Trends of in-hospital cardiac arrests in a single tertiary hospital with a mature rapid response system.

BACKGROUND: Most studies on rapid response system (RRS) have simply focused on its role and effectiveness in reducing in-hospital cardiac arrests (IHCAs) or hospital mortality, regardless of the predictability of IHCA. This study aimed to identify the characteristics of IHCAs including predictability of the IHCAs as our RRS matures for 10 years, to determine the best measure for RRS evaluation.
METHODS: Data on all consecutive adult patients who experienced IHCA and received cardiopulmonary resuscitation in general wards between January 2010 and December 2019 were reviewed. IHCAs were classified into three groups: preventable IHCA (P-IHCA), non-preventable IHCA (NP-IHCA), and inevitable IHCA (I-IHCA). The annual changes of three groups of IHCAs were analyzed with Poisson regression models.
RESULTS: Of a total of 800 IHCA patients, 149 (18.6%) had P-IHCA, 465 (58.1%) had NP-IHCA, and 186 (23.2%) had I-IHCA. The number of the RRS activations increased significantly from 1,164 in 2010 to 1,560 in 2019 (P = 0.009), and in-hospital mortality rate was significantly decreased from 9.20/1,000 patients in 2010 to 7.23/1000 patients in 2019 (P = 0.009). The trend for the overall IHCA rate was stable, from 0.77/1,000 patients in 2010 to 1.06/1,000 patients in 2019 (P = 0.929). However, while the incidence of NP-IHCA (P = 0.927) and I-IHCA (P = 0.421) was relatively unchanged over time, the incidence of P-IHCA decreased from 0.19/1,000 patients in 2010 to 0.12/1,000 patients in 2019 (P = 0.025).
CONCLUSIONS: The incidence of P-IHCA could be a quality metric to measure the clinical outcomes of RRS implementation and maturation than overall IHCAs.

Introduction

Despite the advances in the management of in-hospital cardiac arrest (IHCA) over the past decade, IHCA remains associated with poor outcomes [1,2]. However, while it is frequently preceded by a more gradual, possibly treatable, decline [3-6], many cases of IHCAs are considered preventable based on retrospective reviews [3,5-7]. To reduce the incidence of IHCA, a rapid response system (RRS) was designed to identify early signs of clinical deterioration and activate a specialized team of caregivers [8]. Most recently, the International Society of RRS recommends that hospitals collect data on IHCAs and their potential predictability [9].

A cardiac arrest is treated with cardiopulmonary resuscitation (CPR), which is lifesaving for patients who have a history of acute, potentially reversible illness. However, this is not effective if cardiac arrest occurs in patients in fatal conditions with terminal illness. “Do not attempt CPR” (DNACPR) decisions allow resuscitation to be withheld when the chance of success is little or when the burdens of CPR outweigh the benefits [10]. Nevertheless, physicians are occasionally faced with patients requesting full resuscitation against medical advice. More commonly, neither patients nor their family members make such a request, but physicians simply presume that providing CPR comports with the patient’s wishes [11,12]. Therefore, performing CPR on all IHCAs, regardless of the severity of the underlying illness and end-of-life medical decision, may be inappropriate [13]. In contrast, the implementation of RRS also increases the likelihood of DNACPR [14], which could be partially attributed to the reduced IHCA cases after RRS implementation but with a lesser impact on hospital mortality.

However, most studies on RRS have simply focused on its role and effectiveness in reducing IHCA or hospital mortality, regardless of the type of IHCA [8]. As a result, it has been difficult to determine the overall rate of potentially avoidable IHCA and if this rate is changing with implementation and maturity of RRS. Therefore, this study aimed to identify the rates and characteristics of IHCAs including predictability of the IHCAs as our RRS matures for 10 years, to determine the best measure for RRS evaluation.

Methods

Study design, setting, and participants

This retrospective observational study included all consecutive patients who experienced IHCA and received CPR in general wards at Samsung Medical Center, Seoul, South Korea between January 2010 and December 2019; this university affiliated tertiary referral hospital has a 1,989-bed capacity with a hospital-wide medical emergency team (MET) for the RRS. To address the primary research question of whether characteristics of IHCAs in hospitalized adult patients is associated with maturity of our MET over 10 years, we reviewed the clinical data of all treated IHCAs through the electronic medical records. This study was approved by the institutional review board of the Samsung Medical Center and performed in compliance with Helsinki declaration. The institutional review board waived the requirement for informed consent due to the observational nature of the research. Additionally, the patients’ information was anonymized and de-identified prior to analysis.

