Efeito da sedação na microcirculação de pacientes em choque séptico

Ao longo dos últimos anos, apesar de todo desenvolvimento e pesquisa, a mortalidade na sepse permanece elevada. Na área de microcirculação foram realizados estudos em modelos experimentais de sepse ao longo das últimas duas décadas, quando se observou, através de técnicas invasivas, alterações como redução expressiva da densidade capilar funcional. A técnica denominada sidestream dark field (SDF) imaging, recentemente desenvolvida, permite a avaliação da microcirculação de forma transcutânea. A utilização desta técnica permitiu evidenciar a redução da densidade capilar funcional em pacientes com sepse grave quando comparado a um indivíduo saudável. Posteriormente, foi demonstrado que alterações persistentes na microcirculação de pacientes sépticos, mesmo com sinais vitais estabilizados, estão associadas com pior prognóstico.Evidentemente, os pacientes com sepse grave ou choque séptico sofrem uma grande quantidade de intervenções terapêuticas, aonde muitas delas alteram a microcirculação. Estudos analisando a microcirculação em pacientes em uso de nitroglicerina, corticóide, recebendo hemotransfusão ou ainda infusão de noradrenalina foram publicados recentemente.Entretanto, até o presente momento, não existem publicações que descrevam a influência dos sedativos na microcirculação de pacientes com choque séptico. As drogas mais comumente utilizadas para sedação de pacientes em ventilação mecânica são o sedativo midazolam e o anestésico propofol. Os objetivos do estudo foram: avaliar o efeito dos principais agentes sedativos utilizados na prática clínica na microcirculação de pacientes com choque séptico utilizando a técnica de sidestream dark field imaging, comparar os efeitos na microcirculação do midazolam com o propofol em pacientes com choque séptico e verificar se existe relação das alterações microcirculatórias provocadas pelos sedativos com as variações de diferentes parâmetros hemodinâmicos, gasométricos ou metabólicos como pressão arterial, índice cardíaco, lactato e saturação venosa central de oxigênio. Foram estudados (estudo prospectivo) 16 pacientes internados no Centro de Terapia Intensiva da Casa de Saúde São José. Os pacientes internados com diagnóstico de choque séptico e que possuíam indicação clínica de ventilação mecânica e de suspensão diária da sedação foram submetidos ao estudo da microcirculação na mucosa sublingual utilizando a técnica de sidestream dark field imaging. Estes pacientes foram sedados conforme orientação do protocolo já existente de sedação, inicialmente com propofol e posteriormente com midazolam. Os principais resultados observados foram:a macrohemodinâmica não diferiu nos 2 momentos do exame, o BIS (bispectral índex of sedation) se manteve na faixa recomendada nos 2 momentos do exame, tendo aumentado quando o paciente acordava, conforme esperado, e a proporção de vasos pequenos perfundidos e o índice de fluxo da microcirculação foram significativamente menores, enquanto o índice de heterogeneidade foi significativamente maior quando os pacientes estavam recebendo infusão de propofol quando comparados com a infusão de midazolam. Concluímos que, em pacientes com choque séptico, a administração de midazolam resulta em uma melhora dos parâmetros microcirculatórios quando comparada com a administração de propofol. Essa diferença não pode ser atribuída a alterações de variáveis hemodinâmicas sistêmicas.

γ-氨基丁酸受体和甘氨酸受体在大鼠丙泊酚麻醉中的作用

目的 研究丙泊酚对大鼠海马CA1区电刺激诱发兴奋性突触后电流(EPSC)的影响,分析γ-氨基丁酸(GABA)受体和甘氨酸受体在丙泊酚麻醉中的作用.方法 断头法分离wistar大鼠(13～19 d)海马半脑,切出400 μm厚度的海马脑片,全细胞膜片钳技术记录CA1区锥体神经元EPSC.80张脑片分为八组:脂肪乳剂组,50 μmol/L丙泊酚组,100 μmol/L丙泊酚组,200 μmol/L丙泊酚组,SR95531组,士的宁组,SR95531+100 μmol/L丙泊酚组,士的宁+100 μmol/L丙泊酚组,每组10张.SR95531+100 μmol/L丙泊酚组和士的宁+100 μmol/L丙泊酚组先在循环液中加入10 μmol/L SR95531或4 μmol/L士的宁预孵脑片30 min.八组均记录基础EPSC 10 min,然后加入不同药物,继续记录EPSC 40 min.膜钳制电压为-70 mV.结果 脂肪乳剂、SR95531和士的宁对EP-SC幅值无影响;丙泊酚呈剂量依赖性的抑制EPSC幅值,50、100、200 μmol/L丙泊酚最大抑制EPSC幅值为14.4%、52.3%、67.8%;SR95531+100 μmol/L丙泊酚组加入丙泊酚后,EPSC幅值基本无改变;士的宁+100 μmol/L丙泊酚组加入丙泊酚后,EPSC幅值仍然下降,最大抑制程度为34.7%.结论 丙泊酚主要通过增强GABAA受体功能使兴奋性突触活动降低,甘氨酸受体在其中起到协同和调节作用.

