Continuous non-invasive arterial pressure measured with CNAP^TM (CNAP) has been shown to be superior to intermittent oscillometric measurements during procedural sedation and spinal anaesthesia. We assessed the performance of CNAP during general anaesthesia by analysis of agreement with invasive measurements of arterial pressure (AP).

Eighty-eight patients undergoing elective abdominal surgery, cardio-, or neurosurgery were included in the study. Systolic, diastolic, and mean AP measured by an intra-arterial catheter in the radial artery (IAP) were compared with those obtained by CNAP from the same arm. Data were analysed to determine the precision (i.e. measurement error) and accuracy (i.e. systematic error) of beat-to-beat CNAP values with respect to IAP. Also, we compared the frequency of fast changes in AP (FCAP) and hypotension (IOH) by both methods.

CNAP precision of 4.5, 3.1, and 3.2 mm Hg (systolic, diastolic, and mean AP, respectively) was not significantly different from IAP precision, and CNAP accuracy was +6.7, –5.6, and –1.6 mm Hg. The frequency of AP pairs having a difference within the calculated limits of agreement was 81%, 64%, and 76% for systolic, diastolic, and mean AP, respectively. The calculated limits of agreement were ±17.6, ±11.4, and ±12.0 mm, Hg, respectively. CNAP and IAP detected simultaneously to 82.1% FCAP and to 84.6% IOH.

CNAP provides real-time estimates of arterial pressure comparable with those generated by an invasive intra-arterial catheter system during general anaesthesia.

Hydroxyethyl starch (HES) solutions compromise blood coagulation. Low molecular weight, low-substituted HES products, and electrolyte-balanced solutions might reduce this effect. We compared the effects of in vitro haemodilution on blood coagulation with a balanced 6% HES 130/0.42 solution (HES_BAL), a saline-based 6% HES 130/0.4 solution (HES_SAL), a balanced lactated Ringer's solution (RL) and a saline-based 4% gelatin solution (GEL).

Blood was obtained from 10 healthy male volunteers and diluted with the test solutions by 33% and 66%. Quality of clot formation was measured using two viscoelastic coagulation tests: SONOCLOT^TM and activated rotation thromboelastometry ROTEM^TM.

Of 16 parameters measured by the viscoelastic devices, we found three statistically significant differences compared with baseline for RL, but 11 for GEL, 10 for HES_SAL, and 11 for HES_BAL in the 33% haemodilution group (P=0.01). Comparing the different solutions, we observed a significant difference between crystalloids and colloids but none between GEL and HES. In the 66% dilution group, effects on blood coagulation were increased when compared with the 33% dilution group. We found no differences in coagulation impairment between balanced and non-balanced HES products and no differences in the detection of impaired blood coagulation due to haemodilution between the two viscoelastic coagulation tests.

Both ROTEM^TM and SONOCLOT^TM are sensitive tests for the detection of impaired blood coagulation due to haemodilution. There are fewer effects on blood coagulation using crystalloids compared with colloids. The effects of GEL and HES are similar. There is no difference between balanced HES 130/0.42 and non-balanced HES 130/0.4.

Laparoscopic liver surgery is evolving rapidly. Carbon dioxide embolism is a potential complication. The aim of this work was to study the frequency and severity of gas embolism (GE) during laparoscopic liver lobe resection in a pig model and the resulting cardiovascular and respiratory changes.

Fifteen anaesthetized piglets underwent laparoscopic left liver lobe resection. Haemodynamic and respiratory variables were monitored, including systemic and pulmonary arterial pressures, end-tidal CO₂, and pulmonary dead space. Online blood gas monitoring and a transoesophageal echocardiography (TOE) were used. GE was graded semi-quantitatively as grade 0 (none), grade 1 (minor), or grade 2 (major), depending on the TOE results.

In 10 of 15 piglets, GE occurred. In total, 33 separate episodes of GE were recorded. All 13 episodes of grade 2 and three of grade 1 were serious enough to cause mainly respiratory, but also haemodynamic effects. Mostly, grade 1 GE caused only minor respiratory or haemodynamic changes. Most variables were affected during grade 2 GE; the most important were Pa_o2, Pa_co2, end-tidal CO₂, Vd/Vt, and mean pulmonary arterial pressure.

GE occurred frequently during laparoscopic liver resection in this experimental study. Approximately half of the embolisms were serious enough to cause respiratory or haemodynamic disturbances or both. Pending further human studies, a combination of several monitoring techniques, with narrow limits for the alarm settings, will ensure correct interpretation of the complex physiological response to GE and reveal it early enough to alert the anaesthetist and the surgeon to the ongoing problem.

To help prevent drug errors, it is recommended that drugs should be confirmed/checked with a second person before administration. We aimed to assess the feasibility of introducing second-person or electronic bar-code confirmation of drugs, administered during anaesthesia, in the National Health Service (NHS) settings in the UK.

Seven NHS sites took part in a pilot study over a 3 month period. Five used a second-person and two used bar-code electronic confirmation of drugs given during anaesthesia. A total of 36 consultant anaesthetists and three trainees, 15 operating department practitioners (ODPs), and seven anaesthetic nurses participated. A group of anaesthetists, ODPs, and nurse practitioners (n=11) from different NHS sites independently observed both methodologies. In addition, each site was visited and observed by one of the study investigators. At the end of the study period, four focus groups (two with participants from pilot sites and two with observers) were held. The discussions were taped, transcribed, and qualitatively analysed. Data were triangulated using observer's notes and investigator's reflective diaries, and processed using line-by-line coding. The codes were then synthesized into themes.

Both methods were perceived to contribute to the prevention of drug errors. For the two-person confirmation to be carried out correctly, there should be no distraction or time pressure. The main limitation to the feasibility was that the continuous presence of the second person was not always possible. The process also met with resistance from the staff at some pilot sites. Electronic confirmation was always feasible, as it did not require the presence of a second person. It was found to be intuitive to the anaesthetist's current working practice. However, there were some practical issues related to introduction of new technology and an initial learning curve.

