The overall aim of the present thesis was to study post-resuscitation care of cardiac arrest (CA) patients treated with target temperature management 33°C with a focus on evaluation of two prognostic tools: variations in cerebral venous saturation and acute magnetic resonance imaging (MRI) findings on the brain post-CA. An additional aim was to investigate patients’ neurological outcome and relatives’ experiences 6 months after the event. Paper I describes the cerebral oxygen saturation of blood obtained from a jugular bulb (SjvO2) catheter The results showed that patients with poor outcome tended to have higher SjvO2values,but this difference was only significant at 96 and108 hours post-CA. The main findings of Paper II were that patients with good outcome displayed a pathological pattern mainly in the frontal and parietal lobes on MRI of the brain. Patients with poor outcome had an extensive pathological pattern in several brain regions. Furthermore, very low apparent diffusion coefficient (ADC) values were associated with poor outcome regardless of brain region. Paper III investigated physical and cognitive function over time, between one month and 6 months post-CA, as well as d life satisfaction at 6 months. The results showed that impairment in physical and cognitive function is common in CA survivors but tends to decrease over time. Despite a severe illness, which has impaired the physical and cognitive functions, satisfaction with life as a whole was reported by 70% of CA survivors. In Paper IV, relatives described their experiences 6 months after a significant others CA. The analysis resulted in three themes reflecting relatives’ everyday life 6 months after the event: Difficulties managing a changed life situation, Feeling like I come second and Feeling new hope for the future. In conclusion, the results of the present thesis have increased our understanding of the two prognostic tools that were investigated; they have generated new and revealed aspects that should be taken into account during prognostication and assessing neurological outcome of this group of patients. The thesis has also shown that the healthcare needs to improve its routines for follow-ups and information provision to both patients and their relatives.

Perinatal asphyxia is a significant contributor to neonatal brain injury. In the clinical environment there is variability in the severity of neural injury in neonates with similar clinical histories. Whilst the duration and intensity of hypoxia is well known to influence the severity of neurological outcome, the global physiological responses to hypoxia may also affect the subsequent variability in neurological outcome. The first step in this project was to identify which physiological response/s during a constant global hypoxic-ischemic insult influence the severity of neurological outcome in the newborn piglet and to assess the relative importance of these responses. Hypoxia/hypercapnia was induced in anaesthetized piglets by reducing the fraction of inspired oxygen to 0.1 (10%) and the ventilation rate from 30-10 breaths per minute for 45 minutes. Neurological outcome was determined by using functional markers including aEEG amplitude and cerebral impedance, and the structural marker microtubule associated protein-2 immunohistochemistry at 6 hours post hypoxia. The results from the initial study indicated that there was significant variability in neurological outcome following a constant hypoxia/hypercapnia insult. Serum cortisol concentrations were highly variable at the end of hypoxia (mean ± SD; 240.7 ± 90.9 nmol/L) and associated with cardiovascular function (time heart rate below baseline; r = 0.69) and neurological outcome (r = 0.70). Cardiovascular function (time heart rate was below baseline) and neurological outcome were strongly associated (r = 0.77). In this study we observed an oscillating pattern in cardiovascular function during hypoxia in some animals. In the regression analysis variability in cortisol concentrations and cardiovascular function explained 68% of the variability in the severity of neurological outcome. Additional physiological factors did not improve the strength of the association with neurological outcome. The variability in the physiological responses, particularly cardiovascular and endocrine responses to hypoxia may be more important determinants of neurological outcome then previously recognised. Results from the initial study opened up several questions about the relationship between cortisol and cardiovascular function during hypoxia and the relationship to the subsequent neurological outcome. Since variability in cortisol concentrations was associated with both cardiovascular function and neurological outcome the second step of this thesis was to investigate what factors contributed to the variability in serum cortisol concentrations during hypoxia. It is important to understand why some individuals produce more cortisol than others, and as a result are protected against brain injury. The aim was to determine if the variability in serum cortisol concentrations was the result of variability in ACTH concentrations during acute global hypoxia. The results from this study showed that early changes in serum cortisol concentration (15 minutes) were not correlated with ACTH (R2 = 0.26, P = 0.1), however, later changes (30 – 45 minutes) were (R2 0.45 - 0.68). This suggests that the primary factor controlling serum cortisol concentrations before hypoxia and during later hypoxia is ACTH concentrations. These data suggest that other factors may control cortisol secretion during early hypoxia; a key mechanism responsible for these changes may be the activity of the sympathetic nervous system and the maturity of the adrenal medullae. Since, higher cortisol concentrations were associated with better cardiovascular function and neurological outcome. As a result of this observation the aim of this study was to determine if cortisol concentrations during hypoxia are the causative factor responsible for improved cardiovascular function and better neurological outcome. The results from this study showed that manipulating serum cortisol concentrations into high (<500nmol/l) and