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Preliminary investigations of the clinical pharmacology of three short-acting non-depolarizing neuromuscular blocking agents, Org 9453, Org 9489 and Org 9487.

Three muscle relaxants, Org 9453, Org 9489 and Org 9487, short-acting in animals, were investigated to establish their profiles in humans. Potency, time course of action, and pharmacokinetic behaviour were studied in 90 healthy patients during fentanyl/halothane/N2O anaesthesia. Neuromuscular function was monitored mechanomyographically. Plasma and urine concentrations (three patients per compound) were measured by HPLC, and these data were analyzed by iterative linear least square regression analysis. The ED90 values for Org 9453, Org 9489 and Org 9487 were 1.4, 0.45 and 1.15 mg.kg-1 respectively. The onset times of Org 9453 (1.5 mg.kg-1, 1.1 X ED90), Org 9489 (0.9 mg.kg-1, 2 X ED90) and Org 9487 (1.5 mg.kg-1, 1.3 X ED90) were 1.2, 1.6 and 1.5 min, and the durations until 25% twitch recovery were 8.6, 22.0 and 8.9 min, respectively. Clearances of these doses were 6.9, 5.8, and 11.1 ml.kg-1.min-1, and mean residence times 26, 79, and 41 min, respectively. Mean renal excretion (parent compound and metabolites) within 24 hr amounted to 5, 11.3 and 12.2% respectively. No side effects other than a moderate short-lasting decrease of blood pressure and a concomittant increase in heart rate were noted. It is concluded that Org 9453 and Org 9487 are short-acting muscle relaxants in humans.

Adolescent↗

Delayed awakening from general anaesthesia in a patient with Hunter syndrome.

Hunter syndrome is one of a heterogeneous group of recessively inherited mucopolysaccharide storage diseases (MPS) with similar biochemical defects manifested by impairments in mucopolysaccharide catabolism with variable but progressive clinical courses. Abnormal accumulation and deposition of mucopolysaccharides in the tissue of several organs to numerous anatomical, musculoskeletal and neurological abnormalities which are known to complicate anaesthetic and airway management. Hunter syndrome has a wide variance of clinical phenotypes ranging from mild to severe. We present a patient having physical and neurological features consistent with a severe clinical presentation of Hunter syndrome (MPS, Type II). Following a seemingly uneventful intraoperative anaesthetic course including isoflurane, nitrous oxide and fentanyl (0.93 microgram.kg-1), resumption of spontaneous ventilation and return to consciousness were delayed until intravenous naloxone (200 micrograms) was administered 110 min after the opioid administration. The cause of delayed recovery from anaesthesia in this patient is unknown.

Anesthesia Recovery Period↗

Unexpected neurological deficits following recovery from anaesthesia.

Two cases of neurological dysfunction are presented. Neurological deficits after recovery from anaesthesia are unusual in young women perioperatively. In the first case, a 39-yr-old woman presented at 36-wk gestation with antepartum haemorrhage and in labour. Pregnancy had been complicated by pre-eclampsia and she underwent emergency Caesarean section under general anaesthesia without complication. The trachea was extubated when she was awake but almost immediately she became hypertensive, obtunded and reintubation was required. Her pupils became fixed and dilated but the Computerised Axial Tomogram (CT) was normal. A coagulopathy was evident. She made a full neurological recovery within 24 hr. On the same day, a previously healthy 41-yr-old woman who had undergone uneventful surgery for uterine prolapse 24 hr previously developed headache, nausea and over the next four hours signs of progressive brainstem ischaemia. The CT scan showed oedema of the mid- and hindbrain. Brainstem death was confirmed 12 hr later and the post-mortem revealed acute dissection of the vertebral artery secondary to cystic medial necrosis. Such dramatic neurological sequelae are rare but the importance of identifying "at risk" groups is underlined as is early recognition of neurological injury postoperatively.

Adult↗

Spinal anaesthesia but not general anaesthesia enhances neutrophil biocidal activity in hip arthroplasty patients.

