Despite the high frequency of sickle cell disease in Europe, the disease is poorly managed. Critical periods are the hospital stays during which the anaesthe-siologist plays an important role. Understanding the molecular basis of polymerization processes of haemoglobin S can help to avoid triggering a crisis. Differentiation of the various haemoglobin phenotypes helps to estimate the individual perioperative risk. Knowledge of the patient's history and the actual haemoglobin S level facilitates general anaesthesia, surgery and postoperative care. Damage to liver, spleen, eyes, bones, lung and central nervous system increases the perioperative risk. Preoperative preparation includes early admission, intravenous volume substitution, continuing pain therapy and prophylactic antibiotic medication. General anaesthesia seems to be better for patients with a high-risk profile rather than regional anaesthesia. Careful perioperative and postoperative monitoring should allow hypoxaemia, hypovolaemia, hypothermia, acidosis and overtrans-fusion to be avoided. Effective pain therapy includes a combination of opioids with peripherally acting analgesia.

Background and objective Polymorphonuclear leucocytes make a decisive contribution to defence against bacterial infections. In particular, the effects of anaesthetics on non-oxidative bactericidal mechanisms have previously only been superficially examined. Although the influence of anaesthetic agents on oxi-dative bactericidal activity has been thoroughly examined, our study concentrated on the effect on non-oxidative processes, which appears to have been a neglected field of research.

Methods The effects of methohexital, etomidate, ketamine, fentanyl and morphine on the activity of lysozyme and β-glucuronidase released from polymorphonuclear leucocytes have been studied in vitro. The activity of lysozyme was determined by recording the changes in the turbidity of a suspension of micro-coccus lysodeicticus caused by the enzymatic action of lysozyme. β-glucuronidase activity was photometrically measured by the enzymatic cleavage of phe-nolphthalein glucuronic acid.

Results High concentrations of methohexital inhibited lysozyme activity; however, etomidate and morphine caused an increase of β-glucuronidase activity in therapeutic plasma concentrations. While there was no effect of etomidate on lysozyme activity, all concentrations tested significantly stimulated β-glucuronidase activity. This result was unexpected because intravenous anaesthetics have previously shown a tendency to suppress polymorphonuclear leucocyte functions. Whereas the inhibition of lysozyme activity by the high concentration of methohexital was no surprise, the increase of β-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine was quite unexpected.

Conclusions At present, the underlying mechanism for the increase of β-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine is unknown. The fact that there was no influence of these agents on lysozyme activity possibly suggests that the anaesthetic agents have different effects on azurophilic and specific granules. Since in vitro investigations have their limitations, it is too early to draw practical consequences from our study. Moreover, at present it is unclear whether an increase of β-glucuronidase activity in vivo is an advantage or not. In any case, we think it advisable to perform further investigations on the influence of anaesthetic agents on oxygen-independent bactericidal mechanisms.

Background and objective Intravenous morphine titration is used to obtain postoperative pain relief, but few studies have assessed the appropriate regimen. In a quality programme, we performed a prospective non-randomized study of morphine titration in a postanaesthesia care unit (PACU).

Methods Four regimens of morphine titration were studied: every 10 (group 1, n = 400) or 5min (group 2, n = 400) with a maximum of five intravenous boluses; every 5min, without any limitation in the number of boluses (groups 3 and 4, n = 400 each); in groups 1, 2, and 3, subcutaneous morphine was administered 4 h after titration. In group 4, administration of subcutaneous morphine was allowed only 2h after titration. A visual analogue pain scale (VAPS) > 30 mm was required to administer morphine and pain relief was defined as a VAPS ≤ 30 mm.

Results After morphine titration, VAPS was lower and the number of patients with pain relief was greater in patients from groups 3 and 4. Patients from group 4 had the lowest VAPS (26±17mm) and the highest percentage of pain relief (73%) at the end of the PACU period. The number of sedated patients increased in groups 3 (62%) and 4 (61%) compared with group 1 (27%). No significant differences in morphine-related adverse effects were observed.

Conclusion Intravenous morphine titration every 5min with an unlimited number of boluses and early subcutaneous administration provided the best analgesic regimen.

Background and objective Insertion of the laryngeal mask airway in the anaesthetized patient can sometimes be difficult and propofol has been advocated as the anaesthetic induction agent of choice because of its depressant effect on laryngeal reflexes compared with other intravenous anaesthetics. However, when used as the sole induction agent, relatively large doses of propofol are required to achieve successful laryngeal mask insertion. This has cost implications and may produce unwanted cardiorespiratory depression.

Methods One hundred and forty-two patients were randomized to receive either: fentanyl 1 μg kg−1 and lidocaine 1.5mgkg−1 (group 1), or fentanyl 1μgkg−1 and midazolam 0.04 mg kg−1 (group 2), or fentanyl 1μg kg−1, midazolam 0.04 mg kg−1 and lidocaine 1.5mgkg−1 (group 3) or fentanyl 1 μg kg−1 (group 4) 2min before induction of anaesthesia. Anaesthesia was established with propofol infused at 33.3mgmin−1.

