Beta-1 blocker improves survival of septic rats through preservation of gut barrier function

Mori, Kota; Morisaki, Hiroshi; Yajima, Satoshi; Suzuki, Takeshi; Ishikawa, Akiko; Nakamura, Norihito; Innami, Yasushi; Takeda, Junzo

doi:10.1007/s00134-011-2326-x

Cited by 60 publications

(56 citation statements)

References 38 publications

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“…[26][27][28][29] A single-center trial 30 demonstrating improved mortality among patients with septic shock and sinus tachycardia randomized to receive the BB esmolol further supports our finding that BBs may have clinical benefit during sepsis. Although potential mechanisms for beneficial effects of BBs during sepsis are unclear, experimental data support enhanced journal.publications.chestnet.org microvascular, 31 antiinflammatory, 32 and gut mucosal integrity 33 with use of BBs during sepsis.…”

Section: Discussionmentioning

confidence: 99%

Practice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis

Walkey

Evans

Winter

et al. 2016

Chest

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BACKGROUND: Atrial fibrillation (AF) during sepsis is associated with increased morbidity and mortality, but practice patterns and outcomes associated with rate-and rhythm-targeted treatments for AF during sepsis are unclear.METHODS: This was a retrospective cohort study using enhanced billing data from approximately 20% of United States hospitals. We identified factors associated with IV AF treatments (b-blockers [BBs], calcium channel blockers [CCBs], digoxin, or amiodarone) during sepsis. We used propensity score matching and instrumental variable approaches to compare mortality between AF treatments.RESULTS: Among 39,693 patients with AF during sepsis, mean age was 77 AE 11 years, 49% were women, and 76% were white. CCBs were the most commonly selected initial AF treatment during sepsis (14,202 patients [36%]), followed by BBs (11,290 [28%]), digoxin (7,937 [20%]), and amiodarone (6,264 [16%]). Initial AF treatment selection differed according to geographic location, hospital teaching status, and physician specialty. In propensity-matched analyses, BBs were associated with lower hospital mortality when compared with CCBs (n ¼ 18,720; relative risk [RR], 0.92; 95% CI, 0.86-0.97), digoxin (n ¼ 13,994; RR, 0.79; 95% CI, 0.75-0.85), and amiodarone (n ¼ 5,378; RR, 0.64; 95% CI, 0.61-0.69). Instrumental variable analysis showed similar results (adjusted RR fifth quintile vs first quintile of hospital BB use rate, 0.67; 95% CI, 0.58-0.79). Results were similar among subgroups with new-onset or preexisting AF, heart failure, vasopressor-dependent shock, or hypertension.CONCLUSIONS: Although CCBs were the most frequently used IV medications for AF during sepsis, BBs were associated with superior clinical outcomes in all subgroups analyzed. Our findings provide rationale for clinical trials comparing the effectiveness of AF rate-and rhythm-targeted treatments during sepsis.

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Section: Discussionmentioning

confidence: 99%

Practice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis

Walkey

Evans

Winter

et al. 2016

Chest

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“…However, they failed to provide any supporting data, and one may argue that anti-inflammatory effects would unlikely have occurred this swiftly, i.e., after only four hours of treatment (12)(13)(14)(15).…”

Section: Study Design and Findingsmentioning

confidence: 99%

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

Kimmoun¹,

Wei

Lévy³

et al. 2016

J. Thorac. Dis.

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“…In rats with fecal peritonitis, an esmolol infusion reduced the local inflammatory response as well as bacterial translocation from the gut into mesenteric lymph nodes [145]. Survival times of septic animals have been prolonged in several animal studies [141,145,146].…”

Section: Beta-blockers In Sepsismentioning

confidence: 99%

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Rudiger¹,

Singer

2013

CVP

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Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning hibernation-like condition. Sepsis-induced cardiac dysfunction may represent an example of such functional shutdown. Sepsis-induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors. Its mechanisms include the attenuation of the adrenergic response at the cardiomyocyte level, alterations of intracellular calcium trafficking and blunted calcium sensitivity of contractile proteins. All these changes are mediated by cytokines. Treatment includes preload optimization with sufficient fluids. However, excessive volume loading is harmful. The first line vasopressor recommended at present is norepinephrine, while vasopressin can be started as a salvage therapy for those not responding to catecholamines. During early sepsis, cardiac output can be increased by dobutamine. While early administration of catecholamines might be necessary to restore adequate organ perfusion, prolonged administration might be harmful. Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine reduces myocardial oxygen expenditure and ameliorates diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. All these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice. While early administration of catecholamines might be necessary to restore adequate organ perfusion and pressure, prolonged administration might be harmful.Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine will reduce myocardial oxygen expenditure and ameliorate diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. However, all these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice.-3 -Alain Rudiger & Mervyn Singer: The heart in sepsis

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Beta-1 blocker improves survival of septic rats through preservation of gut barrier function

Abstract: Beta-1 blocker therapy improves outcome in sepsis possibly through modulation of gut mucosal integrity and local inflammatory response.

Cited by 60 publications

References 38 publications

Practice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis

Practice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

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