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Prehospital care
Effects of pre-arrest comorbidities on 90-day survival of patients resuscitated from out-of-hospital cardiac arrest
  1. Chien-Chang Lee1,2,
  2. Min-Shan Tsai1,
  3. Cheng-Chung Fang1,
  4. Yi-Jung Chen1,
  5. Matthew Hui-Ming1,
  6. Chien-Hwua Huang1,3,
  7. Wen-Jone Chen1,
  8. Shyr-Chyr Chen1
  1. 1Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
  2. 2Department of Epidemiology, Harvard School of Public Health, Boston, USA
  3. 3Division of Intensive Care Unit, Department of Emergency Department, National Taiwan University, Taipei, Taiwan
  1. Correspondence to Shyr-Chyr Chen, Department of Emergency Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No.7 Chun-Shan South Road, Taipei 100, Taiwan; scchen{at}ntu.edu.tw

Abstract

Background Factors that affect prognosis in successfully resuscitated out-of-hospital cardiopulmonary arrest (OHCA) patients in the intensive care unit (ICU) who survived the initial 24 h period of post-resuscitation have not been established. This study was conducted to evaluate the clinical prognostic factors associated with 90-day survival in patients who were successfully resuscitated from OHCA.

Methods This study was conducted at a tertiary large university hospital. Clinical data were obtained from the medical records of 224 adult non-traumatic patients who were successfully resuscitated from OHCA and who survived the initial 24 h post-resuscitation phase. Univariate and multivariate analyses were performed to identify independent predictors associated with 90-day survival.

Results Significant adverse prognosticators included liver cirrhosis (HR 4.36, 95% CI 1.76 to 10.79), prolonged cardiopulmonary resuscitation (CPR) duration >20 min (HR 1.95, 95% CI 1.27 to 3.00) and underlying malignancy (HR 1.64, 95% CI 1.06 to 2.54). Favourable prognostic factors included the best Glasgow Coma Scale within 24–48 h after return of spontaneous circulation >5 (HR 0.16, 95% CI 0.04 to 0.68), mean arterial pressure on ICU admission >100 mmHg (HR 0.81, 95% CI 0.43 to 0.94) and the presenting rhythm of pulseless electrical activity (HR 0.44, 95% CI 0.1 to 0.63). A high burden of comorbidities (by Charlson score >5) was associated with significantly poorer 90-day survival (HR 1.60, 95% CI 1.03 to 2.49).

Conclusions Underlying comorbidities have a significant influence on survival. CPR duration, post-resuscitative blood pressure and early neurological recovery may serve as practical clinical predictors of short-term survival.

  • Out-of-hospital cardiopulmonary arrest
  • survival
  • resuscitation
  • comorbidity
  • blood pressure
  • Glasgow coma scale
  • nursing
  • emergency departments

https://doi.org/10.1136/emj.2009.087593

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    Introduction

    In the past decade, the focus on survival after out-of-hospital cardiopulmonary arrest (OHCA) has concentrated mainly on prehospital factors and emergency medical services (EMS) intervention.1–6 Since the introduction of the Utstein reporting style, reporting on the survival data of OHCA patients has been standardised. The number of studies reporting survival data based on this template has grown rapidly.1–6 However, even with uniform reporting, there is still a tremendous variability in outcome. The reported survival to discharge rate ranges from 2% to 49% in patients with a bystander-witnessed cardiac arrest of cardiac aetiology.7 This wide discrepancy is not explained entirely by the variability of traditional poor prognostic factors. Thus, it is possible that other important factors influence outcome.

    Recent studies note that some post-resuscitation factors may play as important roles on survival as previously emphasised prehospital factors.8 9 In addition, pre-existing chronic illnesses may also affect the outcome of OHCA patients. Although premorbid conditions have been extensively examined among in-hospital cardiac arrest (IHCA) patients,10–13 reports on OHCA patients have not been as extensive.14–16

    The purpose of this study was to analyse factors that affect prognosis in successfully resuscitated OHCA patients in the intensive care unit (ICU) who survived the initial 24 h period of post-resuscitation. The special focus was on the pre-existing comorbidity and post-resuscitation clinical parameters.

