Article, Emergency Medicine

The association of emergency department administration of sodium bicarbonate after out of hospital cardiac arrest with outcomes

a b s t r a c t

Background: Sodium bicarbonate administration is mostly restricted to in-hospital use in Taiwan. This study was conducted to investigate the effect of sodium bicarbonate on outcomes among patients with out-of-hospital car- diac arrest (OHCA).

Methods: This population-based study used a 16-year database to analyze the association between sodium bicar- bonate administration for resuscitation in the emergency department (ED) and outcomes. All adult patients with OHCA were identified through diagnostic and procedure codes. The primary outcome was Survival to hospital admission and secondary outcome was the rate of death within the first 30 days of Incidence of cardiac arrest. Cox proportional-hazards regression, logistic regression, and propensity analyses were conducted.

Results: Among 5589 total OHCA patients, 15.1% (844) had survival to hospital admission. For all patients, a positive association was noted between sodium bicarbonate administration during resuscitation in the ED and survival to hospital admission (adjusted odds ratio [OR]: 4.47; 95% confidence interval [CI]: 3.82-5.22, p b 0.001). In propen-

sity-matched patients, a positive association was also noted (adjusted OR, 4.61; 95% CI: 3.90-5.46, p b 0.001).

Conclusions: Among patients with OHCA in Taiwan, administration of sodium bicarbonate during ED resuscitation was significantly associated with an increased rate of survival to hospital admission.

(C) 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://

creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Out-of-hospital cardiac arrest (OHCA) remains a leading cause of mortality and a substantial issue of Public health concern worldwide. Overall, survival to hospital discharge rates are lower in the Asian population, ranging from 0.5% to 8.5% [1-3]. In comparison with the Asian population, the rates of survival to hospital discharge are higher in the European countries and United states, ranging from 1.1% to 30.8% [4,5]. To help restore cardiac and cerebral perfusion during

? All authors read and approved the final manuscript.

* Correspondence to: C.-T.Hsiao, Department of Emergency Medicine, Chang Gung Memorial Hospital, No.6, W. Sec., Jiapu Rd., Puzih City, Chiayi County 613, Taiwan.

?? Correspondence to: Y.-H. Yang, Department for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan.

E-mail addresses: [email protected] (M.-S. Hung), [email protected], [email protected] (C.-T. Hsiao), [email protected] (Y.-H. Yang).

1 Cheng-Ting Hsiao and Yao-Hsu Yang have the same contributions to the manuscript and thus are both co-corresponding authors.

cardiopulmonary resuscitation (CPR) and accomplish a favorable neurological outcome, the programs and guidelines of the Advanced cardiac life support are widely disseminated and applied inter- nationally. The ACLS guidelines recommend the administration of spe- cific drugs under certain conditions [6]. The administration of sodium bicarbonate during CPR is controversial, despite its widespread use in OHCA patients [7]. Moreover, supporting evidence of its benefit and efficacy is lacking [8,9]. One previous study reported that early use of sodium bicarbonate and more frequent use during out-of-hospital CPR resulted in better short- and long-term outcomes [10]. Another recent report demonstrated that sodium bicarbonate administration during CPR in the emergency department (ED) was associated with increased return of spontaneous circulation (ROSC) [11]. In contrast, several studies failed to demonstrate the benefit of buffer therapy with sodium bicarbonate in OHCA [12-15]. Thus, the routine use of sodium bicarbon- ate during CPR was not recommend in the 2010 American Heart Associ- ation (AHA) guidelines, and the use of sodium bicarbonate was limited to specific conditions such as pre-existing metabolic acidosis, hyperkalemia and tricyclic antidepressant intoxication [8].

https://doi.org/10.1016/j.ajem.2018.03.010

0735-6757/(C) 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The aim of our study was to assess the association between admin- istration of sodium bicarbonate in the ED setting and outcomes of OHCA patients.

