Point-of-Care Ultrasound and Right Ventricular Strain: Utility in the Diagnosis of Pulmonary Embolism

Ramzi Ibrahim MD, João Paulo Ferreira MD

Department of Medicine, University of Arizona – Tucson and Banner University Medical Center

Tucson AZ USA

Abstract

Pulmonary emboli are associated with high morbidity and mortality, prompting early diagnostic and therapeutic considerations. Utilization of rapid point-of-care ultrasound (POCUS) to assess for signs of pulmonary emboli can provide valuable information to support immediate treatment. We present a case of suspected pulmonary embolism in the setting of pharmacological prophylaxis for venous thromboembolism with identification of right heart strain on bedside POCUS exam. Early treatment with anticoagulation was initiated considering the clinical presentation and POCUS findings. CT angiogram of the chest revealed bilateral pulmonary emboli, confirming our suspicion. Utilizing POCUS in a case of suspected pulmonary emboli can aid in clinical decision making.

Case Presentation

Our patient is a 50-year-old man with a history of morbid obesity, obstructive sleep apnea, and poorly controlled diabetes mellitus type 2 who was admitted to the hospital for sepsis secondary to left foot cellulitis and found to have left foot osteomyelitis with necrosis of the calcaneus. The patient was started on intravenous antimicrobials, underwent incision and debridement, and completed a partial calcanectomy of the left foot. During the hospital course, he remained on subcutaneous unfractionated heparin at 7,500 units three times a day for prevention of deep vein thrombosis. On post-operative day 12, he developed acute onset of dyspnea requiring 2 liters of supplemental oxygen and was slightly tachycardic in the low 100s. He complained of chest tightness without pain, however, he denied lower extremity discomfort, palpitations, orthopnea, or diaphoresis. Electrocardiogram was remarkable for sinus tachycardia without significant ST changes, T-wave inversions, conduction defects, or QTc prolongation. Rapid point-of-care ultrasound (POCUS) at bedside revealed interventricular septal bowing, hypokinesia of the mid free right ventricular wall, and increased right ventricle to left ventricle size ratio (>1:1 respectively) (Figures 1 and 2).

Figure 1. A: Static apical 4-chamber view showing interventricular bowing into the left ventricle (blue arrow), significantly enlarged right ventricle, and right ventricular free wall hypokinesia (green arrow). B: Video of apical 4-chamber view.

Figure 2. A: Static parasternal short axis view showing interventricular septal bowing in the left ventricle (green arrow). B: Video of parasternal short axis view.

With these findings, the patient was started on therapeutic anticoagulation. CT angiogram of the chest revealed a large burden of bilateral pulmonary emboli (PE). The pulmonary embolism severity index (PESI) score was 130 points which is associated with a 10%-24.5% mortality rate in the following 30 days. Formal echocardiogram showed a severely dilated right ventricle with reduced systolic function, paradoxical septal movement, and a D-shaped left ventricle. Patient remained hemodynamically stable and was discharged home after transition from heparin to rivaroxaban.

Discussion

Pulmonary emboli remain a commonly encountered pathological phenomenon in the hospital setting with a mortality rate ranging from <5% to 50% (1). Venous thromboembolism prophylaxis has been shown to reduce the risk of VTE in hospitalized patients, however, this does not eliminate the risk completely. Prompt diagnosis allows earlier treatment and improved outcomes however this is often challenging given the lack of specificity associated with its characteristic clinical symptoms (2). In the proper context, utilization of POCUS can aid the diagnosis of PE by assessing for signs of right ventricular strain. Characteristic findings seen on a cardiac-focused POCUS that represent right ventricular strain include McConnell’s sign (defined as right ventricular free wall akinesis/hypokinesis with sparing of the apex), septal flattening, right ventricular enlargement, tricuspid regurgitation, and tricuspid annular plane systolic excursion under 1.6 cm (3). Their respective sensitivities and specificities are highly dependent on the pre-test probability. For example, a prospective cohort study completed by Daley et al. (4) in 2019 showed that for patients with a clinical suspicion of PE, sensitivity of right ventricular strain was 100% for a PE in patients with a heart rate (HR) >110 beats per minute, and a sensitivity of 92% if HR >100 BPM. This study provides evidence to support the use of cardiac focused POCUS in ruling out pulmonary emboli in patients with signs of right ventricular strain and abnormal hemodynamic parameters such as tachycardia. Additionally, in settings where hemodynamic instability is present and the patient cannot be taken to the CT scanner for fear of decompensation, rapid POCUS assessment can be helpful. In our patient, given the acute need for supplemental oxygenation and dyspnea, along with his risk factors for a thromboembolic event, the use of POCUS aided in our clinical decision making. The yield of information that can be provided by POCUS is vital for early diagnostic and therapeutic decision making for patients with a clinical suspicion of pulmonary emboli.

