We have studied the optimal diluent volume for post-operative analgesia and sedation produced by epidurally administered midazolam after upper abdominal surgery. Sixty patients were randomly allocated to four groups of 15 patients. When patients complained of pain after surgery, epidural midazolam 0.05 mg kg−1 in 3 mL saline (Group A), in 5 mL saline (Group B), in 10 mL saline (Group C) or in 15 mL saline (Group D) were injected as a bolus. The sedation was better and lasted longer in groups B and C than in the other two groups. Groups B and C also had significantly more extensive areas of analgesia than groups A and D from 30 min after the administration of midazolam. The interval to the second request for an analgesic was significantly shorter in Group D than in the other three groups. Memory retention of the pin-prick examination was reported by four patients in Group A. The present results indicate that 5–10 mL saline is the optimal volume for epidural injection when using midazolam 0.05 mg kg−1 for post-operative analgesia following upper abdominal surgery.

The incidence of sore throat after the use of the laryngeal mask was assessed with a randomized trial in 839 patients. Sore throat occurred more often in women, older patients or after multiple insertion attempts. It was found that the frequency in women, but not in men, was lowered from 11.9% to 3.9% (P=0.012) by reducing intracuff pressure to the minimum required for an effective seal.

The use of suppositories has been examined following a recent case in which an anaesthetist was reported to the United Kingdom General Medical Council. This study examined the preference for routes of administration of post-operative analgesia. A semi-structured interview with a written questionnaire was administered to 610 subjects (49 doctors; 62 nurses; 67 paramedical staff; 44 other hospital employees; 388 patients). Four hundred and fifty (74%) preferred the intravenous (i.v.) route, 24 (4%) preferred a suppository while 136 (22%) found either route acceptable. The i.v. route was most popular with young (98% under 20 years) females (79%) social class I subjects (90%), doctors (96%), nurses (95%), those who had never had a suppository (81%) and those who had ill effects following a previous suppository (95%). This result suggests that patients are more tolerant of suppositories than hospital staff but the majority prefer the i.v. route.

Hypoventilation as a consequence of deep intravenous sedation is the most frequently reported cause of cardiac arrest during upper gastrointestinal endoscopy (UGIE). Haemodynamic stress can contribute to myocardial ischaemia; therefore, this study was designed to observe prospectively the cardio-respiratory changes during UGIE using either midazolam or propofol for conscious sedation. Thirty-four patients, aged 50 years and older, ASA physical status I–III, scheduled for elective UGIE with sedation, were studied. Oxygen saturation, heart rate, non-invasive blood pressure and Holter ECG were recorded continuously starting 15 min before sedation until 15 min after the endoscopy. In addition, plasma catecholamine concentrations were determined. The results of this study are consistent with previous reports that cardiopulmonary events may occur during endoscopy, with or without sedation. Both midazolam and propofol sedation may provide some protection against haemodynamic stress in response to insertion and manipulation of the endoscope, but sedation can also contribute to the occurrence of hypoxaemia.

The influence of acute moderate haemodilution on the relation between dose and response for rocuronium was evaluated in 60 adult patients, ASA grade I, undergoing elective plastic surgery. The patients were randomly allocated to either the control or the haemodilution group. Following the induction of general anaesthesia, the status of acute moderate haemodilution in the haemodilution group was achieved by draining venous blood, and intravenous infusion of lactated Ringer's solution, 6% dextran or gelofusine, during which the levels of haemoatocrit and haemoglobin dropped from 44% to 27.5% and from 148.3 to 91.3 g L−1, respectively. Neuromuscular function was assessed mechanomyographically with train-of-four stimulation at the wrist every 12 s and the percentage depression of T1 response was used as the study parameter. The relation between dose and response for rocuronium in the two groups was determined by the cumulative dose–response technique. The results showed that the dose–response curve for rocuronium during acute moderate haemodilution was shifted in a parallel fashion to the left and the potency of rocuronium was increased. There were significant differences in ED50, ED90 and ED95 between the two groups. The ED50, ED90 and ED95 of rocuronium in the haemodilution group was decreased by 28.2%, 35.4% and 38.8%, respectively, compared with the control group.