The purpose of this study was to compare neutrophil cidal activity during general or spinal anaesthesia. Assays were performed on neutrophils extracted from the blood of patients after surgery had been under way for one hour. First, the ability of the neutrophils to kill a standard laboratory strain of S. aureus was examined. Neutrophils extracted from the blood during surgery in the spinal anaesthetic group and incubated with the staphylococci for one hour killed twice as many bacteria than those from two groups of patients that received halothane or isoflurane general anaesthesia (P < 0.05). This effect persisted, to a lesser extent, in the spinal group neutrophils after two hours of incubation with the bacteria. Second, neutrophils from patients under the same conditions of surgery and anaesthesia were tested to examine the effect of the different anaesthetic techniques on neutrophil biocidal mechanisms. Neutrophils extracted during surgery in the spinal group released more superoxide in response to phorbol-12-myristate-13-acetate (PMA) than those from both groups of patients that received general anaesthesia (P < 0.05). It is concluded that there is an increased state of reactivity of the neutrophil cell membrane NADPH oxidase system in patients receiving spinal anaesthesia than in patients receiving general anaesthesia.

Adult↗

Propofol anaesthesia reduces early postoperative emesis after paediatric strabismus surgery.

Propofol anaesthesia may reduce postoperative emesis. The purpose of this study was to compare the incidence of emesis after propofol anaesthesia with and without nitrous oxide, compared with thiopentone and halothane anaesthesia, in hospital and up to 24 hr postoperatively, in outpatient paediatric patients after strabismus surgery. Seventy-five ASA class I or II, unpremedicated patients, aged 2-12 yr were randomly assigned to one of three groups: Thiopentone, 6.0 mg.kg-1 i.v. induction followed by halothane and N2O/O2 for maintenance (T/H); propofol for induction, followed by propofol and oxygen for maintenance (P/O2); and propofol for i.v. induction, followed by propofol infusion and N2O/O2 for maintenance (P/N2O). All received vecuronium, controlled ventilation, and acetaminophen pr. Morphine was given as needed for postoperative analgesia. There were no differences in age, weight, number of eye muscles operated upon, duration of anaesthesia or surgery. The P/N2O group (255 +/- 80 micrograms.kg-1 x min-1) received less propofol than the P/O2 group (344 +/- 60 micrograms.kg-1 x min-1) (P < or = 0.0001) and had shorter extubation (P < 0.001) and recovery (P < 0.01) times. Emesis in the hospital, in both the P/N2O (4.0%) and P/O2 group (4.0%) was less than in the T/H group (32%) (P < 0.01). Antiemetics were required in four patients in the T/H group (16.0%). Overall emesis after surgery was not different among the groups: T/H (48%), P/O2 (28%) and P/N2O (42%). The use of propofol anaesthesia with and without N2O decreased only early emesis. This supports the concept of a short-acting, specific antiemetic effect of propofol.

Ambulatory Surgical Procedures↗

Anaesthesia for non-cardiac surgery in heart-transplanted patients.

This review documents the anaesthetic management, haemodynamic function and outcome in 18 of 86 heart-transplanted recipients, who returned for 32 non-cardiac surgical procedures at the Toronto Hospital from 1985 to 1990. General anaesthesia was administered in eight of the 27 elective operations and four of the five emergency operations. Induction medications included thiopentone (2-4 mg.kg-1), fentanyl (1-7 micrograms.kg-1) and succinylcholine (1-1.5 mg.kg-1). Anaesthesia was maintained with a combination of oxygen/nitrous oxide and isoflurane or enflurane. Muscle relaxation was maintained with vecuronium or pancuronium. No delayed awakening or unplanned postoperative ventilation was observed. Neurolept-anaesthesia was administered to 63.0% and 20.0% of the elective and emergency operations, respectively. The anaesthetics included fentanyl (25-100 micrograms) and midazolam (0.5-1.5 mg) or diazemuls (2.5-5.0 mg). Spinal anaesthesia (75 mg lidocaine) was administered to only two of the 27 elective operations. No important haemodynamic changes were observed in any anaesthetic group, but lower systolic BP was found after induction and during maintenance periods in the patients who received general anaesthesia than in those who received neurolept-anaesthesia. However, no anaesthesia-related morbidity or mortality was noted. This suggests that general, neurolept- and spinal anaesthesia do not affect haemodynamic function or postoperative outcome in heart-transplanted recipients undergoing subsequent non-cardiac surgery.

