Abstract
Objective
Cardiopulmonary arrest (CPA) rhythms are classified into shockable and non-shockable categories. Pulseless electrical activity (PEA) is a non-shockable rhythm defined as the absence of a palpable pulse despite organized electrical activity on the monitor. However, PEA encompasses a spectrum from complete cardiac inactivity to cardiogenic shock. Pseudo-PEA (p-PEA) represents an intermediate state, marked by electrical activity and varying degrees of myocardial motion. While PEA and p-PEA are treated in a similar manner to asystole, their distinct characteristics suggest a potential need for differential treatment, especially for p-PEA, which may benefit from positive inotropic therapy. This study aims to establish diagnostic criteria for PEA, p-PEA, and cardiogenic shock and assess their responses to inotropic therapy.
Materials and Methods
This retrospective, video-based study was conducted in the emergency department of a university hospital. Archived ultrasound (USG) video recordings from August 2017 to April 2021 were analyzed. Adult CPA patients with documented cardiac activity and positive inotropic therapy during cardiopulmonary resuscitation (CPR) were included. Data on demographic details, CPR characteristics, treatment interventions, and clinical outcomes were collected. Statistical analysis was performed using SPSS v24.0 with a significance level of p<0.05.
Results
Out of 94 patients, 12 met the inclusion criteria. Patients were divided into three groups: those with valvular motion alone (n=4), valvular and myocardial motion (n=6), and cardiogenic shock (n=2). Return of spontaneous circulation was achieved in all patients with both valvular and myocardial motion after inotropic therapy (p=0.002), but not in those with only valvular motion.
Conclusion
Patients with valvular motion alone were classified as PEA, while those with myocardial activity were defined as p-PEA. Positive inotropic therapy was effective in p-PEA but not in PEA. USG, including carotid and femoral examinations, can aid in differentiating cardiogenic shock from p-PEA, emphasizing the need for specific treatment protocols. Further research is essential to validate these findings.
Introduction
Cardiopulmonary arrest (CPA) rhythms are generally categorized into shockable and non-shockable rhythms [1, 2]. To date, significantly more research has focused on shockable rhythms, including the development of defibrillation [3], with many guidelines providing more extensive coverage on this topic [4]. Shockable rhythms in CPA are characterized by irregular electrical activity accompanied by the absence of a palpable pulse, and defibrillation forms the cornerstone of their treatment. Non-shockable rhythms, on the other hand, are divided into asystole and pulseless electrical activity (PEA). Unlike shockable rhythms, PEA demonstrates organized electrical activity and frequently a certain degree of regular cardiac activity. However, its treatment follows the same protocol asystole, which lacks both electrical activity and cardiac motion entirely [4].
PEA is defined as an arrest rhythm characterized by the absence of a palpable pulse despite the presence of an organized electrical rhythm on the monitor [5, 6]. However, this definition is rather superficial, as PEA encompasses a wide spectrum ranging from a complete absence of cardiac activity to cardiogenic shock with the return of spontaneous circulation (ROSC), including various degrees of cardiac activity in between. This ambiguity is particularly notable in the absence of cardiac imaging, as routine use of cardiac ultrasound (USG) for rhythm assessment remains a topic of debate [2, 7, 8]. The intermediate condition, between PEA and cardiogenic shock, where varying degrees of valvular and myocardial activity accompany electrical activity, is often referred to as pseudo-PEA (p-PEA) [9]. p-PEA can only be diagnosed through cardiac USG. It is considered a more severe form of cardiogenic shock, in which perfusion pressure is inadequately maintained, ultimately resulting in an undetectable pulse [10]. As evident, p-PEA shares close ties with both PEA, and cardiogenic shock and lacks clearly defined boundaries. The differentiation among these entities fundamentally revolves around two factors: the presence or absence of a palpable pulse and the existence of cardiac activity. Despite numerous studies on pulse detection [11], manual palpation remains the standard method for assessing the pulse during cardiopulmonary resuscitation (CPR) in routine practice. However, manual pulse checks are subjective, varying between patients and practitioners [11, 12]. The debate regarding whether the carotid or femoral artery is the most accurate site for pulse palpation further complicates the matter, as the optimal site may vary depending on the patient [12]. It is evident that a practitioner may not perceive identical pulse intensities in a morbidly obese versus an extremely thin patient, and even two practitioners assessing the same patient may arrive at differing conclusions. The second challenge lies in the confusion surrounding the distinction between PEA, p-PEA, and cardiogenic shock based on cardiac