Operation of the RRS

The hospital-wide MET at the Samsung Medical Center was introduced at the beginning of March 2009, consisted of either fellows that were training in critical care or senior residents in internal medicine [15-18]. Since March 2013, the MET consists of dedicated intensivist physicians, including critical care fellows and attending intensivists, which provide round-the-clock coverage. All hospital medical personnel were presented with information about the MET and educated to prevent inadequate clinical assessments of patient deterioration that cause delays in the MET activation. Before implementation of the automated system, physicians and nurses directly contacted the MET using a dedicated phone number when a patient met any single criterion (Table 1). Activation was also allowed when the medical staff was concerned about changes in their patient’s clinical condition, even in the absence of physiological disorders that meet the criteria. In August 2016, the MET initiated an automated alert and activation system for all ward patients using a modified early warning score (MEWS) [19]. The MEWS was automatically calculated using five physiological parameters (systolic blood pressure, heart rate, respiratory rate, body temperature, and level of consciousness) when nurses records the patient’s vital signs on the electronic medical record. Patient vital signs were recorded at the bedside immediately after measurement using a laptop or portable device whenever possible. MEWS was automatically updated with each new vital sign recorded. The frequency of measuring vital signs was made according to the order of the attending physician, but vital signs were usually measured at least four times a day and more often when the patient’s clinical condition changed. If the MEWS was 7 or higher, an automated alert was sent to MET as a text message in real-time, 24-hours a day, 7 days a week, and MET was automatically activated. Calls for MET activation were available for all patients regardless of do-not-resuscitate status during the study period.

Table 1

Calling criteria for the medical emergency team.

Airway and breathing	Acute respiratory distress: respiratory rate ≥ 30 breaths/min Acute hypoxia: oxygen saturation derived from pulse oximetry < 90% for 5 min, despite previous oxygen administration Acute hypercapnia and acute acidosis: arterial carbon dioxide pressure > 50 mmHg and pH < 7.3 Upper airway obstruction: stridor or use of respiratory accessory muscle
Circulation	Unexplained hypotension: systolic blood pressure < 90 mmHg Acute chest pain Bradycardia or tachycardia: heart rate < 50 beats/min or > 130 beats/min Arrhythmia with symptom
Neurology	Sudden mental change or unexplained agitation Seizure
Other	Bedside concern about overall deterioration

When activated, the MET is expected to arrive within 10 min, complete patient assessments within 30 min, and order diagnostic tests and therapeutic treatments relevant to the patient’s condition. In certain clinical problems requiring specialized expertise, other teams such as acute myocardial infarction team, acute stroke team, and acute care surgery team also can be activated. Following assessment and initial treatment, an individual treatment plan is created for each patient, and a joint decision is made about whether to transfer the patient to the intensive care unit (ICU). The issue of limitation on medical intervention and end-of-life care can also be discussed at this point. After assessment and therapeutic interventions by the MET, patients who are considered to require treatment and monitoring that cannot be provided outside of the ICU are transferred to the ICU, while patients in a stable condition remain on the general ward. For patients who are not fully stabilized and require intensive monitoring but are able to manage with lower levels of care than in the ICU, admission to the unit is decided on a case-by-case basis. The MET determined the patient’s disposition and shared information about the advance care plan with the primary care team. Discussion about end-of-life care and ceiling of care were also included in certain patient populations. The decisions about completion of intervention and disposition were left to the judgment of each member of the MET without specific criteria, but the decision making generally followed international guidelines [20].

Details of all MET calls were recorded as soon as possible after the event by a member of the team and were entered into a registry. This recorded patient demographics, reasons for the MET activation based on calling criteria, time of the first documented physiological disorder, modified early warning score, time of the MET activation and deactivation, vital signs at the time of the MET activation and deactivation, interventions delivered by the MET, and the final outcomes including the patient’s disposition after the clinical episode [21,22]. These data were supplemented on the next day with a retrospective review of hospital medical records before registration for quality control of registry data.

Definitions

All IHCAs were classified into three groups [23,24]: Preventable IHCA (P-IHCA) was defined as a cardiac arrest with preexisting signs of acute physiologic disturbance that fulfilled the MET activation criteria from 8 hours to 30 minutes before arrest. Non-preventable IHCA (NP-IHCA) was defined as a cardiac arrest that occurred within 8 hours after admission, or without any record of vital signs within 8 hours before arrest, or within 30 minutes after drug administration or procedures, or from unexpected lethal arrhythmia; this includes cardiac arrest that occurred within 30 minutes after MET activation. Inevitable IHCA (I-IHCA) was defined as IHCA in patients who had already requested a DNACPR order or were in terminal health conditions. Cases that were difficult to be classified were resolved by consensus of the MET team.