Adult↗

Sodium citrate in paediatric outpatients.

To determine whether the gastric content pH of paediatric patients could be raised in an effort to decrease post-aspiration morbidity and mortality, the antacid sodium citrate (0.4 ml.kg-1) was given preoperatively to 25 patients aged 1 to 14 (6.0 +/- 3.5, mean +/- SD) years. Their gastric content pH was measured following induction of anaesthesia. These values were compared to those obtained from a control group (n = 20) ranging in age from seven months to nine (3.3 +/- 2.7) years. A gastric content pH value of greater than 2.5 was measured in 23 of the 25 patients who received sodium citrate. There were only two patients in the control group with a gastric content pH greater than 2.5, p less than 0.001, Fisher exact test. Only one child refused to take the medication. The administration of sodium citrate appears to be an effective method of raising the gastric content pH in paediatric patients.

Ambulatory Care↗

Oral ondansetron decreases vomiting after tonsillectomy in children.

Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our double-blind, placebo-controlled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2-14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg.kg-1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N2O. Vecuronium 0.1 mg.kg-1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N2O, 50 micrograms.kg-1 midazolam iv and 1-1.5 mg.kg-1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of in-hospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg.kg-1 dimenhydrinate iv for vomiting x 2 and 50 micrograms.kg-1 droperidol iv for vomiting x 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic in-hospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children.

Administration, Oral↗

Circulatory responses to laryngoscopy: the comparative effects of placebo, fentanyl and esmolol.

The circulatory response to a 30-second laryngoscopy followed by orotracheal intubation was recorded in 60 patients of ASA physical status III or IV undergoing a variety of non-cardiac surgical procedures. Patients were randomly allocated to either the placebo, esmolol (500 micrograms.kg-1.min-1 X 6 minutes, followed by 300 micrograms.kg-1.min-1 X 9 minutes), or fentanyl (0.8 microgram.kg-1.min-1 X 10 minutes) group, and the observer was blinded to the infusion administered. Esmolol blunted the heart rate (HR) response, while fentanyl decreased it below the baseline and maintained it there, in spite of laryngoscopy. Similarly, fentanyl decreased the systolic (SBP), mean (MBP) and diastolic blood pressures (DBP) significantly below the baseline, while these pressures were either retained at or elevated slightly above control in the esmolol group. In these doses, the HR response to laryngoscopy was more effectively blocked by fentanyl, while esmolol better retained perfusion pressure. There were no complications or ischaemic electrocardiographic changes in any patient.

Adrenergic beta-Antagonists↗

Anaesthesia for the achondroplastic dwarf.

Over the past three years, 36 anaesthetics were administered to 27 patients with achondroplastic dwarfism. Twenty-four patients underwent craniectomy for foramen magnum stenosis. Sixteen of the operations were undertaken in the sitting position with nine incidents of venous air embolism (VAE), all of which occurred in patients under 12 years of age. Six major complications occurred: two C-1 level spinal cord infarctions, two brachial plexus palsies, one severe macroglossia, and one accidental extubation. Intravenous access in the small child with achondroplastic dwarfism is made difficult because of the excess, lax skin and subcutaneous tissue. Airway management and laryngoscopy were not difficult and we found that endotracheal tube size was best predicted by the patient's weight and not age. Blood loss was 38 +/- 9 mg X kg-1 in the prone position (n = 8) and 18 +/- 4 mg X kg-1 in the sitting position (n = 16), and was related to the surgical procedure rather than to dwarfism. Our data indicate that complications are more likely to occur in the sitting position, and that these complications are of a serious nature, and every precaution should be taken to avoid their occurrence.