activity, even when cardiac USG is employed. For instance, in a patient with organized electrical activity and no detectable pulse, echocardiography may reveal no cardiac activity, isolated valvular motion, partial myocardial motion in addition to valvular movement, or coordinated myocardial motion involving the entire myocardium. This spectrum blurs the line between where PEA ends and p-PEA begins. In terms of treatment, PEA and p-PEA are currently managed in the same way as asystole. However, p-PEA, given its close relationship with cardiogenic shock, represents a distinct clinical condition that may benefit from adjunctive pharmacological therapies, such as positive inotropes, in addition to CPR, potentially leading to different outcomes [9, 13]. Cardiogenic shock, on the other hand, is not a cardiac arrest state but rather a condition with a specific therapeutic approach, primarily involving positive inotropic agents. These entities represent clinical conditions with distinct treatment needs and outcomes, yet they are almost uniformly categorized as PEA in current guidelines [2]. Distinguishing among these definitions has significant implications for treatment, particularly in determining the need for ongoing CPR and the initiation of positive inotropic therapy, both of which are of critical importance.
This retrospective study, based on echocardiographic video recordings, aims seeks to establish the differential diagnosis of PEA, p-PEA, and cardiogenic shock with a treatment-focused approach, as well as to identify patients who may benefit from positive inotropic therapy.
Materials and Methods
Study Design and Setting
This study was conducted as a retrospective video-based analysis in the critical care unit of the emergency medicine department at a tertiary university hospital. The critical care area of this emergency department is equipped with 16 beds for vital monitoring, 6 mechanical ventilators, and USG devices, including two portable units, one fixed unit, and one with a transesophageal probe. All critical patients and those experiencing CPA are managed in this area. Bedside USG examinations of patients in the critical care unit are performed by senior residents under the supervision of five attending physicians or faculty members, and video recordings are systematically archived. The study retrospectively reviewed archived video recordings from August 2017, when regular video archiving began on the USG devices, to April 2021. Ethical approval for the study was obtained from the İzmir Katip Çelebi University Non-Interventional Clinical Research Ethics Committee on April 15, 2021 (decision number:0214, date: 15.04.2021).
Study Population
The study included patients aged 18 years or older who experienced in-hospital or out-of-hospital CPA and had cardiac USG imaging performed during CPR. The study population consisted of patients in whom any degree of cardiac activity was detected on these USG images, and who were subsequently initiated on positive inotropic therapy. Cardiogenic shock was defined as the presence of organized rhythm, echocardiographic evidence of myocardial activity, a weak palpable pulse with hypotension, and hemodynamic instability following ROSC. Patients were excluded if they had incomplete cardiac USG video recordings either before or after the initiation of positive inotropic therapy, if information was missing in physician or nurse observation forms, or if clinical outcome data were unavailable due to transfer to another hospital or incomplete contact information.
Data Collection and Study Protocol
During the study period, all recorded images from the three available USG devices were reviewed. All patients who underwent cardiac USG imaging during CPR were identified. These patients were cross-referenced with the hospital’s patient records; and those who received positive inotropic therapy during CPR were identified. The study population comprised patients with complete video recordings both before and after the initiation of positive inotropic therapy. Demographic data, chronic conditions, laboratory test results, CPR durations and outcomes, rhythms observed during CPR, treatment regimens, and interventions were applied, and, if ROSC was achieved, the return rhythm and vital signs were collected from the hospital’s digital patient records and follow-up forms. These details were recorded on patient data forms. Patients who achieved ROSC were followed until hospital discharge or death, and data on 24-hour and in-hospital clinical outcomes were documented.
Statistical Analysis
Descriptive statistics were calculated, including frequency, percentage, median, minimum (min.), and maximum (max.) values. Counts and percentages were reported for categorical variables, while min. and max. values and interquartile ranges were determined for numerical variables The normality of the distribution for continuous variables was assessed using histogram curves, Kurtosis-Skewness values, and the Shapiro-Wilks test. Group comparisons were performed using the chi-square test. All statistical analyses were conducted with SPSS version 24.0 software using a 95% confidence interval, with a significance level set at p<0.05.
