Hyperkalaemia in the emergency department: Epidemiology, management and monitoring of treatment outcomes.

OBJECTIVE: To describe the epidemiology, treatment and monitoring of treatment outcomes of patients presenting to the ED with hyperkalaemia. METHODS: We undertook a retrospective observational study in a mixed adult/paediatric ED over five 3-month periods. Consecutive patients were included if they had an initial serum or blood gas potassium ≥6.0 mmol/L. Patients were excluded if their principal diagnosis was diabetic ketoacidosis, their blood sample was haemolysed or the blood gas result was inconsistent with a subsequent serum potassium. Data were extracted from electronic medical records and two senior emergency registrars independently assessed available ECGs. Moderate and severe hyperkalaemia were potassium 6.0-6.4 and ≥6.5 mmol/L, respectively. RESULTS: Overall, 392 patients were included (mean age 73.7 years, triage category 1 or 2 28.3%, admitted 91.3%). Three hundred and twenty-one (81.9%, 95% confidence interval [CI] 77.6-85.5%) patients took one or more medications that predispose to hyperkalaemia and 335 (85.5%, 95% CI 81.5-88.7%) had one or more predisposing comorbidities. Two hundred and seventy-one (69.1%, 95% CI 64.3-73.6%) patients had moderately severe and 121 (30.9%, 95% CI 26.4-35.7%) had severe hyperkalaemia. Two hundred and fifty-nine (66.1%, 95% CI 61.1-70.7%) patients were administered at least one medication in ED to lower the potassium concentration and 51 (13.0%, 95% CI 9.9-16.8%) were dialysed. One hundred and eighty-seven patients received intravenous insulin: 40 (21.4%) had documented biochemical hypoglycaemia, but 45 (24.1%) had no post-insulin blood glucose level documented. Hyperkalaemia-associated ECG changes were uncommon. CONCLUSION: Most ED patients with hyperkalaemia have identifiable clinical and medication-related risk factors. Variations in care were widespread and monitoring for iatrogenic adverse events was suboptimal.

An Investigation of Sodium Fusidate and Recombinant Cytochrome P450 Enzymes Inhibition In-Vitro.

BACKGROUND: Sodium fusidate (fusidic acid) is an antimicrobial agent that is used in the treatment of staphylococcal and streptococcal infections. Several case reports have noted a drug interaction between sodium fusidate and CYP3A4 metabolised statins, leading to statin toxicity. It is unclear whether sodium fusidate has the potential to cause interactions with other cytochrome P450 enzymes. OBJECTIVE: To investigate the effects of sodium fusidate on recombinant cytochrome P450 enzymes (1A2, 2C9, 2C19, 2D6 and 3A4) in-vitro. METHODS: A range of sodium fusidate concentrations (0.1µM, 1µM, 10µM, 100µM, 300µM, 1000µM and 10000µM) were tested to examine its activity on rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 and rCYP3A4 using a luminescent assay with a luciferin substrate. RESULTS: Sodium fusidate inhibited all enzymes at tested concentrations which are relevant to those likely to be achieved in clinical practice. Further, sodium fusidate was found to be a time-dependent inhibitor of all the tested isoenzymes, with the exception of rCYP2C9. CONCLUSION: These findings suggest that there is a potential for sodium fusidate to cause drug interactions when used with other agents that are substrates for rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 or rCYP3A4. Understanding the basis of this potential drug interaction will assist in safer use of sodium fusidate in clinical practice.