The objectives of this study were, firstly, to characterize the inter-patient variability in the dose of propofol required to achieve a bispectral index <70 and ‘time to eye opening’ following propofol infusion and, secondly, to determine if the pharmacodynamic parameter ‘time to achieve bispectral index <70’ was influenced by genotype of the sex-linked drug receptor gene GABRE or if pharmacokinetic parameters such as clearance and ‘time to eye opening’ were influenced by the genotype of the metabolizing enzyme CYP2B6.

One hundred and fifty patients received a standardized anaesthetic. Apparent systemic clearance values were estimated. Correlation was sought between carriers of different CYP2B6 and GABRE genotypes and apparent systemic clearance, ‘time to achieve bispectral index <70’ and ‘time to eye opening’.

Propofol induction/emergence characteristics varied, with slow recovery times in a subset of males. Time to loss of verbal contact and time to bispectral index <70 varied 6.6- and 4.3-fold, respectively. At emergence, there was a 15.5- to 111-fold variability in the measured time intervals. Clearance varied from 9.1 to 55.8 mL min−1 kg−1. The CYP2B6 C1459T (R487C) genotype frequencies were TT 1%, TC 22% and CC 67%. The three major haplotypes of CYP2B6 (R487C, K262R and Q172H variants) were not significantly associated with time to eye opening or clearance. Clearance was similar in 487C carriers and 487RR genotypes. There was no statistically significant correlation between the four major haplotypes of GABRE variants investigated ([mRNA358]G/T, 20118C/T, 20326C/T and 20502 A/T) and the observed anaesthesia induction time.

Great inter-patient variability exists in the dose of propofol required to achieve bispectral index <70, apparent systemic propofol clearance and time to eye opening. Common haplotypic differences at the CYP2B6 and GABRE genes do not appear to account for the majority of the observed inter-patient variability.

Target-controlled infusion, via the calculated effect compartment concentrations, may help anaesthesiologists to titrate anaesthetic depth and to shorten recovery from anaesthesia.

In this prospective, randomized clinical study, we compared the performance of six inexperienced anaesthesiologists with <1 yr of training when using target- or manually controlled infusion of propofol, combined with manual dosing of fentanyl. Ninety-two premedicated ASA I–III patients undergoing minor elective urological or gynaecological surgery were assigned to the manual- or target-controlled infusion group. Bispectral index was recorded in a blinded manner. Subjective assessment of anaesthetic depth on a 10 point numerical scale (1 = very deep anaesthesia, 10 = awake) was asked at regular intervals and the correlation with the blinded bispectral index was analysed using the prediction probability, PK. The propofol concentration profile was calculated post hoc.

Propofol administration was similar in both groups with no significant difference for the administered amount and concentrations of propofol. Recovery times were also not different. In both groups, a large percentage of the bispectral index data points recorded during surgery showed bispectral index values below the recommended value of 40, but in the target-controlled infusion group there were significantly less bispectral index values above the recommended upper limit of 60 (2.5% vs. 5.1%).

A target-controlled infusion system does not help inexperienced anaesthesiologists to assess anaesthetic depth or to shorten recovery times, but may reduce episodes of overly light anaesthesia and thus help to prevent awareness.

Insufficient blood flow and oxygenation in the intestinal tract is associated with increased incidence of postoperative complications after bowel surgery. High fluid volume administration may prevent occult regional hypoperfusion and intestinal tissue hypoxia. We tested the hypothesis that high intraoperative fluid volume administration increases intestinal wall tissue oxygen pressure during laparotomy.

In all, 27 pigs were anaesthetized, ventilated and randomly assigned to one of the three treatment groups (n = 9 in each) receiving low (3 mL kg−1 h−1), medium (7 mL kg−1 h−1) or high (20 mL kg−1 h−1) fluid volume treatment with lactated Ringer’s solution. All animals received 30% and 100% inspired oxygen in random order. Cardiac index was measured with thermodilution and tissue oxygen pressure with a micro-oximetry system in the jejunum and colon wall and subcutaneous tissue.

Groups receiving low and medium fluid volume treatment had similar systemic haemodynamics. The high fluid volume group had significantly higher mean arterial pressure, cardiac index and subcutaneous tissue oxygenation. Tissue oxygen pressures in the jejunum and colon were comparable in all three groups.

