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\begin{document}

\title{Sudden cardiac death due to ciprofloxacin induced torsade de pointes}



\author[1]{Semir Usmael}%
\author[1]{Teferi Seyoum}%
\affil[1]{Haramaya University College of Health and Medical Sciences}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\textbf{Introduction}

Long QT syndrome (LQTS) is a disorder of myocardial repolarization
characterized by a prolonged QT interval on the electrocardiogram (ECG).
This syndrome is associated with an increased risk of polymorphic
ventricular tachycardia (VT) and a characteristic life-threatening
cardiac arrhythmia also known as torsade de pointes (TdP). TdP is an
uncommon and fatal polymorphic ventricular tachyarrhythmia, which often
occurs in association with a prolonged QT interval. It is usually
asymptomatic and terminates spontaneously; nevertheless it can cause
syncope, dizziness, palpitations, seizures, and sudden cardiac death
(SCD).

QT prolongation has traditionally been separated into two general
categories: congenital LQTS and acquired LQTS. The acquired causes
include drugs (antiarrhythmic, antibiotic, antipsychotic,
antihistamines, and antiemetic), electrolyte abnormality (hypokalemia,
hypocalcemia, and hypomagnesemia), bradycardia, ischemia, stroke, and
structural heart disease {[}1-3{]}.

Quinolone antibiotics are frequently prescribed agents due to their
broad-spectrum antimicrobial efficacy. QT prolongation is a class effect
of fluoroquinolones, but there are great differences between the various
members of this group in their proarrhythmic potential. Ciprofloxacin is
considered to be safer than the other agents in this class {[}4{]}.
Current clinical studies suggest that among quinolones, ciprofloxacin
has no effect on QT interval in healthy subjects with no predisposing
factors {[}5-6{]} and a weak effect in patients with preexisting risk
factors for torsade de Pointes {[}4, 7{]}.

We report a case 40-years old Ethiopian man with no previous history of
cardiac disease who died due to recurrent cardiac arrest secondary to
ciprofloxacin-induced torsade de pointes.

\textbf{Case presentation}

A 40-year-old Ethiopian man with no previous history of cardiac disease
presented with a 7-days history of profuse watery diarrhea associated
with vomiting and crampy abdominal pain. He denied a history of
shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, and
palpitation. He had no family history of sudden cardiac death and
cardiac illness.

On physical examination, the patient appeared acutely ill and his vital
signs were as follows: blood pressure (BP)-70/50 mmHg, pulse rate
(PR)-104 beat per minute which was feeble, respiratory rate-20,
temperature- 35-degree Celsius, and saturation of 96\% on room air.
There was conjunctival pallor. There were signs of peripheral
hypoperfusion such as cold extremities and delayed capillary refill.
Cardiac and nervous system examinations were non-revealing.

Laboratory work-up revealed; serum potassium: 2.27mmol/L, sodium:
127mmol/L, chloride: 99.7mmol/L, serum creatinine: 2.33mg/dl, and blood
urea nitrogen: 108.8 mg/dl. White cell count (WBC) level was 8800 and
Hemoglobin (Hgb) was 10.2 g/dl. Liver enzymes were within the normal
range and total and direct bilirubin level was 1.62 mg/dl and 1.05
mg/dl, respectively. There were numerous puss cells on microspic stool
exam. Blood and stool culture were sent.

With this finding, a working diagnosis of septic shock of GI focus,
acute kidney injury, severe hypokalemia, and hypovolemic hyponatremia
was established.

The patient was admitted and managed as follows: intravenous (IV)
epinephrine infusion was started after BP failed to respond to initial
fluid resuscitation, IV ceftriaxone 1 gram BID and metronidazole 500 mg
TID, IV potassium chloride infusion 40 meq in 400 ml of normal saline
TID, and Oral rehydration solution 300 ml per loss.

Despite the above management, there was poor clinical response, and
laboratory work-up 2 days after admission revealed a high WBC level (28,
080) and Hgb level of 6.2 g/dl. Serum potassium become 3.72 mmol/l.
There was no growth on blood and stool culture. Subsequently, the
initial antibiotics were discontinued and IV ciprofloxacin 400 mg BID
and vancomycin 1g BID was initiated. He was transfused with 2 units of
packed red blood cell and given IV hydrocortisone 100mg TID. IV
potassium chloride infusion was discontinued. The remaining treatment
was continued.

Within 16 hours of ciprofloxacin initiation, he developed sudden onset
shortness of breath followed by loss of consciousness. On examination,
he was unresponsive, pulse was not palpable, BP was unrecordable, and
had no spontaneous breathing effort. The random blood sugar level was
195 mg/dl. ECG done at this time revealed a sustained polymorphic
tachycardia with a feature of torsade de pointes (Figure 1).

With a diagnosis of sudden cardiac arrest due to polymorphic ventricular
tachycardia induced by ciprofloxacin, cardiopulmonary resuscitation
(CPR) was started immediately; epinephrine infusion at a rate of 0.3
microgram/kg/minute commenced and amiodarone 150 mg IV bolus was
administered. After 5 cycles of CPR and defibrillation return of
spontaneous circulation was achieved. However, 30 minutes later he
developed additional episodes of recurrent torsade de pointes and
cardiac arrest. CPR and defibrillation were attempted but it was not
successful and the patient passed away. The possible cause of death was
cardiac arrest secondary to torsade de pointes induced by ciprofloxacin.

