Analyser les données actuelles sur la curarisation chez les patients de réanimation et proposer un fil conducteur pour sa pratique.Nous avons effectué une recherche sur Medline® d'articles en langue française et anglaise sur l'utilisation des curares en réanimation entre 1960 et 1998. Les données figurant dans nos documents et livres personnels ont aussi été relevées.Les articles originaux, les cas cliniques, les lettres à l'éditeur et les revues générales ont été sélectionnés.Les données sur la pharmacologie des curares administrés aux patients de réanimation, ainsi que celles sur les modalités d'administration et le coût ont été extraites.Les indications des curares en réanimation concernent soit l'utilisation de courte durée, comme en anesthésie, ou l'administration au long cours pour la facilitation de la ventilation mécanique, le contrôle de l'hypertension intracrânienne, de l'état de mal épileptique, du tétanos, la diminution de la consommation d'oxygène dans les états d'hyperactivité musculaire, la facilitation des actes diagnostiques et thérapeutiques. À ce jour, un effet bénéfique des myorésolutifs sur le pronostic de l'affection pour l'aquelle la curarisation a été utilisée n'est pas prouvé.Le suxaméthonium, du fait de son court délai d'action et sa courte durée d'action est l'agent de choix pour l'intubation endotrachéale, quand celle-ci requiert une curarisation. Parmi les benzylisoquinolines, l'atracurium et le bésilate de cisatracurium sont des agents adaptés aux patients de réanimation, alors que le mivacurium ne présente pas d'intérêt particulier chez eux. Parmi les aminostéroïdes, le pancuronium et le vécuronium sont les agents les plus utilisés en réanimation. Le rocuronium n'a pas encore été l'objet d'une évaluation suffisante.Les myorelaxants comportent un risque de morbidité et de mortalité. La difficulté d'évaluer l'état neurologique et en particulier la profondeur de la sedation est un effet indésirable reconnu. La déconnexion accidentelle du ventilateur, donc le risque d'asphyxie, est de nos jours reconnue sans délai par l'appareil. Les myorelaxants augmentent l'incidence des infections bronchopulmonaires. Les complications cardiovasculaires sont la bradycardie voire la pause sinusale déterminée par le vécuronium et l'arrêt cardiaque suivant l'administration de suxaméthonium à des traumatisés et des brûlés. Contrairement à l'anesthésie, les curares ne comportent pas en réanimation un risque significatif d'accident anaphylactique ou anaphylactoïde. La tachyphylaxie s'observe principalement en cas de brûlures et d'autres pathologies modifiant les récepteurs à acétylcholine. Les complications neuromusculaires comportent la myopathie aux stéroïdes, le syndrome postparalytique, la myopathie cachectique et la polyneuropathie de réanimation. La curarisation anormalement prolongée après l'arrêt de l'agent a une pathogénie multifactorielle et doit être différenciée des complications neuromusculaires. Pour une administration prolongée, le pancuronium, le vécuronium et l'atracurium sont des agents de choix. L'association d'une sedation adéquate est indispensable. La détermination de la profondeur de la curarisation ne repose pas sur des signes cliniques mais le monitorage du train de quatre. Une curarisation de base adéquate correspond généralement à la suppression des deux dernières réponses au train de quatre.L'emploi des curares en réanimation devrait passer par une démarche décisionnelle rationnelle, la curarisation être titrée à l'aide d'un moniteur du train de quatre et maintenue le plus superficiellement et le moins longtemps possible.To analyse current data on use of neuromuscular blocking agents (NBA) in the intensive therapy unit (ITU) patients and to propose practice guidelines.We did a Medline® search of French and English language articles on NBA administration in ITU patients from 1960 to 1998. Data were also selected from our own collection of articles and books.Original articles, clinical cases, letters to the editor and review articles were considered. Data extraction: Data on pharmacology of NBA in the ITU patient were extracted, as well as data on administration patterns and cost.The indications for myorelaxation in ITU patients include either short term use, as in anaesthesia, or long term administration for facilitation of mechanical ventilation, control of increased intracranial pressure, status epilepticus, tetanus and oxygen demand in case