The Prognosis After Cardiac Arrest

Evidence on the Short- and Long-Term Course

Background: Each year, approximately 84 out of 100 000 individuals in Europe sustain a cardiac arrest; many die or suffer long-term neurological injury. Early prognostication can be of assistance for treatment planning and for the holding of evidence-based discussions with these patients’ families to make decisions about treatment.

Methods: This narrative review is based on pertinent guidelines and on publications retrieved by a selective search in Medline/PubMed.

Results: The survival rate of in-hospital cardiac arrest (IHCA) is 15–34%, that of out-of-hospital cardiac arrest (OHCA) approximately 10%. Survivors have an elevated risk of severe neurological injury: 22.9% (IHCA) and 67.7% (OHCA) go on to die in an intensive care unit of severe brain damage. Among those who are still alive one year after cardiac arrest, 83.3% have a good neurological outcome (cerebral performance category [CPC] score, 1–2), although many suffer from post–intensive care syndrome. Early prognostication is generally difficult, and an initial assessment can often only be made 72 hours or more after the event, on the basis of multimodal diagnostic testing. Risk models and biomarkers are available as aids to early prognostication but have not yet come into broad use.

Conclusion: Many successfully resuscitated patients die shortly thereafter. Those who survive for one year generally have good neurological function. Early prognostication is of fundamental importance for decision-making about continuing treatment or whether resuscitation should be attempted again in the case of a second arrest. Physicians communicating with the affected patients and their families should also be mindful of the commonly associated emotional stress.

Cite this as: Zumbrunn SK, Blatter R, Bissmann B, Amacher SA, Sutter R, Hunziker S: The prognosis after cardiac arrest: Evidence on the short- and long-term course. Dtsch Arztebl Int 2024; 121: 173–9. DOI: 10.3238/arztebl.m2025.0006

The annual incidence of cardiac arrest in Europe is approximately 84 out of 100 000 individuals (1). In Germany, the emergency services initiate around 55 000 resuscitation attempts per year (2). In Europe, 74.3% of patients die before or shortly after hospital admission despite resuscitation attempts (3). Following initially successful resuscitation, the prognosis remains serious. The risk of death in the further course is significantly elevated, with a 1-year survival rate of 7.7% worldwide and 9.2% in Europe. Likewise, observational studies show that, at 6 months, there is a high risk (up to 64%) that patients have permanent neurological deficits due to hypoxic-ischemic brain injury if treatment measures are carried out in an unrestricted manner (3, 4, e1). Following successful resuscitation, a clinical assessment of the further course is generally difficult (5). This uncertainty places family members under significant emotional strain on the one hand, while on the other, medical decisions need to be taken.

Many of these decisions need to be made in the aftermath of resuscitation, given that immediate response is necessary in the case of sudden cardiac arrest and the wishes of patients are often unclear in the first instance. Particularly in the case of out-of-hospital cardiac arrest, the following applies: In the absence of a clear advance directive or unequivocal medical exclusion criteria, resuscitation should be initiated (6). Studies show that uncertainty or discussions within the medical team regarding their approach can increase the interval between the onset of cardiac arrest and the start of resuscitation measures (referred to as no-flow time, the time without circulation), thereby reducing the chances of survival (7). In hospital, on the other hand, one has the option to achieve greater certainty by discussing a patient’s resuscitation preferences in code status discussions at an early stage. This highlights the need to check advance directives in the prehospital phase and to proactively discuss possible scenarios with patients and their relatives. Thus, in an emergency, decisions can be made more rapidly and in line with the patient’s wishes.

The key issues that also need to be discussed with relatives following resuscitation are the probability of survival and the expected impairments in the event of survival (8). Studies have shown that the early empirical assessment of prognosis, as made by the treating physicians at the time of resuscitation, frequently does not correlate well with the actual course and is often overly pessimistic (9). This can mean that potentially effective treatments are, unjustifiably, not initiated or are prematurely withdrawn (e2). On the other hand, life-sustaining measures can cause unnecessary suffering and incur high costs that are difficult to justify if they are not in line with patients’ desired treatment goals (e3). Therefore, prognostication that is as reliable as possible and which takes into account various objective parameters and predictors is essential (5). The current ERC guidelines (5) provide the basis for a prognostic approach that is, as far as possible, standardized. A retrospective validation study showed a sensitivity of 27.2–79.6% and a specificity of 100%, depending on the combination of diagnostic parameters, for the prediction of a poor outcome (CPC > 2 at 6 months) (e4). This means that the prognosis of a poor neurological outcome is highly reliable (no false-positive predictions). However, due to the low sensitivity in the prediction of a good outcome, a poor outcome may be overlooked. Therefore, results should always be interpreted on the basis of the clinical context as a whole.

