Transcranial Doppler is an innovative, flexible, accessible tool for the bedside monitoring of static and dynamic cerebral flow and treatment response. Introduced by Rune Aaslid in 1982, it has become indispensable in clinical practice. The main obstacle to ultrasound penetration of the skull is bone. Low frequencies, 1–2 MHz, reduce the attenuation of the ultrasound wave caused by bone. Transcranial Doppler also provides the advantage of acoustic windows representing specific points of the skull where the bone is thin enough to allow ultrasounds to penetrate. There are four acoustic windows: transtemporal, transorbital, suboccipital and retromandibular. The identification of each intracranial vessel is based on the following elements: (a) velocity and direction; (b) depth of signal capture; (c) possibility of following the vessel its whole length; (d) spatial relationship with other vessels; and (e) response to homolateral and contralateral carotid compression. The main fields of clinical application of transcranial Doppler are assessment of vasospasm, detection of stenosis of the intracranial arteries, evaluation of cerebrovascular autoregulation, non-invasive estimation of intracranial pressure, measure of effective downstream pressure and assessment of brain death. Mean flow velocity is directly proportional to flow and inversely proportional to the section of the vessel. Any circumstance that leads to a variation of one of these factors can thus affect mean velocity. The main pathological condition affecting flow velocity is the vasospasm. Vasospasm is a frequent complication of subarachnoid haemorrhage, it often remains clinically silent and the factors that make it symptomatic are largely unknown. Threshold velocities above which vasospasm comes into place are well defined as regards the median cerebral artery, while there is no consensus for the other vessels. Nevertheless, an increase in velocity alone is not sufficient to arrive at a diagnosis of vasospasm; a condition of hyperaemia also presents with an increase in flow velocity. The Lindegaard Index has therefore been introduced, which is defined by the ratio between the mean flow velocity in the median cerebral artery and the mean flow velocity in the internal carotid artery. Criteria for diagnosis of a stenosis >50% of an intracranial vessel with transcranial Doppler include: (a) segmentary acceleration of flow velocity; (b) drop in velocity below the stenotic segment; (c) asymmetry; and (d) circumscribed flow disturbances (turbulence and musical murmur). The transcranial Doppler enables us to assess both components of self-regulation. The static component is measured by observing changes in flow velocity caused by pharmacologically induced episodes of hypertension and hypotension. The dynamic component of autoregulation can be measured using a method devised by Aaslid known as the ‘cuff test’. A very effective and safe device for measuring cerebral autoregulation is the transient hyperaemic response test. This test is based on the compensatory vasodilatation of the arterioles, which occurs after brief compression of the common carotid. Csonyka proposed the following formula based on clinical observation for the calculation of cerebral perfusion pressure: CPP = MAP × FVd/FVm + 14. Brain death is defined as the irreversible cessation of all functions of the whole brain. The clinical criteria are usually considered sufficient to establish a diagnosis of brain death; however, they might not be sufficient in patients who have been on sedatives or when there are ethical or legal controversies. Many authors have demonstrated the existence of a transcranial Doppler pattern, which is typical of brain death.

Summary

Background and objective: Reducing postoperative mechanical ventilation in patients undergoing liver transplantation may have clinical and organizational advantages. On the basis of our experience, we here evaluate the possibility of practising immediate tracheal extubation in the operating theatre. Methods: In this prospective study, patients consecutively undergoing liver transplantation between 1 June 1999 and 31 May 2004 were extubated in the operating theatre at the end of surgery on the basis of standardized and universally accepted criteria, under conditions of haemodynamic and metabolic stability. Results: Two hundred and seven of the 354 patients (58.5%) were extubated immediately after the completion of the surgical procedure (mean time between end of surgery and extubation: 0.4 ± 1.4 min); two were re-intubated. In the last of the 5 yr of the study, the percentage of immediate extubations increased to 82.5%. During the study period, there was a progressive increase in the number of immediate extubations per individual member of the team of anaesthetists. The pre-transplant Child-Pugh severity of the underlying liver disease did not predict rapid extubation, but the Model for End-stage Liver Disease score of <11 did (receiver operator characteristic area under the curve = 0.61; P < 0.05). Conclusions: Immediate extubation after liver transplantation is possible in a substantial percentage of cases; confidence, habit and a spirit of emulation are decisive factors in encouraging anaesthetists to extend this practice to the largest possible number of patients. A successful immediate extubation may be an important indicator of perioperative quality of care in liver transplantation.

Background and objective: Magnesium has antinociceptive effects in animal and human models of pain. These effects are primarily based on the regulation of calcium influx into the cell. The aim of this study was to determine whether perioperative infusion of magnesium would reduce postoperative pain and anxiety.

