key: cord-254919-fi3inp67
authors: Molina, Melanie F.; Al Saud, Ahad A.; Al Mulhim, Abdullah A.; Liteplo, Andrew S.; Shokoohi, Hamid
title: Nitrous oxide inhalant abuse and massive pulmonary embolism in COVID-19
date: 2020-05-16
journal: Am J Emerg Med
DOI: 10.1016/j.ajem.2020.05.023
sha: 
doc_id: 254919
cord_uid: fi3inp67

A patient presented to the emergency department with altered mental status and lower extremity weakness in the setting of nitrous oxide inhalant abuse and Coronavirus Disease-2019 (COVID-19) infection. He subsequently developed hypotension and severe hypoxia, found to have a saddle pulmonary embolus (PE) with right heart strain requiring alteplase (tPA).

J o u r n a l P r e -p r o o f Laboratory investigations revealed elevated troponin T-hs of 70 ng/L, creatine kinase of 2,414 U/L, d-dimer of 7,386 ng/mL, lactate dehydrogenase of 424 U/L, procalcitonin of 0.10 ng/mL, lactate of 3.9 mmol/L, ferritin of 587 ug/L, homocysteine of 104.5 umol/L, and low vitamin B12 of <150 pg/mL. Initial venous blood gas revealed a PCO2 of 37 mmHg and a venous pH of 7.4. The patient was tested for COVID-19 using polymerase chain reaction (PCR). Although initial testing was negative, a second test was positive.

Subsequent hematology studies revealed the presence of lupus anticoagulant (LAC).

Electrocardiogram revealed sinus tachycardia with incomplete right bundle branch block.

Lower-limb compression ultrasonography was positive for a nonocclusive deep venous thromboses (DVT) in the bilateral popliteal veins. The left internal jugular vein, which had been cannulated for central access, was also noted to subsequently develop thrombosis (Video 1).

Bedside transthoracic echocardiography (TTE) demonstrated right ventricular dilatation suggestive of right heart strain (Video 2). Given the high concern for pulmonary embolism with the above findings, computed tomography (CT) was performed and analysis of 183 confirmed COVID-19 patients demonstrating an 11.5% death rate. Of the patients who died, 86% had elevated d-dimers of ≥ 3 µg/ml, and 71% of them developed disseminated intravascular coagulation [3] . In a separate study by Zhou et al, they also found that a d-dimer > 1 µg/ml was a predictor of mortality, with an 81% rate of mortality in those having an elevated d-dimer [2] . In a retrospective study of 449 patients with severe COVID-19 pneumonia, 99 patients received heparin. The study showed a decrease in 28-day mortality among the subgroup of patients with a sepsis-induced coagulopathy (SIC) score ≥4 or a d-dimer result that was 6 times the upper limit of normal [4] . Recent guidelines have also suggested that an elevated d-dimer levels are J o u r n a l P r e -p r o o f associated with higher risk of requiring mechanical ventilation, ICU admission, or death [5] .

This patient's coagulopathy may have been secondary to a combination of COVID-19 infection and N2O inhalant abuse leading to hyperhomocysteinemia. It is worth noting that while initial COVID-19 PCR testing was negative, repeat testing was positive, which raises concerns regarding the sensitivity of the COVID-19 PCR. In highly suspicious cases, two tests may be necessary to ensure adequate sensitivity. The role of the previously undetected lupus anticoagulant in the patient's coagulopathy is unclear and may have contributed as well.

Both COVID-19 and nitrous oxide (N2O) could theoretically contribute to a hypercoagulable state. There are case reports illustrating a higher risk of VTE associated with chronic N2O inhalant abuse [6, 7] . Nitrous oxide leads to decreased Vitamin B12 levels with chronic abuse, which leads to increased homocysteinemia by inhibition of methionine synthase [7] . 

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up

Pulmonary embolism and deep vein thrombosis caused by nitrous oxide abuse: A case report

Aortic arch thrombus caused by nitrous oxide abuse