Emergency Medicine

Delayed arrival of advanced life support adversely affects the neurological outcome in a multi-tier emergency response system

a b s t r a c t

Aim: prehospital management of out-of-hospital cardiac arrest (OHCA) is based on basic life support, with the ad- dition of Advanced life support if possible. This study aimed to investigate the effect of delayed arrival of ALS on neurological outcomes of patients with OHCA at hospital discharge.

Methods: This was a retrospective study of a registry of patients with OHCA. A multi-tier emergency response sys- tem was established in the study area. ALS was initiated when the second-arrival team arrived at the scene. A re- stricted cubic spline curve was used to investigate the relationship between the response time interval of the second-arrival team and neurological outcomes at hospital discharge. Multivariable logistic regression analysis was performed to assess the independent association between the response time interval of the second-arrival team and neurological outcomes of patients at hospital discharge.

Results: A total of 3186 adult OHCA patients who received ALS at the scene were included in the final analysis. A restricted cubic spline curve showed that a long response time interval of the second-arrival team was correlated with a high likelihood of poor neurological outcomes. Meanwhile, multivariable logistic regression analysis showed that a long response time interval of the second-arrival team was independently associated with poor neurological outcomes (odds ratio, 1.10; 95% confidence interval, 1.03-1.17).

Conclusion: In a multi-tiered prehospital emergency response system, the delayed arrival of ALS was associated with poor neurological outcomes at hospital discharge.

(C) 2023

  1. Introduction

Out-of-hospital cardiac arrest (OHCA) is a major global medical issue with a high mortality rate. Despite advances in prehospital and hospital management, the proportion of survivors with favourable neurological outcomes in most countries is <10% [1]. As treatment delay can lead to fatal adverse effects on the prognosis of patients with cardiac arrest, prompt and appropriate management by an emergency medical service

* Correspondence to: D K Lee, Department of Emergency Medicine, Seoul National University Bundang Hospital, 13620, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam- si, Gyeonggi-do, Republic of Korea.

?? Correspondence to: Department of Public Healthcare Service, Seoul National University Bundang Hospital, 13620, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam- si, Gyeonggi-do, Republic of Korea.

E-mail addresses: [email protected] (D.K. Lee), [email protected] (D.-H. Jang).

1 These authors contributed equally to this work.

(EMS) at the Prehospital stage is essential for achieving good outcomes in patients with OHCA. Previous studies have reported that a short re- sponse time interval of the EMS is associated with improved patient prognosis [2-4].

Prehospital management of patients with OHCA is largely based on basic life support (BLS) involving chest compression and ventilation while applying an automated external defibrillator, with the addition of Advanced Life Support if possible. Previous reports have demon- strated that achieving prehospital return of spontaneous circulation (ROSC) has a profound effect on the outcomes of patients with OHCA. Accordingly, ALS at the scene has been introduced in many developed countries [5,6].

Several studies have suggested that early intravenous drug adminis- tration or securing an advanced airway at the prehospital stage in pa- tients with OHCA may improve prognosis [7-11]. However, the positive effects have been found to be inconsistent [9,12-15]. Moreover,

https://doi.org/10.1016/j.ajem.2023.06.001

0735-6757/(C) 2023

studies comparing prehospital ALS and BLS have reported conflicting re- sults with regard to the superiority of ALS at the scene relative to BLS [16-21]. However, most of these studies assessed the effectiveness of a subset of procedures rather than the entire ALS procedure or compared whether BLS or ALS was performed at the beginning of EMS management. We hypothesised that in a multi-tiered emergency response system, even if appropriate BLS is performed by emergency medical technicians at the scene by the first-arrival team, the delayed arrival of ALS may adversely affect the prognoses of patients with OHCA. Therefore, this study aimed to investigate the effects of delayed arrival of ALS on the neurological outcomes of patients with OHCA at hospital discharge

with adjustment for BLS arrival time.

  1. Methods
    1. Study setting and design

The present study was a retrospective analysis of a prospectively col- lected registry of patients with OHCA from January 2017 to December 2018 in Gyeonggi province, South Korea [10,22,23].

