3CPR

As an AHA Early Career Blogger and member of the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation (3CPR), I am pleased to have the opportunity to summarize the recently published paper in the Journal of the American Heart Association (JAHA), “Do Sex Differences Exist in the Establishment of ‘Do Not Attempt Resuscitation’ Orders and Survival in Patients Successfully Resuscitated From In-Hospital Cardiac Arrest?”¹ This paper was published in February during American Heart Month in the JAHA Spotlight: Go Red for Women 2020 series in conjunction with AHA’s Go Red for Women initiative.

In summary, Perman et al.¹ used the Get With The Guidelines^®-Resuscitation registry to determine whether there are sex differences in the establishment of “do not attempt resuscitation” (DNAR) orders after resuscitation from in-hospital cardiac arrest and whether the differences in DNAR use lead to differences in survival. They examined 71820 patients across 571 hospitals who had return of spontaneous circulation (ROSC) after in-hospital cardiac arrest and examined the association between de novo DNAR orders (any time after ROSC, within 12 hours of ROSC, or within 72 hours of ROSC) and sex and the association between sex, DNAR orders, and survival. The 72-hour time point was selected since after this time is when patients who are comatose after cardiac arrest begin to have neurologic findings that indicate poor prognosis and AHA guidelines recommend that the determination of neurologic prognosis should be delayed until at least 72 hours after ROSC (or 72 hours after reaching normothermia if targeted temperature management is used).

Of the 71820 patients, 42.4% of the cohort were women and women were on average older (mean±SD: 65.5±15.8 vs. 64.6±15.1 years; P<0.0001), less frequently of non-Hispanic white race (61.7% vs. 67.5%, P<0.0001), more likely to have a non-shockable cardiac arrest rhythm such as pulseless electrical activity (PEA) or asystole (81.6% vs. 78.0%, P<0.0001), and more likely to have a noncardiac illness at the time of admission (47.2% vs. 41.1%, P<0.0001) while men had a higher incidence of cardiac premorbid conditions.

Of the total cohort, 44.1% had a de novo DNAR order placed after ROSC. Of the entire cohort, 45.0% of women and 43.5% of men had a DNAR order after ROSC (unadjusted RR: 1.16; 95% CI, 1.12-1.21; adjusted RR [ARR]: 1.15; 95% CI, 1.10-1.20). Women had a higher rate of DNAR status early after resuscitation. Of those who had any DNAR order during the hospitalization, 51.8% of women compared to 46.5% of men had a DNAR order placed <12 hours after ROSC and 75.9% of women compared to 70.9% of men had a DNAR order placed <72 hours after ROSC. When adjusting for the patients’ demographics and cardiac arrest characteristics, female sex was associated with a higher likelihood of early DNAR <12 hours after ROSC (ARR: 1.40; 95% CI, 1.30-1.52) and DNAR <72 hours after ROSC (ARR: 1.35; 95% CI, 1.26-1.45) among those who had a DNAR order any time after ROSC.

Interestingly, after adjusting for patient and arrest characteristics, female sex was mildly associated with lower rates of survival to hospital discharge (ARR: 0.98; 95% CI, 0.96-1.00; P=0.04) and there were no differences in survival rate between men and women after adjusting for DNAR status within 72 hours. However, early DNAR status made within 72 hours of ROSC (combining data from men and women) was associated with decreased survival rate compared to those without a DNAR order or a DNAR order placed ≥72 hours after arrest (RR: 0.15; 95% CI, 0.14-0.17; P<0.0001).

This study by Perman et al.¹ is not the first study to note differences in rates of do not resuscitate (DNR)/DNAR orders between men and women. Nakagawa et al.² showed that women with acute intracranial hemorrhage were more likely to receive early (<24 hours from presentation) DNR orders than men. In a study of patients who received emergency surgery, women were more likely to receive a DNR order but morbidity and mortality rates were similar between men and women³.

Unfortunately, the reasons for women to more likely receive earlier DNR/DNAR orders are unknown at this time. Perhaps these differences could be due to patient preferences (e.g. women having earlier end of life discussions with family/surrogate decision-makers), implicit provider biases (e.g. female cancer patients were found to be more likely to receive early DNR orders from female physicians⁴), surrogate decision-maker biases, sociocultural factors, religious factors, situational influences, etc. Although DNR/DNAR orders are not requests for withdrawal of life-sustaining therapy, the presence of DNR/DNAR orders has previously been associated with decreased aggressive interventions and decreased survival to discharge for patients with out-of-hospital cardiac arrest⁵. This suggests that health care providers should be vigilant of the tendency to be less aggressive with care for patients with DNR/DNAR orders and ensure that their management plans align with the expectations of surrogate decision-makers. More robust qualitative data are needed in order to understand these differences.

References:

1. Perman SM, Beaty BL, Daugherty SL, Havranek EP, Haukoos JS, Juarez-Colunga E, Bradley SM, Fendler TJ, Chan PS, † AHAGWTGRI. Do sex differences exist in the establishment of “Do not attempt resuscitation” Orders and survival in patients successfully resuscitated from in-hospital cardiac arrest? J Am Heart Assoc. 2020;9:e014200
2. Nakagawa K, Vento MA, Seto TB, Koenig MA, Asai SM, Chang CW, Hemphill JC. Sex differences in the use of early do-not-resuscitate orders after intracerebral hemorrhage. Stroke. 2013;44:3229-3231
3. Eachempati SR, Hydo L, Shou J, Barie PS. Sex differences in creation of do-not-resuscitate orders for critically ill elderly patients following emergency surgery. J Trauma. 2006;60:193-197; discussion 197-198
4. Crosby MA, Cheng L, DeJesus AY, Travis EL, Rodriguez MA. Provider and patient gender influence on timing of do-not-resuscitate orders in hospitalized patients with cancer. J Palliat Med. 2016;19:728-733
5. Richardson DK, Zive D, Daya M, Newgard CD. The impact of early do not resuscitate (dnr) orders on patient care and outcomes following resuscitation from out of hospital cardiac arrest. Resuscitation. 2013;84:483-487

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