- Email: [email protected]
Changing Incidence in Emergency Department Visits for Stroke
Research Forum Abstracts after, OR 0.11 [95% CI: 0.006 - 2.09]). The rate of transfers increased significantly at the study site (15.4% vs. 35.7%, OR 3.47 [95% CI: 1.12 - 10.76]), but did not change at the control site (48.5% vs. 50%, OR 0.94 [95% CI: 0.35 - 2.53]). Conclusions: Initiation of a rural ED acute stroke pathway increased the frequency of patient transfers but did not significantly impact the rate of tPA delivery. Larger studies are needed to further assess this strategy in terms of patient-centered outcomes.
367
Acute Headache in a Pediatric Emergency Department Muñiz A/Dallas Regional Medical Center, Mesquite, TX
Background: Headache is a common presenting complaint to pediatric emergency departments. The overwhelming majority headaches in children are benign, however it can be the initial symptom of life-threatening disorders. The appropriate diagnostic evaluation of children with headaches is unknown. Study Objective: The primary objective was to determine the clinical features that are more likely associated with serious conditions in children presenting with headache to a pediatric emergency department. The secondary objective was to determine the causes of these headaches. Methods: Prospective observational study of consecutive children less than 18 years old who presented to a pediatric ED with the chief complaint of headache. No patients were excluded. Demographic data was extracted and recorded. Etiologies were classified according to the International Headache Society. Data were analyzed using Stata 11 with continuous variables expressed as means and Student’s t test or KruskallWallis test used to asses significance, while categorical variables were summarized as frequencies of occurrence and assessed for statistical significance using chi-squared test or Fisher’s exact. Results: There were 275 children with 140 (51%) males. Mean age was 9.8 + 4.4 (95% CI, 9.2, 10.3), with a range of 1 to 17 years-old. There were 190 (69%) African Americans, 72 (26.1%) Caucasians, and 8 (2.9%) Hispanics. There were 80 (29.0%) children with fever. Location of the headache: bifrontal 111 (40.3%), diffuse 103 (37.4%), localized 49 917.8%), posterior 9 (3.2%) and bitemporal 3 (1%). Only 8 (2.9%) had an aura. Diagnostic test included: CBC count 72 (26.1%), basic metabolic profile 41 (14.9%), urinalysis 8 (2.9%), urine pregnancy test 1 (0.36%), rapid streptococcal antigen 12 (4.3%), CXR 2 (1.09%), CT scan of the head 95 (34.5%), and lumbar puncture 6 (2.1%). A neurologic consult was obtained in 4 (1.4%). Most common diagnosis included: viral syndrome (26.9%), nonspecific 61 (22.1%), migraine 33 (12%), contusion 32 (11%), ventriculoperitoneal (VP) shunt malfunction 20 (7.2%), streptococcal pharyngitis 15 (5.4%), otitis media (2.9%), rhinitis 6 (2.1%), sinusitis 6 (2.1%), meningitis 6 (2.1%), tension headache 2 (.07%), UTI 2 (0.7%), pneumonia 2 (0.7%), dental infection 2 (0.7%), tumor 1, subarachnoid hemorrhage 1, atlantoaxial rotary subluxation 1, Rocky Mountain spotted fever 1, and CO poisoning 1. Posterior location of the headache and the presence of a VP shunt were associated with serious underlying disease (p < 0.05). Conclusions: Headaches are a common presentation to a pediatric emergency department. Viral syndrome, nonspecific, migraine, contusions, VP shunt malfunction and streptococcus pharyngitis account for the majority of the cases. CT scan showed new abnormalities in a minority of patients and should be reserved for those with significant head trauma, VP shunt, neurologic abnormality or posterior location of headache.