Statistical analysis

The MET dose was calculated by the number of MET calls per annum divided by the total number of discharged patients per year, represented as cases per 1,000 patients. In addition, each rates of IHCAs according to the classification or in-hospital mortality was calculated by the number of IHCA or in-hospital mortality per annum divided and represented as cases per 1,000 patients. Data were presented as number and percentages. The annual changes of the numbers and rates were analyzed with Spearman correlation analysis and Poisson regression models, respectively. All data were analyzed using SPSS version 22 (IBM Corp., Armonk, NY).

Results

During the 10-years study period, 843,180 patients were admitted to Samsung Medical Center and a total of 824 consecutive IHCAs were recorded for adult patients. After excluding duplicated CPRs for the same IHCAs (n = 24), a total of 800 treated IHCAs with CPR on the general ward were retrieved for the primary analysis (0.95/1,000 patients). The baseline characteristics of 800 IHCA patients are given in Table 1. There were 467 (58.4%) male, and the median age was 64.5 (IQR, 53.0–74.0) years. Malignant disease (47.8%) and cardiovascular disease (26.8%) were the most frequent comorbidities. The median hospital admission day before arrest was 9.7 (IQR 4.0–22.7) days. The most IHCA was occurred during weekdays (68.9%) and half of events occurred at daytime. Common location was general ward (58.3%), followed by monitoring room (36.4%). Cardiovascular (29.5%) was common cause of arrest, and 50.6% initially presented with pulseless electrical activity rhythm. Extracorporeal cardiopulmonary resuscitation was applied to 22 (7.2%) patients.

As MET matured, the number of the MET activations increased significantly from 1,164 in 2010 to 1,560 in 2019 (P = 0.002) (Fig 1). In addition, the median time from derangement to MET activation decreased from 66 minutes in 2010 to 40 minutes in 2019 (P < 0.001).

Fig 1

Medical emergency team (MET) maturation per year since 2010.

The circles and lines represent of the number of MET activations. The number of MET activations increased from 1,164 in 2010 to 1,560 in 2019 (P for trend = 0.002). The diamonds and dotted lines represent the time from derangement to MET activation. The time from derangement to MET activation decreased from 66 minutes in 2010 to 40 minutes in 2019 (P for trend < 0.001). MET, medical emergency team.

Of the 800 IHCA patients, 149 (18.6%) had P-IHCA, 465 (58.1%) had NP-IHCA, and 186 (23.2%) had I-IHCA (Table 2).

Table 2

Clinical characteristics of in-hospital cardiac arrests (N = 800).

Variables	No. of patients or median (IQR)
Sex, male	467 (58.4)
Age, year	64.5 (53.0–74.0)
Medical department admission	583 (72.9)
Comorbidities
Cardiovascular disease	214 (26.8)
Respiratory disease	36 (4.5)
Malignant disease	382 (47.8)
Central nervous system	63 (7.9)
Hepatobiliary disease	37 (4.6)
Chronic kidney disease	42 (5.3)
Documented treatment limitation	103 (12.9)
Hospitalization prior to arrest, day	9.7 (4.0–22.7)
IHCA day and time period
Weekday	551 (68.9)
Daytime hours (8:00 ~ 18:00)	368 (46.0)
Location of arrest
General ward	466 (58.3)
Monitoring room	291 (36.4)
Procedure room	18 (2.3)
Others	25 (3.1)
Monitored patients	543 (67.9)
MET activation within 24 hours of IHCA	121 (15.1)
Witnessed arrest	683 (85.4)
Presumed reason for arrest
Cardiovascular arrest	236 (29.5)
Respiratory arrest	352 (44)
Hypovolemic shock	60 (7.5)
Sepsis	43 (5.4)
Brain injury	10 (1.3)
Anaphylaxis	8 (1.0)
Unknown	91 (11.4)
Initial rhythm
Shockable	147 (18.4)
Pulseless electrical activity	405 (50.6)
Asystole	216 (27.0)
Not available	32 (4.0)
Extracorporeal cardiopulmonary resuscitation	58 (7.2)
Classification of IHCA
P-IHCA	149 (18.6)
NP-IHCA	465 (58.1)
I-IHCA	186 (23.2)
Survivor at hospital discharge	252 (31.5)

No., number; IQR, interquartile range; IHCA, in-hospital cardiac arrest; P-IHCA, preventable in-hospital cardiac arrest; NP-IHCA, non-preventable in-hospital cardiac arrest; I-IHCA, inevitable in-hospital cardiac arrest; MET, medical emergency team.

