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Resuscitation and post resuscitation care of the very old after out-of-hospital cardiac arrest is worthwhile
International Journal of Cardiology 201 (2015) 616–623
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Resuscitation and post resuscitation care of the very old after out-of-hospital cardiac arrest is worthwhile☆ Matilde Winther-Jensen a,⁎, Jesper Kjaergaard a, Christian Hassager a, John Bro-Jeppesen a, Niklas Nielsen b, Freddy K. Lippert c, Lars Køber a, Michael Wanscher d, Helle Søholm a a
Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Denmark Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden Emergency Medical Services, The Capital Region of Denmark, Denmark d Department of Thoracic Anesthesiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Denmark b c
a r t i c l e
i n f o
Article history: Received 3 July 2015 Received in revised form 14 August 2015 Accepted 19 August 2015 Available online 24 August 2015 Keywords: Age Outcome Neurological outcome Mortality Comorbidity Ethics
a b s t r a c t Background: Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis. As comorbidity and frailty increase with age; ethical dilemmas may arise when OHCA occur in the very old. Objectives: We aimed to investigate mortality, neurological outcome and post resuscitation care in octogenarians (≥80) to assess whether resuscitation and post resuscitation care should be avoided. Methods: During 2007–2011 consecutive OHCA-patients were attended by the physician-based Emergency Medical Services-system in Copenhagen. Pre-hospital data based on Utstein-criteria, and data on post resuscitation care were collected. Primary outcome was successful resuscitation; secondary endpoints were 30-day mortality and neurological outcome (Cerebral Performance Category (CPC)). Results: 2509 OHCA-patients with attempted resuscitation were recorded, 22% (n = 558) were octogenarians/ nonagenarians. 166 (30% of all octogenarians with resuscitation attempted) octogenarians were successfully resuscitated compared to 830 (43% with resuscitation attempted) patients b 80 years. 30-day mortality in octogenarians was significantly higher after adjustment for prognostic factors (HR = 1.61 CI: 1.22–2.13, p b 0.001). Octogenarians received fewer coronary angiographies (CAG) (14 vs. 37%, p b 0.001), and had lower odds of receiving CAG by multivariate logistic regression (OR: 0.19, CI: 0.08–0.44, p b 0.001). A favorable neurological outcome (CPC 1/2) in survivors to discharge was found in 70% (n = 26) of octogenarians compared to 86% (n = 317, p = 0.03) in the younger patients. Conclusion: OHCA in octogenarians was associated with a significantly higher mortality rate after adjustment for prognostic factors. However, the majority of octogenarian survivors were discharged with a favorable neurological outcome. Withholding resuscitation and post resuscitation care in octogenarians does not seem justified. © 2015 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Suffering from an out-of-hospital cardiac arrest (OHCA) still carries a high mortality, despite lower overall mortality in recent years [1]. It is well-known that higher age is associated with increasing morbidity and mortality in various diseases and conditions [2,3], and as comorbidity and general frailty increases with age [2,4]; ethical dilemmas concerning resuscitation may arise, when elderly suffer from critical illnesses such as cardiac arrest [2,5].
☆ All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 9441, 2100 Copenhagen East, Denmark. E-mail address: [email protected] (M. Winther-Jensen).
http://dx.doi.org/10.1016/j.ijcard.2015.08.143 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Higher age has previously been associated with increased incidence and mortality after OHCA [6], however higher age may not necessarily be associated with a worse neurological outcome [2,7]. As the OHCAincidence increase with age, and the worldwide elderly population is growing, reliable tools to distinguish between elderly who will benefit from a resuscitation attempt is increasingly important [5,8,9]. Currently, no standard procedure for assessing patient wishes with regard to a resuscitation attempt is available in the acute setting [5]. However, patient wishes such as do-not-resuscitate orders are more common in the elderly [10]. Elderly heart failure patients have been found to change their resuscitation preferences with decline in clinical status [11], but both the elderly patients as well as the physician have higher expectations of the chances of successful resuscitation in case of cardiac arrest than reported [12]. In addition, elderly successfully resuscitated OHCA-patients residing in nursing homes have been found to have similar 30-day survival probabilities as younger patients living at home
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2. Methods
Multivariate Cox regression analysis adjusting for CCI, gender, primary rhythm, witnessed arrest, bystander CPR, public location of OHCA, time to ROSC and cardiac etiology was used to estimate hazard ratio (HR) with 95% CI for 30-day mortality in octogenarians compared to patients b80 years. Mortality was assessed by Kaplan–Meier curves and differences were tested with the log-rank test. In order to illustrate temporal changes in successful resuscitation and 30-day mortality in patients b80 years and octogenarians, percentages of successfully resuscitated patients and 30-day survival were plotted for each year, and differences during the study period were tested using the Cochran–Mantel–Haenszel Chi-square trend test. All statistical analyses were carried out in SAS Statistics version 9.3 (Cary, NC, USA) or R. 3.0.1 [20] with a level of significance defined as p b 0.05. The R package ‘survival’ was used for Cox regression and the log rank test [21,22].
2.1. Patients and study area
3. Results
after adjustment for prognostic factors [13]. Age used as a stand-alone marker therefore does not seem to be a good criterion for selecting treatment options [2,3]. In this study we aimed to investigate mortality, neurological outcome and post resuscitation care in octogenarians (all patients 80 years of age or older, including nonagenarians) suffering from OHCA, in order to assess whether resuscitation and post resuscitation care of the very old patients is meaningful or should be avoided.
Patients with OHCA were consecutively included in the study from 2007 through 2011. OHCA of all causes with attempted resuscitation (initiation of cardiopulmonary resuscitation (CPR)) and/or more advanced resuscitative efforts (intubation, medication) in the greater Copenhagen area with dispatch by the EMS (Emergency Medical Service) were included. Patients b18 years were excluded from the study. In addition, patients who were found with obvious signs of death (rigor/livor mortis, decapitation, maceration) with no attempted CPR were identified, but these were only used to assess the distribution of patients found dead among age groups. The Copenhagen area covers 675 km2 (260 mi2), and is inhabited by approximately 1.2 million people. The EMS in Copenhagen consists of an emergency ambulance with Basic Life Support (BLS) equipment, defibrillator, and a response unit in a separate vehicle staffed with a paramedic and an attending physician (anesthesiologist). The EMS are dispatched to all patients with presumed OHCA with the treatment protocol according to the advanced life support guidelines by the European Resuscitation Council [14,15]. An Utstein registration sheet is used by the attending physician as documentation, and the pre-hospital data is entered into an OHCA-database immediately after each dispatch [16,17]. The Utstein sheet is a template that ensures uniform international reporting on factors related to OHCA, such as whether OHCA is witnessed or not, where OHCA takes place, primary rhythm and etiology of the arrest [17]. Patients who were successfully resuscitated (return of spontaneous circulation (ROSC) at hospital admission) or who were brought to the hospital with on-going CPR were admitted for post resuscitation care at one of eight hospitals in the greater Copenhagen area. The Danish personal identification number is provided to all residents and by linking the OHCA-cohort to The National Patient Registry, data on comorbidity (diagnoses from primary care physician are not included), age, coexisting conditions and surgical procedures prior to OHCA were obtained [18]. The Charlson Comorbidity Index (CCI) was calculated based on these data. The CCI is a validated weighted index used to predict short-term mortality taking into account the severity of 22 conditions [19]. The regional ethics committee waived informed consent to the study with the reference number: H-2-2012-56, and the study was approved by the Danish Data Protection Agency. 2.2. Outcome The primary end point of the study was successful resuscitation, and secondary endpoints were all-cause 30-day mortality and neurological outcome at discharge measured by Cerebral Performance Category scale (CPC) [17]. The CPC score ranges from 1–5, where 1–2 was defined as favorable, 3–4 was defined as unfavorable, and 5 as dead [17]. CPC was assessed by reviewing patient records, blinded to previous assessment. Inter-observer reliability for CPC at discharge was kappa weighted = 1.0, showing complete agreement. Patients with CPC 3 prior to OHCA were analyzed separately to assess differences in changes from CPC 3. Patients with CPC 4 were not analyzed, as there were only 5 patients in this group. Mortality data were acquired from the Civil Registration system, which holds data on vital status by using the personal identification number. Outcome was analyzed only for patients in whom resuscitation was attempted, excluding those found dead.
2.3. Statistics Normally distributed continuous variables are presented as mean ± standard deviation while non-normally distributed variables are presented as median with 25– 75% quartile ranges. We used Student's unpaired t-test or Wilcoxon rank sum test to assess differences, as appropriate. For categorical variables data are presented as number (n) and percent and we used chi-square test to assess differences. To test the association between successful resuscitation and age, as well as age and favorable neurological outcome (CPC 1 or 2) multivariate logistic regression was used with adjustment for CCI, shockable rhythm, witnessed OHCA, bystander CPR, OHCA in public, sex, time to ROSC (omitted for outcome of resuscitation attempt), with estimation of odds ratios (OR) for successful resuscitation/ favorable neurological outcome and 95% confidence intervals (CI). Furthermore, we tested the association between being octogenarian and odds of having coronary angiography (CAG) performed within 24 h of ROSC by multivariate logistic regression, adjusting for sex, primary rhythm, public arrest, witnessed arrest, CCI level, STEMI presence and bystander CPR. This analysis was performed only in patients that did not die in the emergency department.
