Schizophrenia has a heterogeneous presentation including both positive and negative symptoms. It is a relatively common disorder, affecting 0.7% of the world’s population.^1,2 Schizophrenia is defined by abnormalities in two or more of five domains:³

• Delusions,
• Hallucinations,
• Disorganized thinking/speech (eg, frequent derailment or incoherence),
• Grossly disorganized or abnormal motor behavior (including catatonia), or
• Negative symptoms (ie, diminished emotional expression or avolition).

Schizophrenia is defined as having two or more of the above domains. Each must present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these must be delusions, hallucinations, or disorganized speech. This must cause dysfunction in a major area, such as work, interpersonal relations, or self-care. Signs of the disturbance persist for at least 6 months. If mood symptoms exist, they may only be present for a minority of the total duration of symptoms. Symptoms are not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication) or another medical condition.³

If symptoms are present for less than 1 month, then the diagnosis is brief psychotic disorder. If symptoms are present between 1 month and 6 months, then the diagnosis is schizophreniform disorder. If a patient has only delusions but does not hallucinate; possesses disorganized speech, grossly disorganized, or catatonic behavior; and negative symptoms, then the diagnosis is delusional disorder.

The exact pathophysiology of schizophrenia is not known at this time. However, it is theorized to be a mix of biological and environmental factors leading to dysfunction of the neurotransmitters dopamine and glutamate, as well as structural changes to the brain.²

Methods

There is an abundance of research on schizophrenia in the psychiatry literature; however, much of this deals with chronic management in patients with established diagnoses, thus this may be hard to translate into the realities of emergency practice. At the same time, although schizophrenia is discussed in the emergency medicine literature, most ED-based research is performed in patients with undifferentiated agitation and not specifically on one diagnostic subset. Therefore, a narrative review was utilized in order to focus in on studies that are relevant to emergency practice.

A narrative literature search was performed utilizing PubMed, the Cochrane database, and American Psychiatric Association Practice Alerts for the past 3 years; bibliographies of major psychiatric textbooks; and reviews and clinical policies in the National Guidelines Clearinghouse.

Epidemiology

The lifetime prevalence of schizophrenia is approximately 0.3% to 0.7%.² In addition, schizophrenia is a frequently deadly disease as one meta-analysis found lifetime suicide to be 4.9 %, which is far higher than the average risk in the United States,⁴ which is approximately 0.5%. From 1992 to 2000 there has been a 15% increase in ED visits for psychiatric problems.⁵ Patients with schizophrenia have been found to be significantly more likely to be “high utilizers” of ED services in comparison to those with other psychiatric diagnoses.⁶

The increase in psychiatric presentations to EDs is coupled with a lack of psychiatrists in many areas of the United States. The American Hospital Association has reported that 40% of American hospitals have difficulty maintaining adequate psychiatric coverage to meet patient demand in the ED, forcing many emergency medicine physicians to act as a primary psychiatrist.⁷

Differential Diagnosis

The characteristic symptoms of schizophrenia can be present in many other illnesses; therefore, the emergency clinician must be able to distinguish schizophrenia from other illnesses presenting with a psychotic component. Furthermore, schizophrenia is a diagnosis of exclusion as the diagnosis can only be made after all medical etiologies of the symptoms have been excluded.

Items on the differential include delirium, a substance induced psychosis,⁸ which can be caused by both substance intoxication and substance withdrawal; as well as psychosis caused by another medical condition.⁸ It should be stressed that a prior diagnosis of schizophrenia does not rule out a medical etiology of a patient’s current psychotic episode; therefore, a thorough history and examination is fundamental, even in patients with a known history of psychiatric illness. Moreover, many patients with schizophrenia present with a medical chief complaint, despite being symptomatic regarding their schizophrenia. In the latter case, providers must be vigilant regarding any medical comorbidities, particularly when patients are actively psychotic.

Finally, within the psychiatric disorders there are multiple disorders other than schizophrenia that may have psychotic features, including depression with psychotic features, bipolar disorder with psychotic features, and the other schizophrenia spectrum disorders; including brief psychotic disorder, schizophreniform disorder, schizoaffective disorder, and delusional disorder.

Emergency Department Evaluation

The process of evaluation of psychiatric patients who present to the ED should be directed towards a determination as to whether hospitalization is warranted, treatment of underlying medical condition is needed, or psychiatric care is indicated. New onset of psychiatric illness will commonly call for extensive evaluation, whereas patients with chronic schizophrenia may not need testing but may need psychiatric hospitalization.⁹ Additionally, emergency clinicians are frequently requested to preform “medical clearance” by their psychiatrist colleagues, before a patient can be transferred to a psychiatry department or psychiatric hospital. However, this is a poor term and a better nomenclature would be “assess for medical stability.”⁹ Emergency clinicians are, in essence, being asked whether the patient is medically stable enough for transfer to a unit or hospital where there is little or no medical support. Prior to transfer to a psychiatric unit, a patient’s non-psychiatric medical conditions should be stable enough for outpatient management.

Interacting with Patients Suffering from Psychosis

Although providers should not pretend to interact in the patient’s reality, they should express understanding in what the patient thinks or feels and kindly direct them back to the current situation.¹⁰ It is important for providers in the acute setting to be non-judgmental about reasons for relapse (in particular non-adherence to medication or substance misuse).¹⁰ Challenging the patient, while at times useful, is best done once the patient is stabilized and in a controlled environment.

History

The history should focus on age of onset; prior history of psychiatric symptoms; history of medical illness and use or abuse of illicit substances, as well as medications; the stability of psychotic symptoms; and if hallucinations are present, whether they are auditory or visual in nature.¹⁰ Table 1 highlights the differences between a patient presenting with a psychiatric complaint and the psychotic symptoms secondary to a medical illness. Table 2 provides salient differences between the examination of a patient with psychosis due to a psychiatric illness or another medical condition. Additionally, Table 3 lists various features, which differentiates schizophrenia from other psychiatric illnesses.

Additionally, patients with schizophrenia can become just as physically ill as anyone else; however, they may have difficulty expressing their specific physical complaints. Furthermore, patients with schizophrenia have a pronounced incidence of early death compared to the general population.¹¹ Therefore, performing a simple physical examination and paying attention to vital signs can rule out or detect a great deal of organic pathology.¹²Once a diagnosis of schizophrenia is made, the next priority is to determine whether the patient is a threat to themselves or others and whether this threat is imminent or not. Statements of suicidal or homicidal ideation, intent, and/or plan are the basic methods of screening for danger. However, physicians also need to screen for command auditory hallucinations, prior history of suicidal behavior, and violence. Finally, even in a patient with previously diagnosed schizophrenia, screening must also be done for substance intoxication and withdrawal.

Diagnostic Studies

The indications for diagnostic studies are influenced by whether the presentation is experiencing first break psychoses vs a presentation in a patient with known schizophrenia. In the former case there is a greater need for laboratory and other diagnostic tests. In the latter case minimal testing will likely be necessary. Patients with new onset psychiatric symptoms generally need extensive laboratory and radiographic evaluations, including a computed tomography scan of the head.⁹

For patients who have an established schizophrenia, extensive evidence supports that there is no need for testing and indeed more often results in false positives,^11,13and selective testing based on findings in the history and physical examination is the correct strategy.¹¹

Complicating the decision to obtain laboratory tests is the fact that many psychiatric facilities rely on referring hospitals to perform baseline testing, as they do not have the resources to perform the tests or to manage any identified abnormalities. Therefore, some tests are needed prior to transfer. In addition, at times, baseline laboratory tests are needed prior to starting antipsychotics.¹⁴

Additionally, some tests are unlikely to affect immediate disposition or treatment but may be useful to psychiatrists for long-term treatment planning.¹⁵ A common disagreement between psychiatrists and emergency providers is the urine toxicology screen or a blood alcohol level. Urine toxicology or a blood alcohol level does not usually affect initial treatment and disposition in the ED.^11,16 However, it may be invalid if collected subsequent to a transfer from the ED, and can determine whether a patient requires specific substance use disorder treatment or not.^16-18 Therefore, many psychiatric providers will request a urine toxicology screening or a blood alcohol level before accepting a transfer. Please note, urine toxicology screens only identify a small number of toxic ingestions. Therefore, a negative screen does not eliminate drug abuse or overdose.

Finally, in the case that a diagnostic examination is being done to satisfy a requirement for an institution to accept a patient or to assist in long-term treatment planning, disposition should not be delayed in order to wait for the result to return.¹¹

Treatment

Unfortunately, no level I or II studies have been found that examine the indications for treatment of the psychiatric patient in the ED.⁹ Additionally, in the ED, there is an ill-defined difference between the use of psychotropic medications as an intervention after patient assessment and plan of care, and the use of these medications to control behavior without an assessment and treatment plan.⁹ Therefore, many treatment recommendations have been made based on studies in other settings.

The first line treatment for a patient with schizophrenia is monotherapy with an antipsychotic agent other than clozapine.^19-21 (Clozapine is not used as a first line agent due to its high side effect burden and the testing necessary before starting.) This is supported by multiple randomized controlled trials and is the standard of care.^22-24 The response rates in treatment with antipsychotics in studies specifically designed to examine treatment of first-episode schizophrenia are high, ranging from 46% to 96%.²³ Therefore, the emergency medicine provider can confidently reassure patients and families that antipsychotic medications are effective in treating schizophrenia. Loading doses of antipsychotics should not be used.¹⁹

Although there are only small and inconsistent differences between different antipsychotics, other than clozapine, with respect to efficacy, there are large differences in adverse effect profiles.^25-30Therefore, the choice of antipsychotic medication is generally made based on previous response to individual antipsychotic medications and relative side effects.³¹

If extrapyramidal symptoms, including tardive dyskinesia, are of particular concern to a patient, then second generation or low potency first generation antipsychotics should be used.^25,32 If a patient complains of previous problems with sedation, then haloperidol or aripiprazole should be preferred.²⁵ Haloperidol, aripiprazole, or amisulpride should be considered for patients who are particularly concerned about weight gain, or who may be at the greatest risk of weight gain.²⁵

If there is no response to medication after 4 weeks,³² despite dose optimization, a change in antipsychotic should be considered.^33,34 Where there is partial response, the patient should be re-assessed after 8 weeks unless there are significant adverse effects.^14,19,20,34 A combination of different antipsychotic medications should not be used, except during transitional periods when patients are being switched from one antipsychotic to another, or when used for clozapine augmentation.¹⁴After an acute episode has passed, providers can consider offering depot/long-acting injectable antipsychotic medication to people with schizophrenia who would prefer such treatment; as long acting injectable antipsychotics have been shown to reduce medication non-adherence.^35,36 Long-acting depot antipsychotics should not be used for acute episodes because it may take 3 to 6 months for the medications to reach a stable state.¹⁴Once a patient achieves a remission of their symptoms, patients are recommended to stay on their antipsychotic medication for at least 2 years since their last acute exacerbation.^14,34 For maintenance therapy,the antipsychotic dose should be reduced gradually to the lowest possible effective dose, which should not be lower than half of the effective dose during the acute phase.³⁷

Clozapine should be offered to people with schizophrenia whose illness has not responded adequately to treatment with adequate doses of at least two different antipsychotic drugs.^38-41There is no indication to using dual antipsychotic agents on patients with schizophrenia prior to starting a clozapine trial.^42,43

Non-Pharmacological Intervention

There is strong evidence that people diagnosed with schizophrenia benefit from psychosocial treatments in addition to pharmacological treatment. Multiple randomized controlled studies, as well as national guidelines, have demonstrated cognitive behavioral therapy and family therapy to be effective for the treatment of schizophrenia.^44-51 Particular focuses of therapy include communication skills, problem solving, psychoeducation, and assisting with family conflict,^18,19 which are feasible in an emergency setting.⁵²

Recent studies have shown promise using a “crisis intervention” approach as an alternative option to the hospital or emergency medical services systems. Treatment usually involves a combination of medication as well as counseling (practical help with living skills and support for close family members). After the crisis has been stabilized, sufferers are carefully introduced to other models of care more suited for the chronic phases of psychiatric illnesses.⁵³ This is particularly important as psychosocial instability, such as changes in the psychosocial environment (ie, a primary caretaker going on vacation, or a patient being distanced from their family or support environment) have been associated with relapse.¹⁹

Acute Agitation

The vast majority of patients suffering from mental illness, including schizophrenia, are not violent and only a small proportion of the violence in our society can be attributed to persons who are mentally ill.⁵⁴ Furthermore, people with psychiatric disabilities are far more likely to be victims than perpetrators of violent crime.⁵⁵ However, schizophrenia and related disorders are associated with substantially increased rates of violence and violent offences compared to those who did not, independent of substance use.^56,57 Furthermore, the majority of acute hospital assaults occur in the ED.⁵⁸

Two emergency medicine evidence-based guidelines state a benzodiazepine (lorazepam or midazolam) or a conventional antipsychotic (droperidol or haloperidol) should be used as monotherapy for the treatment of acute undifferentiated agitation in the ED.^12,59 However, in cases of patients with a diagnosis or suspicion of schizophrenia, an antipsychotic should be used in order to start a “disease modifying agent” earlier in the course of treatment.^20,59,60Where possible, the same antipsychotic should be used as monotherapy for treatment of both acute agitation and standing antipsychotic medication.¹³The choice of medication for the treatment of acute agitation should be based on patient preference, past experience of antipsychotic treatment, the adverse effect profile, and concurrent medical history.^19,58 This is supported by a case controlled study, which showed patients’ subjective experiences in the acute phase of treatment affected their long-term adherence to medication.⁶¹

Haloperidol is the most commonly used medication for agitation in patients with schizophrenia.^59,62 When haloperidol is used to treat acute violence, it is almost always used in combination with a benzodiazepine unless medically compromised.^62,63 Intramuscular olanzapine has been shown to be effective in managing acute aggression or agitation in patients with schizophrenia, especially where it is necessary to avoid some of the older treatments. Olanzapine causes fewer movement disorders than halopridol.⁶⁴ Chlorpromazine is available in both per os and intramuscular formulations. However, chlorpromazine is associated with more side effects than other antipsychotics, including a higher incidence of prolonged QT and Torsades.⁶⁵ However, where choices are limited, chlorpromazine may be the only treatment available for acute agitation. If used, the close monitoring of blood pressure is indicated.⁶⁵ Inhaled loxapine received US Food and Drug Administration approval for treatment of acute agitation in 2012.⁶⁶ This is a useful option for an agitated patient who is calm enough to receive an inhaler, but is unable to take medication per os.

