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.

In human beings, pain and taste perception are two major sensory inputs. We investigated whether increasing bitter taste sensitivity would increase intensity or incidence of pain associated with propofol, and whether there is a relationship between bitter sensitivity and venepuncture pain.

One hundred (50 males, 50 females) American Society of Anesthesiologists Grade I adults undergoing elective surgery were included in this study. Determination of the taste thresholds employed a series of propylthiouracil solutions. The filter paper disk method was used to measure the taste threshold. A 20-G intravenous (i.v.) cannula was inserted in the dorsum of the non-dominant hand. Venepuncture pain was assessed by using a numerical rating scale (NRS; 0, no pain and 10, extreme pain). Propofol 10 mL (100 mg) was injected over 30 s. Assessment of pain with i.v. propofol was made using a 4-point scale: 0, no pain; 1, mild pain; 2, moderate pain; 3, severe pain.

The NRS score of venepuncture pain was 2.8 ± 1.5. Sixty patients had pain during propofol injection. There was statistically significant correlation between bitter sensitivity and propofol injection pain, and between bitter sensitivity and venepuncture pain (P < 0.05).

We conclude that increased bitter taste sensitivity correlates with increased intensity or incidence of propofol injection pain and NRS of venepuncture pain.

The aim of this study was to compare the efficacy of topical levobupivacaine drops 0.75% vs. lidocaine drops 4% in cataract surgery.

We examined 203 patients undergoing cataract surgery by phacoemulsification. They were randomized into two groups: one received four drops of lidocaine 4% and the other received four drops of levobupivacaine 0.75%. The onset and offset times of sensory block were evaluated. Application, intraoperative and postoperative subjective pain was quantified by the patients using a verbal pain score. Complications, rates of supplemental anaesthesia, and the satisfaction of surgeon and patients were also recorded.

The mean sensory onset and offset times were significantly higher for the levobupivacaine group (P < 0.01). Pain score was lower in the levobupivacaine group than in the lidocaine one and the difference was statistically significant at all stages (P < 0.01). The mean satisfaction scores of patients and surgeon were also statistically higher for levobupivacaine (P < 0.01). No significant differences for complications and rates of supplemental anaesthesia were found.

Topical levobupivacaine 0.75% shows the same efficacy and safety as lidocaine 4% in cataract surgery by phacoemulsification. There was an adequate block with a good level of satisfaction of surgeon and patients. Levobupivacaine 0.75% offers a new and acceptable choice for topical anaesthesia in cataract surgery.

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.

The A-Line® auditory evoked potential index (AAI) (AEP Monitor/2, Danmeter A/S, Odense, Denmark) is a newly developed composite parameter representing the degree of hypnosis. We conducted a prospective, observational study to explore the performance and validity of the AAI during conventional sedation for gastrointestinal (GI) endoscopy.

Thirty adults of either sex, age <65, scheduled for combined oesophagogastroduodenoscopy (OGD) and colonoscopy under sedation with intravenous (i.v.) midazolam and alfentanil were enrolled. The sedative end-point was set at the Observer’s Assessment of Alertness/Sedation (OAA/S) score less than 4. An AEP Monitor/2 was used in all patients. AAI, sedation scores, heart rate (HR), blood pressure (BP) and SPO2 were recorded every 2 min up to the end of the procedure. Receiver operator characteristic analysis was used to test validity and to select optimal sedation.

There was a significantly positive correlation between AAI and OAA/S scores (ρ = 0.886; P < 0.001). The AAI also showed significant differences between subsequent levels of sedation scores (P < 0.001). AAI greater than 54 indicated fully awake or minimal sedation and values between 54 and 42 were suggestive of moderate sedation. Values between 42 and 34 were associated with moderate to deep sedation and readings below 34 were associated with deep sedation. The relative risk of SPO2 < 95% for OAA/S = 2 compared with 3 was 15.98 (95% confidence interval (CI): 3.94–64.81).

AAI is an effective tool for monitoring sedation during GI endoscopy induced by i.v. midazolam and alfentanil.

