outofhospital cardiac arrest ( ohca ) is a major public health problem affecting 300  000 people in the united states each year.1 past studies demonstrate that there are sex differences in survival from cardiac arrest .
studies have consistently found more favorable arrest characteristics in men , including younger age and a higher frequency of initial shockable rhythm , witnessed arrest , and bystander cardiopulmonary resuscitation ( cpr).2 , 3 , 4 , 5 however , there is conflicting evidence regarding patient outcomes ( survival and neurological outcome ) . whereas some studies have reported improved survival in women,2 , 3 , 6 particularly those of childbearing age,7 others show no difference or even lower survival in women.4 , 5 , 8 , 9 
  the implications for differences in care also remain undefined . the majority of past studies included patients treated before regional systems of care and advanced postresuscitation management , including widespread adoption of early percutaneous coronary intervention ( pci ) and targeted temperature management ( ttm ) .
a recent metaanalysis of these studies reported increased survival in women , but outcomes may be very different with current management approaches.10 
  the 2014 academic emergency medicine consensus conference cardiovascular resuscitation working group identified ohca epidemiology as a research priority , noting that exploring sexspecifics in ohca can allow targeted improvements in resuscitation and outcomes.11 the goal of this study was to evaluate sex differences in ohca characteristics , interventions , and outcomes , including survival to hospital discharge and survival with good neurological outcome , in a large regional cardiac system of care with established pci and ttm protocols .
this is a retrospective study of registry data from the los angeles ( la ) county emergency medical services ( ems ) system .
the study was reviewed and approved with exemption of informed consent by the institutional review board .
la county is a large metropolis , comprising 88 cities spanning over 4000 square miles with a population of 10.2  million .
la county ems operates a regional cardiac system of care for patients with stsegment elevation myocardial infarction ( stemi ) and/or ohca that has been previously described.12 , 13 ems providers transport patients resuscitated from ohca to 1 of 35 currently designated cardiac arrest receiving centers .
these centers are capable of providing immediate coronary angiography and primary pci 24  hours per day , 7  days per week , and have cardiovascular surgeons available . in addition
, all centers are required to have a robust quality improvement program and internal policies for pci , fibrinolysis , and ttm .
cardiac arrest receiving centers submit data on all adult patients with return of spontaneous circulation ( rosc ) postohca to a single registry maintained by the la county ems agency .
data abstraction from prehospital and hospital records is completed by registered nurses ( rns ) in the departments of emergency medicine , cardiology , and/or quality improvement .
completeness and accuracy of the entered data is reviewed by the ems agency with verification performed during site visits .
study variables included age , sex , race / ethnicity , initial cardiac rhythm , arrest location , witness , bystander cpr , electrocardiogram ( ecg ) findings ( stemi or no stemi ) , length of stay , induction of hypothermia , and whether the patient received coronary angiography and pci .
stemi was indicated in the database if stemi was identified on the ecg , either in the field by software interpretation or in the emergency department by physician interpretation .
the primary outcome of the study was survival to hospital discharge with good neurological outcome in women compared to men , as defined by a cerebral performance category ( cpc ) score at hospital discharge of 1 or 2 .
a cpc of 1 corresponds to a return to normal or mildly impaired cerebral function and independence with activities of daily living ( adl ) .
a cpc of 2 corresponds to moderate cerebral disability but sufficient function to remain independent with the adl .
the cpc scores documented by physician , nurse , or occupational therapy assessment at the time of discharge were abstracted from the medical record and recorded in the database .
patient characteristics , interventions , and outcomes were evaluated by sex for the entire cohort as well as the subgroup of witnessed cardiac arrest with initial shockable rhythm . the adjusted odds ratio ( or ) for survival with good neurological outcome
all data were entered into microsoft excel ( microsoft corporation , redmond wa ) and transferred to sas software ( version 9.4 ; sas institute inc . ,
we report the neurologically intact survival rates as proportions with risk differences and exact binomial confidence intervals . adjusted ors and their p values
variables in regression , which included patient characteristics ( age , sex ) , arrest characteristics ( initial rhythm , witness , and bystander cpr ) , and interventions ( coronary angiography , pci , and ttm ) , were selected based on previous knowledge of their contribution to cardiac arrest outcomes . in order to specifically evaluate the confounding effects of hospital treatment on the association of sex with outcome , we constructed 2 primary models : the first limited to baseline patient and arrest characteristics without hospital interventions and the second inclusive of all variables above entered simultaneously into the model .
