Adverse Events in Coronavirus Disease Patients Management: A Pictorial Essay

Bleeding complications

Bleeding is the principal adverse event of treatment with any anticoagulants which can be non-major or major [Figure 1], potentially life threatening and result in long-term morbidity.^[4]

Close

Figure 1:

Axial view of the CT angiogram showing a spontaneous heterogeneous 18.7 × 8.8 × 10.8 cm right iliopsoas hematoma with two areas of active arterial bleeding (white arrows) (a and b), possibly originating from the ipsilateral lumbar artery.

Export to PPT

Recent studies have shown that prophylactic doses of low-molecular-weight heparin (LMWH) and unfractionated heparin are associated with a reduced 28-day mortality in sepsis-induced coagulopathy in COVID-19 patients.^[1] The precise dosages, types of anticoagulant, and their routes of administration are yet to be defined to ensure effective and safe treatments.

Spontaneous iliopsoas hematoma [Figure 1]

A 59-year-old man hospitalized for a COVID-19 pneumonia on invasive mechanical ventilation for 11 days, in treatment with hydroxychloroquine (hydroxychloroquine 200 mg) twice daily, anakinra (anakinra 100 mg) 3 times daily, and enoxaparin sodium (enoxaparin sodium 6000 IU) twice daily. Two days after being extubated he suffered an episode of hypotension. The patient was hemodynamically unstable, and blood analysis showed a hemoglobin value of 5.5 g/dl so a computer tomography (CT) angiogram was requested

This showed a spontaneous heterogeneous 18.7 × 8.8 × 10.8 cm right iliopsoas hematoma with two areas of active arterial bleeding (white arrows) [Figure 1a and b], possibly originating from the ipsilateral lumbar artery.

Barotrauma

Every patient on positive pressure ventilation risks developing pulmonary barotrauma. This is usually due to alveolar rupture, which results in leakage of air in extra-alveolar spaces which can in severe cases result in pneumothorax [Figure 2], pneumomediastinum [Figure 3], subcutaneous emphysema, and rarely pneumoperitoneum [Figure 4]. In 2004, a prospective cohort study conducted in 361 ICU on 5184 patients estimated that incidence of barotrauma was 2.9% in general, with a different prevalence depending on the clinical indication of ventilation. The prevalence in ARDS patients was 6.5%, showing that ARDS may predispose to pulmonary barotrauma. Most patients with ARDS due to COVID-19 require intubation and mechanical ventilation. Therefore, the risk of barotrauma for these patients is high.^[5]

Close

Figure 2:

Non-contrast computer tomography was carried out showing a massive subcutaneous emphysema (dashed black arrows), extending from the thoracic outlet and the axillae to the laterocervical areas, surrounding the rhomboids muscles posteriorly. It also demonstrated compressive pneumomediastinum (black arrow heads), located predominantly in the anterior and superior mediastinum, and a right pneumothorax (black arrows), located in the anterolateral region of the apical segment of the right superior lobe (a and b).

Export to PPT

Close

Figure 3:

Axial view of a non contrast CT scan showing progressive pneumomediastinum (white arrows). This completely resolved after CPAP suspension.

Export to PPT

Close

Figure 4:

Bedside Chest-XR showing a massive subcutaneous emphysema and a small quantity of subphrenic air (a) (white arrows). Axial view of CT-scan demonstrating an extensive compressive pneumomediastinum (black arrow) (b) and pneumoperitoneum located predominantly under the anterior wall, around the liver and spleen (c and d).

Export to PPT

Pneumothorax, pneumomediastinum, and subcutaneous emphysema [Figure 2]

A 48-year-old man was admitted with worsening COVID-19 pneumonia. The patient was initially on Venturi mask but, CPAP ventilation had to be commenced for 5 days.

The patient was initially on Venturi mask, due to the worsening of his pneumonia, CPAP ventilation was started and kept for 5 days, eventually, the ventilation support was switched into invasive mechanical ventilation. He developed extensive subcutaneous emphysema and a non-contrast CT was carried out which showed massive subcutaneous emphysema (dashed black arrows), extending from the thoracic outlet and the axillae to the laterocervical areas, surrounding the rhomboids muscles posteriorly.

It also demonstrated compressive pneumomediastinum (black arrow heads), located predominantly in the anterior and superior mediastinum, and a right pneumothorax (black arrows), located in the anterolateral region of the apical segment of the right superior lobe [Figure 2a and b].

Pneumomediastinum [Figure 3]

A 50-year-old female patient underwent CPAP support for persistent hypoxia but developed a progressive pneumomediastinum (white arrows). This completely resolved after CPAP suspension.

