Delayed vasopressor initiation is associated with increased mortality in patients with septic shock

This research by Hidalgo and others was first published online in the Journal of Critical Care during November 2019.
Purpose:  Mortality rate for septic shock, despite advancements in knowledge and treatment, remains high. Treatment includes administration of broad-spectrum antibiotics and stabilization of the mean arterial pressure (MAP) with intravenous fluid resuscitation. Fluid-refractory shock warrants vasopressor initiation. There is a paucity of evidence regarding the timing of vasopressor initiation and its effect on patient outcomes.
Materials and methods:  This retrospective, single-centered, cohort study included patients with septic shock from January 2017 to July 2017. Time from initial hypotension to vasopressor initiation was measured for each patient. The primary outcome was 30-day mortality.
Results:  Of 530 patients screened,119 patients were included. There were no differences in baseline patient characteristics. Thirty-day mortality was higher in patients who received vasopressors after 6 h (51.1% vs 25%, p < .01). Patients who received vasopressors within the first 6 h had more vasopressor-free hours at 72 h (34.5 h vs 13.1, p = .03) and shorter time to MAP of 65 mmHg (1.5 h vs 3.0, p < .01).
Conclusion:  Vasopressor initiation after 6 h from shock recognition is associated with a significant increase in 30-day mortality. Vasopressor administration within 6 h was associated with shorter time to achievement of MAP goals and higher vasopressor-free hours within the first 72 h.
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.

Gender differences in mortality and quality of life after septic shock: A post-hoc analysis of the ARISE study

This article by Luethi and others was published online in the Journal of Critical Care during November 2019.
Purpose:  To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock.
Material and methods:  Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age (≤ 50 years).
Results:  641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50 years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (≤50 years) (adjusted Odds Ratio (aOR): 0.91 (0.46–1.89), p = .85) nor in the older (>50 years) age-group (aOR: 1.10 (0.81–1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures.
Conclusions:  This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group.
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.

Acute kidney injury as a risk factor of hyperactive delirium: A case control study

This article by Wan and others was published online in the Journal of Critical Care during November 2019.
Purpose:  Delirium and acute kidney injury (AKI) are common organ dysfunctions during critical illness. Both conditions are associated with serious short- and long-term complications. We investigated whether AKI is a risk factor for hyperactive delirium.
Methods:  This was a single-centre case control study conducted in a 30 bedded mixed Intensive Care Unit in the UK. Hyperactive delirium cases were identified by antipsychotic initiation and confirmation of delirium diagnosis through validated chart review. Cases were compared with non-delirium controls matched by Acute Physiology and Chronic Health Evaluation II score and gender. AKI was defined by the KDIGO criteria.
Results:  142 cases and 142 matched controls were identified. AKI stage 3 was independently associated with hyperactive delirium [Odds ratio (OR) 5.40 (95% confidence interval (CI) 2.33–12.51]. Other independent risk factors were mechanical ventilation [OR 2.70 (95% CI 1.40–5.21)], alcohol use disorder [OR 5.80 (95% CI 1.90–17.72)], and dementia [OR 9.76 (95% CI 1.09–87.56)]. Hospital length of stay was significantly longer in delirium cases (29 versus 20 days; p = .004) but hospital mortality was not different.
Conclusions:  AKI stage 3 is independently associated with hyperactive delirium. Further research is required to explore the factors that contribute to this association.
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.