Methods

This study was a retrospective population-based cohort research. The National Health Insurance (NHI) program was started in 1995, pro- viding compulsory universal health insurance, and the duration of our study database was from January 1, 1997 through December 31, 2012. The National Health Insurance (NHI) program is a longitudinal ongoing program. It enrolls approximately 99% of the Taiwanese population, which was about 23,000,000 individuals, and contracts with 97% of all the country’s health care services [16]. For research purposes, a random sample of 1,000,000 people who still participated in the NHI program at 2005 was selected as sample population. Using data from all registered patients would result in possible identification of persons. Thus, the NHI encourages researchers to use randomly-selected-patient database for research purposes. According to the Taiwan National Health Research Institute (NHRI), the random sample group is considered representative of the entire population since the group did not differ significantly from the whole cohort in age, sex, or Health care costs. This random sample of 1,000,000 people was used as our study cohort. Information about ad- missions and outpatient visits, both of which included information on patient characteristics (i.e., sex, date of birth, date of admission, date of discharge, and dates of visits) and up to five discharge diagnoses or three outpatient visit diagnoses, using the International Classification of Diseases, Ninth Revision (ICD-9) classification, were collected [17]. We also gathered information on patient prescriptions, including the names of prescribed drugs, dosage, duration, and total expenditure. Previously used for epidemiologic research, the NHRI database provides high quality information on Prescription use, diagnoses, and hospitali- zations [18]; this database had been previously used for OHCA research [19,20]. The NHRI strictly followed confidentiality guidelines in accor- dance with personal electronic data protection regulations, making the NHI reimbursement data suitable for research [21]. In addition, this study was approved by the Chang Gung Medical Foundation Institu- tional Review Board.

We conducted a population-based cohort study with a total of 7555

patients. All patients aged older than 18 years who experienced cardiac arrest (ICD-9 codes 427.5, 798.9, 798.1, 798.2, and 798) and were admit- ted to the ED between January 1, 1997, and December 31, 2012, formed the study cohort. Those who did not receive any CPR, defibrillation, or endotracheal intubation during ED stay were excluded (n = 1996). Pa- tients who suffered from Traumatic cardiac arrest (ICD-9 codes 800-999 and E800-999) were not excluded. Individuals with cardiac arrest whose death was announced by the emergency medical services (EMS) at the scene or without transportation to the hospital were not included because EMS records were not available in our NHI database. In Taiwan, Pre-hospital emergency care is provided by emergency medical technicians from different fire bureaus. Most EMTs are EMT-II, trained to perform basic life support, intravenous access, and laryngeal mask airway insertion, but not to administer Intravenous medications. Some cities have paramedics (EMT-Ps) who are allowed to perform advanced life support procedures, including intravenous drug administration. Complete pre-hospital ACLS is performed only in some urban areas since the number of EMT-Ps is limited, and most of ACLS was initiated in the ED, including administration of sodium bicarbonate. The primary outcome was survival to hospital admission, whilst secondary outcome was the rate of death within the first 30 days of incident of cardiac arrest. Survival to hospital admission in this study

was defined as sustained ROSC with hospital admission.

We identified in a systematic way, any co-morbid condition or dis- ease as a potential confounder, defined by diagnoses recorded before January 1, 2005, including angina, acute myocardial infarction, coronary artery disease, diabetes, malignancies, heart failure, cerebrovascular

disease, and Charlson Comorbidity Index (CCI). The CCI is a scoring system that strengthens important concomitant diseases and has been validated for studies that employ ICD-9 data [19,22,23].

We also considered socio-demographic characteristics (age, sex, level of urbanization, level of hospital, and level of monthly income) in the modelling. Level of hospital was classified as either medical center or non-medical center. The definition of medical centers in Taiwan were the highest level of teaching hospitals with capability of providing 24-h, 7 days per week emergency cardiac catheterizations for acute ST elevation myocardial infarction and providing highest level of trauma cares, including emergent surgeries [24]. Urbanization levels in Taiwan are divided into seven groups, according to publications of the Taiwan National Health Research Institute [25], as follows: group 1, highly ur- banized area; group 2, moderately urbanized area; group 3, emerging area; group 4, general rural area; group 5, aging area; group 6, agricul- tural area; and group 7, remote area [25]. In our study, group 4, group 5, group 6, and group 7 are merged into a single group that is called “general rural area.” Thus, the urbanization levels in our report are classified as highly urbanized area, moderately urbanized area, emerg- ing area, and general rural area. Individual monthly income with new Taiwan dollar (NTD) is divided into four groups: 0; 1-15,840; 15,841- 25,000; and ?25,001. According to the Ministry of Health and