    Methods

    Study design and setting

    This cohort study was conducted from May 1995 to May 2005 in the Emergency Department (ED) and medical ICU of a university hospital. The hospital was a primary and tertiary care medical centre with an annual caseload of more than 100 000 visits. The hospital's review board approved this study.

    Selection of participants and data collection

    The source population consisted of patients aged ≥18 years who were admitted to the ED from May 1995 to May 2005. Since 1995, the prehospital EMS data was retrospectively collected in a standardised form, which included data on prehospital events such as the presence of a witness, presence of bystander cardiopulmonary resuscitation (CPR), presenting cardiac rhythm recorded by automatic external defibrillator (AED) and course of prehospital resuscitation. The inclusion criteria were non-traumatic OHCA adult patients, resuscitation duration 10 min, successful resuscitation and admission to the ICU, and survival longer than 24 h. After successful resuscitation, patients with blood pressures less than 90 mmHg received inotropic infusion.

    Those who had treatment withdrawn despite successful resuscitation were excluded from the study, as well as patients with return of spontaneous circulation (ROSC) after 10 min of resuscitation, because this category of patients could not recover without a small risk of organ dysfunction related to hypoxaemia or asphyxia.9 Comorbid conditions and post-resuscitation clinical parameters were extracted from the ED medical records and computerised ICU database.

    The principal investigators designed a structured form for data recording. The following information was collected: possible cause and initial ECG rhythm of cardiac arrest, duration of CPR, the presence of a witness on collapse and bystander CPR, the best Glasgow Coma Score (GCS) within 48 h after successful resuscitation, and the mean arterial pressure (MAP) on ICU admission.

    Comorbidities were recoded and measured by the Charlson index, a validated 19-item index for predicting short- and long-term mortality.17 In-hospital mortality and the length of hospitalisation of the survivors were also recorded. Because outcome was defined as 90-day all-cause mortality, the survival of those hospitalised less than 90 days was confirmed through follow-up, outpatient records or by telephone interview.

    Statistical analysis

    Statistics were performed by calculating the mean and SD for continuous variables, whereas absolute and relative frequencies were calculated for categorical variables. For between-group comparisons in univariate analysis, Fisher's exact test was used with categorical variables and the Mann-Whitney U tests for continuous variables. The Wilcoxon test was used to compare Kaplan-Meier survival curves with mild (Charlson score 0–2), moderate (Charlson score 3–4) and severe (Charlson score >5) burden of comorbidities.

    Variables associated with mortality by univariate analysis (p<0.10), as well as age and sex, were investigated using the Cox proportional hazards regression model for multivariate analysis. Significant independent explanatory factors were then identified by backward selection. The strength of the association between prognostic variables and outcome of interest was expressed as HRs, and their corresponding 95% CIs were calculated. All tests were two-tailed and p values <0.05 were considered statistically significant. Data were analysed using the STATA/SE software (Release 8.0).

    Results

    During the study period, a total of 1527 OHCA patients were admitted to the ED and 224 of those met the inclusion criteria (figure 1). There were 119 men and 105 women, with a mean age of 72±15 years. The crude 90-day survival rate was 40.2% (90/224). Diabetes mellitus was the most common pre-existing comorbidity at 36.6% (82/224), with chronic pulmonary disease the second most common (n=41, 18.3%). Hemiplegic stroke (n=39, 17.4%) and malignancy (n=39, 17.4%) were also prevalent.

    Figure 1
    Figure 1

    Flow diagram of patients. DNAR, do not attempt resuscitation; ED, emergency department; ICU, intensive care unit; OHCA, out-of-hospital cardiac arrest; ROSC, return of spontaneous circulation.

    Univariate analysis showed that underlying malignancy (p=0.042) was significantly associated with adverse outcome on 90-day survival, whereas liver cirrhosis (p=0.083) and high Charlson comorbidity score (p=0.073) were not. Univariate analysis of the effects of underlying disease on 90-day survival is summarised in table 1. The effects of prehospital events on survival were further analysed. The presence of a witness on collapse or bystander resuscitation before the arrival of the EMS did not favourably associate survival in this cohort. Patents who presented with asystole had poorer outcome, whereas pulseless electrical activity (PEA) was associated with better 90-day survival (p=0.03). The percentage of ventricular tachycardia/fibrillation in this study cohort was smaller than in most previous Western country series (12.5%), but was comparable to those of Asian countries (Taiwan or Japan).18–22 The CPR duration was longer in patients with adverse outcome (17.53±13.34 vs 11.18±5.82, p<0.001).

