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Long-term survival and health-related quality of life after in-hospital cardiac arrest

Open AccessPublished:July 13, 2021DOI:https://doi.org/10.1016/j.resuscitation.2021.07.006

      Abstract

      Introduction

      In-hospital cardiac arrest (IHCA) is an adverse event associated with high mortality. Because of the impact of IHCA more data is needed on incidence, outcomes and associated factors that are present prior to cardiac arrest. The aim was to assess one-year survival, patient-centred outcomes after IHCA and their associated pre-arrest factors.

      Methods

      A multicentre prospective cohort study in 25 hospitals between January 1st 2017 and May 31st 2018. Patients ≥ 18 years receiving cardiopulmonary resuscitation (CPR) for IHCA were included. Data were collected using Utstein and COSCA-criteria, supplemented by pre-arrest Modified Rankin Scale (MRS, functional status) and morbidity through the Charlson Comorbidity Index (CCI). Main outcomes were survival, health-related quality of life (HRQoL, EuroQoL) and functional status (MRS) after one-year.

      Results

      A total of 713 patients were included, 64.5% was male, median age was 63 years (IQR 52–72) and 72.8% had a non-shockable rhythm, 394 (55.3%) achieved ROSC, 231 (32.4%) survived to hospital discharge and 198 (27.8%) survived one year after cardiac arrest. Higher pre-arrest MRS, age and CCI were associated with mortality. At one year, patients rated HRQoL 72/100 points on the EQ-VAS and 69.7% was functionally independent.

      Conclusion

      One-year survival after IHCA in this study is 27.8%, which is relatively high compared to previous studies. Survival is associated with a patient’s pre-arrest functional status and morbidity. HRQoL appears acceptable, however functional rehabilitation warrants attention. These findings provide a comprehensive insight in in-hospital cardiac arrest prognosis.

      Keywords

      Introduction

      In-hospital cardiac arrest (IHCA) is a serious adverse event that can potentially affect any hospitalized patient. Although it still occurs frequently, evidence is relatively scarce.
      • Andersen L.W.
      • Holmberg M.J.
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      In-Hospital Cardiac Arrest.
      • Schluep M.
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      • Stolker R.J.
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      • Hoeks S.E.
      One-year survival after in-hospital cardiac arrest: a systematic review and meta-analysis.
      Because of this, there is much interest in long-term outcomes of IHCA and its predictors.
      • Andersen L.W.
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      • Løfgren B.
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      Adult in-hospital cardiac arrest in Denmark.
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      • et al.
      Health status and psychological distress among in-hospital cardiac arrest survivors in relation to gender.
      Several strategies to improve outcomes have been proposed, aimed at both prevention and treatment.
      • Nallamothu B.K.
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      • Harrod M.
      • et al.
      How Do Resuscitation Teams at Top-Performing Hospitals for In-Hospital Cardiac Arrest Succeed?.
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      • Chan P.S.
      • Xu Y.
      • et al.
      Delays in Cardiopulmonary Resuscitation, Defibrillation, and Epinephrine Administration All Decrease Survival in In-hospital Cardiac Arrest.
      Prevention focuses on early recognition of patients who are at risk of cardiac arrest, as well as patient-centred counselling to install do-not-resuscitate (DNR) orders for patients in whom cardiopulmonary resuscitation (CPR) is not expected to be successful.
      • Andersen L.W.
      • Holmberg M.J.
      • Berg K.M.
      • Donnino M.W.
      • Granfeldt A.
      In-Hospital Cardiac Arrest.
      • Fritz Z.
      • Slowther A.-M.
      • Perkins G.D.
      Resuscitation policy should focus on the patient, not the decision.
      • Becker C.
      • Lecheler L.
      • Hochstrasser S.
      • et al.
      Association of Communication Interventions to Discuss Code Status With Patient Decisions for Do-Not-Resuscitate Orders.
      Preferably, the decision to attempt or refrain from CPR is made based on patient preferences and characteristics that are present prior to cardiac arrest.
      • Fernando S.M.
      • Tran A.
      • Cheng W.
      • et al.
      Pre-arrest and intra-arrest prognostic factors associated with survival after in-hospital cardiac arrest: systematic review and meta-analysis.
      Outcomes should focus on good long-term quality of life, rather than survival to hospital discharge. Studies from different populations will allow for international comparison and increase learning from good practice.
      • Andersen L.W.
      • Holmberg M.J.
      • Løfgren B.
      • Kirkegaard H.
      • Granfeldt A.
      Adult in-hospital cardiac arrest in Denmark.
      • Fernando S.M.
      • Tran A.
      • Cheng W.
      • et al.
      Pre-arrest and intra-arrest prognostic factors associated with survival after in-hospital cardiac arrest: systematic review and meta-analysis.
      Although 1-year long-term survival data is available, there is limited knowledge on long-term functional outcomes and factors that predict these outcomes. As previously reported, survival in European studies is 20.0% (95% prediction interval: 16.0–26.0%) and we reported a one-year survival rate of 23.0% from a single-centre retrospective study.
      • Schluep M.
      • Gravesteijn B.Y.
      • Stolker R.J.
      • Endeman H.
      • Hoeks S.E.
      One-year survival after in-hospital cardiac arrest: a systematic review and meta-analysis.
      • Schluep M.
      • Rijkenberg S.
      • Stolker R.J.
      • Hoeks S.
      • Endeman H.
      One-year mortality of patients admitted to the intensive care unit after in-hospital cardiac arrest: a retrospective study.
      The majority of evidence has been derived from retrospective single-centre studies or studies that do not assess the relationship between pre-arrest variables and long-term outcomes.
      • Schluep M.
      • Gravesteijn B.Y.
      • Stolker R.J.
      • Endeman H.
      • Hoeks S.E.
      One-year survival after in-hospital cardiac arrest: a systematic review and meta-analysis.
      We therefore initiated a prospective cohort study to describe IHCA epidemiology in the Netherlands. The overall goal of our endeavour is to provide information in order to establish patient-centred CPR-directives. This also means that patients can then make an informed decision about their CPR-directive. The primary objective of the current study is to assess the one-year survival of adult patients after IHCA. The secondary objectives are to determine pre-arrest factors for prognostication of outcome and to describe overall functional outcome and health-related quality of life after IHCA. In this paper we report on variables that are present prior to cardiac arrest (age, functional status, comorbidity) and hospital factors (patient monitoring, admission specialty, post-arrest treatment).