3.1. Overall patient characteristics In total the EMS attended 3679 OHCA-patients during the five yearstudy period, divided into 2 groups: Patients found with obvious signs of death (hereafter: patients found dead) (n = 1170, 32% of all patients), and patients with resuscitation attempted (n = 2509, 68% of all patients, hereafter: patients with resuscitation attempted) (Fig. 1). The latter were further stratified into patients successfully resuscitated in the pre-hospital setting/on-going CPR at hospital arrival, 40% of all patients with attempted resuscitation (n = 996, hereafter: successfully resuscitated patients), and patients with unsuccessful resuscitation (n = 1513, 60% of patients with attempted resuscitation, hereafter: unsuccessfully resuscitated patients). Of the successfully resuscitated patients, 15% (n = 144) were octogenarians and 2% (n = 22) of these were nonagenarians, while 20% (n = 296) of the unsuccessfully-resuscitated patients were octogenarians, and 6% (n = 96) were nonagenarians. In patients found dead, 28% (n = 325) were octogenarians, 11% (n = 130) were nonagenarians and 0.25% (n = 3) were centenarians (Figs. 1 and 2A). For further analysis, all patients ≥80 are referred to as octogenarians. 3.2. Successfully resuscitated octogenarians and resuscitated patients b 80 years In successfully resuscitated patients b 80 years, 75% were men vs. 53% (p b 0.001) in successfully resuscitated octogenarians. Compared to the successfully resuscitated patients b 80 years, successfully resuscitated octogenarians had a higher comorbidity burden; with more octogenarians having CCI ≥3 than patients b80 years (30 vs. 19%, p b 0.001). Fewer had OHCA in public (26 vs. 39%, p = 0.002) and fewer had a witnessed arrest (84 vs. 87%, p = 0.04) (Table 1). A higher proportion of successfully resuscitated octogenarians had active therapy withdrawn in the emergency department (19 vs. 10%, p b 0.01, Table 2), and with regard to post resuscitation care, fewer successfully resuscitated octogenarians received therapeutic hypothermia (32 vs. 52%) had an acute coronary angiography (CAG b 24 h, 14 vs. 37%), non-acute CAG (16 vs. 49%), and percutaneous coronary intervention (PCI, 10 vs. 27%), all at p b 0.001. These differences were still present when assessing differences in only patients with VF/VT. Being octogenarian was associated with lower odds of acute CAG in multivariate logistic regression at OR: 0.19, CI: 0.08–0.44, p b 0.001. The same differences were found for neurological prognostication, where fewer octogenarians had computed tomography (CT) of the head (24 vs. 42%, p b 0.001), neuro-prognostication with electroencephalography (EEG) (6 vs. 21%, p b 0.001) as well as somatosensory evoked potential (SSEP) (2 vs. 11%, p b 0.01, Table 2). Coronary artery bypass grafting (CABG) was not performed in any octogenarians during the study period. 3.3. Characteristics of unsuccessfully resuscitated patients In the population of unsuccessfully resuscitated patients there were significantly fewer men among the octogenarians than patients b 80 (50
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Fig. 1. Included patients: flow chart of included patients. Abbreviations: EMS: Emergency Medical Services, CPR: Cardiopulmonary Resuscitation, CPC: Cerebral Performance Category.
vs. 68%, p b 0.001, Table 1), and octogenarians had higher comorbidity burden (CCI ≥ 3) than patients b 80 years (28 vs. 25%, p = 0.001). Fewer octogenarians had OHCA in public (8 vs. 16%, p b 0.001) and witnessed arrest (50 vs. 57%, p = 0.001). More octogenarians had EMS witnessed arrest (5 vs. 3%, p = 0.04), cardiac etiology (76 vs. 69%, p b 0.001) and fewer had shockable rhythm (14 vs. 17%, p b 0.01). The distribution of arrests during day, evening and nighttime did differ between octogenarians and patients b80 years, p b 0.01. We found no differences in bystander CPR, time to EMS arrival and time to
direct current defibrillation between octogenarians and patients b 80 years. 3.4. Demographic and prehospital parameters in successfully versus not successfully resuscitated octogenarians Successfully resuscitated octogenarians were younger (85 vs. 87 years, p b 0.001) than those with unsuccessful resuscitation, they more often had OHCA in public places (26 vs. 8%, p b 0.001), more
Fig. 2. Resuscitation in different age groups: A: Percentage of patients with OHCA (2007–2011) with successful resuscitation, attempted but unsuccessful resuscitation, and found dead stratified by 10 years of age. N in each patient group is indicated by numbers in the bar. B: Probability of unsuccessful resuscitation with age in patients with resuscitation attempted between 2007 and 2011 (by linear regression modeling). The population density of successfully and unsuccessfully resuscitated are shown as density lines at 0 = unsuccessfully resuscitated and 1 = successfully resuscitated. Abbreviations: OHCA: out-of-hospital cardiac arrest.
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Table 1 Characteristics of octogenarians and patients b80 years with resuscitation attempted. Total population (n = 2509) Age (years) Male sex CCI 0 1 2 ≥3 OHCA in public Bystander witnessed Bystander CPR Time from OHCA to ROSC Time to EMS arrival Time to DC EMS witnessed OHCA First monitored rhythm VF/VT PEA Asystole Other/unknown Time of arrest Daytime Evening time Night time Cardiac etiology
Successfully resuscitated octogenarians (n = 166)
Successfully resuscitated b80 years (n = 830)
Unsuccessfully resuscitated octogenarians (n = 392)
Unsuccessfully resuscitated b80 years (n = 1121)
61 (53–71)* 620 (75%)
87 (83–90)* 197 (50%)
63 (55–73)a 767 (68%)a
67 (57–79) 1672 (67%)
85 (82–87) 88 (53%)
1123 (45%) 432 (17%) 350 (14%) 604 (24%) 579 (23%) 1630 (65%) 1018 (41%) 15 (9–22) 7 (5–10) 6 (3–10) 121 (5%)
25 (16%) 48 (29%) 41 (25%) 50 (30%) 43 (26%) 145 (87%) 79 (48%) 14 (10–19) 7 (5–10) 6 (3–11) 12 (7%)
335 (40%) 204 (25%)* 124 (75%) 160 (19%) 324 (39%)* 699 (84%)* 479 (58%) 15 (9–22) 7 (5–10) 5 (3–10) 57 (7%)
135 (35%) 80 (20%) 69 (18%) 108 (28%) 33 (8%)* 225 (57%)* 111 (28%)* – 7 (5–10) 7 (3.75–13) 20 (5%)
523 (47%) 172 (44%)a 142 (13%) 284 (25%) 180 (16%)a 561 (50%)a 349 (31%) – 7 (5–10) 7.5 (4–12) 32 (3%)a
770 (31%) 463 (19%) 1086 (43%) 185 (7%)
66 (40%) 41 (24%) 40 (24%) 19 (12%)
456 (55%) 157 (19%)* 167 (20%) 50 (6%)
53 (14%) 81 (21%)* 213 (54%) 43 (11%)
195 (17%) 184 (16%)a 666 (59%) 73 (7%)
1157 (46%) 927 (37%) 427 (17%) 1802 (72%)
97 (58%) 54 (33%) 15 (9%) 129 (78%)
388 (47%) 331 (40%)* 111 (13%) 669 (81%)
202 (52%) 130 (33%) 60 (15%) 299 (76%)
469 (42%) 411 (37%)a 242 (22%) 776 (69%)a
Patients found dead are not included. Data are presented as mean ± standard deviation, number (percentage) or median (interquartile range). Abbreviations: CCI: Charlson comorbidity index, CPR: cardiopulmonary resuscitation, DC: direct current defibrillation, EMS: emergency medical service, OHCA: out-of-hospital cardiac arrest, PEA: pulseless electrical activity, ROSC: return of spontaneous circulation, VF: ventricular fibrillation, VT: ventricular tachycardia, Asterisks indicate significant differences between the group and resuscitated octogenarians with a p value b 0.05. p-Values were corrected for multiple testing using Bonferroni–Holm correction. a Indicate significant differences between unsuccessfully resuscitated octogenarians vs. unsuccessfully resuscitated b 80 years.
often had witnessed OHCA (87 vs. 57%, p b 0.001), a higher rate of bystander CPR was noted (48 vs. 28%, p = 0.001), and more had shockable rhythm (40 vs. 14%, p b 0.001). The proportion of men, time to EMS arrival, time to defibrillation, cardiac cause of OHCA and EMS witnessed OHCA were not found to differ in successfully resuscitated compared with unsuccessfully resuscitated octogenarians.
