Studies have shown that patients receiving mechanical ventilation in an intensive care unit (ICU), who are entirely dependent on the nursing staff, often experience frustration due to a temporary loss of the voice source. Limited communication is an important factor contributing to patient discomfort. Nursing staff also report communication as frustrating and difficult. The aim of the present study is to introduce a neck-type electrolarynx as a communication aid in an ICU, to study the nursing staff experiences of communication with tracheotomized patients receiving mechanical ventilation, and to examine the patient´s experiences regarding communicative abilities. Communication between a ventilator treated, tracheotomized patient and members of the nursing staff was recorded and analyzed according to principles of Conversation Analysis (CA). The results show that several members of the nursing staff experience difficulties communicating with tracheotomized patients receiving mechanical ventilation. A majority believe that the conditions for communication could be improved. The results of CA also indicate that an electrolarynx may be an effective and appropriate communication aid for ventilator treated, tracheostomized patients. Further research is needed to broaden the knowledge of the electrolarynx as a communication aid for these patients. Keywords: communication, mechanical ventilation, electrolarynx, patient experience, nursing staff experience, Conversation Analysis (CA).

Long-term oxygen therapy (LTOT) or home mechanical ventilation (HMV) can improve survival time in chronic respiratory failure. A national quality register could be an aid to identifying risk markers and optimizing therapy for respiratory failure. Aims: ▪To identify risk markers for chronic respiratory failure, especially when triggered by chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). ▪To predict sex-related differences in the future need of LTOT for COPD and to study sex related survival rate in COPD patients starting LTOT. ▪To investigate if HMV is more effective than LTOT alone in treating chronic respiratory failure caused by kyphoscoliosis. ▪To evaluate the use of quality indicators in LTOT. Methods: Swedish national registers for LTOT and HMV were established in 1987 and 1996 respectively. They were reconstructed in 2004 to form the web-based register Swedevox. Indications for LTOT were based on the guidelines from the Swedish Society for Respiratory Medicine. The incidence and prevalence of LTOT for COPD were measured annually from 1987 to 2000, and the future need for LTOT was estimated on the basis of the frequency of ever smoking in Sweden in 2001 in different age groups. A postal questionnaire on occupational exposures was completed by 181 patients with severe pulmonary fibrosis who started LTOT between 1997 and 2000, and by 757 controls. Odds ratios (ORs) were calculated. Time to death was evaluated in kyphoscoliotic patients starting HMV or LTOT alone in 1996-2004. Ten quality indicators were defined and evaluated based on data from patients starting LTOT in 1987-2005. Results: The incidence each year of LTOT in COPD patients increased more rapidly in women than in men (from 2.0 and 2.8/100,000 in 1987 to 7.6 and 7.1/100,000 in 2000 respectively, (p < 0.001)). Women ran a 1.9 times higher risk than men to develop chronic hypoxemia from COPD and had a higher survival rate during LTOT. In men, IPF was associated with exposure to birch dust with an OR 2.7, (95% confidence interval (CI) 1.30–5.65) and with hardwood dust, OR 2.7 (95% CI 1.14–6.52). Patients with kyphoscoliosis showed a better survival rate with HMV than with LTOT alone with a hazard ratio of 0.30 (95%CI 0.18-0.51), adjusted for age, sex, concomitant respiratory diseases, and blood gas levels. There were improvements in the following eight quality indicators for LTOT: access to LTOT, PaO2 ≤ 7.3 kPa without oxygen, no current smoking, low number of thoracic deformity patients without concomitant HMV, LTOT > 16 hours of oxygen/day, mobile oxygen equipment, reassessment of hypoxemia when LTOT was not started in a stable state COPD, and avoidance of continuous oral steroids in COPD. There was a decline in the indicator PaO2 > 8 kPa on oxygen. First-year survival rate in COPD was unchanged. Conclusions: The incidence and prevalence of LTOT increase more rapidly in women than in men. Survival rate during LTOT in COPD is better in women than in men. Exposure to birch and hardwood dust may contribute to the risk of IPF in men. Survival rate in patients with kyphoscoliosis was three times better with HMV than with LTOT alone. The national quality register for LTOT showed improvements in eight out of ten quality indicators. Levels for excellent quality in the indicators are suggested.