      Methods

      Design and setting

      A multicentre prospective cohort study was performed in 25 hospital localizations. The call for participation were done through the Dutch Society for CPR-coordinators (NVCR). Data were collected through an online registration system (OpenClinica, Walton, MA, USA). CPR practice and hospital characteristics of all Dutch hospitals were assessed through a prior nationwide survey.
      • Schluep M.
      • van Limpt G.J.C.
      • Stolker R.J.
      • Hoeks S.E.
      • Endeman H.
      Cardiopulmonary resuscitation practices in the Netherlands: results from a nationwide survey.
      The study was registered at clinicaltrials.gov (NCT03120507) and the Dutch trial registry (NTR6145).

      Patient population and follow-up process

      The population included were adults (≥18 years of age), who received cardiopulmonary resuscitation, defined by starting manual chest compressions for a circulatory arrest occurring in-hospital. The inclusion period was January 1st 2017–May 31st 2018. Patients from all hospital wards, departments, outpatient clinics and common areas were included. This means we also included patients from the intensive care (ICU) and cardiac care units (CCU), as well as the emergency room (ER). Exclusion criteria were: OHCA < 24 hours prior to IHCA, purposely induced arrhythmia (e.g. electrophysiological interventions) or cardiac arrest (e.g. cardioplegia in cardiac surgery) or refusal to participate. The CPR-team generally attends all cases of IHCA, except for some peri-operative cases in the OR. Therefore all patients were prospectively included through registrations done by each hospital’s CPR-team and crosschecked with ICU-admissions for cardiac arrest. In-hospital follow-up was done by the local investigator in each hospital until hospital discharge. After discharge survival was checked with the Dutch Personal Records Database (BRP) at 3 months and 12 months after cardiac arrest. Surviving patients received questionnaires addressing their functional status and quality of life. Up to two reminders were sent and subsequently patients received a phone call to ask for follow-up data.
      Ethical considerations
      Study participants were asked to provide informed consent, unless they did not survive initial CPR. For patients who survived CPR and died subsequently in-hospital without regaining consciousness, a letter was sent to the next of kin to inform of inclusion. Patients who regained consciousness received information about study participation. At this point informed consent was obtained to participate in follow-up. Patients were informed of the non-interventional design and were given the possibility to opt-out at any time. Patients were only able to refuse or opt-out of follow-up. This study was considered subject to the Dutch Medical Research Involving Human Subjects act (WMO) and was approved by the Erasmus University Medical Centre Medical Ethics Committee (ABR55661.078.16).

      Data collection

      Data was collected from the Electronic Medical Records of patients, according to the Utstein-template and the Core Outcome Set for Cardiac Arrest (COSCA) recommendations.
      • Perkins G.D.
      • Jacobs I.G.
      • Nadkarni V.M.
      • et al.
      Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: Update of the Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest.
      • Haywood K.
      • Whitehead L.
      • Nadkarni V.M.
      • et al.
      COSCA (Core Outcome Set for Cardiac Arrest) in Adults: An Advisory Statement From the International Liaison Committee on Resuscitation.
      Pre-arrest data were gathered retrospectively.

      Outcome measures

      The primary outcome measure was one-year survival. Secondary outcome measures were return of spontaneous circulation (ROSC), survival to hospital discharge, 3-month survival, quality of life, functional status and psychological distress at 3 and 12 months after cardiac arrest. Functional status was determined through a Modified Rankin Scale (MRS) score. MRS was assessed by the local investigators after cardiac arrest had occurred, either through a proxy, general practitioner or extensive chart review. Post-discharge MRS was reported via questionnaires. At follow-up CCI was assessed via self-reporting, as were new health issues. Patients were asked if they had prior employment and what their current employment status was. Quality of life and psychological distress was determined through validated questionnaires, including the EQ-5D-5L (EuroQoL). This questionnaire has been used before in cardiac arrest research and allows for good comparison. The EQ-5D measures the HRQoL on five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) in which patients can report problems in 5 severity levels. EQ-5D-5L Utility Index scores (EQ-Index) were calculated from the five dimensions of the EQ-5D-5L, with a standard set of population based weights validated for the Netherlands.
      • Mols F.
      • Pelle A.J.
      • Kupper N.
      Normative data of the SF-12 health survey with validation using postmyocardial infarction patients in the Dutch population.

