Train-of-four recovery after pharmacologic antagonism of pancuronium-, pipecuronium-, and doxacurium-induced neuromuscular block in anaesthetized humans.

Previous studies have suggested that the increased duration of action of long-acting neuromuscular relaxants may make their pharmacologic antagonism more difficult and, thus, increase the likelihood of residual block. This hypothesis was tested in healthy, adult humans who received a background of isoflurane/N2O/fentanyl anaesthesia. Study subjects were paralyzed with either pancuronium (N = 8), pipecuronium (N = 8), or the longer-acting relaxant, doxacurium (N = 8). Neuromuscular function was monitored, and, using a blinded, randomized study design, the relaxants were titrated to identify the ED95 dose in each patient. Thereafter, spontaneous recovery was observed until there was 25% of baseline response to the first supramaximal twitch (T1) in a train-of-four (TOF). At this time, the block was antagonized with neostigmine 0.07 mg/kg and glycopyrrolate 0.014 mg/kg i.v., and recovery of TOF was recorded. Spontaneous recovery to 25% of the baseline T1 response occurred at 52 +/- 14 min (mean +/- SD) following administration of either pancuronium and pipecuronium, and 85 +/- 33 min following doxacurium (P < 0.05 for doxacurium versus pancuronium and pipecuronium). In doxacurium-treated patients, reversal of block with neostigmine was less predictable and less complete than with the other two relaxants. For example, the ratio of the fourth to first twitch (T4/T1) of the TOF at 10 and 15 min after reversal was significantly less with doxacurium (59 +/- 14% and 61 +/- 16%, respectively) than with either pancuronium (75 +/- 6% and 75 +/- 10%) or pipecuronium (76 +/- 9% for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Antagonism of pancuronium- and pipecuronium-induced neuromuscular block.

We have compared the antagonism of neuromuscular block produced by pipecuronium with pancuronium in 80 anaesthetized surgical patients using mechanomyography and electromyography. Pancuronium 0.1 mg kg-1 or pipecuronium 0.07 mg kg-1 was given after induction of anaesthesia and neuromuscular block was adjusted to 75% twitch depression at the time of antagonism. The following regimens were used: edrophonium 0.5 and 1.0 mg kg-1, neostigmine 0.04 mg kg-1, pyridostigmine 0.3 mg kg-1 and edrophonium 0.25 mg kg-1 with pyridostigmine 0.15 mg kg-1. Antagonism was evaluated also by the head lift test. There was no difference between the reversibility of neuromuscular block produced by pancuronium or pipecuronium. Edrophonium produced a significantly faster antagonism than neostigmine or pyridostigmine but onset of action was not significantly faster than that of edrophonium with pyridostigmine. All regimens produced 100% (or near 100%) antagonism of twitch response within 15 min. However, TOF fade antagonism was more complete with pyridostigmine, neostigmine and edrophonium 1.0 mg kg-1 than with edrophonium 0.5 mg kg-1. The head lift test indicated somewhat less antagonism with edrophonium 0.5 and 1.0 mg kg-1. Using five monitoring methods, the rank order of reversal potency was: pyridostigmine approximately neostigmine > edrophonium 1.0 mg kg-1 > edrophonium+pyridostigmine > edrophonium 0.5 mg kg-1.

Dose-response relationships for edrophonium and neostigmine antagonism of pipecuronium-induced neuromuscular block.

We have studied the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by pipecuronium bromide. Fifty-six ASA physical status I or II adults were given pipecuronium 70 micrograms/kg during fentanylthiopental-nitrous oxide-halothane anesthesia. Train-of-four (TOF) stimulation was applied to the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 20% of its initial control value, edrophonium (0.125, 0.25, 0.75, or 1 mg/kg) or neostigmine (0.015, 0.03, 0.045, or 0.06 mg/kg) was administered by random allocation. Neuromuscular function in another seven subjects was allowed to recover spontaneously. This study demonstrated that the dose-response curves for these two drugs for reversal of first twitch and TOF ratio were not parallel. The doses of neostigmine required to achieve 50% (ED50) and 80% (ED80) recovery of the first twitch after 10 min were 8.5 (7.3-9.7) and 17.4 (16.2-18.7) microgram/kg [mean (95% confidence intervals)], respectively. Corresponding ED50 and ED80 values for endrophonium were 84.1 (72.9-96.9) and 233 (215.7-253.3) microgram/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 9.89 (7.4-12.3) and 13.4 (11.8-14.9) for first twitch ED50 and ED80 height, respectively. The calculated doses producing 50% (ED50) recovery of the TOF ratio at 10 min were 18.8 (17.5-20.2) and 271.3 (246.5-298.6) microgram/kg for neostigmine and edrophonium, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of antibiotics on pipecuronium-induced neuromuscular blockade.

STUDY OBJECTIVE: To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug). DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Inpatient gynecologic and gastroenterologic service at a university medical center. PATIENTS: Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia. INTERVENTIONS: Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen. Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response. At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo. MEASUREMENTS AND MAIN RESULTS: The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist. RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test. Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin. CONCLUSIONS: When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.