a b s t r a c t

Background: The emergency physician should diagnose and treat the Critical illnesses that cause syncope/ presyncope in patients presenting to the emergency department (ED). Whole-body ultrasonography can detect the critical etiology of syncope with high diagnostic sensitivity. We aimed to reveal whether whole-body ultra- sonography for syncope (WHOBUS-Syncope) protocol recognizes high-risk syncope patients and the effect of WHOBUS-Syncope protocol on the management of patients.

Method: This is a prospective, cross-sectional study. Patients over the age of 18 years who presented to the ED with syncope or near syncope were included consecutively. Carotid, lung, cardiac, collapsibility of inferior vena cava, abdominal and compression ultrasonography of the lower extremity veins was performed among the WHOBUS-Syncope protocol. Frequency of abnormal Sonographic findings associated with syncope/presyncope and requirement of critical intervention for abnormal sonographic findings were assessed.

Results: 152 patients were included in the study. The median age of the patients was 61.5 years (IQR: 41-71.8) and 52.6% were female. The most common (64.3%) abnormal sonographic finding was >50% collapse of vena cava inferior during inspiration. In addition, abnormal sonographic findings thought to cause syncope/ presyncope were detected in 35.5% of the patients. Bolus fluid resuscitation were given in in 62 patients (40.8%) with increased inferior vena cava collapse. Critical interventions other than fluid resuscitation were per- formed for abnormal sonographic findings in 35 (23%) of the patients. Advanced age, increased heart rate and the presence of high-risk criteria in the ‘European Society of Cardiology Guidelines for Syncope’ were independent risk factors for detection of abnormal ultrasonographic findings related to syncope/presyncope.

Conclusion: WHOBUS-Syncope protocol can be included in emergency practice as part of the standard evaluation in Patients with syncope or presyncope presenting to the ED.

(C) 2023

1. Introduction

Syncope is a temporary loss of consciousness and postural tone due to Cerebral hypoperfusion, which resolves spontaneously without intervention. Syncope may be the first and the main symptom of life-threatening critical illness. The primary priority of emergency phy- sicians is to reveal and treat the critical etiologies in patients presenting to the emergency department (ED) with syncope or presyncope.

There are 1-2 million hospital admissions due to syncope annually and 3% to 5% of admissions to ED are caused by syncope in the United

* Correspomding author at: Emergency Medicine, Dokuz Eylul University School of Medicine, Department of Emergency Medicine, Narlidere, Izmir, Turkey.

E-mail address: [email protected] (E. Aksay).

States [1]. risk classification and decision for hospitalization are still challenging for emergency physicians. Many patients are routinely sub- jected to laboratory and imaging tests with a low diagnostic utility but the etiology cannot be elucidated in a significant proportion of patients [2]. Clinical decision rules such as San Francisco Syncope Rule and the OESIL Score have been developed to identify high-risk syncope patients by age, comorbidities, presence of prodrome, blood pressure on admis- sion, hematocrit count, and ECG findings. However, imaging modalities such as whole-body Ultrasonography are not yet routinely used in the identification of syncope patients with high risk.

In recent years, US-based Diagnostic protocols have become a part of

Standard care in emergency medicine practice in critical illness, trauma or shock [3]. Ultrasound is known to detect hypovolemia, pulmonary embolism, aortic catastrophes, heart failure, aortic stenosis, and carotid

https://doi.org/10.1016/j.ajem.2023.01.043

0735-6757/(C) 2023

stenosis with high sensitivity [3]. However, these critical diagnoses have never been evaluated before in syncope patients using an extensive ul- trasonography protocol.

We aimed to reveal whether whole-body ultrasonography for syn- cope (WHOBUS-Syncope) protocol recognizes high-risk syncope pa- tients presented to the emergency department and the effect of (WHOBUS-Syncope) protocol on the management of patients.

1. Method
   1. Study design

This is a prospective, cross-sectional study. Patients over the age of 18 years who presented to the tertiary Emergency Department of the (Dokuz Eylul) University School of Medicine with syncope or near syn- cope between December 2020 and May 2021 were included consecu- tively. The following patients were excluded from the study: (1) Those unable to perform WHOBUS-Syncope for any reason, (2) Patient’s re- fusal to participate in the study; (3) Patients who had been made a clear diagnosis other than syncope / near syncope (such as hypoglyce- mia or seizure) during follow-up in the ED. The study was approved by the Local Ethics Committee of Dokuz Eylul University. (Decision date: 07.12.2020, decision no: 2020/29-56).