Welfare of Taiwan, individual monthly income b150% of the poverty

level amount is defined as a low-income level [26]. Thus, we classified these four groups as follows: no income (0), low and medium low in- come (1-15,840), middle income (15,841-25,000), and high income (?25,001).

Post-arrest treatments were not included as independent variables

since the cohort consisted of OHCA patients. To analyze the association of post-arrest treatments with outcomes, another study containing only those patients with survival to hospital admission would be more appropriate.

Several important factors, such as location of cardiac arrest, by- stander cardiopulmonary resuscitation, initial rhythm on cardia moni- tor, witness status, causes of cardiac arrest and pH value of arterial blood gas, were unavailable in our NHI database. Thus, we collected these data from a single hospital, from 2011 to 2013 by chart review. This chart review was also approved by the hospital’s institutional reviewing board and the results of these data are shown in Supplemen- tary Tables 1, 2, 3.

Sodium bicarbonate use in the ED was not randomly assigned in the patient population and most use of sodium bicarbonate depends on ED physicians’ discretion whether laboratory data was available or not; therefore, we developed a propensity score for sodium bicarbonate use in the ED and controlled for potential confounding and selection bias [27,28]. Using multivariable logistic regression analysis, which did not consider patient outcome, the propensity score for sodium bicar- bonate use in the ED was determined. A full logistic regression model was carried out with sodium bicarbonate use in the ED as a dependent variable, which included every variable in Table 1 as independent variables. A propensity score for sodium bicarbonate use in the ED was calculated from the logistic regression equation for each patient. This propensity score represented the probability that a patient with OHCA would be given sodium bicarbonate in the ED. Using the SAS macro program by Parsons et al. [29], and the propensity score, a nearest-neighbor matching procedure, matched patients with OHCA who were given sodium bicarbonate with control patients who were not given sodium bicarbonate in the ED at a ratio of 1:2.

Mann-Whitney U test, a Student’s t-test, and chi-square test or

Fisher’s exact test were used to compare the statistically significant differences between sodium bicarbonate use and non-use in OHCA patients [30]. Cox proportional hazards models were used to compute the Hazard ratios (HRs) for mortality of OHCA patients. A logistic regression model was applied for risk analysis of survival to hospital admission for OHCA patients accompanying 95% confidence interval (CI) after adjustment for the variables mentioned. A two-tailed, p-value

Table 1

Demographic and characteristics of out-of-hospital cardiac arrest patients with sodium bicarbonate or without sodium bicarbonate injection.

co-morbidity disease, and CCI, patients who were administered sodium bicarbonate still had significantly higher rates of survival to hospital ad- mission than those who had not been administered sodium bicarbonate

Variables No sodium

bicarbonate

(N = 3704)

(N = 1885)

n

%

n

%

Sex Female

1325

35.8

745

39.5

?0.006

Male

2379

64.2

1140

60.5

Sodium bicarbonate

p-Value

(28.4 vs. 8.1, p b 0.0001) (Table 2).

Logistic regression for the risk factor of survival to hospital admis- sion of the 5589 OHCA patients showed that age >= 50 (OR: 0.72; 95% CI: 0.59-0.88, p = 0.002) was associated with a lower rate of survival to hospital admission. Treatment at a medical center (OR: 1.34; 95%

CI: 1.13-1.60, p = 0.001) and sodium bicarbonate administration (OR: 4.47; 95% CI: 3.82-5.22, p b 0.001) were associated with a higher

