The direct cardiac effects of morphine, alfentanil, ketamine, etomidate, thiopentone, midazolam and propofol were measured in isolated Wistar rat hearts. Experiments were performed using a multiple conlumnar Langendorff apparatus and the hearts were perfused with a modified Tyrode solution under constant pressure. Each drug was applied from a different column in rising concentrations at 5-min intervals. Dose ranges were chosen to compare effects at sub-clinical, clinically relevant and more than clinical concentrations. Six rat hearts were chosen at random for each drug. Only thiopentone reduced contractile force at a clinically relevant concentration: measured as g contractility per g heart weight−1 (mean±standard deviation), base-line contractility was 8.8±2.4, and contractility at 10−4 mol litre−1 thiopentone was 7.1±1.5 (P<0.01). Alfentanil was the only drug to have no significant effect on the isolated heart at any concentration. Propofol was not cardiodepressant at clinically relevant concentrations, but had a lower therapeutic range than the other drugs.

Patient-controlled sedation (PCS) has been used during many different surgical procedures, both alone and as an adjunct to local or regional anaesthesia. Sedation with an admixture of propofol and alfentanil during transvaginal oocyte retrieval has been used successfully in this unit and this study was performed to assess the degree of patient acceptance of patient-controlled sedation, as other studies have indicated that self-administration of sedation may confer additional benefits on the patient, unrelated to the choice of sedation agent.

An admixture of 50 mL propofol 1% with alfentanil 2 mg was loaded into a Graseby 3300 patient-controlled analgesia pump and administered as increments of 0.3 mL with a zero lock-out interval. This method of sedation provided safe and highly satisfactory sedation for this group of patients with 55 of 56 patients indicating that they would opt for this type of sedation again. There was a very low incidence of over-sedation, and this sedation method is likely to produce a relaxed and co-operative patient for a wide variety of surgical procedures.

Fifty-five consecutive patients undergoing a short-stay ophthalmic operation (orbital hydroxyapatite implantation) were recruited over 1 year to assess the frequency and duration of post-operative nausea and vomiting over 7 days. The incidence of nausea and vomiting in hospital was recorded. Patients scored their nausea and vomiting four times daily at home. By the end of the first day after surgery, 31 (75%) patients had experienced mild to severe nausea. Eighteen (38%) patients became nauseated on five or more occasions. Nineteen (35%) patients had vomited by the end of the first day after surgery and, over 7 days, 24 (43%) patients had vomited on one or more occasion. Three patients reported that they had vomited during the journey home. Vomiting was not correlated with pain or a past history of post-operative nausea and vomiting. However, there was a statistically significant correlation between nausea and pain. The high incidence of nausea and vomiting observed in this study appears to provide additional evidence of an oculo-emetic reflex. The timing of discharge and appropriate patient education are discussed.

A randomized crossover study was designed using the chronically instrumented pregnant sheep preparation to study the possible effects of epidural injection of adrenaline as a single compound on the circulation of mother and fetus. Three consecutive identical doses of adrenaline were administered epidurally with a 30 min interval between treatments. In a randomized crossover fashion two dosages (10 and 15 μg) were tested on different days. The day after the last epidural experiment the same doses of adrenaline were given intravenously (i.v.). Between the two i.v. doses a 30 min interval was allowed for values to return to baseline. Twenty-seven experiments were performed in eight ewes. Epidural administration of adrenaline did not affect maternal mean arterial pressure, maternal heart rate, uterine blood flow, fetal mean arterial pressure, fetal heat rate, or maternal and fetal blood gases and acid-base status. After i.v. administration of adrenaline the uterine blood flow decreased in a dose-dependent fashion, but the other haemodynamic variables were not affected. In conclusion, this study indicates that consecutive epidural injections of adrenaline have no significant effect on maternal and fetal haemodynamic responses, uterine blood flow, blood gases and acid–base status in the gravid ewe. However, an i.v. injection of 10 or 15 μg adrenaline decreases the uterine blood flow and could compromise the fetus.

