Highlights
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The rate of patients with favorable neurological outcomes was lower in patients who converted to PEA than in those with a sustained shockable rhythm (12.9 % vs 26.4 %, P <.01).
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By multivariable analysis, conversion to PEA was significantly associated with a lower rate of favorable neurological outcomes (odds ratio 0.42, 95% confidence interval 0.27-0.66; P < 0.01).
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The rate of favorable neurologic outcomes did not significantly differ between the patients who converted to PEA after hospital arrival and those with a sustainable shockable rhythm.
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Early conversion to PEA may be a factor for lower favorable neurological outcomes compared to those with sustained shockable rhythm.
ABSTRACT
Aim
Shockable rhythm on initial electrocardiogram is a predictor of favorable neurological outcomes of out-of-hospital cardiac arrest in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). The present study evaluated the impact of conversion from shockable rhythm to pulseless electrical activity (PEA) before ECPR on patient outcomes.
Methods
In this secondary analysis of the data from SAVE-J II, a retrospective multicenter registry including 36 participating institutions in Japan, patients with initial shockable rhythm were categorized into those with conversion to PEA and sustained shockable rhythm. The primary outcome was favorable neurological outcome, defined as a cerebral performance category of 1-2 at hospital discharge.
Results
The final cohort included 718 patients. The rate of favorable neurological outcomes was lower in patients who were converted to PEA than in those with sustained shockable rhythm (12.9 % vs 26.4 %, P <.01). By multivariable analysis, conversion to PEA was significantly associated with a lower rate of favorable neurological outcomes (odds ratio 0.42, 95% confidence interval 0.27-0.66; P <.01). The rates of favorable neurologic outcomes were 9.8%, 18.0%, and 21.4% ( P =.06) in patients who converted to PEA, during emergency medical services transport, at hospital arrival, and before ECMO initiation, respectively. However, outcomes did not significantly differ between the patients who converted to PEA after hospital arrival and those with sustained shockable rhythm (19.6% vs 26.4%, P =.19).
Conclusions
Patients with conversion to PEA before ECPR were associated with a lower rate of favorable neurological outcomes in those with an initial shockable rhythm. Especially, early conversion to PEA, ie, during EMS transport, may be a factor for lower favorable neurological outcomes compared to those with sustained shockable rhythm.
Background
Extracorporeal cardiopulmonary resuscitation (ECPR) rapidly deploys venoarterial extracorporeal membrane oxygenation (VA ECMO) to provide immediate cardiovascular support for patients with cardiac arrest (CA) who are unresponsive to conventional cardiopulmonary resuscitation (CPR). Favorable neurological outcomes may be achieved using ECPR in patients with CA and shockable rhythms, such as ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT), on initial electrocardiogram (ECG). Therefore, previous studies investigating the utility and efficacy of ECPR have selected shockable rhythms as the initial rhythms. ,,
In clinical settings, initial shockable rhythms often convert to nonshockable rhythms, such as pulseless electrical activity (PEA) and asystole before ECMO initiation. Importantly, studies reported that conversion to asystole from an initial shockable rhythm was associated with unfavorable outcomes on ECPR. , In patients with CA, PEA was associated with more favorable outcomes compared to asystole ; however, neurological outcomes of conversion to PEA from an initial shockable rhythm in patients undergoing ECPR remain unclear and no study has evaluated the associations of the details of conversion, such as the timing of conversion, with patient outcomes.
We hypothesized that conversion to PEA was associated with a lower rate of favorable neurological outcomes in patients with an initial shockable rhythm. This study aimed to investigate the relationship of conversion from an initial shockable rhythm to PEA with neurological outcomes and survival, including the timing of conversion, in patients who underwent ECPR using the largest ECPR registry database of patients with out-of-hospital cardiac arrest (OHCA) in Japan.