Age, y

?0.036

rate of survival to hospital admission. Similarly, for the matched and

b50

663

17.9

381

20.2

control groups, sodium bicarbonate was still associated with a higher

>=50

3041

82.1

1504

79.8

Urbanized level

Highly urbanized area 850 22.9 513 27.2

Moderately urbanized area 1781 48.1 855 45.4

Emerging area 715 19.3 324 17.2

General rural area 358 9.7 193 10.2

Income

No income 259 7.0 138 7.3

Medium low and low income 1229 33.2 652 34.6

Middle income 1556 42.0 830 44.0

High income 660 17.8 265 14.1

Comorbid disease

?0.002

?0.005

rate of survival to hospital admission (OR: 4.61; 95% CI: 3.90-5.46, p b 0.001) (Table 3).

The risk of death within 30 days was significantly lower with sodium bicarbonate use, after adjustment for baseline risk factors for death (hazard ratio (HR), 0.84; 95% CI: 0.79-0.89, p b 0.001) (Table 4).

Because the prehospital information was unavailable in our NHI data base, we conducted a retrospective, single-institutional, chart-review investigation and prehospital variables were included. The characteris- tics of patients from this investigation is shown in Supplementary Table 1. A total of 464 OHCA patients (including trauma and non-

Angina 75 2.0 46 2.4 0.3

Acute myocardial infarction 98 2.7 80 4.2 ?0.001

Ischemic heart disease 56 1.5 33 1.8 0.5

Diabetes mellitus 194 5.2 98 5.2 0.9

CCI 0.5

0 1213 32.7 598 31.7

1 1288 34.8 648 34.4

>=2

1203

32.5

639

33.9

Medical center treatment

0.8

Medical center

945

25.5

487

25.8

Non-medical center

2759

74.5

1398

74.2

TCA use

0.9

Yes

69

1.9

34

1.8

No

3661

98.1

1825

98.2

Survival to hospital admission

*

b 0.0001

Yes

304

8.2

540

28.6

No

3400

91.8

1345

71.4

CCI: Charlson Comorbidity Index; TCA: triCyclic antidepressants.

* Indicates significance at p b 0.05.

b0.05 was considered significant. All analyses were conducted using SAS statistical software (version 9.4; SAS Institute, Cary, NC).

Results

Fig. 1 illustrates the Selection process of study participants.

A total of 5589 OHCA patients, of whom 15.1% (844) had survival to hospital admission, were included as the study cohort. Of these 5589 patients, 1885 (33.7%) received sodium bicarbonate administration during ED stay and 415 (7.4%) survived within 30 days. No patient received TRIS-Buffer since it was not available for human use in our country. Patients who received chest compressions had a lower propor- tion of bicarbonate use than non-use (91.8% vs 93.9%, p = 0.0032). Furthermore, patients who received assisted ventilation and patients who received any defibrillation attempt had a higher proportion of sodium bicarbonate use than non-use (91.8% vs 88.0%, p b 0.0001, 26.2% vs 13.4%, p b 0.0001, respectively). Table 1 lists the demographic characteristics, hospital level, and urbanization group of OHCA patients with or without injection of sodium bicarbonate.

There were significant differences between sodium bicarbonate use and non-use in terms of sex, age, urbanized levels, income levels, and comorbid disease with acute myocardial infarction. Patients in whom sodium bicarbonate was administered, had lower rate of mortality within 30 days (88.1 vs. 94.8, p b 0.0001). After matching using propen- sity scores with independent variables including age, sex, level of hospi- tal, urbanization grouping, income level, use of Tricyclic antidepressants,

trauma) were included. However, the pH value was available for 400 (86.2%) patients. The difference in pH value between sodium bicarbon- ate use and sodium bicarbonate non-use was insignificant (Supplemen- tary Table 1).

The results of logistic regression analysis for survival to hospital admission in the 464 patients are shown in Supplementary Table 2. In consistence with Table 3, sodium bicarbonate use was associated with increased rate of survival to hospital admission (OR:4.06; 95%CI: 2.54- 4.68, p b 0.001) (Supplementary Table 3).

