Landiolol in patients with septic shock resident in an intensive care unit (LANDI-SEP): study protocol for a randomized controlled trial.

BACKGROUND: In patients with septic shock, the presence of an elevated heart rate (HR) after fluid resuscitation marks a subgroup of patients with a particularly poor prognosis. Several studies have shown that HR control in this population is safe and can potentially improve outcomes. However, all were conducted in a single-center setting. The aim of this multicenter study is to demonstrate that administration of the highly beta1-selective and ultrashort-acting beta blocker landiolol in patients with septic shock and persistent tachycardia (HR ≥ 95 beats per minute [bpm]) is effective in reducing and maintaining HR without increasing vasopressor requirements. METHODS: A phase IV, multicenter, prospective, randomized, open-label, controlled study is being conducted. The study will enroll a total of 200 patients with septic shock as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization period of 24-36 h. Patients are randomized (1:1) to receive either standard treatment (according to the Surviving Sepsis Campaign Guidelines 2016) and continuous landiolol infusion to reach a target HR of 80-94 bpm or standard treatment alone. The primary endpoint is HR response (HR 80-94 bpm), the maintenance thereof, and the absence of increased vasopressor requirements during the first 24 h after initiating treatment. DISCUSSION: Despite recent studies, the role of beta blockers in the treatment of patients with septic shock remains unclear. This study will investigate whether HR control using landiolol is safe, feasible, and effective, and further enhance the understanding of beta blockade in patients with septic shock. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2017-002138-22 . Registered on 8 August 2017.

Landiolol for rate control management of atrial fibrillation in patients with cardiac dysfunction.

Atrial fibrillation (AFib) is frequently associated with heart failure. Guidelines for AFib management have been recently updated and include an algorithm for acute heart rate control based on left ventricular ejection fraction and haemodynamics. Landiolol is an injectable ultra-short beta-blocker with very high beta-1 selectivity, listed in Japanese Guidelines for AFib management as potential option for rate control of patient with heart failure. Landiolol is now available in Europe with indication of controlling heart rate in AFib and supraventricular tachycardia. This review discusses existing clinical data in Japan and perspectives of landiolol use for acute rate control of AFib patients with cardiac dysfunction.

Vasopressin in Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize the results of randomized controlled trials on the use of vasopressin as a vasopressor agent in cardiac surgery. DESIGN: Meta-analysis. PARTICIPANTS: Six-hundred-twenty-five adult patients undergoing elective or emergency cardiac surgery. INTERVENTIONS: Arginine vasopressin infusion (n = 313) or control/standard therapy (n = 312). MEASUREMENTS AND MAIN RESULTS: The rates of perioperative complications and postoperative mortality were used as primary and secondary endpoints, respectively. Fixed and/or random effects models were used to compare pooled odds ratios. Arginine vasopressin reduced the pooled odds ratio (OR) of perioperative complications (OR, 0.33; 95% confidence interval [CI], 0.2-0.54; p < 0.0001). A sensitivity analysis excluding the largest trial showed an unchanged reduction in perioperative complications (OR, 0.35; 95% CI, 0.18-0.69; p = 0.002). When analyzing each perioperative complication separately, vasopressin reduced the pooled OR of vasodilatory shock (OR, 0.4; 95% CI, 0.16-0.97; p = 0.04) and new-onset atrial fibrillation (OR, 0.42; 95% CI, 0.21-0.82; p = 0.01). The pooled OR of postoperative death was not different between patients treated with arginine vasopressin and those receiving standard therapy or placebo (OR, 0.83; 95% CI, 0.45-1.53; p = 0.55). The funnel plot for the primary endpoint suggested a relevant publication bias. All included trials suffered from a high risk of bias. CONCLUSION: Our meta-analysis suggests that arginine vasopressin may reduce the rate of perioperative complications in patients undergoing elective or emergency cardiac surgery. No difference in postoperative mortality was observed. An adequately powered multicenter trial is required for reliable estimation of the effects of arginine vasopressin on perioperative complication rates and mortality in cardiac surgical patients.