Although the PROWESS trial demonstrated a mortality benefit, subsequent studies in different patient populations have not reproduced the effect. As a result, concerns have been expressed about the clinical effectiveness of drotrecogin alfa (activated). Therefore the aim of this audit was to review the clinical impact of drotrecogin alfa (activated) when used outside clinical trials.

A retrospective review of ICU charts and medical records of patients who had received drotrecogin alfa (activated) in the five largest users of drotrecogin alfa (activated) in England. Patients characteristics details at ICU admission and vital status at hospital discharge were recorded. The severity of illness was assessed by the APACHE II score (using first 24 h admission data) and the number of organ dysfunctions. Adverse incidents were recorded and any sequence effect explored.

In all, 351 patients received drotrecogin alfa (activated) between December 2002 and November 2005. Of those, 201 (57.2%) were male, and 177 (50.4%) were admitted after recent surgery. The patients’ average age was 61.8 yr. The mean admission APACHE II score was 23.3 and the average number of dysfunctional organs on admission was 3.3. The hospital mortality was 46.7% (164 deaths). The expected number of deaths calculated by using the APACHE II risk of death was 173 (49.3%) and by number of sepsis induced organ failures 210 (59.7%). Overall, there were 33 (9.4%) adverse incidents.

Expected mortality derived from both the APACHE II score and organ dysfunctions suggests that drotrecogin alfa (activated) does reduce mortality. Serious adverse incidents occurred in 5.1% patients; however, the direct contributing effect of drotrecogin alfa (activated) cannot be established from this type of audit.

Intrathecal ketamine produces a short period of analgesia with stable haemodynamics. Midazolam with bupivacaine prolongs the duration of analgesia when administered intrathecally but does not prevent hypotension. The objective of this study was to assess the effect of a combination of intrathecal bupivacaine, ketamine and midazolam on the duration of analgesia and haemodynamic parameters.

A prospective, randomized, double-blind study was carried out in 60 ASA I and II patients undergoing lower limb surgery under spinal anaesthesia. Patients were divided into three groups of 20 each. Patients in all the three groups received 3 mL of hyperbaric bupivacaine (0.5%) intrathecally. In addition, patients in Groups II and III received intrathecal ketamine (0.1 mg kg−1) and the same dose of ketamine along with midazolam (0.02 mg kg−1), respectively. All patients were evaluated for block characteristics, duration of pain-free period, total rescue analgesic requirement in the 24-h postoperative period, total dose of mephenteramine to treat hypotension and any central or neurological complication.

No patients in Group II required mephenteramine while 40% of patients in Group I and 10% in Group III required mephenteramine to maintain blood pressure after spinal anaesthesia. The mean ± standard deviation duration of pain-free period was 331.5 ± 89.9, 369.7 ± 124.2 and 730.5 ± 81.5 min in Group I, II and III, respectively. The pain-free interval was significantly greater in Group III compared to Groups I and II (P < 0.001). No patient had any complications.

A low dose of midazolam and ketamine with bupivacaine intrathecally results in prolonged analgesia and less haemodynamic fluctuations. However, the safety of this combination needs to be proved before its use in clinical practice.

The Bullard laryngoscope can be useful in management of difficult airway. When the endotracheal tube is advanced over the original Bullard laryngoscope stylet, the endotracheal tube sometimes makes contact with structures around the vocal cords, especially the right arytenoids. A similar problem also occurs with flexible fibreoptic intubation and it has been shown that use of the Parker Flex-Tip™ tube usually resolves the problem. In this study we tested our hypothesis that use of the Parker Flex-Tip™ tube might improve endotracheal tube passage with the Bullard laryngoscope.

Forty patients scheduled for elective anaesthesia were randomly assigned into group ST (standard tube) or Group PT (Parker Flex-Tip™ tube). The time taken to achieve successful endotracheal tube placement after obtaining the best laryngeal view, the number of attempts at intubation and the incidences of successful intubation at first attempt and of re-direction of the Bullard laryngoscope during intubation were recorded. Unpaired t-test and χ2-test were employed and P < 0.05 was considered significant.