Methods: Twenty-four patients, undergoing elective hysterectomy, received a bolus of 30 mg kg−1 magnesium sulphate or the same volume of isotonic sodium chloride solution intravenously before the start of surgery and 0.5 g h−1 infusion for the next 20 h. Intraoperative and postoperative analgesia were achieved with fentanyl and morphine respectively. Patients were evaluated pre- and postoperatively for anxiety.

Results: Fentanyl consumption and total morphine requirements were significantly decreased in the magnesium group compared to the control group. Postoperative anxiety scores and sedation were similar between groups.

Conclusions: Continuous magnesium infusion, including the pre-, intra-, and postoperative periods reduces analgesic requirements. These results demonstrate that magnesium can be an adjuvant for perioperative analgesic management.

Background and objective Midazolam may occasionally precipitate hostility and violence instead of tranquillity. We characterized these episodes, their rate of occurrence, the potential paradoxical responders and possible predisposing circumstances among patients undergoing lower body surgery under spinal or epidural anaesthesia and midazolam sedation.

Patients and methods Fifty-eight patients who fulfilled the study entry criteria and who underwent surgery within a 3-month period in a large metropolitan, university-affiliated hospital were enrolled. Sedation and restlessness in all patients were controlled by midazolam administered intravenously by the attending anaesthesiologist; these parameters were later objectively confirmed by recorded actigrams. If ‘paradoxical’ events occurred, flumazenil 0.1 mg 10 s−1 was injected until the aberrant behaviour ceased. Patients with paradoxical reactions were later compared with matched control patients selected from the study group to identify epidemiological characteristics.

Results The incidence of paradoxical events was 10.2% (six out of 58 patients, confidence limits 2.3–18.3%) and they occurred 45–210 min after sedation started; the only independent predictor was an age older than that of the entire study group. The mean cumulative and per weight doses of midazolam were similar for both the experimental and the study groups of patients: 7.3 ± 2.8 to 10.1 ± 3.6 mg, and 0.1 ± 0.04 to 0.12 ± 0.05 mg kg−1. Flumazenil 0.2–0.3 mg (range 0.1–0.5 mg) effectively stopped the midazolam-induced paradoxical activity within 30 s and surgery continued uneventfully.

Conclusions Flumazenil completely reverses midazolam-induced paradoxical reactions and they are more frequent in older patients.

Prothrombin complex concentrates are haemostatic blood products containing four vitamin K-dependent clotting factors (II, VII, IX and X). They are a useful, reliable and fast alternative to fresh frozen plasma for the reversal of the effects of oral anticoagulant treatments (vitamin K antagonists). They are sometimes used for factor II or factor X replacement in patients with congenital or acquired deficiencies. They are widely prescribed in Europe. Several retrospective and prospective studies have demonstrated their efficacy in normalizing coagulation and in helping to control life-threatening bleeding. Few side-effects, mainly thromboembolic events, have been reported. The link between these events and prothrombin complex concentrate infusion has, however, often been brought into question. The use of prothrombin complex concentrates in new promising indications such as the management of massive bleeding requires prospective studies providing a high level of evidence in a high-risk setting.

Background and objective The amount of procalcitonin eliminated in the urine and the plasma disappearance rate of procalcitonin were evaluated in patients with normal and impaired renal function, because patients with sepsis are a main target group for procalcitonin measurement, and these patients often develop renal dysfunction.

Methods Elimination of procalcitonin in the urine (μg 12 h−1) was measured in 76 patients. In another 67 patients, the 50% plasma disappearance rate (t½, h) was evaluated 48 h after peak concentrations (procalcitonin >2 μg L−1). Renal function was assessed by creatinine clearance.

Results Procalcitonin elimination in the urine was significantly reduced in patients with severe renal dysfunction. However, the plasma disappearance rate correlated only weakly with renal dysfunction (Spearman's rank correlation R = −0.36, P = 0.004, regression t½ = 49.87−0.15 creatinine clearance). The 25% quartile and median were 25.2 h and 30.0 h in patients with normal renal function, and 36.3 h and 44.7 h in patients with severely impaired renal function (creatinine clearance <30 mL min−1).

Conclusions Renal elimination of procalcitonin is not a major mechanism for procalcitonin removal from the plasma. Although the plasma disappearance rate may be prolonged up to 30–50% in some patients with renal dysfunction, clinical diagnostic decisions may not be severely influenced by this moderate prolongation of procalcitonin elimination. We conclude that procalcitonin can be used diagnostically in patients with renal failure as well as in those with normal renal function.

