The study was conducted in the intensive care unit of a tertiary teaching hospital. All patients with PAC in situ were eligible. Simultaneous CO readings were taken when clinically indicated. Investigators and clinicians were blinded to each other's results. The CO values used were the mean of three consecutive supra-sternal Doppler readings for patients with a sinus rhythm and seven for atrial fibrillation, and the mean of three thermodilution curves with acceptable form and values within 10% of each other for the PAC. Agreement was measured using both the paired t-test to calculate bias and limits of agreement and the intraclass correlation (ICC) coefficient.

Ninety-four subjects were enrolled. From 89 subjects, 250 paired comparisons were obtained. USCOM monitor readings were unobtainable in five patients. Mean supra-sternal Doppler CO was 5.5 litre min^–1. Bias was –0.09 litre min^–1 and levels of agreement were ± 2.92 litre min^–1 when compared with PAC. ICC was 0.46 (95% CI 0.36–0.56), and mean percentage difference was 19 (IQR 6–31)%.

In our subjects, there was poor agreement between CO measurements done with the supra-sternal Doppler monitor and PAC.

Isolated CPB was conducted according to strict standardized clinical criteria using blood from healthy volunteers. They were randomized to an air–oxygen mixture (control group) vs xenon–oxygen mixture (xenon group). Blood samples were drawn at 5, 15, 30, 60, and 90 min from commencement of circuits and analysed for haemoglobin concentrations, white cell, neutrophil, monocyte, lymphocyte, and platelet counts. Leucocyte and platelet activation and also complex formation were determined by measuring levels of CD14++ monocytes, CD16+ monocytes, platelet–monocyte complexes, and platelet–neutrophil complexes (PNC). Differences between and within the groups were analysed with Student's t-test.

Biomarker levels were not different between the groups. The data were pooled to identify the effects of isolated bypass. The neutrophils, monocytes, platelets, CD14++ monocytes, and CD16+ monocytes decreased within 5 min of the bypass experiments, whereas the percentage of platelet–CD++ monocyte complexes and PNC increased.

Isolated CPB elicited rapid, substantial leucocyte and platelet activation, and xenon had no impact on inhibiting these changes.

Fifty patients undergoing thoracic surgery with a single-lung ventilation (SLV) of >45 min duration were enrolled. Regional cerebral oxygen saturation was measured using absolute oximetry; standard clinical variables, and SOFA and Clavien scores were recorded. Correlation between minimum S_ctO₂ during SLV and postoperative complication scores was analysed using Pearson's correlation test, ² test, and logistic regression.

Forty-seven patients underwent lobectomy, two patients a pneumonectomy and 1 patient a chest wall resection. Eighty-two per cent of the patients had a decrease in S_ctO₂ of >15% from baseline value, and 10% of the patients had a minimal absolute S_ctO₂ value between 45% and 55%. The minimal absolute S_ctO₂ values during SLV correlated with the Clavien score (R²=0.098, P=0.0201) and the non-respiratory SOFA score (R²=0.090, P=0.0287). By defining a threshold of S_ctO₂=65%, the odds ratio of having a non-respiratory organ failure was 2.37 (95% CI 1.18–4.39, P=0.043) and a complication according to the Clavien score (Clavien score >0) was 3.19 (95% CI 1.60–6.34, P=0.0272).

Thoracic surgery with SLV seemed to be associated with a significant decrease in S_ctO₂, and minimal S_ctO₂ values correlated positively with postoperative complications.

Forty patients undergoing endoscopic sinus surgery under general anaesthesia using total i.v. anaesthesia (propofol and remifentanil) were randomly allocated to a control group (n=20) or remifentanil group (n=20) during emergence from anaesthesia. At the end of surgery, propofol was ceased and the infusion of remifentanil was stopped in the control group and maintained in the remifentanil group at a target organ concentration of 1.5 ng ml^–1 until extubation. Heart rate (HR), mean arterial pressure (MAP), and recovery profiles were measured and evaluated.

There was no significant difference in sex ratio, age, weight, height, time to eye opening, time to extubation, nausea, visual analogue scale, and time to discharge. Increases in HR and MAP occurred during emergence in the control group compared with baseline values. Increases in HR were attenuated in the remifentanil group and MAP decreased during recovery compared with baseline values. HR and MAP values were significantly higher in the control group [103 (23) beats min^–1, 129 (17) mm Hg] compared with the remifentanil group [79 (17) beats min^–1, 112 (15) mm Hg] during emergence and tracheal extubation. Moderate or severe coughing was observed only in the control group (8/20 vs 0/20, P<0.001).

Maintaining a remifentanil infusion reduced haemodynamic changes and coughing associated with tracheal extubation almost without significantly delaying recovery from anaesthesia.

Thirteen patients, ASA I or II, undergoing elective ENT surgery were studied. Anaesthesia was induced with propofol 2.1 (0.7) mg kg^–1, rocuronium 0.5 (0.1) mg kg^–1, and remifentanil 0.5 µg kg^–1 min^–1. After tracheal intubation, anaesthesia was maintained with a continuous infusion of propofol 3.9 (1.8) mg kg^–1 h^–1 and remifentanil 0.5 µg kg^–1 min^–1. Simultaneously, a venous blood sample was obtained. Propofol concentrations in serum were determined by GC–MS and compared with the height of the respective propofol signals achieved by MCC–IMS.

Twenty-four pairs of samples were obtained. The comparison of propofol concentrations in exhaled air and serum presented a bias of –10.5% and a precision of ± 12.3%. With these values, the 95% limits of agreement were 14.1% and –35.1%.

MCC–IMS may be a suitable method to determine propofol concentrations in exhaled air, and may be used to predict propofol concentrations in serum.

Thirty-four weaning trials were reported in 29 consecutive mechanically ventilated patients with different causes of initiation of ventilation. During the SBT, the patient was breathing through a conventional T-piece connected to the tracheal tube. FOT (5 Hz, ± 1 cm H₂O, 30 s) was applied at 5, 10, 15, 20, 25, and 30 min. Respiratory resistance (Rrs) and reactance (Xrs) were computed from pressure and flow measurements. The frequency to tidal volume ratio f/V_t was obtained from the flow signal. At the end of the trial, patients were divided into two groups: SBT success and failure.

Mixed model analysis showed no significant differences in Rrs and Xrs over the course of the SBT, or between the success (n=16) and the failure (n=18) groups. In contrast, f/V_t was significantly (P<0.001) higher in the failure group.

Worsening of respiratory impedance measured by FOT is not a common finding during a failed SBT in a typically heterogeneous intensive care unit population of mechanically ventilated patients.

Human endothelial cells were cultured with lipopolysaccharide 2 µg ml^–1, peptidoglycan G 20 µg ml^–1, tumour necrosis factor (TNF) 10 ng ml^–1, interleukin-1 (IL-1) β 20 ng ml^–1, or killed Candida albicans yeast cells plus either N-acetylcysteine (NAC) 25 mM, trolox 100 mM, or idebenone 1 µM. Plasma samples were obtained from 15 patients with sepsis and 11 healthy volunteers.

