et al.¹ discuss the utility of urine eosinophils (UEs) in evaluating for acute interstitial nephritis (AIN) in patients with acute kidney injury (AKI), an important and oft-confused concern in medicine. I can’t think of a more appropriate topic for the “Things We Do for No Reason” (TWDFNR) series. Numerous tests are ordered in the evaluation of AKI.² Many, such as batteries of serological tests, are unnecessary and add little diagnostic information. Some, such as UEs and fractional excretion of sodium (FENa), provide misinformation. And others, such as contrast-enhanced computed tomography scans, are potentially harmful.² In a previous TWDFNR article, the limitations of FENa in the evaluation of AKI were reviewed.³ There are common threads linking the shortcomings of UEs and FENa and even new diagnostic tests. What are the lessons from these studies, and how might clinicians best apply them in their practice?

As reviewed in this issue, UE testing is employed in AKI to evaluate for hospital-acquired AIN. Small initial studies led to widespread use of this test, despite methodological flaws.⁴ A later, definitive study involving 566 patients who had both UEs and kidney biopsies performed within the same week demonstrated that UEs offered no diagnostic value in AKI.⁵ The same pattern occurred in the increased use of FENa to distinguish prerenal azotemia from acute tubular necrosis in AKI patients.³ Small studies in highly select patients supported its use for this purpose.⁶ Subsequently, larger studies in more diverse populations noted that FENa was associated with many false positive and negative results,⁶ likely due to more widespread use of this test in disease states such as cirrhosis, congestive heart failure, chronic kidney disease, and diabetes, which were not included in initial studies.

It is apparent that clinicians have been led astray by small, flawed positive studies employed in highly selected populations. These initial positive studies based on excessively large effect size estimates were subsequently shown to be negative in larger studies with more plausible effect sizes. Examples of this error are seen in publications involving prophylactic measures to reduce contrast nephrotoxicity.⁷ Early studies on N-acetylcysteine administration prior to radiocontrast exposure showed positive results. Examination of these studies, however, demonstrates 2 key problems: 1) inclusion of small numbers of patients due to power calculations based on excessively large effect sizes, and 2) use of clinically unimportant endpoints such as serum creatinine changes.⁷ The same issue complicates studies evaluating isotonic sodium bicarbonate vs. normal saline for contrast prophylaxis.⁷

The past 10-plus years have seen a proliferation of studies evaluating the utility of novel biomarkers for early diagnosis and prognosis in AKI. Have we fallen down the same rabbit hole in evaluating these new diagnostic tests for AKI? There is reason for concern if we examine published studies of novel biomarkers in other areas of medicine. To this point, many highly cited novel biomarker studies used for various diagnostic purposes (eg, cancer, infection, cardiovascular disease) employed excessively large effect size estimates for postulated associations that resulted in small, underpowered studies with initially positive results.⁸ Subsequent large studies and meta-analyses reported negative or modestly positive test results when examining these same associations.⁸ But we may be moving in the right direction. An early urine biomarker publication from a small, single center study⁹ revealed overly optimistic results (area under the curve [AUC], 0.998; sensitivity, 100%; specificity, 98%) for AKI prediction. Subsequent large, multicenter biomarker studies showed only modest improvement in their discriminative value when compared with traditional clinical models.¹⁰ These results precluded U.S. Food and Drug Administration (FDA) approval of most novel biomarkers for clinical practice and they were not adopted. In 2014, the FDA approved the point-of-care urinary biomarker TIMP-2/IGFBP7 (NephroCheck^®) for predicting risk of AKI based on fairly rigorous testing using larger numbers of patients, heterogeneous populations, and important clinical endpoints.¹¹ In a 522-patient discovery cohort, this biomarker had an AUC of 0.80 for AKI prediction, which was validated in a 722-patient cohort and subsequently followed by a 420-patient multicenter cohort study revealing similar test characteristics (AUC, 0.82; sensitivity, 92%; specificity, 46%).¹¹ A study involving 382 critically ill AKI patients noted that this biomarker had a hazard ratio of 2.16 (95% confidence interval [CI] 1.32 to 3.53) for predicting dialysis requirement or death.¹¹ And while this test has yet to find its clinical niche, its operating characteristics are well-studied and likely valid. While predicting AKI earlier does not currently result in effective therapy, it may allow more timely discontinuation or avoidance of potentially nephrotoxic medications, ultimately reducing the severity of AKI and its consequences.

In summary, clinicians should be aware of the strengths and limitations of diagnostic tests ordered in AKI patients, as seen with the overly optimistic results in small, flawed UE and FENa studies. While we have taken a step in the right direction with diagnostic and prognostic biomarkers for AKI, we must apply rigorous study design to diagnostic tests under evaluation before adopting them into clinical practice. Only then can we move the field forward and improve patient care.

Disclosure

Nothing to report.

We both attend on the Infectious Disease consult team in Veterans Affairs (VA) Hospitals, and predictably the conversation on afternoon rounds often revolves around antibiotics. When we have those discussions, our focus is not on a need to “preserve antibiotics” so they might be available to some unknown patient in the future. Rather, we are working with the primary team to provide the very best treatment for the patient entrusted to our care in the bed right in front of us. We believe it is in this context—providing optimal patient care—that the current efforts in the United States to improve antibiotic use should be viewed.

The growing challenges posed by antibiotic-resistant infections and the related threat of Clostridium difficile infection combine to sicken more than 2 million people each year and contribute to the deaths of more than 25,000 patients.¹ Improving antibiotic use through antibiotic stewardship is often proposed to hospitalists as an important part of stemming this tide. While this is true, even as infectious disease specialists with strong interests in antimicrobial stewardship we do not find that pitch compelling when we are on clinical service.

What motivates us to optimize antibiotic use for our patients is the evidence that doing so will have direct and immediate benefits to the patients under our care. Improving antibiotic use has been proven to decrease a patient’s risk of acquiring C. difficile infection or an antibiotic-resistant infection not at some ill-defined time in the future, but during their current hospital stay.^2,3 Even more important, support from antibiotic stewardship programs has been proven to improve infection cure rates and reduce the risk of treatment failure for hospitalized patients.⁴ The bottom line of antibiotic stewardship is better patient care. Sometimes that means narrowing or stopping antibiotics to reduce the risks of adverse events. In other cases, like in the treatment of suspected sepsis, it means ensuring patients get broad spectrum antibiotics quickly.

