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Patients with COVID-19 are staying longer than the average three to four days in the intensive care unit (ICU), says Megan Hosey, a rehabilitation psychologist at The Johns Hopkins Hospital’s medical ICU. This puts them at greater risk for developing post-intensive care syndrome (PICS).

While more patients than ever are surviving after treatment in the ICU, research over the last two decades shows that survival can come with the cluster of physical, psychological and cognitive symptoms associated with PICS — hindering patients’ quality of life for weeks or years to come. Although the exact prevalence of PICS is unknown, “it happens in more patients than we probably realize,” says Hosey, and it is occurring in some patients with COVID-19.

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Sepsis and acute respiratory distress syndrome (ARDS) are life threating diseases with high mortality and morbidity in all the critical care units around the world. After decades of research, and numerous pre-clinical and clinical trials, sepsis and ARDS remain without a specific and effective pharmacotherapy and essentially the management remains supportive. In the last years cell therapies gained potential as a therapeutic treatment for ARDS and sepsis. Based on numerous pre-clinical studies, there is a growing evidence of the potential benefits of cell based therapies for the treatment of sepsis and ARDS. Several cell types are used in the last years for the treatment of both syndromes showing high efficiency. Embryonic stem cells (ESC), multipotent stem (or stromal) cells (MSC) and epithelial progenitors cells (EpPC) have been used for both diseases. Nowadays, the major part of the pre-clinical studies are using MSC, however other relevant groups are also using induced pluripotent stem cells (iPSC) for the treatment of both syndromes and alveolar type II cells for ARDS treatment. Numerous questions need further study including: determining the best source for the progenitor cells isolation, their large scale production and cryopreservation. Also, the heterogeneity of patients with sepsis and ARDS is massive, and establish a target population or the stratification of the patients will help us to determine better the therapeutic effect of these cell therapies. In this review we are going to describe briefly the different cell types, their potential sources and characteristics and mechanism of action. Here, also we elucidate the results of several pre-clicinical and clinical studies in ARDS and in sepsis and the future directions of these studies.

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Central line-associated bloodstream infections (CLABSIs) are considered a significant cause of mortality in hospitalized patients; however, the incidence of CLABSIs in limited-resource countries has not been explored analytically. Likewise, the appropriate interventions to prevent, control, and reduce CLABSIs have yet to be analyzed thoroughly. This review demonstrates that the CLABSI rate ranged from 1.6 to 44.6 cases per 1000 central line days in adult and pediatric intensive care units (ICUs) and from 2.6 to 60.0 cases per 1000 central line days in neonatal ICUs and is associated with significant extra mortality, with an odds ratio ranging from 2.8 to 9.5. The results of 6 sequential prospective interventional studies showed that hand hygiene and educational programs were related to a significant reduction in CLABSI rates. CLABSI rates in limited-resource countries are higher than US National Healthcare Safety Network benchmark rates and have a significant impact on mortality. Studies showing successful interventions for a reduction in CLABSIs are few. Subsequently, it can be inferred that additional epidemiological studies need to be conducted to achieve an appreciation of the effects of CLABSIs and to develop more-definitive approaches for CLABSI prevention in the form of practical, low-cost, low-technology measures that are feasible to implement in limited-resource countries.

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Over the past decade, survival from critical illness has dramatically increased due to a better understanding of the pathophysiological mechanisms of disease, improved treatment strategies and advancements in medical technology. Several studies have shown improved survival and long-term outcomes in survivors of critically illness. However, surviving the intensive care unit (ICU) stay is just the start of a long road to recovery for a majority of these patients. The discharge from the ICU opens the path to a long journey of challenging physical rehabilitation, mood disorders, cognitive impairment, psychological distress, financial hardship, and caregiver burden and burnout.
In recent years there has been a growing recognition of impairments that affect the physical, psychological, social, and emotional aspects of the individual after ICU discharge that may adversely impact daily functioning and quality of life (QOL). Recently, the term “post-intensive care syndrome” (PICS) is used to describe any new or worsening impairments in physical, cognitive, or mental health status arising after critical illness and persisting beyond the acute care hospitalization.1 PICS may persist for months to years after hospital discharge. Most impairments will diminish with time but some may linger on until the patient’s actual demise. This chapter will explore in detail the different domains affected in PICS, its impact on the individual and society, and offer insights into future developments.

