Reversal of Deep Pipecuronium-Induced Neuromuscular Block With Moderate Versus Standard Dose of Sugammadex: A Randomized, Double-Blind, Noninferiority Trial.

BACKGROUND: Certain surgical interventions may require a deep neuromuscular block (NMB). Reversal of such a block before tracheal extubation is challenging. Because anticholinesterases are ineffective in deep block, sugammadex 4 mg/kg has been recommended for the reversal of rocuronium- or vecuronium-induced deep NMB. However, this recommendation requires opening 2 vials of 200 mg sugammadex, which results in an increase in drug costs. Therefore, we sought a less expensive solution for the induction and reversal of deep NMB. Although the optimal dose of sugammadex for antagonism of deep block from pipecuronium has not been established, data pertaining to moderate block are available. Accordingly, we hypothesized that sugammadex 2 mg/kg would be a proper dose to reverse deep pipecuronium block, enabling us to avoid cost increases. In the present study, we compared sugammadex 2 mg/kg with the standard dose of 4 mg/kg for reversal of deep block from pipecuronium. METHODS: This single-center, randomized, double-blind, 2 parallel-arms, noninferiority study comprised 50 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and pipecuronium. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch SX). Noninferiority margin was specified beforehand as an increase in reversal time of no >10% (corresponding to 1 minute for the primary outcome). When the block spontaneously recovered to posttetanic count 1, the patients randomly received sugammadex 2 or 4 mg/kg, and the time from the injection to the train-of-four (TOF) ratio of 1.0 was measured. Primary outcome was the time to achieve the normalized TOF ratio of 0.9 in a particular patient. Residual or recurrent postoperative NMB was additional end point. RESULTS: Each patient recovered to the normalized TOF ratio of 0.9. In the 2 mg/kg group, reversal time was 1.73 ± 1.03 minutes (95% confidence interval [CI], 1.33-2.13; n = 25), and in the 4 mg/kg group, reversal time was 1.42 ± 0.63 minutes (mean ± standard deviation) (95% CI, 1.17-1.67; n = 25). The mean difference in reversal times between the 2 groups was 0.31 minutes (95% CI, -0.18 to 0.8), and the upper limit of CI was below the noninferiority margin of 1 minute. Postoperative block did not occur. CONCLUSIONS: The effect of sugammadex 2 mg/kg was noninferior to that of 4 mg/kg in reversing posttetanic count-1 degree pipecuronium block. Sugammadex reversal of deep pipecuronium block appears to be effective.

Reversal of Pipecuronium-Induced Moderate Neuromuscular Block with Sugammadex in the Presence of a Sevoflurane Anesthetic: A Randomized Trial.

BACKGROUND: Pipecuronium is a steroidal neuromuscular blocking agent. Sugammadex, a relaxant binding γ-cyclodextrin derivative, reverses the effect of rocuronium, vecuronium, and pancuronium. We investigated whether sugammadex reverses moderate pipecuronium-induced neuromuscular blockade (NMB) and the doses required to achieve reversal. METHODS: This single-center, randomized, double-blind, 5-group parallel-arm study comprised 50 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and pipecuronium. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch SX) according to international standards. When the NMB recovered spontaneously to train-of-four count 2, patients randomly received 1.0, 2.0, 3.0, or 4.0 mg/kg of sugammadex or placebo. Recovery time from sugammadex injection to normalized train-of-four (TOF) ratio 0.9 was the primary outcome variable. The recovery time from the sugammadex injection to final T1 was the secondary end point. Postoperative neuromuscular functions were also assessed. RESULTS: Each patient who received sugammadex recovered to a normalized TOF ratio of 0.9 within 5.0 minutes (95% lower confidence interval for the lowest dose 70.1%; for all doses 90.8%) and 79% of these patients reached a normalized TOF ratio 0.9 within 2.0 minutes (95% lower confidence interval for the lowest dose 26.7%; for all doses 63.7%). T1 recovered several minutes after the TOF ratio. No residual postoperative NMB was observed. CONCLUSIONS: Sugammadex adequately and rapidly reverses pipecuronium-induced moderate NMB during sevoflurane anesthesia. Once the train-of-four count has spontaneously returned to 2 responses following pipecuronium administration, a dose of 2.0 mg/kg of sugammadex is sufficient to reverse the NMB.

[New russian myorelaxant vero-pipecuronium (pipecuronium bromide) used for the anesthetic management of operations on the thorax and abdomen organs]. / Novyi otechestvennyi miorelaksant vero-pipekuronii (pipekuronii bromid) v anesteziologicheskom obespechenii operatsii na organakh grudnoi i briushnoi polosti.

The experience of clinical use of the new Russian myorelaxant of the non-depolarizing action vero-pipecuronium (pipecuronium bromided) manufactured by "Veropharm" is described. Vero-pipecuronium was found to ensure splendid and good conditions for the intubation of the trachea and to maintain reliably myorelaxation. The recommended doses and availability of an antidote (prozerine) provide for a sufficiently controllable myorelaxation. Vero-pipecuronium does not virtually exert any effect on the parameters of hemodynamics and can be successfully used in patients with a high anesthetic risk including heart surgeries. Thus, Russian vero-pipecuronium has now an effective and safe myorelaxant manufactured inside the country, whose parameters are not inferior to those of pipecuronium bromide (arduan) manufactured by "Gedeon Richter", Hungary. Since the described drug is made in Russia, one can hope it will be highly effective both economically and pharmacologically.

[Investigation of neuromuscular blocking agents at Richter Ltd]. / Szteroid izomrelaxánsok kutatása a Richterben.