Results Patients who were given midazolam required significantly less propofol to achieve satisfactory laryngeal mask insertion, median propofol doses: group 1, 1.63mgkg−1; group 2, 1.16mgkg−1; group 3, 1.01 mgkg−1; group 4, 1.9mgkg−1, P < 0.0001 (analysis of variance). Patients given midazolam reported less pain on injection with propofol 13% and 3% groups (2 and 3) compared with 37.5% and 77% (groups 1 and 4) P = 0.002 (χ2).

Conclusions Midazolam reduces the dose of propofol required for induction of anaesthesia and successful insertion of the laryngeal mask airway. There was no clinical benefit to be gained from the addition of lidocaine.

Background and objective Patients with end-stage chronic renal failure are at risk of developing several serious postanaesthetic complications. Many anaes-thesiologists perform brachial plexus anaesthesia with high doses of local anaesthetic in order to achieve an extensive blockade of the upper limb. Brachial plexus block is a suitable technique for anaesthesia for creation, repair or removal of vascular access for haemo-dialysis. The aim of this study was to measure mepivacaine plasma concentrations after axillary block with 650 mg plain mepivacaine in patients with end-stage chronic renal failure.

Methods Mepivacaine plasma concentrations were assessed throughout a 150-min period, in 10 patients after axillary block with 650 mg plain mepivacaine (600 mg for axillary block and 50 mg for supplementation).

Results Mepivacaine plasma concentrations expressed in μg mL−1 as medians and their ranges were: 1.69 (1.23–7.78) at 5min, 5.61 (4.36–8.19) at 30min, 8.28 (3.83–11.21) at 60min, 7.93 (5.63–11.1) at 90min and 6.49 (5.56–8.35) at 150 min without any symptoms of toxicity.

Conclusions Brachial plexus anaesthesia with 650 mg plain mepivacaine did not result in serious systemic toxicity in these patients despite the high mepivacaine plasma concentrations found.

Background and objective Interaction of intravenous anaesthetic agents with voltage-dependent potassium channels significantly correlates with clinical concentrations. If potassium channels were to play an important part in anaesthesia, one might expect different effects at the molecular level of those anaesthetics that show different clinical effects. Our aim was to analyse the interaction of general anaesthetics with voltage-dependent K channels.

Methods Whole cell patch-clamp experiments were analysed in detail in order to compare the effects of two clinically diverse intravenous hypnotics, ketamine and propofol, on voltage-dependent potassium channels in human neuroblastoma SH-SY5Y cells.

Results Both anaesthetics inhibited the potassium conductance in a concentration-dependent and reversible manner with IC50-values of 300μM and 45μM for ketamine and propofol respectively. Whereas ketamine shifted the midpoint of current activation by maximally 14 mV to more hyperpolarized potentials, propofol had the opposite effect on the activation midpoint. Current inhibition by ketamine increased with voltage but decreased with propofol at higher membrane potentials. Propofol but not ketamine induced concentration-dependent but voltage-independent decline, akin to inactivation, of the voltage-dependent potassium channels.

Conclusions The anaesthetics differed not only in their clinical profiles but they also showed differential actions on voltage-dependent potassium channels in several ways. This provides additional evidence for the hypothesis that voltage-dependent potassium channels play an important role in anaesthesia.

Background and objective Although there is concern that cibenzoline, an antidysrhythmic drug for the treatment of ventricular and supraventricular dysrhy-thmias, may be associated with dose-dependent inhibition of myocardial contractility there are few reports about the relationship between myocardial metabolism and cardiac function when it is used. The present study was designed to investigate the effects of cibenzoline on cardiac function and metabolism. The effects of cibenzoline on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation.

Methods Thirty-two male Wistar-ST rats were divided into four groups: control, and those to receive cibenzoline, either 300, 900 or 3000 ngmL−1. The cibenzoline was administered into the perfusate 5min after the start of perfusion. Heart rates in the 3000ngmL−1 group were significantly lower than those in the control group. Cardiac output in the 3000 ng mL−1 group at 15 and 30 min was significantly lower than in the control group. In all groups, values for %LV dP/df max (the ratio of values at each time to those at 5 min) at 20, 25, 30 min were significantly higher than at 5min. Myocardial adenosine tripho-sphate concentration in the 3000ngmL−1 group was significantly lower than in controls. There was no difference between groups in the lactate/pyruvate ratio.

Conclusion The therapeutic range of cibenzoline has few effects on cardiac function and metabolism, although concentrations 10 times greater may cause a deterioration in myocardial metabolism.

We report a patient who suffered negative pressure pulmonary oedema because of tracheal obstruction after cryotherapy to granulation tissue in the trachea. The pathophysiology and clinical course of negative pressure pulmonary oedema is described. Though there are reports of negative pressure pulmonary oedema after airway obstruction, to our knowledge this is the first case reported after cryotherapy.