Effect of mannitol on regional cerebral blood flow in patients with intracerebral hemorrhage

doi:10.1016/j.jns.2004.05.019

Journal of the Neurological Sciences

Volume 224, Issues 1–2, 15 September 2004, Pages 19-22

https://doi.org/10.1016/j.jns.2004.05.019 Get rights and content

Abstract

Aim

To evaluate the regional cerebral blood flow (rCBF) changes following IV mannitol bolus in patients with intracerebral hemorrhage (ICH).

Methods

In a hospital based randomized placebo controlled study, 21 CT proven ICH patients with Glasgow coma scale (GCS) score of 5 or more were subjected to clinical evaluation including GCS and Canadian Neurological stroke (CNS) scale. Cranial SPECT study was undertaken before and 60 min after 20% mannitol 100 ml IV in 20 min or sham infusion. The SPECT images were semi-quantitatively analyzed and asymmetry index of basal ganglia, frontal, parietal and occipital regions were calculated.

Results

There were 12 patients in mannitol and nine in control group who were evenly matched for age, mean arterial blood pressure, GCS score and size of hematoma. Only one patient died in mannitol group. Following mannitol, GCS score improved in six, worsened in two and remained unaltered in four patients. In the control group, GCS improved in seven, worsened in none and was unchanged in two patients. SPECT studies revealed reduction in asymmetry index in basal ganglia in four, frontal region in six, parietal in four and occipital region in five patients in mannitol group. In control group, asymmetry index was reduced in basal ganglia in one, frontal and parietal region in three each and occipital region in five patients. These differences between control and study group were not significant.

Conclusion

Mannitol does not seem to significantly change the regional cerebral blood flow (rCBF) in ICH patients as evaluated by SPECT study.

Introduction

In the acute stage, stroke-related mortality is attributed to brain herniation. Raised intracranial pressure (ICP) results in cerebral blood flow alterations, which may even result in brain infarction. Lowering the intra cranial pressure is crucial for the management of acute stroke. Mannitol has been used in the management of acute stroke since long time. American Heart Association has recommended it for the management of spontaneous intracerebral hemorrhage (ICH) with type B ICP waves, progressively increasing ICP and clinical deterioration due to mass effect [1]. About 70% of physicians in China use mannitol or glycerol in acute stroke [2]. Mannitol is also used routinely in several European centers and is listed amongst the therapeutic interventions in the consensus statement of Hungarian stroke society for the patients where raised ICP is proven in stroke [3]. A survey of prescribing pattern of anti edema measure in stroke in Indian physicians and neurologists revealed its universal use [4]. In spite of this widespread use, there is limited scientific information available regarding its benefit and the possible mechanism in stroke. In a study on six patients with acute middle cerebral arterial infarction and CT evidence of midline shift, the effect of intravenous bolus of mannitol was evaluated. At 50–55 min after the baseline scan, total brain volume significantly decreased but the non-infarcted hemisphere shrank more than the infarcted one [5]. Cochrane review has shown that 34% of control and 33% in mannitol group improved, whereas patients who worsened were 44% in each group. Neither beneficial nor harmful effect of mannitol could be found in this review [6]. SPECT studies provide a semi quantitative measure of blood flow changes to monitor the effect the mannitol in ICH. We have not found such a study in the available medical literature. The present study aims at evaluating the effect of IV mannitol bolus on cerebral blood flow and compare it with a sham infusion.

Section snippets

Subject and methods

The patients with CT proven ICH within 6 days of ictus (mean 2.5, range 1–6 days) were enrolled based on the availability of radiotracer and considered clinically suitable (Glasgow coma scale (GCS) score at least 5 or more) for SPECT study. This study was approved by the ethical committee of our institute. All the patients underwent neurological evaluation. Consciousness was evaluated by GCS and severity of stroke by the Canadian Neurological scale score [7]. Presence of hyperventilation,

Results

Twenty-nine patients were randomized in study (15) and control (14) group. Out of them, eight patients (three study and five control) were excluded because of unsatisfactory SPECT images. The clinical and radiological parameters of control and study groups are summarized in Table 1. The surrogate markers of raised intracranial pressure such as hyperventilation was present in nine, midline shift on CT scan in 12, pupillary asymmetry in one and motor dysfunction on nonhemiplegic side in eight

Discussion

This study shows that mannitol therapy does not significantly change the rCBF as assessed by SPECT in patients with ICH. The lack of change in blood flow was also supported by lack of insignificant difference in GCS between the two groups. Majority of our patients had medium or small size hematoma because the patients with large hematoma were too sick to undergo SPECT study. We had therefore randomized those patients who were considered suitable for SPECT study.

