Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation: A Randomized Clinical Trial

This research by van Meenen et al was published in JAMA in February 2018.
Importance:  It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation.
Objective:  To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization.
Design, Setting, and Participants:  Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands.
Interventions:  On-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473).
Main Outcomes and Measures:  The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events.
Results:  Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, -0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001).
Conclusions and Relevance:  Among ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization.
The full text of this article is available via this link.  The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.


Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation with Sepsis

This randomised clinical trial by Kawazoe and colleagues is part of the Dexmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation (DESIRE) Trial.  It was published in the Journal of the American Medical Association (JAMA) in April 2017.  The physical journal is available in Rotherham Health Care Library.  The electronic version of this article is available via this link with a Rotherham NHS Athens Password.

Importance:  Dexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among patients with sepsis.

Objectives:  To examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation.

Design, Setting, and Participants:  Open-label, multicenter randomized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours.

Interventions:  Patients were randomized to receive either sedation with dexmedetomidine (n = 100) or sedation without dexmedetomidine (control group; n = 101). Other agents used in both groups were fentanyl, propofol, and midazolam.

Main Outcomes and Measures:  The co-primary outcomes were mortality and ventilator-free days (over a 28-day duration). Sequential Organ Failure Assessment score (days 1, 2, 4, 6, 8), sedation control, occurrence of delirium and coma, intensive care unit stay duration, renal function, inflammation, and nutrition state were assessed as secondary outcomes.

Results:  Of the 203 screened patients, 201 were randomized. The mean age was 69 years (SD, 14 years); 63% were male. Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group (19 patients [22.8%] vs 28 patients [30.8%]; hazard ratio, 0.69; 95% CI, 0.38-1.22; P = .20). Ventilator-free days over 28 days were not significantly different between groups (dexmedetomidine group: median, 20 [interquartile range, 5-24] days; control group: median, 18 [interquartile range, 0.5-23] days; P = .20). The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation (range, 17%-58% vs 20%-39%; P = .01); other outcomes were not significantly different between groups. Adverse events occurred in 8 (8%) and 3 (3%) patients in the dexmedetomidine and control groups, respectively.

Conclusions and Relevance:  Among patients requiring mechanical ventilation, the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days. However, the study may have been underpowered for mortality, and additional research may be needed to evaluate this further.

Oral care in ventilated intensive care unit patients

Diaz, T.L. et al. American Journal of Infection Control. Published online: 23 January 2017



  • A quality improvement project was developed to evaluate the pre/post effects of standardized placement and supply of oral care equipment in patient rooms.
  • Daily audits were performed to assess nursing behavior related to the performance of oral care on intubated patients with components from a 24 hour kit.
  • Increasing supply and creating uniform placement of oral care tools in patient rooms contributes to increased performance of oral hygiene interventions by nurses.

Read the full abstract here

Use of noninvasive ventilation in immunocompromised patients with acute respiratory failure

Huang, H-B et al. Critical Care. 21:4

Background: Acute respiratory failure (ARF) remains a common hazardous complication in immunocompromised patients and is associated with increased mortality rates when endotracheal intubation is needed. We aimed to evaluate the effect of early noninvasive ventilation (NIV) compared with oxygen therapy alone in this patient population.


Conclusions: The limited evidence indicates that early use of NIV could reduce short-term mortality in selected immunocompromised patients with ARF. Further studies are needed to identify in which selected patients NIV could be more beneficial, before wider application of this ventilator strategy.

Read the full abstract and article here 

Antibiotics for ventilator-associated pneumonia: Cochrane Review

This review by Arthur et al was published on 20th October 2016.  The plain language summary is shown below.  Full details of the review can be found via this link.

Background.  Ventilators are machines that breathe for patients. The ventilator tube goes into the mouth and through the windpipe. Sometimes there are bacteria on the ventilator tube that infect the patient’s lungs, leading to a disease called ventilator-associated pneumonia. Ventilator-associated pneumonia can cause significant harmful effects, and can sometimes lead to death. When treating people with ventilator-associated pneumonia, doctors must decide which antibiotic therapy to prescribe, usually without knowing the particular type of bacterial infection. This decision is important because inappropriate initial treatment may increase risk of harmful effects and longer hospital stays.

Search date  We searched for studies to December 2015.

Study characteristics  We looked at studies involving adults aged over 18 years who were treated in intensive care units for ventilator-associated pneumonia and needed antibiotic treatment. We analysed 12 studies with 3571 participants.

Key results  All included studies looked at the use of one antibiotic treatment plan versus another, but these varied among studies. There was potential for bias because some studies did not report outcomes for all participants, and funding for many was provided by pharmaceutical companies and study authors were affiliated with these companies.

We used statistical techniques to evaluate our results. For single versus multiple antibiotics, we found no difference in rates of death or cure, or adverse events. For our comparison of combination therapies with optional adjunctives we were only able to analyse clinical cure for one the antibiotics Tigecycline and imipenem-cilastatin for which imipenem-cilastatin was found to have higher clinica cure. We also looked at carbapenem (antibiotics used to treat infections caused by multidrug-resistant bacteria) versus non-carbapenem treatment; we found no difference in death rate or adverse effects, but we found that carbapenems are associated with an increase in clinical cure.

Quality of evidence  We assessed evidence quality as moderate for most outcomes, and very low for clinical cure when single-antibiotic treatment was compared with multiple antibiotic therapy. We also found that evidence quality was low for adverse events when carbapenem was compared with non-carbapenem treatment.

Conclusions  We did not find differences between single and combination therapy, lending support to use of a single-antibiotic treatment plan for people with ventilator-associated pneumonia. This may not be applicable to all patients because studies did not identify patients who are at risk of exposure to harmful types of bacteria.

We could not evaluate the best single-antibiotic choice to treat people with ventilator-associated pneumonia because there were too few studies, but carbapenems may achieve better cure rates than other tested antibiotics.