PubMed Health⌕ Search

Biomedical subjects

G Bikhazi

Publications and source records attributed to G Bikhazi.

9 recordsLinked to original sources

A multicenter evaluation of the time-course of action of two doses of rapacuronium after early and late reversal with neostigmine.

UNLABELLED: Early reversal of rapacuronium may accelerate return of neuromuscular function. This study was designed to compare early (2 min after rapacuronium) or late (at 25% recovery of the first twitch [T1] of train-of-four) reversal of rapacuronium with neostigmine. We studied 119 subjects between the ages of 18 and 75 yr. Anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide, propofol, and fentanyl. Mechanomyographic neuromuscular monitoring was performed by using train-of-four stimulation of the ulnar nerve. Two groups received 1.5 mg/kg rapacuronium followed by neostigmine (50 microg/kg) and glycopyrrolate (10 microg/kg) either at 2 min after rapacuronium bolus or at 25% T1 recovery. The other two groups received 2.0 mg/kg rapacuronium, after which neostigmine was similarly given. For each rapacuronium dose, the time from the administration of rapacuronium to the start of T1 recovery or 25% T1 recovery was significantly shorter in subjects who received the reversal 2 min after rapacuronium. However, late recovery, defined by times from administration of rapacuronium to 70%, or 80% T4/T1 recovery, was not influenced by early reversal administration. We conclude that initial recovery is accelerated by early administration of neostigmine. Time to full recovery after rapacuronium administration is, however, dose-dependent and not significantly altered by early administration of neostigmine. IMPLICATIONS: "Rescue reversal," which includes the administration of neostigmine shortly after the administration of rapacuronium, may accelerate the return of spontaneous breathing (early recovery), but does not shorten the time to complete recovery of upper airway function.

Adolescent↗

Rapacuronium for modified rapid sequence induction in elective caesarean section: neuromuscular blocking effects and safety compared with succinylcholine, and placental transfer.

We have compared rapacuronium 2.5 mg kg-1 (n = 20) with succinylcholine 1.5 mg kg-1 (n = 22) in a multicentre, blinded, randomized study in full-term parturients undergoing elective Caesarean section under general anaesthesia. Thiopental 5 mg kg-1 was given i.v. followed by the neuromuscular blocking agent. Sixty seconds later intubation was performed. Intubating conditions, evaluated as excellent, good or poor, were good to excellent in 95% and 91% in the intent-to-treat patients after rapacuronium and succinylcholine, respectively (ns). Mean onset times at the adductor pollicis muscle for rapacuronium and succinylcholine were 80.4 (SEM 14.4) s and 63.9 (5.6) s (ns) while maximum block was 96 (1.9)% and 99 (0.4)%, respectively (ns). Rate of recovery was significantly longer after rapacuronium; times for return of T1 to 25% were 16.9 (1.5) min and 9.6 (1.1) min for rapacuronium and succinylcholine, respectively (P = 0.0004). Maternal side effects included more tachycardia and skin erythema with rapacuronium; no maternal mortality or morbidity, including bronchospasm, occurred in either group. There were no neonatal adverse effects in either group based on: Apgar scores at 1 and 5 min; times to sustained respiration; neuroadaptive capacity scores at 15 min, 2 h and 24 h; and umbilical venous and arterial blood-gas values and acid-base status. At delivery (17.7 (3.2) min), mean maternal plasma concentrations of rapacuronium were 9041.4 (1259.1) ng ml-1 and 506.4 (24.9) ng ml-1 for Org 9488 (the main metabolite). Corresponding values for umbilical venous plasma were 808.0 (92.1) ng ml-1 and 59.1 (6.5) ng ml-1, and for umbilical arterial plasma, 361.4 (56.4) ng ml-1 and 29.7 (4.6) ng ml-1, respectively. Umbilical venous to maternal venous ratios for rapacuronium and Org 9488 were 8.8% (1.3)% and 10.2 (1.7)%, respectively.

Adolescent↗

Factors affecting the pharmacokinetic characteristics of rapacuronium.

