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Background: The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown.

Methods: We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores).

Results: In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36-0.59; p < 0.001) and higher in patients with SOFA > 19 at baseline (OR 8.54; 95% CI 2.09-34.91; p < 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64-3.65; p < 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47-3.22; p < 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07-27.63; p < 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11-17.24; p < 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02-10.27; p < 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32-23.96; p < 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68-9.42; p < 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22-3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mortality without heterogeneity. In ICU survivors, eight markers of liver and renal failure predicted 6-month mortality, including Child-Pugh stage C (OR 2.43; 95% CI 1.44-4.10; p < 0.001; PPV = 0.57), baseline MELD > 26 (OR 3.97; 95% CI 1.92-8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24-17.64; p = 0.022; PPV = 0.88).

Conclusions: Prognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child-Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality.

Keywords: CLIF-SOFA; Cirrhosis; Extrahepatic organ failure; MELD; Mortality; Organ replacement therapy; Prognostic scores.

Brief description of media:

Background

The sedation needs of critically ill patients have been recognized as a core component of critical care that is vital to assist recovery and ensure humane treatment. Evidence suggests that sedation requirements are not always optimally managed. Suboptimal sedation, both under‐ and over‐sedation, have been linked to short‐term (e.g. length of stay) and long‐term (e.g. psychological recovery) outcomes. Strategies to improve sedation assessment and management have been proposed. This review was originally published in 2015 and updated in 2018.
Objectives

To assess the effects of protocol‐directed sedation management compared to usual care on the duration of mechanical ventilation, intensive care unit (ICU) and hospital mortality and other patient outcomes in mechanically ventilated ICU adults and children.
Search methods

We used the standard search strategy of the Cochrane Anaesthesia, Critical and Emergency Care Group (ACE). We searched the Cochrane Central Register of Controlled trials (CENTRAL) (December 2017), MEDLINE (OvidSP) (2013 to December 2017), Embase (OvidSP) (2013 to December 2017), CINAHL (BIREME host) (2013 to December 2017), LILACS (2013 to December 2017), trial registries and reference lists of articles. (The original search was run in November 2013).
Selection criteria

We included randomized controlled trials (RCTs) and quasi‐randomized controlled trials conducted in ICUs comparing management with and without protocol‐directed sedation in intensive care adults and children.
Data collection and analysis

Two authors screened the titles and abstracts and then full‐text reports identified from our electronic search. We assessed seven domains of potential risk of bias for the included studies. We examined clinical, methodological and statistical heterogeneity and used the random‐effects model for meta‐analysis where we considered it appropriate. We calculated the mean difference (MD) for duration of mechanical ventilation and risk ratio (RR) for mortality across studies, with 95% confidence intervals (CIs).
Main results

We included four studies with a total of 3323 participants (864 adults and 2459 paediatrics) in this update. Three studies were single‐centre, patient‐level RCTs and one study was a multicentre cluster‐RCT. The settings were in metropolitan centres and included general, mixed medical‐surgical, medical only and a range of paediatric units. All four included studies compared the use of protocol‐directed sedation, specifically protocols delivered by nurses, with usual care. We rated the risk of selection bias due to random sequence generation low for two studies and unclear for two studies. The risk of bias was highly variable across the domains and studies, with the risk of selection and performance bias generally rated high and the risk of detection and attrition bias generally rated low.

When comparing protocol‐directed sedation with usual care, there was no clear evidence of difference in duration of mechanical ventilation in hours for the entire duration of the first ICU stay for each patient (MD ‐28.15 hours, 95% CI ‐69.15 to 12.84; I2 = 85%; 4 studies; adjusted sample 2210 participants; low‐quality evidence). There was no clear evidence of difference in ICU mortality (RR 0.77, 95% CI 0.39 to 1.50; I2 = 67%; 2 studies; 513 participants; low‐quality evidence), or hospital mortality (RR 0.90, 95% CI 0.72 to 1.13; I2 = 10%; 3 studies; adjusted sample 2088 participants; low‐quality evidence). There was no clear evidence of difference in ICU length of stay (MD ‐1.70 days, 95% CI‐3.71 to 0.31; I2 = 82%; 4 studies; adjusted sample of 2123 participants; low‐quality of evidence), however there was evidence of a significant reduction in hospital length of stay (MD ‐3.09 days, 95% CI ‐5.08 to ‐1.10; I2 = 2%; 3 studies; adjusted sample of 1922 participants; moderate‐quality evidence). There was no clear evidence of difference in the incidence of self‐extubation (RR 0.88, 95% CI 0.55 to 1.42; I2 = 0%; 2 studies; adjusted sample of 1687 participants; high‐quality evidence), or incidence of tracheostomy (RR 0.67, 95% CI 0.35 to 1.30; I2 = 66%; 3 studies; adjusted sample of 2008 participants; low‐quality evidence). Only one study examined incidence of reintubation, therefore we could not pool data; there was no clear evidence of difference (RR 0.65, 95% CI 0.35 to 1.24; 1 study; 321 participants; low‐quality evidence).
Authors' conclusions

There is currently limited evidence from RCTs evaluating the effectiveness of protocol‐directed sedation on patient outcomes. The four included RCTs reported conflicting results and heterogeneity limited the interpretation of results for the primary outcomes of duration of mechanical ventilation and mortality. Further studies, taking into account differing contextual characteristics, are necessary to inform future practice. Methodological strategies to reduce the risk of bias need to be considered in future studies.

Brief description of media:

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19.

Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality.

Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality.

Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term.

