key: cord-0727938-f2t3o9au
authors: Karfunkle, Benjamin; Gill, Joseph; Shirey, Setphanie; Gordon, Richard
title: COVID-19 ARDS and Pulmonary Embolism - A Case Report of Nebulized Nitroglycerin and Systemic Thrombolysis for Right Ventricular Failure
date: 2021-07-09
journal: J Emerg Med
DOI: 10.1016/j.jemermed.2021.07.014
sha: c7e25e80ac0f2078f6cd5b3c7e0a06898181dcb8
doc_id: 727938
cord_uid: f2t3o9au

Background: Acute respiratory compromise due to complications of COVID-19, such as acute respiratory distress syndrome (ARDS) or thromboembolic disease, is a complex syndrome with unique challenges in treatment. Management often requires time and intensive care through a multi-professional, multi-specialty approach. Initial management is particularly challenging within the limited resource environment of the emergency department (ED). The emergency physician's toolbox of treatments with reasonably rapid onset remains limited to respiratory support, prone positioning, steroids, and anticoagulation. Case Report: Here we present a case of a patient with COVID-19 complicated by ARDS and bilateral pulmonary emboli with severe right ventricular dysfunction and systemic hypotension treated with nebulized nitroglycerin and systemic thrombolytic therapy in the ED. Serial evaluation of right ventricular function using point of care ultrasound over the next two hours showed improvement of function with both agents as well as improvement in the patient's respiratory rate and work of breathing. Why Should an Emergency Physician Be Aware of This?: This case describes a novel use of a widely available medication for patients suffering from COVID-19 induced right ventricular dysfunction. Nebulized nitroglycerin may be an option to improve right ventricular function when other inhaled pulmonary vasodilators are not available in the initial ED setting.

syndrome with unique challenges in treatment. Management often requires time and 24 intensive care through a multi-professional, multi-specialty approach. Initial 25 management is particularly challenging within the limited resource environment of the 26 emergency department (ED). The emergency physician's toolbox of treatments with 27 reasonably rapid onset remains limited to respiratory support, prone positioning, 28 steroids, and anticoagulation. 29

Here we present a case of a patient with COVID-19 complicated by ARDS and bilateral 31 pulmonary emboli with severe right ventricular dysfunction and systemic hypotension 32 treated with nebulized nitroglycerin and systemic thrombolytic therapy in the ED. 33

Serial evaluation of right ventricular function using point of care ultrasound over the 34 next two hours showed improvement of function with both agents as well as 35 improvement in the patient's respiratory rate and work of breathing. 36

This case describes a novel use of a widely available medication for patients suffering 38 from COVID-19 induced right ventricular dysfunction. Nebulized nitroglycerin may be 39 an option to improve right ventricular function when other inhaled pulmonary 40 vasodilators are not available in the initial ED setting.

The respiratory compromise caused by COVID-19 pneumonia can be profound, and 52 complicated by severe hypoxia, thromboembolic disease, and Acute Respiratory 53

Distress Syndrome (ARDS). Treatment in the acute setting consists of respiratory 54 support, corticosteroids, and anticoagulation. The pathogenesis of severe respiratory 55 compromise in COVID-19 is at least partly related to thrombotic events in the 56 pulmonary microvasculature(1). Pulmonary hypertension (PH) and right ventricular 57 dysfunction (RVD) have been demonstrated to correlate with more severe COVID-19 58 symptoms and worse in-hospital clinical outcomes (2) . RVD with some benefit in the ED setting(5). Inhaled nitric oxide (iNO) is being explored as a 71 potential treatment for ARDS caused by COVID-19 and has been shown in small 72 studies to improve arterial oxygenation(6,7). 73

