Article, Emergency Medicine

The effect of hydrocortisone on the outcome of out-of-hospital cardiac arrest patients: a pilot study

The effect of hydrocortisone on the outcome of

out-of-hospital cardiac arrest patients: a pilot study

Min-Shan Tsai MD, Chien-Hua Huang MD, Wei-Tien Chang MD,

Wen-Jone Chen MD, PhD*, Chiung-Yuan Hsu MD, Cheng-Chun Hsieh MD, Chih-Wei Yang MD, Wen-Chu Chiang MD,

Matthew Huei-Ming Ma MD, PhD, Shyr-Chyr Chen MD

Department of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan

Received 25 September 2006; received in revised form 12 December 2006; accepted 13 December 2006

Abstract

Objective: Several studies have disclosed the importance of serum adrenocorticotropic hormone and Cortisol levels in resuscitation. The objective of this study was to observe the effect of hydrocortisone on the outcome of out-of-hospital cardiac arrest (OHCA) patients.

Design: Prospective, nonrandomized, open-labeled clinical trial.

Setting: Emergency department (ED) of National Taiwan University Hospital.

Patients and Participants: Ninety-seven nontraumatic adult OHCA victims.

Interventions: Serum adrenocorticotropic hormone and total cortisol levels were examined in all patients. The hydrocortisone group (n = 36) received 100 mg intravenous hydrocortisone during resuscitation, and the nonhydrocortisone group (n = 61) received 0.9% saline as placebo.

Measurements and Results: Comparison of return of the spontaneous circulation (ROSC) rates between the 2 groups was analyzed. The hydrocortisone group had a significantly higher ROSC rate than the nonhydrocortisone group (61% vs 39%, P = .038). Hydrocortisone administration within 6 minutes after ED arrival led to an increased ROSC rate (90% vs 50%, P = .045). The hydrocortisone and nonhydrocortisone groups did not differ in the development of electrolyte disturbances, gastrointestinal tract bleeding, or infection during early postresuscitation period (gastrointestinal bleeding: 41% vs 46%, P = .89; infection: 50% vs 75%, P = .335). There was no significant difference between the hydrocortisone and nonhydrocortisone groups in terms of 1- and 7-day survival and hospital discharge rates.

Conclusions: Hydrocortisone treatment during resuscitation, particularly when administrated within 6 minutes of ED arrival, may be associated with an improved ROSC rate in OHCA patients.

D 2007

This study was supported in part by a grant form the National Taiwan University Hospital (NTUH 94S161), Taipei, Taiwan.

* Corresponding author. Tel.: +886 2 23562831; fax: +886 2

23223150.

E-mail address: [email protected] (W.-J. Chen).

Introduction

The resuscitation of patients with cardiac arrest has remained challenging despite efforts in the past decades. Much effort has been invested in improving the success rate for the return of spontaneous circulation (ROSC) and

0735-6757/$ – see front matter D 2007 doi:10.1016/j.ajem.2006.12.007

outcomes in these patients. Several research efforts, based on animal and human studies, have disclosed the importance of the hypothalamic-pituitary-adrenal axis in resuscitation [1-8]. Successfully resuscitated patients were reported to have increased serum adrenocorticotropic hormone (ACTH) levels compared to nonresuscitated patients [2,3,6]. Low Serum cortisol concentrations were also documented to be associated with early postresuscitation mortality [2,4,5]. These findings have raised questions concerning the relationship between cardiac arrest and adrenal function. Cardiac arrest has been documented to impair cortisol release from the adrenal cortex [6]. Frequent relative Adrenal insufficiency in postresuscita- tion survivors may reflect cortisol levels that are insufficient in cases of extreme stress, as seen in patients with cardiac arrest [2,9]. Therefore, we hypothesized that a high probabil- ity of cardiac arrest patients may encounter adrenal insuf- ficiency during resuscitation, which results from either pre- existed undiscovered adrenal insufficiency or cardiac arrest- induced adrenal dysfunction. Corticosteroid supplements during resuscitation significantly increased ROSC rates in an animal study [8]. To the best of our knowledge, there has not been any research performed on humans addressing the effect of corticosteroid use in cardiac arrests. The objective of this prospective clinical trial is to evaluate the effect of hydrocor- tisone administration during resuscitation on the outcomes in out-of-hospital cardiac arrest (OHCA) patients.