异丙酚对大鼠海马CAI区自发性兴奋性突触后电流的影响

目的:研究异丙酚对大鼠海马CA1区自发性兴奋性突触后电流(sEPSC)的影响。方法:断头法分离Wistar大鼠(13~19 d)海马半脑,用切片机切出400μm厚度的海马脑片,全细胞膜片钳记录CA1区锥体神经元sEPSC。20张脑片分为两组:脂肪乳剂组(n=10)和异丙酚组(n=10)。两组细胞稳定10~15 min后,加入90μl脂肪乳剂或异丙酚(相当于100μmol/L),记录40 min sEPSC。膜钳制电压为-70 mV。结果:100μmol/L异丙酚降低sEPSC的频率达68.1%,降低sEPSC的幅值达29.1%,缩短sEPSC的半衰期达49.3%;另外,异丙酚缩短sEPSC的上升时间达29.1%,减少曲线下面积达74.7%。结论:异丙酚通过影响突触前膜递质释放和突触后膜受体功能两个因素抑制兴奋性突触活动

丙泊酚对大鼠海马CA1 区兴奋性突触传递的影响

　目的　观察500μmol/ L 丙泊酚对大鼠海马CA1 区电刺激诱发的兴奋性突触后电流 ( EPSC) 的影响,分析丙泊酚的可能作用机制。方法　断头法分离Wistar 大鼠(13～19 d) 海马半脑, 用切片机切出400μm 厚度的海马脑片,全细胞膜片钳技术记录CA1 区锥体神经元EPSC。实验分 两组:脂肪乳剂组( n = 6) 和丙泊酚组( n = 10) 。先以50μmol/ L 印防己毒素预孵脑片30 min 后,记录 基础EPSC 10 min ,然后加入450μl 脂肪乳剂或丙泊酚(相当于500 μmol/ L ) , 继续记录EPSC 40 min ;继而以配对刺激代替单刺激,观察EPSC2/ EPSC1 比率的变化;改变膜钳制电压( - 80～ + 60 mV) ,观察电流2电压( I2V) 曲线的变化。结果　脂肪乳剂对EPSC 无影响,500μmol/ L 丙泊酚降低 大鼠海马CA1 区EPSC 值,25～30 min 左右达最大抑制效果,EPSC 幅值下降至基础值的6715 % ,明 显低于脂肪乳剂组( P < 0105) ;而且500μmol/ L 丙泊酚明显降低EPSC2/ EPSC1 比率,也使I2V 曲线 左移,降低反转电位至- 35 mV 左右。结论　500μmol/ L 丙泊酚对大鼠海马CA1 区兴奋性突触传 递产生抑制作用,这可能与其增强突触前膜、突触后膜GABAA 受体活性有关。

咪唑安定或丙泊酚拮抗戊四氮对突触传递的影响

目的: 观察咪唑安定或丙泊酚复合戊四氮对突触传递的影响。方法: 分离大鼠海马半脑, 切出400 Lm 厚度的海马脑片, 全细胞膜片钳记录戊四氮+ 咪唑安定组, 戊四氮+ 脂肪乳剂组, 戊四氮+ 丙泊酚组海马CA 1 区神经元兴奋性突触后电流(EP2 SC) 变化。结果: 各组加入10 mmolöL 戊四氮均使EPSC 降至基线值的3510% 左右; 10 LmolöL 咪唑安定使EPSC 幅值上升至 基线值的8612% , 脂肪乳剂不改变EPSC, 100 LmolöL 丙泊酚使EPSC 值上升至基线值的7117%。结论: 戊四氮对正常突触传 递具有抑制作用, 咪唑安定或丙泊酚拮抗戊四氮抑制突触传递的作用, 使已减小的EPSC 有所升高。