low (>50nmol/l) levels during hypoxia did not affect cardiovascular function (P = 0.68) or neurological outcome (P = 46). Within each group (low, high and control hypoxia group) there was significant variability in cardiovascular function during hypoxia, which was associated with neurological outcome. (r = -0.63, p = 0.01). This study showed that serum cortisol concentrations during hypoxia are not the causative factor impacting on improved cardiovascular function and neurological outcome. It is possible that factors affecting both cardiovascular function and cortisol production such as activity of the sympathetic nervous system, may be a possible mechanism behind the variability in neurological outcome and cardiovascular function. Additionally, this study showed that cortisol concentrations at 3 hours post hypoxia were associated with neurological outcome (r = -0.67, p = 0.01). The animals with poorer outcome may also be those with greater multi-organ damage and thus reduced ability to clear cortisol from the systemic circulation. In light of this finding it may be interesting to assess cortisol concentration in the human neonate at 3 hours post hypoxia and determine the relationship to neurological outcome. In the final study of this thesis the function of the cardiovascular system during hypoxia was investigated in more detail because of its strong association with neurological outcome (results observed in Chapter 2 and 4. Few researchers have reported on oscillations in cardiovascular function, particularly type-3 waves, during hypoxia in the neonate. The aim of this study was to determine the characteristics and occurrence of type-3 waves in the neonatal piglet and their relationship to neurological outcome following acute global hypoxia. The result showed that the development of type-3 waves in cardiovascular function occurred in 56% of animals. An oscillating pattern was significantly associated with better neurological outcome (p = 0.01) and a lower duration of hypotension during hypoxia (p = 0.02), and occurred more frequently in females (p = 0.024). The development of type-3 waves during acute global hypoxia is a key mechanism in promoting natural tolerance; and may be the result of greater activity, maturity or sensitivity of the sympathetic nervous system in females compared to males. This may explain the improved neurological outcome following hypoxia in the female neonate seen in the clinical setting.

Perinatal asphyxia is a significant contributor to neonatal brain injury. In the clinical environment there is variability in the severity of neural injury in neonates with similar clinical histories. Whilst the duration and intensity of hypoxia is well known to influence the severity of neurological outcome, the global physiological responses to hypoxia may also affect the subsequent variability in neurological outcome. The first step in this project was to identify which physiological response/s during a constant global hypoxic-ischemic insult influence the severity of neurological outcome in the newborn piglet and to assess the relative importance of these responses. Hypoxia/hypercapnia was induced in anaesthetized piglets by reducing the fraction of inspired oxygen to 0.1 (10%) and the ventilation rate from 30-10 breaths per minute for 45 minutes. Neurological outcome was determined by using functional markers including aEEG amplitude and cerebral impedance, and the structural marker microtubule associated protein-2 immunohistochemistry at 6 hours post hypoxia. The results from the initial study indicated that there was significant variability in neurological outcome following a constant hypoxia/hypercapnia insult. Serum cortisol concentrations were highly variable at the end of hypoxia (mean ± SD; 240.7 ± 90.9 nmol/L) and associated with cardiovascular function (time heart rate below baseline; r = 0.69) and neurological outcome (r = 0.70). Cardiovascular function (time heart rate was below baseline) and neurological outcome were strongly associated (r = 0.77). In this study we observed an oscillating pattern in cardiovascular function during hypoxia in some animals. In the regression analysis variability in cortisol concentrations and cardiovascular function explained 68% of the variability in the severity of neurological outcome. Additional physiological factors did not improve the strength of the association with neurological outcome. The variability in the physiological responses, particularly cardiovascular and endocrine responses to hypoxia may be more important determinants of neurological outcome then previously recognised. Results from the initial study opened up several questions about the relationship between cortisol and cardiovascular function during hypoxia and the relationship to the subsequent neurological outcome. Since variability in cortisol concentrations was associated with both cardiovascular function and neurological outcome the second step of this thesis was to investigate what factors contributed to the variability in serum cortisol concentrations during hypoxia. It is important to understand why some individuals produce more cortisol than others, and as a result are protected against brain injury. The aim was to determine if the variability in serum cortisol concentrations was the result of variability in ACTH concentrations during acute global hypoxia. The results from this study showed that early changes in serum cortisol concentration (15 minutes) were not correlated with ACTH (R2 = 0.26, P = 0.1), however, later changes (30 – 45 minutes) were (R2 0.45 - 0.68). This suggests that the primary factor controlling serum cortisol concentrations before hypoxia and during later hypoxia is ACTH concentrations. These data suggest that other factors may control cortisol secretion during early hypoxia; a key mechanism responsible for these changes may be the activity of the sympathetic nervous system and the maturity of the adrenal medullae. Since, higher cortisol concentrations were associated with better cardiovascular function and neurological outcome. As a result of this observation the aim of this study was to determine if cortisol concentrations during hypoxia are the causative factor