The introduction of two-person confirmation to the NHS would have a significant impact on the existing working practices. Issues related to resources and a cultural change will need to be addressed. Electronic confirmation was more feasible, but the technological aspects of its integration into the operating theatre environment, and learning, will require further attention.

Studies of preoperative cardiopulmonary exercise testing (CPET) have shown that a reduced oxygen uptake at anaerobic threshold (AT) and elevated ventilatory equivalent for carbon dioxide (VE/VCO₂) were associated with reduced short- and medium-term survival after major surgery. The aim of this study was to determine the relative values of these, and also clinical risk factors, in identifying patients at risk of death after major intra-abdominal, non-vascular surgery.

Patients aged >55 yr, undergoing elective colorectal resection, radical nephrectomy, or cystectomy between June 2004 and May 2009 had CPET during their routine pre-assessment clinic visit. We performed a retrospective analysis of known clinical risk factors and data from CPET to assess their relationship to all-cause mortality after surgery.

Eight hundred and forty-seven patients underwent surgery, of whom 18 (2.1%) died. A clinical history of ischaemic heart disease (RR 3.1, 95% CI 1.3–7.7), a VE/VCO₂ >34 (RR 4.6, 95% CI 1.4–14.8), and an AT ≤10.9 ml kg^–1 min^–1 (RR 6.8, 95% CI 1.6–29.5) were all significant predictors of all-cause hospital and 90 day mortality. The effect of reduced AT was most pronounced in patients with no history of cardiac risk factors (RR 10.0, 95% CI 1.7–61.0).

The routine measurement of AT and VE/VCO₂ using CPET for patients undergoing high-risk surgery can accurately identify the majority of high-risk patients, while the use of clinical risk factors alone will only identify a relatively small proportion of at-risk patients.

Postoperative residual curarization (PORC) [train-of-four ratio (T4/T1) <0.9] is associated with increased morbidity and may delay postoperative recovery room (PACU) discharge. We tested the hypothesis that postoperative T4/T1 <0.9 increases PACU length of stay.

At admission to the PACU, neuromuscular transmission was assessed by acceleromyography (stimulation current: 30 mA) in 246 consecutive patients. The potential consequences of PORC-induced increases in PACU length of stay on PACU throughput were estimated by application of a validated queuing model taking into account the rate of PACU admissions and mean length of stay in the joint system of the PACU plus patients recovering in operation theatre waiting for PACU beds.

PACU length of stay was significantly longer in patients with T4/T1 <0.9 (323 min), compared with patients with adequate recovery of neuromuscular transmission (243 min). Age (P=0.021) and diagnosis of T4/T1 <0.9 (P=0.027), but not the type of neuromuscular blocking agent, were independently associated with PACU length of stay. The incidence of T4/T1 <0.9 was higher in patients receiving vecuronium. Delayed discharge significantly increases the chances of patients having to wait to enter the PACU. The presence of PORC is estimated to be associated with significant delays in recovery room admission.

PORC is associated with a delayed PACU discharge. The magnitude of the effect is clinically significant. In our system, PORC increases the chances of patients having to wait to enter the PACU.

Studies comparing acceleromyography and mechanomyography indicate that the two methods cannot be used interchangeably. However, it is uncertain to what extent differences in precision between the methods and the naturally occurring arm-to-arm variation have influenced the results of these studies. Accordingly, the purpose of this study was to examine the precision and the arm-to-arm variation, when the same method is used on both of the arms.

In the first part (n=20), mechanomyography was applied bilaterally and in the second part acceleromyography (n=20). Anaesthesia was induced with propofol and opioid, and neuromuscular block with rocuronium 0.6 mg kg^–1. The precision of the two methods and the bias and limits of agreement between the arms were evaluated using train-of-four (TOF) stimulation, without and with referral to the initial baseline value, that is, normalization.

Both methods were found to be precise (<5% variation) without any difference between the dominant and non-dominant arms. There were no significant biases between the arms, except for the onset time obtained with acceleromyography, which was 10% longer for the dominant arm. However, the individual differences (limits of agreement) were wide (0.20–0.25 at TOF 0.90). Normalization during recovery did not change bias or limits of agreement between the arms.

In the research setting, acceleromyography and mechanomyography are both precise methods without difference between the arms. Although there is no mean bias between the arms, both methods show wide individual differences (limits of agreement), which might to a large extend explain the differences often found when two different methods are compared on the contralateral arms.

ClinicalTrial.gov identifier: NCT00472121; URL: http://clinicaltrials.gov/ct2/show/study/NCT00472121

Recent studies have found plasma C-reactive protein (CRP) to be a predictor of outcome after discharge from the intensive care unit (ICU). To assess the generalizability of this finding, we assessed the value of CRP on the day of ICU discharge as a predictor of unplanned ICU readmission and unexpected death within 2 weeks. Plasma albumin and white cell count at discharge were also considered as markers associated with ongoing inflammation.

This was a single-centre observational study involving a medical–surgical ICU in a university teaching hospital. Data were prospectively collected from 1487 admissions involving 1401 patients over a 12 month period. Patients' admission details and APACHE II score were collected in addition to plasma CRP, white cell count, and albumin values from the day of discharge from ICU. We assessed the difference in these variables between patients who were readmitted, who died unexpectedly, and those who did not.

We found that 9.9% of patients discharged were either readmitted (7.0%) or died unexpectedly (2.9%). Patients who were readmitted had a lower plasma albumin concentration [20 (16, 24) vs 22 (19, 27), P<0.001] and a higher admission APACHE II score [median (inter-quartile range, IQR) 16.5 (13, 21) vs 15 (12, 18), P=0.02]. Patients who died unexpectedly on the ward were older [mean (sd): 76 (12) vs 59 (19), P<0.001] and had a higher APACHE II score [21 (17.25, 26) vs 15 (12, 18), P<0.001]. There was not a statistically significant difference in CRP concentration between patients who either required ICU readmissions or died unexpectedly on the ward and those who did not.

