To examine a possible mechanism for the antinociceptive action of the N-methyl-d-aspartate receptor antagonist ifenprodil, we compared its effects with those of ketamine on tetrodotoxin-resistant Na+ channels in rat dorsal root ganglion neurons, which play an important role in the nociceptive pain pathway.

Experiments were performed on dorsal root ganglion neurons from Sprague–Dawley rats, recordings of whole-cell membrane currents being made using patch-clamp technique.

Both drugs blocked tetrodotoxin-resistant Na+ currents dose dependently, their half-maximal inhibitory concentrations being 145 ± 12.1 μmol (ketamine) and 2.6 ± 0.95 μmol (ifenprodil). Ifenprodil shifted the inactivation curve for tetrodotoxin-resistant Na+ channels in the hyperpolarizing direction and shifted the activation curve in the depolarizing direction. Use-dependent blockade of tetrodotoxin-resistant Na+ channels was more marked with ifenprodil than with ketamine. When paired with lidocaine, these drugs produced similar additive inhibitions of tetrodotoxin-resistant Na+ channel activity.

The observed suppressive effects on tetrodotoxin-resistant Na+ channel activity may, at least in part, underlie the antinociceptive effects of these N-methyl-d-aspartate receptor antagonists.

Early recovery after anaesthesia is gaining importance in fast track management. The aim of this study was to quantify psychomotor recovery within the first 24 h after propofol/remifentanil anaesthesia using the Short Performance Test (Syndrom Kurztest (SKT)), consisting of nine subtests. The hypothesis was that psychomotor performance remains reduced 24 h after anaesthesia.

Thirty-seven patients scheduled for elective surgery took part in the study. The SKT was performed on the day before general anaesthesia (T0), 10, 30, 90 min and 24 h after extubation (T1). Parallel versions were used to minimize learning effects. Anaesthesia was introduced and maintained with remifentanil/propofol as a target controlled infusion. Propofol plasma concentration was measured 10 and 90 min after extubation. Perioperative pain management included novaminsulfon and piritramide.

Up till 90 min after surgery and anaesthesia, psychomotor performances were significantly reduced as the lower test results in all SKT subtests indicated (P ⩽ 0.007 vs. baseline T0). In the three memory subtests (ST 2, ST 8 and ST 9), psychomotor performance was still reduced on the first postoperative day (P ⩽ 0.005; T1 vs. T0). There was no correlation between propofol plasma concentration and the psychometric test results.

Propofol/remifentanil-based target controlled general anaesthesia for surgery is associated with a reduced psychomotor function up to the first postoperative day. Further studies are needed to confirm the usefulness of the SKT in the perioperative period and to clarify which components in the perioperative period are responsible for a lower performance in the SKT.

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.

Despite the absence of cardiopulmonary bypass, systemic anticoagulation is needed for off-pump coronary artery bypass (OPCAB) surgery. The aim of the current review is to describe the influence of OPCAB surgery on hemostatic activation and to review the literature with regard to perioperative anticoagulation protocols in OPCAB surgery.

Research of the pertinent literature with appropriate terms for anticoagulation in OPCAB surgery.

While during on-pump cardiac surgery a target activated clotting time (ACT) value of 400–480 is generally accepted, to date no standardized target ACT value for OPCAB surgery has been established. However, an ACT value of > 300 seconds is accepted by approximately 80% of US/Canadian surgeons and 60% of European surgeons. Even given the large variation commercially available heparins, the inter-individual variability of the effect of heparins on the ACT, and large differences in coagulation activation and ‘clot detection’ of currently used ACT systems, this target ACT corresponds to a heparin dose of approximately 150–300 IU/kg. New anticoagulant drugs have been proposed, acting through a selective anti-Xa activity (danaparoid) or directly inhibiting thrombin (bivalirudin).

Anticoagulation management is performed without any internationally accepted standard and, due to this and the lack of adequately powered studies, there is scarce information about the effects of OPCAB surgery on hemostatic activation in the immediate perioperative period. Although limited to two modest studies, bivalirudin appears to be an interesting option for the future.

A number of algorithms for the prevention of postoperative nausea and vomiting have been proposed. Their efficacy and efficiency remains unclear.

We assumed that four antiemetic interventions were similarly effective and achieved additive effects when combined. We applied published and hypothetical algorithms for the prevention of postoperative nausea and vomiting to patient populations with different baseline risks. As indicators of efficacy and efficiency we computed for each baseline risk and each algorithm the total number of patients receiving prophylaxis, the total number of administered interventions, the cumulative 24 h incidence of postoperative nausea and vomiting, and an Efficiency Index (i.e. the number of administered interventions divided by the achieved absolute risk reduction). This was done for cohorts of 100 patients.

