Symptoms after surgery and anaesthesia influence the patient´s ability to resume daily activities. If postoperative symptoms are controlled rehabilitation may be accelerated. The aims of this dissertation were to identify disturbing symptoms reported by patients after gynaecological surgery, to investigate what effect prohylactic treatment with antiemetics has on these symptoms and whether or not sensory simulation of the P6-acupressure has an effect on postoperative nausea and vomiting (PONV) and motion sickness.

Methods: Total 1138 women participated in three clinical trials (Studies I, II, III) and one experimental study (Study IV). A questionnaire investigating postoperative symptoms was constructed and validated. The questionnaire was used in a prospective, consecutive, doubleblind, randomised, multicentre, and controlled study to identify incidence, and intensity of postoperative symptoms and the effect of common antiemetics (droperidol and granisetron) (Study III). The patients were followed for 24 h. In two studies (I, II) P6-acupressure was compared (prospective, double-blind, ransomised, controlled) with placebo acupressure and a reference group where the effect on PONV was followed over 24 h. The effect of P6-acupressure and placebo acupressure on motion sickness induced by a nauseogenic motion challenge was studied (Study III).

Results: A high incidence and severity of postoperative symptoms were found after gynaecological surgery in a group with a high risk (>30%) for PONV. Sixty-four per cent (107/165) of the patients experienced disturbing symptoms after surgery and 46 % (76/165) scored their symptoms as moderate to very severe. Fourty-eight per cent (79/165) had two or more symptoms. A higher incidence of symptoms were reported in the groups with prophylactic treatment, granisetron 74% (123/165) and droperidol 80% (133/165) compared to the control group 41% (69/165) (P <0.05). The relative risk reduction for PONV with granisetron or droperidol prophylaxis is 27% respective 22%. The relative risk increase for headache is 63% after granisetron, and 44% for difficulty with accommodation after droperidol. Less PONV was seen after P6-acupressure, 33% (44/135) compared to reference group 46% (63/136) (p = 0.019), number needed to treat (NNT) was 7 [95% confidence interval (CI) 4- 6]. When comparing laparoscopic and vaginal surgery (subgroup analysis) the main effect was in the vaginal group (day-case surgery), 36% (27/75) in the reference group to 27% (23/86) in the placebo group and to 20% (17/84) in the P6-acupressure group, (P = 0.017), NNT for the vaginal group was 6 [95% CI 3-18]. P6-acupressure increased time to nausea after a laboratory motion challenge and reduced the total number of symptoms reported (p <0.009).

Conclusions: There is no clinical efficacy in the form of reduced postoperative symptoms after prophylactic antiemetics (droperidol and granisetron) in females with a high risk (>30%) for PONV undergoing gynaecological surgery. P6-acupressure reduces the incidence of PONV after gynaecological surgery in females with a high (>30%) risk for PONV. The effect seems to be most prominent after vaginal surgery. P6-acupressure increased tolerance to experimental nausogenic stimuli and reduced the total number of symptoms reported in females with a history of motion sickness.

Purpose: To investigate the effect of sensory stimulation of the P6 point on postoperative nausea and vomiting (PONV) after gynecological surgery in the everyday clinical setting (effectiveness study).

Methods: Four hundred and ten women undergoing general anesthesia for elective gynecological surgery were included in a prospective, consecutive, randomized, multicentre, placebo-controlled, double-blind clinical trial with a reference group. One group was given bilateral P6 acupressure (n = 135), a second group similar pressure on bilateral non-acupressure points (n = 139), and a third group (n = 136) served as reference group. Nausea (scale 0–6), vomiting, pain, and satisfaction with the treatment were recorded. Primary outcome was complete response, i.e., no nausea, vomiting or rescue medication for 24 hr. Results were analyzed by applying logistic regression with indicators of treatments, type of operation and risk score for PONV as explanatory variables.

Results: Complete response was more frequent in the P6 acupressure group than in the reference group (P = 0.0194) Conversely, the incidence of PONV was 46% in the reference group, 38% after pressure on a non-acupoint and 33% after P6 acupressure. The decrease from 46% to 33% was statistically significant. When considering vaginal cases separately, the decrease in PONV was from 36% to 20% (P = 0.0168). The corresponding decrease from 59% to 55% in the laparoscopic surgery group was not statistically significant.

Conclusion: P6 acupressure is a non-invasive method that may have a place as prophylactic antiemetic therapy during gynecological surgery.

BACKGROUND: To give prophylactics or timely treatment for post-operative nausea and vomiting (PONV) is the question. We compared the intensity and number of disturbing post-operative symptoms (i.e. pain, PONV, headache, fatigue, etc.) after prophylactic antiemetic treatment in a group of patients with >30% risk for post-operative vomiting. METHODS: Four hundred and ninety-five patients, from three hospitals, planned for gynaecological surgery were randomized double blind. They were given granisetron 3 mg, droperidol 1.25 mg or no prophylactic antiemetic. Post-operative symptoms were followed for 24 h using a questionnaire. Symptoms were analyzed both according to their intensity and in a dichotomous fashion. RESULTS: The intensity of different symptoms differed depending on whether droperidol, granisetron or no antiemetic had been given (P = 0.005) but the overall incidence of moderate to very severe symptoms was similar in all groups. No group fared better in general. The total number of symptoms was higher in the groups given prophylactic treatment (P < 0.05). The relative risk reduction for PONV with granisetron or droperidol prophylaxis was 27%[95% confidence interval (CI) 8-43] and 22% (2-38), respectively. The NNT (number needed to treat) for granisetron (0-24 h) was 7 and for droperidol 8. The NNH (number needed to harm) (0-24 h) for headache and visual disturbances was 6 and 13 (NS) for granisteron and, 50 (NS) and 6 for droperidol. CONCLUSION: The intensity of symptoms or the total number of disturbing symptoms did not decrease after prophylactic antiemetic treatment in a group of patients, but the profile of disturbing symptoms changed. The relevance of post-operative symptoms in terms of patients' well-being needs to be addressed.

Purpose: In a previous study we noticed that P6 acupressure decreased postoperative nausea and vomiting (PONV) more markedly after discharge. As motion sickness susceptibility is increased by, for example, opioids we hypothesized that P6 acu-pressure decreased PONV by decreasing motion sickness susceptibility. We studied time to nausea by a laboratory motion challenge in a group of volunteers, during P6 and placebo acupressure.

Methods: 60 women with high and low susceptibilities for motion sickness participated in a randomized and double-blind study with an active P6 acupressure, placebo acupressure, and a control group (n = 20 in each group). The risk score for PONV was over 50%. The motion challenge was by eccentric rotation in a chair, blindfolded and with chin to chest movements of the head. The challenge was stopped when women reported moderate nausea. Symptoms were recorded.

Results: Mean time to moderate nausea was longer in the P6 acu-pressure group compared to the control group. P6 acupressure = 352 (259–445), mean (95% confidence interval) in seconds, control = 151 (121–181) and placebo acupressure = 280 (161–340); (P = 0.006). No difference was found between P6 and placebo acupressure or placebo acupressure and control groups. Previous severity of motion sickness did not influence time to nausea (P = 0.107). The cumulative number of symptoms differed between the three groups (P < 0.05). Fewer symptoms were reported in the P6 acupressure compared to the control group P < 0.009. Overall, P6 acupressure was only marginally more effective than placebo acupressure on the forearms.

Conclusion: In females with a history of motion sickness P6 acu-pressure increased tolerance to experimental nauseogenic stimuli, and reduced the total number of symptoms reported.

