The Section and Board of Anaesthesiology of the European Union of Medical Specialists aims (EUMS/UEMS) at harmonization of training of anaesthesiologists and at improvement of patient care throughout Europe. Pain medicine is considered to be an area of expertise in anaesthesiology although exclusivity is not claimed. The Section and Board has approved both a core syllabus for pain medicine to be part of the specialist training in anaesthesiology and an additional qualification in pain medicine following the completion of a 5 yr basic specialty training in anaesthesiology. These proposals were prepared by the Working Party on Pain Medicine of the Section and Board. It considers a multidisciplinary approach to pain to contribute to quality in care and has taken the initiative to set up a Multidisciplinary Joint Committee on Pain Medicine within the EUMS/UEMS, for which these guidelines define the area of expertise of anaesthesiology.

Summary

Background and objective: Even moderate hyperglycaemia increases mortality/morbidity after coronary artery bypass grafting, stroke and myocardial infarction. The goal of this prospective study was to determine if using thoracic epidural analgesia from start of surgery until the end of the third postoperative day would blunt postoperative hyperglycaemia. Methods: Forty-four patients had diabetes mellitus, 60 did not; half of each group had an epidural with continuous local anaesthetics. All patients received continuous insulin infusions during the initial 24 h period beginning with surgery. Blood glucose was measured four times daily (fasting or 2–3 h post-prandial) until end of the third postoperative day. Results: For patients without diabetes, the epidural group had lower mean blood glucose and insulin requirements (P < 0.02) than controls during the initial 24 h period beginning with surgery. For patients with diabetes mellitus, thoracic epidural analgesia reduced mean blood glucose (P = 0.017) with unchanged insulin requirements. Epidural did not diminish the increase (vs. preoperative) in fasting blood glucose on the third postoperative day (32% vs. 22%, P < 0.001) for non-diabetics. Epidural analgesia was not able to attenuate hyperglycaemia during the first 3 postoperative days. Conclusions: Epidural analgesia improved glucose homeostasis minimally during the initial 24 postoperative hours but did not attenuate hyperglycaemia during the subsequent 3 postoperative days.

In order to compare the neuromuscular effects following rocuronium 0.6 mg kg−1 and atracurium 0.5 mg kg−1 30 children aged from 18 to 67 months were studied under the same anaesthetic conditions. After induction of anaesthesia with etomidate and fentanyl, neuromuscular blockade was monitored by recording the electromyographic response of the adductor pollicis muscle to a supramaximal train-of-four (TOF) stimulation of the ulnar nerve at 2 Hz for 2 s at 20-s intervals. Intubation was performed when more than 90% muscle relaxation was achieved, thereafter anaesthesia was maintained with 70% nitrous oxide in oxygen and isoflurane 0.5% end-tidal. Mean onset of action was significantly faster following rocuronium (86±44.9 s) (mean±SD) compared with atracurium (126.3±61.0 s). Clinical duration with rocuronium was 22.8±5.31 min and thus significantly shorter than that of atracurium, which was 31.5±6.01 min. A statistically significant difference between rocuronium and atracurium also had been found for recovery of T1 to 50%, 75% and 90% as well as for the time taken to a TOF ratio of 70%. The recovery index for rocuronium and atracurium was not significantly different with 9.2±3.43 min and 10.9±2.65 min, respectively. Thus, rocuronium may be more advantageous than atracurium for short-lasting surgical procedures in young children.

This randomized double blind study investigates the relative efficacies of controlled analgesia (PCA) regimens in three different patient groups: epidural diamorphine 2.5mg followed by PCA bolus 1mg with a 20-min lockout (Gp1), subcutaneous diamorphine 2.5mg followed by PCA bolus with a 10-min lockout period (Gp2) and epidural diamorphine 2.5mg in 4mL of 0.125% (w/v) bupivacaine followed by a PCA bolus of 1mg diamorphine in 4mL 0.125% (w/v) bupivacaine with a 20-min lockout (Gp3). Patients were evaluated at 0, 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 h. Patients in Gp2 consumed significantly more diamorphine than those in Gp1 or Gp3 (P>0.05), but their pain scores were higher only at 1, 2 and 3 h (P>0.05) with respect to Gp3 and at 1 h with respect to Gp1. Fewer side effects (sedation, pruritis and nausea as assessed by antiemetic requirements) occurred in Gp2 compared to Gp1 (P>0.05). Fewer patients in Gp2 required catheterization than in Gp3 (P>0.05). This study indicates that the use of PCA epidural diamorphine, either alone or in combination with bupivacaine, reduces the dose requirement for analgesia but offers little clinical advantage over subcutaneous PCA diamorphine.