• 1. Study protocol

Patients admitted to the ED were evaluated by residents of emer- gency medicine first. If emergency physicians considered syncope or presyncope as the Initial diagnosis, then patients were included in the study. Afterward, sonographers participating in the study were called. Sonographers were blinded and not informed of the patient’s pre- hospital treatments, history, clinical features, imaging, and Laboratory test results. After evaluating the patient’s history, physical examination, and ECG findings, ED physicians were asked whether the patient needed to admit, and it was recorded. After the US examination, after US findings were reported to the primary physician, it was asked whether there was a change in admit or discharge decisions and their decisions were recorded.

The sonographic examination was intended to be initiated within the first 15 min after the patient’s admission to the ED.

• 1. Sonographic examination

Carotid, lung, cardiac, abdominal US, and compression ultrasonogra- phy of the lower extremity veins was performed among the WHOBUS- Syncope protocol (Appendix-1) ultrasonographic imaging was performed by using Phased Array (5 Hz), Curvilinear (3-5 Hz), and Lin- ear (12 Hz) probes of General Electric Vivid S5(R) ultrasound. The dura- tion of the US protocol was determined by the stopwatch of the smartphones.

WHOBUS-Syncope protocol was carried out by 4 sonographers: Three of them were PGY 4 EM residents and one was the Faculty of Emergency Medicine (BB). BB is the former president of the Ultrasonog-

The patient’s age, gender, vital findings on ED admission, the pres- ence of high-risk criteria for syncope in the ‘2018 European Society of Cardiology Guidelines (ESC) for Diagnosis/Management of Syncope, the treatments, and interventions applied to the patients were recorded in the data collection form by the patient’s primary physician [4]. The duration of the WHOBUS-Syncope protocol and sonographic findings was recorded by sonographers in another data collection form.

• 1. Analysis

The study data were recorded in the SPSS (Statistical Package for the Social Sciences, IBM(R)) version 22 program and analyzed. The distribu- tion of continuous variables for normality was assessed by the Kolmogorov-Smirnov test. Continuous variables with the normal distri- bution were shown with mean and standard deviation (SD), and data with abnormal distribution were shown with the median and inter- quartile range (IQR). Student-t-test was used in the analysis of continu- ous variables and the chi-square test was used for the analysis of categorical variables. Logistic regression analyses were performed to identify the independent risk factors for abnormal US findings. As a re- sult of univariate analysis, a logistic regression model was created from the variables with p-value <0.2. We used the ‘Backward/Wald’ method in logistic regression. The goodness of fit of the model was eval- uated by the Hosmer-Lemeshow test. A p-value of <0.05 is considered statistically significant.

1. Results
   1. Patient characteristics

During the study, 184 patients were admitted to the ED with a pre- diagnosis of syncope/presyncope. Sixteen of the patients were excluded from the study due to the absence of a sonographer in the ED shift, 9 of them refused to participate in the study, and 7 of them received another diagnosis other than syncope and presyncope during the observation in the ED. A total of 152 patients were included in the study. The clinical characteristics of the patients are shown in Table 1. The mean age of the patients excluded from the study was 46.5 years (31-71.5).

Table 1

Characteristics of patients. Variables

Age (years, median, IQR) 61.5, (41-71.8)

Female (n, %) 80, (52.6)

Syncope (n, %) 102, (67.1)

Near-syncope (n, %) 50, (32.9)

Symptomatic at emergency department admission (n, %) 25, (16.4) Systolic blood pressure (mmHg, median, IQR) 129.5

(118.1-147.8)

Diastolic blood pressure (mmHg, median, IQR) 80 (70-90)

Pulse (beats/min, median, IQR) 78 (68.5-90)

SpO₂ (%, median, IQR) 97 (96-98)

Temperature (?C, median, IQR) 36 (36-36.2)

Risk factors (ESC* Syncope Guideline) (n, %) 68 (44.7)

raphy Task Group of the Emergency Medicine Association of Turkey (EMAT-US). EM residents had previously attended the basic and ad-

• New onset shortness of breath or chest-head-abdominal pain

24 (15.8)

vanced ultrasonography course of EMAT-US. EM residents were also given 4-h theoretical and practical focused ultrasonography training by BB, especially for carotid and aortic valve imaging before the study.

• Syncope in supine position and during exertion 7 (4.6)
• Syncope after palpitations 2 (1.3)
• Absence of prodromal symptoms or lasting <10 s 16 (10.5)
• Family history for structural heart disease 6 (3.9)

After WHOBUS for Syncope protocol was completed, the US findings were reported to the patient’s primary physician. During the WHOBUS- Syncope protocol, if life-threatening conditions were identified (aortic

• Presence of structural heart disease or coronary artery disease
• Unexplained hypotension (Systolic blood pressure < 90

mmHg)

30 (19.7)

9 (5.9)

dissection, left ventricular segmental wall movement deficits suggest-

ing acute myocardial ischemia, etc.) the protocol was terminated, and the primary physician informed. ultrasound images were not evaluated by another sonographer afterward the initial sonographic examination.