in addition , we accounted for clustering by hospital with generalized estimating equations ( gees ) using the proc genmod option in sas 9.4 .
given that there is evidence that women are less likely to undergo treatments , such as coronary angiography and ttm,8 , 14 , 15 , 16 as part of a sensitivity analysis , the sexeffect estimate was evaluated in an additional model , one in which the interaction terms between sex and ttm and between sex and coronary angiography were included .
there were 5174 ohcas in the registry during the study period , including 3080 males and 2094 females .
women were older , median 71  ( interquartile range [ iqr ] , 5982 ) versus 66 years ( iqr , 5578 ) . despite a similar frequency of witnessed arrest , women were less likely to present with a shockable rhythm ( 22% vs 35% ; risk difference [ rd ] , 13% ; 95% ci , 1115 ) compared to men .
characteristics , treatment and outcome by sex ( n=5174 ) cpc indicates cerebral performance category ; cpr , cardiopulmonary resuscitation ; iqr , interquartile range ; pci , percutaneous coronary intervention ; stemi , stsegment elevation myocardial infarction ; ttm , targeted temperature management . regarding interventions ,
women were less likely to have stemi on the ecg ( 23% vs 32% ; rd , 13% ; 95% ci , 711 ) , receive emergent coronary angiography ( 11% vs 25% ; rd , 14% ; 95% ci , 1216 ) , pci ( 5% vs 14% ; rd , 9% ; 95% ci , 711 ) , or ttm ( 33% vs 40% ; rd , 7% ; 95% ci , 410 ) . in the unadjusted comparison ,
women had decreased survival to hospital discharge ( 33% vs 40% ; rd , 7% ; 95% ci , 410 ) and a lower proportion survived with good neurological outcome ( 16% vs 24% ; rd , 8% ; 95% ci , 610 ) . among patients with a witnessed cardiac arrest with an initial shockable rhythm shown in table  2 ,
of whom there were 974 males and 390 females , sex differences were similar , with a few exceptions .
in addition , survival to hospital discharge was the same as compared to men . however , survival with good neurological outcome among women remained lower ( 38% vs 45% ; rd , 7% ; 95% ci , 113 ) .
characteristics , treatment , and outcome by sex for patients with witnessed arrest and initial shockable rhythm ( n=1364 ) cpc indicates cerebral performance category ;
cpr , cardiopulmonary resuscitation ; iqr , interquartile range ; pci , percutaneous coronary intervention ; stemi , stsegment elevation myocardial infarction ; ttm , targeted temperature management . tables  3 and 4 show the results of the regression analyses . with adjustment for age and arrest characteristics , there is a borderline statistically significant association between female sex and worse neurological outcome ( or , 0.8 ; 95% ci , 0.71.0 ; table  3 ) .
however , after adjustment for age , arrest characteristics ( initial rhythm , witness , and bystander cpr ) , and interventions ( coronary angiography , pci , and ttm ) , female sex was not associated with decreased survival with good neurological outcome ( or , 0.9 ; 95% ci , 0.81.1 ; table  4 ) . the sensitivity analysis , shown in table  5 , including the interaction terms between sex and ttm and between sex and catheterization , demonstrated similar results with a wider confidence interval ( or , 1.0 ; 95% ci , 0.71.4 ) . that is , taking into account the potential differing effects of hospital interventions in males and females ,
when coronary angiography and ttm are performed , there is no association of sex on outcome . in both models
odds ratios for survival to hospital discharge with good neurological outcome adjusting for age and arrest characteristics and accounting for clustering by hospital ( n=4504 ) cpr indicates cardiopulmonary resuscitation ; or , odds ratio . *
odds ratios for survival to hospital discharge with good neurological outcome adjusting for age , arrest characteristics and interventions , and accounting for clustering by hospital ( n=4477 ) cpr indicates cardiopulmonary resuscitation ; or , odds ratio ; pci , percutaneous coronary intervention ; ttm , targeted temperature management . *
odds ratios for survival to hospital discharge with good neurological outcome adjusting for age , arrest characteristics , and interventions including sextreatment interaction terms and accounting for clustering by hospital ( n=4477 ) cpr indicates cardiopulmonary resuscitation ; or , odds ratio ; pci , percutaneous coronary intervention ; ttm , targeted temperature management . at coronary angiography and ttm
in this contemporary cohort of consecutive patients treated in a large , regional care system , we found significant sex differences in ohca .
