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Introduction: Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO2 by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO2 response to INO. Methods: After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion. Results: Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 >= 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO. Conclusions: ET-1 may therefore be involved in mediating the response to INO.

Objective: Automated external defibrillators (AEDs) are becoming increasingly available in public places to be used by citizens in case of cardiac arrest. Most AEDs are semi-automatic (SAEDs), but some are fully automatic (FAEDs) and there is ongoing debate and concern that they may lead to inadvertent shocks to rescuers or bystanders because the timing of the shock is not controlled by the rescuer. We therefore compared the behaviour of untrained citizens using an FAED or an SAED in a simulated cardiac arrest scenario. Design and participants: One hundred and seventy-six laypeople were randomised to use an FAED or an SAED (Lifepak CR+, Medtronic, Redmond, USA) in a simulated cardiac arrest scenario on a manikin (Ambu, Denmark) where a bystander was touching the victim's upper arm. Each rescuer's performance was recorded on video and analysed afterwards using a modified Cardiff Score. The rescuer or the bystander was considered unsafe if either of them touched the victim during shock delivery. Results: Eleven cases could not be analysed because of technical problems. Fifteen participants violated the protocol making further analysis impossible. Of the remaining 150 participants, 68 used the FAED and 82 used the SAED. The rescuers were safe in 97/150 (65%) cases, without a difference between FAED and SAED. The bystander was safe in 25/68 (37%) cases in the FAED group versus 19/82 (23%) in the SAED group (p=0.07). Combined safety of both rescuer and bystander was observed in 23/68 (34%) cases in the FAED group versus 15/82 (18%) in the SAED group (p=0.03). Conclusions: Safety was not compromised when untrained lay rescuers used an FAED compared with an SAED. The observation of overall safer behaviour by FAED users in the presence of bystanders may be related to the additional instructions provided by the FAED, and the reduced interaction of the rescuer with the bystander when using the SAED. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Primary objective: The aim of the present study was to explore the concurrent validity, inter-rater agreement and diagnostic sensitivity of a French adaptation of the Coma Recovery Scale-Revised (CRS-R) as compared to other coma scales such as the Glasgow Coma Scale (GCS), the Full Outline of UnResponsiveness scale (FOUR) and the Wessex Head Injury Matrix (WHIM). Research design: Multi-centric prospective study. Method and procedures: To test concurrent validity and diagnostic sensitivity, the four behavioural scales were administered in a randomized order in 77 vegetative and minimally conscious patients. Twenty-four clinicians with different professional backgrounds, levels of expertise and CRS-R experience were recruited to assess inter-rater agreement. Main outcomes and results: Good concurrent validity was obtained between the CRS-R and the three other standardized behavioural scales. Inter-rater reliability for the CRS-R total score and sub-scores was good, indicating that the scale yields reproducible findings across examiners and does not appear to be systematically biased by profession, level of expertise or CRS-R experience. Finally, the CRS-R demonstrated a significantly higher sensitivity to detect MCS patients, as compared to the GCS, the FOUR and the WHIM. Conclusion: The results show that the French version of the CRS-R is a valid and sensitive scale which can be used in severely brain damaged patients by all members of the medical staff., SCOPUS: ar.j, info:eu-repo/semantics/published

The following recommendations, which aim at standardising and rationalising clinical indications for the transfusion of red cells in Belgium, were drawn up by a working group of the Superior Health Council. To this end, the Superior Health Council organised an expert meeting devoted to "Guidelines for the transfusion of red cells" in collaboration with the Belgian Hematological Society. The experts discussed the indications for red cell transfusions, the ideal red cell concentrate, the practical issues of administering red cells, and red cell transfusions in patients in a critical condition. The recommendations formulated by the experts were validated by the working group with the purpose of harmonising red cell transfusion in Belgian hospitals., SCOPUS: re.j, info:eu-repo/semantics/published

Over the last fifteen years, child's pain has become one of our major concerns. In spite of this evolution, it remains one of the most frequent complications after ambulatory surgery. It is thus essential to implement all the resources we have at our disposal in order to optimize pain management This can be obtained by basing our strategy on the concept of multimode analgesia. It is consequently essential that each team can achieve its own quality program; the corollary will be the development of clear recommendations for the parents with a systematic analgesics regulation at home and the possibility to resort to the family doctor or to the ambulatory centre in the event of persistence of pain., SCOPUS: ar.j, info:eu-repo/semantics/published