3.5. Outcome of the resuscitation attempt During the study period the number of OHCA-patients who were successfully resuscitated increased both in the patients b 80 years and the octogenarians from approximately 40% to 46% and 28% to 32% (ptrend b 0.001), Fig. 3A. By multivariate logistic regression adjusting for prognostic factors, applied on all patients with attempted resuscitation, octogenarians had a higher probability of unsuccessful resuscitation (OR = 1.66,
CI: 1.30–2.11, p b 0.001) (Table 3), and the probability of unsuccessful resuscitation increased significantly with age (OR per year older = 1.02, CI = 1.01–1.03, p b 0.001, Fig. 2B). Other significant variables associated with unsuccessful resuscitation included shockable rhythm, witnessed OHCA, bystander CPR and OHCA in public. The percentage of patients successfully resuscitated, unsuccessfully resuscitated and found dead stratified into age decades are plotted in Fig. 2A and the figure shows that the risk of being found dead is higher from age 70 and onwards, while the percentage of patients with a successful resuscitation attempt decreases.
3.6. Mortality 30-day mortality was significantly lower in patients b 80 years compared with octogenarians (p b 0.001) (Fig. 4), however, 30-day
Table 2 In-hospital treatment of successfully resuscitated octogenarians and patients b 80 years.
Emergency department Active therapy terminated in ED Therapeutic hypothermia Revascularization Acute coronary angiography (b24 h) Coronary angiography Percutaneous coronary intervention Coronary artery bypass grafting Neurological prognostication Computed tomography of the head Electroencephalography Somatosensory evoked potentials
Successfully resuscitated octogenarians (n = 166)
Successfully resuscitated b80 years (n = 830)
p-Value
31 (19%) 43 (32%)
82 (10%) 391 (52%)
b0.01 b0.001
19 (14%) 22 (16%) 14 (10%) 0
276 (37%) 364 (49%) 201 (27%) 40 (5%)
b0.001 b0.001 b0.001 0.01
33 (24%) 8 (6%) 3 (2%)
308 (42%) 159 (21%) 81 (11%)
b0.001 b0.001 b0.01
Data are presented as number (percentage). Patients who died in ED were excluded from analyses of differences in performance of procedures. Abbreviations: ED: emergency department.
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Fig. 3. Resuscitation and 30-day survival pr. year during the study period: A: Percentages of attempted resuscitated patients b80 years and octogenarians, who were successfully resuscitated each year during the study period, p-value by Cochran–Mantel–Haenszel test b0.001. B: 30-day survival in patients b80 years and octogenarians who were successfully resuscitated, p = 0.03.
mortality was found to decrease significantly in both patients b80 years and octogenarians each year throughout the study period from approximately 72% to 75% and 94% to 93%, p = 0.03, Fig. 3B. Being an octogenarian was significantly associated with a higher 30-day mortality rate by univariate Cox regression analysis (HR = 2.02 CI: 1.67–2.46, p b 0.001, Table 4), which remained significant after adjusting for prognostic factors (HR = 1.61, CI: 1.22–2.13, p = 0.001) (Table 4).
3.7. Neurological outcome Fig. 5 illustrates CPC scores prior to OHCA and at hospital discharge in patients with successful resuscitation, stratified by age above and below 80 years. Prior to OHCA, octogenarians had a significantly different and lower frequency of favorable scores with 89% with CPC 1–2 compared to 96% in b 80 years (p b 0.001). At hospital discharge 70% of the surviving octogenarians had a favorable neurological outcome (CPC 1–2) compared to 86% of b80 years (p = 0.03). Surviving octogenarians had a lower chance of good neurological outcome estimated by multivariate logistic regression analysis with adjustment for demographic and prehospital factors compared with b80 years (CPC 1–2) (OR: 0.35, CI: 0.14–0.89, p = 0.02). When including patients not surviving to hospital discharge (CPC5), octogenarians still had a lower chance of favorable outcome at OR = 0.38, CI = 0.22–0.63, p b 0.001. In subanalysis of patients with CPC 3 (n = 43) prior to OHCA, 19% of octogenarians survived with CPC 3 vs. 11% in patients b 80 years. No patients survived with CPC 4, p = 0.64.
Table 3 Factors associated with successful resuscitation in patients with resuscitation attempted between 2007 and 2011. Univariate and multivariable factors associated with unsuccessful resuscitation for all patients with resuscitation attempted and complete data (n = 2207, 88% of total population). Univariate OR (95% CI) Octogenarians Charlson comorbidity index 0 1 2 ≥3 Male sex Shockable primary rhythm Witnessed OHCA Bystander CPR OHCA in public
4. Discussion In the current study we found that the percentage of patients with successful resuscitation and the 30-day mortality improved in both octogenarians and patients b80 years during the study period, however, the 30-day mortality rate was significantly higher in octogenarians compared with patients b80 years. Even though octogenarians had a higher chance of not being resuscitated, and a higher risk of death than those b80 years, the majority of surviving octogenarians were discharged with a favorable neurological outcome. In addition, octogenarians less often had OHCA in public and shockable rhythm, and the presence of these factors was associated with the outcome of the resuscitation attempt. The level of post resuscitation care in successfully resuscitated octogenarians was significantly lower, with fewer inhospital procedures such as CAG and PCI, fewer octogenarians receiving therapeutic hypothermia and neurological prognostication procedures (CT, EEG and SSEP). Furthermore, being octogenarian was associated with lower odds of having CAG performed within the first 24 h after ROSC, when adjusting for confounders. It is not clear to what extent these differences in post resuscitation care reflects an actual undertreatment, or the fact that octogenarians were found to have a higher comorbidity burden and thus at higher peri-procedure risk and thereby an estimated lower successful outcome. 4.1. Factors at resuscitation Fewer octogenarian OHCA-patients in the current cohort were male, likely because the sex distribution of the elderly population is skewed, as females tend to get older [23]. Fewer octogenarians suffered OHCA in public, which is similar to findings in other studies [24,25], and
Multivariate p-Value OR (95% CI)
p-Value
1.75 (1.43–2.15) b0.001
1.66 (1.30–2.11) b0.001
0.99 (0.79–1.24) 0.93 1.07 (0.84–1.37) 0.57 1.31 (1.07–1.61) 0.01 0.71 (0.60–0.85) b0.001 0.18 (0.15–0.22) b0.001
0.77 (0.59–1.02) 0.07 0.96 (0.72–1.29) 0.78 1.03 (0.80–1.31) 0.84 1.17 (0.95–1.44) 0.14 0.30 (0.24–0.37) b0.001
0.24 (0.19–0.30) b0.001 0.41 (0.35–0.49) b0.001 0.29 (0.24–0.35) b0.001
0.32 (0.25–0.41) b0.001 0.67 (0.55–0.82) b0.001 0.45 (0.36–0.57) b0.001
Abbreviations: CI: confidence intervals, CPR: cardiopulmonary resuscitation, OHCA: outof-hospital cardiac arrest, OR: odds ratio.
Fig. 4. Mortality in octogenarians vs. patients b80 years: 30-day Kaplan–Meier survival plot stratified in octogenarians and patients b80 years. Differences by the log-rank test.
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Table 4 Factors associated with mortality in patients with successful resuscitation. Univariate and multivariate factors associated with 30-day mortality for successfully resuscitated patients (ROSC or on-going CPR at hospital arrival) suffering from out-of-hospital cardiac arrest. Univariate
Octogenarians Charlson comorbidity index 0 1 2 ≥3 Male sex Shockable primary rhythm Witnessed cardiac arrest Bystander CPR Public arrest Time to ROSC (per min longer) Cardiac etiology Temperature management
Multivariate
HR (95% CI)
p-Value
HR (95% CI)
p-Value
2.02 (1.67–2.46)
b0.001
1.61 (1.22–2.13)
0.001
Ref 1.42 (1.14–1.78) 1.86 (1.47–2.37) 2.13 (1.71–2.66) 0.66 (0.55–0.78) 0.36 (0.30-0.42) 0.71 (0.57–0.88) 0.52 (0.44–0.61) 0.55 (0.46–0.66) 1.01 (1.01–1.02) 0.63 (0.52–0.76) 0.27 (0.22–0.33)
0.002 b0.001 b0.001 b0.001 b0.001 0.002 b0.001 b0.001 b0.001 b0.001 b0.001
Ref 1.26 (0.93–1.70) 1.41 (1.03–1.94) 1.18 (0.86–1.61) 0.98 (0.77–1.25) 0.43 (0.33–0.55) 1.06 (0.77–1.47) 0.76 (0.60–0.94) 0.73 (0.57–0.94) 1.02 (1.01–1.03) 1.25 (0.88–1.78) 0.39 (0.31–0.51)
0.13 0.03 0.30 0.87 b0.001 0.73 0.01 0.02 b0.001 0.22 b0.001
Abbreviations: CI: confidence intervals, CPR: cardiopulmonary resuscitation, HR: hazard ratio, ROSC: return of spontaneous circulation.
consistent with a higher proportion being retired. Witnessed OHCA, OHCA in public places, and bystander CPR were all significantly associated with a successful resuscitation attempt. To a large extent, the factors associated with successful resuscitation (witnessed OHCA, OHCA in public, and bystander CPR) are known to be associated with survival [26], and these were all less common in the octogenarians [24]. In our population OHCA at home was more common in unsuccessfully resuscitated octogenarians, and associated with unsuccessful resuscitation, but not mortality. This might indicate that living alone, or with a spouse untrained/too fragile to perform CPR is an important risk factor in the elderly.