The EMS system in South Korea is government-based and is oper- ated by the National Fire Agency. In Gyeonggi province, a metropolitan area located in the suburban area of the capital city of Seoul, a two-tier dispatch system is operated for patients with suspected cardiac arrest. When suspected cardiac arrest victims are reported to the EMS, two paramedic teams of 2-3 crew members each are dispatched from the two nearest fire stations. Each paramedic team includes at least one level-1 paramedic (EMT-Paramedics in the US) besides level-2 para- medics (EMT-Basics in the US) or nurses.

When one of the two dispatched teams arrive at the scene, BLS, in- cluding chest compression and ventilation, is commenced. When the second team arrives at the scene, the transition from BLS to ALS is imple- mented as rapidly as possible. All dispatched teams in the study area could provide ALS. However, when the first team arrives, it focuses on BLS, and ALS is initiated after the arrival of the second team. ALS at the scene includes the establishment of an intravenous line, administration of medications such as epinephrine and amiodarone, as needed, and se- curing an advanced airway under direct medical control by an emer- gency physician via Video call.

To secure an advanced airway, an i-gel supraglottic airway device is used, or endotracheal intubation is performed at the discretion of the EMTs at the scene. Emergency physicians providing direct medical con- trol during ALS receive certification after completing formal training in ALS. The BLS and ALS provided to the patients are performed according to the American Heart Association (AHA) guidelines [24,25]. The deci- sion to transfer to a hospital is made when ROSC is achieved at the scene or when the emergency physician providing direct medical con- trol determines that transfer to a hospital while continuing ALS is more favourable than staying longer at the scene.

This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (B-2211-793-101).

    1. Data collection and processing

This study included all adult (aged >=18 years) patients with OHCA of medical cause who received ALS by EMTs at the scene and were trans- ferred to an emergency department. Patients aged <18 years, patients who did not receive ALS at the scene because the additional team did not arrive, patients with cardiac arrest of non-medical cause, patients with cerebral performance category 3 or 4 before cardiac arrest, and pa- tients with invalid data were excluded.

Data on the response time interval of the second-arrival team (time interval from reporting to the EMS to the arrival of the second team at the scene), the main interest of the present study, were collected from the registry. Additionally, data on age, sex, comorbidities, location of cardiac arrest, presence of a witness, cardiopulmonary resuscitation

(CPR) by a bystander, response time interval of the first-arrival team (time interval from reporting to the EMS to the arrival of the first team at the scene), duration of ALS at the scene (time interval from the arrival of the second team to departure to the emergency depart- ment), transport time, and achievement of prehospital ROSC were col- lected. Outcome variables such as survival admission, survival discharge, and neurological outcomes at discharge were also collected. Location of arrest was classified into public and non-public places. First-monitored rhythm was classified into shockable and non- Shockable rhythms.

The primary outcome of this study was the neurological outcome at hospital discharge. The Cerebral Performance Category score was used to evaluate the neurological outcomes at hospital discharge. A CPC score of 1 or 2 indicated a favourable neurological outcome, whereas a CPC score of 3-5 indicated a poor neurological outcome. The CPC score at hospital discharge was determined by the attending physician.

    1. Statistical analyses

The clinical characteristics of the study population are presented as medians (interquartile ranges) for continuous variables or as numbers (percentages) for categorical variables. Continuous variables were ex- amined with the Shapiro-Wilk test to determine the normality of the distribution, and Students’ t-test or the Wilcoxon rank sum test was per- formed, as appropriate. Categorical variables are described as a number with a percentage and were compared using the chi-square test or Fisher’s exact test, as appropriate.

To assess the clinical characteristics of the enrolled patients, they were divided according to neurological outcomes. In addition, to assess whether there was a difference in patient characteristics according to the response time of the second-arrival team, the enrolled patients were divided into quartiles based on the response time of the second- arrival team.

A restricted cubic spline curve with three knots was generated to in- vestigate the relationship between the response time interval of the second-arrival team and neurological outcomes at hospital discharge. Multivariable logistic regression analysis was performed to assess the independent association between the response time interval of the second-arrival team and neurological outcomes of patients at hospital discharge. The multivariable analysis included variables potentially re- lated to the neurological outcome of the patients, such as age, sex, loca- tion of arrest, presence of a witness, CPR by a bystander, response time interval of the first-arrival team, first-monitored rhythm, ALS duration at the scene, transport time, and achievement of prehospital ROSC.