异丙酚对大鼠海马区突触传递可塑性的影响

目的研究异丙酚对海马区突触传递和可塑性的影响。方法断头分离大 鼠海马半脑, 制备加阿厚度海马脑片。张脑片分为六组。脂肪乳剂组和异丙酚组的脑片以印防 己毒素预孵而, 然后加人川脂肪乳剂或异丙酚相当于拌, 观察对兴奋性突触后电流 的影响。月旨肪乳剂长时程增强】」下组、脂肪乳剂长时程抑制组、异丙酚功下组、异丙酚 组的脑片以川脂肪乳剂或异丙酚相当于脚预孵而, 给予高频刺激或低频 刺激, 记录或的发生情况。结果脂肪乳剂对无影响脚异 丙酚使细胞下降至基础值的尸, 使细胞玲上升至基础值的 。脂肪乳剂组给予邓后玲值为基础值的, 脂肪乳剂汀〕组给 予⋯乃后值为基础值的异丙酚组给予后, 可以产生但不能维 持, 后值为基础值的, 异丙酚几组给予后值为基础值的 , 明显低于脂肪乳剂组尸。结论异丙酚对大鼠海马区突触传递 具有双重影响, 出现抑制和兴奋两种效果异丙酚损害大鼠海马区锥体神经元的维持而易 化。 【关键

丙泊酚对大鼠海马CA1 区长时程抑制的影响

　目的　观察丙泊酚对大鼠海马CA1 区锥体神经元产生的长时程抑制(L TD) 的影响,并 分析其可能机制。方法　断头法分离wistar 大鼠(13～19 d) 海马半脑,用切片机切出400μm 厚度的 海马脑片。实验分三组:脂肪乳剂组( I 组) ,丙泊酚组(P 组) ,SR95531 + 丙泊酚组( GP 组) 。I 组和P 组以90μL 脂肪乳剂或丙泊酚(相当于100μmol/ L) 预孵脑片60 min ,然后给予低频刺激(L FS) ,记录 L TD 的表达情况; GP 组先在循环液中加入10μmol/ L SR95531 预孵脑片30 min ,再加入100μmol/ L 丙泊酚继续孵育60 min ,继而给予L FS ,记录L TD 的表达情况。结果　I 组给予L FS 后,产生L TD , L FS 后10～40 min 的兴奋性突触后电流( EPSC) 值为基础值的57185 %;P 组给予L FS 后10～40 min 的EPSC 值为基础值的40182 % ,明显低于I 组( P < 0105) ; GP 组给予L FS 后10～40 min 的EPSC 值为基础值的56151 % ,与I 组比较差异无显著意义( P > 0105) ,与P 组比较差异有显著意义( P < 0105) 。结论　100μmol/ L 丙泊酚使大鼠海马CA1 区锥体神经元L TD 表达增强,这种作用与其增强 GABAA 受体功能有关;当阻断GABAA 受体后,这种易化作用消失。

Adenosine-induced flow arrest to facilitate intracranial aneurysm clip ligation: dose-response data and safety profile.

BACKGROUND: Adenosine-induced transient flow arrest has been used to facilitate clip ligation of intracranial aneurysms. However, the starting dose that is most likely to produce an adequate duration of profound hypotension remains unclear. We reviewed our experience to determine the dose-response relationship and apparent perioperative safety profile of adenosine in intracranial aneurysm patients. METHODS: This case series describes 24 aneurysm clip ligation procedures performed under an anesthetic consisting of remifentanil, low-dose volatile anesthetic, and propofol in which adenosine was used. The report focuses on the doses administered; duration of systolic blood pressure <60 mm Hg (SBP(<60 mm Hg)); and any cardiovascular, neurologic, or pulmonary complications observed in the perioperative period. RESULTS: A median dose of 0.34 mg/kg ideal body weight (range: 0.29-0.44 mg/kg) resulted in a SBP(<60 mm Hg) for a median of 57 seconds (range: 26-105 seconds). There was a linear relationship between the log-transformed dose of adenosine and the duration of a SBP(<60 mm Hg) (R(2) = 0.38). Two patients developed transient, hemodynamically stable atrial fibrillation, 2 had postoperative troponin levels >0.03 ng/mL without any evidence of cardiac dysfunction, and 3 had postoperative neurologic changes. CONCLUSIONS: For intracranial aneurysms in which temporary occlusion is impractical or difficult, adenosine is capable of providing brief periods of profound systemic hypotension with low perioperative morbidity. On the basis of these data, a dose of 0.3 to 0.4 mg/kg ideal body weight may be the recommended starting dose to achieve approximately 45 seconds of profound systemic hypotension during a remifentanil/low-dose volatile anesthetic with propofol induced burst suppression.

Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care units: a systematic review

BACKGROUND: Care of critically ill patients in intensive care units (ICUs) often requires potentially invasive or uncomfortable procedures, such as mechanical ventilation (MV). Sedation can alleviate pain and discomfort, provide protection from stressful or harmful events, prevent anxiety and promote sleep. Various sedative agents are available for use in ICUs. In the UK, the most commonly used sedatives are propofol (Diprivan(®), AstraZeneca), benzodiazepines [e.g. midazolam (Hypnovel(®), Roche) and lorazepam (Ativan(®), Pfizer)] and alpha-2 adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor(®), Orion Corporation) and clonidine (Catapres(®), Boehringer Ingelheim)]. Sedative agents vary in onset/duration of effects and in their side effects. The pattern of sedation of alpha-2 agonists is quite different from that of other sedatives in that patients can be aroused readily and their cognitive performance on psychometric tests is usually preserved. Moreover, respiratory depression is less frequent after alpha-2 agonists than after other sedative agents.

OBJECTIVES: To conduct a systematic review to evaluate the comparative effects of alpha-2 agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs.

DATA SOURCES: We searched major electronic databases (e.g. MEDLINE without revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane Central Register of Controlled Trials) from 1999 to 2014.

METHODS: Evidence was considered from randomised controlled trials (RCTs) comparing dexmedetomidine with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines such as midazolam, lorazepam and diazepam (Diazemuls(®), Actavis UK Limited). Primary outcomes included mortality, duration of MV, length of ICU stay and adverse events. One reviewer extracted data and assessed the risk of bias of included trials. A second reviewer cross-checked all the data extracted. Random-effects meta-analyses were used for data synthesis.

RESULTS: Eighteen RCTs (2489 adult patients) were included. One trial at unclear risk of bias compared dexmedetomidine with clonidine and found that target sedation was achieved in a higher number of patients treated with dexmedetomidine with lesser need for additional sedation. The remaining 17 trials compared dexmedetomidine with propofol or benzodiazepines (midazolam or lorazepam). Trials varied considerably with regard to clinical population, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded outcome assessors. Compared with propofol or benzodiazepines (midazolam or lorazepam), dexmedetomidine had no significant effects on mortality [risk ratio (RR) 1.03, 95% confidence interval (CI) 0.85 to 1.24, I (2) = 0%; p = 0.78]. Length of ICU stay (mean difference -1.26 days, 95% CI -1.96 to -0.55 days, I (2) = 31%; p = 0.0004) and time to extubation (mean difference -1.85 days, 95% CI -2.61 to -1.09 days, I (2) = 0%; p < 0.00001) were significantly shorter among patients who received dexmedetomidine. No difference in time to target sedation range was observed between sedative interventions (I (2) = 0%; p = 0.14). Dexmedetomidine was associated with a higher risk of bradycardia (RR 1.88, 95% CI 1.28 to 2.77, I (2) = 46%; p = 0.001).

LIMITATIONS: Trials varied considerably with regard to participants, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded assessors.

CONCLUSIONS: Evidence on the use of clonidine in ICUs is very limited. Dexmedetomidine may be effective in reducing ICU length of stay and time to extubation in critically ill ICU patients. Risk of bradycardia but not of overall mortality is higher among patients treated with dexmedetomidine. Well-designed RCTs are needed to assess the use of clonidine in ICUs and identify subgroups of patients that are more likely to benefit from the use of dexmedetomidine.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42014014101.

FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.

Modelos de resposta à interação entre fármacos anestésicos : análise de regressão e análise de Clusters

