Actualités sur le choc hémorragique

Hemorrhagic shock is characterized by a decreased circulating blood volume that leads to an alteration of the venous return. The initial adaptative response relies on a central sympathetic activation in an attempt to distribute the residual blood volume to the protected organs (brain and heart). At the opposite, splanchnic as well as muscular and kidney vasculature beds are sacrificed during the ischemic period. Volume resuscitation is the first therapeutic measure to undertake, with a systolic arterial pressure target of 80?C100 mmHg and a mean cerebral perfusion pressure of 65?C70 mmHg in the case of an associated brain injury. Massive fluid resuscitation is associated with a significant morbidity. Some authors advocated the early use of vasopressors (norepinephrine) along with a controlled volume resuscitation. In the setting of moderate-volume resuscitation, the use of hypertonic saline solution is encouraged. Red blood cells should be transfused as soon as possible, especially when hemoglobinemia is < 7 g/dl. Fresh frozen plasma (FFP) should be used to maintain a prothrombin ratio > 40%. A transfusion strategy using FFP and red blood cells at a 1:1 ratio is recommended. Platelet concentrates are used to maintain a platelet count > 50 G/l and > 100 G/l when traumatic brain injuries are associated. Fibrinogen treatment should be considered and systematically administered when fibrinogen concentration is < 1.5 g/l. An adrenal insufficiency is frequent, and a stress dose of 200 mg/day of hydrocortisone decreases morbidity after a traumatic shock.     

Ventilation à haute fréquence chez le nouveau-né

Neonatal high-frequency ventilation, which has been used for 15 years, allows for CO₂ elimination while using low tidal volume, generated by small pressure variations. The main expected benefit is a decrease in baro / volutrauma, and the possibility of using high mean airway pressures. Elective use of this technique for the treatment of respiratory distress syndrome in premature infants may reduce the rate of occurrence of prolonged respiratory courses toward bronchopulmonary dysplasia. Despite several animal experiments supporting this, randomized clinical trials gave inconsistent results. In the most recent trial which showed benefits of using high-frequency ventilation, those benefits were actually modest. This highlights the fact that bronchopulmonary dysplasia is a prematurity-related multifactorial disease, rather than a simple ventilator-related disease. High-frequency ventilation, however, is among the most useful techniques in neonatal intensive care. This technique indeed allows the treatment of severe cases of respiratory failure, such as those resulting from congenital diaphragmatic hernia, or to restore gas exchanges when conventional ventilation has failed. High-frequency ventilation has contributed to the observed decrease in the number of neonates who require extracorporeal membrane oxygenation.     

Modèle animaux d’obésité

Animal models provide major contribution to our understanding of the physiological, environmental, genetic and epigenetic bases of obesity. Most rodent models of obesity have been investigated since the early fifties, but it??s only more recently that the mechanisms underlying their phenotype were identified, thanks to the development of molecular biology. This article reviews various models of rodent obesity, naturally occurring or created by researchers: nutritional obesity induced by a high fat diet, hypothalamic obesity resulting from lesions in areas controlling food intake and genetic obesity due to spontaneous mutations in crucial genes for energy balance, such as leptin and leptin receptor genes. Each model provides information related to specific aspects of human obesity, particularly in the field of monogenic obesities that are rare but often severe as in leptin-deficient patients. Models of obese rodents represent precious and necessary tools to explore the complexity of energy balance regulation and for innovative therapeutic intervention in obesity, of which the success of leptin treatment for leptin-deficient patients is a striking example.     

Impact du rôle des médecins hospitaliers dans le dépistage du cancer colorectal

Objective

Too many patients with colorectal cancer (CRC) are still diagnosed when they are already symptomatic. In our hospital, many patients have been attending various departments in the years before the diagnosis of CRC, but never had CRC screening. We studied whether specially targeting information to hospital specialists might enhance CRC screening awareness.