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By this letter, we aimed to address the need of an adequate assessment of functional status in post‐intensive care unit (ICU) coronavirus disease 2019 (COVID‐19) patients. COVID‐19 patients are at risk for post intensive care syndrome, with an impaired functional status. Physical and Rehabilitation Medicine (PRM) physicians have to face both acute and post-acute COVID‐19 patients and provide them with an adequate respiratory and neuromotor rehabilitation plan. To date, specific assessment tools are warranted to provide information regarding COVID‐19 patients' functioning.
Chelsea Critical Care Physical Assessment Tool (CPAx) is a bedside assessment tool specifically designed to assess function in post‐ICU patients and has demonstrated validity, reliability, and responsiveness in critical care population. Taken together, we retain that the CPAx, due to its characteristics, might be used by PRM physicians for assessing functioning in post‐ICU COVID‐19 patients. COVID‐19 pandemic has reached more than 96.2 million of cases and more than 2 million of deaths at the moment of writing, putting under heavy stress health systems worldwide, especially ICUs. COVID‐19 survivors are at risk for post intensive care syndrome, including ICU‐acquired weakness and a consequent impairment in terms of functioning.

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Post–intensive care syndrome (PICS) is a myriad of chronically
debilitating symptoms, often including chronic pain, associated with prolonged
ICU care. Though the exact mechanism of chronic post-ICU pain is unknown, it is
postulated that the severity of inflammation associated with many forms of
critical illness leads to chronic pain in patients long after resolution of their acute
critical illness. Increasing emphasis on long-term outcomes of ICU survivors
makes prevention of chronic pain and PICS a priority for multidisciplinary ICU
teams. This article discusses the prevalence and mechanisms of chronic post-ICU
pain and suggests strategies to reduce the impact of chronic pain on quality of life
in ICU survivors.

Brief description of media:

Post–intensive care syndrome (PICS) is a myriad of chronically debilitating symptoms, often including chronic pain, associated with prolonged ICU care. Though the exact mechanism of chronic post-ICU pain is unknown, it is postulated that the severity of inflammation associated with many forms of critical illness leads to chronic pain in patients long after resolution of their acute critical illness. Increasing emphasis on long-term outcomes of ICU survivors makes prevention of chronic pain and PICS a priority for multidisciplinary ICU teams. This article discusses the prevalence and mechanisms of chronic post-ICU pain and suggests strategies to reduce the impact of chronic pain on quality of life in ICU survivors.

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Objective: To provide ICU clinicians with evidence-based guidance on safe medication use practices for the critically ill.

Data Sources: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and ISI Web of Science for relevant material to December 2015.

Study Selection: Based on three key components: 1) environment and patients, 2) the medication use process, and 3) the patient safety surveillance system. The committee collectively developed Population, Intervention, Comparator, Outcome questions and quality of evidence statements pertaining to medication errors and adverse drug events addressing the key components. A total of 34 Population, Intervention, Comparator, Outcome questions, five quality of evidence statements, and one commentary on disclosure was developed.

Data Extraction: Subcommittee members were assigned selected Population, Intervention, Comparator, Outcome questions or quality of evidence statements. Subcommittee members completed their Grading of Recommendations Assessment, Development, and Evaluation of the question with his/her quality of evidence assessment and proposed strength of recommendation, then the draft was reviewed by the relevant subcommittee. The subcommittee collectively reviewed the evidence profiles for each question they developed. After the draft was discussed and approved by the entire committee, then the document was circulated among all members for voting on the quality of evidence and strength of recommendation.

Data Synthesis: The committee followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation system to determine quality of evidence and strength of recommendations.

Conclusions: This guideline evaluates the ICU environment as a risk for medication-related events and the environmental changes that are possible to improve safe medication use. Prevention strategies for medication-related events are reviewed by medication use process node (prescribing, distribution, administration, monitoring). Detailed considerations to an active surveillance system that includes reporting, identification, and evaluation are discussed. Also, highlighted is the need for future research for safe medication practices that is specific to critically ill patients.

