Nusinersen treatment in adults with severe spinal muscular atrophy: A real-life retrospective observational cohort study.

BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease due to homozygous loss-of-function of the survival motor neuron gene SMN1 with absence of the functional SMN protein. Nusinersen, a costly intrathecally administered drug approved in 2017 in Europe, induces alternative splicing of the SMN2 gene, which then produces functional SMN protein, whose amount generally increases with the number of SMN2 gene copies. METHODS: We retrospectively collected data from consecutive wheelchair-bound adults with SMA managed at a single center in 2018-2020. The following were collected at each injection, on days 1, 14, 28, 63, 183, and 303: 32-item Motor Function Measurement (MFM) total score and D2 and D3 subscores; the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores; and lung function tests. The patients were divided into two groups based on whether their MFM total score was

Perioperative fluid management for major elective surgery.

BACKGROUND: Adequate fluid balance before, during and after surgery may reduce morbidity. This review examines current concepts surrounding fluid management in major elective surgery. METHOD: A narrative review was undertaken following a PubMed search for English language reports published before July 2019 using the terms 'surgery', 'fluids', 'fluid therapy', 'colloids', 'crystalloids', 'albumin', 'starch', 'saline', 'gelatin' and 'goal directed therapy'. Additional reports were identified by examining the reference lists of selected articles. RESULTS: Fluid therapy is a cornerstone of the haemodynamic management of patients undergoing major elective surgery. Both fluid overload and hypovolaemia are deleterious during the perioperative phase. Zero-balance fluid therapy should be aimed for. In high-risk patients, individualized haemodynamic management should be titrated through the use of goal-directed therapy. The optimal type of fluid to be administered during major surgery remains to be determined. CONCLUSION: Perioperative fluid management is a key challenge during major surgery. Individualized volume optimization by means of goal-directed therapy is warranted during high-risk surgery. In most patients, balanced crystalloids are the first choice of fluids to be used in the operating theatre. Additional research on the optimal type of fluid for use during major surgery is needed.

ANTECEDENTES: Un equilibrio de líquido adecuado antes, durante y después de la cirugía puede reducir la morbilidad. Esta revisión presenta los conceptos actuales del manejo de líquidos en cirugía mayor electiva. MÉTODOS: Se realizó una revisión descriptiva tras llevar a cabo una búsqueda en PubMed de artículos publicados en inglés antes de julio 2019, utilizando los términos 'cirugía ' (surgery), 'líquidos' (fluids), `fluidoterapia` (fluid therapy), 'coloides' (colloids), 'cristaloides' (crystalloids), 'albúmina' (albumin), 'hidroxietil-almidón' (starch), 'salino' (saline), 'gelatina' (gelatin) y 'terapia dirigida por objetivo' (goald directed therapy). Se identificaron artículos adicionales a través de la lista de referencias bibliográficas de los artículos seleccionados. RESULTADOS: El tratamiento con líquidos constituye la piedra angular del manejo hemodinámico de los pacientes sometidos a cirugía mayor electiva. Tanto la sobrecarga de líquidos como la hipovolemia son perjudiciales durante el periodo perioperatorio. El tratamiento de líquidos con balance cero debe considerarse el objetivo. En pacientes de alto riesgo, el manejo hemodinámico personalizado se debe ajustar mediante la utilización del tratamiento dirigido por objetivos. El tipo óptimo de líquido que debe ser administrado durante la cirugía mayor todavía no se ha determinado. CONCLUSIÓN: El manejo perioperatorio de líquidos es un desafío clave durante la cirugía mayor. La optimización del volumen individualizado a través de un tratamiento dirigido por objetivos está justificada durante la cirugía de alto riesgo. En la mayoría de los casos, la administración equilibrada de cristaloides es la primera fluidoterapia de elección en el quirófano. Se necesitan más investigaciones sobre el tipo de líquidos más adecuado para utilizar durante la cirugía mayor.

Mismatch negativity to predict subsequent awakening in deeply sedated critically ill patients.

