Laudanosine is a metabolite of the neuromuscular-blocking drugs atracurium and cisatracurium with potentially toxic systemic effects. It crosses the blood-brain barrier and may cause excitement and seizure activity. Its interest in recent years has increased because of the recognized interaction with γ-aminobutyric acid, opioid and nicotinic acetylcholine receptors. It has been shown to produce analgesia in animals. In the cardiovascular system, high plasma concentrations produce hypotension and bradycardia. In hepatic failure, its elimination halflife is prolonged but only moderate accumulation occurs in adults, whereas in infants and children plasma concentration are greater. In patients undergoing liver transplantation, laudanosine concentrations are increased during preanhepatic, anhepatic and postanhepatic stages. Patients with renal failure have higher plasma concentrations and a longer mean elimination half-life. In pregnancy, laudanosine crosses the placental barrier. The mean transplacental transfer is 14% of maternal blood concentrations. Except for prolonged administration of atracurium in intensive care units, laudanosine accumulation and related toxicity seem unlikely to be achieved in clinical practice. When cisatracurium is used, plasma concentrations of laudanosine are lower. Further studies are needed, especially around the interactions with γ-aminobutyric acid, opioid and nicotinic acetylcholine receptors.

Background and objective: Thiopental in clinically relevant concentrations inhibits the oxidative function of neutrophils, whereas only very high, non-therapeutic concentrations of methohexital induce a similar effect. The study characterized the molecular basis of this differential action of oxy- and thiobarbiturates on neutrophils.

Methods: Neutrophils were incubated in vitro with thiopental or methohexital using concentrations within the therapeutic range. Neutrophil responses were induced using different stimuli: N-formyl-L-methionyl-Lleucyl-L-phenylalanine (FMLP), C5a and 1,2-dioctanoyl-sn-glycerol (DiC8-DAG). FMLP and C5a bind to specific G-protein-coupled receptors that share the same second messenger cascade. In contrast, DiC8-DAG, an activator of protein kinase C, bypasses the signal transduction pathway downstream of the receptors. Hydrogen peroxide production by neutrophils was assessed using flow cytometry. To characterize the localization of the interaction site, FMLP receptor expression and cytosolic-free calcium were further analysed.

Results: FMLP and C5a-induced hydrogen peroxide production were both significantly impaired by thiopental, but not by methohexital. When postreceptor signalling was bypassed, by stimulation with DiC8-DAG, neither thiopental nor methohexital affected hydrogen peroxide production. Additionally, neither of the barbiturates impaired the cytosolic Ca2+ response.

Conclusions: We conclude that neither protein kinase C nor the hydrogen peroxide-generating enzymes are affected by thiopental or methohexital. The unimpaired Ca2+ response suggests that the function of the receptors and G-proteins were also unimpaired. Taken together, this indicates that the site of action of thiopental is in the cellular signalling upstream of protein kinase C.

Background and objective: Previous studies have shown that general anaesthetic agents modulate the production of hypothalamic prostaglandins (PG) D2 and E2, which are mediators of sleep and wakefulness respectively. Although flurbiprofen, a cyclo-oxygenase inhibitor, is used clinically as a non-steroidal anti-inflammatory agent and postoperative analgesic, it reduces prostaglandin production. Thus, this agent may affect the depth of sedation during general anaesthesia. In this study, we examined if flurbiprofen affects the bispectral index, which correlates with sedation levels.

Methods: Fifteen patients who underwent elective surgery under total intravenous anaesthesia with propofol and fentanyl were studied. The sedation level was monitored using a bispectral index monitor. On attainment of stable haemodynamics and a bispectral index, patients were given flurbiprofen axetil 50 mg intravenously. A bispectral index and 95% spectral edge frequency were recorded before and 5, 10, 15, 20 and 30 min after flurbiprofen axetil intravenously.

Results: Bispectral indexes of 51.7 (95% CI: 47.3–56.8), 51.7 (47.1–56.3), 51.3 (46.3–56.3), 50.3 (45.8–54.2), 48.9 (43.6–54.1) and 50.3 (45.5–55.2) at 0, 5, 10, 15, 20, 30 min after flurbiprofen axetil intravenously were observed. There was no change in this or 95% spectral edge frequency.

Conclusions: Clinical dose of flurbiprofen axetil does not alter the bispectral index and 95% spectral edge frequency under total intravenous anaesthesia with propofol and fentanyl.

Background and objective: The study investigated the effect of acute normovolaemic haemodilution on haemodynamics, blood flow and oxygen transport variables with regard to skeletal muscle tissue oxygenation in a canine model.