of muscular hyperactivity, diagnostic and therapeutic procedures facilitation. A beneficial effect of NBA on the prognosis of the disease for which these agents have been used is not yet proven.Suxamethonium, because for its short onset time and duration of action, is the agent of choice for endotracheal intubation if myorelaxation is required. Among the benzylisoquinolines, atracurium and besilate of cisatracurium are convenient agents in ITU patients, whereas mivacurium is of no special interest. Among the aminosteroids, pancuronium and vecuronium are the most often used agents in the ITU. Rocuronium has not yet been extensively assessed.Myorelaxants carry risks for morbidity and mortality. The difficulty to assess the neurological status and the level of sedation is a recognised adverse effect. An accidental disconnection from the circuit and the resulting asphyxia is nowadays recognised without delay by the ventilator. NBAs increase the rate of bronchopulmonary infections. Cardiovascular complications include extreme bradycardia or sinus arrest following vecuronium administration, and cardiac arrest after suxamethonium injection mainly in burned or traumatised patients. Conversely to anaesthesia, NBAs do not carry a significant risk for anaphylactic or anaphylactoid complications in the ITU. Tachyphylaxis occurs mainly in burns and other pathologies modifying acetylcholine receptors. Neuromuscular complications include myopathy from steroids, postparalytic syndrome, deconditioning syndrome and intensive care polyneuropathy. Prolonged curarisation after discontinuation of NBA administration has a multifactorial origin and must be differentiated from neuromuscular complications. For prolonged neuromuscular blockade, pancuronium, vecuronium and atracurium are the agents of choice. The association with an adequate sedation is essential. Assessment of depth of neuromuscular blockade is not based on clinical symptoms but on train-of-four (TOF) twitch monitoring. A convenient basic relaxation is usually obtained with the suppression of the two last responses to TOF.The use of NBA in ITU patient should result from a rational decision making procedure, the blockade titrated with a TOF monitor and maintained as superficially and shortly as possible.
The effector activity of IgG antibodies is regulated at several levels, including IgG subclass, modifications of the Fc glycan, and the distribution of Type I and II Fcγ receptors (FcγR) on effector cells. Here, we explore how Fc glycosylation, particularly sialylation and fucosylation, tunes cellular responses to immune complexes. We review the current understanding of the pathways and mechanisms underlying this biology, address FcγR in antigen presentation, and discuss aspects of the clinical understanding of Fc glycans in therapies and disease.
Temperature response of gross primary productivity (GPP) is a well-known property of ecosystem, but GPP at the optimum temperature (GPP_Topt) has not been fully discussed. Our understanding of how GPP_Topt responds to warming and water availability is highly limited. In this study, we analyzed data at 326 globally distributed eddy covariance sites (79oN-37oS), to identify controlling factors of GPP_Topt. Although GPP_Topt was significantly influenced by soil moisture, global solar radiation, mean annual temperature, and vapor pressure deficit in a non-linear pattern (R2 = 0.47), the direction and magnitude of these climate variables’ effects on GPP_Topt depend on the dryness index (DI), a ratio of potential evapotranspiration to precipitation. The spatial pattern showed that soil moisture did not affect GPP_Topt across energy-limited sites with DI < 1 while dominated GPP_Topt across water-limited sites with DI >1. The temporal pattern showed that GPP_Topt was lowered by warming or low precipitation in water-limited sites while energy-limited sites tended to maintain a stable GPP_Topt regardless of changes in air temperature. Vegetation types in humid climates tended to have higher GPP_Topt and were more likely to benefit from a warmer climate since it was not restricted by water conditions. This study highlights that the response of GPP_Topt to global warming depends on the dryness conditions, which explains the nonlinear control of water and temperature over GPP_Topt. Our finding is essential to realistic prediction of terrestrial carbon uptake under future climate and vegetation conditions.