• Signs of gastrointestinal bleeding 1 (0.7)
• Ongoing bradycardia (<40 beats/min) 4 (2.6)
• Undiagnosed murmur 1 (0.7)

* ESC: European Society of Cardiology.

The most common types of syncope considered by the patient’s pri- mary physician were reflex (57.9%), orthostatic (13.2%), and cardiac (19.7%) syncope, respectively. The most frequent Abnormal ECG find- ings were sinus tachycardia (17.1%), right branch block (17.1%), non- specific ST-T wave changes (13%), Sinus bradycardia (11.4%) and atrial fibrillation (10%), respectively. A hundred eighteen of the patients

Table 2

Abnormal US findings detected by WHOBUS Syncope protocol.

Abnormal sonographic findings Number of appropriate visualizations

1. VCI diameter / collapsibility 146

Positive findings n (%)

were discharged from ED, 11 were admitted to the hospital, 17 were admitted to the intensive care unit, 6 voluntarily left the ED before the extensive evaluation was completed and, 4 (2.6%) died within 30 days.

• 1. Results of WHOBUS-Syncope protocol

The median duration of the WHOBUS-Syncope protocol was 14 min (12-16 min). The WHOBUS-Syncope protocol was completely per- formed in 131 (86.1%) patients and all targeted imaging was obtained from these patients. The areas that could not be evaluated by WHOBUS were abdominal aorta in 8, Ascending aorta in 7, inferior vena cava in 6, compression ultrasonography in 5, carotid in 4, cardiac

• • • Total collapse 69, (47.2)

- 1.5-2.5 cm, degree of collapse >50% 25, (17.1)

- 1.5-2.5 cm, degree of collapse <50% 40, (27.3)

• • • >2.5 cm, degree of collapse <50% 4, (2.7)
    • >2.5 cm, no collapse 8, (5.4)

1. Abnormal sonographic findings (other than VCI diameter)

reduced ejection fraction 151 19, (12.6)

Aortic stenosis 148 15, (10.2)

Increased RV/LV ratio 149 14, (9.4)

Carotid stenosis 148 12, (8.1)

B - lines (bilaterally) 151 9, (5.9)

Intra-abdominal free fluid 152 8, (5.3)

Pericardial effusion 151 7, (4.6)

Left ventricular wall motion defect 148 7, (4.8)

in 4 patients, and B- line imaging in 1 patient. The inability to obtain a	D- Shape left ventricle	149	5, (3.4)
quality sonographic image suitable for evaluation in the examined	Pleural effusion (bilaterally)	152	4, (2.6)
area and abrupt termination of the procedure due to a diagnosis requir-	Myoma uteri (in patients with vaginal	152	3, (1.9)
ing emergent intervention by the WHOBUS-Syncope protocol (such as aortic dissection) were reported as the reasons for the inability to per-	bleeding) Deep vein thrombosis in popliteal vein Pleural effusion (unilaterally)	149 152	3, (2) 2, (1.3)
form imaging in these areas.	B - lines (unilaterally)	151	1, (0.7)
>50% collapse of vena cava inferior during inspiration is the most (in	Deep vein thrombosis in iliac vein	149	1, (0.7)
94 patients, 64.3% of patients) commonly detected abnormal sono-	Dissection of abdominal aorta	144	1, (0.7)

graphic findings with the WHOBUS-Syncope protocol. Other abnormal

sonographic findings that were thought to cause syncope/presyncope	Newly diagnosed mass in the bladder	152	1, (0.7)
were detected in 54 (35.5%) patients. Abnormal US findings detected	Newly diagnosed metastatic lesions of the	152	1, (0.7)

Thrombus in the left atrium + Jugular vein thrombosis

152 1, (0.7)

by WHOBUS Syncope protocol are shown in Table 2. The most common intervention (in 62 patients, 40.8% of patients) is bolus fluid resuscita- tion in patients with increased inferior vena cava collapse. The critical

liver and hydroureteronephrosis

Liver abscess (patient with sepsis) 152 1, (0.7)

Nephrolithiasis and dilatation of collecting 152 1, (0.7) structures

interventions (other than fluid resuscitation) were performed for ab-	Ovarian cyst rupture	152	1, (0.7)
normal WHOBUS findings in 35 (23%) of the patients (Table 3).	Chronic cholecystitis	152	1, (0.7)