4.2. Mortality and age Being an octogenarian was associated with a significantly higher risk of death in univariate as well as multivariate analyses. Even though mortality was higher, we found that 19% of resuscitated octogenarians were alive after 30 days. Similarly, others also found a lower survival rate in octogenarians as well as nonagenarians suffering from OHCA, but also with a significant proportion surviving [25,27]. In general, studies concerning age as a prognostic factor after OHCA do not recommend withholding CPR and aggressive treatment [2,7,10,28], and some conclude that long-term survival and survival to discharge depend more on the circumstances with regards to the OHCA such as initial rhythm, lactate level and no-flow time rather than age alone [28,29].
However, survival should not stand alone when assessing the impact of age on prognosis after OHCA, as neurological impairment has a major impact on quality of life. When compared to younger OHCA-patients, those older than 65 years have lower quality-of-life scores after OHCA [30], but in general the impact of age on quality of life is not well investigated [2]. Beesems et al. found that octogenarians have lower quality of life scores after OHCA, even though these seem to be related to old age rather than OHCA [31]. Aging is known to impact several factors, such as cognitive impairment, and to diminish frontal cortex function [32–34]. Cerebrovascular auto-regulation seems to deteriorate with age [35], and in patients suffering from ischemic stroke, age has been found to predict worse outcome when assessed by the modified Rankin scale (mRS) [36]. These findings suggest that the elderly brain may be more vulnerable to ischemia than the younger brain, and that the frequency of unfavorable neurological outcome after OHCA is therefore likely higher in the elderly. In our study, we found that even though fewer octogenarians were discharged with a favorable neurological outcome compared with the younger patients, the majority were discharged with a CPC score of 1 or 2, which enables the OHCAsurvivors to carry out daily activities independently and on their own. Octogenarian patients with CPC 3 prior to OHCA did not have worse post-arrest neurological outcome than patients b 80 years with prearrest CPC 3, and thus the combination of old age and CPC 3 does not seem to be a marker of unfavorable outcome after OHCA.
Fig. 5. Neurological outcome after OHCA: CPC score in octogenarians and patients b80 years prior to OHCA, in survivors, and in all patients at hospital discharge. The elderly have a lower frequency of CPC 1–2 (defined as favorable neurological outcome) prior to OHCA at p b 0.001, as well as in survivors, p b 0.001 and including CPC5: death, p = 0.03. Patients found dead are not included. Abbreviations: CPC: Cerebral Performance Category, OHCA: out of hospital cardiac arrest.
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4.3. Post resuscitation care — are we managing the elderly patients appropriately? The resuscitated octogenarians received fewer acute CAGs; and being octogenarian was associated with lower odds of acute CAG being performed, even when adjusting for confounders. Furthermore, CAGs in general, PCI, but also prognostic examinations such as CT and EEG were performed less frequently on octogenarians. In previous studies, elderly patients have been found to be triaged differently [37,38], and less often examined with CAG and PCI [39,40]. It is not known to what extent these differences in treatment are clinically justified, as the elderly often suffer from a higher degree of comorbidity, the degree of frailty is often higher, and more have renal dysfunction that may contraindicate CAG/PCI [2,4,41]. In the current population, data on why CAG/PCI was not performed was unfortunately not available, and it was thus not possible to determine whether the lower frequency of CAG/PCI was an effect of under-treatment or due to other factors such as a higher comorbidity burden. 4.4. Ethical dilemmas As the elderly group of citizens make up an increasingly larger proportion of the population, especially in Western countries, ethical dilemmas on when and how to decide to initiate or withhold a resuscitation attempt is very important. Some authors conclude that withholding aggressive treatment from elderly patients does not seem justified [7, 10], whereas others find it obsolete, as many elderly patients may not benefit from a resuscitation attempt as the comorbidity burden is higher, and as elderly patients more often are discharged with a poorer quality of life after OHCA compared to younger patients [2]. A recent meta-analysis found very few studies looking at comorbidity as a predictor of survival in relation to age, and they concluded that resuscitation should be attempted even in older patients as no studies had proven otherwise [2]. Wissenberg et al. were recently able to identify patients with almost no chance of 30-day survival using only two criteria (no ROSC upon hospital arrival and no pre-hospital shock from defibrillator), but point out that 3 patients who met these criteria did survive [6]. This illustrates the limitations of setting up guidelines, as individual cases may differ from group findings. Future generations of elderly may likely become more healthy, with an overall better functional status, which should be taken into account, as a recent cohort study of elderly born in 1915 and 1905 showed that the elderly born in 1915 did significantly better both physically and cognitively than the ones born in 1905, when assessed at the same biological age [42]. In the current study we found a statistically significant trend showing increasing survival in the elderly during our study period. This has also been found in other studies with elderly OHCApatients [43]. The elderly may have wishes regarding end of life, and these have been found to be influenced by severity of comorbidities in survivors of OHCA, as this influenced whether patients had signed do not resuscitate-orders [10]. Guidelines rightfully underline the importance of balancing benefit and risk in order not to do further harm in cases where resuscitation is futile, and that patient wishes should be taken into account [5], which is, however, difficult to assess in the acute setting. 4.5. Limitations The retrospective nature of this study is a limitation. Missing data were found in a few variables; especially the pre-hospital circumstances in the unsuccessfully resuscitated patients (such as shockable rhythm, OHCA location, bystander CPR and witnessed OHCA) were not complete with missing values varying between 0.2% and 11%. Reasons for withholding the resuscitation attempt in the pre-hospital setting were not available, and these may differ between age groups. The CPC score is assessed at hospital discharge, however this score may not be sensitive
enough to reflect final functional status months later. No data on civil status, and whether patients were living alone were available, which might have shed light on why octogenarians have a higher risk of unwitnessed arrest and thus a worse prognosis. 5. Conclusion OHCA in octogenarians was associated with a significantly higher mortality rate compared with the younger OHCA-patients, which was also present after adjustment for prognostic factors including comorbidity. Octogenarians received fewer CAG, PCI and prognostic examinations such as CT and EEG, but it is not clear to what extent this is a result of a higher degree of comorbidity or frailty. Survival increased in octogenarians as well as patients b80 years during the study period and the majority of octogenarian survivors were discharged with a favorable neurological outcome. Refraining from initiation of resuscitation and post resuscitation care in the elderly in general does not seem justified. Funding This work was supported by the European Regional Development Fund through the Interreg IV A OKS programme [NYPS ID: 167157] and the Danish Heart Foundation [grant no: 13-04-R94-A451622755]. The funding sources were not involved in any part of planning the study, or in interpretation of results. Conflict of interest Dr. Kjaergaard reports grants from The EU Interreg IV A programme funding for establishing ‘Centre for Resuscitation Science in the Oresund Region’ 2013–2014, used for funding of the work of Dr. Søholm and MSc. Winther-Jensen, grants from Danish Heart Foundation: cofunding for the ‘Centre for Resuscitation Science in the Oresund Region’ 2013–2014, used for funding of the work of MSc. Winther-Jensen, during the conduct of the study. Dr. Nielsen has lectured for BARD Medical. Dr. Hassager has lectured for AstraZeneca and ViCare Medical. All other authors report no conflicts of interest. Acknowledgments None. References [1] M. Wissenberg, F.K. Lippert, F. Folke, et al., Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest, JAMA 310 (13) (Oct. 2, 2013) 1377–1384 ([cited 2013 Dec 28]). [2] Van de Glind EMM, B.C. van Munster, F.T. van de Wetering, J.J.M. van Delden, R.J.P.M. Scholten, L. Hooft, Pre-arrest predictors of survival after resuscitation from out-ofhospital cardiac arrest in the elderly: a systematic review, BMC Geriatr. 13 (Jan 2013) 68. [3] US Burden of Disease Collaborators, The state of US health, 1990–2010: burden of diseases, injuries, and risk factors, JAMA 310 (6) (2013) 591–608 (Available from: http://www.ncbi.nlm.nih.gov/pubmed/23842577). [4] A. Clegg, J. Young, S. Iliffe, M.O. Rikkert, K. Rockwood, Frailty in elderly people, Lancet 381 (9868) (Mar. 2, 2013) 752–762. [5] F.K. Lippert, V. Raffay, M. Georgiou, P.A. Steen, L. Bossaert, European Resuscitation Council Guidelines for Resuscitation 2010 Section 10. The ethics of resuscitation and end-of-life decisions, Resuscitation 81 (2010) 1445–1451. [6] M. Wissenberg, F. Folke, C. Malta Hansen, et al., Survival after out-of-hospital cardiac arrest in relation to age and early identification of patients with minimal chance of long-term survival, Circulation 131 (2015) 1536–1545. [7] M. Pleskot, R. Hazukova, H. Stritecka, E. Cermakova, Five-year survival of patients after out-of-hospital cardiac arrest depending on age, Arch. Gerontol. Geriatr. 53 (2011) 88–92. [8] World Health Organization — ageing [Internet][cited 2014 Oct 27] Available from http://www.who.int/topics/ageing/en/. [9] L.B. Becker, T.P. Aufderheide, R.G. Geocadin, et al., Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association, Circulation 124 (19) (Nov. 8, 2011) 2158–2177.
