Breakthrough Seizure Secondary to
Hypocalcaemia in an Adolescent with Chronic
Kidney Failure: A Case Report
School of Pharmacy, International Medical University, Malaysia
Submission: December 04, 2018; Published: December 17, 2018
*Corresponding author: Yeevon Poh, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia
How to cite this article: Yeevon Poh. Breakthrough Seizure Secondary to Hypocalcaemia in an Adolescent with Chronic Kidney Failure: A Case
Report. J Anest & Inten Care Med. 2018; 8(1): 555729. DOI:: 10.19080/JAICM.2018.08.555729
Introduction: Epilepsy is the third most common neurological disorder worldwide, following stroke and Alzheimer’s disease. Generally, the recommended effective dose of anticonvulsants was enough in attaining seizure control in 70-80% of the patients. However, there are also occasions where patients who are on stable regimen of anticonvulsants associated with breakthrough seizure either induced directly by hypocalcaemia or resulting from chronic kidney failure induced hypocalcaemia. Current paper presents the therapeutic approach for breakthrough seizure secondary to hypocalcaemia in the case of an adolescent with chronic kidney failure.
Case narrative: An epileptic male adolescent was admitted due to fitting lasted for 1 minute, followed by postictal drowsiness. Laboratory tests revealed optimal therapeutic range of Sodium Valproate serum concentration, but low serum calcium level. Hence, calcium replacement therapy was given as the main management plan.
Discussion: It is recommended that hypocalcaemia with neurological manifestations, without the underlying cause, should be managed with parenteral calcium. In chronic kidney failure patient, oral calcium and vitamin D should be started as soon as practical and maintained even after discharged. Whereas, anticonvulsants should be reserved only for persistent seizure even after correction of calcium level.
Conclusion: The management of breakthrough seizure should be individualised depending on clinical data and general condition of the patients.
Seizure is characterised by an abrupt intense electrical impulse outburst in the brain, which begins with a small number of neuron fire abnormalities, followed by the breakdown of normal membrane conductance’s and inhibitory synaptic currents . The excitability is then spread locally (focal seizure) or more widely (generalised seizure) [1,2]. Whereas for epilepsy, it is considered only when involving synchronisation of excessive neuronal firing [1-3]. A basic assumption in epilepsy research proposed that the chronic recurrent paroxysmal changes of neuronal activity are generally arisen from an imbalance between g-aminobutyric acid (GABA)-mediated inhibitory and glutamate-medicated excitatory neurotransmission in favour at the latter. [3,4] Therefore, most of antiepileptic drugs work by hindering the metabolism of GABA or exhibiting GABA mimetic effect [1,4]. However, there are still chances where epileptic patient exhibits seizure activity despite, he/she is on a stable regimen of antiepileptic drugs.
This phenomenon is typically defined as breakthrough seizure. It is shown to frequently exhibit in patients with predisposing endocrinological abnormalities or renal insufficiency with overall poor calcium homeostasis [5-7].
Globally, an estimated 50 million people are diagnosed with epilepsy, making it one of the most common neurological diseases worldwide and 80% of them live in developing countries including Malaysia . However, the understanding and attitudes towards epilepsy in Malaysia are still unsatisfied, whereby it is often recognised as condition due to mythic causes, such as demonic possession . Generally, it is estimated that epilepsy occurs in up to about 1% of the total Malaysia population . The current paper focuses on the treatment approach for the case of a Malaysian adolescent presented with breakthrough seizures secondary to hypocalcaemia.
A 13-year-old Malay male patient (height /weight =
155cm/45kg, calculated BMI=18.7kg/m2), with 3 years’ history
of peritoneal dialysis presented following a sudden episode of
fitting during sleep. He was referred to current hospital due to
uncontrolled hypertension. The episode of breakthrough seizures
lasted for 1 min, followed by postictal drowsiness. During
the seizure, there was loss of consciousness with consecutive
muscular contractions and relaxation. However, no trauma such
as a fall or impact took place. Before admission, he was on Tab.