Methods

We studied the knowledge and implication of hospital physicians before and after a specially targeted information campaign about CRC screening in our hospital. We conducted two paper questionnaire surveys at 12-month interval. The results were compared to the colonoscopy activity of our endoscopy unit.

Results

Participation was 55% in the first survey and 51% in the second survey. Knowledge about screening principles was fairly good. A large majority of physicians (90%) declared adhering personally to CRC screening. However, only 40% of physicians recommended screening frequently or regularly to patients (after the campaign: 50%, NS). Colonoscopies raised 11% in the 6 months after the campaign.

Conclusion

The large majority of hospital physicians report adhering personally to CRC screening guidelines. However, this translates only infrequently into screening recommendations for their patients. One-off information campaigns may help change specialist physicians’ attitudes but have only a small impact on CCR screening attendance.     

L'analgésie contrôlée par le patient âgé

Résumé  L'analgésie postopératoire contr?lée par le patient (ACP) est encore sous utilisé chez la personne agée. Cette technique permet toutefois d'apporter une réponse efficace adaptée aux difficiles problèmes posés par la prise en charge de la douleur chez l'opéré agé. D'une part, le patient peut gérer lui-même le traitement de sa douleur. D'autre part, l'ACP permet une titration continue des analgésiques. Ainsi, avec les morphiniques, dont l'activité intrinsèque augmente avec l'age, le risque de surdosage est réduit. L'ACP morphine permet d'obtenir un meilleur niveau d'analgésie que la technique conventionnelle par voie intramusculaire avec une qualité supérieure des suites opératoires. Cette technique s'avère toutefois inférieure aux possibilités de l'analgésie locorégionale. L'existence de troubles cognitifs préopératoires, éventualité fréquente chez les personnes agées, contreindiquent toutefois la mise en place d'une ACP. Les paramètres de réglage de la pompe d'ACP morphine sont identiques à ceux décrits pour l'adulte jeune. Chez le patient à risque, une dose de bolus de 1 mg ne devrait pas être dépassée. A la surveillance habituelle de la qualité d'analgésie, de la fonction respiratoire et du niveau de vigilance, il est utile d'adjoindre chez le vieillard, une évaluation quotidienne du statut mental pour dépister l'apparition éventuelle d'un délire postopératoire.      

Pour ou contre le phénotypage/génotypage des patients traités par le 5-fluorouracile pour prévenir les effets indésirables ?

5-fluorouracil, (5-FU) is an antimetabolite used in many types of cancers. It has a narrow therapeutic index. More than 80% of administered 5-FU is detoxified in 5-fluoro-5,6-dihydrouracil (5-FUH2) by an enzyme: dihydropyrimidine dehydrogenase (DPD). Half life increased with DPD deficiency. Thus, patients presenting a partial or profound DPD deficiency have an increased risk of severe or lethal toxicity. DPD deficiency was estimated between 3 to 5% in the normal population. Different approaches have been developed: Pharmacogenetic on the DPD gene or pharmacologic measuring DPD activity. More than 30 mutations have been reported on this gene. The more common mutation is the slice-site mutation IVS14+1G>A. Analysis of the various mutations allowed to identify a population at risk with a DPD deficiency. DPD activity is determined in peripheral blood mononuclear cells. This assay offers the capability of identifying individuals who are completely deficient in DPD activity and those who are partially deficient. Assays to detect DPD deficiency are not used as a screening test to prevent 5-FU toxicity.     

