Effects of diazepam on BOLD activation during the processing of aversive faces

This study aimed to measure, using fMRI, the effect of diazepam on the haemodynamic response to emotional faces. Twelve healthy male volunteers (mean age = 24.83 +/- 3.16 years), were evaluated in a randomized, balanced-order, double-blind, placebo-controlled crossover design. Diazepam (10 mg) or placebo was given 1 h before the neuroimaging acquisition. In a blocked design covert face emotional task, subjects were presented with neutral (A) and aversive (B) (angry or fearful) faces. Participants were also submitted to an explicit emotional face recognition task, and subjective anxiety was evaluated throughout the procedures. Diazepam attenuated the activation of right amygdala and right orbitofrontal cortex and enhanced the activation of right anterior cingulate cortex (ACC) to fearful faces. In contrast, diazepam enhanced the activation of posterior left insula and attenuated the activation of bilateral ACC to angry faces. In the behavioural task, diazepam impaired the recognition of fear in female faces. Under the action of diazepam, volunteers were less anxious at the end of the experimental session. These results suggest that benzodiazepines can differentially modulate brain activation to aversive stimuli, depending on the stimulus features and indicate a role of amygdala and insula in the anxiolytic action of benzodiazepines.

Avaliação morfométrica e hemodinâmica comparativa dos vasos envolvidos no shunt portossistêmico congênito em cães

Foram realizados o estudo morfométrico e o estudo hemodinâmico da veia porta em vinte cães clinicamente normais, de idade igual e inferior a 120 dias e em quatorze cães portadores de shunt portossistêmico, de idades entre 90 e 360 dias. Nos cães do grupo controle, as margens hepáticas apresentaram-se entre 1,50cm e 3,00cm caudalmente à margem costal. Os diâmetros médios da veia porta (VP), veia cava caudal (VCC) e aorta abdominal (AO) obtidas foram respectivamente, 0,38cm, 0,37cm e 0,41cm. As proporções entre os diâmetros médios VP/VCC e VP/AO apresentaram médias de 1,10 e 0,94, respectivamente. As médias das áreas da VP, VCC e AO resultaram respectivamente em 0,12cm2 , 0,11cm2 e 0,14cm2. No estudo hemodinâmico da VP destes animais, utilizando-se o ultrassom Doppler, a velocidade média de fluxo sangüíneo portal (VMFSP) mediu 17,76cm/s. A média de fluxo sangüíneo portal (FSP) resultou em 83,11ml/min/kg. O índice de congestão (IC) apresentou média de 0,006. Para o grupo de cães portadores de shunt portossistêmico, o fígado apresentou redução de seu volume, sendo as margens hepáticas visibilizadas entre 1,00cm e 2,00cm cranialmente à margem costal. No estudo morfométrico, as médias dos diâmetros médios obtidos de VP, VCC e AO resultaram respectivamente em 0,40cm, 0,74cm e 0,56cm. As proporções entre os diâmetros médios VP/VCC e VP/AO resultaram respectivamente em 0,54 e 0,69. As médias das áreas de VP, VCC e AO resultaram respectivamente em 0,14cm2, 0,31cm2 e 0,25cm2. Ao ultrassom Doppler a VMFSP mediu 22,29cm/s e a média do IC da VP obtido foi de 0,006.

Aspetti Ultrasonografici in Corso di Sviluppo Placentare e Adattamento Cardiovascolare nella Cavalla Gravida: ecografia bidimensionale, ecocardiografia ed ecocontrastografia (CEUS)