Carotid artery imaging revealed stenosis in the carotid artery in 12 patients, narrowing the carotid lumen by >50%. In 2 of these cases, the carotid artery was completely occluded. In 7 of 12 patients, carotid stenosis was confirmed in the ED observation (in 3 patients with Dopp- ler US performed by a radiologist, and in 4 patients with CT angiogra- phy). Since these 7 patients had not been diagnosed before, long-term antiaggregant treatment was started in 6 patients in the ED. Carotid endarterectomy was recommended but this treatment was refused by one patient. The mean age of 9 patients who were confirmed to have more than %50 carotid stenosis in ED was 74.2 years, and 6 of the patients were male.

The aortic valve was found to be abnormal (limited opening, calcific, or both) in 15 (9.8%) patients on aortic imaging. Comprehensive echo- cardiography was performed in 11 of these patients by a cardiologist in the ED; 7 of them were found to have aortic stenosis, and 3 of them were admitted to the intensive care unit and underwent Transcatheter Aortic Valve Implantation (TAVI). The mean age of 7 patients who were confirmed to have aortic stenosis was 77.8 years, and 4 of the patients were female.

• 1. The effect of WHOBUS-Syncope protocol on the hospitalization and discharge decisions

After the initial ED assessment (including history, physical examina- tion, and ECG) the emergency physicians decided there was no need for hospitalization in 121 patients. After the WHOBUS-Syncope protocol, emergency physicians changed their decision to require hospitalization in 12 (9.9%) of these patients. In 9 (29%) of the 31 patients who were thought to need hospitalization before the WHOBUS-Syncope protocol, the decision was changed to not require hospitalization. As a result, in 13.8% of the patients, the WHOBUS protocol changed the decision on the hospitalization requirement of the patients.

Dilated bowel loops and intra-abdominal 152 1, (0.7) free fluid

mitral stenosis 152 1, (0.7)

Pericardial tamponade 151 -

Dissection or aneurysm of ascending aorta 145 -

Pneumothorax 152 -

Total? 54 (35.5%)

* Some patients have more than one abnormal sonographic findings.

• 1. Logistic regression analysis

Nine variables were included in the univariate analysis to investigate the independent risk factors for the detection of abnormal USG findings associated with syncope or presyncope detected by WHOBUS: Age, gen- der, systolic blood pressure on admission, diastolic blood pressure on admission, pulse rate on admission, peripheral oxygen saturation on ad- mission, presence of abnormal ECG findings, presence of any of the ESC high-risk criteria, and the patient being symptomatic on admission. A logistic regression model was created with 6 variables with p-value

<0.2 for univariate regression analysis. The goodness of fit of the regres- sion model was found as p = 0.818. In the multivariate analysis, ad- vanced age, increased heart rate, and the presence of ESC high-risk criteria were determined as independent risk factors for the detection of abnormal findings related to syncope/presyncope in the WHOBUS- Syncope protocol (Table 4). The frequency of critical abnormal US find- ings increases with age (Table 5).

1. Discussion

In our study, we aimed to evaluate the Diagnostic efficacy of the WHOBUS-Syncope protocol in the determination of syncope/ presyncope etiology. We found that the WHOBUS-Syncope protocol

Table 3

Performed interventions to the abnormal sonographic findings detected by WHOBUS protocol.

Table 5

Abnormal findings on WHOBUS-Syncope protocol according to the age of the study patients.

Total Interventions

n (%)

Years

Number

Abnormal

More

Aortic

Reduced

Inferior

Abscess drainage for liver abscess 1 (0.6)

Bolus fluid resuscitation for vena cava inferior collapse Critical Intervention or Treatment (other than fluid resuscitation) Long-term anticoagulant therapy for pulmonary embolism Long-term antiaggregant therapy for carotid stenosis Coronary angiography for segmental left ventricle wall motion defect	62 (40.8) 7 (4.6) 6 (3.9) 3 (1.9)	of sonographic than stenosis ejection Vena patients findings 50% fraction Cava associated carotid collapse with syncope or stenosis >50% presyncope
TAVI* for critical aortic stenosis	3 (1.9)	<30	18	0	0	0	0	9
Intravenous administration of diuretics and nitroglycerin for heart	5 (3.3)	31-40	18	4	0	0	0	9
failure-related** sonographic findings		41-50	17	4	0	0	0	13
Emergency surgery for active bleeding uterine myoma	2 (1.3)	51-60	19	3	2	0	2	14
Fibrinolytic therapy for high-risk pulmonary embolism	2 (1.3)	61-70	32	16	4	2	5	21
Long-term anticoagulant therapy for deep vein thrombosis	1 (0.6)	71-80	28	14	3	6	5	16
Emergency surgery for dissection of abdominal aorta	1 (0.6)	>80	20	20	3	7	7	12
Long-term anticoagulant for jugular venous thrombosis and thrombus	1 (0.6)	Total	152	54	9*	7*	19	94
in the left atrium ? Patients with confirmed diagnosis of aortic and carotid stenosis at subsequent

examinations in ED or follow-up.

