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Is there a difference in survival between men and women suffering in-hospital cardiac arrest?
Heart & Lung 43 (2014) 510e515
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Care of Patients With Electrocardiographic Abnormalities
Is there a difference in survival between men and women suffering in-hospital cardiac arrest? Johan Israelsson, RN, MSc a, b, *, Carina Persson, RPT, PhD c, Anna Strömberg, RN, PhD d, Kristofer Årestedt, RN, PhD c, d, e a
Department of Internal Medicine, Division of Cardiology, Kalmar County Hospital, SE-39185 Kalmar, Sweden Kalmar Maritime Academy, Linnaeus University, SE-39182 Kalmar, Sweden c School of Health and Caring Sciences, Linnaeus University, SE-39182 Kalmar, Sweden d Department of Medical and Health Sciences, Division of Nursing Science, Linköping University, SE-58183 Linköping, Sweden e Palliative Research Centre, Ersta Sköndal University College and Ersta Hospital, SE-10061 Stockholm, Sweden b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 21 January 2014 Received in revised form 30 May 2014 Accepted 30 May 2014 Available online 5 July 2014
Objectives: To describe in-hospital cardiac arrest (CA) events with regard to sex and to investigate if sex is associated with survival. Background: Previous studies exploring differences between sexes are incongruent with regard to clinical outcomes. In order to provide equality and improve care, further investigations into these aspects are warranted. Methods: This registry study included 286 CAs. To investigate if sex was associated with survival, logistic regression analyses were performed. Results: The proportion of CA with a resuscitation attempt compared to CA without resuscitation was higher among men. There were no associations between sex and survival when controlling for previously known predictors and interaction effects. Conclusions: Sex does not appear to be a predictor for survival among patients suffering CA where resuscitation is attempted. The difference regarding proportion of resuscitation attempts requires more attention. It is important to consider possible interaction effects when studying the sex perspective. Ó 2014 Elsevier Inc. All rights reserved.
Keywords: Heart arrest Hospital Sex Survival Predictor
Introduction Every year, approximately 360,000 people in the United States suffer an out-of-hospital cardiac arrest (OHCA).1 The number of inhospital cardiac arrest (IHCA) is estimated to approximately 200,000.2 In Europe, the number of OHCA is estimated to 275,000,3 while the number of IHCA is not known. In Sweden, more than 10,000 people are estimated to suffer a cardiac arrest (CA) every year, of which about one third occur in a hospital setting. In Sweden, the survival rate after IHCA is higher compared to OHCA,4 almost 30%5 vs. approximately 10%.6 Factors described as predictors for IHCA survival in previous research are; sex,7,8 age,9,10 initial rhythm,9,10 witnessed CA,9,10 CA during daytime,10,11 etiology,9,11 time to treatment,4 absence of intubation12 and duration of CA.13,14 Few studies have investigated the sex perspective in Abbreviations: OHCA, Out-of-hospital cardiac arrest; IHCA, In-hospital cardiac arrest; CA, Cardiac arrest; AMI, Acute myocardial infarction; ACLS, Advanced cardiovascular life support. * Corresponding author. Department of Internal Medicine, Division of Cardiology, Kalmar County Hospital, SE-39185 Kalmar, Sweden. Tel.: þ46 480 81130; fax þ46 480 448797. E-mail address: [email protected] (J. Israelsson). 0147-9563/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.hrtlng.2014.05.012
relation to survival, and the findings are incongruent.7,8,15e19 In addition, the majority of these studies is performed out-of hospital where conditions are quite different from an in-hospital context. According to previous research, approximately 60% of the patients suffering IHCA are men.8,13 Women seem to have a slightly better chance of surviving to hospital discharge compared to men.7 However, this association could be dependent on age, as higher survival rates only occur among younger women.8 This indicates the possibility of an interaction between sex and age. Another reason for the incongruent findings could be that different covariates have been used to adjust the survival models. There is a need for more knowledge in order to improve the treatment of IHCA in both sexes. The aim of this study was therefore to describe IHCA events with regard to sex and investigate if sex is associated with survival after controlling for previously known predictors and interaction effects. Methods Design, settings and data collection This observational registry study is based on data from the Swedish national IHCA register. During the study period,
J. Israelsson et al. / Heart & Lung 43 (2014) 510e515
approximately 85% of emergency hospitals in Sweden reported data to this register (https://www.hjartstoppsjh.se/). The register is Internet based and clinics report data by using two protocols. The first one concerns patient baseline information and CA events. The second protocol is for follow-up and is completed 30 days after CA. This protocol contains data on post resuscitation care, hospital discharge and survival. Survival is recorded on three occasions; after completed resuscitation attempt, at hospital discharge and 30 days after CA. Co-morbidities included in the register are acute myocardial infarction (AMI), stroke, heart failure, diabetes and cancer. The register is validated by random inspections of the data, performed by the National Registry Committee. For the present study, data from one hospital was analyzed. The data consists of all reported CAs (n ¼ 286) where any resuscitation attempts were made, at a county hospital in the southeast of Sweden, from January 2007 to June 2011. This hospital is located in a middle-sized Swedish town. The catchment area includes approximately 230,000 inhabitants. The hospital has 372 beds and approximately 60 CAs, with a resuscitation attempt, each year. The treatment of CA is very similar to most hospitals in Sweden and did not change during the research period. The hospital where the data was collected uses the Swedish Advanced Cardiovascular Life Support (ACLS) algorithm. The ACLS Guidelines were changed in Sweden in October 2006 and in October 2011, in accordance with guidelines by the European Resuscitation Council.20 The survival rates are approximately at the same level as national register data. Outcomes and predictors were selected with consideration to prior research and the aim of the present study. In addition, we chose to include drugs at CA since this treatment often is conducted and recommended in ERC guidelines.20 To investigate the proportion of resuscitation attempts in relation to sex, data (number of deceased patients at the hospital and their sex) from electronic patient records was used. The study was approved by the Regional Ethical Review Board at Linköping University (study code: 2013/70-32). Data analysis To compare differences in characteristics of CA events in relation to sex, chi-square statistics was used on nominal data. Student’s t-test was used to compare sex differences regarding age and time variables.21 If the assumption of equal variance was not fulfilled, Student’s t-test adjusted for unequal variances (Satterthwaite’s approximation formula) was used.22 Hierarchical multiple binary logistic regression analyses were conducted to investigate the association between sex and survival.23,24 Three survival outcomes were tested; survival after resuscitation attempt, survival at hospital discharge and survival 30 days after resuscitation. In the first block (Model I), sex was included as a single predictor for survival. To adjust for covariates, age, shockable initial rhythm, time to treatment, witnessed CA, medical treatment, intubation, cardiac etiology and CA during daytime were included in the second block (Model II). The variable time to treatment consisted of time to defibrillation for CAs with shockable (Ventricular Fibrillation or Ventricular Tachycardia) initial rhythm and time to cardiopulmonary resuscitation for CAs with nonshockable (Asystole or Pulseless Electrical Activity) initial rhythm. The variable medical treatment included administration of Adrenaline and/or Amiodarone. Cardiac etiology was defined as heart disease (ischemic heart disease, arrhythmia or heart failure) causing the CA. The variable CA during daytime was defined as a CA between 06:00 AM and 06:00 PM. A multiplicative interaction term (sex age) was included in the final block (Model III) to test for interaction effects between sex and age. McFadden pseudo R2 change was used to illustrate model development. As the
