β1-blocker in sepsis.
Hasegawa Daisuke,Sato Ryota,Nishida Osamu
Journal of intensive care
BACKGROUND:The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical evidence of ultrashort-acting β1-blockers. MAIN BODY:A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation. CONCLUSION:Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted.
Esmolol for septic shock: more than just heart rate control?
Orbegozo Cortes D,Njimi H,Dell'Anna A M,Taccone F S
Excessive adrenergic stimulation may be associated with several adverse events and contribute to increase mortality in critically ill septic patients. Few clinical data exist on the effects of adrenergic blockade in this setting. The objective of this study was to investigate the effect of a short acting b-blocker (esmolol) in septic shock patients. In a single-center, controlled, open-label, phase 2 trial (from November 2010 to July 2012), Morelli et al. randomized patients with a need of norepinephrine to maintain a mean arterial pressure above 65 mmHg to receive either esmolol or standard of care. Patients were included if, after 24 hours of initial resuscitation, hypovolemia was excluded (wedge pressure ≥12 mmHg or central venous pressure ≥8 mmHg) and heart rate was above 95 bpm. Patients were excluded if they were younger than 18 years, had previous b-blockers therapy, cardiac index was ≤2.2 L/min/m² with wedge pressure >18 mmHg, were diagnosed with significant cardiac valvular diseases or were pregnant. The primary outcome was the reduction in heart rate between 80 and 94 bpm over a 96-hr period. Secondary outcomes included norepinephrine requirement, hemodynamic changes, organ function, adverse events and 28-day mortality. A total of 154 patients, 77 for each group, were enrolled. Esmolol was more effective than standard treatment to reduce heart rate within target limits; also, b-blocker therapy was associated with an increased stroke volume and left ventricular work index when compared to the control group. These favorable hemodynamic effects were associated with a better control of lactate levels, a higher reduction in norepinephrine and fluids requirement. Mortality was 49.4% in the esmolol group and 80.5% in the control group (P<0.01). This is the first study showing an improvement in cardiac function and 28-day mortality in septic patients adding b-blockers to standard therapy. We discussed several statistical and methodological limitations that may influence the generability of these results.
Beta-blocker use in severe sepsis and septic shock: a systematic review.
Sanfilippo Filippo,Santonocito Cristina,Morelli Andrea,Foex Pierre
Current medical research and opinion
OBJECTIVE:Recent growing evidence suggests that beta-blocker treatment could improve cardiovascular dynamics and possibly the outcome of patients admitted to intensive care with severe sepsis or septic shock. DESIGN:Systematic review. DATA SOURCES:MEDLINE and EMBASE healthcare databases. REVIEW METHODS:To investigate this topic, we conducted a systematic review of the above databases up to 31 May 2015. Due to the clinical novelty of the subject, we also included non-randomized clinical studies. We focused on the impact of beta-blocker treatment on mortality, also investigating its effects on cardiovascular, immune and metabolic function. Evidence from experimental studies was reviewed as well. RESULTS:From the initial search we selected 10 relevant clinical studies. Five prospective studies (two randomized) assessed the hemodynamic effects of the beta1-blocker esmolol. Heart rate decreased significantly in all, but the impact on other parameters differed. The imbalance between prospective studies' size (10 to 144 patients) and the differences in their design disfavor a meta-analysis. One retrospective study showed improved hemodynamics combining metoprolol and milrinone in septic patients, and another retrospective study found no association between beta-blocker administration and mortality. We also found three case series. Twenty-one experimental studies evaluated the hemodynamic, immune and/or metabolic effects of selective and/or non-selective beta-blockers in animal models of sepsis (dogs, mice, pigs, rats, sheep), yielding conflicting results. CONCLUSIONS:Whilst there is not enough prospective data to conduct a meta-analysis, the available clinical data are promising. We discuss the ability of beta blockade to modulate sepsis-induced alterations at cardiovascular, metabolic, immunologic and coagulation levels.