The patient care benefits of improving antibiotic use led the Centers for Disease Control and Prevention (CDC) to issue a call in 2014 for all hospitals to have antibiotic stewardship programs, and to the development of The Core Elements of Hospital Antibiotic Stewardship Programs to support that effort. As of January 1, 2017, antibiotic stewardship programs that incorporate all the CDC core elements became an accreditation requirement of The Joint Commission, and the Centers for Medicare and Medicaid Services has proposed making the same requirement of all hospitals that participate in their payment programs.

This means the question is no longer whether we should have antibiotic stewardship efforts in hospitals, but how we can do this most effectively. As the physicians who provide the most care in hospitals, hospitalists are best positioned to turn stewardship theories into practice. The article from Graber et al.⁵ in this issue of the Journal of Hospital Medicine provides some important information that can help busy hospitalists incorporate stewardship into daily practice. The authors reviewed their experience with implementing stewardship efforts in VA hospitals to see which specific interventions were most likely to translate into improved antibiotic use. Based on their findings, we offer some suggestions for three conditions: pneumonia, urinary tract infection (UTI), and skin and soft tissue infection (SSTI). Together, these conditions drive roughly two-thirds of all antibiotic use in US hospitals.⁶

The literature on treatment of pneumonia is increasingly demonstrating that shorter use of antibiotics is often better.⁷ Even though current guidelines recommend 5 to 7 days of antibiotics for uncomplicated community-acquired pneumonia, average durations of therapy are often longer.⁸ Previous work published in the Journal of Hospital Medicine focused on improving antimicrobial documentation as well as access to local clinical guidelines and implementing a 72-hour antimicrobial “time out” by hospitalists.⁹ When these multimodal interventions tailored for hospitalists were in place, utilization of antibiotics improved. Graber et al.⁵ also found that facility educational programs for prudent antimicrobial use and frequency of de-escalation review were associated with decreased overall antimicrobial use. Providing vague recommendations on antibiotic course, or none at all, at discharge or sign-out can lead to unnecessary antibiotics or an extended course of them. Pneumonia-specific interventions could target duration by outlining antibiotic course in hospitalist progress notes and at hand-off.

Misuse of antibiotics in UTI often stems from overtreatment of asymptomatic bacteriuria or unneeded diagnostic testing. Often, the pivotal step in avoiding unnecessary treatment lies in the ordering of the urine culture.¹⁰ Graber et al.⁵ showed that order sets were associated with decreased antimicrobial use. In the case of UTI, hospitalists could work with the stewardship team to design order sets that guide providers to appropriate reasons for ordering a urine culture. Order sets could also help providers recognize important patient-specific risks for certain antibiotics, such as the risk of C. difficile with fluoroquinolones in an elderly patient. Targeting different steps in overutilization of antibiotics would encompass more prescribers and could lead to reducing other unnecessary testing, which is a current focus for many hospitalists.

Skin and soft tissue infections (SSTI) also offer a specific disease state to use order sets and education to improve duration of antibiotics, decrease overuse of broad spectrum antibiotics, and reduce unnecessary diagnostic studies. For example, gram negative and/or anaerobic coverage are rarely indicated in treating SSTIs but are often used. SSTI-specific order sets and guidelines have already been shown to improve both diagnostic work-up and antibiotic treatment.¹¹ As the providers who manage most of these infections in hospitals, hospitalists are ideally positioned to inform the development of SSTI order sets and pathways. The work by Graber et al.⁵ provides some important insights into how we can effectively implement interventions to improve antibiotic use. These insights have never been more important as more hospitals move toward starting or expanding antibiotic stewardship programs. As leaders in patient safety and quality, and as the most important antibiotic prescribers in hospitals, hospitalists must play a central role in stewardship if we are to make meaningful progress.

Disclosure

Nothing to report.

We both attend on the Infectious Disease consult team in Veterans Affairs (VA) Hospitals, and predictably the conversation on afternoon rounds often revolves around antibiotics. When we have those discussions, our focus is not on a need to “preserve antibiotics” so they might be available to some unknown patient in the future. Rather, we are working with the primary team to provide the very best treatment for the patient entrusted to our care in the bed right in front of us. We believe it is in this context—providing optimal patient care—that the current efforts in the United States to improve antibiotic use should be viewed.

The growing challenges posed by antibiotic-resistant infections and the related threat of Clostridium difficile infection combine to sicken more than 2 million people each year and contribute to the deaths of more than 25,000 patients.¹ Improving antibiotic use through antibiotic stewardship is often proposed to hospitalists as an important part of stemming this tide. While this is true, even as infectious disease specialists with strong interests in antimicrobial stewardship we do not find that pitch compelling when we are on clinical service.

What motivates us to optimize antibiotic use for our patients is the evidence that doing so will have direct and immediate benefits to the patients under our care. Improving antibiotic use has been proven to decrease a patient’s risk of acquiring C. difficile infection or an antibiotic-resistant infection not at some ill-defined time in the future, but during their current hospital stay.^2,3 Even more important, support from antibiotic stewardship programs has been proven to improve infection cure rates and reduce the risk of treatment failure for hospitalized patients.⁴ The bottom line of antibiotic stewardship is better patient care. Sometimes that means narrowing or stopping antibiotics to reduce the risks of adverse events. In other cases, like in the treatment of suspected sepsis, it means ensuring patients get broad spectrum antibiotics quickly.

The patient care benefits of improving antibiotic use led the Centers for Disease Control and Prevention (CDC) to issue a call in 2014 for all hospitals to have antibiotic stewardship programs, and to the development of The Core Elements of Hospital Antibiotic Stewardship Programs to support that effort. As of January 1, 2017, antibiotic stewardship programs that incorporate all the CDC core elements became an accreditation requirement of The Joint Commission, and the Centers for Medicare and Medicaid Services has proposed making the same requirement of all hospitals that participate in their payment programs.