The dose response relationship for the intermediateacting non-depolarising muscle relaxant, atracurium besylate in the pig was determined using evoked electromyography. An incremental dose technique was used in seven Large White/Landrace crossbred pigs anaesthetised with nitrous oxide and halothane. ED50 and ED95 were 510 ± 87 μg kg−1 and 1150 ± 270 μg kg−1, respectively. Although these values may represent an overestimate, they provide a reasonable guideline for the use of atracurium by veterinary anaesthetists.
Temperature response of gross primary productivity (GPP) is a well-known property of ecosystem, but GPP at the optimum temperature (GPP_Topt) has not been fully discussed. Our understanding of how GPP_Topt responds to warming and water availability is highly limited. In this study, we analyzed data at 326 globally distributed eddy covariance sites (79oN-37oS), to identify controlling factors of GPP_Topt. Although GPP_Topt was significantly influenced by soil moisture, global solar radiation, mean annual temperature, and vapor pressure deficit in a non-linear pattern (R2 = 0.47), the direction and magnitude of these climate variables’ effects on GPP_Topt depend on the dryness index (DI), a ratio of potential evapotranspiration to precipitation. The spatial pattern showed that soil moisture did not affect GPP_Topt across energy-limited sites with DI < 1 while dominated GPP_Topt across water-limited sites with DI >1. The temporal pattern showed that GPP_Topt was lowered by warming or low precipitation in water-limited sites while energy-limited sites tended to maintain a stable GPP_Topt regardless of changes in air temperature. Vegetation types in humid climates tended to have higher GPP_Topt and were more likely to benefit from a warmer climate since it was not restricted by water conditions. This study highlights that the response of GPP_Topt to global warming depends on the dryness conditions, which explains the nonlinear control of water and temperature over GPP_Topt. Our finding is essential to realistic prediction of terrestrial carbon uptake under future climate and vegetation conditions.
ABSTRACT The efficacy of buprenorphine and pentazocine in controlling pain in dogs following orthopaedic surgery was compared with that of morphine. All three analgesics provided effective pain relief with no undesirable side effects.
The so-called “anesthetic state” is a dynamic combination of hypnosis, amnesia, analgesia, neuromuscular and neurohumoral blockade. To achieve this state, different combinations of drug effects must be induced in the patient undergoing the surgical procedure under anesthesia. Patients are routinely and exhaustively monitored during anesthesia. This makes it easy to observe and quantify the effects of anesthetic drugs, and also to attempt to establish the relations between drugs administered, degree of effect and the factors that can influence this relation. Based on the above, important concepts like the “effect compartment model” have been developed. In this case, anesthesia has served clinical pharmacology to describe and validate the concept of the effect compartment. This relation works also in the other way. The effect compartment model has been routinely used to study the profile of different drugs used in anesthesia like opioids (fentanyl, alfentanil, sufentanil and remifentanil), hypnotics (propofol, barbiturates), benzodiazepines (diazepam, midazolam) and neuromuscular blocking agents (pancuronium, vecuronium, atracurium). Based on this approach, it has been possible to develop rational dosing guidelines according to the specific characteristics of the patient for most of the drugs used in anesthesia. More sophisticated modeling techniques, as well as improved designs of clinical trials, made possible to investigate the effect of covariate factors in the PK/PD model. Using this approach has allowed the study of how altered physiologic states as well as the presence of disease can affect the relation between drugs and effect in a particular patient. In addition, different models can be used to study more complex relations like the pharmacokinetics of inhaled anesthetics or the pharmacodynamics of intraspinally administered local anesthetics. The model has been recently described for the interaction between two or three different intravenous agents, enabling the clinician to assess how the use of another drug can influence the effect profile of a given one. Anesthesiology is a very safe medical specialty in terms of morbidity and mortality directly derived from the effect of drugs. The more we know about the relations between drugs, drug effects and the factors that can affect them, the best it will be for the patients. The application of quantitative modeling in pharmacokinetics and pharmacodynamics enables the clinician to use rationally the anesthetics and, hence, to provide more benefit to the patient undergoing anesthesia.
