The influence of the anesthesia-to-stimulation time interval on seizure quality parameters in electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) continues to be the most efficacious treatment for severe depression and other life-threatening acute psychiatric conditions. Treatment efficacy is dependent upon the induced seizure quality, which may be influenced by a range of treatment related factors. Recently, the time interval from anesthesia to the electrical stimulation (ASTI) has been suggested to be an important determinant of seizure quality. METHODS: We measured ASTI in 73 ECT sessions given to 22 individual patients, and analyzed its influence on five seizure quality parameters (EEG seizure time, power, coherence, postictal suppression, and peak heart rate). RESULTS: Longer ASTI was significantly associated with higher peak heart rate during the seizure (p = .003). After adjustment for confounders, the association continued to be significant, even after Bonferroni correction for multiple comparisons (p = .005). ASTI was not significantly associated with other seizure parameters. LIMITATIONS: The relatively low number of sessions may lead to false negative findings. The study did not include clinical outcomes. CONCLUSIONS: Longer ASTI is associated with higher peak heart rate; a phenomenon which is thought to reflect better seizure propagation to subcortical areas of the brain. The finding indicates that delay of stimulation after anesthesia could be a simple way of improving seizure quality and thereby the clinical effect of ECT.

Muscle oxygen saturation increases during head-up tilt-induced (pre)syncope.

AIM: To evaluate whether muscle vasodilatation plays a role for hypotension developed during central hypovolaemia, muscle oxygenation (Sm O2 ) was examined during (pre)syncope induced by head-up tilt (HUT). Skin blood flow (SkBF) and oxygenation (Sskin O2 ) were determined because evaluation of Sm O2 may be affected by superficial tissue oxygenation. Furthermore, we evaluated cerebral oxygenation (Sc O2 ) and middle cerebral artery mean blood flow velocity (MCAvmean ). METHODS: Twenty healthy male volunteers (median age 24 years; range 19-38) were subjected to passive 50° HUT for 1 h or until (pre)syncope. Sc O2 and Sm O2 (near-infrared spectroscopy), MCAvmean (transcranial Doppler) along with mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) (Modelflow® ) were determined. RESULTS: (Pre)syncopal symptoms appeared in 17 subjects after 11 min (median; range 2-34) accompanied by a decrease in MAP, SV, CO and TPR, while HR remained elevated. During (pre)syncope, Sc O2 decreased [73% (71-76; mean and 95% CI) to 68% (65-71), P < 0.0001] along with MCAvmean [40 (37-43) to 32 (29-35) cm s-1 , P < 0.0001]. In contrast, Sm O2 increased [63 (56-69)% to 71% (65-78), P < 0.0001], while Sskin O2 [64% (58-69) to 53% (47-58), P < 0.0001] and SkBF [71 (44-98) compared to a baseline of 99 (72-125) units, P = 0.020] were reduced. CONCLUSION: We confirm that the decrease in MAP during HUT is associated with a reduction in indices of cerebral perfusion. (Pre)syncope was associated with an increase in Sm O2 despite reduced Sskin O2 and SkBF, supporting that muscle vasodilation plays an important role in the circulatory events leading to hypotension during HUT.

Release of erythropoietin and neuron-specific enolase after breath holding in competing free divers.

Free diving is associated with extreme hypoxia. This study evaluated the combined effect of maximal static breath holding and underwater swimming on plasma biomarkers of tissue hypoxemia: erythropoietin, neuron-specific enolase and S100B, C-reactive protein, pro-atrial natriuretic peptide, and troponin T. Venous blood samples were obtained from 17 competing free divers before and 3 h after sessions of static apnea and underwater swimming. The heart was evaluated by echocardiography. Static apnea for 293 ± 78 s (mean ± SD) and subsequent 88 ± 21 m underwater swimming increased plasma erythropoietin from 10.6 ± 3.4 to 12.4 ± 4.1 mIU/L (P = 0.013) and neuron-specific enolase from 14.5 ± 5.3 to 24.6 ± 6.4 ng/mL (P = 0.017); C-reactive protein decreased from 0.84 ± 1.0 to 0.71 ± 0.67 mmol/L (P = 0.013). In contrast, plasma concentrations of S100B (P = 0.394), pro-atrial natriuretic peptide (P = 0.549), and troponin T (P = 0.125) remained unchanged and, as assessed by echocardiography, the heart was not affected. In competitive free divers, bouts of static and dynamic apnea increase plasma erythropoietin and neuron-specific enolase, suggesting that renal and neural tissue, rather than the heart, is affected by the hypoxia developed during apnea and underwater swimming.