511
assumption of non-dependency was violated (i.e. nested data with 15 patients who suffered two to four CAs, median ¼ 2), all regression models were re-analyzed using robust variance estimates to test that this violation did not bias the findings. No multicollinearity problems were detected across the predictors as no variable had a variance inflation factor (VIF) above 1.50 and the mean was 1.25. An additional analysis was performed to compare the proportion of resuscitation attempts in relation to sex, using Pearson chi-square test. Between January 2009 and December 2010, the number of patients where resuscitation was attempted (n ¼ 126) were compared to the number of patients suffering CA without a resuscitation attempt, e.g. patients with do-not-attemptresuscitation (DNAR) decisions (n ¼ 1067). The significance level was set to p < 0.05. All statistical analyses were performed by STATA 12.1 for Windows (StataCorp LP, College Station, TX, USA). Results Descriptions of in-hospital CA events with regard to sex The 286 in-hospital CA events are presented in Table 1. Sixtynine percent (n ¼ 196) of the afflicted were men. Mean age was 74.1 years, with the women being significantly older than the men (D ¼ 4.3 1.6, p ¼ 0.006). Heart disease, especially AMI, was the most common cause for CA, among both men and women. However, cardiac etiology was significantly more common among the men compared to the women (p ¼ 0.043). In addition to AMI, the most common co-morbidities, were heart failure (37.4%) and diabetes (21.3%). The men more often suffered from cancer (p ¼ 0.012). In 53.5% of the CA events, the patient survived the resuscitation attempt, 37.4% survived to hospital discharge and 35.0% were still alive at 30 days following resuscitation attempt. Proportion of resuscitation attempts in relation to sex Resuscitation attempts were more common (14.8% vs. 6.2%) among men compared to women. From January 2009 to December 2010, 37 resuscitation attempts were made among women and 89 among men. No attempts were made in 556 women suffering CA, compared to 511 in men (c2(1) ¼ 23.32, p < 0.001). Association between sex and survival after resuscitation attempt More than half of the patients suffering CA (53.5%) survived the resuscitation attempt. No significant association between sex and survival was identified in any of the regression models (Table 2). Before and after the interaction term of sex and age was included (Model II vs. III), having a shockable initial rhythm (OR ¼ 22.40 vs. 22.24), witnessed CA (OR ¼ 20.17 vs. 20.35) and not being intubated (OR ¼ 0.33 vs. 0.33) were significantly (p < 0.01) associated with survival. Model II and III explained 41% of the total variance. The associations remained when nested data was taken into account. Association between sex and survival at hospital discharge Among the patients who survived the resuscitation attempt, 69.9% were alive at hospital discharge. No significant bivariate association between sex and survival was identified in Model I. When adjusting covariates were included (Model II), being a man (OR ¼ 2.69), and younger age (OR ¼ 0.97) were significantly (p < 0.05) associated with higher survival. However, these associations did not remain once the interaction term of sex and age had been included. Before and after the interaction term of sex and age was included (Model II vs. III), having a shockable initial rhythm
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J. Israelsson et al. / Heart & Lung 43 (2014) 510e515
Table 1 Characteristics of the SCA in relation to sex (n ¼ 286). Variable
Number of observations (women/men)
All patients
Women
Men
df
p-value
Age, mean (sd) Cardiac etiology, n (%) On-going AMI, n (%) Co-morbidity, n (%) Prior AMI Respiratory insufficiency Stroke Diabetes Heart failure Cancer Treatment & organization, n (%) SCA at daytime SCA at supervised wards SCA during ECG VF/VT as initial rhythm Witnessed SCA Intubated Drugs given at SCA Time in minutes, mean (sd) Time SCA e alarm Time SCA e CPR Time SCA e defibrillationa Time SCA e MET Time SCA e treatment Survival, n (%) Survival after resuscitation Survival at hospital discharge Survival at 30 days
286 (90/196) 286 (90/196) 238 (74/164)
74.1 (12.6) 171 (59.8) 108 (45.4)
77.1 (11.5) 46 (51.1) 35 (47.3)
72.8 (12.8) 125 (63.8) 73 (44.5)
284 1 1
0.006b 0.043d 0.690d
266 267 272 273 257 273
(79/187) (82/185) (83/189) (84/189) (77/180) (84/189)
91 28 46 58 96 29
(34.2) (10.5) (16.9) (21.3) (37.4) (10.6)
23 7 10 16 27 3
(29.1) (8.5) (12.1) (19.1) (35.1) (3.6)
68 21 36 42 69 26
(36.4) (11.4) (19.1) (22.2) (38.3) (13.8)
1 1 1 1 1 1
0.255d 0.489d 0.156d 0.554d 0.620d 0.012d
286 286 286 286 286 286 286
(90/196) (90/196) (90/196) (90/196) (90/196) (90/196) (90/196)
168 160 152 110 247 113 175
(58.7) (55.9) (53.2) (38.5) (86.4) (39.5) (61.2)
55 48 48 29 78 31 53
(61.1) (53.3) (53.3) (32.2) (86.7) (34.4) (58.9)
113 112 104 81 169 82 122
(57.7) (57.1) (53.1) (41.3) (86.2) (41.8) (62.2)
1 1 1 1 1 1 1
0.581d 0.547d 0.966d 0.142d 0.919d 0.235d 0.589d
229 239 109 218 286
(69/160) (73/166) (29/80) (65/153) (90/196)
1.5 0.5 1.3 5.5 0.7
(3.0) (1.1) (2.1) (4.0) (1.5)
1.3 0.6 0.8 5.7 0.6
(2.1) (1.3) (1.7) (3.1) (1.3)
1.6 0.4 1.5 5.4 0.8
(3.3) (0.9) (2.2) (4.3) (1.6)
197.8 106.1 107 166.4 213.1
0.382c 0.475c 0.143b 0.487c 0.243c
1 1 1
0.117d 0.079d 0.144d
286 (90/196) 286 (90/196) 286 (90/196)
153 (53.5) 107 (37.4) 100 (35.0)
42 (46.7) 27 (30.0) 26 (28.9)
111 (56.6) 80 (40.8) 74 (37.8)
AMI ¼ Acute myocardial infarction, ECG ¼ Electrocardiography, SCA ¼ Sudden cardiac arrest, CPR ¼ Cardiopulmonary resuscitation, VF ¼ Ventricular fibrillation, VT ¼ Ventricular tachycardia, MET ¼ Medical emergency team. a If the initial rhythm was VF/VT. b Students t-test. c Students t-test adjusted for unequal variances (Satterthwait’s approximation formula). d c2-test.
(OR ¼ 21.4 vs. 21.8), shorter time to treatment (OR ¼ 0.58 vs. 0.58), witnessed CA (OR ¼ 11.36 vs. 11.12), not receiving medical treatment (OR ¼ 0.29 vs. 0.29), and not being intubated (OR ¼ 0.12 vs. 0.11) were significantly (p < 0.05) associated with survival at hospital discharge. Model II and III explained 53% of the total variance. The associations remained when nested data was taken into account. Association between sex and survival at 30 days after resuscitation Most of the patients who survived until hospital discharge were alive at 30 days after resuscitation (93.5%). No significant association between sex and survival was identified in any of the regression models (Table 2). Before and after the interaction term of sex and age was included (Model II vs. III), having a shockable initial rhythm (OR ¼ 19.05 vs. 19.13), shorter time to treatment (OR ¼ 0.53 vs. 0.53), not receiving medical treatment (OR ¼ 0.27 vs. 0.27), and not being intubated (OR ¼ 0.14 vs. 0.14) were significantly (p < 0.01) associated with survival. Younger age (OR ¼ 0.95 vs. 0.96), and witnessed CA (OR ¼ 8.20 vs. 8.15) were significantly (p < 0.05) associated with survival in Model II, but not in Model III. Model II and III explained 54% of the total variance. The associations remained when nested data was taken into account. Discussion The most important findings in the present study were that we did not find any associations between sex and survival after IHCA among patients receiving resuscitation. Furthermore, the proportion of CAs with a resuscitation attempt was higher among men, compared to CAs without resuscitation.