The overall aim of this thesis is to illuminate meanings of the relation between human beings, technology and care, as narrated by critical care nurses and people in need of home mechanical ventilation (HMV). The data are based on narrative research interviews with six intensive care nurses (I), 13 people who were about to start HMV (II), these 13 people were interviewed for a second time six to eight months after HMV had started (III), and nine persons with more than two years HMV experience (IV). The text was analysed using a phenomenological-hermeneutic research method as described by Lindseth and Norberg. The method is developed from the writings of the French philosopher Paul Ricoeur. The findings illuminate meanings of nursing care in an intensive care unit (I) as undertaking the role of advocacy as a caring response to another human being. The basic condition for this caring response depends on the nurses' openness and sensitivity to the needs of patients or patients' next of kin. The nurses were aware of the influence of technology and tried to modify its negative effects. Meanings of becoming dependent on HMV (II) are interpreted and metaphorically expressed as "to get one's breath" and "to hold one's breath" respectively. On the one hand, breathing ensures the cellular oxidation process within the body, but on the other hand there can be "shortness of breath" in "spiritual breathing", and starting HMV will influence patients' whole life situation, body and spirit. After using a ventilator six to eight months, meanings of a life dependent on a ventilator was interpretd as either a closure or an opening of the lived body to oneself, other people and the world. This interpretation is illustrated by two images. A life on a ventilator at home is not to be seen as static being. On the contrary, it is a being which moves and changes over time. Being dependent on a ventilator and living at home, as narrated by adults with more than two years of HMV experience (IV), was interpreted as being able to rise above yourself and your personal boundaries in order to live a good life. These meanings are bound up with experiencing a vital force and interdependency, and despite fragility being able to reach others and the outside world. Design and function of technology had an impact on the lived body. The comprehensive understanding of the four articles (I-IV) unfolded meanings of the relation between human beings, technology and care, as an interchange and a creation of physical and spiritual energy among humans and between human and technology. It could be an experience of the lived body being filled with as well as emptied of energy. This interpretation points at a call for the caring personnel to be attentive and to listen to the voices of the lived body in health and illness, and to bear witness to those who suffer. Technology acts between the person and the world and in order to be embodied, technology must be "transparent", i.e. beautiful and fit to its use.

The lungs are particularly vulnerable to acute, critical illness. Respiratory failure can result not only from primary lung pathology, such as pneumonia, but also as a secondary consequence of heart failure or inflammatory illness, such as sepsis or trauma. When this occurs, it is essential to support patients with mechanical ventilation while the fundamental disease process is addressed. The goal of mechanical ventilation is to ensure adequate ventilation, which involves a magnitude of gas exchange that leads to the desired blood level of carbon dioxide, and adequate oxygenation that ensures organ function. Achieving these goals is complicated by the fact that mechanical ventilation can actually cause acute lung injury, either by inflating the lungs to excessive volumes or by using excessive pressures to inflate the lungs. Thus, the challenge to mechanical ventilation is to produce the desired blood levels of carbon dioxide and oxygen without causing further acute lung injury. In this research, we develop an analysis and control synthesis framework for a pressure-limited respirator and lung mechanics system using compartment models. Specifically, a general mathematical model is developed for the dynamic behavior of a multicompartment respiratory system. Then, based on this multicompartment model, an optimal respiratory pattern is characterized using classical calculus of variations minimization techniques for inspiratory and expiratory breathing cycles. Furthermore, model predictive controller frameworks are designed to track the given optimal respiratory air flow pattern while satisfying control input amplitude and rate constrains.