Use of the Parker Flex-Tip™ tube reduced the time required for successful endotracheal tube placement after the best laryngeal view was obtained from 14 ± 6 to 6 ± 2 s (P < 0.01). It also reduced the incidence of requirement for re-direction of the Bullard laryngoscope during intubation from 10/19 to 1/19 (P < 0.01). The incidence of successful intubation at the first attempt (18/19 vs. 15/19) was higher in the PT group but the difference was not statistically significant.

During intubation with the Bullard laryngoscope, use of the Parker Flex-Tip™ tube is associated with more rapid success and a lower incidence of re-direction of the Bullard laryngoscope during endotracheal intubation when compared to a standard endotracheal tube.

The aetiology of parenteral nutrition-associated hepatic injury remains unresolved. The aim of the study was to evaluate the effects of structured triglycerides in parenteral nutrition compared either to a physical medium-chain triglycerides (MCT)/long-chain triglcerides (LCT) mixture or to a LCT emulsion on hepatic integrity.

In a randomized, double-blinded trial, we studied 45 patients undergoing abdominal surgery, who were expected to receive parenteral nutrition for 5 days. Patients were allocated to one of three nutrition regimens: Group A (n = 15) received structured triglycerides, Group B (n = 15) a MCT/LCT and Group C (n = 15) a LCT lipid emulsion. Before the start of parenteral nutrition (T0), 24 h (T1), 48 h (T2), 72 h (T3) and 120 h (T4) after start of infusion the following parameters were measured: Alpha-glutathione S-transferase (α-GST), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose and serum triglycerides.

At T3 and T4, α-GST levels were significantly higher in Group B (T3: 9.4 ± 9.9; T4: 14.6 ± 19.5 μg L−1) and Group C (T3: 14.2 ± 20.8; T4: 22.4 ± 39.3 μg L−1) compared with the patients receiving structured triglycerides (T3: 1.9 ± 1.8; T4: 3.2 ± 2.7 μg L−1). Whereas the mean α-GST-levels in structured triglycerides group always remained in the normal range, this was not the case in both other groups at T3 and T4. There were no significant differences concerning ALT, AST and glucose levels. At T3 and T4, triglyceride levels were significantly lower in Group A than in Groups B and C.

Hepatic integrity was well retained with the administration of structured triglycerides, whereas both MCT/LCT emulsion and LCT emulsion caused subclinical hepatic injury.

Blood oxygen concentration decrease may be associated with haemostatic impairments. We aimed to study the effect of oxygen decrease in a rabbit model of thrombosis and bleeding.

A total of 44 rabbits were anaesthetized, ventilated and monitored for blood pressure, blood arterial gas, temperature and carotid blood flow. The Folts model was used: a stenosis (75%) and an injury were carried out on the carotid artery, inducing thrombosis. Blood flow decreased as thrombus size increased until the pressure gradient was such that the thrombus was released and local arterial blood flow was suddenly restored. This is known as a cyclic flow reduction. After counting baseline cyclic flow reductions during a 20-min period (P1), rabbits were randomized blindly to one of three groups: hyperoxic, FiO2=100%; normoxic, FiO2 was decreased to obtain a PaO2 between 80 and 120 mmHg; hypoxic, PaO2 < 80 mmHg. Then CFRs were recorded over a second 20-min period (P2). At the end of the experiment, a hepatosplenic section was done and the amount of blood loss was recorded. After each period, the following parameters were measured: blood gas, ear-immersion bleeding time, haemoglobin, platelet count, prothrombin time, activated partial thromboplastin time and fibrinogen.

Oxygen decrease during hypoxic and normoxic periods was associated with a decrease in cyclic flow reductions. Bleeding time increased in the hypoxic group unless hepatosplenic bleeding remained stable. A slight increase in activated partial thromboplastin time was observed in the normoxic and hypoxic groups.

An abrupt decrease in oxygen administration was responsible for an antithrombotic effect. Increase in bleeding time occurred during hypoxia. No clinically relevant variation of any haemostasis parameters was observed.