In a mixed medical–surgical intensive care, plasma CRP measured at the day of discharge from intensive care is not a predictor of readmissions or deaths.

The value of respiratory variables as weaning predictors in the intensive care unit (ICU) is controversial. We evaluated the ability of tidal volume (Vt_exp), respiratory rate (f), minute volume (MV_exp), rapid shallow breathing index (f/Vt), inspired–expired oxygen concentration difference [(I–E)O₂], and end-tidal carbon dioxide concentration (Pe'_co2) at the end of a weaning trial to predict early weaning outcomes.

Seventy-three patients who required >24 h of mechanical ventilation were studied. A controlled pressure support weaning trial was undertaken until 5 cm H₂O continuous positive airway pressure or predefined criteria were reached. The ability of data from the last 5 min of the trial to predict whether a predefined endpoint indicating discontinuation of ventilator support within the next 24 h was evaluated.

Pre-test probability for achieving the outcome was 44% in the cohort (n=32). Non-achievers were older, had higher APACHE II and organ failure scores before the trial, and higher baseline arterial H⁺ concentrations. The Vt, MV, f, and f/Vt had no predictive power using a range of cut-off values or from receiver operating characteristic (ROC) analysis. The [I–E]O₂ and Pe'_co2 had weak discriminatory power [area under the ROC curve: [I–E]O₂ 0.64 (P=0.03); Pe'_co2 0.63 (P=0.05)]. Using best cut-off values for [I–E]O₂ of 5.6% and Pe'_co2 of 5.1 kPa, positive and negative likelihood ratios were 2 and 0.5, respectively, which only changed the pre- to post-test probability by about 20%.

In unselected ICU patients, respiratory variables predict early weaning from mechanical ventilation poorly.

None of the currently available hypnosis monitoring systems have evaluated balanced xenon anaesthesia. We investigated the performance of the bispectral index (BIS) and the composite A-line autoregressive index (cAAI) while comparing balanced xenon with sevoflurane anaesthesia.

Sixty patients undergoing elective abdominal surgery participated in this registered double-blinded, controlled trial and—after written informed consent—were randomly assigned to one of the study groups (xenon, n=30; sevoflurane, n=30). After induction, general anaesthesia was maintained with xenon 60% or sevoflurane 2.0% in 30% O₂. Remifentanil was titrated to clinical needs. BIS and cAAI values were recorded electronically and blinded to the performing physician. Emergence from anaesthesia was evaluated and during 12 h follow-up, patients were questioned twice for signs of recalls.

During induction and maintenance of anaesthesia, BIS values in the xenon group were comparable with sevoflurane anaesthesia and within the recommended range. Although the cAAI remained stable in the sevoflurane group, values increased during balanced xenon anaesthesia and exceeded the recommended upper limit after 65 min. Emergence from xenon anaesthesia was significantly faster than from sevoflurane (eye opening at 3.8 vs 10.3 min, P<0.001), and BIS values were concordant with the washout of both anaesthetics. No incident of recall was reported.

During surgery, xenon/remifentanil anaesthesia can be monitored using BIS and cAAI. However, cAAI values changed after about 1 h of anaesthesia. Further studies will be needed to address the question whether auditory signal processing is altered during extended xenon exposure.

The loss of cholinergic neurones in the basal forebrain has been shown to correlate to the extent of cognitive dysfunction during ageing in humans and to the hypnotic potency of propofol in animal models. We examined how the preoperative cognitive status, as assessed by mini-mental state examination (MMSE), may interact with propofol consumption during anaesthesia in the elderly.

In a prospective study, we recruited 41 patients (65–99 yr) undergoing surgery for hip fracture. Femoral nerve block was performed for analgesia. Target-controlled infusion of propofol (Schnider's model) was adjusted to the bispectral index within the range 40–60. Multiple linear regression analysis determined whether age, BMI, gender, duration of anaesthesia, and preoperative MMSE score affected the propofol consumption (general linear model, Systat 8.0).

BMI and MMSE score significantly affected the mean value of propofol consumption. A low MMSE score (below 19) was associated with an observed decrease in propofol requirement in patients >65 yr of age. No significant effect of age, gender, and duration of anaesthesia on the propofol consumption was observed.

Propofol requirement to maintain hypnosis during general anaesthesia appears to decrease with deterioration in the cognitive status in the elderly. We suggest that a cognitive dysfunction linked to a cerebral cholinergic dysfunction may influence the brain sensitivity for propofol in aged patients.

Ketamine has been shown to have neurotoxic properties, when administered neuraxially. The mechanism of this local toxicity is still unknown. Therefore, we investigated the mechanism of cytotoxicity in different human cell lines in vitro.

We incubated the following cell types for 24 h with increasing concentrations of S(+)-ketamine and racemic ketamine: (i) human Jurkat T-lymphoma cells overexpressing the antiapoptotic B-cell lymphoma 2 protein, (ii) cells deficient of caspase-9, caspase-8, or Fas-associated protein with death domain and parental cells, and (iii) neuroblastoma cells (SHEP). N-Methyl-d-aspartate (NMDA) receptors and caspase-3 cleavage were identified by immunoblotting. Cell viability and apoptotic cell death were evaluated flowcytometrically by Annexin V and 7-aminoactinomycin D double staining. Mitochondrial metabolic activity and caspase-3 activation were measured.

Ketamine, in a concentration-dependent manner, induced apoptosis in lymphocytes and neuroblastoma cell lines. Cell lines with alterations of the mitochondrial pathway of apoptosis were protected against ketamine-induced apoptosis, whereas alterations of the death receptor pathway did not reduce apoptosis. S(+)-Ketamine and racemic ketamine induced the same percentage of cell death in Jurkat cells, whereas in neuroblastoma cells, S(+)-ketamine was slightly less toxic.