PTX3 levels in plasma were higher in patients with sepsis than in healthy people [26 (1–202) ng ml^–1 compared with 6 (1–12) ng ml^–1, P=0.01]. Antioxidant capacity was lower in patients with sepsis than healthy controls [0.99 (0.1–1.7) mM compared with 2.2 (1.3–3.3) mM, P=0.01]. In patients with sepsis, lipid hydroperoxide levels were 3.32 (0.3–10.6) nM and undetectable in controls. We found no relationship between PTX3 and antioxidant capacity or lipid hydroperoxides. Cell expression of PTX3 increased with all inflammatory stimulants but was highest in cells treated with TNF plus IL-1β. PTX3 concentrations were lower in cells co-treated with antioxidants (all P<0.05), associated with lower nuclear factor B expression for NAC and trolox (P<0.05).

PTX3 expression is down-regulated in vitro by antioxidants. Plasma levels of PTX3 are elevated in sepsis but seem to be unrelated to markers of oxidant stress or antioxidant capacity.

The pharmacokinetics of i.v. and i.m. NN1731 was evaluated in eight minipigs, and the effects of dose and administration route of NN1731 (i.v. 180 µg kg^–1, n=6; i.m. 540 µg kg^–1, n=4, or 2000 µg kg^–1, n=6) vs vehicle (n=16) were studied on a liver laceration injury in pigs. To simulate a pre-hospital setting, the administration of NN1731 was delayed by 1 min for i.m. administration and 7 min for i.v. administration, at which time fluid resuscitation also began.

In the minipigs, NN1731 exposure was similar after i.v. 180 µg kg^–1 and i.m. 540 µg kg^–1, with a bioavailability of ~35%. The injury and blood loss at 7 min was comparable between the four groups of pigs; however, after 60 min, the blood loss was lower in the i.v. treated animals: 1.3 (0.3) (i.v.) vs 2.2 (0.8) litres (i.m.₅₄₀, i.m.₂₀₀₀, and vehicle) (P<0.001). Also, the survival time was increased: 117 (14) (i.v.) vs 84 (28) min (i.m.₅₄₀, i.m.₂₀₀₀, and vehicle) (P<0.001).

After a liver trauma in the pig, i.v. administration of NN1731 reduced the bleeding and increased the survival time. In contrast, i.m. administration had no effect, presumably because reduced muscle perfusion during haemorrhage reduced the uptake of NN1731.

The effect of a range of doses of CNS 7056, midazolam, and propofol on depth of sedation, the respiratory system, and the cardiovascular system was studied in chronically instrumented sheep (n=5 or 6). The low, medium, and high doses of CNS 7056, midazolam, and propofol were 0.37, 0.74, and 1.47 mg kg^–1; 0.05, 0.1, and 0.2 mg kg^–1; and 1, 2, and 4 mg kg^–1, respectively.

CNS 7056 produced substantial sedation with rapid onset and offset for all doses, with duration rather than depth of sedation increasing with the dose. The lower doses of midazolam had minimal sedative effect; increasing the dose produced variable but longer term sedation. Sedation from propofol was comparable with that of CNS 7056 for the medium and high doses only. The high doses produced ~20 min of sedation. All three drugs produced dose-dependent respiratory (e.g. reductions in arterial oxygen tension) and cardiovascular depression (e.g. reductions in mean arterial pressure). For CNS 7056, midazolam, and propofol, the magnitude of the cardiovascular and respiratory depression was proportional to the depth of sedation achieved for any given drug or dose. For all three drugs, the respiratory and cardiovascular depression was not of sufficient magnitude to endanger the animals.

CNS 7056 is a powerful and short-acting anaesthetic in sheep with respiratory and cardiovascular effects consistent with its sedative/anaesthetic qualities.

Seventy-two patients undergoing Caesarean section were randomly assigned to receive i.v. saline (control group) or magnesium sulphate 30 mg kg^–1 bolus+10 mg kg^–1 h^–1 continuous infusion (Mg 30 group) or 45 mg kg^–1 bolus+15 mg kg^–1 h^–1 continuous infusion (Mg 45 group) after induction. Bispectral index (BIS) value, mean arterial pressure (MAP), and midazolam, fentanyl, and atracurium consumptions were recorded.

BIS values [mean (sd)] at 7.5 and 10 min after surgery and before delivery in the control [64 (9), 66 (8), 67 (8), P<0.001] and the Mg 30 groups [62 (8), P<0.01; 64 (7), 63 (9), P<0.001] were higher than in the Mg 45 group [56 (8), 55 (8), 55 (7)]. MAP was greater in the control group (P<0.05) than in the Mg 30 and Mg 45 groups during the pre-delivery period. The magnesium groups required less midazolam (P<0.05), fentanyl (Mg 30, P<0.05; Mg 45, P<0.01), and atracurium (P<0.001) vs the control group.

Preoperative i.v. magnesium sulphate attenuated BIS and arterial pressure increases during the pre-delivery period. Magnesium sulphate can be recommended as an adjuvant during general anaesthesia for Caesarean section to avoid perioperative awareness and pressor response resulting from inadequate anaesthesia, analgesia, or both.

Patients aged from birth to 5 yr requiring general anaesthesia with TT intubation were included in 24 European paediatric anaesthesia centres. Patients were prospectively randomized into a cuffed TT group (Microcuff® PET) and an uncuffed TT group (Mallinckrodt®, Portex®, Rüsch®, Sheridan®). Endpoints were incidence of post-extubation stridor and the number of TT exchanges to find an appropriate-sized tube. For cuffed TTs, minimal cuff pressure required to seal the airway was noted; maximal cuff pressure was limited at 20 cm H₂O with a pressure release valve. Data are mean (sd).

A total of 2246 children were studied (1119/1127 cuffed/uncuffed). The age was 1.93 (1.48) yr in the cuffed and 1.87 (1.45) yr in the uncuffed groups. Post-extubation stridor was noted in 4.4% of patients with cuffed and in 4.7% with uncuffed TTs (P=0.543). TT exchange rate was 2.1% in the cuffed and 30.8% in the uncuffed groups (P<0.0001). Minimal cuff pressure required to seal the trachea was 10.6 (4.3) cm H₂O.

The use of cuffed TTs in small children provides a reliably sealed airway at cuff pressures of ≤20 cm H₂O, reduces the need for TT exchanges, and does not increase the risk for post-extubation stridor compared with uncuffed TTs.

We analysed individual patient information from five randomized trials (913 patients) of i.v. patient-controlled analgesia (IVPCA) plus epidural placebo, morphine sulphate (MS) 5 mg, or extended-release epidural morphine (EREM; DepoDur^TM) at doses of 5–30 mg, to explore effects of a range of epidural morphine doses. Pain and opioid requirement on first and second postoperative days, dose–response, clinically relevant comparisons of IVPCA without epidural morphine, 5 mg MS, and 10 mg EREM, and relationship between patient rating and other measures were described.

There were three strong findings. Epidural morphine resulted in greater patient satisfaction, despite higher rates of adverse events. Those describing their analgesic medication as ‘very good’ or ‘excellent’ used IVPCA opioid less and had pain scores significantly below the global mean, whereas those describing their medication as ‘poor’ or ‘fair’ had pain scores significantly above the mean. Epidural morphine meant less need for postoperative IVPCA opioid than epidural placebo. The therapeutic gain with EREM was lower pain scores with less IVPCA opioid. Moderate or severe pruritus was more common with IVPCA plus epidural morphine, whatever the formulation, compared with IVPCA plus placebo.

Analysis of individual patient data from high-quality clinical trials provides important insights into characteristics of new agents not immediately apparent from original trials, and also informing clinical practice. Prophylactic epidural morphine provides a better patient experience than IVPCA alone.

