Background

Death after resuscitation from cardiac arrest is common. Although associated factors have been identified, knowledge about their relationship with specific modes of death is limited.

Objective

To identify clinical factors associated with specific modes of death following cardiac arrest.

Methods

This study involved a retrospective medical record review of patients admitted to a single health care center from January 2015 to March 2020 after resuscitation from cardiac arrest who died during their index hospitalization. Mode of death was categorized as either brain death, withdrawal of life-sustaining therapies due to neurologic causes, death due to medical causes, or withdrawal of life-sustaining therapies due to patient preference. Clinical characteristics across modes of death were compared.

Results

The analysis included 731 patients. Death due to medical causes was the most common mode of death. Compared with the other groups of patients, those with brain death were younger, had fewer comorbidities, were more likely to have experienced unwitnessed and longer cardiac arrest, and had more severe acidosis and hyperglycemia on presentation. Patients who died owing to medical causes or withdrawal of life-sustaining therapies due to patient preference were older and had more comorbidities, fewer unfavorable cardiac arrest characteristics, and fewer days between cardiac arrest and death.

Conclusions

Significant associations were found between several clinical characteristics and specific mode of death following cardiac arrest. Decision-making regarding withdrawal of care after resuscitation from cardiac arrest should be based on a multimodal approach that takes account of a variety of personal and clinical factors.

The mortality rate of individuals who experience cardiac arrest is high.1  Common modes of death among patients who survive to receive hospital care after resuscitation from cardiac arrest include brain death, withdrawal of life-sustaining therapies due to neurologic causes (anoxic brain injury, perceived poor neurologic prognosis), withdrawal of life-sustaining therapies due to medical causes (eg, multiorgan failure, rearrest despite aggressive resuscitative measures), and withdrawal of life-sustaining therapies due to patients’ wishes, values, or preferences.

Family members are often asked to make medical decisions on behalf of patients but are offered varying amounts of information about likely clinical courses and outcomes. Numerous studies have identified predictors of survival after cardiac arrest,24  which conversely indicate predictors of poor outcome. Such predictors include initial cardiac rhythm, arrest duration, sex, and existing comorbidities (eg, chronic kidney disease, active cancer). Although several tools predicting survival have been identified and validated across studies, they are influenced by self-fulfilling prophecies and may fail to identify important factors that are relevant to patients and families, such as quality of life.510  Several studies have explored various patterns and risks of withdrawal of life-sustaining therapies in general following cardiac arrest.1113  Nevertheless, understanding of the relationship between various clinical factors and specific modes of death is limited. Knowledge of these factors will provide an opportunity for targeted intervention in specific groups of patients. Thus, this study was conducted to identify risk factors associated with specific modes of death following cardiac arrest.

Study Design and Participants

Before conducting this study, we obtained approval from the Ohio State University Institutional Review Board (approval number 2020E0341). We retrospectively reviewed the medical records of patients admitted to our tertiary care center after resuscitation from in-hospital or out-of-hospital cardiac arrest between January 2015 and March 2020. We included consecutive patients aged 18 years or older who subsequently died during hospitalization. We excluded individuals who did not survive to admission. We identified patients using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for cardiac arrest as the primary diagnosis and codes for acute myocardial infarction, cardiopulmonary resuscitation, pulseless electrical activity, asystole, ventricular tachycardia, and ventricular fibrillation as secondary diagnoses. We manually reviewed all medical records to confirm that patients met the inclusion criteria.

Mortality rates after cardiac arrest are high.

We categorized each patient’s mode of death as either brain death, withdrawal of life-sustaining therapies due to neurologic causes, death due to medical causes, or withdrawal of life-sustaining therapies due to patient preference.12,13  Information on the mode of death was obtained through medical record review, including notes made by treating physicians, palliative care team members, nurses, and allied health care workers, as well as documentation of advance care directives. Neurologic causes of withdrawal of life-sustaining therapies included evidence of anoxic brain damage, cerebral edema on imaging, and perceived poor neurologic prognosis. Medical causes of death included instability leading to multiorgan failure and recurrent cardiac arrest without return of spontaneous circulation. Reasons for withdrawal of life-sustaining therapies due to patient preference included patients’ formerly stated wishes, values, or preferences, including preexisting “do not resuscitate” orders or other advance directives; antecedent terminal illness; and surrogates’ understanding of patients’ wishes. If a patient met the criteria for more than 1 category, the key driving factor that precipitated death was determined from thorough medical record review. Two investigators (E.I. and A.H.) reviewed each patient’s medical record to determine the mode of death. A third investigator (B.S.) adjudicated any cases of disagreement.