BACKGROUND: Acupuncture and acupressure have previously been reported to possess antiemetic effect. We wanted to investigate the "true" and placebo effect of acupressure in prevention of postoperative nausea and vomiting (PONV). PATIENTS AND METHODS: Sixty women undergoing outpatient minor gynaecological surgery were entered into a double-blind and randomised study. One group received acupressure with bilateral stimulation of P6 (A), a second group received bilateral placebo stimulation (P) and a third group received no acupressure wrist band and served as a reference group (R). PONV was evaluated as number of patients with complete response (no PONV), nausea only or vomiting. In addition, the need for rescue antiemetic medication and nausea after 24 h was registered. RESULTS: Complete response was obtained in 11, 11 and 9 patients in groups, A, P and R, respectively. Nine, 7 and 6 patients had nausea before discharge home, and 1, 1 and 8 patients were nauseated (8 vs 1 patient: P < 0.05) 24 h after operation in A, P and R groups, respectively. When compared to placebo acupressure (2 patients vomited and 5 needed rescue), significantly (P < 0.05) fewer needed rescue antiemetic medication after acupressure at P6 (no vomiting or rescue medication). When compared to the observation group (5 vomited and 4 needed rescue antiemetics), significantly fewer vomited after acupressure (P < 0.05) CONCLUSION: In patients undergoing brief gynaecological surgery, placebo effect of acupressure decreased nausea after 24 h but vomiting and need of rescue antiemetics was reduced only by acupressure with the correct P6 point stimulation.

Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1) protein, on lysosomal stability and sensitivity to lysosome-mediated cell death. We found that neurons with lysosomal cholesterol accumulation were protected from oxidative stress-induced apoptosis. In addition, human fibroblasts with cholesterol-loaded lysosomes showed higher lysosomal membrane stability than controls. Previous studies have shown that cholesterol accumulation is accompanied by the storage of lipids such as sphingomyelin, glycosphingolipids and sphingosine and an up regulation of lysosomal associated membrane protein-2 (LAMP-2), which may also influence lysosomal stability. However, in this study the use of myriocin and LAMP deficient fibroblasts excluded these factors as responsible for the rescuing effect and instead suggested that primarily lysosomal cholesterol content determined the cellular sensitivity to toxic insults. Further strengthening this concept, depletion of cholesterol using methyl-β-cyclodextrin or 25-hydroxycholesterol decreased the stability of lysosomes and cells became more prone to undergo apoptosis. In conclusion, cholesterol content regulated lysosomal membrane permeabilization and thereby influenced cell death sensitivity. Our data suggests that lysosomal cholesterol modulation might be used as a therapeutic strategy for conditions associated with accelerated or repressed apoptosis.

Purpose of review To present a review of the literature on the importance and the clinical characteristics relevant to adjuvants added to local anaesthetics in neuraxial and peripheral nerve blocks. Recent findings In neuraxial anaesthesia, both opioids and alpha-2 receptor agonists have beneficial effects. Intrathecally, fentanyl and sufentanil not only improve the postoperative analgesia but also make it possible to allow a decrease in the local anaesthetic dose. When clonidine or dexmedetomidine was added to intrathecal local anaesthetics, the regression of sensory, motor block increased dose-dependently and postoperative analgesia was prolonged. The potency of intrathecal clonidine:dexmedetomidine seems to be 10:1. In peripheral nerve block, when opioid was combined with local anaesthetics, no increased improvement in analgesia was reported in comparison with systemic controls in most of the studies, except buprenorphine. Also clonidine is controversial as an analgesic adjuvant. Special factors, such as type of local anaesthetics, block of upper or lower limb, are important for its the beneficial effect. Other adjuvants, except neuraxial low-dose neostigmine, are of minor importance. Summary Opioids and alpha-2 receptor agonists are important as neuraxial adjuvants to improve the quality of peroperative and postoperative analgesia in high-risk patients and in ambulatory procedures. In peripheral nerve blocks, however, some benefit is found only when clonidine is added to local anaesthetics under certain circumstances.

The last decades less invasive monitoring and analytical tools have been developed for the evaluation of myocardial mechanics in clinical praxis. In critical care, these are longed-for complements to pulmonary artery catheter monitoring, additionally offering previously inaccessible information. This work is aimed, during fluid-replacement and oxygen therapy, to determine the physiological interface of ventricular and vascular mechanical properties, which result in the transfer of blood from the heart to appropriate circulatory beds. In prospective clinical studies we investigated previously cardiovascular healthy adults during hyperoxemia, and during preoperative acute normovolemic hemodilution or early fluid resuscitation of severe burn victims. Echocardiography was used in all studies, transthoracic for healthy volunteers and transesophageal for patients. For vascular parameters and for control purposes pulmonary artery Swan-Ganz catheter, calibrated external pulse recordings, whole body impedance cardiography, and transpulmonel thermodilution method were applied.

We detected no significant change in blood pressure or heart rate, the two most often used parameters for patient monitoring. During preoperative acute normovolemic hemodilution a reduction of hemoglobin to 80 g/l did not compromise systolic or diastolic myocardial function. Cardiac volumes and flow increased with a concomitant fall in systemic vascular resistance while oxygen delivery seemed maintained. Supplemental oxygen therapy resulted in a linear dose-response between arterial oxygen and cardiovascular parameters, suggesting a direct vascular effect. Cardiac flow decreased and vascular resistance increased from hyperoxemia, and a decrease of venous return implied extracardial blood-pooling. Severe burns result in hypovolemic shock if not properly treated. The commonly used Parkland fluid replacement strategy, with urinary output and mean arterial pressure as endpoints, has recently been questioned. Applying this strategy, only transient early central hypovolemia was recorded, while dimensional preload, global left ventricular systolic function and oxygen delivery or consumption remained within normal ranges during the first 36 hours after accident. Signs of restrictive left ventricular diastolic function were detected in all patients and regional unstable systolic dysfunction was recognized in every other patient, and was consistent with myocardial marker leakage. Severe burns thereby cause myocardial stiffness and systolic regional dysfunction, which may not be prevented only by central normovolemia and adequate oxygenation.

Background: Preoperative acute normovolemic hemodilution may compromise oxygen transport. The aims of our study were to describe the hemodynamic effects of normovolemic hemodilution and to determine its effect on systolic and diastolic cardiac function by multiplane transesophageal echocardiography.

Methods: In eight anesthetized patients (aged 13-51 yr) without heart disease, hemoglobin was reduced in steps from 123 ± 8 (mean ± SD) to 98 ± 3 and to 79 ± 5 g/l. Hemodynamic measurements (intravascular pressures, thermodilution cardiac output, and echocardiographic recordings) were obtained during a stabilization period and at each level of hemodilution. Left ventricular wall motion was monitored continuously, and Doppler variables, annular motion, and changes in ejection fractional area were analyzed off-line.

Results: During hemodilution, cardiac output by thermodilution increased by 16 ± 7% and 26 ± 10%, corresponding well to the increase in cardiac output as measured by Doppler (difference, 0.32 ± 1.2 l/min). Systemic vascular resistance fell 16 ± 14% and 23 ± 9% and pulmonary capillary wedge pressure increased slightly (2 ± 2 mmHg), whereas other pressures, heart rate, wall motion, and diastolic Doppler variables remained unchanged. Ejection fractional area change increased from 44 ± 7% to 54 ± 10% and 60 ± 9% as a result of reduced end-systolic and increased end-diastolic left ventricular areas.

Conclusions: A reduction in hemoglobin to 80 g/l during acute normovolemic hemodilution does not normally compromise systolic or diastolic myocardial function as determined by transesophageal echocardiography. Preload, left ventricular ejection fraction, and cardiac output increase with a concomitant fall in systemic vascular resistance.

Background: The Parkland formula (2-4 mL/kg/burned area of total body surface area %) with urine output and mean arterial pressure (MAP) as endpoints; for the fluid resuscitation in burns is recommended all over the world. There has recently been a discussion on whether central circulatory endpoints should be used instead, and also whether volumes of fluid should be larger. Despite this, there are few central hemodynamic data available in the literature about the results when the formula is used correctly.

