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-invasive ventilation support during fiberoptic bronchoscopy-guided nasotracheal intubation effectively prevents severe hypoxemia

This article by Nong and others was first published online in the Journal of Critical Care during November 2019.
Purpose:  This study investigated the feasibility and efficacy of continuous noninvasive ventilation (NIV) support with 100% oxygen using a specially designed face mask, for reducing desaturation during fiberoptic bronchoscopy (FOB)-guided intubation in critically ill patients with respiratory failure.
Materials and methods: This was a single-center prospective randomized study. All patients undergoing FOB-guided nasal tracheal intubation were randomized to bag-valve-mask ventilation or NIV for preoxygenation followed by intubation. The NIV group were intubated through a sealed hole in a specially designed face mask during continuous NIV support with 100% oxygen. Control patients were intubated with removal of the mask and no ventilatory support.
Results:  We enrolled 106 patients, including 53 in each group. Pulse oxygen saturation (SpO2) after preoxygenation (99% (96%–100%) vs. 96% (90%–99%), p = .001) and minimum SpO2 during intubation (95% (87%–100%) vs. 83% (74%–91%), p < .01) were both significantly higher in the NIV compared with the control group. Severe hypoxemic events (SpO2 < 80%) occurred less frequently in the NIV group than in controls (7.4% vs. 37.7%, respectively; p < .01).
Conclusions:  Continuous NIV support during FOB-guided nasal intubation can prevent severe desaturation during intubation in critically ill patients with respiratory failure.
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Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure: A Randomized Clinical Trial.

This article from the HIGH WEAN Study Group and REVA Research Network was published in JAMA during 2019.
Importance:  High-flow nasal oxygen may prevent postextubation respiratory failure in the intensive care unit (ICU). The combination of high-flow nasal oxygen with noninvasive ventilation (NIV) may be an optimal strategy of ventilation to avoid reintubation.
Objective:  To determine whether high-flow nasal oxygen with prophylactic NIV applied immediately after extubation could reduce the rate of reintubation, compared with high-flow nasal oxygen alone, in patients at high risk of extubation failure in the ICU.
Design, Setting, and Participants:  Multicenter randomized clinical trial conducted from April 2017 to January 2018 among 641 patients at high risk of extubation failure (ie, older than 65 years or with an underlying cardiac or respiratory disease) at 30 ICUs in France; follow-up was until April 2018.
Interventions: Patients were randomly assigned to high-flow nasal oxygen alone (n = 306) or high-flow nasal oxygen with NIV (n = 342) immediately after extubation.
Main Outcomes and Measures:  The primary outcome was the proportion of patients reintubated at day 7; secondary outcomes included postextubation respiratory failure at day 7, reintubation rates up until ICU discharge, and ICU mortality.
Results:  Among 648 patients who were randomized (mean [SD] age, 70 [10] years; 219 women [34%]), 641 patients completed the trial. The reintubation rate at day 7 was 11.8% (95% CI, 8.4%-15.2%) (40/339) with high-flow nasal oxygen and NIV and 18.2% (95% CI, 13.9%-22.6%) (55/302) with high-flow nasal oxygen alone (difference, -6.4% [95% CI, -12.0% to -0.9%]; P = .02). Among the 11 prespecified secondary outcomes, 6 showed no significant difference. The proportion of patients with postextubation respiratory failure at day 7 (21% vs 29%; difference, -8.7% [95% CI, -15.2% to -1.8%]; P = .01) and reintubation rates up until ICU discharge (12% vs 20%, difference -7.4% [95% CI, -13.2% to -1.8%]; P = .009) were significantly lower with high-flow nasal oxygen and NIV than with high-flow nasal oxygen alone. ICU mortality rates were not significantly different: 6% with high-flow nasal oxygen and NIV and 9% with high-flow nasal oxygen alone (difference, -2.4% [95% CI, -6.7% to 1.7%]; P = .25).
Conclusions and Relevance:  In mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

Conservative Oxygen Therapy during Mechanical Ventilation in the ICU.

This publication from the ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group was published in the New England Journal of Medicine during 2019
Background:  Patients who are undergoing mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation).
Methods:  We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2. The primary outcome was the number of ventilator-free days from randomization until day 28.
Results:  The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of -0.3 days (95% confidence interval [CI], -2.1 to 1.6; P = 0.80). The conservative-oxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37).
Conclusions:  In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days.

The printed copy of the New England Journal of Medicine is available in the Health Care Library on D Level of Rotherham Hospital.

Effect of an ICU Diary on Post traumatic Stress Disorder Symptoms Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