BACKGROUND: Mismatch negativity (MMN) is the neurophysiological correlate of cognitive integration of novel stimuli. Although MMN is a well-established predictor of awakening in non-sedated comatose patients, its prognostic value in deeply sedated critically ill patients remains unknown. The aim of this prospective, observational pilot study was to investigate the prognostic value of MMN for subsequent awakening in deeply sedated critically ill patients. METHODS: MMN was recorded in 43 deeply sedated critically ill patients on Day 3 of ICU admission using a classical 'odd-ball' paradigm that delivers rare deviant sounds in a train of frequent standard sounds. Individual visual analyses and a group level analysis of recordings were performed. MMN amplitudes were then analysed according to the neurological status (awake vs not awake) at Day 28. RESULTS: Median (inter-quartile range) Richmond Assessment Sedation Scale (RASS) at the time of recording was -5 (range, from -5 to -4.5). Visual detection of MMN revealed a poor inter-rater agreement [kappa=0.17, 95% confidence interval (0.07-0.26)]. On Day 28, 30 (70%) patients had regained consciousness while 13 (30%) had not. Quantitative group level analysis revealed a significantly greater MMN amplitude for patients who awakened compared with those who had not [mean (standard deviation) = -0.65 (1.4) vs 0.08 (0.17) µV, respectively; P=0.003). CONCLUSIONS: MMN can be observed in deeply sedated critically ill patients and could help predict subsequent awakening. However, visual analysis alone is unreliable and should be systematically completed with individual level statistics.

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

OBJECTIVE: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients. PARTICIPANTS: A multispecialty task force of 16 international experts in Critical Care Medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine. DESIGN/METHODS: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members. RESULTS: The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of <9 µg/dl) after cosyntropin (250 µg) administration and a random plasma cortisol of <10 µg/dl may be used by clinicians. We suggest against using plasma free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using intravenous (IV) hydrocortisone <400 mg/day for ≥3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence). CONCLUSIONS: Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy wasdeveloped at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroupsand among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.(AU)

Outcome of bloodstream infections among spinal cord injury patients and impact of multidrug-resistant organisms.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Our study aimed to describe the outcome of bloodstream infection (BSI) in spinal cord injury (SCI) patients and their associated risk factors for severity and mortality. SETTING: A French University Hospital. METHODS: We conducted a retrospective cohort study of all BSIs occurring in hospitalized SCI patients. We analyzed their outcome and risk factors especially the impact of multidrug-resistant organisms (MDROs). RESULTS: Overall, 318 BSIs occurring among 256 patients were included in the analysis. Mean age was 50.8 years and gender ratio (M/F) was 2.70, with a mean injury duration of 11.6 years.Severity and 30-day mortality of BSI episodes were, respectively, 43.4% and 7.9%. BSI severity was significantly more frequent when caused by respiratory tract infections (RTIs) (odds ratio (OR)=1.38; 95% confidence interval (CI): 1.13-1.44) and significantly lower when caused by urinary tract infections (UTIs) (OR=0.47; 95% CI: 0.28-0.76). BSI mortality was significantly higher when caused by RTIs (OR=3.08; 95% CI: 1.05-8.99), catheter-related bloodstream infections (OR=3.54; 95% CI: 1.36-9.18) or Pseudomonas aeruginosa infections (OR=3.79; 95% CI: 1.14-12.55).MDROs were responsible for 41.2% of all BSI. They have no impact on severity and mortality, whichever be the primary site of infection.In multivariate analysis, mortality was higher when BSI episodes were due to RTIs (OR=3.26; 95% CI: 1.29-8.22) and Pseudomonas aeruginosa infections (OR=3.53; 95% CI: 1.06-11.70), or when associated with immunosuppressive therapy (OR=2.57; 95% CI: 1.14-5.78) or initial severity signs (OR=1.68; 95% CI: 1.01-2.81). CONCLUSION: BSI occurring in SCI population were often severe but mortality remained low. MDROs were frequent but not associated with severity or mortality of BSI episodes. Risk factors associated with mortality were initial severe presentation, RTI, immunosuppressive therapy and BSI due to Pseudomonas aeruginosa.

Blood stream infections due to multidrug-resistant organisms among spinal cord-injured patients, epidemiology over 16 years and associated risks: a comparative study.