Results
During the study period, cardiac USG recordings of 94 patients who underwent CPR in the emergency department’s critical care area were reviewed. Among these patients, 63 were identified as having received positive inotropic therapy during CPR. Of these, 11 had incomplete observation forms, and 40 lacked either pre- or post-inotropic therapy cardiac USG recordings. Consequently, 12 patients with complete cardiac USG recordings before and after positive inotropic therapy were included in the study. Among the included patients, 5 (42%) were female, and the mean age was 67±16 years. For 10 patients, dopamine and dobutamine were administered at a dose of 20 mcg/kg/min. during CPR, while 2 patients were classified as post-CPR cardiogenic shock and received 10 mcg/kg/min. of dopamine and dobutamine after CPR was completed. Patients in CPA at the initiation of positive inotropic therapy underwent CPR for a max. of an additional 30 minutes.
Of the patients with organized electrical activity on the monitor during CPR but no palpable pulse (Figure 1a-d) 4 (33%) exhibited only valvular motion on cardiac USG imaging obtained before positive inotropic therapy (Video 1a-4a). None of these patients showed significant changes in cardiac activity following inotropic therapy (Video 1b-4b). The general characteristics and CPR details for these patients are presented in Table 1.
In 6 patients (50%) who exhibited organized electrical activity on the monitor but no palpable pulse during CPR (Figure 2a-g), cardiac USG imaging before positive inotropic therapy revealed valvular motion with varying degrees of myocardial motion (Video 5a-10a). All these patients demonstrated significant improvement in cardiac activity following inotropic therapy (Video 5b-10b); and ROSC was achieved in all cases, allowing CPR to be terminated. However, all these patients experienced recurrent CPA within 24 hours and succumbed in the clinical units where they were admitted. The general characteristics and CPR details of these patients are presented in Table 2. A statistically significant difference was found between the group with only valvular motion and the group with both valvular and myocardial motion in terms of response to positive inotropic therapy (ROSC, p=0.002).
In the remaining two patients, ROSC was achieved during formal CPR, evidenced by the presence of a weak pulse and low blood pressure, in addition to the organized rhythm observed on the monitor (Figure 3a, b). Positive inotropic therapy was initiated after CPR completion. Pre-therapy cardiac USG revealed valvular motion with varying degrees of myocardial motion (Video 11a and 12a). Post-inotropic therapy, the USG showed significant improvement in cardiac activity (Video 11b, 12b). Among these, case 11 achieved 24-hour survival and was discharged without sequelae, while case 12 experienced recurrent CPA but succumbed within 24 hours. The general characteristics and CPR details for patients in cardiogenic shock are presented in Table 3.
The contractile strength comparison of the contractile strength of cardiogenic shock cases (case 11 and case 12) with p-PEA cases (case 6 and case 9) through echocardiographic evaluation, it was observed that their findings were remarkably similar.
The odds of ROSC were 117 times higher in p-PEA patients, with phi coefficient of 0.998, indicating an exceptionally large effect size. Clinically, this strongly supports the importance of identifying myocardial motion via echocardiography during CPR and suggests that p-PEA patients should not be treated identically to PEA patients without myocardial activity. Positive inotropic therapy may have a markedly different and more favorable impact in pseudo-PEA cases (Table 4).
