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.

Successful cardiopulmonary resuscitation is the first step to rescue life during cardiac arrest. High mortality even after successful restoration of spontaneous circulation is substantially caused by patophysiological process associated with ischemia-reperfusion injury and it is widely called post-cardiac arrest syndrome (PCAS). There are many patophysiological mechanisms involved in the development and progress of this syndrom; the key role seems to play oxidative stress, triggering the activation cascade of systemic inflammatory reaction. In our study we have tested different possibilities of influencing the post-cardiac arrest syndrom. In the first experimental study we have compared the effect of mild therapeutic hypothermia with controlled normothermia on PCAS in a porcine model of cardiac arrest. In the second study we have compared in the same model the protective effects of mild therapeutic hypothermia, administration of nitric oxide and ischemic postconditioning. Results of the first experiment have revealed that mild therapeutic hypotermia is superior in the resuscitability, maintenance of blood pressure, oxidative stress suppression and organ damage protection than controlled normothermia. In the second experiment we have shown that neither nitric oxide administration, nor ischemic...

Background Anticipatory and compensatory balance responses are used by the central nervous system (CNS) to preserve balance, hence they significantly contribute to the understanding of physiological mechanisms of postural control. It is well established that various sensory systems contribute to the regulation of balance. However, it is still unclear which role each individual sensory system (e.g. plantar mechanoreceptors) plays in balance regulation. This becomes also evident in various patient populations, for instance in diabetics with reduced plantar sensitivity. To investigate these sensory mechanisms, approaches like hypothermia to deliberately reduce plantar afferent input have been applied. But there are some limitations regarding hypothermic procedures in previous studies: Not only plantar aspects of the feet might be affected and maintaining the hypothermic effect during data collection. Therefore, the aim of the present study was to induce a permanent and controlled plantar hypothermia and to examine its effects on anticipatory and compensatory balance responses. We hypothesized deteriorations in anticipatory and compensatory balance responses as increased center of pressure excursions (COP) and electromyographic activity (EMG) in response to the hypothermic plantar procedure. 52 healthy and young subjects (23.6 ± 3.0 years) performed balance tests (unexpected perturbations). Subjects’ foot soles were exposed to three temperatures while standing upright: 25, 12 and 0 °C. COP and EMG were analyzed during two intervals of anticipatory and one interval of compensatory balance responses (intervals 0, 1 and 2, respectively). Results Similar plantar temperatures confirmed the successful implementation of the thermal platform. No significant COP and EMG differences were found for the anticipatory responses (intervals 0 and 1) under the hyperthermia procedure. Parameters in interval 2 showed generally decreased values in response to cooling. Conclusion No changes in anticipatory responses were found possibly due to sensory compensation processes of other intact afferents. Decreased compensatory responses may be interpreted as the additional balance threat, creating a more cautious behavior causing the CNS to generate a kind of over-compensatory behavior. Contrary to the expectations, there were different anticipatory and compensatory responses after reduced plantar inputs, thereby, revealing alterations in the organization of CNS inputs and outputs according to different task difficulties.

Hypotermi är en vanligt förekommande intraoperativ komplikation. Intraoperativ hypotermi är konstaterat i samband med såväl anestesiologiska som kirurgiska interventioner. Ett hypotermt tillstånd har stor inverkan både för patientens fysiska och psykiska status under hela det perioperativa förloppet. Komplikationerna vid intraoperativ hypotermi är många och välkända men intraoperativ hypotermi kan relativt enkelt förebyggas genom god planering och konkreta omvårdnadsåtgärder. Anestesisjuksköterskan har en grundläggande roll i detta arbete för att bedriva en säker vård. Syfte: Att kartlägga de rutiner och omvårdnadsåtgärder som tillämpas av anestesisjuksköterskor vid förebyggandet av intraoperativ hypotermi. Metod: Kvantitativ tvärsnittsstudie. Data samlades in via en egenkonstruerad webbenkät och analyserades i Statistical Package for Social Science (SPSS). Studien genomfördes på 14 utvalda operationsavdelningar. Resultat: Majoriteten av anestesisjuksköterskorna kände till de hypotermiförebyggande rutiner som fanns på arbetsplatsen. Det fanns vissa skillnader gällande de omvårdnadsåtgärder som användes för att förebygga hypotermi vid korta respektive långa ingrepp. Flera metoder tillämpades för att mäta temperaturen, den vanligaste metoden var örontermometer. Mätfrekvensen varierande, men oftast genomfördes temperaturmätning under pågående ingrepp. Mätning vid induktion förekom i något mindre utsträckning, majoriteten mätte temperaturen innan väckning. Inget signifikant samband fanns mellan upplevd följsamhet till rutiner på enheten och om deltagarna mätte temperaturen inför induktion eller väckning. Slutsats: Resultatet indikerar att det finns medvetenhet bland anestesisjuksköterskorna om rutiner och omvårdnadsåtgärder för att förebygga intraoperativ hypotermi på de studerade operationsavdelningarna. Vidare studier skulle behövas för att tydligare kartlägga faktorer för mätmetoder och mätintervaller. Även kartläggning för huruvida åtgärder varierar med den kirurgiska kontexten, samt om individuella bedömningar görs utifrån patientens riskfaktorer erfordras. Tydligare nationella riktlinjer skulle underlätta utformandet av standardiserade och evidensbaserade rutiner.