This means the question is no longer whether we should have antibiotic stewardship efforts in hospitals, but how we can do this most effectively. As the physicians who provide the most care in hospitals, hospitalists are best positioned to turn stewardship theories into practice. The article from Graber et al.⁵ in this issue of the Journal of Hospital Medicine provides some important information that can help busy hospitalists incorporate stewardship into daily practice. The authors reviewed their experience with implementing stewardship efforts in VA hospitals to see which specific interventions were most likely to translate into improved antibiotic use. Based on their findings, we offer some suggestions for three conditions: pneumonia, urinary tract infection (UTI), and skin and soft tissue infection (SSTI). Together, these conditions drive roughly two-thirds of all antibiotic use in US hospitals.⁶

The literature on treatment of pneumonia is increasingly demonstrating that shorter use of antibiotics is often better.⁷ Even though current guidelines recommend 5 to 7 days of antibiotics for uncomplicated community-acquired pneumonia, average durations of therapy are often longer.⁸ Previous work published in the Journal of Hospital Medicine focused on improving antimicrobial documentation as well as access to local clinical guidelines and implementing a 72-hour antimicrobial “time out” by hospitalists.⁹ When these multimodal interventions tailored for hospitalists were in place, utilization of antibiotics improved. Graber et al.⁵ also found that facility educational programs for prudent antimicrobial use and frequency of de-escalation review were associated with decreased overall antimicrobial use. Providing vague recommendations on antibiotic course, or none at all, at discharge or sign-out can lead to unnecessary antibiotics or an extended course of them. Pneumonia-specific interventions could target duration by outlining antibiotic course in hospitalist progress notes and at hand-off.

Misuse of antibiotics in UTI often stems from overtreatment of asymptomatic bacteriuria or unneeded diagnostic testing. Often, the pivotal step in avoiding unnecessary treatment lies in the ordering of the urine culture.¹⁰ Graber et al.⁵ showed that order sets were associated with decreased antimicrobial use. In the case of UTI, hospitalists could work with the stewardship team to design order sets that guide providers to appropriate reasons for ordering a urine culture. Order sets could also help providers recognize important patient-specific risks for certain antibiotics, such as the risk of C. difficile with fluoroquinolones in an elderly patient. Targeting different steps in overutilization of antibiotics would encompass more prescribers and could lead to reducing other unnecessary testing, which is a current focus for many hospitalists.

Skin and soft tissue infections (SSTI) also offer a specific disease state to use order sets and education to improve duration of antibiotics, decrease overuse of broad spectrum antibiotics, and reduce unnecessary diagnostic studies. For example, gram negative and/or anaerobic coverage are rarely indicated in treating SSTIs but are often used. SSTI-specific order sets and guidelines have already been shown to improve both diagnostic work-up and antibiotic treatment.¹¹ As the providers who manage most of these infections in hospitals, hospitalists are ideally positioned to inform the development of SSTI order sets and pathways. The work by Graber et al.⁵ provides some important insights into how we can effectively implement interventions to improve antibiotic use. These insights have never been more important as more hospitals move toward starting or expanding antibiotic stewardship programs. As leaders in patient safety and quality, and as the most important antibiotic prescribers in hospitals, hospitalists must play a central role in stewardship if we are to make meaningful progress.

Disclosure

Nothing to report.

We both attend on the Infectious Disease consult team in Veterans Affairs (VA) Hospitals, and predictably the conversation on afternoon rounds often revolves around antibiotics. When we have those discussions, our focus is not on a need to “preserve antibiotics” so they might be available to some unknown patient in the future. Rather, we are working with the primary team to provide the very best treatment for the patient entrusted to our care in the bed right in front of us. We believe it is in this context—providing optimal patient care—that the current efforts in the United States to improve antibiotic use should be viewed.

The growing challenges posed by antibiotic-resistant infections and the related threat of Clostridium difficile infection combine to sicken more than 2 million people each year and contribute to the deaths of more than 25,000 patients.¹ Improving antibiotic use through antibiotic stewardship is often proposed to hospitalists as an important part of stemming this tide. While this is true, even as infectious disease specialists with strong interests in antimicrobial stewardship we do not find that pitch compelling when we are on clinical service.

What motivates us to optimize antibiotic use for our patients is the evidence that doing so will have direct and immediate benefits to the patients under our care. Improving antibiotic use has been proven to decrease a patient’s risk of acquiring C. difficile infection or an antibiotic-resistant infection not at some ill-defined time in the future, but during their current hospital stay.^2,3 Even more important, support from antibiotic stewardship programs has been proven to improve infection cure rates and reduce the risk of treatment failure for hospitalized patients.⁴ The bottom line of antibiotic stewardship is better patient care. Sometimes that means narrowing or stopping antibiotics to reduce the risks of adverse events. In other cases, like in the treatment of suspected sepsis, it means ensuring patients get broad spectrum antibiotics quickly.

The patient care benefits of improving antibiotic use led the Centers for Disease Control and Prevention (CDC) to issue a call in 2014 for all hospitals to have antibiotic stewardship programs, and to the development of The Core Elements of Hospital Antibiotic Stewardship Programs to support that effort. As of January 1, 2017, antibiotic stewardship programs that incorporate all the CDC core elements became an accreditation requirement of The Joint Commission, and the Centers for Medicare and Medicaid Services has proposed making the same requirement of all hospitals that participate in their payment programs.

This means the question is no longer whether we should have antibiotic stewardship efforts in hospitals, but how we can do this most effectively. As the physicians who provide the most care in hospitals, hospitalists are best positioned to turn stewardship theories into practice. The article from Graber et al.⁵ in this issue of the Journal of Hospital Medicine provides some important information that can help busy hospitalists incorporate stewardship into daily practice. The authors reviewed their experience with implementing stewardship efforts in VA hospitals to see which specific interventions were most likely to translate into improved antibiotic use. Based on their findings, we offer some suggestions for three conditions: pneumonia, urinary tract infection (UTI), and skin and soft tissue infection (SSTI). Together, these conditions drive roughly two-thirds of all antibiotic use in US hospitals.⁶

The literature on treatment of pneumonia is increasingly demonstrating that shorter use of antibiotics is often better.⁷ Even though current guidelines recommend 5 to 7 days of antibiotics for uncomplicated community-acquired pneumonia, average durations of therapy are often longer.⁸ Previous work published in the Journal of Hospital Medicine focused on improving antimicrobial documentation as well as access to local clinical guidelines and implementing a 72-hour antimicrobial “time out” by hospitalists.⁹ When these multimodal interventions tailored for hospitalists were in place, utilization of antibiotics improved. Graber et al.⁵ also found that facility educational programs for prudent antimicrobial use and frequency of de-escalation review were associated with decreased overall antimicrobial use. Providing vague recommendations on antibiotic course, or none at all, at discharge or sign-out can lead to unnecessary antibiotics or an extended course of them. Pneumonia-specific interventions could target duration by outlining antibiotic course in hospitalist progress notes and at hand-off.

