Search

L'encéphalopathie hypoxique ischémique néonatale (EHI) reste la cause principale de mortalité chez le nouveau-né à terme. Un tiers des survivants vont développer des séquelles neurologiques, dont la paralysie cérébrale (PC), l'épilepsie et un retard intellectuel. Afin d'améliorer leur pronostic, ces nouveau-nés sont soumis à l'hypothermie thérapeutique (HT) qui débute au plus tard 6 heures après la naissance, pour une durée totale de 72 heures, suivie d'un réchauffement graduel (0.5°C/h). Il a été démontré que cette thérapie à effet neuroprotecteur diminue considérablement l'étendue des lésions cérébrales et la fréquence des séquelles neurologiques. Or, des études animales suggèrent que l'hypothermie sans sédation avec opioïdes n'est pas bénéfique. Selon les observations qui ont été réalisées, les porcelets traités avec la thérapie, mais sans l’administration d’analgésique ont manifesté des signes d’instabilités et de tremblements exagérés. On ignorait jusqu’à présent dans quelle mesure ces résultats tirés des expérimentations animales pouvaient être généralisables au nouveau-né. Ainsi, mon projet de maîtrise vise à mieux comprendre les facteurs qui risquent de compromettre les effets bénéfiques de la thérapie de refroidissement, dans le but d’optimiser la neuroprotection et d’améliorer le développement des nourrissons atteints d’EHI. Nous avons comme objectif principal d’évaluer l’association entre les doses d’opioïdes consommées pendant l’HT, le degrée de tremblement, et l’évolution de l’index de discontinuité à l’EEG au fil des 72h de l’HT, du réchauffement et jusqu’à 12 heures post-HT. Pour répondre à l’objectif, nous avons conduit une étude chez 21 nouveau-nés avec EHI soumis à l’HT, et dont les principaux résultats ont montré des associations significatives entre les fortes doses d’opioïdes administrés à l’enfant (r = - 0.493, p = 0.023), les frissons réduits pendant l’HT (r = 0.513, p = 0.017) et l’amélioration du rythme cérébrale d’EEG. Ces résultats sont décrits de manière plus approfondie dans le Chapitre 2 qui présente la version de l’article soumis à la revue Journal of Pediatrics, et le Chapitre 3 qui présente un retour sur la littérature à la lumière de nos trouvailles. Quant au Chapitre 4, nous y élaborons les possibilités de perspectives futures et les retombées cliniques de nos résultats. À long terme, nous espérons que nos travaux permettront l’ouverture d’une nouvelle piste d’amélioration de la neuroprotection, en favorisant systématiquement une meilleure prise en charge de la douleur et du stress induit par le refroidissement., Neonatal hypoxic-ischemic encephalopathy (HIE) remains the leading cause of death and mortality in the term infant. A third of the survivors will develop neurological sequelae including cerebral palsy (CP), epilepsy and mental retardation. In order to improve their prognosis, these newborns undergo therapeutic hypothermia (TH), which begins no later than 6 hours after birth, maintained for a total duration of 72 hours and followed by gradual rewarming (0.5°C/h). This neuroprotective therapy has been shown to significantly decrease the extent of brain injury and the frequency of neurological sequelae. Results from animal studies revealed that ongoing hypothermia without proper anesthesia is not beneficial. Based on the observations that have been reported, piglets treated with TH with no analgesics have shown signs of instability and excessive tremors. Until now, the extent to which these results from animal experiments could be generalized to the newborn remained unknown. Thus, the purpose of my master’s project was to better understand the clinical factors that may compromise the beneficial effects of TH, in an attempt to optimize neuroprotection and improve the neurological outcome of HIE infants. Our main objective was to assess the associations between opioid doses consumed during TH, shivering recorded during TH, and the evolution of EEG discontinuity index over the course of TH, rewarming and up to 12 hours post-TH. To meet the objective, we conducted a study in 21 newborns with HIE undergoing TH, and the results have shown significant associations between high doses of opioid administered (r = - 0.493, p = 0.023), reduced shivering stress (r = 0.513, p = 0.017) and improved EEG background activity. The key findings of the study are described in more detail in Chapter 2, which presents the original manuscript submitted for publication to the “Journal of Pediatrics”, and Chapter 3, which presents a review of the literature in light of our results. In Chapter 4, we discuss future perspectives and the clinical significance of our results. At last, we hope that our study will open up new avenues for improving neuroprotection, by systematically promoting a better management of pain and cooling-induced stress.