responsible for improved cardiovascular function and better neurological outcome. The results from this study showed that manipulating serum cortisol concentrations into high (<500nmol/l) and low (>50nmol/l) levels during hypoxia did not affect cardiovascular function (P = 0.68) or neurological outcome (P = 46). Within each group (low, high and control hypoxia group) there was significant variability in cardiovascular function during hypoxia, which was associated with neurological outcome. (r = -0.63, p = 0.01). This study showed that serum cortisol concentrations during hypoxia are not the causative factor impacting on improved cardiovascular function and neurological outcome. It is possible that factors affecting both cardiovascular function and cortisol production such as activity of the sympathetic nervous system, may be a possible mechanism behind the variability in neurological outcome and cardiovascular function. Additionally, this study showed that cortisol concentrations at 3 hours post hypoxia were associated with neurological outcome (r = -0.67, p = 0.01). The animals with poorer outcome may also be those with greater multi-organ damage and thus reduced ability to clear cortisol from the systemic circulation. In light of this finding it may be interesting to assess cortisol concentration in the human neonate at 3 hours post hypoxia and determine the relationship to neurological outcome. In the final study of this thesis the function of the cardiovascular system during hypoxia was investigated in more detail because of its strong association with neurological outcome (results observed in Chapter 2 and 4. Few researchers have reported on oscillations in cardiovascular function, particularly type-3 waves, during hypoxia in the neonate. The aim of this study was to determine the characteristics and occurrence of type-3 waves in the neonatal piglet and their relationship to neurological outcome following acute global hypoxia. The result showed that the development of type-3 waves in cardiovascular function occurred in 56% of animals. An oscillating pattern was significantly associated with better neurological outcome (p = 0.01) and a lower duration of hypotension during hypoxia (p = 0.02), and occurred more frequently in females (p = 0.024). The development of type-3 waves during acute global hypoxia is a key mechanism in promoting natural tolerance; and may be the result of greater activity, maturity or sensitivity of the sympathetic nervous system in females compared to males. This may explain the improved neurological outcome following hypoxia in the female neonate seen in the clinical setting.

Objetivo: determinar a associação de crises epilépticas neonatais por diagnóstico clínico em pré-termos de muito baixo peso ao nascer com o desfecho neurológico no segundo ano de vida. Métodos: estudo de coorte, com análise retrospectiva de dados coletados prospectivamente. Incluídos recém nascidos pré-termos de muito baixo peso ao nascer (menor que 1500g) que tenham sobrevivido ao período neonatal e acompanhados no ambulatório de follow up da instituição. As crises epilépticas neonatais foram determinadas por critério clínico. O desfecho foi avaliado através da escala de Bayley II, medidas de perímetro cefálico, presença de deficiências sensoriais e óbito. O grupo com crises foi comparado ao grupo sem crises de acordo com o desfecho neurológico. Testes empregados na análise estatística: Qui-quadrado ou exato de Fisher (variáveis qualitativas), teste t de Student (variáveis quantitativas), risco relativo como medida de associação, Regressão de Poisson. Resultados: Trezentos e dois pacientes foram incluídos no estudo, com idade gestacional média de 30,4 ± 2,28 semanas e peso de nascimento médio 1182 ± 228,6 gramas. Sessenta pacientes (20%) tiveram crise epiléptica neonatal por diagnóstico clínico. O grupo com crises tinha médias de idade gestacional e peso significativamente menores, além de uma maior incidência de morbidades neonatais. Em relação ao desfecho neurológico, a diferença entre os grupos foi significativa, com um risco relativo estimado de 1,34 , com IC 95% 1,09-1,66 (p=0,006). Corrigindo-se com a regressão passo a passo, este efeito diminuiu, especialmente quando incluídas as variáveis de morbidade neurológica. Conclusão: Pacientes pré-termos com crises epilépticas neonatais apresentam um risco aumentado de desfecho neurológico adverso no segundo ano de vida. sobreposição entre as crises neonatais e as patologias que o pré-termo está exposto dificultam a determinação do seu impacto no desenvolvimento desses pacientes. / Purpose: to establish the association between clinical neonatal seizures in very low birth weight preterm infants and the neurological outcome in the second year of corrected age. Methods: cohort study, with retrospective analyses of prospective collected data. We included very low birth weight newborns (less than 1500g), which survived to the neonatal period, in regular follow-up, who were born between November/2003 and June/2010. Neonatal seizures were determined by clinical criteria. The outcome was assessed by the results of Bayley II scales, head circumference measurements, presence of sensorial deficits and death. The group with seizures was compared to the group without seizures. Statistical methods included Chi-square, Student’s t, Fisher’s exact tests and Poisson regression. Results: we included 302 patients, with mean gestational age and birth weight of respectively 30.4 ± 2.28 weeks and 1182 ± 228.6 grams. Sixty patients (20%) had clinical neonatal seizures. The group with seizures had lower gestational age and birth weight, and a greater incidence of neonatal morbidities. The relative risk of a worse neurological outcome was 1.34, with a CI 95% of 1.09 – 1.66 (p=0.006). After the Poisson regression this effect was reduced, especially when the neurological variables were included. Conclusion: preterm newborns with neonatal seizures are at increased risk for worse neurological outcome in the second year of life. The overlap among the neonatal seizures and the morbidities that these infants are exposed to increases the difficulty to define its impact in the patient neurological outcome.

