Outcome after out-of-hospital ventricular fibrillation or pulseless ventricular tachycardia: comparison of before and after the implementation of the 2010 Guidelines in a single centre

METHODS: In a retrospective chart review, we analysed the outcomes of 182 patients who suffered bystander-witnessed, out-of-hospital ventricular fibrillation or pulseless ventricular tachycardia of cardiac aetiology. These definitions were based on the Utstein style. Survival at hospital discharge (study period 2006 to 2015), 1-year survival (study period 2011 to 2015), neurological outcome (cerebral performance category [CPC] score) and the corresponding changes over time were evaluated. In addition, the results were compared with results obtained from a systematic review of the literature.


Introduction
The emergency medical services (EMS) of northern St Gallen cover a population of about 200,000 (year: 2015) in eastern Switzerland and carry out around 15,000 responses annually.Paramedics are primarily in charge, but in life-threatening cases an emergency physician is also dispatched (around 2600 missions per year).Emergency physicians at our hospital are residents, the majority in anaesthesiology, with two or more years of clinical experience, who have completed an emergency physician course with the Swiss Society of Emergency and Rescue Medicine (SGNOR) and Advanced Cardiac Life Support (ACLS) training.
Based on population data and our cardiac arrest database, there was a mean incidence of 70 out-of-hospital cardiac arrests (OHCA) per 100,000 people annually in the EMScovered population in northern St Gallen (2006-2015).The outcome of OHCAs is expected to have improved over the last few decades due to continuously improving cardiopulmonary resuscitation (CPR) training in laypersons, dispatcher-guided resuscitation and automated external defibrillator (AED) availability [1][2][3].Furthermore, resuscitation guidelines for professionals have been adapted multiple times over the past few years.The American Heart Association (AHA) and the European Resuscitation Council (ERC) launch resuscitation guidelines, based on the International Liaison Committee on Resuscitation (ILCOR) [4,5], every five years.The most recent updates were published in 2010 and 2015 [6][7][8][9].The optimisation of the guidelines should allow better outcomes among treated patients.Our EMS staff's training is based on the AHA guidelines.Accordingly, we hypothesised that the outcomes of the patients treated in our region would improve over time.In particular, the outcomes were expected to be better after the implementation of the 2010 update.
Many studies have analysed outcomes at hospital discharge, but less is known about the long-term survival and neurological outcomes of patients who suffer an OHCA.The primary goals of this study were: (1) to define the short-(hospital discharge) and long-term (1 year post-arrest) ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT) survival rates and neurological outcomes in the region of northern St Gallen, Switzerland; (2) to estimate the annual changes and the differences between the periods 2006-2010 and 2011-2015; and (3) to compare the results with the international literature based on a systematic review of OHCA studies.

Methods
Ethical approval for this study (No.EKSG 15/187) was provided by the Ethics Committee St Gallen, Switzerland.It complies with the principles stated in the Declaration of Helsinki.
For these analyses, prospectively collected data from all patients who suffered an OHCA between January 2006 and December 2015 were retrieved from an electronic database.The data contained information about demographics (age, gender), location (collapse spot), time course (date, time of collapse, alarm at EMS central, arrival of EMS team, start of CPR, first defibrillation, departure of EMS team, ROSC time, abort of resuscitation, arrival at hospital), aetiology and details of cardiac arrest (cardiac, presumed cardiac, non-cardiac with initial rhythm), management (pre-hospital measures such as ventilation, intubation, defibrillation and medication use), survival (until emergency room arrival, intensive care unit and hospital discharge), other factors (bystander witnessed, bystander resuscitation, bystander AED use), and neurological outcomes (CPC score and Glasgow Coma Score) until hospital discharge.

Cardiac arrest definition
Out-of-hospital cardiac arrest was defined as the stop in effective blood flow due to the heart failing to contract efficiently [10].In the pre-hospital clinical practice, the emergency physician used clinical signs such as pulselessness, apnoea or agonal breathing.As soon as an electrocardiography was monitored, the four cardiac dysrhythmias of VF, pVT, asystole or pulseless electrical activity were used as confirmation of cardiac arrest.
If return of spontaneous circulation (ROSC) was achieved, the patient was transferred to the Kantonsspital St. Gallen, the largest tertiary care hospital in eastern Switzerland, where percutaneous coronary intervention is immediately available.

