Impact of emergency physician performed ultrasound in the evaluation of adult patients with acute abdominal pain: a prospective randomized bicentric trial

Background Abdominal pain is common in patients visiting the emergency department (ED). The aim of this study was to assess the diagnostic contribution of point-of-care ultrasound (POCUS) in patients presenting to the ED with acute abdominal pain. Methods We designed an interventional randomized, controlled, open label, parallel-group, trial in two French EDs. We included adult patients presenting to the ED with acute abdominal pain. Exclusion criteria were a documented end-of-life, an immediate need of life-support therapy and pregnant or breast-feeding women. Patients were randomized in the experimental group (i.e., workup including POCUS) or control group (usual care). The primary objective of the study was to assess the added value of POCUS on diagnostic pathway in the ED, according to the diagnostic established a posteriori by an adjudication committee. The primary endpoint was the proportion of exact preliminary diagnosis between the 2 groups. The preliminary diagnosis made after clinical examination and biological results with POCUS (intervention arm) or without POCUS (usual care) was considered exact if it was similar to the adjudication committee diagnosis. Results Between June 2021 11th and June 2022 23th, 256 patients were randomized, but five were not included in the primary analysis, leaving 125 patients in the POCUS group and 126 patients in the usual care group (130 women and 121 men, median [Q1-Q3] age: 42 [30;57]). There was no difference for exact diagnosis between the two groups (POCUS 70/125, 56% versus control 78/126 (62%), RD 1.23 [95% CI 0.74–2.04]). There was no difference in the accuracy for the diagnosis of non-specific abdominal pain nor number of biological or radiological exams. Diagnostic delays and length of stay in the ED were also similar. Conclusions In this trial, systematic POCUS did not improve the rate of diagnostic accuracy in unselected patients presenting to the ED with acute abdominal pain. However, as it was a safe procedure, further research should focus on patients with suspected etiologies where POCUS is particularly useful. Trial registration: This trial was registered on ClinicalTrials.gov on 2022/07/20 (https://clinicaltrials.gov/study/NCT04912206?id=NCT04912206&rank=1) (NCT04912206).


Background
Non-traumatic abdominal pain is one of the most common complaints in patients visiting the emergency department (ED) [1].It represented 6.5% of patients admitted in a US ED in 2007 [1].Many etiologies may be involved in adult patients presenting with acute abdominal pain: surgical (appendicitis, bowel obstruction…), medical (diverticulitis, cholelithiasis, gastritis, renal colic, urinary tract infections …) but also non-specific abdominal pains [2].It therefore remains a daily diagnostic challenge for emergency physicians (EP).Diagnosis accuracy relies on improvements in the advanced imaging tools such as computed tomography (CT) or ultrasound (US) [1,3].Currently, the diagnostic workup in a patient presenting with acute abdominal pain, is based on clinical examination and if necessary, laboratory tests and, in many cases, imaging procedures.
Beside ultrasound performed by the radiology department, point-of-care ultrasound (POCUS) is increasingly used to assess patients in emergency medicine (EM) for many years [4].It has become an integrated part of the EM curriculum [5].US is particularly suited to assess patients with acute abdominal pain as many organs are easily explored [6].Diagnostic performances, both sensitivity and specificity, are higher for cholelithiasis, renal colic and small bowel obstruction when compared with other illnesses such as diverticulitis.Lindelius demonstrated that a surgeon-performed US was able to increase diagnosis accuracy in patients with acute abdominal pain [7].Furthermore, in this same study, POCUS decreased short-term complementary examinations [8] and increased patient's satisfaction.It was demonstrated that POCUS could decrease the hospitalization rate ( − 7%), imaging prescriptions ( − 18%) and increase the direct orientation toward surgery by 18% without increasing rates of rehospitalization or death [9].Another study showed that POCUS increased the diagnostic accuracy and planned diagnosis workup by 45% [36-54%] in a population of 128 patients admitted to the ED with abdominal pain without previous diagnostic orientation [10].This improvement was achieved by comparing diagnosis before and after POCUS realization.POCUS can also be used as a first-line imaging procedure followed by a computed tomography if necessary.This strategy has been considered as the most accurate according to sensitivity and exposure to radiation [2].POCUS could therefore be considered as an extension of the clinical examination and can increase the whole diagnostic performance, in particular in some illnesses as cholelithiasis or renal colic.However, despite these few studies, the added value of POCUS performed by an emergency physician on patients with non-selected abdominal pain remains controversial.Actually, (i) it has rarely been evaluated by randomized controlled trial (RCT), (ii) US performances have only been demonstrated for some conditions such as renal colic, cholelithiasis, appendicitis or bowel obstruction and (iii), previous studies were performed by highly trained Emergency Physicians.
Here, we conducted a RCT to investigate the added value of early POCUS on the accuracy of the preliminary diagnosis made by the emergency physician before any radiologist-performed imaging study in patients presenting to the ED with acute abdominal pain [11].