Objetivo: determinar a associação de crises epilépticas neonatais por diagnóstico clínico em pré-termos de muito baixo peso ao nascer com o desfecho neurológico no segundo ano de vida. Métodos: estudo de coorte, com análise retrospectiva de dados coletados prospectivamente. Incluídos recém nascidos pré-termos de muito baixo peso ao nascer (menor que 1500g) que tenham sobrevivido ao período neonatal e acompanhados no ambulatório de follow up da instituição. As crises epilépticas neonatais foram determinadas por critério clínico. O desfecho foi avaliado através da escala de Bayley II, medidas de perímetro cefálico, presença de deficiências sensoriais e óbito. O grupo com crises foi comparado ao grupo sem crises de acordo com o desfecho neurológico. Testes empregados na análise estatística: Qui-quadrado ou exato de Fisher (variáveis qualitativas), teste t de Student (variáveis quantitativas), risco relativo como medida de associação, Regressão de Poisson. Resultados: Trezentos e dois pacientes foram incluídos no estudo, com idade gestacional média de 30,4 ± 2,28 semanas e peso de nascimento médio 1182 ± 228,6 gramas. Sessenta pacientes (20%) tiveram crise epiléptica neonatal por diagnóstico clínico. O grupo com crises tinha médias de idade gestacional e peso significativamente menores, além de uma maior incidência de morbidades neonatais. Em relação ao desfecho neurológico, a diferença entre os grupos foi significativa, com um risco relativo estimado de 1,34 , com IC 95% 1,09-1,66 (p=0,006). Corrigindo-se com a regressão passo a passo, este efeito diminuiu, especialmente quando incluídas as variáveis de morbidade neurológica. Conclusão: Pacientes pré-termos com crises epilépticas neonatais apresentam um risco aumentado de desfecho neurológico adverso no segundo ano de vida. sobreposição entre as crises neonatais e as patologias que o pré-termo está exposto dificultam a determinação do seu impacto no desenvolvimento desses pacientes. / Purpose: to establish the association between clinical neonatal seizures in very low birth weight preterm infants and the neurological outcome in the second year of corrected age. Methods: cohort study, with retrospective analyses of prospective collected data. We included very low birth weight newborns (less than 1500g), which survived to the neonatal period, in regular follow-up, who were born between November/2003 and June/2010. Neonatal seizures were determined by clinical criteria. The outcome was assessed by the results of Bayley II scales, head circumference measurements, presence of sensorial deficits and death. The group with seizures was compared to the group without seizures. Statistical methods included Chi-square, Student’s t, Fisher’s exact tests and Poisson regression. Results: we included 302 patients, with mean gestational age and birth weight of respectively 30.4 ± 2.28 weeks and 1182 ± 228.6 grams. Sixty patients (20%) had clinical neonatal seizures. The group with seizures had lower gestational age and birth weight, and a greater incidence of neonatal morbidities. The relative risk of a worse neurological outcome was 1.34, with a CI 95% of 1.09 – 1.66 (p=0.006). After the Poisson regression this effect was reduced, especially when the neurological variables were included. Conclusion: preterm newborns with neonatal seizures are at increased risk for worse neurological outcome in the second year of life. The overlap among the neonatal seizures and the morbidities that these infants are exposed to increases the difficulty to define its impact in the patient neurological outcome.