References

1. Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008 Sep;29(18):2276-315. [CrossRef][PubMed]
2. Roy PM, Meyer G, Vielle B, et al. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006 Feb 7;144(3):157-64. [CrossRef][PubMed]
3. Alerhand S, Sundaram T, Gottlieb M. What are the echocardiographic findings of acute right ventricular strain that suggest pulmonary embolism? Anaesth Crit Care Pain Med. 2021 Apr;40(2):100852. [CrossRef] [PubMed]
4. Daley JI, Dwyer KH, Grunwald Z, et al. Increased Sensitivity of Focused Cardiac Ultrasound for Pulmonary Embolism in Emergency Department Patients With Abnormal Vital Signs. Acad Emerg Med. 2019 Nov;26(11):1211-1220. [CrossRef][PubMed]

Cite as: Ibrahim R, Ferreira JP. Point-of-Care Ultrasound and Right Ventricular Strain: Utility in the Diagnosis of Pulmonary Embolism. Southwest J Pulm Crit Care Sleep. 2022;25(2):34-36. doi: https://doi.org/10.13175/swjpccs040-22 PDF

Choosing Among Unproven Therapies for the Treatment of Life-Threatening COVID-19 Infection: A Clinician’s Opinion from the Bedside

Robert A. Raschke, MD

HonorHealth Scottsdale Osborn Medical Center

Scottsdale, AZ USA

We are clearly in unprecedented times. As clinicians watch patients die from COVID-19 infection in the ICU, many feel they cannot wait for clinical trials to prove that various proposed therapies are efficacious. Treatments for which any rationale suggest the possibility of benefit are being administered to patients and the literature abounds with reports of case series or poorly-designed observational trials in which small numbers of patients seem to have favorable outcomes when given these unproven therapies (1). In many cases, these reports are made globally available via social networking without the benefit of peer-review or are being published despite severe methodological flaws that would not have been acceptable prior to the COVID-19 outbreak. 

Standard therapy for COVID-19 has recently been published by the Surviving Sepsis Campaign, which have taken a conservative, evidence-based approach (2). But many clinicians are not able to maintain such equipoise in the face of catastrophe. Therefore, I propose an approach to consideration of bedside implementation of unproven therapies for life-threatening COVID-19 for comment and criticism. None of the therapies discussed below have even marginally-acceptable empirical evidence of clinical benefit in patients with COVID-19, so let us put critical appraisal of the literature aside for the moment, and accept that we cannot evaluate these therapies using the normal rules of evidence-based practice (3), application of which would exclude all from further consideration were this any other disease than COVID-19.

I will focus on four unproven therapies that are currently being given to patients with COVID-19 infection: hydroxychloroquine (4), tissue plasminogen activator (tPA) and heparin for presumed pulmonary microthrombosis (5), immunosuppressive treatment of “cytokine storm” (6), and transfusion of convalescent serum (7).

I based my opinions on these four unproven therapies on the following principles:

1. COVID-19 is a viral pneumonia. Although it may prove to have some distinctive features, it is likely to be similar to other viral pneumonias (such as SARS CoV-1, MERS, and H1N1 influenza) in terms of its clinical manifestations and response to therapy. We are more likely to gain helpful insights by looking at previous clinical data related to viral pneumonia than to data regarding various noninfectious entities such as high-altitude pulmonary edema or pulmonary venous occlusive disease, as some authors have suggested. COVID-19 viral pneumonia is unlikely, a priori, to respond to therapies that have never shown clinical benefit in the treatment of other viruses, particularly viral pneumonias.
2. Demonstration of in-vitro activity rarely translates into clinical efficacy (8,9). In-vitro activity should be a basis for clinical trials, not bedside implementation.
3. If unproven therapies are to be given, their safety must be an important consideration. First do no harm.
4. We should be willing to apply any treatment recommendation we make for patients to ourselves or beloved family members.