Summary

Background and objective: Despite the introduction of various less-invasive concepts of cardiac output measurement, pulmonary arterial thermodilution is still the most common measurement technique. Methods: This prospective controlled study was designed to compare different methods of cardiac output measurement simultaneously. Pulmonary arterial thermodilution, transpulmonary thermodilution (PiCCO™), trans-oesophageal echo-Doppler probe (HemoSonic™) and partial carbon dioxide rebreathing technique (NICO™ monitor) were evaluated against a peri-aortic transit-time flow-probe as reference method in a clinically relevant animal model. After approval from the Local Ethics Committee on Animal Research, the investigations were conducted in nine anesthetized domestic pigs. Systemic haemodynamics were modulated systematically by the application of catecholamines, caval occlusion and exsanguination. Statistical analysis was performed with Bland–Altman and linear regression. Results: A total of 366 paired cardiac output measurements were carried out at a reference cardiac output between 0.5 and 7 L min−1. The correlation coefficients for pulmonary arterial and transpulmonary thermodilution against reference were 0.93 and 0.95, for trans-oesophageal Doppler and partial rebreathing technique 0.84 and 0.77. Pulmonary arterial thermodilution and transpulmonary thermodilution showed comparable bias and limits of agreement. Where HemoSonic™ showed an overestimation of cardiac output at a higher precision, NICO™ overestimated low and underestimated higher cardiac output values. Conclusions: Our data suggest that pulmonary arterial thermodilution and PiCCO™ may be interchangeably used for cardiac output measurement even under acute haemodynamic changes. The method described by Bland and Altman demonstrated an overestimation of cardiac output for both thermodilution methods. HemoSonic™ and NICO™ offer non-invasive alternatives and complementary monitoring tools in numerous clinical situations. Trend monitoring and haemodynamic optimizing can be applied sufficiently, when absolute measures are judged critically in a clinical context. The use of the NICO™ system seems to be limited during acute circulatory changes.

Background and objective: Thymol is a naturally occurring phenol derivative used in anaesthetic practice as a stabilizer and preservative of halothane, usually at a concentration of 0.01%. Although analgesic effects have long been described for thymol and its structural homologue menthol, a molecular basis for these effects is still lacking. We studied the blocking effects of thymol and menthol on voltage-activated sodium currents in vitro as possible molecular target sites.

Methods: Whole cell sodium inward currents via heterologously (HEK293 cells) expressed rat neuronal (rat type IIA) and human skeletal muscle (hSkM1) sodium channels were recorded in the absence and presence of definite concentrations of either thymol or menthol.

Results: When depolarizing pulses to 0 mV were started from a holding potential of-70 mV, halfmaximum blocking concentrations (IC50) for the skeletal muscle and the neuronal sodium channel were 104 and 149 µmol for thymol and 376 and 571 µmol for menthol. The blocking potency of both compounds increased at depolarized holding potentials with the fraction of inactivated channels. The estimated dissociation constant K d for thymol and menthol from the inactivated state was 22 and 106 µmol for the neuronal and 23 and 97 µmol for the skeletal muscle sodium channel, respectively.

Conclusions: The results suggest that antinociceptive and local anaesthetic effects of thymol and menthol might be mediated via blockade of voltage-operated sodium channels with the phenol derivative thymol being as potent as the local anaesthetic lidocaine.

Summary

Background: The aim of this prospective, randomized, blinded study was to compare analgesic efficacy of continuous paravertebral and epidural analgesia for post-thoracotomy pain. Methods: Forty-two ASA physical status II–III patients undergoing lung resection surgery were randomly allocated to receive post-thoracotomy analgesia with either a thoracic epidural (group EPI, n = 21) or paravertebral (group PVB, n = 21) infusion of 0.2% ropivacaine (infusion rate: 5–10 mL h−1). The degree of pain at rest and during coughing, haemodynamic variables and blood gas analysis were recorded every 12 h for the first 48 h. Results: The area under the curve of the visual analogue pain score during coughing over time was 192 (60–444) cm h−1 in group EPI and 228 (72–456) cm h−1 in group PVB (P = 0.29). Rescue morphine analgesia was required in four patients of group EPI (19%) and five patients of group PVB (23%) (P = 0.99). The PaO2/FiO2 ratio reduced significantly from baseline values in both groups without between-group differences. The median (range) percentage reduction of systolic arterial pressure from baseline was −9 (0 to −9)% in group PVB and −17 (0 to −38)% in group EPI (P = 0.02); while clinically relevant hypotension (systolic arterial pressure decrease >30% of baseline) was observed in four patients of group EPI only (19%) (P = 0.04). Patient satisfaction with the analgesia technique was 8.5 (8–9.8) cm in group EPI and 9 (7.5–10) cm in group PVB (P = 0.65). Conclusions: Continuous thoracic paravertebral analgesia is as effective as epidural blockade in controlling post-thoracotomy pain, but is associated with less haemodynamic effects.