Subgroup analyses were performed to determine possible differ- ences in the effect of ALS arrival time according to the clinical character- istics of the patients before the arrival of the ALS. The association between the response time interval of the second-arrival team and neu- rological outcomes at hospital discharge was analysed for subgroups ac- cording to the following criteria: location of arrest, presence of a witness, and whether bystander CPR was performed.

All data processing and statistical analyses were performed using R- package software, version 4.1.3 (R Foundation for Statistical Computing, Vienna, Austria). A two-tailed p-value of <0.05 was considered statisti- cally significant.

  1. Results

During the study period, 5199 patients with OHCA were eligible for ALS at the scene. Of these patients, 1623 were excluded based on the ex- clusion criteria and 390 because of invalid time or outcome data. A total of 3186 patients were included in the final analysis (Fig. 1). Table 1 pre- sents the clinical characteristics of the two groups divided according to the neurological outcomes at hospital discharge. The Response times of the first- and second-arrival teams were both significantly longer in the group with poor neurological outcomes.

Image of Fig. 1

Fig. 1. Flowchart of the study population.

The restricted cubic spline curve of the association between the re- sponse time interval of the second-arrival team and likelihood of poor neurological outcomes showed the presence of a consistent relationship between the two factors. The restricted cubic spline curve indicates that a longer response time interval of the second-arrival team was corre- lated with a higher likelihood of poor neurological outcomes (Fig. 2). Table 2 summarises the clinical characteristics of the patients divided into quartiles according to the response time of the second-arrival team. Table 3 presents the results of multivariable logistic regression analysis: the response time interval of the second-arrival team was in- dependently associated with poor neurological outcomes (odds ratio, 1.10; 95% confidence interval, 1.03-1.17).

Subgroup analyses showed a significant association between the re-

sponse time interval of the second-arrival team and neurological out- comes in the following groups: occurrence of OHCA in a public place, presence of a witness, and performance of CPR by a bystander (Fig. 3).

  1. Discussion

The present study demonstrated that when the response time of the second-arrival team is delayed, that is, the arrival of the ALS team at the scene is delayed, the neurological outcomes of patients with OHCA can be adversely affected. Despite adjusting for the time taken to commence the provision of BLS by the EMS at the scene (response time interval of the first-arrival team), the delayed arrival of the ALS team adversely af- fected the prognoses of patients with OHCA.

The need for prehospital ALS was instigated due to the suggestion that early administration of medications such as epinephrine or amio- darone and securing an advanced airway would be beneficial for the prognosis of patients with OHCA. In two large studies on the effects of epinephrine administration at the prehospital stage, epinephrine administration had a positive effect on ROSC and survival but not on achieving favourable neurological outcomes [7,9]. Among them,

Table 1

Baseline characteristics of patients according to the neurological outcome at hospital discharge

Total (N = 3186)

Favourable neurological outcome (n = 209)

Poor neurological outcome (n = 2977)

p

Age

71.0 (57.2-80.8)

55.0 (47.0-62.0)

72.0 (59.0-81.0)

<0.001

Male sex

2073 (65.1)

171 (81.8)

1902 (63.9)

<0.001

Hypertension

1008 (31.6)

42 (20.1)

966 (32.4)

<0.001

Diabetes

732 (23.0)

27 (12.9)

705 (23.7)

<0.001

Public place

2229 (70.0)

113 (54.1)

2116 (71.1)

<0.001

witnessed arrest

1449 (45.5)

154 (73.7)

1295 (43.5)

<0.001

Bystander CPR

1940 (60.9)

143 (68.4)

1797 (60.4)

0.025

Response time of first-arrival team (min)

7.0 (5.0-9.0)

6.0 (5.0-8.0)

7.0 (5.0-9.0)

<0.001

Initial shockable rhythm

580 (18.2)

175 (83.7)

405 (13.6)

<0.001

Response time of second-arrival team (min)