Optimal control of long-term sedation during therapy in the intensive care unit is difficult to achieve in a number of patients when based on commonly used clinical sedation scores alone. We therefore used the median frequency of the EEG power spectrum as a quantitative measure for closed-loop administration of propofol in 21 artificially ventilated patients (nine trauma, 12 non-trauma). The EEG setpoint was correlated with a clinical sedation score and defined such, that mechanical ventilation was tolerated. The sedative therapy was given for 31±30 h. Non-trauma patients required sedation with an EEG median frequency between 2 and 3 Hz (propofol consumption: 1.4±0.8 mg kg−1 H−1) and sedation seemed to follow some circadian patterns, whereas trauma patients needed significantly deeper sedation (EEG median frequency: 1–2 Hz; propofol consumption: 2.6±0.8 mg kg−1 h−1). We conclude that the EEG closed-loop system could safely and reliably administer propofol to maintain a predetermined level of sedation for patients in intensive care unit over a protracted time.

Summary

Background and objective: Recent studies have suggested that cytochrome P-450 isoenzyme 1A2 has an important role in lidocaine biotransformation. We have studied the effect of a cytochrome P-450 1A2 inhibitor, ciprofloxacin, on the pharmacokinetics of lidocaine. Methods: In a randomized, double-blinded, cross-over study, nine healthy volunteers ingested for 2.5 days 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 1.5 mg kg−1 lidocaine intravenously over 60 min. Plasma concentrations of lidocaine, 3-hydroxylidocaine and monoethylglycinexylidide were determined for 11 h after the start of the lidocaine infusion. Results: Ciprofloxacin increased the mean peak concentration and area under plasma concentration–time curve of lidocaine by 12% (range −6 to +46%; P < 0.05) and 26% (8–59%; P < 0.01), respectively. The mean plasma clearance of lidocaine was decreased by ciprofloxacin by 22% (7–38%; P < 0.01). Ciprofloxacin decreased the area under the plasma concentration–time curve of monoethylglycinexylidide by 21% (P < 0.01) and that of 3-hydroxylidocaine by 14% (P < 0.01). Conclusion: The plasma decay of intravenously administered lidocaine is modestly delayed by concomitantly administered ciprofloxacin. Ciprofloxacin may increase the systemic toxicity of lidocaine.

This prospective, randomized and double-blinded study was designed to evaluate the anti-emetic efficacy of a combination of ondansetron and metoclopramide in 100 ASA physical status I and II children of either sex and 1–15 years of age undergoing elective surgery for strabismus. A standardized anaesthetic technique and post-operative analgesia were used for all the children. Children were divided into four groups. They received saline, metoclopromide 250 μg kg−1, ondansetron 150 μg kg−1 or a combination of metoclopramide 150 μg kg−1 and ondansetron 100 μg kg−1 intravenously immediately after the insertion of an intravenous cannulae. There were no differences between the groups in their age, gender, weight, duration of surgery, number of muscles subjected to surgery or intravenous fluids received. In the first 24 post-operative hours, 18 (72%) patients in the placebo group, 15 (60%) patients in the metoclopramide group, 10 (40%) patients in the ondansetron group and 11 (44%) patients in the combination group had nausea or vomiting. The overall incidence of post-operative nausea and vomiting was significantly (P<0.05) lower in the combination group and in the ondansetron group compared with the placebo group. Nine (36%) patients in both the placebo and the metoclopramide groups and one (4%) patient in the ondansetron group required rescue anti-emetic treatment. None of the patients in the combination group required rescue anti-emetic and this was significantly less (P <0.01) when compared with the placebo and the metoclopramide groups. Recovery and sedation scores were comparable in all the four groups. A combination of metoclopramide 150 μg kg−1 and ondansetron 100 μg kg−1 administered prior to surgery was not found to be more effective than ondansetron 150 μg kg−1 alone for the prophylaxis of nausea and vomiting following surgical repair of strabismus in paediatric patients.

Background and objective: Pharmacokinetics of propofol in rats have usually been described using linear models. Furthermore, there are only a few investigations for a pharmacodynamic model of the electroencephalographic effects of propofol in rats. We investigated pharmacokinetics and pharmacodynamics of propofol in rats with special regard to linearity in pharmacokinetics and development of tolerance.