368
Emergency Department Initiation of Levetiracetam for Seizure: A Cohort Study Examining Psychiatric Risk Assessment and Counseling
Afazal U, Oostema JA, Smith B/Michigan State University/Grand Rapids Medical Education Partners, Grand Rapids, MI; Spectrum Health, Michigan State University College of Human Medicine, Grand Rapids, MI; Spectrum Health, Michigan State Univsersity College of Human Medicine, Grand Rapids, MI
Study Objectives: Levetiracetam (LEV) is an antiepileptic drug (AED) used in both partial and generalized epilepsies and epilepsy syndromes. LEV has been associated with the development or exacerbation of psychiatric symptoms, especially among those with underlying mood or anxiety disorders. Aggression and psychosis have been reported, as well as depression, nervousness, hostility and emotional lability. These symptoms raise concern for the possibility of suicidal behavior. Therefore, it is important to consider the psychiatric history prior to initiating treatment with LEV. However, knowledge regarding these side effects may not be common among clinicians who only occasionally prescribe this medicine. The purpose of this study was to examine the frequency of
Volume 62, no. 4s : October 2013
documentation of psychiatric risk assessment and counseling for patients who receive LEV as a new AED in the emergency department (ED). Methods: This retrospective cohort study enrolled patients for whom LEV was initiated from the ED. Hospital administrative data was queried to identify ED patients with a diagnostic impression of seizure who received LEV in the ED. Patients were excluded if LEV was initiated previously or if the patient’s mental status precluded meaningful discussion of psychiatric history and side effects. Patient demographics, psychiatric history, previous suicide attempts, and antecedent use of antidepressants were recorded from anywhere in the electronic record before the index visit. ED clinician documentation of psychiatric history, counseling regarding psychiatric side effects, and neurology consultation were recorded. Finally, we reviewed all outpatient and subsequent ED visits or 90 days following the index visit and documented the occurrence of psychiatric side effects or counseling. The proportion of ED visits where LEV side-effect risk assessment or counseling was documented was the primary endpoint. The proportion of patients who presented subsequent to their index ED visit with psychiatric complaints was calculated as a secondary endpoint. Results: We identified 23 patients over a 12-month period who met inclusion criteria, 13 (57%) of whom were pediatric patients. Six patients (26%) had a previously documented history of psychiatric disease, including one suicide attempt. During the index visit, the psychiatric history was documented for 4 of these patients and neurology consultation was obtained for 19 (82%). Counseling regarding psychiatric side effects was documented in 4 (17%) cases, one of which had a prior history of psychiatric disease. Four patients had no further follow-up available. Of the 19 patients with follow-up, 6 (32%, 4 pediatric, 2 adult) reported psychiatric side effects. Only one of these individuals had a prior history of psychiatric disease. LEV was ultimately stopped for 3 of these patients and one required psychiatric hospitalization. Conclusions: Psychiatric risk assessment and counseling are not routinely documented by ED clinicians initiating LEV therapy for seizure. Psychiatric side effects are common in this population.
369
Changing Incidence in Emergency Department Visits for Stroke
Edwards KJ, Eskin B, Allegra JR/Morristown Medical Center, Morristown, NJ; Morrisotwn Medical Center, Morristown, NJ
Study Objectives: A British study showed stroke incidence declined 30% from 1999 to 2008. However, in a US national survey, strokes in women 35-54 years old tripled from 1988 to 2004 but did not change in men in the same age group. Our goal was to determine if similar changes occurred in visits for strokes in a US emergency department (ED) database from 1996 to 2010. This extends the period of time studied beyond the US national survey by 6 years. Methods: Design: Retrospective cohort. Setting: 19 suburban, urban and rural New York and New Jersey EDs with annual visits of 23,000 to 83,000. Subjects: Consecutive patients seen by ED physicians from 1/1/1996 to 12/31/2010. Observations: We identified stroke patients using ICD9 codes. We calculated the percent of ED visits that were for stroke for all patients, those > 35 years old and for each sex for the 35-44, 45-54, 55-64, and > 65 age groups. Preliminary review of the data showed few patients with strokes in the youngest age groups. In order to have sufficient numbers in each group to perform meaningful statistical analysis, we a priori pooled data for the five 3-year intervals of the study. We used the Chi square-test for statistical significance (alpha ¼ 0.05). Results: Of the 7,267,104 visits in the database, 32,042 (0.44%) were for stroke. The average age for all stroke patients was 73 +/- 15 years, 99% were > 35 years old and 55% were female. The incidence of stroke in patients > 35 years old declined 37% from 1996-1998 to 2008-2010. From 1996-8 to 2008-10, strokes in the females and males > 65 decreased significantly, but those in the two youngest female groups and males 45-54 years old increased. Particularly noticeable is the difference between genders for the 35-44 age group, where strokes increased markedly in females but did not change significantly in males. Conclusions: We found the same trends in the incidence of strokes found in earlier studies. Strokes in patients > 65 decreased significantly, but those in the two youngest female groups increased markedly. We speculate that the decrease in those > 65 is due to more use of antihypertensive and lipid-lowering medications and the increase in the youngest females and males aged 45-54 is due to increasing obesity. However, why the youngest females showed a striking (almost 60%) increase in strokes whereas the youngest males in contrast showed no significant change remains to be explained.
