Indications, Clinical Impact, and Complications of Critical Care Transesophageal Echocardiography: A Scoping Review

Background Critical care transesophageal echocardiography (ccTEE) is an increasingly popular tool used by intensivists to characterize and manage hemodynamics at the bedside. Its usage appears to be driven by expanded diagnostic scope as well as the limitations of transthoracic echocardiography (TTE) – lack of acoustic windows, patient positioning, and competing clinical interests (eg, the need to perform chest compressions). The objectives of this scoping review were to determine the indications, clinical impact, and complications of ccTEE. Methods MEDLINE, EMBASE, Cochrane, and six major conferences were searched without a time or language restriction on March 31st, 2021. Studies were included if they assessed TEE performed for adult critically ill patients by intensivists, emergency physicians, or anesthesiologists. Intraoperative or post-cardiac surgical TEE studies were excluded. Study demographics, indication for TEE, main results, and complications were extracted in duplicate. Results Of the 4403 abstracts screened, 289 studies underwent full-text review, with 108 studies (6739 patients) included. Most studies were retrospective (66%), performed in academic centers (84%), in the intensive care unit (73%), and were observational (55%). The most common indications for ccTEE were hemodynamic instability, trauma, cardiac arrest, respiratory failure, and procedural guidance. Across multiple indications, ccTEE was reported to change the diagnosis in 52% to 78% of patients and change management in 32% to79% patients. During cardiac arrest, ccTEE identified the cause of arrest in 25% to 35% of cases. Complications of ccTEE included two cases of significant gastrointestinal bleeding requiring intervention, but no other major complications (death or esophageal perforation) reported. Conclusions The use of ccTEE has been described for the diagnosis and management of a broad range of clinical problems. Overall, ccTEE was commonly reported to offer additional diagnostic yield beyond TTE with a low observed complication rate. Additional high quality ccTEE studies will permit stronger conclusions and a more precise understanding of the trends observed in this scoping review.

compressions. 10,11-13 These factors have led the American Society of Echocardiography to state that a primary indication for TEE is the lack of transthoracic windows in a critically ill patient where echo is expected to change management. 9 ccTEE is a modality of scalable complexity, from goal-directed TEE that uses "core" views to guide resuscitation, 14 to detailed assessments of hemodynamics and the assessment of extra-cardiac structures in the thorax and abdomen. [15][16][17] ccTEE differs from consultative TEE (eg, cardiology performed) in that the ccTEE provider's role in patient care includes the real time integration of findings into diagnosis, hemodynamic management and prognosis. 18 As the literature supporting ccTEE grows, a synthesis of primary studies is expected to aid in understanding and influencing the adoption of ccTEE among intensivists. In conducting this scoping review, our objectives were to characterize the indications, clinical impact, complications and domains requiring further inquiry for the ccTEE modality.

Methods
The study protocol and all data are available on Open Science Framework (OSF) (https://osf.io/fsnt3/). Ethics approval for scoping reviews is not required at our institutions. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews (PRSIMA-SCR) guidelines. 19

Search Strategy
The search strategy was designed with the help of a research librarian (RS) and is summarized in Appendix 1. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched without a time or language restriction on March 31 st , 2021. Clinicaltrials.gov and OSF were also searched for ongoing TEE studies (Appendix 2). Six critical care and emergency medicine conferences had their abstracts searched form 2018 to present (Appendix 3). Any relevant systematic review identified by our search had its references screened. Google Translate (Google, USA) was used for non-English studies with a human translator employed when needed.

Study Selection
Studies were included if they: (1) assessed adult human subjects (≥ 16 years old); (2) investigated the use of TEE in critically ill patients; (3) the TEE was performed in a critical care context with focused indications (as opposed to comprehensive TEE performed by cardiologists); (4) the TEE was performed in the intensive care unit (ICU), emergency department (ED), or pre-hospital setting (eg, ambulance). Goal directed TEE performed by cardiologists were included.
Studies were excluded if they: (1) investigated comprehensive cardiology performed TEE; (2) investigated intra-operative or postcardiac surgical TEE; (3) used TEE to determine cardiac dimensions without a direct clinical application; (4) were reviews, opinion pieces, educational studies, or letters to the editors.
Covidence software (Veritas Health Innovation, Australia) was used for abstract and full-text screening. Abstracts and full texts were screened independently and in duplicate by 2 authors (RP and JB) with consensus used for discrepancies. Screening of the conference literature was done in duplicate by RP and MP.

Data Extraction
The following data was extracted independently and in duplicate by two authors (RP and JB), with discrepancies resolved through consensus discussion: study author, year of publication, country of corresponding author, setting (academic, community, mixed), study type, study design (prospective, retrospective), clinician performing TEE (intensivist, anesthesiologist, emergency physician), training of clinician performing TEE, number of patients, indication for TEE, primary outcome being measured, main finding(s), and TEE-related complications. Two pilot extractions were done by RP and JB.