External carotid artery flow maintains near infrared spectroscopy-determined frontal lobe oxygenation during ephedrine administration.

BACKGROUND: Phenylephrine and ephedrine affect frontal lobe oxygenation ([Formula: see text]) differently when assessed by spatially resolved near infrared spectroscopy. We evaluated the effect of phenylephrine and ephedrine on extra- vs intra-cerebral blood flow and on [Formula: see text]. METHODS: In 10 healthy males (age 20-54 yr), phenylephrine or ephedrine was infused for an ∼20 mm Hg increase in mean arterial pressure. Cerebral oxygenation (SavO2) was calculated from the arterial and jugular bulb oxygen saturations. Blood flow in the internal carotid artery (ICAf) and blood flow in the external carotid artery (ECAf) were assessed by duplex ultrasonography. Invos-5100c (SinvosO2) and Foresight (SforeO2) determined [Formula: see text] while forehead skin oxygenation (SskinO2) was assessed. RESULTS: Phenylephrine reduced SforeO2 by 6.9% (95% confidence interval: 4.8-9.0%; P<0.0001), SinvosO2 by 10.5 (8.2-12.9%; P<0.0001), and ECAf (6-28%; P=0.0001), but increased ICAf (5-21%; P=0.003) albeit with no consequence for SskinO2 or SavO2. In contrast, SforeO2 was maintained with administration of ephedrine while SinvosO2 and SavO2 decreased [by 3.1 (0.7-4.5%; P=0.017) and 2.1 (0.5-3.3%; P=0.012)] as arterial carbon dioxide pressure decreased (P=0.003). ICAf was stable and ECAf increased by 11 (4-18%; P=0.005) with administration of ephedrine while SskinO2 did not change. CONCLUSIONS: The effect of phenylephrine on ScO2 is governed by a decrease in external carotid blood flow since it increases cerebral blood flow as determined by flow in the internal carotid artery. In contrast, ScO2 is largely maintained with administration of ephedrine because blood flow to extracerebral tissue increases.

Impaired endothelial function after aneurysmal subarachnoid haemorrhage correlates with arginine:asymmetric dimethylarginine ratio.

BACKGROUND: Endothelial dysfunction might be involved in the development of cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH). METHODS: This prospective observational study of 48 SAH subjects and 23 control subjects examined associations between reactive hyperaemia index (RHI) measured by peripheral arterial tonometry and plasma concentrations of S-100B protein, nitrite/nitrate, arginine, and asymmetric dimethyl arginine (ADMA). Clinical variables were flow velocity in the middle cerebral artery (VMCA), angiographic vasospasm, delayed neurological deficit, and 30 day survival. Five consecutive measurements were obtained at days 0-2, 3-5, 6-8, 9-11, and 12-15. RESULTS: RHI was 1.67 (0.46) at days 0-2 after SAH but increased at days 3-15 to the same levels as in controls (P<0.05 compared with days 0-2). RHI was lower in subjects who died before day 30 (P=0.07), but no trends were observed in relation to angiographic vasospasm or delayed neurological deficit. Both arginine and ADMA increased after SAH compared with days 0-2 (P<0.05). S-100B was highest in non-survivors (P<0.01) and in subjects with neurological deficit (P<0.01). A positive correlation was found between RHI and arginine:ADMA ratio (r=0.43, P<0.005), but not with nitrite/nitrate, VMCA, or S-100B. CONCLUSIONS: Peripheral flow-mediated vasodilation is attenuated in the first days after SAH indicating acute systemic endothelial dysfunction. Impairment of endothelial function after SAH correlates with imbalance of the arginine/ADMA pathway.

Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats.

Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication.

Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets.