Annals of Emergency Medicine S131
Research Forum Abstracts
371
Ecallantide for the Acute Treatment of Angiotensin Converting Enzyme Inhibitor-Induced Angioedema: A Multicenter Randomized Controlled Trial
Lewis L, Graffeo C, Crosley P, Klausner HA, Clark CL, Frank A, Miner J, Iarrobino R, Chyung Y/Washington University School of Medicine, St. Louis, MO; Sentara Norfolk General Hospital, Norfolk, VA; DeKalb Medical Center, Decatur, GA; Henry Ford Health System, Detroit, MI; William Beaumont Hospital, Royal Oak, MI; ECU Emergency Medicine, Greenville, NC; Hennepin County Medical Center, Minneapolis, MN; Dyax, Burlington, MA
370
Long-Term, Organ-Specific Outcomes in Survivors of Severe Sepsis or Septic Shock: A Systematic Review
Guirgis FW, Khadpe J, Kuntz G, Wears R, Kalynych C, Jones AE/University of Florida, Jacksonville, FL; State University of New York, Downstate, New York, NY; University of Mississippi, Jackson, MS
Study Objectives: Sepsis is a prevalent disease with a high mortality; however, in recent years patients are surviving with increased morbidity, including organ dysfunction. Our objective is to review original research studies evaluating long-term, organ-specific outcomes in patients surviving severe sepsis admission. Methods: We performed a systematic review of long-term, organ-specific outcomes in patients surviving severe sepsis admission. Scopus, Pubmed, the Cochrane Library, and Web of Science databases were searched by our medical librarian as of November 28, 2012. Two authors independently reviewed citations, abstracts, and full articles. Original research studies were included if they met the following inclusion criteria: studies of adult patients that referred to “prognosis,” or “outcome” or that mentioned “organ dysfunction,” “organ failure,” “multi-organ dysfunction syndrome,” or “multi-organ failure” in patients with sepsis, severe sepsis or septic shock with follow-up of 28 days or longer. Results: We identified 1,307 citations with our search strategy. After removal of 134 duplicates, 1,173 titles were reviewed. Five articles met our inclusion criteria. There was very good agreement between the two reviewers on inclusion of abstracts (91% agreement, k¼.81) and excellent agreement on inclusion of full articles (100%, k¼1). The main outcomes of interest were long-term (>28 days from admission) organ dysfunction and organ failure resolution in sepsis survivors. Four studies (Cohen, Abraham 1997, Abraham 1998, and Chen) contributed to rates of organ dysfunction at 1 month and four studies (Bone, Cohen, Abraham 1997, and Chen) contributed to organ failure resolution at 1 month. Tests of heterogeneity by organ system showed the results to be heterogeneous (I2>95%) therefore a meta-analysis was not performed. Two studies by Abraham et al contributed the majority of patients to our review. For these two studies, fairly stable rates of 1-month organ dysfunction for ARDS (8-9%), renal (7-7.7%), hepatic (3-6.6%), and CNS (1.5-5%) were reported. The study by Cohen et al reported higher rates of dysfunction for pulmonary (non-ARDS and ARDS), hepatic and renal but similar rates for CNS and DIC when compared to the studies by Abraham. The study by Chen et al had the highest rates of dysfunction across all organ systems reporting rates of at least 47% dysfunction or higher at 28 days but had only 51 sepsis survivors. If this study is left out, the most consistent rates of 1 month dysfunction were reported for ARDS with a range of 8 to 12.3% and CNS with a range of 1.5 to 5.0% across 3 studies. For organ failure resolution the rates of dysfunction were too variable to summarize. Conclusions: Our findings suggest that the rates of organ dysfunction are varied across studies. Though there was significant heterogeneity when trying to combine the results, it appears that the most consistent rates of 1 month organ dysfunction across 3 studies were reported for ARDS and CNS with rates of 8 to 12.3% and 1.5 to 5%, respectively. When looking at data from the two largest studies by Abraham et al, the prevalence of 1-month organ dysfunction is under 10% for ARDS, renal, hepatic and CNS. Our study has helped to describe the prevalence of organ dysfunction but prospective studies are needed to better characterize organ dysfunction in survivors of sepsis further out from time of sepsis admission.
