We analysed individual patient information from five randomized trials (913 patients) of i.v. patient-controlled analgesia (IVPCA) plus epidural placebo, morphine sulphate (MS) 5 mg, or extended-release epidural morphine (EREM; DepoDur^TM) at doses of 5–30 mg, to explore effects of a range of epidural morphine doses. Pain and opioid requirement on first and second postoperative days, dose–response, clinically relevant comparisons of IVPCA without epidural morphine, 5 mg MS, and 10 mg EREM, and relationship between patient rating and other measures were described.

There were three strong findings. Epidural morphine resulted in greater patient satisfaction, despite higher rates of adverse events. Those describing their analgesic medication as ‘very good’ or ‘excellent’ used IVPCA opioid less and had pain scores significantly below the global mean, whereas those describing their medication as ‘poor’ or ‘fair’ had pain scores significantly above the mean. Epidural morphine meant less need for postoperative IVPCA opioid than epidural placebo. The therapeutic gain with EREM was lower pain scores with less IVPCA opioid. Moderate or severe pruritus was more common with IVPCA plus epidural morphine, whatever the formulation, compared with IVPCA plus placebo.

Analysis of individual patient data from high-quality clinical trials provides important insights into characteristics of new agents not immediately apparent from original trials, and also informing clinical practice. Prophylactic epidural morphine provides a better patient experience than IVPCA alone.

Thirteen patients, ASA I or II, undergoing elective ENT surgery were studied. Anaesthesia was induced with propofol 2.1 (0.7) mg kg^–1, rocuronium 0.5 (0.1) mg kg^–1, and remifentanil 0.5 µg kg^–1 min^–1. After tracheal intubation, anaesthesia was maintained with a continuous infusion of propofol 3.9 (1.8) mg kg^–1 h^–1 and remifentanil 0.5 µg kg^–1 min^–1. Simultaneously, a venous blood sample was obtained. Propofol concentrations in serum were determined by GC–MS and compared with the height of the respective propofol signals achieved by MCC–IMS.

Twenty-four pairs of samples were obtained. The comparison of propofol concentrations in exhaled air and serum presented a bias of –10.5% and a precision of ±12.3%. With these values, the 95% limits of agreement were 14.1% and –35.1%.

MCC–IMS may be a suitable method to determine propofol concentrations in exhaled air, and may be used to predict propofol concentrations in serum.

Thirty-four weaning trials were reported in 29 consecutive mechanically ventilated patients with different causes of initiation of ventilation. During the SBT, the patient was breathing through a conventional T-piece connected to the tracheal tube. FOT (5 Hz, ±1 cm H₂O, 30 s) was applied at 5, 10, 15, 20, 25, and 30 min. Respiratory resistance (Rrs) and reactance (Xrs) were computed from pressure and flow measurements. The frequency to tidal volume ratio f/V_t was obtained from the flow signal. At the end of the trial, patients were divided into two groups: SBT success and failure.

Mixed model analysis showed no significant differences in Rrs and Xrs over the course of the SBT, or between the success (n=16) and the failure (n=18) groups. In contrast, f/V_t was significantly (P<0.001) higher in the failure group.

Worsening of respiratory impedance measured by FOT is not a common finding during a failed SBT in a typically heterogeneous intensive care unit population of mechanically ventilated patients.

Patients aged from birth to 5 yr requiring general anaesthesia with TT intubation were included in 24 European paediatric anaesthesia centres. Patients were prospectively randomized into a cuffed TT group (Microcuff^® PET) and an uncuffed TT group (Mallinckrodt^®, Portex^®, Rüsch^®, Sheridan^®). Endpoints were incidence of post-extubation stridor and the number of TT exchanges to find an appropriate-sized tube. For cuffed TTs, minimal cuff pressure required to seal the airway was noted; maximal cuff pressure was limited at 20 cm H₂O with a pressure release valve. Data are mean (sd).