Quelques aspects pharmacologiques sur un modèle de douleur neuropathique périphérique chez le rat

Résumé  Quelques aspects pharmacologiques obtenus sur un modèle animal de neuropathie périphérique obtenu par constriction partielle du nerf sciatique sont présentées ici. Les antidépresseurs réduisent les anomalies du comportement nociceptif de ces animaux, et ceci à très faible dose. La sympathectomie chimique, ou chirurgicale, prévient ou réduit la réactivité des animaux aux stimulations thermiques chaudes (45°C) ou froides (10°C). La clonidine, agoniste α-2 noradrenergique, a une action antinociceptive prononcée sur la réactivité des animaux aux stimulations thermiques, mais un effet modéré sur leur réactivité aux stimulations mécaniques (seuil de vocalisation induite par pression de la patte). Les substances morphiniques sont efficaces à faibles doses sur les réactions comportementales anormales induites par des stimulations mécaniques ou thermiques nociceptives (46°C) mais cependant, ne le sont pas sur les réactions anormales à la plupart des stimulations thermiques (de 10 à 44°C). Des antagonistes de la cholécystokinine ou du récepteur NMDA accroissent ou révèlent l’action antinociceptive de la morphine. La participation d’une composante périphérique dans l’action antinociceptive des substances opio?des administrées par voie systémique, est mise en évidence. L’administration répétée de morphine induit l’apparition de phénomènes de tolérance et dépendance aux opio?des, qui sont prévenus par l’administration simultanée de l’antagoniste des récepteurs B de la cholécystokinine.

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Summary  Some pharmacological aspects obtained in a well-established rat model of painful peripheral unilateral neuropathy (chronic constriction of the common sciatic nerve) are described: acute and chronic injections of tricyclic antidepressant drugs reduced abnormal pain-related behaviour in these animals. Chemical or surgical sympathectomy prevented or reduced thermal (10°C or 45°C) pain-related behaviour. The α-2 adrenoceptor agonist, clonidine had a moderate effect on the abnormal reactions to mechanical stimuli. By contrast, it dramatically attenuated abnormal responses to hot or cold stimuli. Opioid substances produced dose-dependent antinociceptive effects against a mechanical and a noxious hot (46°C) stimulus. In contrast, morphine was ineffective against a non-noxious cold (10°C) and a non-noxious warm (44°C) stimulus. A NMDA or CCK-B receptor antagonist enhanced the antinociceptive action of systemic morphine. A peripheral component in the antinociceptive effect of systemic opioids is revealed. Morphine pretreatment resulted in tolerance to the antinociceptive effects of systemic morphine. Pretreatment with a CCK-B antagonist prevented the development of tolerance to the antinociceptive effect of morphine as well as morphine dependence.

     

L’échographie endoanale dans le bilan préopératoire des fistules anales

Purpose

The aim of this study is to assess the efficacy of endoanal ultrasound in the pre-operative evaluation of anal fistulas.

Equipment and methods

A consecutive series of 67 patients with anal fistulas received a pre-operative endoanal ultrasound, either with or without the use of hydrogen peroxide. The position of the internal opening, the type of fistula and the presence of secondary channels were all recorded. The consistency between the surgical data and that of the endoanal ultrasound was assessed.

Results

The average age of patients was 40.5 years and they were predominantly male (4M/1F). In 26 cases (38.8%), the anal fistula was upper transsphincteric (UTAF) and for 22 patients (32.8%) it was lower transsphincteric (LTAF). It was intersphincteric in 13 cases (19.4%), suprasphincteric in 3 cases (4.4%) and a horseshoe shape for 3 patients (4.4%). The results of the EAU were consistent with those from surgery in 74.6% of cases (50/67). This consistency decreased proportionally with the height of the fistula. The internal opening was accurately predicted in 94% of cases (63/67).

Conclusion

Endoanal ultrasound is a highly accurate method of predicting the position of an internal opening. It can also be used to assess the type and the height of the anal fistula. The information is useful pre-operatively in making relevant surgical decisions.     

