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Cardiac arrest, gender and resuscitation outcomes

  • Yigal Helviz
  • Marcus Ong
  • Sharon Einav
Editorial

The symptoms of death are incontrovertible. It would therefore seem safe to assume that men and women fare similarly following cardiac arrest. However, there are currently insufficient data to support this assumption throughout all the stages of the acute care process. Although the literature on this topic is not abundant, several findings are reported that require further investigation .

Women undergoing OHCA tend to be older than men and have more comorbidities [1]. Women arrest more in the privacy of their home whereas men arrest more in public locations. Accordingly, there are fewer witnessed arrests [2] and greater delays in calling for emergency medical system assistance for women [3]. The prevalence of the different presenting rhythms differs between the sexes; women present with more non-shockable rhythms than males [1, 2].

None of these disadvantages seem amenable to change, making it easy to assume that these are reasonable grounds for poorer outcomes among women. However, preventable causes have recently begun to emerge. Women receive less bystander CPR [4]. The interval to first rhythm recording and first chest compression is longer in women. There are more difficulties in achieving intravenous access in women than in men during OHCA. Women receive fewer per-protocol resuscitation medications [3]. However, despite all of these disadvantages, women usually have a higher rate of return of spontaneous circulation (ROSC) after OHCA [1,2,5,6].

Looking forward, assessment of the functional outcomes and quality of life of survivors at meaningful time points (e.g., 3–6 months after hospital discharge) should be the end targets of any comparison between the sexes regarding resuscitation outcomes. However, multiple quality indicators are easily identifiable along the way to this final outcome. These include both interim outcome and process measures.

One traditional interim outcome measure is survival to hospital discharge. Conflicting data exist regarding the association between sex and the likelihood of discharge from hospital following OHCA—some studies show better outcomes in women [2, 6, 7], some demonstrate similar outcomes [8, 9, 10], and some show worse outcomes compared with men [4, 11]. Another interim outcome measure is the rate of neurologically intact survival at the time of hospital discharge. Few studies provide insight into this outcome; these show that women have outcomes that are similar to or poorer than those of men [11, 12, 13, 14, 15, 16] (Table 1).
Table 1

Studies providing information on the outcomes of men and women after OHCA. Note the paucity of studies directed toward meaningful end points (i.e., neurologic and long-term outcomes) and the loss of initial survival benefit that women have at the time of hospital admission

Outcome

Women do better

Women do no differently or worse than men

Reference

n

OR

95% CI

Reference

n

OR

95% CI

ROSC/admission to hospital alive

[Kim C. Circulation. 2001:104:2699]

9651a

1.27

1.14, 1.41

Dicker B. Emerg Med J. 2018;35:367

3862

0.94

0.81, 1.09

Herlitz J. Resuscitation. 2004;60:197

23583a

1.66

1.49, 1.84

Ng YY. Resuscitation 2016;102: 116

40,159

1

0.92, 1.09

Wigginton JG. Crit Care Med. 2002:30:S131

4147

1.3

1.06, 1.67

Safdar B. Acad Emerg Med. 2014;21:1503

11470h

0.95dh

 

Perers E. Resuscitation. 1999;40:133

4401

1.37

ND

[Kitamura T. Eur Heart J 2010;31:1365]c

24449a,e

1.05

0.98, 1.13

Vukmir RB. J Womens Health (Larchmt)0.2003;12:667

874

0.55a

 

[Cline SL. Heart Rhythm 2005;2:492]

388a

0.95

0.53, 1.7

[Ahn KO. Am J Emerg Med. 2012 Nov;30(9):1810]

13,922

1.32

1.17, 1.48

 

[Adielsson A et al. Heart 2011;97:1391]f

7187

1.82

1.57, 2.1

[Akahane M. Am J Med 2011;124:325]

276,590

1.06

1.02, 1.1

[Bray JE. Resuscitation 2013;84:957]

10,453

3.47

2.19, 5.5

Survival to hospital discharge

[Teodorescu C. J. Interv Card Electrophysiol. 2012;34:219]

869

1.85

1.12, 3.04

Perers E. Resuscitation. 1999;40:133

4401

NS

Herlitz J. Resuscitation. 2004;60:197b

23,400

1.27

1.03,1.56

Morrison L. Resuscitation 2016;100:76

14,690

1.16

0.98, 1.36

[Johnson MA. Resuscitation 2013;84:639]

19,398

1.23

1.09, 1.38

[Ahn KO. Am J Emerg Med. 2012;30(9):1810]

13,922

0.82

0.63, 1.05

[Kitamura T. Eur Heart J 2010;31:1365]b,c

24449a,e

1.19

1.03, 1.37

Ng YY. Resuscitation 2016;102:116

40,159

0.94

0.77, 1.15

[Adielsson A. Heart 2011;97:1391] f

7187

1.43

1.17, 1.75

[Bray JE. Resuscitation 2013;84:957]

10,453

1.11

0.92,1.33

 

Safdar B. Acad Emerg Med. 2014;21:1503d

10,860

0.55

0.41, 0.72

[Akahane M. Am J Med 2011;124:325]

276,590

1.03

0.97, 1.09

[Cline SL. Heart Rhythm 2005;2:492]

388a

0.29

0.08, 1.00

[Arrich J. Medicine (Baltimore) 2006;85:288] g

774

1.09

0.72, 1.65

[Mahapatra S. Resuscitation 2005;65:197]f

200

0.8a,e

0.38, 1.68

[Pell JP. Eur Heart J 2000;21:239]

22,161

0.96

0.8, 1.14

[Wissenberg M. Resuscitation 2014;85:1212]

17,637

1.1

0.92, 1.33

 