Variables

We recorded basic demographic information (age, sex, race), existing medical comorbidities (hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, congestive heart failure, atrial fibrillation, chronic obstructive pulmonary disease, stroke, peripheral vascular disease, current or prior smoking status, current or prior alcohol use), presumed cause(s) of cardiac arrest (cardiac, noncardiac), initial recorded rhythm (pulseless electrical activity, asystole, ventricular tachycardia or ventricular fibrillation, or unknown), duration of cardiac arrest (in minutes), Glasgow Coma Scale (GCS) score on presentation, vasopressors used during cardiac arrest, first arterial blood gas values following cardiac arrest (pH, Paco2, Pao2 bicarbonate [HCO3], lactic acid), first blood glucose level following cardiac arrest, targeted temperature management (TTM) strategy used (33 °C vs 36 °C), days between cardiac arrest and death, and length of intensive care unit and hospital stays.

The most common mode of death among patients with out-of-hospital cardiac arrest was withdrawal of life-sustaining therapies due to neurologic causes.

We defined cardiac arrest duration as time between collapse and regaining pulses. In cases of unwitnessed cardiac arrest, cardiac arrest time was defined as the time that cardiac arrest was first recognized by a bystander or a family member. In cases of cardiac rearrest, we summed the individual cardiac arrest durations to determine the total cardiac arrest duration. We defined witnessed out-of-hospital cardiac arrest as that occurring while a family member or bystander was present, and witnessed in-hospital cardiac arrest as that occurring while the patient was receiving telemetric monitoring or in the presence of a health care professional, family member, or visitor.

Statistical Analysis

We used frequencies and percentages to summarize categorical variables and means with SDs or medians with IQRs to summarize continuous variables. We compared demographics, medical comorbidities, and clinical characteristics across modes of death using χ2 tests (or Fisher exact tests, when appropriate) for categorical variables and analysis of variance or Kruskal-Wallis tests (or Wilcoxon rank sum tests) for continuous variables. In cases of overall statistical significance (2-sided P < .05), we performed pairwise comparisons using the Holm-Bonferroni method for multiple testing to control the overall type I error rate at α = .05 (the lowest P value was evaluated at the .02 threshold). We used SAS, version 9.4 (SAS Institute Inc) for our analysis and defined statistical significance as a 2-sided P less than .05.

Of 1351 patients screened, 731 died during their hospital stay following cardiac arrest. The mode of death was brain death in 45 patients (6.2%), withdrawal of life-sustaining therapies due to neurologic causes in 219 patients (30%), death due to medical causes in 331 patients (45.3%), of whom 64 had rearrest, and withdrawal of life-sustaining therapies due to patient preference in 136 patients (18.6%). The most common mode of death among patients with out-of-hospital cardiac arrest was withdrawal of life-sustaining therapies due to neurologic causes, and that among patients with in-hospital arrest was death due to medical causes. The interrater-agreement reliability for mode of death was 81%. The median (IQR) number of days between cardiac arrest and death was 4 (2-6) for brain death, 5 (2-8) for withdrawal of life-sustaining therapies due to neurologic causes, 1 (1-4) for death due to medical causes, and 3 (1-12) for withdrawal of life-sustaining therapies due to patient preference (see Figure). Two patients experienced a second injury due to medical instability and rearrest that led to progressive cerebral edema, herniation, and delayed declaration of brain death.

With unadjusted analysis, we observed significant differences across patients with different modes of death in terms of age, race, hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, cumulative presence of any of these vascular comorbidities, atrial fibrillation, smoking, unwitnessed cardiac arrest, duration of cardiac arrest, location of cardiac arrest, GCS score after return of spontaneous circulation, epinephrine use, TTM status, initial pH, initial Paco2, initial lactic acid level, initial blood glucose level, and days between cardiac arrest and death (see Table).