Design
We designed an interventional randomized, controlled, open label, parallel-group, trial in two French EDs.The two recruiting centers were a university hospital and a community hospital.POCUS was added to the usual diagnosis workup in the experimental group.POCUS, performed in B mode only with a curvilinear probe, assessed the major spots and search for main anomalies.This study followed the CONSORT reporting guidelines [12].

Intervention
Since there is no international consensus-based guideline, the exploration protocol was collectively designed after a literature review.It was focused on aorta (aneurysm, aortic dissection), gallbladder (lithiasis, cholecystitis), kidneys (hydronephrosis), bladder, small bowel loops, appendix and ovaries (Table 1).POCUS was performed using Mindray TE7 or Philips CX50 with a curvilinear probe (3.5-5MHz) or a linear probe (7-10 MHz) for the appendix exploration.It was performed by a trained EP.Theses EP previously attend a refresher course [12], and were not necessarily the EP in charge of the patient.The investigators have previously completed a validated training program.It could be a certified one-year facultybased training program or a short training session (two days).The study protocol was published [11].

Participants
We included patients strictly over 17 years old presenting to the ED with acute abdominal pain, when an EP trained in POCUS was present.They were identified from the referral system.An informed consent was obtained before randomization.It was a convenience sample since an EP trained in POCUS was not always available.Exclusion criteria were a documented end-of-life, immediate need of life-support therapy, pregnant or breast-feeding women and patient under guardianship.

Outcomes
The final diagnosis was established a posteriori by an adjudication committee composed of three independent experts in EM, radiology and abdominal surgery.The committee was blind regarding the group (POCUS vs control).They had access to all data from patient files including advanced imaging results excepted the preliminary diagnosis made by the emergency physician in charge of the patient and POCUS results.The preliminary diagnosis was made by the treating EP before any radiologist-performed imaging study (including ultrasound, CT-scan, MRI).The preliminary diagnosis was based on clinical examination and results of laboratory tests in both arms, associated with POCUS in the intervention arm.The treating EP were not blind of the POCUS results in the intervention arm.
The primary endpoint was the proportion of exact preliminary diagnosis.The preliminary diagnosis made by the EP was considered exact/correct when it was similar to the final diagnosis made by adjudication committee.Diagnosis were chosen in a predefined list.The diagnostic criteria were not specified since the adjudication committee was composed of experts.Non-specific abdominal pain was defined as an acute abdominal pain of under 7 days' duration, and with no diagnosis after examination and baseline investigations.Secondary endpoints were the time between admission at the ED and diagnosis, ED length of stay, diagnostic accuracy for nonspecific abdominal pain, prescription of biological and radiological exams during the ED length of stay and hospitalization rate.A post-hoc analysis on diagnostic performance was performed on a sub-group of patients with diagnosis accessible to US.

Randomization
Patients were randomized 1:1 to POCUS or control group by a computed-based program in random block sizes and stratified by centre.Randomization list were generated using SAS software.