12.0 (9.0-16.0)

10.0 (8.0-13.0)

12.0 (9.0-16.0)

<0.001

Advanced airway

2918 (91.6)

177 (84.7)

2741 (92.1)

<0.001

Intravenous line secured

2627 (82.5)

163 (78.0)

2464 (82.8)

0.097

Epinephrine administered

2166 (68.0)

71 (34.0)

2095 (70.4)

<0.001

Amiodarone administered

264 (8.3)

37 (17.7)

227 (7.6)

<0.001

Received intravenous medication or advanced airway

3070 (96.4)

183 (87.6)

2887 (97.0)

<0.001

Call to first epinephrine administration (min)

19.0 (16.0-23.0)

16.0 (14.0-19.0)

19.00 (16.0-23.0)

<0.001

Call to first amiodarone administration (min)

24.0 (19.0-28.0)

19.0 (18.0-22.0)

24.00 (20.0-29.0)

<0.001

Duration of ALS at the scene (min)

19.0 (14.0-24.0)

12.0 (9.0-17.0)

19.0 (14.0-24.0)

<0.001

Transport time (min)

6.0 (4.0-9.0)

7.0 (4.0-11.0)

6.0 (4.0-9.0)

<0.001

Prehospital ROSC

661 (20.7)

200 (95.7)

461 (15.5)

<0.001

Image of Fig. 2

Fig. 2. Restricted cubic spline curve of the association between the arrival time of the second-arrival team and likelihood of poor neurological outcomes at hospital discharge. The dark line indicates the likelihood of poor neurological outcomes at hospital discharge, while the grey shaded area represents the 95% confidence interval.

Tanaka et al. [7] further analysed the difference in prognosis according to the time of the first administration of epinephrine after the EMS call and reported that epinephrine administration within 19 min was more likely to result in survival and favourable neurological outcomes than administration after 19 min. Similarly, a previous study on the

timing of amiodarone administration at the prehospital stage reported that in patients with recurrent shockable rhythms, early amiodarone administration was associated with an increased likelihood of achieving favourable neurological outcomes [10]. Previous studies on the timing of advanced airway management in the prehospital stage have reported

Table 2

Patient baseline characteristics according to the response time of the second-arrival team

Response time of second-arrival team

<9 min

Response time of second-arrival team 9-12 min

Response time of second-arrival team 12-16 min

Response time of second-arrival team

>=16 min

p

(n = 936)

(n = 820)

(n = 776)

(n = 654)

Age

71.0 (58.0-81.0)

71.0 (57.0-81.0)

71.0 (57.0-80.0)

71.0 (58.0-80.0)

0.956

Male sex

611 (65.3)

531 (64.8)

504 (64.9)

427 (65.3)

0.995

Hypertension

290 (31.0)

258 (31.5)

256 (33.0)

204 (31.2)

0.822

Diabetes

214 (22.9)

173 (21.1)

190 (24.5)

155 (23.7)

0.418

Public place

674 (72.0)

582 (71.0)

529 (68.2)

444 (67.9)

0.188

Witnessed arrest

422 (45.1)

386 (47.1)

330 (42.5)

311 (47.6)

0.190

Bystander CPR

594 (63.5)

558 (68.0)

468 (60.3)

320 (48.9)

<0.001

Response time of first-arrival team (min)

5.0 (4.0-6.0)

7.0 (6.0-8.0)

8.0 (6.0-10.0)

9.0 (7.0-12.0)

<0.001

Initial shockable rhythm

172 (18.4)

158 (19.3)

154 (19.8)

96 (14.7)

0.057

Response time of second-arrival team (min)

8.0 (7.0-9.0)

11.0 (10.0-12.0)

14.0 (13.0-15.0)

20.0 (18.0-21.0)

<0.001

Advanced airway

847 (90.5)

760 (92.7)

709 (91.4)

602 (92.0)

0.397

Intravenous line secured

748 (79.9)

686 (83.7)

647 (83.4)

546 (83.5)

0.115

Epinephrine administered

608 (65.0)

573 (69.9)

549 (70.7)

436 (66.7)

0.036

Amiodarone administered

80 (8.5)