Tricyclic antidepressants are commonly employed orally to treat major depressive disorders and have been shown to be of substantial benefit in various chronic pain conditions. Among other properties they are potent Na+ channel blockers in vitro and show local anaesthetic properties in vivo. The present study aimed to determine their differential neurotoxicity, and that of novel derivatives as prerequisite for their potential use in regional anaesthesia.

To directly test neurotoxicity in adult peripheral neurons, the culture model of dissociated adult rat primary sensory neurons was employed. Neurons were incubated for 24 h with amitriptyline, N-methyl-amitriptyline, doxepin, N-methyl-doxepin, N-propyl-doxepin, desipramine, imipramine and trimipramine at 100 μmol, and at concentrations correlating to their respective potency in blocking sodium channels.

All investigated substances showed considerable neurotoxic potency as represented in significantly decreased neuron numbers in cultures as compared to controls. Specifically, doxepin was more neurotoxic than amitriptyline, and both imipramine and trimipramine were more toxic than desipramine or amitriptyline. Novel derivatives of tricyclic antidepressants were, in general, more toxic than the parent compound.

Tricyclic antidepressants and novel derivatives thereof show differential neurotoxic potential in vitro. The rank order of toxicity relative to sodium channel blocking potency was desipramine < amitriptyline < N-methyl amitriptyline < doxepin < trimipramine < imipramine < N-methyl doxepin < N-propyl doxepin.

In isolated–perfused lungs of lipopolysaccharide (LPS)-challenged rats, vasodilatation to inhaled nitric oxide (NO) is impaired. Inhibition of nitric oxide synthase 2 (NOS2) by aminoguanidine (AG) prevented hyporesponsiveness to inhaled NO. Here, we investigated whether NOS2-mediated nitrite/nitrate synthesis modulates responsiveness to inhaled NO.

Sprague–Dawley rats received intraperitoneally 0.5 mg kg−1 LPS. Four hours later, LPS-treated rats received 3, 10 or 30 mg kg−1 AG or 0.01, 0.1 or 1 mg kg−1S-methylisothiourea (SMT) by intraperitoneal injection. Sixteen to eighteen hours later, lungs were isolated and perfused, and pulmonary artery pressure (PAP) was elevated by 6–8 mmHg using the thromboxane analogue U46619. The decrease of PAP in response to inhaled NO and nitrate/nitrite levels in serum and perfusate was measured.

In rats treated with LPS alone or 0.01 or 0.1 mg kg−1 SMT, 40 ppm NO decreased PAP less than in rats treated with AG and 1 mg kg−1 SMT (−1.8 mmHg (95% confidence interval: −1.5 to −2.1) vs. −6.0 mmHg (−5.7 to −6.3), P < 0.01). Improved NO responsiveness was associated with lower serum and perfusate nitrite/nitrate levels than in rats with hyporesponsiveness to inhaled NO (102 μmol (82–122) vs. 282 μmol (261–303) and 8.1 μmol (6.9–9.3) vs. 19.8 μmol (17.2–22.4), respectively, P < 0.01).

These observations demonstrate that in isolated–perfused lungs of LPS-treated rats, NOS2 inhibition improved responsiveness to inhaled NO. Here, responsiveness to inhaled NO is dependent on the ability of NOS2 inhibitors to reduce nitrite and nitrate levels in serum and released in the lung.

Tissue depletion of adenosine during endotoxaemia has previously been described in the lung. Therapeutic approaches to prevent adenosine depletion and the role of A1 and A2 receptor agonists, however, have not been investigated until now.

In isolated and ventilated rabbit lungs, it was tested whether pretreatment with adenosine A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 10−7 mol, n = 6) or A2 receptor agonist 5′-(N-cyclopropyl)-carboxyamido adenosine (CPCA; 10−7 mol, n = 6) prior to injection of lipopolysaccharide (LPS) (500 pg mL−1) influenced pulmonary artery pressure (PAP), pulmonary energy content and oedema formation as compared with controls, solely infused with LPS (n = 6). Release rates of adenosine and uric acid were determined by high-performance liquid chromatography. Pulmonary tissue concentrations of high-energy phosphates were measured and the adenine nucleotide pool, adenosine 5′-triphosphate (ATP)/adenosine 5′-diphosphate (ADP) ratio and adenylate energy charge of the pulmonary tissue were calculated.

