Relative tachycardia in patients with sepsis: an independent risk factor for mortality

Leibovici, Leonard; Gafter‐Gvili, Anat; Paul, Michal; Almanasreh, N.; Tacconelli, Evelina; Andreassen, Steen; Nielsen, Anders Paarup; Frank, Uwe; Cauda, Roberto

doi:10.1093/qjmed/hcm074

Cited by 72 publications

(67 citation statements)

References 14 publications

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“…The MAP is one of the most practical clinical measures for sepsis which is known to decrease in endotoxemia, mainly due to overproduction of NO, various cytokines, and CO (2,13). The pulse rate is also known as a measure for sepsis which is known to increase in endotoxemia (8). The decrease in MAP along with the increase in pulse rate was measured to confirm the systemic response to LPS and other agents administered.…”

Section: Resultsmentioning

confidence: 99%

The reciprocal relationship between heme oxygenase and nitric oxide synthase in the organs of lipopolysaccharide-treated rodents

et al. 2009

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The production of nitric oxide (NO) by inducible NO synthase (NOS) and carbon monoxide (CO) by inducible heme oxygenase (HO) contributes greatly to endotoxemia. Reciprocal relationships have been proposed between the NO/NOS and CO/HO systems. However, the interaction between these systems during endotoxemia is unclear, and it is unknown whether the interactive behavior differs among organs. Using endotoxic rats, we studied the effects of the inducible NOS (iNOS) inhibitor L-canavanine (CAN), and the HO inhibitor zinc protoporphyrin (ZPP) on gene expression and protein levels of iNOS, endothelial NOS (eNOS), inducible HO (HO-1), and constitutive HO (HO-2) in the brain, lung, heart, liver and kidney tissue. Intravenous injection of LPS significantly increased iNOS and HO-1 gene expression in all organs. The effects of LPS on eNOS gene expression differed among organs, with increased expression in the liver and kidney, and no change in the lung, brain and heart. ZPP administration down-regulated the LPS-induced increase in HO-1 expression and produced a further increase in iNOS expression in all organs. These data suggest that the CO/HO system modifies the NO/NOS system in endotoxic organs, and that there were only minor organ-specific behaviors in terms of the relationship between these systems in the organs examined.Endotoxemia, which can lead to shock, is a detrimental consequence of severe Gram-negative bacterial infection. Endotoxic shock is initiated by the release of bacterial cell wall-derived lipopolysaccharide (LPS) and the subsequent production of cytokines and vasoactive mediators (13). Gaseous mediators, namely nitric oxide (NO) and carbon monoxide (CO), and the major endogenous sources of these mediators, nitric oxide synthase (NOS) and heme oxygenase (HO), serve a pivotal role in endotoxemia. NO is an extensively studied molecule, and is known for its vasorelaxation and oxidative stressor properties during endotoxemia and septic shock. NO is produced by three distinct NOS enzymes. Two of these NOS isozymes are predominantly constitutively expressed in endothelial cells (eNOS) and in neuronal cells (nNOS), whereas the expression of the third isozyme (iNOS) is inducible in a variety of cells (e.g., macrophages, hepatocytes, vascular smooth muscle cells and cardiac myocytes) by numerous stimuli, including LPS (5, 13). iNOS is responsible for producing most of the NO that causes hypotension and oxidative stress during endotoxic shock, while eNOS is reported to have only a minor role in the pathophysiology of endotoxemia (9, 18). CO has been perceived for many years to be a life-threatening gas; recently, however, CO has become recognized to have anti-inflammatory and vasorelaxative properties and is essential for life. HO is the rate-limiting enzyme in the catabolism of heme, a process that promotes the formation of equimolar amounts of the bile pigment biliverdin, free iron, and CO (1). Together with the anti-inflam-

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Section: Resultsmentioning

confidence: 99%

The reciprocal relationship between heme oxygenase and nitric oxide synthase in the organs of lipopolysaccharide-treated rodents

et al. 2009

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“…Other clinical aspects of sepsis-induced cardiac dysfunction are tachyarrhythmias [44,45], right heart failure [46,47], elevated troponin [48,49] and B-type natriuretic peptide levels [50][51][52].…”

Section: The Heart In Sepsismentioning

confidence: 99%

“…The most commonly used vasopressor in septic patients is norepinephrine, which is administered at doses up to 1.0 µg/kg/min. In a direct comparison with dopamine, noradrenaline caused less arrhythmia [45] and less skin ischaemia [114,115]. While catecholamines are effective in counteracting haemodynamic instability [116], excessive use might be harmful.…”

Section: Inotropes For Contractilitymentioning

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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“…(28,29) High levels of catecholamines as well as a persistently high heart rate predict poor patient outcomes in sepsis. (30,31) While high catecholamine levels could simply be a marker of disease severity, they may also be a perpetrator of further organ dysfunction. (21) Increasing catecholamine doses were associated with increasing mortality, independent of effects on blood pressure.…”

Section: Adrenergic Overloadmentioning

confidence: 99%

Do we need an individual approach to atrial fibrillation and adrenergic overload in the critically ill?

2017

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Despite catecholamines being lifesaving drugs, they can also be harmful. Adrenergic overload is one of the major causes of supra-and ventricular arrhythmias, which induce haemodynamic instability of critically ill patients. In this paper we will focus on the pathophysiology of atrial fibrillation (AF), the importance of adrenergic overload for triggering AF, the importance of the autonomic nervous system and we will challenge the importance of decreasing adrenergic load with selective and nonselective β-blockers, which have different effects on the metabolism of the severely ill. We will also emphasize the importance of an individual approach due to pharmacogenetic differences in β-adrenergic signalling.

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Relative tachycardia in patients with sepsis: an independent risk factor for mortality

Abstract: Our data are compatible with the hypothesis that some patients with sepsis experience an excess activation of the sympathetic nervous system, leading to a fatal outcome.

Cited by 72 publications

References 14 publications

The reciprocal relationship between heme oxygenase and nitric oxide synthase in the organs of lipopolysaccharide-treated rodents

The reciprocal relationship between heme oxygenase and nitric oxide synthase in the organs of lipopolysaccharide-treated rodents

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Do we need an individual approach to atrial fibrillation and adrenergic overload in the critically ill?

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