A pilot study of hyperoxemia on neurological injury, inflammation and oxidative stress.

BACKGROUND: Normobaric hyperoxia is used to alleviate secondary brain ischaemia in patients with traumatic brain injury (TBI), but clinical evidence is limited and hyperoxia may cause adverse events. METHODS: An open label, randomised controlled pilot study comparing blood concentrations of reactive oxygen species (ROS), interleukin 6 (IL-6) and neuron-specific enolase (NSE) between two different fractions of inspired oxygen in severe TBI patients on mechanical ventilation. RESULTS: We enrolled 27 patients in the Fi O2 0.40 group and 38 in the Fi O2 0.70 group; 19 and 23 patients, respectively, completed biochemical analyses. In baseline, there were no differences between Fi O2 0.40 and Fi O2 0.70 groups, respectively, in ROS (64.8 nM [22.6-102.1] vs. 64.9 nM [26.8-96.3], P = 0.80), IL-6 (group 92.4 pg/ml [52.9-171.6] vs. 94.3 pg/ml [54.8-133.1], P = 0.52) or NSE (21.04 ug/l [14.0-30.7] vs. 17.8 ug/l [14.1-23.9], P = 0.35). ROS levels did not differ at Day 1 (24.2 nM [20.6-33.5] vs. 29.2 nM [22.7-69.2], P = 0.10) or at Day 2 (25.4 nM [21.7-37.4] vs. 47.3 nM [34.4-126.1], P = 0.95). IL-6 concentrations did not differ at Day 1 (112.7 pg/ml [65.9-168.9) vs. 83.9 pg/ml [51.8-144.3], P = 0.41) or at Day 3 (55.0 pg/ml [34.2-115.6] vs. 49.3 pg/ml [34.4-126.1], P = 0.95). NSE levels did not differ at Day 1 (15.9 ug/l [9.0-24.3] vs. 15.3 ug/l [12.2-26.3], P = 0.62). There were no differences between groups in the incidence of pulmonary complications. CONCLUSION: Higher fraction of inspired oxygen did not increase blood concentrations of markers of oxidative stress, inflammation or neurological injury or the incidence of pulmonary complications in severe TBI patients on mechanical ventilation.

Associations between brain morphology and outcome in schizophrenia in a general population sample.

OBJECTIVE: To analyse associations between brain morphology and longitudinal and cross-sectional measures of outcomes in schizophrenia in a general population sample. METHODS: The sample was the Northern Finland 1966 Birth Cohort. In 1999-2001, structural brain MRI and measures of clinical and functional outcomes were analysed for 54 individuals with schizophrenia around the age of 34. Sex, total grey matter, duration of illness and the use of antipsychotic medication were used as covariates. RESULTS: After controlling for multiple covariates, increased density of the left limbic area was associated with less hospitalisations and increased total white matter volume with being in remission. Higher density of left frontal grey matter was associated with not being on a disability pension and higher density of the left frontal lobe and left limbic area were related to better functioning. Higher density of the left limbic area was associated with better longitudinal course of illness. CONCLUSIONS: This study, based on unselected general population data, long follow-up and an extensive database, confirms findings of previous studies, that morphological abnormalities in several brain structures are associated with outcome. The difference in brain morphology in patients with good and poor outcomes may reflect separable aetiologies and developmental trajectories in schizophrenia.

Dexmedetomidine as an anaesthetic adjuvant in patients undergoing intracranial tumour surgery: a double-blind, randomized and placebo-controlled study.

