As of September 1, 2020, the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has accounted for more than 183,000 deaths in the United States, and more than 5,600 deaths in the state of Georgia alone (1). This virus primarily affects the respiratory system through angiotensin-converting enzyme (ACE) 2 receptor on host cells, but it also affects other systems as ACE2 is present in the heart, gastrointestinal tract, and kidneys (2).
Infection with this virus leads to imbalance between ACE and ACE2 eventually causing increased activity of angiotensin II, leading to vasoconstriction, pro-inflammatory, and pro-fibrotic pathways, which play a major role in the progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients (3). In a study of 50 patients at Aachen University Hospital in Heinsberg, Germany, many of the patients who developed ARDS were older and had coexisting conditions such as preexisting respiratory disease and obesity (4).
Several studies have identified the risk factors for COVID-19 and a number of related outcomes. The most common comorbidities in COVID-19 patients are hypertension, diabetes, and coronary artery disease (CAD) (5–8).
There is paucity of data on the outcomes of COVID-19 related in-hospital cardiac arrest (IHCA). We are aware of only one study detailing such outcomes in the Chinese population (9). Our study aims to contribute to this important body of knowledge by describing the characteristics and outcomes of IHCA in COVID-19 patients at our institution, a hospital in the rural Southwest Georgia, “Black belt” where the counties have high percentages of African American residents.
MATERIALS AND METHODS
We performed a retrospective study of COVID-19 patients admitted to Phoebe Putney Health System, which serves over 40 counties and a population of approximately 825,000 in rural Southwest Georgia. The Augusta University institutional review board approved the study and waived the requirement for informed consent due to minimal risk. Patients were admitted to one of the three Phoebe Putney hospitals between March 2, 2020, and August 26, 2020, inclusive of those dates. All hospitalized patients with confirmed COVID-19, who had IHCA and underwent cardiopulmonary resuscitation were included in this study.
Data were collected from the electronic medical records (Meditech and Athena Health). All patients were confirmed positive for COVID-19 by nasopharyngeal swab using a polymerase chain reaction test. Patients were considered to have confirmed infection if the initial test result was positive or if a repeat test was positive. Repeat tests were performed on inpatients during hospitalization shortly after initial test results were available if there was a high clinical pretest probability of COVID-19 or if the initial negative test result had been judged likely to be a false-negative due to poor sampling technique. Transfers from one in-system hospital to another were merged and considered as a single visit.
We collected data on demographics, insurance, baseline comorbidities, tobacco use, alcohol use, illicit drug use, home medications, symptoms on presentation, vitals, laboratory tests, electrocardiogram, the severity of presenting illness, a need for ICU admission, mechanical ventilation, new requirement for dialysis, length of stay (LOS), discharge, and mortality. Comorbidities included hypertension, diabetes mellitus (DM), CAD, congestive heart failure (CHF), peripheral arterial disease (PAD), cerebrovascular disease (CVA), chronic obstructive pulmonary disease, asthma, chronic kidney disease (CKD), dementia, cancer, immunosuppression, and chronic liver disease. All comorbidities except immunosuppression were adjudicated based on the 10th Version of the International Classification of Diseases. Patients were considered immunosuppressed if they had been on chronic steroids or other immunosuppressive therapy. Based on comorbidities, the Charlson Comorbidity Index (CCI) score was calculated. CCI is a validated tool to estimate long-term survival based on chronic health conditions (9). To calculate the LOS, the difference between actual admission and discharge/death times were used. We also collected information on the following during the hospital course: cardiac arrhythmias, septic shock, ARDS, left ventricular (LV) systolic dysfunction, venous thromboembolism (VTE), and the highest laboratory values (if obtained) of d-dimer, lactate dehydrogenase, procalcitonin, ferritin, C-reactive protein (CRP), and troponin I.