Summary

Background and objective: To produce up-to-date clinical practice guidelines on the prevention of venous thromboembolism in surgery and obstetrics. Methods: A Steering Committee defined the scope of the topic, the questions to be answered, and the assessment criteria. Eight multidisciplinary working groups (total of 70 experts) performed a critical appraisal of the literature in the following disciplines: pharmacology of antithrombotic agents, orthopaedics; general surgery (gastrointestinal (GI) and varicose vein surgery); urology; gynaecology and obstetrics; thoracic, cardiac and vascular surgery; surgery of the head, neck and spine; and surgery of burns patients. The resultant reports and guidelines were submitted for comment and completion of the Appraisal of Guidelines Research & Evaluation questionnaire to a total of 150 peer reviewers, before producing definite guidelines. Results: The report answers the following questions for each type of surgery: (i) What is the venous thromboembolism incidence according to clinical and/or paraclinical criteria in the absence of prophylaxis? (with stratification of venous thromboembolism risk into low, moderate and high categories); (ii) What is the efficacy and safety of the prophylactic measures used? (iii) When should prophylaxis be introduced and how long should it last? (iv) Does ambulatory surgery affect efficacy and safety of prophylaxis? Conclusions: Apart from answering the above questions, the guidelines provide a summary table for each discipline. This table stratifies types of surgery into the three risk categories, specifies the recommended prophylaxis for venous thromboembolism (pharmacological and/or mechanical) and grades each recommendation. In addition, whenever appropriate, the recommended prophylaxis is adjusted to low- and high-risk patients.

An acute pain service (APS) was set up to improve pain management after operation. We attempted to reduce the length of stay in the intensive care unit (ICU) of patients undergoing major surgery and to improve their homeostasis and rehabilitation using a multimodal approach (pain relief, stress reduction, early extubation). Patient-controlled epidural analgesia (PCEA) was a keystone of this approach. If PCEA was not applicable, patients received patient-controlled intravenous analgesia (PCIA) instead. Brachial plexus blockade (BPB) was used for surgery of the upper limbs. A computer based documentation system was used to help evaluate prospectively (a) the quality of analgesia, (b) adverse effects and risks of the special pain management techniques, and (c) cost-effectiveness.

Patients receiving PCEA (n = 5.602) received a patient-titrated continuous infusion into the epidural space of either bupivacaine 0.175% or ropivacaine 0.2%, with 1 μg sufentanil mL−1 added, followed by patient-controlled boluses of 2 mL (lockout time 20 min). For patients receiving PCIA (n = 634) an initial bolus of 7.5–15 mg piritramide was given, and the subsequent bolus was 2 mg (lockout time 10 min). A continuous infusion of bupivacaine 0.25% was administered to patients receiving BPB (n = 113). The dose was titrated to a dynamic visual analogue scale (VAS) scores < 40.

The mean treatment periods were: BPB = 4.33 days, PCEA = 5.6 days, PCIA = 5.0 days. In the case of PCEA, the quality of pain relief, vigilance and satisfaction were superior compared with the PCIA method, which resulted in greater sedation and nausea. Although personal supervision was higher for the PCEA-treated patients, cost analysis revealed final savings of €91 620 for the year 1998 obviating the need for an ICU stay totalling 433 days.

Provided that PCEA is part of a fast-track protocol employing early tracheal extubation and optimal perioperative management, the associated initial higher costs will be recouped by the benefits to patients of better pain relief after surgery and fewer days subsequently spent in the ITU.

Summary

Background and objective: Unlike midazolam, melatonin premedication is not associated with cognitive impairment in adults despite its anxiolytic properties. The use of melatonin as a premedicant in children has not been reported. This randomized, double-blind, placebo-controlled study compared the perioperative effects of different doses of melatonin and midazolam in children.

Methods: Seven groups of children (n = 15 in each) were randomly assigned to receive one of the following premedicants. Midazolam 0.1, 0.25 or 0.5 mg kg−1 orally, melatonin 0.1, 0.25 or 0.5 mg kg−1 orally each mixed in 15 mg kg−1 acetaminophen, or placebo only (15 mg kg−1 acetaminophen). Anxiety and temperament were evaluated before and after administration of the study drug, on separation from parents and on the introduction of the anaesthesia mask. At week 2 postoperatively, the behaviour of the children was measured by the Post Hospitalization Behaviour Questionnaire.

