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Biomedical subjects

N G Goudsouzian

Publications and source records attributed to N G Goudsouzian.

At least 19 recordsLinked to original sources
PubMed2002

Pharmacodynamics of mivacurium chloride in 13- to 18-yr-old adolescents with thermal injury.

BACKGROUND: Burned patients demonstrate resistance to the effects of non-depolarizing blocking drugs as a result of acetylcholine receptor changes. They also have decreased activity of plasma cholinesterase (PCHE), which metabolizes mivacurium. We hypothesized that decreased PCHE activity would decrease metabolism of mivacurium, and counteract the receptor-related resistance following burns. METHODS: Thirteen burned patients and six controls, aged 13-18 yr were followed in 27 studies. The burned patients were sub-classified as having 10-30% or >30% body surface area burn and were studied whenever possible at < or =6 days, and at 1-12 weeks after the burn. Mivacurium pharmacodynamics were examined following a bolus (0.15 mg kg(-1)) dose, and during and after a continuous infusion. RESULTS: Following a bolus, the onset time and the maximal effect were similar to controls. Recovery was prolonged in the 10-30% burn group at 1-12 weeks (P<0.008), with a similar trend in the >30% burn group at < or =6 days (P<0.082) compared with controls. The infusion requirements for mivacurium were not increased in the burned groups. The PCHE activity was decreased in all burn groups and was inversely related to recovery following the bolus (r=0.73, P<0.001) and the infusion (r=0.69, P<0.001). CONCLUSION: In contrast to previous studies with non-depolarizers in burned patients, normal mivacurium doses can produce paralysis, at least as rapidly as in controls, but with a possibility of a prolonged recovery from block. The standard dose of mivacurium in the presence of decreased PCHE activity is in effect, a relative overdose that explains the above findings. Mivacurium is an effective drug for use in burns, irrespective of time after, or magnitude of burn injury.

Adolescent↗
PubMed2001

Intramuscular rapacuronium in infants and children: a comparative multicenter study to confirm the efficacy and safety of the age-related tracheal intubating doses of intramuscular rapacuronium (ORG 9487) in two groups of pediatric subjects.

BACKGROUND: This multicenter, assessor, blinded, randomized study was conducted to confirm and extend a pilot study in which intramuscular rapacuronium was given to infants and children to confirm efficacy and to evaluate tracheal intubating conditions. METHODS: Ninety-six pediatric patients were studied in two groups: infants aged 1 to 12 months (n = 46) and children aged 1 to 3 yr (n = 50). Infants received 2.8 mg/kg and children 4.8 mg/kg of intramuscular rapacuronium during 1 minimum alveolar concentration halothane anesthesia. These two groups were studied in three subgroups, depending on the time (1.5, 3, or 4 min) at which tracheal intubation was attempted after the administration of intramuscular rapacuronium into the deltoid muscle. Neuromuscular data collected included onset time, duration of action, and recovery data during train-of-four stimulation at 0.1 Hz. Data were analyzed by the Cochran-Mantel-Haenszel procedure. RESULTS: The tracheal intubating conditions were deemed acceptable in 17, 36, and 64% of infants and 20, 47, and 71% of children at 1.5, 3, or 4 min, respectively. The mean values for % of control twitch height (T1) 2 min after rapacuronium in both groups were similar. The mean (SD) time required to achieve more than or equal to 95% twitch depression in infants was 6.0 (3.7) versus 5.5 (3.8) min in children. CONCLUSIONS: Only 27% of patients achieved clinically acceptable tracheal intubating conditions at 1.5 or 3 min after administration of 2.8 mg/kg and 4.8 mg/kg rapacuronium during 1 minimum alveolar concentration halothane anesthesia. Tracheal intubation conditions at 4 min were acceptable in 69% of subjects. The duration of action of 4.8 mg/kg of rapacuronium in children was longer than 2.8 mg/kg of rapacuronium in infants.

Anesthesia, Inhalation↗
PubMed2000

Neuromuscular effects of mivacurium in 2- to 12-yr-old children with burn injury.