Cardiac arrest was defined as termination of cardiac mechanical activity, confirmed by pulselessness. Details regarding resuscitative measures were entered into the database by the attending physician. We collected information on the location of IHCA (ICU, medical floor, or emergency department), initial electrocardiogram rhythm (shockable: ventricular tachycardia/ventricular fibrillation or nonshockable: pulseless electrical activity [PEA] and asystole), response interval, need for: vasopressors, mechanical ventilation, or dialysis at the time of arrest, the most recent Pao2/Fio2 ratio prior to arrest (within 24 hr of arrest), return of spontaneous circulation (ROSC), and survival to discharge.
Continuous variables were reported as median and interquartile range (IQR), whereas categorical variables were reported as numbers and percentages. We performed the analyses in SAS Version 9.4 (SAS Institute, Cary, NC).
All authors reviewed the article and take responsibility for accuracy and completeness of data presented.
RESULTS
A total of 1,094 patients were hospitalized for COVID-19 at our health system in the study period. Out of those, 149 died (13.6%). A total of 63 patients (5.8%) had IHCA and had advanced cardiac life support (ACLS) measures performed. The baseline demographics and characteristics of these 63 patients are presented in Table 1. The median age was 66 years, 49.2% were males, and the majority of patients were African Americans (n = 57, 90.5%). The most common comorbidities were hypertension (n = 56, 88.9%), obesity (n = 44, 69.8%), DM (n = 38, 60.3%), and CKD (n = 23, 33.3%). A total of 19.1% had CHF and 15.9% had CAD. CVA and PAD were present in 17.5% of these patients. Eighteen patients (28.6%) had a CCI of 0–2, whereas 25 patients (39.7%) had CCI of greater than or equal to 5. Of those with CCI of 0–2, 61% were morbidly obese and another 28% were obese.
TABLE 1. -
Demographic, Comorbidities, Severity, and Common Presenting Symptoms of 63 Hospitalized Coronavirus Disease 2019 Patients With Cardiac Arrest
| Characteristics |
Overall (n = 63) |
| Median age, yr, median (IQR) |
66 (59–74) |
| African American race, n (%) |
57 (90.5) |
| Male, n (%) |
31 (49.2) |
| Median body mass index, kg/m2, median (IQR) |
35 (29–44) |
| Obesity categories, n (%) |
|
| Obese (> 30 kg/m2) |
44 (69.8) |
| Morbidly obese (> 40 kg/m2) |
21 (33.3) |
| Hypertension, n (%) |
56 (88.9) |
| Coronary artery disease, n (%) |
10 (15.9) |
| Congestive heart failure, n (%) |
12 (19.1) |
| With reduced ejection fraction |
3 (4.8) |
| With preserved ejection fraction |
9 (14.3) |
| Cerebrovascular disease, n (%) |
11 (17.5) |
| Peripheral vascular disease, n (%) |
11 (17.5) |
| Chronic obstructive pulmonary disease, n (%) |
4 (6.3) |
| Asthma, n (%) |
6 (9.5) |
| Chronic kidney disease I–IV, n (%) |
15 (23.8) |
| End-stage renal disease (dialysis), n (%) |
6 (9.5) |
| Diabetes, n (%) |
38 (60.3) |
| Cancer, n (%) |
6 (9.5) |
| Immunosuppression, n (%) |
6 (9.5) |
| Tobacco use, smoker, n (%) |
17 (27) |
| Charlson Comorbidity Index, n (%) |
|
| 0–2a |
18 (28.6) |
| 3–4b |
20 (31.7) |
| ≥ 5c |
25 (39.7) |
| Symptoms and severity, n (%) |
|
| Mild symptoms |
6 (9.5) |
| Pneumonia |
6 (9.5) |
| Severe pneumonia |
47 (74.6) |
| Sepsis |
25 (39.7) |
| Septic shock |
2 (3.2) |
| Acute respiratory distress syndrome |
6 (9.5) |
| Common presenting symptoms |
|
| Shortness of breath, n (%) |
40 (63.5) |
| Fever, n (%) |
33 (52.4) |
| Cough, n (%) |
29 (46) |
| Altered mental status, n (%) |
9 (14.3) |
| Gastrointestinal symptoms (nausea, vomiting, diarrhea), n (%) |
9 (14.3) |
| Days of symptoms, median (IQR) |
14 (7–23) |
| Length of stay, d, median (IQR) |
11 (6–18) |
IQR = interquartile range.
a28% obese, 61% morbidly obese.
b50% obese, 35% morbidly obese.
c36% obese, 12% morbidly obese.