BACKGROUND: Mitochondrial dysfunction is an important factor contributing to tissue damage in both severe traumatic brain injury and ischemic stroke. This experimental study explores the possibility to diagnose the condition bedside by utilising intracerebral microdialysis and analysis of chemical variables related to energy metabolism. METHODS: Mitochondrial dysfunction was induced in piglets and evaluated by monitoring brain tissue oxygen tension (PbtO2 ) and cerebral levels of glucose, lactate, pyruvate, glutamate, and glycerol bilaterally. The biochemical variables were obtained by microdialysis and immediate enzymatic analysis. Mitochondrial function was blocked by unilateral infusion of NaCN/KCN (0.5 mol/L) through the microdialysis catheter (N = 5). As a reference, NaCl (0.5 mol/L) was infused by intracerebral microdialysis in one group of animals (N = 3). RESULTS: PbtO2 increased during cyanide infusion and returned to baseline afterwards. The lactate/pyruvate (LP) ratio increased significantly following cyanide infusion because of a marked increase in lactate level while pyruvate remained within normal limits. Glutamate and glycerol increased after cyanide infusion indicating insufficient energy metabolism and degradation of cellular membranes, respectively. CONCLUSION: Mitochondrial dysfunction is characterised by an increased LP ratio signifying a shift in cytoplasmatic redox state at normal or elevated PbtO2 . The condition is biochemically characterised by a marked increase in cerebral lactate with a normal or elevated pyruvate level. The metabolic pattern is different from cerebral ischemia, which is characterised by simultaneous decreases in intracerebral pyruvate and PbtO2 . The study supports the hypothesis that cerebral ischemia and mitochondrial dysfunction may be identified and separated at the bedside by utilising intracerebral microdialysis.

Transcranial Doppler velocimetry in aneurysmal subarachnoid haemorrhage: intra- and interobserver agreement and relation to angiographic vasospasm and mortality.

BACKGROUND: Transcranial Doppler measurements of the middle cerebral artery flow velocity are widely used as an indicator of vasospasm after aneurysmal subarachnoid haemorrhage (SAH). We investigated inter- and intraoperator agreement in SAH patients and healthy volunteers using colour-coded transcranial Doppler (TCCD), with the secondary aim of describing prediction of angiographic vasospasm and mortality. METHODS: Sixty patients and 70 healthy controls were each examined in duplicate by alternating operators. A total of 939 measurements divided on 201 examination sets were conducted by four observers. The Bland-Altman limits of agreement (LoA) were calculated using a variance components analysis. Angiography was performed on clinical indication and survival recorded at 30 days. RESULTS: Differences between measurements increased with increasing average, and therefore, we analysed log-transformed values. Thus, LoA are given as ratios between measurements. There were no systematic intra- or interobserver differences (bias). The intraobserver LoA was 0.62-1.61 in patients and 0.67-1.50 in controls. However, they were 0.55-1.82 in patients with angiographic vasospasm, whereas in patients without, they were 0.66-1.52. The interobserver LoA was 0.55-1.81 in patients and 0.65-1.55 in controls, while in patients with and without angiographic vasospasm, they were 0.45-2.22 and 0.60-1.67, respectively. Flow velocity measurements day 6-10 were positively associated with 30 day mortality risk (P=0.02, logistic regression). CONCLUSIONS: TCCD measurement variability is wider in patient measurements than in controls. This discrepancy can largely be explained by a higher degree of error in patients with angiographic vasospasm. Despite the considerable measurement variability in TCCD, values are predictive of outcome in SAH.

Problems in obtaining sufficient anaesthesia with propofol and remifentanil: three cases, a test infusion, and a review.

BACKGROUND: Over a 5 yr period, we have encountered three patients in whom remifentanil appeared to have no clinical effect during general anaesthesia (GA). We describe seven anaesthetics in these three patients. METHODS: We reviewed the literature on this subject. A simple reproducible test to explore this response was designed. This involved a controlled infusion of increasing doses of remifentanil while observing respiratory variables, pain threshold, pupil size, and Glasgow coma scale score. In addition, blood was sampled for genotyping. RESULTS: No description of this impaired response was found in the review of the literature. Two of the patients agreed to participate in the test. In both patients, we found a seemingly normal analgesic response but a lack of respiratory depression and almost no depression of consciousness, even at doses well above the recommended level for clinical use. The genotyping did not explain the results of the test. CONCLUSIONS: The potential causes of this effect are discussed. We advise clinicians to be aware of this unusual response to remifentanil. If such a response is suspected, we recommend the use of another opioid. If this is suspected before GA, we propose the use of our test as a diagnostic tool.