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Resuscitation and post resuscitation care of the very old after out-of-hospital cardiac arrest is worthwhile☆ Matilde Winther-Jensen a,⁎, Jesper Kjaergaard a, Christian Hassager a, John Bro-Jeppesen a, Niklas Nielsen b, Freddy K. Lippert c, Lars Køber a, Michael Wanscher d, Helle Søholm a a
Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Denmark Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden Emergency Medical Services, The Capital Region of Denmark, Denmark d Department of Thoracic Anesthesiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Denmark b c
a r t i c l e
i n f o
Article history: Received 3 July 2015 Received in revised form 14 August 2015 Accepted 19 August 2015 Available online 24 August 2015 Keywords: Age Outcome Neurological outcome Mortality Comorbidity Ethics
a b s t r a c t Background: Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis. As comorbidity and frailty increase with age; ethical dilemmas may arise when OHCA occur in the very old. Objectives: We aimed to investigate mortality, neurological outcome and post resuscitation care in octogenarians (≥80) to assess whether resuscitation and post resuscitation care should be avoided. Methods: During 2007–2011 consecutive OHCA-patients were attended by the physician-based Emergency Medical Services-system in Copenhagen. Pre-hospital data based on Utstein-criteria, and data on post resuscitation care were collected. Primary outcome was successful resuscitation; secondary endpoints were 30-day mortality and neurological outcome (Cerebral Performance Category (CPC)). Results: 2509 OHCA-patients with attempted resuscitation were recorded, 22% (n = 558) were octogenarians/ nonagenarians. 166 (30% of all octogenarians with resuscitation attempted) octogenarians were successfully resuscitated compared to 830 (43% with resuscitation attempted) patients b 80 years. 30-day mortality in octogenarians was significantly higher after adjustment for prognostic factors (HR = 1.61 CI: 1.22–2.13, p b 0.001). Octogenarians received fewer coronary angiographies (CAG) (14 vs. 37%, p b 0.001), and had lower odds of receiving CAG by multivariate logistic regression (OR: 0.19, CI: 0.08–0.44, p b 0.001). A favorable neurological outcome (CPC 1/2) in survivors to discharge was found in 70% (n = 26) of octogenarians compared to 86% (n = 317, p = 0.03) in the younger patients. Conclusion: OHCA in octogenarians was associated with a significantly higher mortality rate after adjustment for prognostic factors. However, the majority of octogenarian survivors were discharged with a favorable neurological outcome. Withholding resuscitation and post resuscitation care in octogenarians does not seem justified. © 2015 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Suffering from an out-of-hospital cardiac arrest (OHCA) still carries a high mortality, despite lower overall mortality in recent years [1]. It is well-known that higher age is associated with increasing morbidity and mortality in various diseases and conditions [2,3], and as comorbidity and general frailty increases with age [2,4]; ethical dilemmas concerning resuscitation may arise, when elderly suffer from critical illnesses such as cardiac arrest [2,5].
☆ All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 9441, 2100 Copenhagen East, Denmark. E-mail address: [email protected] (M. Winther-Jensen).
http://dx.doi.org/10.1016/j.ijcard.2015.08.143 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Higher age has previously been associated with increased incidence and mortality after OHCA [6], however higher age may not necessarily be associated with a worse neurological outcome [2,7]. As the OHCAincidence increase with age, and the worldwide elderly population is growing, reliable tools to distinguish between elderly who will benefit from a resuscitation attempt is increasingly important [5,8,9]. Currently, no standard procedure for assessing patient wishes with regard to a resuscitation attempt is available in the acute setting [5]. However, patient wishes such as do-not-resuscitate orders are more common in the elderly [10]. Elderly heart failure patients have been found to change their resuscitation preferences with decline in clinical status [11], but both the elderly patients as well as the physician have higher expectations of the chances of successful resuscitation in case of cardiac arrest than reported [12]. In addition, elderly successfully resuscitated OHCA-patients residing in nursing homes have been found to have similar 30-day survival probabilities as younger patients living at home
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2. Methods
Multivariate Cox regression analysis adjusting for CCI, gender, primary rhythm, witnessed arrest, bystander CPR, public location of OHCA, time to ROSC and cardiac etiology was used to estimate hazard ratio (HR) with 95% CI for 30-day mortality in octogenarians compared to patients b80 years. Mortality was assessed by Kaplan–Meier curves and differences were tested with the log-rank test. In order to illustrate temporal changes in successful resuscitation and 30-day mortality in patients b80 years and octogenarians, percentages of successfully resuscitated patients and 30-day survival were plotted for each year, and differences during the study period were tested using the Cochran–Mantel–Haenszel Chi-square trend test. All statistical analyses were carried out in SAS Statistics version 9.3 (Cary, NC, USA) or R. 3.0.1 [20] with a level of significance defined as p b 0.05. The R package ‘survival’ was used for Cox regression and the log rank test [21,22].
2.1. Patients and study area
3. Results
after adjustment for prognostic factors [13]. Age used as a stand-alone marker therefore does not seem to be a good criterion for selecting treatment options [2,3]. In this study we aimed to investigate mortality, neurological outcome and post resuscitation care in octogenarians (all patients 80 years of age or older, including nonagenarians) suffering from OHCA, in order to assess whether resuscitation and post resuscitation care of the very old patients is meaningful or should be avoided.
Patients with OHCA were consecutively included in the study from 2007 through 2011. OHCA of all causes with attempted resuscitation (initiation of cardiopulmonary resuscitation (CPR)) and/or more advanced resuscitative efforts (intubation, medication) in the greater Copenhagen area with dispatch by the EMS (Emergency Medical Service) were included. Patients b18 years were excluded from the study. In addition, patients who were found with obvious signs of death (rigor/livor mortis, decapitation, maceration) with no attempted CPR were identified, but these were only used to assess the distribution of patients found dead among age groups. The Copenhagen area covers 675 km2 (260 mi2), and is inhabited by approximately 1.2 million people. The EMS in Copenhagen consists of an emergency ambulance with Basic Life Support (BLS) equipment, defibrillator, and a response unit in a separate vehicle staffed with a paramedic and an attending physician (anesthesiologist). The EMS are dispatched to all patients with presumed OHCA with the treatment protocol according to the advanced life support guidelines by the European Resuscitation Council [14,15]. An Utstein registration sheet is used by the attending physician as documentation, and the pre-hospital data is entered into an OHCA-database immediately after each dispatch [16,17]. The Utstein sheet is a template that ensures uniform international reporting on factors related to OHCA, such as whether OHCA is witnessed or not, where OHCA takes place, primary rhythm and etiology of the arrest [17]. Patients who were successfully resuscitated (return of spontaneous circulation (ROSC) at hospital admission) or who were brought to the hospital with on-going CPR were admitted for post resuscitation care at one of eight hospitals in the greater Copenhagen area. The Danish personal identification number is provided to all residents and by linking the OHCA-cohort to The National Patient Registry, data on comorbidity (diagnoses from primary care physician are not included), age, coexisting conditions and surgical procedures prior to OHCA were obtained [18]. The Charlson Comorbidity Index (CCI) was calculated based on these data. The CCI is a validated weighted index used to predict short-term mortality taking into account the severity of 22 conditions [19]. The regional ethics committee waived informed consent to the study with the reference number: H-2-2012-56, and the study was approved by the Danish Data Protection Agency. 2.2. Outcome The primary end point of the study was successful resuscitation, and secondary endpoints were all-cause 30-day mortality and neurological outcome at discharge measured by Cerebral Performance Category scale (CPC) [17]. The CPC score ranges from 1–5, where 1–2 was defined as favorable, 3–4 was defined as unfavorable, and 5 as dead [17]. CPC was assessed by reviewing patient records, blinded to previous assessment. Inter-observer reliability for CPC at discharge was kappa weighted = 1.0, showing complete agreement. Patients with CPC 3 prior to OHCA were analyzed separately to assess differences in changes from CPC 3. Patients with CPC 4 were not analyzed, as there were only 5 patients in this group. Mortality data were acquired from the Civil Registration system, which holds data on vital status by using the personal identification number. Outcome was analyzed only for patients in whom resuscitation was attempted, excluding those found dead.
2.3. Statistics Normally distributed continuous variables are presented as mean ± standard deviation while non-normally distributed variables are presented as median with 25– 75% quartile ranges. We used Student's unpaired t-test or Wilcoxon rank sum test to assess differences, as appropriate. For categorical variables data are presented as number (n) and percent and we used chi-square test to assess differences. To test the association between successful resuscitation and age, as well as age and favorable neurological outcome (CPC 1 or 2) multivariate logistic regression was used with adjustment for CCI, shockable rhythm, witnessed OHCA, bystander CPR, OHCA in public, sex, time to ROSC (omitted for outcome of resuscitation attempt), with estimation of odds ratios (OR) for successful resuscitation/ favorable neurological outcome and 95% confidence intervals (CI). Furthermore, we tested the association between being octogenarian and odds of having coronary angiography (CAG) performed within 24 h of ROSC by multivariate logistic regression, adjusting for sex, primary rhythm, public arrest, witnessed arrest, CCI level, STEMI presence and bystander CPR. This analysis was performed only in patients that did not die in the emergency department.