      Janssen B, Szende A. Population Norms for the EQ-5D. Self-Reported Popul. Heal. An Int. Perspect. based EQ-5D. Dordrecht: Springer Netherlands; 2014, p. 19–30. https://doi.org/10.1007/978-94-007-7596-1_3.

      Calculated index scores range from 1 (best health state) to −0.446 for the worst health state possible. Additionally, part of the EQ-5D-5L is a visual analogue scale (EQ-VAS) where patients score their current health state from 0 (indicating worst health state imaginable) to 100 (indicating best health state imaginable).
      • Herdman M.
      • Gudex C.
      • Lloyd A.
      • et al.
      Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L).
      The EQ VAS provides a quantitative measure of the patient’s perception of their overall state of health. We compared the EQ-5D-5L dimensions to the Dutch referent population and to the population of hospitalized patients we studied in our previous study to assess advance care directives.

      Schluep M, Hoeks SE, Endeman H, et al. A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals. Resuscitation 2020. https://doi.org/10.1016/j.resuscitation.2020.04.004.

      Other outcome measures that were used are the Short Form 12 SF-12 with its physical and mental component scale (PCS and MCS), and the hospital anxiety and depression scale (HADS). Strain on the relationship between the patient and his/her partner or next of kin was assessed using the caregiver strain index (CSI). In the design of this study we described using Telephonic Interview of Cognitive Status (TICS), but this was not feasible.

      Statistical analysis

      Data were reported using mean (standard deviation) or median (interquartile range) where appropriate. Comparison between groups was done using designated statistic tests. Kaplan-Meier survival analysis was used. Survival differences were assessed for predefined subgroups: 1) shockable and non-shockable arrest rhythm 2) an Age-combined Charlson Comorbidity Index (ACCI) stratified for low (0–4 points), medium (5–7 points) or high (8+ points) burden of age and disease; 3) pre-admission functional status by Modified Rankin Scale scores. We assessed ACCI because a high ACCI was previously associated with lower survival in IHCA patients.
      • Schluep M.
      • Rijkenberg S.
      • Stolker R.J.
      • Hoeks S.
      • Endeman H.
      One-year mortality of patients admitted to the intensive care unit after in-hospital cardiac arrest: a retrospective study.
      • Piscator E.
      • Hedberg P.
      • Goransson K.
      • Djarv T.
      Survival after in-hospital cardiac arrest is highly associated with the Age-combined Charlson Co-morbidity Index in a cohort study from a two-site Swedish University hospital.
      The method of ACCI calculation is summarized in supplemental Table 1. Incidences of IHCA were calculated in two ways: (1) by division of the number of IHCA by the total number of hospital admissions during the study period, (2) by division of the number of IHCA by the sum of days of inclusion of all hospitals. For survival differences Log-Rank tests were calculated and hazard ratios (HR) were calculated through Cox regression. Variables that were univariately associated with survival (p < 0.05) were included in multivariate survival analysis. Data were analysed using SPSS statistics v25.0 (IBM, Chicago, IL, USA) and R. (R Foundation for Statistical Computing, Vienna, Austria).