BACKGROUND: Dexmedetomidine (DEX) has been shown to provide good perioperative haemodynamic stability with decreased intraoperative opioid requirements. It may have neural protective effects, and thus may be a suitable anaesthetic adjuvant to neurosurgical anaesthesia. METHODS: Fifty-four patients scheduled for elective surgery of supratentorial brain tumour were randomized to receive in a double-blind manner a continuous DEX infusion (plasma target concentration 0.2 or 0.4 ng ml(-1)) or placebo, beginning 20 min before anaesthesia and continuing until the start of skin closure. The DEX groups received fentanyl 2 microg kg(-1) at the induction of anaesthesia and before the start of operation, the placebo group 4 microg kg(-1), respectively. Anaesthesia was maintained with nitrous oxide in oxygen and isoflurane. RESULTS: The median times from the termination of N2O to extubation were 6 (3-27), 3 (0-20) and 4 (0-13) min in placebo, DEX-0.2 and DEX-0.4 groups, respectively (P<0.05 anova all-over effect). The median percentage of time points when systolic blood pressure was within more or less than 20% of the intraoperative mean was 72, 77 and 85, respectively (P<0.01), DEX-0.4 group differed significantly from the other groups. DEX blunted the tachycardic response to intubation (P<0.01) and the hypertensive response to extubation (P<0.01). DEX-0.4 group differed in the heart rate variability from placebo (93 vs 82%, P<0.01). CONCLUSIONS: DEX increased perioperative haemodynamic stability in patients undergoing brain tumour surgery. Compared with fentanyl, the trachea was extubated [corrected] faster without respiratory depression.

Composition and dynamics of plasma in Saturn's magnetosphere.

During Cassini's initial orbit, we observed a dynamic magnetosphere composed primarily of a complex mixture of water-derived atomic and molecular ions. We have identified four distinct regions characterized by differences in both bulk plasma properties and ion composition. Protons are the dominant species outside about 9 RS (where RS is the radial distance from the center of Saturn), whereas inside, the plasma consists primarily of a corotating comet-like mix of water-derived ions with approximately 3% N+. Over the A and B rings, we found an ionosphere in which O2+ and O+ are dominant, which suggests the possible existence of a layer of O2 gas similar to the atmospheres of Europa and Ganymede.

QT interval and QT dispersion during the induction of anaesthesia in patients with subarachnoid haemorrhage: a comparison of thiopental and propofol.

BACKGROUND AND OBJECTIVE: Thiopental prolongs the QT interval more than propofol, and the two induction agents were compared in patients with subarachnoid haemorrhage predisposed to electrocardiographic abnormalities and cardiac dysrhythmias. METHODS: Twenty-nine patients were studied randomly. Anaesthesia was induced with either thiopental or propofol and fentanyl; vecuronium was used as a neuromuscular blocking agent. The electrocardiogram and arterial blood pressure were monitored from before the induction of anaesthesia to 2 min after endotracheal intubation. RESULTS: The median QT interval was at baseline 423 ms in the thiopental group and at 432 ms in the propofol group, and it increased in the thiopental group to 446 ms and decreased in the propofol group to 425 ms (P < 0.01 between groups). After induction and endotracheal intubation, the number of patients with increased QT dispersion was greater in the propofol group (P < 0.05). The incidence of cardiac dysrhythmias was similar in the study groups. CONCLUSIONS: Thiopental and propofol are equally suitable for the induction of anaesthesia in patients with subarachnoid haemorrhage.

Hip arthroscopy in osteoarthritis. A review of 68 patients.

BACKGROUND AND AIMS: A few studies have investigated therapeutic effect of hip arthroscopy in osteoarthritis, and therefore the use of hip arthroscopy in osteoarthritis has remained controversial. The aim of this study was to evaluate diagnostic and therapeutic aspects of hip arthroscopy in primary osteoarthritis. MATERIAL AND METHODS: During a time period from 1995 to 1999, a total of 68 patients had an arthroscopic evaluation of primary hip osteoarthritis at the Päijät-Häme Central Hospital, Lahti, Finland. The mean (range) follow-up was 1.3 (0.3 to 4) years. Arthroscopy was diagnostic in 38 (56%), while six (9%) patients received either long-lasting anaesthetic or prednisolone, and in 24 (35%) debridement was possible. Partial synovectomy was performed in two (3%). RESULTS: Three months after the arthroscopy, 49 (72%) patients reported that their hip pain had decreased. One year after the arthroscopy, 18 (26%) patients stated that their hip pain was less pronounced than before the arthroscopy. The severity of hip osteoarthritis in preoperative x-rays correlated significantly (p = 0.035) with the subjective result: the milder the osteoarthritis, the more often patients reported that their hip pain had decreased after arthroscopy. No association was observed between age, sex, modified Outerbridge grade of chondropathy, or whether a debridement was done or not and the symptomatic relief after the arthroscopy. CONCLUSIONS: Hip arthroscopy with or without debridement of loose cartilage may, at least temporarily, reduce the pain of mild or moderate osteoarthritis of the hip. Still, repeated arthroscopies had no therapeutic effect.