Based on these principles, I propose the following:

Hydroxychloroquine. The non-specific anti-viral properties of chloroquine and hydroxychloroquine were demonstrated in cell cultures 40 years ago. Although active in vitro against Dengue, HIV, Ebola, Influenza and other viruses, this has never convincingly translated into clinical effectiveness (9). A large cohort study focusing on prevention of influenza pneumonia included over 4000 patients receiving HCQ, and showed that they had an increased risk of hospitalization for pneumonia compared to controls (10). Given this long track record, it seems unlikely that HCQ will suddenly be found to have clinical anti-viral benefit in 2020. When it is nevertheless given, care should be exercised to monitor QTc, especially if used in conjunction with other QTc-prolonging drugs like azithromycin and/or in patients with cardiomyopathy.

tPA and heparin. A high incidence of venous thromboembolism has been observed in some cohorts of COVID-19 patients, as has previously been described in patients with H1N1 pneumonia (11).  Standard thromboprophylaxis should be employed and venous thromboembolism should be diagnosed and treated in patients with COVID-19 infection. However, some clinicians are administering tPA and therapeutic-dose heparin to patients with COVID-19 and elevated D-dimer in the absence of documented DVT or PE, based on the theory that these patients have microvascular thrombosis requiring treatment. Several large multicenter RCTs examined the use of human activated protein C (Xigris®) to prevent/treat microvascular thrombosis in patients with severe sepsis and convincingly demonstrated no clinical benefit (12). There is no other infectious disease for which the use of tPA or treatment-dose heparin has been proven to be clinically beneficial in the absence of standard indications related to documented venous thromboembolism. Lytic/antithrombotic therapy has a relatively high potential for causing life-threatening hemorrhage. In my opinion, it should not be employed without support from well-designed clinical trials. 

Cytokine Storm or HLH. The terms cytokine storm and hemophagocytic lymphohistiocytosis (HLH) have been used to describe similar (perhaps identical) maladaptive immune responses to viral infections. HLH has been well-described in H1N1 pneumonia, SARS-CoV-1 and MERS. There is a rich history of (mostly) observational clinical research supporting the use of immunosuppressive therapies including steroids, anakinra and tocilizumab to treat HLH secondary to viral infection (13). Although immunosuppression can be associated with life-threatening secondary opportunistic infections, treating secondary HLH in selected patients is an approach with a long track record and could be considered standard therapy in Covid19 patients fulfilling HLH diagnostic criteria.

Convalescent Serum. The use of convalescent serum is supported by low-quality observational data going back over 100 years. Although never proven effective in well-designed clinical trials, prior reports in patients with Spanish influenza, SARS-CoV-1 and H1N1 all suggest potentially significant reductions in mortality with acceptable safety (14-16). This therapy is more difficult to operationalize, requiring (expedited) FDA approval, collection, processing and testing of neutralizing antibody titers by a licensed blood bank (17), however based on the principles outlined above, its benefit/harm ratio seems to support its use as an investigational therapy in patients with life-threatening COVID-19.

References

1. Booth CM, Tannock IF. Randomised controlled trials and population-based observational research: partners in the evolution of medical evidence. Br J Cancer 2014;110:551-5. [CrossRef] [PubMed]
2. Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). Crit Care Med. 2020 Mar 27. [Epub ahead of print]. [CrossRef] [PubMed]
3. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA. 1993 Dec 1;270(21):2598-601. [CrossRef] [PubMed]
4. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print, 2020 Mar 20]. Int J Antimicrob Agents. 2020;105949. [CrossRef] [PubMed]
5. Wang J., Hajizadeh N, Moore EE, et al. Tissue plasminogen activator (tpa) treatment for COVID‐19 associated acute respiratory distress syndrome (ARDS): a case series. J Thromb Haemost. 2020 (in press). [CrossRef] [PubMed]
6. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-4.[CrossRef] [PubMed]
7. Duan K, Liu B, Cesheng L, Zhang H, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 6. pii: 202004168. [CrossRef] [PubMed]
8. Seyhan, A.A. Lost in translation: the valley of death across preclinical and clinical divide - identification of problems and overcoming obstacles. Transl Med Commun. 2019;4:18. [CrossRef]
9. Dyall J, Gross R, Kindrachuk J, et al. Middle east respiratory syndrome and severe acute respiratory syndrome: current therapeutic options and potential targets for novel therapies. Drugs. 2017;77:1935-66. [CrossRef] [PubMed]
10. Vanasse A, Courteau J, Chiu Y, Cantin A, Leduc R. Hydroxychloroquine: an observational cohort study in primary and secondary prevention of pneumonia in an at-risk population. MedRxIv .April 10, 2020. [CrossRef]
11. Bunce PE, High SM, Nadjafi M, Stanley K, Liles WC, Christian MD. Pandemic H1N1 influenza infection and vascular thrombosis.Clin Infect Dis. 2011 Jan 15;52(2):e14-7.
12. Ranieri VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64. [CrossRef] [PubMed]
13. Yildiz H, Van Den Neste E, Defour JP, Danse E, Yombi JC. Adult haemophagocytic lymphohistiocytosis: a review. QJM. 2020 Jan 14. [Epub ahead of print] [CrossRef] [PubMed]
14. Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis: convalescent blood products for spanish influenza pneumonia: a future H5N1 treatment?. Ann Intern Med. 2006;145:599-609. [CrossRef] [PubMed]
15. Hung IF, To KK, Lee CK, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. [CrossRef] [PubMed]
16. Yeh KM, Chiueh TS, Siu LK, et al. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005 Nov;56(5):919-22. [CrossRef] [PubMed]
17. US Food & Drug Administration. Recommendations for Investigational COVID-19 Convalescent Plasma. April 8, 2020. Available at:https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19-convalescent-plasma (accessed 4/10/20).