Restrictive intervention (restraints or seclusion) should only be used if de-escalation and other preventive strategies, including medication as needed, have failed and there is potential for harm to the patient or other people if no action is taken.⁵⁸

Telepsychiatry Consultation

Telepsychiatry is an approach, where by EDs that do not have access to psychiatrists can see patients in the ED itself, by forming a contract with either psychiatrists or companies to allow a psychiatrist at another location to perform an examination on a patient via video connection and advise the emergency room providers on treatment and intervention. There is very little data in the peer-reviewed literature on the use of telepsychiatry. The literature is limited to case reports, program descriptions, and randomized studies for reliability.^67,68 One randomized controlled trial showed that a telepsychiatry evaluation had a reliable diagnosis and disposition when compared to a face-to-face assessment.⁶⁹ One case control showed reduction in time-to-consult done in the ED, length of stay, and door-to-consult stay, once a telepsychiatry program was initiated.⁷⁰ A large case control study showed that telepsychiatry recipients were more likely to receive 30-day follow-up, 90-day follow-up, and total inpatient length of stay, totaling both initial admission and subsequent admissions.⁷¹ Therefore, it is reasonable for EDs to take advantage of telepsychiatry services if no immediate psychiatrist coverage is available.

Disposition

The primary disposition question regarding a patient presenting with a psychiatric chief complaint to the ED, including schizophrenia, is whether they require a psychiatric admission or not. If a patient requires hospitalization but refuses, the emergency clinician must decide if the patient meets criteria for involuntarily hospitalization. If a patient does not require an inpatient admission or would benefit from an inpatient admission but does not meet criteria for civil commitment, then the next major question is what type of outpatient treatment is sufficient for this particular patient (Figure).

For a patient with schizophrenia to require inpatient psychiatric admission he must be either a danger to himself or others or has failed outpatient treatment. In addition, the patient must currently have undergone a clinical evaluation of any suspected medical illness, and any medical problems the patient is experiencing must be sufficiently stable to allow safe transport and treatment at a psychiatric hospital unit.⁹ If a patient’s medical condition is not sufficiently stable for either transport or hospitalization at a psychiatric hospital but the patient still requires inpatient psychiatric treatment, the patient should be hospitalized on a standard medical ward and receive psychiatric care on that unit.

Patients with mental illness pose an additional challenge, in that their illness often time interferes with their judgment about whether they require treatment. Because of this possible lack of capacity and the potential danger of a patient with mental illness to self or others, most jurisdictions have a legal code that allows for involuntary hospitalization of the mentally ill. However, which patients qualify for involuntary hospitalizations vary by jurisdiction. Case law criteria for emergencies range from a risk of “imminent” harm to self or others to a deterioration in the patient’s mental condition if treatment is halted.⁷² Providers are recommended to familiarize themselves with laws regarding inpatient civil commitment in their particular jurisdiction.

When a patient is being discharged from the ED, either because they do not require a psychiatric inpatient admission or because they don’t meet criteria for involuntary commitment, there are various outpatient dispositions available. Any patient with a diagnosis of schizophrenia should have outpatient follow-up with a mental health provider upon discharge from the ED.

For patients who have a failed community treatment in the past, who do not have a significant support network, or whose disease is too severe for a regular outpatient clinic to handle would be better suited for a disposition to a transitional program over a standard outpatient appointment; such as partial hospitalization programs, intensive outpatient programs, and community mental health treatment teams (CMHT). Assertive community treatment (ACT) teams are a form of CMHT comprised of several disciplines, including nurses, occupational therapists, psychiatrists, psychologists, and social workers.⁷³ A large prospective cohort study found homeless patients to have made gains in multiple spheres of mental health while enrolled in ACT programs, and these benefits were retained after discharge from the ACT program.⁷⁴

Conclusion

Schizophrenia is characterized primarily by delusions, hallucinations, and disorganized thinking. Emergency medicine providers are frequently at the front lines of diagnosing, initiating treatment, and managing relapses for these individuals. As schizophrenia is an exclusion, the primary task of an emergency physician is to rule out all “organic”, for lack of a better term, causes of the psychosis or disordered thinking before making a definitive diagnosis of schizophrenia. As many EDs do not have sufficient psychiatry support and many patients with schizophrenia are using the ED as their location for primary mental health, many emergency physicians are finding themselves acting as the main providers for these individuals. The primary treatment for patients with schizophrenia remains monotherapy with antipsychotic medication. Although the highest-level disposition for a patient with schizophrenia remains the inpatient psychiatry department, there are many transitional dispositions that can bridge the gap between a discharge to standard community care and an inpatient admission.

Schizophrenia has a heterogeneous presentation including both positive and negative symptoms. It is a relatively common disorder, affecting 0.7% of the world’s population.^1,2 Schizophrenia is defined by abnormalities in two or more of five domains:³

• Delusions,
• Hallucinations,
• Disorganized thinking/speech (eg, frequent derailment or incoherence),
• Grossly disorganized or abnormal motor behavior (including catatonia), or
• Negative symptoms (ie, diminished emotional expression or avolition).

Schizophrenia is defined as having two or more of the above domains. Each must present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these must be delusions, hallucinations, or disorganized speech. This must cause dysfunction in a major area, such as work, interpersonal relations, or self-care. Signs of the disturbance persist for at least 6 months. If mood symptoms exist, they may only be present for a minority of the total duration of symptoms. Symptoms are not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication) or another medical condition.³

If symptoms are present for less than 1 month, then the diagnosis is brief psychotic disorder. If symptoms are present between 1 month and 6 months, then the diagnosis is schizophreniform disorder. If a patient has only delusions but does not hallucinate; possesses disorganized speech, grossly disorganized, or catatonic behavior; and negative symptoms, then the diagnosis is delusional disorder.

The exact pathophysiology of schizophrenia is not known at this time. However, it is theorized to be a mix of biological and environmental factors leading to dysfunction of the neurotransmitters dopamine and glutamate, as well as structural changes to the brain.²

Methods

There is an abundance of research on schizophrenia in the psychiatry literature; however, much of this deals with chronic management in patients with established diagnoses, thus this may be hard to translate into the realities of emergency practice. At the same time, although schizophrenia is discussed in the emergency medicine literature, most ED-based research is performed in patients with undifferentiated agitation and not specifically on one diagnostic subset. Therefore, a narrative review was utilized in order to focus in on studies that are relevant to emergency practice.

A narrative literature search was performed utilizing PubMed, the Cochrane database, and American Psychiatric Association Practice Alerts for the past 3 years; bibliographies of major psychiatric textbooks; and reviews and clinical policies in the National Guidelines Clearinghouse.

Epidemiology

The lifetime prevalence of schizophrenia is approximately 0.3% to 0.7%.² In addition, schizophrenia is a frequently deadly disease as one meta-analysis found lifetime suicide to be 4.9 %, which is far higher than the average risk in the United States,⁴ which is approximately 0.5%. From 1992 to 2000 there has been a 15% increase in ED visits for psychiatric problems.⁵ Patients with schizophrenia have been found to be significantly more likely to be “high utilizers” of ED services in comparison to those with other psychiatric diagnoses.⁶

The increase in psychiatric presentations to EDs is coupled with a lack of psychiatrists in many areas of the United States. The American Hospital Association has reported that 40% of American hospitals have difficulty maintaining adequate psychiatric coverage to meet patient demand in the ED, forcing many emergency medicine physicians to act as a primary psychiatrist.⁷

Differential Diagnosis

The characteristic symptoms of schizophrenia can be present in many other illnesses; therefore, the emergency clinician must be able to distinguish schizophrenia from other illnesses presenting with a psychotic component. Furthermore, schizophrenia is a diagnosis of exclusion as the diagnosis can only be made after all medical etiologies of the symptoms have been excluded.

Items on the differential include delirium, a substance induced psychosis,⁸ which can be caused by both substance intoxication and substance withdrawal; as well as psychosis caused by another medical condition.⁸ It should be stressed that a prior diagnosis of schizophrenia does not rule out a medical etiology of a patient’s current psychotic episode; therefore, a thorough history and examination is fundamental, even in patients with a known history of psychiatric illness. Moreover, many patients with schizophrenia present with a medical chief complaint, despite being symptomatic regarding their schizophrenia. In the latter case, providers must be vigilant regarding any medical comorbidities, particularly when patients are actively psychotic.

Finally, within the psychiatric disorders there are multiple disorders other than schizophrenia that may have psychotic features, including depression with psychotic features, bipolar disorder with psychotic features, and the other schizophrenia spectrum disorders; including brief psychotic disorder, schizophreniform disorder, schizoaffective disorder, and delusional disorder.

Emergency Department Evaluation

The process of evaluation of psychiatric patients who present to the ED should be directed towards a determination as to whether hospitalization is warranted, treatment of underlying medical condition is needed, or psychiatric care is indicated. New onset of psychiatric illness will commonly call for extensive evaluation, whereas patients with chronic schizophrenia may not need testing but may need psychiatric hospitalization.⁹ Additionally, emergency clinicians are frequently requested to preform “medical clearance” by their psychiatrist colleagues, before a patient can be transferred to a psychiatry department or psychiatric hospital. However, this is a poor term and a better nomenclature would be “assess for medical stability.”⁹ Emergency clinicians are, in essence, being asked whether the patient is medically stable enough for transfer to a unit or hospital where there is little or no medical support. Prior to transfer to a psychiatric unit, a patient’s non-psychiatric medical conditions should be stable enough for outpatient management.

Interacting with Patients Suffering from Psychosis

Although providers should not pretend to interact in the patient’s reality, they should express understanding in what the patient thinks or feels and kindly direct them back to the current situation.¹⁰ It is important for providers in the acute setting to be non-judgmental about reasons for relapse (in particular non-adherence to medication or substance misuse).¹⁰ Challenging the patient, while at times useful, is best done once the patient is stabilized and in a controlled environment.

History

The history should focus on age of onset; prior history of psychiatric symptoms; history of medical illness and use or abuse of illicit substances, as well as medications; the stability of psychotic symptoms; and if hallucinations are present, whether they are auditory or visual in nature.¹⁰ Table 1 highlights the differences between a patient presenting with a psychiatric complaint and the psychotic symptoms secondary to a medical illness. Table 2 provides salient differences between the examination of a patient with psychosis due to a psychiatric illness or another medical condition. Additionally, Table 3 lists various features, which differentiates schizophrenia from other psychiatric illnesses.

Additionally, patients with schizophrenia can become just as physically ill as anyone else; however, they may have difficulty expressing their specific physical complaints. Furthermore, patients with schizophrenia have a pronounced incidence of early death compared to the general population.¹¹ Therefore, performing a simple physical examination and paying attention to vital signs can rule out or detect a great deal of organic pathology.¹²Once a diagnosis of schizophrenia is made, the next priority is to determine whether the patient is a threat to themselves or others and whether this threat is imminent or not. Statements of suicidal or homicidal ideation, intent, and/or plan are the basic methods of screening for danger. However, physicians also need to screen for command auditory hallucinations, prior history of suicidal behavior, and violence. Finally, even in a patient with previously diagnosed schizophrenia, screening must also be done for substance intoxication and withdrawal.

Diagnostic Studies

The indications for diagnostic studies are influenced by whether the presentation is experiencing first break psychoses vs a presentation in a patient with known schizophrenia. In the former case there is a greater need for laboratory and other diagnostic tests. In the latter case minimal testing will likely be necessary. Patients with new onset psychiatric symptoms generally need extensive laboratory and radiographic evaluations, including a computed tomography scan of the head.⁹

For patients who have an established schizophrenia, extensive evidence supports that there is no need for testing and indeed more often results in false positives,^11,13and selective testing based on findings in the history and physical examination is the correct strategy.¹¹

Complicating the decision to obtain laboratory tests is the fact that many psychiatric facilities rely on referring hospitals to perform baseline testing, as they do not have the resources to perform the tests or to manage any identified abnormalities. Therefore, some tests are needed prior to transfer. In addition, at times, baseline laboratory tests are needed prior to starting antipsychotics.¹⁴

Additionally, some tests are unlikely to affect immediate disposition or treatment but may be useful to psychiatrists for long-term treatment planning.¹⁵ A common disagreement between psychiatrists and emergency providers is the urine toxicology screen or a blood alcohol level. Urine toxicology or a blood alcohol level does not usually affect initial treatment and disposition in the ED.^11,16 However, it may be invalid if collected subsequent to a transfer from the ED, and can determine whether a patient requires specific substance use disorder treatment or not.^16-18 Therefore, many psychiatric providers will request a urine toxicology screening or a blood alcohol level before accepting a transfer. Please note, urine toxicology screens only identify a small number of toxic ingestions. Therefore, a negative screen does not eliminate drug abuse or overdose.

Finally, in the case that a diagnostic examination is being done to satisfy a requirement for an institution to accept a patient or to assist in long-term treatment planning, disposition should not be delayed in order to wait for the result to return.¹¹

Treatment

Unfortunately, no level I or II studies have been found that examine the indications for treatment of the psychiatric patient in the ED.⁹ Additionally, in the ED, there is an ill-defined difference between the use of psychotropic medications as an intervention after patient assessment and plan of care, and the use of these medications to control behavior without an assessment and treatment plan.⁹ Therefore, many treatment recommendations have been made based on studies in other settings.