Discussion
Pulse assessment is one of the primary diagnostic tools guiding CPR and is currently performed predominantly through manual palpation, a rudimentary method. However, numerous studies have demonstrated that this technique is practitioner- and patient-dependent, with limited reliability in low-cardiac-output ROSC scenarios and susceptibility to various factors such as cold extremities and obesity [14-17]. For these reasons, although not yet part of routine practice, alternative methods such as carotid USG, femoral USG, and cardiac USG are gaining popularity [11, 18]. Even with these instruments, the diagnostic boundaries between PEA, p-PEA, and cardiogenic shock remain unclear. Clinically, these entities exist on a spectrum. According to common understanding, PEA, characterized by a rhythm without any cardiac movement, lies at one end of the spectrum. p-PEA, where rhythm is accompanied by some degree of cardiac activity but no palpable pulse, occupies the middle. At the other end lies cardiogenic shock, characterized by rhythm, cardiac activity, a weak pulse, and low blood pressure [15, 19]. However, these broad definitions leave gaps, and no consensus has been established among researchers. For instance, in their study, Wu et al. [18] did not classify patients with only valvular motion observed on cardiac USG into either the PEA or p-PEA groups. Conversely, Devia Jaramillo et al. [20] classified patients with valvular motion alone as p-PEA. Similarly, no clear data exist regarding the threshold at which myocardial contractility transitions from p-PEA to cardiogenic shock. This distinction is typically made using manual pulse palpation, a subjective and potentially unreliable method. Thus, under current definitions, PEA, p-PEA, and even cardiogenic shock are closely related entities with potential clinical overlap [10, 21, 22]. Furthermore, p-PEA patients with organized rhythm and some degree of myocardial contraction are treated in the same way as asystole patients, who lack rhythm and cardiac activity entirely. To our knowledge, this study is the first to evaluate the differential diagnosis of PEA, p-PEA, and cardiogenic shock, as well as their responses to positive inotropic therapy, through detailed echocardiographic analysis. Among the four patients with only valvular motion observed on cardiac USG, none responded favorably to additional positive inotropic therapy. Conversely, all six patients with valvular motion and varying degrees of myocardial motion demonstrated a positive response to inotropic therapy, achieving ROSC. These findings suggest that patients with only valvular motion should be categorized as PEA and treated accordingly. Meanwhile, patients with both valvular motion and varying degrees of myocardial motion should be classified as p-PEA, and their treatment may benefit from the addition of positive inotropes. Furthermore, carotid and femoral USG could be effective tools for distinguishing between p-PEA and cardiogenic shock in the differential diagnosis.
Importantly, this study does not aim to recommend a specific pharmacological agent, but rather to highlight a subgroup of patients (p-PEA) that may respond to inotropic support, and to stimulate further research in this area.
The most significant secondary finding of this study is the contribution of bedside USG to the diagnosis of patients. particularly in the p-PEA group, where ROSC was achieved with positive inotropic therapy allowing these patients to be accurately diagnosed and provided with specific treatment opportunities.
Bedside USG enabled the diagnosis of pulmonary thromboembolism (PTE) in case 5, aortic dissection in case 7, and free wall rupture in case 8, while also supporting the presumptive diagnosis of PTE in case 6. This study highlights that cardiac USG can be a valuable guide in cases where organized electrical activity is observed on the monitor during CPR, but the pulse is absent. Bedside USG provided these high-mortality patients with a chance for specific treatment, a finding consistent with earlier studies [23].
In this study, carotid and femoral USG, as well as cardiac USG, were utilized alongside manual pulse palpation for the differential diagnosis of p-PEA and cardiogenic shock. This was necessary because distinguishing these conditions based solely on echocardiographic visual assessment proved challenging. For example, no significant difference in contractile strength was observed between cardiogenic shock patients (case 11 and case 12) and p-PEA patients (case 6 and case 9). In morbidly obese patients like case 9, manual pulse detection might be difficult, as previous studies have indicated a high failure rate for manual pulse checks in obese patients [12]. Thus, even echocardiography may be insufficient for distinguishing p-PEA from cardiogenic shock, and combined methods such as carotid USG, femoral USG, or ETCO2 may be necessary. In cases where none of these tools is available and a rhythm is present but no pulse is palpable, adding positive inotropic therapy may be beneficial.
In this study, all p-PEA patients with higher cardiac activity who were treated with positive inotropic agents achieved ROSC, while none of the PEA patients with less cardiac activity did. Väyrynen et al. [15] previously reported that the most significant factors influencing survival in PEA patients were the use of adrenaline and the presence of cardiac activity. These findings are consistent with our results. Mehta and Brady [10] previously reported achieving ROSC in a PEA patient during CPR by administering vasopressin, a vasopressor agent, in addition to standard resuscitation. Similarly, Wenzel et al. [24] demonstrated that vasopressin increased the ROSC rate in PEA patients during CPR. However, these studies did not differentiate between PEA and p-PEA, leaving the group classification of ROSC-achieved patients unclear. Prosen et al. [13] advanced this field by using capnography and USG to distinguish PEA from p-PEA, reporting that vasopressin was more strongly associated with ROSC and survival in p-PEA patients. In our study, consistent with Prosen et al. [13] findings, all p-PEA patients treated with positive inotropes, achieved ROSC, while no PEA patients did. Thus, cardiac activity during CPR may be a key determinant of treatment response. Supporting this, Wu et al. [18] reported that PEA patients with detectable cardiac activity had a 4.09-fold higher likelihood of achieving ROSC, compared to those without. Beyond vasopressin, Myerburg et al. [25] suggested that curcumin might be effective in achieving ROSC in PEA patients. While not all studies differentiated between PEA and p-PEA, it appears that p-PEA patients with greater myocardial movement may have a higher likelihood of responding to certain drug therapies, warranting further targeted research.
