Sudden cardiac arrest pharmacotherapy with prefilled syringes improves adherence to Advanced Life Support protocol in understaffed resuscitation pre-hospital care teams

1. Introduction

Sudden cardiac arrest (SCA) it is becoming the most common cause of death in the developed countries. It occurs particularly often to patients with preexisting cardiac pathologies [1, 2, 3]. A recent study EuReCa ONE conducted in 27 European countries estimated the incidence rate at 84.0 for 100 000 [2]. The survival of patients depends crucially on the quality of pre- and in-hospital phases of first aid [4]. In Polish Medical Emergency System there are usually two-person teams, who are obliged to follow the Advanced Life Support (ALS) procedures [5].

All contemporary guidelines on resuscitation recommend routine pharmacotherapy in SCA- mostly indicating epinephrine (for all SCA cases) and amiodarone (in ventricular fibrillation/pulseless ventricular tachycardia VF/pVT cases that do not respond to initial shocks). There is no evidence that this pharmacotherapy significantly improves the outcome in out-of-hospital cardiac arrest (OHCA), nevertheless it is a routinely recommended medical treatment in 2015 European Resuscitation Council (ERC) guidelines and paramedics are expected to provide it when performing advanced life support [6, 7]. Preparing and administering epinephrine and amiodarone is time-consuming and thus it can possibly affect resuscitation quality when resuscitation team is understaffed, common in prehospital care [8]. Most European countries utilize two-person paramedical teams in prehospital emergency medical services, while ERC recommend six people in resuscitation team. It has been found, that two-member ambulance team is not able to adhere to ALS protocol, especially in terms of pharmacotherapy and when first dose of epinephrine is administered after 7 minutes of resuscitation [9].

European guidelines on resuscitation do not focus on the technical aspects of drug preparation for resuscitation teams, moreover it is not mentioned in the official document whether any specific type of storage and injectors should be favored. There is a clear indication though that pharmacotherapy should be initiated when sufficient staff is present, unfortunately there is no clarification what number of medical professionals should be considered as sufficient [10].

Throughout recent years, the use of prefilled syringes has been analyzed in various fields of medicine. It has turned out that they have numerous advantages including better quality of cardiopulmonary resuscitation improved patients’ safety and optimal drug administration [11, 12].

The aim of this study was to assess the impact of adrenaline in prefilled syringes on improving the adherence to Advanced Life Support protocol by understaffed teams.

2. Materials and methods

3. Results

Sixty three paramedical teams participated in the simulator-based study and they carried out 126 scenarios. However, due to technical failure of the simulator, 4 of them had to be excluded thus eventually 122 scenarios were entered into further analysis (61 in control and 61 in experimental group).

3.1 Adherence to CPR protocol

After initial assessment of the rhythm that lasted comparably between groups, the first shock applications were done at the same time, whereas the subsequent ones were applied earlier in the experimental group. Additionally, time between shocks differed markedly between all but one (exception between fourth and fifth). The breaks are presented graphically in Fig. 1. However, it must be pointed that only in 19 cases in group C (31.1%) but in 49 in group E (80.3%) the fifth electric shocks were carried out (P $<$ 0.001).

Fig. 1.Breaks between electric shocks. # break “1” applies to time difference between shock No.1 and shock No.2; “2” between shock No.2 and No.3 etc. & it applies to the difference between groups regarding number of scenarios with applied electric shock. In group C, less than one thirds had the fifth electric shock. Abbreviations: group C = control group; group E = experimental group; NA = non-applicable.

Generally, paramedics in group C did not change regularly in chest compressions, which was also a more observable case in group E (see Fig. 2). In 2nd minute of CPR, nobody changed in group C whereas only in 10 (16.4%) scenarios in group E. The best adherence to CPR protocol was noted after 4 minutes in group C (45.8%; n = 28) and 2 minutes later in group E (75.4%; n = 46), then dropped, however more dramatically in group C.

Fig. 2.Changes of paramedics in chest compressions. The first change should be implemented after two minutes of CPR, second (2nd) two minutes later (4th minute of CPR) etc. Abbreviations: group C = control group; group E = experimental group.

Moreover, IV access was obtained significantly earlier in group E than in group C, despite of comparable time of its insertion (25.9 $\pm$ 15.9 sec and 24.8 $\pm$ 16.1 sec, in group C and group E, respectively; P = 0.713). This difference resulted from later starting point of IV access introduction. The detailed data are presented in Table 1.

Table 1.Detailed data regarding time and adherence to valid CPR protocol.