    View this table:
    Table 1

    Basic demographic data and pre-existing comorbidity of the study patients

    The post-resuscitation best GCS was significantly higher in 90-day survivors than in 90-day non-survivors (3.51±1.13 vs 3.12±0.44, p=0.009). Patients with post-resuscitation MAP >100 mmHg were associated with a better odds of hospital survival. The prehospital and hospital clinical parameters, and their crude associations with 90-day survival are summarised in table 2.

    View this table:
    Table 2

    Prehospital events and clinical and laboratory parameters on presentation at the emergency department

    To investigate separately the independent effects of categorical comorbidities and total burden of comorbidities on outcome, two multivariate models were created. Model one included comorbidity variables as individual categories, such as malignancy or liver cirrhosis, whereas model two included comorbidity variables as a summary of the Charlson score category, representing an individual's total burden of comorbidities. Aside from comorbidities, the same set of potential predictors, including age, sex, PEA, ventricular tachycardia/ventricular fibrillation (VT/VF), prolonged CPR, best GCS >5 and MAP on ICU admission >100 mmHg, were entered into the two models.

    Model one showed that liver cirrhosis and cancer were significantly associated with adverse outcome. Model two showed that the burden of the comorbidities, as defined by three escalating ranges of Charlson scores, was associated with poor prognosis. Both models also identified presenting rhythm of PEA, best GCS in the first 24–48 h >5 and MAP on ICU admission >100 mmHg as favourable predictors, whereas prolonged CPR >20 min was a poor prognosticator. The corresponding adjusted HR with 95% CI of these predictors in the two different models are listed in table 3.

    View this table:
    Table 3

    Independent predictors of 90-day mortality in resuscitated post-OHCA patients

    The Kaplan-Meier survival curves demonstrated the adverse influence of total burden of comorbidities (figure 2). The Wilcoxon tests revealed that patients with severe burden of comorbidities (Charlson >5) had significantly poorer 90-day survival than patients with moderate (Charlson score 3–4, p=0.041) or mild (Charlson score 0–2, p=0.002) burden.

    Figure 2
    Figure 2

    Kaplan-Meier mortality curves stratified by the burden of comorbidities as defined by the Charlson score.

    Discussion

    Previous efforts in analysing factors that predict survival of OHCA patients have mainly focused on prehospital peri-arrest events.1–6 This study, however, focused on the effects of pre-existing chronic conditions. Liver cirrhosis, cancer and high burden of comorbidities (Charlson score >5) are significantly associated with adverse outcome. In addition, the study has identified several practical clinical indicators that can be applied to predict 90-day survival among OHCA patients who are successfully resuscitated and who survive the first 24 h.

    The impact of pre-existing comorbidities on outcome after cardiac arrest has been studied on IHCA patients. Age, congestive heart failure, renal failure, stroke, malignancy, duration of CPR and presenting rhythm of VT/VF have been shown as major predictors of short-term survival.10–13 The results of this study are consistent with previous findings on two unfavourable predictors: malignancy and prolonged CPR duration.

    The prognostic meaning of liver cirrhosis in OHCA patients has not yet been systematically studied. A study investigating predictors of survival on cirrhotic ICU patients has observed that all cirrhotic patients (n=13) admitted to the ICU for post-resuscitation care died despite successful resuscitation.23 The results here confirm such findings, as it is observed that none of the cirrhotic patients (n=6) in this study survived up to discharge. Furthermore, after controlling for other covariates, liver cirrhosis remains the most influential poor prognosticator. Therefore, a decision on aggressive life support for post-cardiac arrest cirrhotic patients should be made after considering the unlikely benefit of invasive measures.