Among 252 patients (31.5%) survived at discharge, only 121 (15.1%) patients were managed by our MET within 24 hours before the IHCA. However, the MET dose was relatively unchanged over time (P = 0.531), since the number of admitted patients increased from 72,468 in 2010 to 100,788 in 2019 (P < 0.001). Finally, in-hospital mortality rate was significantly decreased from 9.20/1,000 patients in 2010 to 7.23/1,000 patients in 2019 (P = 0.004) (Table 3).

Table 3

Annual trend of the MET activation and in-hospital mortality.

	2010	2011	2012	2013	2014	2015	2016	2017	2018	2019	P for trend
Number of MET activation	1,164	1,068	1,311	1,359	1,316	1,284	1,608	1,500	1,680	1,560	0.002
MET dose, /1000 patients	16.1	14.6	18.0	16.4	14.8	16.9	17.8	16.1	18.3	15.5	0.603
In-hospital mortality, /1000 patients	9.20	10.10	9.64	8.13	8.14	8.37	8.10	8.26	7.97	7.23	0.004
Admitted patients	72,468	73,308	72,960	83,100	89,064	75,852	90,588	93,384	91,668	100,788	<0.001

MET, medical emergency team.

The trend for the overall IHCA rate was stable from 0.77/1,000 patients in 2010 to 1.06/1,000 patients in 2019 (P for trend = 0.720) (Fig 2). However, the incidence of NP-IHCA (P for trend = 0.382) and I-IHCA (P for trend = 0.054) was relatively unchanged over time, while that of P-IHCA decreased from 0.19/1,000 patients in 2010 to 0.12/1,000 patients in 2019 (P for trend = 0.006) (Fig 2).

Fig 2

Annual trend of in-hospital cardiac arrests (IHCAs) by classification.

P-IHCA, preventable in-hospital cardiac arrest; NP-IHCA, non-preventable in-hospital cardiac arrest; I-IHCA, inevitable in-hospital cardiac arrest.

Discussion

This study investigated the change of overall and various type of IHCAs following RRS implementation and maturation over 10 years. The major finding is that the RRS call had been increased significantly as the RRS had been maturated, and the P-IHCA and in-hospital mortality were decreased significantly. However, the overall rate of IHCAs did not change significantly during the study period.

Although there is no standard measure for evaluating the maturity of RRS from the existing literature on RRS maturity, several studies have revealed the correlation of the number of activation with the maturity of RRS [25-27]. In a long-term observational study, Herod R et al. found that progressively increased number of RRS activations concurred with lower hospital mortality [25]. Moriarty JP et al. also found that the reduction in rescue failure rates was associated with a substantial increase in the number of RRS activation [26]. In addition, timeless response to patient deterioration has been recommended as quality metrics of RRS process [9], since delayed activation of RRS is associated with higher in-hospital mortality [28,29]. In the present study, the increased number of the RRS activations and decreased the time from derangement to RRS activation concurred with lowered in-hospital mortality over 10 years, although no causality could be concluded. Therefore, it might be considered that our RRS has matured over the past decade.

Several previous studies have shown reduced incidence of IHCAs after the implementation and maturity of RRS [30,31]. However, these studies simply focused on reducing IHCAs regardless of the predictability of IHCA, although the overall rate of IHCAs might be limited for the evaluation of RRS [8]. Therefore, potentially preventable IHCAs, rather than total number of IHCAs, is recommended as a quality metric for the evaluation of RRS by the International Society of RRS [9]. In this study, the trend for the overall IHCA rate was stable with maturity of our RRS over 10 years. The lack of change in the overall rate of IHCAs might be associated with the number of I-IHCAs that were not suitable for resuscitation, which contributed to the overall rate of IHCAs. Therefore, 23.2% of IHCAs might receive inappropriate CPR despite the futile situation reflecting both a low chance of survival and likely poorer quality of life afterward if spontaneous circulation is returned. This highlights a potential problem with using the overall rate of IHCAs as an outcome measure for RRS, which could explain the failure of previous studies to demonstrate consistently the efficacy of RRS in decreasing total hospital mortality [32].