The most common presenting symptoms were shortness of breath (n = 40, 63.5%), fever (n = 33, 52.4%), and cough (n = 29, 46%). Altered mental status and gastrointestinal symptoms (nausea, vomiting, and/or diarrhea) were present in nine patients (14.3%) each. Median duration of symptoms prior to admission was 14 days (IQR, 7–24 d) (Table 1).
At admission, six patients (9.5%) had mild symptoms, and six patients (9.5%) had pneumonia. Forty-seven patients (74.6%) had severe pneumonia, and 25 patients (39.7%) met the criteria for sepsis at admission. Septic shock and ARDS were present at admission in 2 (3.2%) and 6 (9.5%) patients, respectively (Table 1). The median LOS was 11 days (IQR, 6–18 d).
During treatment course, 42 patients (66.7%) developed septic shock, and 53 (84.1%) developed ARDS. Arrhythmias occurred in eight patients (12.7%). All of them were atrial arrhythmias and majority were atrial fibrillation/flutter. New onset LV systolic dysfunction occurred in six patients (9.5%). Four patients (6.3%) developed VTE. A total of 51 patients (81%) were on mechanical ventilator and 25 patients (39.7%) were on dialysis prior to IHCA. Thirty-eight patients (60.3%) were on vasopressor support prior to IHCA (Table 2).
Markers of inflammation were significantly elevated in these patients. Median ferritin level was 1,753 ng/mL (IQR, 955–4,235 ng/mL; normal value < 300 ng/mL) and median CRP level was 30 mg/L (IQR, 18–37 mg/L; normal value < 5 mg/L). Median procalcitonin level was greater than 10 times the upper limit of normal with a value of 6 ng/mL (IQR, 1–31 ng/mL; normal value < 0.5 ng/mL). d-dimer levels were 18 times the upper limit of normal with median of 9 μg/mL (IQR, 2–17 μg/mL; normal value < 0.5 μg/mL). Troponin I was also elevated in majority of these patients with median value of 0.2 ng/mL (IQR, 0.03–1.0 ng/mL) (Table 2).
TABLE 2. -
Clinical Course, Treatment, and Laboratory Values of 63 Hospitalized Coronavirus Disease 2019 Patients With Cardiac Arrest
| Characteristics |
Overall (n = 63) |
| Septic shock, n (%) |
42 (66.7) |
| Acute respiratory distress syndrome, n (%) |
53 (84.1) |
| Left ventricular systolic dysfunction, n (%) |
6 (9.5) |
| Arrhythmias, n (%) |
8 (12.7) |
| Venous thromboembolism, n (%) |
4 (6.3) |
| Treatments, n (%) |
|
| Ventilator |
51 (81) |
| Dialysis |
25 (39.7) |
| Prior to arrest |
19 (30.2) |
| Prior to hospitalization |
6 (9.5) |
| Vasopressors prior to arrest |
38 (60.3) |
| Location of cardiac arrest, n (%) |
|
| ICU |
53 (84.1) |
| Floor |
9 (14.3) |
| Emergency department |
1 (1.6) |
| Rhythm, n (%) |
|
| Asystole |
21 (33.3) |
| Pulseless electrical activity |
37 (58.7) |
| Ventricular tachycardia/ ventricular fibrillation |
5 (7.9) |
| Pao
2 to Fio
2 ratio (within 24 hr of arrest), n (%) |
|
| < 100 |
40 (63.5) |
| 100–200 |
13 (20.6) |
| > 200 |
1 (1.6) |
| NA |
9 (14.3) |
| Pco
2, mm Hg (within 24 hr of arrest), n (%) |
|
| < 45 |
20 (31.7) |
| 45–60 |
12 (19) |
| > 60 |
22 (34.9) |
| NA |
9 (14.3) |
| Biomarkers, median (interquartile range) |
|
| Procalcitonin (ng/mL) |
6.0 (1.0–35.0) |
| Ferritin (ng/mL) |
1753.0 (955.0–4235.0) |
|
d-dimer (μg/mL) |
9.0 (2.0–17.0) |
| Troponin (ng/mL) |
0.2 (0.03–1.0) |
| Lactate dehydrogenase (U/L) |
481.0 (371.0–650.0) |
| C-reactive protein (mg/L) |
30.0 (18.0–37.0) |