Posant la question d’une universalité des émotions, cette étude prend l’exemple des larmes et du frisson pour démontrer, dans un cheminement qui remonte de Platon à Homère, les divergences et contradictions de leurs interprétations. Dans la République, Platon prend à dessein l’exemple du frisson de peur et des plaintes pour renverser les valeurs de l’Iliade et démontrer le danger d’une telle poésie dans la cité idéale. Dans une démonstration qui postule un effet émollient de la peur et des pleurs, il dénonce une poésie qui amollit, en la réchauffant, la virilité des auditeurs. Ce postulat platonicien est en totale contradiction avec la poésie homérique où les larmes chaudes (dakrua therma) constituent, ainsi que les pleurs abondants, un signe de virilité. Dans la poésie homérique, les larmes chaudes ont un effet amollissant et liquéfiant sur la seule beauté féminine. Quant au frisson de peur, loin de réchauffer, il a, sur les héros homériques, un effet glaçant. Le chaud et le froid ne sont pas chez Homère ce que Platon affirme. Rien d’universel donc dans la manière de décrire et ressentir une émotion. Taking into account the cultural diversity of emotions, this study considers the examples of tears and shivering (phrikê). It aims to confront Plato’s and Homer’s opposite conceptions. In the Republic, Plato examines the effects of poetry on listeners. He claims that descriptions of tears and scenes of fear affect the soul and make it warmer and softer; this process affects the virility. Poetry of lamentation should be left to women. Such a conception is in total contradiction with the Homeric poems, where hot tears (dakrua therma) are, as well as abundant tears, a sign of virility. In Homeric poetry, the hot tears are dangerous only for women. We must emphasize another opposition. Shivering does not have a warming effect (as for Plato) but is described as cold and glacial. Hot and cold emotions in Homer are not what Plato makes us to believe. Plato invents a new theory of emotion that supports his critic of Homeric poetry.

International audience; Taking into account the cultural diversity of emotions, this study considers the examples of tears and shivering (phrikê). It aims to confront Plato’s and Homer’s opposite conceptions. In the Republic, Plato examines the effects of poetry on listeners. He claims that descriptions of tears and scenes of fear affect the soul and make it warmer and softer; this process affects the virility. Poetry of lamentation should be left to women. Such a conception is in total contradiction with the Homeric poems, where hot tears (dakrua therma) are, as well as abundant tears, a sign of virility. In Homeric poetry, the hot tears are dangerous only for women. We must emphasize another opposition. Shivering does not have a warming effect (as for Plato) but is described as cold and glacial. Hot and cold emotions in Homer are not what Plato makes us to believe. Plato invents a new theory of emotion that supports his critic of Homeric poetry.; Posant la question d’une universalité des émotions, cette étude prend l’exemple des larmes et du frisson pour démontrer, dans un cheminement qui remonte de Platon à Homère, les divergences et contradictions de leurs interprétations. Dans la République, Platon prend à dessein l’exemple du frisson de peur et des plaintes pour renverser les valeurs de l’Iliade et démontrer le danger d’une telle poésie dans la cité idéale. Dans une démonstration qui postule un effet émollient de la peur et des pleurs, il dénonce une poésie qui amollit, en la réchauffant, la virilité des auditeurs. Ce postulat platonicien est en totale contradiction avec la poésie homérique où les larmes chaudes (dakrua therma) constituent, ainsi que les pleurs abondants, un signe de virilité. Dans la poésie homérique, les larmes chaudes ont un effet amollissant et liquéfiant sur la seule beauté féminine. Quant au frisson de peur, loin de réchauffer, il a, sur les héros homériques, un effet glaçant. Le chaud et le froid ne sont pas chez Homère ce que Platon affirme. Rien d’universel donc dans la manière de décrire et ressentir une émotion.

Fever-shivers reaction (FSR) is the most frequent transfusion immediate incident related to platelet transfusions. The aim of our prospective study was to assess the frequency of the different immediate incidents, especially the frequency and the causes of the FSR, observed during the transfusion of standard platelet concentrates (SPC). For each FSR, analysis of causes included: a bacterial culture of the implicated SPC, a blood culture and HLA antibody screening (lymphocytotoxicity assay) among the patients. In the study period, 34 patients were followed during 74 transfusions. Ten immediate incidents were noted; FSR: N = 8, erythema-urticaria: N = 1 and nausea-vomit: N = 1. The FSR was observed in 6 patients who received 56 SPC. Analysis of causes of this reaction revealed that: HLA antibodies were present in one patient; bacterial contamination was not found neither among the patients nor in the implicated SPC, and the risk of the FSR occurrence rose with increased storage time of the SPC transfused. Indeed, a significant difference was noted between the mean age of the SPC implicated in the FSR and the mean age of those not implicated (P = 0,0028). In conclusion, the FSR is a frequent incident observed during SPC transfusions. In the majority of cases, the cause of this reaction was not identified. Further studies will be necessary to better understand the physiological mechanisms of the FSR.

