Norepinephrine and metaraminol in septic shock: a comparison of the hemodynamic effects

Natalini, Giuseppe; Schivalocchi, Valeria; Rosanò, Antonio; Taranto, Maria; Pletti, Cristina; Bernardini, Achille

doi:10.1007/s00134-005-2607-3

Cited by 33 publications

(33 citation statements)

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“…Metaraminol has also been in use for a long time to maintain MAP during subarachnoid anesthesia. Only recently, the effect of metaraminol was compared with norepinephrine in patients with septic shock (21). Because both agents perform similarly well in maintaining MAP, metaraminol could potentially be used as a salvage therapy in norepinephrine-resistant septic shock.…”

Section: Phenylephrine and Metaraminolmentioning

confidence: 99%

Approach to Hemodynamic Shock and Vasopressors

Herget–Rosenthal¹,

Saner²,

Chawla³

2008

Clinical Journal of the American Society of Nephrology

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H emodynamic shock (HS) is a clinical syndrome that is commonly observed in hospitalized patients. Prompt recognition and intervention are the cornerstones of mitigating the dire consequences of HS. Untreated HS usually leads to death. Unlike other types of clinical syndromes (e.g., chest pain), for which a clinical diagnosis is made before treatment is initiated in earnest, the treatment of shock often occurs concurrently or ahead of the diagnostic process. The maintenance of end-organ perfusion is critical to prevent irreversible organ injury and failure, and this frequently requires the use of fluid resuscitation and vasopressors. A complete review of all of the signs and symptoms, diagnosis, and treatment of HS has been reviewed in detail elsewhere (1). This article provides a concise summary of how to approach the patient in HS, diagnostic and therapeutic decision making, and the use of vasopressors. In addition, the effects of vasopressors on end organs with particular focus on renal hemodynamics is reviewed. Clinical Manifestations and Recognition of Hemodynamic ShockHS is classically described as "an acute clinical syndrome initiated by ineffective perfusion, resulting in severe dysfunction of organs vital to survival" (1). As clinicians, we take great pains to teach our trainees that shock is not just hypotension, but that shock represents hypoperfusion of end organs. This rationale leads to the common refrain: "Normotensive patients can often suffer from shock." The clinical manifestations of HS are related directly to the end organs that are not receiving adequate perfusion and can be categorized on the basis of the organ affected. Besides hypotension, the classic signs and symptoms of HS are tachycardia, relative hypotension (a decrease in baseline BP of 40 mmHg), tachypnea, cool and clammy extremities, oliguria, dysglycemia, and delirium (1). Patients who are hypotensive (systolic BP Ͻ90 mmHg in patients whose baseline BP is usually low) but show no signs or symptoms of shock should have their BP rechecked. An indwelling arterial catheter or Doppler may be necessary to resolve a false low BP reading (1). In the absence of hypotension, the diagnosis of HS can be more challenging and will require the clinician to increase his or her scrutiny of the patient and either rule in or rule out HS with further clinical investigations. For patients who are normotensive, the measurement of serum lactate will often reveal the presence of HS in a patient whose clinical evaluation is equivocal. This entity of a normotensive patient with some clinical signs of HS with an elevated lactate is often referred to as "cryptic shock." In this condition, the patient is not yet in critical condition but cannot meet their body's oxygen demand, resulting in evidence of significant anaerobic metabolism. Previous trials showed that presence of HS and a serum lactate concentration of Ͼ4.0 mmol/L are associated with a mortality of 30 to 45% (2).Once HS is recognized, interventions to restore tissue perfusion are mandatory. Three ...

