Randomized, Controlled Trial of Immediate Versus Delayed Goal-Directed Ultrasound To Identify The Cause of Nontraumatic Hypotension In Emergency Department Patients.

Danielle Parker, DO | EM PGY3

 The Article: Randomized, Controlled Trial of Immediate Versus Delayed Goal-Directed Ultrasound To Identify The Cause of Nontraumatic Hypotension In Emergency Department Patients. Jones et al. (2004), Crit Care Med Vol 32, No. 8               

The Idea: To determine if the use of physician-performed immediate vs. delayed goal-directed ultrasound protocol in the management of non-traumatic, symptomatic, hypotensive ER patients led to increased diagnosis accuracy

The Study: This was a randomized, control trial performed between July 2002 and September 2003 in the emergency department of Carolinas Medical Center which is an urban tertiary care center with over 100,000 patient visits per year. 184 patients were randomized into two groups: group 1 received immediate (time 0) goal-directed ultrasound in addition to standard care (history, physical, lab work, x ray); group 2 received a delayed goal-directed ultrasound 15 mins after receiving standard care.

Inclusion criteria included: nontrauma emergency department patients age of 17 or older; initial vitals consistent with shock (systolic blood pressure < 100 mmHg systolic or shock index >1) and agreement of two independent observers for at least one sign and one symptom of shock (inadequate tissue perfusion). Once a patient was deemed to be eligible for the study, attending ER physicians and third year ER residents received a random numbered, sealed envelope that contained the randomization assignment (group 1 (immediate US) or 2 (delayed US)) and data collection sheets. Both groups of patients received standard history and physical, lab work, blood gases and xrays. Group 1 received an immediate ultrasound (at time 0) which included the following views: subcostal to assess for RV diastolic collapse, IVC to assess intravascular volume status, parasternal long axis to assess LV function and pericardial effusion, apical 4 chamber to compare ventricle size, hepatorenal recess to assess for free intraperitoneal fluid, pelvis to assess for intraperitoneal fluid and aorta to assess for AAA. Goal-directed US was performed by either a board certified ER attending or a third year ER resident. At time 15 mins examining physicians in both groups completed a data sheet with their differential diagnoses based on the information they had acquired. Group 2 participants then received the same goal-directed US after 15 minutes (time = 15). At 30 mins both groups completed the data sheets again.

The Findings:

Outcomes included the number of viable diagnoses at 15 mins and the rank of their likelihood of occurrence at both 15 and 30 mins. At 15 minutes, group 1 had a median of 4 differential diagnoses while group 2 had a median of 9 (median difference= 5; 95% CI, 4 - 6; Mann-Whitney U test, p < .0001). At 30 minutes group 1 still had a median of 4 diagnoses while group 2 had a revised median of 3 diagnoses (Mann-Whitney U test, p < .4463). At time 15 mins physicians in group one indicated the correct diagnosis in 80% (95% CI, 70 – 87%) of their patients while group 2 was only 50% (95% CI, 40-60%). There was no difference in mortality between patients in group 1 and 2.

The Takeaway:

It was determined that the incorporation of goal-directed ultrasound in the evaluation of nontraumatic, symptomatic, undifferentiated hypotension helped physicians determine fewer viable diagnoses and causes. Goal-directed ultrasound results in a more accurate impression of patients and final diagnosis.

Quantifying systemic congestion with Point-Of-Care ultrasound: development of the venous excess ultrasound grading system

Amy Han, DO | EM PGY3

The Article: Quantifying Systemic Congestion With Point-of-Care Ultrasound: Development of the Venous Excess Ultrasound Grading System. Beaubien-Souligny et al. (2020). The Ultrasound Journal. 12(1):16.

The Idea:

To develop several grading system prototypes using POCUS and to determine their respective ability to predict acute kidney injury (AKI) after cardiac surgery.

The Study:

This was a prospective cohort study at a tertiary cardiac surgery center from August 2016 to July 2017, of non-critically ill patients 18 years and older undergoing cardiac surgery with the use of cardiopulmonary bypass. All patients underwent POCUS assessment the day before surgery, at ICU admission after surgery, and daily from postoperative days 1 to 3. Each US assessment consisted of hepatic vein Doppler, portal vein Doppler, intra-renal venous Doppler, and inferior vena cava US.