Both devices were studied in 39 anaesthetized, paralysed patients in a randomized crossover trial. The primary outcome was airway leak pressure. Secondary outcomes included time to insertion, the number of insertion and reposition attempts, leak volumes, and leak fractions.

There was no significant difference between the airway leak pressures of the two devices [median (IQR) leak pressures 25 (22–30) vs 22 (20–28) cm H₂O for the i-gel and LMA-U, respectively; P=0.083, 95% CI of the mean difference –0.32 to 4.88 cm H₂O]. The median (IQR) insertion time for the i-gel was significantly less than for the LMA-U [12.2 (9.7–14.3) vs 15.2 (13.2–17.3) s; P=0.007]. All the LMA-U devices and 38 of 39 i-gel airways were inserted at the first attempt. The number of manipulations required after insertion to achieve a clear airway was the same in both the groups (four in each). There were no statistically significant differences in leak volumes or leak fractions during controlled ventilation.

We found no difference in leak pressures and success rate of first-time insertion between the i-gel and the LMA-U. Time to successful insertion was significantly shorter for the i-gel. We conclude that the i-gel provides a reasonable alternative to the LMA-U for controlled ventilation during anaesthesia.

Nasopharyngeal airway pressure was measured in 15 postoperative cardiac surgery adult patients who received both NHF and standard facemask therapy at a flow rate of 35 litre min^–1. Measurements were repeated in the open mouth and closed mouth positions. Mean airway pressure was determined by averaging the pressures at the peak of inspiration of each breath within a 1 min period, allowing the entire pressure profile of each breath to be included within the calculation.

Low level positive pressure was demonstrated with NHF at 35 litre min^–1 with mouth closed when compared with a facemask. NHF generated a mean nasopharyngeal airway pressure of mean (sd) 2.7 (1.04) cm H₂O with the mouth closed. Airway pressure was significantly higher when breathing with mouth closed compared with mouth open (P≤0.0001).

This study demonstrated that a low level of positive pressure was generated with NHF at 35 litre min^–1 of gas flow. This is consistent with results obtained in healthy volunteers.

Australian Clinical Trials Registry www.actr.org.au ACTRN012606000139572.

Using a bench-top trachea–lung model (comprising a Siemens test lung attached to commercially available breathing system tubing), we compared delivered minute volumes (MVs) for five methods of ventilation administered through cannulae of diameters 20, 16, 14, and 13 G. The ventilation methods were: an ENK oxygen flow modulator, a Manujet, a self-inflating resuscitation bag, the oxygen flush of an anaesthetic machine, and oxygen from a wall-mounted flow meter attached via a three-way tap to the cannula. All experiments were performed with and without a proximal 2.5 mm diameter constriction to simulate partial upper airway obstruction.

MVs increased with increasing cannula diameter. In the absence of a proximal constriction, MVs delivered via a 20 G cannula were <1 litre min^–1 with all devices; only the Manujet delivered MVs >2 litre min^–1, at cannula sizes of ≥16 G. MVs were greater in the presence of a proximal constriction, but did not exceed 4 litre min^–1 using the low-pressure devices.

Extrapolated to the clinical situation, these data suggest that low-pressure devices will not deliver adequate MVs via a cannula cricothroidotomy and should no longer be advocated. Purpose-made devices should be available in all areas where anaesthesia is administered or airway interventions are performed.

One thousand and ten patients undergoing non-emergent cardiac surgery were recruited prospectively. Baseline clinical details were obtained and the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Parsonnet score were calculated. Preoperative NT-proBNP levels were measured using the Roche Elecsys assay. The primary endpoint was 30 day mortality.

Median NT-proBNP levels were 624 ng litre^–1 among patients who died within 30 days of surgery (n=29), compared with 279 ng litre^–1 in survivors [odds ratio (OR) 1.03 per 250 ng litre^–1, 95% confidence interval 1.01–1.05, P=0.001). NT-proBNP levels remained predictors of 30 day mortality in models including either the additive EuroSCORE (OR 1.03 per 250 ng litre^–1, P=0.01), the logistic EuroSCORE (OR 1.03 per 250 ng litre^–1, P=0.004), or the Parsonnet score (OR 1.02 per 250 ng litre^–1, P=0.04). Levels of NT-proBNP were also predictors of prolonged (>1 day) stay in the intensive care unit (OR 1.03 per 250 ng litre^–1, P<0.001) and of a hospital stay >1 week (OR 1.07 per 250 ng litre^–1, P<0.001). They remained predictive of these outcomes in regression models that included either the EuroSCORE or the Parsonnet score and in a model that included all study variables.

NT-proBNP levels predict early outcome after cardiac surgery. Their prognostic utility is modest—but is independent of traditional indicators and conventional risk prediction scores.

Male New Zealand White rabbits (n=48) were anaesthetized with propofol (70 mg kg^–1 h^–1), desflurane (8.9%), or sevoflurane (3.8%) and randomized to receive IR or non-ischaemic time-matched (TC) perfusion protocol. IR groups (desIR, propIR, and sevIR) underwent 30 min of left anterior descending coronary artery occlusion and then 120 min of reperfusion. TC groups (desTC, propTC, and sevTC) were anaesthetized for 150 min without ischaemia. Haemodynamic endpoints included mean arterial pressure, heart rate, cardiac index, systemic vascular resistance index, preload-recruitable stroke-work, time constant of relaxation (), and end-diastolic PV relationship (EDPVR). Ventricles in the IR groups were excised and stained with 2,3,5-triphenyl-tetrazolium chloride in order to measure infarct size.

Myocardial infarction size was greater in the propIR group [35.74 (sd 11.32)%] compared with the desIR [13.44 (3.09)%] and sevIR [17.96 (6.63)%] groups (P<0.001). EDPVR deteriorated in the sevIR and propIR groups compared with their TC groups, sevTC (P=0.03) and propTC (P=0.044), respectively. There was no difference in any haemodynamic endpoints for the desIR group compared with its TC control (desTC).

During ischaemia, all anaesthetics provide haemodynamic stability and preservation of LV contractility, whereas propofol and sevoflurane, but not desflurane, caused increased LV diastolic stiffness. Desflurane and sevoflurane provide superior cardioprotection compared with propofol.

Ten trainee anaesthetists were exposed to a simulated crisis, similar to that used in a previous study. The mental workload of the trainees was assessed by measuring their response times to a wireless vibrotactile device.

Although all subjects treated the ‘patient’ adequately, response times increased significantly during the crisis (P=0.005). These findings are consistent with increased mental workload and with the findings of other studies using similar techniques.

These findings confirm the importance of mental workload to the performance of anaesthetists, and suggest that raised mental workload is likely to be a common problem. Although further studies are required, the method described may provide a useful method for the measurement of the mental workload of anaesthetists.

Four interface displays of the IMA^TM were developed, including one numerical, one numerical and graphical (mixed numerical–graphical), one only graphical, and one an advanced two-dimensional graphical display. Each of the four displays was evaluated in a random order by 10 staff anaesthetists and 10 residents/fellows using a set of five scenarios. Scenarios involved one or more abnormal variables that participants had to verbally phrase. For each interface test, reaction time, response accuracy, and NASA-Task Load Index were measured and compared.