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Section: Phenylephrine and Metaraminolmentioning

confidence: 99%

Approach to Hemodynamic Shock and Vasopressors

Herget–Rosenthal¹,

Saner²,

Chawla³

2008

Clinical Journal of the American Society of Nephrology

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“…However it is questionable whether the effects of pure α 1 ‐agonism are always beneficial in septic shock, again due to concerns regarding the effect of pure vasoconstrictor agents on microvascular flow. There is some limited data to suggest that metaraminol could be used as a vasopressor agent in septic shock (Natalini et al ., 2005). Because this agent may be administered via a peripheral vein as well as a central venous catheter, it has some application as a vasopressor in the early period of stabilization when a patient with haemodynamic shock is first identified but has yet to have a central venous catheter inserted.…”

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confidence: 99%

Use of inotropes and vasopressor agents in critically ill patients

Bangash

Kong

Pearse

2012

British J Pharmacology

165

138

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Inotropes and vasopressors are biologically and clinically important compounds that originate from different pharmacological groups and act at some of the most fundamental receptor and signal transduction systems in the body. More than 20 such agents are in common clinical use, yet few reviews of their pharmacology exist outside of physiology and pharmacology textbooks. Despite widespread use in critically ill patients, understanding of the clinical effects of these drugs in pathological states is poor. The purpose of this article is to describe the pharmacology and clinical applications of inotropic and vasopressor agents in critically ill patients. LINKED ARTICLESThis article is commented on by Bracht et al., pp. 2009 and De Backer and Scolletta, pp. 2012-2014 ]i, Intracellular calcium concentration; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; CPR, cardiopulmonary resuscitation; DO2, systemic oxygen delivery; GPCR, G-protein coupled receptor; GTP/GDP, guanosine triphosphate/diphosphate; PKA/PKC, protein kinase A/C; PLC, phospholipase C; SvO2, mixed/central venous oxygen saturation; TNF-a, tumour necrosis factor alpha; VO2, oxygen consumption IntroductionInotropes are agents administered to increase myocardial contractility whereas vasopressor agents are administered to increase vascular tone. The use of these potent agents is largely confined to critically ill patients with profound haemodynamic impairment such that tissue blood flow is not sufficient to meet metabolic requirements. Examples include patients with severe heart failure and septic or cardiogenic shock, as well as patients undergoing major surgery and victims of major trauma. They are generally administered via a large central vein and, in some specific situations, via a peripheral vein. These agents have a diverse range of actions including metabolic and immune effects, many of which are poorly understood. The objective of this review is to describe the underlying cardiovascular mechanisms that clinicians seek to influence through the use of inotropic agents, to describe the basic pharmacology of those drugs in common use and, finally, to explore the evidence base for specific approaches to inotrope and vasopressor therapy in clinical practice. As many of the commonly used agents exert both inotropic and vasopressor effects, the term 'inotrope' will be generally used in this review to describe agents with a spectrum of actions. The physiological basis for the actions of inotropic agentsMyocyte excitation and contraction. Cardiac muscle fibres contract through the sliding filament mechanism. Actin and myosin filaments are propelled past each other through repeated cross-bridge linking and unlinking. Each cardiac action potential results in the opening of voltage-gated myocyte calcium channels and a rise in intracellular calcium concentration ([Ca 2+ ]i). This triggers a further release of calcium from the sarcoplasmic reticulum, which accounts for around three quarters of the total increase in [Ca 2+ ]i (Levick, 2003...

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“…To our knowledge, no formula for such dose conversion exists, potentially because of there being no relationship between doses of metaraminol and noradrenaline. 71 As a pragmatic trial that uses an efficient design and parsimonious data set, no mechanistic data were collected, which meant that the attributable mortality could not be adjudicated. In addition, we did not carry out an integrated process evaluation, which could have provided additional contextual factors around clinician and team behaviour.…”

Section: Limitationsmentioning

confidence: 99%

Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill people aged 65 and over: the 65 RCT