Unlike Herlitz et al, who found that female sex was related to better survival,7 we did not find that sex was associated with survival in any of our final models. One possible explanation could be that we included the interaction term in our study, whereas Herlitz and co-workers did not.7 In an American study by Topjian et al, being a woman of child-bearing age was related to better survival.8 However, that study did not find any differences between older men and women. The results are not fully comparable to our study, since patients between 44 and 56 years of age were excluded. Almost all women in our study were above child-bearing age. In addition, survival rates are lower in the US compared to Sweden.6,8,9 Nonetheless, the results from Topjian and co-workers support our hypothesis of an existing interaction between sex and age in relation to survival.8 In addition, Arrich et al found that sex modifies the influence of age on survival. Among men who initially survived a CA, older age was related to a worse prognosis. Among women, the prognosis was not equally affected by age.25 However, those results are difficult to compare with ours since only initial survivors after OHCA were studied. Most previous studies have shown that the majority receiving resuscitation after an IHCA are men.10,13 This corresponds with our results. In addition, when comparing CAs with a resuscitation attempt to CAs without resuscitation, the proportion of attempts was higher among men. This corresponds with results from the study by Herlitz et al. In their study, resuscitation attempts were started in 14% of all CAs in men, and 11% in women. Herlitz et al reported no sex differences in age or etiology. In addition, they found no significant differences between men and women in a retrospective evaluation of the justification to start resuscitation.7 However, those not receiving resuscitation were not evaluated. In another study, by Aune et al, characteristics among those not
J. Israelsson et al. / Heart & Lung 43 (2014) 510e515
513
Table 2 The association between sex and survival based on binary logistic regression analyses (n ¼ 286). Model I
Model II
Model III
Outcomes
Predictors
OR (SE)
95% CI for OR
OR (SE)
95% CI for OR
OR (SE)
Survival after resuscitation attempt
Sex (being man) Age Shockable initial rhythm Time to treatment Witnessed Medical treatment Intubation Cardiac etiology Daytime Sex age Overall model statistics Hosmer and Lemeshow test McFadden pseudo R2 Sex (being man) Age Shockable initial rhythm Time to treatment Witnessed Medical treatment Intubation Cardiac etiology Daytime Sex age Overall model statistics Hosmer and Lemeshow test McFadden pseudo R2 Sex (being man) Age Shockable initial rhythm Time to treatment Witnessed Medical treatment Intubation Cardiac etiology Daytime Sex age Overall model statistics Hosmer and Lemeshow test McFadden pseudo R2
1.49 (0.38)
0.90e2.46
1.72 1.01 22.40 0.76 20.17 0.67 0.33 1.11 1.17
0.83e3.55 0.98e1.03 8.36e60.06 0.55e1.04 4.33e93.75 0.30e1.45 0.16e0.69 0.56e2.20 0.60e2.29
1.05 (2.69) 0.01e160.73 1.00 (0.03) 0.95e1.06 22.24 (11.22)*** 8.27e59.78 0.76 (0.12) 0.56e1.04 20.35 (15.99)*** 4.37e94.89 0.66 (0.26) 0.30e1.45 0.33 (0.12)** 0.16e0.68 1.11 (0.39) 0.56e2.19 1.17 (0.40) 0.60e2.28 1.01 (0.03) 0.94e1.07 c2(10) ¼ 160.63, p < 0.001 c2(8) ¼ 5.55, p < 0.698
Survival at hospital discharge
Survival at 30 days
(0.64) (0.01) (11.27)*** (0.12) (15.81)*** (0.26) (0.12)** (0.39) (0.40)
c2(1) ¼ 2.46, p ¼ 0.117
c2(9) ¼ 160.59, p < 0.001 c2(8) ¼ 5.83, p < 0.666
0.01 1.61 (0.44)
0.41 2.69 0.97 21.38 0.58 11.36 0.29 0.12 1.44 1.23
0.94e2.74
(1.26)* (0.02)* (10.46)*** (0.11)** (12.10)* (0.13)** (0.06)*** (0.62) (0.50)
1.08e6.72 0.94e1.00 8.19e55.80 0.40e0.83 1.41e91.66 0.12e0.68 0.04e0.32 0.62e3.36 0.55e2.74
c2(1) ¼ 3.14, p ¼ 0.077
c2(9) ¼ 201.43, p < 0.001 c2(8) ¼ 4.88, p < 0.771
0.01 1.49 (0.41)
0.53 2.11 0.95 19.05 0.53 8.20 0.27 0.14 1.86 1.53
95% CI for OR
0.41 5.84 (17.90) 0.01e2382.51 0.98 (0.03) 0.91e1.04 21.80 (10.84)*** 8.23e57.76 0.58 (0.11)** 0.40e0.83 11.12 (11.87)* 1.37e90.21 0.29 (0.13)** 0.12e0.69 0.11 (0.06)*** 0.04e0.32 1.46 (0.63) 0.62e3.42 1.23 (0.50) 0.55e2.74 0.99 (0.04) 0.92e1.07 c2(10) ¼ 201.50, p < 0.001 c2(8) ¼ 4.80, p < 0.779
c2(1) ¼ 2.17, p ¼ 0.141
c2(9) ¼ 198.63, p < 0.001 c2(8) ¼ 4.42, p < 0.817
0.53 2.71 (8.59) 0.01e1356.16 0.96 (0.35) 0.89e1.03 19.13 (9.29)*** 7.38e49.58 0.53 (0.10)** 0.37e0.77 8.15 (8.71) 1.00e66.18 0.27 (0.12)** 0.11e0.67 0.14 (0.07)*** 0.05e0.40 1.87 (0.84) 0.77e4.53 1.53 (0.64) 0.67e3.48 1.00 (0.04) 0.92e1.08 c2(10) ¼ 198.64, p < 0.001 c2(8) ¼ 4.43, p < 0.817
0.01
0.54
0.54
0.87e2.56
(0.99) (0.02)** (9.19)*** (0.10)** (8.74)* (0.12)** (0.07)*** (0.84) (0.64)
0.84e5.29 0.92e0.98 7.40e49.02 0.37e0.77 1.02e66.20 0.11e0.66 0.05e0.39 0.78e4.49 0.48e35.41
Test of statistical significance: *p < 0.05, **p < 0.01, ***p < 0.001.
receiving resuscitation during one year at one hospital were described. Of 674 patients, 53% were men vs. 47% women. They compared this group to another group (n ¼ 89) who did receive resuscitation during the same time period: 72% men vs. 28% women.26 However, the sex perspective was not the main focus in their study and therefore not further analyzed. In the present study, the women receiving resuscitation were older than the men and were less likely to have a CA with cardiac etiology. This could possibly explain some of the differences in the proportion of resuscitation attempts. However, no data were available regarding age, etiology and other characteristics in the group not receiving resuscitation, which certainly are important factors. In our results, men (receiving resuscitation) suffered from more cancer, which ought to be a significant factor when making decisions about starting resuscitation or not. A recently published systematic review study by de Decker et al, investigating the impact of morbidity on DNAR decision making, concluded that cancer was significantly associated with DNAR orders among patients of 80 years of age or older.27 Previous studies indicate that women suffering acute coronary syndrome have lower incidence of typical symptoms, are treated less intensively, and are less likely to be admitted to coronary care units than men.28,29 In the present study, there were no significant sex-related differences in the location of the CAs
(supervised wards or not), or if they were witnessed or not. This corresponds with the study by Herlitz et al7 Nonetheless, since we found a sex difference in the proportion of resuscitation attempts, one can pose the question if men are over treated and women under treated with regard to resuscitation. If this is the case, the women receiving resuscitation in our study could have constituted a more selective group with a better chance of survival. This could also be a possible explanation to why female sex has been a predictor for survival in earlier studies. A study by Becerra et al, found no difference between men and women when comparing patients with CPR or DNAR orders. In their study, the most important factors associated with a DNAR order were worse prognosis and poorer quality of life. One of the most common justifications for decision making, beside important co-morbidities, was the patients’ and family members’ preferences. Family members were frequently involved in DNAR decisions.30 Since women in general die at an older age compared to men,31 they are more likely to be alone when becoming seriously ill. It is possible that the absence of a spouse could influence therapy wishes and decisions. This issue requires more attention and further investigation. Shockable initial rhythm was the most important predictor for survival outcomes in both men and women. Its impact on survival after IHCA has been shown in a number of previous
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studies.10,13,32e34 Absence of intubation and absence of drugs given at CA were significant predictors for survival outcomes. Past research has shown the same findings concerning intubation.12 These relationships are probably not due to harm caused by these recommended interventions, but more likely to the prolonged duration of the CAs. Time to treatment was another important predictor for all survival outcomes in the present study. This has not always been described in past research,13,35 but corresponds with some studies.36,37 The overall survival in the present study was high compared to previous research.9,38 This could be an effect of well-functioning hospital routines for resuscitation.
among those not receiving resuscitation have to be further investigated from a sex perspective in future research. In addition, it is important to consider possible interaction effects when studying the sex perspective and its relation to survival after CA. Shockable initial heart rhythm and time to treatment were the most important predictors for survival, regardless of sex. Thus, efforts should be made to detect CA at an early stage. There should be more observations of patients with suspected AMI, combined with well-trained personnel with the ability to provide cardiopulmonary resuscitation and defibrillation without delay, in order to improve CA care for both men and women.
Limitations
Acknowledgments
A strength with the present study is that it includes all patients suffering CA at the hospital during the study period. For this reason, no sample size calculation was conducted before the start of the study. The sample size was deemed to be sufficient as 15 to 20 observations were provided for each predictor variable.39 The data from the hospital does not diverge from national data, and the result could be transferred to other hospitals of the same size and with similar organization. Since we could not access complete data (CAs with no resuscitation attempt) for a longer time period, the results regarding the proportion of resuscitation attempts consist of data from January 2009 to December 2010. In addition, it was not possible to control this variable for age, which could be considered a limitation. The major difference in proportion of resuscitation attempts between men and women could have biased the results of this study, since it will make the groups less comparable. The results should therefore be treated with some caution. More research is needed to investigate the reason for this difference, e.g. by examining the characteristics among patients not receiving resuscitation from a sex perspective. However, almost all CA research has focused on those receiving resuscitation, and this group was the primary population in the present study as well. There are also methodological issues to address regarding the predictor time to treatment. In the present study, time to treatment consists of time to defibrillation, or time to CPR, depending on the type of CA and the intervention considered to be the most important. The reason was that several of the CAs with shockable initial rhythm did not receive any CPR. Since the time factor has been studied by using a number of definitions, the results concerning this variable should be interpreted with caution.10,13 One variable of potential importance is the duration of CA. This variable was not included in the register until the revision in 2013. Therapeutic hypothermia was not included as only one patient received this treatment. Some patients suffer more than one CA. This fact violates the statistical assumption of non-dependency. Previous studies have often solved this problem by including only the first CA event.7,40 However, there are different ways to analyze nested data, for example by multilevel modeling.41 As the problem with repeated CAs was limited to a few cases, we re-analyzed all regression models using robust variance estimates to make sure that this violation did not bias the findings.24
We would like to thank the hospital personnel involved in the study and the national register committee for providing the data. We would also like to thank the county council of Kalmar for support and practical assistance in the data collection. A special thanks to Professor Jörg Carlson for valuable input and to Jean Stevenson-Ågren and Sofia McGarvey for revising the language.