This article provides an overview of the current state of evidence on outcomes following cardiac arrest, early prognostication, resuscitation decision-making, and advance directives.

Methods

This narrative review article is based on a selective literature search in PubMed up to January 2025 and takes into consideration the recommendations of the current guidelines of the European Resuscitation Council and the S1 guideline on hypoxic-ischemic encephalopathy (HIE) (4, 5, 6, 10).

Outcomes following cardiac arrest

The outcomes following cardiac arrest for which the most research has been conducted are mortality and neurological sequelae. The chances of survival vary significantly depending on location of cardiac arrest and its circumstances: Approximately 15–34% of patients survive an in-hospital cardiac arrest (IHCA) up to the time of discharge from an acute care hospital, whereas only around 10% survive an out-of-hospital cardiac arrest (OHCA) for the same time period (1, 3, e5, e6). According to a systematic review and meta-analysis, the mean survival time of patients following successful resuscitation from OHCA and discharge from hospital was 5.4 years (11).

Neurological outcome is usually assessed at the time of hospital discharge using the Cerebral Performance Category (CPC) scale and the modified Rankin Scale (mRS), which classify patients into five or seven groups, respectively, based on functional impairment (Table 1) (12, 13). A good neurological outcome is generally defined as CPC 1–2 (14).

Table 1

Scores for the quantification of neurological outcome

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of poor neurological outcomes and in-hospital death among successfully resuscitated patients, usually as a result of a change in treatment goals due to irreversible deterioration (according to a retrospective observational study, in 22.9% of IHCA and 67.7% of OHCA patients) (4, 15, e7).

In a meta-analysis, survivors discharged with CPC 1–2 had a predominantly good long-term prognosis (83.3% CPC 1–2 at 1 year). However, the chances of a significant improvement in patients with CPC 3–4 are extremely remote (16). Interestingly, some studies report a quality of life comparable to that of the general population at 1- to 15-year follow-up, while others found a reduced quality of life, particularly in emotional or physical aspects (16).

Prognostication following successful resuscitation

The current guidelines of the European Resuscitation Council (5) and the S1 guidelines on hypoxic-ischemic encephalopathy (HIE) in adults (10) recommend waiting at least 72 h prior to prognostication of neurological outcome in order to be able to perform a clinical assessment after a possible initial neurological recovery. The guidelines define clear criteria and recommendations for this timing depending on a number of additional investigations. For patients who remain comatose with a motor Glasgow Coma Score of ≤ 3 points at 72 h, the guidelines recommend multimodal prognostication by means of a neurological consultation, including the results of clinical examinations, biomarkers, neurophysiological investigations (electroencephalography [EEG] and somatosensory evoked potentials [SSEP] following median nerve stimulation), and brain imaging (Table 2) (5). On a clinical level, neurological examinations should be performed daily and pupillary and corneal reflexes checked at 72 h (10). The question of a highly malignant EEG arises after at least 24 h (ERC) or 48 h (S1 guideline) as well as after sedation and the end of targeted temperature management (TTM), defined as a suppressed background, possibly with periodic discharges or burst suppressions. The absence of the cortical N20 SSEP response is also considered a predictor of poor prognosis. Brain imaging using computed tomography or magnetic resonance imaging raises, among other things, the question of generalized brain edema (5, 10).

Table 2

Predictors of poor neurological outcome (CPC > 2) in comatose patients at ≥ 72 h following ROSC

A poor neurological outcome (CPC > 2) is highly likely if at least two of the criteria in Table 2 are met at 72 h (5). The approach described here is shown in the Figure. It is important to note that, in contrast to the ERC guidelines, the S1 guidelines on HIE do not consider status myoclonus to be a possible predictor of poor neurological outcome, based on the different definitions of, and sometimes difficult distinction from, status epilepticus without HIE (10).