3.1. Overall patient characteristics In total the EMS attended 3679 OHCA-patients during the five yearstudy period, divided into 2 groups: Patients found with obvious signs of death (hereafter: patients found dead) (n = 1170, 32% of all patients), and patients with resuscitation attempted (n = 2509, 68% of all patients, hereafter: patients with resuscitation attempted) (Fig. 1). The latter were further stratified into patients successfully resuscitated in the pre-hospital setting/on-going CPR at hospital arrival, 40% of all patients with attempted resuscitation (n = 996, hereafter: successfully resuscitated patients), and patients with unsuccessful resuscitation (n = 1513, 60% of patients with attempted resuscitation, hereafter: unsuccessfully resuscitated patients). Of the successfully resuscitated patients, 15% (n = 144) were octogenarians and 2% (n = 22) of these were nonagenarians, while 20% (n = 296) of the unsuccessfully-resuscitated patients were octogenarians, and 6% (n = 96) were nonagenarians. In patients found dead, 28% (n = 325) were octogenarians, 11% (n = 130) were nonagenarians and 0.25% (n = 3) were centenarians (Figs. 1 and 2A). For further analysis, all patients ≥80 are referred to as octogenarians. 3.2. Successfully resuscitated octogenarians and resuscitated patients b 80 years In successfully resuscitated patients b 80 years, 75% were men vs. 53% (p b 0.001) in successfully resuscitated octogenarians. Compared to the successfully resuscitated patients b 80 years, successfully resuscitated octogenarians had a higher comorbidity burden; with more octogenarians having CCI ≥3 than patients b80 years (30 vs. 19%, p b 0.001). Fewer had OHCA in public (26 vs. 39%, p = 0.002) and fewer had a witnessed arrest (84 vs. 87%, p = 0.04) (Table 1). A higher proportion of successfully resuscitated octogenarians had active therapy withdrawn in the emergency department (19 vs. 10%, p b 0.01, Table 2), and with regard to post resuscitation care, fewer successfully resuscitated octogenarians received therapeutic hypothermia (32 vs. 52%) had an acute coronary angiography (CAG b 24 h, 14 vs. 37%), non-acute CAG (16 vs. 49%), and percutaneous coronary intervention (PCI, 10 vs. 27%), all at p b 0.001. These differences were still present when assessing differences in only patients with VF/VT. Being octogenarian was associated with lower odds of acute CAG in multivariate logistic regression at OR: 0.19, CI: 0.08–0.44, p b 0.001. The same differences were found for neurological prognostication, where fewer octogenarians had computed tomography (CT) of the head (24 vs. 42%, p b 0.001), neuro-prognostication with electroencephalography (EEG) (6 vs. 21%, p b 0.001) as well as somatosensory evoked potential (SSEP) (2 vs. 11%, p b 0.01, Table 2). Coronary artery bypass grafting (CABG) was not performed in any octogenarians during the study period. 3.3. Characteristics of unsuccessfully resuscitated patients In the population of unsuccessfully resuscitated patients there were significantly fewer men among the octogenarians than patients b 80 (50
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Fig. 1. Included patients: flow chart of included patients. Abbreviations: EMS: Emergency Medical Services, CPR: Cardiopulmonary Resuscitation, CPC: Cerebral Performance Category.
vs. 68%, p b 0.001, Table 1), and octogenarians had higher comorbidity burden (CCI ≥ 3) than patients b 80 years (28 vs. 25%, p = 0.001). Fewer octogenarians had OHCA in public (8 vs. 16%, p b 0.001) and witnessed arrest (50 vs. 57%, p = 0.001). More octogenarians had EMS witnessed arrest (5 vs. 3%, p = 0.04), cardiac etiology (76 vs. 69%, p b 0.001) and fewer had shockable rhythm (14 vs. 17%, p b 0.01). The distribution of arrests during day, evening and nighttime did differ between octogenarians and patients b80 years, p b 0.01. We found no differences in bystander CPR, time to EMS arrival and time to
direct current defibrillation between octogenarians and patients b 80 years. 3.4. Demographic and prehospital parameters in successfully versus not successfully resuscitated octogenarians Successfully resuscitated octogenarians were younger (85 vs. 87 years, p b 0.001) than those with unsuccessful resuscitation, they more often had OHCA in public places (26 vs. 8%, p b 0.001), more
Fig. 2. Resuscitation in different age groups: A: Percentage of patients with OHCA (2007–2011) with successful resuscitation, attempted but unsuccessful resuscitation, and found dead stratified by 10 years of age. N in each patient group is indicated by numbers in the bar. B: Probability of unsuccessful resuscitation with age in patients with resuscitation attempted between 2007 and 2011 (by linear regression modeling). The population density of successfully and unsuccessfully resuscitated are shown as density lines at 0 = unsuccessfully resuscitated and 1 = successfully resuscitated. Abbreviations: OHCA: out-of-hospital cardiac arrest.
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Table 1 Characteristics of octogenarians and patients b80 years with resuscitation attempted. Total population (n = 2509) Age (years) Male sex CCI 0 1 2 ≥3 OHCA in public Bystander witnessed Bystander CPR Time from OHCA to ROSC Time to EMS arrival Time to DC EMS witnessed OHCA First monitored rhythm VF/VT PEA Asystole Other/unknown Time of arrest Daytime Evening time Night time Cardiac etiology
Successfully resuscitated octogenarians (n = 166)
Successfully resuscitated b80 years (n = 830)
Unsuccessfully resuscitated octogenarians (n = 392)
Unsuccessfully resuscitated b80 years (n = 1121)
61 (53–71)* 620 (75%)
87 (83–90)* 197 (50%)
63 (55–73)a 767 (68%)a
67 (57–79) 1672 (67%)
85 (82–87) 88 (53%)
1123 (45%) 432 (17%) 350 (14%) 604 (24%) 579 (23%) 1630 (65%) 1018 (41%) 15 (9–22) 7 (5–10) 6 (3–10) 121 (5%)
25 (16%) 48 (29%) 41 (25%) 50 (30%) 43 (26%) 145 (87%) 79 (48%) 14 (10–19) 7 (5–10) 6 (3–11) 12 (7%)
335 (40%) 204 (25%)* 124 (75%) 160 (19%) 324 (39%)* 699 (84%)* 479 (58%) 15 (9–22) 7 (5–10) 5 (3–10) 57 (7%)
135 (35%) 80 (20%) 69 (18%) 108 (28%) 33 (8%)* 225 (57%)* 111 (28%)* – 7 (5–10) 7 (3.75–13) 20 (5%)
523 (47%) 172 (44%)a 142 (13%) 284 (25%) 180 (16%)a 561 (50%)a 349 (31%) – 7 (5–10) 7.5 (4–12) 32 (3%)a
770 (31%) 463 (19%) 1086 (43%) 185 (7%)
66 (40%) 41 (24%) 40 (24%) 19 (12%)
456 (55%) 157 (19%)* 167 (20%) 50 (6%)
53 (14%) 81 (21%)* 213 (54%) 43 (11%)
195 (17%) 184 (16%)a 666 (59%) 73 (7%)
1157 (46%) 927 (37%) 427 (17%) 1802 (72%)
97 (58%) 54 (33%) 15 (9%) 129 (78%)
388 (47%) 331 (40%)* 111 (13%) 669 (81%)
202 (52%) 130 (33%) 60 (15%) 299 (76%)
469 (42%) 411 (37%)a 242 (22%) 776 (69%)a
Patients found dead are not included. Data are presented as mean ± standard deviation, number (percentage) or median (interquartile range). Abbreviations: CCI: Charlson comorbidity index, CPR: cardiopulmonary resuscitation, DC: direct current defibrillation, EMS: emergency medical service, OHCA: out-of-hospital cardiac arrest, PEA: pulseless electrical activity, ROSC: return of spontaneous circulation, VF: ventricular fibrillation, VT: ventricular tachycardia, Asterisks indicate significant differences between the group and resuscitated octogenarians with a p value b 0.05. p-Values were corrected for multiple testing using Bonferroni–Holm correction. a Indicate significant differences between unsuccessfully resuscitated octogenarians vs. unsuccessfully resuscitated b 80 years.
often had witnessed OHCA (87 vs. 57%, p b 0.001), a higher rate of bystander CPR was noted (48 vs. 28%, p = 0.001), and more had shockable rhythm (40 vs. 14%, p b 0.001). The proportion of men, time to EMS arrival, time to defibrillation, cardiac cause of OHCA and EMS witnessed OHCA were not found to differ in successfully resuscitated compared with unsuccessfully resuscitated octogenarians.