The majority of the IHCA occurred in ICU (n = 53, 84.1%), remaining on the medical floor (n = 9, 14.3%) and emergency department (n = 1, 1.6%). Time to initiation of ACLS protocol after IHCA was less than 1 minute for all IHCA occurring in ICU, and less than 2 minutes for the remaining patients. The most common initial rhythms were PEA in 37 patients (58.7%), and asystole in 21 patients (33.3%). An initial shockable rhythm was present in only five patients (7.9%) (Table 2). In the 24 hours prior to IHCA, the Pao2/Fio2 ratio was less than 100 in almost two-thirds of the patients (n = 40, 63.5%). Most of the remaining patients had Pao2/Fio2 ratio between 100 and 200 (n = 13, 20.6%), and one patient (1.6%) had the ratio above 200 in the 24 hours preceding the arrest. There were nine patients (14.3%) who did not have a Pao2/Fio2 ratio in the 24 hours prior to arrest. All of these nine patients were on the medical floor and had rapid deterioration. Since they were on medical floor prior to arrest and were relatively stable prior to rapid deterioration, they did not have a blood gas within 24 hours prior to arrest. Similarly, in 24 hours prior to IHCA, the Paco2 was greater than 45 mm Hg in 34 patients (53.9%), with values greater than 60 mm Hg in 22 patients (34.9%) (Table 2).
The in-hospital mortality was 100%. ROSC was achieved in a total of 18 patients (29%). However, nine of those 17 patients suffered another cardiac arrest within 2 hours and died. Eight patients were made do not resuscitate (DNR) and died the same day except for one patient who died 2 days later. One patient survived the cardiac arrest but remained critically ill and suffered another cardiac arrest a week later and died.
DISCUSSION
To our knowledge, this is the first study to report outcomes of IHCA in COVID-19 patients in the United States. Only one prior study has reported outcomes of IHCA in COVID-19, which was from China (10). The in-hospital mortality in our study was 100%, a finding different from the Chinese study. Although that study reported a 30-day survival of 2.9%, only one out of 136 patients (0.7%) had a favorable neurologic outcome at 30 days. ROSC was reported 13.2% in their study (10). In our study, as many as 29% patients had ROSC, but almost all were brief and did not impact final outcomes.
Our overall IHCA cohort was sicker compared with the one in Chinese study (hypertension—88.9% vs 30.2%, DM—60.3% vs 19.9%, and CAD—15.9% vs 11%). They did not report the prevalence of obesity or morbid obesity in that study (10). In our study, a total of 69.8% patients were obese, and 33.3% were morbidly obese. These differences could explain the marginally better outcomes in that study. Although our patient population had higher overall comorbidity burden, there were 17 patients (27%) under the age of 60 years, and 18 patients (28.6%) had a CCI of 2 or less. A CCI of 2 or lower is associated with greater than 90% 10-year survival (11,12). Although CCI is not typically used in acute setting, it gives an idea of overall baseline health of an individual. In our study, the final outcomes were same regardless of the baseline CCI once patients had IHCA. One possible explanation for that could be the high prevalence of morbid obesity in our study population. Neither morbid obesity nor obesity is a part of CCI calculation. Among those with low CCI, 61% were morbidly obese and other 28% were obese. Morbid obesity has been shown to be independent predictor of mortality in COVID-19 in prior studies (13,14). African Americans consisted of the majority of our study cohort. Overall survival to discharge among African Americans is significantly lower compared with Caucasians after IHCA (15). This could be another reason for the poor outcomes observed in our study.
