What factors predict length of stay in the intensive care unit? Systematic review and meta-analysis

Purpose:  Studies have shown that a small percentage of ICU patients have prolonged length of stay (LoS) and account for a large proportion of resource use. Therefore, the identification of prolonged stay patients can improve unit efficiency. In this study, we performed a systematic review and meta-analysis to understand the risk factors of ICU LoS.
Materials and methods:  We searched MEDLINE, Embase and Scopus databases from inception to November 2018. The searching process focused on papers presenting risk factors of ICU LoS. A meta-analysis was performed for studies reporting appropriate statistics.
Results:  From 6906 citations, 113 met the eligibility criteria and were reviewed. A meta-analysis was performed for six factors from 28 papers and concluded that patients with mechanical ventilation, hypomagnesemia, delirium, and malnutrition tend to have longer stay, and that age and gender were not significant factors.
Conclusions:  This work suggested a list of risk factors that should be considered in prediction models for ICU LoS, as follows: severity scores, mechanical ventilation, hypomagnesemia, delirium, malnutrition, infection, trauma, red blood cells, and PaO2:FiO2. Our findings can be used by prediction models to improve their predictive capacity of prolonged stay patients, assisting in resource allocation, quality improvement actions, and benchmarking analysis.
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Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review.

This article by Wiersinga and colleagues was first published online in JAMA in July 2020.
Importance:  The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.
Observations:  SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies.
Conclusions and Relevance:  As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.
This article is freely available to all via this link

Early warning scores for detecting deterioration in adult hospital patients: systematic review and critical appraisal of methodology.

This article by Gerry and others was first published in the BMJ online during May 2020.
Objective:  To provide an overview and critical appraisal of early warning scores for adult hospital patients.
Design:  Systematic review.
Data Sources:  Medline, CINAHL, PsycInfo, and Embase until June 2019.#
Eligibility Criteria for Study Selection:  Studies describing the development or external validation of an early warning score for adult hospital inpatients.
Results:  13 171 references were screened and 95 articles were included in the review. 11 studies were development only, 23 were development and external validation, and 61 were external validation only. Most early warning scores were developed for use in the United States (n=13/34, 38%) and the United Kingdom (n=10/34, 29%). Death was the most frequent prediction outcome for development studies (n=10/23, 44%) and validation studies (n=66/84, 79%), with different time horizons (the most frequent was 24 hours). The most common predictors were respiratory rate (n=30/34, 88%), heart rate (n=28/34, 83%), oxygen saturation, temperature, and systolic blood pressure (all n=24/34, 71%). Age (n=13/34, 38%) and sex (n=3/34, 9%) were less frequently included. Key details of the analysis populations were often not reported in development studies (n=12/29, 41%) or validation studies (n=33/84, 39%). Small sample sizes and insufficient numbers of event patients were common in model development and external validation studies. Missing data were often discarded, with just one study using multiple imputation. Only nine of the early warning scores that were developed were presented in sufficient detail to allow individualised risk prediction. Internal validation was carried out in 19 studies, but recommended approaches such as bootstrapping or cross validation were rarely used (n=4/19, 22%). Model performance was frequently assessed using discrimination (development n=18/22, 82%; validation n=69/84, 82%), while calibration was seldom assessed (validation n=13/84, 15%). All included studies were rated at high risk of bias.
Conclusions:  Early warning scores are widely used prediction models that are often mandated in daily clinical practice to identify early clinical deterioration in hospital patients. However, many early warning scores in clinical use were found to have methodological weaknesses. Early warning scores might not perform as well as expected and therefore they could have a detrimental effect on patient care. Future work should focus on following recommended approaches for developing and evaluating early warning scores, and investigating the impact and safety of using these scores in clinical practice.
This article is freely available this link.

Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: systematic review and network meta-analysis.

