Original Article
Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey*
Cephalalgia 2015, Vol. 35(4) 301–309 ! International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102414539055 cep.sagepub.com
Benjamin W Friedman1, Jason West1, David R Vinson2, Mia T Minen3, Andrew Restivo1 and E John Gallagher1 Abstract Background: Published data from 1998 revealed that most patients treated for migraine in an emergency department received opioids. Over the intervening years, a large body of evidence has emerged demonstrating the efficacy and safety of non-opioid alternatives. Expert opinion during these years has cautioned against use of opioids for migraine. Our objectives were to compare current frequency of use of various medications for acute migraine in US emergency departments with use of these same medications in 1998 and to identify factors independently associated with opioid use. Methods: We analyzed National Hospital Ambulatory Medical Care Survey data from 2010, the most current dataset available. The National Hospital Ambulatory Medical Care Survey is a public dataset collected and distributed by the Centers for Disease Control and Prevention. It is a multi-stage probability sample from randomly selected emergency departments across the country, designed to be representative of all US emergency department visits. We included in our analysis all patients with the ICD9 emergency department discharge diagnosis of migraine. We tabulated frequency of use of specific medications in 2010 and compared these results with the 1998 data. Using a logistic regression model, into which all of the following variables were entered, we explored the independent association between any opioid use in 2010 and sex, age, race/ethnicity, geographic region, type of hospital, triage pain score and history of emergency department use within the previous 12 months. Results: In 2010, there were 1.2 (95% confidence interval 0.9, 1.4) million migraine visits to US emergency departments. Including opioid-containing oral analgesic combinations, opioids were administered in 59% of visits (95% confidence interval 51, 67). The most commonly used parenteral agent, hydromorphone, was used in 25% (95% confidence interval 19, 33) of visits in 2010 versus less than 1% (95% confidence interval 0, 3) in 1998. Conversely, use of meperidine had decreased markedly over the same timeframe. In 2010, it was used in just 7% (95% confidence interval 4, 12) of visits compared to 37% (95% confidence interval 29, 45) in 1998. Metoclopramide, the most commonly used anti-dopaminergic, was administered in 17% (95% confidence interval 12, 23) of visits in 2010 and 3% (95% confidence interval 1, 6) of visits in 1998. Use of any triptan was relatively uncommon in 2010 (7% (95% confidence interval 4, 11) of visits) and in 1998 (10% (95% confidence interval 6, 15) of visits). Of the predictor variables listed above, only emergency department use within the previous 12 months was associated with opioid administration (adjusted odds ratio: 2.87 (95% confidence interval 1.03, 7.97)). Conclusions: In spite of recommendations to the contrary, opioids are still used in more than half of all emergency department visits for migraine. Though use of meperidine has decreased markedly between 1998 and 2010, it has largely been replaced by hydromorphone. Opioid use in migraine visits is independently associated with prior visits to the same emergency department in the previous 12 months.
1
Department of Emergency Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, NY, USA 2 Department of Emergency Medicine, Kaiser Permanente Sacramento Medical Center, CA, USA 3 John Graham Headache Center, Department of Neurology, Brigham and Women’s Faulkner Hospital and Harvard Medical School, MA, USA
*Meetings at which this work has since been presented: Society for Academic Emergency Medicine, Dallas, Texas, May 2014. Corresponding author: Benjamin W Friedman, Department of Emergency Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, USA. Email: [email protected]
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Cephalalgia 35(4)
Keywords Migraine, emergency department, opioid, anti-emetics Date received: 29 March 2014; revised: 12 April 2014; accepted: 2 May 2014
Introduction Migraine, an episodic headache disorder characterized by acutely disabling headaches, causes the majority of the five million headache visits to US emergency departments (EDs) annually (1,2). A large variety of different medications, and classes of medications, are used to treat migraine, including triptans, ergotamines, opioids, non-steroidal anti-inflammatory drugs, dopamine antagonists, anti-epileptics, barbituates and magnesium (1). Perhaps because of the broad range of therapeutic options available, substantial heterogeneity in practice patterns exists across EDs (3,4). Published data from 1998 revealed that 51% of patients treated for migraine in a US ED received parenteral opioids (1). Over the intervening years, a large body of evidence has emerged demonstrating the efficacy and safety of many non-opioid alternatives (5). Expert opinion during this same time period has cautioned against use of opioids for migraine, with reports linking opioid use to ED recidivism (3), ‘chronification’ of migraine (6) and refractoriness to triptan medication (7). The objective of this analysis was to use the most current National Hospital Ambulatory Medical Care Survey (NHAMCS), a descriptive, ED-oriented US dataset, to compare current frequency of use of various medications for acute migraine with use of these same medications in 1998 and to determine factors independently associated with opioid use.
