ABSTRACT
Background: Septic shock is associated with systemic inflammatory response, hemodynamic instability, impaired sympathetic control, and the development of multiorgan dysfunction that requires vasopressor or inotropic support. The regulation of immune function in sepsis is complex and varies over time. However, activating Beta-2 receptors and blocking Beta-1 receptors reduces the proinflammatory response by influencing cytokine production. Evidence that supports the concomitant use of ultra short beta-blockers with inotropes and vasopressors in patients with septic shock is still limited. This study aimed to evaluate the use of ultra short beta-blockers and its impact on the ICU related outcomes such as mortality, length of stay, heart rate control, shock resolution, and vasopressors/inotropes requirements. Methods: A systematic review and meta-analysis of randomized controlled trials including critically ill patients with septic shock who received inotropes and vasopressors. Patients who received either epinephrine or norepinephrine without beta-blockers "control group" were compared to patients who received ultra short beta-blockers concomitantly with either epinephrine or norepinephrine "Intervention group". MEDLINE and Embase databases were utilized to systematically search for studies investigating the use of ultra short beta-blockers in critically ill patients on either epinephrine or norepinephrine from inception to October 10, 2023. The primary outcome was the 28-day mortality. While, length of stay, heart rate control, and inotropes/ vasopressors requirements were considered secondary outcomes. Results: Among 47 potentially relevant studies, nine were included in the analysis. The 28-day mortality risk was lower in patients with septic shock who used ultra short beta-blockers concomitantly with either epinephrine or norepinephrine compared with the control group (RR (95%CI): 0.69 (0.53, 0.89), I2=26%; P=0.24). In addition, heart rate was statistically significantly lower with a standardized mean difference (SMD) of -22.39 (95% CI: -24.71, -20.06) among the beta-blockers group than the control group. The SMD for hospital length of stay and the inotropes requirement were not statistically different between the two groups (SMD (95%CI): -0.57 (-2.77, 1.64), and SMD (95%CI): 0.08 (-0.02, 0.19), respectively). Conclusion: The use of ultra short beta-blockers concomitantly with either epinephrine or norepinephrine in critically ill patients with septic shock was associated with better heart rate control and survival benefits without increment in the inotropes and vasopressors requirement.
ABSTRACT
AIM/OBJECTIVE: Recently, the glucagon-like peptide-1 receptor agonists (GLP-1RA) class showed a significant reduction in heart failure (HF) hospitalization in several meta-analyses of cardiovascular outcome trials (CVOTs). The objective of this systematic review is to summarize the real-world evidence regarding HF outcomes of GLP-1RAs. METHODS: We searched the PubMed and EMBASE databases for observational studies that investigated HF outcomes of GLP-1RAs. RESULTS: Our search yielded 10 observational studies. Of those, 7 were cohort studies, and 3 were nested case-control studies. The risk of HF was the outcome in four cohort studies. One study that compared exenatide and exenatide combined with insulin to insulin showed a reduction in HF risk in the exenatide and exenatide plus insulin groups (HR 0.34, 95% CI 0.22-0.52, p-value <0.001 and HR 0.40, 95% CI 0.32-0.50, p-value <0.001, respectively). The other three cohort studies did not show a statistically significant result. In the three cohort studies that investigated HF hospitalization as an outcome, two showed a lower rate of HF hospitalization [48 (16.7%) vs. 76 (28%), p-value <0.05 and HR 0.51, 95% CI 0.34-0.77, p = 0.002] in the GLP-1RA groups. Conversely, the remaining study showed a reduction of 14% in HF hospitalization in the dipeptidyl peptidase-4 inhibitors (DPP-4i) group compared to the GLP-1RA group (HR 0.86, 95% CI 0.83-0.90). In contrast to the cohort studies, the three nested case-control studies showed similar results of no association of GLP-1RA use and HF hospitalization with OR 0.67 (95% CI 0.32-1.42), HR 0.95 (95% CI 0.83-1.10), and OR 0.84 (95% CI 0.48-1.47), respectively. CONCLUSION: The real-world evidence regarding the reduction in HF risk and hospitalization in GLP-1RA users is conflicting. Further well-designed, large multicenter, observational studies are needed to show clearer evidence.