[sec]	Control group [n = 61]	Experimental group [n = 61]	P value${}^{\mathrm{\#}}$
1. CPR start	14.1 $\pm$ 4.6	14.4 $\pm$ 6.4	0.733 (NS)
2. Shock No.1	43.3 $\pm$ 15.6	39.8 $\pm$ 14.9	0.436 (NS)
[61${}^{\mathrm{\&}}$]	[61]	NA
3. IV access start obtained
	124.3 $\pm$ 65.6	89.9 $\pm$ 43.9	0.001
	150.2 $\pm$ 68.6	114.7 $\pm$ 52.2	0.002
4. Shock No.2	213.1 $\pm$ 65.6	158.1 $\pm$ 30.4	$<$ 0.001
[61]	[61]	NA
5. Shock No.3	366.6 $\pm$ 85.3	284.9 $\pm$ 32.4	$<$ 0.001
[61]	[61]	NA
6. Epinephrine 1${}^{st}$ dose	438.8 $\pm$ 64.8	308.2 $\pm$ 41.8	$<$ 0.001
[61]	[61]	NA
7. Amiodarone 1${}^{st}$dose	476.3 $\pm$ 76.4	325.9 $\pm$ 48.6	$<$ 0.001
[46]	[61]	$<$ 0.001
8. Shock No.4	480.0 $\pm$ 53.9	412.2 $\pm$ 41.7	$<$ 0.001
[42]	[61]	$<$ 0.001
9. Epinephrine 2${}^{nd}$ dose	542.6 $\pm$ 28.8	534.1 $\pm$ 23.1	0.356 (NS)
[12]	[61]	$<$ 0.001
10. Amiodarone 2${}^{nd}$ dose	551. 9 $\pm$ 27.6	531.7 $\pm$ 48.8	0.051 (NS)
[13]	[61]	$<$ 0.001
11. Shock No.5	559.1 $\pm$ 27.6	517.5 $\pm$ 25.5	$<$ 0.001
[19]	[49]	$<$ 0.001
Continuous data (time) are expressed as the means with standard deviation, whereas categorical variable (&, number of scenarios with application of a given point of CPR algorithm) as number (n) with percentage (%). #, data were compared by the means of either unpaired Student T test (continuous data; upper rows) or Yates corrected $\chi$2 test (categorical data; lower rows). Abbreviations: NA = non-applicable; NS = not statistically significant difference.

Poor adherence to the CPR algorithm regarding optimal administration of emergency medicine (ie., epinephrine and amiodarone) was obviously noted in group C. Although, the first dose of epinephrine was given in all scenarios in both groups, the second dose in all scenarios in group E, whereas only in 12 in group C. The worse situation regarded amiodarone injections in group C. During those, the first dose was administered in 75% and the second only in less than 20%.

Time to achieve airways patency did not differ significantly between groups and mean time was equal 128.9 $\pm$ 80.3 sec in group E and 132.9 $\pm$ 67.9 sec in group C (P = 0.767).

4. Discussion

In our simulation-based study prefilled syringe with adrenaline was chosen due to its easy availability and common use in daily clinical practice. Although its administration is recommended in SCA subjects in valid guidelines of the European Resuscitation Council (ERC), the outcomes of its use in these individuals are not consistent [13, 14, 15, 16]. According to the aforementioned recommendations, the first dose of adrenaline should be administered immediately after insertion intravenous or interosseous cannula in initial non-shockable whereas after the third shock in the shockable rhythms [17]. Therefore, in our study we did not test the impact of adrenaline injection itself on CPR efficacy nor its outcomes, but we assessed the significance of two different and available methods of drug preparation prior to its application. These two methods could impact the adherence to all aspects of ALS protocol. We have tested not only appropriate time and number of recommended drug injections but also defibrillations, changes of paramedics in CCs, airways patency and eventually CPR quality expressed as CCF. Moreover, scenario of OHCA with initial shockable rhythm was assessed because it was found before that paramedics committed most errors in SCA in ventricular fibrillation [18]. Of note, two-person prehospital resuscitation teams are common in some European countries. However, there are no specific guidelines available for them to address the issue of such understaffed teams and also other types of limited prehospital resources.

It was found before that high-quality CCs and early defibrillation are the most important actions to be taken during SCA. It has been also proven that pauses during CCSs significantly reduce the coronary vessels pressure, what inseparably leads to the decrease in the probability of returning the spontaneous circulation (ROSC) [19]. This issue was also stressed in 2015 Guidelines of the American Heart Association (AHA). AHA define the chest compression fraction (CCF) parameter as a proportion of time dedicated to continuant CCSs and its value should exceed 60% [20, 21]. Current analysis has proven that teams working with prefilled syringes with adrenaline reached higher CCF rate than group C. With this facilitation the teams could focus on providing high-quality chest compressions. The changes between paramedics after every two minutes of CCs are crucial components of high-quality CPR [10]. Our study has proven that paramedics switched irregularly, especially during initial phase of CPR. Although those having prefilled syringes at their disposal followed ALS protocol better than in group C, they were still not optimal regarding this aspect of CC.

