Clinical Pharmacology of Pipecuronium Bromide

The neuromuscular blocking and cardiovascular effects of pipecuronium, in doses ranging 2--3 times its ED95, were evaluated in 46 patients during thiopental, fentanyl, N2O/O2 anesthesia. The neuromuscular blocking effect of pipecuronium was evaluated by recording of the mechanical twitch of the adductor pollicis muscle in response to stimulation of the ulnar nerve at the wrist. Heart rate, systolic and diastolic blood pressures, and cardiac output were noninvasively measured during the onset of the neuromuscular blockade and compared to a saline control group to separate the effect of anesthesia from those of pipecuronium.The mean ± SD time from administration of pipecuronium to 90% suppression of the first twitch (T1) of the tram-of-four was 2.6 ± 0.8, 2.0 ± 0.6, and 2.1 ± 0.6 min following the 70 μg/kg, 85 μg/kg, and 100 μg/kg dose, respectively. There was no significant difference between the different doses of pipecuronium in the time to 90% suppression of T1. In general, all three doses of pipecuronium provided good to excellent intubating conditions within 3 minutes after its administration. The time from the administration of pipecuronium to 5% recovery of T1 was 52.3 ± 18.2 min in the group given 70 μg/kg. This was significantly longer in patients given 85 μg/kg (71.9 ± 15.7 min) or 100 μg/kg (71.8 ± 22.1 min). Times to the start of recovery of T1 and to 25% recovery of T1 showed a similar significant pattern. In 2/3 of the patients, administration of neostigmine (2.5 mg) resulted in adequate recovery of muscle function within 10 minutes. Only patients with T1 recovery to less than 15% of control or a T4/T1 ratio of zero tended to take longer than 10 minutes for full recovery. Heart rate and systolic and diastolic blood pressures decreased significantly after the induction of anesthesia and during the onset of neuromuscular blockade. The hernody-namic variables, however, were similar between the three pipecuronium groups and a control group (N=16) that received only saline. Therefore, no cardiovascular changes could be attributed to pipecuronium when compared to the control group. Cardiac output did not change significantly over the time course of the study.Pipecuronium bromide produces a long-acting, nondepolarizing neuromuscular blockade. A dose of 70 μg/kg can be expected to provide good intubating conditions in 3 minutes with a clinical duration of approximately one hour. Larger doses (85 μg/kg and 100 μg/kg) may shorten the onset time and increase duration on average by 20 minutes. Higher doses are thus best reserved for procedures of long duration. Because no cardiovascular effects were observed with doses ranging from 2--3 times its ED95, pipecuronium can be recommended for patients in whom cardiovascular stability is desired.