Median symptom duration was 14 days in our study. This would suggest that many patients presented late in the inflammatory phase of the viral illness, which likely accounts for the poor outcomes in our study (16). The severity of presenting symptoms did not seem to affect the outcome once patients had IHCA in our study. Although the median duration of symptom onset to admission was 14 days, 19% patients did not have severe symptoms at admission. The location for majority of IHCA in the Chinese study was general ward, which was thought to be one of the reasons for poor overall outcomes (10). However, the majority of IHCA in our study occurred in the ICU with response time of less than 1 minute. Location of the arrest did not seem to improve overall outcomes in our study. Also, 81% patients were already on the ventilator at the time of arrest, and hence they already had a secure airway.
In our own health system, there were a total of 144 IHCA between March 2019 and August 2019, out of which 50 (34.7%) survived to discharge. This shows that our survival to discharge in IHCA patients prior to COVID-19 are comparable to general literature. A recent study from Australia reported 39.5% survival to discharge after IHCA (17). The overall survival to discharge after IHCA was reported at 31.2% in a cohort including patients from 101 Veterans Administration hospitals from 2008 to 2012 (18). The largest registry of IHCA reported improvement in survival to discharge from 17% in 2000 to 25% in 2016 (19). However, a shockable rhythm was present in approximately 20% IHCA and the cause of arrest was determined to be cardiac in more than 60% of the patients (19,20). In contrast, a shockable rhythm was present in about 8% in our study and 5.9% in the Chinese study. An initial nonshockable cardiac rhythm is associated with significantly worse outcomes compared with an initial shockable cardiac rhythm in IHCA (21). Also, the cause of arrest was respiratory in approximately 90% in our cohort as well as in the study from China (10). The significantly higher percentage of nonshockable initial rhythm and respiratory cause of arrest are likely responsible for dismal outcomes after IHCA in COVID-19 patients.
There were 86 other deaths in hospitalized COVID-19 patients during the study period. Out of those, seven patients had an advance directive prior to hospital admission and had DNR orders accordingly at admission. The remaining 79 patients were made DNR after discussion with the family during the course of the hospitalization due to multiple organ failure and poor prognosis. They were deemed not likely to survive the resuscitation efforts. Accordingly, none of these 86 patients underwent cardiopulmonary resuscitation.
To our knowledge, this is the first study reporting outcomes after IHCA among COVID-19 patients in the United States. Based on our data, COVID-19 related IHCA is associated with an extremely high mortality rate. It raises important questions about the futility of ACLS measures in these patients. Some hospitals have considered universal DNR for these patients, whereas some other places have ordered physicians not to perform resuscitation for these patients (22,23). Our study highlights the importance of instituting measures to ensure that goals of care discussions are incorporated into the care pathway of COVID-19 patients, particularly those that are critically ill.
Our study has certain limitations that need to be acknowledged. We did not have data on the quality of chest compressions during the ACLS. It is possible that use of personal protective equipment could have affected the quality of chest compressions. However, if that is the case, we believe it to be a universal phenomenon. We do not have information on duration of resuscitation on all the patients. The majority of our patients were African Americans, and hence, the findings may not be applicable to the general U.S. population. This was a single-center study, and the findings may not be generalizable to other institutions. Finally, this was a retrospective study with data abstraction from the electronic medical record, and hence some data elements might not be accurately captured.
CONCLUSIONS
In this study, we observed 100% in-hospital mortality after IHCA in COVID-19 patients regardless of their baseline comorbidities, severity of presenting illness, and the location of cardiac arrest. The majority of patients were African Americans, the majority of patients had an initial nonshockable rhythm, and in most cases, the cause of arrest was thought to be respiratory failure. The outcomes data after IHCA from other large institutions are urgently needed to guide the best management strategies for these patients.
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