S132 Annals of Emergency Medicine
Study Objectives: Compare the safety and effectiveness of conventional therapy plus escalating doses of ecallantide to conventional therapy plus placebo for ACE inhibitor-induced angioedema (ACEIA). Methods: A multicenter phase 2 double-blinded study with subjects randomized in a 1:1:1:1 distribution to receive a single subcutaneous dose of ecallantide (10, 30, or 60 mg) or placebo, plus conventional therapy. Adults presenting to the emergency department within 12 hours of onset of ACEIA of the head/neck were eligible. The primary endpoint was defined as meeting the following predetermined discharge eligibility criteria within 6 hours of receiving study drug or placebo: Improvement of edema to “a little better” or “a lot better” using a 5-point scale Stable vital signs Absence of stridor Absence of dyspnea or use of accessory muscles during respiration Absence of drooling Able to drink without difficulty. Secondary outcomes included adverse event (AE) rate and rates of admission to the intensive care unit (ICU). A sample size of 176 patients was calculated to provide 80% power to determine a significant difference in primary endpoint response rates between ecallantide and placebo. Statistical analysis was conducted on an intention-to-treat basis. Results: An interim analysis of blinded study data indicated that a majority of all study subjects were meeting the primary endpoint, and the study was halted. Overall, 76 eligible subjects were enrolled; 79% were African-American. ACE inhibitor as monotherapy was taken in 82% of patients, and lisinopril was the ACE inhibitor prescribed in 80% of patients. Most patients had mild (45%) or moderate (42%) ACEIA at the time of ED evaluation. Based on the Ishoo classification of edema (Class I ¼ facial rash, facial edema, lip edema; Class II ¼ soft palate edema; class III ¼ tongue edema; Class IV ¼ laryngeal edema), 45% of patients were Class I, 5% were Class II, 41% were Class III, and 8% were Class IV. The primary endpoint was met by 72% (13/18) of the placebo group, 85% (17/20) of the 10 mg ecallantide group, 89% (17/19) of the 30 mg ecallantide group, and 89% (17/19) of the 60 mg ecallantide group. Comparing all dosages of ecallantide to placebo, there was a non-significant absolute difference of 15.7% (95%CI -10.9 to 41.2) in favor of ecallantide. The incidence of treatment-emergent AEs was 44% in the placebo group and 35%, 58%, and 63% in the 10, 30, and 60 mg ecallantide groups, respectively. No new safety signals related to ecallantide were identified. ICU admission rate was low and not significantly different between the combined treatment and placebo groups (8.6% [5/58] vs 16.7% [3/18] respectively; p¼.385). Conclusions: Compared with conventional therapy alone, the addition of ecallantide did not demonstrate a benefit in this small study of ED patients with mostly mild to moderate ACE inhibitor-induced angioedema. The majority of patients with mild to moderate angioedema are likely to meet discharge eligibility criteria within 6 hours of ED presentation regardless of intervention. No unexpected AEs related to ecallantide were reported. Further study is warranted to assess the utility of ecallantide in subjects with more moderate to severe Ishoo Class III, and IV angioedema.