    In addition to specific types of comorbidities, the total burden of comorbidity also may have a significant impact on survival after OHCA. Previous studies have shown that an increasing number of chronic conditions is inversely related to the odds of survival.14 15 This study has sought to verify such reports by re-analysing the effect of the number of chronic conditions in the dataset. The results show that the total number of chronic illnesses is significantly associated with poor survival on crude analysis (Kaplan-Meier survival analysis with Wilcoxon test, p=0.024), which is consistent with previous findings. However, on adjusted analysis, the Cox proportional hazard model does not show an association between the number of chronic illnesses and 90-day survival (p=0.45).

    Previous work does not give proper weight to different types of comorbid conditions. Chronic conditions such as hypertension or active cancer may have very different impacts on survival. By using a weighted Charlson score, this study has shown a significant association between total burden of comorbidity and survival on both crude and adjusted analysis, which more validly reflects clinical reality. Although the original investigation of the Charlson Comorbidity Index is derived from an in-patients database to predict 1-year mortality,16 its recent application in acute illness also shows its capacity to predict short-term death with high specificity.24 25 Prior to the current study, it has not been previously used in outcome studies of OHCA patients. As the results show, a weighted summary index for total burden of comorbidities has a higher sensitivity of detecting survival differences than the mere count of chronic conditions.

    Aside from comorbidities, prolonged CPR duration is adversely associated with 90-day survival among OHCA patients, which is consistent with findings of previous reports involving IHCA patients.10–13 In OHCA patients, the actual arrest time cannot be accurately estimated in many cases. Thus, CPR duration is used as a biologically plausible surrogate marker for duration of arrest. In this series, the 90-day survival rate is 47% for CPR duration less than 20 min, but is 13% for CPR longer than 20 min.

    A GCS ≥5 within 24–48 h is an identified independent favourable prognosticator in this study. The GCS has been extensively investigated as a predictor of individual outcome following cardiac arrest with ROSC. Mullie et al, in a study of 133 patients, have shown that only one of 54 patients with GCS ≤4 at 48 h after ROSC recovered consciousness.26 A systematic review of clinical signs in prognostication following cardiac arrest with ROSC demonstrates that an absent motor response at 72 h has a likelihood ratio for death or poor neurological outcome of 9.2.27 It should be noted that a significant limitation in all prognostication studies is that in many cases, active support is withdrawn as soon as the patient appears to demonstrate poor neurological recovery. This may unduly bias results in favour of poor outcome.

    Observations of the association between post-resuscitation MAP and better survival among OHCA patients were noted. Although MAP >100 mmHg is associated with survival, this relationship could simply be a marker of the severity of underlying heart or systemic illness. It is unclear whether treatments (pressors) that increase MAP will automatically result in better outcomes. This association is corroborated by Mally et al, who report in a study of 598 OHCA patients that MAP is a strong prognostic factor of outcome, whereas the use of vasopressin during CPR is associated with higher MAP levels and better survival.28 The results of this study should be viewed in light of several limitations. First, the different background epidemiology of OHCA patients, especially the relatively low prevalence of ischaemic heart disease, and the low incidence of ventricular dysrhythmias, may affect the external validity of some prognostic factors. Although this study identifies several independent prognosticators, the predictive power of the established survival model is far from optimal. Thus, there may still be several important but undiscovered factors affecting survival. Furthermore, the neurological functional status of the survivors is not available for all patients. This important outcome measure is excluded from the study. Lastly, some factors associated with survival by univariate analysis are no longer significant in multivariate analysis. This can be due to the limited statistical power after controlling for multiple covariates in the model. As some significant factors may be epiphenomena, it is reasonable to mention them only in the univariate analysis.

    Conclusions

    This study represents one of the few outcome analyses of OHCA patients that address the effects of pre-arrest comorbidities. Cancer, liver cirrhosis and the total burden of underlying comorbidity have significant impact on post-OHCA survival. Furthermore, CPR duration, post-resuscitative blood pressure and early neurological recovery may serve as important intermediate indicators for short-term survival that can be a guide for better clinical decision-making.

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    Footnotes

    • Competing interests None declared.

    • Ethics approval This study was conducted with the approval of the National Taiwan University Hospital.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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