QT prolongation associated with hydroxychloroquine and protease inhibitors in COVID-19.

WHAT IS KNOWN AND OBJECTIVE: Hydroxychloroquine and protease inhibitors were widely used as off-label treatment options for COVID-19 but the safety data of these drugs among the COVID-19 population are largely lacking. Drug-induced QTc prolongation is a known adverse reaction of hydroxychloroquine, especially during chronic treatment. However, when administered concurrently with potential pro-arrhythmic drugs such as protease inhibitors, the risk of QTc prolongation imposed on these patients is not known. We aim to investigate the incidence of QTc prolongation events and potential factors associated with its occurrence in COVID-19 population. METHODS: We included 446 SARS-CoV-2 RT-PCR-positive patients taking at least one treatment drug for COVID-19 within a period of one month (March-April 2020). In addition to COVID-19-related treatment (HCQ/PI), concomitant drugs with risks of QTc prolongation were considered. We defined QTc prolongation as QTc interval of ≥470 ms in postpubertal males, and ≥480 ms in postpubertal females. RESULTS AND DISCUSSION: QTc prolongation events occurred in 28/446 (6.3%) patients with an incidence rate of 1 case per 100 person-days. A total of 26/28 (93%) patients who had prolonged QTc intervals received at least two pro-QT drugs. Multivariate analysis showed that HCQ and PI combination therapy had five times higher odds of QTc prolongation as compared to HCQ-only therapy after controlling for age, cardiovascular disease, SIRS and the use of concurrent QTc-prolonging agents besides HCQ and/or PI (OR 5.2; 95% CI, 1.11-24.49; p = 0.036). Independent of drug therapy, presence of SIRS resulted in four times higher odds of QTc prolongation (OR 4.3; 95% CI, 1.66-11.06; p = 0.003). In HCQ-PI combination group, having concomitant pro-QT drugs led to four times higher odds of QTc prolongation (OR 3.8; 95% CI, 1.53-9.73; p = 0.004). Four patients who had prolonged QTc intervals died but none were cardiac-related deaths. WHAT IS NEW AND CONCLUSION: In our cohort, hydroxychloroquine monotherapy had low potential to increase QTc intervals. However, when given concurrently with protease inhibitors which have possible or conditional risk, the odds of QTc prolongation increased fivefold. Interestingly, independent of drug therapy, the presence of systemic inflammatory response syndrome (SIRS) resulted in four times higher odds of QTc prolongation, leading to the postulation that some QTc events seen in COVID-19 patients may be due to the disease itself. ECG monitoring should be continued for at least a week from the initiation of treatment.

Effects of a nutrition support team on clinical outcomes, metabolic complications and electrolyte abnormalities in patients receiving parenteral nutrition.

The effectiveness of the Nutrition Support Team (NST) at Hospital Sungai Buloh, a large public hospital in Kuala Lumpur, Malaysia, in optimising parenteral nutrition (PN) has not been evaluated. To evaluate the effects of this NST in optimising patient outcomes, treatment outcomes, and adherence to biochemical monitoring guidelines, two groups of patients, those given PN before (n = 106) NST intervention and those given PN after (n=106) NST intervention, were retrospectively compared. Intervention by the NST significantly reduced metabolic abnormalities, reducing sodium abnormalities from 67% to 44% (p<0.01); potassium abnormalities from 42% to 15% (p<0.01); magnesium abnormalities from 13% to 3% (p<0.05) and phosphate abnormalities from 21% to 9% (p=0.01). Intervention by the NST also significantly reduced the incidence of hypertriglyceridemia from 68% to 45% (p=0.002) and significantly improved adherence to biochemical monitoring guidelines from 46% to 72% (p<0.01). However, the length of hospital stay, patient mortality, and duration of PN were similar in both groups. This study failed to demonstrate that the establishment of a NST gave better outcomes in terms of the common measures of effectiveness. In conclusion, although management by an NST significantly reduced metabolic abnormalities and improved adherence to biochemical monitoring guidelines, the NST did not improve patient mortality rates and length of hospital stay.