372
Life After Sepsis Therapy: A One-Year Follow-Up Study of Early Goal-Directed Therapy Outcomes
Chettipally UK, Reed ME, Huang J, Rauchwerger AS, Ballard DW, Offerman SR, Vinson DR, CREST Network/Kaiser Permanente, South San Francisco, CA; Division of Research, Kaiser Permanente, Oakland, CA; Kaiser Permanente, San Rafael, CA; Kaiser Permanente, South Sacramento, CA; Kaiser Permanente, Sacramento/ Roseville, CA
Study Objectives: Severe sepsis and septic shock are major health care problems. More than 750,000 people in the United States are diagnosed with severe sepsis each year. The mortality of patients with sepsis is about 10 times that of the average non-septic
Volume 62, no. 4s : October 2013
367
Acute Headache in a Pediatric Emergency Department Muñiz A/Dallas Regional Medical Center, Mesquite, TX
Background: Headache is a common presenting complaint to pediatric emergency departments. The overwhelming majority headaches in children are benign, however it can be the initial symptom of life-threatening disorders. The appropriate diagnostic evaluation of children with headaches is unknown. Study Objective: The primary objective was to determine the clinical features that are more likely associated with serious conditions in children presenting with headache to a pediatric emergency department. The secondary objective was to determine the causes of these headaches. Methods: Prospective observational study of consecutive children less than 18 years old who presented to a pediatric ED with the chief complaint of headache. No patients were excluded. Demographic data was extracted and recorded. Etiologies were classified according to the International Headache Society. Data were analyzed using Stata 11 with continuous variables expressed as means and Student’s t test or KruskallWallis test used to asses significance, while categorical variables were summarized as frequencies of occurrence and assessed for statistical significance using chi-squared test or Fisher’s exact. Results: There were 275 children with 140 (51%) males. Mean age was 9.8 + 4.4 (95% CI, 9.2, 10.3), with a range of 1 to 17 years-old. There were 190 (69%) African Americans, 72 (26.1%) Caucasians, and 8 (2.9%) Hispanics. There were 80 (29.0%) children with fever. Location of the headache: bifrontal 111 (40.3%), diffuse 103 (37.4%), localized 49 917.8%), posterior 9 (3.2%) and bitemporal 3 (1%). Only 8 (2.9%) had an aura. Diagnostic test included: CBC count 72 (26.1%), basic metabolic profile 41 (14.9%), urinalysis 8 (2.9%), urine pregnancy test 1 (0.36%), rapid streptococcal antigen 12 (4.3%), CXR 2 (1.09%), CT scan of the head 95 (34.5%), and lumbar puncture 6 (2.1%). A neurologic consult was obtained in 4 (1.4%). Most common diagnosis included: viral syndrome (26.9%), nonspecific 61 (22.1%), migraine 33 (12%), contusion 32 (11%), ventriculoperitoneal (VP) shunt malfunction 20 (7.2%), streptococcal pharyngitis 15 (5.4%), otitis media (2.9%), rhinitis 6 (2.1%), sinusitis 6 (2.1%), meningitis 6 (2.1%), tension headache 2 (.07%), UTI 2 (0.7%), pneumonia 2 (0.7%), dental infection 2 (0.7%), tumor 1, subarachnoid hemorrhage 1, atlantoaxial rotary subluxation 1, Rocky Mountain spotted fever 1, and CO poisoning 1. Posterior location of the headache and the presence of a VP shunt were associated with serious underlying disease (p < 0.05). Conclusions: Headaches are a common presentation to a pediatric emergency department. Viral syndrome, nonspecific, migraine, contusions, VP shunt malfunction and streptococcus pharyngitis account for the majority of the cases. CT scan showed new abnormalities in a minority of patients and should be reserved for those with significant head trauma, VP shunt, neurologic abnormality or posterior location of headache.