The anaesthetic method for intracranial neurosurgery must provide haemodynamic stability on emergence and allow early evaluation of the neurological status. In this study, we examined the effects of the α-2 agonist dexmedetomidine given at the end of the procedure to prevent hyperdynamic responses during extubation and to allow a comfortable and high-quality recovery.

Forty ASA I–III patients, aged between 18 and 75 yr, having elective intracranial surgery, were divided into two random groups. Standard procedures and drugs were used for monitoring, induction and maintenance. Isoflurane was reduced by 50% 5 min before the end of the surgery, and in Group I dexmedetomidine 0.5 μg kg−1 and in Group II 20 mL of 0.9% NaCl were administrated intravenously over 60 s. Systolic, diastolic and mean arterial pressures, and heart rate were recorded before intravenous administration and also at 1, 3 and 5 min after administration, 1 min before extubation, during extubation, 1, 3, 5, 10, 15, 20 and 30 min after extubation. Duration of extubation and recovery were noted, and the quality of extubation was evaluated on a 5-point scale.

Mean arterial pressure and heart rate were significantly higher in Group II than in Group I (P < 0.01). There were no statistically significant differences between groups regarding the duration of extubation and recovery (P > 0.05). Extubation quality score of all the patients were 1 in Group I; and in Group II, the quality scores were 1 for 35%, 2 for 45% and 3 for 20% of the patients (P < 0.001). None of the patients in Group I and Group II showed respiratory depression, nausea or vomiting.

Without interfering in recovery time, dexmedetomidine 0.5 μg kg−1 administered 5 min before the end of surgery stabilizes haemodynamics, allows easy extubation, provides a more comfortable recovery and early neurological examination following intracranial operations.

This study was carried out to clarify the effect of the combination of acute hypervolaemic haemodilution and hypotensive anaesthesia induced with sevoflurane on human middle cerebral artery flow velocity using transcranial Doppler ultrasonography.

Thirty patients who were maintained with N2O–O2–sevoflurane anaesthesia undergoing hip surgery were randomly divided into two groups (no controlled hypotension group, Group A, and controlled hypotension group, Group B). Haemodilution was produced by acute preoperative infusion of 1000 mL of hydroxyethylstarch without removing blood in both groups. Mean arterial pressure was maintained at approximately 95 mmHg in Group A and at 55 mmHg for 80 min by increasing the inspired concentration of sevoflurane in Group B. Middle cerebral artery flow velocity was measured before haemodilution, after haemodilution, 80 min after starting hypotension, and 60 min after recovery from hypotension.

Middle cerebral artery flow velocity significantly increased in both groups after haemodilution; by 28%, in Group A, P < 0.05 vs. before haemodilution and by 30% vs. before haemodilution in Group B, P < 0.05). During controlled hypotension, it decreased towards the pre-haemodilution value (P < 0.05 vs. after haemodilution).

Sevoflurane-induced hypotension to a mean arterial pressure of 55 mmHg would reduce middle cerebral artery flow that had been increased by acute hypervolaemic haemodilution, such as haematocrit value of 26%, whereas it could preserve the flow in pre-haemodilution condition during normocapnia.

Patients exhibiting considerable blood loss are prone to develop dilutional coagulopathy following volume supply. In such patients, in addition to transfusing stored blood components, cell saver systems are used to minimize allogeneic transfusion. Since red cell transfusion might influence the haemostatic system by further dilution, we investigated the effects of re-transfusion of salvaged washed red blood cells on the haemostatic process in an animal model of controlled haemorrhage using rotational thrombelastometry (ROTEM®; Pentapharm Co., Munich, Germany).

Anaesthetized pigs (n = 20) developed coagulopathy following haemorrhagic shock (withdrawal of 66% of estimated blood volume) and volume resuscitation with 6% hydroxyethyl starch 130/0.4. The shed blood was processed in a Cellsaver device (CATS ®; Fresenius AG, Bad Homburg, Germany), and the resulting salvaged red blood cells were re-transfused. ROTEM assays were performed at baseline, after blood loss, after volume resuscitation and following re-transfusion of salvaged red blood cells.