We have also noted two-person teams were not able to follow the ALS protocol regarding defibrillations. The delays resulted in the numbers of electric shocks, whereas introduction of prefilled syringes significantly improved adherence to guidelines. It is also interesting that paramedics using prefilled syringes controlled the 2-minute defibrillation loops, whereas those working with standard ampoules prolonged the loops even to 160 seconds, especially during first 2 changes. The time needed to draw, dissolve and inject the ampouled drug seemed to be an important contributing factor. The medicine preparation not only caused delay in the specific steps of the protocol, but also had significant impact of other crucial actions during CPR, particularly in OHCA scenario, such as airway management and uninterrupted chest compressions (CCF). The different time of obtaining the intravenous access may result from many factors. One of them can be psychological comfort having prefilled syringes at disposal. When decision is made not to provide pharmacotherapy in shockable rhythm (at least initially) in group C, which is a reasonable approach and is encouraged by the guidelines, the teams of two professionals can reach acceptable parameters of CPR quality and all major steps of CPR are not delayed. Teams that decided to withhold the pharmacotherapy and focus on other parts of ALS had clearly better CPR quality and adherence to the protocol. Of note, such delay is not justified if initial rhythm is a non-shockable one [9].

The authors have not come across any similar analyses in the medical literature that would assess the impact of using prefilled syringes on following the ALS protocols by 2-membered teams. There are analyses however that clearly prove that the use of adrenaline in a prefilled syringe significantly fastens and facilitates drug administration [8]. Authors working on the impact of prefilled syringes on the quality of cardiopulmonary resuscitation in SCA patients in unshockable rhythms have reached similar conclusion. It turned out that the first dose of adrenaline was administered faster by the paramedics who had prefilled syringes at their disposal. Additonally, the improvement of chest compressions parameters was observed, followed by visible better implementation of ALS protocol [19, 22].

Paramedic Self-Reported Medication Errors has published a list of the most common errors committed by paramedics. Nearly 10% of the respondents confirmed to have made a mistake during drug administration in recent 12 months. More than 60% of those errors were related to the dose, 33% to administering drug discordantly to the protocol, 21% to the paramedics choosing the wrong administration method and 4% to a wrong drug administration [23]. Using prefilled syringes has its indisputable advantages. It facilitates faster drug administration as the method eliminates most of the phases related to preparation of proper doses [24]. Moreover, it increases safety both of the patient and the paramedic because it limits the probability of pricking with sharp elements of an ampoule. Furthermore, a prefilled syringe does not require using aspirating needle, what in turn eliminates the risk of paramedic pricking themselves [24]. Similar results were reported by Stevens et al. in a prospective randomized study in simulated scenario of SCA in children. Ready-to-use prefilled color-marked syringes have shortened the time of drug administration and enabled to eliminate the critical errors during simulation scenario featuring prehospital resuscitation [25].

5. Limitations of the study

The authors are aware of the limitations of the research. The scenarios were conducted in a high-fidelity simulation, which naturally cannot fully mirror the conditions of real life or clinical trials. The research enabled repeatability of the conditions, which is not possible in reality. Paramedics in prehospital situations act in different conditions with various equipment at their disposal. Often, the environment or the behavior of incident’s witnesses may lead to a stressful situation, what is minimized during simulation. There were no distractors planned for the simulation, which could impact the results. During simulation only one type of prefilled syringes was used. Currently on the market there are many manufacturers producing various prefilled syringes in different packaging. The described limitations may influence the studies parameters.

6. Conclusions

The simulation study has proved that for two-membered paramedic teams, having at their disposal standard ampoules, it is not possible to follow the international CPR guidelines. A usage of prefilled syringes not only does enhance the flow of ALS procedure, but it also improves the quality of CPR, what may increase the survival rate.

Ethics approval and consent to participate

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Author contribution

(I) Conception and design: RZ, WT, MP. (II) Administrative support: RZ, MP, BP, LS, WT. (III) Provision of study materials or patients: RZ, WT, MP, LS. (IV) Collection and assembly of data: RZ, WT, MD. (V) Data analysis and interpretation: RZ, BP, MP, WT, LS. (VI) Manuscript writing: RZ, MP, WT, BP, LS, MD. (VII) Final approval of manuscript: RZ, MP, WT, MD, BP, LS.

Acknowledgements

Thanks to all the peer reviewers and editors for their opinions and suggestions.

Conflicts of interest

The authors declare that there is no conflict of interest regarding the publication of this article.