Figure

Prognostication strategy algorithm

Depending on results and the known or presumed wishes of the patient, one must then discuss a change in treatment goal against the backdrop of an overall assessment.

In the event that the multimodal neurological examination confirms an infaust prognosis, the ERC guidelines recommend considering the possibility of organ donation (5, 10).

Researchers are making efforts to identify predictors that enable a reliable prognosis even earlier than 72 h after cardiac arrest. This could help to save resources and reduce the period of uncertainty, and thus also the psychological distress of family members. One approach in this regard is clinical prediction models, known as post-cardiac arrest scores, such as the Cardiac Arrest Hospital Prognosis (CAHP) score, the Out-of-Hospital Cardiac Arrest (OHCA) score, and the Prognostication using Logistic regression model for unselected cardiac arrest patients in the Early stages (PROLOGUE) score (Table 4) (17, 18, 19). The calculation of both the CAHP and the OHCA scores includes no-flow and low-flow time, which correlated with poor neurological outcomes in observational studies (18, 19, 20).

Table 4

Prospective observational studies on the prognostic accuracy of the biomarkers mentioned

Previous observational studies showed that the three abovementioned post-cardiac arrest scores enable the prediction of short-term neurological outcome (Table 3, for test accuracy). In comparison, conventional prognostic instruments to assess the severity of illness on the intensive care unit have a significantly lower discriminatory performance (Table 3) (21, 22, e8, e9). Likewise for longer-term outcomes at 2 years, a prospective observational study showed that the abovementioned scores could have a predictive value in relation to mortality (AUC: CAHP 0.87, OHCA 0.82, APACHE II 0.83, SAPS II 0.81) and neurological impairments (AUC: CAHP 0.86, OHCA 0.81, APACHE II 0.83, SAPS II 0.78) (23). However, clinical application studies demonstrating the practical benefit of these scores are still lacking, meaning that the guidelines do not currently recommend their routine use (5, e10).

Table 3

Observational studies on the prognostic accuracy of the prognostic scores

It is important to note that an initial prognostication should be reevaluated if the clinical situation changes over time, and the treatment goal should be adjusted accordingly. This applies not only in the acute phase but also in the further course of hospitalization and rehabilitation. A deterioration in the clinical situation or a divergence between the patient’s wishes and the treatment goal, for example, must also be taken into account here (10).

Prognostication in critically ill patients, especially the use of scores, also carries risks. In particular, the effect of the self-fulfilling prophecy describes how the determination of a poor prognosis increases the probability that treatment will be withdrawn, which ultimately leads to a poor outcome (24).

The value of biomarkers in prognostication

As part of prognostication, the current guidelines recommend measuring neuron-specific enolase (NSE) 48 or 72 h following cardiac arrest. Elevated levels (ERC guidelines: > 60 μg/L, S1 guideline (HIE): > 90 µg/L) are signs of a poor neurological prognosis—typically indicative of an HIE (5, 10). NSE is a neuronal enzyme, the serum level of which rises in the case of neuronal injury (25). The diagnostic reliability of NSE is particularly high on day 3 following cardiac arrest (Table 4). Observational studies suggest that it may well be possible to further improve neurological prognostication by combining NSE with established scores (e.g., the Cardiac Arrest Hospital Prognosis [CAHP] score) (26). This biomarker also seems to discriminate for long-term mortality and neurological outcome at 2 years, with a worse prognosis at values above 33 µg/L on day 3 (27). On the other hand, severe HIE is unlikely at very low serum levels (< 17 µg/L) (10). However, NSE may be falsely elevated due to its susceptibility to confounders such as hemolysis, malignant disease, and cerebral events (5, 10, 28). Moreover, it has been shown that the dynamics of levels over time have a higher predictive value than individual measurements, which explains why increasing values between 24 and 48 or 72 h are also considered a sign of a poor prognosis in the ERC guidelines (5, e11). Finally, it is essential, therefore, to always establish precise threshold values in collaboration with the laboratory performing the analyses (5).

There are also other biomarkers, such as neurofilament-light chains (NfL) in serum. In previous studies, these markers have shown good prognostic results as early on as at 24 h following resuscitation (Table 4). Elevated NfL levels are associated with a poorer short- and long-term prognosis regarding neurological outcome and mortality (29, e12). NfL is not yet well-established in clinical practice, as further research is needed on this topic (5).

