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The anaesthetic-sparing activity of dexmedetomidine during isoflurane anaesthesia was examined, using the end-point of lack of response to tetanic nerve stimulation. Nine subjects were given two doses of dexmedetomidine (target plasma concentrations of 0.3 ng ml-1 and 0.6 ng ml-1, respectively) and saline on separate occasions. We measured auditory (AER) and somatosensory (SER) evoked responses at end-tidal isoflurane concentrations of 0.2-1.4%. Pa and P25-N35 amplitudes increased as isoflurane concentration was reduced (P0.001). Dexmedetomidine had no significant effect on this relationship. In contrast, P15-N20 (SER) amplitude increased (P0.001) as isoflurane concentration was reduced. The dose of dexmedetomidine had a significant interaction with this trend (P0.002). Decreasing the concentration of isoflurane at the high dose of dexmedetomidine had less impact on P15-N20 amplitude than decreasing isoflurane at the low dose or with saline. The mechanism by which dexmedetomidine spares isoflurane is discussed in the light of these evoked response changes.

Background: ANQ 9040 is an experimental nondepolarizing neuromuscular relaxant. Initial investigations in animals had indicated a rapid onset of action comparable to that of succinylcholine. The purpose of this study was to assess the safety and potency of ANQ 9040 in humans. Methods: ANQ 9040 was assessed in 41 male volunteers. Anesthesia was induced with propofol and maintained with a propofol infusion and 60% N 2 O/40% O 2 . Neuromuscular function was measured by mechanomyography using train-of-four stimulation of the ulnar nerve every 12 s. After an initial pilot study, 23 volunteers received a single dose of ANQ 9040 of between 0.5 and 1.1 mg/kg to determine the dose-response relationship. The final 10 volunteers were given twice the estimated ED 95 of ANQ 9040 as a single bolus dose. Results: The estimated ED 50 and ED 95 of ANQ 9040 were 0.6 and 1.3 mg/kg, respectively. Apart from an increase in heart rate, no important adverse effects were noted after ANQ 9040 administration in the dose range 0.5-1.1 mg/kg. In the volunteers who received 2.6 mg/kg ANQ 9040, a substantial increase in plasma histamine was observed. This was associated with a 12% decrease in mean arterial pressure and a 49% increase in heart rate. In this group, the mean onset time to neuromuscular block was 51.3 s. Conclusions: ANQ 9040 is a rapid-onset neuromuscular blocking agent. However, twice the ED 95 dose is associated with significant histamine release and tachycardia. This finding suggests that this drug will not be useful in clinical practice

Patients who smoke cigarettes suffer increased postoperative morbidity. A prospective, controlled trial was designed to evaluate the effectiveness of written pre-operative advice to stop smoking before admission for elective surgery and to record the duration of abstinence immediately before the operation. Although the advice was ineffective in persuading patients to stop smoking, it was associated with a reduction in the amount of tobacco consumed. Nicotine and carbon monoxide have important short-term adverse effects but 15% of all patients continued to smoke within an hour of surgery. If patients are unable to give up cigarette smoking completely, it is still worthwhile stopping on admission to hospital.

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with anaesthetic-sparing effects. We have determined the pharmacodynamic and pharmacokinetic interactions between dexmedetomidine and isoflurane in volunteers. Nine male subjects were allocated randomly to receive isoflurane anaesthesia preceded by infusion of dexmedetomidine on three separate occasions, 2 weeks apart. Dexmedetomidine target plasma concentrations were 0.0 (placebo), 0.3 ng ml-1 (low-dex) and 0.6 ng ml-1 (high-dex). End-tidal isoflurane concentrations at which gross purposeful movement and response to verbal commands occurred were identified. In the recovery period, sedation scores and digit symbol substitution tests were recorded. Venous blood samples were obtained before, during and after anaesthesia at predetermined intervals for measurement of plasma concentrations of dexmedetomidine and calculation of standard pharmacokinetic indices (AUC, Cl, Vss, T1/2 alpha, T1/2 beta). The end-tidal isoflurane concentration at which 50% of subjects first responded to the tetanic stimulus was 1.05% in the placebo group, 0.72% in the low-dex group and 0.52% in the high-dex group. We conclude that dexmedetomidine decreased isoflurane requirements in a dose-dependent manner and reduced heart rate, systolic and diastolic arterial pressures. Sedation and slight impairment of cognitive function persisted for several hours after anaesthesia and the end of infusion of dexmedetomidine. Isoflurane did not appear to influence the pharmacokinetics of dexmedetomidine.