The numerical, graphical, and advanced-graphical interfaces yielded similar median reaction times, respectively, 7.99 s (5.15–10.79), 8.21 s (6.20–11.88), and 9.43 s (6.19–13.3). Reaction times were significantly shorter (P<0.006) with the mixed numerical–graphical interface: 6.26 s (4.52–8.32). The correct response rate was significantly lower in the graphical interface. The three others presented no statistical difference when compared among each other. The mixed numerical–graphical interface yielded a significantly lower NASA-TLX than the numerical and the advanced-graphical interfaces (19/100 vs 34/100, P<0.003).

A mixed numerical–graphical display design appears to present the best results in terms of user reaction times, response accuracy, and performance index when detecting abnormal critical events.

We conducted a prospective study of 56 fluid challenges given for haemodynamic instability in 11 patients undergoing major abdominal surgery. Fluid responsiveness was defined as an increase in stroke volume index (SVI) >10%. PPV_ref, PPV_auto, SVV_auto, and SVI (oesophageal Doppler) were recorded simultaneously before and after each fluid challenge.

PPV_auto and SVV_auto both correlated with PPV_ref [r_corr=0.87 (P<0.0001) and 0.84 (P<0.0001), respectively; n=77]. All three indices measured before fluid challenges were higher in responder (n=32) than in non-responder (n=24) fluid challenges (P≤0.02). The mean areas under the receiver operating characteristic curves were 0.96 (PPV_ref), 0.96 (PPV_auto), and 0.95 (SVV_auto), and the optimal threshold value for each variable was 13%, 13%, and 12%, respectively. All indices correlated with the fluid challenge-induced changes in SVI (PPV_ref: r_corr=0.65; PPV_auto: r_corr=0.58; SVV_auto: r_corr=0.58, P<0.001 for all).

PPV_auto and SVV_auto predict fluid responsiveness as accurately as off-line PPV_ref in patients with haemodynamic instability during major abdominal surgery.

Patients were randomized to receive propofol/paravertebral anaesthesia–analgesia (propofol/paravertebral, n=11) or sevoflurane general anaesthesia with opioid analgesia (sevoflurane/opioid, n=11). The ER-negative MDA-MB-231 cell line was treated with patient serum from both groups. The effects on proliferation and migration were measured.

Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathology. Pain scores were lower at 1 and 2 h in the propofol/paravertebral analgesia group. Compared with preoperative values, proliferation of MDA-MB-231 cells treated with postoperative patient serum at 10% concentration from the propofol/paravertebral group was significantly reduced compared with the sevoflurane/opioid group (–24% vs 73%, P=0.01). There was no significant change in MDA-MB-231 cell migration after treatment with patient serum between the two groups.

Serum from patients receiving propofol/paravertebral anaesthesia for breast cancer surgery inhibited proliferation, but not migration, of ER-MDA-MB-231 cells in vitro, to a greater extent than that from patients receiving sevoflurane/opioid anaesthesia–analgesia. This implies that anaesthetic technique alters the serum molecular milieu in ways that may affect breast cancer cell function, possibly by altering anaesthetic and opioid drug administration and resultant pain scores.

In this prospective, randomized, experimental study on 24 domestic pigs, jejunal mucosal tissue Po₂ (Po₂muc) was measured using two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular haemoglobin (HbO₂j) was determined by tissue reflectance spectrophotometry. Systemic haemodynamic variables, mesenteric-venous and systemic acid–base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli lipopolysaccharide (LPS) administration, and at 20 min intervals during incremental NE infusion (0.05, 0.1, 0.5, 1.0, and 2 µg kg^–1 min^–1, respectively) with 57 mU kg^–1 h^–1 AVP (n=8; NE+AVP group) or without (n=8; NE group); or infusion of an equal amount of normal saline (n=8; CON group).

LPS infusion led to a significant (P<0.05) decrease of Po₂muc and HbO₂j. Both NE and NE+AVP increased arterial pressure, cardiac output, and mesenteric artery blood flow. Concomitant to an increase in systemic oxygen delivery, NE improved Po₂muc and HbO₂j. NE alone was superior in restoration of Po₂muc when compared with NE+AVP.

Both NE and NE+AVP improved global haemodynamics and systemic oxygen transport variables when compared with control animals in an acute endotoxic pig model. NE improved jejunal Po₂muc at all dosages. NE effects were significantly blunted by simultaneous administration of AVP.

We studied single glomus cells from neonatal rat carotid bodies. Halothane and sevoflurane were administered in concentrations ranging from 0.18 to 1.45 and 0.1 to 2 minimum alveolar concentration (MAC), respectively (rat values). The intracellular calcium response to a ~90 s period of hypoxia was measured using indo-1 dye. We also assessed if these agents influenced the calcium response to exposure to potassium 100 mM.

Halothane depressed the increase in intracellular calcium with hypoxia more than did sevoflurane (P=0.036). Although halothane was depressive at all concentrations tested, sevoflurane depressed the calcium response only at 2 MAC. Both agents also depressed the calcium response to elevated extracellular potassium—halothane more so than sevoflurane (P=0.004).

The actions of the agents in single cells reflect their known influence on human hypoxic ventilatory response, consistent with the notion that the cellular process underlies the whole-body effect. The responses to elevated extracellular potassium, which depolarizes the cell membrane, indicate that (in addition to molecular mechanisms previously proposed), voltage-activated calcium channels may also be involved in the anaesthetic effect.

Neuroblastoma cells (SHEP) were incubated with eight local anaesthetics, two of the ester and six of the amide types. At least, five concentrations of each local anaesthetic were evaluated. After incubation for 24 h, rates of cells in early apoptotic stages and overall cell death were evaluated by annexin V and 7-amino-actinomycin D double staining by flow cytometry. The concentrations that led to half-maximal neurotoxic effects (LD₅₀) were calculated and compared for all local anaesthetics.

All local anaesthetics were neurotoxic in a concentration-dependent manner. All drugs induced similar rates of early apoptotic cell formation at low concentrations, whereas at high concentrations, late apoptotic or necrotic cell death predominated. Comparison of LD₅₀ values of the different local anaesthetics resulted in the following order of apoptotic potency from high to low toxicity: tetracaine>bupivacaine>prilocaine=mepivacaine=ropivacaine>lidocaine>procaine=articaine. The toxicity correlated with octanol/buffer coefficients and also with experimental potency of the local anaesthetic, but was unrelated to the structure (ester or amide type).

All commonly used local anaesthetics induce neuronal apoptosis in clinically used concentrations. The neurotoxicity correlates with lipid solubility and thus with the conduction blocking potency of the local anaesthetic, but is independent of the chemical class (ester/amide).

Cell death after local anaesthetic treatment was evaluated with a lactate dehydrogenase (LDH) assay. To examine the mechanisms of cell death, reactive oxygen species (ROS) measurement and western blots of poly-ADP ribose polymerase (PARP), procaspase-3, and mitogen-activated protein kinases family members were performed.

Of the local anaesthetics, which were applied at <1 mM for 18 h, only tetracaine significantly increased LDH leakage (P<0.05) and cell death in a dose- and time-dependent manner. Hoechst 33258–propidium iodide staining and western blots with PARP and procaspase-3 antibodies suggested that tetracaine induced apoptosis. ROS levels increased 2-fold at 30 min after tetracaine treatment compared with the control and then decreased. The antioxidants, N-acetylcysteine and trolox, markedly inhibited tetracaine-induced apoptosis.

Tetracaine induced apoptosis through ROS generation. Further studies focusing on the neurotoxicity of tetracaine are needed.

