β-Blockade in Subarachnoid Haemorrhage

To ask if the determination of central-nervous-system-derived catecholamine metabolites in peripheral circulation could be a useful index of brain dysfunction after subarachnoid hemorrhage, 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid concentrations in plasma, together with those of free catecholamines (noradrenaline, adrenaline, and dopamine), were serially measured for up to 3 weeks after the initiation of symptoms in 23 patients with aneurysmal subarachnoid hemorrhage as compared to 17 healthy and 9 patient controls. Catecholamines and their metabolites were determined by using high-performance liquid chromatography with electrochemical detection. Plasma 3-methoxy-4-hydroxyphenylethylenegtycol concentrations were markedly elevated in subarachnoid hemorrhage patients with coma compared to those without, and the maximal concentrations observed in comatose patients never occurred in normal subjects or in patients with other neurological disorders. The mean maximal plasma concentrations of free catecholamines did not differ significantly between the comatose and noncomatose groups. Combining 3-methoxy-4-hydroxyphenylethyleneglycol with homovanillic acid level data more clearly discriminated between the comatose and noncomatose subarachnoid hemorrhage groups. The results suggest that plasma concentration of 3-methoxy-4-hydroxyphenylethyleneglycol, a major metabolite of brain noradrenaline, can be a prognostic discriminator for patients with subarachnoid hemorrhage and its discriminating power can be strengthened by combining it with homovanillic acid data. (Stroke 1987;18:223-228) D URING the past decade, convincing evidence I has accumulated indicating that free 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), a major metabolite of brain noradrenaline, in the systemic circulation reflects a functional activity of noradrenergic neurons in the central nervous system (CNS).1 Free MHPG concentration in plasma is considered a reliable index of central noradrenergic turnover from the highly significant relation between plasma and brain levels in primates treated with drugs altering the central noradrenaline metabolism.2 In humans, a centrally acting a-adrenergic agonist, clonidine, is reported to reduce plasma MHPG level.3 Maas et al 4 have demonstrated that approximately 60% of total MHPG production in humans is derived from the brain, while others have indicated that the proportion may be lower because of the possible peripheral conversion of MHPG to vanillylmandelic acid.3 As well as of MHPG, plasma concentration of a major dopamine

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“…1931 - 32 This also supports our hypothesis. Monoaminergic function(s) in humans cannot be measured directly.…”

Section: Resultssupporting

confidence: 90%

Plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid concentrations in patients with subarachnoid hemorrhage.

Minegishi¹,

Ishizaki²,

Yoshida³

et al. 1987

Stroke

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“…Beta-blockade has been associated with improved outcomes after SAH 26,27 and traumatic brain injury, 28 perhaps by reducing adrenergic feedback to the central nervous system. 27 Coghlan et al 29 recently called for a reevaluation of therapeutic options to reduce heart rate in SAH patients after finding a relationship between tachycardia and poor outcome in the Intraoperative Hypothermia Aneurysm Surgery Trial.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Elevated Heart Rate is a Risk Factor for Adverse Cardiac Events and Poor Outcome after Subarachnoid Hemorrhage

Schmidt¹,

Crimmins²,

Lantigua³

et al. 2013

Neurocrit Care

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Introduction Sympathetic nervous system hyperactivity is common after subarachnoid hemorrhage (SAH). We sought to determine whether uncontrolled prolonged heart rate elevation is a risk factor for adverse cardiopulmonary events and poor outcome after SAH. Methods We prospectively studied 447 SAH patients between March 2006 and April 2012. Prior studies define prolonged elevated heart rate (PEHR) as heart rate >95 beats/min for >12 hours. Major adverse cardiopulmonary events were documented according to predefined criteria. Global outcome at 3 months was assessed with the modified Rankin Scale (mRS). Results 175 (39%) patients experienced PEHR. Nonwhite race/ethnicity, admission Hunt-Hess grade ≥4, elevated APACHE-2 physiological subscore, and modified Fisher score were significant admission predictors of PEHR, whereas documented pre-hospital beta-blocker use was protective. After controlling for admission Hunt-Hess grade, Cox regression using time-lagged covariates revealed that PEHR onset in the previous 48 hours was associated with an increased hazard for delayed cerebral ischemia, myocardial injury and pulmonary edema. PEHR was associated with 3-month poor outcome (mRS 4-6) after controlling for known predictors. Conclusions PEHR is associated with major adverse cardiopulmonary events and poor outcome after SAH. Further study is warranted to determine if early sympatholytic therapy targeted at sustained heart rate control can improve outcome after SAH.

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“…Indeed it has already been shown that propranolol prevents catecholamine-linked myocardial necrosis in SAH (Neil-Dwyer et al. 1978) and that the quality of survival in cases of SAH is improved (Neil-Dwyer et al. 1979).…”

Section: Discussionmentioning

confidence: 99%

Beta‐adrenoceptor blockers and the blood‐brian barrier.

Neil‐Dwyer¹,

Bartlett²,

McAinsh³

et al. 1981

Brit J Clinical Pharma

212

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1This study on 21 neurosurgical patients was set up to investigate the extent to which four chronically administered ,3-adrenoceptor blockers, propranolol, oxprenolol, metoprolol and atenolol, cross the blood-brain barrier and enter the cerebrospinal fluid (CSF) and brain tissue. The concentration in the CSF of the three lipophilic,/3-adrenoceptor blockers, propranolol, oxprenolol and metoprolol, approximated to the free drug concentration in the plasma, and was a poor predictor of brain concentration. These three lipophilic ,3-adrenoceptor blockers appeared in brain tissue at concentrations 10-20 times greater than that of hydrophilic atenolol. The approximate brain/plasma ratio for propranolol was 26, for oxprenolol 50, for metoprolol 12 and for atenolol 0.2. 2 The low concentration of atenolol in brain tissue is possibly responsible for the low incidence of central nervous system-related side effects in patients on this agent compared to lipophilic 3-adrenoceptor blockers.

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β-Blockade in Subarachnoid Haemorrhage

Cited by 7 publications

References 21 publications

Plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid concentrations in patients with subarachnoid hemorrhage.

Plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid concentrations in patients with subarachnoid hemorrhage.

Prolonged Elevated Heart Rate is a Risk Factor for Adverse Cardiac Events and Poor Outcome after Subarachnoid Hemorrhage

Beta‐adrenoceptor blockers and the blood‐brian barrier.

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