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PubMed1997

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.

Adult↗
PubMed1993

Isobolographic and dose-response analysis of the interaction between pipecuronium and vecuronium.

We have studied the neuromuscular effects of pipecuronium, vecuronium and their combination in 130 ASA group I or II patients. Patients were anaesthetized with 0.8% halothane and 60% nitrous oxide in oxygen. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 10-s intervals). The dose-response curves were determined by probit analysis. The calculated doses producing 50% depression of the first twitch height were 15.6, 16.9 and 15.0 micrograms kg-1 for the pipecuronium, vecuronium and pipecuronium-vecuronium combination groups, respectively. Isobolographic and algebraic (fractional) analyses were used to assess quantitatively the combined neuromuscular effect of pipecuronium and vecuronium and to define the type of interaction between these drugs. The interaction between pipecuronium and vecuronium was found to be additive.

Adolescent↗
PubMed1994

Neuromuscular blockade of the fetus with pancuronium or pipecuronium for intra-uterine procedures.

Fetal movement during intra-uterine fetal therapy makes these procedures technically more difficult and increases the likelihood of trauma to the fetus. Pancuronium or pipecuronium were used in a randomised study to temporarily arrest movement in 16 fetuses undergoing intra-uterine procedures. Under ultrasound guidance, pancuronium or pipecuronium 0.2 mg.kg-1 was injected into the fetal gluteal region. Fetal movements ceased within 4.6 +/- 2.3 min in the pancuronium group and 4.5 +/- 2.8 min in the pipecuronium group and returned by 115 +/- 26 min in the pancuronium group and 121 +/- 32 min in the pipecuronium group. No adverse effects of the relaxant were observed in the mothers. There was no evidence of soft tissue, nerve or muscle damage at the fetal injection site after delivery. Both muscle relaxants provided a safer method for diagnostic and therapeutic procedures. However, four cases in the pancuronium group (50%) developed a fetal tachycardia, and two cases in the same group showed loss of beat-to-beat variability. Pipecuronium appeared to be more suitable for intra-uterine procedures.

Female↗
PubMed1992

Myasthenia gravis and pipecuronium--report of two cases.

The use of pipecuronium in two patients with myasthenia gravis undergoing thymectomy is described. Neuromuscular function was monitored throughout using the train-of-four (TOF) mechanical twitch response. The cumulative dose-response to pipecuronium was determined in both patients during nitrous oxide-oxygen-narcotic anaesthesia. Both patients were sensitive to pipecuronium. The ED50 doses of pipecuronium were 11.6 and 11.1 micrograms.kg-1 and the ED95 doses were 35 and 33.3 micrograms.kg-1 in patients #1 and 2 respectively. Edrophonium 1 mg.kg-1 and neostigmine 0.06 mg.kg-1 were administered to patients #1 and 2 respectively for antagonism of residual neuromuscular blockade at 25 per cent spontaneous recovery of first twitch (T1) of the TOF stimulation. As with other non-depolarizing muscle relaxants pipecuronium in reduced dosage and with careful neuromuscular monitoring can be used to provide surgical relaxation safely in patients with controlled myasthenia gravis.

Adult↗
PubMed1989

Dose-response relation and time course of action of pipecuronium bromide in humans anesthetized with nitrous oxide and isoflurane, halothane, or droperidol and fentanyl.

The dose-response of pipecuronium bromide, the time course of its neuromuscular blocking effects, and the reversibility of the residual block by neostigmine and edrophonium have been investigated in patients undergoing various types of anesthesia. The estimated doses of pipecuronium required for 95% depression of the twitch height were 44.6, 46.9, and 48.7 micrograms.kg-1 during anesthesia with nitrous oxide (65%) and isoflurane (group 1), halothane (group 2), or droperidol/fentanyl (group 3), respectively. The potentiating effects of the volatile anesthetics were reflected by the significant prolongation of the duration of both initial (50.0 +/- 4.3, 36.0 +/- 3.3, and 29.0 +/- 2.0 minutes) and maintenance doses (56.0 +/- 2.5, 49.5 +/- 3.3, and 41.2 +/- 1.6 minutes) of pipecuronium during anesthesia with nitrous oxide and isoflurane, halothane, or droperidol/fentanyl, respectively. Both edrophonium chloride (0.5 mg.kg-1) and neostigmine methylsulphate (40 micrograms.kg-1) promptly reversed the residual block induced by pipecuronium. No side effects attributable to pipecuronium were seen in this study.