368
Emergency Department Initiation of Levetiracetam for Seizure: A Cohort Study Examining Psychiatric Risk Assessment and Counseling
Afazal U, Oostema JA, Smith B/Michigan State University/Grand Rapids Medical Education Partners, Grand Rapids, MI; Spectrum Health, Michigan State University College of Human Medicine, Grand Rapids, MI; Spectrum Health, Michigan State Univsersity College of Human Medicine, Grand Rapids, MI
Study Objectives: Levetiracetam (LEV) is an antiepileptic drug (AED) used in both partial and generalized epilepsies and epilepsy syndromes. LEV has been associated with the development or exacerbation of psychiatric symptoms, especially among those with underlying mood or anxiety disorders. Aggression and psychosis have been reported, as well as depression, nervousness, hostility and emotional lability. These symptoms raise concern for the possibility of suicidal behavior. Therefore, it is important to consider the psychiatric history prior to initiating treatment with LEV. However, knowledge regarding these side effects may not be common among clinicians who only occasionally prescribe this medicine. The purpose of this study was to examine the frequency of
Volume 62, no. 4s : October 2013
documentation of psychiatric risk assessment and counseling for patients who receive LEV as a new AED in the emergency department (ED). Methods: This retrospective cohort study enrolled patients for whom LEV was initiated from the ED. Hospital administrative data was queried to identify ED patients with a diagnostic impression of seizure who received LEV in the ED. Patients were excluded if LEV was initiated previously or if the patient’s mental status precluded meaningful discussion of psychiatric history and side effects. Patient demographics, psychiatric history, previous suicide attempts, and antecedent use of antidepressants were recorded from anywhere in the electronic record before the index visit. ED clinician documentation of psychiatric history, counseling regarding psychiatric side effects, and neurology consultation were recorded. Finally, we reviewed all outpatient and subsequent ED visits or 90 days following the index visit and documented the occurrence of psychiatric side effects or counseling. The proportion of ED visits where LEV side-effect risk assessment or counseling was documented was the primary endpoint. The proportion of patients who presented subsequent to their index ED visit with psychiatric complaints was calculated as a secondary endpoint. Results: We identified 23 patients over a 12-month period who met inclusion criteria, 13 (57%) of whom were pediatric patients. Six patients (26%) had a previously documented history of psychiatric disease, including one suicide attempt. During the index visit, the psychiatric history was documented for 4 of these patients and neurology consultation was obtained for 19 (82%). Counseling regarding psychiatric side effects was documented in 4 (17%) cases, one of which had a prior history of psychiatric disease. Four patients had no further follow-up available. Of the 19 patients with follow-up, 6 (32%, 4 pediatric, 2 adult) reported psychiatric side effects. Only one of these individuals had a prior history of psychiatric disease. LEV was ultimately stopped for 3 of these patients and one required psychiatric hospitalization. Conclusions: Psychiatric risk assessment and counseling are not routinely documented by ED clinicians initiating LEV therapy for seizure. Psychiatric side effects are common in this population.
369
Changing Incidence in Emergency Department Visits for Stroke
Edwards KJ, Eskin B, Allegra JR/Morristown Medical Center, Morristown, NJ; Morrisotwn Medical Center, Morristown, NJ
Study Objectives: A British study showed stroke incidence declined 30% from 1999 to 2008. However, in a US national survey, strokes in women 35-54 years old tripled from 1988 to 2004 but did not change in men in the same age group. Our goal was to determine if similar changes occurred in visits for strokes in a US emergency department (ED) database from 1996 to 2010. This extends the period of time studied beyond the US national survey by 6 years. Methods: Design: Retrospective cohort. Setting: 19 suburban, urban and rural New York and New Jersey EDs with annual visits of 23,000 to 83,000. Subjects: Consecutive patients seen by ED physicians from 1/1/1996 to 12/31/2010. Observations: We identified stroke patients using ICD9 codes. We calculated the percent of ED visits that were for stroke for all patients, those > 35 years old and for each sex for the 35-44, 45-54, 55-64, and > 65 age groups. Preliminary review of the data showed few patients with strokes in the youngest age groups. In order to have sufficient numbers in each group to perform meaningful statistical analysis, we a priori pooled data for the five 3-year intervals of the study. We used the Chi square-test for statistical significance (alpha ¼ 0.05). Results: Of the 7,267,104 visits in the database, 32,042 (0.44%) were for stroke. The average age for all stroke patients was 73 +/- 15 years, 99% were > 35 years old and 55% were female. The incidence of stroke in patients > 35 years old declined 37% from 1996-1998 to 2008-2010. From 1996-8 to 2008-10, strokes in the females and males > 65 decreased significantly, but those in the two youngest female groups and males 45-54 years old increased. Particularly noticeable is the difference between genders for the 35-44 age group, where strokes increased markedly in females but did not change significantly in males. Conclusions: We found the same trends in the incidence of strokes found in earlier studies. Strokes in patients > 65 decreased significantly, but those in the two youngest female groups increased markedly. We speculate that the decrease in those > 65 is due to more use of antihypertensive and lipid-lowering medications and the increase in the youngest females and males aged 45-54 is due to increasing obesity. However, why the youngest females showed a striking (almost 60%) increase in strokes whereas the youngest males in contrast showed no significant change remains to be explained.