Ringer's solution expands blood volume by between 20% and 25% in awake volunteers, but little is known about its volume effect during general anaesthesia. In 35 men with a mean age of 70 years, the power of various intra-operative factors to change blood volume as estimated by the haemoglobin dilution method were analysed by multiple linear regression every 10 min during transurethral resection of the prostate performed under enflurane anaesthesia. The results show that blood volume increased by 60% of the infused Ringer's solution and by 35% of the irrigating fluid absorbed directly into the blood, while it decreased by slightly more than 100% of the bled volume. There was no correlation between systolic pressure and blood volume changes. This suggests that the volume effect of Ringer's solution in the blood is greater than generally believed during general anaesthesia.

The effects of adding midazolam and bupivacaine to human cerebrospinal fluid in glass test tubes were examined by looking for changes in pH and a reduction in the transparency of the solution. Midazolam (n=6), 0.25% bupivacaine (n=6), 5 mg of midazolam in 6 mL of 0.25% bupivacaine (n=6) and 5 mg of midazolam in 10 mL of saline (n=6) were added to 1.5-mL samples (n=24) of cerebrospinal fluid taken at the time spinal anaesthesia was begun. Transparency and pH were checked after each increment. Cerebrospinal pH was decreased to below 7.0 by adding more than 3 mg of midazolam, more than 1.9 mL of 0.25% bupivacaine or 1.3 mL of the mixture. Cerebrospinal transparency was decreased by adding more than 0.7 mg of midazolam, 1.1 mL of 0.25% bupivacaine or 0.6 mL of the mixture. Midazolam in saline neither decreased the pH below 7.0 nor reduced transparency. These results do not suggest that clinically useful doses of intrathecal or epidural midazolam are neurotoxic.

In a prospective, randomized, double-blind study, we compared intravenous tenoxicam with rectal diclofenac for post-operative pain relief after day case arthroscopy or laparoscopic sterilization. Intravenous tenoxicam (40 mg) was administered as a single bolus at induction, or rectal diclofenac (100 mg) was administered immediately after induction. Both groups were similar with respect to age, weight, sex of the patients, the operation performed and the operative time. There were no significant differences observed between the groups for pain scores at 30 min, 60 min and 24 h post-operatively. The time to first analgesic requirement, the dose of pethidine administered and total analgesic requirements in the first 24 h post-operatively were equivalent in both groups. In view of the similar efficacy of both of these drugs, patient preference and ease of administration, the use of tenoxicam is appropriate in many patients undergoing day case surgery.

The antioxidant capacity of plasma taken from 10 patients before and during propofol anaesthesia was measured. Mean total plasma antioxidant activity fell from 1.73 to 1.64 mM L−1 trolox equivalents (P=0.047). This was caused by haemodilution since mean haemoglobin concentration fell from 13.0 to 12.5 g dL−1 (P=0.016). The time to 50% haemolysis (H50) of 10% red blood cell suspensions induced by 2,2'azo-bis(2-am-idinopropane) dihydrochloride (ABAP) was measured in blood from six patients. There was no change when red cells alone were studied, but when the patients' plasma was added to red cell suspensions (producing 10% plasma and 10% red cell suspensions), mean H50 increased from 291 to 308 min (P=0.049). Despite there being no overall increase in plasma antioxidant activity, the lipid soluble component of blood antioxidant activity appears to be increased by propofol.