Emergency surgery for dilated bowel loops compatible with ileus and free fluid in the abdomen

Carotid end-artherectomy plan for severe carotid stenosis (The

patient refused the intervention)

1 (0.6)

1 (0.6)

One of the surprising findings of this study was we detected com-

Paracentesis for free fluid in the abdomen 1 (0.6)

Total Interventions or Treatments (other than fluid resuscitation) 35 (23%)

* TAVI: Transcatheter aortic valve implantation.

?? Findings related to heart failure due to one or more: reduced EF, B- line sign, pleural effusion, VCI dilatation or no collapsibility during inspiration.

both detected important etiologies that led to syncope/presyncope and caused significant changes in treatment and intervention plans in most of the patients. The WHOBUS-Syncope protocol identified the etiology of syncope/presyncope in >1/3 of the patients. Medical treatment or surgical interventions were performed in 35 (23%) of the patients ac- cording to the abnormal WHOBUS-Syncope protocol findings. For ex- ample, 6 of the patients underwent long-term antiaggregant treatment due to carotid stenosis, 4 patients underwent emergent sur- gery intervention, 3 patients underwent TAVI, 7 patients were given long-term anticoagulant therapy, and 2 patients were given fibrinolytic for pulmonary embolism.

Table 4 Univariate and multivariate logistic regression analysis regarding independent risk factors for detection of abnormal ultrasonographic findings.

Univariate analysis OR* 95% CI** p value

Age 1.055 1.031-1.079 <0.001

Gender 0.935 0.481-1.820 0.844

Systolic blood pressure 0.998 0.987-1.010 0.783

Diastolic blood pressure 0.989 0.970-1.009 0.290

Pulse 1.020 1.001-1.039 0.037

Oxygen saturation 0.906 0.853-0.988 0.020

ECG abnormalities 2.720 1.319-5.610 0.007

plete or > 50% IVC collapse in almost 2/3 of our patients. To our knowl- edge, the measurement of IVC diameter or collapsibility of IVC has not been studied in patients with syncope, previously. The mortality rate in the patients included in our study was quite low, and emergency phy- sicians categorized most of the cases as reflex syncope/presyncope or orthostatic hypotension-associated syncope/presyncope. We think that the detection of sonographic findings reflecting intravascular fluid deficiency or loss of vasomotor tone in most patients with benign syn- cope is unexpected. This suggests that even after the patient regains consciousness, vasoplegia has not improved sufficiently within the first hours of syncope. However, our study did not focus on whether there was a causal relationship between VCI collapse and syncope. Fu- ture studies may further reveal the role of VCI collapse in the etiology of syncope.

In the literature, we did not find a study on whole body-approached ultrasonography study in syncope patients. In several studies, specific US examination was investigated in syncope patients. Ghani et al. retro- spectively analyzed 139 syncope patients who underwent echocardiog- raphy out of 369 syncope patients older than 18 years of age [5]. According to physical examination and ECG findings, positive echocar- diography findings (<45% ejection fraction, valvular disease, ventricular hypertrophy, pericardial effusion, and pulmonary hypertension) were detected in 43.7% of patients with “high risk”, while in low-risk patients it was 10%. They concluded that echocardiography should be performed in patients with abnormal ECG and physical examination. However, 80% of the patients were over the age of 65; therefore, they included only the patients who underwent echocardiography. In our study, patients presenting with syncope were included in the study consecutively, regardless of age, ECG findings, and examination find- ings, and almost all the cases were evaluated by the WHOBUS- Syncope protocol. In the Echocardiographic examination of our study,

Presence at least one of the “European Society of

Cardiology Guideline for Syncope” high risk criteria

Presence of Persistent symptoms in emergency department admission

8.293 3.858-17.827 <0.001

1.311 1.056-1.628 0.014

we found aortic stenosis in 7 patients (confirmed by Comprehensive echocardiography), low EF in 19 patients, pericardial effusion in 7 pa- tients, increased right ventricle/left ventricle ratio in 14 patients, D- Shaped left ventricle in 5 patients, and segmental left ventricular wall

Multivariate analysis OR 95% CI p value

motion defect in 7 patients.