New anaesthetic agents are continually being developed in an effort to prepare the ideal agent. Isoflurane is the first choice of many anaesthetists, although it clearly falls short of the ideal on a number of counts. The need and place for any new agent depends on comparing the properties of a theoretically ideal agent with those of isoflurane and the new agent. Desflurane is a step towards a more ideal inhaled agent ; however, there is still the need to synthesise and evaluate new chemical entities in order that the ideal can more nearly be approached.

The characteristics of neuromuscular block induced by doxacurium were compared in patients with and without renal function. Seventeen patients with end stage chronic renal failure and 18 patients with normal renal function were anaesthetized with 0.5% halothane and nitrous oxide in oxygen and received doxacurium in an initial dose of 25 micrograms kg-1 (estimated from available data as an ED95 dose), with incremental doses of 5 micrograms kg-1. At the end of surgery, residual neuromuscular block was antagonized with either edrophonium 1.0 mg kg-1 or neostigmine 0.08 mg kg-1. There was no significant difference between the mean maximum blocks achieved with doxacurium: 17.4% (renal failure group) and 11.6% (control group) of control twitch heights, or between the mean times to achieve maximum block (10.9 min and 10.8 min, respectively). The mean duration of action of doxacurium, indicated by the time for twitch height to recover to 25% of control, was longer in the renal failure group (120.8 min vs 66.7 min in the control group) (ns). Similarly, the mean duration of action of increments was longer in the renal failure group (27.4 min vs 20.5 min in the control group). The rate of spontaneous recovery from doxacurium as indicated by the time for twitch height to recover from 0 to 5%, 5 to 10% and 10 to 25%, was not significantly different in the two groups. Antagonism of doxacurium was achieved more reliably with neostigmine than with edrophonium in both groups. The administration of doxacurium was associated with minimal cardiovascular effects.

The purpose of this study was to measure the serum fluoride concentration after enflurane or sevoflurane anesthesia and to compare the effects of prolonged anesthesia with these drugs on renal concentrating function in male volunteers. The study was subdivided into three stages; an ascending dose study of 3.0 and 6.0 minimum alveolar anesthetic concentration (MAC) hours of sevoflurane alone, a 6.0-MAC-hour comparison of enflurane and sevoflurane, and a 9.0-MAC-hour comparison of enflurane and sevoflurane. Renal concentrating function was assessed by an 18-h period of fluid deprivation and the serum fluoride concentration was measured at intervals until 60 h postanesthesia. The maximum serum fluoride concentration was greater in the volunteers exposed to sevoflurane and reached a peak in the 9-MAC-hour sevoflurane group of 36.6 microM (SD 4.3) compared with 27.5 microM (SD 2.6) in the 9-MAC-hour enflurane group. However, the rapid decrease in the serum fluoride concentration after sevoflurane was such that there was no difference between the areas under the fluoride concentration-time curves. There were no significant differences between the median maximum urine osmolalities after enflurane or sevoflurane anesthesia. Prolonged anesthesia with enflurane or sevoflurane is not associated with impaired renal concentrating function despite an increase in the serum fluoride concentration.

We have compared, in 51 ASA II and III patients undergoing coronary artery bypass surgery, an inhaled anaesthetic technique based on desflurane, supplemented with low-dose (10 micrograms kg-1) fentanyl, with an i.v. technique using high-dose (50 micrograms kg-1) fentanyl with midazolam for induction. Satisfactory records were available for analysis in 50 patients. There were no differences between groups in operating time, cardiopulmonary bypass time, aortic cross-clamp time or duration of stay in the intensive care unit after surgery. Desflurane maintained mean systemic arterial pressure at the awake level during incision and sternotomy (end-tidal concentrations 3.7% and 4.6%, respectively) but decreased it significantly at all other times. With fentanyl, mean systemic arterial pressure was unchanged from awake values during induction and laryngoscopy but increased significantly at incision and sternotomy by 8% and 12.8%, respectively, to exceed the desflurane group at sternotomy by 20 mm Hg (P0.001). With desflurane, heart rate remained at 60-67 beat min-1 at all times before cardiopulmonary bypass. This was always lower than the fentanyl group by 5-15 beat min-1 and the difference was significant at induction, during skin preparation and before aortic cannulation. In comparison with the desflurane group, cardiac index was significantly greater in the fentanyl group at induction, laryngoscopy and during skin preparation, but was significantly less before aortic cannulation. The need for vasodilator intervention was significantly more common in the fentanyl group before, during and after cardiopulmonary bypass and for beta adrenoceptor block before cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

The ability to evoke reversal of dense vecuronium- and pancuronium-induced paralysis (T1 10% of control) with edrophonium 1.0 mg · kg-1 was studied using train-of-four nerve stimulation and electromyographic monitoring. Two different end-points, train-of-four ratios of 0.5 and 0.7, were used to define “adequate reversal”, and the results for both relaxants were compared. Reversal was reliable and rapid for vecuronium if either ratio was used with times of 2.8 (1.5) and 9 (3) min required to achieve ratios of 0.5 and 0.7, respectively. However, if the block was due to pancuronium, reversal was unreliable with 2 of 9 and 4 of 9 patients not achieving ratios of 0.5 and 0.7, respectively. Reversal was also markedly prolonged in this group with a mean time of 37 (23) min to achieve a ratio of 0.7, and in almost half these patients a supplementary dose of edrophonium was required.