Forty-two children (aged 27–16 years) were randomly assigned to receive either sevoflurane (n=21) or halothane (n=21) in nitrous oxide/oxygen. After premedication with midazolam, anaesthesia was induced by facemask and the anaesthetic concentration was increased until loss of eyelash reflex (sevoflurane, 6%; halothane, 2.5%). Thereafter, 1–1.5 MAC of the inhalational agents were maintained until skin closure. Intra-operative analgesia was provided either by intermittent intravenous (i.v.) bolus doses of fentanyl (2–3 μg kg−1) or by a regional blockade. Induction was smooth and the time to loss of eyelash reflex was slightly shorter with sevoflurane than with halothane, the difference not quite reaching statistical significance (P=0.06). In both groups, heart rate remained stable and blood pressure decreased significantly during induction. Haemodynamic parameters remained stable during anaesthetic maintenance; no cardiac dysrhythmias were observed. Emergence time with sevoflurane was 12.9 min vs. 16.3 min with halothane, but this difference was not statistically significant. It is concluded that sevoflurane is as suitable for paediatric patients as halothane. The slightly faster emergence time offered by sevoflurane over halothane was of no clinical significance in the present study.

This study was undertaken to determine the minimum effective dose of granisetron, a selective 5-hydroxy-tryptamine type 3 receptor antagonist, for the prevention of post-operative nausea and vomiting (PONV) in female patients undergoing elective laparoscopic cholecystectomy. In randomized, placebo-controlled, double-blind study, 120 women were assigned to receive either placebo (saline) or granisetron at three different doses (20 μg kg−1, 40 μg kg−1 or 80 μg kg−1) intravenously immediately before the induction of anaesthesia. All patients received standardized aesthesia consisting of isoflurane and nitrous oxide in oxygen. The incidence of PONV during the first 24 hours after anaesthesia was 43, 40, 13 and 13% after administration of placebo and granisetron 20 μg kg−1, 40 μg kg−1 and 80 μg kg−1, respectively (P<0.05, overall Fisher's exact probability test). Adverse effects post-operatively were not different among the groups. In conclusion, granisetron 40 μg kg−1 is the minimum effective dose in the prevention of PONV after laparoscopic cholecystectomy.

Sixty children undergoing inguinal or urogenital surgery were allocated randomly to three groups to receive a caudal injection of either 0.125% bupivacaine 0.75 mL kg−1 with 0.5% midazolam 50 μg kg−1 (n=20) or with 1% morphine chlorhydrate 0.05mg kg−1 (n=20), or bupivacaine alone (n=20) after surgery under general anaesthesia. There were no significant changes in heart rate, blood pressure, respiratory rate or oxygen haemoglobin saturation values in all groups, and there were no significant differences in the incidence of vomiting and pruritus between the groups (P>0.05). Sedation scores were higher in the bupivacaine-midazolam and the bupivacaine-morphine groups than in the bupivacaine group at 8–12 h post-operatively (P<0.01). The durations of analgesia were 21.15±1.2 h in the bupivacaine-midazolam group, 14.50±1.6 h in the bupivacaine-morphine group and 8.15±1.3 h in the bupivacaine group. Differences between the bupivacaine-midazolam group and the bupivacaine group (P<0.001), the bupivacaine-midazolam group and the bupivacaine-morphine group (P<0.01), and the bupivacaine-morphine group and the bupivacaine group (P<0.01) were significant. It is suggested that caudal administration of a bupivacaine-midazolam mixture produces a longer duration of post-operative analgesia than a bupivacaine-morphine mixture and bupivacaine alone with sedation for 8–12 h post-operatively.

A number of prospective randomized comparator studies have suggested that there is a reduction in post-operative nausea and vomiting following maintenance of anaesthesia with propofol compared with inhalational agents. We analysed these studies in more detail by examining the effects of induction agent, choice of inhalation agent, presence/absence of nitrous oxide, age of patient or use of opiate on the incidence of emesis. A search of the Zeneca database MEDLEY was undertaken and prospective randomized comparator studies identified. These were examined individually and independently by two of the authors and log-odds ratios, calculated from the incidence data of each individual trial, were determined and combined using a fixed-effects meta-analysis approach. Patients who received maintenance of anaesthesia with propofol had a significantly lower incidence of post-operative nausea and vomiting in comparison with inhalational agents regardless of induction agent, choice of inhalation agent, presence/absence of nitrous oxide, age of patient or use of opiate.