The effects of a pharmacy-based intervention on the knowledge and attitudes of asthma patients.

The effects of a pharmacy-based intervention on the knowledge and attitudes of asthma patients was studied with a small convenience sample in four Finnish community pharmacies. The intervention consisted of patient education, counselling and outcomes monitoring according to Therapeutic Outcomes Monitoring (TOM) concept. Twenty-eight patients aged 20-64 years suffering from asthma and having problems in asthma management were involved. Measurements were done at baseline, immediately after the intervention (12 months) and 1 year after the intervention (24 months) using a pre/post-test design, with the patients being their own controls. Both knowledge about and attitudes towards asthma as a disease improved significantly during the intervention. Also knowledge about medication improved significantly during the intervention, though the patients' attitudes towards the medication remained unchanged. The negative correlation between knowledge about and attitudes towards asthma (-0.35) at baseline disappeared after the intervention (0.21). There was a positive correlation between knowledge about and attitudes towards medication at 12 months (0.40, P=0.04) which was still significant 1 year after the intervention (0.40, P=0.04).

Therapeutic outcomes monitoring by community pharmacists for improving clinical outcomes in asthma.

OBJECTIVE: To determine the effect of enhanced therapeutic monitoring by community pharmacists on clinical outcomes of a convenience sample of asthma patients. METHODS: A one-year intervention study with scheduled visits and follow-ups at baseline, 4, 8, 12 and 24 months using a pre/post-test design, with a small convenience sample of 28 study patients, who performed their own controls. Outcomes measured were the severity of asthma symptoms, changes in the number of patients having peak expiratory flow (PEF) values below 85% or 70% of the optimal, changes in daily asthma medication and number of patients needing courses of oral steroids. RESULTS: A positive change was noticed in all the measures used, most clearly in the severity of asthma symptoms. During the intervention, mean scores of three out of five symptom measures improved significantly. Twenty-two (79%) patients had a net improvement in one or more asthma symptom indicators. The number of patients with PEF values below 85% of the optimal decreased from seven to four at 12 months. The number of patients having courses of oral steroids for asthma decreased. More than half (57%) of the patients had changes in their daily asthma medication. The effects lasted partly over one year after the intervention. CONCLUSIONS: The results of this study suggest that pharmacist intervention can have a positive effect on clinical outcomes of asthma patients. The results need to be confirmed with a study using a randomized controlled design.

Counselling patients on psychotropic medication: physicians' opinions on the role of community pharmacists.

OBJECTIVES: To study physicians' opinions on community pharmacists' involvement in counselling patients on use of psychotropic medication. DESIGN: A postal questionnaire with open-ended questions completed by physicians. SUBJECTS: A six per cent random sample (n = 759) of the members of the Finnish Medical Association representing physicians working in hospitals, community health centres, private practices and occupational health services (response rate 64%, n = 487). MAIN MEASURES: Physicians' opinions concerning community pharmacists' involvement in counselling patients about purpose of the medication and adverse effects of benzodiazepines and neuroleptics. RESULTS: When classifying opinions into five categories, majority (72%) of the physicians regarded community pharmacists as a provider of comprehensive or at least general information about adverse effects of benzodiazepines, but only 43% about the purpose of the medication. Correspondingly, 60% of the physicians regarded community pharmacists as a provider of comprehensive or general information about adverse effects of neuroleptics, but only 35% about the purpose of the medication. There was a strong correlation between physicians' opinions concerning pharmacists' involvement in counselling patients about the purpose of the medication of benzodiazepines and neuroleptics (Spearman's coefficient 0.667), and about adverse effects of both type of medication (0.668). Male physicians had more fixed opinions, both positive and negative, than female physicians. CONCLUSIONS: Finnish physicians are still quite critical about community pharmacists involvement in counselling patients on psychotropic medication. Especially with neuroleptics, physicians feel that pharmacists should be cautious when discussing the purpose of the medication if it is excluded from the prescription.