Our results are in agreement with

Acknowledgements

We gratefully acknowledge the help of Dr. S.K. Mandal, Central Drug Research Institute, Lucknow for statistical analysis and Rakesh Kumar Nigam for the preparation of the manuscript.

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The Effect of Mannitol in the Early Stage of Supratentorial Hypertensive Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis
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However, some limitations existed in these studies: 1) the included studies were incomplete; 2) the judgment of study types for some included studies was incorrect; and 3) the outcomes for the comparison between the mannitol and nonmannitol groups were limited. A recent review15 from the Cochrane Library included 3 randomized controlled trials (RCTs)17-19 to test the effect of mannitol in the acute stroke (ischemic stroke and nontraumatic intracerebral hemorrhage), but it did not find enough evidence to decide whether the routine use of mannitol in acute stroke would result in any beneficial or harmful effect. Therefore, we included all relevant RCTs and observational studies (OSs) and conducted this meta-analysis comprehensively to evaluate the effect of mannitol in the early stage of HICH.
Mannitol has been widely applied as a priority drug in the clinical treatment for brain edema and increased intracranial pressure after intracerebral hemorrhage. However, no consensus on the efficacy and safety of mannitol has been achieved. Our meta-analysis was conducted to assess the effect of mannitol in the early stage of supratentorial hypertensive intracerebral hemorrhage (HICH) and provided a treatment reference for clinicians.
All relevant studies on mannitol treatment of supratentorial HICH were identified from the databases including PubMed, EMBASE, Cochrane Library, VIP, CNKI, and Wan Fang. Our outcome measures included the incidence of hematoma enlargement, the neurologic function improvement rate, mortality, and the incidence of aggravated brain edema. The subgroup analysis was performed to explore the impact of study type, year of publication, intervention time, and dose on the outcome measures. Publication bias was assessed by the funnel plot.
Thirty-four studies consisting of 3627 patients with supratentorial HICH were included in this study (from 2000 to 2018). Significant statistical difference was found between the mannitol and nonmannitol group in terms of all the outcome measures, including the incidence of hematoma enlargement (P < 0.00001), the neurologic function improvement rate (P < 0.00001), mortality (P < 0.00001), and the incidence of aggravated cerebral edema (P = 0.0002). In subgroup analysis, the results showed that study type and intervention time did not significantly affect the outcome measures. No significant statistical difference was found in the subgroups of publication time (after 2010) (P = 0.08) and half-dose of mannitol (P = 0.20) on mortality. In addition, the further analysis showed that whatever the dose (250 mL or 125 mL) and intervention time (<24, <12, or <6 hours), mannitol could lead to hematoma enlargement.
For patients without obvious symptoms of intracranial hypertension or cerebral palsy, it is not recommended to use mannitol routinely in the early stage of supratentorial HICH. More high-quality trials should be included to confirm our conclusion and to ascertain the best time and dose of mannitol to use.
Intracerebral Hemorrhage: A Common and Devastating Disease in Need of Better Treatment
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Citation Excerpt :
Unfortunately, INTERACT II failed to demonstrate a reduced rate of death or major disability with aggressive blood pressure management. Furthermore, trials of aggressive medical management of cerebral edema with mannitol have also failed to demonstrate any clinical benefit (10, 22, 33). Further complicating matters, there are limited data on the natural history of varying sizes of ICH with or without mass effect and midline shift, which limits our treatment decisions.
To review the poor natural history of intracerebral hemorrhage (ICH), current treatment options for ICH, discuss ongoing trials evaluating minimally invasive techniques for clot evacuation, and offer future directions of investigation for the management of this devastating disease.
A selective review of recent trials regarding treatment of ICH was performed.
Completed trials of medical and surgical management are reviewed. The supportive research for clot evacuation to limit secondary injury is surveyed. We also provide a comprehensive discussion of current data evaluating minimally invasive techniques to achieve clot removal, including Minimally Invasive Surgery plus tPA for ICH Evacuation (MISTIE), Clot Lysis: Evaluating Accelerated Resolution (CLEAR), and endoscopic evacuation.