This article by Wang and others was published online in the BMJ during January 2020
Objective:  To determine, in critically ill patients, the relative impact of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, or no gastrointestinal bleeding prophylaxis (or stress ulcer prophylaxis) on outcomes important to patients.
Design:  Systematic review and network meta-analysis.
Data Sources:  Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature up to March 2019.
Eligibility Criteria For Selecting Studies and Methods:  We included randomised controlled trials that compared gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. A parallel guideline committee (BMJ Rapid Recommendation) provided critical oversight of the systematic review, including identifying outcomes important to patients. We performed random-effects pairwise and network meta-analyses and used GRADE to assess certainty of evidence for each outcome. When results differed between low risk and high risk of bias studies, we used the former as best estimates.
Results:  Seventy two trials including 12 660 patients proved eligible. For patients at highest risk (>8%) or high risk (4-8%) of bleeding, both PPIs and H2RAs probably reduce clinically important gastrointestinal bleeding compared with placebo or no prophylaxis (odds ratio for PPIs 0.61 (95% confidence interval 0.42 to 0.89), 3.3% fewer for highest risk and 2.3% fewer for high risk patients, moderate certainty; odds ratio for H2RAs 0.46 (0.27 to 0.79), 4.6% fewer for highest risk and 3.1% fewer for high risk patients, moderate certainty). Both may increase the risk of pneumonia compared with no prophylaxis (odds ratio for PPIs 1.39 (0.98 to 2.10), 5.0% more, low certainty; odds ratio for H2RAs 1.26 (0.89 to 1.85), 3.4% more, low certainty). It is likely that neither affect mortality (PPIs 1.06 (0.90 to 1.28), 1.3% more, moderate certainty; H2RAs 0.96 (0.79 to 1.19), 0.9% fewer, moderate certainty). Otherwise, results provided no support for any affect on mortality, Clostridium difficile infection, length of intensive care stay, length of hospital stay, or duration of mechanical ventilation (varying certainty of evidence).
Conclusions:  For higher risk critically ill patients, PPIs and H2RAs likely result in important reductions in gastrointestinal bleeding compared with no prophylaxis; for patients at low risk, the reduction in bleeding may be unimportant. Both PPIs and H2RAs may result in important increases in pneumonia. Variable quality evidence suggested no important effects of interventions on mortality or other in-hospital morbidity outcomes.
The full text of this article is freely available via this link.

Pulmonary mucormycosis in a patient with acute liver failure: A case report and systematic review of the literature

This article by Huang and colleagues was first published online in the “Journal of Critical Care” during December 2019.

Purpose:  Pulmonary mucormycosis is a highly lethal invasive fungal infection usually found in immunocompromised patients. We report herein the case of an adult woman who developed pulmonary mucormycosis with possible systemic dissemination after recovering from acute liver failure secondary to acetaminophen overdose.

Results:  Our case developed an invasive pulmonary mucormycosis with probable potential systemic dissemination. She did not suffer from any immunocompromising disease other than severe acute liver failure. She did not survive the disease, although she received appropriate antifungal treatment. We also performed a systematic review of the literature on pulmonary mucormycosis, with or without dissemination, in immunocompetent patients. We found 16 cases of pulmonary or disseminated mucormycosis in immunocompetent patients. Fifty-seven percent of them died and none occurred after an acute liver failure episode.

Conclusion:  This case report is the first one to present an invasive pulmonary mucormycosis infection after acute liver failure in an adult patient. The clinical course of this disease is highly lethal, even in immunocompetent adults.

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Chlorhexidine bathing of the critically ill for the prevention of hospital‐acquired infection

This Cochrane Systematic Review by Lewis and colleagues was first published online in August 2019.

What is the aim of this review?
The aim of this review was to find out whether people who are critically ill in hospital should be bathed with the antiseptic chlorhexidine, in order to prevent them from developing infections. Researchers from Cochrane collected and analysed all relevant studies to answer this question and found eight relevant randomised trials. Randomised trials are medical studies where people are chosen at random to receive different treatments. This study design provides the most reliable evidence on whether treatments have a relationship with desired or undesired health outcomes.

Key messages
This review assesses whether using chlorhexidine (instead of soap and water) to bathe patients in an intensive care unit (ICU), or a high‐dependency or critical care unit reduces the number of hospital‐acquired infections. The evidence available from the studies we analysed was very low quality, meaning that we cannot be certain whether bathing with chlorhexidine reduces the likelihood of critically‐ill patients developing an infection, or dying. We are also uncertain whether bathing critically ill patients with chlorhexidine shortens the length of time people spend in hospital, or lowers their risk of developing skin reactions.

