From Dr. S (RMO): Thank you for your explanation about Ondansetron!
I have another question for you. Recently, a (previously fit) young male was admitted to Emergency unit with nausea all the time and had a frequent small amount of vomiting. The investigations revealed multiple brain cancer mass (new diagnosis). We tried different anti-emetic drugs but not very helpful. We gave Metoclopramide inj 10mg stat, and then, we gave 8 hourly.
As vomiting persists, we tried Prochlorperazine (Stemetil) 5mg and later Ondansetron 4mg tds. Our local medical team reviewed and gave 8mg dexamethasone sc stat. His nausea reduced to some extent after 4 hours. Next day, we transferred this patient to Launceston GH for further management / radiotherapy.
How do we manage this symptom?
You make your differential diagnosis from the history and examinations, then, eliminate your differential diagnosis one by one through investigations (blood / radiology). Here… you found Brain metastasis (a new diagnosis).
I presume that you are not sure whether this is primary cancer (?GBM) or unknown primary with secondaries in the brain.
Q-1) Why are brain tumours causing nausea and vomiting?
The increase ICP with Brain Oedema stimulates the vomiting centre in the brainstem ==> N & V
(Q- 2) How Brain Cancer mass causes Oedema? ( What is the Theory behind this pathology?)
The blood–brain barrier (BBB) is formed by of tight junctions in the endothelium of brain vessels & thick basal lamina surrounding the external face of the capillary & feet of astrocytes. It separates circulating blood and cerebrospinal fluid (CSF) in the brain.
Physical barrier; system of cellular transport mechanisms; maintains homeostasis (restrict entrances of harmful chemicals from the blood, and allowing entrance of essential nutrients)
Cancerous glial cells of the brain can increase secretion of vascular endothelial growth factor (VEGF), which weakens the junctions of the blood brain barrier. Then, the vaso-genic oedema occurs due to a breakdown of the tight endothelial junctions and allows intravascular proteins and fluid to penetrate into the parenchymal extracellular space.
Dexamethasone found to be of benefit in reducing VEGF secretion. (Clinically, dexamethasone reduces brain tumour-associated vascular permeability through poorly understood mechanisms).
(1) The management of brain edema in brain tumors
by Evert C.A. Kaal and Charles J. Vecht.
Current Opinion in Oncology 2004, 16:593–600
(2) Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats; Involvement of the glucocorticoid receptor and vascular permeability factor
J D Heiss, E Papavassiliou, M J Merrill, L Nieman, J J Knightly, S Walbridge, N A Edwards, E H Oldfield
J Clin Invest. 1996; 98(6):1400–1408 doi:10.1172/JCI118927
(Q- 3) How to manage this symptom (N &V) in the DEM / Medical ward?
The drugs used in this situation:
(a) We use ‘high dose steroid trial’ to reduce the peri-tumour oedema in the brain. This will reduce the intra-cranial pressure to some extent. ==> My drug of choice is Dexamethasone. (Reasons: Dexamethasone is more potent than Prednisolone and available in injectable form).
Either we can give Dexamethasone 8mg PO/SC BD (morning and mid-day) or Dexamethasone 16mg in the syringe driver over 1 hour daily
==> Five to seven day – Trial (we will see the clinical response at least by 5th day) and then, trying to tail off the dose to the lowest possible to avoid serious side effects such as myopathy or diabetes.
* Higher doses of dexamethasone (16 mg/day), sometimes together with osmotherapy (mannitol, glycerol) or surgery, may be used in (rare) emergency situations. On tapering, one should be aware of the possible development of corticosteroid dependency or withdrawal effects.
(b) Vomiting Centre in the brain is affected here…. Therefore, we have to select the anti-emetic acting on the vomiting centre. ==> My drug of choice is Cyclizine
(Mode of action: Cyclizine decrease the excitability of the inner-ear labyrinth and block conduction in the vestibular-cerebellar pathways as well as acting directly on the vomiting centre in the brain stem).
Either we can give
Cyclizine 50mg SC/PO stat & bd – tds or
Cyclizine 50mg SC 150mg /24h in the Syringe driver
Alternative 1st line drug:
** Haloperidol is used in some Pal. care centres
Either Haloperidol 1 – 1.5mg sc prn or 2.5 – 3mg in the S /driver over 24h
This is a D2 – antagonist (selective dopaminergic agent) act on CTZ
2nd Line drug: (patient has more cerebral irritation / agitation as well)
Levomepromazine Inj 5 -6.25mg sc prn or 6.25 to 12.5mg sc in the
S/driver over 24 hours
New Research work on the following Therapies:
Novel therapies include vascular endothelial growth factor receptor inhibitors (VEGF -Inhibitor) and Corticotropin-releasing factor (crf), which should undergo further clinical testing before they can be recommended in practice (from the above-mentioned References)
Although you found a reason for his nausea and vomiting (increased intracranial pressure), you have to look for other reasons…. as a routine! Usually, the cause for nausea & vomiting is multifactorial in palliative care population. Always keep an open mind and not to close the symptom management plans with your 1st confirmed diagnosis!
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