Cox regression analysis result of the chart-review investigation is shown in Supplementary Table 3. Contrary to the results of the popula- tion-based data shown in Table 4, sodium bicarbonate administration was not associated with 30-day mortality after including prehospital variables and pH value as a variable (HR: 0.91; 95% CI: 0.72-1.15, p = 0.45) (Supplementary Table 3).

Discussion

The main finding in this study was that sodium bicarbonate admin- istration was associated with a higher rate of survival to hospital admission.

Administration of sodium bicarbonate in cardiac arrest has been a debate for decades. tissue hypoxia due to hypoventilation or inade- quate perfusion during cardiac arrest results in metabolic acidosis and increased lactate levels [31,32]. To correct metabolic acidosis and allevi- ate serious adverse effects caused by severe acidosis, thereby improving the response to exogenous catecholamines and coronary perfusion pressure, sodium bicarbonate administration was recommended in early ACLS guidelines from 1976 and widely used in the 1980s [33-35]. However, concerns regarding the unfavorable effects of injection of sodium bicarbonate during cardiac arrest, such as reduction of systemic vascular resistance, hypernatremia, hyper-osmolality, have recently been raised [8,36]. In addition, failure to provide benefits from sodium bicarbonate administration in clinical data have waived the routine use of sodium bicarbonate in cardiac arrest [7,12,14]. Sodium bicarbon- ate is only recommended for patients in some special situations, such as pre-existing metabolic acidosis, hyperkalemia, or tricyclic antidepres- sant intoxication [8], and both metabolic acidosis and hyperkalemia are usually confirmed by laboratory tests, which might be limited in the EMS setting. In our study, 73.9% of patients with sodium bicarbonate use had blood gas analysis but only 37.6% of patients without sodium bi- carbonate use had blood gas analysis (p b 0.0001), suggesting that most use of sodium bicarbonate was based on results of laboratory data. After including blood gas analysis as an independent variable in our

Fig. 1. Flow chart of identification of study sample and follow up. NHI: National Health Insurance, EMS: emergency medical system, ICD-9: International Classification of Diseases, ninth revision, ED: emergency department, CPR: cardiopulmonary resuscitation, OHCA: out-of-hospital cardiac arrest.

propensity analysis, the result of logistic regression of survival to hospi- tal admission still demonstrated that sodium bicarbonate administra- tion is associated with higher rate of survival to hospital admission (OR: 2.88; 95% CI: 2.42-3.44, p b 0.001).

Although there are concerns about adverse effects and limited ben- efits of sodium bicarbonate administration in cardiac arrest, this drug is still commonly used in clinical practice. Similar to other studies from Taiwan and Korea [11,15], 33.7% of all patients in our study had re- ceived sodium bicarbonate therapy. One large study, including 264 EMS agencies, reported that the rate of sodium bicarbonate administration in OHCA patients was 19%, ranging from 0.3% to 71% [7]. Insufficient evidence from clinical trials that support the benefits of sodium bicar- bonate likely contribute to this discrepancy between practice in the real world and knowledge.

Several studies have reported that the use of sodium bicarbonate has a beneficial role in prolonged duration of Cardiac resuscitations. In the second trial conducted at Western Pennsylvania, Vukmir et al. demon- strated that there was a significant trend toward increased survival to ED arrival in the subgroup of patients with prolonged (N15 min) cardiac arrest. Other clinical or experimental studies have shown that sodium bicarbonate has a role in favorable outcomes during resuscitation [10,13,15,37-40]. In addition, a recent study in Korea reveals that sodium bicarbonate is associated with increased ROSC during on- going resuscitation after matching patients with ROSC to non-ROSC with blood bicarbonate level and Resuscitation duration [11]. As in Korea, most ACLS is restricted to hospital use in Taiwan. Our study, in contrast with the study in Korea and another study in Taiwan, demon- strated that sodium bicarbonate was associated with increased ROSC,

Table 2

Matched patients with or without sodium bicarbonate injection.

Table 4

Cox regression analysis for risk factors of death within 30 days.