We encourage the neurosurgical community to pursue improved therapies for ICH.
New minimally invasive treatments for ICH are being developed.
Treatment of ICH is an important area of research and should continue to be aggressively pursued because of the significant societal burden and poor outcomes associated with ICH.
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We report clinical and MRI findings of 17 patients with oromandibular dystonia (OMD) due to Japanese encephalitis (14) and nonspecific encephalitis (3). Their median age was 14(2–53) years and 9 were females. 8 patients had jaw open and 9 jaw close OMD. The severity ranged between 2 and 4 on a 0–4 scale, 11 patients were anarthric and needed tube feeding. Cranial MRI was abnormal in 13 patients; the abnormalities were in thalamus in 9, substantia nigra in 10, caudate in 3, globus pallidus and putamen in 2 each and pons in 1 patient. SPECT revealed hypoperfusion in thalamus in 4, basal ganglia in 1, frontal in 6, parietal in 3 and temporal in 1 patient. By 6 months, OMD regressed completely in 6, by 1 grade in 2 and remained unchanged in 7 patients. OMD in encephalitis is mainly due to JE and half of these patients improve.
Acute Hemorrhagic Stroke Pathophysiology and Medical Interventions: Blood Pressure Control, Management of Anticoagulant-Associated Brain Hemorrhage and General Management Principles
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Osmotic agents, such as mannitol and hypertonic saline (3%–23.4%) are often used to treat elevated ICP. Mannitol is an osmotically active agent that increases diuresis and lowers the ICP by drawing fluid from edematous and nonedematous brain tissue; however, single-photon emission computed tomography studies did not show evidence of regional CBF changes after mannitol infusion in ICH patients [94]. It has been proposed that by decreasing the blood viscosity, mannitol may cause reflex vasoconstriction and lower the cerebral blood volume [95].
Nontraumatic intracerebral hemorrhage is a neurologic emergency that accounts for about 10% to 20% of all strokes. Few patients suffering from intracerebral hemorrhage are expected to be independent 6 months after the event. This article reviews the pathophysiology and general medical management principles of spontaneous intracerebral hemorrhage, including the acute management of elevated blood pressure and management of anticoagulant-associated intracerebral hemorrhage.
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2009, The Lancet
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Intensive care leading to controlled cerebral perfusion pressure of 50–70 mm Hg might improve outcome.83 Two randomised trials showed no benefit on regional cerebral blood flow, neurological improvement, mortality, and functional outcomes from regular use of intravenous mannitol boluses.84–87 Therefore, only short-term use of mannitol in patients with intracerebral haemorrhage under special circumstances, such as transtentorial herniation or acute neurological deterioration associated with high intracranial pressure or mass-effect, should be considered.
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Acute intracranial hemorrhage and intraventricular hemorrhage are devastating disorders. The goal of this review is to familiarize clinicians with recent information pertaining to the acute care of intracranial hemorrhage and intraventricular hemorrhage.
PubMed search and review of the relevant medical literature.
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Effect of mannitol on regional cerebral blood flow in patients with intracerebral hemorrhage

Abstract

Aim

Methods

Results

Conclusion

Introduction

Section snippets

Subject and methods

Results

Discussion

Acknowledgements

J. Stroke Cerebrovasc. Dis.

Guidelines for the management of intracerebral haemorrhages: a statement for health care professional from a special writing group of stroke council, American Heart Association

Stroke

Consensus for the treatment of cerebrovascular disorders: prevention, diagnostics, acute treatment, early rehabilitation

Agyerbetegsegek

Prescribing pattern of antiedema therapy in stroke by neurologist and general physicians in India

Neurol. India

Mannitol bolus preferentially shrink non infracted brain in patients with ischemic stroke

Neurology

Cochrane report: a systemic review of mannitol therapy for acute stroke and cerebral parenchymal hemorrhage

Stroke