A randomized, double-blind, placebo-controlled trial was performed at a tertiary maternity hospital. Fifty women undergoing Caesarean delivery received bilateral US-guided TAP blocks with either ropivacaine 0.5% or saline. All participants received a spinal anaesthetic with bupivacaine and fentanyl, followed by postoperative acetaminophen, non-steroidal anti-inflammatory drugs, and patient-controlled i.v. morphine without long-acting intrathecal opioids. Each patient was assessed 24 h after delivery for morphine usage, average pain score, nausea, vomiting, pruritus, drowsiness, and satisfaction with pain relief.

Forty-seven participants completed the trial, 23 in the active group and 24 in the placebo group. Total morphine use in 24 h was reduced in the active group (median 18.0 mg) compared with the placebo group (median 31.5 mg, P<0.05). The active group reported improved satisfaction with their pain relief measured by visual analogue scale compared with the placebo group (median 96 vs 77 mm, P=0.008). Fewer patients required antiemetics in the active group (P=0.03). There were no local complications attributable to the TAP block, but one participant had an anaphylactoid reaction after ropivacaine injection.

The US-guided TAP block reduces morphine requirements after Caesarean delivery when used as a component of a multimodal analgesic regimen.

Registered with the Australia New Zealand Clinical Trials Registry ACTRN12608000540314. URL: http://www.anzctr.org.au/trial_view.aspx?ID=83176.

We performed a two-stage study to determine the ED₅₀, the ED₉₅, and the relative analgesic potency of isobaric spinal bupivacaine, levobupivacaine, and ropivacaine in infants. In phase 1, 81 infants were randomized in a Dixon–Massey study to describe the minimum local analgesic dose. In phase 2, a further 70 patients were randomly allocated to receive spinal anaesthesia with doses in the upper dose–response range to define the ED₉₅.

The ED₅₀ doses for bupivacaine, levobupivacaine, and ropivacaine were estimated by isotonic regression to be 0.30 mg kg^–1 [95% confidence interval (CI) 0.25–0.43], 0.55 mg kg^–1 (0.50–0.64), and 0.50 mg kg^–1 (0.43–0.64), respectively. The ED₉₅, respectively, of bupivacaine, levobupivacaine, and ropivacaine were 0.96 mg kg^–1 (95% CI 0.83–0.98), 1.18 mg kg^–1 (1.05–1.22), and 0.99 mg kg^–1 (0.73–1.50). The relative potency ratios at the ED₅₀ were bupivacaine:levobupivacaine 0.55 (95% CI 0.39–0.88), bupivacaine:ropivacaine 0.61 (0.41–1.00), and levobupivacaine:ropivacaine 1.09 (0.84–1.45).

Appropriate doses for infant spinal anaesthesia are 1 mg kg^–1 of isobaric 0.5% bupivacaine and ropivacaine and 1.2 mg kg^–1 of isobaric 0.5% levobupivacaine.

In a randomized, observer-blinded trial, after obtaining institutional ethical committee approval and parental consent, 200 ASA grade I–II children aged 5–16 yr were allocated to receive either a sub-Tenon's block (Group SB) or 2 µg kg^–1 i.v. fentanyl (Group F) after induction of anaesthesia and topical anaesthesia of the conjunctiva with proparacaine 0.5% drops. Patients in Group F received fentanyl 0.5 µg kg^–1 and those in Group SB were given a corresponding volume of normal saline i.v. every hour from preloaded syringes. Increases in heart rate or mean arterial pressure by more than 20% of baseline were treated with additional 0.5 µg kg^–1 i.v. fentanyl boluses in both groups. The incidence of oculocardiac reflex (OCR), need for additional analgesics, postoperative pain, and PONV were recorded for the first 24 h after surgery.

More patients in Group F (47.96%) had moderate to severe pain in the first 24 h when compared with Group SB (31.36%) (P=0.023). The need for postoperative ibuprofen was higher in Group F (66.3%) compared with Group SB (47.95%) (P=0.012). The incidence of OCR was significantly higher in Group F (31.6%) compared with Group SB (5.1%) (P<0.001). The incidence of PONV was similar in both groups.

Sub-Tenon's block provides more effective analgesia than i.v. fentanyl for paediatric VR surgery.

Minimum alveolar concentrations (MACs) for sevoflurane, isoflurane, and halothane, and the sevoflurane MAC-sparing effect of N₂O were determined in homozygous MOP-KO and WT mice. The analgesic effect of N₂O and the suppressive effect of naloxone on N₂O analgesia were assessed in a writhing test and a hot-plate test. Immunohistochemical staining was used to visualize N₂O-induced c-Fos expression in the lumbar spinal cord.

There were no significant differences in the MAC values of the three volatile anaesthetics or in the sevoflurane MAC-sparing effect of N₂O 70% between MOP-KO and WT mice. There was also no significant difference in the analgesic effect of N₂O 70% or in the level of c-Fos expression induced by N₂O 70% between the two genotypes. In the writhing test, naloxone significantly attenuated N₂O analgesia in MOP-KO and WT mice.

These results suggest that MOP is not required for the anaesthetic action of volatile anaesthetics and the analgesic effect of N₂O. Opioid receptors other than MOP may mediate the analgesic action of N₂O.

Seventy patients undergoing TURP were randomly allocated into two groups. Group F (n=35) received fentanyl 25 µg+bupivacaine 0.5% (0.8 ml)+normal saline 0.3 ml and Group S (n=35) received sufentanil 5 µg+bupivacaine 0.5% (0.8 ml)+normal saline 0.7 ml—in total, bupivacaine 0.25% (1.6 ml) intrathecally. Onset and duration of the sensory block, the degree of the motor block, side-effects, and the perioperative analgesic requirements were assessed.

The median peak level of the sensory block was significantly higher in Group S than in Group F (P=0.049). Group S required fewer perioperative analgesics than Group F (P=0.008). The time to the first analgesic request was longer in Group S (P=0.025). There were no differences between the groups for the onset and recovery time of the sensory block, degree of the motor block, quality of anaesthesia, or adverse effects.

Low-dose diluted bupivacaine with fentanyl 25 µg or sufentanil 5 µg can provide adequate anaesthesia without haemodynamic instability for TURP in elderly patients. However, sufentanil was superior to fentanyl in the quality of the spinal block produced.

Twenty-two non-anaesthetists, 21 trainees, and 20 consultant anaesthetists attempted tracheal intubation of a Laerdal^® SimMan manikin, comparing a normal with a difficult airway scenario for each intubation device. The time taken to view the vocal cords and time to intubate were recorded. Also success rate and ease of use for each device were scored, alongside scope preference for each scenario.

Time to intubate was significantly shorter with the Macintosh compared with all three novel devices. All the devices had a high first-attempt success rate, but the Glidescope^® had a 100% first time successful intubation for all participants in both a normal and a difficult airway. Non-anaesthetists took significantly longer time to intubate compared with consultant anaesthetists, but there was no difference between trainee and consultant anaesthetists. Higher proportions of participants found the Glidescope^® easy to use, compared with other devices. For the normal airway, the Macintosh was the preferred device, but for the difficult airway, the Glidescope^® was favoured.

In this study, the Macintosh laryngoscope outperformed the other devices. However, the Glidescope^® was considered easy to use regardless of previous experience and was the preferred device for the simulated difficult airway.

