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,, 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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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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Sleep deprivation determinants as perceived by intensive care unit patients: Findings from a systematic review, meta-summary and meta-synthesis

This research by Mattiussi and others was published in “Intensive and Critical Care Nursing” during March 2019.
Objectives:  To summarise evidence on sleep deprivation and/or poor sleep determinants as experienced by intensive care unit patients.
Research methodology/design:  A systematic review of qualitative studies identified through PubMed, CINAHL and Scopus databases published in English up to 2018 was performed following PRISMA guidelines. The included studies were critically evaluated by using the Critical Appraisal Screening Programme tool. Study findings were then subjected to a meta-summary and a meta-synthesis.
Setting:  Intensive Care Units.
Main outcome measures:  Critically ill patients’ experiences of sleep deprivation.
Results:  Seven qualitative studies were included documenting the experience of 109 adult patients. A total of 12 codes emerged as causes of sleep deprivation and ‘feeling fear/concern’ was reported with the greatest frequency (71.4%) in the meta-summary. The 12 codes were categorised into three main themes influencing both directly and also interdependently the quality of sleep: (1) Experiencing complex interactions with the environment (nursing activities, frightening or disturbing sounds, acceptable sounds, time and space disorientation); (2) Undergoing intensive emotions and feelings (fear/concerns, state of abandon, inexplicable insomnia, inability to move, inability to talk) and (3) Receiving an appropriate standard of care (physical pain, feeling safe/unsafe).
Conclusions:  Despite the increased relevance of sleep deprivation and poor sleep quality, only a few studies have been performed to date aimed at identifying the factors involved in the phenomenon according to patient experience. The majority of determinants as identified from patients’ perspective are modifiable.
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Utility of pleural effusion drainage in the ICU: An updated systematic review and META-analysis

This research by Vetrugno and colleagues was published online in the “Journal of Critical Care” in March 2019.
Purpose:  The effects on the respiratory or hemodynamic function of drainage of pleural effusion on critically ill patients are not completely understood. First outcome was to evaluate the PiO2/FiO2 (P/F) ratio before and after pleural drainage. Secondary outcomes: evaluation of A-a gradient, End-Expiratory lung volume (EELV), heart rate (HR), mean arterial pressure (mAP), left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac output (CO), ejection fraction (EF), and E/A waves ratio (E/A). A tertiary outcome: evaluation of pneumothorax and hemothorax complications.
Materials and methods:  Searches were performed on MEDLINE, EMBASE, COCHRANE LIBRARY, SCOPUS and WEB OF SCIENCE databases from inception to June 2018 (PROSPERO CRD42018105794).
Results:  We included 31 studies (2265 patients). Pleural drainage improved the P/F ratio (SMD: −0.668; CI: -0.947–0.389; p < .001), EELV (SMD: -0.615; CI: -1.102–0.219; p = .013), but not A-a gradient (SMD: 0.218; CI: -0.273-0.710; p = .384). HR, mAP, LVEDV, SV, CO, E/A and EF were not affected. The risks of pneumothorax (proportion: 0.008; CI: 0.002–0.014; p = .138) and hemothorax (proportion: 0.006; CI: 0.001–0.011; p = .962) were negligible.
Conclusions:  Pleural effusion drainage improves oxygenation of critically ill patients. It is a safe procedure. Further studies are needed to assess the hemodynamic effects of pleural drainage.
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The Effect of ICU Diaries on Psychological Outcomes and Quality of Life of Survivors of Critical Illness and Their Relatives: A Systematic Review and Meta-Analysis