Annals of Emergency Medicine S131
Research Forum Abstracts
371
Ecallantide for the Acute Treatment of Angiotensin Converting Enzyme Inhibitor-Induced Angioedema: A Multicenter Randomized Controlled Trial
Lewis L, Graffeo C, Crosley P, Klausner HA, Clark CL, Frank A, Miner J, Iarrobino R, Chyung Y/Washington University School of Medicine, St. Louis, MO; Sentara Norfolk General Hospital, Norfolk, VA; DeKalb Medical Center, Decatur, GA; Henry Ford Health System, Detroit, MI; William Beaumont Hospital, Royal Oak, MI; ECU Emergency Medicine, Greenville, NC; Hennepin County Medical Center, Minneapolis, MN; Dyax, Burlington, MA
370
Long-Term, Organ-Specific Outcomes in Survivors of Severe Sepsis or Septic Shock: A Systematic Review
Guirgis FW, Khadpe J, Kuntz G, Wears R, Kalynych C, Jones AE/University of Florida, Jacksonville, FL; State University of New York, Downstate, New York, NY; University of Mississippi, Jackson, MS
Study Objectives: Sepsis is a prevalent disease with a high mortality; however, in recent years patients are surviving with increased morbidity, including organ dysfunction. Our objective is to review original research studies evaluating long-term, organ-specific outcomes in patients surviving severe sepsis admission. Methods: We performed a systematic review of long-term, organ-specific outcomes in patients surviving severe sepsis admission. Scopus, Pubmed, the Cochrane Library, and Web of Science databases were searched by our medical librarian as of November 28, 2012. Two authors independently reviewed citations, abstracts, and full articles. Original research studies were included if they met the following inclusion criteria: studies of adult patients that referred to “prognosis,” or “outcome” or that mentioned “organ dysfunction,” “organ failure,” “multi-organ dysfunction syndrome,” or “multi-organ failure” in patients with sepsis, severe sepsis or septic shock with follow-up of 28 days or longer. Results: We identified 1,307 citations with our search strategy. After removal of 134 duplicates, 1,173 titles were reviewed. Five articles met our inclusion criteria. There was very good agreement between the two reviewers on inclusion of abstracts (91% agreement, k¼.81) and excellent agreement on inclusion of full articles (100%, k¼1). The main outcomes of interest were long-term (>28 days from admission) organ dysfunction and organ failure resolution in sepsis survivors. Four studies (Cohen, Abraham 1997, Abraham 1998, and Chen) contributed to rates of organ dysfunction at 1 month and four studies (Bone, Cohen, Abraham 1997, and Chen) contributed to organ failure resolution at 1 month. Tests of heterogeneity by organ system showed the results to be heterogeneous (I2>95%) therefore a meta-analysis was not performed. Two studies by Abraham et al contributed the majority of patients to our review. For these two studies, fairly stable rates of 1-month organ dysfunction for ARDS (8-9%), renal (7-7.7%), hepatic (3-6.6%), and CNS (1.5-5%) were reported. The study by Cohen et al reported higher rates of dysfunction for pulmonary (non-ARDS and ARDS), hepatic and renal but similar rates for CNS and DIC when compared to the studies by Abraham. The study by Chen et al had the highest rates of dysfunction across all organ systems reporting rates of at least 47% dysfunction or higher at 28 days but had only 51 sepsis survivors. If this study is left out, the most consistent rates of 1 month dysfunction were reported for ARDS with a range of 8 to 12.3% and CNS with a range of 1.5 to 5.0% across 3 studies. For organ failure resolution the rates of dysfunction were too variable to summarize. Conclusions: Our findings suggest that the rates of organ dysfunction are varied across studies. Though there was significant heterogeneity when trying to combine the results, it appears that the most consistent rates of 1 month organ dysfunction across 3 studies were reported for ARDS and CNS with rates of 8 to 12.3% and 1.5 to 5%, respectively. When looking at data from the two largest studies by Abraham et al, the prevalence of 1-month organ dysfunction is under 10% for ARDS, renal, hepatic and CNS. Our study has helped to describe the prevalence of organ dysfunction but prospective studies are needed to better characterize organ dysfunction in survivors of sepsis further out from time of sepsis admission.