Sample size calculation
Based on previous studies [7][8][9][10], a correct diagnostic rate of 57% was expected in the control group and 74% in the experimental group.With an alpha value of 0.05 and a power level of 80%, 244 patients were required.A 5% attrition rate (patients randomized but presenting an exclusion criteria) was expected, thus 256 randomized patients were needed.

Statistical analysis
The primary endpoint was compared between the two groups using a mixed model taking into account the recruiting centre.The delays were compared by a mixed linear generalized model adjusted on the recruiting centres.Sensitivity, specificity, positive and negative predictive values were estimated with their 95% confidence intervals.The rates of readmission and hospitalization were compared using a logistic generalized mixed model adjusted on the centre.In the experimental group (with POCUS), duration and self-assessed difficulty of POCUS were described by means and standard deviations.

Discussion
In this bicentric randomized controlled study, systematic POCUS performed by an EP did not improve the rate of exact diagnosis in adult patients presenting to ED with acute abdominal pain.This particular endpoint, rate of exact diagnosis in patients with unselected abdominal pain, has not been frequently addressed.Lindelius [7] showed a positive effect on diagnostic performance with an improvement of exact preliminary diagnosis from 57 to 65%.In a population with similar inclusion criteria, Durgun [13] found that POCUS was able to narrow the number of suspected diagnoses, to reduce the ED length of stay, but not the whole cost.When comparing population between our study and the one from Lindelius, there was no obvious differences.Distribution of final diagnosis and diagnostic accuracy in the control group, were similar.The lack of positive effect of POCUS on diagnostic accuracy could be explained by several factors: (I) insufficient POCUS skills of investigators.They were diverse even if a validated training session was required to be an investigator.However, duration and modalities of these training programs could be different" In the study from Lindelius, surgeons had a 4-week training session which is longer than the ones of some of our investigators.(ii) POCUS could be performed by an investigator who was not the EP in charge of the patient.Therefore, US findings were possibly not fully integrated with other clinical findings.In addition, we did not observe a decrease in US performed by a radiologist ordered by the emergency physician in charge of the patient in the POCUS group compared to the control group.This result contrasted with Lindelius study in which less radiological US were performed in the PoCUS group.It could be related to the lack of integration of PoCUS findings in the diagnostic process or to the lack of confidence of investigators.
Other studies investigated the diagnostic accuracy of POCUS in specific presentations such as suspected bowel obstruction [14,15], acute flank pain [14], suspected appendicitis [15].In all these studies, POCUS improved the diagnostic accuracy.Another approach was the diagnosis or management changes when POCUS was performed.Jang [10] showed that POCUS improved the decision making process by 45% [CI 95% 36-54%].
Our study had some limitations: (I) varied POCUS skills of investigators; (ii) Overestimation of the potential diagnostic improvement induced by PoCUS, (iii) The experts reviewed the patient's file together which could introduce bias and (iv) US clips quality were not adjudicated since it should have require a full review process.
Despite these limitations, it was a prospective randomized control study without major deviation.Moreover, POCUS was harmless as there was no difference in safety criteria (same hospitalization and 7-day readmission rates between the two groups).Indeed, abdominal US, including POCUS, only provides useful insights in some etiologies (cholelithiasis, renal colic, appendicitis, small

Conclusion
Our study did not demonstrate a positive effect of POCUS in the diagnostic process of adult patients with abdominal pain.Other diagnostic strategies including PoCUS could be tested for patients consulting for acute abdominal pain.Further research should focus on the accuracy of strategies including PoCUS only if an etiology where it is accurate, are suspected.This approach was investigated with some success [2] but still need confirmation [16].

Fig. 1
Fig. 1 Flow-chart of 256 patients included in the study

Table 1
Spots and focused anomalies visualized by POCUS in the echoPAIN study

Table 2
Baseline characteristics and final diagnosis of 251 patients included in the study BMI Body mass index, VAS Visual assessment scale

Table 3
comparison of secondary outcomes in 248 patients included in the study (3 patients with missing data) CT Computed tomography, US Ultrasound, ED: Emergency department, POCUS: Point-of-care Ultrasound