Although often clinically silent, pancreatic cellular injury (PCI) is relatively frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and time course are largely unknown. We defined PCI as the simultaneous presence of abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The frequency and time evolution of PCI were assessed in this condition using assays for specific exocrine pancreatic enzymes. Correlations with inflammatory markers were searched for preoperative risk factors. One hundred ninety-three patients submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase, pancreatic isoamylase, lipase, and markers of inflammation (alpha1-protease inhibitor, alpha2-macroglobulin, myeloperoxidase) were measured preoperatively and postoperatively until day 8. The postoperative increase in plasma levels of pancreatic enzymes and urinary IRT was biphasic in all patients: early after surgery and later (from day 4 to 8 after surgery). One hundred thirty-three patients (69%) experienced PCI, with mean IRT, isoamylase, and alpha1-protease inhibitor values higher for each sample than that in patients without PCI. By multiple regression analysis, we found preoperative values of plasma IRT >or=40 ng/mL, amylase >or=42 IU/mL, and pancreatic isoamylase >or=20 IU/L associated with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a significant correlation was found between the 4 pancreatic enzymes and urinary IRT, total calcium, myeloperoxidase, alpha1-protease inhibitor, and alpha2-macroglobulin. These data support a high prevalence of postoperative PCI after cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically silent, especially when pancreatic enzymes were elevated preoperatively., Clinical Trial, Journal Article, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e. have no means of producing speech, limb or facial movements. Acute ventral pontine lesions are its most common cause. People with such brainstem lesions often remain comatose for some days or weeks, needing artificial respiration and then gradually wake up, but remaining paralyzed and voiceless, superficially resembling patients in a vegetative state or akinetic mutism. In acute locked-in syndrome (LIS), eye-coded communication and evaluation of cognitive and emotional functioning is very limited because vigilance is fluctuating and eye movements may be inconsistent, very small, and easily exhausted. It has been shown that more than half of the time it is the family and not the physician who first realized that the patient was aware. Distressingly, recent studies reported that the diagnosis of LIS on average takes over 2.5 months. In some cases it took 4-6 years before aware and sensitive patients, locked in an immobile body, were recognized as being conscious. Once a LIS patient becomes medically stable, and given appropriate medical care, life expectancy increases to several decades. Even if the chances of good motor recovery are very limited, existing eye-controlled, computer-based communication technology currently allow the patient to control his environment, use a word processor coupled to a speech synthesizer, and access the worldwide net. Healthy individuals and medical professionals sometimes assume that the quality of life of an LIS patient is so poor that it is not worth living. On the contrary, chronic LIS patients typically self-report meaningful quality of life and their demand for euthanasia is surprisingly infrequent. Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed LIS patient is competent to consent, Journal Article, Research Support, Non-U.S. Gov't, Review, info:eu-repo/semantics/published

We review cerebral processing of auditory and noxious stimuli in minimally conscious state (MCS) and vegetative state (VS) patients. In contrast with limited brain activation found in VS patients, MCS patients show activation similar to controls in response to auditory, emotional and noxious stimuli. Despite an apparent clinical similarity between MCS and VS patients, functional imaging data show striking differences in cortical segregation and integration between these two conditions. However, in the absence of a generally accepted neural correlate of consciousness as measured by functional neuroimaging, clinical assessment remains the gold standard for the evaluation and management of severely brain damaged patients., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

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Comatose, vegetative, minimally conscious or locked-in patients represent a problem in terms of diagnosis, prognosis, treatment and everyday management at the intensive care unit. The evaluation of possible cognitive functions in these patients is difficult because voluntary movements may be very small, inconsistent and easily exhausted. Functional neuroimaging cannot replace the clinical assessment of patients with altered states of consciousness. Nevertheless, it can describe objectively how deviant from normal the cerebral activity is and its regional distribution at rest and under various conditions of stimulation. The quantification of brain activity differentiates patients who sometimes only differ by a brief and incomplete blink of an eye. In the present paper, we will first try to define consciousness as it can be assessed at the patient's bedside. We then review the major clinical entities of altered states of consciousness encountered in the intensive care unit. Finally, we discuss the functional neuroanatomy of these conditions as assessed by positron emission tomography (PET) scanning., English Abstract, Journal Article, Review, info:eu-repo/semantics/published

Background. This single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care. Methods: Subjects (N = 492) with hemoglobin concentrations of 12-15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 ± 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 ± 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 ± 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 ± 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 ± 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion. Results: Both groups had similar hemoglobin concentrations at screening (13.5 ± 1.0 g/dl) and at discharge: 10.8 ± 1.2 g/dl (PFC) and 11.1 ± 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53% vs. 43%, P < 0.05), and fewer erythrocytes were transfused (1.5 ± 4.8 vs. 2.1 ± 3.9 units; median, 0 vs. 1 unit; P = 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696 vs. 846 units). In the protocol-define

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e. change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction., Journal Article, Research Support, Non-U.S. Gov't, Review, info:eu-repo/semantics/published

The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. We used positron emission tomography to assess the central processing of noxious somatosensory stimuli in the PVS. Changes in regional cerebral blood flow were measured during high-intensity electrical stimulation of the median nerve compared with rest in 15 nonsedated patients and in 15 healthy controls. Evoked potentials were recorded simultaneously. The stimuli were experienced as highly unpleasant to painful in controls. Brain glucose metabolism was also studied with [(18)F]fluorodeoxyglucose in resting conditions. In PVS patients, overall cerebral metabolism was 40% of normal values. Nevertheless, noxious somatosensory stimulation-activated midbrain, contralateral thalamus, and primary somatosensory cortex in each and every PVS patient, even in the absence of detectable cortical evoked potentials. Secondary somatosensory, bilateral insular, posterior parietal, and anterior cingulate cortices did not show activation in any patient. Moreover, in PVS patients, the activated primary somatosensory cortex was functionally disconnected from secondary somatosensory, bilateral posterior parietal, premotor, polysensory superior temporal, and prefrontal cortices. In conclusion, somatosensory stimulation of PVS patients, at intensities that elicited pain in controls, resulted in increased neuronal activity in primary somatosensory cortex, even if resting brain metabolism was severely impaired. However, this activation of primary cortex seems to be isolated and dissociated from higher-order associative cortices., Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

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