S132 Annals of Emergency Medicine
Study Objectives: Compare the safety and effectiveness of conventional therapy plus escalating doses of ecallantide to conventional therapy plus placebo for ACE inhibitor-induced angioedema (ACEIA). Methods: A multicenter phase 2 double-blinded study with subjects randomized in a 1:1:1:1 distribution to receive a single subcutaneous dose of ecallantide (10, 30, or 60 mg) or placebo, plus conventional therapy. Adults presenting to the emergency department within 12 hours of onset of ACEIA of the head/neck were eligible. The primary endpoint was defined as meeting the following predetermined discharge eligibility criteria within 6 hours of receiving study drug or placebo: Improvement of edema to “a little better” or “a lot better” using a 5-point scale Stable vital signs Absence of stridor Absence of dyspnea or use of accessory muscles during respiration Absence of drooling Able to drink without difficulty. Secondary outcomes included adverse event (AE) rate and rates of admission to the intensive care unit (ICU). A sample size of 176 patients was calculated to provide 80% power to determine a significant difference in primary endpoint response rates between ecallantide and placebo. Statistical analysis was conducted on an intention-to-treat basis. Results: An interim analysis of blinded study data indicated that a majority of all study subjects were meeting the primary endpoint, and the study was halted. Overall, 76 eligible subjects were enrolled; 79% were African-American. ACE inhibitor as monotherapy was taken in 82% of patients, and lisinopril was the ACE inhibitor prescribed in 80% of patients. Most patients had mild (45%) or moderate (42%) ACEIA at the time of ED evaluation. Based on the Ishoo classification of edema (Class I ¼ facial rash, facial edema, lip edema; Class II ¼ soft palate edema; class III ¼ tongue edema; Class IV ¼ laryngeal edema), 45% of patients were Class I, 5% were Class II, 41% were Class III, and 8% were Class IV. The primary endpoint was met by 72% (13/18) of the placebo group, 85% (17/20) of the 10 mg ecallantide group, 89% (17/19) of the 30 mg ecallantide group, and 89% (17/19) of the 60 mg ecallantide group. Comparing all dosages of ecallantide to placebo, there was a non-significant absolute difference of 15.7% (95%CI -10.9 to 41.2) in favor of ecallantide. The incidence of treatment-emergent AEs was 44% in the placebo group and 35%, 58%, and 63% in the 10, 30, and 60 mg ecallantide groups, respectively. No new safety signals related to ecallantide were identified. ICU admission rate was low and not significantly different between the combined treatment and placebo groups (8.6% [5/58] vs 16.7% [3/18] respectively; p¼.385). Conclusions: Compared with conventional therapy alone, the addition of ecallantide did not demonstrate a benefit in this small study of ED patients with mostly mild to moderate ACE inhibitor-induced angioedema. The majority of patients with mild to moderate angioedema are likely to meet discharge eligibility criteria within 6 hours of ED presentation regardless of intervention. No unexpected AEs related to ecallantide were reported. Further study is warranted to assess the utility of ecallantide in subjects with more moderate to severe Ishoo Class III, and IV angioedema.
372
Life After Sepsis Therapy: A One-Year Follow-Up Study of Early Goal-Directed Therapy Outcomes
Chettipally UK, Reed ME, Huang J, Rauchwerger AS, Ballard DW, Offerman SR, Vinson DR, CREST Network/Kaiser Permanente, South San Francisco, CA; Division of Research, Kaiser Permanente, Oakland, CA; Kaiser Permanente, San Rafael, CA; Kaiser Permanente, South Sacramento, CA; Kaiser Permanente, Sacramento/ Roseville, CA
Study Objectives: Severe sepsis and septic shock are major health care problems. More than 750,000 people in the United States are diagnosed with severe sepsis each year. The mortality of patients with sepsis is about 10 times that of the average non-septic
Volume 62, no. 4s : October 2013