Bias Assessment
In keeping with the PRISMA-SCR guidelines, studies were not assessed for applicability, risk of bias, or publication bias.

Outcomes
The primary questions addressed by this review are: (1) What are the reported indications for ccTEE? (2) What is the reported impact of ccTEE on diagnosis, management, and patient outcomes? The secondary questions addressed by this review are: (1) What are the study demographics? (2) What complications are reported for ccTEE? to rule out endocarditis (18%-33% of patients), 10,20-22 and for cardiac arrest (20% of patients) ( Table 2). 10 ccTEE was reported to help change diagnosis in 52% to 78% of cases 23,24 and resulted in a change in management in 32% to 79% of cases. 10,20,21,23,25,26 When miniature or disposable TEE probes were compared to standard TEE probes, the miniature probes had similar diagnostic performance for 2 dimensional echocardiography. [27][28][29] ccTEE to Investigate Hemodynamic Instability and Shock In many cases, ccTEE was reported to help clarify the etiology of shock (Table 3). ccTEE was used to correctly identify right ventricular (RV) failure from acute pulmonary embolism, 30-34 for managing the peripartum patient with hemodynamic collapse, 35,36 and for identifying unexpected causes of shock like dynamic left ventricular outflow tract (LVOT) obstruction. 37,38 There were a number of case reports of ccTEE identifying rare causes of shock that may not have been visualized on TTE: right atrial compression from intrabdominal hematoma, 39 thoracic tamponade post lung transplant, 40 and regional pericardial tamponade in the ED after discharge home from cardiac surgery. 41 For patients who already had TTE performed, ccTEE resulted in additional changes in management in 40% of cases, and refuted TTE diagnoses in approximately 20% of cases (Table 3). 42,43 For patients in shock, ccTEE was also able to predict fluid responsiveness. 44-46 Superior vena cava (SVC) collapsibility assessment performed using TEE had moderate diagnostic accuracy to predict fluid responsiveness, with thresholds for collapsibility of 21% to 29% yielding a sensitivity of 54% to 61% and specificity of 85% to 89%. 44,45 ccTEE also identified ventricular failure that resulted in the initiation or titration of vasopressors and inotropes in 4% to 73% of cases. 43,47,48 Although most ccTEE studies are observational, a randomized controlled trial (n = 550) was performed to determine whether a disposable TEE (hTEE) impacted time to resolution of hemodynamic instability for critically ill patients. Although there was no difference in the intention-to-treat (ITT) analysis of the primary outcome of resolution of hemodynamic instability at 6 days (sub-hazard ratio (SHR) 1.20, 95% confidence interval (CI) 0.98-1.46), there was a reduction in time to resolution of hemodynamic stability within 72 h of placement of the hTEE probe (SHR 1.26, 95% CI 1.02-1.55). 49 ccTEE use in Cardiac Arrest ccTEE in cardiac arrest identified the etiology of cardiac arrest in 25% to 35% of cases, 50-53 and in one study was reported to change management in 97% of cases in the intra or peri-arrest period. 52 Multiple studies reported that ccTEE identified fine ventricular fibrillation (VF) not seen on surface electrodes. 32,36,52 In one study, ccTEE detected pseudo-pulseless electrical activity (PEA) in 28% of cases of PEA, where ventricular contraction occurred but did not generate a palpable pulse. 52 Intra-arrest TEE was reported to improve CPR quality through guiding chest compressions to avoid ineffective compressions over the LVOT or aortic root. 11,23,52 Proper compression location over the LV was associated with increased stroke volume generated by chest compressions, and potentially improved survival. 13,52,54 ccTEE was also associated with shorter pulse checks when compared to both TTE and manual pulse checks. 11 Using protocols that focus on core TEE views, ccTEE in cardiac arrest was feasible and safe for providers with limited training. 11,50-52,55 A summary of the use of ccTEE in cardiac arrest is provided in Table 4.
Procedural Guidance with ccTEE ccTEE was also used to help guide invasive procedures, including confirming guidewire placement during the initiation of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) ( Table 5). 40,52,55-59 Once ECMO was established, ccTEE was used to troubleshoot flow issues and guide cannula repositioning, which was required in up to 38% of patients in one VV-ECMO cohort. 59 In one small cohort of patients on VA-ECMO, TEE guided weaning protocols performed by intensivists had high predictive accuracy (100%) for successful weaning. 60 TEE was also used to provide real-time guidance for the insertion of transvenous pacemakers. 36, 61,62 ccTEE use in Trauma TEE use in trauma had high diagnostic accuracy (>90%) for the detection of traumatic aortic injuries. [63][64][65] After initial surgical hemostasis, TEE helped identify other etiologies of shock including LV and RV dysfunction, blunt cardiac injury, and traumatic valvular abnormalities. 66,67 TEE was also described during the management of critically ill burn patients, with its use associated with a change in diagnosis and management in several small studies. [68][69][70][71] The use of TEE in trauma is summarized in Table 6.