This research by Garrouste-Orgeas and colleagues was published in JAMA during July 2019.
Importance:  Keeping a diary for patients while they are in the intensive care unit (ICU) might reduce their posttraumatic stress disorder (PTSD) symptoms.
Objectives:  To assess the effect of an ICU diary on the psychological consequences of an ICU hospitalization.
Design, Setting, and Participants:  Assessor-blinded, multicenter, randomized clinical trial in 35 French ICUs from October 2015 to January 2017, with follow-up until July 2017. Among 2631 approached patients, 709 adult patients (with 1 family member each) who received mechanical ventilation within 48 hours after ICU admission for at least 2 days were eligible, 657 were randomized, and 339 were assessed 3 months after ICU discharge.
Interventions:  Patients in the intervention group (n = 355) had an ICU diary filled in by clinicians and family members. Patients in the control group (n = 354) had usual ICU care without an ICU diary.
Main Outcomes and Measures:  The primary outcome was significant PTSD symptoms, defined as an Impact Event Scale-Revised (IES-R) score greater than 22 (range, 0-88; a higher score indicates more severe symptoms), measured in patients 3 months after ICU discharge. Secondary outcomes, also measured at 3 months and compared between groups, included significant PTSD symptoms in family members; significant anxiety and depression symptoms in patients and family members, based on a Hospital Anxiety and Depression Scale score greater than 8 for each subscale (range, 0-42; higher scores indicate more severe symptoms; minimal clinically important difference, 2.5); and patient memories of the ICU stay, reported with the ICU memory tool.
Results:  Among 657 patients who were randomized (median [interquartile range] age, 62 [51-70] years; 126 women [37.2%]), 339 (51.6%) completed the trial. At 3 months, significant PTSD symptoms were reported by 49 of 164 patients (29.9%) in the intervention group vs 60 of 175 (34.3%) in the control group (risk difference, -4% [95% CI, -15% to 6%]; P = .39). The median (interquartile range) IES-R score was 12 (5-25) in the intervention group vs 13 (6-27) in the control group (difference, -1.47 [95% CI, -1.93 to 4.87]; P = .38). There were no significant differences in any of the 6 prespecified comparative secondary outcomes.
Conclusions and Relevance:  Among patients who received mechanical ventilation in the ICU, the use of an ICU diary filled in by clinicians and family members did not significantly reduce the number of patients who reported significant PTSD symptoms at 3 months. These findings do not support the use of ICU diaries for preventing PTSD symptoms.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

Caring for non-sedated mechanically ventilated patients in ICU: A qualitative study comparing perspectives of expert and competent nurses

This article by Mortensen and colleagues was published on line in February 2019 in the Journal of Intensive and Critical Care Nursing.
Background:  Sedation practice has evolved from deep to lighter or no sedation in mechanically ventilated patients in the intensive care unit (ICU). The care of conscious intubated patients constitutes a change in the nurse-patient interaction.
Objective:  We aimed to compare the perspectives of expert and competent nurses regarding their interaction with non-sedated mechanically ventilated ICU patients.
Method:  The study had a qualitative comparative design applying semi-structured dyadic interviews. We interviewed five pairs of expert and competent ICU nurses with respectively >8 and 2–3 years of ICU experience and performed qualitative content analysis to explore the two perspectives.
Findings:  We identified four main categories illustrating complexities of nurse-patient interaction: Managing frustration, Attempting dialogue, Negotiating reality and Alleviating discomfort. Expert nurses expressed more frustration and ambivalence towards light sedation than competent nurses, who took awake patients for granted. All nurses experienced communication issues, demanding patients, and inability to provide adequate patient comfort.
Conclusion:  Our study added to the knowledge of nurse-patient interaction by describing issues of frustration, ambivalence and insecurity in a contemporary context of minimal sedation. Expert nurses were mere concerned by awake patients than competent nurses. Lighter sedation in ICU requires better staffing and improved communication tools.
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Effect of Protocolized Weaning With Early Extubation to Non-invasive Ventilation vs Invasive Weaning on Time to Liberation From Mechanical Ventilation Among Patients With Respiratory Failure: The Breathe Randomized Clinical Trial

This article by Perkins and colleagues was published in JAMA during November 2018.
Importance:  In adults in whom weaning from invasive mechanical ventilation is difficult, non-invasive ventilation may facilitate early liberation, but there is uncertainty about its effectiveness in a general intensive care patient population.
Objective:  To investigate among patients with difficulty weaning the effects of protocolized weaning with early extubation to non-invasive ventilation on time to liberation from ventilation compared with protocolized invasive weaning.
Design,Setting, and Participants:  Randomized,allocation-concealed, open-label, multicenter clinical trial enrolling patients between March 2013 and October 2016 from 41 intensive care units in the UK National Health Service. Follow-up continued until April 2017. Adults who received invasive mechanical ventilation for more than 48 hours and in whom a spontaneous breathing trial failed were enrolled.
Interventions:  Patients were randomized to receive either protocolized weaning via early extubation to non-invasive ventilation (n = 182)or protocolized standard weaning (continued invasive ventilation until successful spontaneous breathing trial, followed by extubation) (n = 182).
Main Outcomes and Measures:  Primary outcome was time from randomization to successful liberation from all forms of mechanical ventilation among survivors, measured in days, with the minimal clinically important difference defined as 1 day. Secondary outcomes were duration of invasive and total ventilation (days), reintubation or tracheostomyrates, and survival.
Results:  Among 364 randomized patients (mean age, 63.1[SD, 14.8] years; 50.5% male), 319 were evaluable for the primary effectiveness outcome (41 died before liberation, 2 withdrew, and 2 were discharged with ongoing ventilation). The median time to liberation was 4.3 days in the non-invasive group vs 4.5 days in the invasive group (adjusted hazard ratio, 1.1; 95% CI, 0.89-1.40).Competing risk analysis accounting for deaths had a similar result (adjusted hazard ratio, 1.1; 95% CI, 0.86-1.34). The non-invasive group received less invasive ventilation (median, 1 day vs 4 days; incidence rate ratio, 0.6; 95%CI, 0.47-0.87) and fewer total ventilator days (median, 3 days vs 4 days;incidence rate ratio, 0.8; 95% CI, 0.62-1.0). There was no significant difference in reintubation, tracheostomy rates, or survival. Adverse events occurred in 45 patients (24.7%) in the non-invasive group compared with 47(25.8%) in the invasive group.
Conclusions and Relevance:  Among patients requiring mechanical ventilation in whom a spontaneous breathing trial had failed, early extubation to non-invasive ventilation did not shorten time to liberation from any ventilation.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital. 
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