Variables Non sodium

bicarbonate

Sodium bicarbonate

p-Value

Variables Adjusted hazard ratio

Hazard ratio 95% CI p-Value

(N = 3220) (N = 1610)

n % n %

Sex

Female 1.00

Sex

0.7

Male

1.02

0.96

1.08

0.6

Female

1119

34.8

567

35.2

Age, y

Male

2101

65.2

1043

64.8

50b

1.00

Age, y

0.9

?50

1.08

0.99

1.17

0.1

b50

562

17.5

280

17.4

>=50

2658

82.5

1330

82.6

Medical center treatment

Urbanized level

0.9

Non-medical center

1.00

Highly urbanized area

659

20.5

342

21.2

Medical center

0.95

0.89

1.02

0.1

Comorbid disease

CCI

0

1.00

1

1.02

0.95

1.09

0.7

>=2

1.03

0.95

1.10

0.5

Sodium bicarbonate injection No 1.00

Comorbid disease

Angina 54

1.7

27

1.7

1

Yes

TCA use

0.84

0.79

0.89

b0.001?

Acute myocardial infarction 40

1.2

18

1.1

0.7

No

1.00

Ischemic heart disease 44

1.4

20

1.2

0.7

Yes

1.01

0.83

1.24

0.9

Diabetes mellitus 172

5.3

87

5.4

0.9

CCI 0.9 CCI: Charlson Comorbidity Index, TCA: tricyclic antidepressants.

0

1073

33.3

529

32.9

* Indicates significance at p b 0.05.

1

1127

35.0

560

34.8

>=2

1020

31.7

521

32.4

There were several potential limitations of this study. First, several

Medical center treatment 1 unmeasured confounders, which were related to pre-hospital factors

Moderately urbanized area

1591

49.4

790

49.1

Emerging area

642

19.9

309

19.2

General rural area

328

10.2

169

10.5

Income

0.9

No income

219

6.8

106

6.6

Medium low and Low income

1049

32.6

536

33.3

Middle income

1438

44.7

711

44.2

High income

515

15.9

257

15.9

Medical center 795 24.7 398 24.7

Non-medical center 2425 75.3 1212 75.3

TCA use 0.8

Yes 57 1.8 30 1.9

and EMS system, including place of occurrence, witnessed collapse, bystander-initiated cardiopulmonary resuscitation (CPR), EMS re- sponse time, initial arrest rhythm, pre-hospital defibrillation, airway

No 3163 98.2 1580 98.1

Survival to hospital admission

Yes

260

8.1

457

28.4

No

2960

91.9

1153

71.6

* b 0.0001

management, and drug administration, were not available in our database. According to one pre-hospital emergency system report from Taiwan, about 2.6% of total cardiac arrest patients resuscitated by

Emergency medical technicians were declared dead without

Two groups are matched with age, sex, urbanized level, income, comorbid disease, CCI, level of hospital and TCA use.

CCI: Charlson Comorbidity Index, TCA: tricyclic antidepressants.

* Indicates significance at p b 0.05.

and even more, survival to hospital admission and decreased 30-day mortality [11,15].

In our study, age ? 50 was associated with lower rate of survival to hospital admission (OR: 0.72; 95% CI: 0.59-0.88, p = 0.002). One recent

study from Austria has shown an increasing rate of 30-day mortality (+21.8%, p b 0.001) and unfavorable neurological outcome (+18.8%, p b 0.001) with increasing age among age groups [41]. A higher level of hospital care, such as at a medical center, was associated with higher rate of survival to hospital admission in our study (OR: 1.34; 95% CI: 1.13-1.60, p = 0.001). Several studies have identified in-hospital factors associated with improved mortality after successful resuscitation from OHCA in patients admitted to different hospitals, with different Levels of care [42,43]. Level of hospital care has been suggested as an important factor for the difference in mortality of OHCA patients [43].