Materials and methods

This prospective, nonrandomized, open-labeled clinical trial, approved by the institutional review board, enrolled OHCA victims from the emergency department (ED) of the National Taiwan University Hospital from October 2004 to July 2005.

Setting

The university hospital, suited in the downtown area of Taipei City, is a tertiary-referred center hospital with about 100000 ED visits per year [10,11]. The emergency medical service configuration is a fire-based, single-tiered, basic- life-support and defibrillation system staffed by emergency medical technicians who have completed at least

264 hours of paramedic training. EMTs can perform laryngeal mask airway and tracheal intubation, and admin- ister intravenous epinephrine. At least 2 EMTs, equipped with an Automated external defibrillator , attend each call. The median call-to-response time is about 4 minutes in OHCA patients, and the median call-to-shock time by AED is about 9 minutes in patients with ventricular tachycardia and fibrillation [12,13].

Selection of participants

Eligible patients included nontraumatic OHCA patients older than 18 years. Patients with do-not-attempt-

resuscitation (DNAR) orders, pregnant women, extracorpo- real membrane oxygenation users during resuscitation, concurrent steroid users, patients with known adrenal insufficiency, patients who were successfully resuscitated before ED arrival or before seeking their willingness to be a trial participant, and OHCA survivors who were transferred to other hospitals for intensive care were all excluded from this clinical trial.

Interventions

The OHCA patients received cardiopulmonary resusci- tation (CPR) according to the advanced cardiovascular life support guidelines established by the American Heart Association in 2000 [14]. Serum ACTH and total cortisol levels were examined upon arrival at the ED in all OHCA patients. The consecutively enrolled patients were divided into 2 groups, namely, the hydrocortisone group and the nonhydrocortisone group. The hydrocortisone group in-

Fig. 1 Flow diagram of enrolled patients. ECMO, extracorporeal membrane oxygenation.

Table 1 Demographic comparison between hydrocortisone and nonhydrocortisone groups

Hydrocortisone

Nonhydrocortisone

P

Patient no.

36

61

Male

18 (50%)

24 (39%)

.236

Age (y) (average)

70.4 F 15.5

73.8 F 16.6

.320

Diabetes mellitus

10 (28%)

19 (31%)

.726

Hypertension

15 (42%)

25 (41%)

.947

Coronary artery disease

5 (14%)

18 (30%)

.081

Heart failure

2 (6%)

4 (7%)

.843

Chronic obstructive pulmonary disease

1 (3%)

4 (7%)

.416

End-stage renal disease

1 (3%)

4 (7%)

.416

Cerebral vascular disease

6 (17%)

10 (17%)

.972

Malignancy

7 (19%)

10 (16%)

.703

ACTH (pg/mL) (mean)

115.3 F 190.2

124.1 F 135.1

.592

High ACTH member (N65 pg/mL)

18 (50%)

36 (59%)

.388

Total cortisol (lg/dL) (mean)

43.0 F 49.9

36.9 F 24.5

.533

Normal-to-high cortisol member (N20 lg/dL)

26 (72%)

49 (80%)

.496

P b .05 was considered statistically significant.

volved patients the families of whom agreed that the patient should receive hydrocortisone during resuscitation, and the nonhydrocortisone group involved patients the families of whom hesitated or refused to have the patient receive the drug because of either the absence of a key person or possible side effects of the hydrocortisone. Patients in the hydrocortisone group were given 100 mg intravenous hydrocortisone (SOLU-CORTEF, Pharmacia & Upjohn Company, Kalamazoo, MI) once an agreement was obtained. Patients in the nonhydrocortisone group were given the same volume of intravenous 0.9% saline. Informed consents had been obtained from the relatives of the enrolled participants after an investigator explained the intent, risks, and benefits of the study. Successfully

Table 2 Resuscitation comparison between hydrocortisone and nonhydrocortisone groups

P b .05 was considered statistically significant.

resuscitated OHCA patients were admitted to the intensive care unit and received postresuscitation care. Patients participating in the trial did not receive therapeutic hypothermia during or after resuscitation.

Methods of measurement

Blood samples were collected from the femoral vein and preserved in a prechilled polysterene tube containing EDTA- disodium salt. Serum ACTH and total cortisol were measured in duplicate using a solid-phase chemiluminescent immuno- metric assay (DPC IMMULITE 2000, Siemens, Berlin, Germany), with respective sensitivity of 5 pg/mL and 1 Ag/dL. Normal ACTH concentrations range from 10 to

Hydrocortisone

Nonhydrocortisone

P

Patient no.