Brief description of media:

The diagnosis and treatment of psychiatric disorders in intensive care patients have been for a long time neglected. They are nowadays better recognized and managed. These disorders are mainly: delirium; anxiety disorders, from simple anxiety to panic disorder with agitation; adaptation disorders with depressive mood; brief psychotic disorders with persecution ideas. The manifestations of psychiatric disorders occur not only during the stay in intensive care unit (ICU) but also after transfer from ICU and several months after discharge from hospital. Part of psychiatric disorders is caused by organic or toxic causes (metabolic disturbances, electrolyte imbalance, withdrawal syndromes, infection, vascular disorders and head trauma). Nevertheless some authors estimate that they are due to the particular environment of ICU. The particularities of these units are: a high sound level (noise level average between 50 and 60 dBA), the absence of normal day-night cycle, a sleep deprivation, a sensory deprivation, the inability for intubated patients to talk, the pain provoked by some medical procedures, the possibility to witness other patients' death. Although most patients feel secure in ICU, some of them perceive ICU's environment as threatening. Simple environmental modifications could prevent the apparition of some psychiatric manifestations: efforts should be made to decrease noise generated by equipment and staff conversations, to provide external windows, visible clocks and calendar, to ensure adequate sleep with normal day-night cycle and to encourage more human contact. Psychotropic drugs are useful but a warm and empathetic attitude can be very helpful. Some authors described specific psychotherapeutic interventions in ICU (hypnosis, coping strategies.). To face anxiety, many patients have defense attitudes as psychological regression and denial. Patient's family is suffering too. Relative's hospitalization causes a crisis in family. Unpredicted illnesses often force family members to reorganize in order to regain their equilibrium. Every family should be proposed a psychological support. Caregivers can be distressed as well. This stress is due to their high responsibility and the fact that they face disease and death. Simple measures can lessen stress'effect and prevent the burn-out syndrome . In conclusion, the importance of a liaison psychiatrist-intensive care physician collaboration must be emphasized in order that patients and their family have a better psychological support. Psychological management should be proposed during the hospitalization and after discharge from hospital.

Brief description of media:

Experiencing treatment on a modern intensive care
unit (ICU) is a potentially traumatic event. People who
experience traumatic events have an increased risk of
depression, anxiety disorders and post-traumatic stress
disorder (PTSD). Extended follow-up has confi rmed
that many patients suff er physical and psychological
consequences of the ICU treatment up to 12 months
after hospital discharge. PTSD in particular has become
increasingly relevant in both the immediate and
longer-term follow-up care of these patients. The
extent to which the consequences of critical illness
and the treatments received in the ICU contribute to
the development of PTSD is poorly understood and
more rigorous studies are needed. Understanding the
factors associated with a poor psychological recovery
after critical illness is essential to generate models of
causality and prognosis, and to guide the delivery of
eff ective, timely interventions.

Brief description of media:

Experiencing treatment on a modern intensive care
unit (ICU) is a potentially traumatic event. People who
experience traumatic events have an increased risk of
depression, anxiety disorders and post-traumatic stress
disorder (PTSD). Extended follow-up has confi rmed
that many patients suff er physical and psychological
consequences of the ICU treatment up to 12 months
after hospital discharge. PTSD in particular has become
increasingly relevant in both the immediate and
longer-term follow-up care of these patients. The
extent to which the consequences of critical illness
and the treatments received in the ICU contribute to
the development of PTSD is poorly understood and
more rigorous studies are needed. Understanding the
factors associated with a poor psychological recovery
after critical illness is essential to generate models of
causality and prognosis, and to guide the delivery of
eff ective, timely interventions.

Brief description of media:

The objective of the review was to evaluate and synthesize the prevalence, risk factors, and trajectory of psychosocial morbidity in informal caregivers of critical care survivors.

Brief description of media:

The COVID-19 pandemic has led to vastly increased admissions into intensive care.Around onein four ICU survivors develop Post-Traumatic Stress Disorder (PTSD) in the months after admission, and others will develop depression or one of several anxiety disorders.This guide aims to provide information for healthcare professionals working with ICU survivors. It will help you recognise PTSD, and know how to help.

Brief description of media:

The COVID-19 pandemic has led to vastly increased admissions into intensive care units (ICU). Around one in four ICU patients develop PTSD symptoms after the admission. Other disorders, including depression and various anxiety disorders are also common.This guide aims to provide information for therapists working with patients who have developed PTSD after an ICU admission, or a similar medical environment.

Brief description of media:

Post-traumatic stress disorder is often thought of as a symptom of warfare, major catastrophes and assault. It’s rarely considered in patients who survive a critical illness and stay in the intensive care unit (ICU). However, in a recent Johns Hopkins study, researchers found that nearly one-quarter of ICU survivors suffer from PTSD. They also identified possible triggers for PTSD and indicated a potential preventive strategy: having patients keep ICU diaries. The findings will be published in the May issue of Critical Care Medicine.

Brief description of media:

Post-traumatic stress disorder is often thought of as a symptom of warfare, major catastrophes and assault. It's rarely considered in patients who survive a critical illness and stay in the intensive care unit (ICU). However, in a recent Johns Hopkins study, researchers found that nearly one-quarter of ICU survivors suffer from PTSD. They also identified possible triggers for PTSD and indicated a potential preventive strategy: having patients keep ICU diaries. The findings will be published in the May issue of Critical Care Medicine.

Brief description of media:

Experiencing critical illness and intensive care can be extremely stressful. Roughly 1 in 5 critical illness
survivors have clinically significant post-traumatic stress disorder (PTSD) symptoms in the year after
intensive care, according to an article in press in the journal Critical Care Clinics.