Ionised hypocalcaemia in emergency and acute medicine.

Acute hypocalcaemia can be life-threatening and must be diagnosed promptly. The gold-standard investigation is ionised calcium, which is measured on most blood gas analysers. Total calcium measurements are inaccurate in severe depletion even if 'corrected' or 'adjusted' for albumin. We present an illustrative case of a woman in her 30s with symptomatic hypocalcaemia and a very low ionised calcium on VBG analysis. Emergency calcium replacement was delayed due to a falsely reassuring corrected calcium result. Our discussion includes a systematic literature review on the use of ionised calcium in emergency and acute medical settings. We suggest cognitive biases that may explain clinical over-reliance on corrected calcium, and call for the inclusion of ionised calcium values in major treatment guidelines for acute hypocalcaemia.

Retrospective case-control study to evaluate hypocalcaemia as a distinguishing feature of COVID-19 compared with other infective pneumonias and its association with disease severity.

OBJECTIVES: To investigate whether calcium derangement was a specific feature of COVID-19 that distinguishes it from other infective pneumonias, and its association with disease severity. DESIGN: A retrospective observational case-control study looking at serum calcium on adult patients with COVID-19, and community-acquired pneumonia (CAP) or viral pneumonia (VP). SETTING: A district general hospital on the outskirts of London, UK. PARTICIPANTS: 506 patients with COVID-19, 95 patients with CAP and 152 patients with VP. OUTCOME MEASURES: Baseline characteristics including hypocalcaemia in patients with COVID-19, CAP and VP were detailed. For patients with COVID-19, the impact of an abnormally low calcium level on the maximum level of hospital care, as a surrogate of COVID-19 severity, was evaluated. The primary outcome of maximal level of care was based on the WHO Clinical Progression Scale for COVID-19. RESULTS: Hypocalcaemia was a specific and common clinical finding in patients with COVID-19 that distinguished it from other respiratory infections. Calcium levels were significantly lower in those with severe disease. Ordinal regression of risk estimates for categorised care levels showed that baseline hypocalcaemia was incrementally associated with OR of 2.33 (95% CI 1.5 to 3.61) for higher level of care, superior to other variables that have previously been shown to predict worse COVID-19 outcome. Serial calcium levels showed improvement by days 7-9 of admission, only in survivors of COVID-19. CONCLUSION: Hypocalcaemia is specific to COVID-19 and may help distinguish it from other infective pneumonias. Hypocalcaemia may independently predict severe disease and warrants detailed prognostic investigation. The fact that decreased serum calcium is observed at the time of clinical presentation in COVID-19, but not other infective pneumonias, suggests that its early derangement is pathophysiological and may influence the deleterious evolution of this disease. TRIAL REGISTRATION NUMBER: 20/HRA/2344.

Predicting ionized hypocalcemia: External validation of an ionized calcium prediction model in patients with COVID-19 and renal failure.

BACKGROUND: Ionized hypocalcemia is common in critically ill patients with COVID-19 and is associated with adverse outcomes. We previously developed a linear model that estimates ionized calcium (ICa) by adjusting total calcium (TCa) for the three components of the anion gap and albumin. On internal validation, it outperformed the popular method that corrects TCa for albumin alone (cTCa) in diagnosing low ICa. In this study, we sought to externally validate our ICa model in hospitalized COVID-19 positive patients. METHODS: We retrospectively studied all 200 patients with COVID-19 who were admitted to the State University of New York Downstate Medical Center between March 11th and April 30th 2020 and referred to the nephrology service for renal failure, and who had ICa measured on a venous blood gas within 25 min of a comprehensive metabolic panel. We compared the performance of the ICa model and cTCa in diagnosing low ICa by ROC analysis, and also examined the accuracy of the absolute values predicted by the two methods relative to measured ICa. RESULTS: On ROC analysis, the ICa model was better than cTCa (area under ROC curve: 0.872 [0.025] vs. 0.835 [0.028]; p = 0.045). The ICa model estimated ICa accurately, but the cTCa method seemed to overcorrect TCa, as a substantial number of patients with clearly normal cTCa values had low ICa. CONCLUSIONS: In an external validation cohort, the ICa model estimated ICa accurately and was better than cTCa in the diagnosis of low ICa. This finding can be useful in guiding direct ICa testing.

Hypocalcemia is associated with severe COVID-19: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Hypocalcemia is commonly in critically ill patients and studies have shown that hypocalcemia is prevalent in patients with COVID-19. This meta-analysis aimed to evaluate the prognostic performance of hypocalcemia in patients with coronavirus disease 2019 (COVID-19). METHODS: We performed a systematic literature search on PubMed, Scopus, and Embase with keywords "SARS-CoV-2″ OR″COVID-19″ OR ″2019-nCoV" AND "hypocalcemia" up until 10 December 2020. The key exposure was hypocalcemia, defined as serum calcium below study-defined cut-off points. The main outcome was poor outcome, which was a composite of mortality and severity. The effect estimate of the main outcome was reported as odds ratio (OR) and its 95% confidence interval (95% CI). We also generate sensitivity, specificity, positive and negative likelihood ratio (PLR & NLR), diagnostic odds ratio (DOR), and area under curve (AUC). RESULTS: There are 2032 patients from 7 studies included in this systematic review and meta-analysis. The incidence of poor outcome in this study was 26%. Serum calcium was lower in patients with poor outcome (mean difference -0.173 mmol/L [-0.259, -0.087], p < 0.001; I2: 31.3%). Hypocalcemia was associated with poor outcome (OR 3.19 [2.02, 5.06], p < 0.001; I2: 32.86%); with sensitivity of 0.74 [0.53, 0.88], specificity of 0.54 [0.29, 0.77], PLR of 1.6 [1.1, 2.3], NLR of 0.49 [0.35, 0.66], DOR of 3 [2, 5], and AUC of 0.70 [0.66, 0.74]. In this pooled analysis, the post-test probability was 36% in patients with hypocalcemia and 15% in patients without hypocalcemia. CONCLUSION: Hypocalcemia was associated with poor outcome in COVID-19 patients. PROSPERO ID: CRD42020225506.