Methods: Twenty foxhounds were anaesthetized, mechanically ventilated with 30% oxygen in air and underwent first-step normovolaemic haemodilution with Ringer's lactate solution to haematocrit (Hct) 30 and 25% and second-step acute normovolaemic haemodilution with 6% Hetastarch 70 000/0.5 to Hcts of 20, 15 and 10%. Catheters were inserted into femoral arteries and veins and into the pulmonary artery for measurements of haemodynamics, temperature, and sampling of arterial and mixed-venous blood. A flow probe was placed around the left femoral artery. Skeletal muscle tissue oxygen tension (tPO2) was measured in the gastrocnemius muscle using a stepwise driven polarographic needle probe creating histograms from 200 single tPO2 measurements.

Results: Until a Hct of 25% was reached, the heart rate, mean arterial pressure, global and muscular oxygen delivery and consumption remained constant, while the cardiac index and oxygen extraction ratio were significantly increased when compared with baseline. The median tPO2 was significantly decreased at Hcts 15 and 10%, despite increased cardiac index and regional blood flow. The ratio of tPO2 and cardiac index as a marker for efficiency of acute normovolaemic haemodilution started to decline beyond Hcts of 25% (change of slope).

Conclusions: In acute normovolaemic haemodilution to the level of Hct of 25%, the ratio between tPO2 and cardiac index decreases in the healthy dog, indicating an uneconomic relation at the threshold of Hct of 25%.

Background and objective: Myocardial ischaemic preconditioning is characterized by a reduction in the rate of glycolysis. Brief myocardial ischaemia also reduces the glycogen content of the heart. The first objective was to determine whether augmenting glucose oxidation by activation of the pyruvate dehydrogenase complex would prevent the infarct limitation of ischaemic preconditioning. The second part of the study evaluates whether glycogen depletion before ischaemia mimics the infarct-limiting effect of ischaemic preconditioning.

Methods: Dichloroacetate (300 + 150 mg kg−1), an activator of the pyruvate dehydrogenase complex, was administered intravenously in the anaesthetized open-chest rabbit. All animals underwent 45 min of regional ischaemia and 3 h of reperfusion. Ischaemic preconditiong was elicited by 5 min of coronary occlusion. Control rabbits, those with ischaemic preconditioning with no dichloroacetate, received a saline vehicle. An isolated perfused rabbit heart model was employed to test the second hypothesis. Hearts were depleted of glycogen by perfusing them with a substrate-free buffer. Infarction was assessed by triphenyl tetrazolium chloride and area at risk determined with fluorescent particles.

Results: (a) Pyruvate dehydrogenase complex activation experiments. Treatment with dichloroacetate alone did not alter infarct size (58 ± 7% control vs. 60 ± 5% dichloroacetate). Addition of dichloroacetate did not attenuate the infarct-limiting effect of ischaemic preconditioning as evidenced by a similar reduction in infarct size in the ischaemic preconditioning group (22 ± 5%) and in the ischaemic preconditioning + dichloroacetate group (27 ± 7%). (b) Glycogen depletion experiments. Compared with control hearts with a normal glycogen content (4.84 ± 0.15 mg g−1 wet weight), glycogen depleted and ischaemic preconditioning hearts had reduced glycogen content before ischaemia (2.15 ± 0.26, 1.62 ± 0.17 mg g−1 wet weight, respectively; P < 0.01). Glycogen depletion did not reduce infarct size: 25.0 ± 4.5% cf. 27.9 ± 3.4% in the control group. However, ischaemic preconditioning resulted in a significant reduction of infarct size (11.5 ± 2.3% vs. 27.9 ± 3.4% control; P < 0.01).

Conclusions: Augmentation of oxidative glycolysis by dichloroacetate in in situ rabbit hearts does not alter the effect of ischaemic preconditioning, and glycogen depletion in the isolated rabbit heart does not influence infarct size after subsequent coronary occlusion.

Background and objective: Diabetes mellitus associated with hypertension often causes perioperative complications. The α1-adrenoceptor antagonist/5-hydroxytryptamine-1A receptor agonist urapidil is an approved drug used in hypertension and hypertensive emergencies. 5-Hydroxytryptamine-1A (5-HT1A) receptor agonists impair glucose metabolism. To evaluate a possible dose-dependent hyperglycaemic effect of urapidil due to its 5-HT1A receptor agonistic properties, the effect of three doses of urapidil on hyperglycaemia in the streptozotocin diabetic rat was investigated.

