Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation





Abstract


Introduction


In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time, the duration between the initiation of conventional cardiopulmonary resuscitation and the establishment of ECPR, and outcomes has not been clearly determined.


Methods


This was a secondary analysis of the retrospective multicenter registry in Japan. This study registered patients ≥18 years old who were admitted to the emergency department for OHCA and underwent ECPR between January, 2013 and December, 2018. Low-flow time was defined as the time from initiation of conventional cardiopulmonary resuscitation to the establishment of ECPR, and patients were categorized into two groups according to the visualized association of the restricted cubic spline curve. The primary outcome was survival discharge. Cubic spline analyses and multivariable logistic regression analyses were performed to assess the nonlinear associations between low-flow time and outcomes.


Results


A total of 1,524 patients were included. The median age was 60 years, and the median low-flow time was 52 (42‐53) mins. The overall survival at hospital discharge and favorable neurological outcomes were 27.8% and 14.2%, respectively. The cubic spline analysis showed a decreased trend of survival discharge rates and favorable neurological outcomes with shorter low-flow time between 20 and 60 mins, with little change between the following 60 and 80 mins. The multivariable logistic regression analyses showed that patients with long low-flow time (>40 mins) compared to those with short low-flow time (0‐40 mins) had significantly worse survival (adjusted odds ratio 0.42; 95% confidence intervals, 0.31-0.57) and neurological outcomes (0.65; 0.45-0.95, respectively).


Conclusions


The survival discharge and neurological outcomes of patients with low-flow time shorter than 40 min are better than those of patients with longer low-flow time.


1


Introduction


Extracorporeal cardiopulmonary resuscitation (ECPR) is the application of extracorporeal membrane oxygenation (ECMO) in patients with cardiac arrest in case sustained return of spontaneous circulation (ROSC) is not achieved with conventional cardiopulmonary resuscitation (conventional CPR) [ ]. Recently, the effectiveness of ECPR for out-of-hospital cardiac arrest (OHCA) patients has gained attention, and randomized control trials have been performed [ ]. However, the socioeconomic cost of ECPR is high, and the appropriate selection of patients must be considered. Predictive factors associated with poor outcomes have not been determined clearly.


Low-flow time, the duration between the initiation of conventional CPR and the establishment of ECPR, might be one of the predictive factors of successful outcomes of ECPR [ , ]. The guidelines recommend initiating ECPR no later than 60 min after initiating conventional CPR and imply that initiating ECPR too early might cause avoidable ECMO-related complications [ , ]. However, these recommendations are not based on robust evidence. Although previous studies have shown the association between shorter low-flow time and better survival or neurological outcomes [ ], these studies did not have sufficient sample sizes. Therefore, more robust evidence on the association between low-flow time and survival or neurological outcomes in OHCA patients who receive ECPR is required.


This study aimed to assess whether short low-flow time was associated with survival discharge and favorable neurological outcome using a large ECPR registry.


2


Methods


2.1


Study design and data


This study is a secondary analysis of the retrospective multicenter registry, the Study of Advanced life support for Ventricular fibrillation with Extracorporeal circulation II (SAVE-J II) in Japan. Thirty-six institutions in Japan participated in this registry. The study was pre-registered at the University Hospital Medical Information Network Clinical Trials Registry, the Japanese clinical trial registry (registration number: UMIN000036490) [ ]. This study was approved by the institutional review board of Kagawa University (approval number: 2018‐110) and of each participating institution. In all the participating institutions, the requirement for patient consent was waived due to the retrospective nature of this study.


SAVE-J II included all patients ≥18 years old who were admitted to the emergency department for OHCA and underwent ECPR between January 1, 2013 and December 31, 2018. In this registry, ECPR was defined as resuscitation for cardiac arrest using veno-arterial ECMO. Exclusion criteria were patients with in-hospital cardiac arrest and patients who declined to participate in the registry through the patients themselves, family, or others. The following data were collected: patient characteristics, prehospital information, information on hospital arrival, diagnosis, interventions, mechanical support information, time course, and outcomes [ ].