In corso di gravidanza normale avvengono modificazioni emodinamiche centrali e periferiche volte a garantire le crescenti richieste nutritive dell'unità feto-placentare. L’ecografia con mezzo di contrasto (CEUS-Contrast Enhanced Ultrasonography) a base di microbolle offre una nuova opportunità di monitorare e quantificare la perfusione utero-placentare in condizioni normali e patologiche. L’ecocardiografia è stata ampiamente usata in medicina umana per valutare l’adattamento morfo-funzionale cardiaco materno durante la gravidanza. Gli scopi di questo lavoro prospettico sono stati di applicare, per la prima volta nella specie equina, un mezzo di contrasto di II generazione (Sonovue®), al fine quantificare la perfusione utero-placentare in corso di gravidanza normale, valutandone gli effetti sul benessere materno-fetale e di descrivere le modificazioni nei parametri ecocardiografici morfometrici e funzionali cardiaci, in particolare relativi alla funzione del ventricolo sinistro nel corso di una gravidanza fisiologica. Due fattrici sane di razza Trottatore sono state monitorate ecograficamente in maniera seriale durante l’intero corso della gravidanza, tramite esame bidimensionale, ecocontrastografia dell'unità utero-placentare, flussimetria Doppler delle arterie uterine, ecocardiografia materna in modalità bidimensionale, M-mode, Doppler e Tissue Doppler Imaging. I neonati sono stati clinicamente monitorati e gli invogli fetali esaminati. Il pattern di microperfusione utero-placentare è valutabile quali-quantitativamente tramite la CEUS e dimostra un’aumento del flusso a livello di microvascolarizzazione uterina con l'avanzare della gravidanza; non è stata rilevata la presenza di microbolle a livello di strutture fetali nè effetti dannosi sul benessere materno-fetale. In questo studio sono state osservate delle modificazioni cardiache materne in corso di gravidanza fisiologica, relative all'aumento della FC, del CO ed in particolare all'aumento delle dimensioni dell'atrio sinistro ed a modificazioni nelle onde di velocità di flusso e tissutali di riempimento del ventricolo sinistro.

Acute fluid ingestion in the treatment of orthostatic intolerance - important implications for daily practice

Rapid water ingestion improves orthostatic intolerance (OI) in multiple system atrophy (MSA) and postural tachycardia syndrome (PoTS). We compared haemodynamic changes after water and clear soup intake, the latter being a common treatment strategy for OI in daily practice.

Chapter I: Definitions, epidemiology, clinical presentation and prognosis

The concept of chronic critical limb ischaemia (CLI) emerged late in the history of peripheral arterial occlusive disease (PAOD). The historical background and changing definitions of CLI over the last decades are important to know in order to understand why epidemiologic data are so difficult to compare between articles and over time. The prevalence of CLI is probably very high and largely underestimated, and significant differences exist between population studies and clinical series. The extremely high costs associated with management of these patients make CLI a real public health issue for the future. In the era of emerging vascular surgery in the 1950s, the initial classification of PAOD by Fontaine, with stages III and IV corresponding to CLI, was based only on clinical symptoms. Later, with increasing access to non-invasive haemodynamic measurements (ankle pressure, toe pressure), the need to prove a causal relationship between PAOD and clinical findings suggestive of CLI became a real concern, and the Rutherford classification published in 1986 included objective haemodynamic criteria. The first consensus document on CLI was published in 1991 and included clinical criteria associated with ankle and toe pressure and transcutaneous oxygen pressure (TcPO(2)) cut-off levels <50 mmHg, <30 mmHg and <10 mmHg respectively). This rigorous definition reflects an arterial insufficiency that is so severe as to cause microcirculatory changes and compromise tissue integrity, with a high rate of major amputation and mortality. The TASC I consensus document published in 2000 used less severe pressure cut-offs (≤ 50-70 mmHg, ≤ 30-50 mmHg and ≤ 30-50 mmHg respectively). The thresholds for toe pressure and especially TcPO(2) (which will be also included in TASC II consensus document) are however just below the lower limit of normality. It is therefore easy to infer that patients qualifying as CLI based on TASC criteria can suffer from far less severe disease than those qualifying as CLI in the initial 1991 consensus document. Furthermore, inclusion criteria of many recent interventional studies have even shifted further from the efforts of definition standardisation with objective criteria, by including patients as CLI based merely on Fontaine classification (stage III and IV) without haemodynamic criteria. The differences in the natural history of patients with CLI, including prognosis of the limb and the patient, are thus difficult to compare between studies in this context. Overall, CLI as defined by clinical and haemodynamic criteria remains a severe condition with poor prognosis, high medical costs and a major impact in terms of public health and patients' loss of functional capacity. The major progresses in best medical therapy of arterial disease and revascularisation procedures will certainly improve the outcome of CLI patients. In the future, an effort to apply a standardised definition with clinical and objective haemodynamic criteria will be needed to better demonstrate and compare the advances in management of these patients.