Age Pulse	1.044 1.024	1.017-1.071 1.00-1.048	<0.001 0.049	We identified 3 studies in the literature to investigate the prevalence of carotid stenosis in syncope patients. Scott et al. retrospectively ana-
Oxygen saturation	0.997	0.905-1.097	0.944	lyzed 313 patients who underwent carotid ultrasound among syncope
ECG abnormalities	1.042	0.417-2.607	0.929	patients who had no abnormal signs of stroke [6]. Carotid stenosis

Presence at least one of the “European Society of Cardiology Guideline for Syncope” high risk criteria

Presence of persistent symptoms in emergency department admission

* OR: odds ratio.

?? CI. Confidence Interval.

5.77 2.43-13.72 <0.001

1.262 0.364-4.350 0.714

narrowing the arterial lumen of >50% was detected in 48 (15.4%) of the patients, but only 7 (2.2%) of these patients underwent a change in medical therapy, and 1 patient had undergone carotid surgery. The mean age of the patients participating in this study was 73.6 years, 54% were male. Kadian-Dodov et al. searched 495 syncope patients who underwent Carotid ultrasonography and found more than critical

stenosis (>70% lumen narrowing) of the Internal carotid artery or com- mon carotid artery in 26 (5.2%) patients [7]. The median age was 70.8 years and 52% of the patients were male. Schnipper et al. analyzed 140 patients admitted to the hospital with syncope or presyncope by trans- cranial Doppler and carotid ultrasonography [8]. Carotid artery ultraso- nography was applied to 109 patients. Severe internal carotid artery or Common carotid artery stenosis was detected in 13 (11.9%) patients and treatment were changed in 11 (7.9%) patients. Forty-nine percent of pa- tients were male, with a median age of 74 years. They concluded that the diagnostic value of carotid ultrasonography and transcranial Dopp- ler imaging for the etiology of syncope was low, and it should be per- formed in patients with focal neurological findings or carotid murmur. In our study, carotid stenosis that >50% narrowing arterial lumen was observed in 8.1% of the patients, medical treatment was initiated for 6 patients and carotid surgery was recommended for one patient. The mean age of the patients participating in our study was lower (61.5 years) than that of the other 3 studies.

Routine carotid artery examination by ultrasound is not recom- mended in current syncope guidelines due to low-cost effectivity. How- ever, symptomatic carotid stenosis, which requires treatment, increases significantly in syncope patients as their age increases. All the patients in our study who were diagnosed with severe carotid stenosis were over 50 years old. Based on our results, we recommended that carotid examination should be a part of the WHOBUS-Syncope protocol in patients over 50 years old.

There are several studies focused on the effectiveness of WHOBUS in critical patients other than syncope. Riishede et al. performed (1) heart,

(2) lung, (3) abdomen, and (4) deep vein imaging on patients over 18 years of age who presented to the ED with a high triage score or had sys- tolic blood pressure < 100 mmHg [9]. Of the 160 patients included in the study, only 128 completed the all 4-part WHOBUS protocol. They detected abnormal findings by ultrasound in 38% of his patients. The 5 most detected abnormal findings were pleural effusion (24.4%), pulmo- nary edema (15.6%), systolic heart failure (11.9%), pericardial effusion (6.2%), and free fluid (0.6%) in the abdominal cavity. No evidence of deep vein thrombosis was found in any patients. The median time dura- tion of the Ultrasonography examination was 28 min. Although more body regions were examined in our study, our examination duration was shorter (14 min. vs 28 min.) The average 14-min examination du- ration can be considered as a tolerable time for the diagnosis of critical syncope patients in ED.

Lichtenstein et al. presented full-body ultrasonography to the litera- ture for the first time, abdominal (hepatobiliary, urinary, and gastroin- testinal tract), thorax, large vein, and femoral vein (compression US) imaging was performed on 150 consecutive patients who were admit- ted to intensive care [10]. It has been shown that ultrasound has a direct effect on the diagnosis in 22% of the patients and guides treatment in 1 in 4 patients. Although there were differences between patient profiles and areas examined by ultrasound, we also showed that 1 out of 4 pa- tients underwent an intervention for abnormal USG findings in our study.

We revealed that the WHOBUS-Syncope protocol could detect criti- cal etiologies and guide the critical treatment in patients who presented to the ED with syncope or presyncope. Performing the WHOBUS- Syncope protocol can prevent subsequent mortalities and morbidities in such patients. We detected critical aortic and carotid stenosis in many patients with the addition of aortic/carotid imaging, which was not routinely examined in the ultrasonography of the syncope patient. The cost-effectiveness of the WHOBUS Syncope protocol may be inves- tigated in future studies.