BACKGROUND: Burned patients are usually resistant to the neuromuscular effects of nondepolarizing relaxants, mostly because of receptor changes. The magnitude of the resistance is related to burn size and time after burn. Mivacurium is a muscle relaxant, degraded by plasma cholinesterase, whose enzyme activity is decreased in burns. The present study tested the hypothesis that burn-induced depressed plasma cholinesterase activity counteracts the receptor-mediated resistance, resulting in a lack of resistance to mivacurium. METHODS: Burned patients (n = 23), aged 2-12 yr, subclassified into burns of 10-30% or > 30% of body surface, were studied at < or = 6 days and again at 1-12 weeks after burn if possible. Thirteen additional patients served as controls. Neuromuscular variables monitored included onset and recovery following bolus dose, continuous infusion rates required to maintain 95 +/- 4% paralysis, and recovery rates following infusion. RESULTS: The onset times of maximal twitch suppression were not different between burns and controls, but recovery to 25% of baseline twitch height was prolonged in patients with > 30% burn irrespective of time after injury. The continuous infusion rates to maintain twitch suppression at 95 +/- 4% were not different between groups. The recovery indices, including train-of-four to > 75%, 25-75%, or 5-95% in burned patients, were similar or prolonged compared with controls. The prolonged recovery in burned patients was inversely related to plasma cholinesterase activity (R2 = 0.86, r = -0.93, P < 0.001), and the decreased plasma cholinesterase activity was related to burn size and time after burn. CONCLUSIONS: A normal mivacurium dosage (0.2 mg/kg) effects good relaxation conditions in burned patients, with an onset time similar to that in controls. This finding contrasts with the response seen with other nondepolarizing drugs, higher doses of which are required to effect paralysis. The decreased metabolism of mivacurium, resulting from depressed plasma cholinesterase activity, probably counteracts the receptor-mediated potential for resistance. Because succinylcholine is contraindicated in burned patients, larger doses of nondepolarizing agents are advocated to effect rapid onset of paralysis. This generalization does not hold for mivacurium. diatrics; plasma cholinesterase; relaxant resistance; succinylcholine, alternative to.)

Body Weight↗
PubMed1997

Mivacurium in infants and children.

Mivacurium is the only available short-acting nondepolarizing muscle relaxant in clinical use. It is a bis-quaternary benzylisoquinolinium ester hydrolysed by plasma-cholinesterase into inactive compounds. The ED50 and ED95 in children are about 50 micrograms.kg-1 and 90 micrograms.kg-1 respectively. In infants, they have a tendency to be lower. A standard intubating dose of 0.25 mg.kg-1 causes complete neuromuscular depression in 1.5-2 min, recovery to 5% in 6-10 min, and complete recovery in 15-20 min. The recent tendency is to use 0.3 mg.kg-1 to obtain better intubating conditions with slight prolongation of effect. Since the recovery profile of mivacurium is independent of the dose and duration, it is most suitable for administration by continuous infusion. The infusion requirement in children is 10-16 micrograms.kg-1 min-1, which is about twice that of adults. Cutaneous flushes from histamine release are commonly seen with the larger doses of mivacurium; however, the associated hypotensive effects are minimal and counteracted by the tracheal intubation. The duration of action of mivacurium is prolonged in patients with cholinesterase deficiency. Mivacurium's neuromuscular effects can be satisfactorily antagonized by edrophonium or neostigmine.

Adjuvants, Anesthesia↗
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↗
PubMed1996

Efficacy and safety of divided dose administration of mivacurium for a 90-second tracheal intubation.

STUDY OBJECTIVE: To compare the safety and effectiveness of 0.25 mg divided doses of mivacurium chloride to succinylcholine for a 90-second tracheal intubation. DESIGN: Randomized, double-blind, multicenter study in two groups. SETTING: Operating rooms at four university medical centers. PATIENTS: 200 healthy ASA status I and II adult patients scheduled for elective surgery with general anesthesia and endotracheal intubation. INTERVENTIONS: Patients were premedicated with 1 to 2 mg midazolam and 2 micrograms/kg fentanyl. Anesthesia was induced with 2 mg/kg propofol. Group A received 0.25 mg/kg mivacurium given as a divided dose (0.15 mg/kg followed in 30 seconds with 0.1 mg/kg). Group B (control) received 1.5 mg/kg succinylcholine (SCh) preceded two minutes earlier by 50 micrograms/kg d-tubocurarine (dtc). MEASUREMENTS AND MAIN RESULTS: Tracheal intubation grading, train-of-four response of the adductor pollicis, heart rate (HR), and mean arterial blood pressure (MAP) were measured and evaluated. Chi-square analysis was performed for comparison between Group A and Group B with respect to the frequency distribution of intubation using the scores excellent, good, and poor and not possible (combined). Group B had a significantly higher excellent score of intubation than Group A, 84% versus 56% (p < 0.0001). No significant difference was found between the two groups when the scores excellent and good were combined (Fisher's Exact test, p = 0.28). The changes in MAP and HR were similar for the two groups. CONCLUSIONS: When Sch is not desirable, mivacurium 0.25 mg/kg given as a divided dose provides good to excellent intubation conditions 90 seconds after the initial dose without significant changes in MAP or HR. It can be an appropriate alternative for short surgical procedures. It must be emphasized that this conclusion does not apply to rapid-sequence induction-intubation.

Adolescent↗
PubMed1996

The influence of the age of the rat on the neuromuscular response to mivacurium in vitro.

