Does intravenous mannitol improve outcome in cerebral malaria? | Archives of Disease in Childhood

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Does intravenous mannitol improve outcome in cerebral malaria?

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Intravenous mannitol should not be routinely recommended for cerebral malaria
Sudhir Kumar
Published on: 22 March 2016
Authors Reply
Richard J Tomlinson
Published on: 22 March 2016

Published on: 22 March 2016
Intravenous mannitol should not be routinely recommended for cerebral malaria
- Sudhir Kumar, Consultant Neurologist
Dear Editor
I read with great interest the recent article by Tomlinson et al.[1] Authors feel that intravenous mannitol may improve the outcome in patients with cerebral malaria, though there are no randomized controlled trials on the subject. However, I would like to make certain observations.
Cerebral oedema in cases of cerebral malaria is often multifactorial.[2] Main pathogenic mechanisms includ...
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Dear Editor
I read with great interest the recent article by Tomlinson et al.[1] Authors feel that intravenous mannitol may improve the outcome in patients with cerebral malaria, though there are no randomized controlled trials on the subject. However, I would like to make certain observations.
Cerebral oedema in cases of cerebral malaria is often multifactorial.[2] Main pathogenic mechanisms include cytoadherence of parasitized erythrocytes to the endothelium (mechanical hypothesis), and neuronal injury by malarial toxin and excessive cytokine (tissue necrosis factor- alpha) production (cytotoxic hypothesis).[3] The cytotoxic hypothesis seems to be the most important factor, which in turn may get triggered by the sequestration of parasites. Several associated systemic complications such as hypoglycemia, hypovolemia, hyperpyrexia, renal failure, and lactic acidosis may contribute to the pathogenesis of cerebral oedema. Recurrent seizures that occur commonly in cerebral malaria could also cause a worsening of cerebral oedema.
Brain imaging studies in cerebral malaria have demonstrated an increased brain volume, which has been thought to be secondary to sequestration of parasitized erythrocytes and compensatory vasodilatation rather than from edema.[4] Other imaging studies[5] have demonstrated, in addition to brain swelling, widespread low-density areas suggestive of ischaemic damage. The patterns of damage were consistent with a critical reduction in cerebral perfusion pressure, hypoglycaemia, or status epilepticus.
Mannitol acts by causing a plasma expansion, thereby increasing the cerebral blood flow (CBF). In addition, mannitol may cause cerebral vasodilatation. Increased CBF and vasodilatation may worsen cerebral oedema as mentioned earlier. Furthermore, mannitol is contraindicated in hypovolemia, renal failure, and pulmonary edema; which are common complications seen in cerebral malaria.
In view of the above, mannitol should not be used routinely but may be used in emergency situations for rapid lowering of raised intracranial pressure (ICP). It is important not to discontinue mannitol abruptly as it may lead to a rebound intracranial hypertension. Another method that could be used to rapidly lower the ICP is mechanical ventilation (hyperventilation)-induced hypocapnia. Vasoconstriction caused by hypocapnia helps in reducing the ICP. This method is also avoided long- term as prolonged vasoconstriction may lead to reduced cerebral perfusion, thereby worsening the cerebral ischaemia, as noted earlier.
Additionally, other factors, which may contribute to cerebral oedema such as hyperpyrexia, hypovolemia, seizures, hypoglycaemia, renal failure and lactic acidosis, should be identified and promptly treated.
In conclusion, mannitol cannot be routinely recommended for lowering ICP in cases of cerebral malaria. Adequate treatment for lowering ICP in cerebral malaria would include mechanical-ventilation-induced hypocapnia, judicious use of mannitol and treatment of precipitating factors.
References
(1) Tomlinson RJ, Morrice J. Does intravenous mannitol improve outcome in cerebral malaria? Arch Dis Child 2003; 88: 640-641.
(2) Garg RK. Cerebral malaria. J Assoc Physicians India 2000; 48:1004-13.
(3) Gachot B, Vachon F. Physiopathology of cerebral malaria. Presse Med 1995; 24:642-6.
(4) Looareesuwan S, Wilairatana P, Krishna S, et al. Magnetic resonance imaging of the brain in patients with cerebral malaria. Clin Infect Dis 1995;21:300-9.
(5) Newton CR, Peshu N, Kendall B, et al. Brain swelling and ischaemia in Kenyans with cerebral malaria. Arch Dis Child 1994; 70: 281-7.
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Conflict of Interest:
None declared.
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Published on: 22 March 2016
Authors Reply
- Richard J Tomlinson, Paediatrician
Dear Editor
Sudhir Kumar writes an excellent review of the likely pathology of cerebral malaria.[1] They state that Mannitol should not be used routinely, an opinion with which I agree. They say however, it should be used judiciously, but on what evidence do they make this summation, and on what clinical indication? I assume this opinion is based on clinical experience. It was anecdotal evidence that led me to searc...
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Dear Editor
Sudhir Kumar writes an excellent review of the likely pathology of cerebral malaria.[1] They state that Mannitol should not be used routinely, an opinion with which I agree. They say however, it should be used judiciously, but on what evidence do they make this summation, and on what clinical indication? I assume this opinion is based on clinical experience. It was anecdotal evidence that led me to search the literature and submit the published article. The evidence for if, and when, to use Mannitol is lacking, so in the meantime it cannot be recommended, judiciously or otherwise.
Reference
(1) Kumar S. Intravenous mannitol should not be routinely recommended for cerebral malaria [electronic response to Tomlinson RJ and Morrice J, Does intravenous mannitol improve outcome in cerebral malaria?] archdischild.com 2003 http://adc.bmjjournals.com/cgi/eletters/archdischild;88/7/640#496
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Conflict of Interest:
None declared.
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