Investigation of new neuromuscular blocking agents was started 30 years ago in Richter Ltd. This paper presents the results obtained by Richter's scientists. 2 compounds out of 100 bisquaternary ammonio steroid having androstane skeleton were selected for further pharmacological study. One of these agents, pipecuronium bromide (Arduan) elicited long-lasting block of neuromuscular transmission without cardiovascular side effects in both animal experiments and clinical studies. Arduan is a powerful competitive antagonist of acetylcholine, since it can bind pre- and postsynaptic (N1) receptors of the transmitters. It has no remarkable cumulative effect. Neostigmine rapidly and completely antagonized the neuromuscular blockade caused by pipecuronium. Arduan was introduced into clinical practice. The second compound, RGH-4201 (Duador) evoked a neuromuscular block of short duration. It showed slight atropin-like cardio-vagolytic effect in animal experiments. In the clinical studies, however, the cardiovascular side effects were found to be too strong. Therefore, it was not introduced in clinical practice.

Effect of pipecuronium and pancuronium on intracranial pressure and cardiovascular parameters in patients with supratentorial tumours.

A prospective, randomised, single blind study was conducted to evaluate and compare the intracranial pressure (ICP) and cardiovascular effects of pipecuronium (PPC) and pancuronium (PNC) in 20 patients undergoing supratentorial surgery. Patients were randomly divided into two groups. Patients in Group I (n = 10) received pancuronium (0.1 mg kg(-1)) and in Group II (n = 10) pipecuronium (0.07 mg kg(-1)) for intubation. Intracranial pressure (ICP), heart rate (HR), systolic, diastolic and mean arterial pressures (SAP, DAP, MAP), central venous pressure (CVP), nasopharyngeal temperature and arterial blood gases (ABG) were monitored at the following time periods: before induction (0 minutes); 3 minutes after thiopentone and muscle relaxant; immediately after intubation; and 4, 6, 8, 10, 20 and 30 minutes following intubation. The rise in intracranial pressure at intubation was significantly greater in group I (21.10+/-3.97 torr, 122.59%) when compared to group II patients (1.80+/-0.70 torr, 10.04%) (p<0.0 1). Cardiovascular parameters also showed a significantly greater degree of rise in group I when compared to group II patients. Heart rate increased by 29+/-6.32 beats min(-1) (33.52%) and systolic arterial pressure by 11.60+/-7.37 torr (9.47%) in group I. These parameters did not change significantly in group II. No significant alterations were observed in the other measured parameters in either of the two groups.

Reversal of pipecuronium bromide with pyridostigmine.

Pipecuronium Bromide (Arduan, Organon, Inc, West Orange) is a long-acting, nondepolarizing neuromuscular blocking agent. The efficacy of pyridostigmine 170 micrograms/kg intravenously (approximately 10 mg/70 kg) for reversing pipecuronium has not been reported. This study was performed to determine the time required to obtain a train-of-four (TOF) ratio of 0.7 after administration of pyridostigmine 140 micrograms/kg at 25% recovery of T1 after pipecuronium-induced neuromuscular blockade. Sixteen, American Society of Anesthesiology (ASA) I or II patients undergoing surgical procedures of at least 90 minutes, requiring intubation and muscle relaxation were included. Neuromuscular blockade was assessed using the Puritan-Bennett/Datex NMT 221 placed for ulnar nerve stimulation. Anesthesia was maintained with a nitrous oxide/narcotic technique and the use of potent inhalational anesthetics was avoided. The mean reversal time was found to be 16.14 minutes, with a minimum of 10.3 minutes and a maximum of 24.3 minutes. The standard error was +/- 1.05 minutes with a variance of 17.68 minutes.

Long-acting nondepolarizing neuromuscular blocking agents.

Patients with compromised cardiovascular function who are undergoing cardiothoracic or other lengthy surgical procedures are at risk of complications from the hemodynamic effects of the long-acting nondepolarizing neuromuscular blocking agents (NMBs), which have been in use for several decades. The development of agents that maintain a stable hemodynamic profile is a potential advantage to this patient population. This literature review, which was completed in May 1992, describes the profiles of doxacurium and pipecuronium, two recently developed long-acting NMBs with increased potency over d-tubocurarine, metocurine, and pancuronium. Doxacurium is a benzylisoquinolinium compound with an ED95 of 0.025 mg/kg. Pipecuronium, a steroidal agent, has an ED95 of 0.04 mg/kg. Twice the ED95 of either agent produces a duration of action comparable to that with 2 times ED95 of pancuronium, but neither doxacurium nor pipecuronium possesses vagolytic or histamine-releasing properties at therapeutic doses. Although no significant differences in serum elimination half-life or plasma clearance of doxacurium have been noted between young and elderly patients, as with other NMBs, the duration of action of doxacurium may be somewhat prolonged and seems to be more variable in older patients and in patients with impaired hepatic or renal function. A similar pattern appears to occur with pipecuronium. Children seem to require higher doses of doxacurium than adults to achieve the same degree of neuromuscular block but recover from the effects more rapidly. Doxacurium and pipecuronium produce no dose-dependent or clinically significant changes in heart rate, mean arterial pressure, or cardiac output either in patients with normal cardiac function or in those with coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Arduan relaxation following norcuron intubation.

Norcuron injection was administered before intubation in the course of anaesthesia in 57 gynaecological operations. Surgical relaxation was performed with Arduan. The patients received varying premedication, introduction, and maintenance narcosis. The combined use of the two non-depolarizing neuromuscular blocking agents proved to be favourable and useful from the anaesthesiological aspect.