Chapter II: Diagnostic methods

Non-invasive vascular studies can provide crucial information on the presence, location, and severity of critical limb ischaemia (CLI), as well as the initial assessment or treatment planning. Ankle-brachial index with Doppler ultrasound, despite limitations in diabetic and end-stage renal failure patients, is the first-line evaluation of CLI. In this group of patients, toe-brachial index measurement may better establish the diagnosis. Other non-invasive measurements, such as segmental limb pressure, continuous-wave Doppler analysis and pulse volume recording, are of limited accuracy. Transcutaneous oxygen pressure (TcPO(2)) measurement may be of value when rest pain and ulcerations of the foot are present. Duplex ultrasound is the most important non-invasive tool in CLI patients combining haemodynamic evaluation with imaging modality. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the next imaging studies in the algorithm for CLI. Both CTA and MRA have been proven effective in aiding the decision-making of clinicians and accurate planning of intervention. The data acquired with CTA and MRA can be manipulated in a multiplanar and 3D fashion and can offer exquisite detail. CTA results are generally equivalent to MRA, and both compare favourably with contrast angiography. The individual use of different imaging modalities depends on local availability, experience, and costs. Contrast angiography represents the gold standard, provides detailed information about arterial anatomy, and is recommended when revascularisation is needed.

Exercise training in heart failure: from theory to practice. A consensus document of the Heart Failure Association and the European Association for Cardiovascular Prevention and Rehabilitation

The European Society of Cardiology heart failure guidelines firmly recommend regular physical activity and structured exercise training (ET), but this recommendation is still poorly implemented in daily clinical practice outside specialized centres and in the real world of heart failure clinics. In reality, exercise intolerance can be successfully tackled by applying ET. We need to encourage the mindset that breathlessness may be evidence of signalling between the periphery and central haemodynamic performance and regular physical activity may ultimately bring about favourable changes in myocardial function, symptoms, functional capacity, and increased hospitalization-free life span and probably survival. In this position paper, we provide practical advice for the application of exercise in heart failure and how to overcome traditional barriers, based on the current scientific and clinical knowledge supporting the beneficial effect of this intervention.

Bone morphogenetic protein receptor 2 in patients with idiopathic portal hypertension

In idiopathic portal hypertension (IPH) typical vascular lesions are present in the branches of the portal vein or in the perisinusoidal area of the liver. Similar histological alterations have been reported in the pulmonary vasculature of patients with idiopathic pulmonary artery hypertension (IPAH). As IPAH is associated with mutations of the bone morphogenetic protein receptor 2 (BMPR2) gene, the aim of this study was to investigate whether this association might also be found in patients with IPH. Twenty-three samples belonging to 21 unrelated caucasian patients with IPH followed in the hepatic haemodynamic laboratory of the Hospital Clinic in Barcelona were included in the study. All patients were studied for the entire open reading frame and splice site of the BMPR2 gene by direct sequencing and multiple ligation probe amplification (MLPA) in order to detect large deletions/duplications. None of the 23 patients had pulmonary artery hypertension. Four patients presented one single nucleotide polymorphism (SNP) in intron 5, four patients had a SNP in exon 12 and a SNP in exon 1 was found in two cases. Two patients had both intron 5 and exon 12 polymorphisms. All SNPs were previously described. Except for these three SNPs, neither mutations nor rearrangements have been identified in the BMPR2 gene in this population. We did not detect mutations or rearrangements in the coding region of the BMPR2 gene in our patients with IPH. These findings suggest that, in contrast to IPAH, mutations in BMPR2 are not involved in the pathogenesis of IPH.