Methods: Ten burned patients, admitted to our unit early, and with a burned area of >20% of total body sur-face area were investigated at 12, 24, and 36 hours after injury. Using transesophageal echocardiography, pulmonary artery catheterization, and transpulmonary thermodilution to monitor them, we evaluated the cardiovascular coupling when urinary output and MAP were used as endpoints.

Results: Oxygen transport variables, heart rate, MAP, and left ventricular fractional area, did not change significantly during fluid resuscitation. Left ventricular end-systolic and end-diastolic area and global end-diastolic volume index increased from subnormal values at 12 hours to normal ranges at 24 hours after the burn. Extravascular lung intrathoracal blood volume ratio was increased 12 hours after the burn.

Conclusions: Preload variables, global systolic function, and oxygen transport recorded simultaneously by three separate methods showed no need to increase the total fluid volume within 36 hours of a major burn. Early (12 hours) signs of central circulatory hypovolemia, however, support more rapid infusion of fluid at the beginning of treatment.

Aim: The aim of the study was to examine the central and peripheral cardiovascular adaptation and its coupling during increasing levels of hyperoxaemia. We hypothesized a dose-related effect of hyperoxaemia on left ventricular performance and the vascular properties of the arterial tree.

Methods: Oscillometrically calibrated arterial subclavian pulse trace data were combined with echocardiographic recordings to obtain non-invasive estimates of left ventricular volumes, aortic root pressure and flow data. For complementary vascular parameters and control purposes whole-body impedance cardiography was applied. In nine (seven males) supine, resting healthy volunteers, aged 23–48 years, data was collected after 15 min of air breathing and at increasing transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group, random order and blinded hyperoxemic protocol.

Results: Left ventricular stroke volume [86 ± 13 to 75 ± 9 mL (mean ± SD)] and end-diastolic area (19.3 ± 4.4 to 16.8 ± 4.3 cm²) declined (P < 0.05), and showed a linear, negative dose–response relationship to increasing arterial oxygen levels in a regression model. Peripheral resistance and characteristic impedance increased in a similar manner. Heart rate, left ventricular fractional area change, end-systolic area, mean arterial pressure, arterial compliance or carbon dioxide levels did not change.

Conclusion: There is a linear dose–response relationship between arterial oxygen and cardiovascular parameters when the systemic oxygen tension increases above normal. A direct effect of supplemental oxygen on the vessels may therefore not be excluded. Proximal aortic and peripheral resistance increases from hyperoxaemia, but a decrease of venous return implies extra cardiac blood-pooling and compensatory relaxation of the capacitance vessels.

Context: Measurement of blood haemoglobin concentration by pulse oximetry could be of value in determining when erythrocytes should be transfused during surgery, but the effect of infusion fluids on the results is unclear.

Objective: To study the effect of crystalloid and colloid fluid on the accuracy (bias) and precision of pulse oximetry haemoglobin estimation to indicate the venous haemoglobin concentration in volunteers.

Design: Open interventional crossover study.

Setting: Single university hospital.

Participants: Ten male volunteers aged 18–28 (mean 22) years.

Interventions: Each volunteer underwent three infusion experiments on separate days and in random order. The infusions were Ringer's acetate (20 ml kg⁻¹), hydroxyethyl starch 130/0.4 (10 ml kg⁻¹) and a combination of both.

Results: At the end of the infusions of Ringer's acetate, pulse oximetry haemoglobin concentration had decreased more than the true haemoglobin concentration (15 vs. 8%; P < 0.005; n  = 10) whereas starch solution decreased pulse oximetry haemoglobin concentration less than true haemoglobin concentration (7 vs. 11%; P < 0.02; n  = 20). The same differences were seen when the fluids were infused separately and when they were combined. The overall difference between all 956 pairs of pulse oximetry haemoglobin concentration and true haemoglobin concentrations (the bias) averaged only −0.7 g l⁻¹ whereas the 95% prediction interval was wide, ranging from −24.9 to 23.7 g l⁻¹. In addition to the choice of infusion fluid, the bias was strongly dependent on the volunteer (each factor, P < 0.001).

Conclusion: The bias of measuring haemoglobin concentration by pulse oximetry is dependent on whether a crystalloid or a colloid fluid is infused.

The anaesthetic propofol interacts with the GABAA receptor, but its cellular signalling pathways are not fully understood. Propofol causes reorganisation of the actin cytoskeleton into ring structures in neurons. Is this reorganisation a specific effect of propofol as apposed to GABA, and which cellular pathways are involved? We used fluorescence-marked actin in cultured rat neurons to evaluate the percentage of actin rings caused by propofol or GABA in combination with rho, rho kinase (ROK), PI3-kinase or tyrosine kinase inhibitors, with or without the presence of extracellular calcium. Confocal microscopy was performed on propofol-stimulated cells and changes in actin between cellular compartments were studied with Western blot. Propofol (3 μg·ml-1), but not GABA (5 μM), caused transcellular actin ring formation, that was dependent on influx of extracellular calcium and blocked by rho, ROK, PI3-kinase or tyrosine kinase inhibitors. Propofol uses rho/ROK to translocate actin from the cytoskeleton to the membrane and its actin ring formation is dependent on an interaction site close to the GABA site on the GABAA receptor. GABA does not cause actin rings, implying that this is a specific effect of propofol.

Anaesthesia is given to approximate 5% of the Swedish population annually, with the great advantage of painless surgery, but it also has side effects such as depression of blood pressure that might give a heart infarction. Exactly how anaesthetic agents cause anaesthesia is poorly known. Most anaesthetics have been shown to interact with the GABA_A receptor, whose endogenous ligand GABA causes down-regulation of the brain and sleep. To further explore the cellular signal system used by anaesthetics this study was performed.

First, two different malignant cell lines, PC-12 and SH-SY5Y, were tested, to evaluate if they could replace animal cells; however, they did not respond with increased intracellular calcium [Ca²⁺]_i upon stimulation with propofol, as the normal rat neurons do. This is probably due to differences in the intracellular signaling systems in these malignant cells. Therefore, the studies in this thesis were performed on rat neurons.

Propofol, an intravenous anaesthetic, was shown to cause a bicucullin insensitive increase in [Ca²⁺]_i, where the release from intracellular stores was dependent on a tyrosine kinase. Sevoflurane, a volatile anaesthetic, also caused an ilrunediate increase in [Ca²⁺]_i, but not nitrous oxide. Increased [Ca²⁺]_, is supposed to augment the influx of chloride ions through the GABA_A receptor, hence hyperpolarising the neuron, and thereby make it anaesthetised.

Tyrosine phosphorylation of the GABA_A receptor is necessary for its function. Propofol tyrosine phosphorylates another ß2 subunit in the membrane then GABA. Propofol, but not GABA, also caused a tyrosine phosphorylation of actin in both the cytoskeletal and cell membrane fraction. Together these changes might explain the difference between sleep and anaesthesia. Isoflurane, sevoflurane and nitrous oxide all tyrosine phosphmylate a protein, suggested to be the GABAA receptor ß subunit, in different cellular compartments. This might explain their different clinical effects.

Propofol and sevoflurane, but not GABA, causes actin rings to be formed in the cell, and for propofol the signal goes via rhoA and rho kinase, that also are involved in the translocation of actin to the cellular membrane. An unl~own 160 kDa protein is tyrosine phosphorylated by propofol, is part of the rho signalling pathway and is regulated by rho, This unknown protein might be involved in the actin reorganisation.