The first line treatment for a patient with schizophrenia is monotherapy with an antipsychotic agent other than clozapine.^19-21 (Clozapine is not used as a first line agent due to its high side effect burden and the testing necessary before starting.) This is supported by multiple randomized controlled trials and is the standard of care.^22-24 The response rates in treatment with antipsychotics in studies specifically designed to examine treatment of first-episode schizophrenia are high, ranging from 46% to 96%.²³ Therefore, the emergency medicine provider can confidently reassure patients and families that antipsychotic medications are effective in treating schizophrenia. Loading doses of antipsychotics should not be used.¹⁹

Although there are only small and inconsistent differences between different antipsychotics, other than clozapine, with respect to efficacy, there are large differences in adverse effect profiles.^25-30Therefore, the choice of antipsychotic medication is generally made based on previous response to individual antipsychotic medications and relative side effects.³¹

If extrapyramidal symptoms, including tardive dyskinesia, are of particular concern to a patient, then second generation or low potency first generation antipsychotics should be used.^25,32 If a patient complains of previous problems with sedation, then haloperidol or aripiprazole should be preferred.²⁵ Haloperidol, aripiprazole, or amisulpride should be considered for patients who are particularly concerned about weight gain, or who may be at the greatest risk of weight gain.²⁵

If there is no response to medication after 4 weeks,³² despite dose optimization, a change in antipsychotic should be considered.^33,34 Where there is partial response, the patient should be re-assessed after 8 weeks unless there are significant adverse effects.^14,19,20,34 A combination of different antipsychotic medications should not be used, except during transitional periods when patients are being switched from one antipsychotic to another, or when used for clozapine augmentation.¹⁴After an acute episode has passed, providers can consider offering depot/long-acting injectable antipsychotic medication to people with schizophrenia who would prefer such treatment; as long acting injectable antipsychotics have been shown to reduce medication non-adherence.^35,36 Long-acting depot antipsychotics should not be used for acute episodes because it may take 3 to 6 months for the medications to reach a stable state.¹⁴Once a patient achieves a remission of their symptoms, patients are recommended to stay on their antipsychotic medication for at least 2 years since their last acute exacerbation.^14,34 For maintenance therapy,the antipsychotic dose should be reduced gradually to the lowest possible effective dose, which should not be lower than half of the effective dose during the acute phase.³⁷

Clozapine should be offered to people with schizophrenia whose illness has not responded adequately to treatment with adequate doses of at least two different antipsychotic drugs.^38-41There is no indication to using dual antipsychotic agents on patients with schizophrenia prior to starting a clozapine trial.^42,43

Non-Pharmacological Intervention

There is strong evidence that people diagnosed with schizophrenia benefit from psychosocial treatments in addition to pharmacological treatment. Multiple randomized controlled studies, as well as national guidelines, have demonstrated cognitive behavioral therapy and family therapy to be effective for the treatment of schizophrenia.^44-51 Particular focuses of therapy include communication skills, problem solving, psychoeducation, and assisting with family conflict,^18,19 which are feasible in an emergency setting.⁵²

Recent studies have shown promise using a “crisis intervention” approach as an alternative option to the hospital or emergency medical services systems. Treatment usually involves a combination of medication as well as counseling (practical help with living skills and support for close family members). After the crisis has been stabilized, sufferers are carefully introduced to other models of care more suited for the chronic phases of psychiatric illnesses.⁵³ This is particularly important as psychosocial instability, such as changes in the psychosocial environment (ie, a primary caretaker going on vacation, or a patient being distanced from their family or support environment) have been associated with relapse.¹⁹

Acute Agitation

The vast majority of patients suffering from mental illness, including schizophrenia, are not violent and only a small proportion of the violence in our society can be attributed to persons who are mentally ill.⁵⁴ Furthermore, people with psychiatric disabilities are far more likely to be victims than perpetrators of violent crime.⁵⁵ However, schizophrenia and related disorders are associated with substantially increased rates of violence and violent offences compared to those who did not, independent of substance use.^56,57 Furthermore, the majority of acute hospital assaults occur in the ED.⁵⁸

Two emergency medicine evidence-based guidelines state a benzodiazepine (lorazepam or midazolam) or a conventional antipsychotic (droperidol or haloperidol) should be used as monotherapy for the treatment of acute undifferentiated agitation in the ED.^12,59 However, in cases of patients with a diagnosis or suspicion of schizophrenia, an antipsychotic should be used in order to start a “disease modifying agent” earlier in the course of treatment.^20,59,60Where possible, the same antipsychotic should be used as monotherapy for treatment of both acute agitation and standing antipsychotic medication.¹³The choice of medication for the treatment of acute agitation should be based on patient preference, past experience of antipsychotic treatment, the adverse effect profile, and concurrent medical history.^19,58 This is supported by a case controlled study, which showed patients’ subjective experiences in the acute phase of treatment affected their long-term adherence to medication.⁶¹

Haloperidol is the most commonly used medication for agitation in patients with schizophrenia.^59,62 When haloperidol is used to treat acute violence, it is almost always used in combination with a benzodiazepine unless medically compromised.^62,63 Intramuscular olanzapine has been shown to be effective in managing acute aggression or agitation in patients with schizophrenia, especially where it is necessary to avoid some of the older treatments. Olanzapine causes fewer movement disorders than halopridol.⁶⁴ Chlorpromazine is available in both per os and intramuscular formulations. However, chlorpromazine is associated with more side effects than other antipsychotics, including a higher incidence of prolonged QT and Torsades.⁶⁵ However, where choices are limited, chlorpromazine may be the only treatment available for acute agitation. If used, the close monitoring of blood pressure is indicated.⁶⁵ Inhaled loxapine received US Food and Drug Administration approval for treatment of acute agitation in 2012.⁶⁶ This is a useful option for an agitated patient who is calm enough to receive an inhaler, but is unable to take medication per os.

Restrictive intervention (restraints or seclusion) should only be used if de-escalation and other preventive strategies, including medication as needed, have failed and there is potential for harm to the patient or other people if no action is taken.⁵⁸

Telepsychiatry Consultation

Telepsychiatry is an approach, where by EDs that do not have access to psychiatrists can see patients in the ED itself, by forming a contract with either psychiatrists or companies to allow a psychiatrist at another location to perform an examination on a patient via video connection and advise the emergency room providers on treatment and intervention. There is very little data in the peer-reviewed literature on the use of telepsychiatry. The literature is limited to case reports, program descriptions, and randomized studies for reliability.^67,68 One randomized controlled trial showed that a telepsychiatry evaluation had a reliable diagnosis and disposition when compared to a face-to-face assessment.⁶⁹ One case control showed reduction in time-to-consult done in the ED, length of stay, and door-to-consult stay, once a telepsychiatry program was initiated.⁷⁰ A large case control study showed that telepsychiatry recipients were more likely to receive 30-day follow-up, 90-day follow-up, and total inpatient length of stay, totaling both initial admission and subsequent admissions.⁷¹ Therefore, it is reasonable for EDs to take advantage of telepsychiatry services if no immediate psychiatrist coverage is available.

Disposition

The primary disposition question regarding a patient presenting with a psychiatric chief complaint to the ED, including schizophrenia, is whether they require a psychiatric admission or not. If a patient requires hospitalization but refuses, the emergency clinician must decide if the patient meets criteria for involuntarily hospitalization. If a patient does not require an inpatient admission or would benefit from an inpatient admission but does not meet criteria for civil commitment, then the next major question is what type of outpatient treatment is sufficient for this particular patient (Figure).

For a patient with schizophrenia to require inpatient psychiatric admission he must be either a danger to himself or others or has failed outpatient treatment. In addition, the patient must currently have undergone a clinical evaluation of any suspected medical illness, and any medical problems the patient is experiencing must be sufficiently stable to allow safe transport and treatment at a psychiatric hospital unit.⁹ If a patient’s medical condition is not sufficiently stable for either transport or hospitalization at a psychiatric hospital but the patient still requires inpatient psychiatric treatment, the patient should be hospitalized on a standard medical ward and receive psychiatric care on that unit.

Patients with mental illness pose an additional challenge, in that their illness often time interferes with their judgment about whether they require treatment. Because of this possible lack of capacity and the potential danger of a patient with mental illness to self or others, most jurisdictions have a legal code that allows for involuntary hospitalization of the mentally ill. However, which patients qualify for involuntary hospitalizations vary by jurisdiction. Case law criteria for emergencies range from a risk of “imminent” harm to self or others to a deterioration in the patient’s mental condition if treatment is halted.⁷² Providers are recommended to familiarize themselves with laws regarding inpatient civil commitment in their particular jurisdiction.

When a patient is being discharged from the ED, either because they do not require a psychiatric inpatient admission or because they don’t meet criteria for involuntary commitment, there are various outpatient dispositions available. Any patient with a diagnosis of schizophrenia should have outpatient follow-up with a mental health provider upon discharge from the ED.

For patients who have a failed community treatment in the past, who do not have a significant support network, or whose disease is too severe for a regular outpatient clinic to handle would be better suited for a disposition to a transitional program over a standard outpatient appointment; such as partial hospitalization programs, intensive outpatient programs, and community mental health treatment teams (CMHT). Assertive community treatment (ACT) teams are a form of CMHT comprised of several disciplines, including nurses, occupational therapists, psychiatrists, psychologists, and social workers.⁷³ A large prospective cohort study found homeless patients to have made gains in multiple spheres of mental health while enrolled in ACT programs, and these benefits were retained after discharge from the ACT program.⁷⁴

Conclusion

Schizophrenia is characterized primarily by delusions, hallucinations, and disorganized thinking. Emergency medicine providers are frequently at the front lines of diagnosing, initiating treatment, and managing relapses for these individuals. As schizophrenia is an exclusion, the primary task of an emergency physician is to rule out all “organic”, for lack of a better term, causes of the psychosis or disordered thinking before making a definitive diagnosis of schizophrenia. As many EDs do not have sufficient psychiatry support and many patients with schizophrenia are using the ED as their location for primary mental health, many emergency physicians are finding themselves acting as the main providers for these individuals. The primary treatment for patients with schizophrenia remains monotherapy with antipsychotic medication. Although the highest-level disposition for a patient with schizophrenia remains the inpatient psychiatry department, there are many transitional dispositions that can bridge the gap between a discharge to standard community care and an inpatient admission.

Schizophrenia has a heterogeneous presentation including both positive and negative symptoms. It is a relatively common disorder, affecting 0.7% of the world’s population.^1,2 Schizophrenia is defined by abnormalities in two or more of five domains:³

• Delusions,
• Hallucinations,
• Disorganized thinking/speech (eg, frequent derailment or incoherence),
• Grossly disorganized or abnormal motor behavior (including catatonia), or
• Negative symptoms (ie, diminished emotional expression or avolition).

Schizophrenia is defined as having two or more of the above domains. Each must present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these must be delusions, hallucinations, or disorganized speech. This must cause dysfunction in a major area, such as work, interpersonal relations, or self-care. Signs of the disturbance persist for at least 6 months. If mood symptoms exist, they may only be present for a minority of the total duration of symptoms. Symptoms are not attributable to the physiological effects of a substance (eg, a drug of abuse, a medication) or another medical condition.³

If symptoms are present for less than 1 month, then the diagnosis is brief psychotic disorder. If symptoms are present between 1 month and 6 months, then the diagnosis is schizophreniform disorder. If a patient has only delusions but does not hallucinate; possesses disorganized speech, grossly disorganized, or catatonic behavior; and negative symptoms, then the diagnosis is delusional disorder.

The exact pathophysiology of schizophrenia is not known at this time. However, it is theorized to be a mix of biological and environmental factors leading to dysfunction of the neurotransmitters dopamine and glutamate, as well as structural changes to the brain.²

Methods

There is an abundance of research on schizophrenia in the psychiatry literature; however, much of this deals with chronic management in patients with established diagnoses, thus this may be hard to translate into the realities of emergency practice. At the same time, although schizophrenia is discussed in the emergency medicine literature, most ED-based research is performed in patients with undifferentiated agitation and not specifically on one diagnostic subset. Therefore, a narrative review was utilized in order to focus in on studies that are relevant to emergency practice.

A narrative literature search was performed utilizing PubMed, the Cochrane database, and American Psychiatric Association Practice Alerts for the past 3 years; bibliographies of major psychiatric textbooks; and reviews and clinical policies in the National Guidelines Clearinghouse.

Epidemiology

The lifetime prevalence of schizophrenia is approximately 0.3% to 0.7%.² In addition, schizophrenia is a frequently deadly disease as one meta-analysis found lifetime suicide to be 4.9 %, which is far higher than the average risk in the United States,⁴ which is approximately 0.5%. From 1992 to 2000 there has been a 15% increase in ED visits for psychiatric problems.⁵ Patients with schizophrenia have been found to be significantly more likely to be “high utilizers” of ED services in comparison to those with other psychiatric diagnoses.⁶

The increase in psychiatric presentations to EDs is coupled with a lack of psychiatrists in many areas of the United States. The American Hospital Association has reported that 40% of American hospitals have difficulty maintaining adequate psychiatric coverage to meet patient demand in the ED, forcing many emergency medicine physicians to act as a primary psychiatrist.⁷

Differential Diagnosis

The characteristic symptoms of schizophrenia can be present in many other illnesses; therefore, the emergency clinician must be able to distinguish schizophrenia from other illnesses presenting with a psychotic component. Furthermore, schizophrenia is a diagnosis of exclusion as the diagnosis can only be made after all medical etiologies of the symptoms have been excluded.

Items on the differential include delirium, a substance induced psychosis,⁸ which can be caused by both substance intoxication and substance withdrawal; as well as psychosis caused by another medical condition.⁸ It should be stressed that a prior diagnosis of schizophrenia does not rule out a medical etiology of a patient’s current psychotic episode; therefore, a thorough history and examination is fundamental, even in patients with a known history of psychiatric illness. Moreover, many patients with schizophrenia present with a medical chief complaint, despite being symptomatic regarding their schizophrenia. In the latter case, providers must be vigilant regarding any medical comorbidities, particularly when patients are actively psychotic.

Finally, within the psychiatric disorders there are multiple disorders other than schizophrenia that may have psychotic features, including depression with psychotic features, bipolar disorder with psychotic features, and the other schizophrenia spectrum disorders; including brief psychotic disorder, schizophreniform disorder, schizoaffective disorder, and delusional disorder.