Objetivo: determinar a associação de crises epilépticas neonatais por diagnóstico clínico em pré-termos de muito baixo peso ao nascer com o desfecho neurológico no segundo ano de vida. Métodos: estudo de coorte, com análise retrospectiva de dados coletados prospectivamente. Incluídos recém nascidos pré-termos de muito baixo peso ao nascer (menor que 1500g) que tenham sobrevivido ao período neonatal e acompanhados no ambulatório de follow up da instituição. As crises epilépticas neonatais foram determinadas por critério clínico. O desfecho foi avaliado através da escala de Bayley II, medidas de perímetro cefálico, presença de deficiências sensoriais e óbito. O grupo com crises foi comparado ao grupo sem crises de acordo com o desfecho neurológico. Testes empregados na análise estatística: Qui-quadrado ou exato de Fisher (variáveis qualitativas), teste t de Student (variáveis quantitativas), risco relativo como medida de associação, Regressão de Poisson. Resultados: Trezentos e dois pacientes foram incluídos no estudo, com idade gestacional média de 30,4 ± 2,28 semanas e peso de nascimento médio 1182 ± 228,6 gramas. Sessenta pacientes (20%) tiveram crise epiléptica neonatal por diagnóstico clínico. O grupo com crises tinha médias de idade gestacional e peso significativamente menores, além de uma maior incidência de morbidades neonatais. Em relação ao desfecho neurológico, a diferença entre os grupos foi significativa, com um risco relativo estimado de 1,34 , com IC 95% 1,09-1,66 (p=0,006). Corrigindo-se com a regressão passo a passo, este efeito diminuiu, especialmente quando incluídas as variáveis de morbidade neurológica. Conclusão: Pacientes pré-termos com crises epilépticas neonatais apresentam um risco aumentado de desfecho neurológico adverso no segundo ano de vida. sobreposição entre as crises neonatais e as patologias que o pré-termo está exposto dificultam a determinação do seu impacto no desenvolvimento desses pacientes. / Purpose: to establish the association between clinical neonatal seizures in very low birth weight preterm infants and the neurological outcome in the second year of corrected age. Methods: cohort study, with retrospective analyses of prospective collected data. We included very low birth weight newborns (less than 1500g), which survived to the neonatal period, in regular follow-up, who were born between November/2003 and June/2010. Neonatal seizures were determined by clinical criteria. The outcome was assessed by the results of Bayley II scales, head circumference measurements, presence of sensorial deficits and death. The group with seizures was compared to the group without seizures. Statistical methods included Chi-square, Student’s t, Fisher’s exact tests and Poisson regression. Results: we included 302 patients, with mean gestational age and birth weight of respectively 30.4 ± 2.28 weeks and 1182 ± 228.6 grams. Sixty patients (20%) had clinical neonatal seizures. The group with seizures had lower gestational age and birth weight, and a greater incidence of neonatal morbidities. The relative risk of a worse neurological outcome was 1.34, with a CI 95% of 1.09 – 1.66 (p=0.006). After the Poisson regression this effect was reduced, especially when the neurological variables were included. Conclusion: preterm newborns with neonatal seizures are at increased risk for worse neurological outcome in the second year of life. The overlap among the neonatal seizures and the morbidities that these infants are exposed to increases the difficulty to define its impact in the patient neurological outcome.

No description available.

Background: The optimal timing of surgical therapy for traumatic spinal cord injury (TSCI) remains unclear. The purpose of this study is to evaluate the impact of “ultra-early” (<4 h) versus “early” (4–24 h) time from injury to surgery in terms of the likelihood of neurologic recovery. Methods: The effect of surgery on neurological recovery was investigated by comparing the assessed initial and final values of the American Spinal Injury Association (ASIA) Impairment Scale (AIS). A post hoc analysis was performed to gain insight into different subgroup regeneration behaviors concerning neurological injury levels. Results: Datasets from 69 cases with traumatic spinal cord injury were analyzed. Overall, 19/46 (41.3%) patients of the “ultra-early” cohort saw neurological recovery compared to 5/23 (21.7%) patients from the “early” cohort (p = 0.112). The subgroup analysis revealed differences based on the neurological level of injury (NLI) of a patient. An optimal cutpoint for patients with a cervical lesion was estimated at 234 min. Regarding the prediction of neurological improvement, sensitivity was 90.9% with a specificity of 68.4%, resulting in an AUC (area under the curve) of 84.2%. In thoracically and lumbar injured cases, the estimate was lower, ranging from 284 (thoracic) to 245 min (lumbar) with an AUC of 51.6% and 54.3%. Conclusions: Treatment within 24 h after TSCI is associated with neurological recovery. Our hypothesis that intervention within 4 h is related to an improvement in the neurological outcome was not confirmed in our collective. In a clinical context, this suggests that after TSCI there is a time frame to get the right patient to the right hospital according to advanced trauma life support (ATLS) guidelines.