Conclusion Sex does not appear to be a predictor for survival among patients suffering IHCA where resuscitation is attempted, and should therefore not influence CA treatment. However, there is a higher proportion of resuscitation attempts among men. This finding could be of importance in order to improve clinical practice and achieve equal care, especially in relation to DNAR orders. The characteristics
References 1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statisticse2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28ee292. 2. Merchant RM, Yang L, Becker LB, et al. Incidence of treated cardiac arrest in hospitalized patients in the United States. Crit Care. 2011;39(11):2401e2406. 3. Atwood C, Eisenberg MS, Herlitz J, Rea TD. Incidence of EMS-treated out-ofhospital cardiac arrest in Europe. Resuscitation. 2005;67(1):75e80. 4. Fredriksson M, Aune S, Bang A, et al. Cardiac arrest outside and inside hospital in a community: mechanisms behind the differences in outcome and outcome in relation to time of arrest. Am Heart J. 2010;159(5):749e756. 5. Aune S, Eldh M, Engdahl J, et al. Improvement in the hospital organisation of CPR training and outcome after cardiac arrest in Sweden during a 10-year period. Resuscitation. 2011;82(4):431e435. 6. Stromsoe A, Afzelius S, Axelsson C, et al. Improvements in logistics could increase survival after out-of-hospital cardiac arrest in Sweden. J Intern Med. 2013;273(6):622e627. 7. Herlitz J, Rundqvist S, Bang A, et al. Is there a difference between women and men in characteristics and outcome after in hospital cardiac arrest? Resuscitation. 2001;49(1):15e23. 8. Topjian AA, Localio AR, Berg RA, et al. Women of child-bearing age have better inhospital cardiac arrest survival outcomes than do equal-aged men. Crit Care. 2010;38(5):1254e1260. 9. Larkin GL, Copes WS, Nathanson BH, Kaye W. Pre-resuscitation factors associated with mortality in 49,130 cases of in-hospital cardiac arrest: a report from the National Registry for Cardiopulmonary Resuscitation. Resuscitation. 2010;81(3):302e311. 10. Skrifvars MB, Castren M, Aune S, Thoren AB, Nurmi J, Herlitz J. Variability in survival after in-hospital cardiac arrest depending on the hospital level of care. Resuscitation. 2007;73(1):73e81. 11. Cooper S, Evans C. Resuscitation Predictor Scoring Scale for inhospital cardiac arrests. Emerg Med J. 2003;20(1):6e9. 12. Cohn AC, Wilson WM, Yan B, et al. Analysis of clinical outcomes following inhospital adult cardiac arrest. Intern Med J. 2004;34(7):398e402. 13. Cooper S, Janghorbani M, Cooper G. A decade of in-hospital resuscitation: outcomes and prediction of survival? Resuscitation. 2006;68(2):231e237. 14. Goldberger ZD, Chan PS, Berg RA, et al. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study. Lancet. 2012;380(9852):1473e1481. 15. Cline SL, von Der Lohe E, Newman MM, Groh WJ. Factors associated with poor survival in women experiencing cardiac arrest in a rural setting. Heart Rhythm. 2005;2(5):492e496. 16. Herlitz J, Engdahl J, Svensson L, Young M, Angquist KA, Holmberg S. Is female sex associated with increased survival after out-of-hospital cardiac arrest? Resuscitation. 2004;60(2):197e203. 17. Iwami T, Hiraide A, Nakanishi N, et al. Age and sex analyses of out-of-hospital cardiac arrest in Osaka, Japan. Resuscitation. 2003;57(2):145e152. 18. Kim C, Fahrenbruch CE, Cobb LA, Eisenberg MS. Out-of-hospital cardiac arrest in men and women. Circulation. 2001;104(22):2699e2703. 19. Vukmir RB. Prehospital cardiac arrest and the adverse effect of male gender, but not age, on outcome. J Womens Health (Larchmt). 2003;12(7):667e673. 20. Deakin CD, Nolan JP, Soar J, et al. European resuscitation Council guidelines for resuscitation 2010 Section 4. Adult advanced life support. Resuscitation. 2010;81(10):1305e1352. 21. Altman DG. Practical Statistics for Medical Research. London: Chapman & Hall; 1991.
J. Israelsson et al. / Heart & Lung 43 (2014) 510e515 22. Satterthwaite FE. An approximate distribution of estimates of variance components. Biometrics. 1946;2(6):110e114. 23. Cohen J, Cohen P, West SG, Aiken LS. Applied Multiple Regression/correlation Analysis for the Behavioral Sciences. 3rd ed. Mahwah, NJ: Lawrence Erlbaum Associates; 2003. 24. Juul S, Frydenberg M. An Introduction to Stata for Health Researchers. 3rd ed. College Station, TX: Stata Press; 2010. 25. Arrich J, Sterz F, Fleischhackl R, et al. Gender modifies the influence of age on outcome after successfully resuscitated cardiac arrest: a retrospective cohort study. Medicine. 2006;85(5):288e294. 26. Aune S, Herlitz J, Bang A. Characteristics of patients who die in hospital with no attempt at resuscitation. Resuscitation. 2005;65(3):291e299. 27. De Decker L, Anneweiler C, Launay C, Fantino B, Beauchet O. Do not resuscitate orders and aging: impact of multimorbidity on the decision-making process. J Nutr Health Aging. 2014;18(3):330e335. 28. Alfredsson J, Stenestrand U, Wallentin L, Swahn E. Gender differences in management and outcome in non-ST-elevation acute coronary syndrome. Heart. 2007;93(11):1357e1362. 29. Isaksson RM, Holmgren L, Lundblad D, Brulin C, Eliasson M. Time trends in symptoms and prehospital delay time in women vs. men with myocardial infarction over a 15-year period. The Northern Sweden MONICA Study. Eur J Cardiovasc Nurs. 2008;7(2):152e158. 30. Becerra M, Hurst SA, Junod Perron N, Cochet S, Elger BS. ‘Do not attempt resuscitation’ and ‘cardiopulmonary resuscitation’ in an inpatient setting: factors influencing physicians’ decisions in Switzerland. Gerontology. 2011;57(5):414e421. 31. Statistics Sweden. Statistical Yearbook of Sweden 2014. Stockholm: Statistics Sweden; 2014.
515
32. Brindley PG, Markland DM, Mayers I, Kutsogiannis DJ. Predictors of survival following in-hospital adult cardiopulmonary resuscitation. CMAJ. 2002;167(4): 343e348. 33. Danciu SC, Klein L, Hosseini MM, Ibrahim L, Coyle BW, Kehoe RF. A predictive model for survival after in-hospital cardiopulmonary arrest. Resuscitation. 2004;62(1):35e42. 34. Rakic D, Rumboldt Z, Carevic V, et al. In-hospital cardiac arrest and resuscitation outcomes: rationale for sudden cardiac death approach. Croat Med J. 2005;46(6):907e912. 35. Skrifvars MB, Castren M, Nurmi J, Thoren AB, Aune S, Herlitz J. Do patient characteristics or factors at resuscitation influence long-term outcome in patients surviving to be discharged following in-hospital cardiac arrest? J Intern Med. 2007;262(4):488e495. 36. Hajbaghery MA, Mousavi G, Akbari H. Factors influencing survival after inhospital cardiopulmonary resuscitation. Resuscitation. 2005;66(3):317e321. 37. Sandroni C, Ferro G, Santangelo S, Tortora F, Mistura L, Cavallaro F, et al. Inhospital cardiac arrest: survival depends mainly on the effectiveness of the emergency response. Resuscitation. 2004;62(3):291e297. 38. Ebell MH, Afonso AM. Pre-arrest predictors of failure to survive after inhospital cardiopulmonary resuscitation: a meta-analysis. Fam Practice. 2011;28(5):505e515. 39. Hair JF, Black WC, Babin BJ, Anderson RE. Multivariate Data Analysis: A Global Perspective. 7th ed. Upper Saddle River, NJ: Pearson Education; 2008. 40. Skrifvars MB, Rosenberg PH, Finne P, Halonen S, Hautamaki R, Kuosa R, et al. Evaluation of the in-hospital Utstein template in cardiopulmonary resuscitation in secondary hospitals. Resuscitation. 2003;56(3):275e282. 41. Snijders TAB, Bosker RJ. Multilevel Analysis: An Introduction to Basic and Advanced Multilevel Modeling. 2nd ed. Thousand Oaks, CA: SAGE; 2012.