The Bernese Hypothermia Algorithm: a consensus paper on in-hospital decision-making and treatment of patients in hypothermic cardiac arrest at an alpine level 1 trauma centre

INTRODUCTION: Guidelines for the treatment of patients in severe hypothermia and mainly in hypothermic cardiac arrest recommend the rewarming using the extracorporeal circulation (ECC). However,guidelines for the further in-hospital diagnostic and therapeutic approach of these patients, who often suffer from additional injuries—especially in avalanche casualties, are lacking. Lack of such algorithms may relevantly delay treatment and put patients at further risk. Together with a multidisciplinary team, the Emergency Department at the University Hospital in Bern, a level I trauma centre, created an algorithm for the in-hospital treatment of patients with hypothermic cardiac arrest. This algorithm primarily focuses on the decision-making process for the administration of ECC. THE BERNESE HYPOTHERMIA ALGORITHM: The major difference between the traditional approach, where all hypothermic patients are primarily admitted to the emergency centre, and our new algorithm is that hypothermic cardiac arrest patients without obvious signs of severe trauma are taken to the operating theatre without delay. Subsequently, the interdisciplinary team decides whether to rewarm the patient using ECC based on a standard clinical trauma assessment, serum potassium levels, core body temperature, sonographic examinations of the abdomen, pleural space, and pericardium, as well as a pelvic X-ray, if needed. During ECC, sonography is repeated and haemodynamic function as well as haemoglobin levels are regularly monitored. Standard radiological investigations according to the local multiple trauma protocol are performed only after ECC. Transfer to the intensive care unit, where mild therapeutic hypothermia is maintained for another 12 h, should not be delayed by additional X-rays for minor injuries. DISCUSSION: The presented algorithm is intended to facilitate in-hospital decision-making and shorten the door-to-reperfusion time for patients with hypothermic cardiac arrest. It was the result of intensive collaboration between different specialties and highlights the importance of high-quality teamwork for rare cases of severe accidental hypothermia. Information derived from the new International Hypothermia Registry will help to answer open questions and further optimize the algorithm.

Stimulation induced variability of pulse plethysmography does not discriminate responsiveness to intubation

BACKGROUND: Hypnotic depth but not haemodynamic response to painful stimulation can be measured with various EEG-based anaesthesia monitors. We evaluated the variation of pulse plethysmography amplitude induced by an electrical tetanic stimulus (PPG variation) as a potential measure for analgesia and predictor of haemodynamic responsiveness during general anaesthesia. METHODS: Ninety-five patients, ASA I or II, were randomly assigned to five groups [Group 1: bispectral index (BIS) (range) 40-50, effect site remifentanil concentration 1 ng ml(-1);Group 2: BIS 40-50, remifentanil 2 ng ml(-1); Group 3: BIS 40-50, remifentanil 4 ng ml(-1); Group 4: BIS 25-35, remifentanil 2 ng ml(-1); Group 5: BIS 55-65, remifentanil 2 ng ml(-1)]. A 60 mA tetanic stimulus was applied for 5 s on the ulnar nerve. From the digitized pulse oximeter wave recorded on a laptop computer, linear and non-linear parameters of PPG variation during the 60 s period after stimulation were computed. The haemodynamic response to subsequent orotracheal intubation was recorded. The PPG variation was compared between groups and between responders and non-responders to intubation (anova). Variables independently predicting the response were determined by logistic regression. RESULTS: The probability of a response to tracheal intubation was 0.77, 0.47, 0.05, 0.18 and 0.52 in Groups 1-5, respectively (P<0.03). The PPG variability was significantly higher in responders than in non-responders but it did not improve the prediction of the response to tracheal intubation based on BIS level and effect site remifentanil concentration. CONCLUSION: Tetanic stimulation induced PPG variation does not reflect the analgesic state in a wide clinical range of surgical anaesthesia.