3.5. Outcome of the resuscitation attempt During the study period the number of OHCA-patients who were successfully resuscitated increased both in the patients b 80 years and the octogenarians from approximately 40% to 46% and 28% to 32% (ptrend b 0.001), Fig. 3A. By multivariate logistic regression adjusting for prognostic factors, applied on all patients with attempted resuscitation, octogenarians had a higher probability of unsuccessful resuscitation (OR = 1.66,
CI: 1.30–2.11, p b 0.001) (Table 3), and the probability of unsuccessful resuscitation increased significantly with age (OR per year older = 1.02, CI = 1.01–1.03, p b 0.001, Fig. 2B). Other significant variables associated with unsuccessful resuscitation included shockable rhythm, witnessed OHCA, bystander CPR and OHCA in public. The percentage of patients successfully resuscitated, unsuccessfully resuscitated and found dead stratified into age decades are plotted in Fig. 2A and the figure shows that the risk of being found dead is higher from age 70 and onwards, while the percentage of patients with a successful resuscitation attempt decreases.
3.6. Mortality 30-day mortality was significantly lower in patients b 80 years compared with octogenarians (p b 0.001) (Fig. 4), however, 30-day
Table 2 In-hospital treatment of successfully resuscitated octogenarians and patients b 80 years.
Emergency department Active therapy terminated in ED Therapeutic hypothermia Revascularization Acute coronary angiography (b24 h) Coronary angiography Percutaneous coronary intervention Coronary artery bypass grafting Neurological prognostication Computed tomography of the head Electroencephalography Somatosensory evoked potentials
Successfully resuscitated octogenarians (n = 166)
Successfully resuscitated b80 years (n = 830)
p-Value
31 (19%) 43 (32%)
82 (10%) 391 (52%)
b0.01 b0.001
19 (14%) 22 (16%) 14 (10%) 0
276 (37%) 364 (49%) 201 (27%) 40 (5%)
b0.001 b0.001 b0.001 0.01
33 (24%) 8 (6%) 3 (2%)
308 (42%) 159 (21%) 81 (11%)
b0.001 b0.001 b0.01
Data are presented as number (percentage). Patients who died in ED were excluded from analyses of differences in performance of procedures. Abbreviations: ED: emergency department.
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Fig. 3. Resuscitation and 30-day survival pr. year during the study period: A: Percentages of attempted resuscitated patients b80 years and octogenarians, who were successfully resuscitated each year during the study period, p-value by Cochran–Mantel–Haenszel test b0.001. B: 30-day survival in patients b80 years and octogenarians who were successfully resuscitated, p = 0.03.
mortality was found to decrease significantly in both patients b80 years and octogenarians each year throughout the study period from approximately 72% to 75% and 94% to 93%, p = 0.03, Fig. 3B. Being an octogenarian was significantly associated with a higher 30-day mortality rate by univariate Cox regression analysis (HR = 2.02 CI: 1.67–2.46, p b 0.001, Table 4), which remained significant after adjusting for prognostic factors (HR = 1.61, CI: 1.22–2.13, p = 0.001) (Table 4).
3.7. Neurological outcome Fig. 5 illustrates CPC scores prior to OHCA and at hospital discharge in patients with successful resuscitation, stratified by age above and below 80 years. Prior to OHCA, octogenarians had a significantly different and lower frequency of favorable scores with 89% with CPC 1–2 compared to 96% in b 80 years (p b 0.001). At hospital discharge 70% of the surviving octogenarians had a favorable neurological outcome (CPC 1–2) compared to 86% of b80 years (p = 0.03). Surviving octogenarians had a lower chance of good neurological outcome estimated by multivariate logistic regression analysis with adjustment for demographic and prehospital factors compared with b80 years (CPC 1–2) (OR: 0.35, CI: 0.14–0.89, p = 0.02). When including patients not surviving to hospital discharge (CPC5), octogenarians still had a lower chance of favorable outcome at OR = 0.38, CI = 0.22–0.63, p b 0.001. In subanalysis of patients with CPC 3 (n = 43) prior to OHCA, 19% of octogenarians survived with CPC 3 vs. 11% in patients b 80 years. No patients survived with CPC 4, p = 0.64.
Table 3 Factors associated with successful resuscitation in patients with resuscitation attempted between 2007 and 2011. Univariate and multivariable factors associated with unsuccessful resuscitation for all patients with resuscitation attempted and complete data (n = 2207, 88% of total population). Univariate OR (95% CI) Octogenarians Charlson comorbidity index 0 1 2 ≥3 Male sex Shockable primary rhythm Witnessed OHCA Bystander CPR OHCA in public
4. Discussion In the current study we found that the percentage of patients with successful resuscitation and the 30-day mortality improved in both octogenarians and patients b80 years during the study period, however, the 30-day mortality rate was significantly higher in octogenarians compared with patients b80 years. Even though octogenarians had a higher chance of not being resuscitated, and a higher risk of death than those b80 years, the majority of surviving octogenarians were discharged with a favorable neurological outcome. In addition, octogenarians less often had OHCA in public and shockable rhythm, and the presence of these factors was associated with the outcome of the resuscitation attempt. The level of post resuscitation care in successfully resuscitated octogenarians was significantly lower, with fewer inhospital procedures such as CAG and PCI, fewer octogenarians receiving therapeutic hypothermia and neurological prognostication procedures (CT, EEG and SSEP). Furthermore, being octogenarian was associated with lower odds of having CAG performed within the first 24 h after ROSC, when adjusting for confounders. It is not clear to what extent these differences in post resuscitation care reflects an actual undertreatment, or the fact that octogenarians were found to have a higher comorbidity burden and thus at higher peri-procedure risk and thereby an estimated lower successful outcome. 4.1. Factors at resuscitation Fewer octogenarian OHCA-patients in the current cohort were male, likely because the sex distribution of the elderly population is skewed, as females tend to get older [23]. Fewer octogenarians suffered OHCA in public, which is similar to findings in other studies [24,25], and
Multivariate p-Value OR (95% CI)
p-Value
1.75 (1.43–2.15) b0.001
1.66 (1.30–2.11) b0.001
0.99 (0.79–1.24) 0.93 1.07 (0.84–1.37) 0.57 1.31 (1.07–1.61) 0.01 0.71 (0.60–0.85) b0.001 0.18 (0.15–0.22) b0.001
0.77 (0.59–1.02) 0.07 0.96 (0.72–1.29) 0.78 1.03 (0.80–1.31) 0.84 1.17 (0.95–1.44) 0.14 0.30 (0.24–0.37) b0.001
0.24 (0.19–0.30) b0.001 0.41 (0.35–0.49) b0.001 0.29 (0.24–0.35) b0.001
0.32 (0.25–0.41) b0.001 0.67 (0.55–0.82) b0.001 0.45 (0.36–0.57) b0.001
Abbreviations: CI: confidence intervals, CPR: cardiopulmonary resuscitation, OHCA: outof-hospital cardiac arrest, OR: odds ratio.
Fig. 4. Mortality in octogenarians vs. patients b80 years: 30-day Kaplan–Meier survival plot stratified in octogenarians and patients b80 years. Differences by the log-rank test.
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Table 4 Factors associated with mortality in patients with successful resuscitation. Univariate and multivariate factors associated with 30-day mortality for successfully resuscitated patients (ROSC or on-going CPR at hospital arrival) suffering from out-of-hospital cardiac arrest. Univariate
Octogenarians Charlson comorbidity index 0 1 2 ≥3 Male sex Shockable primary rhythm Witnessed cardiac arrest Bystander CPR Public arrest Time to ROSC (per min longer) Cardiac etiology Temperature management
Multivariate
HR (95% CI)
p-Value
HR (95% CI)
p-Value
2.02 (1.67–2.46)
b0.001
1.61 (1.22–2.13)
0.001
Ref 1.42 (1.14–1.78) 1.86 (1.47–2.37) 2.13 (1.71–2.66) 0.66 (0.55–0.78) 0.36 (0.30-0.42) 0.71 (0.57–0.88) 0.52 (0.44–0.61) 0.55 (0.46–0.66) 1.01 (1.01–1.02) 0.63 (0.52–0.76) 0.27 (0.22–0.33)
0.002 b0.001 b0.001 b0.001 b0.001 0.002 b0.001 b0.001 b0.001 b0.001 b0.001
Ref 1.26 (0.93–1.70) 1.41 (1.03–1.94) 1.18 (0.86–1.61) 0.98 (0.77–1.25) 0.43 (0.33–0.55) 1.06 (0.77–1.47) 0.76 (0.60–0.94) 0.73 (0.57–0.94) 1.02 (1.01–1.03) 1.25 (0.88–1.78) 0.39 (0.31–0.51)
0.13 0.03 0.30 0.87 b0.001 0.73 0.01 0.02 b0.001 0.22 b0.001
Abbreviations: CI: confidence intervals, CPR: cardiopulmonary resuscitation, HR: hazard ratio, ROSC: return of spontaneous circulation.
consistent with a higher proportion being retired. Witnessed OHCA, OHCA in public places, and bystander CPR were all significantly associated with a successful resuscitation attempt. To a large extent, the factors associated with successful resuscitation (witnessed OHCA, OHCA in public, and bystander CPR) are known to be associated with survival [26], and these were all less common in the octogenarians [24]. In our population OHCA at home was more common in unsuccessfully resuscitated octogenarians, and associated with unsuccessful resuscitation, but not mortality. This might indicate that living alone, or with a spouse untrained/too fragile to perform CPR is an important risk factor in the elderly.