Misuse of antibiotics in UTI often stems from overtreatment of asymptomatic bacteriuria or unneeded diagnostic testing. Often, the pivotal step in avoiding unnecessary treatment lies in the ordering of the urine culture.¹⁰ Graber et al.⁵ showed that order sets were associated with decreased antimicrobial use. In the case of UTI, hospitalists could work with the stewardship team to design order sets that guide providers to appropriate reasons for ordering a urine culture. Order sets could also help providers recognize important patient-specific risks for certain antibiotics, such as the risk of C. difficile with fluoroquinolones in an elderly patient. Targeting different steps in overutilization of antibiotics would encompass more prescribers and could lead to reducing other unnecessary testing, which is a current focus for many hospitalists.

Skin and soft tissue infections (SSTI) also offer a specific disease state to use order sets and education to improve duration of antibiotics, decrease overuse of broad spectrum antibiotics, and reduce unnecessary diagnostic studies. For example, gram negative and/or anaerobic coverage are rarely indicated in treating SSTIs but are often used. SSTI-specific order sets and guidelines have already been shown to improve both diagnostic work-up and antibiotic treatment.¹¹ As the providers who manage most of these infections in hospitals, hospitalists are ideally positioned to inform the development of SSTI order sets and pathways. The work by Graber et al.⁵ provides some important insights into how we can effectively implement interventions to improve antibiotic use. These insights have never been more important as more hospitals move toward starting or expanding antibiotic stewardship programs. As leaders in patient safety and quality, and as the most important antibiotic prescribers in hospitals, hospitalists must play a central role in stewardship if we are to make meaningful progress.

Disclosure

Nothing to report.

Andrew Auerbach, MD, MPH, SFHM, and Vineet Arora, MD, MPP, MHM, recently were elected to the new member class of American Society for Clinical Investigation (ASCI) for 2017. Members must have “accomplished meritorious, original, creative, and independent investigations in the clinical or allied sciences of medicine and enjoy an unimpeachable moral standing in the medical profession.”

Dr. Auerbach and Dr. Arora are just the third and fourth hospitalists to become ASCI members. Dr. Auerbach is the professor of medicine in residence and director of the research division of hospital medicine at the University of California, San Francisco. Dr. Aurora is associate professor of medicine, assistant dean for scholarship and discovery, and director of graduate medical education’s clinical learning environment innovation at the University of Chicago.

Mark V. Williams, MD, FACP, MHM, director of the University of Kentucky’s Center for Health Services Research (CHSR), recently presented at the International Conference of Hospital Medicine held in Taiwan.

Olevia M. Pitts, MD, SFHM, made history at Research Medical Center in Kansas City, becoming the first woman and the first person of color to be named the facility’s chief medical officer. Dr. Pitts assumed her role at the 131-year-old RMC on January 30.

Greta Boynton, MD, SFHM, was promoted to the role of associate chief medical officer of Sound Physicians’ northeast region. She was elevated from her position as regional medical director for Sound Physicians, a health care organization that serves as a provider practice in 225 hospitals in 38 states.

Dr. Boynton will be charged with overseeing clinical operation of 13 programs, 120 providers, and a team of regional medical directors. She joined Sound Physicians in 2013 as chief hospitalist and divisional chief at Baystate Medical Center in Springfield, Mass. She was, previously, chief of hospital medicine for Eastern Connecticut Health Network, Manchester, from 2008-2013.
 

Business Moves

Sound Physicians, Tacoma, Wash., added to its list of partners on March 1, when Eagle Hospital Medicine Practices, Atlanta, joined the Sound group’s organization. Eagle’s 150 providers in 16 hospitals across the United States raises Sound’s resume to more than 2,500 providers.

Eagle will continue to run its own Locum Connections and Telemedicine divisions.
 

The Society of Hospital Medicine’s Center for Quality Improvement recently was recognized and honored by the Centers for Medicare & Medicaid Services (CMS) for its patient-safety partnership with CMS. The two entities have maintained a relationship since August 2016.

SHM’s Center for QI has participated in weekly CMS webinars to generate strategies intended to limit opioid use, including SHM’s pilot RADEO – Reducing Adverse Drug Events Related to Opioids – program. In January 2017, CMS contacted SHM to provide best practices for patients receiving opioids and better use data to monitor those patients.
 

University of Iowa Health Care, Iowa City, and Van Buren County Hospital, Keosauqua, Iowa, have created a partnership, allowing patients at VBCH access to UI hospitalists through a telemedicine connection. The relationship will allow VBCH patients to remain at their local hospital – located 90 minutes from Iowa City – while getting care and treatment advice from UI hospitalists through videoconferencing and a shared electronic health record.

With their VBCH provider bedside, patients meet face-to–virtual face with the UI hospitalist during twice-daily virtual rounding.
 

Unity Medical Center, Manchester, Tenn., recently partnered with physician-owned and -operated Concord Medical Group, Knoxville, Tenn., to provide hospitalist services at its facility in Manchester. Unity now will have hospitalists on duty 24 hours per day thanks to the relationship with Concord, a hospital management and staffing specialist group.

Andrew Auerbach, MD, MPH, SFHM, and Vineet Arora, MD, MPP, MHM, recently were elected to the new member class of American Society for Clinical Investigation (ASCI) for 2017. Members must have “accomplished meritorious, original, creative, and independent investigations in the clinical or allied sciences of medicine and enjoy an unimpeachable moral standing in the medical profession.”

Dr. Auerbach and Dr. Arora are just the third and fourth hospitalists to become ASCI members. Dr. Auerbach is the professor of medicine in residence and director of the research division of hospital medicine at the University of California, San Francisco. Dr. Aurora is associate professor of medicine, assistant dean for scholarship and discovery, and director of graduate medical education’s clinical learning environment innovation at the University of Chicago.

Mark V. Williams, MD, FACP, MHM, director of the University of Kentucky’s Center for Health Services Research (CHSR), recently presented at the International Conference of Hospital Medicine held in Taiwan.

