Pyrogen reaction is a febrile phenomenon caused by infusion of solution contaminated, and commonly manifested by cold, chill and fever [¹]. With improved sterilization and generalized application of infusion set (single-use), the prevalence of pyrogen reaction has been controlled, but still exists in clinical practice. Sustained ventricular tachycardia (three or more consecutive ventricular complexes that last more than 30 seconds) is a serious arrhythmia, should be converted with medical therapy or defibrillator [²,³]. But when sustained ventricular tachycardia was refractory to medical therapy and happened to be followed by pyrogen reaction, the arrhythmia was surprisingly converted to sinus rhythm after the reaction, which is really rare.

We describe two patients with sustained ventricular tachycardia refractory to lidocaine, an only available drug, who were converted to sinus rhythm after pyrogen reaction.

Sustained ventricular tachycardia (SVT) can occur in patients with structurally normal and abnormal hearts, as did in case report 1 and case 2. Because SVT can lead to hemodynamic instability, it should be converted to sinus rhythm. Lidocaine is a common antiarrhythmic agent for treatment of SVT that does not cause hemodynamic decompensation. If lidocaine fails, amiodarone is another good choice for most cases without contraindication. If the arrhythmia does not respond to medical therapy, direct current cardioversion can be used. When SVT precipitates hypotension, shock, angina, congestive heart failure, or symptoms of cerebral hypoperfusion, it should be treated promptly with direct current cardioversion [²,³]. In the two patients, especially in cases 2, SVT failed to response to lidocaine should have been managed with direct current cardioversion, but because of no defibrillator, cardioversion could not be performed, which resulted in hypotension and shock. The conversion of SVT was due to pyrogen reaction.

Pyrogen reaction was frequently observed in the rural hospital in China during 1980s, when infusion equipment was reusable, because endotoxin, heat-stable denatured proteins, and other materials were difficult to remove from glass and rubber parts. Endotoxin, an exogenic pyrogen, can act on the thermoregulatory center located in anterior and posterior hypothalamus though leucocytic (endogenic) pyrogens, which shift upwards the thermostat setting in the hypothalamus. This results in signals from the posterior hypothalamus to increase heat production and decrease peripheral heat loss. Heat production from muscle contractions and heat conservation from peripheral vasoconstriction continue until the temperature of blood supplying the hypothalamus matches the higher thermostat setting and body temperature rises. So, pyrogen reaction is characteristically manifested by sudden cold, chill and fever during or after infusion, and lasts about half to one hour [¹,⁴]-[⁶]. When the reaction happens, infusion should be stopped immediately, and antipyretic, antihistamine and steroids can be administered for releasing symptoms.

In this report, promethazine, an antihistamine, was used for treatment of pyrogen reaction in both patients. Perhaps promethazine had some relationship with the conversion of SVT. It has been reported that histamine could increase spontaneous rate and cause ventricular tachycardia in animal experiments [⁷,⁸]. But some second generation, not the first generation, antihistamines have also been reported to induce torsades de pointes ventricular tachycardia in human [⁹,¹⁰]. When used as a psychotropic drug, promethazine was reported to induce polymorphous ventricular tachycardia and torsades de pointes [¹¹]. Therefore, it is hard to explain how promethazine converted the SVT to sinus rhythm.

When the two patients with SVT failed to response to lidocaine which once converted the SVT and was in danger because of no other choice (without other antiarrhythmic drugs and defibrillator), the pyrogen reaction happened. After the reaction the SVTs were astonishingly converted to sinus rhythm. The conversion of sustained ventricular tachycardia might be related to pyrogen reaction. The phenomenon might imply a new therapy of SVT. The underlying mechanism is not clear and remains to be researched.

SVT: Sustained ventricular tachycardia.

Written informed consents were obtained from the patient's relative for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

The authors declare that they have no competing interests.

QZF and XJM were involved in the patient care, acquisition of data, analysis and interpretation of data, QZF involved in review of literature, drafting and revising the manuscript. Authors have read and approved the final manuscript.