Cerebral energy metabolism during induced mitochondrial dysfunction.

BACKGROUND: In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets. METHODS: Ten piglets were included, seven in the experimental group (anesthetized with sevoflurane) and three in the control group (anesthetized with midazolam). PbtO(2) and cerebral levels of glucose, lactate, and pyruvate were monitored bilaterally. The biochemical variables were obtained by intracerebral microdialysis. RESULTS: All global variables were within normal range and did not differ significantly between the groups except for blood lactate that was slightly higher in the experimental group. Mitochondrial dysfunction was observed in the group of animals initially anesthetized with sevoflurane. Cerebral glucose was significantly lower in the experimental group than in the control group whereas lactate and lactate/pyruvate ratio were significantly higher. Pyruvate and tissue oxygen tension remained within normal range in both groups. Changes of intracerebral variables indicating mitochondrial dysfunction were present already from the very start of the monitoring period. CONCLUSION: Intracerebral microdialysis revealed mitochondrial dysfunction by marked increases in cerebral lactate and lactate/pyruvate ratio simultaneously with normal levels of pyruvate and a normal PbtO(2). This metabolic pattern is distinctively different from cerebral ischemia, which is characterized by simultaneous decreases in PbtO(2) and intracerebral pyruvate.

Hyperbaric oxygen therapy or hydroxycobalamin attenuates surges in brain interstitial lactate and glucose; and hyperbaric oxygen improves respiratory status in cyanide-intoxicated rats.

Cyanide (CN) intoxication inhibits cellular oxidative metabolism and may result in brain damage. Hydroxycobalamin (OHCob) is one among other antidotes that may be used following intoxication with CN. Hyperbaric oxygen (HBO2) is recommended when supportive measures or antidotes fail. However, the effect of hydroxycobalamin or HBO2 on brain lactate and glucose concentrations during CN intoxication is unknown. We used intracerebral microdialysis to study the in vivo effect of hydroxycobalamin or HBO2 treatment on acute CN-induced deterioration in brain metabolism. Anesthetized rats were allocated to four groups receiving potassium CN (KCN) 5.4 mg/kg or vehicle intra-arterially: 1) vehicle-treated control rats; 2) KCN-poisoned rats; 3) KCN-poisoned rats receiving hydroxycobalamin (25 mg); and 4) KCN-poisoned rats treated with HBO2 (284 kPa for 90 minutes). KCN alone caused a prompt increase in interstitial brain lactate and glucose concentrations peaking at 60 minutes. Both hydroxycobalamin and HBO2 abolished KCN-induced increases in brain lactate and glucose concentration. However, whereas HBO2 treatment increased cerebral PtO2 and reduced respiratory distress and cyanosis, OHCob did not have this beneficial effect. In conclusion, CN intoxication in anesthetized rats produces specific uncoupling of cerebral oxidative metabolism resulting in interstitial lactate and glucose surges that may be ameliorated by treatment with either hydroxycobalamin or HBO2.

Erythropoietin and vascular endothelial growth factor as risk markers for severe hypoglycaemia in type 1 diabetes.

OBJECTIVE: Circulating erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increase during hypoglycaemia and may represent protective hormonal counter-regulatory responses. We tested the hypothesis that low levels of EPO and VEGF are associated with a higher frequency of severe hypoglycaemia in a cohort of patients with type 1 diabetes. DESIGN: Prospective observational follow-up study. METHODS: Totally 219 patients with type 1 diabetes (41% females, age 46+/-13 years (mean+/-s.d.), duration of diabetes 21+/-12 years, and HbAlc 8.5+/-1.1%) were followed in a 1-year observational study. Plasma EPO and serum VEGF levels were measured at baseline with ELISA. Events of severe hypoglycaemia defined by third party assistance were recorded and validated in telephone interviews within 24 h. RESULTS: Totally 235 episodes of severe hypoglycaemia (1.1 episodes per patient-year) were reported by 82 patients (37%). At baseline, plasma EPO was 8.6 (3.1-34.3) U/l (median (range)), and serum VEGF was 52.2 (6.6-337) pg/ml. The levels of EPO and VEGF were not associated with frequency of severe and mild hypoglycaemia. The levels of EPO were not associated with age, sex, duration of diabetes, body mass index, HbAlc, C-peptide level or hypoglycaemia awareness status. The levels of VEGF were positively associated with age and female sex. CONCLUSIONS: Although several studies suggest that VEGF and EPO may affect brain function during hypoglycaemia, this study does not support random VEGF or EPO levels to determine future risk of severe hypoglycaemia in people with type 1 diabetes.

Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men.

Recombinant human erythropoietin (EPO) increases exercise capacity by stimulating erythropoiesis and subsequently enhancing oxygen delivery to the working muscles. In a large dose, EPO crosses the BBB and may reduce central fatigue and improve cognition. In turn, this would augment exercise capacity independent of erythropoiesis. To test this hypothesis, 15 healthy young men (18-34 years old, 74 + or - 7 kg) received either 3 days of high-dose (30,000 IU/day; n = 7) double-blinded placebo controlled or 3 mo of low-dose (5,000 IU/wk; n = 8) counter-balanced open but controlled administration of EPO. We recorded exercise capacity, transcranial ultrasonography-derived middle cerebral artery blood velocity, and arterial-internal jugular venous concentration differences of glucose and lactate. In addition, cognitive function, ratings of perceived exertion, ventilation, and voluntary activation by transcranial magnetic stimulation-induced twitch force were evaluated. Although EPO in a high dose increased cerebrospinal fluid EPO concentration approximately 20-fold and affected ventilation and cerebral glucose and lactate metabolism (P < 0.05), 3 days of high-dose EPO administration had no effect on cognition, voluntary activation, or exercise capacity, but ratings of perceived exertion increased (P < 0.05). We confirmed that 3 mo of administration of EPO increases exercise capacity, but the improvement could not be accounted for by other mechanisms than enhanced oxygen delivery. In conclusion, EPO does not attenuate central fatigue or change cognitive performance strategy, suggesting that EPO enhances exercise capacity exclusively by increased oxygen delivery to the working muscles.

NT-pro-BNP during hypoglycemia and hypoxemia in normal subjects: impact of renin-angiotensin system activity.

Brain-derived natriuretic peptide (BNP) is a cardioprotective peptide released, together with the inactive NH(2)-terminal part of its prohormone (NT-pro-BNP), in response to different kinds of myocardial stress. Hypoglycemia and hypoxemia are conditions that threaten cellular function and hence potentially stimulate BNP release. BNP interacts with the renin-angiotensin system (RAS). The aim of this study was, therefore, to explore if basal RAS activity has an impact on NT-pro-BNP concentrations during myocardial stress induced by hypoglycemia and hypoxemia. From a cohort of 303 healthy young men, 10 subjects with high-RAS activity and 10 subjects with low-RAS activity (age 26 +/- 1 yr; mean +/- SE) were studied in a single-blinded, randomized, counterbalanced, crossover study on three occasions separated by at least 3 wk: 1) hypoglycemia (mean nadir plasma glucose 2.7 +/- 0.5 mmol/l), 2) hypoxemia (mean nadir Po(2) 5.8 +/- 0.5 kPa), and 3) normoglycemic normoxia (control). NT-pro-BNP was measured at baseline, during the stimuli, and in the recovery phase. Hypoxemia was associated with a 9% increase in NT-pro-BNP from 2.2 +/- 1.5 pmol/l at baseline to 2.4 +/- 1.5 pmol/l during hypoxemia (P < 0.001). Hypoglycemia did not affect the NT-pro-BNP level. RAS activity had no impact on NT-pro-BNP levels during hypoglycemia and hypoxemia. Hypoxemia, but not hypoglycemia, stimulates NT-pro-BNP. This indicates that cardiac defense mechanisms against hypoglycemia, if any, are probably different from those against hypoxemia. Basal RAS activity had no impact on NT-pro-BNP levels.

Erythropoietin in patients with aneurysmal subarachnoid haemorrhage: a double blind randomised clinical trial.