When we performed post hoc pairwise comparisons, we observed multiple differences between groups (see Supplemental Tables 1, 2, 3, 4, and 5, available online only at ajcconline.org). Compared with other groups, patients with brain death were younger, were less likely to be White, had fewer vascular comorbidities, were more likely to have acidosis as evidenced by pH and Paco2 values, and had longer cardiac arrest duration. Compared with other groups, patients with withdrawal of life-sustaining therapies due to patient preference were significantly older, had shorter cardiac arrest duration, and had higher GCS scores following resuscitation. Compared with patients who died owing to medical causes and those with withdrawal of life-sustaining therapies due to patient preference, patients with either brain death or withdrawal of life-sustaining therapies due to neurologic causes were less likely to have vascular risk factors and more likely to have experienced unwitnessed cardiac arrest, have hyperglycemia, have undergone TTM following cardiac arrest, and have prolonged duration between cardiac arrest and death, especially 3 days or longer.

Death is a common occurrence following resuscitation from cardiac arrest. Some patients succumb to death due to neurologic causes or rearrest. More often, families face the challenging decision of whether to continue with aggressive, life-sustaining treatments or focus on quality of life and comfort measures. Although tools to predict all-cause mortality are available, they should not be relied upon in individual decision-making, which should be based on a variety of factors including baseline comorbidities, previously stated patient wishes, advance directives, systemic illness, timing, and discussions about goals of care.8  All of these factors, as well as the number and severity of medical and neurologic conditions, must be taken into account in unbiased planning with the surrogate decision makers.

In this study, we identified various factors associated with specific modes of death. We found significant differences between patients with brain death and those with withdrawal of life-sustaining therapies due to patient preference in terms of age, comorbidities, duration of cardiac arrest, and other characteristics of cardiac arrest. Patients in whom life-sustaining therapies were withdrawn due to neurologic causes had several features in common with patients with brain death, and patients who died due to medical reasons had several features in common with patients in whom life-sustaining therapies were withdrawn due to patient preference.

Although death due to medical causes was the most common mode of death in the entire cohort, withdrawal of life-sustaining therapies due to neurologic causes was the dominant mode among patients with out-of-hospital cardiac arrest, and death due to medical causes was the dominant mode among patients with in-hospital cardiac arrest. Although several studies identified withdrawal of life-sustaining therapies due to neurologic causes as the most common mode of death following cardiac arrest, others have identified medical instability as the most common cause of death.1214  We suspect that death due to medical causes was the most common mode of death in our cohort because of the inclusion of more patients who were resuscitated after in-hospital cardiac arrest, who made up 52% of the participants.

In our study, younger patients were more likely to die as a result of brain death than as a result of other causes. It is possible that older patients with early withdrawal of life-sustaining therapies did not have the opportunity to progress to brain death. Because younger patients often have fewer medical comorbidities, families tend to pursue aggressive medical care until the patient is declared brain dead or deemed to have a high likelihood of poor neurologic outcome because of anoxic brain injury, or unless they had another terminal illness such as cancer. Younger age has been identified as a risk factor for brain death.15  Younger patients have a greater likelihood of developing intracranial hypertension due to cerebral edema because they lack age-related brain atrophy.16,17  The rate of brain death in our study was much lower than the rates reported in the literature, which has implications for organ donation, as individuals with brain death make excellent organ donors.15,18,19  Interestingly, White individuals were less likely to be declared brain dead than patients of other races, which is consistent with previous findings that African American individuals were less likely than people of other races to have early withdrawal of life-sustaining therapy.20,21  Because of the retrospective nature of our study, we lacked detailed information about race. Sufficient time should be allowed for patients with diffuse cerebral edema to progress to brain death, thus increasing the likelihood of organ procurement.

In our study, older patients were more likely to have withdrawal of life-sustaining therapy due to their values and preferences, especially within 3 days of initial cardiac arrest, despite having a shorter mean duration of cardiac arrest, a higher rate of witnessed arrest, and higher GCS scores after arrest, indicating that age and medical comorbidities are major contributors to this decision. Also, older age was a strong predictor of withdrawal of life-sustaining therapies, which is consistent with the results of previous studies.11,13,20,21  Other researchers have found that preexisting medical comorbidities, shock on admission, and medical instability are influential factors in early withdrawal of life-sustaining treatment.11,13,2022  Similarly, medical instability and previously stated patient preferences were strong drivers of death in our study, especially within 3 days of cardiac arrest. Even in such situations, it is important to adopt a multimodal approach to neurologic prognostication and provide appropriate guidance to the surrogate decision makers to prevent premature withdrawal of life-sustaining therapies. A detailed understanding of the patient’s wishes and preferences is crucial to accurately determine the acceptable quality of life. A standardized procedure for detailed documentation of code status is essential to reduce the rate of undesired resuscitation in the event of cardiac arrest, especially among hospitalized patients.