transportation to the ED [44]. These deaths were distributed randomly and were unrelated to any observed or unobserved variables. Thus, these patients were defined as missing completely at random, and thus, not included in the study, thereby, eliminating bias in the study population [45]. To overcome the shortness of unavailable prehospital data, we performed a chart review study from one institution including prehospital information, and the result of primary outcome was consis- tent, sodium bicarbonate use was associated with increased survival to hospital admission. Second, the data were obtained from an administra- tive database, which has been shown in the past to have inaccuracies when used for cardiac arrest research [46]. To overcome this, proce- dures and drugs administrated during resuscitation were another key element in data selection, in addition to ICD-9 Diagnosis codes. Only those with attempts to resuscitation were enrolled in the analysis. Third, this was a retrospective cohort study; therefore, information on dosage and timing of administration of sodium bicarbonate in each pa- tient was missing. Furthermore, due to the duration of the study, incon- sistencies in treatment due to different guidelines may be present. Fourth, we were unable to document non-sustained ROSC and duration

Table 3

Logistic regression analysis for factors of survival to hospital admission.

Variables

All patients

Matched and control groups

N = 5589

Adjusted odds ratio

95% CI

p-Value

N = 4830

Adjusted odds ratio

95% CI

p-Value

Age ? 50

0.72

0.59-0.88

0.002?

0.64

0.51-0.80

b0.001?

Medical center treatment

1.34

1.13-1.60

0.001?

1.29

1.06-1.56

0.009?

Sodium bicarbonate use

4.47

3.82-5.22

b0.001?

4.61

3.90-5.46

b0.001?

* Indicates significance at p b 0.05.

of resuscitation in ED, but merely those who sustained ROSC with survival to hospital admission. We could not evaluate the association between long-term neurologic outcomes. Therefore, although adminis- tration of sodium bicarbonate was associated with an increased survival to hospital admission and decreased 30-day mortality in this study, it is possible that sodium bicarbonate has no benefit on neurologic outcome, or even worse, it might be associated with an unfavorable outcome, as a previous study on the effect of adrenaline (epinephrine) demonstrated increased ROSC but decreased one-month survival [47]. The result of Cox regression analysis of chart-review investigation (Supplementary Table 3) was inconsistent with the current population-based data, im- plying that the association between sodium bicarbonate administration and 30-day mortality needs further prospective, prehospital and hospi- tal, multi-institutional randomized investigations.

Conclusion

This population-based study in Taiwan revealed that administration of sodium bicarbonate was associated with a higher rate of survival to hospital admission in OHCA patients. Further prospective randomized studies including both prehospital and hospital variables would be help- ful to evaluate the benefits or harms of sodium bicarbonate.

Declarations

    • Ethics Approval and Consent to Participate

The institutional review board of Chang Gung Medical Foundation approved this study with approval number 201600118B1 and waived the requirement of informed consent.

  • Consent for publication

Not applicable.

  • Availability of data and supporting materials section

Data sharing not applicable to this article as no datasets were gener- ated or analyzed during the current study.

Author contributions

YCC, MSH, CTH and YHY conceived the study, designed the method. CYL and YHY supervised the conduct of the data collection. CYL and YHY undertook recruitment of participating centers and patients and man- aged the data, including quality control. CYL and YHY provided statisti- cal advice on study design and analyzed the data; YHY chaired the data oversight committee. YCC, CTH and MSH drafted the manuscript, and all authors contributed substantially to its revision. YHY and CTH takes re- sponsibility for the paper as a whole.

Conflict of interest statements

There is no conflict of interest in this study.

Financial support

This study was supported by a grant from Chiayi Chang Gung Memo- rial Hospital, Taiwan (CLRPG6G0041).

Acknowledgements

The authors would like to thank the Health Information and Epide- miology Laboratory of Chang Gung Memorial Hospital, Chia-yi Branch (CLRPG6G0041) for the comments and assistance in data analysis. This study was supported by a grant from Chang Gung Memorial Hospital, Chiayi Branch. It was based on the National Health Insurance Research Database, which is provided by the Central Bureau of National Health In- surance, Department of Health, and National Health Research Institutes. The interpretation and conclusions contained herein do not represent those of Bureau of National Health Insurance, Department of Health, or National Health Research Institutes.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi. org/10.1016/j.ajem.2018.03.010.

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