Rôle de l’enzyme 11β-hydroxystéroïde-déshydrogénase de type 1 dans le risque métabolique associé à l’obésité

Similarities between metabolic syndrome associated with abdominal obesity and Cushing syndrome led to the search of excessive local tissue exposition to glucocorticoids at the cellular levels, despite normal circulating plasma levels of cortisol. To this respect, 11β-hydroxysteroid-dehydrogenase type 1 (11HSD1), which converts cortisone (inactive) to cortisol (active) in target tissues, raises much interest. Both increased expression and activity of this enzyme has been reported in presence of obesity, at least in some tissues that play a major role in metabolic regulations, such as adipose tissue. Experimental data in rodents showed a direct link between increased 11HSD1 activity and the development of metabolic disturbances. Furthermore, studies in mice KO for 11HSD1 demonstrated the potential of the inhibition of this enzyme to alleviate the metabolic abnormalities related to diet-induced obesity. The administration of specific inhibitors of 11HSD1 resulted in significant improvement of glucose and lipid profiles, together with a weight reduction, provided that 11HSD1 activity was blocked in the adipose tissue (rather than in the liver). Preliminary observations when various, potent and selective, inhibitors of 11HSD1 given in humans also showed a diminution of insulin resistance, an improvement of glucose tolerance or glucose control and an amelioration of lipid profile. In case of confirmation of such promising results, selective inhibitors of 11HSD1 might represent a new pharmacological class aiming at treating metabolic abnormalities associated with obesity, including type 2 diabetes.     

Place de la réanimation chez le cirrhotique

In cirrhotic patients, liver insufficiency and portal hypertension represent a source of potentially life threatening complications, which may justify intensive care. In addition to specific complications (variceal bleeding, hepatic encephalopathy and hepatorenal syndrome), cirrhosis is a condition which favors non-specific complications including severe bacterial infections and acute renal failure. Apart from these complications, cirrhosis is constantly associated with dysfunctions of several organs and systems (cardiocirculatory system, respiratory system, central nervous system, immune system and coagulation). When severe complications occur, dysfunctions of these organs and system can progress and lead to multi-organ failure. As a result, the prognosis of cirrhotics in intensive care units is poor. A major issue is to determine which patients should be admitted to intensive care. Different prognostic scores have been proposed but none is perfect. Practically, admission in an intensive care unit is justified in the absence of significant hepatic insufficiency or when hepatic insufficiency is reversible, when liver transplantation is possible, and in case of iatrogenic complications. In other conditions, mortality is close to 100% and intensive care may not be justified. Theoretically, the correction of hepatic insufficiency could help to improve the results of intensive care in cirrhotic patients. The tolerance and efficacy of artificial liver support systems (albumin dialysis and bioartificial liver) remain unclear. However, these systems offer attractive perspectives.     

Delirium en réanimation chez l’adulte: le choix des molécules a-t-il un rôle ?

Characteristics of sedation and analgesia have moved from deep toward lightened and cooperative sedation and analgesia with control of delirium. Although sedative drugs potently modulate neurotransmission in the central nervous system (CNS) to provide their sedative effects, a body of recent work suggests that some of these properties may contribute to delirium and in turn to the long-term impairment of cognitive recovery after intensive care unit (ICU) stay. Delirium has been shown to predict both long-term mortality and severe cognitive sequelae after ICU stay. Classical sedatives (propofol, benzodiazepines) and analgesics are causative factors for delirium. Recently, dexmedetomidine, a potent, and short acting agonist of the alpha2-adrenergic receptors, has been developed as a primary sedative for ICU mechanically ventilated patients. This agent exerts its effects via a unique mechanism (agonist of the alpha2-adrenoceptors) which confers some favorable properties with respect to the goals to be achieved in a sedated, mechanically ventilated patient (cooperative sedation). This agent has been shown to reduce the prevalence of delirium and days with coma in comparison with a benzodiazepine-based sedation regimen. Its sedation profile preserves arousability and its mechanism of action preserves non rapid eye movement sleep, which may contribute to its delirium-sparing effects as well. The need for CNS acting drugs, such as sedatives and analgesics, has to be carefully evaluated on a daily basis at the bedside to limit the potential detrimental effects associated with oversedation in critically ills.