Introduction: The most appropriate airway management technique for use by paramedics in out-of-hospital cardiac arrest is yet to be determined and evidence relating to the influence of airway management strategy on outcome remains equivocal. In cases where return of spontaneous circulation (ROSC) occurs following out-of-hospital cardiac arrest, patients may undergo direct transfer to a specialist heart attack centre (HAC) where the post resuscitation 12 lead ECG demonstrates evidence of ST elevation myocardial infarction. To date, no studies have investigated the role of airway management strategy on outcomes in this sub-set of patients. The AMICABLE (Airway Management In Cardiac Arrest, Basic, Laryngeal mask airway, Endotracheal intubation) study therefore sought to investigate the influence of prehospital airway management strategy on outcomes in patients transferred by the ambulance service directly to a HAC post ROSC. Methods: Adults with ROSC post out-of-hospital cardiac arrest who met local criteria for transfer to a HAC were identified prospectively. Ambulance records were reviewed to determine prehospital airway management approach and collect physiological and demographic data. HAC notes were obtained to determine in-hospital course and quantify neurological outcome via the Cerebral Performance Category (CPC) scale. Neurologically intact survivors were contacted post discharge to assess quality of life via the SF-36 health survey. Statistical analyses were performed via Chi-square, Mann Whitney U test, odds ratios, and binomial logistic regression. Results: A total of 220 patients were recruited between August 2013 and August 2014, with complete outcome data available for 209. The age of patients ranged from 22-96 years and 71.3% were male (n=149). Airway management was undertaken using a supraglottic airway (SGA) in 72.7% of cases (n=152) with the remainder undergoing endotracheal intubation (ETI). There was no significant difference in the proportion of patients with good neurological outcome (CPC 1&2) between the SGA and ETI groups (p=.286). Similarly, binomial logistic regression incorporating factors known to influence outcome demonstrated no significant difference between the SGA and ETI groups (Adjusted OR 0.725, 95% CI 0.337-1.561). Clinical and demographic variables associated with good neurological outcome included the presence of a shockable rhythm (p < .001), exposure to angiography (p < .001), younger age (p < .001) and shorter time to ROSC (p < .001). Due to an inadequate response rate (25.4%, n=15) analysis of SF36 data was limited to descriptive statistics. Limitations: The study only included patients who achieved ROSC and met the criteria for direct transfer to a HAC. Results are therefore not generalisable to more heterogenous resuscitation populations. Accuracy of clinical decision making and ECG interpretation were not assessed and therefore some patients included in the study may have been inappropriately transferred to a HAC. The low SF-36 survey response rate limited the level of neurological outcome analysis that could be undertaken. Conclusion: In this study, there was no significant difference in the proportion of good neurological outcomes in patients managed with SGA versus ETI during cardiac arrest. Further research incorporating randomised controlled trials is required to provide more definitive evidence in relation to the optimal airway management strategy in out-of-hospital cardiac arrest.

Σκοπός: Η θυμεκτομή αποτελεί κοινώς αποδεκτή θεραπεία της μυασθένειας με τις διάφορες προσπελάσεις να αναφέρονται ως ανάλογης αξίας για την επίτευξη ύφεσης της νόσου. Έχοντας πλέον την μόνιμη σταθερή ύφεση ως καθαρή και μετρήσιμη νευρολογική έκβαση των μυασθενικών ασθενών μετά θυμεκτομή και γνωρίζοντας ότι η ύφεση της νόσου αποτελεί χρόνο-εξαρτώμενο γεγονός, πραγματοποιήσαμε μια αναδρομική μελέτη των ασθενών με μυασθένεια που αντιμετωπίστηκαν χειρουργικά με σκοπό τον πιο αξιόπιστο καθορισμό του ρόλου των μεγίστων θυμικών εκτομών και την ταυτοποίηση προγνωστικών παραγόντων για ύφεση της νόσου μετά θυμεκτομή. Υλικό και μέθοδος. Η μελέτη περιλαμβάνει 78 ασθενείς που υποβλήθηκαν σε τροποποιημένη μέγιστη θυμεκτομή από το 1990 έως το 2007. Οι ενδείξεις θυμεκτομής περιελάμβαναν: οφθαλμική μυασθένεια ανθιστάμενη στη φαρμακευτική αγωγή, γενικευμένη μυασθένεια και μυασθένεια με θύμωμα. Τα στοιχεία που συλλέχθηκαν αφορούσαν τη βαρύτητα της νόσου (τροποποιημένη Osserman ταξινόμηση), την προεγχειρητική φαρμακευτική αγωγή, την ηλικία έναρξης της νόσου (≤ 40/ > 40 έτη), το χρονικό διάστημα που μεσολάβησε από τη διάγνωση στη θυμεκτομή (≤ 12/ > 12 μήνες), το φύλο, την ιστολογία του θύμου αδένα, τη θνητότητα και τις