a b s t r a c t

Aim: We evaluated the relationship between hyperkalemia and wide QRS complex in patients with Pulseless electrical activity cardiac arrest.

Methods: This was a single-center, retrospective observational study of patients over the age of 18 treated for car- diac arrest at a tertiary referral hospital whose initial electrocardiogram rhythm was PEA from February 2010 to December 2019. Wide QRS PEA was defined as a QRS interval of 120 ms or more. Hyperkalemia was defined as serum potassium level > 5.5 mmol/L. The primary outcome was hyperkalemia. Multivariable logistic regression analysis was used to evaluate the relationship between wide QRS and hyperkalemia.

Results: Among 617 patients, we analyzed 111 episodes in the wide QRS group and 506 episodes in the nar- row QRS group. The potassium level in the wide QRS group was significantly higher than in the narrow QRS group (5.4 mmol/L, IQR 4.4-6.7 vs. 4.6 mmol/L, IQR 4.0-5.6, P < 0.001). Among all patients, 49.6% (n = 55/111) in the wide QRS group had hyperkalemia, which was significantly higher than the 26.7% (n = 135/506) in the narrow QRS group (P < 0.001). In multivariable logistic regression analysis, wide QRS PEA was significantly associated with hyperkalemia (odds ratio = 2.86, 95% confidence interval: 1.80-4.53, P < 0.001).

Conclusions: Wide QRS PEA as an initial cardiac rhythm was significantly associated with hyperkalemia in cardiac arrest patients.

(C) 2021

1. Introduction

Sudden cardiac arrest is a major Public health concern with an extremely poor prognosis. Survival until hospital discharge for out-of- hospital cardiac arrest (OHCA) cases is ~10%, and the survival until hos- pital discharge for in-hospital cardiac arrest cases is ~20% [1-3]. To improve the prognosis of cardiac arrest patients, the Advanced life support guidelines of the American Heart Association (AHA) rec- ommend rapid electrocardiogram (ECG) evaluation and treatment of reversible conditions that contribute to cardiac arrest during high- quality cardiopulmonary resuscitation (CPR) [4].

* Corresponding authors at: Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.

E-mail addresses: [email protected] (Y.-M. Kim), [email protected] (G.T. Lee), [email protected] (T.G. Shin).

In approximately 20%-30% of OHCA and 30%-50% of IHCA cases, pulseless electrical activity was reported as the first documented initial rhythm [5-8]. Once PEA is observed, it is important to quickly find and treat the Reversible causes of cardiac arrest, as represented by the “Hs & Ts” (hypovolemia, hypoxia, hydrogen ion (acidosis), hypo-/ hyperkalemia, hypothermia, Tension pneumothorax, cardiac tamponade, toxins, pulmonary thrombosis, Coronary thrombosis) [4]. Among these, hyperkalemia is an electrolyte imbalance that can cause fatal arrhythmia and lead to cardiac arrest [9-13]. Emergent treatments including Calcium gluconate/chloride (to stabilize the cardiac myocyte membrane) and potassium-lowering agents should be administered to manage hyperkalemia [14]. ECG characteristics observed in the pres- ence of hyperkalemia include Conduction abnormalities, bradycardia, and wide QRS interval with bizarre QRS morphology. These characteris- tics increase suspicion of hyperkalemia according to the clinical scenario [15]. However, the relationship between hyperkalemia and initial rhythm pattern in cardiac arrest patients is still unknown.

https://doi.org/10.1016/j.ajem.2021.02.024

0735-6757/(C) 2021

The aim of this study was to evaluate the relationship between hyperkalemia and wide QRS complex in cardiac arrest patients showing PEA for initial ECG rhythm.

1. Methods
   1. Study design and population

This was a retrospective observational study of patients whose initial ECG rhythm showed PEA when treated for cardiac arrest at Samsung Medical Center (a 1960-bed, university-affiliated, tertiary referral hos- pital with an annual census of 70,000 patients located in Seoul, South Korea), from February 2010 to December 2019. All OHCA and IHCA pa- tients over the age of 18 who showed initial PEA rhythm during this pe- riod were included in the study. Patients were excluded if their potassium level was not measured during cardiac arrest, there was no record of initial ECG rhythms, the quality of scanned ECG rhythms was poor, or rhythms were poorly recorded, making them unreadable.