Lignocaine is a suitable and safe agent for intravenous regional anaesthesia (IVRA) with rapid onset of good surgical anaesthesia. The onset time of the local anaesthetic action of lignocaine was 11.2±5.1 min. Satisfactory surgical conditions, evidenced by good sensory blockade were achieved within 20 min, and no additional analgesics were required. There was no trend towards a fixed sequence, radial, median and ulnar in the development of sensory blockade. No patient exhibited objective symptoms of toxicity, either local or systemic, after release of the tourniquet, nor were there any subjective complaints. No changes in blood pressure, heart rate or oxygen saturation were observed at any time during the procedure, or after deflation of the tourniquet. After releasing the tourniquet lignocaine is rapidly and biexponentially eliminated, with a t1/2a of 4.3±2.1 min and a t1/2β of 79.1±31.2 min. Total body clearance was 0.86 ± 0.39L min−1. Eight patients showed rapid release of lignocaine from the exsanguinated area. In two patients the systemic plasma concentration of lignocaine increased more slowly than in the remaining eight. This can be explained by a greater degree of lignocaine absorbtion in the tissues of the arm. Pharmacokinetic constants after rapid and slow absorption were calculated.

Axillary brachial plexus block using 20 mL of 0.75% ropivacaine or 2% mepivacaine was compared in a prospective, randomized, double-blind study of two groups of 15 patients. The times to onset of sensory and motor block and to resolution of motor block, as well as the time to onset and degree of post-operative pain were recorded by an observer blinded to the identity of drug. Times to onset of sensory block were similar in the two groups (ropivacaine 10 min, mepivacaine 8 min). Resolution of motor block in the operated hand and the time to first requirement of post-operative analgesia occurred later with ropivacaine (9 h 50 min and 10 h) than with mepivacaine (3 h 50 min and 6 h), P<0.01 for both measurements. Nine patients who received ropivacaine and two patients who received mepivacaine did not require further post-operative analgesia (P<0.05). Ropivacaine is less toxic than other long-acting local anaesthetics, and 0.75% ropivacaine may be better for brachial plexus block when fast onset is required and prolonged pain relief is useful.

This study evaluates the prophylactic anti-emetic efficacy of granisetron, droperidol and metoclopramide, for the prevention of post-operative nausea and vomiting in female patients undergoing elective laparoscopic cholecystectomy. The patients were randomly assigned to one of four groups (n=30 for each group): granisetron 3 mg, droperidol 1.25 mg, metoclopramide 10 mg and placebo (saline). These medications were given immediately before the induction of anaesthesia. During the first 24 h after an-aesthesia, the incidence of post-operative nausea and vomiting was 13, 30, 33 and 37% after administration of granisetron, droperidol, metoclopramide and placebo, respectively (P>0.05, overall Fisher's exact probability test). No clinically important adverse effects were observed in either group. Our results suggest that granisetron is a better anti-emetic than droperidol or metoclopramide for the prevention of post-operative nausea and vomiting after laparoscopic cholecystectomy when compared with a placebo.

A double-blind randomized study was performed in 100 patients undergoing thyroidectomy to evaluate the effect of positive therapeutic suggestions made during neurolept-anaesthesia. The classic droperidol-fentanyl-N2O technique was used as these drugs preserve the neurophysiological functions required to process the information in the therapeutic suggestions given during general anaesthesia. Patients in the suggestion group heard positive non-affirmative suggestions during the whole operation. An autoreverse tape player was used. The control group listened to an empty tape. Both groups were comparable with respect to demographic variables, anaesthetic technique, drug dosage, duration of anaesthesia and surgery. Patients in the suggestion group suffered significantly less from post-operative nausea or volumiting (suggestion: 47.2% vs. control: 85.7%) and required less anti-emetic treatment (suggestion: 30.6% vs. control: 68.6%). We conclude that therapeutic suggestions heard during neurolept-anaesthesia are processed and decrease post-operative nausea and vomiting in patients after thyroidectomy.