Adult↗
PubMed1987

Interactions between pipecuronium and suxamethonium in the dog.

The depolarising muscle relaxant suxamethonium (0.3 mg kg-1) and the non-depolarising muscle relaxant pipecuronium (0.05 mg kg-1) were administered to four dogs. In the first series of experiments pipecuronium was administered intravenously, followed at 50 per cent of return of neuromuscular activity by suxamethonium. At 50 per cent return of activity atropine and neostigmine were administered to reverse the neuromuscular block. In the second series the sequence was reversed and pipecuronium was administered after suxamethonium. At 50 per cent recovery atropine and neostigmine were given. In the first series of experiments the time for the onset of suxamethonium block was significantly increased after prior administration of pipecuronium. However, in the second series of experiments the prior administration of suxamethonium had no significant effect on the duration of action of pipecuronium.

Androstane-3,17-diol↗
PubMed1996

Effects of pipecuronium and pancuronium on cerebrospinal fluid pressure in neurosurgical patients.

Arterial hypertension and/or tachycardia may alter intracranial pressure in neurosurgical patients. We compared the effects of pancuronium 0.1 mg/kg and pipecuronium 0.1 mg/kg given as i.v. bolus on cerebrospinal fluid (CSF) pressure in 2 groups of 10 patients each scheduled for intracranial surgery in the supine position. Before surgery, no patient presented clinical symptoms of elevated intracranial pressure (ICP). Anesthesia was induced and maintained with fentanyl and midazolam. Ventilation with 50% nitrous oxide in oxygen was adjusted to maintain arterial pCO2 at 30-35 mmHg. After induction of anesthesia, CSF pressure was registered via a lumbar subarachnoid catheter before and 3, 5, 10, and 30 min after pipecuronium or pancuronium administration. Hemodynamics were monitored using radial and pulmonary artery catheters. All variables underwent analyses of variance for repeated measures with p < 0.05 considered significant. Mean CSF pressure decreased insignificantly from 15 +/- 5 mmHg (before injection) to 14 +/- 4 mmHg in patients given pipecuronium and from 13 +/- 4 mmHg to 10 +/- 3 mmHg in the pancuronium group without significant differences between the study groups. Heart rate and arterial pressure increased significantly (p < 0.001) in patients given pancuronium but remained stable after pipecuronium. Onset and duration of neuromuscular blockade were comparable between groups. Based on our results, pipecuronium is a safe alternative to pancuronium during neurosurgical procedures in patients without abnormally high intracranial pressure.

Adult↗
PubMed1993

Dose-response relation and time course of action of pipecuronium in patients anesthetized with nitrous oxide and sevoflurane.

The dose-response relation of pipecuronium, the time course of its neuromuscular blocking effects, and the reversibility of the residual block by neostigmine have been investigated in patients under sevoflurane/N2O Anesthesia using a neuromuscular transmission analyzer (Accelograph, Biometer, Denmark). After an initial dose of pipecuronium (0.04 mg.kg(-1), i.v.), the maximum block rate, onset time, the time from administration until 25% recovery and 50% recovery of control twitch height of the first response to train-of-four nerve stimulation and the interval time of administration of maintenance dose (0.005 mg.kg(-1), i.v.) were 93.7 +/- 7.68%, 5.0 +/- 1.84, 55.4 +/- 23.92, 73.0 +/- 29.44 and 38.7 +/- 15.50 minutes, respectively. The average intubation score (excellent; 0, good; 1 fair; 2, poor; 3) was 0.63 +/- 0.56 at the level of 95.88 +/- 5.06% block. Neostigmine (1.5 mg) promptly reversed the residual neuromuscular blockade induced by pipecuronium (reversal time: 10.1 +/- 2.98 minutes). No side effects attributable to pipecuronium was seen in this study. In conclusion, pipecuronium is a very useful nondepolarizing neuromuscular blocking agent especially for moderately long surgical procedure over 4-5 hours.

Journal Article↗
PubMed1989

A dose-response evaluation of pipecuronium bromide in elderly patients under balanced anesthesia.

