Glycopyrrolate and Theophylline for the Treatment of Severe Pallid Breath-holding Spells

Abstract

Severe pallid breath-holding spells (BHSs) are based on parasympathetic hyperactivity, leading to cardiac asystole, pallor, brain ischemia, loss of consciousness, and reflex anoxic seizures. In recent years, an increasing number of patients with severe pallid BHSs have been successfully treated with pacemaker implantation. We present the case of a 13-month-old girl suffering from repeated severe pallid BHSs, causing asystole, loss of consciousness, and generalized anoxic seizures. She underwent treatment with oral glycopyrrolate, an anticholinergic drug, and an oral retard preparation of theophylline. The aim of the treatment was to decrease cardiac inhibition with glycopyrrolate and to bring about a positive chronotropic effect with theophylline. In our case, the combined therapy was effective in suppressing syncope and reflex anoxic seizures associated with BHSs This avoided the need for ventricular pacemaker implantation.

Case Report of Successful Treatment of Pallid Breath-Holding Spells With Glycopyrrolate

“…In Carano et al, a 13-month-old patient was successfully treated with a combination of glycopyrrolate and theophylline, with resolution of severe recurrent pallid breathholding spells. 5 Glycopyrrolate is a synthetic quaternary ammonium compound, known for its antimuscarinic effects. 12 Given its properties, including being highly ionized, glycopyrrolate has variable absorption in the gastrointestinal tract and does not cross the blood-brain barrier.…”

“…Normally used in anesthesia to reduce oral secretions, glycopyrrolate is a synthetic anticholinergic drug with longer-acting properties than atropine that provides treatment against cardiac inhibition in severe recurrent breath-holding spells. 5 In 1 case report, the use of glycopyrrolate resulted in resolution of syncope in 1 patient with severe recurrent spells without the significant side effects seen with cardiac pacemaker implantation. 5 In our retrospective study, we examine the use of glycopyrrolate in 4 patients with similar recurrent syncope and bradycardia and report that glycopyrrolate is beneficial and is an alternative treatment modality.…”

“…4 The natural course of breath-holding spells is usually transient, with cessation by early toddler years. 5 Long-term prognosis is generally excellent, with the expectation of normal development. The standard of care is reassurance for most patients, but children with severe sequelae require further treatment.…”

Fisiopatología, diagnóstico diferencial y tratamiento de la apnea emotiva grave: A propósito de un caso clínico

“…La función vagal, evaluada mediante diversos test neurofisiológicos, como el reflejo oculocardíaco, el test de pilocarpina y parámetros de variabilidad de la frecuencia cardíaca en Holter de 24 h, han evidenciado una sobre-reactividad, más que sobreactividad vagal [14][15][16] . Para antagonizar la sobre-reactividad vagal y prevenir la AE se han usado drogas anticolinérgicas como atropina, escopolamina y glicopirrolate 17,18 . también se ha usado teofilina, principalmente por su función inótro-pa positiva, considerándola en segundo plano como estimuladora de los centros respiratorios bulbares.…”

“…El mayor consumo de fierro favorecido por la secreción de eritropoyetina disminuiría aún más los depósitos, perpetuando la anemia 21 . Consistente con estos hallaz-gos, oreii et y zehetner, demostraron que la suplementación con fierro en anemia ferropriva sería efectiva en optimizar la disregulación del sistema nervioso autonómo y prevenir las AE 21,22 , quedando aún pendiente estudiar este efecto en poblaciones no deficientes 17 . Igualmente, la deficiencia de fierro per se, agrega estrés oxidativo que altera el metabolismo de las catecolaminas y la función de neurotransmisores 23 .…”