Bakgrund: Patienter som riskerar att drabbas av/har drabbats av accidentell hypotermi förekommer i all akutsjukvård. Accidentell hypotermi innebär oavsiktlig nedkylning till följd av skada eller sjukdom. Akutsjuksköterskor utgör en viktig funktion i att identifiera denna patientgrupp tidigt, såväl pre-, som intrahospitalt men även för att påbörja behandling. Tillståndet innebär obehandlat en hög risk för mortalitet. Det saknas tillräcklig kunskap som beskriver vårdåtgärder och påverkande faktorer vid accidentell hypotermi. Genom en sådan sammanställning kan akutsjuksköterskor få stöd i vårdandet av denna patientgrupp. Syfte: Syftet med litteraturstudien var att sammanställa faktorer och vårdåtgärder i det akuta omhändertagandet vid behandling eller förebyggande av accidentell hypotermi. Metod: En integrativ litteraturstudie genomfördes enligt Whittemore och Knafls femstegsprocess. Artiklar söktes fram i databaserna PubMed och Cinahl på ett systematiskt sätt genomsök block utvecklade enligt PEO-struktur. Tolv artiklar svarade till studiens syfte och kvalitetsgranskades för att sedan användas i resultatet. Dataanalysen genomfördes utifrån Braun och Clarkes tematiska analys. Resultat: Två huvudteman identifierades; De vårdande åtgärderna med subtema Passiv uppvärmning och Aktiv uppvärmning samt De påverkande faktorerna med subtema Behovet av kunskap, Omgivningens temperatur, Akutsjuksköterskans vårdande attityd samt Frysa och bli varm. Slutsats: Ur resultatet framkom att det fanns flertalet sätt att behandla och förebygga accidentell hypotermi samt att kombinationer av olika metoder förekom. Viktiga faktorer var kunskap och attityder hos akutsjuksköterskor för att få en struktur idet akuta omhändertagandet av accidentell hypotermi samt en ökad patientsäkerhet. Känslan av att frysa är en obehaglig upplevelse för patienter där värme upplevs som tryggt och avslappnande. / Background: Patients at risk of/suffering from accidental hypothermia due to injury or illness occur in all emergency settings. Emergency nurses have a key role in identifying these patients early, pre-, or intrahospital, and in initiating treatment. The condition carries a high risk of mortality if left untreated. There is currently a lack of knowledge regarding care measures and influencing factors for this condition. Such a review may assist emergency nurses in the management of these patients. Aim: The aim of this literature review was to compile factors and care measures in the acute management of treatment or prevention of accidental hypothermia. Method: An integrative literature review was conducted according to Whittmore and Knafls five step process. Articles were searched in the PubMed and Cinahl databases in a systematic manner using the PEO-structure. Twelve articles were quality reviewed for use in the results. Data analysis was performed following Braun and Clarke’s thematic analysis. Result: Two main themes were identified; The caring measures with subthemes Passive warming and Active warming as well as The influencing factors with subthemes The need for knowledge, The temperature of the environment, The caring attitude of the emergency nurse and Freezing and getting warm. Conclusion: There were several ways to treat and prevent accidental hypothermia and combinations of different methods were used. Important factors were knowledge and attitude of emergency nurses to manage structure and to provide patient safe care. The feeling of freezing is unpleasant for patients where warmth is perceived as safe and relaxing.

It is a major clinical problem that survival rates after out-of-hospital cardiac arrest have not markedly improved during the last decades, despite extensive research and the introduction of new interventions. However, recent studies have demonstrated promising treatments such as targeted temperature management (TTM) and methylene blue (MB). In our first study, we investigated the effect of MB administered during experi-mental cardiopulmonary resuscitation (CPR) in the setting of postponed hypother-mia in piglets. We set out to study if MB could compensate for a delay to establish targeted TTM. The study demonstrated that MB more than compensated for 30 min delay in induction of TTM. The effect of MB added to that of TTM. The second study examined the effects of TTM and S-PBN on the endothelin system and nitric oxide synthases (NOS) after prolonged CA in a porcine CPR mod-el. The study was designed to understand the cardioprotective mechanism of S-PBN and TTM by their influence on the endothelin system and NOS regulation. We veri-fied for the first time, that these two cardioprotective postresuscitative interventions activate endothelin-1 and its receptors concomitantly with eNOS and nNOS in the myocardium. We concluded that nitric oxide and endothelin pathways are implicated in the postresuscitative cardioprotective effects of TTM. The third study compared survival and hemodynamic effects of low-dose amio-darone and vasopressin to vasopressin in a porcine hypovolemic CA model. The study was designed to evaluate whether resuscitation with amiodarone and vasopressin compared to vasopressin alone would have an impact on resuscitation success, survival, and hemodynamic parameters after hemorrhagic CA. We found that combined resuscitation with amiodarone and vasopressin after hemorrhagic circulatory arrest resulted in greater 3-hour survival, better preserved hemodynamic parameters and smaller myocardial injury compared to resuscitation with vasopressin only. In our fourth study we planned to compare hemodynamic parameters between the treatment group (milrinone, esmolol and vasopressin; MEV) and control group (vasopressin only) during resuscitation from prolonged cardiac arrest in piglets. The study was designed to demonstrate if MEV treatment improved hemodynamics or cardiac damage compared to controls. We demonstrated that MEV treatment reduced cardiac injury compared with vasopressin alone.

No description available.

Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)