επιπλοκές. Στους ασθενείς με θύμωμα περαιτέρω στοιχεία που ελήφθησαν υπόψη αφορούσαν τον ιστολογικό τύπο του θυμώματος κατά την Παγκόσμια Οργάνωση Υγείας και το στάδιο του όγκου κατά Masaoka. Η εκτίμηση της νευρολογικής έκβασης στο τέλος του μετεγχειρητικού follow up έγινε βάση της νέας ταξινόμησης του Αμερικανικού Ιδρύματος για τη Βαρεία Μυασθένεια με την πλήρη σταθερή ύφεση να λαμβάνεται υπόψη για τον καθορισμό της επάρκειας της διενεργηθείσας εκτομής και για τη σύγκριση των αποτελεσμάτων μας με αυτά προηγουμένων μελετών. Η στατιστική ανάλυση των αποτελεσμάτων έγινε με το SPSS 17 και αφορούσε δύο ομάδες ασθενών ανάλογα με την παρουσία ή μη θυμώματος. Η μέθοδος Kaplan-Meier χρησιμοποιήθηκε για την εκτίμηση της επίπτωσης των υπό εκτίμηση προγνωστικών παραγόντων στην επίτευξη της πλήρους ύφεσης ενώ η Cox Regression ανάλυση αποτέλεσε το μοντέλο για την ανάλυση της ταυτόχρονης επίδρασης των υπό μελέτη παραμέτρων στην επίτευξη πλήρους σταθερής ύφεσης. Τιμές του p < 0.05 θεωρήθηκαν στατιστικά σημαντικές. Αποτελέσματα: 51 ασθενείς είχαν μυασθένεια χωρίς θύμωμα και 27 ασθενείς παρανεοπλασματική μυασθένεια. Δεν υπήρχαν στατιστικά σημαντικές διαφορές στα προεγχειρητικά κλινικά χαρακτηριστικά των ασθενών πλην της αναμενομένης εμφάνισης της νόσου σε απώτερη ηλικία στους ασθενείς με θύμωμα. Η θνητότητα ήταν μηδενική ενώ η χειρουργική νοσηρότητα, ανάλογη προηγουμένων μελετών θυμεκτομής με διαφορετικού τύπου προσπέλασεις, ανήλθε στο 7,7% και ήταν ως επί το πλείστον ήσσονος σημασίας. Το ποσοστό μετεγχειρητικής μυασθενικής κρίσης ήταν μόλις 3,8%. Οι ασθενείς με μυασθένεια και θύμωμα βίωσαν όψιμη νευρολογική έκβαση ανάλογη αυτής των ασθενών χωρίς θύμωμα (πιθανότητα ύφεσης 74,5% vs 85,7%, p= 0.632). Η μη χρήση στεροειδών στην προεγχειρητική φαρμακευτική αγωγή, ως έμμεσος δείκτης της βαρύτητας της νόσου, σχετίστηκε με στατιστικά καλύτερη πιθανότητα για πλήρη ύφεση των συμπτωμάτων τόσο στους ασθενείς με θύμωμα (95% CI 2.687-339.182, p= 0.006) όσο και σε αυτούς χωρίς θύμωμα (CI 95% 1.607-19.183, P= 0.007) στην πολυπαραγοντική ανάλυση. Αξιόλογη διαφορά, αν και στατιστικά μη σημαντική, για τη έκβαση της νόσου είχε η πρώιμη σε σχέση με την απώτερη χειρουργική αντιμετώπιση των ασθενών. Στη σύγκριση των 27 ασθενών με μυασθένεια και θύμωμα με 12 επιπλέον ασθενείς που υποβλήθηκαν στην ίδια επέμβαση για θύμωμα άνευ μυασθένειας η παρουσία των συμπτωμάτων μυϊκής αδυναμίας συνδυάστηκε με στατιστικά σημαντική βελτίωση της επιβίωσης των ασθενών (100% vs 38,8% στη 10ετία, p< 0.001). Στους ασθενείς με μυασθένεια χωρίς θύμωμα και απώτερης ηλικιακά έναρξης της νόσου το ποσοστό σημαντικής βελτίωσης των μυασθενικών συμπτωμάτων, εξαιρουμένης της πλήρους ύφεσης, ήταν 70%. Στους ασθενείς με μυασθένεια και θύμωμα η ιστολογική ταυτοποίηση των θυμωμάτων κατά την Παγκόσμια Οργάνωση Υγείας προέκυψε στατιστικά σημαντική τόσο στην μονοπαραγοντική όσο και στην πολυπαραγοντική ανάλυση με τα θυμώματα τύπου Β2, Α και Β3 να επιτυγχάνουν από πολύ καλή έως άριστη πιθανότητα πλήρους ύφεσης και τα θυμώματα τύπου ΑΒ, Β1 και C να έχουν απογοητευτική έκβαση όσον αφορά την ίαση. Συμπεράσματα: Η παρούσα μελέτη δείχνει ότι η τροποποιημένη μεγίστη θυμεκτομή είναι ασφαλής και σχετίζεται με υψηλή πιθανότητα για ίαση των μυασθενικών ασθενών με και χωρίς θύμωμα. Οι ασθενείς πρέπει να αντιμετωπίζονται χειρουργικά πρώιμα μετά τη διάγνωση με κυριότερο προγνωστικό παράγοντα για το απώτερο νευρολογικό αποτέλεσμα την προεγχειρητική βαρύτητα της νόσου. Η ασφαλής και πιο αξιόπιστη εκτίμηση της τελευταίας απαιτεί πιο αντικειμενικά κριτήρια όπως αυτά που θεσπίστηκαν από το Αμερικανικό Ίδρυμα για τη Βαρεία Μυασθένεια. Η ενσωμάτωση σε αυτά τα κριτήρια μοριακών παραμέτρων που φαίνεται να επηρεάζουν την πρόγνωση της νόσου, ενδεχόμενα να βελτιώσουν την αξιοπιστία της κλινικής σταδιοποίησης του MGFA και να αναδείξουν υποομάδες ασθενών με διαφορετική νευρολογική πρόγνωση μετά από θυμεκτομή. Επίσης η πρώιμη διάγνωση των θυμωμάτων εξαιτίας των συνυπαρχόντων μυασθενικών συμπτωμάτων μπορεί να οδηγήσει σε καλύτερη επιβίωση τους συγκεκριμένους ασθενείς. Τέλος η νευρολογική έκβαση των ασθενών με θυμωματώδη μυασθένεια σχετίζεται με τον ιστολογικό τύπο των θυμωμάτων, αλλά όχι αναγκαία και με την κακοήθη συμπεριφορά τους. / Objective: Thymectomy represents a widely accepted treatment for myasthenia gravis with different surgical approaches reported as comparably efficient in achieving disease’s remission. With the complete stable remission being currently accepted as a clear measurable outcome of patients with myasthenia undergoing surgical treatment and the knowledge that disease’s remission should be evaluated as a time dependent event we proceeded to a retrospective analysis of our experience on the surgical management