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.
The full text of this article is available to subscribers via this link to the journal’s homepage.  The full text of articles from issues older than sixty days is available via this link to an archive of issues of Journal of Critical Care.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.

High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis

This article was published on-line in Intensive Care Medicine during April 2019 by Rochwerg and colleagues.
Background:  This systematic review and meta-analysis summarizes the safety and efficacy of high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure.
Methods:  We performed a comprehensive search of MEDLINE, EMBASE, and Web of Science. We identified randomized controlled trials that compared HFNC to conventional oxygen therapy. We pooled data and report summary estimates of effect using relative risk for dichotomous outcomes and mean difference or standardized mean difference for continuous outcomes, with 95% confidence intervals. We assessed risk of bias of included studies using the Cochrane tool and certainty in pooled effect estimates using GRADE methods.
Results:  We included 9 RCTs (n = 2093 patients). We found no difference in mortality in patients treated with HFNC (relative risk [RR] 0.94, 95% confidence interval [CI] 0.67–1.31, moderate certainty) compared to conventional oxygen therapy. We found a decreased risk of requiring intubation (RR 0.85, 95% CI 0.74–0.99) or escalation of oxygen therapy (defined as crossover to HFNC in the control group, or initiation of non-invasive ventilation or invasive mechanical ventilation in either group) favouring HFNC-treated patients (RR 0.71, 95% CI 0.51–0.98), although certainty in both outcomes was low due to imprecision and issues related to risk of bias. HFNC had no effect on intensive care unit length of stay (mean difference [MD] 1.38 days more, 95% CI 0.90 days fewer to 3.66 days more, low certainty), hospital length of stay (MD 0.85 days fewer, 95% CI 2.07 days fewer to 0.37 days more, moderate certainty), patient reported comfort (SMD 0.12 lower, 95% CI 0.61 lower to 0.37 higher, very low certainty) or patient reported dyspnea (standardized mean difference [SMD] 0.16 lower, 95% CI 1.10 lower to 1.42 higher, low certainty). Complications of treatment were variably reported amongst included studies, but little harm was associated with HFNC use.
Conclusion:  In patients with acute hypoxemic respiratory failure, HFNC may decrease the need for tracheal intubation without impacting mortality.
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