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Care of Patients With Electrocardiographic Abnormalities
Is there a difference in survival between men and women suffering in-hospital cardiac arrest? Johan Israelsson, RN, MSc a, b, *, Carina Persson, RPT, PhD c, Anna Strömberg, RN, PhD d, Kristofer Årestedt, RN, PhD c, d, e a
Department of Internal Medicine, Division of Cardiology, Kalmar County Hospital, SE-39185 Kalmar, Sweden Kalmar Maritime Academy, Linnaeus University, SE-39182 Kalmar, Sweden c School of Health and Caring Sciences, Linnaeus University, SE-39182 Kalmar, Sweden d Department of Medical and Health Sciences, Division of Nursing Science, Linköping University, SE-58183 Linköping, Sweden e Palliative Research Centre, Ersta Sköndal University College and Ersta Hospital, SE-10061 Stockholm, Sweden b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 21 January 2014 Received in revised form 30 May 2014 Accepted 30 May 2014 Available online 5 July 2014
Objectives: To describe in-hospital cardiac arrest (CA) events with regard to sex and to investigate if sex is associated with survival. Background: Previous studies exploring differences between sexes are incongruent with regard to clinical outcomes. In order to provide equality and improve care, further investigations into these aspects are warranted. Methods: This registry study included 286 CAs. To investigate if sex was associated with survival, logistic regression analyses were performed. Results: The proportion of CA with a resuscitation attempt compared to CA without resuscitation was higher among men. There were no associations between sex and survival when controlling for previously known predictors and interaction effects. Conclusions: Sex does not appear to be a predictor for survival among patients suffering CA where resuscitation is attempted. The difference regarding proportion of resuscitation attempts requires more attention. It is important to consider possible interaction effects when studying the sex perspective. Ó 2014 Elsevier Inc. All rights reserved.
Keywords: Heart arrest Hospital Sex Survival Predictor
Introduction Every year, approximately 360,000 people in the United States suffer an out-of-hospital cardiac arrest (OHCA).1 The number of inhospital cardiac arrest (IHCA) is estimated to approximately 200,000.2 In Europe, the number of OHCA is estimated to 275,000,3 while the number of IHCA is not known. In Sweden, more than 10,000 people are estimated to suffer a cardiac arrest (CA) every year, of which about one third occur in a hospital setting. In Sweden, the survival rate after IHCA is higher compared to OHCA,4 almost 30%5 vs. approximately 10%.6 Factors described as predictors for IHCA survival in previous research are; sex,7,8 age,9,10 initial rhythm,9,10 witnessed CA,9,10 CA during daytime,10,11 etiology,9,11 time to treatment,4 absence of intubation12 and duration of CA.13,14 Few studies have investigated the sex perspective in Abbreviations: OHCA, Out-of-hospital cardiac arrest; IHCA, In-hospital cardiac arrest; CA, Cardiac arrest; AMI, Acute myocardial infarction; ACLS, Advanced cardiovascular life support. * Corresponding author. Department of Internal Medicine, Division of Cardiology, Kalmar County Hospital, SE-39185 Kalmar, Sweden. Tel.: þ46 480 81130; fax þ46 480 448797. E-mail address: [email protected] (J. Israelsson). 0147-9563/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.hrtlng.2014.05.012
relation to survival, and the findings are incongruent.7,8,15e19 In addition, the majority of these studies is performed out-of hospital where conditions are quite different from an in-hospital context. According to previous research, approximately 60% of the patients suffering IHCA are men.8,13 Women seem to have a slightly better chance of surviving to hospital discharge compared to men.7 However, this association could be dependent on age, as higher survival rates only occur among younger women.8 This indicates the possibility of an interaction between sex and age. Another reason for the incongruent findings could be that different covariates have been used to adjust the survival models. There is a need for more knowledge in order to improve the treatment of IHCA in both sexes. The aim of this study was therefore to describe IHCA events with regard to sex and investigate if sex is associated with survival after controlling for previously known predictors and interaction effects. Methods Design, settings and data collection This observational registry study is based on data from the Swedish national IHCA register. During the study period,
J. Israelsson et al. / Heart & Lung 43 (2014) 510e515
approximately 85% of emergency hospitals in Sweden reported data to this register (https://www.hjartstoppsjh.se/). The register is Internet based and clinics report data by using two protocols. The first one concerns patient baseline information and CA events. The second protocol is for follow-up and is completed 30 days after CA. This protocol contains data on post resuscitation care, hospital discharge and survival. Survival is recorded on three occasions; after completed resuscitation attempt, at hospital discharge and 30 days after CA. Co-morbidities included in the register are acute myocardial infarction (AMI), stroke, heart failure, diabetes and cancer. The register is validated by random inspections of the data, performed by the National Registry Committee. For the present study, data from one hospital was analyzed. The data consists of all reported CAs (n ¼ 286) where any resuscitation attempts were made, at a county hospital in the southeast of Sweden, from January 2007 to June 2011. This hospital is located in a middle-sized Swedish town. The catchment area includes approximately 230,000 inhabitants. The hospital has 372 beds and approximately 60 CAs, with a resuscitation attempt, each year. The treatment of CA is very similar to most hospitals in Sweden and did not change during the research period. The hospital where the data was collected uses the Swedish Advanced Cardiovascular Life Support (ACLS) algorithm. The ACLS Guidelines were changed in Sweden in October 2006 and in October 2011, in accordance with guidelines by the European Resuscitation Council.20 The survival rates are approximately at the same level as national register data. Outcomes and predictors were selected with consideration to prior research and the aim of the present study. In addition, we chose to include drugs at CA since this treatment often is conducted and recommended in ERC guidelines.20 To investigate the proportion of resuscitation attempts in relation to sex, data (number of deceased patients at the hospital and their sex) from electronic patient records was used. The study was approved by the Regional Ethical Review Board at Linköping University (study code: 2013/70-32). Data analysis To compare differences in characteristics of CA events in relation to sex, chi-square statistics was used on nominal data. Student’s t-test was used to compare sex differences regarding age and time variables.21 If the assumption of equal variance was not fulfilled, Student’s t-test adjusted for unequal variances (Satterthwaite’s approximation formula) was used.22 Hierarchical multiple binary logistic regression analyses were conducted to investigate the association between sex and survival.23,24 Three survival outcomes were tested; survival after resuscitation attempt, survival at hospital discharge and survival 30 days after resuscitation. In the first block (Model I), sex was included as a single predictor for survival. To adjust for covariates, age, shockable initial rhythm, time to treatment, witnessed CA, medical treatment, intubation, cardiac etiology and CA during daytime were included in the second block (Model II). The variable time to treatment consisted of time to defibrillation for CAs with shockable (Ventricular Fibrillation or Ventricular Tachycardia) initial rhythm and time to cardiopulmonary resuscitation for CAs with nonshockable (Asystole or Pulseless Electrical Activity) initial rhythm. The variable medical treatment included administration of Adrenaline and/or Amiodarone. Cardiac etiology was defined as heart disease (ischemic heart disease, arrhythmia or heart failure) causing the CA. The variable CA during daytime was defined as a CA between 06:00 AM and 06:00 PM. A multiplicative interaction term (sex age) was included in the final block (Model III) to test for interaction effects between sex and age. McFadden pseudo R2 change was used to illustrate model development. As the