Patient inclusion
Patients were screened and selected according to the Utstein form [11] to allow for a uniform comparison with other studies.The selection criteria were as follows: 1. Attempted resuscitation by EMS professionals, i.e., no signs of clear death evident and no "do not resuscitate" (DNR) order evident.
2. Patients with cardiac or presumed cardiac origin.All patients with other causes, such as intoxication, submersion or trauma, were excluded.
3. Cardiac arrest witnessed by layperson bystanders or EMS.
At the end of this selection process, only the remaining patients, those with VF and pVT, were analysed for primary and secondary outcomes.

Primary and secondary outcomes
The primary endpoints were survival and a favourable neurological outcome (CPC 1-2) at hospital discharge from 2006 to 2015.CPC 1 is defined as "good cerebral performance", CPC 2 as "moderate cerebral disability", CPC 3 as "severe cerebral disability", CPC 4 as "coma or vegetative state", and CPC 5 as "brain death".
The secondary outcomes were survival and a CPC score of 1-2 1 year after OHCA from 2011 to 2015.The secondary outcome data were not registered in the database, but were obtained through individual chart reviews and by a written questionnaire mailed to the patients.We defined the long-term outcome as the outcome at 1 year post-OHCA.The chart and questionnaire reviews were performed by two reviewers (TvH and PI) independently, and any CPC scores that did not match were resolved by consensus with a third reviewer (MF).Patients who did not return the questionnaire were contacted and interviewed by phone.Informed consent was obtained from all surviving patients approached by mail or telephone.

Study selection for systematic literature review
To compare our results with international data, we conducted a systematic literature search.For the full search strategy, review protocol and Prisma flow chart, see appendices 1-3.Two authors (TvH and CK) individually searched for eligible observational studies using a systematic PubMed search restricted to studies published in English or German and with a search timeframe of January 2000 to April 2018.First, titles and abstracts were screened, then full text reviews were conducted where applicable.The search was restricted to studies reporting on 1000 or more OHCAs treated in or after the year 2000.We followed the PRISMA checklist [12].The search terms were defined as follows: out-of-hospital cardiac arrest/epidemiology, mortality, therapy, complications, rehabilitation, and cardiopulmonary resuscitation/adverse effects, epidemiology, mortality, therapy and trends.

Statistical analysis
Continuous variables were shown as means ± standard deviation (SD) or rounded percentages ± 95% confidence interval.Differences in outcomes between the two time periods were assessed by chi-square statistics.Potential annual changes were analysed by logistic regression.A p-value of <0.05 was considered significant.Analyses were performed by SPSS Version 24.0 (IBM, Armonk, USA) for windows (Microsoft, Redmond, USA).The results of the systematic literature review were visualised in figures 3-6, which were created in Excel (Microsoft, Redmond, USA).The figures show the point estimates (including 95% CIs) of the survival rates and the reported CPC scores, as well as the weight of the corresponding study, at the described timepoint (discharge or 1 year).We did not perform a meta-analysis.