FUNDAMENTO: análisis de la aplicación de un ciclo de garantía de calidad sobre las tasas de infección nosocomial (IN) en una UCI polivalente de nivel II. MÉTODO: Estudio prospectivo de cohortes, de dos años de duración, sobre 568 pacientes; Grupo A (n=281), observacional y Grupo B (n=287), en el que se aplicaron medidas de mejora (administración de sucralfato, correcta profilaxis antibiótica quirúrgica y medidas estrictas de asepsia) Se comparan las tasas de IN asociada a ventilación mecánica (NAVM), sonda uretral, catéter venoso central e infección de herida quirúrgica en ambos grupos, así como la estancia y mortalidad intra-UCI. RESULTADOS Tras la aplicación del ciclo de mejora de calidad mediante el cumplimiento de criterios de calidad, obtuvimos una reducción significativa de las tasas de incidencia de todas las infecciones controladas. No apreciamos diferencias en la mortalidad global intra-UCI entre ambos grupos, aunque sí en los que desarrollaron una IN. Los pacientes con NAVM, mostraron una reducción no significativa de la mortalidad. El subgrupo de pacientes que recibió sucralfato presentó una disminución de la frecuencia de IN y mortalidad relacionada. Sin embargo, el grado de incumplimientos del protocolo de mejora se mostró elevado (diagrama de Pareto). CONCLUSIONES: La instauración de un sistema de vigilancia y la aplicación de medidas de mejora han logrado reducir tanto la incidencia como la mortalidad de la IN, no así la mortalidad global intra-UCI. / BACKGROUND: To analyze the effects of implementation of a quality assurance cycle on rates of nosocomial infection (NI) in a level II intensive care unit (ICU.) METHOD: Prospective cohort study of two years on 568 patients divided in Group A (n = 281, cohort observational control group) and Group B (n = 287; experimental cohort group), which were implemented improvement measures (administration of oral sucralfate, surgical prophylaxis and aseptic measures). We compare the rates of follow aspects: ventilator-associated pneumonia (VAP), urethral catheter, central venous catheter and surgical wound infections, length and ICU mortality in both groups. RESULTS: After the implementation of quality improvement cycle by meeting quality criteria, we obtained a significant reduction in incidence rates of all infections under control. We found no differences in overall mortality ICU between the two groups, except in those who developed one NI. Patients with VAP showed a non significant reduction in mortality. The subgroup of patients receiving sucralfate showed a decrease in the frequency of NI and related mortality. However, the degree of improvement protocol violations was high (analyzed by Diagram’ s Pareto). CONCLUSIONS: The establishment of a surveillance system and implementation of improvement measures have reduced both the incidence and mortality of NI, but not the overall ICU mortality.

Bei Patienten mit einem akuten Lungenversagen (ALI oder ARDS) ist der Sauerstoffverbrauch der Lunge (VO2pulm) durch pathophysiologische Prozesse insbesondere die Ausbildung von Atelektasen stark beeinträchtigt. Aufgrund der Annahme, dass eine Steigerung der Anzahl ventilierter Lungenareale zu einer Erhöhung des pulmonalen Sauerstoffverbrauchs führt, haben wir den Einfluss eines definierten Rekrutierungsmanövers (PEEP/PEAK + 10 cmH2O) auf den pulmonalen Sauerstoffverbrauch (VO2pulm), pulmonalen kapillären Blutfluss (PCBF), der den nicht geshunteten Anteil am HZV darstellt, und den transpulmonalen Shunt (Qs/Qt) untersucht. In der vorliegenden Studie wurde der VO2pulm als Differenz zwischen dem Sauerstoffverbrauch des gesamten Körpers, gemessen über die indirekte Kalorimetrie (VO2cal), und dem über das inverse Fick`sche Prinzip errechneten Sauerstoffverbrauch (VO2Fick) bestimmt. Im Rahmen einer klinisch-prospektiven Studie konnten nach Annahme des Studienprotokolls durch die zuständige Ethikkommission 13 beatmete Patienten, welche die Consensus-Kriterien eines ALI oder ARDS erfüllten, eingeschlossen werden. Nach Sicherstellung einer adäquaten Volumensituation und Messung der Ausgangsparameter wurde der PEEP um 10 cmH2O erhöht. Um ein stabiles Atemzugvolumen (VT 6-8 ml/kgKG) und damit gleichbleibende Bedingungen für die alveoläre Ventilation bis auf das von uns durchgeführte Rekrutierungsmanöver zu gewährleisten, wurde zeitgleich der Spitzendruck ebenfalls um 10 cmH2O erhöht. Nach 15 und 60 min wurden die Zieldeterminanten pulmonaler Sauerstoffverbrauch (VO2pulm), PCBF und transpulmonaler Shunt erneut bestimmt. Die Messung der indirekten Kalorimetrie (VO2cal) wurde mit dem Deltatrac TM, MBM 200® durchgeführt, VO2Fick über die Thermodilutionsmethode ermittelt, die partielle CO2-Rückatmungsmethode (David®) zur Bestimmung des PCBF genutzt und der transpulmonale Shunt (Qs/Qt) mittels der Formel nach BERGGREN berechnet. Die statistische Auswertung der Daten erfolgte mittels T-Tests für gepaarte Stichproben. Nach dem Manöver konnte eine signifikante Steigerung