The aim of the present study was to evaluate the effects of neostigmine as a final anaesthetic manoeuvre on colonic anastomoses. A colonic anastomosis was constructed in 40 Sprague-Dawley rats. The animals were divided into two groups: (1) rats receiving intravenous saline solution (placebo); and (2) rats receiving an intravenous injection of neostigmine. The size of the caecum, and the diameters of the pre-anastomotic and post-anastomotic colon were measured during the operation and 4 days after surgery, when all the animals were sacrificed. At this time, the presence of adhesions was also investigated. Each segment containing an anastomosis was removed, and the bursting pressure and bursting wall tension were determined. Loss of caecum diameter was significantly greater in group 2 than in group 1 (P=0.03). Dilatation and obstruction of the colon were significantly more frequent in group 1 (dilatation, P=0.01; obstruction, P=0.047). Also, consumption of water by group 2 was greater than that by group 1 (P=0.049). No statistically significant differences were found between the diameters of the colon (pre- and post-anastomosis), or with respect to general adhesions and adhesions to the anastomotic line. No significant differences were found between anastomotic resistance (determined in terms of bursting pressure and bursting wall tension) in the two groups. The inclusion of neostigmine in an anaesthetic protocol under experimental setting did not reduce the resistance of colonic anastomoses and did not compromise normal healing. Moreover, obstruction caused by peristaltic weakness might be prevented by the expulsion of stool that is induced by the strong contraction of the colonic smooth muscle.

Sevoflurane has been reported to generate oxygen free radicals. We have investigated whether sevoflurane or isoflurane enhances oxygen free radical formation in the post-ischaemic reperfused heart. An isolated rat heart–lung preparation was used. Thirty male Wistar rats were allocated to four groups: control, no drug, 2.5% sevoflurane and 1.4% isoflurane. The heart was perfused initially at a cardiac output of 30 mL min−1 and a mean arterial pressure of 70 mmHg. Ten minutes after the start of perfusion, the heart was rendered globally ischaemic for 10 min by reducing the preload and afterload to zero. Then, the heart was reperfused for 10 min. At the end of reperfusion, the heart was freeze dried for 6 days. The perfusate blood was collected just before and just after ischaemia and at the end of reperfusion. The formation of hydroxyl radicals in perfusate blood and heart was measured with high-performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding 2,3-, 2,4-, 2,5- and 3,4-dihydroxybenzoic acid (DHBA). Before and after ischaemia, there were no significant differences in cardiac output, systolic pressure, heart rate and right arterial pressure among the groups. The concentrations of 2,3-, 2,4-, 2,5- and 3,4-DHBA in the perfusate blood after ischaemia and reperfusion were significantly higher than those before ischaemia in all groups. However, there were no differences in the DHBA levels among groups. This study indicates that sevoflurane and isoflurane do not enhance hydroxyl radical formation in the post-ischaemic reperfused heart.

The aim of the present study was to investigate the effect of intravenously (i.v.) administered fentanyl and clonidine on ventilation in 12 healthy male volunteers (age 30.8±4.9 years) who either received fentanyl alone (1.5≥μg kg−1) or fentanyl (1.5≥μg kg−1) in combination with clonidine (3≥μg kg−1). The effect on ventilation was measured with a CO2 rebreathing system. The respiratory depression caused by fentanyl disappeared 120 min after injection. The corresponding slopes were 7430±2075 mL kPa−1 prior to (t0) and 6263±1864 mL kPa−1 120 min post-application (base-line vs. t120; P=0.106). An impaired ventilatory response was observed during CO2 rebreathing at t120 after the injection of fentanyl and clonidine. Before drug administration, the slope of the response curves was 7700±2800 mL kPa−1, which was reduced to 5480±2135 mL kPa−1 (P<0.035) at t120. These data suggest a prolongation of a fentanyl-induced ventilatory depression when used in combination with clonidine.