Material and methods
Study design and setting
This was a secondary analysis of the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan II (SAVE-J II) study. The SAVE-J II study was a retrospective multicenter registry study including patients with OHCA resuscitated using ECPR, including 36 participating institutions in Japan. The study design and data collection methods have been previously described. Briefly, the SAVE-J II study included consecutive patients aged ≥18 years who were resuscitated using ECPR for OHCA. The patients were admitted to the participating institutions between January 1, 2013 and December 31, 2018. In the present study, ECPR was defined as resuscitation using VA ECMO in patients with refractory CA.
The SAVE-J II study was registered in the University Hospital Medical Information Network Clinical Trials Registry and the Japanese Clinical Trial Registry (registration number: UMIN000036490). The SAVE-J II study was approved by the Institutional Review Boards of Kagawa University (approval number: 2018-110) and all participating institutions, including the Hyogo Emergency Medical Center (approval number: 2019002). The secondary analysis of the deidentified data in the present study was approved by the Institutional Review Board of the Hyogo Emergency Medical Center (approval number: 2024014). The requirement for informed consent was waived due to the retrospective study design.
Study population
Among the patients in the SAVE-J II study cohort, those aged ≥18 years who had an initial shockable rhythm and were initiated on VA ECMO before intensive care unit admission were included in the present study. An initial shockable rhythm was defined as a rhythm determined to be shockable by the emergency medical services (EMS) at the scene. The exclusion criteria were as follows: (1) patients with an initial nonshockable rhythm, such as PEA and asystole, or unknown rhythm; (2) those with an external OHCA etiology, such as hypothermia, drug intoxication, trauma, suffocation, and unknown intrinsic or extrinsic OHCA etiology; (3) those who achieved conversion to asystole or return of spontaneous circulation (ROSC) between EMS transport and ECMO initiation; and (4) those transferred from another hospital.
Data collection
The following data were collected from the SAVE-J II study database: age; sex; comorbidities; location of CA; the incidence of witnessed CA and bystander CPR; defibrillation; prehospital administration of adrenaline, cardiac rhythm at hospital arrival, body temperature; time course; CA etiology; in-hospital treatments, such as emergency coronary angiography, percutaneous coronary intervention, and targeted temperature management; in-hospital survival; and neurological outcome. The prehospital was defined as the duration from EMS arrival at the scene to hospital arrival, and the in-hospital as the duration after arrival at the hospital. Shockable rhythms were defined as VF, pVT, and rhythm for defibrillation detected with an automated external defibrillator by emergency medical staff. ROSC was defined as the confirmation of continuous pulsation for ≥1 min, whereas transient ROSC was defined as any palpable pulse or measurable blood pressure of >1 min before ECMO initiation, before and after hospital arrival. Cardiac waveform conversion to PEA was defined as conversion of the waveform from the initial shockable rhythm to PEA at any time between EMS arrival and ECMO initiation. Time courses, such as the time from collapse and ambulance call to arrival, and time from arrival to ECMO initiation, were based on previously reported definitions. Estimated low-flow time was defined as the time from CA to the establishment of ECMO in patients who had CA in an ambulance and as the time from calling an ambulance to the establishment of ECMO in patients who had CA at a location other than the ambulance. The definitions of CA etiology were based on a previous study. Hypothermia was defined as being diagnosed by a physician or a body temperature of ˂30°C at admission.
Outcome measures
The primary outcome was the favorable neurological outcome evaluated based on the cerebral performance category (CPC) at the time of hospital discharge. Favorable and unfavorable outcomes were defined as CPCs of 1or 2 and 3, 4, or 5, respectively. The secondary outcome was the rate of survival at the time of hospital discharge.