Methods Overview This is an analysis of migraine management in EDs across the USA, drawn from the NHAMCS. NHAMCS is a retrospective probability sample from randomly selected US EDs, designed through a fourtiered sampling strategy, to be representative of all US ED visits. We compared the frequency of use of specific medications for migraine in 2010, the most current dataset available at the time of our analysis, with the frequency of use of the same medications in 1998, the only other time a similar analysis was published (1). We were particularly interested in changes in frequency and type of opioid use for migraine over this time interval.
We also examined these data for independent associations between opioid use and the various socio-demographic and clinical variables of interest discussed below. The Albert Einstein College of Medicine Institutional Review Board reviewed our research protocol administratively and determined it to be exempt from further review.
Subject selection We included in our analysis all patients in the NHAMCS 2010 dataset with the ED discharge diagnosis of ‘migraine’ (ICD9 346). NHAMCS is a dataset available in the public domain, collected and distributed by the National Center for Health Statistics of the Centers for Disease Control and Prevention (http:// www.cdc.gov/nchs/ahcd.htm). NHAMCS personnel identify random ED patient visits from randomly selected emergency service areas within randomly selected hospitals, drawn from randomly selected geographic regions of the USA. Trained analysts extract from the medical record the patient’s sociodemographic characteristics, characteristics of the patient’s chief complaint and treatment (8).
Variables of interest The NHAMCS patient record form is available at http://www.cdc.gov/nchs/data/ahcd/nhamcs100ed_ 2010.pdf. Opioids. In 2010, NHAMCS used the Multum classification of therapeutics, a proprietary system of classifying individual medications. Each medication administered or prescribed can be assigned up to four separate therapeutic classes. We counted a medication as an opioid if it was categorized as ‘060: narcotic analgesic’ and as an oral opioid analgesic combination if it was categorized as ‘191: narcotic analgesic combination’. Unfortunately, there is no mechanism in NHAMCS for differentiating route of medication administration. We therefore assumed that most of the opioids were administered parenterally and all of the opioid analgesic combinations were administered orally, since they are not generally available for parenteral use. The 1998 dataset does not contain a similar
303
Friedman et al. classification scheme. Therefore, summary data for medication classes in that dataset could be obtained only by summing frequency of use of all the specific opioids. Medications. We created a list of medications drawn from the published 1998 NHAMCS data and those medications with known efficacy or frequent usage in migraine. Opioids of interest included meperidine, hydromorphone, morphine, nalbuphine and butorphanol. Oral opioid analgesic combinations included those containing oxycodone, hydrocodone and codeine. Anti-emetics of interest included metoclopramide, prochlorperazine, droperidol and promethazine. We counted a medication as an anti-emetic if it was categorized as one of the following: ‘195: 5HT3 receptor antagonist’, ‘196: phenothiazine antiemetics’, ‘197: anticholinergic anti-emetics’ or ‘198: miscellaneous anti-emetics’. Triptan medications were aggregated into a single variable called ‘any triptan’. Also included were the non-steroidal anti-inflammatory drug ketorolac and the corticosteroid dexamethasone, both medications with established efficacy for acute migraine (9,10). Other than promethazine, an antihistamine with some anti-dopaminergic anti-emetic activity, two other anti-histamines, diphenhydramine and hydroxyzine, are commonly used as adjunctive therapy in migraine and are included in this analysis as well. In NHAMCS, all prescribed medications are assigned at least two five digit numeric codes based on generic and brand name. For example, acetaminophen has a code distinct from Tylenol. To identify all possible names of a particular medication, we searched for different brand names of generic medications using the