overall , men were more likely to present with favorable arrest characteristics ( initial shockable rhythm ) and more likely to receive interventions ( emergent coronary angiography and ttm ) . however , there was no association with sex and neurologically intact survival after adjustment for these factors .
our data support underlying differences in the presentation and management of cardiac arrest between men and women as the cause for noted outcome disparities .
kim et  al evaluated sex 's modification of the effect of therapeutic hypothermia on neurological outcome and reported an overall lower mortality in men .
the researchers noted that the favorable arrest characteristics , including increased frequency of initial shockable rhythm , witnessed arrest , and bystander cpr , were a potential reason.4 a large study in japan reported better unadjusted survival in men compared to women and attributed this to a higher proportion of initial shockable rhythm and witnessed arrest.3 the differences in arrest characteristics were also noted in a subsequent analysis of the lucas in cardiac arrest trial .
similar to our study , women were older and less frequently presented with an initial shockable rhythm , although there was no difference in the frequency of bystander witness arrests or cpr .
with adjustment for these factors , there was no association between sex and survival to hospital discharge or at 6  months.5 
  our study differs from much of the past literature in the population and setting .
the majority of past studies included in the recent metaanalysis by bougouin et  al , which noted improved survival in women , spanned a time frame when current postresuscitation management was not available.10 in addition , much of the more recent studies are from cohorts in asia and scandinavia and inclusive of all ohca resuscitations.3 , 4 , 14 , 17 , 18 our us study population , with racial and ethnic diversity , is limited to those patients with rosc , regardless of whether sustained , because that is the entry criteria into the data registry . despite these dissimilarities ,
the differences in arrest characteristics between men and women are consistent across these various populations .
interestingly , earlier studies suggested protective benefits of female sex,2 , 6 , 7 whereas in later studies that account for the current standards of patient care the results are less clear.9 , 14 , 17 , 18 several population studies have continued to find a survival advantage to female sex within strata of shockable and/or nonshockable rhythm ; however , these studies have not reported frequency of interventions in postresuscitation care.19 , 20 
  changes in resuscitation care may differentially affect men and women . in la county , advanced postresuscitation care capabilities , including pci and ttm , are required at the cardiac arrest receiving centers .
in addition to the differences in arrest characteristics , we found differences in frequency of these interventions between men and women . in our cohort , women were less likely to receive interventions , including emergent coronary angiography and ttm , even among those most likely to have good neurological outcome , with witnessed arrest and initial shockable rhythm .
yet , the sensitivity analysis accounting for effect modification between sex and interventions , further confirmed that female sex was not associated with differences in neurological outcome .
other studies have noted similar sex disparities in interventions.8 , 14 , 15 , 16 given the retrospective nature of this study , the reason for this difference is not known .
it is likely attributable , in part , to a higher frequency of stemi on the ecg and initial shockable rhythm for men .
aggressive postresuscitation care , including early coronary angiography , is more likely in patients with favorable arrest characteristics . as such
it is notable that , among those patients who received early coronary angiography , men and women had a similar proportion of pci .
furthermore , although both crude analysis and initial adjustment for patient and arrest characteristics alone showed worse outcomes for women , once accounting for interventions in the regression model , we did not find a difference in survival with good neurological outcome between men and women .