A total of 2246 children were studied (1119/1127 cuffed/uncuffed). The age was 1.93 (1.48) yr in the cuffed and 1.87 (1.45) yr in the uncuffed groups. Post-extubation stridor was noted in 4.4% of patients with cuffed and in 4.7% with uncuffed TTs (P=0.543). TT exchange rate was 2.1% in the cuffed and 30.8% in the uncuffed groups (P<0.0001). Minimal cuff pressure required to seal the trachea was 10.6 (4.3) cm H₂O.

The use of cuffed TTs in small children provides a reliably sealed airway at cuff pressures of ≤20 cm H₂O, reduces the need for TT exchanges, and does not increase the risk for post-extubation stridor compared with uncuffed TTs.

Forty patients undergoing endoscopic sinus surgery under general anaesthesia using total i.v. anaesthesia (propofol and remifentanil) were randomly allocated to a control group (n=20) or remifentanil group (n=20) during emergence from anaesthesia. At the end of surgery, propofol was ceased and the infusion of remifentanil was stopped in the control group and maintained in the remifentanil group at a target organ concentration of 1.5 ng ml^–1 until extubation. Heart rate (HR), mean arterial pressure (MAP), and recovery profiles were measured and evaluated.

There was no significant difference in sex ratio, age, weight, height, time to eye opening, time to extubation, nausea, visual analogue scale, and time to discharge. Increases in HR and MAP occurred during emergence in the control group compared with baseline values. Increases in HR were attenuated in the remifentanil group and MAP decreased during recovery compared with baseline values. HR and MAP values were significantly higher in the control group [103 (23) beats min^–1, 129 (17) mm Hg] compared with the remifentanil group [79 (17) beats min^–1, 112 (15) mm Hg] during emergence and tracheal extubation. Moderate or severe coughing was observed only in the control group (8/20 vs 0/20, P<0.001).

Maintaining a remifentanil infusion reduced haemodynamic changes and coughing associated with tracheal extubation almost without significantly delaying recovery from anaesthesia.

Human endothelial cells were cultured with lipopolysaccharide 2 µg ml^–1, peptidoglycan G 20 µg ml^–1, tumour necrosis factor (TNF) 10 ng ml^–1, interleukin-1 (IL-1) β 20 ng ml^–1, or killed Candida albicans yeast cells plus either N-acetylcysteine (NAC) 25 mM, trolox 100 mM, or idebenone 1 µM. Plasma samples were obtained from 15 patients with sepsis and 11 healthy volunteers.

PTX3 levels in plasma were higher in patients with sepsis than in healthy people [26 (1–202) ng ml^–1 compared with 6 (1–12) ng ml^–1, P=0.01]. Antioxidant capacity was lower in patients with sepsis than healthy controls [0.99 (0.1–1.7) mM compared with 2.2 (1.3–3.3) mM, P=0.01]. In patients with sepsis, lipid hydroperoxide levels were 3.32 (0.3–10.6) nM and undetectable in controls. We found no relationship between PTX3 and antioxidant capacity or lipid hydroperoxides. Cell expression of PTX3 increased with all inflammatory stimulants but was highest in cells treated with TNF plus IL-1β. PTX3 concentrations were lower in cells co-treated with antioxidants (all P<0.05), associated with lower nuclear factor B expression for NAC and trolox (P<0.05).

PTX3 expression is down-regulated in vitro by antioxidants. Plasma levels of PTX3 are elevated in sepsis but seem to be unrelated to markers of oxidant stress or antioxidant capacity.

The study was conducted in the intensive care unit of a tertiary teaching hospital. All patients with PAC in situ were eligible. Simultaneous CO readings were taken when clinically indicated. Investigators and clinicians were blinded to each other's results. The CO values used were the mean of three consecutive supra-sternal Doppler readings for patients with a sinus rhythm and seven for atrial fibrillation, and the mean of three thermodilution curves with acceptable form and values within 10% of each other for the PAC. Agreement was measured using both the paired t-test to calculate bias and limits of agreement and the intraclass correlation (ICC) coefficient.