Ondansetron 4 mg was compared with metoclopramide 10 mg for prevention of post-operative nausea and emesis in in-patients undergoing major gynaecological surgery in this double-blind, randomized, placebo-controlled, multicentre study. A total of 1044 patients received a single intravenous (i.v.) injection of study medication immediately before induction of anaesthesia. Nausea and emesis were assessed over the 24 h post-operative period. Significantly more patients who received ondansetron experienced no emetic episodes (44%) compared with those who received metoclopramide (37%, P=0.049) or placebo (25%, P<0.001). No nausea was experienced by significantly more patients who received ondansetron (32%) than with patients who received metoclopramide (24%, P=0.009) or placebo (16%, P<0.001). In addition, fewer emetic episodes, less severe nausea and a reduced need for rescue antiemetics were also observed with ondansetron (P<0.05 vs. metoclopramide and placebo). Metoclopramide and placebo-treated patients were also 1.5 times (95% CI 1.5–4.2) and 2.5 times (95% CI 1.1–2.0) more likely, respectively, to experience nausea post-operatively. Overall, ondansetron was the most effective antiemetic in this patient population.

5-Hydroxytryptamine has wide-ranging effects on a number of physiological systems. In addition the exogenous application of 5-hydroxytryptamine or 5-hydroxytryptamine type drugs to tissue bath preparations has revealed the presence of a large and ever growing population of 5-hydroxytryptamine receptors. The discovery that 5-hydroxytryptamine is released at the neuromuscular junction raises the question as to whether it has a physiological function and whether or not applying low concentrations of 5-hydroxytryptamine transmitter would have any significant effect on twitch response at different rates of stimulation. Previous studies have demonstrated both facilitatory and depressant effects upon twitch responses in a variety of animal models. Single twitch responses of the rat phrenic nerve diaphragm preparation at non-fatiguing (0.3 Hz) and tetanic rates of stimulation (50 Hz) were recorded under conditions of indirect (nerve) stimulation at 4 g resting tension. The preparation was incubated with 0.5, 1, 2, 4, 16 μmol litre−1 concentrations of 5-hydroxytryptamine. The results of our investigations demonstrate that while low concentrations of 5-hydroxytryptamine have no effect upon the single twitch response at resting rates of stimulation (0.3 Hz), the initial single twitch and the subsequent eighteen responses immediately following a tetanus are facilitated (P<0.05). This work demonstrates that 5-hydroxytryptamine does have significant effects upon the neuromuscular junction under conditions of physiological compromise (following tetanus). These observations are the first step, therefore, in a series of studies aimed at identifying the resident 5-hydroxytryptamine receptors within the neuromuscular junction which will subsequently enable us to predict therapeutic effect or toxicity.

Application of high-silica zeolites in a special adsorber anallows complete selective adsorption of the inhalation anaesthetic desflurane from the outlet port of the scavenging system of the anaesthesia machine. In comparison with charcoal filters, zeolites allow almost complete desorption at moderate temperatures followed by condensation of the desflurane to the liquid phase. The adsorption of scavenged desflurane by zeolites was measured in 13 patients. The duration of the anaesthesia was between 70 and 130 min. A minimal-flow regime (0.5 L min−1 fresh gas inflow) was used for maintenance in seven patients and a higher-flow regime (3 L min−1 fresh gas flow) was used for maintenance in six patients. In minimal-flow anaesthesia, 62% of the delivered desflurane was adsorbed by the zeolite while 86% of the delivered desflurane was adsorbed in higher-flow anaesthesia. Preliminary results show that about 85% of the adsorbed desflurane could be recovered as liquid with high purity via desorption.