Ten algorithms were tested in seven populations with different baseline risks. Algorithms were fixed (⩾ 1 intervention given to all patients, independent of baseline risk) or risk-adapted (⩾ 1 intervention administered depending on the presumed baseline risk). Risk-adapted algorithms were escalating (the greater the baseline risk, the more interventions are given) or dichotomous (a fixed number of interventions is given to high-risk patients only). With some algorithms, when applied to selected patient populations, the average postoperative nausea and vomiting incidence could be decreased below 15%; however, none produced consistent postoperative nausea and vomiting incidences below 20% across all populations. With all, the number of administered antiemetic interventions was the major factor for improved efficacy. Depending on the baseline risk, some algorithms offered potential towards improved efficiency.

Despite improved knowledge on risk factors and antiemetic strategies, none of the tested algorithms completely prevents postoperative nausea and vomiting and none is universally applicable. Anesthesiologists should try to identify the most useful antiemetic strategy for a specific setting. That strategy may be prophylactic or therapeutic or a combination of both, and it should consider institutional policies and individual baseline risks.

Significant start-up delays are inherent to syringe infusion pumps, particularly at low infusion rates, as routinely used in children’s anaesthesia and intensive care. Such delays are mainly the result of engagement of gears in the mechanical drive or compliance of the syringe assembly. The purpose of the present study was to determine the effect of flow rate, syringe size and syringe architecture on fluid delivery during infusion start-up.

Elapsed time from infusion start to achievement of steady-state flow was gravimetrically determined for various infusion rates (0.1, 0.5, 1 mL h−1), different syringe sizes (10-, 20-, 30-, 50-mL) and syringes of two different brands (BD and Codan). Four measurements for each condition were performed with two identical Alaris® Asena™ GH syringe infusion pumps (total of eight experiments). Statistical analysis was done by two-way ANOVA with Bonferroni’s post-test; P < 0.05 was considered significant.

Start-up time was from 3.6 ± 0.9 min (BD 10-mL syringe, 1.0 mL h−1) to 74.5 ± 26.6 min (BD 50-mL syringe, 0.1 mL h−1). Overall, the start-up time markedly increased with lower flow rate (0.1 mL h−1 vs. 1 mL h−1; P < 0.0001), larger syringe size (50 mL vs. 10 mL; P < 0.01), and the BD brand in comparison with the Codan syringes (P < 0.01).

Highest possible flow rate, smaller sized syringes and syringe plungers with reduced compressibility should be preferred in order to avoid significant start-up delays in fluid delivery.

Preoperative evaluation is important in the detection of patients at risk for difficult airway management. It is still unclear whether true prediction is possible and which variables should be chosen for evaluation. The aim of this prospective, multi-centre study was to investigate the incidence of difficult intubation, the sensitivity and positive predictive values of clinical screening tests and whether combining two or more of these tests will improve the prediction of difficult intubation in Turkish patients.

Seven study sites from six regions in Turkey participated in this study. One thousand six hundred and seventy-four ASA physical status I–III patients, scheduled to undergo elective surgery under general anaesthesia, were included.

The incidence of difficult intubation was 4.8% and increased with age (P < 0.05). The incidence of difficult intubation was significantly higher in patients who had a Mallampati III or IV score, a decreased average thyromental and sternomental distance, decreased mouth opening, or decreased protrusion of the mandible (P < 0.05). Mouth opening and Mallampati III–IV were found to be the most sensitive criteria when used alone (43% and 35%, respectively). Combination of tests did not improve these results.

There is still no individual test or a combination of tests that predict difficult intubations accurately. Tests with higher specificity despite low positive predictive value are needed.

Respiratory variations in pulse oximetry plethysmographic waveform amplitude (ΔPOP) are related to respiratory variations in arterial pulse pressure (ΔPP) in the critical care setting. The aims of this study were to test the hypothesis that in mechanically ventilated patients undergoing general anaesthesia, ΔPOP calculation is feasible and can detect changes in preload.

Twenty-five mechanically ventilated patients were studied immediately after induction of general anaesthesia. Haemodynamic data (mean arterial pressure [MAP], central venous pressure [CVP], ΔPP and ΔPOP) were recorded at baseline, before and after tilting the patient from anti-Trendelenburg to Trendelenburg position in order to induce preload changes.