Our results indicate that the most common circumstances of P-IHCAs were sudden critical illness in under-monitored patients and delays in initiating RRS response for monitored patients who met crisis criteria, which are consistent with previous reports [3,5-7]. Therefore, more IHCAs might be preventable by closer monitoring on floors and by preventing delays in addressing deterioration in patient condition. Effective risk management necessitates that preventable IHCA is minimized. Therefore, the effort for reducing preventable IHCA, rather than overall IHCA, could be a more appropriate quality metric to measure the clinical outcomes of RRS implementation and maturation; however, inconsistent definitions have limited its generalizability in a wide range of healthcare settings [9].

Although this study provides additional information on a more appropriate quality metric for RRS implementation and maturation using simple methods that are reproducible within the existing resources of most hospitals, there are several limitations that should be acknowledged. First, the study was limited by its inherent retrospective observational nature. However, data on treated IHCAs were prospectively collected from consecutive patients received CPRs. Therefore, our cohort is more likely to reflect the patients encountered in routine practice and thus can be readily applicable in similar settings. Second, the present study was conducted at a single institution with physician-based MET. Accordingly, our findings may have limited generalizability in other RRS. Finally, an automated alert and activation system was integrated into the original RRS activation process in August 2016. However, this change of activation process could be itself a sign of the maturation of our RRS (S1 Table).

Conclusion

In conclusion, the incidence of P-IHCA could be a more appropriate quality metric to measure the clinical outcomes of RRS implementation and maturation than overall IHCA.

Comparison of MET activation, incidence of IHCAs, and in-hospital mortality before and after implementing the automated alert and activation system in August 2016.

(DOCX)

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27 Oct 2021

PONE-D-21-31238Trends of in-hospital cardiac arrests in a single tertiary hospital with a mature rapid response systemPLOS ONE

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Reviewer #1: Dear Editor

Dear Authors

This is a retrospective observational study focusing on the consequences of implementing a RRS on the incidence and distribution of IHCA in a major hospital. Of note, only patients who suffered of IHCA in the general wards were included, according to the quality metrics published by the third international consensus conference on RRS (2019), which is correctly cited in the manuscript (9). The authors analyzed the yearly distribution between I-IHCA, P-IHCA and NP-IHCA from the start (2010) to the end (2019) of the period in exam and found a statistically significant decrease in P-IHCA from 0.19/1000 patients in 2010 to 0.12/1000 patients in 2019, with a number of total IHCA stable through the years and consistent with the rest of the literature (around 1/1000 patients). Attributing this decrease to implementation and maturation of RRS, the authors conclude that the incidence of P-IHCA (as opposed to overall IHCA) may be a better indicator of the effects of the implementation and maturation of a RRS in a major hospital.

One of the strengths of the article is the number of the patients suffering from IHCA, unusually high for a study of this type, thanks to a decade-long thorough follow-up. Another point in favour of the research would be the prospectively collection of consecutive patients. It must also be noted that the article is well written, concise, with clear infographics and no major spelling errors (to my knowledge).

However, there are a few issues, stated below:

Major issues:

1) The definition of preventable IHCA used by the authors in the article is different from the one adopted in the 2019 consensus statement on RRS (9), first and foremost regarding the time window before the event of IHCA: “at least 30 min prior to and within 24” as stated by the consensus VS “from 8 hours to 30 minutes before arrest” as used by the authors in the article at line 96. Another (reported here for simplicity) minor issue on this definition is the diction of “preventable” IHCA used by the authors opposed to the one of “predictable” used in the consensus.

2) The results of the study presented in terms of reduction of P-IHCA between 2010 and 2019 as stated in line 160-161 “P-IHCA decreased from 0.19/1,000 patients in 2010 to 0.12/1,000 patients in 2019 (P = 0.006)” may be seen as misleading: examining FIGURE 2 one would note that the incidence of P-IHCA in 2018 was around 0.2/1000 patients (higher than 2010), hinting to the paradoxical conclusion that if the study would have stopped in 2018 it might have shown an increase in P-IHCA. It is also evident from the same table that in 2011 the incidence of P-IHCA was around 0.3/1000 patients (highest in the decade). Given the conclusion stated by the authors in line 208-209 “the incidence of P-IHCA could be a more appropriate quality metric to measure the clinical outcomes of RRS implementation and maturation than overall IHCA” (this is also the opinion of the reviewer on the matter), a single analysis of the incidence of P-IHCA in 2010 VS the incidence of P-IHCA in 2019 may not be seen by the reader as sufficient to back this conclusion. A suggestion to address this issue (and other minor issues stated below) would be to pool the data from 2010 to July 2016 vs August 2016 to 2019, the latter representing the period with a more experienced MET, with dedicated staff (since March 2013) and an automated activation system (since August 2016). If significant, this analysis would point toward the conclusion that the incidence of P-IHCA is reduced by the implementation and maturation of RRS and thus may be itself a more accurate quality metric than the incidence of overall IHCA.