Besides the fast tetrodotoxin-sensitive Na+ current, small dorsal root ganglion neurones of rats also possess a slower tetrodotoxin-resistant Na+ current. The blocking effect of commonly used local anaesthetics upon the tetrodotoxin-resistant Na+ current was investigated in the present paper. Dorsal root ganglia were dissected from adult rats and cells were enzymatically isolated. The whole-cell patch clamp technique was then used to measure inward Na+ currents of small dorsal root ganglion neurones. Externally applied local anaesthetics reversibly blocked the tetrodotoxin-resistant Na+ current in a dose-dependent manner. Half-maximal blocking concentrations for tonic block were: lignocaine, 326 μm; prilocaine, 253 μm; mepivacaine, 166 μm; etidocaine, 196 μm bupivacaine, 57 μm procaine, 518 μm benzocaine, 489 μm; tetracaine, 21 μm; and dibucaine, 23 μm. Blocking of the current by lignocaine was independent of temperature. The quaternary lignocaine derivative QX-314 did not have any effect upon the tetrodotoxin-resistant Na+ current when applied externally. High concentrations of tetrodotoxin also blocked the tetrodotoxin-resistant Na+ current with a half-maximal blocking concentration of 115 μm. The block by high tetrodotoxin concentrations did not compete with the lignocaine block, suggesting that there were two independent blocking mechanisms for the two substances. The tetrodotoxin-resistant Na+ currents also showed a marked sensitivity to phasic (use-dependent) block by local anaesthetics.

An audit of post-operative nausea and vomiting (PONV) was undertaken in 935 female patients who used morphine patient-controlled analgesia (PCA) for pain relief after major gynaecological operations in a district general hospital. We investigated retrospectively five different antiemetic policies and a reference group without policy from January 1993 to July 1995. The department’s computerized audit system was used to analyse the observations. At the beginning of the audit, the incidence of nausea and vomiting was as high as 71.5%. But as a consequence of this audit, a departmental policy was adopted 3 years later, which had an incidence of PONV of only 51.7%. During this time the compliance with antiemetic protocols increased from 41% to 76%. There was significantly less PONV if an antiemetic protocol was followed (P=0.002). This emphasizes the importance of corporate involvement in the development, formulation and evaluation of departmental protocols if compliance is to be high. We conclude that audit as a corporate effort improves the acceptance of departmental protocols. This reduces PONV significantly irrespective of the type of antiemetic drug used.

The contractile response of smooth muscles to spasmogens can be divided into two components by modifying the extracellular Ca2+ concentration. The phasic component depends on the mobilization of Ca2+ from intracellular stores whereas the tonic component depends, to a large extent, on the influx of extracellular Ca2+. The present study was designed to investigate the effect of ketamine on the tonic response to carbachol or histamine in the guinea pig trachea. Tracheal spirals from female guinea pigs were mounted in organ baths filled with aerated physiological buffer, and their isometric tension was measured. The phasic response to 10−7m carbachol or 10−5m histamine in Ca2+ -free, ethylene glycol-bis(β-aminoethyl ether)-N, N,N',N'-tetraacetic acid-containing buffer and the tonic response to each spasmogen after restoring [Ca2+] in the buffer was measured in the absence or presence of ketamine. In the presence of normal physiological buffer, ketamine decreased the contractions induced by carbachol or histamine in a dose-dependent fashion. No measurable phasic response to either carbachol or histamine was obtained in our preparation. Ketamine (5 × 10−5m−10−3m) reduced the tonic response to 10−7m carbachol to 79.5±2.7−4.3±0.7% of the response without ketamine. Similarly, ketamine (5 × 10−4m−2 × 10−3m) decreased the tonic response to 10−5m histamine to 80.7±3.9−23.0±3.2% of the response in the absence of ketamine. Our findings support the hypothesis that ketamine inhibits the paracrine agent-induced contractions of smooth muscles by interfering with the influx of extracellular Ca2+ or with an intracellular event(s) requiring extracellular Ca2+.

We report a case of post-operative rhabdomyolysis following transmandibular buccopharyngectomy without reconstruction in a patient remaining in the supine position throughout the procedure. Muscle compression induced by a cushion used during the procedure had probably contributed to the rhabdomyolysis. Outcome was favourable without acute renal failure. Prevention, early diagnosis and treatment are the keys to a successful recovery.