Fast-track is a multimodal strategy aimed at reducing the physiological burden of surgery to achieve an enhanced postoperative recovery. The strategy combines unimodal evidence-based interventions in the areas of preoperative preparation, anesthesia, surgical factors and postoperative care. The advantages of fast-track most likely extend to gynecology, although so far have scarcely been reported. This review summarizes current evidence concerning use of fast-track in general and in gynecological surgery. The main findings of this review are that there are benefits within elective gynecological surgery, but studies of quality of life, patient satisfaction and health economics in elective surgery are needed. Studies of fast-track within the field of non-elective gynecological surgery are lacking. Widespread education is needed to improve the rate of implementation of fast-track. Close involvement of the entire surgical team is imperative to ensure a structured perioperative care aiming for enhanced postoperative recovery.

Objective. To determine whether postoperative symptoms differ between women who undergo abdominal benign hysterectomy in a fast-track model under general anesthesia or spinal anesthesia with intrathecal morphine. Design. Secondary analysis from a randomized, open, multicenter study. Setting. Five hospitals in south-east Sweden. Population. One-hundred and eighty women scheduled for benign hysterectomy were randomized; 162 completed the study; 82 were allocated to spinal and 80 to general anesthesia. Methods. The Swedish Postoperative Symptoms Questionnaire, completed daily for 1 week and thereafter once a week until 5 weeks postoperatively. Main Outcome Measures. Occurrence, intensity and duration of postoperative symptoms. Results. Women who had hysterectomy under spinal anesthesia with intrathecal morphine experienced significantly less discomfort postoperatively compared with those who had the operation under general anesthesia. Spinal anesthesia reduced the need for opioids postoperatively. The most common symptoms were pain, nausea and vomiting, itching, drowsiness and fatigue. Abdominal pain, drowsiness and fatigue occurred significantly less often and with lower intensity among the spinal anesthesia group. Although postoperative nausea and vomiting was reported equally in the two groups, vomiting episodes were reported significantly more often during the first day after surgery in the spinal anesthesia group. Spinal anesthesia was associated with a higher prevalence of postoperative itching. Conclusions. Spinal anesthesia with intrathecal morphine carries advantages regarding postoperative symptoms and recovery following fast-track abdominal hysterectomy.

Objective: The study objective was to compare total costs for hospital stay and postoperative recovery for two groups of women who underwent fast track abdominal benign hysterectomy, one group under general anesthesia, the other under spinal anesthesia. Costs were evaluated in relation to health related quality of life.

Study Design: Costs of treatment using data from a randomized multicenter study at five hospitals in Sweden were analyzed retrospectively. Of 180 women scheduled for benign abdominal hysterectomy; 162 were randomized for the study, 80 allocated to general anesthesia and 82 to spinal anesthesia.

Results: Total costs (hospital costs plus costs reduced productivity costs) were lower for the spinal anesthesia group. Women who had spinal anesthesia had a faster recovery measured by health related quality of life and QALYs gained in postoperative month one.

Conclusion: Use of spinal anesthesia for fast track benign abdominal hysterectomy was more cost-effective than general anesthesia.

Objective. To determine whether health-related quality of life (HRQoL) and postoperative recovery of women who undergo abdominal hysterectomy in a fast-track program under general anesthesia (GA) differ from women who receive spinal anesthesia with intrathecal morphine (SA). Design. Secondary analysis from an open randomized controlled multicenter study. Setting. Five hospitals in south-east Sweden. Population. One hundred and eighty women admitted for abdominal hysterectomy for benign disease were randomized; 162 completed the study, 80 with GA and 82 with SA. Methods. The HRQoL was measured preoperatively using the EuroQoL EQ-5D and the Short-Form-36 health survey (SF-36) questionnaires. The EQ-5D was used daily for 1 week; thereafter, once weekly for 4 weeks and again 6 months after operation. The SF-36 was completed at 5 weeks and 6 months. Dates of commencing and ending sick leave were registered. Main Outcome Measures. Changes in HRQoL; duration of sick leave. Results. The HRQoL improved significantly faster in women after SA than after GA. Sick leave was significantly shorter after SA than after GA (median 22.5 vs. 28 days). Recovery of HRQoL and duration of sick leave were negatively influenced by postoperative complications. In particular, the mental component of HRQoL was negatively affected by minor complications, even 6 months after the operation. Conclusions. Spinal anesthesia with intrathecal morphine provided substantial advantages in fast-track abdominal hysterectomy for benign gynecological disorders by providing faster recovery and shorter sick leave compared with general anesthesia.

Objective To determine whether the duration of hospital stay after abdominal hysterectomy in a fast-track setting differed between women operated under general anaesthesia or in spinal anaesthesia with intrathecal morphine. Design An open randomised controlled multicentre study. Setting Five hospitals in the south-east of Sweden. Population One hundred and eighty women scheduled for benign hysterectomy were randomised: 162 completed the study, 82 were allocated to spinal anaesthesia and 80 were allocated to general anaesthesia. Methods Fast-track model comprising no use of sedatives for premedication, pre-emptive anti-emetic therapy, intravenous fluid restriction, analgesics based on non-opioids, early enteral nutrition and mobilisation, and standard criteria for discharge. Spinal anaesthesia with 20 mg hyperbaric bupivacaine and 0.2 mg morphine. General anaesthesia with propofol, fentanyl and rocuronium, and with continuous propofol and ventilation with oxygen-in-air for maintenance of anaesthesia. Main outcome measures Hospital stay, consumption of analgesics, vomiting, pruritus and bowel function recovery. Results Median hospitalisation did not differ significantly between women who had hysterectomy with spinal or general anaesthesia (46 and 50 hours, respectively). Spinal anaesthesia was associated with a significantly lower use of opioids and a faster recovery of bowel function, although vomiting and pruritus were more prevalent. Conclusions In a fast-track model the duration of hospitalisation after abdominal hysterectomy was andlt; 50 hours, independent of the mode of anaesthesia. Spinal anaesthesia reduced the need for postoperative morphine compared with general anaesthesia. In order to improve patient recovery after gynaecological surgery further studies based on fast-track programmes are needed.

Objective: To test the hypothesis that hypoproteinemia reduces plasma volume expansion produced by a bolus of crystalloid solution given to awake sheep. Design: Prospective and observational. Setting: Laboratory. Subjects: Five female merino sheep (n = 5) weighing 37 +/- 3 kg were anesthetized. Interventions: Each animal was subjected to a 5-day test period: day 1: 50 mL/min 0.9% saline infusion over 20 mins. Days 2-4: daily plasmapheresis and replacement of the shed plasma with 6 L of 0.9% saline were performed in increments. Measurements and Main Results: Fractional plasma volume expansion after rapid infusion of saline on days 1 and 5 was calculated from changes in hemoglobin concentration. There was a significant reduction in total plasma protein concentration after plasmapheresis (p andlt; .05). Colloid osmotic pressures were also significantly lowered (p andlt; .05). A crystalloid infusion of 0.9% saline did not alter any of these values compared with baseline. The hemodynamic measurements did not show significant differences between the experiments. The plasma volume expansion reached approximately 20% at the end of infusion and stayed at 10-15% during the experiments. No difference was found in plasma volume expansion produced by a bolus of 50 mL/min of 0.9% in the hypoproteinemic state when compared with the euproteinemic state (p = .61). No difference in cumulative urinary output was found between the two states. Conclusions: In contrast to our hypothesis, severe acute hypoproteinemia does not reduce plasma volume expansion in response to 50 mL/min 0.9% saline infusion in nonspleenectomized sheep when compared with the resultant plasma volume expansion after a 50 mL/min of 0.9% infusion in the euproteinemic state.