Achondroplasia↗

Comparison of two and ten per cent rectal methohexitone for induction of anaesthesia in children.

Plasma methohexitone concentrations were determined in 30 children, aged one to six years, who received 25 mg.kg-1 rectal methohexitone as either a two per cent or ten per cent solution for induction of anaesthesia. Venous blood samples were obtained 15, 30, 45 and 120 minutes following drug administration. Twenty-six of 30 children were asleep within fifteen minutes. Mean plasma methohexitone concentrations were 5.39, 4.42, 3.40 and 1.54 micrograms.ml-1 at 15, 30, 45 and 120 minutes following administration of two per cent methohexitone. Use of the ten per cent solution resulted in mean plasma methohexitone concentrations of 3.81, 3.12, 2.31 and 1.07 micrograms.ml-1 at the same time intervals. Plasma methohexitone concentrations were significantly higher at 15, 30 and 45 minutes following administration of two per cent methohexitone, when compared to the ten per cent solution.

Anesthesia Recovery Period↗

Large doses of vecuronium and plasma histamine concentrations.

The authors studied 20 surgical patients to determine the effect of large doses of vecuronium on plasma histamine concentrations. Patients were unpremedicated and anaesthetized with nitrous oxide and halothane via a mask. Tracheal intubation was performed without the use of muscle relaxants. Fifteen min later and before surgery had begun, vecuronium, in doses of 0.1 and 0.2 mg.kg-1 (n = 10 for each dose), was administered as an IV bolus. Arterial blood samples were obtained prior to and 2, 5, and 10 min after vecuronium administration and analyzed for plasma histamine by a radioenzymatic method. Arterial blood pressure and heart rate were measured continuously. In one patient who received 0.1 mg.kg-1 of vecuronium, plasma histamine concentrations at 2 min were 275 per cent of the control histamine value but fell below control at 10 min. This increase in plasma histamine was not associated with clinically important changes in blood pressure or heart rate. As a group, study patients had no significant changes in plasma histamine concentrations with either dose of vecuronium. In addition, mean plasma histamine values for each sampling interval did not differ between the two patient groups. Mean arterial blood pressure (MAP) decreased significantly at 10 min in patients receiving vecuronium 0.1 mg.kg-1, and at 2 and 10 min in patients receiving 0.2 mg.kg-1 of vecuronium. However, these decreases in MAP were not clinically important. Changes in plasma histamine concentrations did not correlate with corresponding changes in MAP. Heart rate did not change significantly in any patient during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pre-treatment with somatostatin in the anaesthetic management of a patient with carcinoid syndrome.

Carcinoid syndrome produces flushing, bronchoconstriction and gastrointestinal hypermotility secondary to serotonin, histamine, bradykinin and prostaglandin release. A variety of drugs, foods and anaesthetic agents may provoke this syndrome. Under anaesthesia, the flushing produced may be associated with acute hypotension and cardiovascular collapse; this phenomenon is called a carcinoid crisis. Recently, somatostatin analogue has been used successfully to treat intraoperative carcinoid crisis. In this report, we present a 66-year-old lady with carcinoid syndrome who was pre-treated with 50 micrograms somatostatin analogue IV and IM prior to surgical manipulation. The anaesthetic course was relatively uneventful and the patient did well postoperatively.

Aged↗

Anaesthesia for caesarean section in a parturient with quintuplet gestation, pulmonary oedema and thrombocytopaenia.