Extracranial contribution to cerebral oximetry in brain dead patients: a report of six cases.

The near infrared spectroscopy offers a noninvasive method to monitor regional brain oxygenation. The problem with the technique appears to be possible extacranial contribution to the measurements. As a part of another study, we monitored regional saturation (rSO2) in six brain dead patients either during the test for spontaneous respiration or in those not eligible for organ donation, after discontinuation of mechanical ventilation. Relatively normal rSO2 values were obtained after brain death, and the values decreased concomitantly with the hemoglobin saturation of oxygen (SpO2) after the discontinuation of mechanical ventilation. A corresponding decrease in SpO2 and rSO2 suggests extracranial contribution to the measured rSO2. The diagnosis of brain death cannot be made based on this technology; furthermore the presence of extracranial contribution may limit its potential value even in other applications.

QT dispersion after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) causes a stress response with increased concentrations of plasma catecholamines and serious cardiac arrhythmias. Increased QT dispersion has been shown to predispose to cardiac arrhythmias. In SAH patients, QT dispersion has not been studied previously. QT dispersion was analyzed in 26 patients with SAH and in 16 patients (control group) scheduled for ligation of a nonruptured cerebral aneurysm. In 15 patients with SAH, the plasma concentrations of catecholamines were analyzed, and an 18-hour continuous electrocardiogram (ECG) recording was obtained. In the other 11 patients, electrocardiography was repeated daily for up to 9 days for analysis of QT dispersion. The median (25th and 75th percentiles) QT dispersion in all SAH patients was 78 milliseconds (50 and 109 milliseconds, respectively), and in control patients, it was 25 milliseconds (15 and 33 milliseconds, respectively) (P < .001). There was a positive correlation with QT dispersion and the plasma concentration of DHPG, a metabolite of norepinephrine (P < .05). All patients had episodes of cardiac arrhythmia during the 18-hour recording period. In conclusion, increased QT dispersion is a common finding after SAH and may be a result of high plasma concentrations of catecholamines in these patients.

Effects of nonsteroidal anti-inflammatory drugs on hemostasis in patients with aneurysmal subarachnoid hemorrhage.

Platelet function is impaired by nonsteroidal anti-inflammatory drugs (NSAIDs) with prominent anti-inflammatory properties. Their safety in patients undergoing intracranial surgery is under debate. Patients with aneurysmal subarachnoid hemorrhage (SAH) were randomized to receive either ketoprofen, 100 mg, three times a day (ketoprofen group, n = 9) or a weak NSAID, acetaminophen, 1 g, three times a day (acetaminophen group, n = 9) starting immediately after the diagnosis of aneurysmal SAH. Treatment was continued for 3 days postoperatively. Test blood samples were taken before treatment and surgery as well as on the first, third, and fifth postoperative mornings. Maximal platelet aggregation induced by 6 microM of adenosine diphosphate decreased after administration of ketoprofen. Aggregation was lower (P < .05) in the ketoprofen group than in the acetaminophen group just before surgery and on the third postoperative day. In contrast, maximal platelet aggregation increased in the acetaminophen group on the third postoperative day as compared with the pretreatment platelet aggregation results (P < .05). One patient in the ketoprofen group developed a postoperative intracranial hematoma. Coagulation (prothrombin time [PT], activated partial thromboplastin time [APPT], fibrinogen concentration, and antithrombin III [AT III]) was comparable between the two groups. Ketoprofen but not acetaminophen impaired platelet function in patients with SAH. If ketoprofen is used before surgery on cerebral artery aneurysms, it may pose an additional risk factor for hemorrhage.