Wikipedia (http://www.wikipedia.org) and Epocrates (http://www.epocrates.com) websites. We then created variables in which all the different generic and brand names for each medication were coded as a single medication variable. Socio-demographic variables. NHAMCS reports age, sex and race/ethnicity for each patient visit. In our analysis, we use the race/ethnicity variable reported as nonHispanic white, non-Hispanic black, Hispanic and non-Hispanic other. Geographic region. In NHAMCS, the USA is divided into four regions: the Northeast; South; Midwest; West. Type of hospital. We used two NHAMCS variables to describe type of hospital. The first variable is hospital ownership, which is categorized as: (1) voluntary nonprofit; (2) Government, non-Federal; (3) proprietary. Federal hospitals, which represent only 4% of US hospitals, are not included in NHAMCS. The second
variable is ‘Seen by resident/ intern?’, which is categorized as yes or no. Presenting level of pain. NHAMCS records the triage pain score, as reported on a standard verbal numerical rating scale from zero to 10. Previous ED visits. NHAMCS personnel determine how many visits the patient had made to the ED under examination in the previous 12 months. For the purpose of our analysis, this variable was dichotomized as ‘previous visits’ or ‘no previous visits’. Length of visit. NHAMCS abstractors calculated the time elapsed between ED arrival and ED discharge in minutes. Number of medications administered in ED. NHAMCS reports the number of different medications administered.
Outcomes The outcomes of interest for this study were the frequency of use of opioid and non-opioid medications for acute migraine in US EDs.
Analysis We used SPSS v.21’s complex samples module to incorporate the relative weight of each patient visit. NHAMCS determines the relative weight by adjusting for sampling strategy, missing data and the relative contribution of various regions of the country. More information on NHAMCS methodology is available at the website (http://www.cdc.gov/nchs/ahcd.htm). We reported frequency of use of each medication in 2010 bounded by 95% confidence interval (CI). We compared the frequency of use of these medications with the same medications in 1998. We re-analyzed the 1998 data to include an updated weighting procedure and to report 95% CI. We also examined the independent association of each of the following eight candidate predictor variables with opioid use: sex; age; race/ethnicity; geographic region of the USA; hospital type; seen by resident/intern; presenting level of pain; previous use of ED in the past 12 months. For each variable, we report the frequency of opioid or opioid analgesic combination use for each response item for the variable. We report raw frequency count, estimated frequency count, and frequency percentage with 95% CI. We computed adjusted odds ratios with 95% CI using a logistic regression model in which all of the variables listed above were included as independent candidate variables. Length of stay is reported
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Cephalalgia 35(4)
as median with inter-quartile range. Number of medications administered in the ED is reported for all migraine patients and for migraine patients who received an opioid. For the continuous variables, age and presenting level of pain, we divided the data at clinically relevant cut-points. For age, this was at 18 years and 50 years. We had hoped to use 65 years as a cut-point, but there was an insufficient number of elderly patients. For pain, we used the categories ‘0’, ‘1–7’ and ‘8–10’. These categories represent no pain, mild to moderate pain and severe pain. Mild and moderate pain were lumped together due to a paucity of patients with mild or moderate pain.
Results In 2010, there were 1.2 (95% CI 0.9, 1.4) million migraine visits to US EDs compared with 1.1 (95% CI 0.9, 1.2) million visits in 1998. In 2010, opioid medications were administered or prescribed in 49% of visits (95% CI 40, 58) (Table 1). Including oral opioid analgesic combinations, which were administered in 19% (95% CI 15, 25) of migraine visits, opioids were administered or prescribed in 59% of visits (95% CI 51, 67).
Table 1. Frequency of use of medications in 2010 and 1998.
