First human exposure to Org 25969.
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Intraoperative magnetic resonance imaging (MRI) has been used for years to update neuronavigation and for intraoperative resection control. For this purpose, low-field (0.1-0.2 T) MR scanners have been installed in the operating room, which, in contrast to machines using higher magnetic field strength, allowed the use of standard anesthetic and surgical equipment. However, these low-field MR systems provided only minor image quality and a limited battery of MR sequences, excluding functional MRI, diffusion-weighted MRI, or MR angiography and spectroscopy. Based on these advantages, a concept using high-field MRI (1.5 T) with intraoperative functional neuronavigational guidance has been developed that required adaptation of the anesthetic regimen to working in the close vicinity to the strong magnetic field. In this paper the authors present their experience with the first 80 consecutive patients who received anesthesia in a specially designed radio frequency-shielded operating room equipped with a high-field (1.5 T) MR scanner. We describe the MR-compatible anesthesia equipment used including ventilator, monitoring, and syringe pumps, which allow standard neuroanesthesia in this new and challenging environment. This equipment provides the use of total intravenous anesthesia with propofol and remifentanil allowing rapid extubation and neurologic examination following surgery. In addition, extended intraoperative monitoring including EEG monitoring required for intracranial surgery is possible. Moreover, problems and dangers related to the effects of the strong magnetic field are discussed.
Org 9426, a new steroidal non-depolarising muscle relaxant, which is stable in solution, was studied in 30 anaesthetised (thiopentone, fentanyl, nitrous oxide) male patients, ASA 1 or 2. A dose-response curve for Org 9426 was constructed and the ED90, mean (SD), was found to be 0.36 (0.031) mg/kg. The onset of action was 3.8 (1.8) minutes, the clinical duration 17.4 (3.2) minutes, the total duration of action 31.9 (6.2) minutes and the recovery time 9.96 (3.2) minutes. No signs of histamine release or cardiovascular effects were observed. Org 9426 thus has a faster onset of action than vecuronium bromide or atracurium dibesylate.
The dose-response relationship of Org 9426, its time course of action and the reversibility of the residual block by neostigmine have been investigated in 100 patients undergoing various anaesthetic techniques. The dose-response was measured immediately following induction of anaesthesia. Doses of Org 9426, required for 50% and 90% depression of the twitch height, were 202 and 328 micrograms.kg-1, respectively. The clinical duration of the maintenance doses, 150 micrograms.kg-1, ranged from 9.5 to 13.4 min and from 12.8 to 18.9 min for the first and fifth maintenance doses, respectively. Spontaneous recovery indices (25%-75%) were between 9.5 and 16.7 min; neostigmine methylsulphate administered at 25% recovery of the twitch height promptly reversed the residual block. No side effects were observed. The extent of the influence of the anaesthetic on the time course of Org 9426 appears to be fractional considering the variation of the time course within the separate groups.
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The interaction of ORG 9426, a new non-depolarizing neuromuscular blocking agent, with intravenous anaesthetic drugs (fentanyl, thiopental, midazolam, droperidol and etomidate) has been investigated in cats. During an infusion of one of the above anaesthetics, the ED95 dose was determined by titration, and thereafter muscle relaxation was maintained with four subsequent doses of ORG 9426. Neither the potency nor the duration of action of the first dose nor that of the maintenance doses of ORG 9426 differed from those observed in a control group of cats anaesthetized with intraperitoneally administered pentobarbital. The recovery rates were similar in all groups. The authors conclude that, under the conditions of this study, commonly used intravenous anaesthetic drugs are not likely to influence the neuromuscular blocking potency and time course of action of ORG 9426 to any appreciable degree.
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A case is described of a difficult intubation in an infant presenting for cleft palate closure, due to an unsuspected sublingual mass. The report stresses the fact that multiple anomalies can coexist in an infant and contribute to difficult intubation through different mechanisms. Various airway management strategies are explored.
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We describe a case of tracheal rupture diagnosed after an apparently routine endotracheal intubation for otherwise uneventful lower abdominal surgery in a 33-year-old woman. Risk factors for tracheal rupture, presenting symptoms and signs, management of tracheal rupture and methods of airway management during the surgical repair of the tracheal laceration are discussed. In this case, "side-by-side" microlaryngoscopy tubes, one endobronchial and the other with the tip in the upper trachea, placed with fibreoptic assistance were used for airway management during the tracheal repair.
