Fwd: Severe Covid-19/A Boy with Seizure and Hypocalcemia

Severe Covid-19/A Boy with Seizure and Hypocalcemia

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Alexandros Sfakianakis SUBSCRIBE

Resident Briefing December 17, 2020

CLINICAL PRACTICE Severe Covid-19 D.A. Berlin, R.M. Gulick, and F.J. Martinez Patients with severe coronavirus disease 2019 (Covid-19) may become critically ill with acute respiratory distress syndrome, which typically begins approximately 1 week after the onset of symptoms.

Clinical Pearls   Who is most at risk for severe Covid-19? Healthy persons of any age may become critically ill with Covid-19. However, age is the most important risk factor for death or critical illness, and the risk increases with each additional decade. People with chronic health conditions such as cardiovascular disease, diabetes mellitus, immunosuppression, and obesity are more likely to become critically ill from Covid-19. Severe disease is more common among men than among women. The risk is also increased among certain racial and ethnic groups such Black and Hispanic persons in the United States. Does dexamethasone have a role in the treatment of patients with severe Covid-19? A large, randomized clinical trial involving more than 6400 hospitalized patients with Covid-19 showed that dexamethasone significantly reduced 30-day mortality (17% reduction); benefit was limited to patients who required oxygen supplementation and appeared greater in patients receiving mechanical ventilation. Consequently, dexamethasone (or potentially other glucocorticoids) is now considered the standard of care for patients with severe Covid-19.

Morning Report Questions   Has remdesivir been shown to reduce mortality in patients with severe Covid-19? Data from a randomized, placebo-controlled trial involving more than 1000 patients with severe Covid-19 showed that the antiviral agent remdesivir reduced time to clinical recovery; the benefit appeared greatest in patients who were receiving supplemental oxygen but were not intubated. The 29-day mortality in that trial was 11.4% with remdesivir and 15.2% with placebo (hazard ratio for death, 0.73; 95% confidence interval, 0.52 to 1.03). These data support the Food and Drug Administration (FDA) approval of remdesivir for the treatment of hospitalized patients with Covid-19 in October 2020. Recent preliminary results of a large, multinational, open-label, randomized trial did not show a reduction in in-hospital mortality with use of remdesivir. The combination of dexamethasone and remdesivir is increasingly used clinically, but its benefit has not been shown in randomized clinical trials. What are some of the areas of uncertainty regarding the management of severe Covid-19? It is unclear whether Covid-19 is associated with a distinct form of acute respiratory distress syndrome (ARDS) that would benefit from a new strategy of mechanical ventilation. However, most autopsies performed on patients with severe Covid-19 reveal the presence of diffuse alveolar damage, which is the hallmark of ARDS. If there are no contraindications, patients should receive standard thromboprophylaxis (e.g., subcutaneous low-molecular-weight heparin). Some case series of patients with severe Covid-19 have shown clinically significant thrombosis despite the use of thromboprophylaxis. However, the benefits and risks of the routine use of more intense prophylactic anticoagulation in patients are unknown. Having awake patients turn to the prone position while they breathe high concentrations of supplemental oxygen may improve oxygenation in patients with severe Covid-19. This approach is supported by data from prospective cohorts describing its use in nonintubated patients with severe hypoxemia. However, whether prone positioning can prevent intubation in patients with severe Covid-19 is unclear.

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL Case 39-2020: A 29-Month-Old Boy with Seizure and Hypocalcemia Y.V. Virkud and Others Childhood causes of vitamin D deficiency include obesity, malabsorption, and low sun exposure, as well as decreased nutritional intake.

Clinical Pearls   Is nutritional rickets rare in high-income countries? Nutritional rickets is often thought of as a historical relic — the discovery of vitamin D and the implementation of supplementation and food-fortification strategies in the early 20th century sharply decreased the prevalence of what had been a common disease, particularly in urban centers. However, the incidence of vitamin D deficiency appears to be rising in high-income countries, and the prevalence is persistently high in low- and middle-income countries. What are some of the risk factors for nutritional rickets? In a 2015 case-finding survey of Canadian pediatricians, risk factors for nutritional rickets included demographic characteristics (recent immigration), physiological features (skin melanin content, food allergies, feeding challenges associated with prematurity, developmental delay, and maternal vitamin D deficiency), and aspects of diet (lack of vitamin D supplementation and dietary restrictions) and behavior (lack of sun exposure).

Morning Report Questions   How is severe, asymptomatic hypocalcemia that is associated with vitamin D deficiency managed? Patients who have profound hypocalcemia that is complicated by severe symptoms (seizure or tetany) receive intravenous calcium to rapidly restore normocalcemia. Unfortunately, there is limited evidence from randomized, controlled trials to guide subsequent repletion of vitamin D stores. In 2016, an international panel developed recommendations for the prevention and management of nutritional rickets. The panel recommended a daily dosing strategy to minimize the risk of hypercalcemia but also recognized that a single high dose may be more feasible in some circumstances and thus offered dosing recommendations for this strategy, as well. Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) have similar efficacy when given in daily doses; some evidence suggests that vitamin D3 has better efficacy than vitamin D2 when given in a single dose. In addition, adequate calcium intake, through dietary calcium or supplementation, is necessary to support bone remineralization. Adequate calcium provision is also necessary to prevent hungry bone syndrome, a condition in which there is paradoxical worsening of hypocalcemia after initiation of vitamin D therapy. This condition is thought to be due to rapid bone-mineral uptake by the demineralized skeleton, and management may require very high doses of calcium, as well as occasional therapeutic doses of calcitriol (1,25-dihydroxyvitamin D), the active form of vitamin D. How quickly do the radiographic changes of nutritional rickets improve with adequate treatment? The response to treatment can be monitored by obtaining blood levels of calcium, phosphate, 25-hydroxyvitamin D, parathyroid hormone, and alkaline phosphatase and the urinary calcium:creatinine ratio approximately 4 weeks after the initiation of treatment and at monthly intervals until resolution of laboratory abnormalities. In most children with nutritional rickets, laboratory values will typically normalize and radiographs will show substantial healing after 3 months of adequate treatment, although some patients may require continued treatment.

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Question of the Week Which one of the following additional tests is most appropriate at this time for an asymptomatic 65-year-old white man who has mild elevations in serum aminotransferases, lipids, and fasting glucose; a normal level of alkaline phosphatase; no history of alcohol use disorder; and negative testing for hepatitis B and C viruses? Antimitochondrial antibodies Serum ceruloplasmin Antinuclear antibodies Serum ferritin and transferrin saturation Liver biopsy

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