Administration of LPS induced increases in PAP within 2 h up to 20.8 ± 2.9 mmHg (P < 0.01). While pretreatment with the A1 agonist merely decelerated pressure increase (13.8 ± 1.1 mmHg, P < 0.05), the A2 agonist completely suppressed the pulmonary pressure reaction (9.6 ± 1.0 mmHg, P < 0.01). Emergence of lung oedema after exclusive injection of LPS up to 12.0 ± 2.9 g was absent after A1 (0.6 ± 0.5 g) and A2 (−0.3 ± 0.2 g) agonists. These observations were paralleled by increased adenosine release rates compared with LPS controls (P < 0.05). Moreover, tissue concentrations of ADP, ATP, guanosine 5′-diphosphate, guanosine 5′-triphosphate, nicotinamide-adenine-dinucleotide and creatine phosphate were significantly reduced after LPS. Consequently, the calculated tissue adenine nucleotide pool and the adenylate energy charge increased after adenosine receptor stimulation (P = 0.001).

Adenosine A1- and A2-receptor agonists reduced LPS-induced vasoconstriction and oedema formation by maintenance of tissue energy content. Thus, adenosine receptor stimulation, in particular of the A2 receptor, might be beneficial during acute lung injury.

Tracheal intubation may be more difficult in morbidly obese patients (body mass index >35 kg m−2) than in the non-obese. Recently, new video-assisted intubation devices have been developed. After some experience with videolaryngoscopy, we hypothesized that it could improve the laryngoscopic view in this specific population and therefore facilitate intubation. The aim of this study was to assess the benefit of a videolaryngoscope on the grade of laryngoscopy in morbid obesity.

We studied 80 morbidly obese patients undergoing bariatric surgery. They were randomly assigned to one of two groups. One group was intubated with the help of the videolaryngoscope and in the control group the screen of the videolaryngoscope was hidden to the intubating anaesthesiologist. The primary end-point of the study was to assess in both groups the Cormack and Lehane direct and indirect grades of laryngoscopy. The duration of intubation, the number of attempts needed as well as the minimal SPO2 reached during the intubation process were measured.

Grade of laryngoscopy was significantly lower with the videolaryngoscope compared with the direct vision (P < 0.001). When the grade of laryngoscopy was higher than one with the direct laryngoscopy (n = 30), it was lower in 28 cases with the videolaryngoscope and remained the same only in two cases (P < 0.001). The minimal SPO2 reached during the intubation was higher with the videolaryngoscope but it did not reach statistical significance.

In morbidly obese patients, the use of the videolaryngoscope significantly improves the visualization of the larynx and thereby facilitates intubation.

Postoperative nausea and vomiting after craniotomy may increase intracranial pressure and morbidity in children. This prospective, randomized, placebo-controlled and double-blinded study was designed to evaluate the antiemetic efficacy of prophylactic ondansetron after intracranial tumour resections in children.

Ninety children were divided into three groups and received saline (Group 1), ondansetron 150 μg kg−1 intravenously at dural closure (Group 2) or two doses of ondansetron 150 μg kg−1 intravenously, the second dose repeated after 6 h (Group 3). Episodes of nausea, emesis and side-effects were noted for 24 h postoperatively.

Overall 24 h incidence of postoperative nausea and vomiting was not significantly different among the three groups (9 (37.5%) in Group 1 vs. 7 (27%) in Group 2 and 8 (32%) in Group 3, P = 0.73). No difference in rescue antiemetic treatment or postoperative nausea and vomiting at specific time intervals (0–6 and 6–24 h postoperative period) was seen among the three groups. No significant side-effects were noted in any of the three groups.