Ketamine at millimolar concentrations induces apoptosis via the mitochondrial pathway, independent of death receptor signalling. At higher concentrations necrosis is the predominant mechanism. Less toxicity of S(+)-ketamine was observed in neuroblastoma cells, but this difference was minor and therefore unlikely to be mediated via the NMDA receptor.

During general anaesthesia (GA) for Caesarean section (CS), fetal oxygenation is increased by administering an inspired oxygen fraction (Fi_o2) of 1.0. However, it is unclear whether such high Fi_o2 will increase oxygen free radical activity.

We randomized 39 ASA I–II parturients undergoing elective CS under GA to receive 30% (Gp 30), 50% (Gp 50), or 100% (Gp 100) oxygen with nitrous oxide and sevoflurane adjusted to provide equivalent minimum alveolar concentration. Baseline maternal arterial blood before preoxygenation and maternal arterial, umbilical arterial and venous blood at delivery were sampled for assays of the by-product of lipid peroxidation, isoprostane, and for measurement of blood gases and oxygen content.

Maternal and umbilical isoprostane concentrations were similar among the three groups at delivery, despite significantly increased maternal and fetal oxygenation in Gp 100. However, paired comparisons of maternal delivery vs baseline concentration of isoprostane showed an increase at delivery for all groups [Gp 30: mean 342 (sd 210) vs 154 (65) pg ml^–1, P=0.016; Gp 50: 284 (129) vs 156 (79) pg ml^–1, P=0.009; Gp 100: 332 (126) vs 158 (68) pg ml^–1, P<0.001]. The magnitude of increase was similar in all three groups and independent of the Fi_o2 or duration after induction.

GA for CS is associated with a marked increase in free radical activity in the mother and baby. The mechanism is unclear but it is independent of the inspired oxygen in the anaesthetic mixture. Therefore, when 100% oxygen is administered with sevoflurane for GA, fetal oxygenation can be increased, without inducing an increase in lipid peroxidation.

Sevoflurane can be used as a sole agent for intubation in children, but studies have suggested that it is associated with emergence agitation. Fentanyl infusions can be used both to facilitate intubation and decrease emergence agitation. We investigated the effects of fentanyl on conditions at intubation and on emergence from sevoflurane anaesthesia without confounding nitrous oxide or premedication.

IRB approval and informed consent were obtained. Subjects comprised 150 ASA physical status I or II (age, 2–6 yr). Anaesthesia was induced with sevoflurane in oxygen and maintained using a predetermined concentration of sevoflurane. Subjects were randomly allocated to receive one of three doses of fentanyl: vehicle only (control group), a bolus dose of 1 µg kg^–1 followed by a continuous infusion of 0.5 µg kg^–1 h^–1 (F1 group), or a bolus dose of 2 µg kg^–1 followed by a continuous infusion of 1 µg kg^–1 h^–1 (F2 group). Sevoflurane minimum alveolar concentration for tracheal intubation (MAC_TI) and emergence agitation score were assessed.

MAC_TI values were 2.49%, 1.61%, and 1.16% in control, F1, and F2 groups, respectively (P<0.05). Agitation scores were 11.5, 7.0, and 2.6 in control, F1, and F2 groups, respectively (P<0.05).

Fentanyl infusion consisting of a bolus dose of 2 µg kg^–1 followed by a continuous infusion of 1 µg kg^–1 h^–1 facilitates tracheal intubation and smooth emergence in children anaesthetized using sevoflurane.

Clinical trial registration: this study was started in 2000 and was finished in 2008. We had no registration number. IRB approval was obtained.

Multimodal analgesia is advocated for perioperative pain management to reduce opioid use and its associated adverse effects. Serotonin and norepinephrine are involved in the modulation of endogenous analgesic mechanisms via descending inhibitory pain pathways in the brain and spinal cord. An increase in serotonin and norepinephrine may increase inhibition of nociceptive input and improve pain relief. Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, has demonstrated efficacy in chronic pain conditions such as painful diabetic neuropathy and post-herpetic neuralgia. The objective of the study was to evaluate the efficacy of duloxetine in reducing morphine requirements in patients after knee replacement surgery.

Fifty patients received either two doses of oral duloxetine 60 mg (2 h before surgery and on first postoperative day) or placebo. All patients received patient-controlled analgesia with morphine for 48 h after operation. Pain and adverse effects were assessed at 0.5, 1, 2, 6, 12, 24, and 48 h after surgery on an 11-point numeric rating scale.

Twenty-three patients in the duloxetine group and 24 patients in the placebo group completed the study. Morphine requirements during the 48 h after surgery were significantly lower in the duloxetine group [19.5 mg, standard deviation (sd) 14.5 mg] compared with the placebo group (30.3 mg, sd 18.1 mg) (P=0.017). There were no statistically significant differences between the groups in pain scores (at rest and on movement) or in adverse effects.

Perioperative administration of duloxetine reduced postoperative morphine requirements during the first 48 h after knee replacement surgery, without significant adverse effects.

Pressure-controlled ventilation (PCV) has been suggested to reduce peak airway pressure (P_peak) and intrapulmonary shunt during one-lung ventilation (OLV) when compared with volume-controlled ventilation (VCV). At the same tidal volume (V_T), the apparent difference in P_peak is mainly related to the presence of a double-lumen tracheal tube. We tested the hypothesis that the decrease in P_peak observed in the breathing circuit is not necessarily associated with a decrease in the bronchus of the dependent lung.

This observational study included 15 consecutive subjects who were ventilated with VCV followed by PCV at constant V_T. Airway pressure was measured simultaneously in the breathing circuit and main bronchus of the dependent lung after 20 min of ventilation.

PCV induced a significant decrease in P_peak [mean (sd)] measured in the breathing circuit [36 (4) to 26 (3) cm H₂0, P<0.0001] and in the bronchus [23 (4) to 22 (3) cm H₂O, P=0.01]. However, the interaction (ventilatory mode x site of measurement) revealed that the decrease in P_peak was significantly higher in the circuit (P<0.0001). Although the mean percentage decrease in P_peak was significant at both sites, the decrease was significantly lower in the bronchus [5 (6)% vs 29 (3)%, P<0.0001].