Seventy-five consenting patients presenting for surgery requiring tracheal intubation, and who were deemed to possess characteristics indicating an increased risk for difficult tracheal intubation, were randomly assigned to undergo intubation using a Macintosh, AWS^®, or Glidescope^® laryngoscope (n=25 patients per group). All patients were intubated by one of three anaesthetists experienced in the use of each laryngoscope.

Both the Glidescope^® and the AWS^® significantly reduced the intubation difficulty score compared with the Macintosh. The rate of successful tracheal intubation was lower with the Macintosh (84%) compared with the Glidescope^® (96%) or the AWS^® (100%). There were no differences in the duration of tracheal intubation attempts between the devices. Both the Glidescope^® and the AWS^® significantly reduced the need for additional manoeuvres and improved the Cormack and Lehane view obtained at laryngoscopy, compared with the Macintosh. Tracheal intubation with the AWS^® but not the Glidescope^® reduced the degree of haemodynamic stimulation compared with the Macintosh laryngoscope.

The AWS^® and the Glidescope^® laryngoscopes reduced the difficulty of tracheal intubation to a similar extent compared with the Macintosh laryngoscope, in patients at increased risk for difficult tracheal intubation.

Thirty-two patients undergoing laparoscopic cholecystectomy were randomly assigned to two groups; a control group was given saline, and a magnesium group received magnesium sulphate 50 mg kg^–1 immediately before pneumoperitoneum. Arterial pressure, heart rate, serum magnesium, plasma renin activity (PRA), and catecholamine, cortisol, and vasopressin levels were measured.

Systolic and diastolic arterial pressures were greater in the control group (P<0.05) than in the magnesium group at 10, 20, and 30 min post-pneumoperitoneum. Norepinephrine or epinephrine levels [pg ml^–1, mean (sd)] were higher in the control group than in the magnesium group at 5 [211 (37) vs 138 (18)] or 10 min [59 (19) vs 39 (9)] post-pneumoperitoneum, respectively (P<0.05). In the control group, vasopressin levels [pg ml^–1, mean (sd)] were higher compared with the magnesium group at 5 [64 (18) vs 35 (9), P<0.01] and 10 min [65 (18) vs 47 (11), P<0.05] post-pneumoperitoneum. There were no significant differences between the groups in PRA and cortisol levels.

I.V. magnesium sulphate before pneumoperitoneum attenuates arterial pressure increases during laparoscopic cholecystectomy. This attenuation is apparently related to reductions in the release of catecholamine, vasopressin, or both.

Eighty patients undergoing middle ear surgery were enrolled in the study. Patients were randomized into two groups of 40 to receive remifentanil (Group R) or magnesium sulphate (Group M) infusion. Propofol 2 mg kg^–1 was administered to induce anaesthesia, which was maintained using sevoflurane. Group R received a continuous infusion of remifentanil titrated between 3 and 4 ng ml^–1 using target-controlled infusion, whereas Group M received an i.v. magnesium sulphate bolus of 50 mg kg^–1 followed by a 15 mg kg^–1 h^–1 continuous infusion to maintain a mean arterial pressure (MAP) between 60 and 70 mm Hg. Haemodynamic variables, surgical conditions, postoperative pain, and adverse effects, such as postoperative nausea and vomiting (PONV) and shivering, were recorded.

Controlled hypotension was well maintained in both groups. MAP and heart rate were higher in Group R than in Group M after operation. Surgical conditions were not different between the two groups. Postoperative pain scores were significantly lower in Group M than in Group R (P<0.05). Seventeen patients in Group R (43%) and seven patients in Group M (18%) developed PONV (P=0.01).

Both magnesium sulphate and remifentanil when combined with sevoflurane provided adequate controlled hypotension and proper surgical conditions for middle ear surgery. However, patients administered magnesium sulphate had a more favourable postoperative course with better analgesia and less shivering and PONV.

Thirty-two anaesthetized, mechanically ventilated rabbits were randomized to one of the four groups. Group G1 received 0.4 g kg^–1 i.v. HBOC-200 25 min before coronary artery occlusion, G2 received the same dose i.v. 10 min after occlusion, and G3 and 4 received i.v. saline. G1, 2, and 3 were subjected to 30 min occlusion of left coronary artery followed by 240 min of reperfusion. G4 was treated without ischaemia–reperfusion. Measurement included assessment of the area at risk and infarct size using triphenyltetrazolium chloride stain and areas of NR using thioflavin stain. Ischaemia–reperfusion was confirmed by microspheres technique.

Infarct size as a percentage of the area at risk was significantly reduced in G1 [25 (sd 13)%, P=0.026] and G2 [22 (20)%, P=0.009] compared with G3 [48 (17)%]. The areas of NR in percentage of the area at risk [G1, 26 (15)%; G2, 34 (22)%; G3, 36 (12)%; G4, 5 (3)%] did not differ between the groups of animals undergoing coronary occlusion and reperfusion.

Prophylactic and therapeutic administration of HBOC-200 reduces infarct size in myocardial ischaemia and reperfusion in rabbits. This reduction of infarct size is not accompanied by an improvement of areas of NR.

Thirty participants with an AAA under surveillance were randomized to either the supervised exercise intervention (n=20) or a usual care control group (n=10). AT was measured using cardiopulmonary exercise testing, at baseline (AT1), week 5 (AT2), and week 7 (AT3). The change in AT (AT3–AT1) between the groups was compared using a mixed model ancova, providing the mean effect together with the standard deviation (sd) for individual patient responses to the intervention. The minimum clinically important difference (MCID) was defined as an improvement in AT of 2 ml O₂ kg^–1 min^–1.

Of the 30 participants recruited, 17 of 20 (exercise) and eight of 10 (control) completed the study. The AT in the intervention group increased by 10% (equivalent to 1.1 ml O₂ kg^–1 min^–1) compared with the control (90% confidence interval 4–16%; P=0.007). The sd for the individual patient responses to the intervention was 8%. The estimated number needed to treat (NNT) for benefit was 5 patients.

The small mean benefit was lower than the MCID. However, the marked variability in the individual patient responses revealed that a proportion of patients did benefit clinically, with an estimated NNT of 5.

This was a prospective, controlled, randomized pilot trial of 60 patients without gastrointestinal disease undergoing normothermic CPB (35.5–36°C) for coronary artery bypass graft surgery. Gastrointestinal permeability was measured by the triple-sugar technique (sucrose, lactulose, and mannitol excretion in urine) before and after CPB. Interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF) were quantified using enzyme-linked immunosorbent assays.

Data from 59 patients (19–21% haematocrit, n=28; 24–26% haematocrit, n=31) were analysed. Data on gastrointestinal permeability were available for 47 patients (19–21% haematocrit, n=23; 24–26% haematocrit, n=24), blood samples for cytokine analysis from 59 patients. Mannitol excretion was normal before and after surgery without significant differences between the groups (after operation: 5.4% vs 2.9%, P=0.193). Lactulose and sucrose excretion was within a normal range before surgery and increased afterwards without differences between the groups. IL-6, IL-10, and TNF were elevated after surgery, but there was no difference between the groups [IL-6 (P=0.78), IL-10 (P=0.74), and TNF (P=0.67)].

Profound haemodilution during normothermic CPB brought about significant changes neither in intestinal permeability nor in cytokine release. It may be concluded that a haematocrit of 19–21% during normothermic CPB does not impair intestinal barrier function and cytokine response in patients without gastrointestinal comorbidity.