Pipecuronium bromide is a new steroidal non-depolarizing muscle relaxant currently under investigation. It is similar to pancuronium with respect to the duration of action, but lacking its cardiovascular side effects. We examined the dose-response relation of pipecuronium in 27 patients, ages 66-79 years, utilizing the incremental dose method under balanced anesthesia. The ED50, ED90 and ED95 were 22.42 (5.2) mcg/kg, 31.81 (6.9) mcg/kg and 35.12 (7.8) mcg/kg, respectively (log probit method). Our recovery data also demonstrate that residual neuromuscular blockade due to pipecuronium can easily be antagonized with neostigmine as long as spontaneous recovery of T1- at the time of reversal administration is greater than 13%. The authors conclude that under balanced anesthesia the cumulative dose-response of pipecuronium in the elderly patients is consistent with those previously described for younger population. Therefore, no dose adjustment appears necessary for the elderly. However, as with all medications, careful administration is appropriate.

Aged↗
PubMed1995

Left ventricular regional wall motion and haemodynamic changes following bolus administration of pipecuronium or pancuronium to adult patients undergoing coronary artery bypass grafting.

The objective of this study was to compare the haemodynamic and myocardial effects of pipecuronium and pancuronium in patients undergoing coronary artery bypass grafting (CABG) during benzodiazepine/sufentanil anaesthesia. Twenty-seven ASA III-IV patients received lorazepam (1-3 mg) po and midazolam ( < 0.1 mg.kg-1) i.v. before induction of anaesthesia with sufentanil (3-8 micrograms.kg-1) was administered to facilitate tracheal intubation. According to random allocation, each patient received either pipecuronium (150 micrograms.kg-1) or pancuronium (120 micrograms.kg-1) after sternotomy but before heparinization. Mean arterial pressure, central venous pressure (CVP), pulmonary artery pressure (PAP), ST segment position and ECG (leads III, V5, AVF) were monitored continuously throughout the procedure. Thermodilution determinations of CO in triplicate were made immediately before, and at two and five minutes after muscle relaxant administration. Multiplane transoesophageal echocardiography (TEE, midpapillary short axis views of the left ventricle) images were continuously recorded from ten minutes before until ten minutes after muscle relaxant administration and graded by two experienced echocardiographic readers. Heart rate, MAP and CO increased after administration of pancuronium (by 13.6 beats.min-1, 10.8 mmHg and 1.0 L.min-1 respectively) but not after pipecuronium (P < 0.05). Evidence of myocardial ischaemia was not detected in any patients using ECG ST segment analysis or TEE assessment of left ventricular wall motion. We conclude that pancuronium caused increases in HR, MAP and CO but that neither pancuronium nor pipecuronium caused myocardial ischaemia.

Adult↗
PubMedDate not supplied

Intubating conditions after pipecuronium bromide: the influence of dose and time.

STUDY OBJECTIVE: To determine the intubating conditions following the administration of pipecuronium bromide in doses of two (0.07 mg/kg) or three (0.1 mg/kg) times ED95 (average dose that gives 95% block of the first twitch). DESIGN: To compare intubating conditions at 11/2 and 21/2 minutes in 41 patients receiving balanced anesthesia. SETTING: Surgical patients at Thomas Jefferson University Hospital. PATIENTS: Forty-one patients undergoing surgical procedure who received general anesthesia. INTERVENTIONS: After obtaining a stable baseline of train-of-four (TOF), 41 patients randomly received either 0.07 mg/kg or 0.1 mg/kg of pipecuronium as a single intravenous (IV) bolus dose, and the trachea was intubated either at 11/2 or 21/2 minutes. MEASUREMENTS AND MAIN RESULTS: Intubating conditions at 21/2 minutes appeared significantly better than those at 11/2 minutes, regardless of the pipecuronium dose. The mean time for T1 (first twitch of TOF) to reach 50% and 90% suppression was 1.36 +/- 0.51 minutes and 2.29 +/- 0.8 minutes, respectively, for the 0.07 mg/kg dose and 1.07 +/- 0.27 minutes and 1.72 +/- 0.45 minutes, respectively, for the 0.1 mg/kg dose. This did not make a significant difference in intubating conditions at either time. The time to 25% recovery of T1 was 68.2 +/- 22 minutes for the 0.07 mg/kg dose and 121.5 +/- 49 minutes for the 0.1 mg/kg dose. In patients who had spontaneous recovery of T1 to between 10% and 25% of control, administration of neostigmine or edrophonium resulted in identical recovery in 10 minutes. However, in patients with less than 10% spontaneous recovery of T1, neostigmine appeared to be superior to edrophonium. CONCLUSION: Pipecuronium has a relatively rapid onset. The trachea could be intubated successfully in 11/2 minutes with a dose of either 0.07 mg/kg or 0.1 mg/kg. If the clinical situation requires perfect relaxation with no movement or bucking, we recommend waiting at least 21/2 minutes.

