Objective:To revise the “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult” published in Critical Care Medicine in 2002.Methods:The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task f

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Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit

Objective:To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU.Design:Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups g

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Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may also be impaired in immune cells under Se deficient conditions. Supplementing diets with above-adequate levels of Se can also impinge on immune cell function, with some types of inflammation and immunity particularly affected and sexually dimorphic effects of Se levels in so...

The Role of Selenium in Inflammation and Immunity: From Molecular Mechanisms to Therapeutic Opportunities

Context The benefit of corticosteroids in severe sepsis and septic shock remains controversial. Objective We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. Data Sources We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. Study Selection Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. Data Extraction All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. Results We identified 17 randomized trials (n = 2138) and 3 quasi-randomized trials (n = 246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P=.05; I 2 =53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P = .83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P = .02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P = .02; I 2  = 4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, –7.04 to –1.94; P  2  = 0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P = .50; I 2  = 0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P = .92; I 2  = 8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P = .58; I 2  = 30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P  2  = 0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P  2  = 0%). Conclusions Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.

https://jamanetwork.com/journals/jama/articlepdf/184029/jce90001_2362_2375.pdf

Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review.

Sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit (ICU), despite advances in healthcare and science. Marked oxidative stress as a result of the inflammatory responses inherent with sepsis initiates changes in mitochondrial function which may result in organ damage. Normally, a complex system of interacting antioxidant defences is able to combat oxidative stress and prevents damage to mitochondria. Despite the accepted role that oxidative stress-mediated injury plays in the development of organ failure, there is still little conclusive evidence of any beneficial effect of systemic antioxidant supplementation in patients with sepsis and organ dysfunction. It has been suggested, however, that antioxidant therapy delivered specifically to mitochondria may be useful.

Oxidative stress and mitochondrial dysfunction in sepsis

Production matrices

We translate the concept of succession rule and the ECO method into matrix notation, introducing the concept of production matrix. This allows us to combine our method with other enumeration techniques using matrices, such as the method of Riordan matrices. Finally we treat the case of rational production matrices, i.e., those leading to rational generating functions.

Production Matrices and Riordan Arrays

Aim. Continuous monitoring is of paramount importance in order to obtain a correct level of sedation in ICU patients. Clinical scoring systems, although simple and inexpensive, are often inadequate in evaluating the patient level of consciousness. Among instrumental tools for sedation monitoring, Bispectral Index (BIS) is now widely used due to its reliability and applicability. Nevertheless some doubts still exist regarding its usefulness in ICU. Methods. Sedation, obtained with propofol or midazolam, was monitored with Ramsay scale and BIS in 40 patients admitted in ICU for postoperative monitoring after major abdominal or vascular surgery. A correlation between Ramsay score and BIS values was searched using Pearson test. Results. A good correlation between Ramsay score and BIS values was observed. At the deeper levels of sedation a wide range of BIS values corresponds to Ramsay score 6, indicating various levels of central nervous system depression that are not identified by clinical evaluation. Conclusion. BIS monitoring is useful in ICU patients and allows a finest differentiation of sedation level in deeply sedated ICU patients.

Bispectral Index compared to Ramsay score for sedation monitoring in intensive care units.

Critical illness and particularly sepsis are associated with a significant redox imbalance resulting from an increased production of oxidant species and a decrease in endogenous antioxidant defences. In critical patients sources of oxidative stress include the mitochondrial respiratory electron transport chain, xanthine oxidase activation, the respiratory burst associated with neutrophil activation, and arachidonic acid metabolism. Several endogenous antioxidants have been identified including enzymes, like superoxide dismutases and glutathione peroxidase, vitamins and other molecules such as uric acid and bilirubin. Recent studies pointed out the correlations between oxidative stress, systemic inflammatory response and apoptosis. Prospective randomized clinical trials regarding antioxidant therapy in critical illness provide increasing evidence in support of selenium, glutamine and omega-3 fatty acids. In particular selenium seems to improve clinical outcome in terms of infections and organ failure, glutamine has been associated with a significant reduction in infectious complications and omega-3 fatty acids could be particularly efficacious in sepsis. Melatonin is a promising molecule that deserves the attention of future research, as well as vitamin C. Further studies should also try to establish the more beneficial combination of antioxidants, as well as the doses, and the timing of administration. When such problems will be resolved hopefully results about antioxidant therapy in critical illness will be more univocal and promising.

Antioxidant Therapy in Critically Septic Patients

We translate the concept of succession rule and the ECO method into matrix notation, introducing the concept of a production matrix. This allows us to combine our method with other enumeration techniques using matrices, such as the method of Riordan matrices. Finally we treat the case of rational production matrices, i.e. those leading to rational generating functions.

Simone Rinaldi

Papers

Production matrices

Production Matrices and Riordan Arrays

Bispectral Index compared to Ramsay score for sedation monitoring in intensive care units.

Antioxidant Therapy in Critically Septic Patients

Production matrices and Riordan arrays