Medication
Frequency of use in 2010 (95% CI)
Frequency of use in 1998 (95% CI)
Opioid Hydromorphone 25% (19, 33)
Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey*
Cephalalgia 2015, Vol. 35(4) 301–309 ! International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102414539055 cep.sagepub.com
Benjamin W Friedman1, Jason West1, David R Vinson2, Mia T Minen3, Andrew Restivo1 and E John Gallagher1 Abstract Background: Published data from 1998 revealed that most patients treated for migraine in an emergency department received opioids. Over the intervening years, a large body of evidence has emerged demonstrating the efficacy and safety of non-opioid alternatives. Expert opinion during these years has cautioned against use of opioids for migraine. Our objectives were to compare current frequency of use of various medications for acute migraine in US emergency departments with use of these same medications in 1998 and to identify factors independently associated with opioid use. Methods: We analyzed National Hospital Ambulatory Medical Care Survey data from 2010, the most current dataset available. The National Hospital Ambulatory Medical Care Survey is a public dataset collected and distributed by the Centers for Disease Control and Prevention. It is a multi-stage probability sample from randomly selected emergency departments across the country, designed to be representative of all US emergency department visits. We included in our analysis all patients with the ICD9 emergency department discharge diagnosis of migraine. We tabulated frequency of use of specific medications in 2010 and compared these results with the 1998 data. Using a logistic regression model, into which all of the following variables were entered, we explored the independent association between any opioid use in 2010 and sex, age, race/ethnicity, geographic region, type of hospital, triage pain score and history of emergency department use within the previous 12 months. Results: In 2010, there were 1.2 (95% confidence interval 0.9, 1.4) million migraine visits to US emergency departments. Including opioid-containing oral analgesic combinations, opioids were administered in 59% of visits (95% confidence interval 51, 67). The most commonly used parenteral agent, hydromorphone, was used in 25% (95% confidence interval 19, 33) of visits in 2010 versus less than 1% (95% confidence interval 0, 3) in 1998. Conversely, use of meperidine had decreased markedly over the same timeframe. In 2010, it was used in just 7% (95% confidence interval 4, 12) of visits compared to 37% (95% confidence interval 29, 45) in 1998. Metoclopramide, the most commonly used anti-dopaminergic, was administered in 17% (95% confidence interval 12, 23) of visits in 2010 and 3% (95% confidence interval 1, 6) of visits in 1998. Use of any triptan was relatively uncommon in 2010 (7% (95% confidence interval 4, 11) of visits) and in 1998 (10% (95% confidence interval 6, 15) of visits). Of the predictor variables listed above, only emergency department use within the previous 12 months was associated with opioid administration (adjusted odds ratio: 2.87 (95% confidence interval 1.03, 7.97)). Conclusions: In spite of recommendations to the contrary, opioids are still used in more than half of all emergency department visits for migraine. Though use of meperidine has decreased markedly between 1998 and 2010, it has largely been replaced by hydromorphone. Opioid use in migraine visits is independently associated with prior visits to the same emergency department in the previous 12 months.
1
Department of Emergency Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, NY, USA 2 Department of Emergency Medicine, Kaiser Permanente Sacramento Medical Center, CA, USA 3 John Graham Headache Center, Department of Neurology, Brigham and Women’s Faulkner Hospital and Harvard Medical School, MA, USA
*Meetings at which this work has since been presented: Society for Academic Emergency Medicine, Dallas, Texas, May 2014. Corresponding author: Benjamin W Friedman, Department of Emergency Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, USA. Email: [email protected]
302
Cephalalgia 35(4)
Keywords Migraine, emergency department, opioid, anti-emetics Date received: 29 March 2014; revised: 12 April 2014; accepted: 2 May 2014
Introduction Migraine, an episodic headache disorder characterized by acutely disabling headaches, causes the majority of the five million headache visits to US emergency departments (EDs) annually (1,2). A large variety of different medications, and classes of medications, are used to treat migraine, including triptans, ergotamines, opioids, non-steroidal anti-inflammatory drugs, dopamine antagonists, anti-epileptics, barbituates and magnesium (1). Perhaps because of the broad range of therapeutic options available, substantial heterogeneity in practice patterns exists across EDs (3,4). Published data from 1998 revealed that 51% of patients treated for migraine in a US ED received parenteral opioids (1). Over the intervening years, a large body of evidence has emerged demonstrating the efficacy and safety of many non-opioid alternatives (5). Expert opinion during this same time period has cautioned against use of opioids for migraine, with reports linking opioid use to ED recidivism (3), ‘chronification’ of migraine (6) and refractoriness to triptan medication (7). The objective of this analysis was to use the most current National Hospital Ambulatory Medical Care Survey (NHAMCS), a descriptive, ED-oriented US dataset, to compare current frequency of use of various medications for acute migraine with use of these same medications in 1998 and to determine factors independently associated with opioid use.