Methods: Twelve adult male Sprague-Dawley rats received propofol in three successive infusion periods of 30 min each with infusion rates of 0.5, 1 and 0.5 mg kg−1 min−1. Propofol plasma concentrations were determined from arterial blood samples. Pharmacokinetics were tested for linearity using the ratio of the concentrations at the end of the first and second infusion interval as a model independent criterion. Several linear and nonlinear models were investigated with population pharmacokinetic analysis. Pharmacodynamics were analysed using the median frequency of the electroencephalographic power spectrum as a quantitative measure of the hypnotic effect.

Results: Pharmacokinetics were found to be nonlinear and were best described by a two-compartment model with Michaelis-Menten elimination (Vm = 2.17 μg mL−1 min−1, Km = 2.65 μg mL−1, k12 = 0.30 min−1, k21 = 0.063 min−1, Vc = 0.13 L). Acute tolerance to the electroencephalographic effect of propofol was observed. The hypnotic effect was best described by a sigmoid Emax model (E0 = 17.8 Hz, Emax = 17.7 Hz, EC50 = 4.1 μg mL−1, γ = 2.3, ke0 = 0.36 min−1) with competitive antagonism of propofol and a hypothetical drug in an additional tolerance compartment.

Conclusions: For the applied infusion scheme, propofol pharmacokinetics in rats were nonlinear and a development of tolerance to the electroencephalographic effect of propofol was observed during an infusion time of 90 min.

In this study, we have sought to establish whether N2O and ketamine alter the bispectral index during propofol–fentanyl anaesthesia. Fourteen surgical patients were randomly assigned to one of two groups: the N2O group (n=7) and the ketamine group (n=7). In both groups, anaesthesia was induced with propofol 1.5–2 mg kg−1 and fentanyl 2 μg kg−1 and maintained with propofol 5–7 mg kg−1 hr−1 to target the bispectral index between 40 and 50. After the bispectral index value had stabilized the propofol infusion rate was fixed. In the N2O group, the following concentrations of N2O were subsequently inhaled at 20-min intervals; 20, 40, 60 and 70%, and then N2O was terminated. In the ketamine group, ketamine (0.4 mg kg−1+1.0 mg kg−1h−1) was given. The bispectral index and 95% spectral edge frequency were recorded 20 min after each change in concentration of N2O or ketamine infusion. The bispectral index and 95% spectral edge frequency did not change significantly in the N2O group, but increased significantly from 44.1±0.7 and 16.0±0.5 to 58.6±1.4 and 19.5±0.3 (P <0.01), respectively, in the ketamine group. Additional N2O or ketamine did not decrease the bispectral index and 95% spectral edge frequency values. The depth of sedation should be assessed carefully using a bispectral index monitor when these anaesthetic agents are used together.

Summary

Background and objective: The beta-adrenergic blocker esmolol and the alpha 2-adrenergic agonist dexmedetomidine have the potential to decrease perioperative myocardial ischaemia. The pathophysiological mechanisms involved in these anti-ischaemic properties have not been thoroughly studied. We compared the effects of esmolol and dexmedetomidine on two indices of overall myocardial oxygen demand and on directly measured myocardial oxygen consumption of the left anterior coronary artery territory.

Methods: Eleven mongrel dogs were instrumented to measure aortic and left ventricular pressure, aortic and left anterior coronary artery flow and myocardial wall thickening. Variables related to myocardial oxygen metabolism were also determined. Measurements were performed during four sequential experimental conditions in each dog (Control 1: esmolol; Control 2: dexmedetomidine).

Results: Esmolol and dexmedetomidine decreased haemodynamic indices of myocardial oxygen demand to a similar extent: esmolol decreased the rate–pressure product by 16 ± 3% and the pressure–work index (PWI) by 16 ± 3%, dexmedetomidine decreased the rate–pressure product by 26 ± 3% and the PWI by 16 ± 7%. However, these similar decreases resulted from different haemodynamic effects of the two study drugs. Dexmedetomidine had a more pronounced bradycardic effect than esmolol (P = 0.01) and increased systolic aortic pressure (SAP) by 15 ± 4% while esmolol decreased SAP by 8 ± 2% (P < 0.01). dP/dtmax and regional myocardial area decrease were lower after esmolol than after dexmedetomidine. Neither drug had an effect on myocardial oxygen consumption.