Survival and neurological outcomes at discharge
In our study of 182 patients with a shockable primary rhythm, 75/182 survived until hospital discharge, most of them (88%) with a good neurological outcome.The introduction of the 2010 AHA guidelines had no beneficial effect on survival.
Our systematic literature review included seven studies and revealed broad variability in hospital and 1-year sur-vival rates (11 to 52% and 6 to 47%, respectively).The outcomes of the patients treated in our region lie within this range reported in the literature.However, some studies used broader inclusion criteria, not strictly following the Utstein-based definitions we used (see table 5 for details).
Another meta-analysis of OHCA outcomes in 67 studies on four different continents (Europe, North America, Asia and Australia) also showed high variability in the reported outcomes (VF survival to discharge rates of 3 to 43%) [20].Reasons for this are differences in methodology, pop-  ulation characteristics, geographical factors and -potentially -quality of care [20].Data from Europe and the United States show more similar results to our own: in a large study from Vienna, Austria, 110/446 (25%) patients with a shockable rhythm survived until hospital discharge, while 91/110 (83%) had a CPC score of 1-2 [17].The authors identified early bystander resuscitation, onsite AED use and first responder dispatching as contributing factors  (80%) having a CPC score of 1-2 [14].The results of this study are very much comparable with our data, which shows a similar in-hospital survival rate (30 vs 34%) and a  similar proportion of patients with CPC scores of 1-2 (80 vs 83%).
Public health measures such as CPR training in laypersons (in driving schools and even elementary schools) and AED availability are important steps for improving outcomes [21,22].These efforts are associated with an improved hospital survival rate [23].In Switzerland, first aid training in driving schools has been mandatory since 1977, and societies have provided voluntary training in basic CPR since 1993.Still, basic CPR training is absent among the general population in many cantons, although there have been more initiatives towards building first responder networks [13].In the canton of St Gallen, first responder networks (e.g.Samaritans, firefighters) are being built up, and these were called out 110 times in 2015 [24].AED use increased in the observed time period, potentially caused by the greater availability of AED devices in the covered area.

Survival and neurological outcomes at 1 year
In our study, 36/44 (82%) patients who survived to discharge were still alive after 1 year, all of them with a good neurological outcome.In the study by Mauri et al., a 1-year survival rate of 121/160 (76%), with a neurologically in-tact status in 115/121 (96%) was reported [13].Data on long-term neurological outcomes after OHCA are surprisingly sparse.Reasons for this are the supposed difficulties of following up patients over a long period of time and a lack of national databases.Also, a national resuscitation outcome register for comparison was absent in Switzerland for a long time, but one is currently being built up, having been begun in 2016 ("Swiss ReCa", Swiss Registry of Cardiac Arrest).Nevertheless, even if all EMS in Switzerland participate, the numbers obtained from this registry might be too small to draw reliable conclusions.Accordingly, a study covering many European countries or participation in European Resuscitation Registries (e.g."EuReCa", European Registry of Cardiac Arrest), is needed.

Changes in survival over time
In our data, there was no significant change in outcomes over time.However, there were differences in clinical practice between the two time periods investigated, giving evidence of the successful implementation of the 2010 AHA resuscitation guidelines.Reasons for the lack of improvement are presumably multifactorial.Firstly, the number of patients in the final analyses is quite small, possibly precluding a statistically significant result.Secondly, the outcome at the beginning of the observed time period was quite favourable (see comparison with the literature), which does not leave much room for substantial improvement.An alternative explanation, however, is that the improvements implemented through the guideline updates are not fundamental enough to allow for a substantial improvement in outcomes.In contrast to our study, Mauri et al., demonstrated an increase in the hospital survival rate from 15% in 2005 to 55% in 2014 (p = 0.0) [13].In the area covered in that study, in the south of Switzerland, a large effort was made to build up an effective first responder network through a mobile phone alarm system, shortening the hands-on time significantly and thereby improving the "chain of survival".Furthermore, CPR training in laypersons and AED availability in that area have been vastly ameliorated over the past decade.In addition, patients were transferred to a tertiary care hospital after 2010.The effort was successful and resulted in an impressive improvement in outcomes.The survival rate at the end of the study period was comparable with ours.The training of laypersons is not as strict in our region as in that described in Mauri's study.[19].Here again, the different parts of the "survival chain" all play a certain role.Although there was an increase in the EMS response time from 8 to 9 minutes and a decline in shockable rhythms, the layperson CPR rate was significantly higher.But most importantly, they successfully implemented therapeutic hypothermia, emergency percutaneous coronary intervention (PCI) and the 2005 ERC (European Resuscitation Council) CPR guidelines.These reasons are a possible (but not proven) explanation for the better outcomes in the second period.
A nationwide study conducted in Denmark from 2001-2010 showed an increase in 1-year survival: 1.3/ 100,000 in 2001 to 3.5/100,000 people in 2010.There are no data from the study on CPC scores, although it reported the presence of anoxic brain damage in 10% of the 1-year survivors [15].In Denmark between 2001 and 2010, CPR training in elementary and driving schools was mandatory, and CPR training kits and first aid certificates were distributed.Furthermore, AED availability was increased, although these devices were only used occasionally (1.1% in 2001 and 2.2% in 2010, p = 0.003).In summary, efforts to give laypersons CPR training and the distribution of AEDs seem to have the potential to improve survival after out-ofhospital cardiac arrest.The optimisation of guidelines for health care professionals might be a less important effect.However, the outcome after CPR does not only depend on the initial management, but is very much modified by the in-hospital treatment and the availability of PCI and intensive care facilities.