BACKGROUND: Rapacuronium is a new nondepolarizing muscle relaxant with rapid onset and offset. As part of a study to determine its neuromuscular effects, the authors sampled plasma sparsely to determine the influence of age, gender, and other covariates on its pharmacokinetic characteristics. METHODS: Of 181 patients receiving a single bolus dose of 0.5-2.5 mg/kg rapacuronium, 43 (aged 24-83 yr) had plasma sampled 3 or 4 times to determine plasma concentrations of rapacuronium and its metabolite, ORG9488. Pharmacokinetic analysis was performed using a population approach (mixed-effects modeling) to determine the influence of demographic characteristics and preoperative laboratory values on the pharmacokinetic parameters. RESULTS: Rapacuronium's weight-normalized plasma clearance was 7.03 x (1 - 0.0507 x (HgB - 13)) ml x kg(-1) x min(-1), where HgB is the patient's preoperative value for hemoglobin (g/100 ml); however, rapacuronium's blood clearance (11.4+/-1.4 ml x kg(-1) x min(-1), mean +/- SD) did not vary with hemoglobin. Rapacuronium's weight-normalized pharmacokinetic parameters were not influenced by age, gender, or other covariates examined. Plasma concentrations of ORG9488 were typically less than 14% those of rapacuronium during the initial 30 min after rapacuronium administration. CONCLUSIONS: In this patient population, neither age nor gender influence elimination of rapacuronium. This finding contrasts to an age-related decrease in plasma clearance observed in a study of 10 healthy volunteers and in a pooled analysis of the pharmacokinetic data from 206 adults in multiple clinical studies. Even if ORG9488 has a potency similar to that of rapacuronium, its plasma concentrations after a single bolus dose of rapacuronium are sufficiently small to contribute minimally to neuromuscular blockade.

Adult↗

Dose-ranging study in younger adult and elderly patients of ORG 9487, a new, rapid-onset, short-duration muscle relaxant.

The purpose of this multicenter, randomized, assessorblind placebo-controlled study was to determine which of five doses of the new, rapid-onset neuromuscular relaxant, ORG 9487, provided both good to excellent tracheal intubating conditions 60 s after administration and a clinical duration of action < 20 min in 120 younger (aged 18-64 yr) and 61 elderly (aged 65-85 yr) adult patients. Anesthesia was induced with fentanyl (2-5 micrograms/kg) and thiopental (3-6 mg/kg) and maintained with N2O/O2 and a propofol infusion (50-300 micrograms.kg-1.min-1). Neuromuscular train-of-four (TOF) monitoring by electromyography (Datex Relaxograph) commenced immediately after anesthetic induction and was followed, within 30 s, by one of five doses of ORG 9487 (0.5, 1.0, 1.5, 2.0, 2.5 mg/kg) or a placebo. Tracheal intubation was attempted at 60 s and again, in the case of failure, at 90 s. Conditions were assessed with a 4-point scale. Maximum block, clinical duration (time to 25% T1 recovery), and recovery (TOF > or = 0.7) were measured. Dose-dependent changes were observed in tracheal intubating conditions and neuromuscular block. Good to excellent intubating conditions at 60 s were present in most younger adult (52 of 60) and elderly (26 of 31) patients administered doses > or = 1.5 mg/kg. Mean clinical durations < 20 min were observed in adult patients at doses up to 2.0 mg/kg and in geriatric patients up to 1.5 mg/kg. Thus, doses of 1.5-2.0 mg/kg ORG 9487 enabled both rapid tracheal intubation and a short clinical duration of action in adult and elderly patients.

Adolescent↗

Neuromuscular blocking action of two brevetoxins from the Florida red tide organism Ptychodiscus brevis.

The action of Ptychodiscus brevis "brevetoxins" T17 and T34 on rat phrenic nerve-stimulated hemidiaphragm contraction is reported. The potency of T34 is greater than the potency of T17, but both cause a complete block of neuromuscular transmission in the nM to pM concentration ranges. Preparations exposed to low concentrations of T17 can recover in the presence of the toxin, whereas the effects of T34 are irreversible. The initial contracture produced by each is prevented by tetrodotoxin or curare. Neuromuscular block does not appear to be due to acetylcholine depletion, as determined by electron microscope examination of the neuromuscular junctions of blocked preparations. Persistent nerve depolarization is believed to be responsible for the neuromuscular block.

Animals↗

Bronchoconstriction caused by Florida red tide toxins.

T17, a toxin purified from laboratory cultures of Florida's redtide organism, Ptychodiscus brevis (formerly Gymnodinium breve), produces bronchoconstriction in anesthetized artificially-ventilated guinea pigs. Bronchoconstriction, measured as a resistance to mechanical pulmonary inflation, was antagonized by atropine, but not by interruption of vagal nerve stimulation or diaphragm dissection.

Animals↗

Oesophageal foreign bodies.

Impaction of foreign bodies in the oesophagus was analysed in 54 patients, 45 of whom were children. Of the 45 children 28 were aged 2-4 years. Coins were the most common foreign body in children (27 cases) while in adults a bolus of meat was most common (nine cases). In 41 children there was no predisposing factor, but an underlying mechanism was detected in 88% of the adults. The mechanisms were of three types: oesophageal (stricture), neuromuscular (myasthenia gravis), and extrinsic and mechanical (ankylosing spondylitis). In children most of the foreign bodies were impacted in the upper oesophagus at the cricopharyngeal junction, which is the narrowest part of the oesophagus, while in adults the foreign body was usually impacted at the site of the predisposing lesion or in the lower oesophagus. In all patients oesophagoscopy was performed under general anaesthesia to remove the impacted foreign body. Complications were more frequent in adults, mainly owing to the underlying condition.

Adult↗