The long QT syndrome (LQTS) is characterized by a prolonged QT interval, as well as a propensity to develop syncope and sudden cardiac death caused by the malignant polymorphic ventricular arrhythmia called torsades de pointes (TdP). The QT interval is measured from the onset of the QRS complex to the end of the T wave and can be affected by both ventricular conduction velocities as well as by the velocity of repolarization. In most cases, QT prolongation is caused by factors that prolong the duration of the action potential, mainly by delaying the repolarization phase 3. The molecular mechanism is partially known. There are two well described mechanisms: blocking of the ion channel cavity of HERG; or causing an abnormal protein trafficking required for the location of HERG subunits in cell membrane. Both of them impair the IKr current. However the blockade of ion channels is not the only condition to generate TdP. Other factors may play an important role, e.g. myocardium heterogeneity, drug-drug interaction, genetic polymorphism, and electrolyte disturbances. Several drugs had been subject of withdrawal because QT-prolongation and arrhythmia. Understanding of processes involved in drug-induced QT prolongation is needed for the study and prevention of life-threatening arrhythmias.

Drug-induced QT interval prolongation is the most frequent cause of Long QT syndrome (LQTS) in the clinical practice. This electrophysiological entity, produced by an extended duration of the myocardial repolarization and reflected as a prolonged QT interval in the superficial electrocardiogram (EKG), increases the risk of polymorphic ventricular tachycardia (Torsades de Pointes) appearance and sudden death. Certain antiarrhythmic drugs such as amiodarone, sotalol, quinidine, procainamide, verapamil and diltiazem are known as drugs that, due to their mechanism of action, prolong the QT interval, demanding constant monitorization. Nevertheless there are other widely used drugs in the Intensive Care Unit (ICU) that have no cardiovascular indication but still are frequently associated with prolonged QT interval such as ondansetron, like macrolides and fluoroquinolones , typical antipsychotic such as haloperidol and thioridazine or atypical such as sertindole. Taking into consideration this unexpected association with the prolongation of the QT interval, these drugs require a closed monitorization in these critical patients. Since ICU patients are particularly vulnerable to this sort of alteration of ventricular repolarization caused by the effect of these drugs itselves or by pharmacological interaction with other medication, which can generate extension of the QT interval as well as other clinical presentation associated with the risk of developing Torsades de Point, the strict and closed control of physicians in charge must be on a daily basis.

Several drugs acting on the nervous system have been implicated in the prolongation of the QT interval. Leaving aside the antidepressant and antipsychotic drugs, some have shown to prolong the QT interval in vivo. These include opioids, particularly methadone, inhalational anesthetics, and some preparations used for treatment of cough. These drugs have a narrow therapeutic interval or possible drug interactions that lead to clinical toxicity manifested by arrhythmias. They share the ability to block potassium channels (HERG), prolong the action potential and QT interval, and generate arrhythmias and Torsades de Pointes like other typicality recognized like antiarrhythmics, antihistamines, prokinetics, psychotropics and anti-infectives agents. Muscle relaxants like alcuronium, pancuronium and atracurium associated with or without atropine prolong significantly the QT interval. Methadone is the opiod most tightly associated with QTc prolongation; with much lesser potency buprenorphine and oxycodone can block HERG channels and depress the IKr current in vitro. Antineoplastic chemotherapy like anthracyclines, alkylating drugs, alkilants and cisplatin are associated with electrocardiographic alterations including prolongation of QT and emesis of different grades. Its very important take in account the synergic effects over the QT prolongation when effective antiemetics like 5-HT3 receptor antagonist (granisetron, ondansetron, and dolasetron) are administered. The Knowledge of their pharmacological properties is of vital importance to avoid exposing particularly vulnerable individuals as those with congenital long QT syndrome, and even the general public to unnecessary risk of potentially fatal arrhythmias.

Background: Hyperbaric oxygen (HBO₂) therapy has been proposed to treat hypoxaemia and reduce inflammation in COVID-19. Our objective was to analyse safety and efficacy of HBO₂in treatment of hypoxaemia in patients with COVID-19 and evaluate time to hypoxaemia correction.Methods: This was a multicentre, open-label randomised controlled trial conducted in Buenos Aires, Argentina, between July and November 2020. Patients with COVID-19 and severe hypoxaemia (SpO₂≤90% despite oxygen supplementation) were assigned to receive either HBO₂treatment or the standard treatment for respiratory symptoms for 7 days. HBO₂treatment was planned for ≥5 sessions (1 /day) for 90 min at 1.45 atmosphere absolute (ATA). Outcomes were time to normalise oxygen requirement to SpO₂≥93%, need for mechanical respiratory assistance, development of acute respiratory distress syndrome and mortality within 30 days. A sample size of 80 patients was estimated, with a planned interim analysis after determining outcomes on 50% of patients.Results: The trial was stopped after the interim analysis. 40 patients were randomised, 20 in each group, age was 55.2±9.2 years. At admission, frequent symptoms were dyspnoea, fever and odynophagia; SpO₂was 85.1%±4.3% for the whole group. Patients in the treatment group received an average of 6.2±1.2 HBO₂sessions. Time to correct hypoxaemia was shorter in treatment group versus control group; median 3 days (IQR 1.0–4.5) versus median 9 days (IQR 5.5–12.5), respectively (p<0.010). OR for recovery from hypoxaemia in the HBO₂group at day 3 compared with the control group was 23.2 (95% CI 1.6 to 329.6; p=0.001) Treatment had no statistically significant effect on acute respiratory distress syndrome, mechanical ventilation or death within 30 days after admission.Conclusion: Our findings support the safety and efficacy of HBO₂in the treatment of COVID-19 and severe hypoxaemia.Trial registration number: NCT04477954.

Prokinetic agents are a very large family of drugs with different mechanisms of action. Only QT prolongation by cisapride has made notable impact and deserved its partial restriction and/or withdrawal from the market. Postmarketing surveillance initially showed that cisapride was generally safe and well tolerated, but in the past decade, more recent data have shown some risk in the patient populations. QT prolongation by prokinetic agents can raised from different mechanisms: some involve increased plasma concentrations of cisapride due to increased bioavailability by inhibiting P glycoprotein, and inhibition of metabolism or deficit in the elimination. On the other hand, pharmacodynamic interactions can also enhance the arrhythmogenic effect of cisapride. The present article presents the mechanisms and reviews the main interactions studied so far, and the role of pharmacovigilance in the detection of rare clinical events. We emphasize the need for physicians to look for conditions (either clinical or not) prone to increase the risk of QT interval prolongation.