The effective concentrations of mivacurium induced neuromuscular block were studied in the phrenic nerve-hemidiaphragm preparations of forty male Sprague-Dawley rats in four groups according to body weight, 10 g, 25 g, 100 g, and 200 g. Mivacurium was added to the Krebs' solution to obtain an initial concentration of 0.275 microgram.ml-1 (2.5 x 10(-7) mole.litre-1). Thereafter, the concentration of mivacurium was increased in increments to obtain more than 90% neuromuscular twitch inhibition at 0.1 Hz. Data were analysed by probit and logistic models. The two statistical techniques yielded very similar results, almost identical values of EC50 and EC95. There were significant decreases in the effective concentrations of mivacurium needed to depress the twitch response in neonatal rats (10 g) compared to older rats. No significant differences were observed between 25, 100 and 200 g rats. We conclude that the neonatal neuromuscular junctions of rats show increased sensitivity to mivacurium related to pharmacodynamic factors.

Aging↗
PubMed1995

The use of the laryngeal mask airway in children with bronchopulmonary dysplasia.

Airway maintenance with the laryngeal mask airway (LMA) was evaluated and compared to the endotracheal (ET) tube in 27 former premature infants and children with bronchopulmonary dysplasia (BPD) during second stage open-sky vitrectomy. The children were randomly assigned to a study group and anesthetized with halothane in N2O:O2. The airway was maintained with the LMA (n = 13) or the ET tube (n = 14). Respiratory and hemodynamic variables were recorded. Intraoperative and postoperative complications were noted. The respiratory rate and the end-tidal CO2 were significantly higher in the LMA group as compared with the ET tube group (P < 0.01); however, the pulse rate and both systolic and diastolic blood pressures throughout the surgical procedure were lower in the LMA group (P < 0.05). The incidence of coughing, with and without desaturation, wheezing, and hoarseness in the postoperative period was higher in the ET tube group. Awakening, after discontinuation of the anesthetic (P < 0.01) was more rapid, and home discharge time (P < 0.002) was shorter in the LMA group (P < 0.0025), although our study design could not isolate the use of the LMA as the factor responsible for this. This study in patients with mild chronic lung disease demonstrated that the LMA can maintain a satisfactory airway during minor surgical procedures in children with bronchopulmonary dysplasia and result in fewer respiratory adverse effects than with the ET tube.

Anesthesia Recovery Period↗
PubMed1995

Evaluation of different induction techniques for tracheal intubation.

Conditions for tracheal intubation and the hemodynamic changes associated with different intravenous anesthetic induction techniques were studied in seventy-two ASA I patients randomly assigned to one of six groups (G). Anesthesia was induced with I.V. propofol 2.5 in G 1, 3, 5 or with thiopental 5 mg/kg (G2, 4, 6). In G 1-4, the standard sequence of administering muscle relaxant was used. G 1 and 2 received succinylcholine 1 mg/kg after induction, and one min later laryngoscopy and orotracheal intubation attempted. G3 and 4 received 0.5 mg/kg atracurium and intubation attempted 3 min later. In G 5 and G 6 the "timing principle" was used; atracurium 0.5 mg/kg was given first followed by propofol and thiopental, and one minute after the induction agent intubation attempted. There was no statistically significant difference in the intubating conditions between the six groups of patients studied. Similar to succinylcholine timing technique with atracurium and propofol or thiopental reliably provided excellent or good intubating conditions in two minutes.

Adolescent↗
PubMed1994

Mivacurium after atracurium in children.

The effect of mivacurium after atracurium was evaluated in 36 children anesthetized with halothane-nitrous oxide-oxygen by measuring the force of contraction of the adductor pollicis during train-of-four stimulation at 0.1 Hz. The children were evaluated in two main groups. In Group 1 the effect of bolus doses of mivacurium after equipotent repeat doses of atracurium were evaluated. When the first twitch of the train-of-four response (T1) had recovered to 25% of control after a tracheally intubating dose of atracurium, a repeat dose of atracurium was given, on subsequent recovery to 25%, an equipotent dose of mivacurium was administered. In Group 2 when T1 had recovered to > 10% from 0.5 mg/kg atracurium, a mivacurium infusion was started; the initial infusion rate was 4 micrograms.kg-1.min-1 with adjustments made to maintain 90%-99% depression of T1. Patients were allowed to recover spontaneously from the effect of the relaxants. In Group 1 prolongation of the effect of mivacurium was noted after atracurium; the recovery indices (25%-75% and 5%-95%) of mivacurium were longer than those seen when mivacurium is the sole relaxant but shorter than atracurium. In Group 2, 15 min after the start of the mivacurium infusion, the dose requirement was 3.7 +/- 0.3 micrograms.kg-1.min-1 (approximately about one-third that required after a tracheally intubating dose of mivacurium). The infusion requirement increased gradually (P < 0.0001) until, at 90 min of infusion, it was 7.4 +/- 0.8 micrograms.kg-1.min-1. In Group 2 the recovery indices were similar to those seen when mivacurium is the sole relaxant given. When mivacurium is given after atracurium, evidence of the residual neuromuscular effects of the atracurium are detected beyond the usual recovery range.

Adolescent↗