      Results

      Fourteen hospital organizations participated, comprising 25 hospital locations (25.3% of Dutch hospitals). Compared to all Dutch hospitals, participating hospitals were mostly classified as teaching hospitals, trauma centres and thoracic/aortic surgery centres when compared to the overall characteristics of Dutch hospitals. A total of 713 patients were included between January 1st 2017 and May 31st 2018, of whom 64.5% was male, median age was 63 years (IQR 52–72) and 72.8% had a non-shockable rhythm (Table 1). Of these patients 394 (55.3%) achieved ROSC, 231 (32.4%) survived to hospital discharge and 198 (27.8%, 95 %CI 23.9%–30.5%) survived one year after cardiac arrest. If death occurred within one year after IHCA, 93.6% occurred while patients were in hospital versus 6.4% after hospital discharge. The inclusion period contained 5867 hospital days and a total of 529,679 admissions were done. This yields an IHCA incidence of 0.12 per hospital day and 1.3 per 1000 admissions. A flowchart of survival is displayed in Fig. 1 and patient characteristics are displayed in Table 1.
      Table 1Characteristics of all in-hospital cardiac arrests; one-year survivors vs. non-survivors. *patients who were lost to follow-up were excluded from analysis (n = 8) (Fig. 1).
      Death <1 year*One-year survivors*Totalp=
      Patient characteristics upon admissionn = 507n = 198n = 713
      AgeMedian (IQR)69(62–77)67(56–73)63(52–72)0.036
      Male sexn (%)327(64.5)125(63.1)460(64.5)0.734
      BMI (kg/m2)Median (IQR)25.7(23.4–29.4)26.6(23.9–30.1)25.7(23.0–30.0)0.039
      Charlson comorbidity indexMedian (IQR)2(0–3)1(0–2)1(0–3)<0.001
      Functional status at home
      (Modified Rankin Scale)**/n(%)<0.001
       0–1 – none/slight disability325(67.0)157(82.2)488(68.4)
       2–3 – moderate disability143(29.5)30(15.7)174(24.4)
       4–5 – severe disability17(3.5)4(2.1)22(3.1)
      Cerebral performance cat.1–2**n(%)438(86.4)188(95.0)634(88.9)0.010
      Presence of malignant diseasen(%)<0.001
       None402(79.3)172(86.9)582(81.6)
       Solid tumour43(8.5)23(11.6)66(9.3)
       Solid tumour with metastases35(6.9)1(0.5)36(5.0)
       Hematologic27(5.3)2(1.0)29(4.1)
      Type of wardn (%)0.005
       Non-monitored ward288(56.8)87(43.9)378(53.0)
       Intensive/cardiac care unit128(25.2)61(30.8)191(26.8)
       Operation Room15(3.0)16(8.1)32(4.5)
       Emergency Room48(9.5)22(11.1)70(9.8)
       Catheterization laboratory28(5.5)12(6.1)42(5.9)
      Type of admissionn(%)<0.001
       Cardiology178(35.1)89(44.9)272(38.1)
       Cardiac surgery14(2.8)18(9.1)32(4.5)
       Medical non-cardiology211(41.6)45(22.7)258(36.2)
       Surgical non-cardiac104(20.5)46(23.2)151(21.2)
      No. of cardiac arrest eventsn(%)0.652
       One event477(94.1)183(92.4)667(93.5)
       Two events
        Current admission12(2.4)7(3.5)19(2.7)
        In prior medical history18(3.6)8(4.0)27(3.8)
      Arrest-related factors
       Time of dayn(%)
       07:00–14:59191(37.7)91(46.0)284(39.8)
       15:00–22:59172(33.9)55(27.8)230(32.3)
       23:00–06:59144(28.4)52(26.3)199(27.9)
      Day of the week
       weekday370(73.0)158(79.8)536(75.2)
       weekend137(27.0)40(20.2)177(24.8)
      Witnessed arrestn(%)372(73.4)182(91.9)561(78.7)0.000
      Time to (min.)Median (IQR)
       basic life support0(0–0)0(0–0)0(0–0)0.127
       advanced life support2(1–4)1(0–2)1(0–3)0.414
      Cause of arrest - cardiacn (%)237(46.9)120(60.3)357(50.7)0.001
      Primary Arrest Rhythmn (%)0.000
       Asystole171(33.7)32(16.2)205(28.8)
       PEA237(46.7)65(32.8)304(42.6)
       VF71(14.0)65(32.8)140(19.6)
       VT27(5.3)27(13.6)54(7.6)
       No rhythm analysis1(0.2)9(4.5)10(1.4)
      After ROSCn = 194n = 200n = 394
      Time to ROSC (min)Median (IQR)10(5–20)5(3–10)9(5–15)0.393
      Glasgow Coma Scale
      (after ROSC)*Median (IQR)3(3–14)9(3–15)3(3–14)<0.001
      Serum lactate (mmol/L)Median (IQR)6.6(2.8–10.8)3.3(1.8–6.5)5.9(2.8–10.0)<0.001
      Coronary interventionn(%)25(11.8)50(24.4)79(11.1)<0.001
      ICU admissionsn(%)168(88.9)124(62.9)299(75.9)<0.001
      At dischargen = 28n = 203n = 231
      Cognitive performance Cat.**n(%)0.116
       1–2 none/slight disability17(60.7)156(78.8)179(77.5)
       3 – severe disability9(32.1)29(14.6)38(16.5)
       4 – coma0(0)2(1.0)2(0.9)
       Unknown‖2(7.1)11(5.6)12(5.2)
      In need of daily assistance§n(%)9(32.1)31(15.7)40(17.3)0.085
      Discharge destinationn(%)0.084
       home or family19(69.2)128(65.0)150(64.9)
       rehab centre3(11.5)26(13.2)31(13.4)
       nursing home1(3.8)14(7.1)16(6.9)
       other hospital (for long-stay ward)3(11.5)29(14.7)34(14.7)
      **data was missing for the following categories (n): MRS at admission (29), CPC at admission (25), CPC at discharge (13). †For 35 patients, there was no MRS score reported; non-survivors (22), survivors (7). ‖CPC was unknown for patients who were discharged to other hospitals earlier than scheduled, therefore CPC at discharge was not known. §Patients requiring assistance for daily activities such as bathing, getting dressed or cooking.
      Figure thumbnail gr1
      Fig. 1Survival flowchart for all-in-hospital cardiac arrest cases. *survival at this time point was assessed through patients’ responses to the questionnaire and was therefore variable with a median follow-up of 94 days (IQR 82–132).