• 1. Data collection and outcome measurements

We retrospectively reviewed a cardiac arrest registry that was pro- spectively collected for CPR quality improvement at Samsung Medical Center. The following variables were collected from the registry and electronic medical records: age, sex, preexisting conditions (cardiovas- cular disease, pulmonary disease, diabetes, chronic kidney disease (CKD), malignancy, cerebrovascular accident (CVA), receiving dialysis), bystander witnessed cardiac arrest, bystander provided CPR, arrest loca- tion, Laboratory test results (including pH, HCO₃, creatinine, and initial potassium level), drug intervention (including sodium bicarbonate, cal- cium gluconate, or epinephrine), one-month survival, six-month sur- vival, and initial ECG rhythm. Wide QRS PEA was defined as a QRS interval of 120 ms or more. QRS intervals from patients’

electrocardiograms were measured separately by two emergency phy- sicians and, if the two physicians agreed, the initial rhythm was consid- ered to be wide QRS PEA. Hyperkalemia was defined as a serum potassium level > 5.5 mmol/L. The primary outcome of this study was the presence of hyperkalemia in initial laboratory tests.

• 1. Statistical analyses

The baseline characteristics of patients with wide versus narrow QRS complexes were compared. Data are represented by median values with interquartile ranges (IQR) for continuous variables and numbers with percentages for categorical variables. We performed Wilcoxon rank- sum tests for continuous variables and chi-square tests for categorical variables. To evaluate the effect of usual kidney function on the relation- ship between wide QRS complex and hyperkalemia, subgroup analyses were performed according to the patient’s medical history of chronic kidney disease. Multivariable logistic regression analysis was performed to evaluate the relationship between wide QRS PEA and hyperkalemia, including adjusted variables that exhibited significant differences be- tween the narrow QRS group and the wide QRS group in the overall study population and subgroups. Odds ratios (OR) with 95% confidence intervals (CI) were calculated and P-values <0.05 were considered sig- nificant. Data were analyzed using STATA software, version 15.1 (STATA Corporation, College Station, TX, USA).

• 1. Ethics

The Samsung Medical Center Institutional Review Board (IRB file number: 2020-08-001-001) approved this study, and the requirement for informed consent was waived because of the retrospective nature of the study. Interventions were not applied and we analyzed anonymized clinical data.

From Feb 2010 to Dec 2019,

Total 3024 OHCA and IHCA episodes were screened for this study

Non-PEA episodes (n=1700)

1324 PEA episodes

No serum potassium measurement (n=378)

946 PEA episodes

With serum potassium measurement

No ECG records or unreadable due to poor quality (n=329)

617 PEA episodes

With serum potassium measurement

Available for analysis of QRS complex

Narrow QRS PEA group (n=506)

Wide QRS PEA group (n=111)

Fig. 1. Study flow diagram.

1. Results
   1. Baseline characteristics

In this study, we screened 3024 episodes of OHCA or IHCA for eligi- bility, among whom, 1324 episodes had an initial electrocardiogram showing PEA at the time of cardiac arrest. Of these PEA cases, there were 378 episodes in which serum potassium level was not measured and 329 episodes for which initial ECG rhythm strip was either not re- corded at the time of cardiac arrest or the strip could not be clearly read due to baseline wandering or low quality of scanned and comput- erized photographs. Finally, a total of 617 episodes were included in this study. Among them, 111 were placed in the wide QRS complex group and 506 episodes were placed in the narrow QRS complex group (Fig. 1).

Table 1

Baseline characteristics of all patients, the narrow QRS group, and the wide QRS group

Characteristics	Overall	Narrow QRS n = 506	Wide QRS n = 111	P
Age, years (range) Male sex, no. (%)	65.0 (53.0-74.0) 365 (59.2%)	64.0 (53.0-74.0) 290 (57.3%)	68.0 (55.0-76.0) 75 (67.6%)	0.047 0.047
Pre-existing conditions, no. (%) Cardiovascular	336 (56.1%)	270 (55.0%)	66 (61.1%)	0.246
Pulmonary	84 (14.0%)	66 (13.4%)	18 (16.7%)	0.382
Diabetes	202 (33.7%)	155 (31.6%)	47 (43.5%)	0.017
Chronic kidney disease	126 (21.0%)	100 (20.4%)	26 (24.1%)	0.392
Malignancy	268 (44.7%)	231 (47.1%)	37 (34.3%)	0.016
CVA	58 (9.7%)	47 (9.6%)	11 (10.2%)	0.850
On dialysis	70 (11.7%)	52 (10.6%)	18 (16.7%)	0.075
Bystander witnessed, no. (%)	571 (93.3%)	469 (93.6%)	102 (92.0%)	0.512

The baseline characteristics of all patients, the narrow QRS complex group, and the wide QRS complex group are described in Table 1. The median age of this study population was 65 years (IQR: 53-74), and the proportion of males was 59.2% (n = 365). The wide QRS group was older (68 years, IQR: 55-76 vs. 64 years, IQR: 53-74; P = 0.047) and had a higher proportion of males (67.6% vs. 57.3%, P = 0.047) than the narrow QRS group. Compared with the narrow QRS group, pa- tients in the wide QRS group were more likely to have a history of dia- betes (43.5% vs. 31.6%, P = 0.017) and less likely to have a history of malignancy (34.3% vs. 47.1%, P = 0.016). In the wide QRS group, by- stander CPR was less frequently performed (75.7% vs. 84.2%, P = 0.033) and there were more OHCA cases (36.9% vs. 21.3%, P = 0.001). There were no significant differences in the 1-month (18.9% vs. 24.0%, P = 0.266) and 6-month (12.8% vs. 14.9%, P = 0.655) survival rates be- tween the two groups.