What was studied in the review?
People who are critically ill (in an ICU, or a high‐dependency or critical care unit) often catch infections during their time in hospital. These infections can lead to longer hospital stays, additional medical complications, permanent disability or even death. Patients in ICUs are particularly vulnerable to infections because the body’s ability to fight infection is reduced by illness or trauma. Surgical tubes and lines (for example to help with feeding or breathing) may enable bacteria to enter the body. Chlorhexidine is a low‐cost product which is used as an antiseptic and disinfectant in hospitals.

What are the main results of the review?
In December 2018 we searched for studies looking at the use of chlorhexidine for bathing critically ill patients. We found eight studies dating from 2005 to 2018, involving a total of 24,472 people across more than 20 ICUs. Seven studies included people who were adults, and one study included only children. All studies included both males and females. All studies compared bathing with chlorhexidine versus bathing with soap and water or non‐antimicrobial washcloths. Four studies received funding from independent funders (government organisations, or from hospital or university departments) or reported no external funding, and four studies received funding from companies that manufactured chlorhexidine products.

The evidence from all eight studies combined is not sufficient to allow us to be certain whether patients bathed in chlorhexidine are less likely to catch an infection during their stay in the ICU. We are also uncertain whether patients bathed in chlorhexidine are less likely to die, because the certainty of the evidence from the six studies that reported on this is very low. We did not pool the evidence from the six studies that reported how long patients had stayed in the ICU, because the results differed widely. We are also uncertain whether patients bathed in chlorhexidine are likely to be in the ICU for less time, because the certainty of the evidence is very low. Reports from five studies provided different evidence about whether chlorhexidine led to more or less skin reactions; we are uncertain whether patients bathed in chlorhexidine are likely to have more or less skin reactions, because the certainty of the evidence is very low.

How up to date is this review and Quality of evidence
We searched for studies that had been published up to December 2018.  Most studies did not use methods to conceal the type of bathing solution that staff were using, which increases the risk that staff may have treated patients differently depending on whether patients were in the chlorhexidine study group or the soap‐and‐water study group. Participants in some studies may have already caught an infection before the start of the study and we were concerned that this might have affected our results. We also noticed wide differences in some results, and some outcomes had few reported events. These were reasons to judge the quality of the evidence to be very low.

Implications for practice
It is not clear whether bathing with chlorhexidine reduces hospital‐acquired infections, mortality or length of stay in the intensive care unit, or whether chlorhexidine use results in more skin reactions, because the certainty of the evidence is very low. One study is awaiting classification and two studies are ongoing; we do not know if inclusion of these studies in future updates of this Cochrane Review will increase our certainty in the results of the review.

Implications for research
Additional research is needed to evaluate whether chlorhexidine bathing may reduce hospital‐acquired infections in the intensive care unit. We recommend that studies are sufficiently powered and methodologically robust, and that attention is paid to reduce the risk of performance bias through blinding of personnel. Cluster‐randomised studies and cross‐over trials would benefit from reporting data in more detail, including important parameters such as the intracluster correlation coefficient and interperiod correlation. Some consensus on the reporting of hospital‐acquired infection rates, for example through the adoption of a core outcome set for trials of infection prevention, would also be helpful.

The full details of this Cochrane Systematic Review are available via this link.

Ketamine sedation in mechanically ventilated patients: A systematic review and meta-analysis

This article by Fuller and colleagues was first published online in the Journal of Critical Care during December 2019.
Purpose:  Ketamine use as a sedative agent in mechanically ventilated patients is increasing. This systematic review and meta-analysis collates existing literature and quantifies the impact of ketamine in mechanically ventilated patients.
Materials and methods:  EMBASE, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, conference proceedings, and reference lists were searched. Randomized and nonrandomized studies were included, and two reviewers independently screened abstracts of identified studies for eligibility.
Results:  Fifteen studies (n = 892 patients) were included. Random effects meta-analytic models revealed that ketamine was associated with a reduction in propofol infusion rate (mean difference in dose, −699 μg/min; 95% CI -1169 to −230, p = .003), but had no impact on fentanyl or midazolam. Ketamine was not associated with mortality, on-target sedation, vasopressor dependence, or hospital length of stay. Cardiovascular complications (e.g. tachycardia and hypertension) were most commonly reported, followed by neurocognitive events, such as agitation and delirium.
Conclusions:  The data regarding ketamine use in mechanically ventilated patients is limited in terms of quantity, methodological quality, and demonstrated clinical benefit. Ketamine may play a role as a sedative-sparing agent, but may be associated with harm. High-quality studies are needed before widespread adoption of ketamine earlier in the sedation pathway.
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Non-opioid analgesics as adjuvants to opioid for pain management in adult patients in the ICU: A systematic review and meta-analysis