A multidisciplinary team developed five venous excess ultrasound (VExUS) grading system prototypes based on the severity of venous ultrasonographic markers. For hepatic vein Doppler, a systolic phase of lesser amplitude than the diastolic phase but toward the liver was considered mild; the presence of a reversed systolic phase (toward the heart) was considered severe. For portal vein Doppler, a pulsatile fraction (PF, variation in velocities during cardiac cycle) of 30-49% was considered mild; a PF>50% was considered severe. For intra-renal venous Doppler, a discontinuous pattern with a systolic and a diastolic phase was considered mild; a discontinuous pattern with only a diastolic phase was considered severe. The prototype grading systems were named VExUS “A” through “E”. The VExUS score was determined for all patients and for all timepoints.

The Findings:

A total of 705 US assessments from 145 participants were analyzed. The association between each score and AKI was assessed using time-dependent Cox models. In post-operative period, severe congestion (Grade 3) defined by the VExUS C grading system was the most strongly associated with AKI (HR 3.69, CI 1.65-8.24, p=0.001). This association remained significant after adjustment for baseline risk for AKI and vasopressor/inotropic support (HR 2.82, CI 1.21-6.55, p=0.02). At time of ICU admission after surgery, severe congestion (Grade 3) defined by the VExUS C grading system had high specificity (96% CI 89-99%) but low sensitivity (27% CI 15-41%) for development of subsequent AKI, resulting in a moderate positive likelihood ratio of 6.37 (CI 2.19-18.5) which outperformed the use of common central venous pressure cut-offs. In comparison, IVC dilatation alone had poor diagnostic performance (specificity 41%), suggesting that this commonly used US assessment is not sufficient to detect clinically significant congestion.

The Takeaway:

Severe congestion, defined as the presence of severe flow abnormalities in multiple Doppler patterns with a dilated IVC (VExUS grading system C - Grade 3), offered the strongest association with the development of subsequent AKI. POCUS may enable the clinician to detect clinically significant systemic venous hypertension.

A Doppler Echocardiographic Pulmonary Flow Marker of Massive or Submassive Acute Pulmonary Embolus

Jessica A. Schumann | EM/IM PGY-3

The Article:

A Doppler Echocardiographic Pulmonary Flow Marker of Massive or Submassive Acute Pulmonary Embolus. Afonso et al. (2019). Journal of the American Society of Echocardiography. 32(7): 799-806.

The Idea:

To explore the clinical utility of early systolic notching (ESN) of the right ventricular outflow tract (RVOT) pulsed-wave Doppler envelope in the detection of massive pulmonary embolism (MPE) or submassive pulmonary embolism (SMPE)

The Study:

Retrospective study at Wayne State University where 277 (187 with PE, 90 control subjects without PE) patients without known pulmonary hypertension, who underwent contrast computed tomographic angiography (CTA) for suspected pulmonary embolism (PE) and underwent transthoracic echocardiography within 48 hours were studied. Patients with suboptimal pulsed-wave Doppler signals across the RVOT, more than moderate valvular disease, known history of PE, established chronic thromboembolic pulmonary hypertension, and preexisting pulmonary hypertension were excluded from the study.

The authors also evaluated other echocardiographic parameters, including McConnell’s sign and 60/60 sign.

Doppler interrogation of the RVOT was performed in the parasternal short-axis view at the level of the aortic valve or from the subcostal short-axis view with sample volume placed approximately 0.5 cm proximal to pulmonic valve.

• Early Systolic Notching: Early systolic notching pattern (spike and dome morphology) Doppler envelope exhibits a narrow peaked initial wave (spike) with early deceleration of the RVOT envelope producing a sharp notch within the first half of systole (notch location within initial 50% of ejection, estimated with caliper tool) followed by a second Doppler wave (dome) that was more curvilinear in appearance.

• Midsystolic Notching: Midsystolic notching is defined as a distinct notch falling within the second half of the systolic ejection period or, if the nadir occurred closer to the end of ejection, dividing the flow profile into two distinct peaks

The Findings:

Two authors blinded to the PE diagnosis evaluated 277 patients’ echocardiograms. Of these patients, 187 patients had a PE diagnosed on CTA within 48 hours of the echocardiogram. There was good interobserver agreement (96.7%).

In patients with massive pulmonary embolus or submassive pulmonary embolus, early systolic notching was observed in 92% of patients and midsystolic notching was observed in 1% of these patients.

In patients with subsegmental pulmonary embolus, early systolic notching was observed in 2% of patients and midsystolic notching was observed in 16% of patients.