      Survival plots for the total population and for predefined subgroups are depicted in Fig. 2. Lower survival was found in patients with a non-shockable cardiac arrest rhythm, an ACCI ≥ 5 points and/or higher pre-admission MRS, indicative of functional disability. One-year survival for patients with no disability prior to admission was 38.2%, for non-significant disability 26.8% and for moderate or severe disability 18.0% (Fig. 2c). After adjustment for peri-arrest factors several pre-admission variables were associated with a higher mortality: age (HR 1.01 per year increase, 95 %CI 1.00–1.02, p = 0.007) and a higher Charlson Comorbidity Index (HR 1.07 per point increase, 95 %CI 1.03–1.10, p < 0.001). The adjusted HR’s are displayed in Table 2.
      Figure thumbnail gr2
      Fig. 2Long-term survival. Survival function is stratified for shockable rhythm, pre-admission functional status (Modified Rankin Scale) and for Age-Combined comorbidity index (ACCI). Log-rank tests were performed: shockable rhythm p < 0.001, MRS p < 0.001, ACCI p < 0.001.
      Table 2Cox regression of factors associated with death <1 year after cardiac arrest, meaning not achieving ROSC, death in-hospital or death after discharge in the year after surgery. Two analyses were performed for pre-arrest variables, both with and without adjustment for peri-arrest variables.
      Patient characteristicsPre-arrest variablesPre and peri-arrest variables
      Hazard ratio at death95% CIp=Hazard ratio at death95% CIp=
      Age, per year increase1.011.00–1.020.0031.011.00–1.020.007
      Body Mass Index (kg/m2) (BMI) per point increase0.980.98–1.010.7221.000.98–1.010.583
      Charlson comorbidity index (CCI) per point increase1.071.03–1.10<0.0011.071.03–1.10<0.001
      Modified Rankin Scale
      (MRS) per point increase1.050.96–1.140.2901.020.94–1.120.616
      Cognitive Performance Category score (CPC) per point increase1.110.97–1.270.1241.060.92–1.210.436
      Non-shockable rhythm1.891.46–2.36<0.001
      Non-cardiac cause of arrest0.940.75–1.170.571
      Non-cardiac admission specialty1.110.87–1.400.354
      Non-monitored ward1.000.81–1.230.968
      Non-witnessed arrest1.501.19–1.890.001
      One-year survival varied between patients who were resuscitated in different hospital areas. One-year survival was highest for IHCA in the operation room (50.0%), followed by the emergency room (31.4%) the intensive/cardiac care units (31.9%), the catheterization laboratory (28.6%) and the non-monitored wards (23.0%) (p = 0.005). Survival also varied when patients were stratified for the specialty to which they were admitted. The highest probability of survival was found in cardiac surgical admissions (56.3%) and the lowest in medical non-cardiology admissions (17.4%).
      Of survivors to discharge 77.5% scored CPC1-2 (none-mild disability), 16.5% CPC3 (severe disability) and 0.9% CPC4 (comatose), and 17.3% was considered to be in need of daily assistance. Need of daily assistance was more numerically prevalent in patients who died in the following year (32.1% vs. 15.7%, p = 0.085).
      After discharge, 212 (29.7%) patients survived 3 months and 198 (27.8%) patients survived one year, of whom 136 (64.2%) and 110 (55.6%) answered the follow-up questionnaires respectively. Median time for first follow-up time was 94 days (IQR 82–132) and for final follow-up it was at least ≥ 12 months. The majority of surviving patients reported having no or a slight disability in functional status (MRS 0–1): 62.7% at 3 months, and 69.7% at 1 year as displayed in supplemental Fig. 1. At one-year follow-up 65.5% of surviving patients retained the same MRS score, and 30.0% had no more than 1-point decrease in MRS, compared to their status before cardiac arrest. Of the patients with a decrease in MRS (n = 49) at 12 months only 23.4% reported having been admitted to a nursing or rehab facility. The change in MRS scores before admission and at follow-up is summarized in supplemental Fig. 1. Of patients who answered the questionnaire at 1-year follow-up reported several problems: readmission to hospital (15.5%), chest pain (8.2%), heart failure (11.8%), heart rhythm disturbances (10.0%) and syncope (4.5%). The proportion of comorbidities in terms of CCI was the similar pre-arrest and at 3- and 12-month follow-up. Of patients who were employed at time of the cardiac arrest, 17.1% had quit working. Caregiver strain was present in 17.1% of patients’ partners or family members. These data are displayed in supplementary Table 3.
      HRQoL was assessed using the EQ-5D VAS score and EQ-5D index score at 3 and 12 months post-IHCA. Median EQ-VAS was 70 (IQR 60–80) at 3 months and 75 (IQR 65–85) at 12 months. Patients reported a median EQ-5D index score of 0.77 (IQR 0.65–0.87) at 3 months and 0.81 (IQR 0.70–0.91) at 12 months. The reported items (scores ≥ 1 point severity) stratified by the EQ-5D-5L domains are displayed in Fig. 3. The most frequent reported problems at 12 months were: usual activities (56.9%), followed by mobility (55.0%), pain (53.2%), anxiety/depression (43.2%) and self-care (17.4%). Only a small proportion of patients (≤2.4%) reported severe problems (score ≥ 4 points severity) for each domain. The percentage of patients reporting severe problems is separately mentioned in Fig. 3. Results from SF-12 and HADS questionnaires are summarized in supplemental Table 3.
      Figure thumbnail gr3
      Fig. 3EQ-5D-5L percentage of patients who report any problem in one of the five domains at 3 months and 12 months after cardiac arrest. Reporting of problems was compared to a cross-sectional sample from Dutch hospitalized patients and the Dutch norm population.