Mouncey

Richards-Belle

Thomas

et al. 2021

Health Technol Assess

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Background Vasopressors are administered to critical care patients to avoid hypotension, which is associated with myocardial injury, kidney injury and death. However, they work by causing vasoconstriction, which may reduce blood flow and cause other adverse effects. A mean arterial pressure target typically guides administration. An individual patient data meta-analysis (Lamontagne F, Day AG, Meade MO, Cook DJ, Guyatt GH, Hylands M, et al. Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock. Intensive Care Med 2018;44:12–21) suggested that greater exposure, through higher mean arterial pressure targets, may increase risk of death in older patients. Objective To estimate the clinical effectiveness and cost-effectiveness of reduced vasopressor exposure through permissive hypotension (i.e. a lower mean arterial pressure target of 60–65 mmHg) in older critically ill patients. Design A pragmatic, randomised clinical trial with integrated economic evaluation. Setting Sixty-five NHS adult general critical care units. Participants Critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension. Interventions Intervention – permissive hypotension (i.e. a mean arterial pressure target of 60–65 mmHg). Control (usual care) – a mean arterial pressure target at the treating clinician’s discretion. Main outcome measures The primary clinical outcome was 90-day all-cause mortality. The primary cost-effectiveness outcome was 90-day incremental net monetary benefit. Secondary outcomes included receipt and duration of advanced respiratory and renal support, mortality at critical care and acute hospital discharge, and questionnaire assessment of cognitive decline and health-related quality of life at 90 days and 1 year. Results Of 2600 patients randomised, 2463 (permissive hypotension, n = 1221; usual care, n = 1242) were analysed for the primary clinical outcome. Permissive hypotension resulted in lower exposure to vasopressors than usual care [mean duration 46.0 vs. 55.9 hours, difference –9.9 hours (95% confidence interval –14.3 to –5.5 hours); total noradrenaline-equivalent dose 31.5 mg vs. 44.3 mg, difference –12.8 mg (95% CI –18.0 mg to –17.6 mg)]. By 90 days, 500 (41.0%) patients in the permissive hypotension group and 544 (43.8%) patients in the usual-care group had died (absolute risk difference –2.85%, 95% confidence interval –6.75% to 1.05%; p = 0.154). Adjustment for prespecified baseline variables resulted in an odds ratio for 90-day mortality of 0.82 (95% confidence interval 0.68 to 0.98) favouring permissive hypotension. There were no significant differences in prespecified secondary outcomes or subgroups; however, patients with chronic hypertension showed a mortality difference favourable to permissive hypotension. At 90 days, permissive hypotension showed similar costs to usual care. However, with higher incremental life-years and quality-adjusted life-years in the permissive hypotension group, the incremental net monetary benefit was positive, but with high statistical uncertainty (£378, 95% confidence interval −£1347 to £2103). Limitations The intervention was unblinded, with risk of bias minimised through central allocation concealment and a primary outcome not subject to observer bias. The control group event rate was higher than anticipated. Conclusions In critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension, permissive hypotension did not significantly reduce 90-day mortality compared with usual care. The absolute treatment effect on 90-day mortality, based on 95% confidence intervals, was between a 6.8-percentage reduction and a 1.1-percentage increase in mortality. Future work Future work should (1) update the individual patient data meta-analysis, (2) explore approaches for evaluating heterogeneity of treatment effect and (3) explore 65 trial conduct, including use of deferred consent, to inform future trials. Trial registration Current Controlled Trials ISRCTN10580502. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 14. See the NIHR Journals Library website for further project information.

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Norepinephrine and metaraminol in septic shock: a comparison of the hemodynamic effects

Abstract: This study shows that metaraminol increases arterial pressure as does norepinephrine in septic shock patients. Despite similar effects of norepinephrine and metaraminol, there was no relationship between the dose of the two drugs.

Cited by 33 publications

References 20 publications

Approach to Hemodynamic Shock and Vasopressors

Approach to Hemodynamic Shock and Vasopressors

Use of inotropes and vasopressor agents in critically ill patients

Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill people aged 65 and over: the 65 RCT

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