68 (8.3)

69 (8.9)

47 (7.2)

0.683

Received intravenous medication or advanced

890 (95.1)

801 (97.7)

747 (96.3)

632 (96.6)

0.035

airway

Call to first epinephrine administration (min)

15.0 (13.0-17.0)

18.0 (15.0-20.0)

21.0 (18.0-23.0)

25.0 (22.0-29.0)

<0.001

Call to first amiodarone administration (min)

20.0 (16.0-24.0)

22.0 (19.0-25.0)

26.0 (22.0-31.0)

26.0 (24.0-33.0)

<0.001

Duration of ALS at the scene (min)

19.0 (15.0-25.0)

19.0 (15.0-24.0)

19.0 (14.0-24.0)

18.0 (12.0-23.0)

<0.001

Transport time (min)

5.0 (3.0-7.0)

6.0 (4.0-9.0)

6.0 (4.0-9.0)

8.0 (5.0-11.0)

<0.001

Prehospital ROSC

222 (23.7)

194 (23.7)

138 (17.8)

107 (16.4)

<0.001

Survival admission

255 (27.2)

210 (25.6)

176 (22.7)

134 (20.5)

0.010

Survival discharge

135 (14.4)

88 (10.7)

67 (8.6)

38 (5.8)

<0.001

Discharge with favourable neurological

87 (9.3)

60 (7.3)

39 (5.0)

23 (3.5)

<0.001

outcome

Table 3

Multivariable logistic regression analyses of the variables associated with poor neurologi- cal outcomes

OR

95% CI

p

Response time of second-arrival team

1.10

1.03-1.17

0.024

Age

1.03

1.02-1.05

<0.001

Male sex

1.05

0.63-1.74

0.847

Public place

1.02

0.66-1.59

0.914

Witnessed arrest

0.69

0.43-1.08

0.107

Bystander CPR

0.91

0.57-1.44

0.685

Response time of first-arrival team

1.01

0.91-1.12

0.880

Initial shockable rhythm

0.10

0.06-0.15

<0.001

Duration of ALS on the field

1.11

1.07-1.15

<0.001

Transport time

0.99

0.96-1.02

0.379

Prehospital ROSC

0.02

0.01-0.05

<0.001

OR, odds ratio; CI, confidence interval; CPR, cardiopulmonary resuscitation; ALS, advanced life support; ROSC, return of spontaneous circulation.

similar results on medication administration. Several studies on the timing of securing an advanced airway in the prehospital stage have reported that rapid application of advanced airway strategies was asso- ciated with favourable outcomes for patients with OHCA [8,11]. Our results suggested that the earlier ALS is applied to patients with OHCA the higher the likelihood of them achieving favourable neurological out- comes, which may also be associated with the earlier application of additional treatments.

Previous studies have comparatively analysed the effects of the addi- tional application of prehospital ALS and of BLS alone for patients with OHCA, but findings have been inconsistent. Two meta-analyses com- pared the survival of patients who received BLS or ALS at the prehospital stage and reported the superiority of ALS in terms of survival [26,27]. However, subsequent studies reported different results regarding the effectiveness of ALS. Cournoyer et al. [17] reported that providing pre- hospital ALS increased the likelihood of achieving prehospital ROSC compared with providing BLS alone but did not increase the likelihood of achieving hospital discharge. Two other studies that analysed the ef- fect of providing prehospital ALS to patients on long-term or neurolog- ical outcomes compared with providing BLS alone reported that providing ALS may adversely affect the prognosis of patients with OHCA [16,20]. These inconsistent results may be attributed to

Image of Fig. 3

Fig. 3. Adjusted odds ratio and 95% confidential interval for the association between the response time of the second-arrival team and poor neurological outcomes in the full cohort and subgroups.

differences in various factors, such as differences in response time, scene time interval, and transport time.