Gordon's syndrome is a rare condition characterized by hypertension and hyperkalemia despite normal renal glomerular function. We report the administration of an anaesthetic to one such patient for an urgent surgical procedure. The patient's serum potassium was only marginally raised at the outset of the procedure. During surgery the serum potassium rose significantly, but responded to conventional management. Hyperkalaemia is a specific electrolyte disturbance that has numerous implications for the administration of an anaesthetic. Most importantly, there is a danger that further acute elevations may occur, caused by the surgery, the anaesthetic, or the condition itself
We describe the case of a woman who had two penroperative hypertensive crises that may have been due to her use of phentermine, a little-known sympathomimetic anti-obesity medication. The currently available anti-obesity medications are discussed: phentermine, diethylpropion, and sibutramine; all of which are sympathomimetics possessing noradrenaline and serotonin reuptake inhibitor activity. These medications should be discontinued one week preoperatively and have potential interactions with tramadol and antidepressants. The drug orlistat inhibits gastrointestinal lipase and may lead to fat soluble vitamin (A, D, E, and K) deficiency, so consideration should be given to checking coagulation status preoperatively.
We studied patients with valvular heart disease to investigate whether chronic preoperative treatment with angiotensin-converting enzyme (ACE) inhibitors modulates the effect of phenylephrine (PE) on anaesthesia-induced hypotension. Sixty-five patients were enrolled in the study and hypotension developed after anaesthesia in 36 (18 in the control group and 18 in the ACE inhibitor group). These patients received PE infusions, which were increased in a stepwise fashion at 10-min intervals. Increased mean arterial pressure due to PE infusion was significant only in the control group. There was no significant difference in pressor response or change in haemodynamic variables with PE infusion between the two groups. Treatment with ACE inhibitors did not increase the incidence of hypotensive episodes or significantly modify pressor response after anaesthesia in patients with valvular heart disease.
Developmental research has been directed toward creating nondepolarizing muscle relaxants with an onset time and duration of actions shorter than that of vecuronium or atracurium. We determined the cardiovascular and neuromuscular effects of three new and promising nondepolarizing muscle relaxants in six dogs anesthetized with halothane. Each dog was anesthetized four times (each time separated from the others by at least 1 wk); one muscle relaxant was studied each time. Three doses (one, three, and five times the ED90) were given as intravenous bolus injections. ORG 9616 and ORG 9991 had shorter durations of action than ORG 9426. The duration of action of the doses that were five times the ED90 was 18 +/- 5.88 and 15.8 +/- 4.41 min (mean +/- SD) with ORG 9616 and ORG 9991, respectively, as compared with 39.7 +/- 17.15 min with ORG 9426 (P less than 0.05). ORG 9426 was virtually free of cardiovascular effects. The ED90 doses of ORG 9616 and ORG 9991 did not cause cardiovascular effects; the doses of three and five times the ED90 caused small decreases in mean arterial blood pressure and increases in heart rate. Mean arterial blood pressure decreased from 99 +/- 10.2 to 88 +/- 13.1 mm Hg and from 98 +/- 11.7 to 77 +/- 8.1 mm Hg with five times the ED90 dose of ORG 9616 and ORG 9991, respectively. The authors conclude that ORG 9426 has a duration of neuromuscular blockade that is probably similar to vecuronium, and one that is free of cardiovascular effects.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine average dose requirements and pharmacodynamic characteristics before general clinical use, the dose-response curve, onset time, and recovery time for the neuromuscular relaxant ORG 9426 were determined in 72 adult patients given doses of 120, 160, 200, or 240 micrograms/kg after establishment of a steady-state expired isoflurane concentration of approximately 1%. Neuromuscular blockade was continuously recorded using the ulnar evoked electromyogram. Using the log probit method, ED95 was 268 micrograms/kg, ED90 was 251 micrograms/kg, and ED50 was 144 micrograms/kg. The time until 80% blockade was 1.9 min at 240 micrograms/kg, and the average time to peak effect was 4.6 min, which did not vary with dose. The clinical duration (injection until T1 returned to 25%) was 20.5 min, and the recovery index (T1 increased from 25% to 75% of control) was 15.4 min, after a total dose of 300 micrograms/kg. The duration of 75-micrograms/kg and 100-micrograms/kg repeat (maintenance) dose was 14.6 and 17.8 min, respectively, and no cumulative effect was apparent after as many as five maintenance doses. No cardiovascular side effects were seen at doses used in the study. We conclude that ORG 9426 is a nondepolarizing muscle relaxant with a rapid onset and short duration of action that deserves further clinical evaluation.
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