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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 gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed
a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines’ development. A general content review was completed face-to-face by all panel members in January 2017.
Methods: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as “strong,” “conditional,” or “good” practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified.
Results: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation.
Conclusions: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population. (Crit Care Med 2018; 46:e825–e873)

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This guideline has been developed to improve the treatment of acute hyperkalaemia and reduce the risk of complications associated with hyperkalaemia and its treatment. 

This guideline is a collaboration between the Renal Association and Resuscitation Council (UK). The multidisciplinary writing group consists of nephrologists, intensivists, resuscitation experts, a clinical biochemist, renal nurses and a renal pharmacist.  Each contributor was nominated by their organisation to represent their specialist area. The group met in November 2010 in Fife, Scotland to agree the scope for the guideline and critically assess the available evidence for the treatment of acute hyperkalaemia. 

This guideline has been reviewed by the Renal Association Clinical Practice Guideline Committee and the Resuscitation Council (UK) Executive Committee.  Wider consultation has also been sought via the Renal Association and Resuscitation Council (UK) website.

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A substantial number of patients admitted to the ICU because of an acute illness, complicated surgery, severe trauma, or burn injury will develop a de novo form of muscle weakness during the ICU stay that is referred to as “intensive care unit acquired weakness” (ICUAW). This ICUAW evoked by critical illness can be due to axonal neuropathy, primary myopathy, or both. Underlying pathophysiological mechanisms comprise microvascular, electrical, metabolic, and bioenergetic alterations, interacting in a complex way and culminating in loss of muscle strength and/or muscle atrophy. ICUAW is typically symmetrical and affects predominantly proximal limb muscles and respiratory muscles, whereas facial and ocular muscles are often spared. The main risk factors for ICUAW include high severity of illness upon admission, sepsis, multiple organ failure, prolonged immobilization, and hyperglycemia, and also older patients have a higher risk. The role of corticosteroids and neuromuscular blocking agents remains unclear. ICUAW is diagnosed in awake and cooperative patients by bedside manual testing of muscle strength and the severity is scored by the Medical Research Council sum score. In cases of atypical clinical presentation or evolution, additional electrophysiological testing may be required for differential diagnosis. The cornerstones of prevention are aggressive treatment of sepsis, early mobilization, preventing hyperglycemia with insulin, and avoiding the use parenteral nutrition during the first week of critical illness. Weak patients clearly have worse acute outcomes and consume more healthcare resources. Recovery usually occurs within weeks or months, although it may be incomplete with weakness persisting up to 2 years after ICU discharge. Prognosis appears compromised when the cause of ICUAW involves critical illness polyneuropathy, whereas isolated critical illness myopathy may have a better prognosis. In addition, ICUAW has shown to contribute to the risk of 1-year mortality. Future research should focus on new preventive and/or therapeutic strategies for this detrimental complication of critical illness and on clarifying how ICUAW contributes to poor longer-term prognosis.

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Background
Illnesses that necessitate intensive care can impair cognitive function severely over the long term, leaving patients less able to cope with the demands of everyday living and markedly lowering their quality of life. There has not yet been any comprehensive study of the cognitive sequelae of critical illness among non-surgical patients treated in intensive care. The purpose of this review is to present the available study findings on cognitive deficits in such patients, with particular attention to prevalence, types of deficit, clinical course, risk factors, prevention, and treatment.
Methods
This review is based on pertinent publications retrieved by a selective search in MEDLINE.
Results
The literature search yielded 3360 hits, among which there were 14 studies that met our inclusion criteria. 17–78% of patients had cognitive deficits after discharge from the intensive care unit; most had never had a cognitive deficit before. Cognitive impairment often persisted for up to several years after discharge (0.5 to 9 years) and tended to improve over time. The only definite risk factor is delirium.
Conclusion
Cognitive dysfunction is a common sequela of the treatment of non-surgical patients in intensive care units. It is a serious problem for the affected persons and an increasingly important socio-economic problem as well. The effective management of delirium is very important. General conclusions are hard to draw from the available data because of heterogeneous study designs, varying methods of measurement, and differences among patient cohorts. Further studies are needed so that study designs and clinical testing procedures can be standardized and effective measures for prevention and treatment can be identified.