Adult↗
PubMedDate not supplied

Accelerated recovery from pipecuronium in patients treated with chronic anticonvulsant therapy.

STUDY OBJECTIVE: To determine whether chronic anticonvulsant therapy affects recovery time from pipecuronium. DESIGN: Open-labeled, controlled study. SETTING: Inpatient neurosurgical service at a university medical center. PATIENTS: ASA physical status II and III patients within 30% of their ideal body weight and without significant history of ethanol abuse or renal or hepatic disease. Nineteen patients were admitted into the study and were divided into three groups based on the number of anticonvulsant medications (MED) they were taking: MED = 0, control group (6 patients); MED = 1, one anticonvulsant (6 patients); MED = 2, two or more anticonvulsants (7 patients). INTERVENTIONS: Intravenous (IV) administration of pipecuronium 80 micrograms/kg with general anesthesia after thiopental sodium 4 to 6 mg/kg IV, maintained with 70% nitrous oxide in oxygen, 0.2% to 0.3% end-tidal isoflurane, and fentanyl. MEASUREMENTS AND MAIN RESULTS: The evoked compound electromyogram (ECEMG) of the adductor pollicis brevis muscle was measured after stimulation of the ulnar nerve by train-of-four (TOF) supramaximal impulses at 2 Hz repeated every 20 seconds. Measurements include T-1% (ECEMG signal at 25%, 50%, and 75% of baseline), TR% (TOF ratio), and recovery index (RI). Patients administered chronic anticonvulsant therapy recovered more rapidly from pipecuronium than untreated patients. For instance, time to 25% recovery of baseline (T-1 25%) was 123 +/- 13 minutes for MED = 0, 91 +/- 7 minutes for MED = 1, and 58 +/- 5 minutes for MED = 2 (p < 0.05). TOF recovery to 20% (TR 20%) and RI were similarly affected. CONCLUSIONS: Patients treated with chronic anticonvulsant therapy recovered from pipecuronium more rapidly than unmedicated patients. Furthermore, there seemed to be a dose-effect relationship between the number of anticonvulsants received and a decreased time to recovery from pipercuronium neuromuscular blockade.

Adolescent↗
PubMed1996

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.

Adult↗
PubMed1994

Comparison of hemodynamic responses to pipecuronium and doxacurium in patients undergoing valvular surgery while anesthetized with fentanyl.

Hemodynamic responses to pipecuronium bromide or doxacurium chloride were compared in patients undergoing valvular heart surgery. Thirty ASA class III-IV patients of either sex, mean age 62 +/- 3 years (+/- SD), weight 70 +/- 3 kg, were randomly selected to receive either doxacurium (0.08 mg/kg) or pipecuronium (0.15 mg/kg). Hemodynamic parameters were determined at preinduction, induction, 2 minutes and 6 minutes following administration of the muscle relaxant. Anesthetic induction consisted of midazolam, 0.10 mg/kg, followed by fentanyl, 5 micrograms/kg. Measured or calculated parameters were as follows: mean arterial pressure, heart rate, cardiac index, mean pulmonary artery pressure, systemic vascular resistance index, central venous pressure, pulmonary capillary wedge pressure, stroke volume index, left and right stroke work indices, and pulmonary vascular resistance index. Awake patients who had been randomly assigned to the pipecuronium group had significantly higher pulmonary capillary wedge pressures (22 +/- 2 v 15 +/- 2 mmHg; P < 0.05) and heart rates (86 +/- 3 v 64 +/- 5 beats/min; P < 0.05) than awake patients in the doxacurium group. Following induction, both wedge pressure and heart rate were not significantly different between the two groups. Compared to hemodynamics at induction, there were no clinically significant changes following administration of pipecuronium or doxacurium.

Anesthesia, Intravenous↗
PubMed1988

Pipecuronium and pancuronium: comparison of pharmacokinetics and duration of action.