Data were extracted from the computerized system for every operating theatre in this Trust. This provided a continuous record of all operations undertaken, and has previously been validated as an accurate record against individual anaesthetists' personal logbooks. We compared recent data with that of 10 yr ago.

Comparing data for 1997 and 2008 showed that registrars and post-fellowship senior registrars (SRs) in anaesthesia continue to be well supervised directly by consultants (49% and 39%) and subspeciality training has been protected in our department. Average case numbers for SRs increased from 442 to 623 yr^–1, including an increase in emergency workload and theatre cases undertaken during the evening and at night. Although average case numbers for both SRs and consultants increased, we detected a small decrease in average case numbers from 394 to 353 yr^–1 for pre-fellowship registrars.

In spite of many pressures on training in the clinical setting, the number of cases and senior supervision in specialist modules for trainee anaesthetists in our teaching hospital has been maintained. Continuous monitoring of in-theatre supervision is one way of confirming that training is not compromised as changes occur in hospital workload.

We conducted surveys, focus groups, and interviews with trainees and specialists. Data were recorded, transcribed, and entered into NVivo 8. Themes were identified and data coded into these themes.

We identified six themes: assessor factors included skills needed to perform the assessments, influences on scoring decisions, and effects on the specialist–trainee relationship; trainee factors related to impact on trainee performance and value at the different training levels; teaching and learning included the effect of focused observation on structuring workplace learning; feedback described how the mini-CEX changed feedback and what was considered useful; mini-CEX process included implementation, initiation of assessments and case selection; and use in assessment included comparisons with existing assessments and the ability to identify poor performers.

Mini-CEX formalized the supervisory relationship, promoting educational interactions. During the observation period, trainees took responsibility for decisions, and specialists learnt more about their abilities. The structured format broadened the scope of feedback and made it easier to address performance gaps. We identified factors that facilitated or hindered implementation, or limited effective feedback and the ability to address poor performance. From this analysis, we propose strategies for the implementation of mini-CEX, and recommendations for assessor training to improve the quality and value of the assessments.

The anaesthetists were randomly allocated to Group A: simulation debriefing; Group B: home study; and Group C: no intervention and secondary randomization to one of two scenarios. Six to nine months later, subjects returned to manage the alternate scenario. Facilitators blinded to study group allocation completed the performance checklists (dichotomously scored checklist, DSC) and Global Rating Scale of Performance (GRS). Two non-expert raters were trained, and assessed all videotaped performances.

Interim analysis indicated no difference between Groups B and C which were merged into one group. Seventy-four subjects were recruited, with 58 complete data sets available. There was no significant effect of group on pre-test scores. A significant improvement was seen between pre- and post-tests on the DSC in debriefed subjects (pre-test 66.8%, post-test 70.3%; F_1,57=4.18, P=0.046). Both groups showed significant improvement in the GRS over time (F_1,57=5.94, P=0.018), but no significant difference between the groups.

We found a modest improvement in performance on a DSC in the debriefed group and overall improvement in both control and debriefed groups using a GRS. Whether this improvement translates into clinical practice has yet to be determined.

The degree of in vitro pharmacological muscle contracture response and the baseline serum creatine kinase (CK) concentration were used to generate a series of quantitative phenotypes for MH. We then undertook the most extensive RYR1 genotype–phenotype correlation in MH to date using 504 individuals from 204 MH families and 23 RYR1 variants. We also determined the association between a clinical phenotype and both the laboratory phenotype and RYR1 genotype.

We report a novel correlation between the degree of in vitro pharmacological muscle contracture responses and the onset time of the clinical MH response in index cases (P<0.05). There was also a significant correlation between baseline CK concentration and clinical onset time (P=0.039). The specific RYR1 variant was a significant determinant of the severity of each laboratory phenotype (P<0.0001).

The MH phenotype differs significantly with different RYR1 variants. Variants leading to more severe MH phenotype are distributed throughout the gene and tend to lie at relatively conserved sites in the protein. Differences in phenotype severity between RYR1 variants may explain the variability in clinical penetrance of MH during anaesthesia and why some variants have been associated with exercise-induced rhabdomyolysis and heat stroke. They may also inform a mutation screening strategy in cases of idiopathic hyperCKaemia.

In this prospective, randomized, double-blinded, placebo-controlled study, 162 healthy patients who were undergoing gynaecological operation under general anaesthesia using sevoflurane were enrolled. Patients were divided into three groups: the ramosetron group (0.3 mg i.v.; n=54), the ondansetron group (8 mg i.v.; n=54), and the placebo group (normal saline i.v.; n=54). The treatments were given before the end of surgery. The incidence of PONV, severity of nausea, and the use of rescue antiemetic requirements during the first 24 h after surgery were evaluated.

The incidence of nausea was lower in the ramosetron (50%) and ondansetron (44%) groups compared with the placebo group (69%) (P<0.05). In addition, the incidence of vomiting was lower in both the ramosetron (17%) and the ondansetron (20%) groups than in the placebo group (44%) during the first 24 h after surgery (P<0.05). The visual analogue scale score for nausea was also lower in the ramosetron and ondansetron groups compared with the placebo group (P<0.05). The proportion of patients requiring rescue antiemetics was significantly lower with ramosetron (15%) when compared with the placebo group (41%) during the 24 h after surgery (P<0.05). However, there were no significant differences in the incidence of nausea and vomiting, severity of nausea, and required rescue PONV between the ramosetron and the ondansetron groups.

Ramosetron 0.3 mg i.v. was as effective as ondansetron 8 mg i.v. in decreasing the incidence of PONV and reducing nausea severity in female patients during the first 24 h after gynaecological surgery.

In this study on rats, the effect of infusion of the selective ₂-agonist, mivazerol, on hypothermic and plasma corticosterone responses induced by bacterial lipopolysaccharide (LPS) was investigated.

Clinically effective doses of mivazerol (4.8 and 10 µg kg^–1 h^–1) had no effect on body temperature alone. However, mivazerol significantly inhibited the typical thermoregulatory response to bacterial LPS in a dose-dependent manner. This effect was mimicked by the selective ₂-agonist, UK14304-18 (6 µg kg^–1 h^–1), and antagonized by the ₂-antagonist, RX811059A (7 µg kg^–1 h^–1). The ₂-ligands had no effect on basal or LPS-induced corticosterone levels.

These data suggest that early thermoregulatory responses to infection can be selectively antagonized by ligands that activate ₂-adrenoreceptors. High dependency patients receiving ₂-adrenoceptor agonists may not be capable of mounting a normal thermal response to infecting organisms and clinical monitoring using core temperature to detect infection may therefore be unreliable in these vulnerable patients.

Twelve healthy men received placebo, low-dose (loading 3 µg kg^–1 h^–1 for 10 min; maintenance 0.2 µg kg^–1 h^–1 for 60 min), and moderate-dose (loading 6 µg kg^–1 h^–1 for 10 min; maintenance 0.4 µg kg^–1 h^–1 for 60 min) dexmedetomidine infusions in a randomized, double-blind, crossover study. After 70 min of drug infusion, systolic arterial pressure (SAP) and HR responses after thigh cuff deflation were evaluated as indices of cardiovascular reflex.

Reduction in SAP (SAP) [placebo 8 (4), low 12 (4), moderate 19 (5) mm Hg] after thigh cuff deflation was significantly greater in dexmedetomidine than placebo infusions, in a dose-dependent manner. The change in HR (HR), HR/SAP, and the percentage restoration of SAP were lower with dexmedetomidine compared with placebo.