Olevia M. Pitts, MD, SFHM, made history at Research Medical Center in Kansas City, becoming the first woman and the first person of color to be named the facility’s chief medical officer. Dr. Pitts assumed her role at the 131-year-old RMC on January 30.

Greta Boynton, MD, SFHM, was promoted to the role of associate chief medical officer of Sound Physicians’ northeast region. She was elevated from her position as regional medical director for Sound Physicians, a health care organization that serves as a provider practice in 225 hospitals in 38 states.

Dr. Boynton will be charged with overseeing clinical operation of 13 programs, 120 providers, and a team of regional medical directors. She joined Sound Physicians in 2013 as chief hospitalist and divisional chief at Baystate Medical Center in Springfield, Mass. She was, previously, chief of hospital medicine for Eastern Connecticut Health Network, Manchester, from 2008-2013.
 

Business Moves

Sound Physicians, Tacoma, Wash., added to its list of partners on March 1, when Eagle Hospital Medicine Practices, Atlanta, joined the Sound group’s organization. Eagle’s 150 providers in 16 hospitals across the United States raises Sound’s resume to more than 2,500 providers.

Eagle will continue to run its own Locum Connections and Telemedicine divisions.
 

The Society of Hospital Medicine’s Center for Quality Improvement recently was recognized and honored by the Centers for Medicare & Medicaid Services (CMS) for its patient-safety partnership with CMS. The two entities have maintained a relationship since August 2016.

SHM’s Center for QI has participated in weekly CMS webinars to generate strategies intended to limit opioid use, including SHM’s pilot RADEO – Reducing Adverse Drug Events Related to Opioids – program. In January 2017, CMS contacted SHM to provide best practices for patients receiving opioids and better use data to monitor those patients.
 

University of Iowa Health Care, Iowa City, and Van Buren County Hospital, Keosauqua, Iowa, have created a partnership, allowing patients at VBCH access to UI hospitalists through a telemedicine connection. The relationship will allow VBCH patients to remain at their local hospital – located 90 minutes from Iowa City – while getting care and treatment advice from UI hospitalists through videoconferencing and a shared electronic health record.

With their VBCH provider bedside, patients meet face-to–virtual face with the UI hospitalist during twice-daily virtual rounding.
 

Unity Medical Center, Manchester, Tenn., recently partnered with physician-owned and -operated Concord Medical Group, Knoxville, Tenn., to provide hospitalist services at its facility in Manchester. Unity now will have hospitalists on duty 24 hours per day thanks to the relationship with Concord, a hospital management and staffing specialist group.

Andrew Auerbach, MD, MPH, SFHM, and Vineet Arora, MD, MPP, MHM, recently were elected to the new member class of American Society for Clinical Investigation (ASCI) for 2017. Members must have “accomplished meritorious, original, creative, and independent investigations in the clinical or allied sciences of medicine and enjoy an unimpeachable moral standing in the medical profession.”

Dr. Auerbach and Dr. Arora are just the third and fourth hospitalists to become ASCI members. Dr. Auerbach is the professor of medicine in residence and director of the research division of hospital medicine at the University of California, San Francisco. Dr. Aurora is associate professor of medicine, assistant dean for scholarship and discovery, and director of graduate medical education’s clinical learning environment innovation at the University of Chicago.

Mark V. Williams, MD, FACP, MHM, director of the University of Kentucky’s Center for Health Services Research (CHSR), recently presented at the International Conference of Hospital Medicine held in Taiwan.

Olevia M. Pitts, MD, SFHM, made history at Research Medical Center in Kansas City, becoming the first woman and the first person of color to be named the facility’s chief medical officer. Dr. Pitts assumed her role at the 131-year-old RMC on January 30.

Greta Boynton, MD, SFHM, was promoted to the role of associate chief medical officer of Sound Physicians’ northeast region. She was elevated from her position as regional medical director for Sound Physicians, a health care organization that serves as a provider practice in 225 hospitals in 38 states.

Dr. Boynton will be charged with overseeing clinical operation of 13 programs, 120 providers, and a team of regional medical directors. She joined Sound Physicians in 2013 as chief hospitalist and divisional chief at Baystate Medical Center in Springfield, Mass. She was, previously, chief of hospital medicine for Eastern Connecticut Health Network, Manchester, from 2008-2013.
 

Business Moves

Sound Physicians, Tacoma, Wash., added to its list of partners on March 1, when Eagle Hospital Medicine Practices, Atlanta, joined the Sound group’s organization. Eagle’s 150 providers in 16 hospitals across the United States raises Sound’s resume to more than 2,500 providers.

Eagle will continue to run its own Locum Connections and Telemedicine divisions.
 

The Society of Hospital Medicine’s Center for Quality Improvement recently was recognized and honored by the Centers for Medicare & Medicaid Services (CMS) for its patient-safety partnership with CMS. The two entities have maintained a relationship since August 2016.

SHM’s Center for QI has participated in weekly CMS webinars to generate strategies intended to limit opioid use, including SHM’s pilot RADEO – Reducing Adverse Drug Events Related to Opioids – program. In January 2017, CMS contacted SHM to provide best practices for patients receiving opioids and better use data to monitor those patients.
 

University of Iowa Health Care, Iowa City, and Van Buren County Hospital, Keosauqua, Iowa, have created a partnership, allowing patients at VBCH access to UI hospitalists through a telemedicine connection. The relationship will allow VBCH patients to remain at their local hospital – located 90 minutes from Iowa City – while getting care and treatment advice from UI hospitalists through videoconferencing and a shared electronic health record.

With their VBCH provider bedside, patients meet face-to–virtual face with the UI hospitalist during twice-daily virtual rounding.
 

Unity Medical Center, Manchester, Tenn., recently partnered with physician-owned and -operated Concord Medical Group, Knoxville, Tenn., to provide hospitalist services at its facility in Manchester. Unity now will have hospitalists on duty 24 hours per day thanks to the relationship with Concord, a hospital management and staffing specialist group.

WASHINGTON – The use of digoxin by Swedish Heart Failure Registry participants with heart failure with reduced ejection fraction was associated with significantly increased risk of all-cause mortality if they had concomitant paroxysmal atrial fibrillation or were in normal sinus rhythm, Gianluigi Savarese, MD, reported at the annual meeting of the American College of Cardiology.