Background A major risk with epidural analgesia is accidental dural puncture (ADP), which may result in post-dural puncture headache (PDPH). This survey was conducted to explore the incidence of ADP, the policy for management of PDPH and the educational practices in epidural analgesia during labour in the Nordic countries. Methods A postal questionnaire was sent to the anaesthesiologist responsible for Obstetric anaesthesia service in all maternity units (n=153) with questions relating to the year 2008. Results The overall response rate was 93%. About 32% (22-47%) of parturients received epidural analgesia for labour. There were databases for registering obstetric epidural complications in 13% of Danish, 24% of Norwegian and Swedish, 43% of Finnish and 100% of hospitals in Iceland. The estimated incidence of ADP was 1% (n approximate to 900). Epidural blood patch (EBP) was performed in 86% (n approximate to 780) of the parturients. The most common time interval from diagnosis to performing EBP was 24-48 h. The success rate for EBP was greater than 75% in 67% (62-79%) of hospitals. The use of diagnostic CT/MRI before the first or the second EBP was exceptional. No major complication was reported. Teaching of epidurals was commonest (86%) in the non-obstetric population and 53% hospitals desired a formal training programme in obstetric analgesia. Conclusion We found the incidence of ADP to be approximately 1%. EBP was the commonest method used for its management, and the success rate was high in most hospitals. Formal training in epidural analgesia was absent in most countries and trainees first performed it in the non-obstetric population.

Background: Airway condition is presumably reflected in epithelial lining fluid (ELF). Exhaled breath condensate (EBC) has been used as a surrogate marker of the composition of ELF.

Objectives: This study aimed at assessing the technical repeatability of chlorine measurements in EBC and comparing two separate condensators (Ecoscreen^® and R Tube^™) regarding recovery and repeatability. Furthermore, the association between condensate recoveries and variations in the airway status were scrutinized.

Methods: EBC was collected using two condensators from 10 healthy volunteers. In addition, 13 asthmatic patients produced EBC with or without an added resistance of 5 cm H₂O (Res5), applied to the outflow tract of Ecoscreen. All tests were done in random order. Chlorine levels (analyzed by a coulometric technique) in EBC served as a tool for investigation.

Results: Chlorine was measurable in all samples. The coefficient of repeatability of chlorine measurements was <10%. Chlorine levels were higher in EBC obtained from R Tube (p < 0.001), and differences in recoveries and variability in chlorine levels were presumably related to technical differences in the condensators and not to the repeatability of chlorine measurements per se. Air-flow-dependent chlorine levels were obtained from healthy volunteers. Application of Res5, recruiting additional alveoli, resulted in increased recovery of the EBC volume, but not of chlorine, from those that had the most pronounced airway obstruction (p = 0.05).

Conclusion: We conclude that by employing a sensitive analysis technique, chlorine is repeatedly measurable in EBC. We suggest that the bulk of chlorine in EBC originates from large airways and not from the alveolar area. Both condensators were comparable regarding repeatability but differed regarding chlorine recover

Background: Infiltration of inflammatory cells in bronchial mucosa and glandular hypersecretion are hallmarks of asthma. It has been postulated that exhaled breath condensate (EBC) mirrors events in epithelial lining fluid of airways, such as presence of local inflammation as well as glandular hypersecretion. It is also well known that eosinophil cationic protein (ECP) and cysteinyl-leukotrienes (cys-LT) are released by circulating inflammatory cells when triggered by antigen stimulation in asthma patients.

Objectives: The aim of this study was to evaluate whether chlorine and/or cys-LT in EBC would reflect changes of exposure of airborne pollen in patients with asthma.

Methods: EBC and serum were collected from 23 patients with allergic asthma during a pollen season and repeated 5 months later during a period with no aeroallergens. Chlorine was measured by means of a sensitive coulometric technique and cys-LT by an EIA technique. Serum ECP was measured and lung function tests were performed and symptoms noted during both occasions.

Results: Significantly higher concentrations of chlorine in EBC (p = 0.007) and ECP in serum (p = 0.003) were found during the pollen season compared to post-season. Chlorine levels tended to be higher in patients who reported of chest symptoms compared to those who denied symptoms during the pollen season (p = 0.06). Areas under the receiver-operated characteristic curves (AUC_ROC) were compared and similar discriminative power to identify exacerbations of asthma was recorded by chlorine in EBC (range 0.67-0.78) and ECP in serum (range 0.64-0.78).

Conclusion: It is concluded that chlorine in EBC and ECP in serum decreased significantly post-season, and this is suggested to mirror the decrement in airborne antigen. It is furthermore proposed that chlorine in EBC and ECP in serum tend to have a similar capacity to identify seasonal variations in airborne pollen in patients with asthma.

Examination of exhaled breath condensate (EBC) has been suggested to give information about inflammatory airway diseases.

The aim of the present study was to compare efficacy and variability in gain of two commercially available condensers, ECoScreen^® [E] and RTube^™ [R] in an in vitro experimental set up.

Methods: Test-fluids containing myeloperoxidase (MPO) or human neutrophil lipocalin (HNL) in addition to saline and bovine serum albumin (BSA) were nebulized. The aerosol was intermittently driven forward by a servoventilator fed by room tempered air, to reach the condenser. Two different concentrations of saline were also dispensed via the same equipment. Analyses of MPO, HNL and chlorine were done by means of ELISA, RIA or a modified adsorbed organic halogen technique (AOX), respectively.

Results: Significantly higher volumes were recovered by ECoScreen than by RTube during 20-minutes experiments (p<0.001) but not in ten-minute experiments (p>0.05). Based on changes of source concentrations in the nebulizer cup, resulting from nebulization per se, recoveries of HNL tended to be higher by E than by R (p<0.05). In contrast there were no significant differences between condensers in recoveries of MPO or chlorine. The spread of data was wide regarding all tested compounds and of similar degree for both condensers, despite acceptable inter-assay coefficients of variations of all analyses.

Conclusion: Condensing efficacy tended to be larger using E than R but there was a large variability in results from both condensers. Individual biomolecules may have their specific characteristics, and this must be taken into consideration when planning studies on EBC. We suggest that further methodological studies of the EBC method are warranted.

Context: Amino-terminal pro-brain-type natriuretic peptide is known to predict outcome in patients with heart failure, but its role in an intensive care setting is not yet fully established. Objective: To assess the incidence of elevated amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) on admission to intensive care and its relation to death in the ICU and within 30 days. Design: Prospective, observational cohort study. Setting: A mixed noncardiothoracic tertiary ICU in Sweden. Patients and main outcome measures NT-pro-BNP was collected from 481 consecutive patients on admission to intensive care, in addition to data on patient characteristics and outcome. A receiver-operating characteristic curve was used to identify a discriminatory level of significance, a stepwise logistic regression analysis to correct for other clinical factors and a Kaplan-Meier analysis to assess survival. The correlation between Simplified Acute Physiology Score (SAPS) 3, Sequential Organ Failure Assessment score (SOFA) and NT-pro-BNP was analysed using Spearmans correlation test. Quartiles of NT-pro-BNP elevation were compared for baseline data and outcome using a logistic regression model. Results: An NT-pro-BNP more than 1380 ng l(-1) on admission was an independent predictor of death in the ICU and within 30 days [odds ratio (OR) 2.6; 95% confidence interval (CI), 1.5 to 4.4] and was present in 44% of patients. Thirty-three percent of patients with NT-pro-BNP more than 1380 ng l(-1), and 14.6% of patients below that threshold died within 30 days (log rank P 0.005). NT-pro-BNP correlated moderately with SAPS 3 and with SOFA on admission (Spearmans rho 0.5552 and 0.5129, respectively). In quartiles of NT-pro-BNP elevation on admission, severity of illness and mortality increased significantly (30-day mortality 36.1%; OR 3.9; 95% CI, 2.0 to 7.3 in the quartile with the highest values, vs. 12.8% in the lowest quartile). Conclusion: We conclude that NT-pro-BNP is commonly elevated on admission to intensive care, that it increases with severity of illness and that it is an independent predictor of mortality.