This research by Zhao and colleagues was published online in the Journal of Critical Care during August 2018.
Purpose:  To identify the impact of non-opioid analgesics as adjuvants to opioid on opioid consumption and its side effects, as well as the analgesic effectiveness in adult patients in the ICU.
Methods:  Only randomized clinical trials using non-opioid analgesics for analgesia in the ICU were included. Pooled analyses with 95% CI were determined.
Results:  Twelve studies (mainly surgical and Guillain-Barre syndrome patients) were included. Non-opioid analgesics as adjuvants to opioid were associated with a significant reduction in the consumption of opioids when compared with opioid use alone at Day 1 (MD -15.40; 95% CI -22.41 to −8.39; P< .001) and Day 2 (MD -22.93; 95% CI -27.70 to −18.16; P< .001). Non-opioid analgesics as adjuvants to opioid were associated with a significantly lower incidence of nausea and vomiting when compared with opioid use alone (RR 0.46; 95% CI 0.30 to 0.68; P< .001). Non-opioid analgesics as adjuvants to opioid significantly decreased the pain score at Day 1 (MD -0.68; 95% CI -1.28 to −0.08; P = .03) and Day 2 (MD -1.36; 95% CI -2.47 to −0.24; P = .02).
Conclusions:  Non-opioid analgesics as adjuvants to opioid reduced the consumption and the side effects of opioids in adult surgical and Guillain-Barre syndrome patients in the ICU.
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Risk factors for new-onset atrial fibrillation on the general adult ICU: A systematic review

This article by Bedford and others was first published online in the Journal of Critical Care during June 2019.
Purpose:  This study was performed to systematically review the available evidence for the risk factors for NOAF on the general adult intensive care unit (ICU) and provide a semi-quantitative evidence synthesis.
Methods:  We searched the MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and the CENTRAL databases from 1970 to 2018.
We included studies of adults based in general ICUs that evaluated potential risk factors for new-onset atrial fibrillation. We excluded studies involving patients with a history of AF.
We semi-qualitatively evaluated the strength of evidence for each identified variable.
Results:  We screened 1447 studies. Seventeen studies were included in the final analysis. We identified strong evidence for age, male sex, preceding cardiovascular disease, acute renal failure, acute respiratory failure, APACHE score and the use of vasopressors as risk factors for the development of NOAF on the ICU. Modifiable risk factors had not been studied in detail.
Conclusions:  We provide the first systematic review with evidence synthesis of risk factors for NOAF on the general adult ICU. Evidence for modifiable risk factors was limited. Further research is therefore required and may contribute towards the evidence-based prevention and management of this important condition.
The full text of this article is fully available to all.

Efficacy of music on sedation, analgesia and delirium in critically ill patients. A systematic review of randomized controlled trials

This article by Gonzalo and colleagues was published online in June 2019 in the Journal of Critical Care.
Purpose:  To systematically synthesize randomized controlled trial data on the efficacy of music to provide sedation and analgesia, and reduce incidence of delirium, in critically ill patients.
Material and methods:  Relevant databases (Medline, PubMed, Embase, CINAHL, Cochrane, Alt Healthwatch, LILACS, PsycINFO, CAIRSS, RILM) were searched from inception to April 26, 2018. We also searched the reference lists of included publications and for ongoing trials. The selection of relevant articles was conducted by two researchers at two levels of screening.
Data collection followed the recommendations from the Cochrane Systematic Reviews Handbook. We used the Cochrane Collaboration’s tool for assessing risk of bias. Quality of the evidence was rated according to GRADE.
Results:  The review identified six adult studies and no neonatal or pediatric studies. A descriptive analysis of study results was performed. Meta-analysis was not feasible due to heterogeneity. One study reported a reduction in sedation requirements with the use of music while the other five did not find any significant differences across groups.
Conclusions:  This systematic review revealed limited evidence to support or refute the use of music to reduce sedation/analgesia requirements, or to reduce delirium in critically ill adults, and no evidence in pediatric and neonatal critically ill patients.
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