We conducted a clinical and biological study in Morocco in order to assess the efficacy of antivenom therapy against scorpion stings. Epidemiological and clinical data were collected in 275 patients envenomed by Androctonus mauretanicus mauretanicus and Buthus occitanus scorpions. Patients received antivenom or symptomatic drugs. Blood samples were collected upon hospital admission, at 1 hr and 3 hrs after the treatment. An enzyme linked immunosorbent assay (ELISA) was set up to quantify the venom levels in serum of envenomed patients. Mean serum venom concentrations showed an association between clinical signs and the venom level. The venom concentration at admission, in patients who received 10 ml of antivenom, was significantly reduced after antivenom therapy. The decrease was less important in patients who received only 2 to 5 ml of antivenom. No difference was shown in the venom concentration of patients not treated with antivenom. The clinical signs decreased significantly after antivenom treatment. The absence of antivenom administration increased the risk to develop clinical signs at the end of hospitalisation. This risk was much higher when the delay between scorpion sting and hospital admission increased. The results of our study have demonstrated the efficacy of antivenom in reducing circulating venom and symptoms. Antivenom therapy is more efficient when administered as soon as possible after envenomation and with appropriate quantities of antivenom. This study is favourable to the use of SAS but a prospective study would be useful to confirm these data.

Temperature monitoring and prevention of hypothermia are rarely used during spinal anaesthesia for caesarean section because hypothermia risk is considered very low. However, in same conditions, we observed two cases of severe hypothermia. We report these two cases and discuss the effects of spinal anaesthesia on thermoregulatory system. Hypothermia seems explained by the effects of perimedullar anaesthesia that decrease the shivering and the vasoconstriction thresholds. These effects are potentiated by morphinomimetic adjunction. At last, we recall prophylactics measures.

To evaluate the clinical and electromyographic (EMG) effects of ketanserin (K), a serotoninergic receptor antagonist (5-HT2), on postoperative shivering (POS).Prospective, randomised, double-blind study.Fifty ASA class 1 and 2 patients with major clinical postoperative tremor were studied.POS was assessed clinically (0 = nil, 1 = moderate, 2 = severe). Inclusion criterion was a POS of 2 at admission in the recovery room. The mean arterial blood pressure, rectal temperature, SpO2 were recorded at admission (T0) and subsequently at T5, T10, T15, T30 and T60 minutes. Either 10 mg of K (n = 25) or a corresponding volume of a placebo (P) (n = 25) were intravenously injected. The EMG activity of the deltoid and quadriceps muscles was recorded continuously. Blood lactic acid concentration was measured at the end of POS. Results are expressed as mean +/- SEM. Parametric values were analysed with unpaired Student's t-test, and nonparametric values with chi 2 analysis. P0.05 was accepted.Demographic data, duration of anaesthesia, postoperative temperature, oxygen saturation, blood pressure and blood lactate concentration were similar between groups. The POS duration in the K group was significantly shorter than in the P group: 8.8 +/- 1.5 min and 15.5 +/- 1.5 min respectively (P0.01). The number of patients in the K group experiencing POS at T5 and T10 was significantly lower, when compared with those who had received the P (P0.05).At a dose of 10 mg, K administered in patients with POS during recovery, reduced significantly the duration and intensity of the shivering without noticeable side effects. This study suggests that this 5-HT2 antagonist is an efficient therapeutic tool for POS in adults.

Leukodepletion of red blood cell or platelet concentrates decreases significantly the number of febrile non hemolytic transfusion reactions. Filtration appears to be very efficient on red blood cell transfusion reactions while its effect with platelet concentrates remains variable.