Ondansetron, in this study of 90 children, was not very effective in preventing nausea and vomiting after neurosurgical operations.

Because the incidence of asthma appears to be increasing, the importance of proper perioperative management of individuals with asthma will also continue to increase. Although its mechanism of smooth muscle relaxation is unknown, propofol has been associated with less bronchoconstriction during anaesthetic induction. The aim of this study was to investigate the possible mechanism of these effects and the effects of propofol on the isolated trachea preparations from control and ovalbumin-sensitized guinea pigs.

Adult male guinea pigs, weighing 280–330 g, were randomly allocated to two experimental groups, each consisting of 10 animals. Ten guinea pigs were sensitized by intramuscular injections of 0.30 mL of a 5% (w/v) ovalbumin/saline solution into each thigh (0.6 mL total) on days 1 and 4, whereas the remaining 10 served as controls receiving a total of 0.6 mL distilled water on days 1 and 4 as placebo. The isolated trachea preparations were mounted in tissue baths with modified Krebs–Henseleit solution and aerated with 95% oxygen and 5% carbon dioxide. We tested the effects of propofol (10−7–10−3 M) on resting tension and after precontraction with carbachol and histamine on isolated trachea preparations from control and ovalbumin-sensitized guinea pigs. We also tested the effect of propofol on isolated trachea preparations precontracted with carbachol and histamine in the absence and presence of different inhibitors or antagonists. We investigated propofol responses in tracheal smooth muscle precontracted with CaCl2.

Propofol (10−7–10−3 M) produced a concentration-dependent relaxation of isolated tracheal preparations precontracted by carbachol (10−6 M) and histamine (10−6 M) in both groups. Preincubation with N(w)-nitro l-arginine methyl ester (3 × 10−5 M), indomethacin (10−5 M) or propranolol (10−4 M) did not produce a significant alteration on propofol-induced relaxation responses (P > 0.05), while preincubation with tetraethylammonium (3 × 10−4 M) significantly decreased the propofol-induced relaxation responses in both groups (P < 0.05). Propofol (10−7–10−3 M) induced concentration-dependently relaxations in isolated trachea rings precontracted with CaCl2 in both the control and ovalbumin-sensitized groups.

Propofol induced concentration-dependent relaxations in precontracted, isolated trachea smooth muscle of guinea pigs in both the control and ovalbumin-sensitized groups. These relaxations were independent of epithelial function and stimulation of β adrenergic receptors. Opened Ca2+-sensitive K+ channels and inhibited L-type Ca2+ channels can contribute to these relaxations.

Gabapentin and local anaesthetics may decrease postoperative pain and analgesic needs. The aim of the study was to investigate the effect of the combination of these drugs on the analgesic needs as well as on acute and late pain after abdominal hysterectomy.

Sixty patients undergoing abdominal hysterectomy were randomly assigned to receive postoperatively oral gabapentin 400 mg 6 hourly for 7 days plus continuous wound infusion of ropivacaine 0.75% for 30 h or placebo capsules identical to those of gabapentin for 7 days and continuous wound infusion of normal saline for 30 h. Morphine consumption (PCA) for 48 h, paracetamol 500 mg plus codeine 30 mg (Lonalgal® tablets) intake on days 3–7, visual analogue pain scores at rest and after cough during the first 7 postoperative days, the need for analgesics at home and the presence and incidence of pain after 1 month were recorded.

The treatment group consumed less cumulative morphine over the first 48 h (31 ± 13.2 mg vs. 50 ± 20.5 mg in controls, P < 0.001) and less Lonalgal® tablets on days 3–7 (z = 2.54, P = 0.011). The visual analogue score values at rest and after cough did not differ between the groups during the first 7 postoperative days. One month postoperatively, fewer patients in the treatment group experienced pain due to surgery than in the control group (17/27 vs. 21/24, P = 0.045).

Gabapentin and continuous wound infusion with ropivacaine 0.75% decreased analgesic needs and late pain in patients undergoing abdominal hysterectomy.