The pharmacokinetics of pipecuronium 0.07 mg kg-1 and pancuronium 0.1 mg kg-1 were compared in 39 ASA class I or II patients. Plasma concentrations of these agents were measured for 6 h following administration, using a sensitive and specific capillary gas chromatographic assay. Concentration v. time data were analysed by non-linear regression and fitted to a two- or three-compartment model as appropriate. Neuromuscular blockade was assessed by measuring the mechanical evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. Pipecuronium had a larger steady-state volume of distribution (Vss) (309 (SD 103) ml kg-1) and greater plasma clearance (Cl) (2.4 (0.6) ml kg-1 min-1) than pancuronium (199 (54) ml kg-1 and 1.5 (0.4) ml kg-1 min-1, respectively). The volumes of the central compartment, distribution and elimination half-lives and mean residence times were similar for both agents and within the range expected for drugs of this type. The durations of action (injection to 25% recovery of twitch tension) of pipecuronium and pancuronium were similar: 98.0 (36.1) min and 117.2 (35.8) min, respectively. We conclude that the time courses of neuromuscular blockade following pipecuronium and pancuronium are similar, despite the differences in Vss and Cl.

Adult↗
PubMed1989

Effects of pipecuronium and pancuronium on the isolated rabbit heart.

We have studied the effects of pipecuronium and pancuronium on myocardial contractility and heart rate in two different animal preparations. Pipecuronium and pancuronium produced no change in isometric contraction of rabbit atria. The chronotropic effects of pipecuronium, pancuronium and vecuronium were investigated using acetylcholine as an agonist in isolated perfused rabbit heart. Pancuronium but not pipecuronium or vecuronium, produced a significant degree of antagonism to the bradycardia produced by acetylcholine.

Androstane-3,17-diol↗
PubMed1999

Do pipecuronium and rocuronium affect human bronchial smooth muscle?

BACKGROUND: Muscle relaxants affect nicotinic and muscarinic receptors. Interaction of muscle relaxants with muscarinic receptors of human airways has been studied incompletely. METHODS: The effects of pipecuronium bromide (long-acting, nondepolarizing) and rocuronium bromide (intermediate-acting, nondepolarizing) on prejunctional and postjunctional muscarinic receptors were studied in 96 isolated human bronchial rings from 12 patients. Contractile isometric responses to electric field stimulation of pilocarpine-stimulated and nonstimulated M2 muscarinic receptors were compared before and after incubation with the two muscle relaxants. The effect on postjunctional muscarinic receptors was studied by comparing acetylcholine concentration-response curves before and after incubation with the two muscle relaxants. RESULTS: Pipecuronium bromide, but not rocuronium bromide, inhibited pilocarpine-stimulated prejunctional M2 muscarinic receptors. Neither pipecuronium bromide nor rocuronium bromide had significant inhibitory effects on nonstimulated M2 muscarinic receptors and on postjunctional M3 muscarinic receptors. CONCLUSIONS: The inhibitory effect of pipecuronium bromide on pilocarpine-stimulated prejunctional M2 muscarinic receptors occurred at clinical concentrations.

Acetylcholine↗
PubMed1995

Effect of plasma anticonvulsant level on pipecuronium-induced neuromuscular blockade: preliminary results.

Patients receiving anticonvulsants are resistant to nondepolarizing muscle relaxants (NDMR). This study examines the effect of plasma anticonvulsant levels on pipecuronium-induced neuromuscular blockade. Twenty adult patients scheduled for neurosurgery were assigned to one of two groups. Group 0 (G0) consisted of 10 patients not on anticonvulsant therapy; group 1 (G1) included 10 patients treated either with phenytoin or carbamazepine. G1 patients were further divided into G1u (n = 4) and G1w (n = 6) subgroups, according to the plasma anticonvulsant level measured the day before surgery--under (G1u) or within (G1w) the therapeutic range. Neuromuscular transmission was monitored with a Biometer International A/S Accelograph. Anesthesia was induced and maintained using propofol and sufentanil. After calibration of the accelograph, a bolus of pipecuronium 0.08 mg/kg was given IV. The time from pipecuronium injection to the peak reduction of T1 was taken as the onset time. The time in min from pipecuronium injection to recovery of T1% (first accelograph response/baseline response) x 100 and TR% (fourth accelograph response/first accelograph response) x 100 were recorded at 25, 50, and 75% of baseline. The recovery index (RI) was taken as the time from 25 to 75% of baseline. The recovery index (RI) was taken as the time from 25 to 75% recovery of the baseline response. The onset time was not different in G0 (203 +/- 60.4 s), G1 (230.5 +/- 79.3 s), and G1u (181.8 +/- 60.4 s) but prolonged in G1w (279.2 +/- 67.7 s).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