Organ hypoxia due to underlying conditions and prolonged downtime leads to initiation of anaerobic respiration and severe acidosis due to elevated Paco2 and lactic acid level, which have been associated with increased mortality and poor neurologic outcomes following cardiac arrest.2330  In our cohort, acidosis was evident in patients declared dead on the basis of neurologic criteria. Hyperglycemia, a marker of increased disease severity in critically ill patients, has been associated with poor neurologic outcomes and increased mortality after cardiac arrest.31,32  Hyperglycemia increases intracellular acidosis during cardiac arrest, and markedly elevated blood glucose and acidosis have been observed in brain-dead patients compared with other cohorts.33  Although some studies have indicated higher mortality among those with higher glycated hemoglobin level and hyperglycemia during hospitalization, others have demonstrated an association of illness severity, but not hyperglycemia, with recovery following cardiac arrest.32,34,35  The impact of hyperglycemia on outcomes after cardiac arrest needs further exploration.

Other factors that have been associated with withdrawal of life-sustaining therapies include longer arrest duration, unwitnessed arrest, and initial nonshockable rhythms.1,3,4,36,37  Although shockable arrhythmias (ventricular fibrillation and ventricular tachycardia) are associated with better survival odds than nonshockable arrhythmias (pulseless electrical activity or asystole), this factor did not differ across modes of death in our study. In our study, patients with brain death had significantly longer arrest duration than other patient groups, and patients with brain death and those with withdrawal of life-sustaining therapies due to neurologic causes were more likely than patients in the other groups to have experienced unwitnessed arrest. Both factors are associated with prolonged and severe primary hypoxic-ischemic injury and poor outcome. Patients with death due to medical causes and those with withdrawal of life-sustaining therapies due to patient preference were less likely to undergo TTM because of medical instability and previously stated wishes, respectively, and had shorter hospital stays, most likely because of early withdrawal of life-sustaining therapies, findings consistent with previous research.21 

The most common mode of death among patients with in-hospital arrest was death due to medical causes.

This study has several limitations. As this was a retrospective, observational, single-center study, the circumstances of death were adjudicated using medical record review. Thus, some patients may have been misclassified. Because we included both out-of-hospital and in-hospital cardiac arrest patients, the clinical characteristics and outcomes of our cohort differ from those in previous studies. For some patients, some values were missing, either because they were not documented or because tests were not performed, which may have affected our results. Because this was a retrospective study, there was no standardized protocol for neurologic evaluation and prognostication, which would primarily affect the groups with withdrawal of life-sustaining therapies due to neurologic causes and death due to medical causes.

In this study, we identified various characteristics associated with specific modes of death following cardiac arrest. Withdrawal of life-sustaining therapies due to medical or neurologic causes was a common mode of death after cardiac arrest. Although a multi-modal approach to prognostication may reduce the rate of premature withdrawal of life-sustaining therapies due to neurologic causes, it is important to incorporate neurologic prognostication and uncertainties into decision-making for all patients with cardiac arrest. Prospective studies focusing on the triggers of withdrawal of life-sustaining therapies are warranted to identify the subset of patients in whom premature withdrawal of care could be avoided to improve outcomes.

Blake Senay and Elochukwu Ibekwe are co–first authors, contributing equally to the work.

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Footnotes

FINANCIAL DISCLOSURES

None reported.

 

SEE ALSO

For more about cardiac arrest, visit the Critical Care Nurse website, www.ccnonline.org, and read the Cochrane Review summary by Cohen, “Hypothermia for Neuro-protection in Adults After Cardiac Arrest” (December 2023).

 

To purchase electronic or print reprints, contact American Association of Critical-Care Nurses, 27071 Aliso Creek Road, Aliso Viejo, CA 92656. Phone, (800) 899-1712 or (949) 362-2050 (ext 532); fax, (949) 362-2049; email, [email protected].