Os avanços tecnológicos e científicos, na área da saúde, têm vindo a aliar áreas como a Medicina e a Matemática, cabendo à ciência adequar de forma mais eficaz os meios de investigação, diagnóstico, monitorização e terapêutica. Os métodos desenvolvidos e os estudos apresentados nesta dissertação resultam da necessidade de encontrar respostas e soluções para os diferentes desafios identificados na área da anestesia. A índole destes problemas conduz, necessariamente, à aplicação, adaptação e conjugação de diferentes métodos e modelos das diversas áreas da matemática. A capacidade para induzir a anestesia em pacientes, de forma segura e confiável, conduz a uma enorme variedade de situações que devem ser levadas em conta, exigindo, por isso, intensivos estudos. Assim, métodos e modelos de previsão, que permitam uma melhor personalização da dosagem a administrar ao paciente e por monitorizar, o efeito induzido pela administração de cada fármaco, com sinais mais fiáveis, são fundamentais para a investigação e progresso neste campo. Neste contexto, com o objetivo de clarificar a utilização em estudos na área da anestesia de um ajustado tratamento estatístico, proponho-me abordar diferentes análises estatísticas para desenvolver um modelo de previsão sobre a resposta cerebral a dois fármacos durante sedação. Dados obtidos de voluntários serão utilizados para estudar a interação farmacodinâmica entre dois fármacos anestésicos. Numa primeira fase são explorados modelos de regressão lineares que permitam modelar o efeito dos fármacos no sinal cerebral BIS (índice bispectral do EEG – indicador da profundidade de anestesia); ou seja estimar o efeito que as concentrações de fármacos têm na depressão do eletroencefalograma (avaliada pelo BIS). Na segunda fase deste trabalho, pretende-se a identificação de diferentes interações com Análise de Clusters bem como a validação do respetivo modelo com Análise Discriminante, identificando grupos homogéneos na amostra obtida através das técnicas de agrupamento. O número de grupos existentes na amostra foi, numa fase exploratória, obtido pelas técnicas de agrupamento hierárquicas, e a caracterização dos grupos identificados foi obtida pelas técnicas de agrupamento k-means. A reprodutibilidade dos modelos de agrupamento obtidos foi testada através da análise discriminante. As principais conclusões apontam que o teste de significância da equação de Regressão Linear indicou que o modelo é altamente significativo. As variáveis propofol e remifentanil influenciam significativamente o BIS e o modelo melhora com a inclusão do remifentanil. Este trabalho demonstra ainda ser possível construir um modelo que permite agrupar as concentrações dos fármacos, com base no efeito no sinal cerebral BIS, com o apoio de técnicas de agrupamento e discriminantes. Os resultados desmontram claramente a interacção farmacodinâmica dos dois fármacos, quando analisamos o Cluster 1 e o Cluster 3. Para concentrações semelhantes de propofol o efeito no BIS é claramente diferente dependendo da grandeza da concentração de remifentanil. Em suma, o estudo demostra claramente, que quando o remifentanil é administrado com o propofol (um hipnótico) o efeito deste último é potenciado, levando o sinal BIS a valores bastante baixos.

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Management of refractory status epilepticus in adults: still more questions than answers.

Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed.