Minor issues:

3) In line 45 “since March 2013 the MET was composed of dedicated intensivist physicians”: it is not stated what was the composition of the MET between 2010 and 2013.

4) A minor limitation of the study would be the switch in the activating process of the MET: the one stated in TABLE 1 until July 2016 vs the one based on MEWS since August 2016. One could argue that the adoption of the automated activation system based upon MEWS may be itself a sign of the “maturation” of the RRS: it could be wise in this case to present the results as before vs after the switch in the activation process (see more in comment 2).

5) It is not clear what was the survival at hospital discharge in the IHCA patients: was it 17.8% as stated in TABLE 2 or 31.5% as stated in line 149? In the same line the phrase “Among 252 patients (31.5%) survived at discharge and only 111 (13.9%) patients…” probably “and” is a typo

Great work, best regards

Reviewer #2: This paper may be of interest as it highlights the importance of MET in the treatment oif cardiac arrest in a big hospital. However, it is a description of MET activity over a time period and it fails to reach conclusions regarding som of the potentially more interesting aspects including the DNACPR Decisions.“

Additionally some data are reported without supporting the causality of those with the main topic of the paper. I.g.

Authors report the in-hospital mortality rate was significantly decreased (from 9.20/1,000 patients in 2010 to 7.23/1,000 patients in 2019). What this due to MEt "maturity"? If this is the underling message, there are not data supporting it.

The definition of NP IHCA is quite wide additionally it is unclear whether the occurrence within 30 minutes form MET activation was also related to a delay in MET arrival at bedside considering that the goal is the get the MET within 10 minutes.

Which is the clinical message of the following sentence: Among 252 patients (31.5%) survived at discharge and only 111 (13.9%) patients were 150 managed by our MET within 24 hours before the event

Discussion section should be widen

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Reviewer #1: Yes: Alessandro Fasolino

Reviewer #2: No

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24 Nov 2021

Response to Reviewers’ Comments

Reviewer#1:

This is a retrospective observational study focusing on the consequences of implementing a RRS on the incidence and distribution of IHCA in a major hospital. Of note, only patients who suffered of IHCA in the general wards were included, according to the quality metrics published by the third international consensus conference on RRS (2019), which is correctly cited in the manuscript (9). The authors analyzed the yearly distribution between I-IHCA, P-IHCA and NP-IHCA from the start (2010) to the end (2019) of the period in exam and found a statistically significant decrease in P-IHCA from 0.19/1000 patients in 2010 to 0.12/1000 patients in 2019, with a number of total IHCA stable through the years and consistent with the rest of the literature (around 1/1000 patients). Attributing this decrease to implementation and maturation of RRS, the authors conclude that the incidence of P-IHCA (as opposed to overall IHCA) may be a better indicator of the effects of the implementation and maturation of a RRS in a major hospital. One of the strengths of the article is the number of the patients suffering from IHCA, unusually high for a study of this type, thanks to a decade-long thorough follow-up. Another point in favour of the research would be the prospectively collection of consecutive patients. It must also be noted that the article is well written, concise, with clear infographics and no major spelling errors (to my knowledge).

: The authors really appreciate the reviewer’s encouraging comments. Regarding to your comments, we revised our manuscript based on your comments and suggestions.

Comments 1 (C1). The definition of preventable IHCA used by the authors in the article is different from the one adopted in the 2019 consensus statement on RRS (9), first and foremost regarding the time window before the event of IHCA: “at least 30 min prior to and within 24” as stated by the consensus VS “from 8 hours to 30 minutes before arrest” as used by the authors in the article at line 96. Another (reported here for simplicity) minor issue on this definition is the diction of “preventable” IHCA used by the authors opposed to the one of “predictable” used in the consensus.

Response 1 (R1). We thank the reviewer for valuable comments. Although, this study was conducted to identify the rates and characteristics of IHCAs according to the quality metrics published by the third international consensus conference on RRS, but, we used the terms of ‘predictability’ which used in the study for mature rapid response system conducted by MERIT committee (1). In this study, predictability was defined as: The events were termed “predictable” if the patient chart indicated objective or clear evidence of patient deterioration in the 6‐h period before the arrest event. In our hospital setting, patients admitted to the general ward checked vital signs at least every 8 hours. Therefore, preventable IHCA was defined as a cardiac arrest with preexisting signs of acute physiologic disturbance that fulfilled the MET activation criteria from 8 hours to 30 minutes before arrest. After reviewing several terms for the definition including avoidable, preventable, and predictable, ‘preventable IHCA’ was selected after discussing with the team members of our MET.