511
assumption of non-dependency was violated (i.e. nested data with 15 patients who suffered two to four CAs, median ¼ 2), all regression models were re-analyzed using robust variance estimates to test that this violation did not bias the findings. No multicollinearity problems were detected across the predictors as no variable had a variance inflation factor (VIF) above 1.50 and the mean was 1.25. An additional analysis was performed to compare the proportion of resuscitation attempts in relation to sex, using Pearson chi-square test. Between January 2009 and December 2010, the number of patients where resuscitation was attempted (n ¼ 126) were compared to the number of patients suffering CA without a resuscitation attempt, e.g. patients with do-not-attemptresuscitation (DNAR) decisions (n ¼ 1067). The significance level was set to p < 0.05. All statistical analyses were performed by STATA 12.1 for Windows (StataCorp LP, College Station, TX, USA). Results Descriptions of in-hospital CA events with regard to sex The 286 in-hospital CA events are presented in Table 1. Sixtynine percent (n ¼ 196) of the afflicted were men. Mean age was 74.1 years, with the women being significantly older than the men (D ¼ 4.3 1.6, p ¼ 0.006). Heart disease, especially AMI, was the most common cause for CA, among both men and women. However, cardiac etiology was significantly more common among the men compared to the women (p ¼ 0.043). In addition to AMI, the most common co-morbidities, were heart failure (37.4%) and diabetes (21.3%). The men more often suffered from cancer (p ¼ 0.012). In 53.5% of the CA events, the patient survived the resuscitation attempt, 37.4% survived to hospital discharge and 35.0% were still alive at 30 days following resuscitation attempt. Proportion of resuscitation attempts in relation to sex Resuscitation attempts were more common (14.8% vs. 6.2%) among men compared to women. From January 2009 to December 2010, 37 resuscitation attempts were made among women and 89 among men. No attempts were made in 556 women suffering CA, compared to 511 in men (c2(1) ¼ 23.32, p < 0.001). Association between sex and survival after resuscitation attempt More than half of the patients suffering CA (53.5%) survived the resuscitation attempt. No significant association between sex and survival was identified in any of the regression models (Table 2). Before and after the interaction term of sex and age was included (Model II vs. III), having a shockable initial rhythm (OR ¼ 22.40 vs. 22.24), witnessed CA (OR ¼ 20.17 vs. 20.35) and not being intubated (OR ¼ 0.33 vs. 0.33) were significantly (p < 0.01) associated with survival. Model II and III explained 41% of the total variance. The associations remained when nested data was taken into account. Association between sex and survival at hospital discharge Among the patients who survived the resuscitation attempt, 69.9% were alive at hospital discharge. No significant bivariate association between sex and survival was identified in Model I. When adjusting covariates were included (Model II), being a man (OR ¼ 2.69), and younger age (OR ¼ 0.97) were significantly (p < 0.05) associated with higher survival. However, these associations did not remain once the interaction term of sex and age had been included. Before and after the interaction term of sex and age was included (Model II vs. III), having a shockable initial rhythm
512
J. Israelsson et al. / Heart & Lung 43 (2014) 510e515
Table 1 Characteristics of the SCA in relation to sex (n ¼ 286). Variable
Number of observations (women/men)
All patients
Women
Men
df
p-value
Age, mean (sd) Cardiac etiology, n (%) On-going AMI, n (%) Co-morbidity, n (%) Prior AMI Respiratory insufficiency Stroke Diabetes Heart failure Cancer Treatment & organization, n (%) SCA at daytime SCA at supervised wards SCA during ECG VF/VT as initial rhythm Witnessed SCA Intubated Drugs given at SCA Time in minutes, mean (sd) Time SCA e alarm Time SCA e CPR Time SCA e defibrillationa Time SCA e MET Time SCA e treatment Survival, n (%) Survival after resuscitation Survival at hospital discharge Survival at 30 days
286 (90/196) 286 (90/196) 238 (74/164)
74.1 (12.6) 171 (59.8) 108 (45.4)
77.1 (11.5) 46 (51.1) 35 (47.3)
72.8 (12.8) 125 (63.8) 73 (44.5)
284 1 1
0.006b 0.043d 0.690d
266 267 272 273 257 273
(79/187) (82/185) (83/189) (84/189) (77/180) (84/189)
91 28 46 58 96 29
(34.2) (10.5) (16.9) (21.3) (37.4) (10.6)
23 7 10 16 27 3
(29.1) (8.5) (12.1) (19.1) (35.1) (3.6)
68 21 36 42 69 26
(36.4) (11.4) (19.1) (22.2) (38.3) (13.8)
1 1 1 1 1 1
0.255d 0.489d 0.156d 0.554d 0.620d 0.012d
286 286 286 286 286 286 286
(90/196) (90/196) (90/196) (90/196) (90/196) (90/196) (90/196)
168 160 152 110 247 113 175
(58.7) (55.9) (53.2) (38.5) (86.4) (39.5) (61.2)
55 48 48 29 78 31 53
(61.1) (53.3) (53.3) (32.2) (86.7) (34.4) (58.9)
113 112 104 81 169 82 122
(57.7) (57.1) (53.1) (41.3) (86.2) (41.8) (62.2)
1 1 1 1 1 1 1
0.581d 0.547d 0.966d 0.142d 0.919d 0.235d 0.589d
229 239 109 218 286
(69/160) (73/166) (29/80) (65/153) (90/196)
1.5 0.5 1.3 5.5 0.7
(3.0) (1.1) (2.1) (4.0) (1.5)
1.3 0.6 0.8 5.7 0.6
(2.1) (1.3) (1.7) (3.1) (1.3)
1.6 0.4 1.5 5.4 0.8
(3.3) (0.9) (2.2) (4.3) (1.6)
197.8 106.1 107 166.4 213.1
0.382c 0.475c 0.143b 0.487c 0.243c
1 1 1
0.117d 0.079d 0.144d
286 (90/196) 286 (90/196) 286 (90/196)
153 (53.5) 107 (37.4) 100 (35.0)
42 (46.7) 27 (30.0) 26 (28.9)
111 (56.6) 80 (40.8) 74 (37.8)
AMI ¼ Acute myocardial infarction, ECG ¼ Electrocardiography, SCA ¼ Sudden cardiac arrest, CPR ¼ Cardiopulmonary resuscitation, VF ¼ Ventricular fibrillation, VT ¼ Ventricular tachycardia, MET ¼ Medical emergency team. a If the initial rhythm was VF/VT. b Students t-test. c Students t-test adjusted for unequal variances (Satterthwait’s approximation formula). d c2-test.
(OR ¼ 21.4 vs. 21.8), shorter time to treatment (OR ¼ 0.58 vs. 0.58), witnessed CA (OR ¼ 11.36 vs. 11.12), not receiving medical treatment (OR ¼ 0.29 vs. 0.29), and not being intubated (OR ¼ 0.12 vs. 0.11) were significantly (p < 0.05) associated with survival at hospital discharge. Model II and III explained 53% of the total variance. The associations remained when nested data was taken into account. Association between sex and survival at 30 days after resuscitation Most of the patients who survived until hospital discharge were alive at 30 days after resuscitation (93.5%). No significant association between sex and survival was identified in any of the regression models (Table 2). Before and after the interaction term of sex and age was included (Model II vs. III), having a shockable initial rhythm (OR ¼ 19.05 vs. 19.13), shorter time to treatment (OR ¼ 0.53 vs. 0.53), not receiving medical treatment (OR ¼ 0.27 vs. 0.27), and not being intubated (OR ¼ 0.14 vs. 0.14) were significantly (p < 0.01) associated with survival. Younger age (OR ¼ 0.95 vs. 0.96), and witnessed CA (OR ¼ 8.20 vs. 8.15) were significantly (p < 0.05) associated with survival in Model II, but not in Model III. Model II and III explained 54% of the total variance. The associations remained when nested data was taken into account. Discussion The most important findings in the present study were that we did not find any associations between sex and survival after IHCA among patients receiving resuscitation. Furthermore, the proportion of CAs with a resuscitation attempt was higher among men, compared to CAs without resuscitation.