Response time is the time taken for the EMS to arrive at the scene and constitutes a key factor in determining the prognosis of patients with OHCA [2-4]. Response time has a strong effect on no-flow or low-flow time in the early stage of treatment flow in patients with OHCA, and this depends largely on the ability of the bystander. If CPR is not performed by a bystander, the entire response time is added to the No-flow time, which adversely affects patients. Even if CPR is per- formed by a bystander, the Quality of CPR may pose as an issue. Further, although high-quality CPR by a well-trained bystander may be per- formed in some cases, high-quality CPR is only performed after EMTs ar- rive at the scene in most cases. Throughout the treatment process, adjusting for differences in performance by a bystander is essentially impossible. In the present study, the response time of the first-arrival team was corrected through multivariate analysis to assume a similar level of treatment as possible before commencing ALS.

In Table 1, fewer patients with favourable neurological outcomes than with poor neurological outcomes had received epinephrine or ad- vanced airway strategies. This can lead to the misunderstanding that performing ALS results in a poor prognosis in patients. The arrival of the second-arrival team to the scene in this study refers to the 1) admin- istration of medication via an intravenous line and securing an ad- vanced airway, 2) Real-time feedback about CPR being performed at the scene from an emergency physician by video call, and 3) an increase in the number of team members performing CPR that enables ALS. The results of the present study suggest that the delay in implementation of the interventions seemed to have a significant impact on the neurolog- ical outcomes of the patients than whether or not the interventions were performed. When the enrolled patients were divided according to the response time of the second-arrival team, there was no significant trend in the proportion of patients who received epinephrine or had an advanced airway secured, based on the response time of the second team; however, there was a trend of worsening patient outcomes as the response time of the second team increased (Table 2). Moreover, in the multivariable analysis, after adjusting for other factors that may affect the prognosis of patients, the response time of the second- arrival team showed an independent association with the neurological outcomes.

Subgroup analyses showed that the delayed arrival of ALS adversely affected the neurological outcomes, particularly in cases of OHCA that occurred in a public place, witnessed OHCA, and CPR performed by a by- stander. Occurrence in a public place, presence of a witness, and perfor- mance of CPR by a bystander have been reported to be the factors associated with good prognoses [28,29]. These results suggest that rapid arrival of ALS is beneficial to patients who are likely to have a good prognosis in case of successful resuscitation.

A previous study that investigated patient prognosis according to the application of prehospital BLS and ALS and timing of ALS reported that patients who received only BLS at the scene had a poorer prognosis than those who received ALS alone or switched from BLS to ALS [18]. Al- though this study did not directly compare the differences in neurolog- ical outcomes of patients depending on the timing of the transition from BLS to ALS, the results suggested that even though BLS by EMTs was per- formed, BLS maintained for a long time without conversion to ALS may lead to poor outcomes for patients with OHCA. Indeed, the results of the present study suggested that delayed arrival of ALS could adversely af- fect the neurological outcomes of patients with OHCA, even if EMTs ad- ministered appropriate BLS before ALS arrival.

The present study has some limitations. First, this study was a Retro- spective analysis based on a registry. Although several factors were corrected through propensity score matching and multivariable analy- sis, unmeasured confounders may have influenced the results. Second, the difference in patient treatment between groups before the start of ALS was assumed to be similar by correcting for factors such as whether bystander CPR was performed and the response time of the first-arrival

team. However, the effect of unmeasured differences according to the performance of bystander CPR cannot be ignored. Third, in the EMS sys- tem of South Korea, it is impossible for EMTs to terminate CPR at the scene unless a sign of apparent death is present before the start of CPR. As such, the characteristics of the EMS system may have affected the results, including the survival or neurological outcomes of patients.

  1. Conclusions

In a multi-tiered prehospital emergency response system, the delayed arrival of ALS was associated with poor neurological outcomes at hospital discharge.

Funding

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Hae Chul Yang: Writing – original draft, Formal analysis, Data curation. Seung Min Park: Resources, Formal analysis, Data curation. Kui Ja Lee: Resources, Data curation. You Hwan Jo: Supervision, Project administration, Investigation. Yu Jin Kim: Validation, Methodology, Conceptualization. Dong Keon Lee: Writing – review & editing, Meth- odology, Conceptualization. Dong-Hyun Jang: Writing – review & editing, Validation, Formal analysis, Data curation.

Declaration of Competing Interest

None.

Acknowledgements

None.

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