Emergency Department Evaluation

The process of evaluation of psychiatric patients who present to the ED should be directed towards a determination as to whether hospitalization is warranted, treatment of underlying medical condition is needed, or psychiatric care is indicated. New onset of psychiatric illness will commonly call for extensive evaluation, whereas patients with chronic schizophrenia may not need testing but may need psychiatric hospitalization.⁹ Additionally, emergency clinicians are frequently requested to preform “medical clearance” by their psychiatrist colleagues, before a patient can be transferred to a psychiatry department or psychiatric hospital. However, this is a poor term and a better nomenclature would be “assess for medical stability.”⁹ Emergency clinicians are, in essence, being asked whether the patient is medically stable enough for transfer to a unit or hospital where there is little or no medical support. Prior to transfer to a psychiatric unit, a patient’s non-psychiatric medical conditions should be stable enough for outpatient management.

Interacting with Patients Suffering from Psychosis

Although providers should not pretend to interact in the patient’s reality, they should express understanding in what the patient thinks or feels and kindly direct them back to the current situation.¹⁰ It is important for providers in the acute setting to be non-judgmental about reasons for relapse (in particular non-adherence to medication or substance misuse).¹⁰ Challenging the patient, while at times useful, is best done once the patient is stabilized and in a controlled environment.

History

The history should focus on age of onset; prior history of psychiatric symptoms; history of medical illness and use or abuse of illicit substances, as well as medications; the stability of psychotic symptoms; and if hallucinations are present, whether they are auditory or visual in nature.¹⁰ Table 1 highlights the differences between a patient presenting with a psychiatric complaint and the psychotic symptoms secondary to a medical illness. Table 2 provides salient differences between the examination of a patient with psychosis due to a psychiatric illness or another medical condition. Additionally, Table 3 lists various features, which differentiates schizophrenia from other psychiatric illnesses.

Additionally, patients with schizophrenia can become just as physically ill as anyone else; however, they may have difficulty expressing their specific physical complaints. Furthermore, patients with schizophrenia have a pronounced incidence of early death compared to the general population.¹¹ Therefore, performing a simple physical examination and paying attention to vital signs can rule out or detect a great deal of organic pathology.¹²Once a diagnosis of schizophrenia is made, the next priority is to determine whether the patient is a threat to themselves or others and whether this threat is imminent or not. Statements of suicidal or homicidal ideation, intent, and/or plan are the basic methods of screening for danger. However, physicians also need to screen for command auditory hallucinations, prior history of suicidal behavior, and violence. Finally, even in a patient with previously diagnosed schizophrenia, screening must also be done for substance intoxication and withdrawal.

Diagnostic Studies

The indications for diagnostic studies are influenced by whether the presentation is experiencing first break psychoses vs a presentation in a patient with known schizophrenia. In the former case there is a greater need for laboratory and other diagnostic tests. In the latter case minimal testing will likely be necessary. Patients with new onset psychiatric symptoms generally need extensive laboratory and radiographic evaluations, including a computed tomography scan of the head.⁹

For patients who have an established schizophrenia, extensive evidence supports that there is no need for testing and indeed more often results in false positives,^11,13and selective testing based on findings in the history and physical examination is the correct strategy.¹¹

Complicating the decision to obtain laboratory tests is the fact that many psychiatric facilities rely on referring hospitals to perform baseline testing, as they do not have the resources to perform the tests or to manage any identified abnormalities. Therefore, some tests are needed prior to transfer. In addition, at times, baseline laboratory tests are needed prior to starting antipsychotics.¹⁴

Additionally, some tests are unlikely to affect immediate disposition or treatment but may be useful to psychiatrists for long-term treatment planning.¹⁵ A common disagreement between psychiatrists and emergency providers is the urine toxicology screen or a blood alcohol level. Urine toxicology or a blood alcohol level does not usually affect initial treatment and disposition in the ED.^11,16 However, it may be invalid if collected subsequent to a transfer from the ED, and can determine whether a patient requires specific substance use disorder treatment or not.^16-18 Therefore, many psychiatric providers will request a urine toxicology screening or a blood alcohol level before accepting a transfer. Please note, urine toxicology screens only identify a small number of toxic ingestions. Therefore, a negative screen does not eliminate drug abuse or overdose.

Finally, in the case that a diagnostic examination is being done to satisfy a requirement for an institution to accept a patient or to assist in long-term treatment planning, disposition should not be delayed in order to wait for the result to return.¹¹

Treatment

Unfortunately, no level I or II studies have been found that examine the indications for treatment of the psychiatric patient in the ED.⁹ Additionally, in the ED, there is an ill-defined difference between the use of psychotropic medications as an intervention after patient assessment and plan of care, and the use of these medications to control behavior without an assessment and treatment plan.⁹ Therefore, many treatment recommendations have been made based on studies in other settings.

The first line treatment for a patient with schizophrenia is monotherapy with an antipsychotic agent other than clozapine.^19-21 (Clozapine is not used as a first line agent due to its high side effect burden and the testing necessary before starting.) This is supported by multiple randomized controlled trials and is the standard of care.^22-24 The response rates in treatment with antipsychotics in studies specifically designed to examine treatment of first-episode schizophrenia are high, ranging from 46% to 96%.²³ Therefore, the emergency medicine provider can confidently reassure patients and families that antipsychotic medications are effective in treating schizophrenia. Loading doses of antipsychotics should not be used.¹⁹

Although there are only small and inconsistent differences between different antipsychotics, other than clozapine, with respect to efficacy, there are large differences in adverse effect profiles.^25-30Therefore, the choice of antipsychotic medication is generally made based on previous response to individual antipsychotic medications and relative side effects.³¹

If extrapyramidal symptoms, including tardive dyskinesia, are of particular concern to a patient, then second generation or low potency first generation antipsychotics should be used.^25,32 If a patient complains of previous problems with sedation, then haloperidol or aripiprazole should be preferred.²⁵ Haloperidol, aripiprazole, or amisulpride should be considered for patients who are particularly concerned about weight gain, or who may be at the greatest risk of weight gain.²⁵

If there is no response to medication after 4 weeks,³² despite dose optimization, a change in antipsychotic should be considered.^33,34 Where there is partial response, the patient should be re-assessed after 8 weeks unless there are significant adverse effects.^14,19,20,34 A combination of different antipsychotic medications should not be used, except during transitional periods when patients are being switched from one antipsychotic to another, or when used for clozapine augmentation.¹⁴After an acute episode has passed, providers can consider offering depot/long-acting injectable antipsychotic medication to people with schizophrenia who would prefer such treatment; as long acting injectable antipsychotics have been shown to reduce medication non-adherence.^35,36 Long-acting depot antipsychotics should not be used for acute episodes because it may take 3 to 6 months for the medications to reach a stable state.¹⁴Once a patient achieves a remission of their symptoms, patients are recommended to stay on their antipsychotic medication for at least 2 years since their last acute exacerbation.^14,34 For maintenance therapy,the antipsychotic dose should be reduced gradually to the lowest possible effective dose, which should not be lower than half of the effective dose during the acute phase.³⁷

Clozapine should be offered to people with schizophrenia whose illness has not responded adequately to treatment with adequate doses of at least two different antipsychotic drugs.^38-41There is no indication to using dual antipsychotic agents on patients with schizophrenia prior to starting a clozapine trial.^42,43

Non-Pharmacological Intervention

There is strong evidence that people diagnosed with schizophrenia benefit from psychosocial treatments in addition to pharmacological treatment. Multiple randomized controlled studies, as well as national guidelines, have demonstrated cognitive behavioral therapy and family therapy to be effective for the treatment of schizophrenia.^44-51 Particular focuses of therapy include communication skills, problem solving, psychoeducation, and assisting with family conflict,^18,19 which are feasible in an emergency setting.⁵²

Recent studies have shown promise using a “crisis intervention” approach as an alternative option to the hospital or emergency medical services systems. Treatment usually involves a combination of medication as well as counseling (practical help with living skills and support for close family members). After the crisis has been stabilized, sufferers are carefully introduced to other models of care more suited for the chronic phases of psychiatric illnesses.⁵³ This is particularly important as psychosocial instability, such as changes in the psychosocial environment (ie, a primary caretaker going on vacation, or a patient being distanced from their family or support environment) have been associated with relapse.¹⁹

Acute Agitation

The vast majority of patients suffering from mental illness, including schizophrenia, are not violent and only a small proportion of the violence in our society can be attributed to persons who are mentally ill.⁵⁴ Furthermore, people with psychiatric disabilities are far more likely to be victims than perpetrators of violent crime.⁵⁵ However, schizophrenia and related disorders are associated with substantially increased rates of violence and violent offences compared to those who did not, independent of substance use.^56,57 Furthermore, the majority of acute hospital assaults occur in the ED.⁵⁸

Two emergency medicine evidence-based guidelines state a benzodiazepine (lorazepam or midazolam) or a conventional antipsychotic (droperidol or haloperidol) should be used as monotherapy for the treatment of acute undifferentiated agitation in the ED.^12,59 However, in cases of patients with a diagnosis or suspicion of schizophrenia, an antipsychotic should be used in order to start a “disease modifying agent” earlier in the course of treatment.^20,59,60Where possible, the same antipsychotic should be used as monotherapy for treatment of both acute agitation and standing antipsychotic medication.¹³The choice of medication for the treatment of acute agitation should be based on patient preference, past experience of antipsychotic treatment, the adverse effect profile, and concurrent medical history.^19,58 This is supported by a case controlled study, which showed patients’ subjective experiences in the acute phase of treatment affected their long-term adherence to medication.⁶¹

Haloperidol is the most commonly used medication for agitation in patients with schizophrenia.^59,62 When haloperidol is used to treat acute violence, it is almost always used in combination with a benzodiazepine unless medically compromised.^62,63 Intramuscular olanzapine has been shown to be effective in managing acute aggression or agitation in patients with schizophrenia, especially where it is necessary to avoid some of the older treatments. Olanzapine causes fewer movement disorders than halopridol.⁶⁴ Chlorpromazine is available in both per os and intramuscular formulations. However, chlorpromazine is associated with more side effects than other antipsychotics, including a higher incidence of prolonged QT and Torsades.⁶⁵ However, where choices are limited, chlorpromazine may be the only treatment available for acute agitation. If used, the close monitoring of blood pressure is indicated.⁶⁵ Inhaled loxapine received US Food and Drug Administration approval for treatment of acute agitation in 2012.⁶⁶ This is a useful option for an agitated patient who is calm enough to receive an inhaler, but is unable to take medication per os.

Restrictive intervention (restraints or seclusion) should only be used if de-escalation and other preventive strategies, including medication as needed, have failed and there is potential for harm to the patient or other people if no action is taken.⁵⁸

Telepsychiatry Consultation

Telepsychiatry is an approach, where by EDs that do not have access to psychiatrists can see patients in the ED itself, by forming a contract with either psychiatrists or companies to allow a psychiatrist at another location to perform an examination on a patient via video connection and advise the emergency room providers on treatment and intervention. There is very little data in the peer-reviewed literature on the use of telepsychiatry. The literature is limited to case reports, program descriptions, and randomized studies for reliability.^67,68 One randomized controlled trial showed that a telepsychiatry evaluation had a reliable diagnosis and disposition when compared to a face-to-face assessment.⁶⁹ One case control showed reduction in time-to-consult done in the ED, length of stay, and door-to-consult stay, once a telepsychiatry program was initiated.⁷⁰ A large case control study showed that telepsychiatry recipients were more likely to receive 30-day follow-up, 90-day follow-up, and total inpatient length of stay, totaling both initial admission and subsequent admissions.⁷¹ Therefore, it is reasonable for EDs to take advantage of telepsychiatry services if no immediate psychiatrist coverage is available.

Disposition

The primary disposition question regarding a patient presenting with a psychiatric chief complaint to the ED, including schizophrenia, is whether they require a psychiatric admission or not. If a patient requires hospitalization but refuses, the emergency clinician must decide if the patient meets criteria for involuntarily hospitalization. If a patient does not require an inpatient admission or would benefit from an inpatient admission but does not meet criteria for civil commitment, then the next major question is what type of outpatient treatment is sufficient for this particular patient (Figure).

For a patient with schizophrenia to require inpatient psychiatric admission he must be either a danger to himself or others or has failed outpatient treatment. In addition, the patient must currently have undergone a clinical evaluation of any suspected medical illness, and any medical problems the patient is experiencing must be sufficiently stable to allow safe transport and treatment at a psychiatric hospital unit.⁹ If a patient’s medical condition is not sufficiently stable for either transport or hospitalization at a psychiatric hospital but the patient still requires inpatient psychiatric treatment, the patient should be hospitalized on a standard medical ward and receive psychiatric care on that unit.

Patients with mental illness pose an additional challenge, in that their illness often time interferes with their judgment about whether they require treatment. Because of this possible lack of capacity and the potential danger of a patient with mental illness to self or others, most jurisdictions have a legal code that allows for involuntary hospitalization of the mentally ill. However, which patients qualify for involuntary hospitalizations vary by jurisdiction. Case law criteria for emergencies range from a risk of “imminent” harm to self or others to a deterioration in the patient’s mental condition if treatment is halted.⁷² Providers are recommended to familiarize themselves with laws regarding inpatient civil commitment in their particular jurisdiction.

When a patient is being discharged from the ED, either because they do not require a psychiatric inpatient admission or because they don’t meet criteria for involuntary commitment, there are various outpatient dispositions available. Any patient with a diagnosis of schizophrenia should have outpatient follow-up with a mental health provider upon discharge from the ED.