Reference:

1. Galhotra S, DeVita MA, Simmons RL, Dew MA; Members of the Medical Emergency Response Improvement Team (MERIT) Committee. Mature rapid response system and potentially avoidable cardiopulmonary arrests in hospital. Qual Saf Health Care. 2007 Aug;16(4):260-5.

C2. The results of the study presented in terms of reduction of P-IHCA between 2010 and 2019 as stated in line 160-161 “P-IHCA decreased from 0.19/1,000 patients in 2010 to 0.12/1,000 patients in 2019 (P = 0.006)” may be seen as misleading: examining FIGURE 2 one would note that the incidence of P-IHCA in 2018 was around 0.2/1000 patients (higher than 2010), hinting to the paradoxical conclusion that if the study would have stopped in 2018 it might have shown an increase in P-IHCA. It is also evident from the same table that in 2011 the incidence of P-IHCA was around 0.3/1000 patients (highest in the decade). Given the conclusion stated by the authors in line 208-209 “the incidence of P-IHCA could be a more appropriate quality metric to measure the clinical outcomes of RRS implementation and maturation than overall IHCA” (this is also the opinion of the reviewer on the matter), a single analysis of the incidence of P-IHCA in 2010 VS the incidence of P-IHCA in 2019 may not be seen by the reader as sufficient to back this conclusion. A suggestion to address this issue (and other minor issues stated below) would be to pool the data from 2010 to July 2016 vs August 2016 to 2019, the latter representing the period with a more experienced MET, with dedicated staff (since March 2013) and an automated activation system (since August 2016). If significant, this analysis would point toward the conclusion that the incidence of P-IHCA is reduced by the implementation and maturation of RRS and thus may be itself a more accurate quality metric than the incidence of overall IHCA.

R2. We thank the reviewer for valuable comments. First of all, the figure 2 may not clearly show the change over time of each group, which may cause confusion for readers. Therefore, line chart in the same manner as figure 1 would be more appropriate. Second, the annual changes of IHCA rates over the study period were analyzed with tests for trend, not just acomparison of arithmetic values between 2010 and 2019, as decribed in the Method section. However, we really appreciate your valuable suggestion for additional comparison of the pool data before and after the switch in the activating process of our MET. As expected, the rate of P-IHCA was reduced after implementing the aumated alert and activation system from 0.192/1000 patients to 0.124/1000 patietns, while the number of MET activation increased and in-hospital mortality decreased. We added this information in the Discussion section and provided as a supplemental table (S1 Table in the supporting information file).

C3. In line 45 “since March 2013 the MET was composed of dedicated intensivist physicians”: it is not stated what was the composition of the MET between 2010 and 2013.

R3. We thank the reviewer for valuable comments. At the beginning, the team was initially consisted of either fellows that were training in critical care or senior residents in internal medicine. We added this information in the Method section of the revised manuscript.

C4. A minor limitation of the study would be the switch in the activating process of the MET: the one stated in TABLE 1 until July 2016 vs the one based on MEWS since August 2016. One could argue that the adoption of the automated activation system based upon MEWS may be itself a sign of the “maturation” of the RRS: it could be wise in this case to present the results as before vs after the switch in the activation process (see more in comment 2).

R4. This is an excellent point of view. We totally agree that the adoption of the automated alert and activation system could be itself a sign of the “maturation” of the RRS. We added this information in the Discussion section and the results from additional comparison of the pool data before and after the system would be provided as a supplemental table (S1 Table in the supporting information file).

C5. It is not clear what was the survival at hospital discharge in the IHCA patients: was it 17.8% as stated in TABLE 2 or 31.5% as stated in line 149? In the same line the phrase “Among 252 patients (31.5%) survived at discharge and only 111 (13.9%) patients…” probably “and” is a typo.

R5. We apologize for our carelessness. We fixed the error in the sentence and modified to clarify the meaning of the sentence.

Reviewer#2:

This paper may be of interest as it highlights the importance of MET in the treatment of cardiac arrest in a big hospital. However, it is a description of MET activity over a time period and it fails to reach conclusions regarding som of the potentially more interesting aspects including the DNACPR Decisions.“

: We understand the reviewer’s concern that this study focused only on the consequences of implementing a RRS on the incidence and distribution of IHCA. However, we strive to analyze the number of patients suffering from IHCA over a 10-year period, and aimed to identify the rates and characteristics of IHCAs including predictability of the IHCAs as our RRS matures. Regarding to your comments, we revised our manuscript based on your comments and suggestions.