Results: Melatonin or midazolam each in doses of 0.25 or 0.5 mg kg−1 were equally effective as premedicants in alleviating separation anxiety and anxiety associated with the introduction of the anaesthesia mask. A trend was noted for midazolam to prolong recovery times as the dosage increased. The use of melatonin was associated with a lower incidence (P = 0.049) of excitement at 10 min postoperatively, and a lower incidence (P = 0.046) of sleep disturbance at week 2 postoperatively than that observed with midazolam and control groups. No postoperative excitement was noted in the melatonin groups at 20, 30 and 45 min.

Discussion: Melatonin was not only as effective as midazolam in alleviating preoperative anxiety in children, but it was also associated with a tendency towards faster recovery, lower incidence of excitement postoperatively and a lower incidence of sleep disturbance at week 2 postoperatively.

Summary

Background and objective: Gabapentin has been suggested to decrease acute postoperative pain. We evaluated the effect of gabapentin on pain after abdominal hysterectomy. Methods: Sixty patients scheduled for abdominal hysterectomy were randomized to receive orally gabapentin 400 mg 6 hourly or placebo. Treatment started 18 h preoperatively and continued for 5 postoperative days. Pain (visual analogue score) and consumption of morphine for 48 h and of oral paracetamol/codeine were recorded after 2, 4, 8, 24 and 48 h and on days 3–5 postoperatively. After 1 month, patients were interviewed by phone for pain, and analgesic intake after hospital discharge. Results: Morphine consumption (mean ± SD) was 35 ± 15.7 mg in the control and 28 ± 12.1 mg in the gabapentin group (P = 0.21). Median number (range) of paracetamol 500 mg/codeine 30 mg tablets taken during days 3–5 was 1.0 (0–6) in the control and 2.0 (0–9) in the gabapentin group (P = 0.35). The visual analogue scores at rest and after cough did not differ between the two groups (F = 0.92, df = 1, P = 0.34 and F = 0.56, df = 1, P = 0.46, respectively). One month after surgery, 22/27 (81%) of the control group and 9/25 (36%) of the gabapentin group reported pain in the surgical area (χ2 = 11.15, P = 0.002), while 11/27 (41%) of controls and 7/25 (28%) of gabapentin patients consumed analgesics for pain (χ2 = 0.93, P = 0.39). The intensity of pain was decreased in the gabapentin group (χ2 = 12.6, P = 0.003). Conclusions: Gabapentin has no effect on immediate pain after abdominal hysterectomy but decreases pain 1 month postoperatively.

Summary

Background and objective: To determine if there is any significant difference between the effects of desflurane, isoflurane and sevoflurane on the QT interval, QT dispersion, heart rate corrected QT interval and QTc dispersion of the electrocardiogram.

Methods: The study was conducted in a prospective, double blind and randomized manner in a teaching hospital. Ninety ASA I patients, aged 16–50 yr, undergoing general anaesthesia for noncardiac surgery were studied.

Results: There was no significant change in QT intervals during the study in any group (P > 0.05). QT dispersion in the sevoflurane group 49 ± 14 ms vs. 37 ± 10 ms; in the desflurane group 55 ± 16 and 62 ± 21 ms vs. 35 ± 14 ms and in the isoflurane group 54 ± 26 and 59 ± 24 ms vs. 42 ± 19 ms were significantly increased at 3 and 10 min after 1 MAC of steady end-tidal anaesthetic concentration compared with baseline values (P < 0.05). QTc values in the sevoflurane group were 444 ± 24 and 435 ± 21ms vs. 413 ± 19 ms (P < 0.05), in the isoflurane group were 450 ± 26 and 455 ± 34 ms vs. 416 ± 34 ms (P < 0.05), in the desflurane group were 450 ± 26 and 455 ± 34 ms vs. 416 ± 34 ms (P < 0.05) at 3 and 10 min after reaching 1 MAC of anaesthetic concentration and significantly increased compared with baseline values. QTc dispersion increased significantly with sevoflurane 62 ± 14 ms vs. 45 ± 16 ms (P < 0.05); isoflurane 70 ± 36 ms at 3 min and 75 ± 36 ms at 10 min after reaching 1 MAC of anaesthetic concentration vs. 50 ± 24 ms (P < 0.05); desflurane 67 ± 25 ms at 3 min and 74 ± 27 ms at 10 min after 1 MAC concentration vs. 41 ± 22 ms (P < 0.05).

Conclusion: Sevoflurane, isoflurane and desflurane all prolonged QTd, QTc and QTcd but there were no significant intergroup differences.