Change from anti-Trendelenburg to Trendelenburg position induced changes in MAP (58 ± 9 to 67 ± 10 mmHg, P < 0.05), CVP (4 ± 4 to 13 ± 5 mmHg, P < 0.05), ΔPP (14 ± 8 to 7 ± 5%, P < 0.05) and ΔPOP (17 ± 12 to 9 ± 5%, P < 0.05). There was a significant relationship between ΔPOP in anti-Trendelenburg position and percent change in MAP after volume expansion (r = 0.82; P < 0.05).

ΔPOP can be determined in the operating room and is influenced by changes in preload. This new index has potential clinical applications for the prediction of fluid responsiveness.

Preoperative oral dextromethorphan and intravenous clonidine attenuate arterial pressure and heart rate increases during tourniquet inflation under general anaesthesia. The effect of preoperative oral clonidine on these variables has not been investigated.

We designed this study to compare the effect of preoperative oral dextromethorphan or clonidine on haemodynamic changes during tourniquet inflation in 75 patients undergoing lower limb surgery under general anaesthesia. Patients were randomly assigned into three groups: dextromethorphan 30 mg (n = 25), clonidine 3 μg kg−1 (n = 25) and placebo (n = 25). Anaesthesia was maintained with isoflurane 1.2% and N2O 50% in oxygen with endotracheal intubation. Dextromethorphan, clonidine or placebo was given orally in a double-blinded fashion 90 min before induction of anaesthesia. Systolic, diastolic and mean arterial pressure and heart rate were measured at 0, 30, 45, 60 min after the start of tourniquet inflation, before tourniquet release and 20 min after tourniquet deflation.

Systolic, diastolic and mean arterial pressure were significantly lower in the clonidine group compared with control after 45, 60 min tourniquet inflation and before tourniquet release (P < 0.05). Twenty minutes after deflation, diastolic and mean arterial pressure in the control group were still increased and significantly higher compared with the clonidine group (P < 0.05). Development of more than a 30% increase in systolic arterial pressure during tourniquet inflation was more frequent in the control group than in the other groups.

Preoperative oral clonidine 3 μg kg−1 significantly prevented tourniquet-induced systemic arterial pressure increase in patients under general anaesthesia better than oral dextromethorphan.

We investigated the effects of prone position on respiratory dead space and gas exchange in 14 anaesthetized healthy patients undergoing elective posterior spinal surgery of more than 3 h of duration.

The patients received a total intravenous anaesthetic with propofol/remifentanil/cisatracurium. They were ventilated at a tidal volume of 8–10 mL kg−1, zero positive end-expiratory pressure and an inspired oxygen fraction of 0.4. Physiological, airway and alveolar dead spaces were calculated by analysis of the volumetric capnography waveform. Measurements were made in supine position (20 min after the beginning of mechanical ventilation) and 30, 120 and 180 min after turning to prone position.

We found that the alveolar dead space/tidal volume ratio did not change. PaO2/FiO2 increased, although not statistically significantly. Dynamic compliance was reduced due to a reduction in tidal volume and an increase in plateau pressure.

Patients undergoing surgery in prone position for a duration of 3 h under general anaesthesia including muscle relaxation and mechanical ventilation without positive end-expiratory pressure have stable haemodynamics and no significant changes in the alveolar dead space to tidal volume ratio. Oxygenation tended to improve.

During high epidural anaesthesia, endothelin only contributes minimally to blood pressure stabilization. This phenomenon could result from the inhibitory action of nitric oxide on the endothelin system. To clarify this, we studied the interaction between nitric oxide and endothelin during high epidural anaesthesia in conscious dogs, in comparison to the interaction of nitric oxide and vasopressin.

Six animals were used in 45 individual experiments randomly arranged as follows: N-ω-nitro-arginine-methylester 0.3–10 mg kg−1 under physiological conditions or during high epidural anaesthesia (lidocaine 1%) and N-ω-nitro-arginine-methylester (l-NAME) 0.3–10 mg kg−1 after preceding endothelin (Tezosentan®) or vasopressin (β-mercapto-β,β-cyclo-penta-methylene-propionyl-O-Me-Tyr-Arg-vasopressin) receptor blockade under physiological conditions or during high epidural anaesthesia. During control experiments normal saline was injected either intravenously (n = 5) or into the epidural space (n = 4).