[No abstract available]

BACKGROUND: Local infiltration analgesia (LIA)-using a combination of local anesthetics, nonsteroidal anti-inflammatory drugs, and epinephrine, injected periarticularly during surgery-has become popular in postoperative pain management after total knee arthroplasty (TKA). We compared intrathecal morphine with LIA after TKA. less thanbrgreater than less thanbrgreater thanMETHODS: In this double-blind study, 50 patients scheduled to undergo TKA under spinal anesthesia were randomized into 2 groups: group M, 0.1 mg morphine was injected intrathecally together with the spinal anesthetic and in group L, LIA using ropivacaine, ketorolac, and epinephrine was infiltrated in the knee during the operation, and 2 bolus injections of the same mixture were given via an intraarticular catheter postoperatively. Postoperative pain, rescue analgesic requirements, mobilization, and home readiness were recorded. Patient-assessed health quality was recorded using the Oxford Knee Score and EQ-5D during 3 months follow-up. The primary endpoint was IV morphine consumption the first 48 postoperative hours. less thanbrgreater than less thanbrgreater thanRESULTS: Mean morphine consumption was significantly lower in group L than in group M during the first 48 postoperative hours: 26 +/- 15 vs 54 +/- 29 mg, i.e., a mean difference for each 24-hour period of 14.2 (95% confidence interval [CI] 7.6 to 20.9) mg. Pain scores at rest and on movement were lower during the first 48 hours in group L than in group M (P andlt; 0.001). Pain score was also lower when walking in group L than in group M at 24 hours and 48 hours postoperatively (P andlt; 0.001). In group L, more patients were able to climb stairs at 24 hours: 50% (11 of 22) versus 4% (1 of 23), i.e., a difference of 46% (95% CI 23.5 to 68.5) and at 48 hours: 70% (16 of 23) versus 22% (5 of 23), i.e., a difference of 48% (95% CI 23 to 73). Median (range) time to fulfillment of discharge criteria was shorter in group L than in group M, 51 (24-166) hours versus 72 (51-170) hours. The difference was 23 (95% CI 18 to 42) hours (P = 0.001). Length of hospital stay was also shorter in group L than in group M: median (range) 3 (2-17) versus 4 (2-14) days (P = 0.029). Patient satisfaction was greater in group L than in group M (P = 0.001), but no differences were found in knee function, side effects, or in patient-related outcomes, Oxford Knee score, or EQ-5D. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: LIA technique provided better postoperative analgesia and earlier mobilization, resulting in shorter hospital stay, than did intrathecal morphine after TKA.

Background and purpose The degree of postoperative pain is usually moderate to severe following knee arthroplasty. We investigated the efficacy of local administration of analgesics into the operating area, both intraoperatively and postoperatively. Methods 40 patients undergoing unicompartmental knee arthroplasty (UKA) were randomized into 2 groups in a double-blind study (ClinicalTrials.gov identifier: NCT00653926). In group A (active), 200 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 106 mL) were infiltrated intraoperatively into the soft tissue, while in group P (placebo), no injections were given. 21 hours postoperatively, 150 mg ropivacain, 30 mg ketorolac, and 0.1 mg epinephrine were injected intraarticularly via a catheter in group A, whereas patients in group P were injected with the same volume of saline (22 mL). Results Median hospital stay was shorter in group A than in group P: 1 (1-6) days as opposed to 3 (1-6) days (p 0.001). Postoperative pain in group A was statistically significantly lower at rest after 6 h and 27 h and on movement after 6, 12, 22, and 27 h. Morphine consumption was statistically significantly lower in group A for the first 48 h, resulting in a lower frequency of nausea, pruritus, and sedation. Postoperatively, there were improved functional scores (Oxford knee score and EQ-5D) in both groups relative to the corresponding preoperative values. Interpretation Local injection of analgesics periarticularly at the end of the operation and intraarticularly at 21 h postoperatively provided excellent pain relief and earlier home discharge following UKA. There was a high degree of patient satisfaction in both groups after 6 months.

Background and purpose Postoperative pain is often severe after total knee arthroplasty (TKA). We investigated the efficacy of the local infiltration analgesia (LIA) technique, both intraoperatively and postoperatively. Methods 48 patients undergoing TKA were randomized into 2 groups in a double-blind study. In group A, 400 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine were infiltrated periarticularly during operation. In group P, no injections were given. 21 h postoperatively, 200 mg ropivacaine, 30 mg ketorolac, and 0.1 mg epinephrine were injected intraarticularly in group A, and the same volume of saline was injected in group P. All patients were followed up for 3 months. Results Median morphine consumption was lower in group A during the first 48 h: 18 (1-74) mg vs. 87 (36-160) mg in group P. Postoperative pain was lower at rest in group A during the first 27 h, and on movement during the first 48 h, except at 21 h. Time to fulfillment of discharge criteria was shorter in group A than in group P: 3 (1-7) vs. 5 (2-8) days. Patient satisfaction was higher in group A than in group P on days 1 and 7. The unbound venous blood concentration of ropivacaine was below systemic toxic blood concentrations. Interpretation The local infiltration analgesia (LIA) technique provides excellent pain relief and lower morphine consumption following TKA, resulting in shorter time to home readiness and higher patient satisfaction. There were few side effects and systemic LA concentrations were low.

Purpose: To compare bipolar resection with the conventional monopolar transurethral resection of the prostate (TURP) with respect to peri- and postoperative complications and long-term outcome. Patients and Methods: Patients with consecutive benign prostatic hyperplasia needing surgery (n = 185) from the hospitals waiting list were randomized to TURP using either a bipolar or a monopolar system. Peri-and postoperative parameters were monitored, complications were registered, and timed micturition/International Prostate Symptom Score (TM/IPSS) forms were collected at 3 and 6 weeks and at 6 and 18 months. Results: Bipolar surgery was followed by a 16% to 20% higher percentage of the patients reporting ongoing improvement (fractional IPSS change greater than2) at 3 and 6 weeks after the surgery (p less than 0.05). There were fewer readmissions in the bipolar group than in the monopolar (5 vs. 13, p less than 0.05). No differences between the groups with respect to hospital stay and catheter duration was recorded. Bipolar and monopolar TURP resulted in marked and sustained improvements of IPSS, bother score, and TM. Conclusions: Bipolar TURP, using the transurethral resection in saline (TURis) system, resulted in significantly fewer postoperative readmissions, faster postoperative recovery, and equally long-lasting good results in TM/IPSS and bother score, as in monopolar TURP.

Purpose: To compare the in vitro degree of vaporization in bipolar and monopolar resection. less thanbrgreater than less thanbrgreater thanMaterials and Methods: Using either a bipolar system or a monopolar system, samples of chicken muscle and lamb kidney were resected in an isolated basin and then desiccated in an incubator. The percentual degree of vaporization for each sample was obtained as a difference between the total fresh weight of the sample and the calculated fresh weights of the resected tissue and remains. less thanbrgreater than less thanbrgreater thanResults: Reference samples showed that the water content was 73% in muscle and 77% in kidney. More muscle (mean 52%) than kidney (32%; P andlt; 0.0001) tissue was vaporized. The fraction of vaporized tissue was significantly higher in the bipolar technique. In muscle, the differences between monopolar and bipolar were 17% (P andlt; 0.05) and 26% (P andlt; 0.001), respectively, depending on the type of irrigation used. For kidney, the differences were 27% (P andlt; 0.01) and 34% (P andlt; 0.01), respectively. Further exploration of the degree of vaporization when using the bipolar resection showed that the choice of loop (P andlt; 0.0001), fluid (P andlt; 0.03), and tissue (P andlt; 0.0001) were all independently associated with the degree of vaporization. less thanbrgreater than less thanbrgreater thanConclusions: This study indicated that vaporization removes 50% more tissue than the weight of the resected tissue during conventional tissue resection. Bipolar standard loop resection resulted in a significantly higher degree of vaporization in both muscle and kidney than did monopolar technique. Bipolar resection worked satisfactorily in Ringers acetate.