Unlike Herlitz et al, who found that female sex was related to better survival,7 we did not find that sex was associated with survival in any of our final models. One possible explanation could be that we included the interaction term in our study, whereas Herlitz and co-workers did not.7 In an American study by Topjian et al, being a woman of child-bearing age was related to better survival.8 However, that study did not find any differences between older men and women. The results are not fully comparable to our study, since patients between 44 and 56 years of age were excluded. Almost all women in our study were above child-bearing age. In addition, survival rates are lower in the US compared to Sweden.6,8,9 Nonetheless, the results from Topjian and co-workers support our hypothesis of an existing interaction between sex and age in relation to survival.8 In addition, Arrich et al found that sex modifies the influence of age on survival. Among men who initially survived a CA, older age was related to a worse prognosis. Among women, the prognosis was not equally affected by age.25 However, those results are difficult to compare with ours since only initial survivors after OHCA were studied. Most previous studies have shown that the majority receiving resuscitation after an IHCA are men.10,13 This corresponds with our results. In addition, when comparing CAs with a resuscitation attempt to CAs without resuscitation, the proportion of attempts was higher among men. This corresponds with results from the study by Herlitz et al. In their study, resuscitation attempts were started in 14% of all CAs in men, and 11% in women. Herlitz et al reported no sex differences in age or etiology. In addition, they found no significant differences between men and women in a retrospective evaluation of the justification to start resuscitation.7 However, those not receiving resuscitation were not evaluated. In another study, by Aune et al, characteristics among those not
J. Israelsson et al. / Heart & Lung 43 (2014) 510e515
513
Table 2 The association between sex and survival based on binary logistic regression analyses (n ¼ 286). Model I
Model II
Model III
Outcomes
Predictors
OR (SE)
95% CI for OR
OR (SE)
95% CI for OR
OR (SE)
Survival after resuscitation attempt
Sex (being man) Age Shockable initial rhythm Time to treatment Witnessed Medical treatment Intubation Cardiac etiology Daytime Sex age Overall model statistics Hosmer and Lemeshow test McFadden pseudo R2 Sex (being man) Age Shockable initial rhythm Time to treatment Witnessed Medical treatment Intubation Cardiac etiology Daytime Sex age Overall model statistics Hosmer and Lemeshow test McFadden pseudo R2 Sex (being man) Age Shockable initial rhythm Time to treatment Witnessed Medical treatment Intubation Cardiac etiology Daytime Sex age Overall model statistics Hosmer and Lemeshow test McFadden pseudo R2
1.49 (0.38)
0.90e2.46
1.72 1.01 22.40 0.76 20.17 0.67 0.33 1.11 1.17
0.83e3.55 0.98e1.03 8.36e60.06 0.55e1.04 4.33e93.75 0.30e1.45 0.16e0.69 0.56e2.20 0.60e2.29
1.05 (2.69) 0.01e160.73 1.00 (0.03) 0.95e1.06 22.24 (11.22)*** 8.27e59.78 0.76 (0.12) 0.56e1.04 20.35 (15.99)*** 4.37e94.89 0.66 (0.26) 0.30e1.45 0.33 (0.12)** 0.16e0.68 1.11 (0.39) 0.56e2.19 1.17 (0.40) 0.60e2.28 1.01 (0.03) 0.94e1.07 c2(10) ¼ 160.63, p < 0.001 c2(8) ¼ 5.55, p < 0.698
Survival at hospital discharge
Survival at 30 days
(0.64) (0.01) (11.27)*** (0.12) (15.81)*** (0.26) (0.12)** (0.39) (0.40)
c2(1) ¼ 2.46, p ¼ 0.117
c2(9) ¼ 160.59, p < 0.001 c2(8) ¼ 5.83, p < 0.666
0.01 1.61 (0.44)
0.41 2.69 0.97 21.38 0.58 11.36 0.29 0.12 1.44 1.23
0.94e2.74
(1.26)* (0.02)* (10.46)*** (0.11)** (12.10)* (0.13)** (0.06)*** (0.62) (0.50)
1.08e6.72 0.94e1.00 8.19e55.80 0.40e0.83 1.41e91.66 0.12e0.68 0.04e0.32 0.62e3.36 0.55e2.74
c2(1) ¼ 3.14, p ¼ 0.077
c2(9) ¼ 201.43, p < 0.001 c2(8) ¼ 4.88, p < 0.771
0.01 1.49 (0.41)
0.53 2.11 0.95 19.05 0.53 8.20 0.27 0.14 1.86 1.53
95% CI for OR
0.41 5.84 (17.90) 0.01e2382.51 0.98 (0.03) 0.91e1.04 21.80 (10.84)*** 8.23e57.76 0.58 (0.11)** 0.40e0.83 11.12 (11.87)* 1.37e90.21 0.29 (0.13)** 0.12e0.69 0.11 (0.06)*** 0.04e0.32 1.46 (0.63) 0.62e3.42 1.23 (0.50) 0.55e2.74 0.99 (0.04) 0.92e1.07 c2(10) ¼ 201.50, p < 0.001 c2(8) ¼ 4.80, p < 0.779
c2(1) ¼ 2.17, p ¼ 0.141
c2(9) ¼ 198.63, p < 0.001 c2(8) ¼ 4.42, p < 0.817
0.53 2.71 (8.59) 0.01e1356.16 0.96 (0.35) 0.89e1.03 19.13 (9.29)*** 7.38e49.58 0.53 (0.10)** 0.37e0.77 8.15 (8.71) 1.00e66.18 0.27 (0.12)** 0.11e0.67 0.14 (0.07)*** 0.05e0.40 1.87 (0.84) 0.77e4.53 1.53 (0.64) 0.67e3.48 1.00 (0.04) 0.92e1.08 c2(10) ¼ 198.64, p < 0.001 c2(8) ¼ 4.43, p < 0.817
0.01
0.54
0.54
0.87e2.56
(0.99) (0.02)** (9.19)*** (0.10)** (8.74)* (0.12)** (0.07)*** (0.84) (0.64)
0.84e5.29 0.92e0.98 7.40e49.02 0.37e0.77 1.02e66.20 0.11e0.66 0.05e0.39 0.78e4.49 0.48e35.41
Test of statistical significance: *p < 0.05, **p < 0.01, ***p < 0.001.
receiving resuscitation during one year at one hospital were described. Of 674 patients, 53% were men vs. 47% women. They compared this group to another group (n ¼ 89) who did receive resuscitation during the same time period: 72% men vs. 28% women.26 However, the sex perspective was not the main focus in their study and therefore not further analyzed. In the present study, the women receiving resuscitation were older than the men and were less likely to have a CA with cardiac etiology. This could possibly explain some of the differences in the proportion of resuscitation attempts. However, no data were available regarding age, etiology and other characteristics in the group not receiving resuscitation, which certainly are important factors. In our results, men (receiving resuscitation) suffered from more cancer, which ought to be a significant factor when making decisions about starting resuscitation or not. A recently published systematic review study by de Decker et al, investigating the impact of morbidity on DNAR decision making, concluded that cancer was significantly associated with DNAR orders among patients of 80 years of age or older.27 Previous studies indicate that women suffering acute coronary syndrome have lower incidence of typical symptoms, are treated less intensively, and are less likely to be admitted to coronary care units than men.28,29 In the present study, there were no significant sex-related differences in the location of the CAs
(supervised wards or not), or if they were witnessed or not. This corresponds with the study by Herlitz et al7 Nonetheless, since we found a sex difference in the proportion of resuscitation attempts, one can pose the question if men are over treated and women under treated with regard to resuscitation. If this is the case, the women receiving resuscitation in our study could have constituted a more selective group with a better chance of survival. This could also be a possible explanation to why female sex has been a predictor for survival in earlier studies. A study by Becerra et al, found no difference between men and women when comparing patients with CPR or DNAR orders. In their study, the most important factors associated with a DNAR order were worse prognosis and poorer quality of life. One of the most common justifications for decision making, beside important co-morbidities, was the patients’ and family members’ preferences. Family members were frequently involved in DNAR decisions.30 Since women in general die at an older age compared to men,31 they are more likely to be alone when becoming seriously ill. It is possible that the absence of a spouse could influence therapy wishes and decisions. This issue requires more attention and further investigation. Shockable initial rhythm was the most important predictor for survival outcomes in both men and women. Its impact on survival after IHCA has been shown in a number of previous
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studies.10,13,32e34 Absence of intubation and absence of drugs given at CA were significant predictors for survival outcomes. Past research has shown the same findings concerning intubation.12 These relationships are probably not due to harm caused by these recommended interventions, but more likely to the prolonged duration of the CAs. Time to treatment was another important predictor for all survival outcomes in the present study. This has not always been described in past research,13,35 but corresponds with some studies.36,37 The overall survival in the present study was high compared to previous research.9,38 This could be an effect of well-functioning hospital routines for resuscitation.
among those not receiving resuscitation have to be further investigated from a sex perspective in future research. In addition, it is important to consider possible interaction effects when studying the sex perspective and its relation to survival after CA. Shockable initial heart rhythm and time to treatment were the most important predictors for survival, regardless of sex. Thus, efforts should be made to detect CA at an early stage. There should be more observations of patients with suspected AMI, combined with well-trained personnel with the ability to provide cardiopulmonary resuscitation and defibrillation without delay, in order to improve CA care for both men and women.
Limitations
Acknowledgments
A strength with the present study is that it includes all patients suffering CA at the hospital during the study period. For this reason, no sample size calculation was conducted before the start of the study. The sample size was deemed to be sufficient as 15 to 20 observations were provided for each predictor variable.39 The data from the hospital does not diverge from national data, and the result could be transferred to other hospitals of the same size and with similar organization. Since we could not access complete data (CAs with no resuscitation attempt) for a longer time period, the results regarding the proportion of resuscitation attempts consist of data from January 2009 to December 2010. In addition, it was not possible to control this variable for age, which could be considered a limitation. The major difference in proportion of resuscitation attempts between men and women could have biased the results of this study, since it will make the groups less comparable. The results should therefore be treated with some caution. More research is needed to investigate the reason for this difference, e.g. by examining the characteristics among patients not receiving resuscitation from a sex perspective. However, almost all CA research has focused on those receiving resuscitation, and this group was the primary population in the present study as well. There are also methodological issues to address regarding the predictor time to treatment. In the present study, time to treatment consists of time to defibrillation, or time to CPR, depending on the type of CA and the intervention considered to be the most important. The reason was that several of the CAs with shockable initial rhythm did not receive any CPR. Since the time factor has been studied by using a number of definitions, the results concerning this variable should be interpreted with caution.10,13 One variable of potential importance is the duration of CA. This variable was not included in the register until the revision in 2013. Therapeutic hypothermia was not included as only one patient received this treatment. Some patients suffer more than one CA. This fact violates the statistical assumption of non-dependency. Previous studies have often solved this problem by including only the first CA event.7,40 However, there are different ways to analyze nested data, for example by multilevel modeling.41 As the problem with repeated CAs was limited to a few cases, we re-analyzed all regression models using robust variance estimates to make sure that this violation did not bias the findings.24
We would like to thank the hospital personnel involved in the study and the national register committee for providing the data. We would also like to thank the county council of Kalmar for support and practical assistance in the data collection. A special thanks to Professor Jörg Carlson for valuable input and to Jean Stevenson-Ågren and Sofia McGarvey for revising the language.