Sodium Valproate 200mg TDS for epilepsy and claimed that he
was compliant with the medication. Besides, he gave a history
of pelvic fracture two years ago due to seizure and orthopaedic
follow up was scheduled on next week.
He had been diagnosed with end-stage renal failure (ESRF)
and hypertension since 2015. Tab Calcium Carbonate 2g TDS and
Tab. Zincofer (contains ferrous fumarate 300mg, folic acid 1mg,
vitamin B6 1.5mg, vitamin B12 5mcg, ascorbic acid 75mg, zinc
sulphate monohydrate 55mg) I/I OD were given to the patient as
the management of chronic kidney disease (CKD), whereas Tab.
Prazosin 2mg TDS, Tab.Telmisartan 80mg OD, Tab.Perindopril
8mg OD and Tab.Bisoprolol 10mg OD were prescribed for the
management of hypertension. He claimed that he generally
compliant with the medications, except Tab.Calcium Carbonate and Tab.Zincofer as he erroneously thought that they are merely
supplements. Other than that, he does not take any supplements
or herbal products. His clinical history was negative in terms of
steroid use, alcohol and tobacco consumption. He does not have
any known drug allergy and family history of related illness 
Urea level, serum creatinine and creatinine clearance of the
patient was out of range because he is diagnosed with end-stage
renal failure (Stage 5 of Chronic Kidney Disease). Decreased renal
phosphate excretion is commonly reported in patient with severe
kidney failure. By precipitating calcium, decreasing vitamin D
production, and interfering with PTH-mediated bone resorption,
hyperphosphatemia can cause hypocalcaemia. That why, oral
calcium, which acts as the phosphate binder is often prescribed to
patient with chronic kidney disease [12,13] (Table 2).
Higher readings of Alkaline Phosphatase (ALP), alanine
aminotransferase (ALT) and low albumin levels suggesting
abnormality of liver tissue, liver disease or bile duct blockages
 (Table 3). Therefore, further investigation should be
recommended to the patient to assess the risk of liver impairment.
Following admission to previous hospital, patient’s blood was
sampled for Sodium Valproate serum concentration monitoring
and optimal therapeutic range of 51mcg/ml Sodium Valproate
serum concentration (Target range: 50-100mcg/ml)  was
reported. Considering that his clinical response was satisfied with
minimal risk of adverse drug reaction, he was continued with Tab.
Sodium Valproate 200mg TDS. Whereas, his Blood Urea Serum
Electrolyte (BUSE) profile demonstrated serum total calcium
level of 1.32mmol/L (normal: 2.1-2.6 mmol/L). Thus, IV Calcium
Gluconate 10% in 10mL was given as initial management of
breakthrough seizure secondary to hypocalcaemia.
However, only slight increment of 0.07mmol/L in serum
calcium level was noted following admission to current hospital.
As the level dropped on the next morning, patient was started on
IV Calcium Gluconate 4 amp in 100cc normal saline over 4 hours
and Tab.Calcium Carbonate 3g TDS. IV Calcium Gluconate 1 amp
in 100cc NS was administered 5 hours later due to insufficient
increment of serum calcium level. On the following day of admission, patient was continued with oral calcium and started
on vitamin D therapy. As a result, patient appeared fit free and
his neurological assessment reviewed normal, despite the serum
calcium level remained out of range (1.79mmol/L on the day of
discharge). He was discharged on the 6th day of admission and,
to the best of our knowledge, has been counselled regarding the
rationale of taking daily calcium and vitamin D supplementation.
Follow up was scheduled 1 week after the date of discharge (Table
4) (Figure 1).
Hypocalcemia is a condition arises by reducing serum
ionised calcium concentration (normal: 2.1-2.6 mmol/L) .