Background. Postoperative pain after radical retropubic prostatectomy is moderate to severe. The primary aim of this study was to assess whether intra-abdominal local anaesthetics provide similar analgesia compared with thoracic epidural analgesia (TEA). less thanbrgreater than less thanbrgreater thanMethods. Fifty patients, ASA I-II, participated in this prospective, double-blinded study. All patients had TEA. After operation, they were randomized into two groups of 25 patients: Group PCLA (patient-controlled local analgesia): self-administration of 10 ml of ropivacaine 2 mg ml(-1) via the intra-abdominal catheter for 48 h. Group TEA: infusion of 10 ml h(-1) of ropivacaine 1 mg ml(-1), fentanyl 2 mg ml(-1), and epinephrine 2 mg ml 21 epidurally for 48 h. The primary endpoint was pain on coughing at 4 h after operation. Rescue medication was morphine i.v. as required. less thanbrgreater than less thanbrgreater thanResults. Pain on coughing at 4, 24, and 48 h was significantly lower in Group TEA [0 (0-10)] compared with Group PCLA [4 (0-10)] (Pandlt;0.05). Significantly lower pain intensity was also found in Group TEA compared with Group PCLA at the incision site, deep pain, and pain on coughing at 4 and 24 h (Pandlt;0.05). Morphine consumption was significantly greater in Group PCLA [12 (0-46)] compared with Group TEA [0 (0-20)] at 0-48 h after operation [median (range)] (P=0.015). Maximum expiratory pressure was higher in Group TEA compared with Group PCLA at 24 h (Pandlt;0.01). less thanbrgreater than less thanbrgreater thanConclusions. TEA provides superior postoperative pain relief with better preservation of expiratory muscle strength compared with PCLA.

Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.

Objective: The aim of this study was to evaluate the urea clearance technique for the measurement of drug-induced blood flow changes in human skin, and compare it with two non-invasive techniques: polarization light spectroscopy and laser Doppler perfusion imaging.

Methods: Fifteen microdialysis catheters were placed intracutaneously on the volar aspect of the forearms of healthy human subjects, and were perfused with nitroglycerine, noradrenaline, and again nitroglycerine, to induce local tissue hyperaemia, hypoperfusion, and hyperaemia, respectively.

Results: Urea clearance, but not the other techniques, detected the changes in blood flow during all three periods of altered flow.  The last hyperaemic response was detected by all three methods.

Conclusion: Urea clearance can be used as a relatively simple method to estimate blood flow changes during microdialysis of vasoactive substances, in particular when the tissue is preconditioned in order to enhance the contrast between baseline and the responses to the provocations. Our results support that, in the model described, urea clearance was superior to the optical methods as it detected both the increases and decrease in blood flow, and the returns to baseline between these periods.

Microdialysis is a well-established technique for continuous sampling of small, water-soluble molecules within the extracellular fluid space in vivo. It also allows the use of microdoses of drugs, and the simultaneous evaluation of their related effects at the site of action. The present study was an experimental, randomized microdose trial to develop a human vascular model of dose response. We aimed to evaluate a microdialysis dosing method using urea clearance as a marker of druginduced changes in dermal blood flow and metabolism (glucose and lactate) in 12 healthy volunteers. We found that asymptomatic vasoconstriction can be detected by continuous microdialysis measurements of urea clearance in dermal tissue. More importantly, dose-effect relations using the E_max model could be constructed using the corresponding data on drug doses and both the urea clearance-based flow estimates and the changes in concentrations of tissue metabolites. This in vivo human experimental skin model offers an interesting tool with which both the dose-response effects on blood flow and concentrations of tissue metabolites of potent vasoactive substances can be evaluated.

Local blood flow reflexes in the foot skin of healthy controls and in young diabetic patients with or without nerve dysfunction have been studied using laser Doppler perfusion imaging (LDPI). A neurophysiological follow-up study on nerve dysfunction is presented as a complerhent to the work on blood flow regulation in the young diabetics.

An enhanced high-resolution LDPI (EHR-LDPI), intended for visualization and interpretation of flow dynamics in separate microvessels, has been adapted and evaluated in in vitro tube models and in an in vivo tissue model (hamster cheek pouch). By focusing the laser beam to 40 µm in the focal plane and reducing the step length to 25 µm, full format images (4096 measurement sites) of microvascular tissue areas as small as 1,5 x 1,5 mm were created.

The objectives of the work were to study if the vasoconstrictor response seen during change in posture is a mechanism elicited by a rise in venous pressure, but also to investigate if young diabetic patients with nerve dysfunction have an impairment in the local regulation of foot skin blood flow (postural vasoconstriction and hyperemic response) compared to diabetics without nerve dysfunction. An additional aim was to elucidate whether abnormal nerve conduction is retarded or even prevented by tight metabolic control in patients with type 1 diabetes mellitus.

The experimental studies aimed to improve the resolution of the EHR-LDPI system, to evaluate the system flow response in an in vitro model and to evaluate the performance, the limitations and the future potentials by studying flow dynamics in a tissue containing separate microvessels. It was concluded that:

(1) The LDPI recorded skin perfusion during variations in venous stasis and posture, adding information on flow distribution changes. The difference in flow distribution seen suggested an additive regulatory mechanism to a venoarteriolar reflex during change in posture.

(2) Subclinical nerve conduction defects were more common than microvascular abnormalities as measured by LDPI in the present models in young diabetic patients. Although, no signs of established retinopathy or nephropathy in this patient group, resting skin blood flow abnormalities were present, and these findings were related to high HbA1c-levels.

(3) Tight longwterm metabolic control, with HbA1c values less than 6,5%, could retard nerve dysfunction in patients with type 1 diabetes mellitus and a mean disease duration of 12 years.

(4) Using EHR-LDPI a decrease in signal level was obtained as the tube diameter increased, although the algorithm scaled linearly with velocity and was found not to be sensitive to hematocrit variations. Individual microvessel diameters could be estimated, which on average resulted in a difference of 11 µm compared to microscopic measurements.

(5) A dynamic overview of the vascular tree with volumetric flow estimate as well as RBC velocities of separate vessels was obtained. The need for further focusing of the beam and reduction of the step length appeared to be important tasks to solve in order to get a more accurate vessel diameter determination and to refine the volumetric flow estimate.

The purpose of the present study was to examine if functional impairment of the skin microvasculature is present in young diabetic patients with and without neurophysiological signs of nerve dysfunction. Dorsal foot skin blood flow was measured in young diabetics and controls using laser Doppler perfusion irnaging (LDPI). Blood flow was- measured during supine resting flow, during change in posture and during post occlusive hyperemia. Peripheral nerve function was measured by electrophysiological studies of peroneal and sural nerve conduction. Fifty seven (57%) percent of the diabetic patients had abnormal nerve conduction in two or several nerves. Diabetics with poor metabolic control (HbAlc > 7,5 %) showed an increase in supine resting blood flow compared to better regulated diabetics and controls. No other differences in skin blood flow between diabetics and controls were seen. During change in posture, blood flow increased instead of decreased in a majority of the study subjects. Low resting blood !low levels are suggested to contribute to this absence of postural vasoconstrictor response. It is concluded that nerve conduction defects arc much more common than microvascular abnormalities measured by LDPI in the present models in young diabetic patients. Our recommendation is to increase basal resting flow before applying vasoconstricting models in yotmg subjects when using LDPI in low flow areas, as the foot skin.

