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.

[Histamine plasma concentration and cardiovascular effects of non-depolarizing muscle relaxants: comparison of atracurium, vecuronium, pancuronium and pipecuronium in coronary surgical patients at risk]. / Histaminplasmakonzentration und kardiovaskuläre Effekte nicht-depolarisierender Muskelrelaxantien: Vergleich von Atracurium, Vecuronium, Pancuronium und Pipecuronium bei koronarchirurgischen Risikopatienten.

OBJECTIVE: Cardiovascular effects of four commonly used non-depolarising muscle relaxants and their ability to increase histamine plasma concentrations were studied in patients scheduled for coronary artery bypass grafting. METHODS: 40 patients were included in the study after informed consent. After premedication with Flunitrazepam (2 mg p.o.) on the evening before and 1 hour prior to surgery anaesthesia was induced with Flunitrazepam (4-6 micrograms kg-1). Fentanyl (3 micrograms kg-1) und Etomidate (150 micrograms kg-1) and the patients were ventilated via face mask with 50% N2O in oxygen. Patients were randomly allocated to one of four groups, and, 15 min after induction of anaesthesia, received equipotent doses of either Pancuronium (0.09 mg kg-1, n = 10). Pipecuronium (0.08 mg kg-1, n = 10), Atracurium (0.6 mg kg-1, n = 10), or Vecuronium (0.1 mg kg-1, n = 10) injected over 20 seconds via a central venous catheter. Cardiovascular variables were determined in the awake patient, 15 min after induction of anaesthesia and following administration of the respective muscle relaxant. In addition, plasma histamine concentrations were assessed before and after relaxation. Evoked muscular response to TOF simulation of the ulnar nerve (plethysmo-mechanogram) was continuously recorded to determine the onset of neuromuscular blockade. RESULTS: Heart rate, mean arterial pressure and cardiac index significantly decreased in all patients following induction of anaesthesia while systemic vascular resistance remained unchanged. Only Pancuronium caused a significant increase in heart rate (53 +/- 11 to 61 +/- 15 min-1) whereas cardiac index and mean arterial pressure did not change significantly. No other neuromuscular blocking agent caused any changes in the cardiovascular variables measured and histamine plasma concentrations remained within the reference range in all of the four groups with no differences detectable between groups. CONCLUSIONS: All investigated neuromuscular blocking agents exhibited marked cardiovascular stability which permits their use, being based exclusively on pharmacodynamic and pharmakokinetic considerations even in patients with coronary heart disease. If an increase in heart rate appears beneficial Pancuronium may be advantageous.

Pipecuronium revisited: dose-response and maintenance requirement in infants, children, and adults.

STUDY OBJECTIVE: To compare dose-response relationship and maintenance requirement of pipecuronium in anesthetized infants, children, and adults. DESIGN: Prospective, consecutive sample trial. SETTING: Operating room at a university hospital. PATIENTS: 15 infants (1-11 months), 15 children (3-10 years), and 15 adults (35-50 years) of ASA physical status I and II. INTERVENTIONS: Anesthesia was induced and maintained with N2O:O2 2:1 and 1 minimum alveolar concentration end-tidal halothane. The neuromuscular function was recorded by adductor pollicis electromyogram evoked by a train-of-four ulnar nerve stimulation at 20 second intervals. An individual cumulative log-probit dose-response curve was established and maintenance requirement of pipecuronium determined. Between-group comparisons were made by analysis of variance and Scheffe F-test. MEASUREMENTS AND MAIN RESULTS: Dose-response curves were parallel with a dose-requirement of pipecuronium similar in infants and adults (ED95 of 40-42 micrograms/kg) and greater in children (ED95 of 52 micrograms/kg). After 30 minutes of surgical neuromuscular block, pipecuronium was required in each age group at a rate of 0.6 to 0.7 individual ED95 doses per hour to maintain an 85% to 95% neuromuscular block. CONCLUSIONS: Bolus dose requirement of pipecuronium is greatest in children. Maintenance requirement is related to potency in each age group studied.

Comparison of neuromuscular, cardiovascular, and histamine-releasing properties of doxacurium and pipecuronium.

STUDY OBJECTIVES: To determine the neuromuscular, cardiovascular, and histamine releasing properties of doxacurium and pipecuronium at three times effective ED95 doses (3XFD95). DESIGN: Prospective, randomized clinical trial of adult patients. SETTING: University teaching hospital. PATIENTS: 20 ASA status I and II adult patients. INTERVENTIONS: Subjects were anesthetized with thiopental sodium, fentanyl, and nitrous oxide and oxygen (N2O:O2). Plasma samples were taken preoperatively, after thiopental, and 2 and 5 minutes after doxacurium 75 micrograms/kg or pipecuronium 123 micrograms/kg were given for the determination of histamine levels. The ulnar nerve was stimulated via surface electrodes using train-of-four stimulation at 0.1 Hz. The force of contraction of adductor pollicis was recorded using a mechanomyograph. Recovery of the twitch response was followed and, if necessary, neuromuscular block was antagonized with neostigmine and glycopyrrolate. MEASUREMENTS AND MAIN RESULTS: Three patients in the doxacurrium group and one patient in the pipecuronium group exhibited a marked increase in plasma histamine levels. In both groups statistically significant changes were seen in heart rate (HR) measurements (p < 0.02). Doxacurium had a slower onset than pipecuronium [3.1 +/- 0.2 min vs. 1.8 +/- 0.1 min (p < 0.0003)] and a more rapid recovery [72 +/- 8 min vs. 123 +/- 9 min (p < 0.01)]. CONCLUSION: Neither drug caused a clinically significant change in HR or histamine release. In the doses chosen for this study, the rate of onset of block is slower with doxacurium while recovery is more rapid. Histamine release in three patients was caused by thiopental, while in a fourth patient it may have been due to doxacurium.