2.2


Study population


In this study, we included all patients in the SAVE-J II registry. The exclusion criteria of this secondary analysis were as follows: implementation of ECPR after intensive care unit admission; non-cardiac conditions including acute aortic syndrome, hypothermia, primary cerebral disorder, infection, drug intoxication, trauma, suffocation, drowning, and other external causes [ ]; patients who achieved ROSC at hospital arrival patients who achieved ROSC before cannulation; OHCA patients who were transferred to the participating institutions from another hospital; those who withdrew after cannulation and before turning the ECMO pump on due to the ROSC; patients with missing data of outcomes; and patients with missing data on low-flow time.


The following patient data were used for this secondary analysis: age, sex, comorbidity of heart disease, location of cardiac arrest (home, public space, or ambulance), witnessed cardiac arrest, bystander CPR, initial cardiac rhythm (shockable, pulseless electrical activity, or asystole) at the scene and hospital arrival, the detailed time course of resuscitation, survival to hospital discharge, and cerebral performance category [ ] at hospital discharge. Initial shockable rhythm was defined as ventricular fibrillation, pulseless ventricular tachycardia, or rhythm for defibrillation in an automated external defibrillator used by emergency medical staff.


2.3


Covariates of interest


The key independent variable was low-flow time, defined as the time from cardiac arrest to the establishment of ECPR when the cardiac arrest occurred in the ambulance, the time from the call for an ambulance to the establishment of ECPR when the location of cardiac arrest was at home or in a public space and bystander CPR was performed, or the time from arrival of emergency medical service to the establishment of ECPR when the cardiac arrest occurred at home or in a public space and bystander CPR was not performed.


2.4


Outcomes


The primary outcome was survival at hospital discharge. The secondary outcome was favorable neurological outcome, defined as a cerebral performance category of 1 or 2 at hospital discharge.


2.5


Statistical analysis


Categorical variables were counted and presented as proportions. Continuous variables were expressed as medians and interquartile ranges (IQRs).


We examined the nonlinear associations between low-flow time and outcomes using restricted cubic spline analyses [ , ]. While an ordinal regression analysis with categorized low-flow time can lose information and power, all data points are used to estimate the dose-response associations between low-flow time as a continuous variable and outcomes in a restricted cubic spline analysis [ ]. We set four knots in the cubic splines, placed on the 5th, 35th, 65th, and 95th percentile of low-flow time. We could not gain the accurate no-flow time, the duration between the cardiac arrest and the initiation of conventional CPR, especially in cases without witnessed cardiac arrest. Therefore, we adjusted for the location of cardiac arrest, witnessed cardiac arrest, bystander CPR, and the initial cardiac rhythm at the scene, as well as age, sex, history of heart disease, and cardiac rhythm upon hospital arrival. We fitted generalized estimating equations accompanied by individual hospitals as the clustering variable to the restricted cubic spline analyses and calculated the odds ratios (ORs) and their 95% confidence intervals (CIs) for each value of low-flow time relative to the reference value of 45 min based on previous studies [ , ]. Next, we stratified the patients into two groups based on the qualitative assessment of the appearance of the restricted cubic spline curves presenting a non-linear relationship [ ]. The cut-off time was decided as the intermediate value of two-time points, during which the decreased trend of the survival discharge rate, was shown in the cubic spline curve. Then, we performed multivariable logistic regression analyses fitted with generalized estimating equations accompanied by individual hospitals as the clustering variable to assess the association between groups and outcomes. The same variables used in the restricted cubic spline analyses were adjusted. The ORs and their 95% CIs on outcomes were calculated for each low-flow time group with respect to the reference group with short low-flow time, using the logit link function. We also conducted subgroup analyses based on the location of cardiac arrest and the initial cardiac rhythm at hospital arrival. Furthermore, we calculated the low-flow time with each cannulation method to investigate the association between low-flow time and cannulation methods. Statistical analyses were performed using STATA/BE 17.0 software (StataCorp, College Station, TX, USA).


3


Results


Of the 2,157 adult OHCA patients who received ECPR in the original study, 1,524 were included in this secondary analysis ( Fig. 1 ).




Fig. 1


Patient flowchart.


3.1


Characteristics of patients at baseline and outcomes


The median age was 60 years, and 84.8% were males ( Table 1 and Supplemental Table 1). The median low-flow time was 52 (42-53) mins. The overall survival at hospital discharge and favorable neurological outcome were 27.8% and 14.2%, respectively.


Tags:
Mar 29, 2024 | Posted by in EMERGENCY MEDICINE | Comments Off on Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation

Full access? Get Clinical Tree
Get Clinical Tree app for offline access