In contrast, digoxin in Swedish patients with heart failure with reduced ejection fraction (HFrEF) and permanent atrial fibrillation (AF) was associated with a reduced risk of heart failure hospitalization but had no impact on mortality, added Dr. Savarese of the Karolinska Institute in Stockholm.

The Swedish Heart Failure Registry includes the majority of heart failure patients in that country. Data on 80 variables gets collected for each participant.

Dr. Savarese reported on 23,708 Swedes with HFrEF, 18% of whom were on digoxin. In a multivariate Cox regression analysis adjusted for numerous potential confounders, the use of digoxin was associated with an 8% increased risk of all-cause mortality and a 10% lower risk of heart failure hospitalizations during up to 11 years of follow-up.

In the 12,162 patients with HFrEF and comorbid AF, 30% of whom were on digoxin, the drug was associated with a 12% reduction in heart failure hospitalizations and had no effect on all-cause mortality.

In contrast, among patients with HFrEF without AF, 5% of whom were taking digoxin, use of the drug was associated with an adjusted 31% increase in mortality risk. But digoxin didn’t affect the risk of heart failure hospitalization one way or the other in this group.

Stratifying subjects by their type of AF, the use of digoxin in patients with HFrEF and permanent AF was associated with a 16% reduction in risk of heart failure hospitalization with no impact on mortality. In contrast, among the 2,723 patients with HFrEF and paroxysmal AF, digoxin was associated with a 29% increase in the risk of mortality and no effect on hospitalization.

Current ACC/American Heart Association heart failure guidelines give digoxin a strong Class IIa recommendation for reducing heart failure hospitalizations in patients with HFrEF. European Society of Cardiology guidelines provide a Class IIb recommendation for digoxin to reduce the risk of hospitalization in patients with symptomatic HFrEF in normal sinus rhythm.

Dr. Savarese said he and his coinvestigators decided to examine the impact of digoxin in the Swedish Heart Failure Registry because despite the guideline support for the drug’s use, recent years have brought conflicting data regarding digoxin’s impact on mortality. For example, a meta-analysis of nine studies in more than 235,000 AF patients, seven studies in patients with heart failure, and three in patients with both disorders showed that digoxin was associated with a 29% increased mortality risk in AF patients and a 14% increase in those with heart failure (Eur Heart J. 2015 Jul 21;36[28]:1831-8).

Moreover, at a late-breaking clinical trial session elsewhere at ACC 17, a secondary analysis of the roughly 18,000-patient ARISTOTLE trial came down emphatically on the side of avoiding the venerable drug in patients with AF, where it was found to be associated with a fourfold increased risk of sudden death.

Session comoderator Lee R. Goldberg, MD, medical director of the University of Pennsylvania Heart Failure and Transplantation Program in Philadelphia, observed that the use of digoxin has become quite controversial. He posed a question to Dr. Savarese: “Every few months someone writes the last paper on digoxin as they look at thousands of patients, and then there’s always a new paper. If you were to rewrite the guidelines now, what would you recommend for digoxin?”

Dr. Savarese replied that the current guidelines rely heavily upon the results of a 20-year-old randomized, double-blind, placebo-controlled trial of digoxin in heart failure (N Engl J Med. 1997 Feb 20;336[8]:525-33). Those study participants look nothing at all like the heart failure patients physicians see today in clinical practice. Hardly any of them were on what today is guideline-directed medical therapy with a beta-blocker or mineralocorticoid receptor antagonist. So the trial’s applicability is dubious.

“Our Swedish data are observational. They are hypothesis-generating. They should drive trialists to design a new trial of digoxin. But I think we all know that’s not going to happen. So actually I don’t think there is still space for a IIb or IIa recommendation for digoxin in the guidelines,” Dr. Savarese said.

He reported having no financial conflicts.

[email protected]

WASHINGTON – The use of digoxin by Swedish Heart Failure Registry participants with heart failure with reduced ejection fraction was associated with significantly increased risk of all-cause mortality if they had concomitant paroxysmal atrial fibrillation or were in normal sinus rhythm, Gianluigi Savarese, MD, reported at the annual meeting of the American College of Cardiology.

In contrast, digoxin in Swedish patients with heart failure with reduced ejection fraction (HFrEF) and permanent atrial fibrillation (AF) was associated with a reduced risk of heart failure hospitalization but had no impact on mortality, added Dr. Savarese of the Karolinska Institute in Stockholm.

The Swedish Heart Failure Registry includes the majority of heart failure patients in that country. Data on 80 variables gets collected for each participant.

Dr. Savarese reported on 23,708 Swedes with HFrEF, 18% of whom were on digoxin. In a multivariate Cox regression analysis adjusted for numerous potential confounders, the use of digoxin was associated with an 8% increased risk of all-cause mortality and a 10% lower risk of heart failure hospitalizations during up to 11 years of follow-up.

In the 12,162 patients with HFrEF and comorbid AF, 30% of whom were on digoxin, the drug was associated with a 12% reduction in heart failure hospitalizations and had no effect on all-cause mortality.

In contrast, among patients with HFrEF without AF, 5% of whom were taking digoxin, use of the drug was associated with an adjusted 31% increase in mortality risk. But digoxin didn’t affect the risk of heart failure hospitalization one way or the other in this group.

Stratifying subjects by their type of AF, the use of digoxin in patients with HFrEF and permanent AF was associated with a 16% reduction in risk of heart failure hospitalization with no impact on mortality. In contrast, among the 2,723 patients with HFrEF and paroxysmal AF, digoxin was associated with a 29% increase in the risk of mortality and no effect on hospitalization.

Current ACC/American Heart Association heart failure guidelines give digoxin a strong Class IIa recommendation for reducing heart failure hospitalizations in patients with HFrEF. European Society of Cardiology guidelines provide a Class IIb recommendation for digoxin to reduce the risk of hospitalization in patients with symptomatic HFrEF in normal sinus rhythm.

Dr. Savarese said he and his coinvestigators decided to examine the impact of digoxin in the Swedish Heart Failure Registry because despite the guideline support for the drug’s use, recent years have brought conflicting data regarding digoxin’s impact on mortality. For example, a meta-analysis of nine studies in more than 235,000 AF patients, seven studies in patients with heart failure, and three in patients with both disorders showed that digoxin was associated with a 29% increased mortality risk in AF patients and a 14% increase in those with heart failure (Eur Heart J. 2015 Jul 21;36[28]:1831-8).