Karlsson V. Critical Care 2015;19:182

1494

1.34

1.01, 1,78

  

Winther-Jensen M. Resuscitation 2015; 96:78

839

1.11

0.87, 1.41

Neurological/functional outcome at hospital discharge

 

Ng YY. Resuscitation 2016;102:116

40,159

1.04

0.76, 1.42

Winther-Jensen M. Eur Heart J Acute Cardiovasc Care. 2018;7:414

704

1.09

0.51, 2.06

Bougouin W. Resuscitation. 2017;114:7

710

1.18a

 

Bosson N et al. J Am Heart Assoc. 2016;15:5(9)

4477

0.9

0.8, 1.1

[Kitamura T. Eur Heart J 2010;31:1365]c

24449a

1.23

0.98, 1.54

[Arrich J. Medicine (Baltimore) 2006;85:288] g

774

1.02

0.67, 1.55

  

Karlsson V. Critical Care 2015;19:182

1494

0.16

0.92, 1.67

OR odds ratio, CI confidence interval, ROSC return of spontaneous circulation, ND no data, NS data reported only as non-significant

Relationship of outcome with sex not the primary outcome of the study are shown in italics

Studies in brackets: Data taken from Bougouin et al. [19] and not necessarily reported in the original study

aCalculated by the authors based on data given in the paper

b30-Day survival

cOnly patients over age 50 years with cardiac cause for OHCA

dOnly unadjusted data given

eData taken from original study (differed from Bougouin et al.)

fOnly patients with ventricular fibrillation

gOnly patients that were bystander-witnessed

hCalculated by the authors based on data from personal communication from the author

Process measures that are only beginning to be studied include the adjusted rates of provision of in-hospital interventions [e.g., targeted temperature management (TTM), coronary catheterization] and complication rates. When men and women were treated equally with TTM, neurologic outcomes as assessed by modified Rankin scales were poorer in women despite an otherwise seemingly similar physiologic response [17]. That catheterization may be underutilized in women after cardiac arrest cases is suggested by studies showing that the adjusted rates of early coronary angiography are significantly lower in women than in men [12, 15, 16, 18] although their rates and outcomes after percutaneous coronary intervention are similar [12]. Younger age, typical pre-arrest chest pain and a higher prevalence of shockable rhythms may explain clinician inclination to perform more diagnostic coronary angiographies in males, but there has been no study proving this. Similarly, no study has examined whether differences in catheterization rates are driven by differences in post-ROSC electrocardiography. Quality measure programs that assess the management of myocardial infarctions typically include only STEMI cases in door-to-balloon registries. Atypical presentation of CAD probably causes more arrests in women, but this has yet to be proven. Some of these women may not undergo coronary catheterization despite potential for benefit. There is also no study comparing post-ROSC echocardiography. Men generally have more systolic heart failure whereas women have more diastolic heart failure, which comprises a greater treatment challenge [19]. Whether such differences affect post-ROSC severity of heart failure, management strategies and overall resuscitation outcomes remains to be elucidated.

Conservative management may stem from concerns regarding possible treatment intolerance or lack of benefit [20]. Women are generally referred less to cardiac interventions (e.g., coronary catheterization, coronary artery bypass graft surgery), and when referred, their outcomes are worse than those observed in men undergoing the same procedures [20]. Unsurprisingly, data from the International Cardiac Arrest Registry (INTCAR) showed differences between men and women in both type and prevalence of complications occurring during ICU care after ROSC as well. However, this study was limited to patients admitted to an ICU and treated with TTM. Such selection criteria assume a priori that care has been equal at all treatment points up to the time of patient inclusion. Concerns regarding potential complications may lead to deferral of invasive interventions. However, whether selective deferral occurs, its justifications or lack thereof, and its relationship with complication rates and outcomes after ROSC remain unknown. Follow-up in the INTCAR study was also limited to the time of hospital discharge, leaving the long-term implications of these complications a topic for speculation [16].

At this time no information is available regarding patient severity and therapeutic intervention scores (e.g., APACHE, TISS), type of admitting ICU and ICU length of stay, resource consumption and rates of withdrawal/withholding of care in men and women. Are men admitted more to specialized coronary care units after ROSC specifically because these provide catheterization? Patients with shockable and non-shockable rhythms are often admitted to different ICUs. Different ICUs have different treatment approaches, which may affect patient outcomes. Many medications currently being used to treat heart disease have undergone less investigation on female subjects and have more side effects in women than in men [21]. Could these affect post-ROSC outcomes? Adjusted comparisons need to be performed to answer these questions and many more.

To provide the best intensive care to our post-ROSC patients, more research must be invested in gender-related aspects of the treatment they receive. Registries that do not include data on post-discharge survival, functional outcomes and quality of life should be encouraged to include such data. Those that already include data on both sex and outcome at or after hospital discharge should be investigated in greater depth. Studies must be specifically targeted to such comparisons, including adjustments for patient background diseases, arrest characteristics and post-ROSC conditions. The risk-benefit ratio of various treatments in female versus male patients requires more in-depth investigation. OHCA registries should be linked to in-hospital data on organ failure and neurologic follow-up, both of which could explain differences in treatment if such are found. If we carry on ignoring the details that we, as intensivists, know are important, we will also continue to remain ignorant of potential inequalities in the care we are delivering to our patients.

Notes

Conflicts of interests

None of the authors has any conflict of interest to disclose regarding the topic of this manuscript.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Intensive Care UnitShaare Zedek Medical CenterJerusalemIsrael
  2. 2.Department of Emergency MedicineSingapore General Hospital and Duke-NUS Medical School, Health Services and Systems Research (HSSR)SingaporeSingapore
  3. 3.Faculty of MedicineHebrew UniversityJerusalemIsrael

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