Patient-controlled analgesia with oxycodone in the treatment of postcraniotomy pain.

BACKGROUND: Moderate to severe pain occurs after craniotomy in 60% of patients. We evaluated the feasibility and safety of patient-controlled analgesia (PCA) with oxycodone in neurosurgical patients, and compared the efficacy of paracetamol with ketoprofen. METHODS: In the study there were 45 patients, who received either paracetamol 1000 mg or ketoprofen 100 mg three times a day. Oxycodone-boluses 0.03 mg/kg were given by PCA-device maximally three times an hour, lock-out time 10 min. The amount of oxycodone used, pain scores and side-effects were recorded. RESULTS: The ketoprofen group required less oxycodone than the paracetamol group (medians 37.1 mg vs 19.6 mg, P < 0.05). The VAS scores were comparable between the groups at the beginning of the study, during the first postoperative evening and the next morning, but the paracetamol group had a higher score at the conclusion of the study (P < 0.05). The patients in both groups were equally satisfied with the pain relief. There were no differences in side-effects between the groups. CONCLUSIONS: PCA with oxycodone is a suitable method for pain control after craniotomy. No progressive hypoventilation, desaturation or excessive sedation were encountered. Ketoprofen appeared to be more effective than paracetamol.

The effect of patient positioning on dynamic lung compliance.

BACKGROUND: Side-stream spirometry offers a non-invasive method to monitor continuously respiratory mechanics in intubated patients. We studied the effects of different positions on dynamic lung compliance during anaesthesia. METHODS: The study consisted of 56 patients, operated in supine, prone, kneeling or lateral park-bench position. Dynamic lung compliance and inspiratory peak pressure were recorded after induction of anaesthesia, 15 min and 1 h after posturing the patient. RESULTS: The first measured compliances were comparable in all groups. The compliance in the lateral and the prone positions was significantly lower than in the supine position at 15 min (P < 0.01) and 1 h (P < 0.001) after the posture change. The peak inspiratory pressure was significantly lower in the kneeling position than in the other groups (P < 0.01 at the first measurement, P < 0.001 at the later measurements). No correlation was found between body mass index and compliance. CONCLUSION: We found that dynamic lung compliance decreased significantly upon change of posture from supine to lateral or prone position, whereas in the kneeling position no change in compliance was observed. We suggest that the kneeling position might be preferable to the prone position.

Comparison of the effects of controlled ventilation with 100% oxygen, 50% oxygen in nitrogen, and 50% oxygen in nitrous oxide on responses to venous air embolism in pigs.

In this randomized, experimental study in 18 pigs, we have investigated the effects of inspiratory air in oxygen, 100% oxygen and 50% nitrous oxide in oxygen on the detection and consequences of venous air embolism. Each animal was tested with injections of 1.0 ml kg-1 and 2.0 ml kg-1 of air. All animals, except one in the nitrous oxide group, survived the air emboli. Systolic and diastolic arterial pressures decreased significantly in all groups after both injections of air. Pulmonary diastolic pressures increased most in the nitrous oxide group. End-tidal concentration of carbon dioxide decreased significantly in all groups after air injections. The difference in concentration of oxygen in the inspiratory and expiratory gas (O2 (I-E)) was lowest in the air group after both injections of air. On the basis of our studies we suggest that nitrous oxide should not be used during surgery associated with an increased risk of venous air embolism.

Propofol influences the electroretinogram to a lesser degree than thiopentone.