As compared with baseline, blood loss and subsequent volume resuscitation resulted in significantly increased median values of clotting time (CT: 47.0, 5 .3 and 103.5 s), and clot formation time (CFT: 36.0, 40.0 and 186.0 s), whigggle maximum clot firmness decreased (MCF: 72.0, 68.5 and 39.5 mm). After re-transfusion of salvaged red blood cells (805 ± 175 mL) all these parameters improved (CT: 80.5 s; P = 0.05, CFT: 144.0 s; P = 0.0008, MCF: 42.0 mm; P = 0.0019) although baseline values were not reached.

In the case of extreme isovolaemic haemodilution, increasing the circulating red cell mass by re-transfusing salvaged red blood cells did not worsen the findings of dilutional coagulopathy but interestingly, at least partially, improves the clot formation process.

Cardiac output is frequently monitored to maintain and improve cardiac function with the primary goal of adequate tissue perfusion. The pulmonary artery catheter is considered to be the gold standard although several non-invasive devices are being introduced and gaining attention. To evaluate the accuracy of the ultrasonic cardiac output monitor (USCOM)-1A (Pty Ltd, Coffs Harbour, NSW, Australia), a non-invasive cardiac output device including its capability to differentiate between different shock states in haemodynamically unstable ICU patients was used in this single-centre, prospective, observational study.

Cardiac output was measured with a pulmonary artery catheter and transcutaneously via a suprasternal approach with the USCOM-1A by continuous-wave Doppler ultrasound in 25 adult patients in a mixed medical and surgical ICU in a major teaching hospital in the Netherlands.

A total of 1315 USCOM-1A cardiac output measurements were performed. In order to reduce time-variability, the mean of five consecutive USCOM-1A measurements was calculated. Total 263 values were compared with 263 thermodilution cardiac output measurements performed with a pulmonary artery catheter. Data were analysed for systematic error, precision and correlation. Systematic and random errors were found. On average USCOM-1A values were 12% lower than thermodilution measurements (systematic error), while the random error was 17% (coefficient of variation). The error comprised an inter-operator variability of 3%, an inter-patient variability of 11% and residual variability of 15%. The correlation coefficient of the calculated cardiac index with the USCOM-1A and the pulmonary artery catheter was r = 0.8024 and 0.6438, respectively. Temperature and gender did not influence correlations. The learning curve for USCOM-1A skill acquisition was steep.

The correlation between the two techniques was acceptable, although relevant systematic and variable errors were detected. USCOM-1A provided adequate data to distinguish non-invasively different shock types in ICU patients.

In Germany there is considerable variability in the organizational forms of intensive-care medicine. We present economical data that arose during the reorganization of an intensive care unit with the implementation of the continuous presence of a trained intensivist. The unit was changed from an intensive-observational unit managed by four surgical departments without continuous presence of a trained intensivist to an interdisciplinary surgical intensive care unit managed by the Department of Anaesthesia in co-operation with the surgical departments with the continuous presence of trained intensivists.

Measurement of costs for personnel, medical equipment and external services, revenues, length of hospital stay and complications of cardiac surgical patients.

Per year costs for personnel increased by approximately €240 000, while expenses for medical equipment were reduced by €245 000. In all, 466 hospital days were saved by the reduction in the length of hospital stay, providing capacity for 22 additional cardiac surgical cases. In addition, the presence of trained intensivists made it possible to provide care for more severely ill patients, which gained approximately 100 additional case-mix points and increased the hospital’s revenues by more than €300 000. Emergency readmission to the intensive care unit was reduced by 17%. The number of patients requiring renal replacement therapy and those developing non-occlusive mesenteric ischaemia was substantially reduced.

In addition to the medical advantages, staffing the intensive care unit with trained intensivists 24 h a day was of appreciable economical benefit.

Visceral pain is one of the most common forms of pain and for which new drugs would be welcome. The aim of this study was to investigate whether gabapentin inhibits induced abdominal contractions in mice and to examine the effect of its co-administration with morphine.