The case of a 32-year-old parturient with a quintuplet pregnancy is described. The pregnancy had been complicated by premature labour which was treated with ritodrine tocolysis. Betamethasone was administered to hasten fetal lung maturation. The ritodrine therapy was complicated with fluid overload and pulmonary oedema requiring intravenous diuretic treatment. The patient presented urgently for Caesarean section, with fluid overload and worsening thrombocytopaenia. Life-threatening pulmonary oedema was manifest in the immediate preinduction period, following insertion of a pulmonary artery catheter and surgery was delayed to improve the mother's condition with intravenous diuretic therapy. Induction was carried out with the patient in the sitting position, with cricoid pressure maintained to protect the airway as the patient was lowered to a wedged, supine position. Intravenous nitroglycerin was used to control blood pressure. Low pressure mask-bag ventilation was utilized to maintain oxygen saturation and the patient was intubated and ventilated with positive end-expiratory pressure. Positive pressure ventilation was continued for 24 hours postoperatively. The perioperative course is reviewed and followed by a discussion of the anaesthetic considerations for multiple gestation pregnancies.

Adult↗

Neuromuscular effects of vecuronium and neostigmine in Montreal and Paris.

The potency of vecuronium was reported to be greater in Montréal than in Paris. This study was designed to determine whether there were differences in onset, duration, and reversibility with neostigmine between both centres. Twenty ASA I or II adults (ten men, ten women), aged 18-65 yr were studied in each of the two cities, during a standard thiopentone-fentanyl-nitrous oxide (60-70%) - isoflurane 0.5% end-tidal anaesthetic. Train-of-four stimulation was applied every 20 sec to the ulnar nerve at the wrist and the force of contraction of the adductor pollicis muscle was measured. Vecuronium, 0.1 mg.kg-1, was given as a bolus, and neostigmine, 0.04 mg.kg-1, was administered, with atropine 0.02 mg.kg-1, at 25% first twitch height recovery. Onset time to maximum blockade was (mean +/- SD) 3.9 +/- 1.3 min in Paris vs 4.5 +/- 1.3 min in Montréal (NS). Duration from injection to 25% first twitch recovery was shorter (28.5 +/- 6.8 min) in Paris than in Montréal (39.1 +/- 7.3 min) (P < 0.0001). Time from injection of neostigmine to a train-of-four ratio of 70% was not different in Paris (6.3 +/- 2.2 min) from Montréal (5.6 +/- 1.9 min). It is concluded that the duration of an "intubating" dose of vecuronium is longer in Montréal, but, when given at 25% first twitch recovery, neostigmine has the same efficacy in Montréal as in Paris.

Adolescent↗

Arterial to end-tidal carbon dioxide tension difference during anaesthesia in early pregnancy.

Sixteen patients requiring general anaesthesia for termination of pregnancy by dilatation and evacuation of the uterus were studied. Arterial and end-tidal carbon dioxide tensions were determined during anaesthesia. The mean arterial to end-tidal carbon dioxide tension difference was 0.07 kPa (-0.02-0.16, 5-95 per cent confidence limits). These results were similar to those observed during Caesarean section and those during anaesthesia for post-delivery tubal ligations. The physiological changes such as increased cardiac output, haemodilution, and increased blood volume which manifest by 12 weeks of gestation probably result in a reduced (a-E')PCO2 value.

Abortion, Induced↗

Anaesthetic considerations for microsurgical repair of limbs.

With the advent of surgery under the operating microscope microvascular surgical techniques requiring prolonged anaesthesia have greatly increased in number. Local anaesthetic techniques, whilst often producing excellent surgical conditions, are limited by the duration of action of the anaesthetic agents and by the ability of the patient to remain still, often in uncomfortable positions, for periods of up to twenty hours. The use of indwelling catheters as a means of prolonging the duration of nerve blocks is discussed along with methods of sedation or general anaesthesia to enable the patient to tolerate lengthy surgical intervention. Present general anaesthetic techniques may not be ideally suited to long surgical procedures. The problems and possible alternatives are discussed. Sympathetic ganglion blockade, intravenous regional blockade and systemic vasodilator therapy are discussed as a means of improving the success rate of these procedures. The general principles of patient management such as fluid balance, temperature control, patient positioning and control of the operating room environment assume a much greater significance when related to the provision of prolonged general anaesthesia, whilst the effect of extended periods of work on operating personnel must also be considered.

Anesthesia↗