The logistics of administering inhaled or intravenous pulmonary vasodilators is 75 cumbersome and often not possible outside of an intensive care unit. Nitroglycerin is 76 widely available in most EDs. Inhaled nitroglycerin (iNTG) has been studied for 77 treatment of pulmonary hypertension as it acts rapidly as a pulmonary vasodilator via nitric oxide donation mechanisms when applied to the pulmonary vasculature(8). In the 79 perioperative setting iNTG has been shown to be a potent pulmonary vasodilator 80 without causing systemic vasodilation (9). It has been discussed as a treatment for 81 massive PE outside of the setting of COVID-19, but has not been systematically 82 studied. Given the patient's progressive hypotension, further treatment modalities were 131 explored. No crystalloid volume resuscitation was administered. Catheter directed 132 fibrinolytic therapy was considered with a multidisciplinary PE team, but the patient 133 was ultimately felt to be too unstable. Vasopressor support was held at bedside ready to 134 deploy but was ultimately never given as the patient's mean arterial pressure did not 135 persist under 65 mmHg despite this significant drop in blood pressure 136

The patient was given iNTG 2.4mg (200 mcg/mL) via inline closed-circuit nebulizer 138 over the next 60 minutes. Minutes after initiating iNTG, RVD was reevaluated and 139 TAPSE improved. Serial measurements are shown in Figure 3 . Systemic thrombolytic 140

infusion was started at the third data point, 12 minutes after iNTG. Alteplase 100 mg 141 was given over two hours without a bolus dose. The first dose of iNTG was completed 142 after 60 minutes. The next evaluation of right ventricular function 13 minutes after the 143 iNTG treatment was completed showed recurrent RVD. Treatment with iNTG was 144 resumed and 10 minutes after resumption, RVD was again improved -see the final data 145 point in Figure 3 . hypertension. The patient's PH and vital sign abnormalities were due in part to COVID-178 19 induced ARDS and in part due to acute PE. At the time, the treating physicians felt 179 that the patient's hemodynamic instability and echo findings were primarily related to 180 ARDS rather than segmental PEs. However, we also recognized COVID-19 induced 181 ARDS may be associated with overwhelming micro thromboemboli (1) and as such the 182 decision was made to administer full dose alteplase 100 mg over two hours without 183 bolus dosing in accordance with FDA guidelines for the management of PE (12). 184

Thrombolysis has been retrospectively reviewed in severe COVID-19 pneumonia with 185 concern for PE by Arachchillage et al who found significant improvement in PaO2/FiO2 186 ratios 24 hours after thrombolytic therapy infusion (11). Dosing for thrombolytic 187 therapies specific to COVID-19 induced acute PH have yet to be determined. 188

Vasopresor support was held at bedside ready to deploy, but was ultimately never used 189 as the patient's mean arterial pressure did not persist under 65 mmHg despite his 190 significant drop in blood pressure. 

Anticoagulant treatment in COVID-19: a narrative review

Echocardiographic features of cardiac injury related to COVID-19 and 248 their prognostic value: a systematic review

Recommendations for cardiac chamber quantification by echocardiography in 252 adults: an update from the American society of echocardiography and the 253

European association of cardiovascular imaging

Responsiveness of inhaled epoprostenol in respiratory 256 failure due to COVID-19

Randomized 258 trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial

Effects of inhaled nitric oxide in COVID-19-induced ARDS -is it worthwhile? Acta 262

Implication of inhaled nitric 265 oxide for the treatment of critically ill COVID-19 patients with pulmonary 266 hypertension

Efficiency of aerosolized nitric oxide donor drugs to achieve sustained 269 pulmonary vasodilation

Acute 271 hemodynamic effects of inhaled nitroglycerine, intravenous nitroglycerine, and 272 their combination with intravenous dobutamine in patients with secondary 273 pulmonary hypertension

SpO2/FiO2 Ratio on hospital admission is an 275 indicator of early acute respiratory distress syndrome development among patients 276 at risk

Thrombolysis restores 278 perfusion in COVID-19 hypoxia

Reduced dose 284 bolus alteplase vs conventional alteplase infusion for pulmonary embolism

approximately 6 hours after completion of the 2 hour infusion (13). Therefore the 215 majority of the improvement seen in this patient's RVD may be attributed to iNTG 216 rather than thrombolytic therapy. The authors declare that they have no known competing financial interests or personal 232 relationships that could have appeared to influence the work reported in this paper.