Short, and long-term mortality among cardiac intensive care unit patients started on continuous renal replacement therapy

This article by Keleshian and others was published online in the Journal of Critical Care during November 2019.
Purpose:  Patients requiring continuous renal replacement therapy (CRRT) are at high risk of death. Predictors of hospital mortality and post-discharge survival in cardiac intensive care unit (CICU) patients requiring CRRT have not been reported.
Materials and methods:  Retrospective review of 198 CICU patients undergoing CRRT from 2006 to 2015. Multivariable regression identified predictors of hospital mortality and Cox proportional-hazards identified predictors of post-discharge mortality among hospital survivors.
Results:  The indication for CRRT was volume overload in 129 (65%) and metabolic abnormalities in 76 (38%). 105 (53%) subjects died in hospital, with 22% dialysis-free hospital survival. Cardiogenic shock was present in 159 (80%) subjects; 150 (76%) subjects received vasopressors and 101 (51%) subjects required mechanical ventilation. Hospital mortality was similar in cardiogenic and non-cardiogenic causes of CICU admission. Predictors of hospital death included semi-quantitative RV function, Braden score, VIS, and PaO2/FIO2 ratio. Median post-discharge Kaplan-Meier survival was 1.9 years. Predictors of post-hospital death included age, VIS, diabetes, Braden score, semi-quantitative RV function, prior heart failure, and dialysis dependence. The indication for CRRT was not predictive of survival.
Conclusion:  Mortality is high among CICU patients requiring CRRT, and is predicted by the Braden score, RV dysfunction, respiratory failure and vasopressor load.
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.

Baclofen for Alcohol Withdrawl

This Cochrane Systematic Review by Liu and Wang was published in November 2019.
Review question:  This review attempted to evaluate the efficacy and safety of baclofen as a therapy for alcohol withdrawal syndrome (AWS) in people with alcoholism.
Background:  AWS is a distressing and life‐threatening condition that usually affects people who are alcohol dependent when they discontinue or decrease their alcohol consumption. The medicine baclofen has demonstrated potential to reduce symptoms of severe AWS in people with alcoholism. Treatment with baclofen is easy to manage, without producing any obvious side effects. This is an updated version of the original Cochrane Review published in 2011 and last updated in 2017.
Search date:  The evidence is current to June 2019.
Study characteristics:  We searched scientific databases for clinical trials comparing baclofen with placebo (a pretend treatment) or another potentially useful medicine in people with AWS. We included four randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 189 participants. One study from the USA compared baclofen to placebo given over at least 72 hours. The 31 participants were mainly men with the average age 47 years. Two studies with 85 participants compared baclofen to diazepam (a calming medicine) for 10 consecutive days, or for 10‐day inpatient stay with flexibility to allow negotiation of the discharge date between day 10 and day 15. One study compared baclofen to chlordiazepoxide given for nine days, in which the 60 participants were all men with an average age of 38 years. None of studies reported any conflict of interest. Addolorato 2006 was supported by Associazione Ricerca in Medicina, Italy. Girish 2016 was supported by KIMS Hospital and Research Centre (Bangalore, India). Jhanwar 2014 reported no funding source. Lyon 2011 was supported by Duluth Clinic Foundation (MN, USA).
Key results:  None of the included studies assess the main outcomes of the review, that is, alcohol withdrawal seizures (fits), alcohol withdrawal delirium (confused thinking and awareness), and craving. We are uncertain whether baclofen improves withdrawal symptoms and signs, and reduces side effects when compared with placebo or other medicines as the quality of the evidence was very low.
Quality of the evidence:  The quality of the evidence from the studies was very low and results should be interpreted with caution. In the future, well‐designed, double‐blind (where neither the participant nor the researcher knows which treatment has been given until after the results have been collected) RCTs with large numbers of participants are required to test how effective and well tolerated baclofen is in people with AWS.
The full text of this review can be found via this link.

Critical Care Reviews Newsletter 413 11th November 2019

The Critical Care Reviews Newsletter delivers the best critical care research and open access articles from across the medical literature over the past seven days.
Articles in this week’s edition include “Resuscitation Fluids in Septic Shock: A Network Meta-Analysis of Randomized Controlled Trials”, “Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia. The LEAP 2 Randomized Clinical Trial” and “Impact of Extracorporeal Membrane Oxygenation on Mortality in Adults With Cardiac Arrest”.
The full text of the newsletter is available via this link.

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.