During PCV for OLV, the decrease in P_peak is observed mainly in the respiratory circuit and is probably not clinically relevant in the bronchus of the dependent lung. This challenges the common clinical perception that PCV offers an advantage over VCV during OLV by reducing bronchial P_peak.

In experimental and clinical studies, volatile anaesthesia has proven to possess cardioprotective properties. However, no randomized controlled trials on the use of isoflurane during the entire cardiac surgical procedure are available. We therefore compared isoflurane–sufentanil vs propofol–sufentanil anaesthesia in patients undergoing coronary artery bypass grafting.

One hundred patients were randomly assigned to receive isoflurane–sufentanil (I) (n = 51) or propofol–sufentanil (P) (n = 49) anaesthesia, aimed at the same hypnotic depth. Postoperative concentrations of cardiac troponin I (cTnI) were followed for 72 h. Secondary outcome variables were length of stay (LOS) in the intensive care unit (ICU) and in hospital, and 30 day and 1 yr mortality and morbidity, defined as acute myocardial infarction, arrhythmias, and cardiac dysfunction. Groups were compared by an on-treatment analysis, using linear mixed models for repeated measures.

Eighty-four patients completed the protocol (I: 41 vs P: 43). Postoperative cTnI concentrations increased to a maximum of I: 2.72 ng ml^–1 (1.78–5.85) and P: 2.64 ng ml^–1 (1.67–4.83), but did not differ between groups (P=0.11). LOS in the ICU and in hospital was similar [ICU I: 18 (17.0–21.5) vs P: 19 (17.0–22.0) h; hospital I: 9 (6.5–8.0) vs P: 8 (6.0–9.0) days]. Cardiac morbidity and mortality in hospital and 30 days after surgery did not differ between groups. One year after surgery, two patients had died of non-cardiac causes. No between-group differences in cardiac morbidity were found.

In this study, the use of isoflurane–sufentanil in comparison with propofol–sufentanil anaesthesia does not afford additional reduction of postoperative cTnI levels.

Clinical trial registration information: NCT00356746 (http://www.clinicaltrials.gov/ct2/show/NCT00356746?term=NCT00356746&rank=1).

Epiaortic ultrasound scanning (EUS) is regarded as the reference standard for detecting atherosclerosis in the ascending aorta (AA). Combined with appropriate surgical modifications, EUS use can significantly reduce the incidence of postoperative stroke when detecting severe AA atherosclerosis. A recently introduced modification of conventional transoesophageal echocardiography (TOE), known as the A-View method, has proven capable of inspecting the distal AA. The objective of this study was to quantify the diagnostic accuracy of modified TOE in assessing atherosclerosis of the distal AA.

After approval by the institutional medical ethical committee and after obtaining written informed consent, 465 consecutive patients above 65 yr old, undergoing elective cardiac surgery with a median sternotomy, were included. The study followed a cross-sectional diagnostic design. All consecutive patients underwent modified TOE followed by EUS (reference standard) to assess the severity of distal AA atherosclerosis. We constructed contingency tables to compare the presence (and severity) of atherosclerosis, detected by the two techniques.

The positive predictive value of modified TOE for the detection of clinically significant atherosclerosis was 67%, and the negative predictive value was 97%. The sensitivity was 95% and the specificity was 79%. One patient suffered a pulmonary haemorrhage, although he recovered without further sequelae. We did not observe any clinical significant haemodynamic or ventilatory effects.

The high negative predictive value and sensitivity show that modified TOE yields adequate diagnostic accuracy for excluding clinically relevant aorta atherosclerosis without significant cardiopulmonary side-effects, provided that the A-View catheter is introduced carefully.

The endocannabinoid system (ECS) is an endogenous signalling system which includes the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and specific G-protein-coupled endocannabinoid receptors (CB1 and CB2). Recent studies have described important roles of the peripheral ECS in human atherosclerosis, cardiometabolic disorders, heart failure, and systemic inflammation. We sought to study changes in plasma endocannabinoid concentrations during cardiac surgery (CS) under general anaesthesia with isoflurane/sufentanil, and during cardiopulmonary bypass (CPB).

We studied 30 patients undergoing CS with CPB. All patients received midazolam and sufentanil for induction and isoflurane and sufentanil for maintenance of general anaesthesia. Blood samples were drawn before and after induction of general anaesthesia, after the beginning of surgery, during and after weaning from CPB, and after admission to intensive care unit (ICU) after surgery. Endocannabinoid measurements were performed by HPLC-tandem mass spectrometry.

Induction of general anaesthesia led to a significant decline in plasma AEA concentrations [from mean (sd) 0.39 (0.03) to 0.27 (0.03) ng ml^–1, P<0.01]. CPB induced a pronounced increase in 2-AG concentrations [from 112.5 (163.5) to 321.0 (120.4) ng ml^–1, P<0.01], whereas AEA concentrations remained persistently low until admission to the ICU. 2-AG concentrations returned to preoperative values after surgery.

General anaesthesia with isoflurane significantly reduces plasma AEA concentrations. This could be a consequence of stress reduction after loss of consciousness. The significant increase in 2-AG after initiation of CPB may be part of an inflammatory response. These findings suggest that anaesthesia and surgery have differential effects on the ECS which could have substantial clinical consequences.

Recent evidence suggests that neuraxial and regional anaesthesia may influence the progression of the underlying malignant disease after surgery.

This retrospective cohort study assessed whether neuraxial anaesthesia would affect the progression of cervical cancer in 132 consecutive patients who were treated with brachytherapy in a tertiary cancer centre in Australia.