Statistical analysis
Continuous and categorical variables were expressed as medians with interquartile ranges (IQRs) and as proportions, respectively. The baseline patient characteristics, neurological outcomes, survival rate at hospital discharge, and cardiac or noncardiac etiologies were compared using the Mann–Whitney U test for continuous variables and Fisher’s exact or the chi-square test for categorical variables, as appropriate. Subgroup analysis included only patients who converted to PEA. Patient characteristics and outcomes were compared between the patients categorized according to the timing of conversion to PEA (during EMS transport, at hospital arrival, or before ECMO initiation). Continuous variables were compared using the Kruskal–Wallis test, and categorical variables were compared using the chi-square test. Multivariate logistic regression analyses were performed to evaluate factors associated with a favorable neurological outcome and survival at hospital discharge, with model. In this model adjustment for the following potential confounding factors: age, sex, witnessed CA, bystander CPR, prehospital administration of adrenaline, sustained shockable rhythm, and estimated low-flow time. ,,,,, For all analyses, statistical significance was set at a 2-sided P value of ≤.05. Statistical analyses were performed using EZR version 1.60 (Saitama Medical Center, Jichi Medical University, Saitama, Japan). Missing data were not replaced or estimated, as the missingness of covariates for primary analysis was not severe and random. ,
Results
Of the 2,157 patients registered in the SAVE-J II study database, 718 patients with an initial shockable rhythm on ECG, including 286 patients who converted to PEA and 432 patients with sustained shockable rhythm, were included in the present study ( Figure 1 ).
Study flow chart.
External etiology included hypothermia (n = 52), drug intoxication (n = 6), trauma (n = 6), suffocation (n = 1), others (n = 8), and unknown intrinsic or extrinsic etiologies (n = 54). ECPR, extracorporeal cardiopulmonary resuscitation; EMS, emergency medical services; ICU, intensive care unit; PEA, pulseless electrical activity; ROSC, return of spontaneous circulation; VA ECMO, venoarterial extracorporeal membrane oxygenation
Baseline characteristics of the study population
The baseline characteristics are presented in Table 1 . Briefly, the median age was 60 (IQR, 49-68) years, and 87.7 % of the patients were male. In the overall, the rate of patients who had witnessed CA, received bystander CPR, and prehospital administration of adrenaline were 80.4, 57.7, and 39.1 %, respectively. The median estimated low-flow time was 52 (44-62) minutes. Overall, 93.2 % of patients had CA due to a cardiac etiology, such as acute coronary syndrome, arrhythmia, and myopathy, among others; 85.4 % of the patients underwent emergency coronary angiography; and 50.1 % of the patients underwent percutaneous coronary intervention. The rates of pupillary reflex, emergency coronary angiography, and intra-aortic balloon pumping were significantly lower in patients who converted to PEA than in those with a sustained shockable rhythm. The time period from hospital arrival to ECMO initiation and the estimated low-flow time were significantly longer in patients with conversion to PEA than in those with a sustained shockable rhythm, whereas the time period from the collapse to the hospital arrival and the time period from the call for an ambulance to the hospital arrival were not significantly different between the 2 groups.
