A Comparison of the Relative Toxicities of β-Sympathomimetic Tocolytic Agents

Abstract

To define the relative toxicities of ritodrine sulfate, terbutaline sulfate, hexaprenaline sulfate, and ritodrine with betamethasone mongrel dogs were treated with these agents for 19 hours. The maximum dose of ritodrine was 900 microgram/min (N = 5), terbutaline 120 micrograms/min (N = 4) and hexaprenaline 1.5 micrograms/min (N = 4). Betamethasone was given intramuscularly (12 mg) at initiation of ritodrine and repeated in 12 hours in four animals. Arrhythmias were responsible for five deaths; 2/4 terbutaline, 2/4 ritodrine and beta-methasone, 1/5 ritodrine, 0/4 hexaprenaline treated animals. Terbutaline-treated animals developed arrhythmias during more treatment cycles (50%) and at lower drug concentrations, whereas hexaprenaline-treated animals developed arrhythmias at higher drug concentrations, with an overall arrhythmia frequency of 14%. Terbutaline animals had the highest heart rate (P = 0.02) and lowest mean arterial pressure (P = 0.18); the least effect on these parameters being seen with hexaprenaline. Cardiac index was higher with terbutaline and hexaprenaline compared to ritodrine with or without beta-methasone (P = 0.02). Hypoxemia was most severe with terbutaline (pO2 = 58 mm Hg) and least severe with hexaprenaline (pO2 = 66 mm Hg); however, this does not explain the difference in the frequency of arrhythmias since the mean pO2 during the initial arrhythmias was 76 mm Hg in terbutaline treated animals compared to a baseline control of 85 mm Hg. Although all animals developed significant acidosis during Phases II-IV, hexaprenaline treated animals were the least acidotic (P = 0.036). Hypokalemia was most pronounced with terbutaline (P = 0.08 Phase II, P = 0.07 Phase III).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute pulmonary edema secondary to long-term use of oral ritodrine in a woman with a triplet pregnancy

“…Although the association between the use of betaadrenergic drugs to prevent preterm labor and acute pulmonary edema has been recognized for some years and reported to occur in up to 9% of cases [6], the mechanism of the association is still not fully understood. It appears to be multifactorial [6,8], but essentially noncardiologic.…”

“…Although the association between the use of betaadrenergic drugs to prevent preterm labor and acute pulmonary edema has been recognized for some years and reported to occur in up to 9% of cases [6], the mechanism of the association is still not fully understood. It appears to be multifactorial [6,8], but essentially noncardiologic. Betaadrenergic agonists that may cause sodium and water retention, leading to volume overload within 24 to 48 h, have also been implicated as a cause of increased capillary permeability, disturbances of cardiac rhythm, and myocardial ischemia [6].…”

“…The betaadrenergic agents terbutaline, ritodrine, and isoxsuprine used to stop premature labor have been implicated in the development of pulmonary edema [3], although the complication has a low incidence (it occurred in only 7 of 2557 patients in one study) [4]. Parenteral ritodrine is the betaadrenergic agent the most extensively used as a tocolytic agent, and acute pulmonary edema secondary to its use is well known [5,6]. However, only 1 case of pulmonary edema associated with long-term use of oral ritodrine had been reported so far [7].…”

Therapie drohender Frühgeburt

“…Die perinatale Mortalitgt konnte trotz eines 48-Smnden-Gewirmes zur Lungenreifeinduktion nicht gesenkt werden [5]. Dem gegenfiber wurde in 3-9% der F/ille ein mfittefliches Lungen6dem gesehen [3]. Die Aufiaahmekriterien flit diese Studie, eine Muttermundserfffnung yon mindestens 2 cm und eine deutliche Verkiirzung der Zer, Tix weisen m6glicher-weise auf das grundsatzliche Problem solcher Untersuchungen -auf das Problem, dab mit der Tokolyse m6gticherweise zu spat begormen x~drd, zu einem Zeitpunkt, wenn die Kaskade der zur Friihgeburt fiihrenden Parameter nicht mehr aufzuhalten ist.…”

The contemporary use of β‐agonists

“…Leveno and Cunningham (1992) cited an article by Hankins (1991) when suggesting such a high incidence. Hankins (1991) used four references to support this contention, in two of which terbutaline was used with inappropriately high volumes of saline. Another is an abstract only, in which no detail of the study protocol is available but suggests that excessive doses of ritodrine were used.…”