Age, American Society of Anesthesiologists status, International Federation of Gynecologists and Obstetricians (FIGO) cancer staging, invasion into the uterus, tumour volume, and tumour cell types were not significantly different between patients who received neuraxial and general anaesthesia during their first brachytherapy treatment. The use of neuraxial anaesthesia during the first brachytherapy was not associated with a reduced risk of local or systemic recurrence [hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.54–1.67; P=0.863], long-term mortality from tumour recurrence (HR 1.46, 95% CI 0.75–2.84; P=0.265), or all-cause mortality (HR 1.46, 95% CI 0.81–2.61; P=0.209), after adjusting for other prognostic factors. Tumour recurrence and long-term survival were only significantly associated with the tumour cell type, tumour volume, and FIGO tumour staging. Sensitivity analyses using proportions of all brachytherapy sessions performed under neuraxial anaesthesia also did not show any beneficial effects of neuraxial anaesthesia on tumour recurrence and long-term survival.

Using neuraxial anaesthesia during brachytherapy for patients with cervical cancer was not associated with a reduced risk of tumour recurrence and mortality when compared with general anaesthesia.

The surgical stress index (SSI) is a new monitoring tool for the assessment of nociception during general anaesthesia. It is calculated based on the heart beat interval and the pulse wave amplitude. Correlation of SSI with nociceptive stimuli and opioid effect-site concentrations has been demonstrated, but the influence of isolated modulation of heart rate (HR) on SSI is still unclear. The aim of this study was to evaluate the effect on SSI of atropine administration and cardiac pacing.

In 18 anaesthetized ASA III ICU patients, either repetitive cardiac pacemaker stimulation or administration of atropine (10 µg kg^–1) was performed, and the effect on SSI, arterial pressure, spectral entropy, and bispectral index was analysed.

Cardiac pacing at 100 beats min^–1 was followed by an increase in SSI from 26 [17–35 (10–41)] to 59 [53–72 (48–78)] {median [inter-quartile range (range)]} (P=0.0006), whereas other variables remained unaffected. Also, atropine administration increased SSI from 27 [20–34 (16–39)] to 58 [48–70 (41–81)] (P=0.007) without significant effect on other variables except HR. A recalibration of SSI during cardiac pacing leads to a significant decrease in SSI to 49 [40–52 (36–57)] (P=0.03), whereas recalibration after atropine administration had no effect.

SSI values measured in patients receiving atropine or in patients with pacemakers should be interpreted cautiously.

The objective of this study was to examine the effects of low-dose pregabalin on the analgesic efficacy, side-effects, and recovery profile in patients undergoing laparoscopic cholecystectomy.

One hundred and sixty-two patients aged 18–65 yr, of ASA physical status I–III, undergoing elective outpatient laparoscopic cholecystectomy were recruited and randomized in this prospective, placebo-controlled, double-blind study to receive one of the following study medications orally: pregabalin 50 mg, pregabalin 75 mg, or placebo, 1 h before surgery and then every 12 h after operation for a total of three doses. Postoperative numeric pain scores, analgesic consumption, recovery score (QoR-40), and side-effects (opioid-related symptom distress scale) were assessed in the early postoperative period (every 15 min during the first hour, at 90, 120 min, 6, and 12 h) and at days 1, 2, and 7. Data were analysed using an intention-to-treat method.

Compared with the placebo group, the pain scores were lower in the pregabalin 75 mg group in the first 90 min after surgery (P<0.05). Pregabalin 50 mg resulted in pain reduction at 30 and 45 min (P<0.05) relative to placebo. The analgesic consumption, side-effects, and recovery scores were similar among the three groups.

Perioperative administration of pregabalin 75 mg provided limited analgesic benefit in the postoperative period. An updated meta-analysis confirms this finding (see Supplementary material).

Remifentanil is associated with increased incidence of post-anaesthetic shivering (PAS). The aim of this study was to compare the effects of intraoperative high and low doses of remifentanil on PAS.

We investigated 50 consecutive patients, aged <60 yr, who underwent gynaecological laparotomy. Patients who underwent prolonged surgery (>4 h) were excluded from the study. Anaesthesia throughout surgery was maintained with i.v. propofol and remifentanil, and epidural ropivacaine, and no nitrous oxide was used. Fifty patients were randomly assigned to receive intraoperative remifentanil at 0.1 µg kg^–1 min^–1 (low-dose group, n=25) or 0.25 µg kg^–1 min^–1 (high-dose group, n=25) until the end of surgery. Intraoperative analgesia was achieved by a fixed infusion rate of remifentanil and titrated epidural ropivacaine. PAS was evaluated by nursing stuff over the first hour after surgery.

PAS occurred more frequently in the high-dose group than in the low-dose group (60% vs 20%, P=0.009). None of the patients complained of pain during the observation period due to epidural analgesia. There were no significant differences in rectal or palm skin temperature after extubation between the two dose groups.

Remifentanil-induced PAS is not a phenomenon of intraoperative hypothermia. The higher incidence of PAS with higher doses of remifentanil probably reflects acute opioid tolerance and stimulation of N-methyl-d-aspartate receptors, similar to hyperalgesia. We conclude that patients administered high doses of remifentanil are sensitive to shivering after sudden drug withdrawal.

The patient state index (PSI) and the bispectral index (BIS) quantify anaesthetic depth based on the EEG using different algorithms. We compared both indices with regard to the prediction of the depth of propofol anaesthesia.

In 17 patients, propofol was infused until burst suppression occurred and stopped thereafter until BIS recovered to values above 60. This was repeated; afterwards, patients were intubated, for subsequent surgery. Without surgical stimulus, PSI and BIS were measured simultaneously and compared with the estimated effect-site concentrations of propofol. These were derived from simultaneous pharmacokinetic and -dynamic modelling in an individual two-stage and a population-based NONMEM approach.