Ninety-four subjects were enrolled. From 89 subjects, 250 paired comparisons were obtained. USCOM monitor readings were unobtainable in five patients. Mean supra-sternal Doppler CO was 5.5 litre min^–1. Bias was –0.09 litre min^–1 and levels of agreement were ±2.92 litre min^–1 when compared with PAC. ICC was 0.46 (95% CI 0.36–0.56), and mean percentage difference was 19 (IQR 6–31)%.

In our subjects, there was poor agreement between CO measurements done with the supra-sternal Doppler monitor and PAC.

Both devices were studied in 39 anaesthetized, paralysed patients in a randomized crossover trial. The primary outcome was airway leak pressure. Secondary outcomes included time to insertion, the number of insertion and reposition attempts, leak volumes, and leak fractions.

There was no significant difference between the airway leak pressures of the two devices [median (IQR) leak pressures 25 (22–30) vs 22 (20–28) cm H₂O for the i-gel and LMA-U, respectively; P=0.083, 95% CI of the mean difference –0.32 to 4.88 cm H₂O]. The median (IQR) insertion time for the i-gel was significantly less than for the LMA-U [12.2 (9.7–14.3) vs 15.2 (13.2–17.3) s; P=0.007]. All the LMA-U devices and 38 of 39 i-gel airways were inserted at the first attempt. The number of manipulations required after insertion to achieve a clear airway was the same in both the groups (four in each). There were no statistically significant differences in leak volumes or leak fractions during controlled ventilation.

We found no difference in leak pressures and success rate of first-time insertion between the i-gel and the LMA-U. Time to successful insertion was significantly shorter for the i-gel. We conclude that the i-gel provides a reasonable alternative to the LMA-U for controlled ventilation during anaesthesia.

Nasopharyngeal airway pressure was measured in 15 postoperative cardiac surgery adult patients who received both NHF and standard facemask therapy at a flow rate of 35 litre min^–1. Measurements were repeated in the open mouth and closed mouth positions. Mean airway pressure was determined by averaging the pressures at the peak of inspiration of each breath within a 1 min period, allowing the entire pressure profile of each breath to be included within the calculation.

Low level positive pressure was demonstrated with NHF at 35 litre min^–1 with mouth closed when compared with a facemask. NHF generated a mean nasopharyngeal airway pressure of mean (sd) 2.7 (1.04) cm H₂O with the mouth closed. Airway pressure was significantly higher when breathing with mouth closed compared with mouth open (P≤0.0001).

This study demonstrated that a low level of positive pressure was generated with NHF at 35 litre min^–1 of gas flow. This is consistent with results obtained in healthy volunteers.

Australian Clinical Trials Registry www.actr.org.au ACTRN012606000139572.

The pharmacokinetics of i.v. and i.m. NN1731 was evaluated in eight minipigs, and the effects of dose and administration route of NN1731 (i.v. 180 µg kg^–1, n=6; i.m. 540 µg kg^–1, n=4, or 2000 µg kg^–1, n=6) vs vehicle (n=16) were studied on a liver laceration injury in pigs. To simulate a pre-hospital setting, the administration of NN1731 was delayed by 1 min for i.m. administration and 7 min for i.v. administration, at which time fluid resuscitation also began.

In the minipigs, NN1731 exposure was similar after i.v. 180 µg kg^–1 and i.m. 540 µg kg^–1, with a bioavailability of ~35%. The injury and blood loss at 7 min was comparable between the four groups of pigs; however, after 60 min, the blood loss was lower in the i.v. treated animals: 1.3 (0.3) (i.v.) vs 2.2 (0.8) litres (i.m.₅₄₀, i.m.₂₀₀₀, and vehicle) (P<0.001). Also, the survival time was increased: 117 (14) (i.v.) vs 84 (28) min (i.m.₅₄₀, i.m.₂₀₀₀, and vehicle) (P<0.001).

After a liver trauma in the pig, i.v. administration of NN1731 reduced the bleeding and increased the survival time. In contrast, i.m. administration had no effect, presumably because reduced muscle perfusion during haemorrhage reduced the uptake of NN1731.