STUDY DESIGN: Retrospective study. OBJECTIVES: We aimed to describe the epidemiology of multidrug-resistant organisms (MDROs) during bloodstream infection (BSI) and identify associated risks of MDROs among patients with spinal cord injury (SCI). SETTING: A teaching hospital, expert center in disability, in France. METHODS: We studied a retrospective cohort of all BSIs occurring in SCI patients hospitalized over 16 years. We described the prevalence of MDRO BSI among this population and its evolution over time and compared the BSI population due to MDROs and due to non-MDROs. RESULTS: A total of 318 BSIs occurring among 256 patients were included in the analysis. The most frequent primary sites of infection were urinary tract infection (34.0%), pressure sore (25.2%) and catheter line-associated bloodstream infection (11.3%). MDROs were responsible for 41.8% of BSIs, and this prevalence was stable over 16 years. No significant associated factor for MDRO BSI could be identified concerning sociodemographic and clinical characteristics, primary site of infection and bacterial species in univariate and multivariate analyses. BSI involving MDROs was not associated with initial severity of sepsis compared with infection without MDROs (43.8 vs 43.6%, respectively) and was not associated either with 30th-day mortality (6.2 vs 9%, respectively). CONCLUSION: During BSI occurrence in an SCI population, MDROs are frequent but remain stable over years. No associated risk can be identified that would help optimize antibiotic treatment. Neither the severity of the episode nor the mortality is significantly different when an MDRO is involved.

Fluid type and the use of renal replacement therapy in sepsis: a systematic review and network meta-analysis.

Fluid resuscitation, along with the early administration of antibiotics, is the cornerstone of treatment for patients with sepsis. However, whether differences in resuscitation fluids impact on the requirements for renal replacement therapy (RRT) remains unclear. To examine this issue, we performed a network meta-analysis (NMA), including direct and indirect comparisons, that addressed the effect of different resuscitation fluids on the use of RRT in patients with sepsis. The data sources MEDLINE, EMBASE, ACPJC, CINAHL and Cochrane Central Register were searched up to March 2014. Eligible studies included randomized trials reported in any language that enrolled adult patients with sepsis or septic shock and addressed the use of RRT associated with alternative resuscitation fluids. The risk of bias for individual studies and the overall certainty of the evidence were assessed. Ten studies (6664 patients) that included a total of nine direct comparisons were assessed. NMA at the four-node level showed that an increased risk of receiving RRT was associated with fluid resuscitation with starch versus crystalloid [odds ratio (OR) 1.39, 95% credibility interval (CrI) 1.17-1.66, high certainty]. The data suggested no difference between fluid resuscitation with albumin and crystalloid (OR 1.04, 95% CrI 0.78-1.38, moderate certainty) or starch (OR 0.74, 95% CrI 0.53-1.04, low certainty). NMA at the six-node level showed a decreased risk of receiving RRT with balanced crystalloid compared to heavy starch (OR 0.50, 95% CrI 0.34-0.74, moderate certainty) or light starch (OR 0.70, 95% CrI 0.49-0.99, high certainty). There was no significant difference between balanced crystalloid and saline (OR 0.85, 95% CrI 0.56-1.30, low certainty) or albumin (OR 0.82, 95% CrI 0.49-1.37, low certainty). Of note, these trials vary in terms of case mix, fluids evaluated, duration of fluid exposure and risk of bias. Imprecise estimates contributed to low confidence in most estimates of effect. Among the patients with sepsis, fluid resuscitation with crystalloids compared to starch resulted in reduced use of RRT; the same may be true for albumin versus starch.

Be careful about abdominal discomfort in adult patients with muscular dystrophy.

Muscular dystrophies are genetic muscular disease with disability. Heart failure is a classical complication mainly in Duchenne muscular dystrophy (DMD). We report 2 cases of severe acute heart failure revealed by abdominal discomfort in a patient with DMD and in a patient with gamma-sarcoglycanopathy.

Increased incidence of Campylobacter jejuni-associated Guillain-Barré syndromes in the Greater Paris area.

The role of Campylobacter jejuni as the triggering agent of Guillain-Barré syndrome (GBS) has not been reassessed since the end of the 1990s in France. We report that the number of C. jejuni-related GBS cases increased continuously between 1996 and 2007 in the Paris region (mean annual increment: 7%, P = 0·007).