Conclusions: Esmolol and dexmedetomidine decreased two haemodynamic indices of overall myocardial oxygen demand to a similar extent but neither drug decreased directly measured myocardial oxygen consumption in the territory of the left anterior descending artery.

Background and objective: Controlled hypotension may alter organ blood flow and tissue oxygenation. The aim of the study was to investigate whether induced hypotension using sodium nitroprusside alters pancreatic function assessed by pancreatitis-associated protein concentrations in the blood.

Methods: Thirty patients undergoing elective radical prostatectomy were allocated randomly into two groups: (a) hypotension group: sodium nitroprusside was administered to lower mean arterial pressure to approximately 50 mmHg; (b) control group: no hypotension was used, mean arterial pressure was kept >70 mmHg. Pancreatitis-associated protein and lipase were measured in arterial blood samples: after induction of anaesthesia (T1), at the end of surgery (T2), 2 h (T3) and 24 h (T4) postoperatively.

Results: Pancreatitis-associated protein plasma concentrations increased significantly in patients in the hypotensive group (from 2.8 ± 1.1 to 5.5 ± 2.0 µg L−1 at T4) and pancreatitis-associated protein plasma concentrations were significantly higher in comparison with controls (5.5 ± 2.0 versus 3.5 ± 2.4 µg L−1) at T4. Lipase concentrations showed a similar course in both groups. None of the patients showed clinical signs of pancreatitis.

Conclusions: Controlled hypotension during surgery was associated with a small but significant increase in pancreatitis-associated protein compared with controls. The absence of concomitant elevation in lipase concentrations and a lack of clinical evidence of pancreatitis damage suggest that hypotension induces mild pancreatic stress.

Summary

Background and objective: High doses of opioid associated with low doses of hypnotic is a popular anaesthetic technique since the use of remifentanil has become widespread. This type of anaesthesia could result in a higher incidence of implicit memory.

Methods: Ten patients were anaesthetised with a target-controlled infusion of remifentanil (target concentration of 8 ng mL−1) combined with a target-controlled infusion of propofol with progressive stepwise increases until loss of consciousness was reached. A tape containing 20 words was then played to the patients. Bispectral index (BIS, Aspect Medical Systems, Newton, MA, USA) was continuously monitored during the whole study period. Implicit and explicit memories were tested between 2 and 4 h after recovery.

Results: Loss of consciousness was obtained with a mean calculated propofol plasma concentration of 1.3 ± 0.4 μg mL−1. At this low hypnotic concentration no implicit or explicit memory was found in the three postoperative memory tests. Median (range) BIS value during word presentation was 93 (80–98).

Conclusions: In our group of young American Society of Anesthesiologists (ASA) I/II patients, no explicit or implicit memory was found when the calculated concentration of propofol combined with a high concentration of remifentanil was maintained at the level associated with loss of consciousness with high BIS values.

Background and objective Low-flow anaesthesia is economical and less polluting. The purpose of this study was to determine the inspired and end-tidal desflurane concentrations during anaesthesia with a vaporizer setting maintained at 5%, during low-flow anaesthesia after 120 min with fresh gas inflows of 1.0 and 2.0 L min−1.

Methods The study was both prospective and randomized, including 56 patients (28 patients in each group) scheduled for elective surgery of an expected anaesthesia time of at least 120 min. Inspired and end-tidal concentrations of desflurane were measured during low-flow anaesthesia with fresh gas inflows of 1.0 and 2.0 L min−1. The vaporizer setting was fixed at 5% desflurane.

Results The inspired and end-tidal concentrations of desflurane in the 1.0 L min−1 group after 120 min were 4.54% vs. 4.37% (P < 0.001). In the 2.0 L min−1 group, the inspired and end-tidal concentrations of desflurane were 4.76% vs. 4.58% (P < 0.001). The estimated end-tidal/inspired ratios at 120 min of anaesthesia were 0.96 in both groups. At a fresh gas flow of 1.0 L min−1, the end-tidal concentration was 0.87 of the vaporizer setting. Increasing the fresh gas flow to 2.0 L min−1 increased the end-tidal value by 0.05.

Conclusion There is a significant difference between the inspired and end-tidal concentrations of desflurane when fresh gas inflows were 1.0 and 2.0 L min−1, but not for the ratio of inspired/end-tidal.