Terlipressin as an adjunct vasopressor in refractory hypotension after tricyclic antidepressant intoxication

AIM OF STUDY: To report the management of cardiovascular failure refractory to standard catecholamine therapy with terlipressin in a patient with tricyclic antidepressant (TCA) intoxication. CASE REPORT: A 41-year-old woman, with suicidal ingestion of 11.25 g amitriptyline and 1500 mg diclofenac, was admitted to the emergency department. After 30 min in ventricular fibrillation, with ongoing CPR, she regained a potentially perfusing rhythm, but with hypotension refractory to standard catecholamine therapy with adrenaline, 2 microg/kg/min (norepinephrine); adrenaline, 1 microg/kg/min (epinephrine) until 55 min after admission. An injection of 1 mg terlipressin restored mean arterial blood pressure >65 mmHg within 10 min. Ten hours after admission to the intensive care unit, catecholamine support could be withdrawn because of a stable haemodynamic state. Within 7 days, all organ function recovered, and the patient regained full neurological function. CONCLUSIONS: Successful management of cardiovascular failure with terlipressin after TCA intoxication refractory to catecholamines suggests a potential role for terlipressin as an adjunct vasopressor in severely hypotensive patients.

Arginine vasopressin in advanced cardiovascular failure during the post-resuscitation phase after cardiac arrest

Arginine vasopressin (AVP) has been employed successfully during cardiopulmonary resuscitation, but there exist only few data about the effects of AVP infusion for cardiovascular failure during the post-cardiac arrest period. Cardiovascular failure is one of the main causes of death after successful resuscitation from cardiac arrest. Although the "post-resuscitation syndrome" has been described as a "sepsis-like" syndrome, there is little information about the haemodynamic response to AVP in advanced cardiovascular failure after cardiac arrest. In this retrospective study, haemodynamic and laboratory variables in 23 patients with cardiovascular failure unresponsive to standard haemodynamic therapy during the post-cardiac arrest period were obtained before, and 30 min, 1, 4, 12, 24, 48, and 72 h after initiation of a supplementary AVP infusion (4 IU/h). During the observation period, AVP significantly increased mean arterial blood pressure (58+/-14 to 75+/-19 mmHg, p < 0.001), and decreased noradrenaline (norepinephrine) (1.31+/-2.14 to 0.23+/-0.3 microg/kg/min, p = 0.03), adrenaline (epinephrine) (0.58+/-0.23 to 0.04+/-0.03 microg/kg/min, p = 0.001), and milrinone requirements (0.46+/-0.15 to 0.33+/-0.22 microg/kg/min, p < 0.001). Pulmonary capillary wedge pressure changed significantly (p < 0.001); an initial increase being followed by a decrease below baseline values. While arterial lactate concentrations (95+/-64 to 21+/-18 mg/dL, p < 0.001) and pH (7.27+/-0.14 to 7.4+/-0.14, p < 0.001) improved significantly, total bilirubin concentrations (1.12+/-0.95 to 3.04+/-3.79 mg/dL, p = 0.001) increased after AVP. There were no differences in the haemodynamic or laboratory response to AVP between survivors and non-survivors. In this study, advanced cardiovascular failure that was unresponsive to standard therapy could be reversed successfully with supplementary AVP infusion in >90% of patients surviving cardiac arrest.

Acute pulmonary embolectomy three days following a coronary artery bypass graft procedure

Pulmonary embolism is very rarely reported early after cardiac surgery, most probably due to full heparinisation during cardiopulmonary bypass. We report a 66-year-old man without thromboembolic history who presented three days after a coronary artery bypass grafting procedure with acute dyspnoea and haemodynamic instability. A CT scan confirmed paracentral bilateral pulmonary embolism requiring an urgent and successful embolectomy. Review of the literature confirms that pulmonary embolism may occur in up to 3% of post-cardiopulmonary bypass patients. The possibility of pulmonary embolism must be taken into consideration in post-cardiopulmonary bypass patients with acute onset of chest pain and respiratory insufficiency.