Methods Overview This is an analysis of migraine management in EDs across the USA, drawn from the NHAMCS. NHAMCS is a retrospective probability sample from randomly selected US EDs, designed through a fourtiered sampling strategy, to be representative of all US ED visits. We compared the frequency of use of specific medications for migraine in 2010, the most current dataset available at the time of our analysis, with the frequency of use of the same medications in 1998, the only other time a similar analysis was published (1). We were particularly interested in changes in frequency and type of opioid use for migraine over this time interval.
We also examined these data for independent associations between opioid use and the various socio-demographic and clinical variables of interest discussed below. The Albert Einstein College of Medicine Institutional Review Board reviewed our research protocol administratively and determined it to be exempt from further review.
Subject selection We included in our analysis all patients in the NHAMCS 2010 dataset with the ED discharge diagnosis of ‘migraine’ (ICD9 346). NHAMCS is a dataset available in the public domain, collected and distributed by the National Center for Health Statistics of the Centers for Disease Control and Prevention (http:// www.cdc.gov/nchs/ahcd.htm). NHAMCS personnel identify random ED patient visits from randomly selected emergency service areas within randomly selected hospitals, drawn from randomly selected geographic regions of the USA. Trained analysts extract from the medical record the patient’s sociodemographic characteristics, characteristics of the patient’s chief complaint and treatment (8).
Variables of interest The NHAMCS patient record form is available at http://www.cdc.gov/nchs/data/ahcd/nhamcs100ed_ 2010.pdf. Opioids. In 2010, NHAMCS used the Multum classification of therapeutics, a proprietary system of classifying individual medications. Each medication administered or prescribed can be assigned up to four separate therapeutic classes. We counted a medication as an opioid if it was categorized as ‘060: narcotic analgesic’ and as an oral opioid analgesic combination if it was categorized as ‘191: narcotic analgesic combination’. Unfortunately, there is no mechanism in NHAMCS for differentiating route of medication administration. We therefore assumed that most of the opioids were administered parenterally and all of the opioid analgesic combinations were administered orally, since they are not generally available for parenteral use. The 1998 dataset does not contain a similar
303
Friedman et al. classification scheme. Therefore, summary data for medication classes in that dataset could be obtained only by summing frequency of use of all the specific opioids. Medications. We created a list of medications drawn from the published 1998 NHAMCS data and those medications with known efficacy or frequent usage in migraine. Opioids of interest included meperidine, hydromorphone, morphine, nalbuphine and butorphanol. Oral opioid analgesic combinations included those containing oxycodone, hydrocodone and codeine. Anti-emetics of interest included metoclopramide, prochlorperazine, droperidol and promethazine. We counted a medication as an anti-emetic if it was categorized as one of the following: ‘195: 5HT3 receptor antagonist’, ‘196: phenothiazine antiemetics’, ‘197: anticholinergic anti-emetics’ or ‘198: miscellaneous anti-emetics’. Triptan medications were aggregated into a single variable called ‘any triptan’. Also included were the non-steroidal anti-inflammatory drug ketorolac and the corticosteroid dexamethasone, both medications with established efficacy for acute migraine (9,10). Other than promethazine, an antihistamine with some anti-dopaminergic anti-emetic activity, two other anti-histamines, diphenhydramine and hydroxyzine, are commonly used as adjunctive therapy in migraine and are included in this analysis as well. In NHAMCS, all prescribed medications are assigned at least two five digit numeric codes based on generic and brand name. For example, acetaminophen has a code distinct from Tylenol. To identify all possible names of a particular medication, we searched for different brand names of generic medications using the Wikipedia (http://www.wikipedia.org) and