BACKGROUND: The Electroretinogram (ERG) is used clinically to assess the function of retina. Anaesthetic agents are known to affect ERG, and as anaesthesia is often needed in children and uncooperative patients, knowledge about its effects is of clinical importance. Barbiturates selectively depress ERG components, and we compared thiopentone with propofol to assess if the latter preserved retinal function better. METHODS: Ten pigs, average weight 17 kg (SD +/- 2 kg) were anaesthetized randomly with propofol 10 mg kg-1 or thiopentone 30 mg kg-1. Anaesthesia was maintained by 65% nitrous oxide in oxygen and continuous infusion of the induction agent, i.e. 10 mg kg-1 h-1 of propofol, or 10 mg kg-1 h-1 for the first hour, then 5 mg kg-1 h-1 of thiopentone, with doses being based on pilot studies. After an interval of one week the programme was repeated using the other agent. After 40 minutes dark-adaptation, responses to single flashes of graded intensities from a xenon flashlamp were recorded at five-minute intervals. The a- and b-wave amplitudes and implicit times (time to peak), and a-wave slopes were determined. RESULTS: The b-wave implicit time was significantly shorter during propofol anaesthesia than when using thiopentone. The effect was most pronounced at the lowest intensities (P < 0.01). No statistically significant differences were found in the amplitudes of the b-waves. The a-wave appeared at lower stimulus intensity (P < 0.05) and the a-wave slopes were significantly steeper (P < 0.01) during propofol anaesthesia. CONCLUSION: Propofol accordingly appeared to preserve the photoreceptor response better than thiopentone, and may therefore be considered to be more suitable for ERG recordings than thiopentone.

Monitoring lung compliance and end-tidal oxygen content for the detection of venous air embolism.

Venous air embolism (VAE) is a recognized complication of surgery performed with the patient in the sitting position, but it occurs also during other operations. We report two cases of VAE, associated with a notable decrease in dynamic lung compliance, detected by side-stream spirometry. Based on these cases, an experiment with 10 pigs was designed to evaluate the usefulness of side-stream spirometry in the diagnosis of VAE. Three doses of air (0.5, 1.0 and 2.0 ml kg-1) were injected via the proximal part of a 5- French gauge pulmonary artery catheter. Only the largest dose was followed by haemodynamic deterioration. Significant increases in end-tidal oxygen content and decreases in dynamic lung compliance were detected with all doses of air together with conventional signs of VAE, that is increases in pulmonary artery pressures and arterial carbon dioxide tensions, and decreases in end-tidal concentration of carbon dioxide. We conclude that continuous monitoring of end-tidal oxygen concentration and side-stream spirometry offers valuable supplements to other monitoring techniques in the detection of VAE.

Long-term results of the Evans procedure for lateral instability of the ankle.

We studied the late outcome of 40 ankles (from a consecutive series of 42) treated by a modified Evans procedure. The peroneus brevis tendon was used to fashion a static tenodesis. All the patients had suffered from persistent lateral instability following an ankle sprain. The follow-up period was between nine and 12 years. Excellent or good results were achieved in 33 ankles (82.5%), three had a fair result, and four were poor. The clinical results were matched by the radiographic results which showed significant talar tilt or anterior talar translation in only three ankles. The functional result showed no positive correlation with the stress-radiographic analysis. We concluded that this modification of the Evans operation gives satisfactory long-term results, which show little change from the good results at 24 to 35 months reported in an earlier paper from our department.

Lateral ligament injuries of the ankle. Results of primary surgical treatment.

76 cases of fresh lateral ligament injuries were operated on by primary suture. The preoperative diagnosis of severe lateral ligament sprain was based on clinical and radiological instability as seen by talar tilt and anterior drawer sign tests. A good diagnostic accuracy was achieved. A walking cast was worn for four weeks after the operation. A follow-up study was undertaken 24 to 44 months after the operation. 71 ankles were excellent or good, three ankles were fair, while only two ankles showed a poor operative result. Both patients with a poor result had suffered a recurrent sprain. It is concluded that operative correction of fresh severe lateral ligament injuries gives satisfactory results.