The Duration of Impairment of Autonomic Control After Anticholinergic Drug Administration in Humans

Abstract

Impaired parasympathetic control of heart rate is associated with increased incidence of cardiac dysrhythmias and ischemia. Anticholinergic drugs, commonly administered during reversal of neuromuscular blockade, suppress parasympathetic control in the early postoperative period. This could potentially be detrimental in patients at risk of cardiovascular complications. The duration of parasympathetic impairment by two anticholinergic drugs were compared in this double-blind randomized cross-over study. Fourteen healthy volunteers received a single intravenous injection of atropine 20 micrograms/kg or glycopyrrolate 8 micrograms/kg during two different study sessions. The methods of spontaneous baroreflex analysis and spectral analysis of heart rate variability generated indices of beat-by-beat parasympathetic modulation of heart rate. Both drugs resulted in a marked decrease in baroreflex sensitivity and high-frequency heart rate variability. The times to return to baseline values were approximately doubled after atropine compared to glycopyrrolate (177 +/- 22 vs 82 +/- 8 min for baroreflex sensitivity, 212 +/- 16 vs 111 +/- 14 min for high-frequency power, and 171 +/- 18 vs 95 +/- 18 min for high-frequency power normalized to total power; P < 0.01 for all variables). Atropine leads to more prolonged impairment of parasympathetic control than equipotent doses of glycopyrrolate, and its use may thus be less desirable in high-risk patients in the early postoperative period.

Ventricular fibrillation related to reversal of the neuromuscular blockade in a patient with long QT syndrome

“…At the end of surgery, just prior to the occurrence of the cardiac arrest, the patient received glycopyrronium and neostigmine for reversal of the neuromuscular blockade. In two placebo-controlled studies (12,13), glycopyrronium was shown to markedly decrease the baroreceptor sensitivity and high-frequency heart rate variability. Such changes are indicative of an impaired parasympathetic control of heart rate, which is associated with an increased incidence of arrhythmias (12,13).…”

“…In two placebo-controlled studies (12,13), glycopyrronium was shown to markedly decrease the baroreceptor sensitivity and high-frequency heart rate variability. Such changes are indicative of an impaired parasympathetic control of heart rate, which is associated with an increased incidence of arrhythmias (12,13). In another study, a marked prolongation of the QTc interval occurring during the first 2 min after the injection of various anticholinesterase-anticholinergic drug combinations was found (14).…”

The impact of autonomic dysfunction on peri‐operative cardiovascular complications

“…In another study, the duration of parasympathetic impairment was compared after the use of two anticholinergic drugs, atropine and glycopyrronium. Both agents suppress parasympathetic control in the early postoperative period, and impaired parasympathetic control of heart rate is associated with increased incidence of cardiac arrhythmias and ischaemia . Parlow et al.…”

Quantifying Effects of Pharmacological Blockers of Cardiac Autonomous Control Using Variability Parameters

“…Administration of atropine is the common method to investigate tonic vagal activity. Spectral analysis of HRV has shown that anticholinergic drugs generally decrease the HF power of HR and blood pressure variability in humans (Pomeranz et al, 1985; Parlow et al, 1997). While low doses of atropine cause a decrease in HR and an increase in HRV, higher doses cause an increase in HR and a decrease in HRV (reviewed in Lewis et al, 2006).…”