In the control group of 90 patients, no systolic notching was observed.

Early systolic notching pattern for MPE and SMPE was shown to have good to excellent predictive ability: 92% sensitive and 99% specific. ESN had a positive predictive value of 96% and a negative predictive value of 96%. This is superior predictive ability when compared to McConnell’s sign, which yielded a sensitivity of 52% in this study.

The Takeaway:

ESN reliably identified patients with MPE and SMPE, but it did not identify those with subsegmental PE. ESN demonstrated superior predictive value with a high negative predictive value. Echocardiography should not be viewed as the primary screening test or gatekeeper for CTA in the diagnosis of acute PE. Prospective studies are required in broader populations, and the findings will need validated. In the future, echocardiography may offer a more cost-effective screening tool when compared to CTA

Accuracy of early RUSH exam for diagnosis of shock etiology in critically ill patients

Robert Cameron Sooby, DO| EM PGY3

The Article:

Accuracy of early rapid ultrasound in shock (RUSH) examination performed by emergency physician for diagnosis of shock etiology in critically ill patients. Ghane et al. (2015). Journal of Emergencies, Trauma, and Shock. 8(1): 5–10.

 The Idea:

To determine the accuracy of early RUSH examination in predicting shock type in critically ill patients, and thus allowing for earlier identification of shock etiology and initiation of shock-specific treatments.

The Study:

This was a prospective study performed between April 2013 and October 2013. A total of 52 patients in shock state (defined as SBP < 100 or shock index (HR/SBP) > 1) were enrolled. Excluded were patients with a clear cause for shock (external hemorrhage, active GI bleeding, etc.). Early bedside RUSH was performed on all patients by a single board-certified ED physician, and all patients received standard of care without delay. All patients were followed to document their final diagnosis. Of note, subsequent physicians were not blinded to results of RUSH examination. A one-page checklist was designed incorporating the main components of the RUSH exam, which included evaluation of heart, IVC, thoracic and abdominal compartments, and large vessels. Five subtypes were defined for shock: hypovolemic, distributive, cardiogenic, obstructive and mixed shock. Agreement (Kappa index) of initial impression provided by RUSH with final diagnosis, and also sensitivity, specificity, PPV, and NPV of RUSH for diagnosis of each shock type were calculated.

The Findings:

The mean duration for exam (patient's arrival till RUSH conclusion) was 20 minutes (range, 10-25 minutes). The most frequent types of shock were cardiogenic shock (12 patients, 23.1%) and mixed shock (10 patients, 19.2%). Eight patients had hypovolemic, eight distributive, and seven obstructive type of shock. Seven cases (13.5%) died before the precise cause of shock could be determined and was classified as “not defined etiology”. Kappa index for general agreement between shock type using RUSH protocol and final diagnosis was 0.70 (P value = 0.000), reflecting acceptable general agreement. For hypovolemic shock, RUSH showed excellent sensitivity and good specificity (100% and 94.6%, respectively). NPV and PPV were 94.6% and 80%, respectively. In hypovolemic patients, RUSH protocol showed 86% agreement with final diagnosis (P value < 0.001). For cardiogenic shock, RUSH showed good sensitivity (91.7%) and specificity (97.0%). RUSH showed 89% agreement (P value < 0.001) with final diagnosis. PPV and NPV were 91.7 and 97.0%, respectively. For obstructive shock, RUSH showed excellent sensitivity (100%) and good specificity (97.0%). It had the largest agreement with final diagnosis (92%, P value < 0.001). PPV and NPV were 87.5% and 100%, respectively. For distributive shock, RUSH had excellent specificity (100%) but low sensitivity (75%). It had an acceptable agreement with final diagnosis (83%, P value < 0.001). PPV and NPV were 100% and 94.9%, respectively. For mixed etiology shock, RUSH had excellent specificity (100%) but had the lowest sensitivity (70%). It also had the lowest agreement (74%, P value < 0.001) with final diagnosis. PPV and NPV were 100% and 92.1%, respectively.

The Takeaway:

When performed by experienced clinicians, RUSH can rapidly and accurately diagnose shock type in the undifferentiated hypotensive patient. This in turn allows the clinician to initiate goal-directed therapies earlier and with greater confidence. Due to its inherently dynamic physiologic nature, RUSH was less sensitive in diagnosing distributive shock. Further studies utilizing more physicians and a larger sample size will need to be conducted to assess the shortcomings of this particular study.