For patients who have a failed community treatment in the past, who do not have a significant support network, or whose disease is too severe for a regular outpatient clinic to handle would be better suited for a disposition to a transitional program over a standard outpatient appointment; such as partial hospitalization programs, intensive outpatient programs, and community mental health treatment teams (CMHT). Assertive community treatment (ACT) teams are a form of CMHT comprised of several disciplines, including nurses, occupational therapists, psychiatrists, psychologists, and social workers.⁷³ A large prospective cohort study found homeless patients to have made gains in multiple spheres of mental health while enrolled in ACT programs, and these benefits were retained after discharge from the ACT program.⁷⁴

Conclusion

Schizophrenia is characterized primarily by delusions, hallucinations, and disorganized thinking. Emergency medicine providers are frequently at the front lines of diagnosing, initiating treatment, and managing relapses for these individuals. As schizophrenia is an exclusion, the primary task of an emergency physician is to rule out all “organic”, for lack of a better term, causes of the psychosis or disordered thinking before making a definitive diagnosis of schizophrenia. As many EDs do not have sufficient psychiatry support and many patients with schizophrenia are using the ED as their location for primary mental health, many emergency physicians are finding themselves acting as the main providers for these individuals. The primary treatment for patients with schizophrenia remains monotherapy with antipsychotic medication. Although the highest-level disposition for a patient with schizophrenia remains the inpatient psychiatry department, there are many transitional dispositions that can bridge the gap between a discharge to standard community care and an inpatient admission.

SAN ANTONIO – While septic shock mortality has decreased since the Surviving Sepsis Campaign guidelines were introduced, discharge trends for survivors have not changed significantly over time, a recent analysis suggests.

invisioner/Thinkstock

The percentage of survivors discharged to subacute rehab or long-term facilities did not change appreciably over time, according to the 10-year retrospective analysis, presented at the annual meeting of the American College of Chest Physicians.

However, average length of stay did significantly trend downward over the decade analyzed, while total charge per septic shock admission significantly increased, according to investigator Di Pan, DO, Icahn School of Medicine at Mount Sinai, New York, and his colleagues.

This is one of few studies looking at outcomes in survivors of septic shock, as most analyses have primarily focused on mortality outcomes, the investigators said.

Their analysis was based on the 2004 to 2014 National (Nationwide) Inpatient Sample databases and included patients with a primary diagnosis of septic shock at discharge.

Out of nearly 1.8 million patients with septic shock in that cohort, about 1 million survived, according to data Dr. Pan and colleagues provided in an abstract of the presentation.

In-hospital mortality decreased from 51.7% in 2004 to 39.3% in 2014 (P less than .001), the investigators reported.

The proportion of survivors discharged to subacute rehab or long-term acute care facilities was 61.9% in 2004, and similarly, 62.4% in 2014 (P = .1), while the percentage discharged home was 17.1% in 2004 and 15.1% in 2014 (P = 0.55).

However, there was a small but statistically significant downtick in mean length of stay, from 12.6 days in 2004 to 11.05 days in 2014, the investigators said. Meanwhile, total hospitalization charges surged from $105,776 in 2004 to $134,394 over the same time period.

The first edition of the Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock was published in March 2004 in Critical Care Medicine.

Future studies and clinical trials should look beyond mortality outcomes to additionally evaluate morbidity outcomes in septic shock survivors, Dr. Pan and coauthors said in their report.

The researchers had no relationships to disclose relevant to the presented study.

SOURCE: Pan D et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.339.

SAN ANTONIO – While septic shock mortality has decreased since the Surviving Sepsis Campaign guidelines were introduced, discharge trends for survivors have not changed significantly over time, a recent analysis suggests.

invisioner/Thinkstock

The percentage of survivors discharged to subacute rehab or long-term facilities did not change appreciably over time, according to the 10-year retrospective analysis, presented at the annual meeting of the American College of Chest Physicians.

However, average length of stay did significantly trend downward over the decade analyzed, while total charge per septic shock admission significantly increased, according to investigator Di Pan, DO, Icahn School of Medicine at Mount Sinai, New York, and his colleagues.

This is one of few studies looking at outcomes in survivors of septic shock, as most analyses have primarily focused on mortality outcomes, the investigators said.

Their analysis was based on the 2004 to 2014 National (Nationwide) Inpatient Sample databases and included patients with a primary diagnosis of septic shock at discharge.

Out of nearly 1.8 million patients with septic shock in that cohort, about 1 million survived, according to data Dr. Pan and colleagues provided in an abstract of the presentation.

In-hospital mortality decreased from 51.7% in 2004 to 39.3% in 2014 (P less than .001), the investigators reported.

The proportion of survivors discharged to subacute rehab or long-term acute care facilities was 61.9% in 2004, and similarly, 62.4% in 2014 (P = .1), while the percentage discharged home was 17.1% in 2004 and 15.1% in 2014 (P = 0.55).

However, there was a small but statistically significant downtick in mean length of stay, from 12.6 days in 2004 to 11.05 days in 2014, the investigators said. Meanwhile, total hospitalization charges surged from $105,776 in 2004 to $134,394 over the same time period.

The first edition of the Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock was published in March 2004 in Critical Care Medicine.

Future studies and clinical trials should look beyond mortality outcomes to additionally evaluate morbidity outcomes in septic shock survivors, Dr. Pan and coauthors said in their report.

The researchers had no relationships to disclose relevant to the presented study.

SOURCE: Pan D et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.339.

SAN ANTONIO – While septic shock mortality has decreased since the Surviving Sepsis Campaign guidelines were introduced, discharge trends for survivors have not changed significantly over time, a recent analysis suggests.

invisioner/Thinkstock

The percentage of survivors discharged to subacute rehab or long-term facilities did not change appreciably over time, according to the 10-year retrospective analysis, presented at the annual meeting of the American College of Chest Physicians.

However, average length of stay did significantly trend downward over the decade analyzed, while total charge per septic shock admission significantly increased, according to investigator Di Pan, DO, Icahn School of Medicine at Mount Sinai, New York, and his colleagues.

This is one of few studies looking at outcomes in survivors of septic shock, as most analyses have primarily focused on mortality outcomes, the investigators said.

Their analysis was based on the 2004 to 2014 National (Nationwide) Inpatient Sample databases and included patients with a primary diagnosis of septic shock at discharge.

Out of nearly 1.8 million patients with septic shock in that cohort, about 1 million survived, according to data Dr. Pan and colleagues provided in an abstract of the presentation.

In-hospital mortality decreased from 51.7% in 2004 to 39.3% in 2014 (P less than .001), the investigators reported.

The proportion of survivors discharged to subacute rehab or long-term acute care facilities was 61.9% in 2004, and similarly, 62.4% in 2014 (P = .1), while the percentage discharged home was 17.1% in 2004 and 15.1% in 2014 (P = 0.55).

However, there was a small but statistically significant downtick in mean length of stay, from 12.6 days in 2004 to 11.05 days in 2014, the investigators said. Meanwhile, total hospitalization charges surged from $105,776 in 2004 to $134,394 over the same time period.

The first edition of the Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock was published in March 2004 in Critical Care Medicine.

Future studies and clinical trials should look beyond mortality outcomes to additionally evaluate morbidity outcomes in septic shock survivors, Dr. Pan and coauthors said in their report.

The researchers had no relationships to disclose relevant to the presented study.

SOURCE: Pan D et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.339.

Background: Previous studies have shown that perioperative gabapentin has no effect on remote pain cessation but have not linked it with effects on remote opioid cessation. Also, most trials were limited to immediate postoperative use during hospital admission; limited data were available with extensive postoperative longitudinal follow-up.

One caveat to the outcomes is that use of a gabapentin regimen may have increased after discharge date, which could have biased the outcome.

Bottom line: Perioperative gabapentin may promote opioid cessation and prevent the development of chronic opioid use after surgery.

Citation: Hah J et al. Effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort. JAMA Surg. 2018;153(4):303-11.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Background: Previous studies have shown that perioperative gabapentin has no effect on remote pain cessation but have not linked it with effects on remote opioid cessation. Also, most trials were limited to immediate postoperative use during hospital admission; limited data were available with extensive postoperative longitudinal follow-up.

One caveat to the outcomes is that use of a gabapentin regimen may have increased after discharge date, which could have biased the outcome.

Bottom line: Perioperative gabapentin may promote opioid cessation and prevent the development of chronic opioid use after surgery.

Citation: Hah J et al. Effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort. JAMA Surg. 2018;153(4):303-11.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Background: Previous studies have shown that perioperative gabapentin has no effect on remote pain cessation but have not linked it with effects on remote opioid cessation. Also, most trials were limited to immediate postoperative use during hospital admission; limited data were available with extensive postoperative longitudinal follow-up.

One caveat to the outcomes is that use of a gabapentin regimen may have increased after discharge date, which could have biased the outcome.

Bottom line: Perioperative gabapentin may promote opioid cessation and prevent the development of chronic opioid use after surgery.

Citation: Hah J et al. Effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort. JAMA Surg. 2018;153(4):303-11.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

On behalf of SHM’s Practice Analysis Committee, I’m thrilled to introduce the 2018 State of Hospital Medicine Report (SoHM) and the resumption of this monthly Survey Insights column written by committee members.

It’s a bit like giving birth. A 9-month–long process that started last January with the excitement of launching the survey and encouraging hospital medicine groups (HMGs) to participate. Then the long, drawn-out process of validating and analyzing data, and organizing it into tables and charts, watching our baby grow and take shape before our eyes, with a few small hiccups along the way. Then graphic design and the agonizing process of copy editing – over and over until our eyes crossed – and printing.

Like all expectant parents, by August we were saying, “Enough already; when will this ever end?”

But we finally have a baby, and what proud parents we are! Here are a couple of key things you should know about the 2018 SoHM:

• The total number of HMGs participating in this year’s survey was marginally lower than in 2016 (569 this year vs. 595 in 2016), but the respondent groups are much more diverse. While more than half of respondent HMGs (52%) are employed by hospitals or health systems, multistate management companies employ 25%, and universities or their affiliates employ 12%. More pediatric hospitalist groups (38) and HMGs that serve both adults and children (31) participated this year, compared with 2016, and almost twice as many academic HMGs participated as in the previous survey (96 this year vs. 59 in 2016).
• The survey content is more wide-ranging than ever. As usual, SHM licensed hospitalist compensation and productivity data from the Medical Group Management Association for inclusion in this report, and the SoHM also covers just about every other aspect of hospitalist group structure and operations imaginable. In addition to traditional questions regarding scope of services, staffing and scheduling models, leadership configuration, and financial support, this year’s report includes new information on:

• Hospitalist comanagement roles with surgical and medical subspecialties.

• Information about unfilled positions and how they are covered (including locum tenens use).
• Utilization of dedicated daytime admitters.
• Prevalence of geographic or unit-based assignment models.
• Responsibility for CPT code selection.
• Amount of financial support per wRVU.

The report has retained its colorful, easy-to-read report layout and the user-friendly interface of the digital version. And because we have more diversity this year with regard to HMG employment models, we have been able to reintroduce findings by employment model.

The 2018 SoHM report is now available for purchase at www.hospitalmedicine.org/sohm. I encourage you to obtain the SoHM report for yourself; you’ll almost certainly find more than one interesting and useful tidbit of information. Use the report to assess how your practice compares to your peers, but always keep in mind that surveys don’t tell you what should be – they tell you only what currently is.

New best practices not reflected in survey data are emerging all the time, and the ways others do things won’t always be right for your group’s unique situation and needs. Whether you are partners or employees, you and your colleagues “own” the success of your practice and are the best judges of what is right for you.
 

Leslie Flores, MHA, SFHM, is a partner with Nelson Flores Hospital Medicine Consultants, and a member of the SHM Practice Analysis Committee.

On behalf of SHM’s Practice Analysis Committee, I’m thrilled to introduce the 2018 State of Hospital Medicine Report (SoHM) and the resumption of this monthly Survey Insights column written by committee members.

It’s a bit like giving birth. A 9-month–long process that started last January with the excitement of launching the survey and encouraging hospital medicine groups (HMGs) to participate. Then the long, drawn-out process of validating and analyzing data, and organizing it into tables and charts, watching our baby grow and take shape before our eyes, with a few small hiccups along the way. Then graphic design and the agonizing process of copy editing – over and over until our eyes crossed – and printing.

Like all expectant parents, by August we were saying, “Enough already; when will this ever end?”

But we finally have a baby, and what proud parents we are! Here are a couple of key things you should know about the 2018 SoHM:

• The total number of HMGs participating in this year’s survey was marginally lower than in 2016 (569 this year vs. 595 in 2016), but the respondent groups are much more diverse. While more than half of respondent HMGs (52%) are employed by hospitals or health systems, multistate management companies employ 25%, and universities or their affiliates employ 12%. More pediatric hospitalist groups (38) and HMGs that serve both adults and children (31) participated this year, compared with 2016, and almost twice as many academic HMGs participated as in the previous survey (96 this year vs. 59 in 2016).
• The survey content is more wide-ranging than ever. As usual, SHM licensed hospitalist compensation and productivity data from the Medical Group Management Association for inclusion in this report, and the SoHM also covers just about every other aspect of hospitalist group structure and operations imaginable. In addition to traditional questions regarding scope of services, staffing and scheduling models, leadership configuration, and financial support, this year’s report includes new information on:

• Hospitalist comanagement roles with surgical and medical subspecialties.

• Information about unfilled positions and how they are covered (including locum tenens use).
• Utilization of dedicated daytime admitters.
• Prevalence of geographic or unit-based assignment models.
• Responsibility for CPT code selection.
• Amount of financial support per wRVU.

The report has retained its colorful, easy-to-read report layout and the user-friendly interface of the digital version. And because we have more diversity this year with regard to HMG employment models, we have been able to reintroduce findings by employment model.

The 2018 SoHM report is now available for purchase at www.hospitalmedicine.org/sohm. I encourage you to obtain the SoHM report for yourself; you’ll almost certainly find more than one interesting and useful tidbit of information. Use the report to assess how your practice compares to your peers, but always keep in mind that surveys don’t tell you what should be – they tell you only what currently is.

New best practices not reflected in survey data are emerging all the time, and the ways others do things won’t always be right for your group’s unique situation and needs. Whether you are partners or employees, you and your colleagues “own” the success of your practice and are the best judges of what is right for you.
 

Leslie Flores, MHA, SFHM, is a partner with Nelson Flores Hospital Medicine Consultants, and a member of the SHM Practice Analysis Committee.