these results raise the possibility of an effect of disparities in treatment shifting outcomes from ohca .
compared to national surveillance data of ohca , women make up a similar proportion of our cohort ( 40% vs 39% ) , but la county data have a much higher proportion of hispanics ( 22% vs 5%).1 there was also a higher proportion of witnessed arrest ( 84% vs 47% ) , bystander cpr ( 41% vs 33% ) , and initial shockable rhythm ( 32% vs 24% ) in these patients transported to specialty centers .
similarly , in comparison to the study population evaluated by daya et  al , representing 139 different ems agencies across the united states , our population had a similar median age , proportion of women , and bystander cpr rate but a higher proportion of witnessed arrest ( 84% vs 49% ) and initial shockable rhythm ( 32% vs 22%).21 
  this study has several additional limitations .
this is a retrospective cohort . as such , we can not determine causality , and the frequency of interventions is subject to selection bias .
our analysis is not inclusive of all patients with cardiac arrest in la county ; the registry includes patients with ohca who achieve rosc , at least transiently , and are treated at a cardiac arrest receiving center .
this likely explains the higher proportion of witnessed arrests and initial shockable rhythm compared with national studies .
patients who were not transported ( met termination of resuscitation criteria ) and those transported to a hospital other than a cardiac arrest receiving center were not included in this analysis .
we were unable to include adjustment for downtime , which is known to affect outcomes , because this was missing in the majority of patients and is likely to be inaccurate when reported.22 , 23 by limiting analysis to complete subjects , we make the assumption that data are missing completely at random , which , if untrue , can lead to bias or incomplete control of confounders . however , because values were missing less than 10% of the time , we believe that imputation or other means of adjusting for missing values would not make a substantive difference in the results . in addition , given the retrospective methodology , there are other potential confounders that remain unmeasured . specifically , the database does not include information on comorbid conditions , arrest etiology , and other risk factors that may differ between men and women presenting with ohca . these factors could not be accounted for in this analysis and causality can not be determined .
 backgroundthe purpose of this study was to evaluate sex differences in outofhospital cardiac arrest ( ohca ) characteristics , interventions , and outcomes.methods and resultsthis is a retrospective analysis from a regionalized cardiac arrest system . 
 data on patients treated for ohca are reported to a single registry , from which all adult patients were identified from 2011 through 2014 . 
 characteristics , treatment , and outcomes were evaluated with stratification by sex . the adjusted odds ratio ( or ) for survival with good neurological outcome ( cerebral performance category 1 or 2 ) 
 was calculated for women compared to men . 
 there were 5174 outofhospital cardiac arrests ( ohcas ; 3080 males and 2094 females ) . 
 women were older , median 71  ( interquartile range [ iqr ] , 5982 ) versus 66 years ( iqr , 5578 ) . despite similar frequency of 
 witnessed arrest , women were less likely to present with a shockable rhythm ( 22% vs 35% ; risk difference [ rd ] , 13% ; 95% ci , 1115 ) , have stsegment elevation myocardial infarction ( 23% vs 32% ; rd , 13% ; 95% ci , 711 ) , or receive coronary angiography ( 11% vs 25% ; rd , 14% ; 95% ci , 1216 ) , percutaneous coronary intervention ( 5% vs 14% ; rd , 9% ; 95% ci , 711 ) , or targeted temperature management ( 33% vs 40% ; rd , 7% ; 95% ci , 410 ) . 
 women had decreased survival to discharge ( 33% vs 40% ; rd , 7% ; 95% ci , 410 ) and a lower proportion of good neurological outcome ( 16% vs 24% ; rd , 8% ; 95% ci , 610 ) . in multivariable modeling 
 , female sex was not associated with decreased survival with good neurological outcome ( or , 0.9 ; 95% ci , 0.81.1).conclusionssexrelated differences in ohca characteristics and treatment are predictors of survival outcome disparities . with adjustment for these factors , 
 sex was not associated with survival or neurological outcome after ohca . 
Introduction
Methods
Results
Discussion
Conclusion
Disclosures