Limitations
The most important limitation is the small number of patients analysed, despite the long data acquisition period of 10 years.This fact is caused by the large number of hospitals and ambulance services all covering relatively small areas in Switzerland.The small sample size limits the statistical power and generalisability of the results and makes the results prone to biases.A second important limitation is the lack of details about post-resuscitation care (e.g.PCI, therapeutic hypothermia) and certain baseline information such as the Charlson Comorbidity Score and/ or ASA status.In addition, no statement could be made about the impact of external resuscitation devices such as AutoPulse® or LUCAS, as these devices are not routinely used in our region.Furthermore, there might have been some recall bias by the attending physicians.The decision as to whether an OHCA is of cardiac cause or not is often a clinical one, and may therefore lead to inaccurate data.The assessment of the neurological status by CPC score might be an oversimplification, and important limitations in daily activities could remain undetected.

Conclusions
Survival rates and neurological outcomes to hospital discharge and 1 year are favourable in our hospital, although there was no improvement in either the primary (survival and CPC score at hospital discharge) or secondary (survival and CPC score after 1 year) outcomes.We found our survival rates to be on a stable, high level in comparison to international studies from Europe and the United States.To compare our findings, further studies are needed, covering larger areas of Switzerland or, preferably, Europe.Further public health measures should be undertaken, and a national register for the analysis of OHCA outcomes is of high importance.
performance category; ROSC = return of spontaneous circulation p-values of trends over years were calculated by logistic regression, p-value of the two time periods by chi-square test.* Missing data = 2 (1.1%) † Missing data = 3 (1.6%)

Figure 2 :
Figure 2: Cerebral Performance Category over time.

Table 1 :
1 January 2006 until 31 December 2015, a total of 1423 confirmed OHCAs were recorded and included in the database.Resuscitation was attempted by EMS in 781 patients, 612 of which were of cardiac or presumed cardiac origin.Baseline and analyses characteristics are presented in tables 1-4.A total of 182 patients (30%) presented a shockable primary rhythm such as VF or pVT at EMS arrival.These were included in the final analysis of survival rates and CPC scores.Seventy-five out of 182 (41%) survived until hospital discharge and 66/75 (88%) had a favourable neurological outcome of a CPC score of 1-2 at discharge.Seven out of 75 patients (11%) had a CPC score of 3-4.Baseline characteristics and collapse spot details.Seven studies were included in the analysis.The hospital and 1-year survival rates varied substantially, from 11 to 52% and from 6 to 47% respectively (figs 3 and 4).At discharge and after 1 year, 66-87% and 83-96% of patients respectively had a CPC score of 1-2 (figs 5 and 6).

Table 2 :
The Utstein form of our analysed population.

Table 3 :
Outcome data from our cardiac arrest database.

Table 4 :
Management details after EMS arrival at the scene.

Table 5 :
Studies included in the systematic literature review.
CPC = cerebral performance category; EMS = emergency medical services; OHCA = out-of-hospital cardiac arrest; ROSC = return of spontaneous circulation * We defined Utstein comparator criteria as cardiac aetiology, witnessed by bystanders and with shockable rhythm (ventricular fibrillation, pulseless ventricular tachycardia).Swiss Medical Weekly • PDF of the online version • www.smw.chPublished under the copyright license "Attribution -Non-Commercial -No Derivatives 4.0".No commercial reuse without permission.See http://emh.ch/en/services/permissions.html.