A total of 96 mice received acetic acid intraperitoneally after administration of saline or gabapentin (1, 5, 10, 50 and 100 mg kg−1) or morphine (0.25, 0.5, 1, 3 and 5 mg kg−1) or a combination of morphine and gabapentin. Other groups also received naloxone. The number of writhes were counted.

Both gabapentin and morphine reduced writhing in a dose-dependent manner. The number of writhes was decreased significantly by gabapentin (50 and 100 mg kg−1) and morphine (0.5, 1, 3 and 5 mg kg−1) (P < 0.001). Also, the lowest dose of morphine 0.25 mg kg−1 when combined with low doses of gabapentin significantly decreased the number of writhes (P < 0.005). The combination of a low effective dose of gabapentin (50 mg kg−1) with a low dose of morphine decreased the writhing by 94% as compared to the controls. The antinociceptive effect of combined administration was not reversed by naloxone.

These data demonstrated the comparable efficacy of gabapentin with morphine in visceral pain. Also, the results showed that the combination of doses of gabapentin and morphine, which were ineffective alone, produced a significant analgesic effect in the writhing model of pain. This may be clinically important in the management of visceral pain.

This study was designed to investigate the potential existence of the response of neurons in the parafascicular nucleus of the thalamus to acute myocardial ischaemia induced by selective coronary artery occlusion and the effects of midazolam on the response in rats.

The left anterior descending branch of the coronary artery was instrumented with a snare occluder in anaesthetized Sprague-Dawley rats. A single-barrel glass microelectrode was used for recording the unit discharges of the neuron in the parafascicular nucleus. The neuron responding only to noxious somatic stimulation was further examined for the response to coronary artery occlusion. Once the effect of coronary artery occlusion on the discharges was detected, the pharmacological effects of midazolam and flumazenil were examined.

It was observed that the discharge rate of the neuron was markedly increased following coronary artery occlusion. Midazolam attenuated the increase in the discharges of the neuron induced by coronary artery occlusion (P < 0.05). The effect of midazolam was reversed by flumazenil.

The parafascicular nucleus is involved in the modulation of cardiac nociception and midazolam possesses antinociceptive property in modulating cardiac pain.

The technology of bispectral index monitoring is based on an algorithm developed from adults. This study was conducted to investigate the difference in bispectral index monitoring between paediatric and adult patients under intravenous anaesthesia.

In all, 68 patients undergoing elective surgery were divided into three groups as follows: Group A (younger children, n = 20, 3 yr ⩽yr ⩽ 5 yr), Group B (older children, n = 20, 6 yr ⩽yr ⩽12 yr), Group C (adults, n = 28, 25 yr ⩽yr ⩽50 yr). All patients were induced by plasma target-controlled infusion of propofol till loss of consciousness (loss of response to verbal commands and eyelash reflex). The plasma concentration (Cppropofol) and effect-site concentration (Cepropofol) of propofol and bispectral index values were compared at loss of consciousness and regaining of consciousness. During the operation, remifentanil was infused at a fixed rate of 0.25μg kg−1 min−1, and the minute average bispectral index values of three groups were also compared at different stable concentrations of propofol (Cepropofol = Cppropofol = 2, 3, 4 and 5 μg mL−1, respectively).

At loss of consciousness and regaining of consciousness, the bispectral index values in Group A (loss of consciousness: 74.7 ± 6.3, regaining of consciousness: 81.1 ± 10.5) were significantly higher than those in Group C (loss of consciousness: 68.6 ± 9.4, regaining of consciousness: 74.5 ± 6.0) (P < 0.01). There was no statistical difference between Cppropofol in all groups at loss of consciousness and regaining of consciousness. The Cepropofol at loss of consciousness in Group A (3.57 ± 0.60 μg mL−1) and B (3.25 ± 0.44 μg mL−1) were significantly higher than those in Group C (2.15 ± 0.86 μg mL−1) (P < 0.01). At the same stable concentrations of propofol, the bispectral index values in Group A and B were significantly higher than those in Group C, and the bispectral index values in Group A were also significantly higher than those in Group B (P < 0.01). The Cepropofol when bispectral index ⩽ 40 in Group A, B, C were approximately at 6, 5 and 3 μg mL−1, respectively.