Moreover, at a late-breaking clinical trial session elsewhere at ACC 17, a secondary analysis of the roughly 18,000-patient ARISTOTLE trial came down emphatically on the side of avoiding the venerable drug in patients with AF, where it was found to be associated with a fourfold increased risk of sudden death.

Session comoderator Lee R. Goldberg, MD, medical director of the University of Pennsylvania Heart Failure and Transplantation Program in Philadelphia, observed that the use of digoxin has become quite controversial. He posed a question to Dr. Savarese: “Every few months someone writes the last paper on digoxin as they look at thousands of patients, and then there’s always a new paper. If you were to rewrite the guidelines now, what would you recommend for digoxin?”

Dr. Savarese replied that the current guidelines rely heavily upon the results of a 20-year-old randomized, double-blind, placebo-controlled trial of digoxin in heart failure (N Engl J Med. 1997 Feb 20;336[8]:525-33). Those study participants look nothing at all like the heart failure patients physicians see today in clinical practice. Hardly any of them were on what today is guideline-directed medical therapy with a beta-blocker or mineralocorticoid receptor antagonist. So the trial’s applicability is dubious.

“Our Swedish data are observational. They are hypothesis-generating. They should drive trialists to design a new trial of digoxin. But I think we all know that’s not going to happen. So actually I don’t think there is still space for a IIb or IIa recommendation for digoxin in the guidelines,” Dr. Savarese said.

He reported having no financial conflicts.

[email protected]

WASHINGTON – The use of digoxin by Swedish Heart Failure Registry participants with heart failure with reduced ejection fraction was associated with significantly increased risk of all-cause mortality if they had concomitant paroxysmal atrial fibrillation or were in normal sinus rhythm, Gianluigi Savarese, MD, reported at the annual meeting of the American College of Cardiology.

In contrast, digoxin in Swedish patients with heart failure with reduced ejection fraction (HFrEF) and permanent atrial fibrillation (AF) was associated with a reduced risk of heart failure hospitalization but had no impact on mortality, added Dr. Savarese of the Karolinska Institute in Stockholm.

The Swedish Heart Failure Registry includes the majority of heart failure patients in that country. Data on 80 variables gets collected for each participant.

Dr. Savarese reported on 23,708 Swedes with HFrEF, 18% of whom were on digoxin. In a multivariate Cox regression analysis adjusted for numerous potential confounders, the use of digoxin was associated with an 8% increased risk of all-cause mortality and a 10% lower risk of heart failure hospitalizations during up to 11 years of follow-up.

In the 12,162 patients with HFrEF and comorbid AF, 30% of whom were on digoxin, the drug was associated with a 12% reduction in heart failure hospitalizations and had no effect on all-cause mortality.

In contrast, among patients with HFrEF without AF, 5% of whom were taking digoxin, use of the drug was associated with an adjusted 31% increase in mortality risk. But digoxin didn’t affect the risk of heart failure hospitalization one way or the other in this group.

Stratifying subjects by their type of AF, the use of digoxin in patients with HFrEF and permanent AF was associated with a 16% reduction in risk of heart failure hospitalization with no impact on mortality. In contrast, among the 2,723 patients with HFrEF and paroxysmal AF, digoxin was associated with a 29% increase in the risk of mortality and no effect on hospitalization.

Current ACC/American Heart Association heart failure guidelines give digoxin a strong Class IIa recommendation for reducing heart failure hospitalizations in patients with HFrEF. European Society of Cardiology guidelines provide a Class IIb recommendation for digoxin to reduce the risk of hospitalization in patients with symptomatic HFrEF in normal sinus rhythm.

Dr. Savarese said he and his coinvestigators decided to examine the impact of digoxin in the Swedish Heart Failure Registry because despite the guideline support for the drug’s use, recent years have brought conflicting data regarding digoxin’s impact on mortality. For example, a meta-analysis of nine studies in more than 235,000 AF patients, seven studies in patients with heart failure, and three in patients with both disorders showed that digoxin was associated with a 29% increased mortality risk in AF patients and a 14% increase in those with heart failure (Eur Heart J. 2015 Jul 21;36[28]:1831-8).

Moreover, at a late-breaking clinical trial session elsewhere at ACC 17, a secondary analysis of the roughly 18,000-patient ARISTOTLE trial came down emphatically on the side of avoiding the venerable drug in patients with AF, where it was found to be associated with a fourfold increased risk of sudden death.

Session comoderator Lee R. Goldberg, MD, medical director of the University of Pennsylvania Heart Failure and Transplantation Program in Philadelphia, observed that the use of digoxin has become quite controversial. He posed a question to Dr. Savarese: “Every few months someone writes the last paper on digoxin as they look at thousands of patients, and then there’s always a new paper. If you were to rewrite the guidelines now, what would you recommend for digoxin?”

Dr. Savarese replied that the current guidelines rely heavily upon the results of a 20-year-old randomized, double-blind, placebo-controlled trial of digoxin in heart failure (N Engl J Med. 1997 Feb 20;336[8]:525-33). Those study participants look nothing at all like the heart failure patients physicians see today in clinical practice. Hardly any of them were on what today is guideline-directed medical therapy with a beta-blocker or mineralocorticoid receptor antagonist. So the trial’s applicability is dubious.

“Our Swedish data are observational. They are hypothesis-generating. They should drive trialists to design a new trial of digoxin. But I think we all know that’s not going to happen. So actually I don’t think there is still space for a IIb or IIa recommendation for digoxin in the guidelines,” Dr. Savarese said.

He reported having no financial conflicts.

[email protected]

Medicaid acceptance was 55% among family physicians in the 2017 edition of an ongoing survey conducted in 15 large cities by physician recruitment firm Merritt Hawkins.

That was up from almost 52% in the previous survey, conducted in 2014, but lower than the average of 64% for FPs in 15 midsized cities that were included for the first time in 2017, the company reported.

There was one large city with a Medicaid acceptance rate of 100% – Minneapolis (up from 35% in 2014) – along with three midsized cities – Billings, Mt.; Dayton, Ohio; and Fargo, N.D. The lowest rate among the large cities was in Denver (20%), with the midsized basement occupied by Lafayette, La., at 20%, Merritt Hawkins reported.

[email protected]

Medicaid acceptance was 55% among family physicians in the 2017 edition of an ongoing survey conducted in 15 large cities by physician recruitment firm Merritt Hawkins.