N-ω-nitro-arginine-methylester increased mean arterial pressure dose-dependently in all groups. However, this effect was substantially reduced in the presence of the endothelin receptor antagonist compared to N-ω-nitro-arginine-methylester alone, both under control conditions (7 ± 3 vs. 21 ± 3 mmHg; P < 0.05) and during high epidural anaesthesia (17 ± 3 vs. 30 ± 1 mmHg; P < 0.05). Blockade of vasopressin showed no similar relationship with N-ω-nitro-arginine-methylester.

The diminished increase in mean arterial pressure after injection of N-ω-nitro-arginine-methylester only during endothelin receptor blockade indicates that endogenous nitric oxide inhibits the action of endothelin during high epidural anaesthesia and might thus explain the reduced efficacy of endothelin in maintaining blood pressure during high epidural anaesthesia.

Medialization thyroplasty is a surgical technique for improving voice quality, cough effort and laryngeal competence in patients with unilateral vocal fold paralysis. Precision surgery is enabled by operating under total intravenous anaesthesia with controlled ventilation and by using a laryngoscopic video-assisted technique. The anaesthetic challenge is to manage the shared airway with the surgeon, provide a stable operative field and ensure patient safety throughout the procedure. The objective of this case series was to evaluate the use of a modified general anaesthetic technique using the laryngeal mask airway, total intravenous anaesthesia with controlled ventilation.

In all, 29 patients underwent medialization thyroplasty using a disposable laryngeal mask airway, total intravenous anaesthesia and controlled ventilation. Standard anaesthetic monitoring including capnography was used intraoperatively. Total intravenous anaesthesia was achieved using effect site target-controlled infusions of propofol and remifentanil.

The technique proved safe with stable haemodynamic observations and only two minor complications. It also provided the surgeon with stable view of the vocal folds in order to perform this precision surgery under an operating microscope.

Postoperative nausea and vomiting is a common complication following strabismus surgery. This randomized and double-blind study was designed to evaluate the efficacy of midazolam alone or in combination with dexamethasone in reducing the incidence of postoperative nausea and vomiting in children undergoing strabismus repair.

One hundred ASA I children, aged 4–12 yr, scheduled to undergo elective strabismus surgery, were enrolled. No premedication was given. Anaesthesia was induced with sevoflurane, nitrous oxide and oxygen. After induction, fentanyl 2 μg kg−1 and cisatracurium 0.1 mg kg−1 were administered and an endotracheal tube was inserted. After induction of anaesthesia and before start of surgery, patients were randomly allocated into one of four groups of 25 children each to receive placebo, midazolam 50 μg kg−1, dexamethasone 0.5 mg kg−1 or a combination of midazolam 50 μg kg−1 and dexamethasone 0.5 mg kg−1. Episodes of nausea, and retching and vomiting were recorded during the first 24 h after surgery.

The incidence of postoperative nausea was 48%, 32%, 12% and 0% with placebo, dexamethasone, midazolam and the midazolam–dexamethasone combination, respectively. The incidence of vomiting was 52% and 32% with placebo and dexamethasone, respectively; no child vomited with midazolam alone, or with the midazolam–dexamethasone combination.

Prophylactic midazolam with or without dexamethasone reduces the incidence of PONV in children undergoing strabismus repair.

Diagnosis of brain death usually requires the absence of spontaneous respiratory movements during the apnoea test and an arterial carbon dioxide partial pressure above 60 mmHg. On the other hand, although capnography (end-tidal CO2) is currently monitored in intensive care unit patients, it has not been evaluated during the apnoea test in brain-dead patients. Therefore, the aim of this prospective study was first to investigate the usefulness of capnography monitoring, and secondly to evaluate the variation of the carbon dioxide partial pressure–end-tidal CO2 gradient during the apnoea test in clinically brain-dead patients.

After local Ethics Committee approval, 60 clinically brain-dead patients were investigated. End-tidal CO2 was continuously recorded before, during and after the apnoea test. Arterial blood gases were sampled immediately before and after the apnoea test for calculation of the carbon dioxide partial pressure–end-tidal CO2 gradient.

The apnoea test was clinically positive in 58 patients, whereas end-tidal CO2 was equal to 0 during the apnoea. During the 20-min apnoea test, carbon dioxide partial pressure increased from 40 ± 7 to 97 ± 19 mmHg (P < 0.001) with a rate of 2.8 ± 0.9 mmHg min−1, end-tidal CO2 increased from 31 ± 6 to 68 ± 17 mmHg (P < 0.001) and carbon dioxide partial pressure–end-tidal CO2 gradient increased from 9 ± 4 to 29 ± 10 mmHg (P < 0.001). In two patients, the apnoea test was clinically negative because of the occurrence of spontaneous respiratory movements, whereas capnography showed contemporaneously significant increases in end-tidal CO2.