Transesophageal echocardiography use during cardiac arrest in the emergency department

Ali Elsaied, DO | EM PGY 3

The Article:

Teran, F., Dean, A. J., Centeno, C., Panebianco, N. L., Zeidan, A. J., Chan, W., & Abella, B. S. (2019). Evaluation of out-of-hospital cardiac arrest using transesophageal echocardiography in the emergency department. Resuscitation, 137, 140–147.

The Idea:

To determine the potential added benefit of utilizing transesophageal echocardiography in out-of-hospital cardiac arrest patients brought to the ED.

The Study:

A prospective observational study at an urban academic tertiary care center of all patients over 18 years old, not pregnant, found to be DNR, or had any visible evidence of trauma who presented to the ED either actively in cardiac arrest, or immediately post-ROSC. The emergency physicians performing the TEEs were trained extensively in its use prior to the study launch. A total of 33 out-of-hospital cardiac arrest patients were enrolled in the study. The emergency physicians performing the ultrasound utilized the real-time TEE images to provide the primary ED team with information that may be beneficial in guiding resuscitative efforts, such as so-called ‘Area of Maximal Compression’ or AMC, sonographic volume status, RV dilation, aortic dissection, and more detailed view of ventricular dysrhythmia, such as very fine VF. The study evaluated how often TEE in cardiac arrest provided additional clinical information which may alter resuscitative management in any way.

The Findings:

Of the 33 patients enrolled in the study, 21 arrived to the ED with ongoing CPR, and 12 arrived having already achieved ROSC, or achieved ROSC within the first five minutes of arriving to the ED. The mean time from patient arrival to the ED to TEE 12 minutes. In the cohort of patients enrolled in this study, 7 patients were found to be in PEA, 6 were in asystole, 2 in non-pulseless ventricular arrythmias, and 16 had ROSC at arrival. 2 of these patients re-arrested shortly after arrival to the ED. 2 of the 7 patients thought to be in PEA by conventional measures were found on TEE to actually be in pseudo-PE, and 3 cases of what was thought to be asystole were found to be in fine VF, all of which were defibrillated.

39% of patients in the study were found to have RV dilatation on TEE, however not all of these patients were thought to have PE by the primary team.

One case identified a mass within the heart, thought to be a thrombus, for which the patient received thrombolysis.

In 17 of the intra-arrest cases, Area of Maximal Compression was evaluated by TEE. Of these, only 8 were found to have compressions over the LV, whereas 9 were receiving compressions over the LVOT or aortic root. Hemodynamic parameters seemed to improve via ETCO2 monitoring and SBP/DBP measurements with correction of compression position.

The Takeaway:

TEE in cardiac arrest may provide emergency physicians with more clinical data, potentially altering management to improve outcomes in out-of-hospital cardiac arrest patients.

FOCUS exam in the detection of Pulmonary Embolism

Zachary Messina, DO | EM/IM PGY3

The Article:

Daley et al. Increased Sensitivity of FOCUS for PE in ED Patients with Abnormal Vitals. Academic Emergency Medicine. November 2019. Vol 26 (11). 1212-1220.

The Idea:

To determine the sensitivity and specificity of the FOCUS exam as well as each component of the focused cardiac ultrasound (FOCUS) in two subsets of patients with abnormal vital signs.

The Study:

This study is a prospective, blinded, observational multicenter cohort study of two subsets of patients. The study was performed at six academic emergency rooms and involved seven ultrasound-fellowship-trained emergency attendings, three PGY-3 emergency room residents, as well as three third year medical students. The enrollment of the study was determined by a power calculation in place of a timeframe. Patients were placed in one of two groups, either the primary grouping which had a requirement of heart rate of greater than 100 and/or hypotension with systolic blood pressure less than 90 mmHg, or a subgroup which required only heart rate to be greater than 110 beats per minute. All patients were 18 years of age or older and all patients underwent computed tomography with angiography (CTA) of the chest. Prisoners, wards of the state, non-English speaking patients, and those where investigators were not able to obtain any echocardiographic data due to technical challenges were excluded. The goal was to have sonographers perform FOCUS prior to CTA; however, if FOCUS was performed after CTA the sonographers were blinded to the results of the CTA. All personnel in the study underwent standardized training consisting of a brief video and 1-hour didactic session. Two of the three residents also underwent an additional didactic session; the third already had prior experience in collecting ultrasounds. The three medical students underwent a 1-hour didactic session and 1-hour hands-on training session by the third resident as well. The medical students were required to perform 20 FOCUS exams prior to the study initiation to ensure competency. The FOCUS exam consisted of the parasternal long axis, parasternal short axis, apical four chamber, and subxyphoid views with a measurement of TAPSE, visual inspection of right ventricular enlargement, septal flattening, presence of tricuspid regurgitation on color Doppler, or monitoring for McConnell’s sign. If any of these components were present, the FOCUS exam was positive, if all components were absent the FOCUS was negative. TAPSE in this study was defined as <2.0cm instead of the conventional <1.7cm to increase sensitivity at the loss of specificity. Finally, inter-rater reliability was also tested as the site principal investigator by their own review in 104 of 136 patients in the right ventricular components in comparison to the sonographer’s interpretation.