Table 5

Outcomes and variables of selected pre- and post-arrest scores

Important points for resuscitation decision-making

and advance directives

The current European Resuscitation Council guidelines recommend a shared decision-making approach with patients regarding resuscitation decision-making (6). In some countries, such as Switzerland, the collection of data on preferences regarding cardiopulmonary resuscitation and intensive care treatment is recommended for every inpatient hospital stay (8). For these discussions, as well as for the drafting of advance directives in general, regardless of an individual’s current medical status, it is important to have a realistic idea of what resuscitation measures mean and how they are carried out as well as of the prognosis following cardiac arrest. In general, the chances of successful resuscitation following cardiac arrest are overestimated by the public, as shown by a survey of the Swiss general population (average estimate of survival with CPC 1–2: OHCA 41.6 %, IHCA 62.9 %) (30). Prognostication is also a major factor when deciding for or against resuscitation. Therefore, this information is important in the discussion regarding code status (8).

Clinical pre-arrest risk scores offer the opportunity to calculate the chances of survival and possible neurological injury on an individual basis; these include the Good Outcome Following Attempted Resuscitation (GO-FAR) score, Prognosis After Resuscitation (PAR) score, Modified Pre-Arrest Morbidity (PAM) Index, and the Prediction of Outcome for In-Hospital Cardiac Arrest (PIHCA) score (31, 32, e13, e14). These scores record relevant health factors such as age, comorbidities, and the level of neurological function before a possible cardiac arrest. Predictive models before resuscitation are particularly useful for the advance prognostic assessment of poor outcomes. However, these models are less reliable following resuscitation since they are not tailored to the parameters measured following cardiac arrest. Instead, post-cardiac arrest scores that take into account specific laboratory values and clinical findings following resuscitation are used here, thereby enabling more precise prognoses (17, 18, 19, 31, 32, e13, e14).

If patient factors and existing comorbidities are such that one cannot expect a positive outcome, one speaks of “medical futility.” This term describes situations in which treatment has an extremely low probability of success. In futile situations of this kind, the guidelines recommend refraining from resuscitation after consulting the patient or their representative (6, 8, 33, e15).

Mental stress and psychological outcomes

following successful resuscitation

Cardiac arrest survivors are at high risk for long-term physical and mental health sequelae. These physical, cognitive, and mental health complications following critical illness fall under the umbrella term post-intensive care syndrome (PICS) (e16). Approximately 50% of patients exhibit symptoms in at least one of these categories (34, 35). Observational studies conducted to date show symptoms of depression in 14–45% and of posttraumatic stress disorder (PTSD) in 19–27% of survivors (e17).

Severity of illness, prolonged intubation time, poor cognitive function, and unemployment represent possible risk factors for the development of PICS (34).

Family members often also exhibit psychosocial stress as a result of severe illness in close relatives. Up to 40% of these individuals experience symptoms of PTSD significantly more frequently than the general population (36, 37). A prospective randomized controlled study on strategies for communicating with the relatives of dying patients showed that proactive communication regarding prognosis and impending decision-making significantly reduces the risk of symptoms of PTSD or PICS (38). Therefore, follow-up care of affected individuals several months following hospital discharge is recommended in order to be able to offer timely support. To this end, ever more outpatient clinics for post-ICU follow-up care specifically focused on these problems are being offered, particularly by university hospitals (39, 40, e18, e19). Although there is only sparse evidence to date for the effect of interventions of this type, initial meta-analyses show that appropriate follow-up care can reduce symptoms of depression and PTSD and improve subjective quality of life (e20).

Conclusions

Only a small proportion of patients survive to hospital discharge. However, those who survive this critical post-cardiac arrest phase and are able to be discharged home often have a good long-term prognosis. In the case of patients in a persistent comatose state, reliable, multimodal prognostication is important and should be performed at 72 h following cardiac arrest at the earliest.

Survivors and their relatives often experience long-term psychosocial stress reactions. It is important to identify these in the context of follow-up care for critical illness in order to initiate targeted treatment options.

Conflict of interest statement
The authors declare that no conflict of interests exists.

Manuscript submitted on 5 September 2024, revised version accepted on

9 January 2025.

Translated from the original German by Christine Rye.

Corresponding author
Prof. Dr. med. Sabina Hunziker

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