Many experts believe that PEA has been an overlooked entity to date [9]. Extensive studies have been conducted on VF and VT, characterized by pulseless and irregular rhythms, leading to the development of specific therapies like defibrillation [26]. These therapies have significantly improved survival rates in these patients [27]. However, despite also being pulseless, regular rhythms like PEA and p-PEA have no specific therapeutic recommendations and are treated the same as asystole in routine CPR. Given the organized contractility and rhythm, especially in p-PEA patients, the ROSC and survival rates could potentially exceed those of irregular rhythms like VF. However, the superior survival rates of VF are primarily due to the availability of specific treatments like defibrillation. Similarly, the introduction of specific therapies for PEA and p-PEA patients could improve their survival outcomes. This study supports the hypothesis that positive inotropic agents, which are beneficial in cardiogenic shock, may also benefit p-PEA patients, who are in a condition similar to cardiogenic shock. Nevertheless, further research is required before this knowledge can be applied in routine practice
Study Limitations
The primary limitation of this study is its retrospective design, which means that data were accessed retrospectively. However, as these cases were recorded with the intent of being used for future training, detailed patient information and clinical data were systematically documented. This allowed access to most of the data necessary for the study. Another significant limitation is that it was conducted at a single center, which may restrict the generalizability of the findings. Furthermore, due to the retrospective nature and limited sample size, the study groups were not homogenous in terms of age or etiology of cardiac arrest, which may affect the comparability of the groups and limit the strength of conclusions.This missing data represents a significant limitation due to its known impact on survival outcomes.
Conclusion
According to the results of this study, valvular motion and myocardial motion can be used as references for the echocardiographic differentiation of PEA and p-PEA. Based on treatment response and outcomes, the group with valvular motion alone can be classified as PEA, while the group with valvular motion and in addition to varying degrees of myocardial motion can be classified as p-PEA. For the differential diagnosis of cardiogenic shock and p-PEA, carotid or femoral USG may serve as a useful tool. In terms of treatment, adding positive inotropic agents to the routine CPR protocol, may benefit patients with p-PEA, whereas such treatment may be ineffective for those in the PEA group. Further studies are required to validate these findings.
Video 1a. Pre-positive inotropic therapy
Video 1b. Post-positive inotropic therapy
Video 2a. Pre-positive inotropic therapy
Video 2b. Post-positive inotropic therapy
Video 3a. Pre-positive inotropic therapy
Video 3b. Post-positive inotropic therapy
Video 4a. Pre-positive inotropic therapy
Video 4b. Post-positive inotropic therapy
Video 5a. Pre-positive inotropic therapy
Video 5b. Post-positive inotropic therapy
Video 6a. Pre-positive inotropic therapy
Video 6b. Post-positive inotropic therapy
Video 7a. Aortic arch from the suprasternal notch
Video 7b. Pre-positive inotropic therapy
Video 7c. Post-positive inotropic therapy
Video 8a. Pre-positive inotropic therapy
Video 8b. Post-positive inotropic therapy
Video 9a. Femoral artery ultrasound
Video 9b. Pre-positive inotropic therapy
Video 9c. Post-positive inotropic therapy
Video 10a. Carotid artery ultrasound
Video 10b. Pre-positive inotropic therapy
Video 10c. Post-positive inotropic therapy
Video 11a. Pre-positive inotropic therapy
Video 11b. Post-positive inotropic therapy
Video 12a. Pre-positive inotropic therapy
Video 12b. Post-positive inotropic therapy