of myasthenic patients. The objective was to access the effect of maximal resection on the neurological outcome and identify predictors of disease remission. Materials and methods: The study group consisted of 78 patients who underwent modified maximal thymectomy for myasthenia from 1990 to 2007. Indications for thymectomy included: ocular myasthenia refractory to medical treatment, generalized myasthenia and thymomatous myasthenia. The data collected included preoperative disease’s severity (modified Osserman classification), preoperative medical treatment, age at onset of the disease (≤ 40/ > 40 years), time elapsed between diagnosis and thymectomy (≤ 12/ > 12 months), gender, thymus gland histology, mortality and morbidity. In thymoma patients further analysis was carried out according the World Health Organization histological classification and the Masaoka stage of the tumors. The evaluation of the neurological outcome at the end of follow up was performed according the Myasthenia Gravis Foundation of America classification. Both the effectiveness of the resection performed and the comparison of our results with those of previous studies were done using the complete stable remission as the end point of the study. The statistical analysis of the results was carried out using the SPSS 17. Kaplan-Meier life table analysis was performed and the log rank test was used to evaluate the effect of the variables examined on the distribution of disease’s remission over time. The Cox proportional hazard model was also applied to verify the concurrent effect of the evaluated factors on the achievement of complete stable remission. P values < 0.05 were considered statistically significant. Results: 51 patients suffered of non thymomatous myasthenia while 27 patients had myasthenia with thymoma. The two groups were comparable in refer to the clinical features of the patients apart the more advanced age at the time of the diagnosis for thymoma patients. There was no perioperative mortality, while the surgical morbidity was comparable to the one reported in other series of patients with different surgical approaches and was 7.7%. The rate of postoperative myasthenic crisis was only 3.8%. Thymoma and non thymoma patients experienced comparable complete stable remission prediction (74.5% vs 85.7% at 15 years, p= 0.632). The absence of steroids in the preoperative medical regimen was statistically associated with the achievement of complete stable remission in both thymoma (95% CI 2.687-339.182, p= 0.006) and non thymoma patients (CI 95% 1.607-19.183, P= 0.007) in multivariate analysis. There was an important difference, although not statistically significant, for the neurological outcome between early and late surgical treatment. When the 27 patients with myasthenia and thymoma were compared with other 12 patients similarly operated for thymoma without symptoms and signs of muscular weakness we found that the presence of myasthenia was statistically associated with improved survival (100% vs 38.8% at 10 years, p< 0.001). Non thymoma patients presenting with late onset myasthenia, experienced high improvement (complete stable remission excluded) rate reaching up to 70% at the end of follow up. Among patients with thymomatous myasthenia gravis the World Health Organization histological classification was statistically associated with the late neurological outcome. Thymoma types A, B3 and B2 reached a high to excellent prediction of disease’s remission while types AB, B2 and C had a disappointing neurological outcome. Conclusons: The present study demonstrated that the modified maximal thymectomy is a safe procedure, associated with an excellent neurological outcome in both thymomatous and non thymomatous myasthenia. The patients should be operated early after the diagnosis is made with the disease’s severity being the prime determinant of the possibility to achieve complete remission of myasthenic symptoms. The evaluation of disease’s severity requires objective criteria like the ones proposed by the Myasthenia Gravis Foundation of America. The inclusion in these criteria of molecular markers related to myasthenia’s prognosis and its neurological outcome after thymectomy may further enhance its validity and may allow the identification of subgroups of patients with different disease prognosis after thymectomy. The presence of muscular weakness may lead to early diagnosis and surgical treatment of thymomas with improved survival. Finally the neurologic outcome in thymoma patients after thymectomy may be statistically associated with the World Health Organization classification subtypes but not necessarily with the aggressiveness of these tumors.