Summary The anaesthetic problems we have encountered in eight patients with the mucopolysaccharidoses are described and the pathophysiology of this group of clinically progressive inherited diseases is reviewed with emphasis on the aspects of importance to the anaesthetist.

The role of two recently introduced muscle relaxants--atracurium and vecuronium--in contemporary anaesthetic practice is assessed. Recent advances in the physiology of neuromuscular transmission, particularly the roles of calcium and calmodulin, are reviewed, and new ideas concerning the reversal and monitoring of neuromuscular blockade are discussed.

Summary Two patients presenting for removal of phaeochromocytoma are described. Vecuronium was used to provide neurornuscular blockade by two different methods of administration: an infusion and a large bolus dose. Both gave satisfactory results and we suggest that vecuroniurn may be the neuromuscular blocking agent of choice for patients with phaeochromocytoma.

The characteristics of the train-of-four response during neuromuscular blockade with two agents, atracurium and vecuronium, have been compared. During onset of blockade, at 75% depression of the initial twitch, atracurium was associated with significantly more fade than was vecuronium, and larger doses of atracurium were associated with less fade than smaller doses of the same agent. In addition, with both agents, the degree of fade at a given amount of initial twitch depression was significantly less during onset than during spontaneous offset of action. The degree of train-of-four fade bears no fixed relationship to depression of the initial twitch.

Summary The effects of three different anaesthetic carrier gases on middle-ear pressure in the operative and postoperative periods was assessed. Patients receiving oxygen and oxygen-enriched air did not have significant changes in middle-ear pressure. The changes associated with the use of nitrous oxide as the carrier gas were reversed with return of pharyngeal reflexes or after prolonged inhalation of 100% oxygen. In patients undergoing middle-ear surgery or those with pre-existing middle-ear disease, we suggest that oxygen-enriched air is the anaesthetic carrier gas of choice.

The management of the period after hypothermic cardiopulmonary bypass has been compared in a group of patients maintained on nifedipine therapy, a group who had the drug withdrawn at least 24 hours prior to cardiac surgery, and a control group who had never received calcium antagonists. Patients in the drug withdrawal group were significantly more likely to need vasodilator intervention than the treated (p less than 0.001) or the control (p less than 0.05) groups. Although nifedipine withdrawal appeared to reduce the need for inotropic support, compared to treated (p less than 0.001) and control groups (p less than 0.005), this may be at the cost of increasing systemic vascular resistance. This observation, coupled with reports of a rebound phenomenon following abrupt withdrawal of calcium antagonist therapy, suggests that nifedipine should be continued up to the time of surgery.

Summary A case of multiple endocrine adenopathy type I associated with a solitary carcinoid tumour is described. During anaesthesia the characteristic syndrome consisting of hypertension, tachycardia and flushing occurred. The possible mechanisms for this are discussed. It is generally agreed that the presence of hepatic metastases is necessary for the development of the typical carcinoid syndrome.’S2 Most carcinoids of the mid-gut secrete a variety of vasoactive substances but detoxication of these products usually occurs in the liver. When hepatic metastases are present, however, vasoactive substances are able to gain access to the suprahepatic circulation. This case report describes the occurrence of a typical ‘malignant’ carcinoid attack occurring during anaesthesia, in a patient not previously suspected of having a carcinoid tumour, but who was known to have multiple endocrine adenopathy (MEA).

There are a number of factors to consider in choosing a muscle relaxant for patients with a phaeochromocytoma. It has been suggested that pancuronium is the muscle relaxant of choice.1-3 This report describes a severe hypertensive response associated with pancuronium in a patient undergoing surgery for the removal of a phaeochromocytoma.