Comments 1 (C1). Additionally some data are reported without supporting the causality of those with the main topic of the paper. I.g. Authors report the in-hospital mortality rate was significantly decreased (from 9.20/1,000 patients in 2010 to 7.23/1,000 patients in 2019). What this due to MET "maturity"? If this is the underling message, there are not data supporting it.

Response 1 (R1). We thank the reviewer for valuable comments. Previous studies have attempted to assess the effect of the RRS with a change of hospital mortality, and meta-analyses have shown that RRS might be associated with reduced in-hospital mortality and IHCA. Therefore, the change of hospital mortality in our hospital could be considered to be related with the implantation and maturity of MET over ten years. However, unfortunately, there is no standard measure for evaluating the maturity of RRS. Several studies have revealed the correlation of the number of activation with the maturity of RRS. In addition, delayed activation is associatd with higher in-hospital mortality so that timeless response to patient deterioration has been recommended as quality metrics of RRS process. In this study, the increased number of the MET activations and decreased the time from derangement to MET activation concurred with lowered in-hospital mortality over 10 years, although no causality could be concluded. Therefore, it might be considered that our MET has matured over the past decade. We added this point in the Discussion section.

C2. The definition of NP IHCA is quite wide additionally it is unclear whether the occurrence within 30 minutes form MET activation was also related to a delay in MET arrival at bedside considering that the goal is the get the MET within 10 minutes.

R2. We thank the reviewer for valuable comments. Previous studies showed that activation of the RRS in the presence of objective escalation criteria in a period of more than 30 minutes prior to an IHCA may allow the RRS to prevent the event from occurring. Periods of less than 30 minutes may not be sufficient to allow the RRS to effectively intervene. Therefore, we defined NP IHCA as a cardiac arrest that occurred within 8 hours after admission, or without any record of vital signs within 8 hours before arrest, or within 30 minutes after drug administration or procedures, or from unexpected lethal arrhythmia; this includes cardiac arrest that occurred within 30 minutes after MET activation.

Reference:

1. Downey AW, Quach JL, Haase M, Haase-Fielitz A, Jones D, Bellomo R. Characteristics and outcomes of patients receiving a medical emergency team review for acute change in conscious state or arrhythmias. Crit Care Med. 2008 Feb;36(2):477-81.

2. Quach JL, Downey AW, Haase M, Haase-Fielitz A, Jones D, Bellomo R. Characteristics and outcomes of patients receiving a medical emergency team review for respiratory distress or hypotension. J Crit Care. 2008 Sep;23(3):325-31.

C3. Which is the clinical message of the following sentence: Among 252 patients (31.5%) survived at discharge and only 111 (13.9%) patients were managed by our MET within 24 hours before the event.

R3. We apologize for lack of clarity. We intended to show that the majority of patients suffered form IHCA was not managed by MET before the IHCA event, even in patient survived to discharge from the hospital. But, there was a typo in the sentence (there should have been no 'and’), which made it fail to convey meaning. We corrected the error in the revised manuscript.

C4. Discussion section should be widen.

C4. We added the discussion of the MET maturity in the Discussion section of the revised manuscript.

Submitted filename: PONE-D-21-31238 R1 Response to reviewrs.docx

Click here for additional data file.

29 Dec 2021

Trends of in-hospital cardiac arrests in a single tertiary hospital with a mature rapid response system

PONE-D-21-31238R1

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Thank you very much for having addressed properly the comments of the reviewers. Now the paper has gain in quality and clarity so it could be suitable for publication.

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Reviewer #1: Dear Editor, dear Authors

my suggestions in the last review were sufficiently addressed by the authors.

One last minor issue lies in the comment. The authors replied in R1 "In our hospital setting, patients admitted to the general ward checked vital signs at least every 8 hours", but in the Method section - operation of RRS it was stated "The frequency of measuring vital signs was made according to the order of the attending physician, but vital signs were usually measured at least four times a day and more often when the patient’s clinical condition changed". Please be more clear on how frequently the minimum of vital signs are collected.

Reviewer #2: The author have imporved the information of the paper. I have no further comments to be addressed.

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Reviewer #1: Yes: Alessandro Fasolino

Reviewer #2: No

6 Jan 2022

PONE-D-21-31238R1

Trends of in-hospital cardiac arrests in a single tertiary hospital with a mature rapid response system

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