A close sigmoid relationship was observed between the propofol effect-site concentration and both PSI [coefficient of determination ²=0.91 (sd 0.05)] and BIS [²=0.92 (0.03)], which was significantly steeper for PSI [=2.2 (0.6)] than for BIS [=1.8 (0.4)], and reached significantly lower values for PSI [E_max=0.3 (1.1)] than for BIS [E_max=5.3 (6.7)] at maximal propofol concentrations. A significantly smaller k_e0 was obtained for PSI [0.09 (0.03) min^–1] compared with BIS [0.10 (0.02) min^–1]. PSI and BIS correlated significantly with each other (²=0.866) and predicted propofol effect-site concentration with a comparable probability [P_K=0.87 (0.05) and 0.86 (0.05), respectively]. NONMEM revealed E₀=89.3 and 92.3, E_max=1.9 and 8.6, C_e50=1.38 and 1.92 µg ml^–1, =1.6 and 1.48, and k_e0=0.103 and 0.131 min^–1 as typical values for PSI and BIS, respectively.

The PSI and the BIS monitors performed equally well in predicting depth of propofol anaesthesia. However, PSI was lower than BIS by ~10–15 points at high propofol concentrations.

The primary goal of this study was to compare the size and depth of the internal jugular vein (IJV) and the subclavian vein (SCV) in infants under general anaesthesia. A secondary goal was to determine the correlation of weight, height, head circumference, and age to the size and depth of these veins.

Sixty small infants weighing from 1.4 to 4.5 kg were included. Using ultrasound, the diameters via short-axis (SAX) and long-axis (LAX) views, cross-sectional area (CSA), and depth of the left and right IJV and SCV were measured.

The diameter of the IJV was 7.9% larger on average than that of the SCV as measured via the SAX and LAX views (mean: 3.1 vs 2.9 mm; Wilcoxon's signed-rank test: P<0.01). The CSA of the IJV was 27% larger on average than that of the SCV (mean: 10.2 vs 8.0 mm²; Wilcoxon's signed-rank test: P<0.01). Seventy-five per cent of the neonates showed a larger CSA of the IJV. The SCV was 8.4% deeper on average from the skin surface than the IJV (mean: 6.4 vs 5.9 mm; Wilcoxon's signed-rank test: P<0.01). There was a significant positive correlation between weight, height, head circumference, and age to the size and depth of the veins (Spearman's rank correlation: P<0.01).

Because of its most likely larger size, the IJV can be recommended as the better choice for cannulation in comparison with the SCV. However, other factors should also be considered.

Capacity to ambulate represents an important milestone in the recovery process after total knee arthroplasty (TKA). The purpose of this study was to determine the analgesic effect of two analgesic techniques and their impact on functional walking capacity as a measure of surgical recovery.

Forty ASA II–III subjects undergoing TKA were enrolled in a randomized, double-blind, single-centre study receiving 48 h postoperative analgesia with either periarticular infiltration of local anaesthetic (Group I) or continuous femoral nerve block (Group F). Breakthrough pain relief was achieved with patient-controlled analgesia (PCA) morphine. The main outcome was postoperative morphine consumption. Early (postoperative days 1–3) and late (6 weeks) functional walking capacity (2 and 6 min walk tests, 2MWT and 6MWT, respectively), degree of physical activity (CHAMPS), health-related quality of life (SF-12), and clinical indicators of knee function (WOMAC, Knee Society evaluation, and range of motion) were measured.

Patients in Group F used the PCA less (P=0.02) to achieve adequate analgesia. Postoperative 2MWT was similar in both groups (P=0.27). Six weeks after surgery, recovery of 6MWT, physical activity, and knee function were significantly improved in Group F (P<0.05). Preoperative walking capacity, physical activity and early total walking time were the independent predictors of early recovery. Distance and time spent walking were the predictors of functional walking exercise capacity at 6 weeks after surgery.

Femoral block is associated with lower opioid consumption and a better recovery at 6 weeks than periarticular infiltration. Early postoperative activity measures (2MWT and walking time) were proved to be possible indicators of knee function recovery at 6 weeks after surgery.

Thoracotomy results in severe postoperative pain potentially leading to chronic pain. We investigated the potential benefits of oral celecoxib on postoperative analgesia combined with thoracic epidural analgesia (TEA).

Forty patients undergoing thoracotomy were included in this prospective, randomized, double-blind, placebo-controlled study. General anaesthesia was standardized. Patient-controlled epidural analgesia (T4–T5) was used during 48 h after surgery (ropivacaine 2 mg ml^–1 with sufentanil 0.5 µg ml^–1). Patients were allocated to receive oral celecoxib or placebo from the evening before surgery until 48 h after operation. Postoperative pain scores, respiratory function, and morbidity were compared between the two groups.

Postoperative pain scores at rest (P=0.026) and during coughing (P=0.021) were lower and patient satisfaction was greater (P=0.0033) in the celecoxib group. Consumption of the local anaesthetic solution was comparable between groups. Postoperative restrictive pulmonary syndrome and morbidity were comparable between groups.

Celecoxib improves postoperative analgesia provided by TEA after thoracotomy.

Choline is a dietary supplement that activates 7 nicotinic receptors. 7 nicotinic activation reduces cytokine production by macrophages and has antinociceptive activity in inflammatory pain models. We hypothesized that systemic administration of choline would reduce the inflammatory response from macrophages and have antinociceptive efficacy in a murine model of postoperative pain.

We studied the response of wild-type and 7 nicotinic knockout mice to heat and punctate pressure after a model surgical procedure. We investigated the effect of genotype and choline treatment on -bungarotoxin binding to, and their production of tumour necrosis factor (TNF) from, macrophages.

Choline provided moderate antinociception. The ED₅₀ for choline inhibition of heat-induced allodynia was 1.7 mg kg^–1 h^–1. The ED₅₀ for punctate pressure threshold was 4.7 mg kg^–1 h^–1 choline. 7 nicotinic knockout mice had no change in hypersensitivity to heat or pressure and were significantly different from littermate controls when treated with choline 5 mg kg^–1 h^–1 (P<0.05, 0.01). Choline 100 mM reduced binding of -bungarotoxin to macrophages by 72% and decreased their release of TNF by up to 51 (sd 11)%. There was no difference by genotype in the inhibition of TNF release by choline.

