Sudden unexpected deaths from heart arrest have been reported with use of non-cardiac drugs since the early 1960s (Iyer 2010). These drugs, which cause sudden death, have centered on torsade de pointes (TdP), a polymorphic ventricular arrhythmia that can progress to ventricular fibrillation and sudden death. Prolongation of the QTc interval is a surrogate marker for the ability of a drug to cause TdP. In individual patients an absolute QTc interval of >500 ms or an increase of 60 ms from baseline is regarded as indicating an increased risk of TdP. However, TdP can occur with lower QTc values or changes. Concern about a relationship between QTc prolongation, TdP, and sudden death applies to a wide range of drugs and has led to the withdrawal or restricted labeling of several. Arrhythmias are more likely to occur if drug-induced QTc prolongation coexists with other risk factors, such as individual susceptibility, presence of congenital long QT syndromes, heart failure, bradycardia, electrolyte imbalance, overdose of a QTc-prolonging drug, female sex, restraint, old age, hepatic or renal impairment, and slow metabolic status. Pharmacodynamic and pharmaco-kinetic interactions can also increase the risk of arrhythmias. The risk should be viewed in the context of the overall risks and benefits of anticancer treatment. It seems prudent, where possible, to select anticancer treatments that are not associated with marked QTc prolongation. If use of a QTc-prolonging drug is warranted, then measures to reduce the risk should be adopted.

l-Asparaginase is marketed as a drug for the treatment of acute lymphoblastic leukemia The main side effect is an allergic or hypersensitivity reaction; anaphylaxis is a possibility. No cardiac arrest effect has been observed before. However, in our clinical practice, a heart arrest was observed in a 1-year-old infant with leukemia.

Before a suspected diagnosis of an ANAPHYLACTIC OR IDIOSINCRATIC REACTION for this cardiac arrest, the child was treated as follows:

Basic and Advanced CPR (ILCOR) protocol

Endotracheal intubation: respiratory Mechanical Assistance (RMA)

Intravenous medications:

Hematological treatment:

After indicating the inotropic support and the volemia expansion by means of crystalloids, laboratory results were received. They confirmed hemostasis alteration, which is corrected by providing K vitamin (see Table 2).

Fortunately, this kid had a favorable evolution, as we can see in his tests controls (see Table 3).

In Figure 1, an ECG sample performed a day after the emergency is shown. It features a frequency of almost 200/min and P wave absence (only catching the last four beats), most presumably due to an inotropic effect.

Cardiac toxicity from these drugs is reported in Goodman–Gilman’s Treatise.

Individual idiosyncratic potential risk increases this danger in the whole of the protocol products (Litchner, 2010). Among them, both Vincristine and l-Asparaginase cause severe hepatotoxicity, derived from their pharmaco-kinetic metabolism, as was shown in the hemostasis defect.

The new decision of spreading the infusions of the protocol drugs within the week was made in order to allow the liver to recover (Swedborg, 2010).

The condition regressed completely at night (around 9:00 pm), and control parameters came back to normal (see Table 2).

Currently, there are many products that can induce QT-interval prolongation at the ECG, thus favoring sudden death (Inchauspe, 2010b).

WHO defines Sudden Death as an episode appearing within 24 h of the beginning of an illness.

Under both eastern and western concepts, the combinations proposed in some protocols (and others enlisted by Dr. Wang (Wang 2010) in the Harvard Office of Toxicology Exploration) could lead to a disruption of the ionic potassium channels of the myocardial cells (Asai 2010), mostly in patients with congenital or acquired Long QT Syndrome. This condition could give rise to the appearance of precocious post-depolarizations (PDPs). Once they have reached a threshold amplitude, the PDPs can trigger highly risky arrhythmia known as “Torsade de pointes” (Dessertenne, 1966; Dessertenne et al., 1966), and a possible cardiac arrest.

Fortunately, today there is the possibility of carrying out ambulatory studies of cardiac frequency variability through continuous monitoring of spectral analysis of R–R^′ (Inchauspe 2011), corrected QT formulas are still a very practical way to determine QT-interval length next to the patient’s bed:

Application of QTc (corrected) Bazett Formula:

or QTp (precision) Rautaharhu Formula:

Both formulas are appropriate as a QT screening since values over 0.45 s will be indicative of a QT-interval prolongation. And rates over 0.66 s would be likely to pose a torsadogenic risk (Lanzotti and Citta 2003).

Proposal of a QTc or QTp screening will allow us to:

Each year 1,500,000 patients severely injured by prescribed drugs require hospitalization.

Out of these, 100,000 die, this being the fourth cause of death in USA.

Careful, long-term evaluation of cardiovascular safety can lead to better medical treatments.

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.