des PCBF von 4,44 ± 1,15 l/min auf 5,4 ± 1,68 l/min nach 15 min, respektive 5,12 ± 1,67 l/min nach 60 min nachgewiesen werden (p&amp;lt;0,025). Dieser Anstieg wurde von einer signifikanten Reduktion des transpulmonalen Shunts (Qs/Qt) von 0,24 ± 0,08 auf 0,16 ± 0,07 nach 15 min und 0,16 ± 0,07 nach 60 min begleitet (p&amp;lt;0,005). Diese Veränderungen der pulmonalen Hämodynamik gehen mit statistisch relevanten Verbesserungen der Oxygenierung sowie der Atemmechanik einher. Eine signifikante Steigerung des pulmonalen Sauerstoffverbrauchs konnte für die gesamte Studienpopulation nicht festgestellt werden. In dieser Untersuchung steigt der Sauerstoffverbrauch der Lunge deskriptiv von baseline 10,1 +/- 30,59 ml/min über 11,42 +/- 27,42 ml/min nach 15 min, respektive auf 28,69 +/- 56,75 ml/min nach 60 min an. Die signifikante Steigerung des pulmonal-kapillären Blutflusses und die konsekutive Reduktion des transpulmonalen Shunts schon 15 min nach dem Manöver impliziert einen Anstieg der an der alveolären Ventilation teilnehmenden alveolokapillären Einheiten, was einer Rekrutierung von vorher atelektatischen Lungenabschnitten entspricht. Insbesondere bei ARDS-Patienten und Respondern konnten Rekrutierungs-induzierte Veränderungen detektiert werden, wohingegen die Patienten mit ALI oder Nonresponder keinerlei statistische Unterschiede während der Intervention zeigten. Trotz stattgefundener Wiederbelüftung von Atelektasen konnte ein statistisch relevanter Unterschied bezüglich des pulmonalen Sauerstoffverbrauchs durch das Rekrutierungsmanöver für die gesamte Studienpopulation nicht festgestellt werden.

Rationnelle. La ventilation mécanique invasive (VI) s’accompagne lorsqu’elle se prolonge, d’une augmentation de la morbimortalité. Jusqu’à 64% des enfants hospitalisés aux soins intensifs sont ventilés et peu de données épidémiologiques existent afin d’estimer précocement la durée du support ventilatoire. Objectifs. Déterminer l’incidence et les facteurs de risque précoces de ventilation mécanique invasive prolongée aux soins intensifs pédiatriques. Méthode. Nous avons conduit une étude descriptive rétroélective sur un an. Tous les épisodes de VI aux soins intensifs du Centre hospitalier universitaire Sainte Justine de Montréal ont été inclus. Les facteurs de risque de VI prolongée (≥ 96 heures) ont été déterminés par régression logistique. Résultats. Parmi les 360 épisodes de VI, 36% ont duré ≥ 96 heures. Les facteurs de risques de ventilation prolongée en analyse multivariée sont : âge <12 mois, score de PRISM ≥ 15 à l’admission, pression moyenne dans les voies aériennes ≥13 cm H2O au jour 1 de ventilation, utilisation de la sédation intraveineuse continue au jour 1 de ventilation et ventilation non invasive avant intubation. Conclusion. La VI prolongée survient chez environ un tiers des patients ventilés. Les patients de moins de 12 mois semblent être plus à risque que les enfants plus âgés et devraient bénéficier de stratégies différentes pour diminuer leur durée de ventilation mécanique. La sévérité de la maladie, l’agressivité du support ventilatoire, l’utilisation d’une sédation continue au premier jour de ventilation sont également des facteurs à considérer dans les études visant à diminuer la durée de support ventilatoire. / Rationale. Invasive mechanical ventilation is associated, if prolonged, with higher morbidity and mortality. Up to 64% of children hospitalized in pediatric intensive care units (PICU) require invasive ventilation but little epidemiological data are available on children requiring prolonged acute invasive mechanical ventilation. Objectives. To determine the incidence rate and early risk factors for prolonged acute invasive mechanical ventilation in children. Methods. We conducted a retrolective longitudinal cohort study over a one-year period. All consecutive episodes of invasive mechanical ventilation in the PICU of Sainte-Justine Hospital were included. Risk factors for prolonged (≥ 96 hours) versus short (< 96 hours) ventilation were determined by logistic regression. Results. Among the 360 episodes of invasive ventilation, 36% had a length ≥ 96 hours. Following multivariate analysis, significant risk factors for prolonged acute invasive mechanical ventilation were: age <12 months, PRISM score ≥ 15 at admission, mean airway pressure ≥13 cm H2O on day one, use of continuous intravenous sedation on day one and use of non-invasive ventilation prior to intubation. Conclusion. Prolonged acute mechanical ventilation occurs in approximately one third of ventilated children. Younger children (aged <12 months) may be different from older patients and may require different strategies to decrease the duration of mechanical ventilation. Severity of illness, the aggressiveness of ventilatory support required and the use of continuous intravenous sedation on the first day of ventilation are also risk factors to consider in trials aimed at reducing mechanical ventilation duration.