The effect of a range of doses of CNS 7056, midazolam, and propofol on depth of sedation, the respiratory system, and the cardiovascular system was studied in chronically instrumented sheep (n=5 or 6). The low, medium, and high doses of CNS 7056, midazolam, and propofol were 0.37, 0.74, and 1.47 mg kg^–1; 0.05, 0.1, and 0.2 mg kg^–1; and 1, 2, and 4 mg kg^–1, respectively.

CNS 7056 produced substantial sedation with rapid onset and offset for all doses, with duration rather than depth of sedation increasing with the dose. The lower doses of midazolam had minimal sedative effect; increasing the dose produced variable but longer term sedation. Sedation from propofol was comparable with that of CNS 7056 for the medium and high doses only. The high doses produced ~20 min of sedation. All three drugs produced dose-dependent respiratory (e.g. reductions in arterial oxygen tension) and cardiovascular depression (e.g. reductions in mean arterial pressure). For CNS 7056, midazolam, and propofol, the magnitude of the cardiovascular and respiratory depression was proportional to the depth of sedation achieved for any given drug or dose. For all three drugs, the respiratory and cardiovascular depression was not of sufficient magnitude to endanger the animals.

CNS 7056 is a powerful and short-acting anaesthetic in sheep with respiratory and cardiovascular effects consistent with its sedative/anaesthetic qualities.

Using a bench-top trachea–lung model (comprising a Siemens test lung attached to commercially available breathing system tubing), we compared delivered minute volumes (MVs) for five methods of ventilation administered through cannulae of diameters 20, 16, 14, and 13 G. The ventilation methods were: an ENK oxygen flow modulator, a Manujet, a self-inflating resuscitation bag, the oxygen flush of an anaesthetic machine, and oxygen from a wall-mounted flow meter attached via a three-way tap to the cannula. All experiments were performed with and without a proximal 2.5 mm diameter constriction to simulate partial upper airway obstruction.

MVs increased with increasing cannula diameter. In the absence of a proximal constriction, MVs delivered via a 20 G cannula were <1 litre min^–1 with all devices; only the Manujet delivered MVs >2 litre min^–1, at cannula sizes of ≥16 G. MVs were greater in the presence of a proximal constriction, but did not exceed 4 litre min^–1 using the low-pressure devices.

Extrapolated to the clinical situation, these data suggest that low-pressure devices will not deliver adequate MVs via a cannula cricothroidotomy and should no longer be advocated. Purpose-made devices should be available in all areas where anaesthesia is administered or airway interventions are performed.

Seventy-two patients undergoing Caesarean section were randomly assigned to receive i.v. saline (control group) or magnesium sulphate 30 mg kg^–1 bolus+10 mg kg^–1 h^–1 continuous infusion (Mg 30 group) or 45 mg kg^–1 bolus+15 mg kg^–1 h^–1 continuous infusion (Mg 45 group) after induction. Bispectral index (BIS) value, mean arterial pressure (MAP), and midazolam, fentanyl, and atracurium consumptions were recorded.

BIS values [mean (sd)] at 7.5 and 10 min after surgery and before delivery in the control [64 (9), 66 (8), 67 (8), P<0.001] and the Mg 30 groups [62 (8), P<0.01; 64 (7), 63 (9), P<0.001] were higher than in the Mg 45 group [56 (8), 55 (8), 55 (7)]. MAP was greater in the control group (P<0.05) than in the Mg 30 and Mg 45 groups during the pre-delivery period. The magnesium groups required less midazolam (P<0.05), fentanyl (Mg 30, P<0.05; Mg 45, P<0.01), and atracurium (P<0.001) vs the control group.

Preoperative i.v. magnesium sulphate attenuated BIS and arterial pressure increases during the pre-delivery period. Magnesium sulphate can be recommended as an adjuvant during general anaesthesia for Caesarean section to avoid perioperative awareness and pressor response resulting from inadequate anaesthesia, analgesia, or both.