QT interval prolongation and the rate of malignant ventricular dysrhythmia and cardiac arrest in adult poisoned patients.

INTRODUCTION: Prolongation of QTc interval, a common electrocardiographic (ECG) abnormality encountered in the toxicology patient, is reportedly associated with an increased risk of malignant ventricular dysrhythmias (MVD), such as ventricular tachycardia (VT, with and without a pulse), ventricular fibrillation (VF), and/or cardiac arrest. Quantifiable cardiac arrest risk in relation to specific QTc interval length is not known in this population. METHODS: We conducted a retrospective, observational study to assess the rate of cardiac arrest and its association with degree of QTc prolongation in a cohort of patients requiring toxicology consultation. RESULTS: 550 patients were included in our analysis (average age 36 years and 49% male). Average QTc was 453 milliseconds (ms). Overall incidence of cardiac arrest in the study cohort was 1.1% with 6 reported cases; when considering patients with QTc > 500 ms, incidence was 1.7%. Two patients with cardiac arrest experienced ventricular dysrhythmia with decompensation prior to cardiac arrest; four patients developed sudden cardiac arrest. CONCLUSIONS: The risk of malignant ventricular dysrhythmia, including cardiac arrest, is low in this poisoned patient population with an overall rate of 1.1%. Two-thirds of cardiac arrest cases occurred in patients with normal QTc intervals. When considering patients with prolonged QTc intervals, the rate of cardiac arrest remains very low at 0.8%. Considering QTc greater than 500 ms, the rate of cardiac arrest is 1.7%. Further prospective studies are required to quantify the risk of malignant ventricular dysrhythmias, including cardiac arrest, and its relation to the degree of QTc interval in poisoned patients.

Prostaglandin F2α FP receptor antagonist improves outcomes after experimental traumatic brain injury.

BACKGROUND: Injuries to the brain promote upregulation of prostaglandins, notably the proinflammatory PGF2α, and overactivation of their cognate G-protein-coupled FP receptor, which could exacerbate neuronal damage. Our study is focused on investigation of the FP receptor as a target for novel neuroprotective drugs in a preclinical animal traumatic brain injury (TBI) model. METHODS: Accordingly, the effects of acute intraperitoneal post-treatment with selective FP antagonist AL-8810 were studied in wildtype (WT) and FP receptor knockout (FP-/-) mice after controlled cortical impact (CCI). Neurological impairments were evaluated using neurological deficit scores (NDS) and the grip strength test. Cortical lesions and overall brain pathology were assessed using immunohistochemistry. RESULTS: Morphological analyses of cerebral vasculature and anastomoses revealed no differences between WT and FP-/- mice. CCI produced cortical lesions characterized by cavitation, neuronal loss, and hematoma with a volume of 20.0 ± 1.0 mm(3) and significant hippocampal swelling (146.5 ± 7.4% of contralateral) compared with sham (P < 0.05). Post-treatment with AL-8810 (1 to 10 mg/kg) had no significant effect on cortical lesions, which suggests the irreversible effect of primary CCI injury, but significantly reduced hippocampal swelling to a size not significantly different from the sham group. Post-treatment with AL-8810 at a dose of 10 mg/kg significantly improved NDS at 24 and 48 hours after CCI (P < 0.001 and P < 0.01, respectively). In the AL-8810 group, CCI-induced decrease in grip strength was three-fold (2.93 ± 1.71) less and significantly different than in the saline-treated group. The FP-/- mice had significantly less hippocampal swelling, but not NDS, compared with WT mice. In addition, immunohistochemistry showed that pharmacologic blockade and genetic deletion of FP receptor led to attenuation of CCI-induced gliosis and microglial activation in selected brain regions. CONCLUSION: This study provides, for the first time, demonstration of the unique role of the FP receptor as a potential target for disease-modifying CNS drugs for treatment of acute traumatic injury.

Stable Ventricular Fibrillation: A Paradigm Rather Than Septal Shift?

Awake patients in ventricular fibrillation is a phenomenon limited to patients who are mechanically supported. We describe a cohort of patients supported by left ventricular assist devices (LVADs) presenting to the emergency department (ED) at a high-volume LVAD center while in awake ventricular fibrillation (VF)/ventricular tachycardia (VT). Among 175 patients reviewed, a total of 19 LVAD patients presented to the ED in awake VF/VT between December 2015 and July 2021. On ED presentation, patients maintained a median mean arterial blood pressure (MAP) of 70 mm Hg with a mean LVAD flow of 3.77 L/minute. ED management included cardioversion in the majority of cases: 58% were defibrillated once, 21% were defibrillated multiple times, 68% received amiodarone, and 21% received lidocaine. Inpatient management included defibrillation, ablation, and antiarrhythmic initiation in 37%, 11%, and 84% of cases, respectively. In total, five patients (26%) died with one death attributed to recurrent VT. Our findings support the short-term tolerability of sustained ventricular arrhythmias in LVAD patients, as evidenced by the maintained MAPs and mental status. Clinical teams, however, should be aware of the potential harbinger for in-hospital mortality heralded by an awake VF/VT presentation.