Pneumoperitoneum [Figure 4]

A 65-year-old man was admitted for COVID-19 pneumonia. The patient underwent early intubation invasive mechanical ventilation due to fast worsening of the oxygen saturation despite CPAP ventilation with high oxygen flow. After the finding of subcutaneous emphysema, a CXR confirmed massive subcutaneous emphysema and a small quantity of subphrenic air [Figure 4a] (white arrows).

In addition, the CT scan showed an extensive compressive pneumomediastinum (black arrow) [Figure 4b] and pneumoperitoneum located predominantly under the anterior wall, around the liver and spleen [Figure 4c and d]. There is also gas within an abdominal wall hernia. The absence of rising WBC and CRP without signs of peritoneal reaction suggested that this was related to ventilation. Conservative management resulted in complete, spontaneous resolution after 10 days after stopping ventilation.

Thromboembolic events

Although most patients with COVID-19 infections will have a mild disease, some progress to respiratory distress, sepsis, and septic shock predisposing patients to thrombotic disease, both in the venous and arterial circulations. This is the result of severe inflammation, platelet activation, endothelial dysfunction, and stasis. Many authors have reported derangements in coagulation function in severely infected patients including elevated D-dimer, fibrin/fibrinogen degradation products, and fibrinogen levels, resembling coagulopathy.^[6] A significant correlation between elevated D-dimer levels on admission and in-hospital COVID-19 mortality has been shown by different authors.^[7,8] Pulmonary embolism [Figure 5] is considered one of the main reasons for the rapid clinical worsening of their lung function and sudden death. Prophylactic LMWH doses are usually given in many countries with the COVID pandemic to mitigate this risk of thromboembolism. However, the most appropriate type of anticoagulation, the dosage levels, and frequency of administration are not clearly understood in this cohort of patients.

Close

Figure 5:

A contrast-enhanced CT of the chest was undertaken, confirming multiple filling defects of the middle lobar artery on both sides (a) indicating acute pulmonary embolism (white arrows). Axial view of CT scan showing with lung window bilateral peripheral ground glass opacities and consolidations in the inferior lobes (b) (black arrows).

Export to PPT

Pulmonary thromboembolism [Figure 5]

This is a 69-year-old COVID-positive man admitted to a subacute ICU for sudden worsening of his respiratory symptoms. He had been managed with a Venturi mask before a sudden loss of the oxygen saturation and his D-dimer values were elevated to 2231 ng/mL.

A contrast-enhanced CT of the chest was undertaken. This confirmed multiple filling defects of the middle lobar artery on both sides [Figure 5a] indicating acute pulmonary embolism (white arrows). – Axial view of CT scan showing with lung window bilateral peripheral ground glass opacities and consolidations in the inferior lobes [Figure 5b] (black arrows).

Brain ischemia/infarction [Figure 6]

Close

Figure 6:

A brain CT and then magnetic resonance imaging scan were undertaken to rule out acute ischemic stroke or viral encephalitis. The axial CT scans showed mild parietal subcortical hypodensity (a) confirmed on the subsequent MRI (b and c) scan, showing multiple linear areas of subcortical restricted diffusion (DWI) in the same territory and hypointensity on correspondent ADC maps (b and c) (white arrows). An acute ischemic stroke was diagnosed.

Export to PPT

Respiratory-related infection is a recognized independent risk factor for acute cerebrovascular disease.^[9,10] The cytokine storm during the infection of COVID-19 can cause coagulopathy in critically ill patients with elevated levels of D-dimer and severe platelet reduction, may expose these patients to sudden acute cerebrovascular events.^[11] A 76-year- old man was admitted to the emergency department with a high fever of 39.5° and sudden worsening of his dyspnea. Blood gases showed a pH of 7.5 with a pCO2 31 and pO2 58 and he was commenced on hi-flow oxygen on a Venturi mask. After 2 days, the patient showed a sudden onset of confusion and slurred speech. On neurologic examination, there was no focal neurology. Laboratory studies showed lymphopenia and eosinophilic granulocytopenia with two throat swab samples, one negative and one positive for SARS- CoV-2 nucleic acid. A brain CT and then magnetic resonance imaging scan were undertaken to rule out acute ischemic stroke or viral encephalitis.

The axial CT scans showed mild parietal subcortical hypodensity [Figure 6a] confirmed on the subsequent MRI [Figure 6b and c] scan, showing multiple linear areas of subcortical restricted diffusion (DWI) in the same territory and hypointensity on correspondent ADC maps [Figure 6b and c] (white arrows). An acute ischemic stroke was diagnosed and clopidogrel (75 mg) was commenced orally. After 25 days of treatment, the patient was discharged without neurological impairment and near- normal speech.