Many important conditions such as aortic stenosis, carotid stenosis, and systolic failure were observed especially over the age of 50 years/ old. As a result of the logistic regression model, advanced age, increased heart rate, and presence of ESC high-risk criteria for syncope were found to be independent risk factors for the detection of abnormal US findings associated with syncope or presyncope. Therefore, in patients with one

of these criteria, the WHOBUS-Syncope protocol can be integrated as a routine part of the clinical Management of patients with syncope or presyncope.

• 1. Limitations

The median age of the patients we included in the study was 61.5 years, and 44% of the patients had at least one of the high-risk criteria in the ESC guideline. The mean age of the patients excluded from our study was 46.5 years. Therefore, the patient population in our study was older than the syncope population presenting to the ED and there- fore more likely to have critical illnesses. Therefore, the rate of abnormal findings in our study may have been higher than it should have been.

Many of the abnormal US findings detected in our study were not

confirmed by gold-standard Diagnostic tests. However, in critical cases requiring intervention, confirmation was already obtained with CT an- giography for patients with abdominal aortic dissection, with echocar- diography for patients who would undergo TAVI, and with CT angiography or Doppler US before the start of antiaggregant therapy for patients with carotid stenosis.

When evaluating the interventions applied to patients due to abnor- mal findings detected in the WHOBUS-Syncope protocol, it should be taken into consideration that the interventions applied may not have been performed solely due to USG findings in some of the patients. For instance, a patient with segmental LV wall motion defect suggesting myocardial ischemia in WHOBUS protocol also had ST-segment eleva- tion in ECG and underwent emergency percutaneous coronary inter- vention. The main factor leading to the indication for reperfusion in this patient may be the ECG finding rather than the US finding. Similarly, 2 patients received fibrinolytic therapy because of the increased RV/LV ratio and D-shape findings, but the decision for fibrinolytic therapy may have been taken because of the deterioration in the hemodynamic parameters of the patient rather than the US findings. Therefore, when making critical intervention decisions in syncope patients, abnormal findings in the WHOBUS syncope protocol should be evaluated together with clinical findings and test results.

In our study, EM residents and an EM faculty member performed the Ultrasonographic evaluation. However, inter-rater reliability analyses for sonographers were not performed. Ultrasonographic examinations were performed by only 4 physicians, which may limit the generaliza- tion of our results.

1. Conclusion

Ultrasonographic findings associated with syncope/presyncope were detected in approximately one-third of the patients with the WHOBUS syncope protocol. Abnormal US findings were detected mostly in patients over 50 years of age. Advanced age, increased heart rate, and presence of ESC high-risk criteria were determined as inde- pendent risk factors for abnormal findings. Approximately 25% of the patients were given intervention for abnormal findings detected by the WHOBUS syncope protocol. Whole-body approach ultrasonography can be included in emergency medicine practice as part of the standard evaluation in patients with syncope or presyncope presenting to the ED.

Funding and support

The authors did not receive support from any organization for the submitted work.

CRediT authorship contribution statement Gucluhan Ucar: Writing - review & editing, Writing - original draft,

Supervision, Methodology, Formal analysis, Data curation, Conceptuali-

zation. Ersin Aksay: Writing - review & editing, Writing - original draft, Visualization, Supervision, Project administration, Methodology,

Investigation, Formal analysis, Data curation, Conceptualization. Basak Bayram: Writing - review & editing, Writing - original draft, Visualization, Supervision, Methodology, Formal analysis, Data curation, Conceptualization. Mustafa Can Guzelce: Writing - review & editing, Writing - original draft, Visualization, Supervision, Methodology, Data curation, Conceptualization. Yagiz Kagan Ergun: Writing - review & editing, Writing - original draft, Visualization, Supervision, Methodol- ogy, Data curation, Conceptualization.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influ- ence the work reported in this paper.

Acknowledgments

None.

Appendix-1 Ultrasonography protocol

1. /ocused lung ultrasonography: Focused Lung ultrasound (F-LUS)

was performed with using a modification of the principles described by Volpicelli [11] and Lichtenstein and colleagues [12]. Curvilinear (3-5 Hz) and Linear (12 Hz) probes of General Electric Vivid S5(R) ultrasound were used together for the examination. During the application, the patient was kept in a sitting or supine position. F-LUS consists of bilateral scan- ning of the anterolateral chest. The correct scan was intercostal with the maximum extension of the visible pleural line. The chest wall was di- vided into 8 areas and 1 image was obtained for each area. The areas were 2 anterior and 2 lateral on each side. The anterior chest wall was delineated from the sternum to the anterior axillary line and divided into upper and lower halves (approximately from the clavicle to the second-third intercostal spaces and from the third space to the dia- phragm). The lateral region was drawn from the anterior to the poste- rior axillary line and divided into the upper and basal halves. Sonographers investigated the presence of pneumothorax signs, inter- stitial syndrome, and pleural effusion in the patient.

