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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 1, January/February 2015
e12
AFRICA
operatively) and 1 g of tranexamic acid (TA) peri-operatively,
with the nurse reporting that 1 g of cefazolin was administered as
an intravenous bolus injection about a minute before the seizure.
Because of the sedation there were no lateralising postictal
features.
Blood work revealed normal sodium, calcium and magnesium
concentrations. The blood glucose level was 152 mg/dl (8.44
mmol/l), urea concentration was slightly elevated at 13.2 mmol/l,
and creatinine was 164 mmol/l. The electroencephalogram
was considered normal. Computerised axial tomography and
magnetic resonance imaging scans of the head were performed
and the results were normal. Electrolyte levels were within
normal limits (sodium 142 mEq/l, potassium 4.3 mEq/l, chloride
104 mEq/l). Other neurological examinations were all within
normal ranges.
The patient was treated with intravenous leviteracetam at a
dose of 1 500 mg/day, administered in three doses over 30 min,
after which he remained seizure free. The patient was easily
extubated three hours later with no further neurological findings.
He was monitored for one more day in the ICU and discharged
to the general ward on postoperative day two.
The patient was discharged and allowed to go home after
seven days with no further incidents of seizure. Leviteracetam
was discontinued after seven days of treatment, and the patient
has remained seizure free since discharge.
Discussion
Cardiac surgery may pose a significant threat to the nervous
system via various mechanisms. Although the incidence of
seizure is usually low, the causes and management are relatively
unique in this setting.
2
Therefore the attending physician must
be well versed in the most likely causes of seizure in this specific
population, such that diagnosis and optimal management can be
initiated rapidly without pursuing unnecessary and costly testing
in all cases.
A targeted approach based on recognising focal versus
generalised seizures, a careful review of the history and
medications, and a focused approach will lead the clinician to
choose the most effective therapy required. If the patient’s history
indicates a generalised seizure, the approach and differential are
likely to be metabolic and/or toxic aetiologies. The usual suspects
include deregulated electrolyte balance, such as hyponatraemia,
hypo-/hyperglycaemia, hypocalcaemia, hypomagnesaemia, and,
less commonly, hypophosphataemia.
1
In the case of the patient
described here, no electrolyte or glucose imbalance was noted.
Renal dysfunction is one of the secondary reasons for seizure
due to uraemia, which is known to lower the seizure threshold.
Seizures may also arise from increased drug levels that may
have proconvulsant effects. Specifically, these include penicillins,
cephalosporins, imipenem (beta-lactam antibiotics) and
fluoroquinolones.
2
In animal models, penicillin is commonly used
to induce generalised epilepsy, characterised by generalised spike
and wave discharges on an electroencephalogram.
2
Cefazolin,
another beta-lactam antibiotic with similar proconvulsant
activities, is the most potent gamma-amino-butyric acid (GABA)
antagonist among the cephalosporins.
3
Cefazolin has been reported to the United States FDA
adverse-event reporting system 15 times between 2004 and 2012
for the induction of convulsions. In the present case, cefazolin
was used as prophylactic antibiotic, 1 g pre-operatively, 1 g
intra-operatively and a third dose was administered just a minute
before the seizure in the intensive care unit.
Cefazolin, which is known to function as a proconvulsant
in overdose, especially in patients with renal dysfunction, may
lead to seizures because of malpractice by the nursing staff. The
nurse’s history in this particular case revealed that 1g of cefazolin
was injected into the central venous port within five to seven
seconds.
A detailed review of the history of all peri- and postoperative
medication is helpful in elucidating the potential responsible
agents. Unless absolutely necessary, no medication should be
administered intravenously at a high rate.
Another important consideration is withdrawal reactions, for
which the usual offenders are GABA agonists such as ethanol,
benzodiazepenes and less commonly, baclofen and narcotics.
These agents cause withdrawal reactions that may resemble
seizure activity. This issue must be evaluated before surgery and
may be the reason for convulsions.
3
Tranexamic acid (TA), which is used as an antifibrinolytic
agent during cardiac surgery, is another medication that has
been shown to have proconvulsant activities
in vitro
.
4
In a
study including a consecutive series of 1 188 patients receiving
aprotinin or TA, 4.6% of the patients receiving TA were
reported to have a seizure.
3
Manji
et al
. reported on a study
sample consisting of 5 958 patients where the incidence of
seizure was 7.4% among the patients receiving TA, compared to
a seizure incidence of 0.94% in the controls.
4
The same authors
also revealed a dose-dependent increase of seizure incidence in
cardiac surgery patients.
4
When the TA dose was reduced, the
seizure rate was concomitantly decreased.
4
In the present case, only 1 g of TA was administered
as an intravenous bolus after the patient was weaned from
cardiopulmonary bypass. This dose (12.5 mg/kg) was very
low when compared to the study reported by Manji
et al
.
4
As
reported in the manufacturer’s statement, the half-life of TA is
three hours. Therefore the plasma concentration of TA may have
been too low to have caused the seizure.
Finally, generalised seizures can be seen in the setting of
multifocal injury, including so-called ‘post-pump encephalo-
pathy’, which most likely represents multiple emboli of various
particulate debris, including thromboemboli.
5
Watershed
ischaemia from sudden hypotension can also result in symmetric
cerebral injury, which has a typical magnetic resonance image
appearance showing infarcts in the border zones between the
major vascular territories. Watershed strokes are especially likely
in the vasculopathic population in which carotid disease is likely
to co-exist with coronary disease, such that relative hypotension
is even less well tolerated.
5
In this case, cranial magnetic
resonance imaging and computed tomography scans revealed
totally normal findings.
Conclusion
Cardiac surgery may result in several complications during all
courses of the procedure. A detailed review of the history of all
peri- and postoperative medication is helpful in elucidating the
possible responsible agent for generalised convulsion with no
other aetiology. More importantly, it was concluded from this
study that the administration of medication intravenously at a