TEE use in Respiratory Failure
Several studies have described the use of transesophageal lung ultrasound (TELUS), which is effective at identifying basal and posterior lung pathology. 72,73 Additionally, ccTEE use in patients with ARDS can identify RV failure and intracardiac shunting. [74][75][76][77] TEE use in respiratory failure is summarized in Appendix 6 and 7.

TEE-Related Complications
There were two significant gastrointestinal bleeds reported as a complication of ccTEE: one requiring endoscopic intervention, and the other requiring transfusion for hypovolemia. 78 There were no other major ccTEE associated complications (death or esophageal perforation) reported. There were 29 minor complications reported in 6739 patients, with those studies reporting a 1.6% to 9.8% minor complication rate (Table 7). One study identified 2 cases of bacteremia that they felt were likely associated with TEE use. 79 Another showed TEE was not associated with biomarkers of aspiration. 80

Discussion
The range of applications for ccTEE is broad, from resuscitative views acquired during cardiac arrest to advanced applications that mimic the complexity of consultative TEE. 18 Given the relative infancy of ccTEE, it's evidentiary base consists largely of case studies and retrospective observational studies, however, there are a number of well-designed prospective studies advancing the field. The existing ccTEE literature has characterized the indications for ccTEE and highlighted cases of additional diagnostic yield compared to TTE but has not consistently demonstrated improvement in patient important outcomes from the integration of ccTEE into existing diagnostic pathways. This is not surprising given the number of steps required for a diagnostic test to improve outcomes: correct patient selection, acquisition, interpretation, synthesis, and then implementation   For the patient in shock, a transthoracic approach is typically used given its availability and non-invasive nature. In many critically ill patients, however, transthoracic windows are limited. 10,42 For these patients, ccTEE is indicated and may give additional diagnostic yield beyond TTE. 42,43,82 Perhaps the most powerful application of ccTEE is its ability to quickly phenotype shock and identify causes that have targeted treatments such as pulmonary embolism, effusion, or severe ventricular dysfunction. 30-40,83,84 Its use to phenotype shock is valuable even when only core "resuscitative" TEE views are used, although refining management often requires additional views and quantitative measurements. A simplified "resuscitative" ccTEE protocol like the one shown in Figure 2 allows for the assessment of LV and RV function, pericardial disease, and catastrophic valvular failure. 23 Given the scalable complexity of ccTEE, these core views can be safely and effectively performed by intensivists with only focused training. 85 After phenotyping shock, ccTEE can play an important role in refining its ongoing management through titration of fluids, inotropes, and vasoactive medications. One approach to fluid resuscitation is to restrict IV fluids to patients with proven fluid responsiveness with signs of end organ hypoperfusion. Transthoracic approaches to predicting fluid responsiveness have variable diagnostic accuracy and generalizability, in part due to requirements for patients to be ventilated, not spontaneously breathing, and in sinus rhythm. 44,45,86-89 ccTEE measured SVC respiratory variability is an attractive approach to assessing fluid responsiveness given its relative ease of acquisition, repeatability, and moderate predictive accuracy, however, additional prospective studies are needed to properly define positivity thresholds. [44][45][46] For patients with ventricular failure, ccTEE is valuable to provide serial assessments of biventricular function during the titration of inotropes, as well as non-invasive cardiac output assessment using LVOT velocity time integral measurements (VTI). Although thermodilution derived cardiac output measurements from pulmonary artery catheters have similar accuracy to TEE, 90 ccTEE provides the advantage of offering anatomic information that may also inform the mechanism behind any distorted cardiac output physiology.
Given the diagnostic potential of ccTEE for the management of shock, there are a number of areas for future research. Prospective studies assessing ccTEE markers of fluid responsiveness are needed to determine the diagnostic accuracy and thresholds for test positivity. Ultimately, however, studies assessing the impact on patient important outcomes from integrating ccTEE into resuscitation  and also distinguish true pulseless electrical activity (PEA) from pseudo-PEA, with the latter having higher survival rates and the potential to respond to pharmacologic therapies. 52, 94 The use of ccTEE in cardiac arrest also has the potential to improve CPR quality. The American Heart Association suggests to perform compressions mid chest on the lower portion of the sternum compressing to a depth of at least 5cm, 95 however, from observational TEE data this results in almost half of chest compressions occurring over the LVOT or aortic root. CPR over the aortic root in animal and human studies is ineffective, with little cardiac output generated and poor survival. 13,52,96 ccTEE can be used to reposition compressions over the LV in real-time (Videos 1 & 2). 52 There are several areas for future research for intra-arrest TEE. These include the feasibility of implementing intra-arrest TEE to improve CPR quality and whether this correlates with improved proximal (end-tidal CO 2 and arterial pressure) and distal outcomes (ROSC and survival). Additionally, as more intra-arrest TEE is performed and pseudo-PEA is detected, determining the optimal therapeutic management of this entity is needed.
Procedural use of ccTEE ccTEE also has a role for the initiation and management of patients on ECMO. In some centers, ECMO cannulation is done with fluoroscopic guidance, however, TEE guided cannulation is an alternate strategy that may increase its portability. 55, 58 For centers performing ECMO, the ability to troubleshoot flow problems and catheter placement is essential. TEE can help identify catheter misplacement, recirculation of venous blood, and mechanical complications from the cannula. Additionally, the weaning of VA-ECMO requires serial assessments of ventricular function which is feasible by intensivists and provides flexibility with respect to the timing of weaning trials, however, the optimal strategy for VA-ECMO weaning is still an area of important research. 60