Methods: Male Wistar-Kyoto rats were made diabetic by streptozotocin and randomly allocated to the following daily treatments for 7 days (n = 6 each): urapidil 6 mg kg−1, urapidil 20 mg kg−1, urapidil 60 mg kg−1, insulin 4 IU kg−1 subcutaneously. One diabetic group and one non-diabetic healthy group served as controls.

Results: Treatment for 7 days with urapidil 20 mg kg−1 and urapidil 60 mg kg−01 reduced mean glucose concentrations significantly (urapidil-20: 15.6 ± 1.1 mmol L−1P = 0.023; urapidil-60: 15.8 ± 0.8 mmol L−1, P = 0.04) compared with diabetic controls (20.9 ± 0.8 mmol L−1), whereas those after urapidil 6 mg kg−1 were similar to diabetic controls. Insulin treatment normalized blood glucose concentrations.

Conclusions: The α1-adrenoceptor antagonist/5-HT1A receptor agonist urapidil has no hyperglycaemic effect on experimental diabetes mellitus, even in high doses, despite its 5-HT1A receptor agonistic properties.

Background and objective: Computers offer the potential for the assessment of children who have difficulties in communication and cannot describe pain using conventional approaches. Such approaches must be reliable and valid. As a preliminary step towards this goal, the validity and reliability of a computer-assisted pain assessment for children (MacInterview) was assessed using children with no known disabilities who had undergone surgery.

Methods: MacInterview uses body outlines and a range of different pain representations with scaling for size and intensity, and associated emotion. Following piloting with non-clinic children, the experience of acute postoperative pain was assessed for 30 children undergoing adenotonsillectomy or tonsillectomy the day following surgery using the MacInterview and three existing standardized assessment measures. Each child self-reported their current experience of postoperative pain on two occasions 30 min apart, and retrospectively on pain the previous evening in the immediate postoperative period.

Results: Analyses indicated good performance of MacInterview, showing positive correlations between 0.65 and 0.88 with standardized pain-intensity measures, and test-retest reliability was 0.9. Face validity was high, and children enjoyed the procedure.

Conclusions: The procedure shows promise and is likely to merit further development for children showing difficulties in communication.

Background and objective: The aim was to compare the effects of two different priming doses and priming intervals with the standard intubating dose of rocuronium on the onset time and intubation conditions.

Methods: After induction of anaesthesia, 75 patients were randomly assigned to one of five groups. Patients in Group 1 received a priming dose of rocuronium 0.06 mg kg−1 followed 2 min later by rocuronium 0.54 mg kg−1, Group 2 received a priming dose of 0.10 mg kg−1 followed 2 min later by a rocuronium injection of 0.50 mg kg−1. Group 3 was given a priming dose of 0.06 mg kg−1 followed 3 min later by administration 0.54 mg kg−1, where Group 4 received a priming dose of 0.10 mg kg−1 followed 3 min later by injection of 0.50 mg kg−1. Group 5 received a placebo injection followed 3 min later by rocuronium 0.60 mg kg−1.

Results: Priming with a 3 min priming interval shortened the onset time of rocuronium irrespective of the dosage of (P < 0.001). Clinical duration of action was significantly longer after priming in Group 4 than in Group 5. Clinically acceptable intubation conditions were obtained in all patients.

Conclusions: Priming with a 3 min priming interval was effective when rapid tracheal intubation with rocuronium was necessary. However, priming with rocuronium should be used carefully with special attention given to the possibility of hypoxia and aspiration of gastric contents in awake patients.

Background and objective: The addition of alfentanil or atracurium to lidocaine solution for intravenous regional anaesthesia of the arm may have advantages with respect to improved muscle relaxation and better analgesia. The study investigates these possibilities.

Methods: We investigated 33 patients. Plain lidocaine solution was administered to Group 1 (n = 11). Alfentanil (0.5 mg) and atracurium (3 mg) were added to the lidocaine solution in Groups 2 (n = 11) and 3 (n = 11), respectively. The onset of sensory and motor block, intra- and postoperative pain scores, and the duration of postoperative analgesia were evaluated.

Results: There was a significant difference in the speed of the onset of sensory block in the hand, but not at the tourniquet site. The onset of the motor block, intra- and postoperative pain scores, and the duration of postoperative analgesia were similar in all groups.

Conclusions: No clinical benefits of adding alfentanil or atracurium to lidocaine solution for intravenous regional anaesthesia of the arm could be shown.