• 1. Comparison of laboratory data

The potassium levels for the QRS complex groups are summarized in Table 2. The median potassium level was 4.8 mmol/L (IQR: 4.0-5.7) for all patients. The median potassium level in the wide QRS group was sig- nificantly higher than in the narrow QRS group (5.4 mmol/L, IQR: 4.4-6.7 vs. 4.6 mmol/L, IQR: 4.0-5.6, P < 0.001). This trend remained constant regardless of CKD presence or dialysis. When QRS groups were further stratified by CKD presence or dialysis, overall potassium levels were higher, and the difference in potassium levels tended to be greater between the wide QRS group and the narrow QRS group in the presence of CKD and dialysis. In terms of laboratory data, the wide QRS group had higher Creatinine levels (1.73 mg/dL, IQR: 1.24-3.14 vs. 1.24 mg/dL, IQR: 0.88-2.01, P < 0.001) and lower pH (7.03, IQR:

6.89-7.16 vs. 7.14, IQR: 6.98-7.27, P < 0.001) than the narrow QRS

Bystander CPR, no. (%) Arrest location, no. (%)	509 (82.6%)	425 (84.2%)	84 (75.7%)	0.033	group (Table 2).
OHCA	149 (24.2%)	108 (21.3%)	41 (36.9%)	0.001
IHCA	468 (75.8%)	398 (78.7%)	70 (63.1%)	0.001
Drug intervention, no.					3.3. Frequency of hyperkalemia

Among all patients, 49.6% (n = 55/111) in the wide QRS group had hyperkalemia, significantly more than the 26.7% of patients (n = 135/

(%)
Sodium bicarbonate	189 (30.6%)	146 (28.9%)	43 (38.7%)	0.041
Calcium gluconate	133 (21.6%)	87 (17.2%)	46 (41.4%)	<0.001
Epinephrine	585 (94.8%)	475 (93.9%)	110 (99.1%)	0.025

One-month survival	142 (23.1%)	121 (24.0%)	21 (18.9%)	0.266	506) in the narrow QRS group (P < 0.001) (Fig. 2). Proportions of
Six-month survival	89 (14.5%)	75 (14.9%)	14 (12.8%)	0.655	hyperkalemia were also higher in the wide QRS group compared with

CVA, cerebrovascular accident; CPR, cardiopulmonary resuscitation; OHCA, out-of-hospi- tal cardiac arrest; IHCA, in-hospital cardiac arrest.

the narrow QRS group among patients with CKD (61.5% vs. 30.0%,

P < 0.001) or dialysis (66.7% vs. 36.5%, P < 0.001) (Fig. 3).

Table 2

Laboratory data

	Overall	Narrow QRS	Wide QRS	P
Potassium, mmol/L Overall	4.8 (4.0-5.7)	4.6 (4.0-5.6)	5.4 (4.4-6.7)	<0.001
Chronic kidney disease	N = 617	n = 506	n = 111
Yes No Dialysis	4.9 (4.2-6.0) n = 126 4.7 (4.0-5.7) n = 473	4.8 (4.2-5.7) n = 100 4.6 (4.0-5.5) n = 391	5.9 (4.5-7.9) n = 26 5.4 (4.4-6.6) n = 82	0.001 <0.001
On dialysis No dialysis pH HCO3, mmol/L	5.3 (4.6-6.1) n = 70 4.7 (4.0-5.7) n = 529 7.11 (6.96-7.26) n = 598 17.3 (12.3-22.5)	5.0 (4.5-5.9) n = 52 4.6 (4.0-5.5) n = 439 7.14 (6.98-7.27) n = 491 17.5 (12.4-23.1)	6.35 (5.3-8.2) n = 18 5.4 (4.4-6.6) n = 90 7.03 (6.89-7.16) n = 107 16.4 (11.8-20.7)	0.010 <0.001 <0.001 0.048
Creatinine, mg/dL	n = 598 1.32 (0.91-2.17) n = 417	n = 491 1.24 (0.88-2.01) n = 339	n = 107 1.73 (1.24-3.14) n = 78	<0.001

Fig. 2. Comparison of hyperkalemia according to wide QRS PEA rhythm in overall patients.