End-tidal CO2 should be systematically monitored and recorded, at least for medico-legal considerations, during the apnoea test in brain-dead patients. The high variability in the carbon dioxide partial pressure–end-tidal CO2 gradient increase precludes any extrapolation of the carbon dioxide partial pressure from the end-tidal CO2 at the end of the apnoea test.

Neuromuscular blocking effects according to the severity of liver dysfunction have not been evaluated. We assessed the neuromuscular effects of mivacurium in carbon tetrachloride (CCl4)-treated rabbits with toxic hepatitis in vivo.

We compared the dose–response relationships and the neuromuscular blocking effects of mivacurium in 66 rabbits randomly treated with 0.3 mL kg−1 of corn oil, 0.3 mL kg−1 of CCl4 or 0.6 mL kg−1 of CCl4 for 11 weeks, respectively. Train-of-four stimuli were applied every 10 s to the common peroneal nerve and the force of contraction of the tibialis anterior muscle was measured.

Severe hepatitis was associated with a rightward shift of the mivacurium dose–response curves, but mild hepatitis had no effect. The calculated ED50 values for the control, mild and severe hepatitis were 17.1 ± 2.6, 18.2 ± 2.7 and 31.8 ± 3.2 μg kg−1, respectively. Rabbits with severe hepatitis had a significantly prolonged recovery time from neuromuscular blockade compared with other rabbits. Cholinesterase activity had a negative correlation with recovery indices of mivacurium even in severe hepatic injury. Severe hepatitis induced a prolongation of action duration of repeated doses, but maintained the constant intervals.

The dose–response and the time course of neuromuscular blockade of mivacurium differ in mild hepatitis compared with severe hepatitis, but required no adjustments of different doses for repeated injection after the desired depth of neuromuscular block, and had a negative correlation with the activity of plasma cholinesterase in both hepatic injuries.

Analgesics and anaesthetics have diverse synaptic actions that nonetheless have a common net inhibitory action on neuronal discharge. It is puzzling, therefore, that these two classes of compounds have fundamentally different affects, one blocking pain and the other consciousness. Indeed, beyond the isolated synapse, little is known of the larger scale mechanisms that mediate actual function, for example, transient neuronal assemblies. It was hypothesized that the two classes of drugs might have, respectively, differential effects on transient activation of these assemblies of neurons working together.

Hippocampal tissue from juvenile Wistar rats was used for in vitro optical imaging with voltage-sensitive dyes and simultaneous field potential recordings. The response to paired pulse stimulation of the hippocampus was recorded in the presence and absence of two types of analgesic (morphine and gabapentin) and two types of anaesthetic (thiopental and propofol).

Optical imaging and electrophysiology used in parallel yield quite different results. Most consistently, the imaging technique was able to detect an enhanced period of activation following anaesthetic, but not analgesic application. This effect was not readily seen from electrophysiology field potential recordings.

These findings suggest that, irrespective of the effects of the two drug classes at a synaptic level, the dynamics of transient neuronal assemblies are modified selectively by anaesthetics and not analgesics.

Recombinant activated factor VII (rFVIIa) is a pharmacologic compound approved for the use in patients with congenital or acquired hemophilia and inhibiting antibodies toward factor VIII or IX. In recent years its use has been proposed in surgical patients demonstrating a lifethreatening bleeding, refractory to the standard therapies. The present study is a review of the clinical information available on the use of rFVIIa in cardiac surgery patients.

Current literature was investigated using a Pubmed search with appropriate key words (rFVIIa OR recombinant activated factor VII AND cardiac surgery).

35 articles were found. These are 11 case reports, 12 case series, 5 review articles, 3 retrospective studies, 2 letters to the Editor, and only one prospective, double-blinded, randomized clinical trial (RCT). The majority of the case reports and case series report a beneficial effect of this drug in the treatment of refractory bleeding. Comparative retrospective studies show conflicting results, and the only RCT demonstrate a significant reduction of allogeneic blood products use in patients treated with rFVIIa. No definitive information is available with respect to thromboembolic complications and general safety of this therapy.

rFVIIa is a promising agent for intractable bleeding in surgical patients. However, large prospective randomized trials are needed to define efficacy, dose, and potential side-effects.