Effect of chest compressions only during experimental basic life support on alveolar collapse and recruitment

AIM: The importance of ventilatory support during cardiac arrest and basic life support is controversial. This experimental study used dynamic computed tomography (CT) to assess the effects of chest compressions only during cardiopulmonary resuscitation (CCO-CPR) on alveolar recruitment and haemodynamic parameters in porcine model of ventricular fibrillation. MATERIALS AND METHODS: Twelve anaesthetized pigs (26+/-1kg) were randomly assigned to one of the following groups: (1) intermittent positive pressure ventilation (IPPV) both during basic life support and advanced cardiac life support, or (2) CCO during basic life support and IPPV during advanced cardiac life support. Measurements were acquired at baseline prior to cardiac arrest, during basic life support, during advanced life support, and after return of spontaneous circulation (ROSC), as follows: dynamic CT series, arterial and central venous pressures, blood gases, and regional organ blood flow. The ventilated and atelectatic lung area was quantified from dynamic CT images. Differences between groups were analyzed using the Kruskal-Wallis test, and a p<0.05 was considered statistically significant. RESULTS: IPPV was associated with cyclic alveolar recruitment and de-recruitment. Compared with controls, the CCO-CPR group had a significantly larger mean fractional area of atelectasis (p=0.009), and significantly lower PaO(2) (p=0.002) and mean arterial pressure (p=0.023). The increase in mean atelectatic lung area observed during basic life support in the CCO-CPR group remained clinically relevant throughout the subsequent advanced cardiac life support period and following ROSC, and was associated with prolonged impaired haemodynamics. No inter-group differences in myocardial and cerebral blood flow were observed. CONCLUSION: A lack of ventilation during basic life support is associated with excessive atelectasis, arterial hypoxaemia and compromised CPR haemodynamics. Moreover, these detrimental effects remain evident even after restoration of IPPV.

Entropy and bispectral index for assessment of sedation, analgesia and the effects of unpleasant stimuli in critically ill patients: an observational study

INTRODUCTION: Sedative and analgesic drugs are frequently used in critically ill patients. Their overuse may prolong mechanical ventilation and length of stay in the intensive care unit. Guidelines recommend use of sedation protocols that include sedation scores and trials of sedation cessation to minimize drug use. We evaluated processed electroencephalography (response and state entropy and bispectral index) as an adjunct to monitoring effects of commonly used sedative and analgesic drugs and intratracheal suctioning. METHODS: Electrodes for monitoring bispectral index and entropy were placed on the foreheads of 44 critically ill patients requiring mechanical ventilation and who previously had no brain dysfunction. Sedation was targeted individually using the Ramsay Sedation Scale, recorded every 2 hours or more frequently. Use of and indications for sedative and analgesic drugs and intratracheal suctioning were recorded manually and using a camera. At the end of the study, processed electroencephalographical and haemodynamic variables collected before and after each drug application and tracheal suctioning were analyzed. Ramsay score was used for comparison with processed electroencephalography when assessed within 15 minutes of an intervention. RESULTS: The indications for boli of sedative drugs exhibited statistically significant, albeit clinically irrelevant, differences in terms of their association with processed electroencephalographical parameters. Electroencephalographical variables decreased significantly after bolus, but a specific pattern in electroencephalographical variables before drug administration was not identified. The same was true for opiate administration. At both 30 minutes and 2 minutes before intratracheal suctioning, there was no difference in electroencephalographical or clinical signs in patients who had or had not received drugs 10 minutes before suctioning. Among patients who received drugs, electroencephalographical parameters returned to baseline more rapidly. In those cases in which Ramsay score was assessed before the event, processed electroencephalography exhibited high variation. CONCLUSIONS: Unpleasant or painful stimuli and sedative and analgesic drugs are associated with significant changes in processed electroencephalographical parameters. However, clinical indications for drug administration were not reflected by these electroencephalographical parameters, and barely by sedation level before drug administration or tracheal suction. This precludes incorporation of entropy and bispectral index as target variables for sedation and analgesia protocols in critically ill patients.