Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions.

BACKGROUND: Ventricular tachycardia (VT)/ventricular fibrillation (VF) rearrest after successful resuscitation is common, and survival is poor. A mechanism of VT/VF, as demonstrated in ex vivo studies, is when repolarization alternans becomes spatially discordant (DIS ALT), which can be enhanced by impaired gap junctions (GJs). However, in vivo spontaneous DIS ALT-induced VT/VF has never been demonstrated, and the effects of GJ on DIS ALT and VT/VF rearrest are unknown. OBJECTIVES: This study aimed to determine whether spontaneous VT/VF rearrest induced by DIS ALT occurs in vivo, and if it can be suppressed by preserving Cx43-mediated GJ coupling and/or connectivity. METHODS: We used an in vivo porcine model of resuscitation from ischemia-induced cardiac arrest combined with ex vivo optical mapping in porcine left ventricular wedge preparations. RESULTS: In vivo, DIS ALT frequently preceded VT/VF and paralleled its incidence at normal (37°C, n = 9) and mild hypothermia (33°C, n = 8) temperatures. Maintaining GJs in vivo with rotigaptide (n = 10) reduced DIS ALT and VT/VF incidence, especially during mild hypothermia, by 90% and 60%, respectively (P < 0.001; P < 0.013). Ex vivo, both rotigaptide (n = 5) and αCT11 (n = 7), a Cx43 mimetic peptide that promotes GJ connectivity, significantly reduced DIS ALT by 60% and 100%, respectively (P < 0.05; P < 0.005), and this reduction was associated with reduced intrinsic heterogeneities of action potential duration rather than changes in conduction velocity restitution. CONCLUSIONS: These results provide the strongest in vivo evidence to date suggesting a causal relationship between spontaneous DIS ALT and VT/VF in a clinically realistic scenario. Furthermore, our results suggest that preserving GJs during resuscitation can suppress VT/VF rearrest.

Improving Timeliness of Antibiotic Administration Using a Provider and Pharmacist Facing Sepsis Early Warning System in the Emergency Department Setting: A Randomized Controlled Quality Improvement Initiative.

OBJECTIVES: Results of pre-post intervention studies of sepsis early warning systems have been mixed, and randomized clinical trials showing efficacy in the emergency department setting are lacking. Additionally, early warning systems can be resource-intensive and may cause unintended consequences such as antibiotic or IV fluid overuse. We assessed the impact of a pharmacist and provider facing sepsis early warning systems on timeliness of antibiotic administration and sepsis-related clinical outcomes in our setting. DESIGN: A randomized, controlled quality improvement initiative. SETTING: The main emergency department of an academic, safety-net healthcare system from August to December 2019. PATIENTS: Adults presenting to the emergency department. INTERVENTION: Patients were randomized to standard sepsis care or standard care augmented by the display of a sepsis early warning system-triggered flag in the electronic health record combined with electronic health record-based emergency department pharmacist notification. MEASUREMENTS AND MAIN RESULTS: The primary process measure was time to antibiotic administration from arrival. A total of 598 patients were included in the study over a 5-month period (285 in the intervention group and 313 in the standard care group). Time to antibiotic administration from emergency department arrival was shorter in the augmented care group than that in the standard care group (median, 2.3 hr [interquartile range, 1.4-4.7 hr] vs 3.0 hr [interquartile range, 1.6-5.5 hr]; p = 0.039). The hierarchical composite clinical outcome measure of days alive and out of hospital at 28 days was greater in the augmented care group than that in the standard care group (median, 24.1 vs 22.5 d; p = 0.011). Rates of fluid resuscitation and antibiotic utilization did not differ. CONCLUSIONS: In this single-center randomized quality improvement initiative, the display of an electronic health record-based sepsis early warning system-triggered flag combined with electronic health record-based pharmacist notification was associated with shorter time to antibiotic administration without an increase in undesirable or potentially harmful clinical interventions.

Hypothermia Modulates Arrhythmia Substrates During Different Phases of Resuscitation From Ischemic Cardiac Arrest.

BACKGROUND: We designed an innovative porcine model of ischemia-induced arrest to determine dynamic arrhythmia substrates during focal infarct, global ischemia from ventricular tachycardia or fibrillation (VT/VF) and then reperfusion to determine the effect of therapeutic hypothermia (TH) on dynamic arrhythmia substrates and resuscitation outcomes. METHODS AND RESULTS: Anesthetized adult pigs underwent thoracotomy and regional plunge electrode placement in the left ventricle. Subjects were then maintained at either control (CT; 37°C, n=9) or TH (33°C, n=8). The left anterior descending artery (LAD) was occluded and ventricular fibrillation occurred spontaneously or was induced after 30 minutes. Advanced cardiac life support was started after 8 minutes, and LAD reperfusion occurred 60 minutes after occlusion. Incidences of VF/VT and survival were compared with ventricular ectopy, cardiac alternans, global dispersion of repolarization during LAD occlusion, and LAD reperfusion. There was no difference in incidence of VT/VF between groups during LAD occlusion (44% in CT versus 50% in TH; P=1s). During LAD occlusion, ectopy was increased in CT and suppressed in TH (33±11 ventricular ectopic beats/min versus 4±6 ventricular ectopic beats/min; P=0.009). Global dispersion of repolarization and cardiac alternans were similar between groups. During LAD reperfusion, TH doubled the incidence of cardiac alternans compared with CT, with a marked increase in VF/VT (100% in TH versus 17% in CT; P=0.004). Ectopy and global dispersion of repolarization were similar between groups during LAD reperfusion. CONCLUSIONS: TH alters arrhythmia substrates in a porcine translational model of resuscitation from ischemic cardiac arrest during the complex phases of resuscitation. TH worsens cardiac alternans, which was associated with an increase in spontaneous VT/VF during reperfusion.