Cite as: Raschke RA. Choosing among unproven therapies for the treatment of life-threatening covid-19 infection: a clinician’s opinion from the beside. Southwest J Pulm Crit Care. 2020;20(4):131-4. doi: https://doi.org/10.13175/swjpcc026-20 PDF 

Ultrasound for Critical Care Physicians: The Martian

Jawad Abukhalaf, MD

Michel Boivin, MD

Division of Pulmonary, Critical care and Sleep Medicine,

University of New Mexico School of Medicine

Albuquerque, NM USA

A 54 year old male with a past medical history significant for granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis) and chronic kidney disease presented with hemoptysis and chest pain.

On presentation, he was found to have a 10 cm right middle lobe cavitary lesion and was subsequently treated with high dose steroids, antibiotics and antifungals based on bronchoalveolar lavage results. On day 9 of his hospital stay the patient was found to have bilateral lower extremity deep venous thromboses that were treated with intravenous heparin. On day 11 of his stay, the patient started experiencing lower abdominal pain and hypotension. The patient was resuscitated with saline. Bedside ultrasonography was performed.

Figure 1. Transverse lower abdominal ultrasound in the pelvis.

What does the transverse view of the lower abdomen (just above the symphysis pubis) demonstrate? (Click on the correct answer for an explanation)

1. Abdominal wall hematoma
2. Distended bladder
3. Horseshoe kidney
4. Psoas hematoma

Cite as: Abukhalaf J, Boivin M. Ultrasound for critical care physicians: the martian. Southwest J Pulm Crit Care. 2015;11(4):186-8. doi: http://dx.doi.org/10.13175/swjpcc135-15 PDF 

August 2013 Critical Care Case of the Month: My, That’s a Big One

Andrew Waas, M.D.

Pulmonary Sciences and Critical Care Medicine

University of Colorado Hospital

Denver, Co

History of Present Illness

A 75 year old male presented to the emergency department with complaints of three days of increasing nausea, generalized weakness, and dyspnea on exertion.  He had undergone a radical prostatectomy 13 days prior to presentation from which he was recovering well until the onset of these symptoms. There was no associated chest pain, cough, fevers, chills or weight loss.

PMH, SH, FH

He had a history of hypertension and prostate cancer for which he underwent a recent prostatectomy.

He was born in Colorado and had not traveled recently.  There was no history of tobacco use, he drank ethanol on rare occasions, and did not use any illicit drugs. 

There was no family history of illnesses of which he was aware.

Medications

• Dutasteride 0.5 mg daily
• Telmisartan 40 mg daily

Physical Exam

Blood pressure 142/85, heart rate 108, temperature 36.7 C, respiratory rate 25, saturating 95% on 2L oxygen. 

Generally, he was in no distress, but was slightly tachypneic.  Lungs were clear to auscultation bilaterally and he was tachycardic but regular.  Otherwise, his exam was normal. 

Laboratory

Laboratory evaluation revealed a mild leukocytosis at 13 x 10⁶ cells/mcL with 72% neutrophils and 20% lymphocytes.  His basic metabolic panel (including creatinine) was normal; his liver function tests were likewise normal. 

Chest Radiography

His initial portable chest x-ray is shown in Figure 1.

Figure 1. Initial portable chest x-ray

Which of the following best describes the chest x-ray?

1. Cardiomegaly
2. Cavitating lung mass
3. Multifocal infiltrates
4. All of the above
5. None of the above

Reference as: Waas A. August 2013 critical care case of the month: my, that's a big one. Southwest J Pulm Crit Care. 2013;7(2):66-74. doi: http://dx.doi.org/10.13175/swjpcc096-13 PDF