This study was carried out in 75 female patients, ranked ASA 1 or 2, during recovery from balanced general anaesthesia. It aimed to find out the main determinants of postoperative shivering and its thermal effects. Skin and oesophageal temperature were recorded every ten minutes. Mean skin and body temperatures, and the intraoperative energy balance were calculated. There was no additional source of heating. Shivering was ranked from 0 to 2. Statistical analysis showed that the starting mean core and body temperatures were the only factors correlated with shivering and its intensity, whereas mean skin temperatures, age and opioid doses were not. Between 33.5 and 36.5 degrees C, there was a linear relationship between the oesophageal temperature at the end of anaesthesia and the incidence of shivering. A decrease of 1 degrees C in core temperature increased the probability of shivering by 33%. At 35.4 degrees C, 50% of patients shivered. There was a homogenous group of patients whose oesophageal temperature at the end of anaesthesia was between 35 and 36 degrees C. In this group, there was no significant difference between starting skin temperatures, whether the patient shivered or not. However, the core temperature of those within that group that did shiver returned to normal levels more quickly than in those that did not shiver. These data underlined the essential role played by core temperature at the end of anaesthesia in postoperative shivering and its intensity, as well as the heat producing value of shivering. It would therefore seem logical to prevent postoperative shivering by avoiding intraoperative hypothermia.

A case is reported of a 40 year-old man, on the waiting-list for heart transplantation, who developed terminal heart failure. Using an Opticath catheter and a radial artery catheter, SV(-)O2 was monitored continuously, and cardiac output, pulmonary arterial and wedged pressures, and right atrial pressure were repeatedly measured. Despite appropriate treatment (adrenaline, dobutamine, glyceryl trinitrate), the patient remained in anuria and cardiogenic shock. External circulatory support (ECS) (BVS 5000 Abiomed) was therefore used as a bridge to cardiac transplantation. The resultant increase in systemic blood flow led to an early and fast rise in SV(-)O2, from 40% to 73%, with a decrease in the oxygen extraction ratio (ERO2) from 50 to 30%. Serum lactate concentrations returned to normal within the first six hours of ECS (less than 120 mg.l-1). During the first 24 h of ECS, SV(-)O2 decreased and ERO2 rose significantly on two occasions: during an episode of shivering, and another of restlessness during nursing. An attempt at weaning the patient from the ventilator at the 39th h also led to a sudden decrease in SV(-)O2, with a rise in ERO2. The Opticath catheter was finally removed after 150 h of ECS because of a decrease in reflected light intensity.

Among 109 subjects who had undergone cardiac surgery under ECC, the authors recorded 50 (45 p. 100) who suffered from shivering during the coming round period. Comparing the series of patients who shivered, with that of the subjects who did not shiver, the authors demonstrate in the first case, an increase in cellular metabolism, the cardiac index, heart rate, central venous pressure and cardiac work. They subsequently note the apprearance of mixed acidosis and an increase in the lactate-pyruvate ratio. Certain patients, in whom the cardiac output did not keep up with the metabolic demand considerably increased the arterio-venous oxygen difference. Blood loss is increased as well as coagulation time showing a more intense heparin rebound. The study of the drugs used during anesthesia showed that the patients who had received chlorprotixene, as the neuroleptic, a neuroleptic with adrenolytic properties, had a very decreased frequency of shivering in comparison with those who had received droperidol. The placing of the patient at the end of the intervention on a heating mattress, combined with the administration of chlorprotixene during anesthesia, prevented the appearance of shivering.

The growth of the subantarctic King penguin chick is distinguished from that of other penguins by its long winter fasting period (from 2 weeks to 3 months). From the moment of hatching the unfledged chicks are brooded by their parents until they are able to maintain their own body temperature. Body temperature increases gradually from 34.3 degrees C after hatching to 39.2 degrees C by about 20 days of age; measured air temperature (Ta) was 16 degrees C on average. Unlike antarctic Penguins, homeothermy and full emancipation does not occur at the same time. This suggests that emancipation may be determined by insulation after thermogenesis mechanisms have become efficient. Close to 90 kcal.kg-1.day-1 after hatching (Ta = 15.8 +/- 3.6 degrees C), the resting metabolic rate increases by 125% during the first three days and then decreases progressively; this appears to be linked with insulation generated by the down. By two months of age, the resting metabolic rate reaches 47 kcal.kg-1.day-1 on average for Ta = 4.3 +/- 1.4 degrees C and then does not evolve significantly until the moult.

In normal pentobarbital-anaesthetized rats (20 mg/kg, i.p.), Ketanserine (2.5 to 10 mg/kg, i.v.) increases the temperature of the paw skin and decreases the central one. A strong thermogenetic shivering appears when central temperature falls below 35 degrees C. This shivering is a specific characteristics of Ketanserine activity, probably related to its fixation on 5-HT2 central receptors.

As indicated by a theophylline administration previously to a norepinephrine infusion, the nonshivering thermogenesis does not seem to be mediated by the cyclic AMP system in constant cold acclimated rats, in opposite to rats acclimated to discontinuous cold. However, in that last thermal condition, the cyclic AMP mediation was not observed in the brown adipose tissue and in the liver.