Les pédiatres intensivistes ont plusieurs éléments disponibles pour guider leurs décisions par rapport à la ventilation mécanique. Par contre, aucune étude prospective ne décrit les éléments auxquels les intensivistes se réfèrent pour modifier les paramètres du respirateur. Objectifs : Décrire la pratique actuelle de la modification des paramètres du respirateur aux soins intensifs du CHU Sainte-Justine, un hôpital pédiatrique tertiaire. Hypothèse : 80% des modifications des paramètres du respirateur influant sur l’épuration du CO2 sont liées à l’analyse de la PCO2 ou du pH et 80% des modifications des paramètres d’oxygénation sont liés à l’analyse de l’oxymétrie de pouls. Méthodes : En se servant d’un logiciel de recueil de données, les soignants ont enregistré un critère de décision primaire et tous les critères de décision secondaires menant à chaque modification de paramètre du respirateur au moment même de la modification. Résultats : Parmi les 194 modifications des paramètres du respirateur influant sur l’épuration du CO2, faites chez vingts patients, 42.3% ±7.0% avaient pour critère primaire la PCO2 ou le pH sanguin. Parmi les 41 modifications de la pression expiratoire positive et les 813 modifications de la fraction d’oxygène inspirée, 34.1% ±14.5% et 84.5% ±2.5% avaient pour critère primaire l’oxymétrie de pouls, respectivement. Conclusion : Les médecins surestiment le rôle de la PCO2 et du pH sanguins et sousestiment le rôle d’autres critères de décision dans la gestion de la ventilation mécanique. L’amélioration de notre compréhension de la pratique courante devrait aider à l’éboration des systèmes d’aide à la décision clinique en assistance respiratoire. / Pediatric intensivists have a multiplicity of elements available to guide them in mechanical ventilator decision-making; however, no prospective studies describe which elements intensivists currently use to make ventilator setting changes. Objectives: We describe the current practice of ventilator setting modification in the intensive care unit at Sainte-Justine Hospital, a tertiary care pediatric hospital. Hypothesis: Eighty percent of ventilator settings affecting carbon dioxide clearance are based on the PCO2 or pH while eighty percent of settings affecting oxygenation are based on pulse oximetry. Methods: Caregivers recorded the primary element and any secondary elements leading to a ventilator setting change at the time of the change via a custom-designed data gathering software. Results: We included twenty patients. Of a combined 194 changes affecting CO2 clearance, 42.3% ±7.0% were in reference to blood PCO2 or pH. Of forty-one changes to positive end-expiratory pressure, 34.1% ±14.5% were in reference to pulse oximetry, as were 84.5% ±2.5% of the 813 changes to the fraction of inspired oxygen. Conclusion: Physicians over-estimate the role of blood pH and PCO2 in their ventilator management, while under-estimating the role of other elements. Improving our understanding of current practice patterns can help in the development of systems to aid in clinical decision-making in mechanical ventilation, improving clinical outcomes.