36

61

OHCA causes

Cardiac event

11 (31%)

20 (33%)

.820

Respiratory event

10 (28%)

19 (31%)

.726

Others (noncardiac and nonrespiratory)

15 (42%)

22 (36%)

.583

First monitored rhythm

Asystole

28 (78%)

51 (84%)

.476

Pulseless electrical activity

4 (11%)

4 (7%)

.464

Ventricular tachycardia/fibrillation

4 (11%)

6 (10%)

.548

CPR events

Witnessed collapse

30 (83%)

43 (71%)

.157

Call-to-response time (min)

6.6 F 5.0

5.6 F 5.4

.444

Prehospital epinephrine use

10 (28%)

14 (23%)

.595

Prehospital AED shock number

0.3 F 0.8

0.2 F 0.8

.651

prehospital intubation

18 (50%)

21 (34%)

.131

Inhospital epinephrine dosage (mg) (median [range])

8.5 (2-19)

8 (1-70)

1.000

Vasopressin use

12 (33%)

11 (18%)

.087

Inhospital defibrillation (patient no.)

12 (33%)

12 (19%)

.132

Table 3 Comparison of outcomes between hydrocortisone and nonhydrocortisone groups

Hydrocortisone (n = 36)

Nonhydrocortisone (n = 61)

P

ROSC

22 (61%)

24 (39%)

.038

Sustained ROSC

21 (58%)

23 (38%)

.049

Total CPR duration in survivors (min) (median [range])

15.5 (7-37)

13.0 (7-41)

.566

APACHE II score in survivors

36.6 F 6.4

35.8 F 7.0

.635

1-d survival

10 (28%)

14 (23%)

.592

7-d survival

7 (19%)

11 (18%)

.863

Hospital discharge

3 (8%)

6 (10%)

.805

CPC scale (median [range])

4 (4)

4 (1-4)

GCS score when discharge (median [range])

4 (4)

4.5 (4-15)

P b .05 was considered statistically significant.

65 pg/mL. Normal total cortisol concentrations in the morning range between 5 and 25 lg/dL.

Outcome measurements

Resuscitation elements were collected according to the Utstein style [15]. Causes of OHCA were classified as cardiac, respiratory, and noncardiac and nonrespiratory events. Return of the spontaneous circulation was defined as a palpable pulse with measurable blood pressure, and sustained ROSC was deemed to have occurred when chest compressions were not required for 20 consecutive minutes. In survivors, we collected the presence of postresuscitation shock and the highest Acute physiology and chronic health evaluation II score taken in the first 24 hours after ROSC, the serum sodium and Potassium levels within 24 hours, gastrointestinal (GI) tract bleeding, or infection within 7 days after ROSC, 1-day and 7-day survival rates, rate of hospital discharge, the Cerebral Performance Category scale [16] and Glasgow Coma Scale scores when discharged, and the duration of hospitalization. The postresuscitation shock was defined as the necessity of vasopressor to keep systolic blood pressure more than 90 mm Hg. Infections that developed within 7 days after ROSC were described in our previous study [11]. Gastrointestinal tract bleeding was considered when the guaiac test was positive for stool samples or for nasogastric tube drainage or when a definitive diagnosis was made by panendoscopy. The CPC scale (1 = good performance, 2 = moderate disability, 3 = severe disability, 4 = coma or vegetative state, and 5 = brain death) was assessed by primary care physicians.

Data collection and processing

Supposed that the hydrocortisone administration might increase the ROSC rate from 30% to 50% with the SD of 10%, the required sample size to achieve an 80% power at a = .05 for correctly detecting such difference was 31. Data was saved in a Microsoft Excel database (Microsoft Excel 2002; Microsoft Corporation, Seattle, Wash) and then analyzed with SPSS software for Windows (Release 10.0; SPSS, Inc, Chicago, Ill). Mean and SDs were used to describe approximately normally distributed data. The

Student t test was used for comparison of normally distributed continuous variables of the 2 groups. Median and range were used to describe data without normal distribution. The Mann-Whitney 2-sample rank sum test was used to compare continuous variables without normal distribution between the 2 groups. Binomial variables were analyzed with v2 or Fisher exact test. P b. 05 was regarded as statistically significant. Univariate covariates with a P value of less than .2 were tested for predicting ROSC through multivariate logistic regression.