\textbf{Discussion}

Fluoroquinolones are commonly used antimicrobial agents because of their
wide antimicrobial efficacy in common respiratory, gastrointestinal, and
genitourinary infections. However, cardiac toxicity can occur as an
unintended consequence of therapy with quinolone. Case reports and other
studies have reported several quinolone-induced arrhythmia-related
cardiac effects, including QT interval prolongation, TdP, ventricular
tachycardia, ventricular fibrillation, and SCD {[}4, 8-9{]}.
Fluoroquinolones prolong the QT interval by blocking the cardiac
voltage-gated rapid potassium channels (IKr). This adverse effect can be
potentiated by the presence of predisposing factors such as female
gender, structural heart disease, concomitant use of
QT-interval-prolonging medication, reduced drug elimination (due to drug
interaction, renal, or hepatic dysfunction), electrolyte abnormalities
(hypokalemia, hypomagnesemia), bradycardia, prolonged QTc interval
before therapy, and congenital LQTS.

The risk of QT prolongation and TdP varies among quinolones;
moxifloxacin appears to have the greatest risk followed by levofloxacin
and ofloxacin. Ciprofloxacin has been associated with the lowest risk
for QT prolongation and torsade de pointes {[}4-6, 9-10{]}. Even though
ciprofloxacin is considered to be the safest quinolone in terms of TdP,
there are several case reports on ciprofloxacin-induced TdP {[}11-15{]}.
This case report suggests that ciprofloxacin should be used with great
caution in patients who are at risk for QT prolongation and QT-mediated
arrhythmias.

The diagnosis of quinolone-induced TdP requires the presence of a clear
temporal relationship between exposure and onset of the ECG features.
Typical ECG features of TdP include an antecedent prolonged QT interval,
particularly in the last heartbeat preceding the onset of the
arrhythmia. Additional typical features include a ventricular rate of
160 to 250 beats per minute, irregular RR intervals, and cycling of the
QRS axis through 180 degrees every 5 to 20 beats. In our case, TdP
developed within 16 hours of ciprofloxacin administration and the
patient had predisposing factors such as hypokalemia and acute kidney
injury.

Prevention of ciprofloxacin-induced QT-interval prolongation and TdP in
a high-risk patient includes, whenever possible alternative antibiotics
that don't prolong QT interval should be used, serum potassium and
magnesium should be maintained in the normal range, and monitoring the
QT-interval before and at least every 8 to 12 hours after initiating the
drug {[}16{]}.

The management of quinolone-induced QT-interval prolongation includes
discontinuation of the offending drug and aggressive correction of any
metabolic and electrolyte abnormalities. Prompt defibrillation in
hemodynamically unstable and in those with syncope due to torsade de
pointes. In conscious patients' treatment with intravenous magnesium
infusion, beta-blockers, and temporary transvenous pacing are indicated
{[}17{]}.

The major limitations in the management of this case were; initiation of
full dose of ciprofloxacin in the presence of acute renal failure and
severe hypokalemia, inadequate monitoring of QT interval after starting
culprit drug, failure to withdraw ciprofloxacin, and inappropriate
treatment of TdP namely failure to administer IV magnesium sulfate and
inappropriate administration of IV amiodarone. Since there is no
baseline ECG before administration of ciprofloxacin, congenital LQTS
can't be ruled out completely.

\textbf{Conclusion}

Cardiac arrest due to TdP in the acquired form of drug-induced LQTS is a
rare but potentially catastrophic event. Although fluoroquinolone is
well tolerated, and effective, they are associated with various cardiac
toxicities. Even though ciprofloxacin is considered to be the safest
agent in this class, it may cause QT-interval prolongation, torsade de
pointes, and sudden cardiac death, especially in the presence of
predisposing factors. This case emphasizes the importance of prevention,
early recognition, and treatment of QT-interval prolongation and TdP
induced by ciprofloxacin.

\textbf{Abbreviation}

ECG, electrocardiogram; IV, intravenous; LQTS, long QT syndrome; SCD,
sudden cardiac death; TdP, torsade de pointes; VT, ventricular
tachycardia

\textbf{Consent} \textbf{for publication}

Written informed consent was obtained from the patient for the
publication of this case report and accompanying image. A copy of
written consent is available for review by an editor in chief of this
journal.

\textbf{Ethical approval and consent to participate}

Not applicable.

\textbf{Competing interest}

The authors declare no competing interest.

\textbf{Funding}

None.

\textbf{Availability of data and material}

Not applicable.

\textbf{Acknowledgement}

We thank the patient and her family for information provided and their
approval for publication of this case.

\textbf{Authors' contribution}

SA and TM contributed to the acquisition of history, laboratory
investigation, and interpretation of the case and the patient data. SA
carried out a literature review and was a major contributor to the
writing of the manuscript. All authors have read and approved the final
manuscript.

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\textbf{Figures}

Figure 1. ECG taken during episode of cardiac arrest showing feature of
Torsade de pointe: initiation of the arrhythmia after a short-long-short
cycle sequence PVC that falls near the peak of the distorted T-wave,
irregular RR interval, and abrupt switching of QRS morphology from
predominately positive to predominately negative complexes (A). Note the
change in polarity of QRS complex about the isoelectric line (B)

\textbf{Hosted file}

\verb`ECG figure.docx`  available at \url{https://authorea.com/users/511482/articles/771220-sudden-cardiac-death-due-to-ciprofloxacin-induced-torsade-de-pointes}

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