Résumé : Cette thèse s’intéresse au temps d’émergence et aux asynchronies patient-ventilateur à l’origine de lésions pulmonaires chez des patients en soins critiques sous algosédation durant la phase aiguë de la ventilation mécanique. L’originalité de cette recherche consiste à comparer un protocole d’algosédation guidé par l’échelle de Ramsay (le standard) à celui guidé par la technologie BIS. Méthodologie. Suivant un devis mixte inter groupe et intrasujets, cette recherche comporte deux groupes de patients adultes et se déroule sur une période de quatre ans. Le premier groupe comprend 23 patients dont le protocole d’algosédation est guidé par l’échelle de Ramsay. Le second groupe compte 18 patients soumis à la même stratégie de ventilation et au même protocole d’algosédation mais guidé cette fois-ci par la technologie BIS. Mesures. Le temps d ’émergence pour un retour à la ventilation spontanée soutenue (TEVSS) suivant l’arrêt de la perfusion de l’algosédation et les interactions patient-ventilateur (synchronies et asynchronies) durant la phase aiguë de ventilation constituent les variables dépendantes. Résultats. Le groupe bénéficiant de la technologie BIS présente un TEVSS médian de 3,1 heures comparé à 22,5 heures pour le groupe guidé par l’échelle de Ramsay (valeur p=0,001). De plus, le groupe bénéficiant de la technologie BIS présente 11% de moins d’asynchronies patient-ventilateur que celui guidé par l’échelle de Ramsay (valeur p<0,001). En outre, parmi les paramètres de la technologie BIS, l’électromyogramme (EMG) s’avère l’élément le plus robuste à prédire l’asynchronie patient-ventilateur. Conclusion. La réduction du TEVSS ainsi que la diminution des asynchronies patient-ventilateur démontrent un avantage considérable à utiliser la technologie BIS en soins critiques chez les patients adultes non communicatifs durant la phase aiguë de ventilation mécanique. De plus, l’EMG de la technologie BIS permettrait vraisemblablement de déceler de façon précoce l’expression préclinique de la douleur. Enfin, cette thèse propose un algorithme de contrôle de l’algosédation en soins critiques en référence à la technologie BIS. // Abstract : This thesis focuses on emergence time from algosédation (for which a prolongation increases complex investigations and costs) and on patient-ventilator interaction (related to lung injuries) in critical care patients undergoing mechanical ventilation with algosedation perfusion during the acute phase of ventilator support. More specifically, the originality of this research stems from the simultaneous comparison of the emergence time for a retum of sustained spontaneous breathing and the presence of asynchronies, by eomparing algosedation guided by the Ramsay scale (gold standard) in a first group and by the BIS technology in a second group. Methodology. Following a mixed design of an inter group, intra subject, this research is performed in two groups of adults over a period of four years. The first group consists of 23 patients where algosedation is guided with the Ramsay scale whereas the second group consists of 18 patients with the same ventilation strategy and same algosédation protocol but guided using the BIS technology. This research evaluates the effectiveness of both instruments to guide algosedation during the acute phase of ventilation. Measures. Dependent variables consist of the emergence time for a sustained spontaneous breathing following cessation o f algosedation and patient-ventilator interaction (asynchronies) during the acute phase of ventilatory support. Results. The group guided with BIS technology has a median emergence time for a sustained spontaneous breathing of 3.1 hours compared to 22.5 hours for the Ramsay scale guided group (p value=0.001). Furthermore, patients benefiting from the BIS technology presented 11% less asynchrony than those with the Ramsay scale (p value <0.001). More specifically, among BIS technology parameters, electromyography (EMG) appeared the best indicator to predict patient-ventilator asynchrony in both groups. Conclusion. In the second group, the reduction in the emergence time for a sustained spontaneous breathing and the decrease of patient-ventilator asynchronies mandates the use o f BIS technology in critical care to guidee algosedation among non-communicative adults during the acute phase of ventilatory support. EMG from the BIS technology might be able to detect pre-clinical pain expression. This thesis also favors the implementation of a décision algorithm in the control of algosedation in critical care.

Critical illness associated muscle weakness and muscle dysfunction in intensive care unit (ICU) patients lead to severe morbidity and mortality as well as significant adverse effect on quality of life. Immobilization, mechanical ventilation, neuromuscular blocking agents, corticosteroids, and sepsis have been implicated as important risk factors, but the underlying molecular and cellular mechanisms remain unclear.  A unique porcine ICU model was employed to investigate the effect of these risk factors on the expression profiles, gene expression and contractile properties of limb and diaphragm muscle, in the early phase of ICU stay. This project has focused on unraveling the underlying molecular and cellular pathways or networks in response to ICU and critical illness interventions. Upregulation of heat shock proteins indicated to play a protective role despite number of differentially transcribed gene groups that would otherwise have a negative effect on muscle fiber structure and function in response to immobilization and mechanical ventilation.  Mechanical ventilation appears to play a critical role in development of diaphragmatic dysfunction. Impaired autophagy, chaperone expression and protein synthesis are indicated to play a pivotal role in exacerbating muscle weakness in response to the combined effect of risk factors in ICU. These results may be of therapeutic importance in alleviating critical illness associated muscle weakness.