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.

To the best of our knowledge, the value of the plasma effect site equilibration rate constant (ke0) of propofol has not been reported in Chinese patients. The aim of this prospective, randomized study was to examine the characteristics of the time to peak effect (TPEAK) of propofol, a pharmacokinetic-independent descriptor of blood–brain equilibration, and ke0 derived from TPEAK with A-line auditory-evoked potential monitor and Aspect A-2000 bispectral index monitor in Chinese patients.

Two-hundred ASA I patients received a submaximal bolus dose of propofol (1.5 mg kg−1). TPEAK was randomly measured by means of the A-line auditory-evoked potential monitor (Group AAI (auditory-evoked potential index), n = 100) or the Aspect A-2000 bispectral index monitor (Group BIS, n = 100). Using TPEAK and four previously validated pharmacokinetic parameter sets of propofol, the ke0 was estimated according to a method proposed recently.

The mean TPEAK was 145 ± 35 s (50–224 s) and 74±24 s (38–143 s) in Groups AAI and BIS, respectively (P < 0.01 between groups). There were no correlations between the patient’s age and TPEAKs (r = 0.147 and 0.031 for Groups AAI and BIS). The median ke0 in Group AAI was 0.64 min−1 with the model of Marsh, 0.17 min−1 with the Schnider model, 0.78 min−1 with the Tackley model and 0.93 min−1 with the Shafer model. The median ke0 in Group BIS was 1.87 min−1 with the model of Marsh, 0.83 min−1 with the Schnider model, 2.14 min−1 with the Tackley model and 2.48 min−1 with the Shafer model (P < 0.01 between groups and models).

The TPEAK of propofol measured by the A-line auditory-evoked potential monitor is different from that measured by the Aspect A-2000 bispectral index monitor. The TPEAKs of propofol from auditory-evoked potential index and bispectral index, and the values of ke0 calculated based on TPEAKs are different from previous reports and appear to be not affected by age. Further studies need to be taken to validate clinically the ke0 values of propofol.

Endoscopic endonasal transphenoidal surgery has been recently proposed as a minimally invasive procedure for the treatment of pituitary adenomas. The main objective of the anaesthesiologist is to induce sufficient haemodynamic control together with rapid recovery at the end of surgery. The aim of this study was to examine recovery profile, surgical operative conditions and haemodynamic differences using remifentanil infusion with either propofol target controlled infusion system or sevoflurane.

Forty-four adult patients were enrolled in a prospective, randomized, single-blind, two-group study: Group P received propofol target controlled infusion system and remifentanil; Group S received sevoflurane and remifentanil for maintenance of anaesthesia.

No statistically significant differences between the two groups with regards to the haemodynamic changes, operative conditions as assessed by a four-step bleeding score (0–3), were obtained. Recovery times were considerably shorter after remifentanil–sevoflurane in comparison with remifentanil–propofol target controlled infusion system group (7.4 vs. 12.8 min, P < 0.01).

This study demonstrates that sevoflurane–remifentanil gives a faster recovery and equivalent intraoperative status compared with propofol target controlled infusion system with remifentanil for the endoscopic endonasal transphenoidal approach.

The French legislature passed a law in 2005 that assigns a new role to the physician and redefines his liability in end-of-life decisions.

This law is presented and discussed in context with current French legal practice.

This law emphasizes patient autonomy, advocating that the patient be fully informed before treatment, and creates specific procedures to be followed according to whether the patient is conscious or unconscious. In the latter situation, the law reinforces the role of both the patient’s surrogate and the patient’s advance directives in establishing consent. In these extreme situations, doctors have the option to request a second medical opinion. This joint decision-making procedure is laid down by law and becomes obligatory in the interests of transparency.

Respect for patients’ consent implies the possibility that they may refuse medical care, creating an ethical and legal dilemma of providing medical care or respecting the patients’ wishes. The key issue concerning end-of-life patients rests in the decisions taken concerning the continuation or withdrawal of life support and the administration of palliative care.