Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients.

This research by Olsen and colleagues was first published in the New England Journal of Medicine during February 2020.
Background:  In critically ill, mechanically ventilated patients, daily interruption of sedation has been shown to reduce the time on ventilation and the length of stay in the intensive care unit (ICU). Data on whether a plan of no sedation, as compared with a plan of light sedation, has an effect on mortality are lacking.
Methods:  In a multicenter, randomized, controlled trial, we assigned, in a 1:1 ratio, mechanically ventilated ICU patients to a plan of no sedation (non-sedation group) or to a plan of light sedation (i.e., to a level at which the patient was arousable, defined as a score of -2 to -3 on the Richmond Agitation and Sedation Scale [RASS], on which scores range from -5 [unresponsive] to +4 [combative]) (sedation group) with daily interruption. The primary outcome was mortality at 90 days. Secondary outcomes were the number of major thromboembolic events, the number of days free from coma or delirium, acute kidney injury according to severity, the number of ICU-free days, and the number of ventilator-free days. Between-group differences were calculated as the value in the non-sedation group minus the value in the sedation group.
Results:  A total of 710 patients underwent randomization, and 700 were included in the modified intention-to-treat analysis. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the non-sedation group than in the sedation group, indicating a greater chance of in-hospital death. The mean RASS score in the non-sedation group increased from -1.3 on day 1 to -0.8 on day 7 and, in the sedation group, from -2.3 on day 1 to -1.8 on day 7. Mortality at 90 days was 42.4% in the non-sedation group and 37.0% in the sedated group (difference, 5.4 percentage points; 95% confidence interval [CI], -2.2 to 12.2; P = 0.65). The number of ICU-free days and of ventilator-free days did not differ significantly between the trial groups. The patients in the non-sedation group had a median of 27 days free from coma or delirium, and those in the sedation group had a median of 26 days free from coma or delirium. A major thromboembolic event occurred in 1 patient (0.3%) in the non-sedation group and in 10 patients (2.8%) in the sedation group (difference, -2.5 percentage points; 95% CI, -4.8 to -0.7 [unadjusted for multiple comparisons]).
Conclusions:  Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption.
The paper copy of the New England Journal of Medicine is available in the Healthcare Library on D Level of Rotherham Hospital.

Effect of Intravenous Interferon β-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

This research by Ranieri and colleagues from the INTEREST Study Group was published during February 2020 in JAMA.
Importance:  Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage.
Objective:  To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS.
Design, Setting, and Participants:  Multicenter, randomized, double-blind, parallel-group trial conducted at 74 intensive care units in 8 European countries (December 2015-December 2017) that included 301 adults with moderate to severe ARDS according to the Berlin definition. The radiological and partial pressure of oxygen, arterial (Pao2)/fraction of inspired oxygen (Fio2) criteria for ARDS had to be met within a 24-hour period, and the administration of the first dose of the study drug had to occur within 48 hours of the diagnosis of ARDS. The last patient visit was on March 6, 2018.InterventionsPatients were randomized to receive an intravenous injection of 10 μg of IFN-β-1a (144 patients) or placebo (152 patients) once daily for 6 days.
Main Outcomes and Measures:  The primary outcome was a score combining death and number of ventilator-free days at day 28 (score ranged from -1 for death to 27 if the patient was off ventilator on the first day). There were 16 secondary outcomes, including 28-day mortality, which were tested hierarchically to control type I error.
Results:  Among 301 patients who were randomized (mean age, 58 years; 103 women [34.2%]), 296 (98.3%) completed the trial and were included in the primary analysis. At 28 days, the median composite score of death and number of ventilator-free days at day 28 was 10 days (interquartile range, -1 to 20) in the IFN-β-1a group and 8.5 days (interquartile range, 0 to 20) in the placebo group (P = .82). There was no significant difference in 28-day mortality between the IFN-β-1a vs placebo groups (26.4% vs 23.0%; difference, 3.4% [95% CI, -8.1% to 14.8%]; P = .53). Seventy-four patients (25.0%) experienced adverse events considered to be related to treatment during the study (41 patients [28.5%] in the IFN-β-1a group and 33 [21.7%] in the placebo group).
Conclusions and Relevance:  Among adults with moderate or severe ARDS, intravenous IFN-β-1a administered for 6 days, compared with placebo, resulted in no significant difference in a composite score that included death and number of ventilator-free days over 28 days. These results do not support the use of IFN-β-1a in the management of ARDS.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

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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Neuromuscular electrical stimulation combined with exercise decreases duration of mechanical ventilation in ICU patients: A randomized controlled trial.

This article by Dos Santos and colleagues was published in “Physiotherapy Theory and Practice”
Background:  Early mobilization can be employed to minimize the duration of intensive care. However, a protocol combining neuromuscular electrical stimulation (NMES) with early mobilization has not yet been tested in ICU patients. Our aim was to assess the efficacy of NMES, exercise (EX), and combined therapy (NMES + EX) on duration of mechanical ventilation (MV) in critically ill patients.
Methods:  The participants in this randomized double-blind trial were prospectively recruited within 24 hours following admission to the intensive care unit of a tertiary hospital. Eligible patients had 18 years of age or older; MV for less than 72 hours; and no known neuromuscular disease. Computer-generated permuted block randomization was used to assign patients to NMES, EX, NMES + EX, or standard care (control group). The main endpoint was duration of MV. Clinical characteristics were also evaluated and intention to treat analysis was employed.
Results:  One hundred forty-four patients were assessed for eligibility to participate in the trial, 51 of whom were enrolled and randomly allocated into four groups: 11 patients in the NMES group, 13 in the EX group, 12 in the NMES + EX group, and 15 in the control group (CG). Duration of MV (days) was significantly shorter in the combined therapy (5.7 ± 1.1) and NMEN (9.0 ± 7.0) groups in comparison to CG (14.8 ± 5.4).
Conclusions:  NMES + EX consisting of NMES and active EXs was well tolerated and resulted in shorter duration of MV in comparison to standard care or isolated therapy (NMES or EX alone).
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