The future of intensive care medicine / El futuro de la medicina intensiva

Intensive care medical training, whether as a primary specialty or as secondary add-on training, should include key competences to ensure a uniform standard of care, and the number of intensive care physicians needs to increase to keep pace with the growing and anticipated need. The organisation of intensive care in multiple specialty or central units is heterogeneous and evolving, but appropriate early treatment and access to a trained intensivist should be assured at all times, and intensivists should play a pivotal role in ensuring communication and high-quality care across hospital departments. Structures now exist to support clinical research in intensive care medicine, which should become part of routine patient management. However, more translational research is urgently needed to identify areas that show clinical promise and to apply research principles to the real-life clinical setting. Likewise, electronic networks can be used to share expertise and support research. Individuals, physicians and policy makers need to allow for individual choices and priorities in the management of critically ill patients while remaining within the limits of economic reality. Professional scientific societies play a pivotal role in supporting the establishment of a defined minimum level of intensive health care and in ensuring standardised levels of training and patient care by promoting interaction between physicians and policy makers. The perception of intensive care medicine among the general public could be improved by concerted efforts to increase awareness of the services provided and of the successes achieved (AU)

La formación en medicina intensiva, ya sea como especialidad primaria o a partir de una troncalidad común para después convertirse en supra-especialidad, debería incluir competencias clave que garanticen un cuidado estándar y homogéneo del paciente crítico, así como proveer al sistema sanitario del número de especialistas en medicina intensiva (intensivistas) de forma ajustada y anticipada al ritmo de crecimiento de la necesidad asistencial. La organización de los cuidados intensivos desde la visión de las distintas especialidades o en unidades centralizadas y jerarquizadas, es heterogénea y está en constante evolución. No obstante el acceso y tratamiento precoz del enfermo crítico por parte de un intensivista, debería estar siempre garantizado, no únicamente en los servicios de medicina intensiva, sino en todos los departamentos de un hospital, actuando el intensivista como elemento central en la comunicación y coordinación entre los diferentes servicios y especialistas, a fin de lograr la más alta calidad y eficacia en la asistencia. La investigación clínica en medicina intensiva está sustentada por la excelencia de conocimiento de sus profesionales, pero son necesarias estructuras de apoyo: la integración de la investigación e innovación en la rutina diaria y un incremento de la investigación traslacional, a fin de identificar áreas que muestren elementos potenciales de avance en el aspecto clínico y la aplicación de los principios de la investigación básica y fisiológica en el entorno de la medicina intensiva. Las tecnologías de la comunicación y la información ofrecen un marco idóneo para compartir y poner en común el conocimiento y apoyar (..) (AU)

The future of intensive care medicine.

Intensive care medical training, whether as a primary specialty or as secondary add-on training, should include key competences to ensure a uniform standard of care, and the number of intensive care physicians needs to increase to keep pace with the growing and anticipated need. The organisation of intensive care in multiple specialty or central units is heterogeneous and evolving, but appropriate early treatment and access to a trained intensivist should be assured at all times, and intensivists should play a pivotal role in ensuring communication and high-quality care across hospital departments. Structures now exist to support clinical research in intensive care medicine, which should become part of routine patient management. However, more translational research is urgently needed to identify areas that show clinical promise and to apply research principles to the real-life clinical setting. Likewise, electronic networks can be used to share expertise and support research. Individuals, physicians and policy makers need to allow for individual choices and priorities in the management of critically ill patients while remaining within the limits of economic reality. Professional scientific societies play a pivotal role in supporting the establishment of a defined minimum level of intensive health care and in ensuring standardised levels of training and patient care by promoting interaction between physicians and policy makers. The perception of intensive care medicine among the general public could be improved by concerted efforts to increase awareness of the services provided and of the successes achieved.

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012

Objective: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. Design: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Results: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7­9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO 2/FiO 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO 2/FI O 2<150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5­10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Conclusions: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

[Heart involvement in sarcoglycanopathies]. / Cœur et sarcoglycanopathies.

Sarcoglycanopathies (SG) are autosomic recessive muscular dystrophies, secondary to mutations of the sarcoglycan complex. Clinical pictures include muscle weakness affecting mainly the proximal limb girdle musculature. We review heart involvement in this group of disease.

Time course of organ failure in patients with septic shock treated with hydrocortisone: results of the Corticus study.