The molecular effects of droperidol (C22H22FN3O2) on single sodium channels from the human brain were investigated using the electrophysiological planar lipid-bilayer technique. Droperidol (0.05–0.8 mm) induced a concentration dependent and voltage independent reduction in the time averaged single channel conductance by two mechanisms: a reduction in the fractional channel open time (major effect, approximately 90%) and a decrease in the channel amplitude (minor effect). The weighted computer fit of the concentration response for the combined effect curve yielded an EC50 of 0.68 mm droperidol and a maximal conductance block of 77%. These blocking effects of droperidol on CNS sodium channels occurred at a concentration range comparable with other specific anaesthetic compounds but far beyond clinical serum levels (up to 0.002 mm). Therefore in contrast with animal preparations (frog peripheral nerve, sodium channel) the human brain sodium channel is not a major target site for droperidol during clinical anaesthesia.

The prediction of difficult intubation in obese patients was investigated by co-estimating the degree of visbility of oropharyngeal structures in conjunction with the respective body mass index. Data were collected prospectively in a series of 1833 consecutive adult patients. Body mass index (BMI) in kg m−2 was used as a measure of obesity (morbid: >40, moderate: 30–40, no obesity: <30). The oropharyngeal class findings were assessed using the original methodology as well as by a modification requiring the tongue to be pulled forward by the examiner. Difficult intubation was defined as inadequate exposure of the glottis by direct laryngoscopy. Both oropharyngeal class methodologies were of equal sensitivity, whereas the modified technique presented a significantly higher positive predictive value (50.0% vs. 37.2%, P<0.01). Statistical analysis revealed an increased risk of dificult laryngoscopy among obese patients compared with subjects with normal body mass index (20.2% vs. 7.6%, P<0.001). When obesity is estimated with respect to oropharyngeal class the positive predictive value is greately improved (66.7% vs. 20.2%, P<0.001). We conclude that obesity which is associated with a disproportionately large base of the tongue, is a predisposing factor for difficult laryngoscopy.

A 43-year-old male received intravenous propofol, atracurium and gentamicin and experienced cardiovascular collapse with the features of an acute drug reaction. Prolonged cardiopulmonary resuscitation with fluids and large amounts of adrenaline and nor-adrenaline led to full recovery without neurological deficit. No biochemical abnormality was detected.

The molecular mechanism of volatile anaesthetic action on presynaptic glutamate release is not clear. An inhibitory effect on voltage-gated calcium channels has been proposed. The present study examines the effect of isoflurane on cytosolic free calcium and synaptic glutamate release from isolated nerve terminals. Synaptosomes from rat cerebral cortex were used. Glutamate was measured with a continuous fluorometric measurement in a spectrophotometer as the fluorescence of NADPH and calcium as the fluorescence of fura-2. Isoflurane reduced the calcium-dependent glutamate release evoked by membrane depolarization with 4-aminopyridine in an inversely dose-dependent manner. The glutamate release was reduced by 56, 43 and 36% in response to isoflurane 0.5, 1.5 and 3.0%, respectively (for all: P<0.05). Membrane depolarization evoked a rise in cytosolic free calcium of ≈34%. Addition of isoflurane (0.5, 1.5 and 3.0%) produced no significant change in cytosolic free calcium. These results indicate that the isoflurane-induced reduction in presynaptic glutamate release is caused by other mechanisms than blocking voltage-gated calcium channels. As the release is inversely dose-dependent, two or more mechanisms could be involved.

A 17-year-old victim of a road traffic accident presented. Following investigation diagnoses of fractured first cervical vertebra, aortic transection, diffuse cerebral oedema, fractured right ribs 2–4 and pubic rami were made. Management of this case presented a number of anaesthetic dilemmas: management of the airway, use of cross-clamp vs. shunting or heparinization and bypass, cardiovascular and neurological monitoring, maintenance of cardiovascular stability during and post cross-clamp, minimizing the risk of post-operative renal and neurological dysfunction.