On behalf of SHM’s Practice Analysis Committee, I’m thrilled to introduce the 2018 State of Hospital Medicine Report (SoHM) and the resumption of this monthly Survey Insights column written by committee members.

It’s a bit like giving birth. A 9-month–long process that started last January with the excitement of launching the survey and encouraging hospital medicine groups (HMGs) to participate. Then the long, drawn-out process of validating and analyzing data, and organizing it into tables and charts, watching our baby grow and take shape before our eyes, with a few small hiccups along the way. Then graphic design and the agonizing process of copy editing – over and over until our eyes crossed – and printing.

Like all expectant parents, by August we were saying, “Enough already; when will this ever end?”

But we finally have a baby, and what proud parents we are! Here are a couple of key things you should know about the 2018 SoHM:

• The total number of HMGs participating in this year’s survey was marginally lower than in 2016 (569 this year vs. 595 in 2016), but the respondent groups are much more diverse. While more than half of respondent HMGs (52%) are employed by hospitals or health systems, multistate management companies employ 25%, and universities or their affiliates employ 12%. More pediatric hospitalist groups (38) and HMGs that serve both adults and children (31) participated this year, compared with 2016, and almost twice as many academic HMGs participated as in the previous survey (96 this year vs. 59 in 2016).
• The survey content is more wide-ranging than ever. As usual, SHM licensed hospitalist compensation and productivity data from the Medical Group Management Association for inclusion in this report, and the SoHM also covers just about every other aspect of hospitalist group structure and operations imaginable. In addition to traditional questions regarding scope of services, staffing and scheduling models, leadership configuration, and financial support, this year’s report includes new information on:

• Hospitalist comanagement roles with surgical and medical subspecialties.

• Information about unfilled positions and how they are covered (including locum tenens use).
• Utilization of dedicated daytime admitters.
• Prevalence of geographic or unit-based assignment models.
• Responsibility for CPT code selection.
• Amount of financial support per wRVU.

The report has retained its colorful, easy-to-read report layout and the user-friendly interface of the digital version. And because we have more diversity this year with regard to HMG employment models, we have been able to reintroduce findings by employment model.

The 2018 SoHM report is now available for purchase at www.hospitalmedicine.org/sohm. I encourage you to obtain the SoHM report for yourself; you’ll almost certainly find more than one interesting and useful tidbit of information. Use the report to assess how your practice compares to your peers, but always keep in mind that surveys don’t tell you what should be – they tell you only what currently is.

New best practices not reflected in survey data are emerging all the time, and the ways others do things won’t always be right for your group’s unique situation and needs. Whether you are partners or employees, you and your colleagues “own” the success of your practice and are the best judges of what is right for you.
 

Leslie Flores, MHA, SFHM, is a partner with Nelson Flores Hospital Medicine Consultants, and a member of the SHM Practice Analysis Committee.

Pediatric status epilepticus (SE) is an expensive disorder and is not uncommon in this patient population, according to a recent review of the medical literature.

• Gurcharran et al note that pediatric SE occurs in about 20per 100,000 children each year.
• The disorder carries a mortality of 3%.
• The most common risk factor for morbidity and death is symptomatic etiology, with acute presentation more common than remote.
• A single episode of status epilepticus costs more than $10,000 to manage and can reach more than $100,000 in children with refractory disease.
• The most common cause of the condition is febrile SE, which usually occurs in early childhood.

Gurcharran K, Grinspan ZM. The burden of pediatric status epilepticus: epidemiology, morbidity, and mortality. [Published online ahead of print August 29, 2018] Seizure. https://doi.org/10.1016/j.seizure.2018.08.021.

Pediatric status epilepticus (SE) is an expensive disorder and is not uncommon in this patient population, according to a recent review of the medical literature.

• Gurcharran et al note that pediatric SE occurs in about 20per 100,000 children each year.
• The disorder carries a mortality of 3%.
• The most common risk factor for morbidity and death is symptomatic etiology, with acute presentation more common than remote.
• A single episode of status epilepticus costs more than $10,000 to manage and can reach more than $100,000 in children with refractory disease.
• The most common cause of the condition is febrile SE, which usually occurs in early childhood.

Gurcharran K, Grinspan ZM. The burden of pediatric status epilepticus: epidemiology, morbidity, and mortality. [Published online ahead of print August 29, 2018] Seizure. https://doi.org/10.1016/j.seizure.2018.08.021.

Pediatric status epilepticus (SE) is an expensive disorder and is not uncommon in this patient population, according to a recent review of the medical literature.

• Gurcharran et al note that pediatric SE occurs in about 20per 100,000 children each year.
• The disorder carries a mortality of 3%.
• The most common risk factor for morbidity and death is symptomatic etiology, with acute presentation more common than remote.
• A single episode of status epilepticus costs more than $10,000 to manage and can reach more than $100,000 in children with refractory disease.
• The most common cause of the condition is febrile SE, which usually occurs in early childhood.

Gurcharran K, Grinspan ZM. The burden of pediatric status epilepticus: epidemiology, morbidity, and mortality. [Published online ahead of print August 29, 2018] Seizure. https://doi.org/10.1016/j.seizure.2018.08.021.

While several emerging treatments have been recommended for children with refractory status epilepticus, most of the research supporting these modalities are anecdotal in nature, according to a review published in Seizure.

• Randomized controlled trials have evaluated hypothermia and found it is no more effective than placebo for refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE).
• Case series have suggested that a ketogenic diet may benefit children with RSE.
• A few case reports involving the ketogenic diet found seizures were stopped within a week in 20-90% of children.
• One double blind trial concluded that brexanolone was no more effective than placebo for weaning patients off 3^rd line anesthetic agents and freedom from RSE after 24 hours.

Arya R, Rotenberg A.  Dietary, immunological, surgical, and other emerging treatments for pediatric refractory status epilepticus.  [Published online ahead of print Sept 14, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.002.

While several emerging treatments have been recommended for children with refractory status epilepticus, most of the research supporting these modalities are anecdotal in nature, according to a review published in Seizure.

• Randomized controlled trials have evaluated hypothermia and found it is no more effective than placebo for refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE).
• Case series have suggested that a ketogenic diet may benefit children with RSE.
• A few case reports involving the ketogenic diet found seizures were stopped within a week in 20-90% of children.
• One double blind trial concluded that brexanolone was no more effective than placebo for weaning patients off 3^rd line anesthetic agents and freedom from RSE after 24 hours.

Arya R, Rotenberg A.  Dietary, immunological, surgical, and other emerging treatments for pediatric refractory status epilepticus.  [Published online ahead of print Sept 14, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.002.

While several emerging treatments have been recommended for children with refractory status epilepticus, most of the research supporting these modalities are anecdotal in nature, according to a review published in Seizure.

• Randomized controlled trials have evaluated hypothermia and found it is no more effective than placebo for refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE).
• Case series have suggested that a ketogenic diet may benefit children with RSE.
• A few case reports involving the ketogenic diet found seizures were stopped within a week in 20-90% of children.
• One double blind trial concluded that brexanolone was no more effective than placebo for weaning patients off 3^rd line anesthetic agents and freedom from RSE after 24 hours.

Arya R, Rotenberg A.  Dietary, immunological, surgical, and other emerging treatments for pediatric refractory status epilepticus.  [Published online ahead of print Sept 14, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.002.

Patients will likely develop intolerable psychiatric and behavioral side effects (IPBSE) to an antiepileptic drug if they are already sensitive to another one, according to researchers from Yale and Columbia University.

• A review of the records of over 2,000 patients found that about 20% were taking at least two antiepileptic drug and had at IPBSE to at least one of the drugs.
• Cross sensitivity was detected between zonisamide and levetiracetam.
• The odds of developing said side effects from levetiracetam or from zonisamide were significantly higher in a patient that had had a side effect to another antiepileptic drug than in patients who had no IPBSE to other antiepileptic drugs (20.5% versus 7.5%.)
•  A history of depression and psychosis increase the risk of IPBSE among patients taking antiepileptic medication.

Chen B, Choi H, Hirsch LJ, et al. Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use. [Published online ahead of print Sept 22, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.014.

Patients will likely develop intolerable psychiatric and behavioral side effects (IPBSE) to an antiepileptic drug if they are already sensitive to another one, according to researchers from Yale and Columbia University.

• A review of the records of over 2,000 patients found that about 20% were taking at least two antiepileptic drug and had at IPBSE to at least one of the drugs.
• Cross sensitivity was detected between zonisamide and levetiracetam.
• The odds of developing said side effects from levetiracetam or from zonisamide were significantly higher in a patient that had had a side effect to another antiepileptic drug than in patients who had no IPBSE to other antiepileptic drugs (20.5% versus 7.5%.)
•  A history of depression and psychosis increase the risk of IPBSE among patients taking antiepileptic medication.

Chen B, Choi H, Hirsch LJ, et al. Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use. [Published online ahead of print Sept 22, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.014.

Patients will likely develop intolerable psychiatric and behavioral side effects (IPBSE) to an antiepileptic drug if they are already sensitive to another one, according to researchers from Yale and Columbia University.

• A review of the records of over 2,000 patients found that about 20% were taking at least two antiepileptic drug and had at IPBSE to at least one of the drugs.
• Cross sensitivity was detected between zonisamide and levetiracetam.
• The odds of developing said side effects from levetiracetam or from zonisamide were significantly higher in a patient that had had a side effect to another antiepileptic drug than in patients who had no IPBSE to other antiepileptic drugs (20.5% versus 7.5%.)
•  A history of depression and psychosis increase the risk of IPBSE among patients taking antiepileptic medication.

Chen B, Choi H, Hirsch LJ, et al. Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use. [Published online ahead of print Sept 22, 2018]. Seizure. https://doi.org/10.1016/j.seizure.2018.09.014.

Audience at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice

DUBROVNIK, CROATIA—An updated scoring system can more accurately identify lymphoma patients who may require thromboprophylaxis, according to researchers.

The revised scoring system, ThroLy, proved more effective than other systems for predicting thromboembolic events in lymphoma patients.

Researchers found the updated ThroLy had a positive predictive value of 22% to 25%, a negative predictive value of 96%, sensitivity of 56% to 57%, and specificity of 85% to 87%.

Darko Antić, MD, PhD, of the University of Belgrade in Serbia, presented these findings at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

Dr. Antić said he and his colleagues developed ThroLy because other systems used to predict venous thromboembolism (VTE) are not quite right for lymphoma. He noted that the Padua score is not designed for cancer patients, and the Khorana score is predominantly for solid tumor malignancies.

“It’s good . . . , but it’s not specific for lymphoma patients,” Dr. Antić said.

With this in mind, he and his colleagues developed ThroLy. They based the scoring system on variables used in the Padua and Khorana systems as well as variables that are specific to lymphoma patients.

In a past study*, the researchers found several variables that were independently associated with risk for VTE in lymphoma:

• Previous VTE
• Previous acute myocardial infarction/stroke
• Mediastinal involvement
• Body mass index > 30 kg/m²
• Reduced mobility
• Extranodal localization
• Development of neutropenia
• Hemoglobin level < 100g/L.

Previous VTE, previous acute myocardial infarction/stroke, obesity, and mediastinal involvement were all worth 2 points, and the other factors were worth a single point.

Patients with scores of 0 to 1 were considered low-risk, patients with scores of 2 to 3 were considered intermediate-risk, and patients with scores of 4 or greater were considered high-risk.

Prospective validation

To validate and refine ThroLy, Dr. Antić and his colleagues used it to assess 1723 lymphoma patients treated at 8 institutions in Austria, Croatia, France, Jordan, Macedonia, Spain, Switzerland, and the United States.

Patients had indolent non-Hodgkin lymphoma (n=467), aggressive non-Hodgkin lymphoma (n=647), chronic lymphocytic leukemia/small lymphocytic lymphoma (n=235), and Hodgkin lymphoma (n=366). Most subjects (84%) were outpatients.

Nine percent of patients had thrombosis (n=142), with 7% having VTE (n=121).

ThroLy had a positive predictive value of 17%, compared to 11% with Khorana and 13% with Padua. The negative predictive value was 93%, 92%, and 95%, respectively.

The sensitivity was 51% with ThroLy, 42% with Khorana, and 70% with Padua. The specificity was 72%, 64%, and 52%, respectively.

“The positive predictive value was low [with ThroLy] but definitely higher than the positive predictive value of the other two [scoring systems],” Dr. Antić noted.

Updated models

To further improve ThroLy, the researchers updated the system, creating two new models.

Model 1 included the following variables:

• Type of lymphoma/clinical stage (aggressive/advanced)—1 point
• Previous VTE—5 points
• Reduced mobility—2 points
• Hemoglobin level < 100 g/L—1 point
• Presence of vascular devices—1 point.

Model 2 included all of the aforementioned variables as well as thrombophilic condition, which was worth 1 point.

With these models, patients were divided into two risk groups—low-risk (≤ 2 points) and high-risk (>2 points).

For Model 1, the positive predictive value was 22%, the negative predictive value was 96%, the sensitivity was 56%, and the specificity was 85%.

For Model 2, the positive predictive value was 25%, the negative predictive value was 96%, the sensitivity was 57%, and the specificity was 87%.

Dr. Antić said there were no major differences in model discrimination and calibration according to the country in which a patient was treated or whether patients were treated in inpatient or outpatient settings.

Dr. Antić did not report any conflicts of interest.

*Antić D et al. Am J Hematol. 2016 Oct;91(10):1014-9. doi: 10.1002/ajh.24466.

Audience at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice

DUBROVNIK, CROATIA—An updated scoring system can more accurately identify lymphoma patients who may require thromboprophylaxis, according to researchers.

The revised scoring system, ThroLy, proved more effective than other systems for predicting thromboembolic events in lymphoma patients.

Researchers found the updated ThroLy had a positive predictive value of 22% to 25%, a negative predictive value of 96%, sensitivity of 56% to 57%, and specificity of 85% to 87%.

Darko Antić, MD, PhD, of the University of Belgrade in Serbia, presented these findings at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

Dr. Antić said he and his colleagues developed ThroLy because other systems used to predict venous thromboembolism (VTE) are not quite right for lymphoma. He noted that the Padua score is not designed for cancer patients, and the Khorana score is predominantly for solid tumor malignancies.