      Discussion

      One-year survival after in-hospital cardiac arrest in this prospective multicentre study is 27.8%. Of all patients who die within one year after cardiac arrest the majority of deaths occurred in hospital (93.6%). In our study the incidence of IHCA is 1.3 per 1000 admissions. We found several pre-arrest variables to influence one-year survival, most notably pre-arrest functional status (MRS) and the combination of age and comorbidity (ACCI).
      Survival in this study is relatively high compared to other studies in populations comprising all hospital wards (including critical care wards).
      • Schluep M.
      • Gravesteijn B.Y.
      • Stolker R.J.
      • Endeman H.
      • Hoeks S.E.
      One-year survival after in-hospital cardiac arrest: a systematic review and meta-analysis.
      • Andersen L.W.
      • Holmberg M.J.
      • Løfgren B.
      • Kirkegaard H.
      • Granfeldt A.
      Adult in-hospital cardiac arrest in Denmark.
      • Schluep M.
      • Rijkenberg S.
      • Stolker R.J.
      • Hoeks S.
      • Endeman H.
      One-year mortality of patients admitted to the intensive care unit after in-hospital cardiac arrest: a retrospective study.
      One-year survival rates from a systematic review range from 9-29% globally, and 16–26% in European studies.
      • Schluep M.
      • Gravesteijn B.Y.
      • Stolker R.J.
      • Endeman H.
      • Hoeks S.E.
      One-year survival after in-hospital cardiac arrest: a systematic review and meta-analysis.
      The survival rate of 27.8% from this study borders the upper margins of both ranges. Our study population was not notably younger or healthier and did not comprise a larger proportion of shockable rhythms than in prior studies. Furthermore all patients suffering IHCA were included and loss to follow-up was low.
      We have two hypotheses to explain this survival rate. The first is that advanced directives are becoming increasingly important. The prevalence of Do Not Resuscitate orders among hospitalized patients is relatively high in the Netherlands: 27.5%.

      Schluep M, Hoeks SE, Endeman H, et al. A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals. Resuscitation 2020. https://doi.org/10.1016/j.resuscitation.2020.04.004.

      As a consequence, CPR with a low chance of success may be attempted less frequently. As mentioned, our population was not younger or healthier in means of comorbidity (ACCI), compared to other cohorts. Perhaps this means the relation between functional performance (MRS) and poor outcome is more important. We have no data to substantiate this hypothesis. Secondly Dutch hospitals have a 96% adherence to ERC guidelines, 91% availability of rapid response systems and all hospitals have dedicated CPR-teams with frequent team training.
      • Schluep M.
      • van Limpt G.J.C.
      • Stolker R.J.
      • Hoeks S.E.
      • Endeman H.
      Cardiopulmonary resuscitation practices in the Netherlands: results from a nationwide survey.
      • Moretti M.A.
      • Cesar L.A.M.
      • Nusbacher A.
      • Kern K.B.
      • Timerman S.
      • Ramires J.A.F.
      Advanced cardiac life support training improves long-term survival from in-hospital cardiac arrest.
      The exact role of these factors needs to be elucidated further in future research. Our hypothesis is supported by the fact that incidence of IHCA in our sample is in the lower margin of what is described in literature, i.e. 1–6 cases per 1000 admissions.
      • Schluep M.
      • Gravesteijn B.Y.
      • Stolker R.J.
      • Endeman H.
      • Hoeks S.E.
      One-year survival after in-hospital cardiac arrest: a systematic review and meta-analysis.
      Compared to studies from the US and Denmark, the incidence of IHCA is relatively low in our study.
      • Andersen L.W.
      • Holmberg M.J.
      • Løfgren B.
      • Kirkegaard H.
      • Granfeldt A.
      Adult in-hospital cardiac arrest in Denmark.
      • Kolte D.
      • Khera S.
      • Aronow W.S.
      • Palaniswamy C.
      • Mujib M.
      • Ahn C.
      • et al.
      Regional variation in the incidence and outcomes of in-hospital cardiac arrest in the United States.
      A likely explanation of this effect is the widespread availability of rapid response systems.
      • Schluep M.
      • van Limpt G.J.C.
      • Stolker R.J.
      • Hoeks S.E.
      • Endeman H.
      Cardiopulmonary resuscitation practices in the Netherlands: results from a nationwide survey.
      Rapid response systems may lower the incidence of IHCA, although its influence on mortality has yet to be proven.

      Yeung J, Scapigliati A, Hsieh M, et al. Rapid Response Systems in adults (EIT #638): Systematic Review; n.d. (Accessed April 12, 2021, at https://costr.ilcor.org/document/rapid-response-systems-in-adults-systematic-review).

      As expected, pre-arrest morbidity and functional status in this study is associated with survival after cardiac arrest.
      • Andersen L.W.
      • Holmberg M.J.
      • Berg K.M.
      • Donnino M.W.
      • Granfeldt A.
      In-Hospital Cardiac Arrest.
      • Schluep M.
      • Rijkenberg S.
      • Stolker R.J.
      • Hoeks S.
      • Endeman H.
      One-year mortality of patients admitted to the intensive care unit after in-hospital cardiac arrest: a retrospective study.
      • Ebell M.H.
      • Afonso A.M.
      Pre-arrest predictors of failure to survive after in-hospital cardiopulmonary resuscitation: a meta-analysis.
      One-year survival for patients with no previous disability in daily life (MRS 0) is 38.2% and for patients with a low burden of age and disease (ACCI 0–4 points) one-year survival is 33.7%. Inversely, survival was low for patients who suffered disability or had a high burden of disease before hospital admission.
      At discharge, 77% of patients had a CPC score of 1–2 and were therefore expected to be able to live independently or with minor assistance. Self-reported functional status at 3 months and 12 months was less than reported by physicians at hospital discharge. In general the health status of IHCA survivors is lower than that of a Dutch norm populations, as reflected by the EQ-5D domains and the EQ-5D index score.