Results

There were 152 OHCA patients in the National Taiwan University Hospital during the trial period. Nine patients were missed in the trial period, and 6 patients had DNAR orders. Among 109 nontraumatic, adult OHCA patients in the study period, we excluded 5 patients with ROSC before seeking permission, 2 patients with extracorporeal mem- brane oxygenation use during resuscitation, 2 patients with prehospital ROSC, 2 concurrent steroid users, and 1 patient who was transferred to another hospital after ROSC. In total, 97 nontraumatic, adult OHCA patients were enrolled in this clinical trial (Fig. 1).

The mean age of the patients was 72.5 F 16.2 years, and 42 patients (43%) were men. Cardiac events accounted for one third of OHCA causes (n = 31, 32 %), and asystole was the most common first monitored rhythm (n = 79, 81%) as

Table 4 multiple logistic regression analysis for independent factors related to the return of spontaneous circulation

OR

95% Confidence interval

Hydrocortisone*

2.96

-1.08-8.09

Witnessed collapse*

4.30

-1.31-14.12

Inhospital defibrillation

2.94

-0.92-9.42

Normal-to-high cortisol level

2.60

-0.78-8.70

Coronary artery disease

0.64

-0.21-1.94

Prehospital intubation

0.39

-0.15-1.02

* P b .05.

Table 5 Comparison of potential complications between survivors in the hydrocortisone and nonhydrocortisone groups

Hydrocortisone

Nonhydrocortisone

P

Patient no. with ROSC

22

24

UGI bleeding in 7 d after ROSC

9 (41%)

11 (46%)

.890

Infection in 7 d after ROSC

11 (50%)

18 (75%)

.335

Serum sodium (mmol/L) level during resuscitation

138.6 F 9.0

138.4 F 11.9

.942

Serum sodium (mmol/L) level within 24 h after ROSC

139.7 F 11.4

140.6 F 7.8

.822

Serum potassium (mmol/L) level during resuscitation

6.2 F 2.4

6.3 F 2.7

.933

Serum potassium (mmol/L) level within 24 h after ROSC

3.9 F 1.2

3.4 F 0.6

.214

P b .05 was considered statistically significant. UGI, upper gastrointestinal tract.

previous studies in the Asian countries [11,12,17,18]. Seventy-three patients (75%) collapsed with witness, but only 2 patients with witnessed collapse (4%) received bystander CPR. Forty-six patients (47%) gained ROSC, 44 (45%) had sustained ROSC, 18 (18%) survived more than 7 days, and only 9 (9.3%) survived to hospital discharge.

There were 36 patients (37%) receiving hydrocortisone and 61 patients (63%) receiving saline during resuscitation. There was no significant difference between the hydrocor- tisone and nonhydrocortisone groups when comparing demographics and levels of serum ACTH and total cortisol (Table 1). The causes of OHCA, first monitored rhythm, and CPR events did not differ in these 2 groups (Table 2). The hydrocortisone group had more patients gaining ROSC (61% vs 39%, P = .038) and sustained ROSC (58% vs 38%, P = .049) than the nonhydrocortisone group. No difference in CPR duration was noted between the survivors from these

2 groups. The 1- and 7-day survival rates, hospital discharge, CPC scales, and GCS scores when discharged also showed no significant difference between these 2 groups (Table 3).

In the nonhydrocortisone group, there was a trend toward increased serum ACTH and total cortisol levels in patients with ROSC when compared with those without ROSC (ACTH: 140.7 F 135.9 pg/mL vs 101.8 F 176.7 pg/mL,

P = .278; total cortisol: 38.7 F 19.2 lg/dL vs. 35.8 F

27.7 lg/dL, P = .696). Random serum total cortisol concentrations less than 20 lg/dL were usually considered

as an adrenal insufficiency [2,4,19-21]. We defined

74 patients with serum total cortisol levels more than 20 lg/dL as the normal-to-high cortisol group and 23 patients with serum total cortisol level less than 20 lg/dL as the low cortisol group. In the univariate analyses for factors relating ROSC, hydrocortisone, witnessed collapse, inhospital defi- brillation, the normal-to-high cortisol level, coronary artery disease, and prehospital intubation were associated with ROSC. Vasopressin use in our study did not associate with ROSC (odds ratio [OR], 0.81, P = .665) although several previous studies have shown the potential benefits of vasopressin in resuscitation. Hydrocortisone and witnessed collapse were independent predictors for an increased ROSC rate after multiple logistic regression analysis (Table 4).