Table 1
Comparison of baseline characteristics of the ECG rhythm group
|
Total
(N = 718) |
Conversion to PEA
(N = 286) |
Sustained shockable rhythm
(N = 432) |
P -value | |
|---|---|---|---|---|
| Age, years | 60 [49-68] | 60 [50-68] | 60 [48-68] | 0.62 |
| Sex, Male | 630 (87.7) | 256 (69.2) | 374 (75.3) | 0.25 |
| Witnessed cardiac arrest | 577 (80.4) | 225 (82.1) | 352 (88.7) | 0.39 |
| Bystander CPR | 414 (57.7) | 159 (55.6) | 255 (64.7) | 0.40 |
| Prehospital AED use | 584 (81.3) | 227 (79.4) | 357 (82.6) | 0.28 |
| Prehospital adrenaline by EMS | 281 (39.1) | 121 (42.3) | 160 (37.0) | 0.16 |
| Time course (min) | ||||
| – Time from collapse to arrival | 30 [24-37] | 34 [27-42] | 33 [26-41] | 0.45 |
| – Time from call ambulance to arrival | 33 [26-41] | 34 [27-42] | 33 [26-41] | 0.22 |
| Body temperature | 35.1 [34.1-35.8] | 35.0 [34.3-35.8] | 35.1 [34.1-35.8] | 0.57 |
| Pupillary reflex | 39 (5.4) | 7 (2.4) | 32 (7.4) | <0.01 |
| Agonal aspiration | 80 (11.1) | 24 (8.4) | 56 (13.0) | 0.09 |
| Laboratory data | ||||
| – pH | 6.95 [6.85-7.07] | 6.92 [6.84-7.05] | 6.96 [6.86-7.07] | 0.06 |
| – Potassium (mEq/L) | 3.8 [3.3-4.5] | 4.0 [3.4-4.5] | 3.8 [3.2-4.5] | 0.09 |
| – Glucose (mg/dl) | 319 [255-382] | 321 [253-389] | 319 [258-380] | 1.00 |
| – Serum lactate level (mmol/L) | 12.9 [10.3-15.9] | 12.7 [10.0-15.6] | 13.0 [10.5-16.0] | 0.18 |
| Time course (min) | ||||
| – Time from arrival to ECMO initiation | 20 (14-29) | 22 [16-31] | 19 [14-28] | <0.01 |
| – Estimated low flow time | 52 (44-62) | 55 [46-65] | 51 [42-61] | <0.01 |
| Etiology | 0.19 | |||
| Cardiac etiology | 669 (93.2) | 259 (90.6) | 410 (94.9) | |
| – Acute coronary syndrome | 457 (63.6) | 183 (64.0) | 274 (63.4) | |
| – Arrhythmia | 117 (16.3) | 41 (14.3) | 76 (17.6) | |
| – Myopathy | 56 (7.8) | 20 (7.0) | 36 (8.3) | |
| – Myocarditis | 8 (1.1) | 2 (0.7) | 6 (1.4) | |
| – Other cardiac etiology | 31 (4.3) | 13 (4.5) | 18 (4.2) | |
| Noncardiac etiology | 49 (6.8) | 27 (9.4) | 22 (5.1) | |
| – Acute aortic disease | 20 (2.8) | 14 (4.9) | 6 (1.4) | |
| – Pulmonary embolism | 3 (0.4) | 1 (0.3) | 2 (0.5) | |
| – Primary cerebral disorders | 3 (0.4) | 1 (0.3) | 2 (0.5) | |
| – Infection | 2 (0.3) | 2 (0.7) | 0 (0) | |
| – Others | 12 (1.7) | 6 (2.1) | 6 (1.4) | |
| – Unknown | 9 (1.3) | 3 (1.0) | 6 (1.4) | |
| Emergency coronary angiography | 603 (85.4) | 225 (78.7) | 378 (87.5) | <0.01 |
| Percutaneous coronary intervention | 360 (50.1) | 145 (50.7) | 215 (49.8) | 0.54 |
| Intra-aortic balloon pumping | 507 (70.6) | 180 (62.9) | 327 (75.7) | <0.01 |
| Anticoagulation | ||||
| – Unfractionated heparin | 502 (69.9) | 194 (67.8) | 308 (71.3) | 0.33 |
| – Nafamostat mesylate | 40 (5.6) | 14 (4.9) | 26 (0.6) | 0.67 |
| Outcome | ||||
| – Neurological outcome | <0.01 | |||
| CPC: 1 | 109 (15.2) | 27 (9.4) | 82 (19.0) | |
| CPC: 2 | 42 (5.8) | 10 (3.5) | 32 (7.4) | |
| CPC: 3 | 37 (5.2) | 12 (4.2) | 25 (5.8) | |
| CPC: 4 | 70 (9.7) | 34 (11.9) | 36 (8.3) | |
| CPC: 5 | 460 (64.1) | 203 (71.0) | 257 (59.5) | |
| – Survival | 258 (35.9) | 83 (29.0) | 175 (40.5) | <0.01 |
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