Imaging fields for focused lung ultrasonography

1. /ocused Cardiac Ultrasonography: ‘Focus Assessed Transthoracic Echocardiography (FATE)’ protocol was applied by using Phased Array (5 Hz) probe of General Electric Vivid S5(R). FATE was initially performed with the patient in the supine position or on the left side. If the quality of the image was sub-optimal, the patient was turned 30o-60o to the left. Four scanning positions were used: Parasternal long and short axis view, subcostal view, and apical view. Pericardial effusion, signs of

pericardial tamponade, ejection fraction (by end-point septal separa- tion method), the ratio of right/left ventricular volumes and d-shape sign, left ventricle dimensions and contractility, left ventricle wall mo- tion defect, increased ascending and descending thoracic aortic diame- ter and dissection, and heart valve pathologies which may cause syncope (such as aortic and mitral stenosis) were investigated. Aortic and mitral valves were assessed by only their limited opening or calcifi- cation. Sonographers did not use velocity and gradient calculations. Car- diologists confirmed or ruled out the diagnosis of all the suspected valve pathologies after their assessment.

1. /ocused Abdominal ultrasonography: Intra-abdominal free fluid,

abdominal aortic diameter, dissection of the abdominal aorta and iliac arteries, and abnormal findings in solid organs were examined by trans- verse and oblique windows of the abdominal aorta and 3 abdominal windows in the RUSH protocol by using the Curvilinear (3-5 Hz) probe. Obvious Abdominal pathologies such as dilated bowel loops, cho- lecystitis, cholelithiasis, ruptured ovarian cyst, dilatation of the urinary tract, nephrolithiasis, abscess, mass in the bladder, and myoma uteri are also recorded.

1. Limited Compression Ultrasonography: Compression ultrasonog- raphy was applied to the femoral, superficial femoral and popliteal veins using a Linear probe and the presence of deep vein thrombosis was in- vestigated. Color flow and Doppler mode were used in suspicion or to confirm the diagnosis.
2. Restricted Carotid Ultrasonography: Transverse and longitudinal

imaging of the Carotid arteries was performed using a high-frequency lin- ear probe and it was investigated whether there was more than 50% ca- rotid stenosis. Patients were positioned supine for the examination. If they were unable to lie supine, they were positioned semi-recumbent at 45 degrees. Their neck was slightly hyper-extended. They turned their head slightly away from the sonographer, about 45 degrees from the mid- line, to enhance exposure. Standard B-mode and Color Doppler images were obtained for each patient following this protocol. The protocol did not include spectral Doppler or velocity calculations. Imaging began in the transverse plane with the identification of the carotid artery. Key areas identified consist of the common carotid artery, carotid bulb and bi- furcation, and internal carotid artery. The longitudinal plane was also scanned. An initial scan was applied of the entire extracranial carotid, and obvious stenosis was searched. If an obvious stenosis was not en- countered, transverse and longitudinal images were generated with color Doppler over the vessel. The sonographer aimed to identify subtle or isoechoic stenosis that could potentially be missed on B-mode. The same procedure was repeated on the vessels on the opposite side.

1. Measurement of inferior vena cava (IVC) diameter and collaps- ibility during respiration: The Curvilinear (3-5 Hz) or Phased Array (5 Hz) probe was positioned in the epigastric area in a long-axis configura- tion along the IVC as it runs from the abdomen into the heart. Firstly, the heart image was obtained in the Subxiphoid 4-chamber plane and then the probe was moved into the subxiphoid 2-chamber plane, with the probe marker oriented anteriorly. Moving the probe to the patient’s right brought the IVC into view, running longitudinally adjacent to the aorta. The IVC was examined at the junction of the right atrium and the cava and followed 2 to 3 cm caudally along the vessel. M-mode Doppler, positioned on the IVC, was used to document the dynamic changes in the vessel caliber during the patient’s respiratory cycle. The IVC diameter was measured with the largest at the end of expiration (IVCe) and with the smallest at the end of inspiration (IVCi) with convex probes in transverse abdominal windows. Collapsibility of IVC was cal- culated as the formula: Collapsibity = [(IVCe - IVCi) / IVCe] x100%.

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