An enhanced high-resolution laser Doppler imager (EHR-LDI), configured to fit the demands of a measurement area containing separate microvessels, was evaluated for perfusion measurements in hamster cheek pouch preparations during ischemia, reperfusion, and pharmacologically induced vasodilation and vasoconstriction. Measurements in separate microvessels where the laser beam was smaller than the vessel diameter were referred to as red blood cell (RBC) velocity estimates, as previously validated in vitro, whereas a relative flow index, RFI (mean RBC velocity/tissue area), was introduced as a volumetric flow measure. Microvessel diameter and RBC velocity changes during ischemia, reperfusion, as well as during vasoconstriction and vasodilation correlated to the data obtained from the microscope. Correspondingly, during the described provocations anticipated volumetric flow changes were registered as changes in the RFI. When data on intravessel RBC velocity profiles are presented they reflect a parabolic flow profile usually seen in this size microvessel. The EHR-LDI appears a promising tool for investigation of the microvasculature, as it almost simultaneously provides information on relative changes of both in vivo RBC velocity and volumetric flow (RFI), although the latter estimate needs to be further refined.

The exact nature of the decrease in foot skin blood flow seen after a change in posture remains unsettled. This mechanism has previously been examined by non-invasive techniques such as the laser Doppler perfusion monitor (laser Doppler flowmetry). Taking into account the shortcomings of laser Doppler perfusion monitoring when applied to the determination of skin blood flow, which normally shows substantial heterogeneity, we have applied an emerging technology, the laser Doppler perfusion imager (LDPI). This technique provides a more comprehensive picture of the blood flow distribution in the skin, as it maps skin blood flow over a surface area (120×120 mm, 4096 measurement sites). It was used to examine if the reduction in tissue perfusion or the alterations in flow distributions seen after a change in posture (supine to dependency) could be fully explained by an increase in venous pressure (venous stasis of 50 mmHg) or if the data suggest a complementary mechanism.

Skin blood flow of the forefoot decreased from 0.60 V (volt) (median) during rest to 0.40 and 0.38 V during venous stasis and dependency, respectively. Although almost identical median values were obtained during stasis and dependency, the flow distributions were different, with a loss of high flow values during venous stasis. Biological zero was 0.24 V.

As the LDPI technique readily records skin perfusion during variations in venous stasis and posture, as well as information on flow distribution changes, it appears promising for future application in stimuli-response studies of skin blood flow. The difference in flow distribution seen between increased venous pressure and dependency suggests an additive regulatory mechanism to the veni-vasomotor reflex during a change in posture.

Purpose of review With the rapid increase in the number of sicker patients with multiple co-morbidities and extremes of age who are undergoing ambulatory surgery, a thorough and detailed preoperative workup has become increasingly important. Case cancellation on the morning of surgery should be an exception. Therefore, much attention is focused on the optimization of the sicker patients. Although the anesthesiologist plays a central role in the preoperative assessment, a multidisciplinary approach is critical. This review was done to provide the reader with current trends and practices in preoperative assessment of the ambulatory surgical patient. Recent findings The risk factors that may influence major morbidity, death or hospital admission include age greater than 85 years, hospital admission within the previous 6 months and invasiveness of surgery. The American Society of Anesthesiologists physical status greater than 2 can predict in-hospital adverse events. Routine preoperative investigations in the healthy patient, including electrocardiogram are, today, unwarranted and have not been shown to improve outcome. Summary Risk management involves the identification of the patient at risk, optimization of preoperative health status, risk reduction through medical intervention as well as appropriate perioperative care. Thus, patient outcome can be improved, specifically for the sicker patients at a higher risk.

Purpose of review Wound infiltration analgesia using local anaesthetics has been used for several decades. Recently, newer techniques to prolong analgesia have developed, including the use of catheters and injection of local anaesthetics or other adjuvants, and local infiltration analgesia using large volumes of local anaesthetics injected into different tissue planes. The aim of this review is to present the current status of wound infiltration analgesia in management of postoperative pain and to highlight the risks of this technique in clinical practice. Recent findings Several studies have shown beneficial effects of local anaesthetics, with or without adjuvant drugs, in the management of postoperative pain. Specifically, the use of local anaesthetics injected via catheters to prolong analgesia reduces postoperative pain, albeit to a limited extent. The use of large volumes of local anaesthetics into tissue planes during surgery is also beneficial in pain management. Single doses of local anaesthetics provide pain relief, but the short duration of effect can be a limiting factor. There is a growing concern about some side-effects associated with the use of local anaesthetics, specifically toxicity when drugs are injected in large doses, chondrotoxicity when bupivacaine is injected intra-articularly in higher concentrations and over a period and finally, infection when using catheters that are retained in situ. Summary Used correctly and in adequate doses, wound infiltration analgesia can be used in a multimodal analgesic regime without major complications. It offers the benefit of providing analgesia at a low cost when used as a single injection.

Background. There is some evidence that epidural analgesia (EDA) reduces tumour recurrence after breast and prostatic cancer surgery. We assessed whether EDA reduces long-term mortality after colorectal cancer surgery. Methods. All patients having colorectal cancer surgery between January 2004 and January 2008 at Linkoping and Orebro were included. Exclusion criteria were: emergency operations, laparoscopic-assisted colorectal resection, and stage 4 cancer. Statistical information was obtained from the Swedish National Register for Deaths. Patients were analysed in two groups: EDA group or patient-controlled analgesia (PCA group) as the primary method of analgesia. Results. A total of 655 patients could be included. All-cause mortality for colorectal cancer (stages 1-3) was 22.7% (colon: 20%, rectal: 26%) after 1-5 yr of surgery. Multivariate regression analysis identified the following statistically significant factors for death after colon cancer (Pless than0.05): age (greater than72 yr) and cancer stage 3 (compared with stage 1). A similar model for rectal cancer found that age (greater than72 yr) and the use of PCA rather than EDA and cancer stages 2 and 3 (compared with stage 1) were associated with a higher risk for death. No significant risk of death was found for colon cancer when comparing EDA with PCA (P=0.23), but a significantly increased risk of death was seen after rectal cancer when PCA was used compared with EDA (P=0.049) [hazards ratio: 0.52 (0.27-1.00)]. Conclusions. We found a reduction in all-cause mortality after rectal but not colon cancer in patients having EDA compared with PCA technique.

Local anesthetics (LA) are injected via catheters placed in surgical wounds for post-operative analgesia. The primary aim of this systematic review was to assess whether LA reduce pain intensity when injected via wound catheters. A literature search was performed from Medline via PubMed, EMBASE and the Cochrane database from 1966 until November 2009. The search strategy included the following key words: pain, postoperative, catheters and local anesthetics. Two co-authors independently read every article that was initially included and extracted data into a pre-defined study record form. A total of 753 studies primarily fit the search criteria and 163 were initially extracted. Of these, 32 studies were included in the meta-analysis. Wound catheters provided no significant analgesia at rest or on activity, except in patients undergoing gynecological and obstetric surgery at 48 h (P = 0.03). The overall morphine consumption was lower (approximate to 13 mg) during 0-24 h (P less than 0.001) in these patients. No significant differences in side effects were found, except for a lower risk of wound breakdown (P = 0.048) and a shorter length of hospital stay (P = 0.04) in patients receiving LA. A statistically significant heterogeneity was seen between the studies in most end-points. LA injected via wound catheters did not reduce pain intensity, except at 48 h in a subgroup of patients undergoing obstetric and gynecological surgery. Rescue analgesic consumption was also lower in this group at 0-24 h. The magnitude of these effects was small and compounded by pronounced heterogeneity.