The Findings:

First, 143 patient’s underwent CTA during the study, but seven were excluded. Three were due to technically difficult FOCUS exams, and only four were due to non-English speaking language barrier. There were 136 patients enrolled during the study, 37 had a pulmonary embolism on CTA. Of these 37 patients, six were hypotensive, 28 were normotensive with at least one right ventricular component identified, and three were normotensive without any component identified. In the comparison of FOCUS versus CTA in patients who had a PE, the following data apply. In the primary group of patients (n = 136), the sensitivity of FOCUS was 92% (95% CI = 78-98%). Of the right ventricular components, TAPSE of <2.0cm was the most sensitive at 88% (95% CI = 72-97%), and in comparison the TAPSE value of <1.7cm was at 67% (95% CI = 48-82%). The other components ranged from a sensitivity of 35% to 51%. The overall specificity of FOCUS was 64% (95% CI = 53-73%), with the McConnell’s sign component being most specific at 99% (95% CI = 94-100%). The other components ranged from 64% to 93% in specificity. 

In the subgroup of patients with a heart rate of >110 (n = 98), the sensitivity of FOCUS for PE was 100% (95% CI = 88-100%), with the most sensitive component being TAPSE of <2.0cm, which was 93% sensitive (95% CI = 75-99%). The sensitivity of TAPSE at <1.7cm was 77% (95% CI = 56-91%). The other components ranged in sensitivity from 36% to 57%. FOCUS specificity in this subgroup was 63% overall (95% CI = 51-74%), the most specific being the McConnell’s sign at 100% specificity (95% CI = 95-100%). The other components ranged from 63% to 93% in specificity. 

Finally, inter-rater reliability for whether the FOCUS exam was positive or negative by two separate sonographers was 1.0 (95% CI = 0.31 to 1.0). Of the individual components, TAPSE had a kappa statistic of 0.61 (95% CI = 0.31 to 1.0), septal flattening had 0.88 (95% CI = 0.69 to 1.0), right ventricular enlargement had 0.89 (95% CI = 0.7 to 1.0), McConnell’s sign had 0.89 (95% CI = 0.7 to 1.0), and tricuspid regurgitation was 0.81 (95% CI = 0.64 to 1.0). 

Limitations of this study:

From the study set-up, one of the three residents performing ultrasound was more experienced. To offset this, additional training was provided to the other residents in hopes this would bridge any gap in experience. In addition, the three medical students were all third year and inexperienced in ultrasound. While their data was also compiled into the resident data, there was concern for inaccuracy given inexperience. This was attempted to be compensated for in additional training and the performance of 20 FOCUS exams prior to the study initiation. These limitations may lead to the acceptance of incorrect data, however, this was demonstrated in terms of Kappa statistics.

In terms of data collection, nine patients had missing data for TAPSE, two for right ventricular enlargement, two for septal flattening, two for McConnell’s sign, and 60 for tricuspid regurgitation. There was also unintentional unblinding of two patients in the study to the sonographer. These limitations may primarily cause the unintentional underestimation of sensitivity or overestimation of specificity in the data collected. 

Finally, the study was created using a statistical power, which may cause bias, however, the power was meant to limit the width of sensitivity to no greater than 20%. Selection bias may also confound these data in terms of the exclusion of patients; however, the number of patients excluded was kept to a minimum.

The Takeaway:

The FOCUS exam in patients with abnormal vital signs may help to significantly lower the likelihood of pulmonary embolism in most patients who are suspected of having a pulmonary embolism. This was especially true in patients with a heart rate of >110 beats per minute. Further study with an unpowered cohort is needed to determine of FOCUS can exclude PE.