3.4. Multivariable logistic regression analysis

In multivariable logistic regression analyses for predicting hyperkalemia, wide QRS was associated with hyperkalemia after adjusting for confounding variables (OR = 2.86, 95% CI: 1.80-4.53, P < 0.001) (Table 3 and Supplementary Table S1), and this trend was

significant regardless of the presence of CKD. The adjusted odds ratio of wide QRS for hyperkalemia was relatively higher in the subgroup with CKD (OR = 4.56, 95% CI: 1.31-15.82, P = 0.017) compared with

the subgroup without CKD (OR = 2.79, 95% CI: 1.63-4.77, P < 0.001) (Table 3).

1. Discussion

The main finding of this study is that wide QRS complex on initial ECG in PEA cardiac arrest was associated with hyperkalemia and that potassium levels in patients with wide QRS PEA were also significantly higher than in those with narrow QRS. The association between wide QRS PEA and hyperkalemia was consistent after adjusting for confound- ing factors including age, sex, preexisting conditions, and cardiac arrest variables, regardless of the presence of chronic kidney disease.

Some researchers have suggested that wide QRS PEA can be used to identify the cause of cardiac arrest [16,17]. However, the association be- tween cause of cardiac arrest and ECG rhythm pattern is controversial. In a previous study, abnormal ECG patterns were frequent in the early stages of PEA occurring in the hospital, but no characteristic patterns re- lated to underlying cause or survival were observed [18]. Another study found that neither the PEA rate nor QRS width was correlated with sur- vival or Neurological prognosis [19]. Although hyperkalemia can cause QRS widening, it remains unclear how the two factors are actually cor- related in cardiac arrest situations.

Emergency physicians can evaluate physical signs, laboratory tests, ultrasound results, and electrocardiograms to identify reversible causes

Fig. 3. Comparison of hyperkalemia according to wide QRS PEA rhythm and kidney dysfunction A. Hyperkalemia in patients without chronic kidney disease B. Hyperkalemia in patients with chronic kidney disease C. Hyperkalemia in patients not receiving regular dialysis treatment D. Hyperkalemia in patients receiving regular dialysis treatment.

Table 3

Odds ratios from wide QRS PEA for hyperkalemia presence

	Unadjusted OR	95% CI	P	Adjusted OR	95% CI	P
Overall (N = 617)	2.70	1.73-4.21	<0.001	2.86	1.80-4.53	<0.001
Chronic kidney disease Yes (n = 126)	3.73	1.40-9.96	0.008	4.56	1.31-15.82	0.017
No (n = 473)	2.60	1.56-4.35	<0.001	2.79	1.63-4.77	<0.001

PEA, pulseless electrical activity.

of cardiac arrest when performing cardiopulmonary resuscitation, but it is very challenging. The results of this study suggest that an initial car- diac rhythm with wide QRS PEA indicates an increased possibility of preexisting hyperkalemia. Additionally, wide QRS complexes were more strongly associated with hyperkalemia in patients with CKD com- pared with patients without CKD. This is consistent with previous find- ings that higher risk of cardiac arrest and hyperkalemia are associated with CKD and are more common in patients receiving dialysis compared with the general population [20,21]. We suggest that wide QRS PEA can be interpreted using clinical information and previous medical history because it is not a confirmatory predictor for hyperkalemia. Anti-hyperkalemic agents may be prepared while physicians await Lab- oratory results if the patient’s initial rhythm shows wide QRS PEA.

This study has several limitations. First, this was a retrospective single-center study in the emergency department of a tertiary referral hospital, and the sample size was small. Thus, our results may not be generalizable to all cardiac arrest patients. Second, due to the unpredict- able and sudden nature of cardiac arrest, a significant number of pa- tients, for whom initial ECG rhythms were not recorded or were unreadable due to poor quality and whose serum potassium levels were not measured, were excluded from this study. This may have caused selection bias. Third, in clinical situations the timings of serum potassium level measurement and initial ECG records are variable. In this study, the first ECG rhythm record and the first serum potassium level measured during resuscitation before the first return of spontane- ous circulation (ROSC) were used. Fourth, wide QRS duration is not spe- cific to hyperkalemia. Several factors, including prolonged arrest or metabolic conditions, may affect the QRS width of PEA rhythm, al- though we adjusted for observed confounders. Finally, hyperkalemia might not be the main cause of arrest. We did not evaluate the effects of potassium-lowering treatment during resuscitation.

1. Conclusions

The observation of wide QRS PEA as the initial cardiac rhythm was associated with hyperkalemia in patients with OHCA or IHCA. Wide QRS PEA rhythm may increase clinical suspicion for hyperkalemia among reversible causes of arrest. Further research is needed to confirm this finding and evaluate its clinical usefulness during resuscitation.

Conflicts of interest

The authors have no conflicts of interest to declare.

Funding

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

Sources of support

None.

Previous presentations

None.

Acknowledgements

None.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi. org/10.1016/j.ajem.2021.02.024.

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