Systemic choline is a moderately effective analgesic via activation of 7 nicotinic acetylcholine receptors. The antinocicepive effect may not be mediated by a reduction of TNF pathway cytokine release from macrophages. Although choline at millimolar concentrations clearly inhibits the release of TNF, this effect is not 7 subunit-dependent and occurs at concentrations likely higher than reached systemically in vivo.

The peripheral deafferentation induced by regional anaesthesia (RA) results in misperception of size-shape (S) and posture (P) of the anesthetized limb. During RA, most patients seem to describe motionless ‘phantom limbs’ fixed in stereotyped illusory positions, suggesting that RA could unmask stable postural patterns. The question of whether movement illusions exist or not after anaesthesia needs a prospective study. This study aimed to describe the phenomenology of RA-induced kinesthetic illusions (K illusions).

We examined prospectively the body image alteration during infraclavicular blocks in 20 patients. Multimodal sensory testing (pinprick, heat-cold, pallesthesia, and arthrokinesia) and assessment of motor function were performed every 5 min for 60 min after administration of the local anaesthetics. Meanwhile, patients described phantom limb sensations (S, P, and K illusions).

We individualized the occurrence of K illusions [44 (8) min] with respect to S illusions [7 (3) min; P<0.005] and P illusions [22 (4) min; P<0.001]. A close relationship between the onset of K illusions and proprioceptive impairment (arthrokinesia: r=0.92, P<0.001; pallesthesia: r=0.89, P<0001) and abolishment of motor activity (r=0.83, P<0.001) was identified. Finally, a principal component analysis showed that S and P illusions were essentially related to the proprioceptive impairment.

This study analyses for the first time the temporal evolution of sensorimotor dysfunction and the onset of K illusions during RA. Our results suggest the involvement of an alteration of proprioception and motor functions in the origin of this phenomenon. These data agree with the motor awareness theory.

Neuraxial anaesthesia improves tissue perfusion and tissue oxygen tension. Vasodilation induced by this technique may result in hypotension requiring the administration of vasoactive drugs. The use of peripheral vasoconstrictors might counteract the improved tissue perfusion and its potentially beneficial effects. We therefore investigated the effect of i.v. norepinephrine and ephedrine on skin perfusion using laser-Doppler flowmetry (LDF) in patients during spinal anaesthesia.

Skin blood flow expressed in perfusion units (PU) provided by LDF was measured simultaneously at the foot and the manubrium levels in 44 patients during spinal anaesthesia with a sensory level below T5. Norepinephrine infusion was then titrated to normalize mean arterial pressure (MAP) in 23 patients (Group NOR). Ephedrine (max. 10 mg) was administered in 21 patients (Group EPH). Changes in relative PU were compared between the two sites of measurements in each group during drug administration. The same doses of norepinephrine were assessed in 11 normal volunteers to assure comparable vasoreactivity at the foot and manubrium levels.

Spinal anaesthesia resulted in a 10% decrease in MAP (P<0.001), an increase in relative PU values at the foot level (P<0.001), and a decrease at the sternum level (P<0.05). Norepinephrine and ephedrine produced a significant increase in relative PU values at the foot level when compared with the sternum level (NOR: P=0.02; EPH: P=0.0035). In volunteers, norepinephrine decreased cutaneous perfusion similarly at the manubrium and foot levels.

Improved skin perfusion induced by spinal anaesthesia was not counteracted by the use of norepinephrine or ephedrine.

The Cormack–Lehane (CL) classification is broadly used to describe laryngeal view during direct laryngoscopy. This classification, however, has been validated by only a few studies reporting inconclusive data concerning its reliability. This discrepancy between widespread use and limited evidence prompted us to investigate the knowledge about the classification among anaesthesiologists and its intra- and inter-observer reliability.

One hundred and twenty interviews were performed at a major European anaesthesia congress. Participants were interviewed about their general knowledge on grading systems to classify laryngeal view during laryngoscopy and were subsequently asked to define the grades of the CL classification. Inter- and intra-observer reliabilities were tested in 20 anaesthesiologists well familiar with the CL classification, who performed 100 laryngoscopies in a full-scale patient simulator.

Although 89% of interviewed subjects claimed to know a classification to describe laryngeal view during laryngoscopy, 53% were able to name a classification. When specifically asked about the CL classification, 74% of the interviewed subjects stated to know this classification, whereas 25% could define all four grades correctly. In the simulator-based part of the study, inter-observer reliability was fair with a coefficient of 0.35 and intra-observer reliability was poor with a of 0.15.

The CL classification is poorly known in detail among anaesthesiologists and reproducibility even in subjects well familiar with this classification is limited.

The LMA-Supreme^TM (SLMA) is a single-use, latex-free, supraglottic airway device with a drain tube which allows immediate assessment of correct positioning of the device at insertion and throughout the procedure and provides access to gastric contents. The anatomically shaped airway tube facilitates easy insertion in anaesthetized patients in the supine, lateral, and prone positions. We present a prospective audit in 205 consecutive adult patients presenting for elective spine surgery in the prone position. Patients positioned themselves in the prone position, on a Montreal or Wilson mattress to optimize patient comfort in this position. Anaesthesia was then induced, and an appropriate-sized SLMA was inserted.

Prospective, descriptive audit of SLMA insertion in 205 consecutive adult patients, anaesthetized in the prone position for elective orthopaedic surgery with spontaneous (n=6) or positive pressure ventilation (PPV) (n=199).

First-pass success was achieved in 184 insertions. Forty-two SLMA insertions were performed by anaesthesia trainees with first-pass success achieved in 38 insertions. All problems encountered during insertion were minor, and no patient had to be turned to the supine position for an airway problem. Problems during insertion were independent of patients' BMI. There were no failures of SLMA insertion or of maintenance of PPV during surgery.

The results suggest that the SLMA is a useful device for airway management in patients anaesthetized in the prone position and for subsequent airway management with PPV, with or without neuromuscular block.