While naproxen pharmacokinetics appear to be altered in the presence of both diminished renal and hepatic function, the degree to which naproxen disposition might be influenced in the elderly by concurrent alteration in these functions is not obvious. Total plasma clearance/bioavailability (CL/F) of naproxen after a single 375 mg oral dose was found to be less in a group of 10 healthy men between 66 and 81 years of age than in 10 healthy men between 22 and 39 years (0.318 +/- 0.078, 0.416 +/- 0.061 l/h). At steady state (375 mg, 12 hourly), however, CL/F was statistically indistinguishable between the two groups. The fraction of naproxen unbound to plasma protein was doubled in elderly subjects, both at peak and trough drug concentrations. The lowered protein binding tended to obscure a 50% decrement in the intrinsic clearance of naproxen in the elderly as estimated by unbound clearance/bioavailability (213 +/- 64, 396 +/- 155 l/h). As a result, mean steady-state plasma concentrations of naproxen were indistinguishable between the elderly and young (64.2 +/- 8.5, 58.2 +/- 8.1 mg/l) but the elderly generated twice the mean steady-state unbound plasma drug concentration (0.157 +/- 0.039, 0.0859 +/- 0.0212 mg/l). Since it is the unbound drug concentration which appears in general to relate more closely to pharmacological and toxic effect, it may be advisable to reduce naproxen doses by half in the elderly, pending plasma drug concentration-response studies in this age group. If a similar perturbation with age occurs in benoxaprofen protein binding as was observed with naproxen, benoxaprofen intrinsic clearance in the elderly might be only one quarter of that in younger individuals; a factor which may contribute to the toxicity of this drug in the elderly.

Summary The incidence of pneumothorax in the neonatal period is reviewed. Most infants who developed a pneumothorax were undergoing intermittent positive pressure ventilation. The most common underlying pathology associated with pneumothorax was idiopathic respiratory distress syndrome. This was the only condition in which a pneumothorax occurred in spontaneously breathing patients. The development of a pneumothorax was not significantly related to gestational age, birth weight, high ventilator inflation pressure, maximum fractional inspired oxygen concentration or the method of delivery. Evidence is presented to suggest that the development of a pneumothorax is not primarily a complication of ventilation but is due to the more severe pulmonary pathology of infants who require ventilatory assistance. Whatever the mechanism, prompt diagnosis and treatment mean that this common complication does not necessarily increase mortality.

Summary A 61-year old woman with severe coronary artery disease underwent three-vessel coronary bypass surgery. Dificulty was encountered in terminating cardiopulmonary bypass, but there was dramatic improvement following the administration of intravenous insulin. The use of insulin to facilitate termination of cardiopulmonary bypass is discussed.

Summary Two patients who developed sleep apnoea following upper cervical cord surgery are described. The underlying mechanisms and management of the sleep apnoea syndrome are discussed.

The demyelinating diseases are classified and the current concepts of the aetiology and pathophysiology of the most common of these diseases, multiple sclerosis, are described. The effects of the impaired function, local responses and known complications of the disease on the choice of anaesthetic, drugs and techniques are discussed.

Summary A patient suffering from severe psychiatric depression underwent a course of electroconvulsive therapy. A marked rise in systemic arterial pressure, heart rate and plasma catecholamines in response to electroconvulsive therapy was attenuated by β-receptor blockade using propranolol. The significance and mechanism of this attenuation are discussed.

Atracurium was studied in day-stay patients undergoing short surgical procedures requiring tracheal intubation. In a dose of 0.25 mg kg −1 and with an anaesthetic technique using enflurane, tracheal intubation could be performed in all patients within 3 min and was readily reversible, unless the duration of surgery was less than 20 min. The administration of an antagonist was indicated in nearly all patients in whom surgery lasted for less than 30 min.

Summary We describe the case of a patient treated for hypertension with the angiotensin converting enzyme inhibitor enalapril, who developed hypotension after recovery from anaesthesia.

1 A new imidazo-pyridine hypnotic (zolpidem 10 mg and 20 mg) was compared with placebo as premedication before general anaesthesia in female patients undergoing minor gynaecological surgery. Efficacy and tolerance before and after anaesthesia were assessed. Psychomotor testing was used to study recovery from anaesthesia. 2 Both doses of zolpidem produced good sedation pre-operatively but only the higher dose was associated with anterograde amnesia. 3 Premorbid anxiety scores were low in the group of patients studied and were unaffected by either dose of zolpidem. 4 There were no significant effects on the course of anaesthesia. However, postoperatively there was a tendency for wake-up to be delayed in those patients who received either dose of zolpidem. 5 Postoperative recovery, as indicated by tests of psychomotor performance, was noticeably delayed with a dose of 20 mg compared with placebo whilst psychomotor performance had returned towards baseline levels 3 h after wake-up in those patients who had received placebo. The zolpidem 10 mg group was intermediate. 6 Zolpidem may be a suitable premedicant when hypnosis and amnesia only are required.