BACKGROUND: Erythropoietin (EPO) is neuroprotective in experimental models of stroke and subarachnoid haemorrhage (SAH) and possibly in patients with thromboembolic stroke. We studied the efficacy and safety of EPO in patients with SAH. METHODS: A larger scale clinical trial was planned but preliminarily terminated because of a lower than expected inclusion rate. However, 73 patients were randomised to treatment with EPO (500 IU/kg/day for three days) or placebo. The primary endpoint was Glasgow Outcome Score at six months. We further studied surrogate measures of secondary ischaemia, i.e. transcranial Doppler (TCD) flow velocity, symptomatic vasospasm, cerebral metabolism (microdialysis) and jugular venous oximetry, biochemical markers of brain damage (S-100beta and neuron specific enolase) and blood-brain barrier integrity. FINDINGS: The limited sample size precluded our primary hypotheses being verified and refuted. However, data from this study are important for any other study of SAH and as much raw data as possible are presented and can be included in future meta analyses. On admission the proportion of patients in a poor condition was higher in the EPO group compared with the placebo group but the difference was statistically insignificant. In the EPO-treated patients the CSF concentration of EPO increased 600-fold. Except for a higher extracelullar concentration of glycerol in the EPO group probably caused by the poorer clinical condition of these patients, there were no statistically significant group differences in the primary or secondary outcome measures. EPO was well tolerated. CONCLUSIONS: Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted.

Deep venous thrombosis and pulmonary embolism following physical restraint.

OBJECTIVE: We describe a case of deep venous thrombosis (DVT) and pulmonary embolism (PE) following the use of physical restraint in a patient with a diagnosis of acute delusional psychotic disorder. METHOD: A new case report of DVT and PE associated with prolonged physical restraint is presented. The literature on physical restraint, DVT, and PE was reviewed using a search of Medline and Psychinfo from 1966 to the present. RESULTS: Four other reported cases of DVT and PE were found in association with physically restrained patients. CONCLUSION: Risk of DVT and PE in association with immobilization during physical restraint may occur in spite of no pre-existing risk factors. Medical guidelines for the prevention of thrombosis following physical restraint are presented. Despite the absence of controlled trials of treatment effectiveness, the catastrophic outcome of DVT and PE warrants early and vigorous intervention in patients undergoing physical restraint.

Trends in monitoring patients with aneurysmal subarachnoid haemorrhage.

After aneurysmal subarachnoid haemorrhage (SAH), the clinical outcome depends upon the primary haemorrhage and a number of secondary insults in the acute post-haemorrhagic period. Some secondary insults are potentially preventable but prevention requires prompt recognition of cerebral or systemic complications. Currently, several neuro-monitoring techniques are available; this review describes the most frequently used techniques and discusses indications for their use, and their value in diagnosis and prognosis. None of the techniques, when considered in isolation, has proved sufficient after SAH. Furthermore, the use of multi-modality monitoring is hampered by a lack of clinical studies that identify combinations of specific techniques in terms of clinical information and reliability. However, ischaemia at the tissue level can be detected by intracerebral microdialysis technique. Used together with the conventional monitoring systems, for example intracranial pressure measurements, transcranial Doppler ultrasound and modern neuro-imaging, direct assessment of biochemical markers by intracerebral microdialysis is promising in the advancement of neurointensive care of patients with SAH. A successfully implemented monitoring system provides answers but it also raises valuable new questions challenging our current understanding of the brain injury after SAH.

Renal 131I-hippuran extraction in man: effects of dopamine.

AIMS: This study examined the 131I-hippuran extraction fraction during baseline renal blood flow rates and at high flow rates induced by dopamine. METHODS: In 12 healthy subjects, arterial and renal venous sampling was used to measure the renal extraction of 131I-hippuran. Effective renal plasma flow values determined by the urinary clearance of 131I-hippuran were compared with renal plasma flow values corrected for incomplete extraction of 131I-hippuran. RESULTS: Dopamine (3 micro g kg-1 min-1) decreased 131I-hippuran extraction from 75 +/- 4% at baseline to 62 +/- 6% (means +/- 95% confidence intervals, P < 0.001). Hence, the increase in renal plasma flow (85 +/- 23%) greatly exceeded the rise in effective renal plasma flow (51 +/- 15%, P < 0.002). CONCLUSIONS: Dopamine induced increases in renal blood flow are largely under-estimated when measurements are not corrected for incomplete extraction of 131I-hippuran.