      Janssen B, Szende A. Population Norms for the EQ-5D. Self-Reported Popul. Heal. An Int. Perspect. based EQ-5D. Dordrecht: Springer Netherlands; 2014, p. 19–30. https://doi.org/10.1007/978-94-007-7596-1_3.

      IHCA survivors reported a median EQ-5D index score of 0.77. When compared to the Dutch population mean of 0.89, there is a gap that indicates that HrQoL is lower for cardiac arrest survivors. EQ-5D index score compares well to other studies done in IHCA and OHCA patients, where HRQoL was measured after discharge.
      • Israelsson J.
      • Bremer A.
      • Herlitz J.
      • et al.
      Health status and psychological distress among in-hospital cardiac arrest survivors in relation to gender.
      • Elliott V.J.
      • Rodgers D.L.
      • Brett S.J.
      Systematic review of quality of life and other patient-centred outcomes after cardiac arrest survival.
      • Wilder Schaaf K.P.
      • Artman L.K.
      • Peberdy M.A.
      • Walker W.C.
      • Ornato J.P.
      • Gossip M.R.
      • et al.
      Anxiety, depression, and PTSD following cardiac arrest: A systematic review of the literature.
      • Wachelder E.M.
      • Moulaert V.R.M.P.
      • van Heugten C.
      • Verbunt J.A.
      • Bekkers S.C.A.M.
      • Wade D.T.
      Life after survival: long-term daily functioning and quality of life after an out-of-hospital cardiac arrest.
      EQ-5D-5L visual analogue score was on average 70 at 3 months and 75 at 12 months, where the Dutch population norm is 82 and 62 in Dutch hospitalized patients as described in our previous cross-sectional study.

      Janssen B, Szende A. Population Norms for the EQ-5D. Self-Reported Popul. Heal. An Int. Perspect. based EQ-5D. Dordrecht: Springer Netherlands; 2014, p. 19–30. https://doi.org/10.1007/978-94-007-7596-1_3.

      Schluep M, Hoeks SE, Endeman H, et al. A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals. Resuscitation 2020. https://doi.org/10.1016/j.resuscitation.2020.04.004.

      Perceived HrQoL (EQ-VAS) in cardiac arrest survivors was lower compared to the Dutch population, but higher than in patients during hospitalization. IHCA survivors perceive less HrQoL than the general population with at least minor problems in all domains of the EQ-5D, but mainly with regard to mobility and daily activities.

      Janssen B, Szende A. Population Norms for the EQ-5D. Self-Reported Popul. Heal. An Int. Perspect. based EQ-5D. Dordrecht: Springer Netherlands; 2014, p. 19–30. https://doi.org/10.1007/978-94-007-7596-1_3.