Serum sodium and potassium levels during resuscitation and within 24 hours after ROSC did not differ in these 2 groups. In addition, these 2 groups did not differ in the development of GI tract bleeding and infection within 7 days after ROSC. In addition to 22 pneumonia cases, there were 11 urinary tract infections, 6 bacteremia, 2 vascular catheter- related infections, 1 intra-Abdominal infection, and 1 skin defect-associated infection within 7 days after ROSC (Table 5).

Patients receiving hydrocortisone showed a trend toward higher ROSC rate in both the normal-to-high and low cortisol groups (Table 6). The arrival-to-drug interval was defined as the duration from ED arrival to the application of study drugs. The involved patients received study drugs after

Table 6 Comparison of outcomes between patients with and without hydrocortisone in groups with different cortisol levels

Hydrocortisone

Nonhydrocortisone

P

Normal-to-high cortisol group (N20 lg/dL)

Patient no.

Total cortisol (lg/dL) (mean)

26

58.8 F 54.0

49

46.5 F 21.2

.325

ROSC

17 (65%)

21 (43%)

.063

7-d survival

5 (19%)

9 (18%)

.927

Hospital discharge

3 (12%)

5 (10%)

.572

Low cortisol group (b20 lg/dL)

Patient no.

Total cortisol (lg/dL) (mean)

10

9.7 F 5.0

12

9.8 F 5.1

.95

ROSC

5 (50%)

3 (25%)

.221

7-d survival

2 (20%)

2 (17%)

1.000

Hospital discharge

0 (0%)

1 (8%)

.545

P b .05 was considered statistically significant.

variable time delays because of differences in the amount of time it took for the first-line physicians to obtain a brief history and the investigators to give an explanation of the study. Hydrocortisone application within 22 minutes after collapse showed a higher ROSC rate in patients with witnessed collapse ( P = .013). Within 6 minutes after ED arrival, patients receiving hydrocortisone had a significantly

Fig. 2 (A-C) Return of spontaneous circulation comparison in terms of different timings of drug application during resuscitation. Collapse-to-drug interval indicates duration from collapse to hydrocortisone application; arrival-to-drug interval, duration from emergency department arrival to the use of the study drugs.

higher ROSC rate than those receiving placebo ( P = .045). However, there was no difference in ROSC when the arrival- to-drug interval was beyond 6 minutes ( P = .173) (Fig. 2).

Discussion

This study evaluated the effect of hydrocortisone during resuscitation in nontraumatic adult OHCA patients. The application of hydrocortisone during resuscitation, especial- ly when administrated within 6 minutes after arrival in the ED, may be associated with improved ROSC rate. The incidence of electrolyte disturbances, infection, and GI tract bleeding in the early phase after ROSC did not increase with hydrocortisone use.

Foley et al [1] disclosed the importance of the adrenal gland during resuscitation when they discovered fewer adrenalectomized dogs were successfully resuscitated than normal ones. Higher serum ACTH and cortisol levels have been associated with increased ROSC rates and better short- and long-term outcomes in resuscitated patients [2-6]. Serum cortisol levels of less than 30 lg/dL were associated with increased 6- and 24-hour mortality rates [2]. Besides, OHCA survivors who died of early refractory shock had lower baseline cortisol levels than those who later died of Neurologic dysfunction [4]. In the non- hydrocortisone group, we also observed a trend toward higher serum ACTH and total cortisol levels in successfully resuscitated patients. These findings raised our interest about the relationship between the hypothalamic-pituitary- adrenal axis and cardiac arrest.