This review by McIlroy and colleagues was published in the November 2018 issue of Critical Care Medicine.
Objectives:  To evaluate the effect of ICU diaries on post traumatic stress disorder symptoms in ICU survivors and their relatives.Secondary objectives were to determine the effect on anxiety, depression, and health-related quality of life in patients and their relatives.
Data Sources:  We searched online databases,trial registries, and references of relevant articles.
Study Selection:  Studies were included if there was an ICU diary intervention group which was compared with a group without a diary.
Data Extraction:  Titles, abstracts, and full-text articles were reviewed independently by two authors. Data was abstracted using a structured template.
Data Synthesis:  Our search identified 1,790 articles and retained eight studies for inclusion in the analysis. Pooled results found no significant reduction in patients’ post traumatic stress disorder symptoms with ICU diaries (risk ratio, 0.75 [0.3-1.73]; p = 0.5; n = 3 studies); however, there was a significant improvement in patients’ anxiety(risk ratio, 0.32 [0.12, 0.86]; p = 0.02; n = 2 studies) and depression (risk ratio, 0.39 [0.17-0.87]; p = 0.02; n = 2 studies) symptoms. Two studies reported significant improvement in post traumatic stress disorder symptoms of relatives of ICU survivors; however, these results could not be pooled due to reporting differences. One study reported no significant improvement in either anxiety (risk ratio, 0.94; 95% [0.66-1.33]; p = 0.72) or depression (risk ratio, 0.98; 95% [0.5-1.9]; p = 0.95) in relatives. There was a significant improvement in health-related quality of life of patients with a mean increase in the Short Form-36 general health score by 11.46 (95% CI, 5.87-17.05; p ≤0.0001; n = 2 studies). No studies addressed health-related quality of life of relatives.  
Conclusions:  ICU diaries decrease anxiety and depression and improve health-related quality of life, but not post traumatic stress disorder among ICU survivors and may result in less post traumatic stress disorder among relatives of ICU patients. Multicenter trials with larger sample sizes are necessary to confirm these findings.
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Dexmedetomidine in prevention and treatment of postoperative and intensive care unit delirium: a systematic review and meta-analysis

This article by Flukiger et al was published in Annals of intensive care September 2018.
Background:  To determine the preventive and therapeutic effect of dexmedetomidine on intensive care unit (ICU) delirium.
Methods:  The literature search using PubMed and the Cochrane Central Register of Controlled Trials was performed (August 1, 2018) to detect all randomized controlled trials (RCTs) of adult ICU patients receiving dexmedetomidine. Articles were included if they assessed the influence of dexmedetomidine compared to a sedative agent on incidence of ICU delirium or treatment of this syndrome. Accordingly, relevant articles were allocated to the following two groups: (1) articles that assessed the delirium incidence (incidence comparison) or articles that assessed the treatment of delirium (treatment comparison). Incidence of delirium and delirium resolution were the primary outcomes. We combined treatment effects comparing dexmedetomidine versus (1) placebo, (2) standard sedatives, and (3) opioids in random-effects meta-analyses. Risk of bias for each included RCT was assessed following Cochrane standards.
Results:  The literature search resulted in 28 articles (25 articles/4975 patients for the incidence comparison and three articles/166 patients for the treatment comparison). In the incidence comparison, heterogeneity was present in different subgroups. Administration of dexmedetomidine was associated with significantly lower overall incidence of delirium when compared to placebo (RR 0.52; 95% CI 0.39-0.70; I2 = 37%), standard sedatives (RR 0.63; 95% CI 0.46-0.86; I2 = 69%), as well as to opioids (RR 0.61; 95% CI 0.44-0.83; I2 = 0%). Use of dexmedetomidine significantly increased the risks of bradycardia and hypotension. Limited data were available on circulatory insufficiency and mortality. In the treatment comparison, the comparison drugs in the three RCTs were placebo, midazolam, and haloperidol. The resolution of delirium was measured differently in each study. Two out of the three studies indicated clear favorable effects for dexmedetomidine (i.e., compared to placebo and midazolam). The study comparing dexmedetomidine with haloperidol was a pilot study (n = 20) with high variability in the results.
Conclusions:  Findings suggest that dexmedetomidine reduces incidence and duration of ICU delirium. Furthermore, our systematic searches show that there is limited evidence if a delirium shall be treated with dexmedetomidine.
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Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials

The secondary research was published in the journal Critical Care in August 2018 by Wirz and others.
Background:  The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection.
Methods:  For this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the “procalcitonin-guided” group) or the current standard of care (the “controls”). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay.
Results:  Mortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient -1.19 days, 95% CI -1.73 to -0.66; p < 0.001).
Conclusion:  Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.
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