INTRODUCTION: Corticosteroids have been proposed to decrease morbidity and mortality in patients with septic shock. An impact on morbidity should be anticipated to be earlier and more easily detected than the impact on mortality. METHODS: Prospective, randomized, double-blind, placebo-controlled study of 28-day mortality in patients with septic shock for <72 h who underwent a short high-dose ACTH test in 52 centers in 9 European countries. Patients received 11-day treatment with hydrocortisone or placebo. Organ dysfunction/failure was quantified by the use of the sequential organ failure assessment (SOFA) score. RESULTS: From March 2002 to November 2005, 499 patients were enrolled (hydrocortisone 251, placebo 248). Both groups presented a similar SOFA score at baseline (hydrocortisone 10.8 ± 3.2 vs. placebo 10.7 ± 3.1 points). There was no difference in 28-day mortality between the two treatment groups (hydrocortisone 34.3% vs. placebo 31.5%). There was a decrease in the SOFA score of hydrocortisone-treated patients from day 0 to day 7 compared to the placebo-treated patients (p = 0.0027), driven by an improvement in cardiovascular organ dysfunction/failure (p = 0.0005) and in liver failure (p < 0.0001) in the hydrocortisone-treated patients. CONCLUSION: Patients randomized to treatment with hydrocortisone demonstrated a faster decrease in total organ dysfunction/failure determined by the SOFA score, primarily driven by a faster improvement in cardiovascular organ dysfunction/failure. This organ dysfunction/failure improvement was not accompanied by a decreased mortality.

Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia.

OBJECTIVE: To assess the effect on survival of macrolides or fluoroquinolones in intubated patients admitted to the intensive care unit (ICU) with severe community-acquired pneumonia (severe CAP). METHODS: Prospective, observational cohort, multicenter study conducted in 27 ICUs of 9 European countries. Two hundred eighteen consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of CAP were recruited. RESULTS: Severe sepsis and septic shock were present in 165 (75.7%) patients. Microbiological documentation was obtained in 102 (46.8%) patients. ICU mortality was 37.6% (n = 82). Non-survivors were older (58.6 +/- 16.1 vs. 63.4 +/- 16.7 years, P < 0.05) and presented a higher score on the simplified Acute Physiology Score II at admission (45.6 +/- 15.4 vs. 50.8 +/- 17.5, P < 0.05). Monotherapy was given in 43 (19.7%) and combination therapy in 175 (80.3%) patients. Empirical antibiotic therapy was in accordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines in 100 (45.9%) patients (macrolides in 46 patients and fluoroquinolones in 54). In this cohort, a Cox regression analysis adjusted by severity identified that macrolide use was associated with lower ICU mortality (hazard ratio, HR 0.48, confidence intervals, 95% CI 0.23-0.97, P = 0.04) when compared to the use of fluoroquinolones. When more severe patients presenting severe sepsis and septic shock were analyzed (n = 92), similar results were obtained (HR 0.44, 95% CI 0.20-0.95, P = 0.03). CONCLUSIONS: Patients with severe community-acquired pneumonia had a low adherence with the 2007 IDSA/ATS guidelines. Combination therapy with macrolides should be preferred in intubated patients with severe CAP.

Tongue weakness is associated with respiratory failure in patients with severe Guillain-Barré syndrome.

OBJECTIVE: Swallowing impairment may worsen respiratory weakness and conduct to respiratory complications such as aspiration pneumonia in Guillain-Barré syndrome (GBS). We prospectively evaluate how tongue weakness could be associated to bulbar dysfunction and respiratory weakness in severe GBS patients. MEASUREMENTS AND MAIN RESULTS: Tongue strength, dysphagia and respiratory parameters were measured in 16 GBS patients at intensive care unit (ICU) admission and discharge and in seven controls. Tongue strength was decreased in the GBS patients compared with the controls. At admission, patients with dysphagia and those requiring mechanical ventilation (MV) had greater tongue weakness. All the patients with initial tongue strength <150 g required MV during ICU stay. Tongue strength correlated significantly with respiratory parameters. CONCLUSION: This study confirms the strong association between bulbar and respiratory dysfunction in GBS admitted to ICU. Tongue weakness may be present in GBS, especially during the phase of increasing paralysis, and resolves during the recovery phase. Tongue strength and indices of global and respiratory strength vary in parallel throughout the course of GBS. Further studies are needed to assess if, when used in combination with other respiratory tests, tongue strength measurement could contribute to identify patients at high risk for respiratory complications.

Complete atrioventricular block in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. It is characterized by progressive muscle wasting and weakness of variable distribution and severity. Heart is involved leading to heart failure. Conduction abnormalities are unusual. We report a case of complete atrio-ventricular block in a DMD patient.