The three different fluid volume regimens tested did not affect tissue oxygen pressure in the jejunum and colon, suggesting efficient autoregulation of intestinal blood flow in healthy subjects undergoing uncomplicated abdominal surgery.

When intrathecally or epidurally administered, α2-adrenoceptor agonists produce potent antinociception by affecting the activity of primary afferent fibres and spinal cord neurons. Recent reports have indicated that in dorsal root ganglion neurons, tetrodotoxin-resistant Na+ channels play important roles in the conduction of nociceptive sensation. We therefore investigated the effects of α2-adrenoceptor agonists on tetrodotoxin-resistant Na+ currents.

Using the whole-cell patch-clamp technique, we recorded tetrodotoxin-resistant Na+ currents from rat dorsal root ganglion neurons.

Both clonidine and dexmedetomidine reduced the peak amplitude of the tetrodotoxin-resistant Na+ current concentration- and use-dependently. The concentration required for a half-maximal effect was significantly lower for dexmedetomidine (58.0 ± 10.2 μmol) than for clonidine (257.2 ± 30.9 μmol) at holding potential −70 mV. The current inhibitions induced by these agonists were not prevented by 1 μmol yohimbine, an α2-adrenoceptor antagonist. Both clonidine and dexmedetomidine shifted the inactivation curve for the tetrodotoxin-resistant Na+ current in the hyperpolarizing direction. The combinations clonidine with lidocaine and dexmedetomidine with lidocaine produced an additive blockade-type interaction on the tetrodotoxin-resistant Na+ current.

The results suggest that a direct inhibition of tetrodotoxin-resistant Na+ channels may contribute to the antinociceptive effects of clonidine and dexmedetomidine when used as additives to regional anaesthesia.

Epidural and intravenous analgesia are widely used for postoperative pain management. Efficacy and safety is enhanced with the establishment of acute pain services. We studied the terms of application of these techniques in Greek hospitals and compared practices between anaesthetic departments with or without acute pain services.

We performed a postal survey regarding departmental policy on the application of epidural and intravenous analgesia, patient monitoring, audit and educational activities, acute pain service teams and proposals for improvement. Pain services were classified according to predetermined quality criteria. Hospitals with or without acute pain services were compared.

Response rate was 46.3% (51 of 110 departments). Epidural analgesia was used in 49 departments, equally applied as intermittent boluses or continuous infusion. Twenty-two of the 39 departments that were using continuous infusion, used exclusively a lumbar approach. Intravenous analgesia was used by 42 (82%) departments; 13 used exclusively continuous infusion. All eight departments that had an established acute pain service fulfilled the predefined quality criteria compared with only ten of the remaining 43 (P < 0.001).

Our study discloses important issues regarding the use of intravenous and epidural analgesia and postoperative patient monitoring in Greek hospitals. Implementation of acute pain services that are satisfying the quality criteria may help to improve patient care.

Debate has proliferated as to the true site of action of opioids when placed in the epidural space. The aim of this study was to compare the analgesic effects of a bolus of diamorphine given by the epidural or intramuscular route.

Sixty patients having elective primary total knee replacements were recruited and randomized to receive epidural or intramuscular diamorphine. A lumbar epidural catheter was sited and 10 mL of bupivacaine 0.5% wt vol−1 was injected. Patients subsequently received diamorphine 5 mg into the epidural space or as an intramuscular injection. Patient-controlled analgesia with intravenous morphine was used for postoperative analgesia. The primary outcome measures included time to first patient-controlled analgesia use and total morphine consumption in 24 h. Secondary end-points considered possible treatment complications.

All primary end-points showed significant differences in favour of epidural diamorphine. Medians for times to first patient-controlled analgesia use and total 24 h morphine requirements were significantly different (P < 0.001) at 418 vs. 198 min and 11 vs. 39 mg, respectively. There were no significant differences in secondary end-points.

This study has shown the superior analgesic efficacy of epidural diamorphine when compared to intramuscular injection.

Activator protein 1 is a transcription factor involved in the regulation of proinflammatory mediators. Activation of phagocytes by lipopolysaccharide depends on the expression of CD14 on the cell surface. In this study, we investigated the effects of morphine and nitric oxide on CD14 expression and activator protein 1 activation in human blood monocytes and neutrophils as well as the leukocyte cell line HL-60.

