Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock

Aboab, Jérôme; Sebille, Véronique; Jourdain, M.; Mangalaboyi, Jacques; Gharbi, Miloud; Mansart, Arnaud; Annane, Djillali

doi:10.1007/s00134-011-2236-y

Cited by 69 publications

(53 citation statements)

References 31 publications

(38 reference statements)

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“…The longer duration of diastole may perhaps allow better diastolic filling. In a pig model of endotoxic shock, the infusion of the short-acting β 1 antagonist esmolol even improved stroke volume over time compared to control animals [142]. Despite reducing heart rate by approximately 20%, no septic animal suffered from cardiovascular collapse during the esmolol infusion period [142].…”

Section: Beta-blockers In Sepsismentioning

confidence: 99%

“…In a pig model of endotoxic shock, the infusion of the short-acting β 1 antagonist esmolol even improved stroke volume over time compared to control animals [142]. Despite reducing heart rate by approximately 20%, no septic animal suffered from cardiovascular collapse during the esmolol infusion period [142]. Initial preliminary studies in humans demonstrate that intravenous esmolol administration is feasible in patients with septic shock [143].…”

Section: Beta-blockers In Sepsismentioning

confidence: 99%

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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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Section: Beta-blockers In Sepsismentioning

confidence: 99%

Section: Beta-blockers In Sepsismentioning

confidence: 99%

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Rudiger¹,

Singer

2013

CVP

View full text Add to dashboard Cite

show abstract

“…While high doses of esmolol have consistently been associated with non-deleterious effects on cardiac and vascular functions in small-animal models of sepsis, the results are more contested in large-animal models [8,9,11,13]. For example, administration of high doses of esmolol in septic pigs has been shown to systematically induce a significant decrease or a trend toward a decrease in the cardiac index [20,21].…”

Section: Effects Of Esmolol In Animals With Septic Shockmentioning

confidence: 99%

Effects of low doses of esmolol on cardiac and vascular function in experimental septic shock

Cui¹,

Louis²,

Schmitt³

et al. 2017

Archives of Cardiovascular Diseases Supplements

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Background: Administration of a selective β1-blocker, such as esmolol, in human septic shock has demonstrated cardiovascular protective effects related to heart rate reduction. Certain experimental data also indicate that esmolol exerts systemic anti-inflammatory and beneficial effects on vascular tone. Thus, the present study aimed to determine whether a non-chronotropic dose of esmolol maintains its protective cardiovascular and anti-inflammatory effects in experimental septic shock. Methods: Four hours after cecal ligation and puncture (CLP), Wistar male rats were randomly allocated to the following groups (n = 8): CLP, CLP + E-1 (esmolol: 1 mg.kg). An additional eight rats underwent sham operation. All rats received a continuous infusion of saline, analgesic and antibiotics 4 hours after the surgery. Assessment at 18 hours included in vivo cardiac function assessed by echocardiography and ex vivo vasoreactivity assessed by myography. Circulating cytokine levels (IL-6 and IL-10) were measured by ELISA. Cardiac and vascular protein expressions of p-NF-κB, IκBα, iNOS, p-AKT/AKT and p-eNOS/eNOS were assessed by western blotting. Results: CLP induced tachycardia, hypotension, cardiac output reduction, hyperlactatemia and vascular hyporesponsiveness to vasopressors. Compared to CLP animals, heart rate was unchanged in CLP + E-1 and CLP + E-5 but was reduced in CLP + E-18. Stroke volume, cardiac output, mean arterial pressure and lactatemia were improved in CLP + E-1 and CLP + E-5, while vascular responsiveness to phenylephrine was only improved in CLP + E-5 and CLP + E-18. Plasma IL-6 levels were decreased in all esmolol groups. p-NF-κB was decreased in both cardiac and vascular tissues in CLP + E-5 and CLP + E-18. Conclusion: In experimental septic shock, low doses of esmolol still improved cardiac function and vasoreactivity. These benefits appear to be associated with a modulation of inflammatory pathways.

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“…The rates of septic cardiomyopathy [91] suggest an associated risk for arrhythmias. The administration of betablockers with concomitant vasopressors has been shown to have beneficial effects in animal models of septic shock and in cohorts of septic patients [92][93][94][95][96].…”

Section: Beta-blockersmentioning

confidence: 99%

Management of arrhythmia in sepsis and septic shock

Borggrefe¹,

Matoušek²,

Malý³

et al. 2017

Anaesthesiol Intensive Ther

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The occurrence of supraventricular arrhythmias is associated with an unfavourable prognosis in septic shock. Available trials are difficult to apply in sepsis and septic shock patients due to included cohorts, control groups and because "one size does not fit all". The priorities in the critically ill are maintenance of the sinus rhythm and diastolic ventricular filling. The rate control modality should be reserved for chronic AF and in situations when the sinus rhythm is difficult to maintain due to extreme stress conditions resulting from a high dosage of vasoactive agents. Electric cardioversion is indicated in unstable patients with an absence of contraindications and is more feasible in combination with an antiarrhythmic agent. Besides amiodarone being preferred for its lower cardiodepressant side effect compared to other agents, drugs with a different degree of betablocking activity are very useful in supraventricular arrhythmias and septic shock, providing echocardiography is routinely used to support their indications within the current summary of product characteristics. A typical patient benefiting from propafenone is without significant structural heart disease, i.e. typically with normal to moderately reduced left ventricular systolic function. Future research should be channelled towards echocardiography-guided prospective controlled trials on antiarrhythmic therapy which may clarify the issue of rhythm versus rate control, the effects of various antiarrhythmic drugs, and a place for electric cardioversion in critically ill patients in septic shock.

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Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock

Abstract: In large animals with endotoxemic shock, continuous infusion of esmolol, a selective beta-1 adrenergic blocker, titrated to decrease heart rate by 20%, was well tolerated and may offset LPS-induced cardiac dysfunction by a preload positive effect.

Cited by 69 publications

References 31 publications

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Effects of low doses of esmolol on cardiac and vascular function in experimental septic shock

Management of arrhythmia in sepsis and septic shock

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