ccTEE use in Trauma
In trauma, the extended focused assessment with sonography in trauma (eFAST) exam has become a well integrated into acute resuscitation. The role of ccTEE in trauma patients is poorly defined, however, it has been shown to be feasible with some  17,41 Additionally, when there are no transabdominal or transthoracic windows due to subcutaneous emphysema or body habitus, ccTEE can potentially sequence immediate priorities or disposition. The "TREE" protocol for acute trauma resuscitation TEE focuses on identifying hypovolemia, aortic injuries, pericardial disease, and pleural pathology, 98 however, prospective studies validating its use are lacking. Given the relative paucity of studies assessing ccTEE use in trauma, prospective research assessing the feasibility of integrating ccTEE into the management of major trauma is warranted to ensure that it offers additional diagnostic information to existing trauma algorithms, and that it does not delay the sequencing of other life saving interventions or disposition.

ccTEE use for Respiratory Failure
A natural extension to TEE use for shock has been for the evaluation of patients with severe respiratory failure. These patients may have acute cor pulmonale and intracardiac shunting that can be identified with ccTEE. [74][75][76]99,100 Identifying these pathologies may help optimize ventilation strategies, PEEP, and the use of inhaled pulmonary vasodilators.
Additionally, transesophageal lung ultrasound (TELUS) is highly effective at imaging the posterior and basal lung zones, which often contain pathology for the intubated critically ill patient (Video 4). 73 TELUS can detect significant consolidation that may account for clinically important hypoxia, even when it is not visible on chest x-ray. 73 Additional research to assess the diagnostic accuracy of TELUS and also the impact of TEE guided lung recruitments is needed (Video 5 & 6).

Safety of ccTEE
Probe insertion is a commonly cited concern for clinicians learning ccTEE. The complication rate of ccTEE in the literature is low, with no major complications such as death or perforation reported, although there is likely underreporting due to the retrospective nature and ad-hoc reporting of studies. Gastrointestinal bleeding is a known risk of TEE, however, most cases are self limited and do not require intervention. 78 As well, incomplete reporting of whether patients were intubated limits the ability to generalize complication rates to different ICU populations. Additional prospective research systematically screening for complications is important to ensure that clinicians can accurately weigh the risks and benefits of ccTEE.

Limitations
There are several limitations to this study. Incomplete reporting of primary TEE studies, particularly with respect to who performed the TEE, made it difficult to assess whether the TEE was consultative or goal-directed. In these cases, discussion between authors was used to generate consensus using other domains like the setting (eg, ED or pre-hospital) and indication (eg, cardiac arrest) to help determine whether the TEE was comprehensive or ccTEE. Given this and the scope of this review, there is likely incomplete retrieval of the ccTEE literature. As well, ad-hoc reporting of complications in many studies means that the true complication rate is still unknown and is an important area for future research.

Conclusions
Although critical care TEE is still in its relative infancy, the indications and clinician-reported impact of ccTEE have been preliminarily characterized. Additional studies evaluating the impact of ccTEE on patient outcomes are still forthcoming and will assuredly have the greatest impact on priority domains for ccTEE adoption.

Abstract Presentation
This work has been presented in abstract form at the Canadian Critical Care Forum on December eighth 2021 in Toronto, Canada.

Author Contributions
RP takes responsibility for the content of the manuscript, including the study design, data extraction, data analysis, and manuscript writing. RP, MP, JB, JC, MM, and RA all contributed to the study design, data analysis, data interpretation, and manuscript writing. RP, MP, JB all performed data extraction.

Availibility of Data and Materials
The study protocol was registered on Open Science Framework (OSF) prior to data collection (https://osf.io/fsnt3/). All study data is publicly available at the same OSF link.

Consent for Publication
Not applicable.

Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics Approval
Ethics approval is not required for this scoping reviews at the authors institutions as it does not involve human participants.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.