Whole blood was incubated with morphine, the nitric oxide donor S-nitroso-N-acetyl-penicillamine, naloxone or nitric oxide synthase inhibitors Nω-nitro-l-arginine and Nω-nitro-l-arginine-methylester and stimulated with lipopolysaccharide. Activator protein 1 nuclear content was determined by flow cytometry in human blood neutrophils and monocytes. CD14 expression on neutrophils was measured after incubation with fluorescein isothiocyanate-labelled antibodies. Electric mobility shift assay served for evaluation of activator protein 1 nuclear binding in HL-60 cells.

Incubation of whole blood with morphine and subsequent stimulation with lipopolysaccharide decreased activator protein 1 nuclear content. Exposure to naloxone before morphine treatment abolished morphine-induced inhibition of activator protein 1 activity in human blood monocytes and neutrophils. Nitric oxide synthase inhibitors also reversed morphine’s effects. CD14 expression on neutrophils was reduced after morphine treatment. These effects were antagonized by nitric oxide synthase inhibitors and naloxone.

Morphine inhibits activator protein 1 activation by a μ opioid receptor pathway coupled to nitric oxide as second messenger. The decrease in CD14 expression caused by morphine may play a role in inhibition of activator protein 1 activation following lipopolysaccharide treatment of phagocytes.

Insulin resistance is frequently observed in critical illness. It can be quantified by the expensive and time-consuming euglycaemic hyperinsulinaemic clamp technique (M-value) and calculated indices of insulin resistance (Quantitative Insulin Sensitivity Check Index; QUICKI and Homeostasis Model Assessment; HOMA) with lower costs and efforts. We performed an observational study to assess the reliability of QUICKI and HOMA to evaluate insulin resistance in critically ill patients compared with the current gold standard method, the euglycaemic hyperinsulinaemic clamp technique.

Insulin resistance was measured in 30 critically ill medical patients by the euglycaemic hyperinsulinaemic clamp technique (M-value) as well as calculated using QUICKI and HOMA. Correlations between the M-values as well as QUICKI and HOMA were assessed by means of the Pearson’s correlation coefficient.

M-value, QUICKI and HOMA indicated insulin resistance in all 30 patients. However, both indices QUICKI and HOMA did not correlate with the M-values in our patients (r2 = 0.008 and 0.0005, respectively). A significant negative correlation was found between the M-value and the severity of illness assessed by the APACHE (Acute Physiology and Chronic Health Evaluation) III score (r2 = 0.16; P < 0.05). In contrast, neither HOMA nor QUICKI correlated with the APACHE III score (r2 = 0.034 and 0.033, respectively).

Although QUICKI and HOMA indicated insulin resistance in the critically ill medical patients, both indices did not correlate with the M-value. Therefore, the euglycaemic hyperinsulinaemic clamp technique remains the gold standard for estimating insulin resistance in critically ill patients.

Ventilator-associated pneumonia is a nosocomial infection that occurs in patients receiving mechanical ventilation for >48 h. Many aspects of its diagnosis, treatment and management are controversial. We used a postal questionnaire to survey current practice within the UK.

Questionnaire study of 207 general intensive care units in the UK.

The response rate was 77.3%. Regarding diagnosis, 30% of units obtained specimens from the lungs invasively, while the remainder relied on tracheal aspirates. In only 28.2% of units using tracheal aspirates were results reported in a quantitative manner. A clinical suspicion of ventilator-associated pneumonia would lead to the administration of empirical antibiotic therapy in the majority of units (77.2%), opinion being almost equally divided on whether this should be mono (49.1%) or combination therapy (50.9%). Although most units received regular microbiology feedback (90.5%), the involvement of a microbiologist in the antibiotic decision-making process was variable. Antibiotics were continued for a median of 7 days (inter-quartile range 5–8.5, range 2–14 days). Compliance with the principal methods of ventilator-associated pneumonia prevention was good.

There is widespread variation in the methods used for the diagnosis of ventilator-associated pneumonia within the UK. The majority of units rely on non-quantitative analysis of tracheal aspirates. This technique has a high percentage of false-positives, and suggests widespread over utilization of antibiotics. However, most agree that antibiotics should be given empirically when there is a clinical suspicion of ventilator-associated pneumonia. The widespread introduction of ‘ventilator bundles’ appears to have ensured that most units actively take measures to prevent ventilator-associated pneumonia.