The present results indicated that dexmedetomidine weakens arterial pressure preservation and HR responses after thigh cuff deflation, suggesting attenuated cardiovascular reflexes. Therefore, it must be cautioned that dexmedetomidine can lead to further and sustained reduction in arterial pressure during transient hypotension induced by postural changes, haemorrhage, and/or other stresses.

We conducted a retrospective analysis of theatre logbook data from 62 Specialist Registrars (SpRs) who had completed a 12 month period of advanced training in paediatric anaesthesia in our institution between 2000 and 2007.

After the implementation of the WTD 56 h week in 2004, the mean total number of cases performed by SpRs per year decreased from 441 to 336, a 24% reduction. We found a statistically significant reduction across all age groups with the largest reduction in the under 1 month of age group. The post-WTD group did not meet the RCoA recommended total minimum caseload or the minimum number of cases of <1 yr of age.

Since the implementation of the WTD, there has been a significant reduction in the number of cases performed by SpRs in paediatric anaesthesia and they are no longer achieving the RCoA recommended minimum numbers for advanced training.

Thirty-two anaesthesia residents were recruited. The intervention group had a poster detailing the NRP algorithm and the control group did not. Video recordings of each of the performances were analysed using a previously validated checklist by a peer, an expert anaesthetist, and an expert neonatologist.

The median (IQR) checklist score in the control group [18.2 (15.0–20.5)] was not significantly different from that in the intervention group [20.3 (18.3–21.3)] (P=0.08). When evaluated by the neonatologist, none of the subjects correctly performed all life-saving interventions necessary to pass the checklist. A minority of the intervention group used the cognitive aid frequently.

Retention of skills after NRP training is poor. The infrequent use of the cognitive aid may be the reason that it did not improve performance. Further research is required to investigate whether cognitive aids can be useful if their use is incorporated into the NRP training.

We searched MEDLINE (1950 to July 2006) and EMBASE (1974 to July 2006) using terms for chronic non-malignant pain and long-acting opioids. Independent review of the search results identified 48 studies that met the study selection criteria. The effect of opioid rescue medication on analgesic efficacy and the incidence of common opioid-related side-effects were analysed using meta-regression.

After adjusting for potentially confounding variables (study design and type of opioid), the difference in analgesic efficacy between the ‘rescue’ and the ‘no rescue’ studies was not significant, with regression coefficients close to 0 and 95% confidence intervals that excluded an effect of more than 18 points on a 0–100 scale in each case. There was also no significant difference between the ‘rescue’ and the ‘no rescue’ studies for the incidence of nausea, constipation, or somnolence in both the unadjusted and the adjusted analyses.

We found no evidence that rescue medication with short-acting opioids for breakthrough pain affects analgesic efficacy of long-acting opioids or the incidence of common opioid-related side-effects among chronic non-malignant pain patients.

Twenty-four patients received incremental or decremental doses of 0, 2, and 4 ng ml^–1 remifentanil effect-site concentration (Ce_remi) during 0.7 MAC sevoflurane. Painful tetanic stimulation was applied at least 5 min after changing Ce_remi. SSI, heart rate (HR), response entropy (RE), state entropy (SE), RE–SE difference, and bispectral index (BIS) were obtained in each patient before and after stimulation. Further prediction of an author-defined response to painful stimulus was analysed.

SSI and BIS, but not HR, SE, RE, or RE–SE difference were significantly altered after stimulation. Change in SSI (SSI) was significantly dependent on Ce_remi, as SSI was [median (inter-quartile range)] 20 (15–31), 10 (1–19), and 3 (1–10) at 0, 2, and 4 ng ml^–1 Ce_remi. In 10 out of 63 cases, SSI detected response to stimulation, not detected by another variable. SSI was unable to predict movement after stimulation as P_K value is 0.59 (0.09).

The SSI response to tetanic stimulation was dependent on the remifentanil concentration.

Registered at Clinicaltrials.gov identifier: NCT00791791.

Individual data were obtained from magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) without contrast agent to represent morphology and the vascular system, respectively. For data handling, registration, and segmentation, an application based on the Medical Imaging Interaction Toolkit was developed. Suitable segmentation algorithms such as the fuzzy c-means clustering approach were integrated, and a hierarchical tree data structure was created to model the flexible anatomical structures of peripheral nerve cords. The simulator was implemented in the VR toolkit ViSTA using modules for collision detection, virtual humanoids, interaction, and visualization. A novel algorithm for electric impulse transmission is the core of the simulation.

In a feasibility study, MRI morphology and MRA were acquired from five subjects for the inguinal region. From these sources, three-dimensional anatomical data sets were created and nerves modelled. The resolution obtained from both MRI and MRA was sufficient for realistic simulations. Our high-fidelity simulator application allows trainees to perform virtual peripheral nerve blocks based on these data sets and models.

Subject-specific training of RA is supported in a virtual environment. We have adapted segmentation algorithms and developed a VR-based simulator for the inguinal region for use in training for different peripheral nerve blocks. In contrast to available VR-based simulators, our simulation offers anatomical variety.

Fifty-two adult patients undergoing open appendicectomy were randomized to undergo standard care (n=26) or to undergo a right-sided TAP block with bupivacaine (n=26). In addition, all patients received patient-controlled i.v. morphine analgesia, regular acetaminophen, and non-steroidal anti-inflammatory drug, as required, in the postoperative period. All patients received standard anaesthetic, and after induction of anaesthesia, the TAP group received an ultrasound-guided unilateral TAP block. Each patient was assessed after operation by a blinded investigator at 30 min and 24 h after surgery.

Ultrasound-guided TAP block significantly reduced postoperative morphine consumption in the first 24 h [mean (sd) 28 (18) vs 50 (19) mg, P<0.002]. Postoperative visual analogue scale pain scores were also reduced in the TAP block group soon after surgery [median (IQR) 4.5 (3–5.3) vs 8.5 (7.5–10), P<0.001] and at 24 h [5.2 (4–6.2) vs 8 (7–8.5), P<0.001]. There were no complications attributable to the TAP block.

Ultrasound-guided TAP block holds considerable promise as a part of a balanced postoperative analgesic regimen for patients undergoing open appendicectomy.

In 153 patients undergoing upper arm surgery using axillary block, we studied nerve arrangements with a three-step approach, combining: (A) cross-sectional ultrasound imaging using a 12 MHz linear ultrasound probe; (B) distal shift of the ultrasound scanhead from the axilla to the elbow joint following the paths of individual nerves; and (C) identifying the distal motor response to electrical nerve stimulation of each nerve. These results were then converted into a 12-section pie chart with the axillary artery (AA) as the axis.

The order of the nerves around the AA was median, ulnar, radial, and musculocutaneous in all cases. The most frequent arrangement was observed in 65% of the patients. Five less frequent variations were observed in 4–20% of the patients, with four other variations seen in <2% of the patients. In 78% of the cases, the four nerves were seen separately using static ultrasound imaging. The musculocutaneous nerve was close to the artery in 18% of the patients.

Topographic variations of the four main nerves at the axilla were found to be numerous, the most frequent arrangement being seen in less than two-thirds of the patients. Four separate nerves were seen on static ultrasound imaging at this sectional level of the axilla in only 78% of the cases.