4.2. Mortality and age Being an octogenarian was associated with a significantly higher risk of death in univariate as well as multivariate analyses. Even though mortality was higher, we found that 19% of resuscitated octogenarians were alive after 30 days. Similarly, others also found a lower survival rate in octogenarians as well as nonagenarians suffering from OHCA, but also with a significant proportion surviving [25,27]. In general, studies concerning age as a prognostic factor after OHCA do not recommend withholding CPR and aggressive treatment [2,7,10,28], and some conclude that long-term survival and survival to discharge depend more on the circumstances with regards to the OHCA such as initial rhythm, lactate level and no-flow time rather than age alone [28,29].
However, survival should not stand alone when assessing the impact of age on prognosis after OHCA, as neurological impairment has a major impact on quality of life. When compared to younger OHCA-patients, those older than 65 years have lower quality-of-life scores after OHCA [30], but in general the impact of age on quality of life is not well investigated [2]. Beesems et al. found that octogenarians have lower quality of life scores after OHCA, even though these seem to be related to old age rather than OHCA [31]. Aging is known to impact several factors, such as cognitive impairment, and to diminish frontal cortex function [32–34]. Cerebrovascular auto-regulation seems to deteriorate with age [35], and in patients suffering from ischemic stroke, age has been found to predict worse outcome when assessed by the modified Rankin scale (mRS) [36]. These findings suggest that the elderly brain may be more vulnerable to ischemia than the younger brain, and that the frequency of unfavorable neurological outcome after OHCA is therefore likely higher in the elderly. In our study, we found that even though fewer octogenarians were discharged with a favorable neurological outcome compared with the younger patients, the majority were discharged with a CPC score of 1 or 2, which enables the OHCAsurvivors to carry out daily activities independently and on their own. Octogenarian patients with CPC 3 prior to OHCA did not have worse post-arrest neurological outcome than patients b 80 years with prearrest CPC 3, and thus the combination of old age and CPC 3 does not seem to be a marker of unfavorable outcome after OHCA.
Fig. 5. Neurological outcome after OHCA: CPC score in octogenarians and patients b80 years prior to OHCA, in survivors, and in all patients at hospital discharge. The elderly have a lower frequency of CPC 1–2 (defined as favorable neurological outcome) prior to OHCA at p b 0.001, as well as in survivors, p b 0.001 and including CPC5: death, p = 0.03. Patients found dead are not included. Abbreviations: CPC: Cerebral Performance Category, OHCA: out of hospital cardiac arrest.
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4.3. Post resuscitation care — are we managing the elderly patients appropriately? The resuscitated octogenarians received fewer acute CAGs; and being octogenarian was associated with lower odds of acute CAG being performed, even when adjusting for confounders. Furthermore, CAGs in general, PCI, but also prognostic examinations such as CT and EEG were performed less frequently on octogenarians. In previous studies, elderly patients have been found to be triaged differently [37,38], and less often examined with CAG and PCI [39,40]. It is not known to what extent these differences in treatment are clinically justified, as the elderly often suffer from a higher degree of comorbidity, the degree of frailty is often higher, and more have renal dysfunction that may contraindicate CAG/PCI [2,4,41]. In the current population, data on why CAG/PCI was not performed was unfortunately not available, and it was thus not possible to determine whether the lower frequency of CAG/PCI was an effect of under-treatment or due to other factors such as a higher comorbidity burden. 4.4. Ethical dilemmas As the elderly group of citizens make up an increasingly larger proportion of the population, especially in Western countries, ethical dilemmas on when and how to decide to initiate or withhold a resuscitation attempt is very important. Some authors conclude that withholding aggressive treatment from elderly patients does not seem justified [7, 10], whereas others find it obsolete, as many elderly patients may not benefit from a resuscitation attempt as the comorbidity burden is higher, and as elderly patients more often are discharged with a poorer quality of life after OHCA compared to younger patients [2]. A recent meta-analysis found very few studies looking at comorbidity as a predictor of survival in relation to age, and they concluded that resuscitation should be attempted even in older patients as no studies had proven otherwise [2]. Wissenberg et al. were recently able to identify patients with almost no chance of 30-day survival using only two criteria (no ROSC upon hospital arrival and no pre-hospital shock from defibrillator), but point out that 3 patients who met these criteria did survive [6]. This illustrates the limitations of setting up guidelines, as individual cases may differ from group findings. Future generations of elderly may likely become more healthy, with an overall better functional status, which should be taken into account, as a recent cohort study of elderly born in 1915 and 1905 showed that the elderly born in 1915 did significantly better both physically and cognitively than the ones born in 1905, when assessed at the same biological age [42]. In the current study we found a statistically significant trend showing increasing survival in the elderly during our study period. This has also been found in other studies with elderly OHCApatients [43]. The elderly may have wishes regarding end of life, and these have been found to be influenced by severity of comorbidities in survivors of OHCA, as this influenced whether patients had signed do not resuscitate-orders [10]. Guidelines rightfully underline the importance of balancing benefit and risk in order not to do further harm in cases where resuscitation is futile, and that patient wishes should be taken into account [5], which is, however, difficult to assess in the acute setting. 4.5. Limitations The retrospective nature of this study is a limitation. Missing data were found in a few variables; especially the pre-hospital circumstances in the unsuccessfully resuscitated patients (such as shockable rhythm, OHCA location, bystander CPR and witnessed OHCA) were not complete with missing values varying between 0.2% and 11%. Reasons for withholding the resuscitation attempt in the pre-hospital setting were not available, and these may differ between age groups. The CPC score is assessed at hospital discharge, however this score may not be sensitive
enough to reflect final functional status months later. No data on civil status, and whether patients were living alone were available, which might have shed light on why octogenarians have a higher risk of unwitnessed arrest and thus a worse prognosis. 5. Conclusion OHCA in octogenarians was associated with a significantly higher mortality rate compared with the younger OHCA-patients, which was also present after adjustment for prognostic factors including comorbidity. Octogenarians received fewer CAG, PCI and prognostic examinations such as CT and EEG, but it is not clear to what extent this is a result of a higher degree of comorbidity or frailty. Survival increased in octogenarians as well as patients b80 years during the study period and the majority of octogenarian survivors were discharged with a favorable neurological outcome. Refraining from initiation of resuscitation and post resuscitation care in the elderly in general does not seem justified. Funding This work was supported by the European Regional Development Fund through the Interreg IV A OKS programme [NYPS ID: 167157] and the Danish Heart Foundation [grant no: 13-04-R94-A451622755]. The funding sources were not involved in any part of planning the study, or in interpretation of results. Conflict of interest Dr. Kjaergaard reports grants from The EU Interreg IV A programme funding for establishing ‘Centre for Resuscitation Science in the Oresund Region’ 2013–2014, used for funding of the work of Dr. Søholm and MSc. Winther-Jensen, grants from Danish Heart Foundation: cofunding for the ‘Centre for Resuscitation Science in the Oresund Region’ 2013–2014, used for funding of the work of MSc. Winther-Jensen, during the conduct of the study. Dr. Nielsen has lectured for BARD Medical. Dr. Hassager has lectured for AstraZeneca and ViCare Medical. All other authors report no conflicts of interest. Acknowledgments None. References [1] M. Wissenberg, F.K. Lippert, F. Folke, et al., Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest, JAMA 310 (13) (Oct. 2, 2013) 1377–1384 ([cited 2013 Dec 28]). [2] Van de Glind EMM, B.C. van Munster, F.T. van de Wetering, J.J.M. van Delden, R.J.P.M. Scholten, L. Hooft, Pre-arrest predictors of survival after resuscitation from out-ofhospital cardiac arrest in the elderly: a systematic review, BMC Geriatr. 13 (Jan 2013) 68. [3] US Burden of Disease Collaborators, The state of US health, 1990–2010: burden of diseases, injuries, and risk factors, JAMA 310 (6) (2013) 591–608 (Available from: http://www.ncbi.nlm.nih.gov/pubmed/23842577). [4] A. Clegg, J. Young, S. Iliffe, M.O. Rikkert, K. Rockwood, Frailty in elderly people, Lancet 381 (9868) (Mar. 2, 2013) 752–762. [5] F.K. Lippert, V. Raffay, M. Georgiou, P.A. Steen, L. Bossaert, European Resuscitation Council Guidelines for Resuscitation 2010 Section 10. The ethics of resuscitation and end-of-life decisions, Resuscitation 81 (2010) 1445–1451. [6] M. Wissenberg, F. Folke, C. Malta Hansen, et al., Survival after out-of-hospital cardiac arrest in relation to age and early identification of patients with minimal chance of long-term survival, Circulation 131 (2015) 1536–1545. [7] M. Pleskot, R. Hazukova, H. Stritecka, E. Cermakova, Five-year survival of patients after out-of-hospital cardiac arrest depending on age, Arch. Gerontol. Geriatr. 53 (2011) 88–92. [8] World Health Organization — ageing [Internet][cited 2014 Oct 27] Available from http://www.who.int/topics/ageing/en/. [9] L.B. Becker, T.P. Aufderheide, R.G. Geocadin, et al., Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association, Circulation 124 (19) (Nov. 8, 2011) 2158–2177.
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