Lindner et al [6] noted that the interval from collapse to the start of CPR was negatively correlated with serum cortisol concentrations during resuscitation, thus implying an impaired cortisol release with cardiac arrest. Vasopressin- treated pigs had better ROSC rates and higher serum ACTH and cortisol concentrations than epinephrine-treated ones. Vasopressin-mediated ACTH, then cortisol release, was postulated to contribute to the improved outcome [7]. Rats receiving 0.25 mg hydrocortisone were also reported to have significantly increased ROSC rates than rats receiving

0.05 mg hydrocortisone and placebo [8]. In our study, more patients in the hydrocortisone group gained ROSC and sustained ROSC. Besides, both different cortisol level groups seemed to benefit from hydrocortisone administra- tion during resuscitation with increasing ROSC (Table 6). Because cardiac arrest impairs cortisol release and cardiac arrest is an extreme stress, most patients with cardiac arrest may be considered as at least relative adrenal dysfunction. In addition to patients with pre-existed undiscovered adrenal insufficiency, the administration of hydrocortisone during resuscitation may improve ROSC rates in cardiac arrest patients through supplying adequate serum cortisol levels in light of such extreme stress. These findings not only correspond to previous published studies but also support our hypothesis.

The hypothalamic-pituitary-adrenal axis plays an impor- tant role in stress response. Adrenocortical dysfunction results in hypotension and shock. Glucocorticoids modulate vascular reactivity to Angiotensin II and to catecholamines [21,22]. Glucocorticoids also modulate vascular permeability and decrease production of vasodilators, such as nitric oxide [23]. Most researches concerning cardiovascular effect of corticosteroid were based on severe sepsis and septic shock models, whether these results can be applied to cardiac arrests needs further researches. However, since more and more studies suggest postresuscitation syndrome as a bsepsis-likeQ syndrome [24,25], it is conceivable that sepsis and cardiac arrests may share similar mechanisms of corticosteroid in cardiovascular systems.

Another interesting topic concerning the application of hydrocortisone during resuscitation was the timing. Neither human nor animal studies have previously mentioned this aspect. Hydrocortisone application within 22 minutes after collapse showed a higher ROSC rate in patients with witnessed collapse. We also observed a significantly increased ROSC rate in patients receiving hydrocortisone within 6 minutes after ED arrival. No increase in electrolyte disturbances, GI tract bleeding, or infection during the early postresuscitation period freed us from the fear of increased complications resulting from hydrocortisone.

There were several limitations to our study. First, unlike other clinical trials, resuscitation for OHCA patients is always critical and is a race against time. It is therefore difficult to conduct a double-blinded, randomized trial for this type of study because it takes a certain length of time to explain the blindness and randomization process to potential trial participants [26]. Randomized controlled trials are possible in systems where concomitant consent is not needed. The current study design could potentially suffer from selection bias. People may question whether informed consent might have been less likely to be obtained in patients who received less attention or who were under more critical conditions. However, patients with DNAR orders, due to a terminal disease state, were already excluded from the trial. As shown in Table 1, there was no significant difference in comorbidities, causes of OHCA, first monitored rhythm, and CPR events between these 2 groups. The APACHE II score between the survivors of these 2 groups did not reveal any difference as well. It is important to note that all the enrolled patients were in cardiac arrest, the most critical status a patient can be in. The first-line physicians, in the study, were independent in treating patients and adhered to advanced cardiovascular life support guidelines during resuscitation. The clinically relevant end point (ROSC) also helped in eliminating observational bias. Secondly, the hydrocortisone group had less coronary artery disease, defibrillation, and more vasopressin use during resuscitation. Although no statistical significance was noted, these demographic varia- bles approached a trend. However, except coronary artery disease (OR, 0.51, P = .168), univariate analyses did not show the confounding effects of vasopressin and defibrilla-

tion on ROSC, and after multiple logistic regression analysis, coronary artery disease was not associated with ROSC. Larger-scale studies may be needed to clarify this possible association. Thirdly, the cortisol level measured in the study was total cortisol rather than free cortisol. However, recent studies discovered that free cortisol, not total cortisol, is associated with adrenal function. Future researches should measure free cortisol instead of total cortisol. Lastly, as a pilot study, the sample size in the study may be too small to address any definitive conclusion. The Poor neurologic outcome in most survivors also limited our analyses on long-term outcomes, and the optimal dosage and duration of hydrocortisone during resuscitation and the early postresus- citation period needs further extensive researches.

Conclusions

In the present study, the administration of hydrocortisone during resuscitation, particularly within 6 minutes after ED arrival, may be associated with improved ROSC rate in OHCA patients. Hydrocortisone use did not increase the incidence of electrolyte disturbances, GI tract bleeding, or infection in the early postresuscitation period. The real effect of hydrocortisone administration during resuscitation and in the early postresuscitation period deserves more extensive and well-designed studies for determining the affected outcomes in cardiac arrest victims.

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