We report a case of non-ketotic hyperosmolar coma, which presented with blood sugar levels far exceeding any previously recorded in the literature. The patient developed acute renal failure, probably because of rhabdomyolysis, which was successfully managed with continuous veno-venous haemofiltration. He developed blurring of vision resulting from biochemical changes, which was managed conservatively. We discuss the mechanisms of causation of the renal failure and visual blurring.

The isoflurane-saving and CO2-retaining effects of a charcoal filter were compared with a Siemens standard heat and moisture (HME) exchanger and an emptied specimen (dummy). Isoflurane was delivered during the inspiratory phase and consumption investigated at 10, 15 and 25 cycles min−1. The investigation was performed by ventilation with humidified air with a constant end-tidal CO2 and temperature. For a comparison, isoflurane was delivered in a conventional manner via the ventilator. The arrangement with a charcoal filter reduced the isoflurane consumption by a factor of 2.0−2.6, depending on ventilatory rate. Most of the saving was a result of the method of isoflurane delivery (factor 1.4−2.0), while adding the reflector gave a further reduction (factor 1.3−1.5). One circumstance that reduced the net efficiency of the charcoal filter was that it also reflected CO2; consequently, total minute ventilation had to be increased to maintain constant end-tidal CO2.

Calcium-channel blockers reduce the in vitro effects of hypothermia and benzodiazepines have been reported to reduce inward calcium flow through L-type cardiac-calcium channels. Thus, this study was designed to determine if diazepam could reduce hypothermia-induced changes in ventricular papillary muscle electromechanical activity. Conventional microelectrode techniques were used while force was recorded using a miniature force transducer. Six experimental groups of electrically paced papillary muscles were formed (n=6 per group). One was exposed to one μm nisoldipine and four were exposed to one of four diazepam concentrations (0.1, 1.0, 10 or 100 μm). A final group had no drug and provided a time-matched control. The effects were determined at 37°C and then at 27°C. At 37°C, diazepam initially increased and then reduced inotropy and APD90. Nisoldipine reduced both APD90 and inotropy. At 27°C, 100 μm diazepam and nisoldipine (1.0 μm) reduced the hyhypothermia-induced lengthening of APD and the increase in force. Although diazepam reduced the hypothermia-induced alterations, the concentration required to do so (100 μm) suggests that this effect has little role in clinical use.

Rocuronium administration may cause tachycardia and an increase in cardiac index. Pancuronium, another steroidal non-depolarizing muscle relaxant, augments release of, and blocks re-uptake of catecholamines at adrenergic nerve endings. This study compared the haemodynamic effects of, and changes in catecholamine concentrations following administration of vecuronium (0.12 mg kg−1) or rocuronium (0.9 mg kg−1) to elderly patients. Thirty patients, 65 years or older, not receiving β-blockers, were studied. During thiopentone, fentanyl, nitrous oxide anaesthesia, either rocuronium (0.9 mg kg−1) or vecuronium (0.12 mg kg−1) was administered, according to random allocation. In all 30 patients, blood pressure and heart rate were measured before induction of anaesthesia, immediately and 1 min after induction, 1 and 2 min after muscle relaxant administration, and immediately, 1 and 2 min after tracheal intubation. In the latter 20 patients, samples for plasma catecholamine estimation were obtained prior to, and 1 min after muscle relaxant administration and 1 min after tracheal intubation. Blood pressure and heart rate were similar in the two groups throughout the study. Plasma noradrenaline concentrations were similar in the vecuronium and rocuronium groups prior to muscle relaxant administration (589(SD240) and 444(SD213) pg mL−1, respectively), 1 min after muscle relaxant administration (602(SD220) and 520(SD392) pg mL−1, respectively) and 1 min after tracheal intubation (597(SD351) and 440(SD181) pg mL, respectively). There was no significant change in either plasma noradrenaline or adrenaline concentrations in either group following muscle relaxant administration or tracheal intubation. The use of rocuronium (0.9 mg kg−1) in elderly patients does not result in a clinically significant change in heart rate, blood pressure or plasma catecholamine concentration.