Epocrates (http://www.epocrates.com) websites. We then created variables in which all the different generic and brand names for each medication were coded as a single medication variable. Socio-demographic variables. NHAMCS reports age, sex and race/ethnicity for each patient visit. In our analysis, we use the race/ethnicity variable reported as nonHispanic white, non-Hispanic black, Hispanic and non-Hispanic other. Geographic region. In NHAMCS, the USA is divided into four regions: the Northeast; South; Midwest; West. Type of hospital. We used two NHAMCS variables to describe type of hospital. The first variable is hospital ownership, which is categorized as: (1) voluntary nonprofit; (2) Government, non-Federal; (3) proprietary. Federal hospitals, which represent only 4% of US hospitals, are not included in NHAMCS. The second
variable is ‘Seen by resident/ intern?’, which is categorized as yes or no. Presenting level of pain. NHAMCS records the triage pain score, as reported on a standard verbal numerical rating scale from zero to 10. Previous ED visits. NHAMCS personnel determine how many visits the patient had made to the ED under examination in the previous 12 months. For the purpose of our analysis, this variable was dichotomized as ‘previous visits’ or ‘no previous visits’. Length of visit. NHAMCS abstractors calculated the time elapsed between ED arrival and ED discharge in minutes. Number of medications administered in ED. NHAMCS reports the number of different medications administered.
Outcomes The outcomes of interest for this study were the frequency of use of opioid and non-opioid medications for acute migraine in US EDs.
Analysis We used SPSS v.21’s complex samples module to incorporate the relative weight of each patient visit. NHAMCS determines the relative weight by adjusting for sampling strategy, missing data and the relative contribution of various regions of the country. More information on NHAMCS methodology is available at the website (http://www.cdc.gov/nchs/ahcd.htm). We reported frequency of use of each medication in 2010 bounded by 95% confidence interval (CI). We compared the frequency of use of these medications with the same medications in 1998. We re-analyzed the 1998 data to include an updated weighting procedure and to report 95% CI. We also examined the independent association of each of the following eight candidate predictor variables with opioid use: sex; age; race/ethnicity; geographic region of the USA; hospital type; seen by resident/intern; presenting level of pain; previous use of ED in the past 12 months. For each variable, we report the frequency of opioid or opioid analgesic combination use for each response item for the variable. We report raw frequency count, estimated frequency count, and frequency percentage with 95% CI. We computed adjusted odds ratios with 95% CI using a logistic regression model in which all of the variables listed above were included as independent candidate variables. Length of stay is reported
304
Cephalalgia 35(4)
as median with inter-quartile range. Number of medications administered in the ED is reported for all migraine patients and for migraine patients who received an opioid. For the continuous variables, age and presenting level of pain, we divided the data at clinically relevant cut-points. For age, this was at 18 years and 50 years. We had hoped to use 65 years as a cut-point, but there was an insufficient number of elderly patients. For pain, we used the categories ‘0’, ‘1–7’ and ‘8–10’. These categories represent no pain, mild to moderate pain and severe pain. Mild and moderate pain were lumped together due to a paucity of patients with mild or moderate pain.
Results In 2010, there were 1.2 (95% CI 0.9, 1.4) million migraine visits to US EDs compared with 1.1 (95% CI 0.9, 1.2) million visits in 1998. In 2010, opioid medications were administered or prescribed in 49% of visits (95% CI 40, 58) (Table 1). Including oral opioid analgesic combinations, which were administered in 19% (95% CI 15, 25) of migraine visits, opioids were administered or prescribed in 59% of visits (95% CI 51, 67).
Table 1. Frequency of use of medications in 2010 and 1998.
Medication
Frequency of use in 2010 (95% CI)
Frequency of use in 1998 (95% CI)
Opioid Hydromorphone 25% (19, 33)