      • Djärv T.
      • Bremer A.
      • Herlitz J.
      • Israelsson J.
      • Cronberg T.
      • Lilja G.
      • et al.
      Health-related quality of life after surviving an out-of-hospital compared to an in-hospital cardiac arrest: A Swedish population-based registry study.
      The same results are reflected in the SF-12 and HADS outcome measures. Notably, the majority of patients with a decrease in MRS did not attend a rehabilitation program. This would imply that cardiac arrest survivors might benefit from rehabilitation programs to improve neurological status and exercise capacity.
      • Boyce L.W.
      • Goossens P.H.
      • Moulaert V.R.
      • Pound G.
      • van Heugten C.M.
      Out-of-hospital cardiac arrest survivors need both cardiological and neurological rehabilitation!.
      It is known that better neurologic status leads to more work participation.
      • Lilja G.
      • Nielsen N.
      • Bro-Jeppesen J.
      • Dunford H.
      • Friberg H.
      • Hofgren C.
      • et al.
      Return to Work and Participation in Society After Out-of-Hospital Cardiac Arrest.
      This poses interesting goals for future post-resuscitation care.
      Several limitations of our study should be taken into account. Firstly, this is an observational study and may be subject to selection bias. Because the study was voluntary and there are no financial or disciplinary consequences for hospitals, we hope this effect is negligible. Our sample has a relatively high number of teaching hospitals. On the one hand this means the complexity of care increases, e.g. more high-risk surgery, and on the other hand the availability of advanced life support certified doctors increases.
      • Schluep M.
      • van Limpt G.J.C.
      • Stolker R.J.
      • Hoeks S.E.
      • Endeman H.
      Cardiopulmonary resuscitation practices in the Netherlands: results from a nationwide survey.
      This difference could however be small as training level and training frequency does not differ, nor does ICU-level or rapid response team availability; other proxies for the chain of survival. Because our sample of participating hospitals was based on voluntary participation, we might have introduced a sampling bias. Although our sample contains more teaching hospitals, no significant differences were found, regarding hospital size, level of care, guideline adherence, and team training,
      • Schluep M.
      • van Limpt G.J.C.
      • Stolker R.J.
      • Hoeks S.E.
      • Endeman H.
      Cardiopulmonary resuscitation practices in the Netherlands: results from a nationwide survey.
      Secondly, MRS was assessed by the local investigators after cardiac arrest had occurred, either through a proxy, general practitioner or extensive chart review. This could have introduced bias. That pre-arrest MRS estimates still produce a survival effect on long-term indicates that a physician estimate of functional status may be a valuable predictor of long-term mortality. Lastly, the response rates were 64.2% at 3 months and 55.6% at 12 months. These numbers are similar to a recent study from Sweden, with a response rate of 55.0% at 3–6 month follow-up.
      • Djärv T.
      • Bremer A.
      • Herlitz J.
      • Israelsson J.
      • Cronberg T.
      • Lilja G.
      • et al.
      Health-related quality of life after surviving an out-of-hospital compared to an in-hospital cardiac arrest: A Swedish population-based registry study.
      All patients who were eligible for follow-up received telephonic reminders to fill out the questionnaires. The most heard reason not to respond was that they found it too strenuous or difficult. Furthermore, pre-admission mRS was lower in the non-responder group, than among responders. Differences between these two groups have been summarized in supplemental Table 2. We therefore think the found HRQoL is possibly overestimated.
      Regarding our overall goal, this study yields important results. It appears that in our sample, we can identify groups of patients for whom CPR would be less likely to succeed. Moreover these groups could have been identified upon hospital admission, by means of MRS or ACCI. Our study warrants validation in other cohorts, but its data may serve as a basis for discussing CPR-directives with patients.
      • Fritz Z.
      • Slowther A.-M.
      • Perkins G.D.
      Resuscitation policy should focus on the patient, not the decision.
      Furthermore, our study yields the positive message that survival after IHCA in our health care system is relatively high, especially in patient categories with a low burden of disease (ACCI ≤ 7) or good pre-arrest functional status (MRS < 2). In these categories survival is at least double when compared to the global average.
      • Schluep M.
      • Gravesteijn B.Y.
      • Stolker R.J.
      • Endeman H.
      • Hoeks S.E.
      One-year survival after in-hospital cardiac arrest: a systematic review and meta-analysis.
      As we have previously assessed, knowledge of CPR-directives is often lacking in patients.

      Schluep M, Hoeks SE, Endeman H, et al. A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals. Resuscitation 2020. https://doi.org/10.1016/j.resuscitation.2020.04.004.

      With our current findings we can improve communication in two ways. First it allows us to reassure young and healthy patients that are overwhelmed by hearing about CPR-directives, that it seldom occurs and that their prognosis is good. Second, it allows us to speak to our older, multimorbid and/or functionally incapacitated patients about their prognosis and it might lower the threshold for clinicians to speak about this subject.
      Our study design has several other merits. Patients were included from different hospitals in different regions, providing a variety of health services We provide a comprehensive view of in-hospital cardiac arrest patients with data on pre-admission status following up to 12 months after cardiac arrest. To combine survival, health-related quality of life (HRQoL) and functional status in a prospective cohort aids in improving the external validity of IHCA prognostication and such studies are scarce.
      • Israelsson J.
      • Bremer A.
      • Herlitz J.
      • et al.
      Health status and psychological distress among in-hospital cardiac arrest survivors in relation to gender.
      • Elliott V.J.
      • Rodgers D.L.
      • Brett S.J.
      Systematic review of quality of life and other patient-centred outcomes after cardiac arrest survival.
      We conclude that in this study one-year survival after in-hospital cardiac arrest is 27.8% in this population and survival is associated with pre-admission functional status and morbidity. Outcomes such as cognitive function, daily functionality and work participation warrant more attention in future research. We think future guidelines should incorporate advanced directive planning, of which prognostication and CPR-directive counselling is a vital part.
      • Fritz Z.
      • Slowther A.-M.
      • Perkins G.D.
      Resuscitation policy should focus on the patient, not the decision.
      • Perkins G.D.
      • Fritz Z.
      Time to Change From Do-Not-Resuscitate Orders to Emergency Care Treatment Plans.
      Similar studies should be repeated in various populations in order to develop tailor-made prognostication tools.

      Funding

      This study was funded by departmental funds of the participating hospitals. Licensing of the SF-12 software (€800) was funded by the ESA Air Liquide unrestricted research grant 2017, as well as printing and postage costs (approx. €300).

      Declaration of Competing Interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      Acknowledgements

      We would like to thank all participating hospital organizations for their help in this multicentre project. In particular we would like to thank the following local investigators for their help in data collection: Elke Berger, Frank Bosch, Andrea Bouts, Mariska Burgmeijer, Ann van Daalen, Merel Erkamp, Benjamin Gravesteijn, Irene Hoekstra, Loes Mandigers, Alice Pap, Koen Rijs, Martin Rinket, Francis de Smet, Ramón Soer, Peggy Sorensen, Friso Wesdorp, Hermien van der Wier, Steven Winkel, Mirjam van der Zeijst.

      Appendix A. Supplementary material

      The following are the Supplementary data to this article:

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