That was up from almost 52% in the previous survey, conducted in 2014, but lower than the average of 64% for FPs in 15 midsized cities that were included for the first time in 2017, the company reported.

There was one large city with a Medicaid acceptance rate of 100% – Minneapolis (up from 35% in 2014) – along with three midsized cities – Billings, Mt.; Dayton, Ohio; and Fargo, N.D. The lowest rate among the large cities was in Denver (20%), with the midsized basement occupied by Lafayette, La., at 20%, Merritt Hawkins reported.

[email protected]

Medicaid acceptance was 55% among family physicians in the 2017 edition of an ongoing survey conducted in 15 large cities by physician recruitment firm Merritt Hawkins.

That was up from almost 52% in the previous survey, conducted in 2014, but lower than the average of 64% for FPs in 15 midsized cities that were included for the first time in 2017, the company reported.

There was one large city with a Medicaid acceptance rate of 100% – Minneapolis (up from 35% in 2014) – along with three midsized cities – Billings, Mt.; Dayton, Ohio; and Fargo, N.D. The lowest rate among the large cities was in Denver (20%), with the midsized basement occupied by Lafayette, La., at 20%, Merritt Hawkins reported.

[email protected]

SAN FRANCISCO – Procrastination, disorganization, indecisiveness, and perfectionism each are significant independent predictors of hoarding severity, even though none of these associated factors is included in the DSM-5 diagnostic criteria for hoarding disorder, according to Sanjaya Saxena, MD.

Of these four associated factors, disorganization and procrastination had the strongest correlation with hoarding severity in his study. Patients meeting the DSM-5 criteria for hoarding disorder scored significantly higher on measures of disorganization and procrastination than did patients with nonhoarding obsessive-compulsive disorder or anxiety disorders, said Dr. Saxena, professor of psychiatry and director of the obsessive-compulsive disorders program at the University of California, San Diego.

Bruce Jancin/Frontline Medical News

[email protected]

SAN FRANCISCO – Procrastination, disorganization, indecisiveness, and perfectionism each are significant independent predictors of hoarding severity, even though none of these associated factors is included in the DSM-5 diagnostic criteria for hoarding disorder, according to Sanjaya Saxena, MD.

Of these four associated factors, disorganization and procrastination had the strongest correlation with hoarding severity in his study. Patients meeting the DSM-5 criteria for hoarding disorder scored significantly higher on measures of disorganization and procrastination than did patients with nonhoarding obsessive-compulsive disorder or anxiety disorders, said Dr. Saxena, professor of psychiatry and director of the obsessive-compulsive disorders program at the University of California, San Diego.

Bruce Jancin/Frontline Medical News

[email protected]

SAN FRANCISCO – Procrastination, disorganization, indecisiveness, and perfectionism each are significant independent predictors of hoarding severity, even though none of these associated factors is included in the DSM-5 diagnostic criteria for hoarding disorder, according to Sanjaya Saxena, MD.

Of these four associated factors, disorganization and procrastination had the strongest correlation with hoarding severity in his study. Patients meeting the DSM-5 criteria for hoarding disorder scored significantly higher on measures of disorganization and procrastination than did patients with nonhoarding obsessive-compulsive disorder or anxiety disorders, said Dr. Saxena, professor of psychiatry and director of the obsessive-compulsive disorders program at the University of California, San Diego.

Bruce Jancin/Frontline Medical News

[email protected]

SAN FRANCISCO – Drinking to alleviate mood or anxiety symptoms is responsible for 12%-16% of cases of new-onset alcohol use disorder in affected individuals, Jitender Sareen, MD, said at the annual conference of the Anxiety and Depression Association of America.

Similarly, the use of prescription or nonprescription drugs to self-medicate mood or anxiety symptoms accounts for 20% of new-onset drug use disorders in this population, added Dr. Sareen, professor and head of the department of psychiatry at the University of Manitoba in Winnipeg.

Bruce Jancin/Frontline Medical News

[email protected]

SAN FRANCISCO – Drinking to alleviate mood or anxiety symptoms is responsible for 12%-16% of cases of new-onset alcohol use disorder in affected individuals, Jitender Sareen, MD, said at the annual conference of the Anxiety and Depression Association of America.

Similarly, the use of prescription or nonprescription drugs to self-medicate mood or anxiety symptoms accounts for 20% of new-onset drug use disorders in this population, added Dr. Sareen, professor and head of the department of psychiatry at the University of Manitoba in Winnipeg.

Bruce Jancin/Frontline Medical News

[email protected]

SAN FRANCISCO – Drinking to alleviate mood or anxiety symptoms is responsible for 12%-16% of cases of new-onset alcohol use disorder in affected individuals, Jitender Sareen, MD, said at the annual conference of the Anxiety and Depression Association of America.

Similarly, the use of prescription or nonprescription drugs to self-medicate mood or anxiety symptoms accounts for 20% of new-onset drug use disorders in this population, added Dr. Sareen, professor and head of the department of psychiatry at the University of Manitoba in Winnipeg.

Bruce Jancin/Frontline Medical News

[email protected]

BIRMINGHAM, ENGLAND – A “durable clinical response and stabilization of structural damage” was observed at 3 years of follow-up in the Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND) study.

Désirée van der Heijde, MD, PhD, who reported the findings of the EXTEND study at the British Society for Rheumatology annual conference, noted that the benefit was seen regardless of the initial treatment that had been given at baseline.

Sara Freeman/Frontline Medical News

BIRMINGHAM, ENGLAND – A “durable clinical response and stabilization of structural damage” was observed at 3 years of follow-up in the Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND) study.

Désirée van der Heijde, MD, PhD, who reported the findings of the EXTEND study at the British Society for Rheumatology annual conference, noted that the benefit was seen regardless of the initial treatment that had been given at baseline.

Sara Freeman/Frontline Medical News

BIRMINGHAM, ENGLAND – A “durable clinical response and stabilization of structural damage” was observed at 3 years of follow-up in the Long Term Evaluation of Sarilumab in Rheumatoid Arthritis Patients (SARIL-RA-EXTEND) study.

Désirée van der Heijde, MD, PhD, who reported the findings of the EXTEND study at the British Society for Rheumatology annual conference, noted that the benefit was seen regardless of the initial treatment that had been given at baseline.

Sara Freeman/Frontline Medical News