Conclusion Sex does not appear to be a predictor for survival among patients suffering IHCA where resuscitation is attempted, and should therefore not influence CA treatment. However, there is a higher proportion of resuscitation attempts among men. This finding could be of importance in order to improve clinical practice and achieve equal care, especially in relation to DNAR orders. The characteristics
References 1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statisticse2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28ee292. 2. Merchant RM, Yang L, Becker LB, et al. Incidence of treated cardiac arrest in hospitalized patients in the United States. Crit Care. 2011;39(11):2401e2406. 3. Atwood C, Eisenberg MS, Herlitz J, Rea TD. Incidence of EMS-treated out-ofhospital cardiac arrest in Europe. Resuscitation. 2005;67(1):75e80. 4. Fredriksson M, Aune S, Bang A, et al. Cardiac arrest outside and inside hospital in a community: mechanisms behind the differences in outcome and outcome in relation to time of arrest. Am Heart J. 2010;159(5):749e756. 5. Aune S, Eldh M, Engdahl J, et al. Improvement in the hospital organisation of CPR training and outcome after cardiac arrest in Sweden during a 10-year period. Resuscitation. 2011;82(4):431e435. 6. Stromsoe A, Afzelius S, Axelsson C, et al. Improvements in logistics could increase survival after out-of-hospital cardiac arrest in Sweden. J Intern Med. 2013;273(6):622e627. 7. Herlitz J, Rundqvist S, Bang A, et al. Is there a difference between women and men in characteristics and outcome after in hospital cardiac arrest? Resuscitation. 2001;49(1):15e23. 8. Topjian AA, Localio AR, Berg RA, et al. Women of child-bearing age have better inhospital cardiac arrest survival outcomes than do equal-aged men. Crit Care. 2010;38(5):1254e1260. 9. Larkin GL, Copes WS, Nathanson BH, Kaye W. Pre-resuscitation factors associated with mortality in 49,130 cases of in-hospital cardiac arrest: a report from the National Registry for Cardiopulmonary Resuscitation. Resuscitation. 2010;81(3):302e311. 10. Skrifvars MB, Castren M, Aune S, Thoren AB, Nurmi J, Herlitz J. Variability in survival after in-hospital cardiac arrest depending on the hospital level of care. Resuscitation. 2007;73(1):73e81. 11. Cooper S, Evans C. Resuscitation Predictor Scoring Scale for inhospital cardiac arrests. Emerg Med J. 2003;20(1):6e9. 12. Cohn AC, Wilson WM, Yan B, et al. Analysis of clinical outcomes following inhospital adult cardiac arrest. Intern Med J. 2004;34(7):398e402. 13. Cooper S, Janghorbani M, Cooper G. A decade of in-hospital resuscitation: outcomes and prediction of survival? Resuscitation. 2006;68(2):231e237. 14. Goldberger ZD, Chan PS, Berg RA, et al. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study. Lancet. 2012;380(9852):1473e1481. 15. Cline SL, von Der Lohe E, Newman MM, Groh WJ. Factors associated with poor survival in women experiencing cardiac arrest in a rural setting. Heart Rhythm. 2005;2(5):492e496. 16. Herlitz J, Engdahl J, Svensson L, Young M, Angquist KA, Holmberg S. Is female sex associated with increased survival after out-of-hospital cardiac arrest? Resuscitation. 2004;60(2):197e203. 17. Iwami T, Hiraide A, Nakanishi N, et al. Age and sex analyses of out-of-hospital cardiac arrest in Osaka, Japan. Resuscitation. 2003;57(2):145e152. 18. Kim C, Fahrenbruch CE, Cobb LA, Eisenberg MS. Out-of-hospital cardiac arrest in men and women. Circulation. 2001;104(22):2699e2703. 19. Vukmir RB. Prehospital cardiac arrest and the adverse effect of male gender, but not age, on outcome. J Womens Health (Larchmt). 2003;12(7):667e673. 20. Deakin CD, Nolan JP, Soar J, et al. European resuscitation Council guidelines for resuscitation 2010 Section 4. Adult advanced life support. Resuscitation. 2010;81(10):1305e1352. 21. Altman DG. Practical Statistics for Medical Research. London: Chapman & Hall; 1991.
J. Israelsson et al. / Heart & Lung 43 (2014) 510e515 22. Satterthwaite FE. An approximate distribution of estimates of variance components. Biometrics. 1946;2(6):110e114. 23. Cohen J, Cohen P, West SG, Aiken LS. Applied Multiple Regression/correlation Analysis for the Behavioral Sciences. 3rd ed. Mahwah, NJ: Lawrence Erlbaum Associates; 2003. 24. Juul S, Frydenberg M. An Introduction to Stata for Health Researchers. 3rd ed. College Station, TX: Stata Press; 2010. 25. Arrich J, Sterz F, Fleischhackl R, et al. Gender modifies the influence of age on outcome after successfully resuscitated cardiac arrest: a retrospective cohort study. Medicine. 2006;85(5):288e294. 26. Aune S, Herlitz J, Bang A. Characteristics of patients who die in hospital with no attempt at resuscitation. Resuscitation. 2005;65(3):291e299. 27. De Decker L, Anneweiler C, Launay C, Fantino B, Beauchet O. Do not resuscitate orders and aging: impact of multimorbidity on the decision-making process. J Nutr Health Aging. 2014;18(3):330e335. 28. Alfredsson J, Stenestrand U, Wallentin L, Swahn E. Gender differences in management and outcome in non-ST-elevation acute coronary syndrome. Heart. 2007;93(11):1357e1362. 29. Isaksson RM, Holmgren L, Lundblad D, Brulin C, Eliasson M. Time trends in symptoms and prehospital delay time in women vs. men with myocardial infarction over a 15-year period. The Northern Sweden MONICA Study. Eur J Cardiovasc Nurs. 2008;7(2):152e158. 30. Becerra M, Hurst SA, Junod Perron N, Cochet S, Elger BS. ‘Do not attempt resuscitation’ and ‘cardiopulmonary resuscitation’ in an inpatient setting: factors influencing physicians’ decisions in Switzerland. Gerontology. 2011;57(5):414e421. 31. Statistics Sweden. Statistical Yearbook of Sweden 2014. Stockholm: Statistics Sweden; 2014.
515
32. Brindley PG, Markland DM, Mayers I, Kutsogiannis DJ. Predictors of survival following in-hospital adult cardiopulmonary resuscitation. CMAJ. 2002;167(4): 343e348. 33. Danciu SC, Klein L, Hosseini MM, Ibrahim L, Coyle BW, Kehoe RF. A predictive model for survival after in-hospital cardiopulmonary arrest. Resuscitation. 2004;62(1):35e42. 34. Rakic D, Rumboldt Z, Carevic V, et al. In-hospital cardiac arrest and resuscitation outcomes: rationale for sudden cardiac death approach. Croat Med J. 2005;46(6):907e912. 35. Skrifvars MB, Castren M, Nurmi J, Thoren AB, Aune S, Herlitz J. Do patient characteristics or factors at resuscitation influence long-term outcome in patients surviving to be discharged following in-hospital cardiac arrest? J Intern Med. 2007;262(4):488e495. 36. Hajbaghery MA, Mousavi G, Akbari H. Factors influencing survival after inhospital cardiopulmonary resuscitation. Resuscitation. 2005;66(3):317e321. 37. Sandroni C, Ferro G, Santangelo S, Tortora F, Mistura L, Cavallaro F, et al. Inhospital cardiac arrest: survival depends mainly on the effectiveness of the emergency response. Resuscitation. 2004;62(3):291e297. 38. Ebell MH, Afonso AM. Pre-arrest predictors of failure to survive after inhospital cardiopulmonary resuscitation: a meta-analysis. Fam Practice. 2011;28(5):505e515. 39. Hair JF, Black WC, Babin BJ, Anderson RE. Multivariate Data Analysis: A Global Perspective. 7th ed. Upper Saddle River, NJ: Pearson Education; 2008. 40. Skrifvars MB, Rosenberg PH, Finne P, Halonen S, Hautamaki R, Kuosa R, et al. Evaluation of the in-hospital Utstein template in cardiopulmonary resuscitation in secondary hospitals. Resuscitation. 2003;56(3):275e282. 41. Snijders TAB, Bosker RJ. Multilevel Analysis: An Introduction to Basic and Advanced Multilevel Modeling. 2nd ed. Thousand Oaks, CA: SAGE; 2012.