At loss of consciousness and regaining of consciousness, the bispectral index values of younger children group are significantly higher than those of adults. At the same stable concentrations of propofol, the bispectral index values are significantly different between children and adults. This study suggests that there is deviation when the adult algorithm of bispectral index monitoring is applied in paediatric patients under intravenous anaesthesia.

Dynamic indices represented by systolic pressure variation and pulse pressure variation have been demonstrated to be more accurate than filling pressures in predicting fluid responsiveness. However, the literature is scarce concerning the impact of different ventilatory modes on these indices. We hypothesized that systolic pressure variation or pulse pressure variation could be affected differently by volume-controlled ventilation and pressure-controlled ventilation in an experimental model, during normovolaemia and hypovolaemia.

Thirty-two anaesthetized rabbits were randomly allocated into four groups according to ventilatory modality and volaemic status where G1-ConPCV was the pressure-controlled ventilation control group, G2-HemPCV was associated with haemorrhage, G3-ConVCV was the volume-controlled ventilation control group and G4-HemVCV was associated with haemorrhage. In the haemorrhage groups, blood was removed in two stages: 15% of the estimated blood volume withdrawal at M1, and, 30 min later, an additional 15% at M2. Data were submitted to analysis of variance for repeated measures; a value of P < 0.05 was considered to be statistically significant.

At M0 (baseline), no significant differences were observed among groups. At M1, dynamic parameters differed significantly among the control and hypovolaemic groups (P < 0.05) but not between ventilation modes. However, when 30% of the estimated blood volume was removed (M2), dynamic parameters became significantly higher in animals under volume-controlled ventilation when compared with those under pressure-controlled ventilation.

Under normovolaemia and moderate haemorrhage, dynamic parameters were not influenced by either ventilatory modalities. However, in the second stage of haemorrhage (30%), animals in volume-controlled ventilation presented higher values of systolic pressure variation and pulse pressure variation when compared with those submitted to pressure-controlled ventilation.

To establish whether caudal with ketamine or penile block provide superior postoperative analgesia for paediatric circumcision.

This was a single centre, prospective, randomized, controlled, double-blind trial. Forty males (aged between 18 months and 16 yr) were randomized to receive either a penile block using 0.25 mL kg−1 0.5% bupivacaine (Group P), or a caudal block using 0.5 mL kg−1 0.25% bupivacaine with 0.5 mg kg−1 ketamine (Group C). All of them were given a standard anaesthetic and rectal paracetamol 40 mg kg−1 and diclofenac 1–1.5 mg kg−1. Postoperative pain scores were assessed in recovery and the time to first analgesia, micturition and walking were recorded.

There were no failures in either group. The time to first analgesia was longer in Group C (C median = 459 min, interquartile range 374–553 min; P median = 374 min, interquartile range 224–507 min; P < 0.05). There was a delay in time to walking in Group C (C median = 162 min, interquartile range 119–208 min; P median = 120 min, interquartile range 92–132 min; P < 0.05). There was no difference between the groups in time to waking or micturition, or the incidence of vomiting, abnormal behaviour or bleeding.

Caudal bupivacaine with ketamine and penile block both provide effective postoperative analgesia for circumcision when given with non-steroidal anti-inflammatory drugs. This study shows that caudal bupivacaine with ketamine provides a longer duration of analgesia than penile block, but also causes delay in walking.

We retrospectively reviewed the first 25 planned cases of awake craniotomies using the ‘asleep–awake’ technique, an alternative to the often-used ‘asleep–awake–asleep’ technique.

The patients were anaesthetized using propofol/remifentanil anaesthesia, a laryngeal mask and controlled ventilation according to a protocol defined before the start of this series of patients. The patients were awakened before the brain mapping and were kept awake throughout the rest of the procedure allowing for additional mapping and modification of the resection of the tumour if symptoms should develop. A small dose of remifentanil was infused during this period if necessary.