“It’s good . . . , but it’s not specific for lymphoma patients,” Dr. Antić said.

With this in mind, he and his colleagues developed ThroLy. They based the scoring system on variables used in the Padua and Khorana systems as well as variables that are specific to lymphoma patients.

In a past study*, the researchers found several variables that were independently associated with risk for VTE in lymphoma:

• Previous VTE
• Previous acute myocardial infarction/stroke
• Mediastinal involvement
• Body mass index > 30 kg/m²
• Reduced mobility
• Extranodal localization
• Development of neutropenia
• Hemoglobin level < 100g/L.

Previous VTE, previous acute myocardial infarction/stroke, obesity, and mediastinal involvement were all worth 2 points, and the other factors were worth a single point.

Patients with scores of 0 to 1 were considered low-risk, patients with scores of 2 to 3 were considered intermediate-risk, and patients with scores of 4 or greater were considered high-risk.

Prospective validation

To validate and refine ThroLy, Dr. Antić and his colleagues used it to assess 1723 lymphoma patients treated at 8 institutions in Austria, Croatia, France, Jordan, Macedonia, Spain, Switzerland, and the United States.

Patients had indolent non-Hodgkin lymphoma (n=467), aggressive non-Hodgkin lymphoma (n=647), chronic lymphocytic leukemia/small lymphocytic lymphoma (n=235), and Hodgkin lymphoma (n=366). Most subjects (84%) were outpatients.

Nine percent of patients had thrombosis (n=142), with 7% having VTE (n=121).

ThroLy had a positive predictive value of 17%, compared to 11% with Khorana and 13% with Padua. The negative predictive value was 93%, 92%, and 95%, respectively.

The sensitivity was 51% with ThroLy, 42% with Khorana, and 70% with Padua. The specificity was 72%, 64%, and 52%, respectively.

“The positive predictive value was low [with ThroLy] but definitely higher than the positive predictive value of the other two [scoring systems],” Dr. Antić noted.

Updated models

To further improve ThroLy, the researchers updated the system, creating two new models.

Model 1 included the following variables:

• Type of lymphoma/clinical stage (aggressive/advanced)—1 point
• Previous VTE—5 points
• Reduced mobility—2 points
• Hemoglobin level < 100 g/L—1 point
• Presence of vascular devices—1 point.

Model 2 included all of the aforementioned variables as well as thrombophilic condition, which was worth 1 point.

With these models, patients were divided into two risk groups—low-risk (≤ 2 points) and high-risk (>2 points).

For Model 1, the positive predictive value was 22%, the negative predictive value was 96%, the sensitivity was 56%, and the specificity was 85%.

For Model 2, the positive predictive value was 25%, the negative predictive value was 96%, the sensitivity was 57%, and the specificity was 87%.

Dr. Antić said there were no major differences in model discrimination and calibration according to the country in which a patient was treated or whether patients were treated in inpatient or outpatient settings.

Dr. Antić did not report any conflicts of interest.

*Antić D et al. Am J Hematol. 2016 Oct;91(10):1014-9. doi: 10.1002/ajh.24466.

Audience at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice

DUBROVNIK, CROATIA—An updated scoring system can more accurately identify lymphoma patients who may require thromboprophylaxis, according to researchers.

The revised scoring system, ThroLy, proved more effective than other systems for predicting thromboembolic events in lymphoma patients.

Researchers found the updated ThroLy had a positive predictive value of 22% to 25%, a negative predictive value of 96%, sensitivity of 56% to 57%, and specificity of 85% to 87%.

Darko Antić, MD, PhD, of the University of Belgrade in Serbia, presented these findings at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

Dr. Antić said he and his colleagues developed ThroLy because other systems used to predict venous thromboembolism (VTE) are not quite right for lymphoma. He noted that the Padua score is not designed for cancer patients, and the Khorana score is predominantly for solid tumor malignancies.

“It’s good . . . , but it’s not specific for lymphoma patients,” Dr. Antić said.

With this in mind, he and his colleagues developed ThroLy. They based the scoring system on variables used in the Padua and Khorana systems as well as variables that are specific to lymphoma patients.

In a past study*, the researchers found several variables that were independently associated with risk for VTE in lymphoma:

• Previous VTE
• Previous acute myocardial infarction/stroke
• Mediastinal involvement
• Body mass index > 30 kg/m²
• Reduced mobility
• Extranodal localization
• Development of neutropenia
• Hemoglobin level < 100g/L.

Previous VTE, previous acute myocardial infarction/stroke, obesity, and mediastinal involvement were all worth 2 points, and the other factors were worth a single point.

Patients with scores of 0 to 1 were considered low-risk, patients with scores of 2 to 3 were considered intermediate-risk, and patients with scores of 4 or greater were considered high-risk.

Prospective validation

To validate and refine ThroLy, Dr. Antić and his colleagues used it to assess 1723 lymphoma patients treated at 8 institutions in Austria, Croatia, France, Jordan, Macedonia, Spain, Switzerland, and the United States.

Patients had indolent non-Hodgkin lymphoma (n=467), aggressive non-Hodgkin lymphoma (n=647), chronic lymphocytic leukemia/small lymphocytic lymphoma (n=235), and Hodgkin lymphoma (n=366). Most subjects (84%) were outpatients.

Nine percent of patients had thrombosis (n=142), with 7% having VTE (n=121).

ThroLy had a positive predictive value of 17%, compared to 11% with Khorana and 13% with Padua. The negative predictive value was 93%, 92%, and 95%, respectively.

The sensitivity was 51% with ThroLy, 42% with Khorana, and 70% with Padua. The specificity was 72%, 64%, and 52%, respectively.

“The positive predictive value was low [with ThroLy] but definitely higher than the positive predictive value of the other two [scoring systems],” Dr. Antić noted.

Updated models

To further improve ThroLy, the researchers updated the system, creating two new models.

Model 1 included the following variables:

• Type of lymphoma/clinical stage (aggressive/advanced)—1 point
• Previous VTE—5 points
• Reduced mobility—2 points
• Hemoglobin level < 100 g/L—1 point
• Presence of vascular devices—1 point.

Model 2 included all of the aforementioned variables as well as thrombophilic condition, which was worth 1 point.

With these models, patients were divided into two risk groups—low-risk (≤ 2 points) and high-risk (>2 points).

For Model 1, the positive predictive value was 22%, the negative predictive value was 96%, the sensitivity was 56%, and the specificity was 85%.

For Model 2, the positive predictive value was 25%, the negative predictive value was 96%, the sensitivity was 57%, and the specificity was 87%.

Dr. Antić said there were no major differences in model discrimination and calibration according to the country in which a patient was treated or whether patients were treated in inpatient or outpatient settings.

Dr. Antić did not report any conflicts of interest.

*Antić D et al. Am J Hematol. 2016 Oct;91(10):1014-9. doi: 10.1002/ajh.24466.

In patients with gout, at least 300 mg of allopurinol daily may reduce the risk of renal function decline, according to a new study.

London_England/Thinkstock

Since no evidence supports allopurinol nephrotoxicity and usage does not appear to worsen chronic kidney disease (CKD), clinicians should consider other causes of declining renal function, according to lead author Ana Beatriz Vargas-Santos, MD, of the rheumatology unit at the State University of Rio de Janeiro and her colleagues.

These findings reinforce the American College of Rheumatology’s 2012 treatment recommendation that the dose of allopurinol, a urate-lowering therapy (ULT), “can be raised above 300 mg daily, even with renal impairment, as long as it is accompanied by adequate patient education and monitoring for drug toxicity may worsen renal function.”*

“Renal-dosing of allopurinol compounds the poor management of gout and adds to the perception that allopurinol may be detrimental for renal function,” the investigators wrote in JAMA Internal Medicine. “In contrast, recent studies provide support for starting allopurinol at a low dose with gradual dose escalation to serum urate target with close monitoring, even among patients with renal insufficiency, without increased risk of allopurinol hypersensitivity syndrome (AHS). Further, there is emerging evidence that ULT may be beneficial for kidney dysfunction.”

Building upon these developments, the investigators “aimed to assess the relation of allopurinol initiation to the risk of developing CKD stage 3 or higher among people with newly diagnosed gout.”

Patients for the cohort study were drawn from the Health Improvement Network (THIN), a database of records from general practitioners in the United Kingdom. Included patients were recently diagnosed with gout but did not have stage 3 or higher chronic kidney disease or ULT usage within a year prior to diagnosis. After screening, 4,760 allopurinol users were matched with 4,760 allopurinol nonusers. Overall, 71% of patients had CKD stage 2, while the remaining 29% had CKD stage 1 or normal kidney function.

The primary outcome of CKD stage 3 or higher was defined as glomerular filtration rate below 60 mL/min (recorded at least twice in 1 year with a 3-month interval between readings and GFR never exceeding 75 mL/min during the intervening period), kidney transplant, or dialysis. The mean follow-up time was 5 years for allopurinol users and 4 years for nonusers.

The investigators found that 579 allopurinol users developed CKD stage 3 or higher, compared with 623 nonusers, suggesting that allopurinol reduced risk of CKD stage 3 or higher by 13%. Allopurinol doses of at least 300 mg/day were associated with a hazard ratio of 0.87, but lower doses did not share this association (HR = 1.02).

In defense of their findings, Dr. Vargas-Santos and her associates evaluated the relevance of their study, compared with previous allopurinol studies.

“This study is one of few that have evaluated the relation of allopurinol to renal function among patients with gout and normal or near-normal kidney function at baseline,” the authors wrote, noting that most gout patients do not have severe kidney disease.

Previous studies have suggested that allopurinol worsens kidney function, but these studies were often conducted in nongout populations, with patients exhibiting CKD stage 3 or higher, they noted. Instead of allopurinol-induced kidney damage, renal decline in gout patients is likely multifactorial.

“Because people with gout have intrinsic differences compared with those with asymptomatic hyperuricemia, including higher mortality, more comorbidities, and more NSAID use, these studies’ results are not directly applicable to gout patients,” the investigators wrote.

“At minimum, allopurinol does not seem to have a detrimental effect on renal function in individuals with gout,” Dr. Vargas-Santos and her associates concluded. “Clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.”
The authors reported funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Ministry of Science, Technology and Innovation of Brazil; and National Institutes of Health. Dr Vargas-Santos has received speaking fees and support for international medical events from Grünenthal. No other disclosures were reported.

SOURCE: Vargas-Santos AB et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4463

*Correction, 11/5/2018: An earlier version of this story incorrectly stated the American College of Rheumatology’s 2012 gout treatment recommendation for using allopurinol in patients with renal impairment.

In patients with gout, at least 300 mg of allopurinol daily may reduce the risk of renal function decline, according to a new study.

London_England/Thinkstock

Since no evidence supports allopurinol nephrotoxicity and usage does not appear to worsen chronic kidney disease (CKD), clinicians should consider other causes of declining renal function, according to lead author Ana Beatriz Vargas-Santos, MD, of the rheumatology unit at the State University of Rio de Janeiro and her colleagues.

These findings reinforce the American College of Rheumatology’s 2012 treatment recommendation that the dose of allopurinol, a urate-lowering therapy (ULT), “can be raised above 300 mg daily, even with renal impairment, as long as it is accompanied by adequate patient education and monitoring for drug toxicity may worsen renal function.”*

“Renal-dosing of allopurinol compounds the poor management of gout and adds to the perception that allopurinol may be detrimental for renal function,” the investigators wrote in JAMA Internal Medicine. “In contrast, recent studies provide support for starting allopurinol at a low dose with gradual dose escalation to serum urate target with close monitoring, even among patients with renal insufficiency, without increased risk of allopurinol hypersensitivity syndrome (AHS). Further, there is emerging evidence that ULT may be beneficial for kidney dysfunction.”

Building upon these developments, the investigators “aimed to assess the relation of allopurinol initiation to the risk of developing CKD stage 3 or higher among people with newly diagnosed gout.”

Patients for the cohort study were drawn from the Health Improvement Network (THIN), a database of records from general practitioners in the United Kingdom. Included patients were recently diagnosed with gout but did not have stage 3 or higher chronic kidney disease or ULT usage within a year prior to diagnosis. After screening, 4,760 allopurinol users were matched with 4,760 allopurinol nonusers. Overall, 71% of patients had CKD stage 2, while the remaining 29% had CKD stage 1 or normal kidney function.

The primary outcome of CKD stage 3 or higher was defined as glomerular filtration rate below 60 mL/min (recorded at least twice in 1 year with a 3-month interval between readings and GFR never exceeding 75 mL/min during the intervening period), kidney transplant, or dialysis. The mean follow-up time was 5 years for allopurinol users and 4 years for nonusers.

The investigators found that 579 allopurinol users developed CKD stage 3 or higher, compared with 623 nonusers, suggesting that allopurinol reduced risk of CKD stage 3 or higher by 13%. Allopurinol doses of at least 300 mg/day were associated with a hazard ratio of 0.87, but lower doses did not share this association (HR = 1.02).

In defense of their findings, Dr. Vargas-Santos and her associates evaluated the relevance of their study, compared with previous allopurinol studies.

“This study is one of few that have evaluated the relation of allopurinol to renal function among patients with gout and normal or near-normal kidney function at baseline,” the authors wrote, noting that most gout patients do not have severe kidney disease.

Previous studies have suggested that allopurinol worsens kidney function, but these studies were often conducted in nongout populations, with patients exhibiting CKD stage 3 or higher, they noted. Instead of allopurinol-induced kidney damage, renal decline in gout patients is likely multifactorial.

“Because people with gout have intrinsic differences compared with those with asymptomatic hyperuricemia, including higher mortality, more comorbidities, and more NSAID use, these studies’ results are not directly applicable to gout patients,” the investigators wrote.

“At minimum, allopurinol does not seem to have a detrimental effect on renal function in individuals with gout,” Dr. Vargas-Santos and her associates concluded. “Clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.”
The authors reported funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Ministry of Science, Technology and Innovation of Brazil; and National Institutes of Health. Dr Vargas-Santos has received speaking fees and support for international medical events from Grünenthal. No other disclosures were reported.