[Evaluation of the hemodynamic effects of pipecuronium bromide. Absence of adverse hemodynamic effects]. / Valutazione degli effetti emodinamici del pipecuronio brumuro. Assenza di effetti emodinamici avversi.

INTRODUCTION: Pipecuronium bromide is a new non depolarising muscle relaxant with a long duration of action; we considered its haemodynamic effects during general anaesthesia. MATERIALS AND METHODS: Eight surgical patients (4 males, 4 females), mean age 44 years (range 29-65 years), ASA I-II, were studied. All patients were undergoing elective neurosurgical procedures (Hunt-Hess I-II). A radial artery-cannula was put in for blood pressure monitoring and a Swan-Ganz volumetric/ejection fraction fiber optic catheter was put in pulmonary artery via right internal jugular vein (EFV/OTDC-Baxter). A diazo-analgesic high dose fentanyl anaesthesia was given. All patients received pipecuronium bromide 0,1 mg/kg during stable haemodynamic conditions. Haemodynamic determinations were performed over following three times: T0 before the pipecuronium administration, T1 and T2, 3 and 15 minutes after administration respectively. These parameters were analysed: HR, MAP, MPAP, RAP, PCWP, CI RVEDVI, RVESVI, RVEF, SVRI, LVWI, RVWI, SvO2, DO2I, VO2I, O2ER, Qs/Qt (statistics: analysis of variance (two ways ANOVA) and orthogonal decomposition; for all statistical comparison, differences were considered significant when p < 0.05). RESULTS: Only MAP and SVRI showed significant changes (p = 0.02 and p = 0.04), even if clinically modest. No other parameter showed any change at all. CONCLUSIONS: Pipecuronium bromide did not show adverse haemodynamic effects; its haemodynamic repercussions are clinically negligible. The drug could be considered as first choice in long lasting operations for patients with potential cardiovascular instability.

Pulmonary function and head lift during spontaneous recovery from pipecuronium neuromuscular block.

We have studied in seven healthy conscious volunteers the correlation between the electromyographic (EMG) and clinical criteria used to identify adequate recovery from sub-paralysing doses of pipecuronium. Pipecuronium (mean dose 1.88 (range 0.92-3.16) mg) was administered to reach a T4/T1 ratio of 0.5; full recovery to 1.0 was produced in a mean time of 25.3 (14-39) min. During recovery from neuromuscular block, we measured tidal volume, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) negative inspiratory pressure (NIP), peak expiratory flow rate (PEFR), mid-expiratory flow rate (MEFR) and 5-s head lift. The assessments were started when the train-of-four (TOF) ratio reached 0.5 +/- 0.001 and repeated at each 0.1 +/- 0.001 increase up to a ratio of 1.0. All volunteers showed ptosis and diplopia after the first dose and difficulty in swallowing with subsequent doses. They also experienced a pleasant, relaxing sedative sensation. All could sustain head lift for 5 s at a TOF ratio of 0.5 and higher, except for one subject who could not lift his head only at a ratio of 0.5. There was a statistically significant decrease in FVC, FEV1 and PEFR with a nonsignificant decrease in other pulmonary measurements, except for NIP which only decreased significantly at a ratio of 0.5. These changes are probably of no clinical importance. All the measured respiratory variables returned to control values at a TOF ratio of 0.9.

[Evaluation of pipecuronium bromide during halothane or enflurane anesthesia--a comparison with pancuronium regarding the optimal dose and the effect of volatile anesthetics on neuromuscular blockade].

Pipecuronium, a new muscle relaxant, was examined in surgical patients in a multi-center cooperative study. Neuromuscular blocking action, circulatory effect and side effects of pipecuronium were investigated in comparison with those of pancuronium bromide. Mechanical twitch responses of adductor pollicis muscle evoked by supramaximal stimulation of the ulnar nerve every ten seconds were recorded. The following results were obtained. 1. Approximately 100% twitch depression was obtained after the administration of pipecuronium 0.04 mg.kg-1. 2. Enflurane and halothane did not influence the onset time and recovery time. But enflurane showed more prolonging effect on the duration of pipecuronium induced block than halothane. 3. No clinically significant changes in heart rate and blood pressure were observed. It was concluded that the minimum of 0.04 mg.kg-1 of pipecuronium is necessary for an initial dose and the maintenance dose of pipecuronium can be reduced under enflurane anesthesia.