Twenty-three patients were mapped as planned. One patient was not awakened due to protrusion of the brain during the awakening phase. Another patient was intubated preoperatively as it was impossible to obtain a tight laryngeal mask. All of the 23 patients were awake as from when the mapping session began and throughout the rest of the operation. In five cases the resection of the tumour was modified as symptoms emerged. These symptoms all subsided in due course. No case of hypoxia was recorded. In no case the respiratory rate was below 10 breaths min−1 in the awake period. Complications were comparable to other studies. The patients in the present study were all satisfied with the method.

Different methods of anaesthesia have been described, but no method has been shown to be superior. The presented method seems to be a rational and useful technique allowing for modification of tumour resection, if symptoms should develop. The method was well tolerated by the patients.

The impact of anaesthesia using target-controlled infusion with propofol on intraoperative stability, recovery and cost compared to manually controlled infusion has been evaluated with inconsistent results. We studied a new device that allows more individual titration of propofol target-controlled infusion by using the effect-site concentration at the loss of eyelash reflex to predict the maintenance infusion rate (FM-TCI).

Fifty-six patients undergoing major abdominal surgery lasting >2 h were randomly assigned to receive either FM-TCI (n = 28) or MCI-controlled (n = 28) anaesthesia. Both groups were Bispectral Index-monitored and thoracic epidural analgesia was established. Anaesthetic stability, incidence of haemodynamic abnormalities, time to extubation, propofol consumption and patient satisfaction were assessed.

In the FM-TCI group, a significantly improved anaesthetic stability was achieved (0.43 ± 0.44 vs. 1.31 ± 0.78 adjustments of propofol infusion per patient per hour, P = 0.003) and time to extubation was significantly shorter (9.6 ± 2.1 vs. 15.7 ± 9.6 min P = 0.011). With FM-TCI, propofol consumption was significantly lower. Haemodynamic stability and patient satisfaction did not differ between the groups.

FM-TCI helps to provide more stable anaesthesia conditions requiring less-frequent adjustments of the propofol infusion compared to manually controlled infusion in patients undergoing major abdominal surgery.

The caffeine/halothane contracture test in North America and the in vitro contracture test in Europe are currently the only validated bioassays for diagnosing malignant hyperthermia susceptibility and phenotyping families. Both tests are invasive requiring surgical muscle biopsy. Here, we report first use of the selective ryanodine receptor type I agonist ryanodine in a percutaneous microdialysis protocol designed to test whether microdialysis-induced local metabolic responses of skeletal muscle due to ryanodine receptor activation can differentiate between malignant hyperthermia-sensitive and normal pigs.

Six microdialysis catheters were implanted percutaneously into the adductor muscles of the right and left thighs of malignant hyperthermia-susceptible (n = 9) and normal (n = 8) anaesthetized (ketamine/propofol) and mechanically ventilated swine. Systemic blood gases, haemodynamic parameters and creatine kinase levels were measured before, during and after microdialysis perfusion of ryanodine. After a post-implantation equilibration period of 30 min, one catheter perfused (2 μL min−1) with 0.9% NaCl (control) and was compared with the remaining five catheters perfused with increasing concentrations of ryanodine (0.2–100 μmol). Lactate and pyruvate levels were measured enzymatically.

Continuous perfusion with ryanodine revealed dose-dependent sigmoidal increases in the dialysate lactate and lactate–pyruvate ratio parameters; these effects were greatly augmented in malignant hyperthermia-susceptible pigs compared to normal pigs (two- to threefold): estimated EC50 greatly decreased (>19-fold) while the maximum effect increased (>twofold) in the malignant hyperthermia-susceptible group.

The in vivo percutaneous microdialysis protocol for skeletal muscle, using ryanodine as the ryanodine receptor type I agonist and dialysed lactate–pyruvate parameters as metabolic index, can reproducibly differentiate between malignant hyperthermia-susceptible and normal swine.