SOURCE: Vargas-Santos AB et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4463

*Correction, 11/5/2018: An earlier version of this story incorrectly stated the American College of Rheumatology’s 2012 gout treatment recommendation for using allopurinol in patients with renal impairment.

In patients with gout, at least 300 mg of allopurinol daily may reduce the risk of renal function decline, according to a new study.

London_England/Thinkstock

Since no evidence supports allopurinol nephrotoxicity and usage does not appear to worsen chronic kidney disease (CKD), clinicians should consider other causes of declining renal function, according to lead author Ana Beatriz Vargas-Santos, MD, of the rheumatology unit at the State University of Rio de Janeiro and her colleagues.

These findings reinforce the American College of Rheumatology’s 2012 treatment recommendation that the dose of allopurinol, a urate-lowering therapy (ULT), “can be raised above 300 mg daily, even with renal impairment, as long as it is accompanied by adequate patient education and monitoring for drug toxicity may worsen renal function.”*

“Renal-dosing of allopurinol compounds the poor management of gout and adds to the perception that allopurinol may be detrimental for renal function,” the investigators wrote in JAMA Internal Medicine. “In contrast, recent studies provide support for starting allopurinol at a low dose with gradual dose escalation to serum urate target with close monitoring, even among patients with renal insufficiency, without increased risk of allopurinol hypersensitivity syndrome (AHS). Further, there is emerging evidence that ULT may be beneficial for kidney dysfunction.”

Building upon these developments, the investigators “aimed to assess the relation of allopurinol initiation to the risk of developing CKD stage 3 or higher among people with newly diagnosed gout.”

Patients for the cohort study were drawn from the Health Improvement Network (THIN), a database of records from general practitioners in the United Kingdom. Included patients were recently diagnosed with gout but did not have stage 3 or higher chronic kidney disease or ULT usage within a year prior to diagnosis. After screening, 4,760 allopurinol users were matched with 4,760 allopurinol nonusers. Overall, 71% of patients had CKD stage 2, while the remaining 29% had CKD stage 1 or normal kidney function.

The primary outcome of CKD stage 3 or higher was defined as glomerular filtration rate below 60 mL/min (recorded at least twice in 1 year with a 3-month interval between readings and GFR never exceeding 75 mL/min during the intervening period), kidney transplant, or dialysis. The mean follow-up time was 5 years for allopurinol users and 4 years for nonusers.

The investigators found that 579 allopurinol users developed CKD stage 3 or higher, compared with 623 nonusers, suggesting that allopurinol reduced risk of CKD stage 3 or higher by 13%. Allopurinol doses of at least 300 mg/day were associated with a hazard ratio of 0.87, but lower doses did not share this association (HR = 1.02).

In defense of their findings, Dr. Vargas-Santos and her associates evaluated the relevance of their study, compared with previous allopurinol studies.

“This study is one of few that have evaluated the relation of allopurinol to renal function among patients with gout and normal or near-normal kidney function at baseline,” the authors wrote, noting that most gout patients do not have severe kidney disease.

Previous studies have suggested that allopurinol worsens kidney function, but these studies were often conducted in nongout populations, with patients exhibiting CKD stage 3 or higher, they noted. Instead of allopurinol-induced kidney damage, renal decline in gout patients is likely multifactorial.

“Because people with gout have intrinsic differences compared with those with asymptomatic hyperuricemia, including higher mortality, more comorbidities, and more NSAID use, these studies’ results are not directly applicable to gout patients,” the investigators wrote.

“At minimum, allopurinol does not seem to have a detrimental effect on renal function in individuals with gout,” Dr. Vargas-Santos and her associates concluded. “Clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.”
The authors reported funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Ministry of Science, Technology and Innovation of Brazil; and National Institutes of Health. Dr Vargas-Santos has received speaking fees and support for international medical events from Grünenthal. No other disclosures were reported.

SOURCE: Vargas-Santos AB et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4463

*Correction, 11/5/2018: An earlier version of this story incorrectly stated the American College of Rheumatology’s 2012 gout treatment recommendation for using allopurinol in patients with renal impairment.

SAN ANTONIO – COPD patients with pulmonary circulation disorders were more than four times as likely to need invasive ventilation after noninvasive ventilation (NIV) failed for acute exacerbations, found a new study.

Tara Haelle/MDedge News

Patients with fluid and electrolyte abnormalities or alcohol abuse also had a greater risk of escalating beyond NIV for exacerbations, according to the findings.

“Patients with these underlying conditions should be monitored closely, especially individuals with existing pulmonary disorders as they are at highest risk,” Di Pan, DO, of Mount Sinai Hospital, New York, reported at annual meeting of the American College of Chest Physicians.

The researchers used the 2012-2014 Nationwide Inpatient Sample database to retrospectively analyze data from 73,480 patients, average age 67.8 years, who had a primary diagnosis of COPD exacerbation and who had received initial treatment with NIV in their first 24 hours after hospitalization. The report is in CHEST^® Journal(2018 Oct. doi: 10.1016/j.chest.2018.08.340).

The researchers examined associations between NIV failure and 29 Elixhauser comorbidity measures to identify what clinical characteristics might predict the need for invasive ventilation. They defined NIV failure as requiring intubation at any time within 30 days of admission.

Pulmonary circulation disorders emerged as the strongest predictor of the need for intubation, with a fourfold increase in relative risk (hazard ratio [HR]: 4.19, P less than .001). Alcohol abuse (HR: 1.85, P = .01) and fluid and electrolyte abnormalities (HR: 1.3, P less than .001) followed as additional factors associated with NIV failure. The latter included irregularities in potassium or sodium, acid-base disorders, hypervolemia and hypovolemia.

Among the 3,740 patients with alcohol abuse, additional statistically significant associations with intubation included a slightly higher mean age, female sex, and the mean Charlson comorbidity index. Mean age of those requiring intubation in this group was 62.28 years, compared 61.47 years among those in whom NIV was adequate (P = .03). Among those intubated, 30.2% of the patients were female, compared with 26.3% female patients in the nonintubated group.

Among the 26,150 patients with fluid, electrolyte and acid-base disturbances, younger patients were more likely to require intubation: The average age of those needing intubation was 67.23 years, compared with 69.3 years for those non-intubated (P less than .001). While a higher Charlson index (2.83 vs. 2.53) was again correlated with greater risk of needing intubation (P less than .001), males were now more likely to require intubation: 58.1% of those without intubation were female, compared with 53.9% of those needing intubation (P less than .001).

Within the 890 patients with pulmonary circulation disorders, mean age was 68.03 years for intubation and 70.77 years for nonintubation (P less than .001). In this group, 56.4% of the patients requiring intubation were female, compared to 47.9% of patients not intubated. The average Charlson index was lower (3.11) among those requiring intubation than among those not needing it (3.57, P less than .001).

The findings were limited by the lack of disease severity stratification and use of now-outdated ICD-9 coding. The researchers also lacked detailed clinical data, such as lab values, imaging results, and vital signs, and Dr. Pan acknowledged the broad variation within the diagnoses of the also-broad Elixhauser comorbidity index.

“For the next steps, we can do a stratified analysis” to identify which specific pulmonary circulation diseases primarily account for the association with intubation, Dr. Pan said.

No external funding was noted. The authors reported having no disclosures.

SOURCE: Pan D. et al. CHEST 2018. https://doi.org/10.1016/j.chest.2018.08.340.

SAN ANTONIO – COPD patients with pulmonary circulation disorders were more than four times as likely to need invasive ventilation after noninvasive ventilation (NIV) failed for acute exacerbations, found a new study.

Tara Haelle/MDedge News

Patients with fluid and electrolyte abnormalities or alcohol abuse also had a greater risk of escalating beyond NIV for exacerbations, according to the findings.

“Patients with these underlying conditions should be monitored closely, especially individuals with existing pulmonary disorders as they are at highest risk,” Di Pan, DO, of Mount Sinai Hospital, New York, reported at annual meeting of the American College of Chest Physicians.

The researchers used the 2012-2014 Nationwide Inpatient Sample database to retrospectively analyze data from 73,480 patients, average age 67.8 years, who had a primary diagnosis of COPD exacerbation and who had received initial treatment with NIV in their first 24 hours after hospitalization. The report is in CHEST^® Journal(2018 Oct. doi: 10.1016/j.chest.2018.08.340).

The researchers examined associations between NIV failure and 29 Elixhauser comorbidity measures to identify what clinical characteristics might predict the need for invasive ventilation. They defined NIV failure as requiring intubation at any time within 30 days of admission.

Pulmonary circulation disorders emerged as the strongest predictor of the need for intubation, with a fourfold increase in relative risk (hazard ratio [HR]: 4.19, P less than .001). Alcohol abuse (HR: 1.85, P = .01) and fluid and electrolyte abnormalities (HR: 1.3, P less than .001) followed as additional factors associated with NIV failure. The latter included irregularities in potassium or sodium, acid-base disorders, hypervolemia and hypovolemia.

Among the 3,740 patients with alcohol abuse, additional statistically significant associations with intubation included a slightly higher mean age, female sex, and the mean Charlson comorbidity index. Mean age of those requiring intubation in this group was 62.28 years, compared 61.47 years among those in whom NIV was adequate (P = .03). Among those intubated, 30.2% of the patients were female, compared with 26.3% female patients in the nonintubated group.

Among the 26,150 patients with fluid, electrolyte and acid-base disturbances, younger patients were more likely to require intubation: The average age of those needing intubation was 67.23 years, compared with 69.3 years for those non-intubated (P less than .001). While a higher Charlson index (2.83 vs. 2.53) was again correlated with greater risk of needing intubation (P less than .001), males were now more likely to require intubation: 58.1% of those without intubation were female, compared with 53.9% of those needing intubation (P less than .001).

Within the 890 patients with pulmonary circulation disorders, mean age was 68.03 years for intubation and 70.77 years for nonintubation (P less than .001). In this group, 56.4% of the patients requiring intubation were female, compared to 47.9% of patients not intubated. The average Charlson index was lower (3.11) among those requiring intubation than among those not needing it (3.57, P less than .001).

The findings were limited by the lack of disease severity stratification and use of now-outdated ICD-9 coding. The researchers also lacked detailed clinical data, such as lab values, imaging results, and vital signs, and Dr. Pan acknowledged the broad variation within the diagnoses of the also-broad Elixhauser comorbidity index.

“For the next steps, we can do a stratified analysis” to identify which specific pulmonary circulation diseases primarily account for the association with intubation, Dr. Pan said.

No external funding was noted. The authors reported having no disclosures.

SOURCE: Pan D. et al. CHEST 2018. https://doi.org/10.1016/j.chest.2018.08.340.

SAN ANTONIO – COPD patients with pulmonary circulation disorders were more than four times as likely to need invasive ventilation after noninvasive ventilation (NIV) failed for acute exacerbations, found a new study.

Tara Haelle/MDedge News

Patients with fluid and electrolyte abnormalities or alcohol abuse also had a greater risk of escalating beyond NIV for exacerbations, according to the findings.

“Patients with these underlying conditions should be monitored closely, especially individuals with existing pulmonary disorders as they are at highest risk,” Di Pan, DO, of Mount Sinai Hospital, New York, reported at annual meeting of the American College of Chest Physicians.

The researchers used the 2012-2014 Nationwide Inpatient Sample database to retrospectively analyze data from 73,480 patients, average age 67.8 years, who had a primary diagnosis of COPD exacerbation and who had received initial treatment with NIV in their first 24 hours after hospitalization. The report is in CHEST^® Journal(2018 Oct. doi: 10.1016/j.chest.2018.08.340).

The researchers examined associations between NIV failure and 29 Elixhauser comorbidity measures to identify what clinical characteristics might predict the need for invasive ventilation. They defined NIV failure as requiring intubation at any time within 30 days of admission.

Pulmonary circulation disorders emerged as the strongest predictor of the need for intubation, with a fourfold increase in relative risk (hazard ratio [HR]: 4.19, P less than .001). Alcohol abuse (HR: 1.85, P = .01) and fluid and electrolyte abnormalities (HR: 1.3, P less than .001) followed as additional factors associated with NIV failure. The latter included irregularities in potassium or sodium, acid-base disorders, hypervolemia and hypovolemia.

Among the 3,740 patients with alcohol abuse, additional statistically significant associations with intubation included a slightly higher mean age, female sex, and the mean Charlson comorbidity index. Mean age of those requiring intubation in this group was 62.28 years, compared 61.47 years among those in whom NIV was adequate (P = .03). Among those intubated, 30.2% of the patients were female, compared with 26.3% female patients in the nonintubated group.

Among the 26,150 patients with fluid, electrolyte and acid-base disturbances, younger patients were more likely to require intubation: The average age of those needing intubation was 67.23 years, compared with 69.3 years for those non-intubated (P less than .001). While a higher Charlson index (2.83 vs. 2.53) was again correlated with greater risk of needing intubation (P less than .001), males were now more likely to require intubation: 58.1% of those without intubation were female, compared with 53.9% of those needing intubation (P less than .001).

Within the 890 patients with pulmonary circulation disorders, mean age was 68.03 years for intubation and 70.77 years for nonintubation (P less than .001). In this group, 56.4% of the patients requiring intubation were female, compared to 47.9% of patients not intubated. The average Charlson index was lower (3.11) among those requiring intubation than among those not needing it (3.57, P less than .001).

The findings were limited by the lack of disease severity stratification and use of now-outdated ICD-9 coding. The researchers also lacked detailed clinical data, such as lab values, imaging results, and vital signs, and Dr. Pan acknowledged the broad variation within the diagnoses of the also-broad Elixhauser comorbidity index.

“For the next steps, we can do a stratified analysis” to identify which specific pulmonary circulation diseases primarily account for the association with intubation, Dr. Pan said.

No external funding was noted. The authors reported having no disclosures.

SOURCE: Pan D. et al. CHEST 2018. https://doi.org/10.1016/j.chest.2018.08.340.