Développement d’un système d’administration de l’anesthésie en boucle fermée

En salle d’opération, les tâches de l’anesthésiste sont nombreuses. Alors que l’utilisation de nouveaux outils technologiques l’informe plus fidèlement sur ce qui se passe pour son patient, ces outils font que ses tâches deviennent plus exigeantes. En vue de diminuer cette charge de travail, nous avons considérer l’administration automatique d’agents anesthésiques en se servant de contrôle en boucle fermée. À cette fin, nous avons développé un système d’administration d’un agent anesthésique (le propofol) visant à maintenir à un niveau optimal la perte de conscience du patient pendant toute la durée d’une chirurgie. Le système comprend un ordinateur, un moniteur d’anesthésie et une pompe de perfusion. L’ordinateur est doté d’un algorithme de contrôle qui, à partir d’un indice (Bispectral IndexTM ou BIS) fournit par le moniteur d’anesthésie détermine le taux d’infusion de l’agent anesthésiant. Au départ, l’anesthésiste choisit une valeur cible pour la variable de contrôle BIS et l’algorithme, basé sur système expert, calcule les doses de perfusion de propofol de sorte que la valeur mesurée de BIS se rapproche le plus possible de la valeur cible établie. Comme interface-utilisateur pour un nouveau moniteur d’anesthésie, quatre sortes d’affichage ont été considérés: purement numérique, purement graphique, un mélange entre graphique et numérique et un affichage graphique intégré (soit bidimensionnel). À partir de 20 scenarios différents où des paramètres normaux et anormaux en anesthésie étaient présentés à des anesthésistes et des résidents, l’étude des temps de réaction, de l’exactitude des réponses et de la convivialité (évaluée par le NASA-TLX) a montré qu’un affichage qui combine des éléments graphiques et numériques était le meilleur choix comme interface du système. Une étude clinique a été réalisée pour comparer le comportement du système d’administration de propofol en boucle fermée comparativement à une anesthésie contrôlée de façon manuelle et conventionnelle où le BIS était aussi utilisé. Suite à l’approbation du comité d’éthique et le consentement de personnes ayant à subir des chirurgies générales et orthopédiques, 40 patients ont été distribués également et aléatoirement soit dans le Groupe contrôle, soit dans le Groupe boucle fermée. Après l’induction manuelle de propofol (1.5 mg/kg), le contrôle en boucle fermée a été déclenché pour maintenir l’anesthésie à une cible de BIS fixée à 45. Dans l’autre groupe, le propofol a été administré à l’aide d’une pompe de perfusion et l’anesthésiste avait aussi à garder manuellement l’indice BIS le plus proche possible de 45. En fonction du BIS mesuré, la performance du contrôle exercé a été définie comme excellente pendant les moments où la valeur du BIS mesurée se situait à ±10% de la valeur cible, bonne si comprise de ±10% à ±20%, faible si comprise de ±20% à ±30% ou inadéquate lorsque >±30%. Dans le Groupe boucle fermée, le système a montré un contrôle excellent durant 55% du temps total de l’intervention, un bon contrôle durant 29% du temps et faible que pendant 9% du temps. Le temps depuis l’arrêt de la perfusion jusqu’à l’extubation est de 9 ± 3.7 min. Dans le Groupe contrôle, un contrôle excellent, bon, et faible a été enregistré durant 33%, 33% et 15% du temps respectivement et les doses ont été changées manuellement par l’anesthésiste en moyenne 9.5±4 fois par h. L’extubation a été accomplie après 11.9 ± 3.3 min de l’arrêt de la perfusion. Dans le Groupe boucle fermée, un contrôle excellent a été obtenu plus longtemps au cours des interventions (P<0.0001) et un contrôle inadéquat moins longtemps (P=0.001) que dans le Groupe contrôle. Le système en boucle fermée d’administration de propofol permet donc de maintenir plus facilement l’anesthésie au voisinage d’une cible choisie que l’administration manuelle.

Patent DE10 2004 037 519 B4 “Sensor Process and Device for Determining a Physical Value“. A Proof of Concept

At present, a fraction of 0.1 - 0.2% of the patients undergoing surgery become aware during the process. The situation is referred to as anesthesia awareness and is obviously very traumatic for the person experiencing it. The reason for its occurrence is mostly an insufficient dosage of the narcotic Propofol combined with the incapability of the technology monitoring the depth of the patient’s anesthetic state to notice the patient becoming aware. A solution can be a highly sensitive and selective real time monitoring device for Propofol based on optical absorption spectroscopy. Its working principle has been postulated by Prof. Dr. habil. H. Hillmer and formulated in DE10 2004 037 519 B4, filed on Aug 30th, 2004. It consists of the exploitation of Intra Cavity Absorption effects in a two mode laser system. In this Dissertation, a two mode external cavity semiconductor laser, which has been developed previously to this work is enhanced and optimized to a functional sensor. Enhancements include the implementation of variable couplers into the system and the implementation of a collimator arrangement into which samples can be introduced. A sample holder and cells are developed and characterized with a focus on compatibility with the measurement approach. Further optimization concerns the overall performance of the system: scattering sources are reduced by re-splicing all fiber-to-fiber connections, parasitic cavities are eliminated by suppressing the Fresnel reflexes of all one fiber ends by means of optical isolators and wavelength stability of the system is improved by the implementation of thermal insulation to the Fiber Bragg Gratings (FBG). The final laser sensor is characterized in detail thermally and optically. Two separate modes are obtained at 1542.0 and 1542.5 nm, tunable in a range of 1nm each. Mode Full Width at Half Maximum (FWHM) is 0.06nm and Signal to Noise Ratio (SNR) is as high as 55 dB. Independent of tuning the two modes of the system can always be equalized in intensity, which is important as the delicacy of the intensity equilibrium is one of the main sensitivity enhancing effects formulated in DE10 2004 037 519 B4. For the proof of concept (POC) measurements the target substance Propofol is diluted in the solvents Acetone and DiChloroMethane (DCM), which have been investigated for compatibility with Propofol beforehand. Eight measurement series (two solvents, two cell lengths and two different mode spacings) are taken, which draw a uniform picture: mode intensity ratio responds linearly to an increase of Propofol in all cases. The slope of the linear response indicates the sensitivity of the system. The eight series are split up into two groups: measurements taken in long cells and measurements taken in short cells.