Diabetic ketoacidosis, cerebral venous sinus thrombosis and fulminant cerebral oedema in COVID-19 infection complicated by Klebsiella pneumoniae infection

Background

Both thromboembolic events and neurological manifestations are frequent in COVID-19 infection and portend a poor prognosis. However, the incidence of cerebral venous sinus thrombosis (CVST) in the setting of COVID-19 is rare.

Case presentation

We present the case of a woman in her 30s who was admitted to our intensive care unit (ICU) for diabetic ketoacidosis (DKA) in the setting of newly diagnosed diabetes mellitus type II, altered mental status and COVID-19). The patient was unable to provide written consent due to her presentation and critical illness.

Her spouse found her confused and agitated for an unknown period before he brought her to an outside emergency department. Her spouse said the patient reportedly had a headache the day prior but denied any history of injury or trauma. On examination in the emergency room, heart rate was 118 bpm, respiratory rate was 43 bpm and Glasgow Coma Scale was 10 without any focal neurological deficit. On laboratory testing, serum glucose was 628 mg/dL (70–140 mg/dL), beta-hydroxybutyrate was 2.3 mmol/L (0–0.5 mmol/L), white cell count was 12 300×10⁹/L (3400–9600×10⁹/L), platelet count 65×10⁹/ L (157–371×10⁹/ L), pH 7.04 (7.35–7.45), bicarbonate 8 mmol/L (22–26 mmol/L), anion gap 26 (7–15), D-dimer 2264 ng/mL (<500 ng/mL), fibrinogen >1000 mg/dL (200–393 mg/dL). Lactate was 1.1 (0.5–2.2 mmol/L), troponin was 6 ng/L (<10 ng/L), then <6 ng/L after 2 hours. Pregnancy test with quantitative human chorionic gonadotropin was negative at 0.7 IU/L (<5 IU/L). Plasma ethanol, acetaminophen and salicylate levels were negative. Serum ethanol, acetone, isopropanol and methanol levels were negative. Urine drug screen and volatile screen were negative. Chest radiograph showed patchy bilateral multifocal pulmonary opacity consistent with viral or bacterial pneumonia. SARS-CoV2 PCR swab came back positive. Head CT without intravenous contrast showed no intracranial abnormality (figure 1). She was given 1 mg of intravenous lorazepam for agitation, intubated for airway protection and sedated with ketamine. A nurse-driven titratable insulin infusion with hourly glucose checks, sodium bicarbonate was initiated, and she received 4 L of normal saline for DKA. She was transferred to our institution directly to the ICU.

On arrival in the ICU, she remained intubated, ventilated and haemodynamically stable. On arterial blood gas, pH was 7.15, PaCO₂ 30 mm Hg (32–45 mm Hg), PaO2 91 mm Hg (83–108 mm Hg) and bicarbonate 10 mmol/L. Calculated PaO2:FiO₂ ratio was 227.5 mm Hg. She remained agitated and was kept sedated with fentanyl and propofol instead of ketamine for ventilator synchrony. Insulin infusion was continued. An arterial line and central line were placed. Chest radiograph showed again bilateral patchy airspace opacities consistent with acute respiratory distress syndrome. She received remdesivir, dexamethasone and tocilizumab for presumed severe COVID-19 pneumonia after emergent consultation with infectious diseases service. She was given deep vein thrombosis prophylaxis with enoxaparin 30 mg subcutaneously (patient’s weight was 43.5 kg, body mass index was 17.65 kg/m²).

Over the next 4 hours, she became progressively hypertensive reaching a blood pressure of 176/101 mm Hg for which she received 10 mg of labetalol intravenously. She stabilised for a few hours before she suddenly developed decerebrate posturing, with fixed and dilated pupils, no corneal or gag reflex and no spontaneous ventilation. Then she became hypotensive and was started on norepinephrine. She also developed polyuria and hypernatremia, with a sodium level of 163 mmol/L (135–145 mmol/L) consistent with diabetes insipidus for which she received desmopressin (four doses of 2 μg over 12 hours), and dextrose 5% water infusion which was initiated at 50 mL/hour, then increased to 125 mL/hour based on sodium levels and increased urine output. An emergent repeat head CT revealed diffuse cerebral oedema without herniation or haemorrhage. Neurology was consulted emergently. Sedation was stopped and mannitol was given. Meanwhile, her blood cultures came back positive for Klebsiella pneumoniae for which she was started on piperacillin–tazobactam.

Brain magnetic resonance venography (figure 2) was performed a few hours later and demonstrated diffuse cerebral oedema with marked attenuation of arterial flow voids at the skull base and non-opacification of the internal cerebral veins, vein of Galen and the dural venous sinuses. She was started on high-intensity heparin. Antiphospholipid serologies were normal (phospholipid Ab IgM 11.1, IgG <9.4 GPL). COVID-19 IgG antibodies came back positive and consistent with late COVID-19 infection. Remdesivir was discontinued, dexamethasone was maintained, and antibiotics were broadened to vancomycin and cefepime.

Head CT angiography (figure 3) the next day revealed worsening diffuse cerebral oedema with signs concerning for increased intracranial pressure, new duret haemorrhages of the midbrain and upper pons, non-opacification of the bilateral supraclinoid internal carotid and vertebral arteries and similar marked attenuation and thrombosis of the deep venous system and dural venous sinuses. She was declared brain dead soon thereafter.