The common hypocalcaemia neurological manifestations include
delirium, tetany and seizure, indicating a role of hypocalcaemia
in causing neurological abnormalities [5,15,16]. Studies
suggested that from inducing neurotransmitters release, to the
electrical mechanical coupling in the myocyte, almost every step
in the neuromuscular function is predicated on calcium [5,17].
Therefore, management in cases of hypocalcaemia seizures has
universally comprised of calcium replacement with or without
Generally, an acute symptomatic hypocalcaemia case involving
cardiovascular and neuromuscular systems (paraesthesia’s,
irritability, seizures, hypotension, and myocardial depression
etc) signals the requirement of intravenous calcium [15,16,20].
Most reviews advocate the use of IV Calcium Gluconate 10%
in 10mL over 10 minutes as initial management [11,15,20].
Due to lower risk of extravasation induced tissue necrosis, it is
preferred to Calcium Chloride . Even so, it is advised that
the administer should be done slowly with approximately 1.5mL
Calcium Gluconate 10% per minute to avoid prompt increases in
the serum calcium . If patient is still symptomatic or desired
serum calcium level is yet to achieve, a chronic intravenous drip
can then be started. Generally, continuous infusion of Calcium
Gluconate 200 to 800mg/kg/day is suggested. The infusion rate
should be guided by signs, symptoms and calcium measurements
every 1-2 hours. Nevertheless, throughout the therapy, an ongoing
electrocardiography monitoring is crucial to observe
patient’s clinical response [5,11,15,20].
In the case of persistent hypocalcaemia despite chronic
intravenous calcium therapy was given, treatment should be
directed to the underlying factor as it can attenuate the therapeutic
effect of calcium and vitamin D . The differential diagnosis
of hypocalcaemia in adolescence includes vitamin D deficiency,
malabsorption, hypomagnesaemia and hypoparathyroidism.
Therefore, once hypocalcaemia is found, it is recommended
to carry out additional evaluations on parathyroid hormone,
magnesium, vitamin D 25-hydroxy and 1,25-dihydroxy levels
. However, in the view of patient’s minimal responsive
towards calcium therapy, no further investigation was performed
throughout his hospital stay.
Oral calcium and a rapidly acting preparation of vitamin
D should be started as soon as practical during the admission
. They are also used in chronic calcium therapy to keep the
patient free of symptoms and to maintain serum calcium at
the normal range. Considering that the pathogenesis of CKD
induced hypocalcaemia is typically recognised as increasing
serum phosphorus and decreasing in renal production of
1,25-dihydroxycholecalciferol, the patient was discharged with
Tab. Calcium Carbonate, a phosphate binder and Cap. Alfacalcidol,
an active form of vitamin D [15,22]. Besides, it is also recommended
that in order to achieve an optimal therapy, patient should hold
vitamin D dose constant and adjust the dose of Calcium Carbonate
when signs, symptoms and measurements of calcium so dictate
[15,22,23] (Table 5).
The usefulness of standard anticonvulsants, in this case, is
debatable. Certainly, in the cases where seizures persist even
after correction of calcium levels, initiation of anticonvulsant
is preferable [16,18,24]. Diazepam is the common medication
indicated for breakthrough seizures. Review suggested that
despite the metabolites of diazepam are active and long lasting,
it is rarely a problem in children . Undoubtedly, intravenous
Diazepam (0.2mg/kg, maximum dose:20mg)  is considered as
the preferred administration route during a seizure  (Table 6).
In short, the current paper illustrates that the case of
breakthrough seizure secondary to hypocalcaemia should be
carefully evaluated, both at the presentation and after patient
recovers from the postictal stage. This is because the underlying
cause of hypocalcaemia should be ruled out in order to ensure
optimal clinical response towards calcium therapy. Besides, it is
also recommended that epileptic adolescent with CKD should be
periodically followed for signs and symptoms of hypocalcaemia
and vitamin D deficiency after discharged from the hospital. By
practice this, it is believed that episode of breakthrough seizure
can be prevented with a reasonable degree of success, provided
that they fully comply with their assigned drug regimen.